LymeMD

HIDA scan and Mycoplasma

2012-02-01T07:47:00.000-08:00

Sick for a long time this patient had already been to many doctors. Previous treatments included 9 months of Rocephin. She first saw me two months ago. Prominent symptoms included: cognitive dysfunction,depression, weakness, seizures, "TIA", headaches, tingling, joint pain, palpitations, neuropathic pains and gastrointestinal issues. The depression was profound, associated with suicidal ideation at times.

She had a history of sporadic abnormal liver test with marked abdominal pain. Belly symptoms including bloating, nausea, anorexia and difficulty eating which was chronic.

She had dysautonomia and POTS.

There is much more to the story.Of course.

Lyme has been confirmed by IgeneX and Stony Brook. A recent Western Blot showed IgM bands: 41,18,20,30,31,37,38,58,60, The test showed 5 IgG bands.

Physical examination showed tenderness over the gallbladder.

The abdominal sonogram was negative for gall stones (it always is).

The HIDA scan was entirely normal. Here's the catch. The injection of CCK which makes the gallbladder contract reproduced her severe pain.

A surgeon friend has found this sign may be associated with gallbladder disease even with normal studies.

Her gallbladder was removed.

Then - something remarkable happened: she felt great, even off antibiotics.

Weakness,cognitive dysfunction,neuropathic pains were all better. Orthostatic tachycardia had improved significantly.

No longer using a cane, she was playing the piano - first time in over a year.

She sent a piece of gallbladder to Clongen for PCR testing for "everything."

The result was surprising: Mycoplasma species. I have no idea what to make of this unexpected finding.

Mycoplasma is an intracellular bacteria. You can never get rid of it.

Definition of insanity

2012-01-22T15:48:00.000-08:00

One patient with chronic Lyme called NIH hoping for acceptance into a new study. More research. Great. At least someone with gravitas thinks the jury is still out. The questionnaire sounds promising: tick bite, EM rash, joint problems, facial palsy, fever or chill, muscle pain, stiff neck, headache, heart problems, swollen lymph nodes, shooting pains in the hands/feet, cognitive problems, trouble finding words. This is the telephone screening questionnaire.

Patient's Western blot pattern: IgMs, 23,41,18,58,66 and 93. IgGs, only 41,64 and 68 A bust. Entry into the study requires a positive ELISA and 5/10 specific IgG bands. Rare findings.

Patients with long-standing Lyme disease have variable antibody responses. New IgM reactions can develop in late Lyme disease. IgM antibodies correlate with active infection, not IgG antibodies which tend to be protective.

Patients with strong persistent IgG bands may on average be healthier than other groups.

My patient complains she is very sick while a neighbor with 8/10 bands is very well.

A prospective study of antibody patterns seen in acute Lyme patients with persistent symptoms over time could help settle the issue and be relatively easy to do.

The unproven "CDC criteria" proposed by Dressler one weekend in 1994 has remained the unchallenged law of the land.

This same patient selection criteria has been used over and over again in NIH sponsored studies.

A definitions of insanity is repeating the same thing over and over expecting a different result.

No box

2012-01-20T13:34:00.000-08:00

In 2002 I didn't know much about Lyme. My patient suffered with a paralyzed diaphragm. He was in misery with every breath: only one lung could expand. A trillion specialist said he was a medical mystery. Idiopathic. Once I heard Gabe Mirkin say: Idiopathic means the doctor is an idiot and the patient is pathological. True in this case. My notes show I actually thought of Lyme even back then. He became one of those troubling patient, anathema to every primary clinic. So many complaints! fatigue, depression - at times suicidal, brain fog, memory loss, total body pain - the list went on. I was empathetic and used all the tools in my box - band aids. Somewhere along the trail I became "Lyme literate." Antibiotics helped a little. The diaphragm still wouldn't move and overall improvements were modest. In 2008 if finally sent off a blood sample to Clongen.Positive Babesia PCR. The PCR was positive!

In short, Mepron turned his life around. He could breath. Everything got better. He was even happy. Unfortunately, every time Mepron was stopped he crashed. Nothing else worked.

Recently,his employer suddenly cancelled Cigna. He was now pushed into Kaiser. He was told that his "Cadillac plan" had to go.

Today he came in just to lament.

He tells me the new Kaiser doctor mumbled something about about hindsight which didn't make any sense. The doctor told him there was no way he was going to prescribe Mepron for something "they" didn't believe in.

The doctor said he didn't know what a PCR is, and there is no box to check on the lab requisition to order a PCR. No Box. I had to repeat this over and over again to make sure I got it right.

The patient doesn't know what to do. He can't afford $1100.00 a month for the drug.

No box.

Babesia: confirmed case

2012-01-19T19:11:00.000-08:00

An unexpected page last Sunday. Call.... about...., 1-800 number, blood parasites. Strange message. I called the number back and ask for the name displayed on my beeper. The caller was a hematology tech from one of the "mill" labs. She had just seen parasites in the red blood cells of one of my patients: ring forms with some extracellular forms. She told me she needed to go over the slide with her supervisor in the morning for "speciation." We were both very excited.

The Maryland state health department states there has been only one confirmed case of Babesia in the state. Hence, all the ID docs dismiss all positive Babesia serologies as "false positives."

One of my patients made a ranting youtube video after consulting two ID docs at Hopkins. He is very sick and showed them: positive serology for B. duncan, a positive FISH test and a positive PCR test. One of the docs didn't know what B duncani is. He was told: " We don't use that lab." (IgeneX) "What lab do you use," he inquired. Response: " Different labs - we just don't use that one."

The health officials says PCR (false positives, experimental) isn't good enough to confirm a case. You need microscopic confirmation.

Here it was, the second confirmed case in the state of Maryland I thought. (Incentally, the same mill lab posted positive serology for B. microti for this patient).

But somewhere in the back of my mind it knew it was too good to be true. The supervisor from the lab in NC told me: " well, its only in a few cells, not enough for me to call it, will report it as a possible parasite, unable to "speciate."

"I am not looking for a species identification, just a genus."

Point ignored: "We see a lot of plasmodium in our lab."

"Well they are easy to see," I told him, "infect a lot of red blood cells. The point with Babesia is only a tiny percent of RBCs are infected - and the ring form is a classic presentation!" I got the impression he didn't know what I was talking about. "How many Babesia do you see in your lab?"

"About one per year, mostly from New England."

He suggested that I order a PCR to confirm the diagnosis if I suspected it. Fat chance.

He agreed that the tech did a great job and was sorry he couldn't help.

Continuous or pulsed

2012-01-13T08:02:00.001-08:00

Two patients yesterday with neuropsychiatric symptoms responsive to amoxicillin. One patient claimed that Moxatag, a long acting drug, was more effective than traditional short acting amoxicillin. The other adamantly claimed the opposite.

The question about continuous therapy versus pulse therapy is controversial and unsettled.

At least one(Lyme)study showed that continuous exposure to drug, even at lower concentration was more effective(had better killing kinetics).

Test tube study.

Clinical support: Long acting Bicillin (penicillin) works very well despite low blood/tissue concentration of drug.

Amoxicillin reaches a peak blood level without hours and is rapidly excreted with preferential penetration to some tissues. In-vivo(you), tissue concentration may be higher than shown with in-vitro(test tubes). Don't know.

IV antibiotics with long half lifes - Rocephin and Zithromax can be very effective.

Oral antibiotics behave differntly in the body than IV for a number of reasons.

I currently prescribe amoxicillin as 500 mg, two twice daily. Perhaps one four times per day would work better. There are practical limitations: better adsorption on an empty stomach, scheduling doses.

My impression: continuous better than pulsed.

Third opinion

2012-01-12T15:42:00.000-08:00

Here is a patient who states he has been sick his entire life - seeing a parade of doctors for as long as he can remember. Childhood was tough and he was maladjusted. Diagnosed with: learning disabilities, ADD, depression and Asberger's syndrome at varying times. Always sickly, missing a lot of school. Abdominal pain, fatigue, fevers, colds, flus, headaches and other ailments. Now treated for depression and sleep apnea he feels he is not thinking as clearly for the last year. He notes: increased anxiety, trouble finding words, worsening depression, more ADD symptoms. He also admits to drinking too much and using marijuana about three days a week. Things have not gone well at work or at home recently.

He recalls removing a tick from his dog a few years ago - not sure what kind. He has some vague pains in his joints and muscles, occasional pins and needles in his hands and feet, some twitching around his eyes and occasional tremors. He grew up in Arizona in the 70s, moved here 10 years ago. And then someone said: get a Lyme test.

An LLMD sent extensive tests to IgeneX. Everything was negative except the Lyme Western Blot. He had IgM bands: 18,31,34. He saw an LLMD who diagnosed Lyme. He was treated with herbs and a month of antibiotics. It didn't help. He saw an infectious disease doctor who ordered a Western Blot through Labcorp. Only a 23 IgM showed up. He was told he did not have Lyme disease.

He now wants a third opinion - great.

A Western Blot from Stony Brook showed IgM bands 41 and 93.

His exam showed a mild postural tremor, otherwise normal.

OK, so maybe you are thinking he got Lyme by vertical transmission from his mother. Seems pretty unlikely in Arizona in the 60s.

The labs are positive for Lyme, right. All three labs found highly specific bands; they just didn't agree. Not even a little. Labcorp, 23 band, OspC. IgeneX 31,34, Osp A and B. Stony Brook 93 band, flagellum protein, only found in Lyme.

He didn't Herx.

I ordered a course of high dose antibiotics and asked the patient to return for a Lyme PCR in two weeks.

I am discouraged about Western Blots. All three labs use different kits and different procedures. I have noticed certain biases. Labcorp gets a lot of 23s. Stony Brook gets a lot of 93s. And IgeneX finds more 31s.

People can interpret the tests according to their own biases. The IDSA is wrong but all test results need to be interpreted with caution.

This is a frustrating case. The next test will likely be negative.

My answer: Lets fix the other stuff and then see what remains. He needs to be checked for: B12, Vit D, Celiac and a few others. Perhaps I can be persuaded to check: DHEAS, Histamine, Copper, Zinc, TIBC/ Ferritin, TSH and thyroid antibodies with new guidelines and screen for heavy metals.

Sorting out the chaff from the grain is not going to be easy.

I would be doing him a disservice if I treat for Lyme now.

Acupuncture and traditional Chinese herbal therapy would be much better than what I have to offer - along side Western psychiatric help.

ILADS' Labs

2011-12-29T18:00:00.000-08:00

There is confusion about FDA approval of Lyme testing. It has been stated (by IDSA experts) that ILADS associated physicians have essentially created their own laboratories which are not FDA approved. And furthermore, these laboratories and physicians use non-peer-reviewed methods to interpret the results.

This is very misleading at the very least.

Laboratories are licensed by state regulatory agencies. Certified laboratories meet strict standards, including proficiency testing.

The FDA is charged with regulating drugs and medical devices. Test kits, commercially prepared for mass distribution are considered medical devices. This is why the FDA licenses these Lyme Western Blot tests. The FDA has licensed more than 70Lyme Western Blot kits made by varying manufactures. There exists no published data validating any one of these kits let alone all 70 or more.

Standard kits report the 13 Western Blot bands specified by the 1994 Dearborn criteria. This standard was created so that various doctors and scientists could communicate with one another reading from the same sheet of music. This surveillance test, never approved for diagnosis, has no peer-reviewed literature supporting its use - especially in light of FDA approval of so many test kits. In fact, a review of the literature shows investigators have used various Band criteria.

Laboratories producing their own testing kits (not for mass distribution) like Stony Brook and IgeneX do not require FDA approval. In fact, these tests cannot be regulated by the FDA. These laboratories must comply with the same regulations and proficiency tests required by all state licensed facilities.

Specialty laboratories likely do a better Lyme Western blot. For example, Stony Brook Lyme lab only does Lyme Western Blots. IgenX has decades of experience. Clongen and MDL are meticulous.

While mass produced Lyme Western Blot kits report 13 bands. Other maligned specialty labs report 28 or even 52 bands.

As stated in the 1994 report the diagnosis of Lyme is(was) largely clinical.

The question then is: How can more be less?

Heart Block

2011-12-23T13:52:00.000-08:00

I first saw this patient 10 months ago. She had been ill with a disabling multi-system illness for 12 years.

She suffered with many symptoms, including but not limited to: profound fatigue global cognitive dysfunction, joint pains, swelling with effusions, weakness and numerous neurological manifestations. Lyme was suggested. She had a positive Western Blot (10 years ago) an IDSA doctor prescribed two weeks of doxycyline.

An LLMD subsequently prescribed over a year of antibiotics including mincycline and Ceftin. Many symptoms improved, except the over-powering fatigue.

She stumbled along for years off antibiotics, symptoms waxing an waning. Still, she managed to functioned as a high level executive.

As of late she was not doing well at all. When I met her she had been sidelined with disability for more than two years. She had no energy or stamina. She was unable to grocery shop or attend to the most basic activities of daily living. She had perpetual flu-like symptoms - a loss of sensation in her fingers and toes. She was stumbling and falling. Joint pain with swelling had returned. She had global cognitive dysfunction with episodes of syncope, confusion and disorientation. She could not speak well, think clearly or read and write. She was a shell of her former self.

Two months before an IDSA doctor refused to treat her because she had a negative Lyme test.

Despite the fact that she nearly died of complete heart block now treated with a permanent pacemaker. And - despite the fact the attending cardiologist suspected Lyme as the culprit.

I became her doctor.

After months of fits and starts with oral therapy she has no been on IV Rocephin for 3 months and tells me she is getting her life back. She is contemplating starting a new business after two years of complete disability.

Now she gets out of the house and can read. Now she can do many things unthinkable a few months before. She is still very sick with many persisting constitutional and neurological symptoms. Her stamina is poor. After brief activites she requires extensive rest for recuperation. But she tells me she getting better almost on a daily basis. Most of the improvement seen after 2 and 1/2 months of therapy.

Lets look at some labs. These are IgM Western Blot results from three different labs. Labcorp found a 23 band. Clongen reported a 41 band and a weak, 23% of control 23 band reaction. Stony Brook found: Bands, 18,37,58,66,72,93.

The 37 and 93 bands either one alone might be enough to make the diagnosis according to some sources. I do not know why there was no 41 or 23 band found. Different strains of Lyme may be used in different kits lending bias to which bands react.

I do not understand not treating heart block with a documented history of Lyme disease. The CDC test is a surveillance test. It has never been validated as a diagnostic test. And the notion that IgG bands show up in late Lyme is not substantiated in any literature I can find.

The highly vaunted NIH/IDSA studies of long-term therapy never included Rocephin use for longer than 10 weeks.

Happy Holidays

Brown powder

2011-12-22T10:58:00.000-08:00

There is always the patient you dread seeing. When I see this particular patient in the waiting room an uneasiness wells up from my gut. Don't misunderstand. She is a lovely person. Maybe it would be easier if she wasn't so nice. It is her disease I take issue with. Progress has been excruciatingly slow with regression the rule. After two years treating her I am frustrated. She knows I can help people. Her son and mother responded beautifully.

She was a park ranger. Now she is disabled, unable to work: Fatigue with a capital F, pain and scrambled brain. She experiences confusion and disorientation at times. She suffers with numerous areas of neurocognitive dysfunction. She has been troubled by severe mood swings with sudden uncontrollable tears.

She has been treated aggressively for co-infections and with intravenous antibiotics.

Finally I insisted again that we go down a different path(having suggested this many times in the past). I referred her to a practitioner of traditional Chinese medicine. She was skeptical given a background in science. Spiritual healing, cupping and acupuncture she felt were of little or no help. But herbs. Herbs were a different story. She was provided with strange bottles containing brown powder and hand written labels. The labels made various claims: anti-Lyme, anti-Bartonella, detoxifying, anti-inflammatory, anti-biofilm and others. Neither she nor I have a clue what is in these foul tasting mixtures to be taken several times daily with water. But they Work. The combination of herbs and antibiotics has been particularly effective.

Unfortunately she regresses if she stops either the herbs or the antibiotics. Herbs, like antibiotics may be required as maintenance therapy.

Take her off the list.

Primay care: Lyme endemic

2011-12-15T07:29:00.000-08:00

Follow up visit. I have known this 50 year old male for a long time. He is a chronic depressive type. Divorced poorly. Working two jobs. Antidepressants help and he needs a refill. He mentions as a side bar he had red bumps on his leg 8 weeks ago, thought it was bug bites and went to a walk in clinic. Told - nothing to worry about. he suffers with anxiety and is disease phobic too. Just updating my files. Great. Thanks for the info. This was three visits ago.

No symptoms except the usual fatigue and depressed mood.

I order a few tests, perhaps the wrong test, including a tick borne disease panel. I have Lyme on my brain. Gotta stop that. Surprise(or not). Labcorp CDC positive for Lyme, ELISA and IgM WB. Babesia duncani titer 1:512 cinches the deal.

I carefully query: " Change in fatigue, Headaches, neck pain, change in vision, night sweats, any sweats, air hunger, joint pain, muscle pain, muscle pain, twitching muscles, Numbness and tingling, brain fog, cognitive issues, anything?"

He pauses to think: Maybe a few night sweats, over the last 6 months. Perhaps the heat was up too high, wearing heavy night clothes, not sure. Nothing else.

I treat him with antibiotics and Mepron for a month.

Now the current follow up visit.

Feels the same, except anxiety has increased; now he is worried about these new exotic sounding and frightening diseases.

It would be a lot easier if he was sick. Then I would know what to do.

There are the perils of a primary care practice - seeing patients on the front line. I suspect most patients infected with Lyme are asymptomatic. It is impossible to test this theory. I know many patients infected with Babesia are asymptomatic.

In a specialty Lyme referral practice you don't have to wrestle with these problems. I spent more time thinking about his case than I did the sick patients I saw that day.

Now I know a lot of readers are thinking: Treat him, treat him! Here's the problem. With Lyme you treat until symptoms are gone. What end point do you suggest I use?

I am still scratching my chin.

"

Lyme Western Blots: another look

2011-12-12T15:49:00.000-08:00

In October 1994 at a weekend conference, a group of experts developed criteria for the the definition of Lyme surveillance testing. The outcome of this conference led to a maelstrom of controversy which continues.

The test has never been re-evelated even though two key bands: 34 OspB and 31 OspA were ommitted.

It was decided that a two tier protocol should be followed. The criteria for the IgM Western Blot came from the work of Engstrom et al. Three strains of Lyme were found to perform equally well. The 23 band, identified as the OspC band, the 39 band, and the Fla (41) band were chosen for the assay. A positive result was 2/3 of these bands. It was noted that the 37 band could be added and that 2/4 of these bands would increase the accuracy of the test. (not accurate)

Dressler et al proposed a different criteria for IgM scoring. A different strain of Lyme was used which did not express the 39 band well. A positive result was the presence of 2/8 bands: 18,21,28,37,45,58 and 93. This test performed about as well as the above test.

Two radically different test and test criteria were found to produce almost the same results!

Padula et al found the 23 band to be of diagnostic significance, especially in early Lyme - and that "this protein may be poorly expressed in a number of North American strains of Borrelia burgdoreri." Weinstein and Johnsone report: "Despite these limitations, the proposed criteria for a positive immunoblot in late Lyme disease - at least 5 or the 10 specified IgG bands - seemed to stand up reasonably well in other laboratories...The criteria (will) be used..pending further studies."

What studies?

Where did the 37 band go?

Stony Brook reports it.

Ah, the missing band that would have made the CDC test more accurate by its own admission.

Two labs prepare their own Lyme Western Blot kits: IgeneX and Stony Brook. IgeneX has developed criteria for a positive result (IgG and IgM) - sounds like the Dressler criteria. They report a positive result if there is a reaction with two highly specific bands, inclding: 23,31,41,34,39,and 93.

Different assays have produced different bands. Dressler reported a 21 band. Stony Brook only reports a 20 band.

Are you as confused as I am?

In addition, in my experience I have found reported Western Blot results differ amongst commonly used "LLMD" laboratories.

In 1994 Gubler reports the two tier test is not the gold standard. (culture is). He states that "in the not too distant future, the development of new tests that use a cocktail of recombinant antigens or chimeric antigens(will increase)the sensitivity and specificity of serological tests for B. burdorferi."

Its been more that 17 years. We are still waiting.

Chasing the sweats

2011-12-01T16:32:00.000-08:00

Let me clarify this confusing post: It is based on a true clinical scenario. I was drawn into a hole chasing Babesia; the symptoms were classic, especially the profound night sweats. The "Babesia" stubbornly wouldn't go away, with everything thrown its way: Mepron, malarone, Artemesia, Coartem and Larium.

I was willing to treat Babesia as a clinical diagnosis with aggressive, long term therapy; positive lab confirmation is rare. I convinced myself that resolution was just around the corner.

I was reluctant to treat Lyme with intravenous therapy(I had been treating Lyme with oral antibiotics) If the clinical picture had been more "Lyme flavored," I may have pulled the trigger for IV therapy more quickly.

The patient had clear symptoms of neuroborreliosis including hallucinations at one point. Still, the clinician could rationalize the marked neuropsychiatric manifestations were the product of cerebral babesiosis.

Over a period of several months the patient requested (stridently) that she needed a PICC and IV therapy.

The diagnosis of tick borne disease is still made clinically. Still, in borderline situations the clinician sometimes turns to laboratory results, as I did here, to help justify the more dangerous step up in therapy.

The patient's mantra for some time was: I need a PICC.

I acquiesced after 9 months of oral therapies.

Incredible improvements with resoltion of both cognitive and physical symptoms were seen within the first month. The so-called classic Babesia symptoms also melted away.

This raises many interesting clinical questions.

I am not offering any clinical advise here. Please do not misinterpret. Every case is different.

In this case, the patient had insights about her care which turned out to be true.

Lyme labs and babs

2011-11-26T17:36:00.000-08:00

A 22 year old female had a tick bite with at rash at age 5 (recalled by mother). Her pediatrician treated her for 3 weeks. No symptoms recalled. At age 10 she had another bite, treated the same way, no problems. At age 12 she found herself not feeling quite right. It started with vague aches and pains, loss of energy. Her pediatrician diagnosed growing pains. She still did not feel well. Her concentration at school lessened, straight As were replaced with Bs. Her pediatrician diagnosed pre-teen hormones and prescribed reassurance. An avid athlete and enthusiastic basketball player, she collapsed on the court at age 13. The cardiologist and neurologist gave her a clean bill of health.

Her state of well being fluctuated. She had good and bad days, good and bad months. High school was a struggle. She had little time for friends or extracurricular activities. She started going to sleep at 7:30 and having a hard time waking up. She maintained her grades, B+: memory, concentration and focus were poor.

At 16 her pediatrician referred her to a psychiatrist. A diagnosed of depression made she was started on Zoloft. Maybe it helped; maybe not.

She finished one year of college but had to drop out. She had more memory problems, fatigue, joint pains, headaches and other symptoms.

Her mother asked her doctor to do a Lyme test. The test showed a negative ELISA and a positive Western Blot with a 41 IgG band and 41 and 23 IgM bands. The ah ha moment. She was treated with doxy for a month. Didn't help. The infectious disease specialist had nothing to offer. A friend referred her to me.

A repeat Lyme Western Blot 6 months later showed now only a 41 IgG band. The co-infection panel was negative.(I later noted that the B duncani test had not been done).

Her symptoms were typical in my experience for chronic Lyme: fatigue, brain fog, cognitive problems, numbness and tingling in the extremities, headaches, neck pain, muscle pains, migratory joint pain of both large and small joints and prominent depression.

She was treated with an aggressive anti-Lyme regimen. She felt worse over the next two months. Two months later a new symptoms emerged: profound night sweats, air hunger, flu-like symptoms with low grade fevers. A repeat round of lab tests showed a positive titer to B. duncani at the lowest cut-off point. Anti-babesia therapy was started. She had prominent nausea and Mepron intolerance. Zofran was needed to manage the nausea. Over time she began to feel better.

A new Lyme Western Blot from a different laboratory showed 58 and 41 IgG bands and a 41 IgM band. There was a partial reaction at the 23 band.

She continued to improve over the next six months. However cognitive problems were slow to respond. Intravenous treatment was discussed. There was an insurance snag. PICC never placed. Two months later she seemed to be better nonetheless.

A year into treatment she is doing pretty well. After a year at home she is back in college doing fairly well. Symptoms, especially night sweats quickly relapse off Malarone. Still a problem.

Follow up LabCorp testing, including B. ducani was negative. We were specifically looking for a positive Lyme test for insurance, not clinical reasons.

An additional Lyme Western Blot was sent to Stony Brook. This test showed: 41 and 60IgG bands and 18,35,41,72 and 93 IgM bands. I thought this was a definite positive.

Clinical note: The odd Babesia scenario has been relatively common in my practice. Initially the patient denies any symptoms suggestive of Babesia. Babesia symptoms only become prominent after Lyme therapy has been started, as if the Lyme Herx somehow awakens the sleeping dog of asymptomatic chronic babesiosis. The two players seem to act together.

Lab comments:

My confidence in Western Blots is waning. Different laboratories frequently come up with divergent results - not even close.

I am sure this patient has a form of babesiosis. Still, one laboratory I use frequently turns up positive results for B dunani at the lowest cut off point, frequently in patients who would otherwise show a negative Lyme/co-infection panel.

Could the reported "WA1" IgG antibody actually cross react with a different organism. Or, are there a lot of false positives? Dr. Fry suggested this may be a cross-reaction to a non-Babesia protozoan which he has identified.

In truth, sometimes I order a lot of Lyme related tests searching for the positive that might justify IV therapy if anyone is looking.

Another lab's Western Blots would have undoubtedly showed different results. Maybe its best to look at Lyme Western Blots from several labs if it doesn't break the bank.

History

2011-11-26T11:51:00.000-08:00

History instructs us, oft the best predictor of the future.

Infectious plagues, epidemics and endemic, have molded the course of human history. The Black plaque, or black death - Bubonic/pneumonic plague of the 14th century has been called the greatest European catastrophe in history. Houses were emptied, villages abandoned, fields were littered with dead. The mysterious disease syphilis followed soon after, infecting many prominent world leaders, forever altering the course of human history. Henry V111, Francis 1 of France, Pope Alexander Borgia, Ivan the Terrible, and many more. Napoleon's madness was perhaps molded by Typhus. Epidemics of malaria, yellow fever, tuberculosis, influenza and AIDS were yet to come. The Spanish flu of 1918-1919 killed more people than WW1. Woodrow Wilson, the American president, contracted the flu while in Paris working out the details of the Treaty of Versailles. One could ponder: would things have worked out differently if he had been well?

Syphilis is perhaps the most pertinent to our story. A painless frequently unseen chancre is followed by a benign secondary stage a long latent stage and then a tertiary disease with protean manifestations. This "great imitator" can attack almost any organ in the body, frequently with central nervous system involvement. End stage disease,"general paresis," manifests itself with various symptoms: headache, "lightening pains," impotence, epilepsy, joint pains, progressive personality and cognitive changes, frank dementia and many more. Some infected have no symptoms and still transmit the disease to the unborn.

Every point in history, has to some extent, been intertwined with and perhaps influenced by its own epidemic(s).

Perhaps epidemics can be less obvious and still alter the history of mankind: no putrid cough and waisting of consumption/tuberculosis.

Perhaps there can exist a silent epidemic: an insidious creeping crawling yet quiet plague.

I know someone. An acquaintance let's say. A fifty something, suffering with fatigue, depression, joint pains and cognitive problems. He believes his family doctor and believes in the "system." The Lyme test was negative. Not Lyme. "Please see 'Under Our Skin.'" Not interested. The person, as of this writing continues to see a panoply of specialists and even non-traditional herbalists. Not Lyme.

I cannot raise the topic of Lyme, now a touchy subject. "You think everything is Lyme."

Arthritis. Fibromyalgia. Chronic fatigue. MS. Early dementia. POTS. "not feeling as well as 80 year old parents." All on the rise - and others.

A quiet epidemic. Denial. "Aches and pains of daily living." "Anti-science. Unseen.

True story: Tall sailing ships, those of Christopher Columbus were sailing to the Island of Hispanola. The natives scanning the horizon could see nothing. Perhaps a perturbation of the waters. After all, such things could not exist in their universe. They called the Shaman. He saw the ships. Only then could the people see them too. (to their detriment, but that's another story)

The 19th century European obstetrician. Semmelweise literally lost his mind trying to convince the experts that puerperal fever (child bed fever). a lethal epidemic, was caused by germs and that hand washing was the cure. He gave up everything to fight the battle against prevailing world opinion. Not living to see the paradigm change - slowly, he died pitifully in a mental hospital.

What can we see in the calm - no turbulent waters?

Iceman

2011-11-10T06:43:00.000-08:00

Readers know - the suffering of Lyme is so great that contemplation of suicide is common. And then to make matters worse - so often, the degree of misery is unseen by those closest.

Many suffering with Lyme have heard from others: "I had Lyme: it was no big deal."

"He should only be in my body for one day!"

Maybe these unsympathetic individuals actually had a different version of the disease.

It turns out "Lyme" may a wide diversity of clinical presentations because patients are frequently infected with different strains of the organism.

Maybe we can begin to answer the question: why do some patients infected with Lyme with the tell tale EM rash never become sick without treatment, while others infected with Lyme disease treated early with recommended doses of antibiotics go on to develop full-blown chronic Lyme disease?

Research has shown that some strains of Borrelia burgdorgeri are more virulent, quickly causing dissemination into tissues, while others strains are relatively benign and may be associated with little or no disease. Borrelia bacteria show a surprising amount of genetic diversity.

Lyme bacteria have been here for thousands of years providing a long time frame for evolution and differentiation. The famous iceman dug up from the permafrost in the Italian alps in 1991 has now had an autopsy. The DNA from a fragment of hip bone showed an unexpected finding: Borrelia burgdorferi. Likely, persisting DNA from cystic forms. Still, I am surprised not only that Bb was found, but that it was found in bone.

The Lyme epidemic is world wide and has been found in all the continents with the possible exception of Australia.

It is confusing that bacteria with names like: B. afzeli, B. bissette, B. miyamotoi all cause "Lyme disease."

The international organization with classifies bacteria calls all species of Borrelia which cause human Lyme-like disease, (12 or more species) "Borrelia burdorgferi sensu latu." These associated illnesses have varying degrees of similarity and dissimilarity to our Lyme disease. Some of these species have crossed borders into other regions.

The Lyme disease bacteria we usually think of(in the US)is called Borrelia burdorferi sensu strictu. Even within this narrower sub-species of the Lyme community the genetic diversity is mind boggling and mostly unknown.

A recent scientific publication from the American Journal of Pathology studied three sub-strains of a sub-strain of Bb sensu stricto and found one sub-sub type to be more pathogenic than the others two.

To illustrate how diverse the Lyme zoo is: The study examined the pathogenicity of three strains of Borrelia burdorferi sensu strictu, Osp C (type A) known as RTST 1,2 and 3.

The Lyme Osp C (outer surface protein) is associated with the 23 band on a Western Blot. Its molecular weight can actually vary from 20-25 Kds. The OsP C protein is quite variable. Twenty-one types have been identified. One of these Osp C types, type A, was subdivided in this study into three more sub-variations based on " ribosomic RNA intragenic spacers." One was nastier than the others.

In other words, there are a gabillion versions of Lyme, some making us sicker than others.

Treatment may be difficult because of this unknown variety of strains. It is well documented that a single host can be simultaneously infected with multiple strains.

Of note: Dr. Allen Steere is one of the authors of the above described study.

Lyme: the tissue pathogen

2011-11-06T17:33:00.000-08:00

It has long perplexed me why Borrelia bacteria appear to be so abundant in the blood of other mammals but so sparse in human blood. An Ixodes tick, generally the poppy seed size nymph form has a blood meal, typically from a mouse, becoming infected with Lyme along with an assorted host of other co-infecting germs. Even though the tick takes many such meals - (how much blood can the tick eat)? - it would appear that spirochetes must exist in fairly high numbers in circulating blood in these other mammalian hosts.

In humans the paradigm/narrative states: the spirochetes stick to the extracellular matrix, become intracellular, convert to cyst forms, avoid immune defenses and antibiotics by avoiding blood and body fluids and finds safe harbor within biofilm communities.

"It is a tissue bacteria, not one to be found in the blood."

Now thinking about these statements they do seem wrong. Textbooks have instructed me the bacteria is spread via the blood stream. I conveniently discarded this explanation along other textbook things Lyme. But - Lyme bacteria cannot spread to many disparate tissues including the central nervous system unless carried by circulating blood. Of course I knew this. Right.

We have looked for the bacteria in blood of infected humans by PCR testing, a direct assay for detection of Lyme DNA. This is what has mislead me. The results have been almost always negative. Getting a positive PCR for Lyme has been like hitting the jackpot.

With improved culture techniques Lyme bacteria have now successfully been cultured from human blood consistently.

Culture is the absolute gold standard for proving the presence of the bacteria and chronic Lyme disease (not post Lyme syndrome).

Why the negative PCRs?. PCR technology uses primer pieces of DNA which target sub-regions of the organism's complete genome. These reactions are amplified and read by a machine. The primers target specific regions of DNA known to be conserved within different strains of the organism.

Sample size may be an issue. The PCR machine may be sampling a small amount of DNA taken from a small sample of blood. PCR testing may not be sensitive enough to detect the most minute traces of DNA. There are also various technical glitches which may occur with the technology.

With culture techniques a larger amount of blood/DNA may be tested. Perhaps this is why culturing has been more successful.

Bottom line: new staining and culturing techniques may be shattering another part of the paradigm. Lyme is not just a tissue pathogen in humans but can usually be found in blood if you just know how to look for it.

More bands

2011-10-04T06:03:00.000-07:00

A 42 year old male came into my office, reluctantly. He thought he was fine. He only came in to mollify an insistent spouse, a spouse familiar with a disease she herself has suffered with.

Ok - He had a tick bite a year ago - attached for a short time; he never became ill.

When I took a history symptoms began to emerge. He had been a little tired recently but thought this normal. He had had some depression and irritability and fragmented sleep. He had had some generalized body stiffness, especially involving his hands and knees. Maybe his memory was not as good as it was a year ago, chalked up to "old age."

His physical exam was unremarkable.

A Lyme Western Blot was sent to Stony Brook University Medical Center. Here are the (IgM) Lyme Western Blot results: The report says indeterminate. An IgM 41 band is reported.

Other "nonspecific IgM" were also found: 18, 37, 72, and 93.

Before you get too excited, let's discus why the IgM report is called indeterminate. In this case, the WB bands are interpreted based on the assumption the patient has already had a positive ELISA test for Lyme. This designation indeterminate assumes the blot is the second -confirmational part of the two tier test endorsed by the CDC surveillance case definition test. Of course the ELISA was never done - so the designation, indeterminate has no significance.(I think).

Based on the same CDC test, the 18 and 93 bands are considered specific only if IgG bands, those included in the second leg of the (IgG) CDC surveillance test. IgM bands are reported specific, by the same logic, only if they are bands 23, 39 and 41.

Of interest to me is the report of a 37 and 72 band.

Stony Brook reports these bands because they manufacture their own Western Blot kits which show many more bands than the other labs. The 37 band is considered specific for Lyme (based on my reading). The 72 band is a cross-reacting spirochete band. When the 37 band is combined with the 41 and 93 bands the evidence for exposure to Bb seems compelling.

The treatment for this disease is discussed elsewhere (somewhere) in this blog.

Babesia, re-visited

2011-09-20T17:19:00.000-07:00

Those in the chronic Lyme community have a narrative for explaining the chronicity of Lyme disease or at least the persistence of Borrelia despite the onslaught of immune responses and antimicrobiobials, including such things as: genetic switching - up and down regulating of key surface proteins at key times, protection of the bacteria within a niche, polymorphic switching from spirochetes to cysts and then back again, biofims, and other proven effective stratagies for survival. Despite this evidence, we are still convincing the few.

With chronic Babesiosi we lack such a narrative. Patients are frequently treated for months or longer without clinical resolution. Patients have repeatedly shown me positive FISH(RNA)results for Babesia after extensive therapy, still sick with the disease. As one of my patients recently described in a YouTube video, two ID specialists at Johns Hopkins dismissed this evidence claiming that IgeneX is not a trustworthy lab and suggested the patient seek psychiatric care.

Although there is a great deal of overlap between the symptoms of Lyme and Babesia, certain symptoms are quite specific for babesiosis, inlcuding: recurrent flu like symptoms with low grade fevers, air hunger and night sweats.

Frequently the diagnosis of babesiosis is made on clinical grounds. There are over 100 known species of Babesia but only a few are though to cause human disease. In the US we look for B. microti and B. duncani. Another, yet unnamed species, MO1 has been shown to cause human disease in the US. Others are likely.

Babesia in humans is an infection of red blood cells. The protozoa invade and reproduces within red blood cells. When the cells rupture Babesia forms quickly attach to other red blood cells. Babesia has two hosts: mouse and tick, both of which are required for the parasite's normal life cycle. The tick is considered the definitive host because this is where sexual reproduction of the organism occurs. Humans are considered an unintended, bystander host, unlucky enough to have been bitten by the wrong tick. In humans Babesia is seen as any of three forms: sporozoites which microscopically have a spherical form, trophozoites which have a ring appearance and merozoites which may have the "Maltese cross" (tetrad) appearance.

Unfortunately, Babesia sp infect only a small percent of circulating red blood cells and direct evidence of its presence via microscopy is rarely evident.

Standard, and largely unchallenged dictum states that the microbe lives only within red blood cells, it does not hide in tissues, all of the forms are killed by the same antimicrobials/antiparasitics. The narrative to support the parasite's longevity seems lacking. Well, lets look at some recent medical literature: Clinical Infectious Diseases, 2008, Florescu, highlighted as important by the IDSA.

Two cases of Spenic Infarct are discussed. Both patients were critically ill, one succumbed. At autopsy Babesia-infected red blood cells were noted with the spleen, liver and lymph nodes. One then wonders, is the parasite seeking safe harbor within the microvasculature of these organs?

Of interest, the authors observed that the first patient who survived was co-infected with anaplasmosis "which may have contributed to the prolonged course of the illness." The implication is obvious to chronic TBD believers. The authors report that Babesia has been associated with retinal damage, ostensibly as a consequence of "microobstruction" of tiny blood vessels (by the parasites).

The authors report that multifocal coagulative necrosis has been shown to occur with B. duncani at least in Syrian hamsters. This means that Babesial infection within narrow blood vessels likely caused blood clotting associated with multi-organ damage.

In May 2011, The CDC reports a study of Babesia sp. EU1 (of reindeer) which found hemosiderin laden macrophages in multiple tissues, meaning that infected red blood cells were ingested by macrophages. Babesia DNA was found in: bone marrow, brain, heart, kidney, liver, lung, lymph nodes, small intestinal wall and spleen. Perhaps Babesia can sequester itself with organs.

In summary: Babesia can likely cause blood clotting with localized tissue damage. It may persist only within tiny blood vessels or it may be able to exist within tissues. There are many species of Babesia. They may exhibit different biological behavior. Little is known here.

The evolving science may help us uncover a better narrative by which we may describe patho-anatomic-physiological mechanisms supporting the notion of chronic Babesiosis.

In the meantime, our clinical experience and our supporting laboratory data cannot and should not be ignored.

Fear

2011-09-01T14:25:00.000-07:00

Every once in a while a patient surprises me and makes it all worthwhile. This is such a story. A 17 year-old female presented in my office in a wheelchair this past spring. She was holding her head, her neck flexed, her face invisible to me. Severe unrelenting daily headaches were unbearable and driving her mad.(in the British sense). She was disoriented - cognitive impairments were profound. For me the most frightening aspect of her presentation was profound weakness. When I asked her to get out of the wheel chair her thighs muscles appeared to contract in a floppy, asynchronous fashion. The analogy that came to my mind was a fish hopelessly flopping on the deck of my boat. I quickly asked her to sit back down. After examining her I thought she was suffering with a severe motor neuropathy.

She had a well documented diagnosis of Lyme disease. She had been treated by another physician in a nearby state with oral antibiotics for an entire year. Despite this, her condition had steadily deteriorated.

I knew that the only treatment that might be effective was IV antibiotics. I ordered a PICC and started Rocephin. I saw her back in two weeks, as is my practice. She was no better. At that point I decided she should be evaluated in a tertiary care center. I sent her to Georgetown. I have found Georgetown more Lyme friendly than hospitals in my own state.

My experience had been with adult side. She was 17, so she was admitted to the pediatric ward. A neurologist barely peaked at her. No EMG/NCV test was performed as I requested. The ID doctor stopped in for a moment I was told. The attending pediatrition diagnosed fibromyagia and a somatoform disorder - a psychiatric condition. The good doctor wanted to stop the IV antibiotics. The youg lady's father insisted otherwise (with some vehemence I suspect) and won the day.

After a few days she was sent to the National Rehabilitation Hospital. This was helpful and she got stronger. The doctors there also reluctantly agreed to continue the Rocephin. Two weeks later she was back in my office.

She looked better. A little better. I felt encouraged and continued the treatment. The brain fog lifted a bit. She asked me if she would be able to attend an important camp activity three months hence. I looked at her in the wheel chair and said: "we'll see."

And then something magical happened. She started getting better - fast. I used the regimen which has served me best. Rocephin layered with Zithromax and the Flagyl IV. I also prescribed Mepron for Babesia symptoms.

After two more months it looked like she might actually be able to go to the activity. A positive thing for her is that she forgot how sick she had been as she improved. Not only was she out of the chair, she was running and dancing.

All of her symptoms gradually began to peel away. She had missed a whole year of school and was now reading and catching up on her studies.

After 3 and 1/2 months, she was looking good. Essentially back to normal. She did no get to go to the camp activity, but she did go to her family beach vaccation, sans PICC line.

Doctors are afraid. They are afraid to prescribe IV antibiotics. To do so you need to be on staff at a local hospital. You have to face the scrutiny of the Infectious disease doctors, the neurologists, the hospital board and various attendant committies - And possibly - the State licensing board. It is safer to prescribe oral antibiotics, to keep plugging away with all the oral medicines in your arsenal. Harder. More. Something will work if you keep trying. It is safer.

Fear.

What else is there to do.

c diff

2011-08-30T20:28:00.000-07:00

C diff - (clostridia difficile) infection is the bane of the existence for patients(and their doctors) who take long term antibiotics for Lyme disease. The infection occurs when normal gut flora are destroyed by antibiotics clearing the way for the opportunistic bacteria to take hold.

The biosphere of the GI tract is composed of trillions of micro-organisms including a wide variety of bacteria, fungi and parasites. Destruction of these "good bacteria" clears the way for c diff, previously contained within a narrow niche of the overall ecosystem of the gut flora, to disseminate and cause disease. The infection can be mild or severe, at times even life threatening.

Although c diff may be a naturally occurring part of the gut flora, infection may be introduced externally through spores or infected individuals. Even in these cases an intact gut flora helps to prevent the development of clinical disease.

So what are these good bacteria? Our bodies are colonized with massive quantities of micro-organisms. These bacteria/organisms may be parasitic or symbiotic. Parasites live off the land, offering nothing in return. Symbionts on the other hand can be either commensal (neutral) or mutualistic: something positive is provided to both the bacteria and the host.

One hears a lot about the beneficial effects of "good" bacteria. It turns out that some bacteria are good and beneficial to our immune systems

Good bacteria may: synthesize and excrete vitamins, prevent the colonization of pathogenic (disease causing) bacteria, provide natural antibiotic effects and aid in the production of natural antibodies (amongst others).

There are two take home points (yet to be made).

Some antibiotics are more commonly associated with c diff and some probiotics may help prevent the disease.

Quinolones such as Levaquin are highly associated with development of c diff. In addition, because of resistance, these agents appear to be associated with more virulent strains of c diff. Cephalosporins are more highly implicated. For example: Ceftin and Omnicef are more frequently associated with c diff then drugs from the penicillin family like amoxicillin. Clindamycin is also highly associated with c diff. This knowledge can help direct the prescription of the safest antibiotics.

In a published clinical study a proprietary mix(yogurt drink)of bacterial probiotics: L casei, L bulgaricus and S thermophilus has been shown to decrease the frequency of c diff. In addtion, the probiotic S boulardii, yeast based, may form a barrier which protects the gut.

Please take your probiotics. C diff can lead to sepsis, emergency surgery and even death. Treatments are available (Flagyl/Vancomycin), but they are not always effective. And, more virulent strains of c diff are starting to appear. More importantly, c diff tends to recur. This can make ongoing treatment very challenging to say the least.

Biofilms

2011-08-04T18:16:00.000-07:00

Biofilms are ubiquitous. Their role in chronic infections in mainstream. Biofims have been found in chronic sinusitis, chronic ear infections, chronic skin and bone infections, kidney stones and many other clinical scenarios.In these other diseases biofilms can be readily identified because the occur on surfaces. The existence of biofilms in Lyme disease is more difficut to establish because of infection within deeper, inaccessible tissues. It is commonly cited that biofilms may play a role in up to 80%of human infections.

Biofilms are indeed complex structures. Previously freely motile bacteria become frozen in a gel-like matrix due to the result of complex molecular and genetic swiching. The organisms within these films are able to communicate and establish a social network. Frequently these bacteria go into a starvation mode and exhibit a very low metabolic rate. Biofilms may release motile bacteria when enviromental factors become favorable. Biofilms may be polymicrobial or consist of a single organism. Biofilms have been cited as a mechanism by which opportunistic germs, eg Pseudomonas, can become pathogenic. Bacteria turn out to be very clever little fellows, after all, they have been on the earth for 3.5 billion years. Biofilm fossils have been uncovered evincing their antiquity.

Bacteria within these biofilms are difficult to kill. They exist in a highly protected niche. They frequently become extremely resistant to antibiotics and destruction through normal immune responses.

Antibiotics such as Beta-lactams (penicillins and cephalosporins) are generally ineffective because these cell wall inhibitors work only when bacteria are rapidly dividing or remodelling their cell walls. Biofilm bacteria are frequently in a state of suspended animation.

The biological characteristics of biofilm contained bacteria quickly begin to resemble those attributed to cystic forms of Borrelia burdorferi (Lyme). Both have a slow metabolic rate and are not typically killed by Beta-lactams, except for the amoxicillin paradox described in my last blog.

One could postulate that antibiotics which are effective against cyst forms of Lyme could also be effective against biofilm forms.

Some have been very critical of Dr. Sapi's work. She has developed "biofilm like" colonies which she does not define. These are not the same thing as actual biofilms which develop within infected tissues.

There are no published studies (in peer reviewed journals) documenting the existence of Lyme biofilms let alone which treatments might be effective.

When you Google the words Lyme and Biofilm it inevitably leads you to MacDonald and Sapi. MacDonald's work is fascinating but unpublsihed or vallidated by other investigators. It also is unhelpful from a clinical perspective.

In the meantime, my patients tell about earthworm extracts, mushroom extracts and a variety of other enzymes. I have found no compelling reasons to believe that any of these treatments would be effective.

At this point we are left at the same place we were two years ago. Lyme may persist because of many mechanisms. The contribution of biofilms remains unknown. Treatments (from the perspective of my allopathic mind) should be rational and based on what we do know from the the science at hand and what we have garnered from clinical experience.

It appears that Lyme infection within the brain is frequently manifested through biofilms and atypical cystic, granular/pleomorphic forms of the organism.

I only discus patient cases after I have recieved their consent. (Some have questioned this)

I have continued to treat patients with severe encephlopathic neuroborreliosis including some diagnosed with premature Alzheimer's disease.

My clinical experiences have been consistent. The addition of IV Flagyl has been very effective for such patients. Perhaps this relates to mechanisms alluded to above.

Lyme tests old and new

2011-07-25T10:30:00.000-07:00

My recommendations for Lyme testing have not changed.

Some new tests have been introduced, unfortunately there are no published studies demonstating their validity. One test is called an immune tolerance test. It measures T cell proliferation after exposure to select Lyme antigens. There exist very few studies regarding such lymphocyte proliferation tests for diagnosing Lyme. Oddly, the background paper published by the manufacturer, describing the underpinnings of this technology, cites an old Wormser study in the foot notes. The Wormser study using somewhat different methods concluded the test was insensitive but specific.

A second test measures an array of cytokines levels in response to antigenic stimulation. This test is also offered without any validation.

I suspect the problem may relate to the way the immune system responds to Lyme infection. The early immune response to Lyme infection, the cell mediated response, is measured here. Lyme bacteria are known to be very immungenic. Early Lyme infections are associated with dramatic immune responses. This is why for example, early EM rashes frequently show marked inflammation. It is also why early Lyme may be associated with fever and a flu like illness(mini-cytokine storm).

I think the concept of a cell mediated immune assay for the diagnosis of Lyme is right.

Such a test has been developed for tuberculosis. It measures a direct cytokine response to antigen presentation.

A new test for Lyme is sorely needed. Current tests remain clearly inadequate.

When I test my patients I continue to skip the ELISA and go right to the Western Blot. Although there are some patient who are ELISA positive and WB negative, these patients generally show some reactivity on WB assays.

Various labs seem to offer complete Lyme Western Blots. These include: IgeneX, Clongen, MDL, and SUNY. The SUNY Lyme lab presents some bands not seen from the other laboratories. Western Blot testing may also be available through the Mayo Clinic I have been informed. (I only have direct experience with IgeneX and Clongen although I have seen reports from other labs)

I like the C6 peptide test. This is a very specific ELISA test. It has a lot of false negatives because the antigen tested can easily change its epitope. Any value greater than 0.1 needs to be considered. With values of 0.4 and greater, I am fairly comfortable suggesting the patient has had prior exposure to Bb even in the face of a negative WB.

Co-infection testing is indispensible. Any positive results significantly increase the likelihood that a co-infection (here Borrelia) is also present.

The best test still remains a careful history and physical examination of the patient.

Everything you thought you knew about cyst busters is wrong

2011-07-24T18:31:00.000-07:00

Eva Sapi's recent research calls into question everything we thought we knew about Lyme "cysts." In fact it destroys the old thinking.

We have heard about cell wall antibiotics, intracellular antibiotics and cyst-busters. Think again.

She investigated the effect of various antibiotics on Lyme spirochetes and round body forms - also know as cystic forms.

Doxycycline worked according to plan. Doxy inhibits protein synthesis - it kills bacteria, including Lyme, by action within the cytoplasm, inhibiting the manufacture of proteins required for the bacteria's survival. Doxy and others are commonly referred to as intracellular antibiotics.

Spirochete loads decreased by about 90% while cyst levels increased by 200% - just as expected.

Then amoxicillin data was presented. Amoxicillin inhibits the formation of bacterial cell walls. Amox and similar drugs should then only be effective in killing spirochetes with an intact cell wall. This is where the results start deviating from the plotted course.

Amoxicillin killed 90% of spirochete forms - OK, but -- it also killed 68% of the cystic forms! Amoxicillin and other cell wall drugs are not cyst busters - only specific anti-parasite drugs kill cysts - or so we thought.

Well lets think again for a second: what are cysts? Are they balled up forms of spirochetes with a different kind of membrane - or blebs (also described) expressed through the spirochete membrane? Maybe the former retain much of the cell wall from the original spirochete - maybe that is why amoxicillin works here.

This would seem to clear up a nagging question raised by others. Are cysts and L-forms really the same thing? These results show that cysts cannot represent a version of L-forms or spheroplasts which result when gram negatives shed their cell walls. If this were the case a cell wall drug would be ineffective. Cysts and L-forms are distinct and different forms. (There may be a hole in this reasoning. I will explain later).

OK So we have learned something new: cell wall antibiotics can also kill some cyst forms which are not L-forms.

Let's look at some more data. Tigecyline is a not a cyst drug either. Wrong. Tigecycline kills 90% of spirochetes, good so far, but it also kills 90% of cysts! Tigecycline is an intracellular antibiotic similar to doxycycline! Another fly in the ointment.

OK. Cysts with their lower metabolic rate, still need ribosomal proteins to survive, just not at the levels of intact spirochetes. Tigecyline is a more powerful drug, higher levels are delivered into the cytoplasm of the cysts. This makes sense. Cyst forms are still essentially a pleomorphic version of Lyme bacteria with somewhat different features. In this scenario, cysts could be L-forms. But we have already shown that this is not true because amoxicillin can kill them. Right?

Amoxil is a cell wall drug. I thought so. Kersten, (antimicrobial agents and chemotherapy, May 1995, p. 1127-1133) states that Beta-lactam antibiotics, which include amox, penicillin and Rocephin, have been shown to cause a specific loss of total intracellular RNA in the absence of cell wall hydrolysis. In other words, amoxil could possibly work in part as an intracellular agent. If this is right cyst forms of Lyme could still be L-forms. So perhaps we have not shown that L-forms and cyst forms are different after all.

The question remains unanswered.

Let's get to the Cyst-busters. It takes antiparasitic drugs, so we thought, to kill the cysts. Cyst-busters, anti-parasite drugs, kill parasites (and Lyme cysts) not bacteria. The so called cyst-busters were heretofore used in combination or cycled with other antibiotics. Previous thinking was that typical antibiotics would kill spirochetes and/or L-forms and that cyst busters would disrupt only the cystic forms.

Cyst-busters do not kill intact spirochetes - so we are told. Very wrong this time.

I cannot cover the whole Sapi study. The most exciting finding is that Tindamax (tinidazole) - our premier Cyst-buster, is the most effective drug overall. This "cyst-buster" kills 90% of cysts and spirochetes: by far the best drug. We don't know it's effect on L-forms, but we can guess. Tindamax probably works by an intracellular mechanism. If this is true it should be equally effective against L-forms.

It gets even better. Tindamax is the only drug which does a great job on biofilm colonies as well!
(not to be discussed now). More on biofilms later.

Tindamax passes the blood brain barrier and penetrates well into most tissues. It has been effective in my patients with neurocognitive deficits - neuroborreliosis.

Recently I tried it on another sort of patient. This patient has had intractable Lyme arthritis of his knees. This young athlete had been extensively treated with IV Rocephin followed by a year of typical oral antibiotics. Knee effusions have persisted - until I prescribed Tindamax. Now, after two months, the fluid in his knees has evaporated. His knees are dry and painless for the first time in over one year.

This raises the question: should Tindamax be used as mono-therapy? Well, I cannot endorse blanket use at this time. Tindamax has a black box warning. It has been associated with cancer in some laboratory animals. Perhaps there are more compelling reasons to use Tindamax, but this will have to wait for another post.

My nagging question:

Why does penicillin kill Lyme? It shouldn't. Lyme is a gram negative bacteria. While certain Beta-lactam antibiotics can kill gram negative bacteria, penicillin cannot. Penicillin is only active against gram positive bacteria.

Maybe this other mechanism alluded to above, the alternative intracellular RNA mechanism is significant and explains why penicillin kills Lyme spirochetes. Maybe not.

We need to continually reevaluate things which we have assumed to be true, because many of them are not.

Immune dysfunction and antibiotics

2011-04-30T13:08:00.000-07:00

Clongen reports many unusual organisms seen swimming around in a drop of blood taken from many of the most ill, chronically afflicted patients. Why? I believe these patients are immunologically compromised. People of the ILADS/chronic Lyme disease community, have long claimed that Lyme disease infection (Borrelia spirochetes) is immunosupressive: this, it is argued, why co-infections, erstwhile opportunists, are able to easily grab a foothold. As one of my patients pointed out to me, there exists research showing a mechanism by which this might occur. Wooten and others have shown that Borrelia infection can lower a specific cytokine ( a mediator of normal immune function), IL 10. This weakens the ability of the immune system to fight or contain certain infections. If one microbe can do this, it is plausible that many others can do so as well, through various mechanisms. For example, XRMV, has been linked to Chronic Fatigue Syndrome. Not CFS. The proper nomenclature is CFIDS (Chronic Fatigue Immunodeficiency Syndrome) because the syndrome is believed to be associated with a yet understood, dysfunction within the immune system

The epidemic of CFS started suddenly in the mid 1980s. The Medical community at first thought it might be caused by Epstein Barr Virus, but ultimately decided the cause was unknown. The CDC was concerned about this new epidemic because they developed a case definition for the disorder, first in 1988, then revised in 1994.

Please visit the CDC website and print out their Case definition of CFS. Compare this to the ILADS published expanded definition of chronic Lyme disease. They match, nearly to a T.

Fibromyalgia arrived on the scene around the same time. For the longest time, most physicians refused to consider it a "real disease." Ultimately, The American Academy of Rheumatology published a case definition, in essence, pronouncing Fibromyalgia a genuine disease.

Fibromyalgia shares many features with chronic Lyme disease and CFS. Even the terminology sounds familiar. Instead of having Brain fog - Patients have "fibro-fog."

Let me turn the table a bit more. Pain - and I will introduce a new variable, Migraines: why does it hurt. Pain occurs when sensory fibers are stimulated, carrying a message to the brain/pain center causing the subjective feeling of pain.

Why Migraines? At first doctors thought it was a vascular disorder caused by constriction and dilation of blood vessels. Then, it was understood to be a brain disorder. Abnormal brain function can be imaged associated with migraines. Now - Botox injections can treat migraines. What is going on here?

Botox paralyzes nerves, relaxes muscles. This decompresses some nerves.

Inflamed, architecturally changed muscle tissue, impinges on nerves which too may be damaged and inflamed, perhaps exacerbated by autoimmune damage of tissues.

A lot of patients with migraines also have fibromyalgia, associated with tight muscles in the back of the neck. It is now understood that pressure applied to tiny nerve fibers, compressed by local abnormal muscles initiates the cascade. Messages are sent to the brain leading to abnormal brain function and then changes in blood vessels. The vessels constrict and then dilate, pressing on nerves. This is why migraines have a pounding quality. The vessels dilate more when the heart contracts. Fibro muscles irritate nerves but in a different way. The same can be said for Lyme patients.

Stardard medical thinking holds that painful conditions like fibro and irritable bowel syndrome are due to overly sensitive nerves. This thinking seems to have a psycho-somatic slant. These sorts of biases need to be replaced with a better understanding of the science and a respect for the suffering of the patients, rather than blaming the patient - as if in some way, the patient is responsible for the illness.

This thinking is fueled by observations that certain illnesses are more prevalent in women - the implication: women are prone to hysteria and psycho-somatic problems. In fact women have more robust immune responses than men and are twice as likely to experience autoimmune disease. This is where we need to look.

Let's go back to the first paragraph. Sick patient have germs in the blood; parasites bacteria, unknowns. The immune system is to some measure broken. These germs should be contained in a box, somewhere else, by a competent immune system.

Perhaps an initial infection: Lyme, Mycoplasm or something else, initiates the process seen in our: chronic Lyme, CFS, fibro, chronic pain syndromes, migraine, IBS, chronic pelvic pain, IC and other patients. The smart, offending germs are in some way programmed to disrupt normal immunological functions(as is known to be the case with Borrelia) causing a wide range of downstream sequelae.

Some antidepressants, Cymbalta, Elavil disrupt the neuronal messages sent to the pain center, or in some way alter the perception of pain in the brain. The same is true for anticonvulsants like Neurontin, Lyrica. They may help some. But they do not get at the root of the cause.

Sometimes - antimicrobials, of various sorts, (from doxycycline to Tindamax to Malarone) work much better for these patients.

Immune compromise, mediated by one infection ( not to discount the role of genetics, stress and other factors) can "activate" heretofore quiescent germs. This explains why patients relapsing with Lyme often experience a rip-roaring relapse of a previously controlled co-infections, like Babesia.

The process may be associated with multiple breakdowns of normal imune function. For example: cytokines become dysregulated, T cell and B cells malfunction, autoantibodies are made. Autoantibodies, the cause of autoimmune disorders, play a huge role in the disease complex.

Bottom line: sometimes it is best not to worry what it is: are bands present or not? Is it fibro or CFS. Not to say you should stop trying to figuring it out.

It comes down to this: either the illness responds to anti-microbial agent or it doesn't.

This begs the question: which antibiotics/anti-malarials or anti-parastic agents. If you don't pick the right ones you won't know if the illness is anti-microbial responsive.

That's the tricky part. That's what you pay us to figure out.

B12

2010-05-05T10:18:00.000-07:00

How important is vitamin B12?

For years doctors gave patients injections of that red liquid in their hips for low energy.
Patients left the office feeling energized with an increased sense of well being.

The practice has been eschewed by conscientious doctors in more recent decades: no scientific rationale - just a placebo effect. The elixir is red - red placebos work best. In evidence based medicine, B12 deficiency may be due to maladsorption or an autoimmune disorder. Blood levels are only low when less than 211. Other countries, including Japan have set the bar for normalcy higher - 500 or more. This is quite a difference.

B12 does many things in the body -- in conjunction with folic acid. It helps regulate the production of red blood cells and DNA synthesis. It facilitates the synthesis of myelin, the protective covering around nerves, and it likely has many other functions which are enumerated in a variety of published sources.

Lower B12 levels, less than 500 have been associated with a variety of neuro-psychiatric disorders, inclusive of cognitive dysfunction. B12 supplementation has helped with neuropathies of various sorts despite normal blood levels according to American standards. Neurologists who discount Lyme as a possible cause of peripheral neuropathy readily recommend generous supplementation with B vitamins.

Commercially, B12 is available as cyanocobalamin, an inactive form. It must be converted into one of two active forms, including methylcobalamine. Many clinicians feel that that the expensive methylcobalamine is the only clinically effective form of the vitamin. Based on my survey of the literature the jury is out on this one.

Patients with neuropathy, cognitive issues and perhaps many other issues may benefit from supplementation. Most of my patients have B12 levels which average around 350. This water soluble vitamin has no toxicity. B12 must be given with folic acid. If oral supplementation is ineffective the old "placebo" (B12 shots) can't hurt.

Gluten

2010-04-02T10:24:00.000-07:00

A very sick Lyme, a middle age male with: Babesia/ neuroborreliosis/abnormal SPECT scan is now feeling normal off antibiotics after 2 years of treatment. He also has "gluten sensitvity." Two children and a sister have celiac disease. He has tested negative for celiac. His TtG Iga is negative (supposedly an accurate screening test). Two gastric biopsies, the "gold standard" for celiac were negative. Nonetheless, tiny amounts of gluten cause symptoms: pains, fatigue, rash, neuropathy, and gastrointestinal symptoms, including GERD. Gluten free diets are difficult. Food advertised as gluten free may contain trace amounts of gluten and rapidly set off symptoms. Conclusion: gluten sensitivity exists along a continuum. Standard tests only reveal gross disease with macroscopic loss of intestinal villae. Other patients may have ultra-microscpic changes, not observed with standard tests. In predisposed individuals, gluten causes extreme immune reactivity. These symptoms must be teased out from those of Lyme

Co-morbidity

2010-03-31T18:37:00.000-07:00

I had a recent conversation with a patient. I told her we need to sort out other co-morbidities. Co-infections? No. This was a new term for this very Lyme literate patient. I was not saying the patient did not have Lyme disease. Not at all. Patients with Lyme disease frequently have a variety of other medical problems which contribute to their illness to varying extents. And, in some cases, it is not Lyme which is making the patient ill, regardless of what the Western Blot says: if the signs and symptoms do not fit -- Lyme may not be the primary issue. Or, perhaps Lyme's contribution to the illness is minor. For example:

Fatigue--profound fatigue, is almost invariably a prominent symptom. What else causes this? Other causes include hypothyroidism, B12 deficiency, anemia, depression and insomnia. After these are excluded, my patients are sent for sleep studies. Sleep disorders are a major cause of fatigue. Lyme patients have higher rates of sleep disorders compared to the general population. Patients may have obstructive sleep apnea (OSA) or central sleep apnea, a brain disease. Sleep apnea is associated with numerous other medical disorders: cardiovascular disease, diabetes and others. Sleep apnea is also associated with neuro-cognitive dysfunction -- sound familiar? And sleep apnea is associated with alterations of immune function. Specifically, high levels of inflammatory cytokines, TNF alpha, interleukins have been measured in these patients. Sleep apnea is a significant co-morbidity which interfers with the healing process.

Oher sleep orders are common as well. Restless leg syndrome is a common cause of poor quality, non-restorative sleep. This condition may be respond to supplementation with high doses of iron, sometimes intravenously, based on ferritin levels (it is not clear why these patients have profound depletion of iron). This movement disorder shares common features with Parkinson's disease, a movement disorder mediated by dopamine deficiency in the basal ganglia, a deep area of the brain. Both disorders are treated with dopamine agonists such as Mirapex. This should not be confused with cortical brain dysfunction--loss of executive dysfunction--related to insufficient dopamine activity in the cerebral cortex. This is treated with dopamine agonists such as stimulants which work in these areas of the brain.

A second sleep test, an MSLT can evaluate for narcolepsy and other disorders. Narcolepsy has been considered a disorder of arousal but is now understood to be a disorder of sleep. This may be effectively treated with Xyrem, a drug which is safe but suffers a bad reputation.

Sleep disorders: a common co-morbidity, cause fatigue and cognitive impairments, as well as mood changes and irritability. Not to say I don't start Lyme therapy early in the process - I must also fix the "non-Lyme" to see what remains.

This is but one example of numerous potential co-morbidities.

Patients may have: rare genetic disorders, rare metabolic disorders - or acquired mutisytem-disorders. One of my patient suffers with stiff man syndrome. This is a rare autoimmune disease caused by destruction of a GABA precursor. Another suffers with a toxic yeast syndrome which mimics chronic Lyme. Neuro-cognitive changes and new onset headaches may be caused a brain tumors or other cancers. It is know that Lyme may be associated with brain tumors.

Medical texts are ripe with esoteric diseases: mystery diagnoses. These are the patients that seek our help. It is not always Lyme.

Text book

2010-03-18T21:07:00.000-07:00

A new patient walked in: a youthful 29 year old female. She wasn't feeling as good as she looked. She suffered with diffuse, migratory muscle and joint pain. She had tingling in her hands, shortness of breath, night sweats, headaches and pain on the soles of her feet. Her brain was foggy: poor concentration, focus and slow processing. She asked me if I thought she might have Lyme disease. I replied: "My G-d, you are right out of the textbook." Then I realized: " Well no, there actually is no text book." One has to be written.

She had a tick bite, a small "seed" tick, 2 years ago. It was accompanied by a red rash, maybe 5cm in size based on her description. "It wasn't a bulls eye."

She saw her family doctor. He told her she was just getting old (29?), that's why she had the symptoms. I asked how old the doctor was. Ancient. She talked her doctor into ordering a Lyme test. The Western Blot showed 28 and 41 bands only. Not Lyme disease.

Her family doctor referred her to: a rheumatologist, a neurologist and an infectious disease specialist. She figured it must be one disease -- she only needed one doctor. Smart girl. An Internet search led her to Lyme disease and then to me.

Doxy failure

2010-03-12T07:34:00.000-08:00

14 months ago, a 47 year old male first consulted with me. His illness started after a physical injury sustained working in his garden. He first developed low back pain -- diagnosed as a strain. He went on to develop knee pain, fevers to 102, a red streaky rash on his abdomen, sweating and color changes in his fingers. He went to the ER: he had been ill for 3 weeks. A two tier, CDC surveillance test was positive for Lyme. He was treated with 3 weeks of Doxycyline and felt better. His past medical history is positive for Chrohn's disease.

Three month later he developed recurrent, progressive symptoms -- muscle pain -- increasing joint pain -- profound fatigue, and, drenching night sweats. New neurological symptoms appeared: numbness and tingling, memory loss and cognitive dysfunction.

He presented to me for further care. A 13 band WB showed 3/3 IgM bands. Non diagnostic Bb IgG WB bands were present. He was seronegative for Babesia microti/duncani. He was treated for chronic Lyme disease and Babesiosis, diagnosed clinically.

After many months of antibiotic therapy his disease is in remission, still on antibiotics.

Additional data: C6 peptide ELISA had been 6.41 initially and is n0w 2.3. C4a levels have been elevated. CD 57 levels have been normal. A wet mount showed no bacteria.

His previously active inflammatory bowel disease is now quiescent. A recent colonoscopy was normal.

Three weeks of Doxy for acute Lyme failed. This may be more frequent that commonly held. It has been suggested by some that this is due to co-infections. I am not sure. The average person, with an intact immune system, should be able to throw off both Babesia and Bartonella.

Perhaps in some cases, Lyme is able to sequester itself quickly. Other explanations may be offered. Perhaps in some, already-infected asymptomatic patients, clinical Lyme is triggered by a new infection. The other possibility is a bit more frightening. Perhaps strains of Lyme are now resistance to Doxy. This could explain some Doxy failures with response to other treatments, such as Amox/Biaxin. This patient did respond to Doxy at first. But, partial resistance is know to occur with other bacteria. This is all thinking out loud conjecture.

Lyme disease is associated with a multitude of autoimmune diseases. Crohn's and ulcerative colitis are both autoimmune diseases. Coincidence?

Lyme Rage

2010-03-05T14:02:00.000-08:00

A 36 year old female was treated for severe Lyme disease and neuroborreliosis. A course of IV antibiotics was successful 2 years ago. I explained to her the need for maintenance therapy. She took oral antibiotics for a few months, but tiring of the medicines, she sought alternatives, such as A Rife machine. She had been treated for Lyme, Babesia and Bartonella. Her case had been well documented: abnormal MRI, abnormal SPECT scan and multiple positive Western Blot Lyme bands. The aches and pains returned, slowly. The mental confusion returned, slowly. She returned for further treatment 6 months ago. This happy-go-lucky soul had turned into someone else. She was was filled with unbridled rage. She told me she literally felt like killing someone. She was just waiting for that someone to cross her path so she could act out her rage. She meant business.

Several months into therapy she returned to her normal self. The anger disappeared gradually, and then it was gone--after treatment with a second course of IV therapy. Now, several months off IVs, she is largely symptom free, the disease controlled with oral antibiotics. The smile has returned to her face. She is once again a kind and gentle soul.

Evidence based medicine: a critical appraisal

2010-02-27T17:00:00.000-08:00

So called "evidence based medicine" has done more to harm medicine than anything else I can recall during my 30 year tenure in medicine. Doctors have become technicians, rather than practitioners following in the traditions of healers who have come before.

When I was in college, science as we know it, existed within a framework-a caste system-a pecking order. Mathematics was considered the purest science: provable with irrefutable equations. Physics took second place. It described fundamental properties of the world/universe around us, supported by mathematical equations. Chemistry followed next and then biology. The order of descent was based on how hard, irrefutable and provable the conclusions were. All science is validated by the scientific method: a theory or hypothesis is proved by well designed experiments which can be replicated in a variety of places, times and circumstances.

When I entered medicine in the 1980s, medicine was more than a job or ordinary profession. It was a commitment, a lofty avocation, a calling of sorts. (at least according to my father)--I agree. Medicine was a healing art, in the tradition of the many who had preceded us, predicated on science. It was not a science.

Sometime around 1995 the term "evidence based medicine" insinuated itself, increasingly into the verbiage of the profession. I suspect it was in large part driven by managed care companies, looking to control costs, and then, high powered medical institutions jumped onto the band-wagon, in the belief that medicine was really science, not art: throwing out the baby with the bathwater.

Properly designed controlled medical studies were carefully analyzed by statisticians. Sometimes multiple studies were combined and analyzed-- meta-analysis. Problem. Only a few potential questions were addressed. Most studies were funded, at least partly, by big Pharma, with pre-existing agendas, undoubtedly tied to feathering the pockets of CEOs and stock holders (follow the money). Medical research, by its very nature, is simplistic. In truth, it is impossible to do proper science when it comes to studying something as complicated as people. Newer studies replace and refute older ones on a regular basis. It is impossible to control the variables, many of which are unknown, poorly understood or yet to be discovered. If it takes a room of statisticians, as is frequently the case, to prove a point, it should give one pause.

The single biggest problem: data obtained from a single study is extrapolated widely, to support wide ranging conclusions, based on faulty logic superimposed on bad science.

To makes things worse, evidence, as it were, is now broken down into levels/categories-- again, a pecking order. Most in the profession have accepted this new and improved medicine without giving its precepts a second thought.

First we have placebo controlled, double blinded, randomized studies, the results of which are statistically validated and replicated in subsequent studies.
Then we have non blinded controlled studies, non-controlled studies, head to head studies, published studies, clinical reports published in journals and lastly recommendations of a body of experts--my perennial favorite.

How can opinion be science?

So, let us get back to Lyme, the subject of this blog. The Klemper, Krupp and Fallon studies, are in my mind, weak science at best. They also all have somewhat different study designs and conclusions. The limitations of these studies has been discussed in detail elsewhere. The "experts" put these findings together and give us a final product: evidence based guidelines.

The better science is what physicians seem to dismiss and ignore: test tube science and other forms of "basic" science. Borrelia has been shown to convert from spirochete to cyst forms in the laboratory and back the other way. Spirochetes have been shown to exist as L-forms. Research in immunology support beliefs that infected hosts cannot be sterilized of Lyme. Human and animal models have proved that Lyme persists in the face of massive doses of antibiotics. This sort of science can control the variables. It can be replicated in multiple settings over time. The same cannot be said for clinical studies, the type of science clinical doctors rely upon, which are pooled into meta-analyses, looking for statistically significant conclusions. I could go on, write a book about this subject, with foot notes and citations. Not here.

This post is a about "evidence based medicine." In my opinion, this is a sham, a fraud. Perhaps it works for HMO physicians who are required to see patients in 6 minutes: cookbook medicine. It is not a useful tool for thoughtful, curious physicians, intent on practicing their art to the best of their ability. Patients are all different as are all physicians. Diseases are nuanced and complex.
The practice of medicine is a mosaic of science, judgment, clinical experience and yes-intuition, a clinical nose, the product of years of practice.

So yes, this dumbed down version of medicine has now framed the basis for the national debate about lower cost, higher quality medicine. According to national political "experts", electronic medical records and evidenced based medicine (the mantra), will solve systemic problems with our health care system.

Who decides which evidence we use? Ivory tower physicians. Iconic figures. The Gary Wormsers of the world. Doctors for the most part, are reassured by practice guidelines: complex decisions have already been decided for them. A few other physicians, the outliers, and their demanding-annoying patients, just won't go away. It is no wonder that many readers shudder when the hear the words: evidence based medicine.

Every pre-med student is ultimately asked the question: why do you want to become a doctor. Inevitably, they all give the same, banal answer: I want to help people.

For those of us who want to be included amongst healers who use science, the state of the art as it exists at any particular point in time, as a basis, but only a starting point for the practice of their art: the art of healing; this answer turns out, in the final analysis, to not be so banal after all.

Evidence based medicine? Thumbs down.

H. pylori

2010-02-26T10:02:00.000-08:00

My patient, age 32: "This is the best I have felt in five years. I feel like a whole organism. Rashes on my body, face-circles under my eyes, they have all cleared. My abdominal pain is all gone. My acid reflux is gone. Total body stiffness and pain are gone--after 5 years. Fatigue is gone: I am so energetic. My body has changed. My middle section has reduced in size. The bloating and swelling is gone. My appetite is better: I am know longer hungry all the time. My taste buds work better. My neighbors have so much energy, now I am like them. Thank you."

"Did you have any side effects from the medicine?"

"For the first two weeks I had nightmares--mild headaches, then everything went away."

One month prior to this visit, a test for H. pylori was positive: the IgM ELISA. Most labs only perform the IgG ELISA. I request the IgA, IgM and IgG antibodies for H. pylori (Helicobacter pylori). Any one could be positive. IgA goes along with mucosal disease and IgM indicates active disease.

This patient has a number of chronic medical problems. The test was ordered because of persistent heartburn (GERD). Her treatment: Nexium 40mg 2x daily, Biaxin 500mg 2x daily and Amoxil one gram 2x daily, for 30 days. She has been off therapy for a week and is continuing to improve. I told her if symptoms return maybe we should retreat.

I leave this vignette for you to interpret.

Three patients today: wet mounts, osteomyelitis and ulcerative colitis

2010-02-25T15:50:00.000-08:00

This 35 year old female went to the local ER in October 2008. She had a rash, fever to 101 f, and chills. She was sent home without treatment. I saw her in the office a few days later. She had a very large and very red inflammed EM rash on her right chest wall. I decided to be aggressive. I double covered with Amoxil one gram twice daily and Doxy 100mg twice daily for 30 days.
I saw her 4 weeks later; everything had resolved. In June 2009 she complained of new onset fatigue--severe, disabling for several months, brain fog and word retrieval difficulties. Lab testing was then performed. A CD57 count was 28. A standard Lyme Western Blot showed 41 bands. The Babesia WA 1 aby reacted 1:256, the lowest positive titer. A Clongen WB showed multiple bands, including IgM 23 and 41. A wet mount was performed. This showed numerous small round bacteria--presumptive of a Bartonella species and "numerous large elongated extracellular motile organisms(look like a protozoan or tiny round worm)." Contemporaneously, she developed pelvic pain. She was treated with: Amoxicillin, Zithromax, Rifampin and Tindamax. This was followed by a course of Levaquin. She improved nearly 100% within 7 months-- except for pelvic pain. At her request, a repeat wet mount was performed. This time scarce, elongated, curved, extracellular organisms were seen. The Bartonella like organisms were gone. Quite a change! I empirically prescribed a course of Levaquin and Tindamax. Her gyn and GI have been unable to diagnose the source of the pelvic pain.

A second patient, a 40 something neuroscientist, has been treated for Lyme with cognitive dysfunction for 6 months. Physical symptoms have improved, but cognitive difficulties remain.
She is unable to focus, concentrate or process. Her short memory is very poor. I asked her to have a brain MRI and a SPECT scan done, but she told me she "forgot." I bring this patient up because of her past medical history. Nine years ago she developed a bone infection- osteomyelitis, in an ankle following surgical repair of a fracture. She was treated with two courses of IV antibiotics, 9 weeks each. In addition, she was treated with extensive courses of oral antibiotics. All told, she took antibiotics for 4 consecutive YEARS. She finally improved after hardware was removed from her ankle. A consultant from the infectious disease department at Johns Hopkins University, where she was treated stated that she might require life-time antibiotic therapy.

A third patient, a 50 year old woman, with a history of ulcerative colitis developed acute Lyme disease in 2007. All 13 Western Blot Bands were present. She also has had a persistent, marked elevated ANA level. She saw me after failing standard treatment (3 weeks of doxycyline). She continued to have joint pain and fatigue. She improved over a couple of months and therapy was discontinued. She had recurrent symptoms over the next year: mostly joint pain. Further courses of antibiotics (short term) were prescribed with improvements. When I saw her in late 2008 she was well. Soon thereafter she experienced a recurrence of ulcerative colitis-- after a 10 year remission. This episode was controlled with steroids and maintenance Cloazol . At the end of 2009 she suffered a severe, uncontrolled relapse of her colitis. She was treated with: Remicaide, high doses of Colazol, 6-MP and steroids. The Remicaide, given at Johns Hopkins, was not effective. The Hopkins' GI recommeded a total colectomy (resection of colon) for non-responsive disease. Not done. Her local GI got the disease under control with high dose, tapered steroids. She remembered something I once told her. She recently sent colon biopsy fragment to Clongen. The PCR test of the biopsy specimen was POSITIVE FOR LYME. Be careful what you wish for! Flagyl has given her diarrhea in the past. I cautiously prescribed a course of Cipro--today. I spoke with Dr. Kilani. "We don't know what these results mean. The presence of DNA in the biopsy material does not tell us if viable organisms are present." The suffers with autoimmune disease. Did Lyme trigger her colitis or did the immunologial effects of treating Lyme trigger the disease. She will see her GI next week. I am sure he will have fun trying to make sense of the results.

I am really not trying to pick on Hopkins. It remains one of the best tertiary medical centers in the country--in most matters.

The eye of the beholder: a specialist

2010-02-21T11:09:00.000-08:00

Published studies do show that chronic Lyme improves with long term antibiotic therapy.

Donta, 1997, Boston University published a study of 277 patients with chronic Lyme disease.
He reported that patients frequently did not improve for several weeks. After 2 months 33% of patients had improved, after 5 months, 61% had improved. He claimed 20% of patients were cured, 10% did not improve, and 70% showed some improvement. The duration of the study was for 1 to 11 months. He concluded: CONTROLLED STUDIES NEED TO BE CONDUCTED TO VALIDATE THESE OBSERVATIONS.

In 2003, Donta published a study on the use of Biaxin, Biaxin with Plaquenil and Plaquenil alone.
The effective therapy was Biaxin and Plaquenil. Conclusion: THESE RESULTS SUPPORT THE HYPOTHESISIS THAT lYME BORRELIA RESIDE IN AN ACID ENDOSOME.....

Cameron, 2008, published a double-blind placebo controlled clinical trial.

He replaced the term chronic Lyme disease with Lyme disease with persistent symptoms (LDPS). He found a 46% improvement of subjective quality of life in treated patients and vs 18% in non treated patients. He concluded: WORTHY OF FURTHER STUDY.

Clarrisou et al, 2009, Med Mal Infect, published: Efficacy of long-term antibiotics in patients with a chronic Tick Associated Poly-organic Syndrome (TAPOS
Investigators keep inventing new terminology for the same disease. Why?
A cohort of 100 patients was followed. The study showed favorable results in subjective symptoms. The authors point out flaws and limitations of their study but recommend: RANDOMIZED, DOUBLE BLIND STUDY.

The number of patients studied in all of these studies was significantly higher than the number of patients studied in the 3 NIH sponsored studies. This has mostly to do with study design and patient selection limitations.

Hopkins-Harvard-Yale-IDSA-CDC: Where are you?

Those folks are sticking with the "Best science."

Problem: best science supports these conclusions (fatigue, qualitly of life) if you take another look at the Krupp and Fallon outcomes. A patient suffering with Lyme and chronic fatigue recently told me: " Hell, I would gladly go on 3 months of IV Rocephin if it only helped with fatigue."

I asked an esteemed professor(infectious disease) from Hopkins about his success with severe neruo-syphilis He told me with pride that he has treated it, (it is rare these days)--the penultimate expert. I asked him about patients with severe brain damage. "When the squash is gone there is no squash." Good answer. Even patients with persistent vegetative states have been shown to frequently have significant neurological and cognitive activity.

Patients with neuroborreliosis have recovered. SPECT scans, PET scans have improved. Patients with neuro-syphilis-dementia (general paresis) have been treated with only penicllin. These patients pathologically have blebs and cysts in their brains, similar to those seen in patients with neuroborrelosis. As stated, there are not many of these patients around anymore. There have been no studies since TUSKEGEE. How would neuro-syphilis patients do if they were treated with other therapies, including IV Flagyl? Not studied

How about this:

Why don't we let psychologists and psychiatrists evaluate cognitive functioning, radiologists evaluate objective, radigrophic signs of improvement and neurologist evaluate for evidence of neurological improvements. How about listening to our patients as well? I know--a novel concept.

Why does a professor of of infectious disease medicine, with little or no knowledge of these other fields, tell us about squash, a "fancy" designation for brain?-- what are his qualifications to tell us that chronic Lyme disease--including neuroborreliosis does not exist?

I went to medical school, internship and residency.
We made round, sometimes with esteemed attendings: we were intimidated: they knew everything, we were abysmally ignorant. We were ready to be chastised; we were swine waiting for pearls to be cast to our feet. I remember, Super-star attendings--Power, honor, prestige: with it comes a sense of infallibility--after all, you are the last word, the highest authority. You have to be self assured. Perfectly understandable. That is why I became a generalist, not a specialist. It is understandable. Nonetheless: sometimes you are wrong, dead wrong.

Fallon and fatigue

2010-02-18T13:04:00.000-08:00

An NIH study published in Neurology, 2008, lead investigator Brian Fallon has been misinterpreted by many in the Lyme community. The study was carefully performed using the highest level of scientific procedures. Patient selection was meticulous. The study was a randomized, placebo controlled study for Lyme encephalopathy (neuroborreliosis) and the results were published in a prestigious, peer reviewed journal. Dr. Fallon reported that the studied patient population suffered with... "moderate cognitive impairment, physical dysfunction comparable to patients with congestive heart failure, and fatigue comparable to patients with multiple sclerosis." The treatment arm of the study evaluated patients with established Lyme disease, seropositive by the CDC requirement of 5/10 positive IgG bands, who had previously been treated with 3 weeks of IV Rocephin. Patients were treated with 10 additional weeks of Rocephin. The study found significant short term improvements in cognitive dysfunction, but not memory in the treated group. A sustained improvement in fatigue was shown.

The investigators reported a 19% rate of complications. This does not comport with my clinical experience.

Dr Fallon recommended against the use of 10 weeks of Rocephin followed by 14 weeks of no therapy. He does report antibiotic associated improvement with regard to disabling symptoms such as pain and fatigue, particularly in patients who suffered the most at the outset of the trial. This was not a primary end point of the study, but the results were significant. Fallon also noted that the Krupp study showed significant improvement in fatigue.

"Conclusions regarding the benefit of repeated IV antibiotic therapy for this set of symptoms must await further investigation."

The IDSA still concludes that this study conclusively demonstrates that chronic Lyme disease does not exist. This is not true. Further study is needed. With regard to cognitive improvements several other conclusions might be suggested: the patients needed longer courses of antibiotic or perhaps gains could be sustained when IV therapy was followed up with oral therapy.

Of course, this study does not address the subject of co-infections. It does not address the need to treat L-forms and especially cyst forms which have been shown to be prominent in the brain.

Yesterday I had the opportunity to discus these issues with a Hopkins professor of infectious disease. He claimed that ALL the good science proves that chronic Lyme does not exist. He was steadfast in his opinion. When queried, he admitted he knows nothing about the Columbia/Fallon study. He asked if it was"good" science. He was oblivious to the fact that the Fallon study was third NIH-sponsored study cited by his colleagues to support the absolute belief that chronic Lyme does not exist. Apparently only the Klempner and Krupp studies are worthy of consideration. But what about that pesky Krupp study?

I have a simple question: how does Rocephin improve fatigue, demonstrated in clinical trials, the best science? If the patients do not have persistent infection with Borrelia burdorferi, what is the mechanism by which antibiotics help fatigue?

Sleep helps fatigue. Caffeine and stimulants help fatigue. Antibiotics?

Maybe when I needed to pull those all nighter to cram for chemistry finals in college I should have been popping penicillin instead of gulping down pots of coffee.

A proposal for a clinical study

2010-02-16T19:22:00.000-08:00

Medical science--clinical studies, must be taken with a grain of salt. It is nearly impossible to do science when the thing being studied is as complex and multi-faceted as a human. Such studies attempt to prove that treatment A is better than a placebo (a pretty low standard) or that treatment A is superior to treatment B. The group under study is supposed to be homogeneous--a cohort with the same disease process. I would suggest it is nearly impossible to find a cohort of patients with exactly the same disease. Ultimately, many confounding variables make this sort of science difficult to do and to validate.

All the randomized-placebo-double blind-peer reviewed studies for chronic or post Lyme disease look at lot alike. All patients had prior, treated Lyme disease. All had had received "standard" therapy. And, all had persistent symptoms in the face of prior therapy. "Long term therapy" was defined as limited courses of Rocephin with or without courses of doxycyline. Generally, patient selection required CDC-IgG positivity, 5/10 bands. Of interest, Klempner also studied "sero-negative" patients. This is anomalous since the IDSA has generally claimed that seronegative patients do not suffer with Lyme disease.

Insanity has been defined as: doing the same thing over and over again-- expecting a different result.

I would suggest that another kind of study be designed and carried out. Patients with the same general set of symptoms, for example: migratory joint pains, fatigue and cognitive impairment plus positive Lyme Western Blocks by IgM or IgG standards should be studied. Patients from this cohort should be randomized into two arms: a head-to-head study. Group A would receive IDSA recommended therapy and group B would receive LLMD style therapy. Objective measurements of progress would be agreed upon. These might include: symptom lists, psychometric testing, physical exams and perhaps lab parameters such as a highly sensitive C-reactive protein. Patients would be periodically assessed over a prolonged period of time. For example, patients could be assessed every 3 months for a period of one to two years.

LLMDS in the study could agree upon some general standards, for example, Babesia could be treated with Mepron and Zithromax for 8 weeks. If there were no clinical response, a second course might be Larium plus Artemesin. In general, the physicians would be given flexibility to treat patients differently, based on clinical experience.

This is the sort of study which might provide convincing evidence that treatment for chronic Lyme disease is effective. The disease is different in every patient. It is nuanced. It is complex. Standard study designs which look at only one variable, will never prove the benefits of long term treatment for Lyme disease.

I hear a lot of talk about the need for Lyme studies.

I think, first potential investigators need to develop a study design. The teams needs then to find a partner with credibility and prestige, such as NIH. The cost could be low, particularly if this sort of head to head study could be "piggy-backed" onto another planned or ongoing study. Results, hopefully favorable ones, could be published in a major, peer reviewed journal.

Lyme 2010: A brief update

2010-02-14T18:41:00.000-08:00

Diagnosis remains clinical. Laboratory data should not be over-emphasized. Lyme Western Blots from Igenex, MDL and Clongen are helpful. I prefer Clongen. They provide quality pictures of blot strips which quantitatively compare patient reactivity to controls. C4a is a good marker of infection, better than CD57. Other clues include: reversed vitamin D levels, elevated CRP, low/normal B12 and folic acid levels, and low white blood cell counts. Blood wet mounts reliably show motile round bacteria---presumptive Bartonella species. A large percent of patient have the BBB triad: Borrelia, Bartonella, Babesia.

Primary oral therapy with Doxycycline and Tindamax is excellent. Killing cysts early seems to improve outcomes. Tindamax is clearly better than Flagyl and Albendazole. Biaxin is a second choice in patient's who cannot tolerate Doxy. When Biaxin is used patients seem to do better when a beta lactam is added:Amoxicillin/Ceftin/Omnicel. The benefits of Plaquenil are not clear. Rather than having an anti-cyst effect, it promotes cyst formation. Many antibiotics used for Lyme also have mild effects against Bartonella as well. In patients with neurocognitive deficits, Lyme and Bart are generally both a factor. Bartonella/brain Herxes can be extremely severe. Anti-Bart therapy is such patients needs to be gradually ramped up. Drugs with low anti-Bart activity include: Doxy and Biaxin even though these drugs are thought to be only Lyme drugs. Minocycline is a little more active against Bart. Zithromax orally is a poor Lyme drug and has mild anti-Bart effects. Rifampin is somewhat more active against Bart. Bactrim is quite effective and quinolones are very active: Cipro followed by Levaquin and then Factive. Cipro and especially Factive are also good Lyme drugs. Factive is a fabulous Lyme drug.

Many strains of Babesia appear to be very resistant. I suspect like malaria, these bugs have a propensity for developing resistance. When Mepron, Malarone and Artemesin are relatively ineffective, Larium may be surprisingly effective. I generally like to treat Lyme first. The exception is patients with dramatic Babesia symptoms: drenching sweats. As a rule, patients respond quickly once the sweating stops.

I agree with the Martz approach to IV antibiotics: layering. I start with Rocephin, add Zithromax and then Flagyl. Works very well. Other IV antibiotics may be helpful but responses are more variable. Tigacyl has been disappointing in my practice.

Patient should be treated with IV antibiotics for at least 12 weeks, longer if possible. Gains from IV therapy require ongoing therapy with potent oral antibiotics or the gains will vanish. Factive and Tindamax are superb. Factive is costly. Doxy is a good alternative. A subset of patients only do well when beta lactams are continued. Biaxin and Amoxicillin remains an excellent choice of therapy.

Supplements? vitamin D3, 2000-4000IU seems helpful. Probiotics are critical. A good mix of acidophilus type, 30 billion twice daily and Sacchromyces works well. Supplementation with yogurt is better yet. A balanced diet is helpful: fruits, berries, nuts, fish and a wide variety of vegetables of different colors--broccoli to red peppers. Sugar is always bad. I am not yet sold on other supplements. Transfer factor which is basically colostrum may be helpful. If B12 and folic acid are low-- supplement. These patients are probably nutritionally depleted and should also be given B complex and multivitamins.

The body cannot be sterilized of Lyme bacteria. Intracellular bacteria will always persist.
Unfortunately, many patients require maintenance therapy. I have seen many patients who have been "cured" by other physicians, but complain of incomplete recovery or relapse.

Not all Lyme infected patients required treatment. I only test patients who are symptomatic.
No--it is not sexually transmitted or transmitted by mosquitoes or flies. It may be transmitted via placenta to newborns. This can be very problematic. I treat pregnant Lyme patients with low dose Amoxicillin.

There is no one right way to treat Lyme disease. At times you have to be creative--and, never give up. Individual responses to therapy are impossible to predict.

Patients with autoimmune neuropathy may get much worse with therapy. This is one of the most challenging group of patients. IViG should be considered if possible. Sometimes steroids are needed, despite all the caveats. Antibiotic therapy must be titrated very gingerly.

Welchol works very well in some patients--especially with neurocognitive issues. Long term therapy may be required. It also lowers CRP and inflammation.

Straight IV fluids, normal saline solution may be given to patients on IV antibiotics to flush out toxins? or circulating immune complexes. It may reduce Herxes and make patients feel better.

Politics: no change except Connecticut. Patients must understand that doctors who treat Lyme disease face ridicule from their colleagues and possible censure from medical boards.

The IgM question: Is it chronic Lyme disease?

2010-02-14T07:19:00.000-08:00

The Lyme debate is not unusual in medicine, or so I say. To other physicians I claim that it is not unusual for doctors to disagree. This makes it more palatable. In truth: I cannot think of another disease that has elicited so much vitriol, controversy and ugly politics. This blog is for new patients; perhaps many others will benefit from what follows. Visits are brief--I try to accommodate many patients. Patient stories are long. By necessity, I have to boil them down to their essence. Many themes are repeated over and over again--as are many questions. My next series of entries are attempts to answer questions which are not as simple as one might think.

Many patients have been told they do not have chronic Lyme disease because Western blot antibodies are in the IgM class, not the IgG class. Normally, the immune system makes IgM antibodies in early infection and then makes IgG antibodies in late infection. Patient selection for major clinical studies have been chosen based on IgG responses. Mainstream thinking claims that the lack of Lyme IgM antibodies into IgG antibodies is evidence the test is false positive. At any rate, this excludes the diagnosis of chronic Lyme disease. All major NIH sponsored studies have only included patients who are CDC positive by IgG standards. In addition, the CDC allows for skipping the 2 stage test (an improvement? I think not): ELISA then Western, if the patient sample is IgG positive. I have recently scoured the medical literature in search of papers which address the Lyme IgM/IgG issue. There are hundreds of scientific paper published about Lyme disease--many recent. The IgM vs IgG issue remains largely untouched.

What I have found is that: Steere published an ancient studyof Lyme patients infected 20 years ago. He found persistent antibodies of both the IgM and IgG class. Igenex has clinical studies: the presence of 2 specific IgM (or IgG) bands shows exposure to Borrelia burgdoreri (Lyme). There are studies which discuss false positive reaction as well as studies which discuss the specificity of certain antibodies. Existing literature supports the idea that certain Western Blot antibodies are highly specific for Lyme. Heuristic reasoning would lead one to a conclusion opposite that posited by mainstream medicine. As stated, IgM antibodies are seen in early and therefore acute infection with Lyme organisms. The persistence of IgM antibodies would suggest the immune system is "chronically" seeing Borrelia as an acute--new infection. IgG antibodies, seen in late infections with other organisms, are frequently used as a measure of immunity. Studies which select chronic Lyme patients with IgG responses may be inherently biased--ommiting the most common patient type. Patient selection for studies has been difficult because of patient recruitment limitations.

Why IgM? There are no studies which acknowledge this anomaly, let alone have studied it. I can postulate. IgM and IgG antibodies are produced by the same cells: B lymphocytes. These lymphocytes may become plasma cells. The switching from IgM to IgG antibodies occurs by amolecular switching. This class switching--IgM to IgG-- frequently fails to occur. Is it because Borrelia hide from the immune system--change the reactive antigens? I don't know. Normally af IgG antibodies are used as a metric for immunity from a particular germ. Memory cells persist. These memory cells produce IgG antibodies which block re-infection. Perhaps memory cells are not produced in chronic infection with Borrelia burgdorferi infection. The question remain unanswered.

What do we know: Lyme is associated with more IgM than IgG antibodies. Certain antibodies, for example: 18, 23, 31, 34, 39 41?, 93 are HIGHLY specific for exposure to Lyme bacteria.

The argument that chronic Lyme can only be diagnosed when 5/10 IgG, CDC surveillance bands are present--which exclude 31 and 34, makes no logical sense. The exclusion of 2 very specific antibodies relates to a failed vaccine. The 10 antibodies were part of an epidemiological tool devised in 1994. This tool was never intended for diagnosis, but has morphed into a diagnostic criteria used by infectious disease physicians for the inclusion/exclusion of Lyme infection. Recently a patient with 7/10 of these antibodies was sent for a C6 peptide test for confirmation, because the infectious disease physician thought these reactions might be a false positive. Side bar: the C6 test measures reactivity to a protein, ViSE. The ability of this particular antigen to mutate is well established; the utility of this test has lessened over time.

A recent patient (last week) told me the previous doctor told her she could not have chronic Lyme because a positive two-tier Western blot showed only IgM antibodies. I was asked to refute this during part of a 30 minute office visit.

Infectious disease physicians read from a script wthout critical analysis (my opinon).

The next series of blog entries will discus questions related to Lyme controversies. All of these entries are my opinions. Readers should be aware that my opinions more often than not, differ from those of mainstream sources including: IDSA, CDC and many experts and clinical investigators.

Post-Lyme syndrome

2010-02-08T06:00:00.000-08:00

A 68 year old female consulted with me one year ago. She had been ill for over 4 years. At the outset she had flu like symptoms and a rash on her neck. A 2 tier Lyme WB was positive by CDC criteria. She was treated with antibiotics 4 four months by her primary care physician. The physician pronounced her cured and refused to extend the course of therapy. Her symptoms returned with a vengeance. She developed more pains, joint swelling, numbness and tingling, fatigue, and cognitive dysfunction. She had progressive memory loss. She could not focus, concentrate, process or retrieve words and thoughts. She had episodes of confusion and disorientation. She saw numerous doctors, all of whom were dismissive, if not rude. She was told her symptoms were normal for a woman her age. Then after doing her own research on the Internet she ordered an IgeneX test.

The Lyme IgM Western showed bands: 18 28, 30, 39, 41 and 58. A C6 peptide antibody was 0.86. Her CD57 was 18.

When I first saw her the physical exam showed difficulty with word search and moderate short term memory deficits. Positive findings included: bilateral weakness in the upper extremities, absent deep tendon reflexes in the knees and ankles, decreased pin-prick sensations in 4 extremities and decreased vibratory sense in the feet and lower extremities.

The brain MRI showed scattered white matter lesions-non-specific. The brain SPECT showed decreased activity in the the left anterior temporal region.

After one year of treatment she is about 90% better. Her cognitive functions are nearly normal. Her treatment included: Omnicef, Biaxin, Plaquenil, Tindamax, Zithromax, Mepron, Malarone, Artemesin, Bactrim, Amoxicillin, and Doxycyline.

Comments:
This patient's story is illustrative of care given to similar patients by many LLMDs.
There is good evidence: patient's history, physical exam, laboratory test result and brain imaging all support the diagnosis of CNS Lyme/Lyme encephalopathy/neuroborreliosis etc --even to well informed IDSA physicians. The science suggests that all such patients should be considered for intravenous antibiotics, no matter which side of the fence you are on. In this case, the patient improved with only oral (extended-plus-co-infection) anti-microbials.

The IDSA view is that chronic Lyme disease does not exist. The IDSA has no argument with the existence of a post-Lyme syndrome. The authors of NIH sponsored studies have expressed empathy for such patients. Their suffering is real. The investigators and CDC claim current evidence does not support the use of long term antibiotics for such patients. It recognizes the genuine suffering of such patients and that this suffering is causally related to previous, (treated) Lyme disease. Fair enough. (I disagree).

But something strange has happened. Patients who seek the attention of ID doctors and rhematologist, even those with "CDC positive" results are treated as pariahs. Despite hard evidence, the patients are herded out of these physicians offices as quickly as possible. They are still told: you are depressed, you just need to exercise and loose weight, you have fibromyalgia, you are just imagining your symptoms, you spend too much time on the Internet, there is nothing wrong with you, I don't care what the tests say--you don't have Lyme and so on.

I went to medical school--admittedly some time ago. I thought doctors are supposed to be empathetic and kind to patients. Instead, many doctors are belittling, dismissive and bellicose.
They don't have to agree with the ILADS/LLMD approach, but for heaven's sake, they have a diagnosis to rest their hats on: post-Lyme syndrome-"a poorly characterized autoimmune syndrome."

They should at least read their own literature. These physicians should be supportive, offer a diagnosis, explain the diagnosis, its pathogenesis prognosis and therapy.(If they believe the party line?). These understanding physicians should prescribe therapies to alleviate or ameliorate the suffering of their patients. Instead, they appear to be taking out their disdain for LLMDS on their patients. Ironically, this may be a good thing because the patients keep looking until they find us. (I don't want to give "the other side" any good ideas).

Lyme does not cause Alzheimer's disease

2010-01-24T12:06:00.001-08:00

All disease results from the interplay of genes and environment. DNA, whose mysteries are slowly being unravelled, is the blue-print of everything we are and everything we will be. Four base pairs- codons- genes- make proteins which control everything else. Infections: viruses, parasites, bacteria--in some cases Borrelia burdorferi, become environmental factors which interact within a genetically encoded milieu. The relative importance of heredity and environment vary greatly depending on the disease. For example, if you are born with the cystic fibrosis gene your fate is predetermined before you are born. On the other hand, as with many other diseases--cancers, diabetes, coronary heart disease, multiple sclerosis and others, this interplay of genes and environment is no so easy to predict.

Alzheimer's disease, multiple sclerosis, lupus, arthritis and many other diseases are not caused by Lyme disease, or at least directly, as many patients mistakenly believe. Lyme may be an environmental factor associated with many diseases.

Susceptibility to Lyme is genetically coded and so is the virulence of a particle strain of the Lyme bacteria. In general, patients with chronic Lyme disease have central nervous system (brain) involvement, more often than not. Their clinical features are all quite different.

Borrelia burdorferi, unlike most other bacteria, is able to readily cross the blood brain barrier-- taking up residence within the brain. Inside the brain the spirochetes are seen as: atypical cystic forms, granular forms, blebs, rolled forms, colonies, rings, stretched strands, spherules and others.

Associated neuro-inflamation is complex and has been well described. Inflammation occurs as Bb encounters local immune cells such as macrophages and dendritic cells. Cytokines and chemokines induce inflammatory responses. Other immune cells, killer T-cells and B cells are activated. Bb can invade local glial cells and astrocytes. OspA is upregulated which induces apoptosis (cell death). Neurotoxins are produced. Nitric oxide and quinolinic acid have neuro-toxic effects. Autoimmune reactions also occur. There are different models of autoimmunity. Perhaps both molecular mimicry and Innocent bystander mechanisms occur. Lyme spirochetes have been observed in patients with concomitant Alzheimer's disease. Lyme does not cause Alzheimer's disease.

Alzheimer's disease has been studied for many decades. Various genetic mechanisms have been clearly established. Pathologically, Alzheimer's is characterized by an accumulation of amyloid protein in the brain neurofibrillary "plaques and tangles" and tau proteins. In animal models it has been shown that Alzheimer's does not occur when the protein which regulates the degradation of amyloid precursor is up-regulated.

Alzheimer's disease is considered the most common type of dementia. Dementia is characterized by chronic, progressive, global loss of cognitive functions. Numerous forms of dementia have been described. BSE (mad cow disease) is called prion disease. It is associated with mutated proteins in the brain. Lewey body dementia is associated with Parkinson's disease.

Rare genetic disorders, such as forms of porphyria can be associated with dementia (The madness of King George). Dementia may be the result of min-strokes and many other syndromes to numerous to list here. These syndromes may appear similar in the peri-morbid state, but they have clear differences in the earlier stages of the disease.

Of course, dementia can be associated with infection. For example, HIV and chronic CNS fungal infection are established causes of dementia. The dementia which most closely resembles Lyme dementia--neuroborreliosis associated dementia, is the dementia of neuro-syphilis. Syphilitic dementia is called "general paresis" and is known to be the cause of death of many historical characters.

Thankfully, most patients with neuroborreliosis do not develop dementia. They may suffer with severe cognitive deficits but these deficits are not global in nature. Patients usually maintain the ability to perform most activities of daily living. Certain cognitive processes in most Lyme patients remain relatively unaffected. SPECT/PET scans show patchy dysfunction. In Alzheimer's disease, the scans are global--not spotty.

Make no mistake. Neuroborreliosis is a devastating disease. Its treatment remains challenging. Still, many patients experience remarkable recoveries/remissions.

Amongst many in the Lyme community there is a reductionist tendency to oversimplify and claim that everything is caused by Lyme disease. This is neither true nor helpful.

Both sides must learn to speak a common language to find areas of disagreement and agreement.

Everyone has Lyme disease

2010-01-03T10:20:00.000-08:00

The last post was not a real patient. It was a composite of several patient. I pushed the envelope a bit--providing the appearance of mixed symptoms. Here is the problem.

Remember, when the original ELISA(EIA) test for Lyme was developed, many "normal" controls tested positive. Lyme couldn't be that prevalent--at least that is what the early investigators thought. This is why the bar was set high, hence, the confirmatory Western Blot.

It unknown how many people in an endemic area are infected with Lyme. Is it 10%? Is it 90%. We have no idea. For the sake of argument, let us say the number is 50%. We then have no clue what percent are "symptomatic". Furthermore, we do not have a clear definition of what "normal" is. There are natural physiological changes which occur with aging. I am 54 years old. If I play tennis, my brain may tell my body to do the same things it did when I was 20---not going to happen.

Asking patients to answer specific questions in inherently problematic. When a patient comes in with a long list of clear symptoms it is one thing. When positives are elicited only when a patient is queried, it may mean something entirely different. If a patient thinks long enough about any question, a positive response may be forthcoming. A lot has to do with the individual's personality.

As physicians know, testing becomes meaningful when the "pretest" clinical sense, points in that direction. Testing for Lyme is unreliable. A basic rule of thumb for me is: treat the patient, not the lab. Most patients don't want to shell out the money for a speciality Lyme WB. "Just send the test to Labcorp." And, if an Igenex is done-- the results borderline positive, what does this mean? Only a physician's clinical judgment can decide if a patient's symptoms are likely the consequences of chronic Lyme disease.

Most major scientific breakthroughs have been made by young people, under age 30. Mathematical abilities decline with age, although verbal abilities do not, and in fact may improve.
So what is there to do when a patient appears "normal" by the physician's best judgement? Again, there is no definition of normal. When queried, most over 50 year olds have some aches and pains with exercises, but recover quickly. Perhaps there are some mild cognitive changes(?normal). Nonetheless, the "patient" feels normal. He has no fatigue or functional incapacity. Testing is not done simply because other family members have chronic Lyme disease.

If I treat what am I treating? What is the goal? What is the endpoint?

This is why I recommended watchful waiting. Otherwise, if one looks hard enough--turns over every rock: everyone has Lyme disease. Patients who suffer with Lyme disease see this case through a different lens--the lens of their illness. It is just not that simple.

Doctor: I want a Lyme disease test

2009-12-22T06:05:00.000-08:00

A patient comes in to the office. Let's say he or she is 5o years old. Many friends and family members have Lyme disease, he wants to know if he has it too. He is generally well but complains of some aches and pains. His joints hurt occasionally, especially after exercise, but recover quickly. His energy level and sleep are good. When asked about memory and cognitive problems he pauses for a moment: Perhaps his memory is not as good as it used to be. There has been some decline over several years. Word retrieval is a problem at times. His focus is not as good as it used to be. His mathematical abilities are not as good as they once were but they are OK. There are no other neurological symptoms. He functions normally at work and at home. These mild changes in cognition have occurred gradually over a period of years but are not bothersome.His family history reveals than a parent developed Alzheimer's disease at age 86. A recent physical has been done. His exam and routine lab work were fine. Should he be tested for Lyme disease?

No. Many patients have asymptomatic infection. This could be the case; still, I would not test. Positive results would only open a Pandora's box. These symptoms are mild and likely within the range of what might be expected in a 50 year old. The normal brain is sharper at age 25-35: minimal cognitive changes--neuronal fall out, occur in normal people. Alzheimer's disease? His risk may be slightly greater than that of the general population. Perhaps general recommendations would be made: exercise brain and body--eat well--perhaps drink coffee and take extra vitamin D.

The patients would be given a list symptoms to watch for. Treatment: watchful waiting--a term frequently used by doctors.

Vitamin D: A retraction--I got it all wrong

2009-12-21T06:04:00.000-08:00

Vitamin D is much more complex than I have indicated earlier. The only thing I can say about the reversed pattern (active D higher than inactive D) is that it appears to be a marker for Lyme disease and/or inflammation--perhaps a very good marker.

Much research has been done on vitamin D. All of it is based on measurement of the inactive form, vitamin D hydroxy 25, which correlates with stored vitamin D. Yes, vitamin D has anti-inflammatory properties, but this may not be a bad thing. It affects cytokines andT-cell activation. But contrary to previous comments, it is active vitamin D that increases production of an anti-microbial peptide: cathelicidin. (Past statements that active D tilts the immune system from Th1 to Th2--causing production of anti-microbial peptides is wrong). The binding of active D to receptors modulates the genetic expression of complex proteins. VDRs (vitamin D receptors) are found in many organs in the body, including: brain, heart, skin, gonads, prostate and breast. Vitamin D receptors are found on a variety of immune cells, including: monocytes, B-cells and activated T-cells. It also has effects on dendritic cells. Vitamin D toxicity is very rare, even in patients with very high levels of active vitamin D, the 1,25 dihydroxy form.

Anti-inflammatory effects of D may lower the risk cancers, autoimmune disease, diabetes, heart disease and others. Recent research has shown that vitamin D is required to activate the histocompatibility gene, HLA-DRB 1501. This activation is necessary for the immune system to differentiate between self and non self in a select group of patients.

A link between vitamin D and MS has been shown. Perhaps the lack of MS in tropical climes
is not related to the absence of Bb and other infectious agents, as some have postulated, but due to higher levels of D from birth on.

The main source of D is sun light. Increased melanin decreases UVB penetration through the skin needed for conversion of D. It has been shown the black skin increases the risk of prostate cancer in the US but not in Africa--perhaps evidence of D's cancer fighting effects.

The Canadian Cancer Society has recommended that all it's citizens supplement with 1000 units of D daily.

D supplements are generally in the form called D3. This is the same form obtained from sun exposure. There are many forms of D and it's metabolism is very complex. Clinically, we only measure D in its stored and active forms.

In these numerous studies, only stored vitamin D is measured. Some doctors on the "cutting edge" have suggested that vitamin D hydroxy 25 levels are optimal at 75 (normal
32 to 100). But they are not looking at lab values I see in my practice. The range for normal active vitamin has been expanded, (10 to 75).

Many of my patients typically have stored vit D levels of 12--very low-- and active vit D levels of 100-- still high even though the range has changed.

In some way, the body--the immune system ostensibly, is trying to rectify the problems related to the infection (maybe). After treatment many patients have D levels in the normal ranges. This varies: some patients have D levels which drop across the board.

It now seems to me that judicious supplementation of D may in fact be very useful. Levels need to be monitored. the use of Benicar to inhibit renal conversion of inactive to active D may be a bad idea. Our bodies are pretty smart: let them balance the levels as needed. If active levels are above 100 I am somewhat hesitant to recommend D supplements. I have no basis for this. Again, vitamin D toxicity is difficult to attain. Reported cases have only been reported in individuals taking 40,000 units daily over a period of time.

Why doesn't my doctor believe in Lyme disease?

2009-11-23T19:09:00.000-08:00

Scientists do research. They work in labs, at Universities. They work with bugs and test tubes; develop hypotheses, and design experiments to prove or disprove their theories. Sometimes they do basic science research-- to discover the basic structure and function of things. They publish their findings in prestigious, peer reviewed journals like Science and Nature. Such scientists have discovered much about the spirochete, Borrelia burdorferi, the causative agent of Lyme disease. This data is called "in vitro." Many doctors will claim that such results may not apply to the "in vivo" processes inside the body.

Physicians do not read these journals. They operate in parallel. They also have hypotheses. They evaluate their hypotheses with controlled clinical trials. Frequently medical trials provide confusing and contradictory data. In such cases the investigators can draw varying conclusions, sometimes informed by pre-existing biases.

Physicians(practitioners) are not scientists, although some may disagree. There are a few exceptions to this rule. Physicians work within the box of their trade. In medical school they are busy learning basic rules: structure and function of the body, types of disease--causes and treatments. Much of this is complex and ever changing. Evidence based medicine has helped physicians develop protocols and algorithms. The evidence is based on an analysis of the published studies in prestigious journals such as The New England Journal of Medicine and others. At times there is no or little data to support diagnoses and therapies. In such cases a body of "experts" informs the public of physicians regarding the best diagnoses and therapies. Even where no "science" exists, these opinions are surrogates for "science" and become-- "evidence based medicine." The waters are muddied. The distinctions between fact and opinion can become blurred.

The field of medicine is vast. It is broken down into various boxes. Some of these would include disciplines such as: internal medicine, orthopedics, rheumatology, neurology and infectious disease. (Of course this is a tiny selection of medical specialties for purposes of this discussion).
Perhaps readers do not know that all infectious disease specialists start out as generalists--internist or pediatricians, followed by a 2 year fellowship in infectious disease medicine. An infectious disease doctor has done: 4 years of college, 4 years of medical school, 3 years of residency and two years of training in infectious diseases. Note: for the first 11 years, the internists or family practitioner has had basically the same training as an "ID" doctor. Infectious disease doctors see sick hospital patients. They familiarize themselves with a wide range of esoteric infections: bacterial, viral, fungal, parasitic and others. They learn by reading text books, rounding with mentors and performing consults on sick patients, generally in hospitals. They spend very little time in an office setting. They become experts. They do not treat patients with chronic, "low grade" illnesses. They do not treat patients with fibromyalgia, depression, chronic fatigue syndrome and a whole other array of syndromes which they sometimes like to diagnose (in lieu of Lyme disease). Of course, they were generalists before they became specialists.

Each specialty has its own box. It works from a list of common diagnoses. Keep in mind--if you are a hammer, everything looks like a nail.

For example, a patient has joint pain. The orthopedist considers: tendinitis, a torn cartilage, a ligament injury, a mechanical injury--or something--not in his specialty, requiring referral to another specialists. The patient may be referred to a rheumatologist who considers: rheumatoid arthritis, lupus, Reiter's syndrome, post-infectious arthritis, gout and Lyme disease and others. He may conclude it is not in his field. He may refer on to an infectious disease specialist where considerations may include: an infected joint with something like gonorrhea, viral synovitis and perhaps Lyme disease. The Lyme results are negative for Lyme by the IDSA /CDC screening test. No answer is found. The patient is referred back to his primary care doctor. Physical therapy and pain medicines are recommended. If the patient asks about Lyme disease he is told this has already been excluded.

Lyme disease--LLMD style-- is outside the normal boxes. It is rejected by practitioners of the traditional boxes. It is foreign and rejected. After all, the true experts have spoken. These new practitioners outside the box, are easily labeled quacks. Paradigms do not change easily.

And in a nutshell, that is why your doctor does not believe in Lyme disease.

Cystic forms and relapse

2009-11-23T15:44:00.000-08:00

It happens all the time. A patient has finally done great. No symptoms. Remission at last.
Symptom free with a "maintenance" med or regimen-- Doxycycline alone or Amoxicillin and Biaxin. Meds are stopped. Lyme symptoms return almost instantly, within days or weeks.

Why?

I have given this some thought. Lyme spirochetes grow slowly. They replicate every 24 hours give or take. The Lyme "load" hasn't suddenly grown exponentially. Is it autoimmune? Antibiotics do have anti-inflammatory properties; have they been suppressing a smoldering autoimmune response lying in wait? No--autoimmune processes generally progress gradually.

This leaves only one possibility. What happens quickly? Cyst forms of Lyme quickly convert to spirochetes, within hours. Ah-ha--the ready source of spirochetes!

As a patient recently told me: "The other antibiotics just cause everything (spirochetes and L-forms) to convert to cysts. Do they?

Cysts are metabolically inactive and generally don't make us sick; the brain seems to be the exception.

In the brain, cyst forms are associated with inflammation. There is experimental evidence supporting this. Tindamax-- the magic drug - sharpens the brain - eliminates vestiges of brain fog.

With the relapse, cognitive functions frequently remain intact while other Lyme symptoms explode. If brain cysts cause more damage than spirochestes there-- I quess this makes sense.

Questions: few answers. Do cyst busters lower relapse rates? Early or late?

Are dreaded L-forms in fact more docile than cysts? Not in the brain.

Perhaps a regimen of a cell wall inhibitor-cyst buster might work better in (in patients lacking cognitive dysfunction), assuming the germs have not passed the blood brain barrier.

Just a thought.

How it is supposed to work

2009-11-11T05:15:00.000-08:00

I tend to write about unusual cases. Here is a more typical case--a successful one.

A 68 year old female visited me in January 2009. In 2005 she was sero-positive for Lyme disease. Treating was aggressive by standards of the day. She was treated with Doxycyline for 4 months. She recalls that her chief complaints then were rash, fatigue and joint pain associated. After treatment she felt better.

Over the past year she had not felt up to snuff. Pains in the large and small joints had returned. She had neck pains and muscle pains. She had numbness and tingling of her extremities. Her energy level was lower, she had fatigue, headaches, night-sweats, shortness of breath, an unsteady gait, poor sleep and a decline in cognition. She had trouble finding words and focusing.
She had brain-fog. Her sleep was disturbed.

Her exam was abnormal (neurological findings):her Igenex was positive IgG --34, 41: her Igenx B. duncani test IgM, 1:20 was borderline: a Clongen wet mount showed motile bacteria, presumed to be a species of Bartonella. Her SPECT scan showed poor perfusion to the left anterior temporal lobe: her MRI showed multiple white matter lesions consistent with Lyme disease or MS.

After treatment with courses of: Omnicef, Biaxin, Plaquenil, Tindamax, Zithromax, Mepron, Amoxicillin, Tindamax and Rifamin (in various combinations) She feels essentially normal. The treatment to date has lasted about 11 months. She is still on antibiotics and weaning will be done gradually. I suspect she will be on maintenance medications for a long time to come.

Lyme kills

2009-11-10T14:39:00.000-08:00

February 2007. A 46 year old female walked into my office for a "Lyme consult." I did not know at of our meeting-- she had recently been found in the middle of a road trying to end her life. Luckily, she was picked up by a police cruiser and subsequently admitted to a psychiatric facility. I did not know, until today, that a past treating physician, a rheumatologist, had called her an "f...ing moron." This patient/human being, has had a long and bumpy ride, but no longer entertains thoughts of suicide. She was sick of being sick. She had been sick for one half of her life, since age 24. She had suffered with total body pain. She had been diagnosed with "seronegative" rheumatoid arthritis. Gold shots, prednisone and other "remedies" offered no respite from her misery. She had swollen lymph node. Her joints and muscles hurt--really hurt. She was told she had "a weak immune system." She had numerous neurological complaints. There was progressive loss of memory and global cognitive function for over 15 years. Most troubling of all was severe, unrelenting abdominal pain. This was her worst symptom. Numerous specialist had been unable to identify the source of the trouble.

Prioritising, the first thing I did was examine her belly. She had right upper quadrant tenderness and a positive Murphy's sign. Gastroenterologists and surgeons insisted there was nothing wrong with her gallbladder. Sonograms and HIDA scans had been abnormal. I sent her for another HIDA CCK test: normal. I told her she had a bad gallbladder--I didn't care what the tests said. Two surgeons refused to operate. A third ( a close friend) reluctantly agreed. Her gallbladder was bad--chronically infected. Her pain was gone! Now she thought I was a genius. No. I have just seen chronic cholecystitis in many Lyme patients. And her physical exam was classic for cholecystitis. I followed a rule one of mentors taught me back in medical school: treat the patient not the lab. I quess most doctors today had a different mentor.

She was seropositive for Babesia at the outset. The Labcorp Western Blot showed no bands. Her Igenex test negative although IgM bands were "inderterminate" at the 39, 41 and 93 positions.
Treat the patient. Rocephin. She Herxed. We went around the block--numerous times. Gradually, after much Mepron, a mix of oral antibiotics and two courses of Rocephin she was significantly better.

We(she) struggled with serious nicotine addiction: 3 packs per day. She ended up with a severe lung infection. I prescribed Levaquin and Cleocin. The Herx brought her to the hospital. It looked like a cavitary mass or abscess. This was February 2009. The surgeons were sure she had a tumor. The biopsies showed no cancer and no microbes would grow in the lab. Faint colonies were seen only to disappear. The surgeons still wanted to operate. Two PET scans later-- no cancer. She had a miracle response to Ivanz. I have written about this before. The pulmonologist gave her months to live(she tells me), severe COPD. I don't think so. She is not short of breath even with moderate excertion. Maybe he is just trying to scare her.

Today I saw her. She is depressed because she retired from her job (voluntarily). She cleans houses part-time! Her pain is mangaged with modest help from "our friends". Good days and bad days. The bad ones aren't that bad. She is nervous: another PET scan. She wants to quit smoking--just can't do it.

I never knew about the suicide attempt--until today.

What do those lab tests mean?

2009-11-09T17:57:00.000-08:00

The CD57 test (only from Labcorp) measures a subset of NKT cells. These are Natural Killer T Cells. These T cells are actors in the innate immune response. In other words, these cells automatically attack what our immune system sees as foreign invaders. Our immune systems are naturally smart (anthropomorphically). They have pattern recognition cells which can determine tissues/cells that belong in our bodies from things (like bacteria) that do not belong in our bodies. The second part of the immune system, the acquired immune system relates to a complex set of reactions by which the immune system learns to make specific antibodies to attack the foreign invader. In some situations only the innate immune system is in play. Primarily this occurs when the "invaders" are intracellular. The acquired responses just don't work here. In the case of Lyme disease it is the intracellula- L-forms which are attacked by the NKT cells. When the CD57 count is low it would appear these cells are busy combating the L-forms of Lyme. Unfortunately, the innate immune system is never 100% effective in eliminating the bacteria. This is one of the mechanisms by which Lyme is able to persist in the face of antibiotics and immune responses.

C3a and C4a (Labcorp) are products of the complement system, cleaved from C3 and C4. These proteins are mobilized by the immune system as part of its acquired and to a lesser extent innate immune responses. These proteins can attach to unwanted bacteria and target them for destruction. These tests are sensitive indicators of a busy immune system attacking unwanted proteins or germs. These markers can provide a general sense of immune activation in the face of infection or inflammation.

C3d (Quest only) is a test for circulating immune complexes (CIC). These antibody/antigen complexes are not supposed to be present in our blood. The presence of these CICs indicates infection or inflammation and can be used as another indicator of disease activity.

C-reactive protein (CRP) is a naturally occurring protein found in blood circulation. It is one of two proteins which activate the complement system associated with immune activation. This is another marker which can help assess disease activity. This marker is elevated in many diseases and is not specific for Lyme disease. When used here, the clincially useful cut-off points may be much lower than the "normal" reported by the lab.

There are many other labs/markers of infection/inflammation. But here a few that seem to confuse many patients (and doctors).

Musings with a patient today

2009-11-06T13:19:00.000-08:00

Biaxin and Plaquenil? We have been taught that Plaquenil makes the intracellular environment more alkaline so Biaxin works better. Is this true? I don't know. I have also read that Plaquenil is anti-cyst. Sapi has now shown that Plaquenil induces cysts. You are on so many meds: let's drop the Plaquenil for now. The Malarone seems to be making the sweats go away. You are not sure, could the the sweats are hormonally induced? Possibly. My guess is that we are fighting Babesia: you tested positive. The low dose anti-malarial drug seems to work. Other patients require much higher doses.Biaxin decreases the Atovaquone by up to 40%. Many doctors switch to Zithromax for Babesia; Biaxin is a much better Lyme drug. We are covering more territory. The Bactrim you are taking for Bartonella also has some anti-Babesia effects; perhaps that is why you are doing so well. Patients seem to do better in the long run when anti-cyst drugs are added. Tindamax is the best--but that is for later.

How long do we treat Babesia for? Good question. Until the symptoms go away. There is no magic number. It has been said treat for 5 months because red blood cells have a 4 month life span. The only problem is that Babesia can also hide in the bone marrow, liver and spleen. The IDSA claims that it only resides in red blood cells--not true.

You followed all of that? You are doing better than you think!

Bartonella: brief report

2009-11-06T13:00:00.000-08:00

A patient with documented chronic Lyme disease had further testing for Bartonella.
A test performed at Fry labs reported abnormally shaped red blood cells without bacteria.

A wet mount at Clongen showed scarce round motile bacteria.
A PCR at Clongen for "Bartonella species," was positive.

In general, PCR testing for Bartonella is not performed because of a low yield.
These results, albeit in a single patient, suggest that: 1) wet mount exams may be more accurate than stained whole blood samples for the identification of these bacteria and 2) these small round organisms seen in patient's blood do in fact suggest ongoing infection with Bartonella species.

Odds and ends and ILADS

2009-10-30T13:28:00.000-07:00

Patients treated for Bartonella seem to experience of lot of itching which may be associated with rashes, bumps or normal skin. It seems to be some sort of Herx reaction.

Eva Sapi's research: very revealing. Lyme in the test tube quickly convert to cyst form when doxycyline is added to the cultures. Plaquenil also increases cyst formation (some Lyme literature claims that Plaquenil is an anti-cyst drug). Three drugs were shown to reduce the cyst load. In order of increasing potency: albendazole, metronidazole (Flagyl) and tinidazole (Tindamax). Of course this is in a test tube or culture medium. There are no cells. L-form transformation cannot be observed.

The ILADS' conference was great this year. Presentations were scientific and evidenced based.
Sessions discussing therapeutic options were great as well. I started my first patient on tigacyline, a drug much favored by Dr. Burasanno.

I have liked the layering approach for very ill patients. Start with IV Rocephin, add IV Zithromax and then add IV Flagyl. Dr. Martz agrees with my approach. We have both found this to be very effective. Other physicians recommend pulsing antibiotics in very high doses, primarily with Rocephin. Dr. Burasanno and Dr. Horowitz were animated and informative. "There is no one right way to treat Lyme."---Dr. Burascanno.

A second opinion

2009-10-27T10:07:00.000-07:00

A 36 year woman recently requested a second opinion after a recent diagnosis of MS.

She reported a history of tick bite. A Lyme WB from Labcorp revealed positive bands: IgG 41 and IgM 23. She was told her test results excluded Lyme in the differential.

One month prior to our visit she complained of numbness in her left upper and lower extremities. She also reported some stiffness in her neck.

Other symptoms were discounted: flu like symptoms with sweats and low grade fevers, swollen glands, joint swelling and pain and fatigue. Additional history revealed Bell's Palsy 15 years ago, heart palpitations and irritability. She initially denied all cognitive symptoms, only after further questioning she did admit to some progressive memory loss of the preceding two years.

An MRI revealed 4 white matter lesions in the brain and one in the cervical spinal cord.

The radiology report: "....demyelination due to multiple sclerosis or Lyme disease." This report was not from a radiology source which is familiar with my work.

As part of the MS work up the neurologist did an LP (spinal tap). I asked her to send a specimen to Clongen for PCR.

A report came to my desk amongst the usual pile of of daily lab reports and various requests.
This one caught my eye. Her spinal fluid was PCR positive for Lyme.

I called back to the office right away.
Her lab result and her appearance were incongruent. She sat across from me smiling, in no distress, appearing healthy in a casual glance.

This patient had Lyme in her spinal fluid. She had lesions in her brain.
She felt minimally ill and looked remarkably well. Of course I started IV Rocephin immediately.

During our most recent visit she told me she had seen "Under Our Skin."
She asked me: "How comes I am not sick like those people with Lyme?"

Thoughts on psych drugs for Lyme patients

2009-10-19T15:36:00.000-07:00

These are my opinions based on my reading and clinical experiences.

Most of the patients I treat with significant chronic Lyme disease suffer with a variety of neuro-psychiatric symptoms. Patients have recently commented to me about the post on Klonopin.

Patients with Lyme-Brain seem to have poor tolerance for SSRIs: drugs which increase serotonin levels in brain synapses. Perhaps the injured brain is sensitive to these drugs. Many patients come to me already taking drugs with a strong affinity for serotonin receptors in the brain such as Lexapro or Cymbalta. These drugs may cause increased brain fog, irritability and a paradoxical increase in depression.

Other anti-depressants act primarily on the brain chemical norepinephrine. Patients seem to tolerate these drugs better. These includes the anti-depressant Wellbutrin and ADD medicines which also effect dopamine. Charts in pharma books show the relative affinity of anti-depressants for serotonin and norepinephrine. If the ratio favors norepinephrine the patients may tolerate this drug better. This includes drugs such as Desipramine, an old TCA antidepressant. These meds are best tolerated in low doses.

Drugs used for ADD can be quite helpful. These drugs target the neuro-transmitter dopamine as
well as norepinephrine. These drugs increase wakefulness and energy and may correct some frontal lobe dysfunction seen in many Lyme patients. My favorite drug here is Ritalin which comes in a variety of doses and can be carefully titrated.

Mood stabilizers can be very helpful as well. These drugs are anti-convulsants which stabilize abnormal chemical/electrical imbalances in the brain. I like Lamictal because it has antidepressant effects and mild glutamate inhibition. This drug has significant toxicity and should only be prescribed by physicians familiar with its side effects. Glutamate toxicity is thought to be a major problem in the injured brain. The best drug for glutamate toxicity may be the anti-Alzheimer's drug Namenda, which frequently improves cognitive dysfunction.(Rocephin also works by this mechanism).

Klonopin binds to the neuro-transmitter GABA, which is a major inhibitory neuro-transmitter.
Lyme patients can suffer with excessive expression of excitatory neurochemical in the brain. Most of this is mediated by serotonin, the "work horse of the brain." This dovetails with my comments about the potential harmful effects of serotonergic drugs.

Other commonly used GABA drugs are Neurontin and Lyrica which may be well tolerated. In my experience, benzodizapines like Klonopin work better. This may be due their increased anti-anxiety effects.

Anti-psychotic medicines, like Seroqel, are certainly helpful for patients experiencing psychotic symptoms such as hallucinations. They may help in other ways. Although they inhibit dopamine, they bind to different receptors, deep in the brain, unlike ADD medications which stimulate dopamine pathways in the cortex of the brain.

Many Lyme patients have sleep disorders. The activating neuro-chemicals, serotonin and norepinephrine are prominent during waking hours. This is counteracted by a predominance of acetlycholine effects which occur during sleep. Restful sleep is important. When a "sleeper" is needed I prefer Restoril which produces a good night's sleep and promotes normal sleep architecture. Lunesta may be a good alternative.

The sick role and Lyme

2009-10-13T18:51:00.000-07:00

I saw a patient today who has been treated by another physician. The patient spends nearly his entire day taking supplements along with a complex regime of antimicrobials meticulously scheduled. The medicines are rotated and pulsed within specific protocols. This patient is going broke, in part because of the high cost of supplements which he assiduously takes per his physician's directions. He has stopped working in part because his illness is a full time job. His life centers around being THE PATIENT. Lyme disease has become his life. There is no time for normalcy. The sick role can become integrated into the disease. Perhaps, ironically, some readers of this BLOG focus all of their attention on their illness--scouring discussion forums, constantly perusing the Internet, seeking some new tidbit of esoteric information. The disease becomes a life style.
Many of my patients have told me that they no longer read my BLOG or read about Lyme disease, the politics and the controversies. Of course when I see such patients we discus the course of their disease and the rationale behind prescribed therapies during each visit.

These patients may be free to pursue a life which is as normal as possible. They spend time with family and friends. They function at the highest level possible in a multitude of domains. Suffering with Lyme disease becomes something they live with: It is not the center of their universe.

Such patients get up every morning, despite pain and other symptoms, put on their best faces and face life head on in spite of adversity. Other patients are constrained within a prison, imagined or real, comprised of walls, esmeshed in the fabric of illness and its attendant disabilites.

So I like to keep the regimens simple, and largely devoid of supplements. Changes are made when patients see me at scheduled appointments.

A word about supplements. Some patients certainly report benefits from a variety of add-ons. Some feel energized from Co-enzyme Q10, which I truly think helps many people. Some swear by teasel root. I may recommend one or two additional supplements but not many. I do not recommend multi-vitamins on a routine basis.

I was reared in medicine with a healthy dose of skepticism regarding vitamins.(I have discussed this before). Vitamin E--the "miracle worker," turned to offer no benefits to heart patients in controlled, published studies. Vitamin C turned out to be potentially harmful to heart patients. It was shown to increase plaque in arteries, increasing the risk of heart disease unexpectedly. Simple chemistry may give us the reason. Vitamin C can exist chemically in a reduced or oxidized form. The reduced form is an anti-oxidant; the oxidized form can be a harmful pro-oxidant. Supplements may not be properly balanced. So I perfer to leave nutrients and vitamins in the capable hands of Mother Nature. I stress a healthy diet with fruits, vegetables and whole grains which gives the body vitamins in their proper form along with the potpourri of photochemicals needed for these nutrients to perform optimally.

A folksy argument I frequently share with patients is something like this: A chronically ill patient is likely to be deficient in a variety of nutrients. This is caused by the illness or chronic infection as in the case of Lyme disease. One can think of such a patient as akin to a gas tank with a hole in its bottom. You keep filling up the tank with gas (supplements) but the tank is perpetually empty because the fuel drains through the gaping hole. Close the hole first--by getting the infection under control, and then the metaphorical tank can become full with the needed fuel.
A case of not putting the cart before the horse.

This does not apply to patients with dramatic deficiencies. And of course, this is just my working hypothesis and I know that most other physicians operate from the opposite paradigm.
My experience tell me that it works both medically and psychologically for my patients.

THREE WEEKS OF DOXYCYCLINE

2009-10-11T12:02:00.000-07:00

"Childhood friend's daughter in ICU for two weeks with-- Lyme disease---It is one thing after the next."
Keith Olbermann on health care.

THREE WEEKS OF DOXYCYCLINE.

"I just saved your life (diagnosing Lyme disease in friend's wife)." Larry David.

THREE WEEKS OF DOXYCYCLINE.

"I heard you never get over Lyme disease; I have a friend in a wheel chair; so many people are so sick, its a very scary disease." A patient.

THREE WEEKS OF DOXYCYCLINE.

"I used to function at a high level (computer engineer), now I can no longer do my job" A patient.

THREE WEEKS OF DOXYCYCLINE.

"I have been to 40 doctors. No one ever took me seriously--thank God you are listening to me."

THREE WEEKS OF DOXYCYCLINE.

" I would like to help you--but we have a two tier test--you never had a rash--NIH studies--
IDSA recommendations--and CDC--I can't treat you I might get in trouble--those ILADS, LLMDS are--I don't know, out there--you don't want to miss another "real" diagnosis like fibromyalgia or depression."

THREE WEEKS OF DOXYCYCLINE.

Cipro and Klonopin

2009-10-06T06:25:00.000-07:00

A 59 year old patient was prescribed Cipro in 1992 for a urinary tract infection. He experienced a variety of progressive symptoms. These included burning sensations, shortness of breath, fatigue, confusion, chills, sleep disturbances, night sweats, a feeling of alternating hot and cold, ocular problems, increasing cognitive dysfunction, a sensation of electric shocks and many other symptoms. After a long evaluation it was decided that he was suffering with a severe quinolone reaction; he was prescribed Klonopin which he has taken every since. The Klonopin has been effective.

He recently visited my office because he was not feeling well. He had been off Klonopin for 5 months and symptoms were returning. Off the Klonopin recently--he developed: severe fatigue, sleep disorders, tinnitus, head pressure, a sensation of electric shocks, numbness and tingling, joint pain, increased anxiety and hot and cold sensations.

Upon further questioning, perhaps he has not felt entirely normal on Klonopin. He has suffered with stiff fingers, anxiety, periodic weakness in his legs. dry mouth with dental carries and progressive brain fog associated with progressive memory loss. He has written these symptoms off to normal aging.

His wife has been successfully treated for chronic Lyme disease.

An exam showed evidence a stocking glove pattern of decreased sensitivity to pin prick, a loss of vibratory sense and absent deep tendon reflexes in his ankles.

A brain MRI showed non specific, periventricular white matter changes compatible with microvascular ischemic changes. He has no risk factors for this disease.

An initial set of lab studies (lLabcorp) showed: CD57 24, Bb Western blot no bands, Bababesia duncani positive, titer 1:256, all other studies negative. He vitamin D levels were properly balanced. There was no evidence of autoimmune dysfunction or inflammation.

He is an outdoors-man. He lives in a wooded area frequented by visiting deer.

I sent off another Lyme Western Blot to Clongen. (pending)

Many questions remain in this case, answered at this point. Is this truly a case of quinolone toxicity? If so, why have symptoms persisted for 17 years. Are quinolone reactions, at least in some cases, really "Herx" reactions in patients with asymptomatic but disseminated Lyme disease? I have documented such a case in a previous post. He does test positive for Babesia; this suggests exposure to tick borne illness. He has many symptoms and signs frequently seen in chronic Lyme disease. Why has Klonopin, a sedative, been so effective in stabilizing many of his symptoms for so many years, and why does he quickly relapse off Klonopin? The persistence of symptoms 5 months after stopping Klonopin makes withdrawal an unlikely explanation for this phenomenon. Does Klonopin. a GABA agonist in the brain have any positive benefits for some Lyme patients? For now, I have questions, not answers.

I hope the second Western Blot will be telling.

Case of Lyme pneumonitis with suspected resistant strain

2009-10-05T15:09:00.000-07:00

See recent post about Lyme resistance to antibiotics.

This case is now much more interesting.

This is the patient as you may recall had neuroborrelios which improved when the patient was given Zosyn for pneumonial

The patient received only a short course of Zosyn in the hospital. She was discharged with oral Levaquin. She went on to develop shortness off breath. Follow up radiographic studies showed a pattern of lung nodules and diffuse interstitial disease. Various diagnoses were entertained, including: sarcoidosis, lung cancer and other better known opportunistic infection.

A brochoscopy was performed to obtain a tissue specimen. The biopsy was negative for the usual suspects with non-specific findings. Slides from the specimen were sent to Clongen Labs. A highly sensitive real time PCR test was positive for Borrelia burdorferi--the agent that causes Lyme disease.

I spoke with the pulmonologist today. He is not familiar with any medical literature supporting cases of disseminated Lyme disease in lung tissue. Lyme may have been a factor in her original pneumonia, but this is not my current hypothesis. Her initial pneumonia was due to aspiration. Perhaps the inflamed/damaged post-pneumonia lung tissue created an environment for the dissemination of Lyme bacteria into the lungs.

I offer the hypothesis that this patient has a resistant form of Lyme. This is why courses of Rocephin and Zithromax have failed. I have restarted Zosyn since it is the drug which has proved effective in the past.

There exists some research data which supports the notion that Lyme can become resistant to antibiotics. One would certainly expect this. Bb has an incredibly complex genomic structure.
It has more plasmids than any other know bacteria. Extra-nuclear DNA in plasmids can recombine with native DNA to create resistant strains of bacteria.

This is an exciting case; I hope to keep you posted.

Stranger than fiction: The third rail?

2009-10-02T07:14:00.000-07:00

I have avoided the topic. But this story must be told.

My patient described in this post is a fifty something year old woman who has suffered with intractable neuroborreliosis for years. She failed numerous courses of IV Rocephin. Several years ago she presented with diffuse, small circular, open skin lesions particularly on her forearms. She told me fibers were coming out of the lesions. The patient had never heard of Morgellon's disease; still, I was a bit skeptical. When I witnessed fibers extruding through her skin while she was in my office I knew something unusual was afoot. Treating Lyme disease pursuant to ILADS methods is troublesome enough in my state. Thankfully, she was able to see another physician in California who has had success treating this strangest of maladies.

In addition to her strange dermatological disorder she experienced chronic weakness, pain and confusion. Psychiatric symptoms included auditory hallucinations and racing manic-like thoughts. Her brain MRI showed diffuse white matter lesions. Her neuro-motor and cognitive disabilities left her disabled and feeling hopeless. She failed numerous courses of intensive treatment for both Lyme and co-infections. Her last fairly-recent course of Rocephin for 6 consecutive months had proved unhelpful. My colleague 3000 miles away treated her aggressively with a unorthodox regimen of Stromectal, Ivermectin and Albendazole in various combinations along with Diflucan and antibiotics.

After a year of these therapies her skin was clearing but the other symptoms remained.
She was seropositive for Babesia and had been treated with Mepron and Zithromax for nearly a year. Still, she continutined to have Babesia-like episodes associated with severe sweating. I decided to head in a new direction.

I started with IV Zithromax and Plaquenil. She had some good days: promising. I added Tindamax--a different anti-parasitic drug. It appeared to offer some further benefits. Then I added Malarone, one three times a day with Artemesin; she was definitely improving but my end point, cessation of sweating, had not occurred. Then I added Cleocin, only 300mg twice daily. The sweats were finally gone. And magically--she was back.

Of course she wasn't 100% better but she was stronger and able to attend to household activities. Her mind was fairly clear. She even helped one her kids with math homework.
None of this would have been conceivable 5 years ago.

So what is Morgellon's disease? Is a parasite? Is it a strange manifestation of a Lyme co-infection? It has been reported that 95% of Morgellon's patients also test positive for Lyme.

Why BLOG?

2009-09-19T10:11:00.000-07:00

As I have said in the past, this BLOG and others are a venue for putting ideas and experiences into the blogosphere for others to consider. My posts have covered many areas of agreement and controvery: mostly controvery. In my mind this is a major the role of this tool. Of course I have meant it to be informative. I learned much from my father. He frequently said outrageous things for the purpose of prodding others into a lively debate: The devil's advocate. If I have "criticized" other LLMDs it must be seen within this context. Please remember that just because something is in writing does not mean it is true.

This war over Lyme disease has been fomenting long before I came into the picture.

A belief in even the possibility of chronic Lyme disease would next exist except for the pioneering work of many who have bravely challenged the establishment, putting their careers and reputations on the line.

I have never intended to impeach the reputations of Burrascano, Jemsek, Jones, Stricker, Singleton, Fry or countless other physicians or scientist involved in this field over a period of 3 decades.

I personally do not know many of the great physicians and scientist involved in this field.
Many of my comments are based on information obtained only indirectly.

I have worked alone in my small corner of the world. By luck alone my office is a stone throw away from Clongen lab: I now have a colleague who helps me contemplate some of the mysteries associated with this illness.

Many clinicians have developed ideas and therapies which have been EFFECTIVE, even though the exact mechanisms were not fully understood by the clinicians at the time. Unable to get attention from mainstream medicine/science many "LLMDs" have functioned independently without the benefit of consultation with others. For example, the small round gram negative bacteria swarming in the blood of so many patients may be the labaoratory equivalent of the BLO described by Dr. Burasccano. The diagnosis was made strictly on clinical grounds. It was Fry labs who first put a face on this organism, giving it a name.

I have tried to the best of my ability to confine many comments to that which I believe has a factual basis supported by evidence of some kind. Much I have written has been editorial: opinion and conjecture; and I hope this has been made clear along the bumpy road.

Lyme disease is now Lyme-Borreliosis-Complex. It is a new and emerging disease. Much remains enigmatic. In essence all I have done is thow my hat into the ring.

I appreciate positive AND negative comments posted here. We are all learning and I suspect we will continue to do so for years to come.

Antibiotic resistance: Wet mounts re-visited: IV Flagyl

2009-09-17T16:20:00.000-07:00

The Bb genome has apparently been sequenced at the Craig Ventnor Institute in Rockville, MD.
The project took an extraordinary amount of time. The genetic structure of Bb unexpectedly complex.

Resistance: It is hard to know if Lyme spirochetes are resistant to antibiotics or not. There is no way to culture the bacteria and test for this. It is known that in vitro (in the test tube) a germ may appear resistant to an antibiotic, but when the antibiotic is administered at super high doses it is able to kill the organism. This begs the question: Do some patients only respond to Rocephin when it is administered at high doses for prolonged periods of time?

Recently, a patient of mine who appeared to have intractable Lyme neuroborreliosis--having failed Rocephin and Zithromax was admitted to a local hospital for pneumonia. In the hospital she was given an intravenous antibiotic called Zosyn. Zosyn is a third generation penicillin with an additional ingredient to protect from the effects of penicillin resistance. Within just a few days the patient had a response which was nothing short of miraculous.

Unfortunately, The only IV antibiotic on the IDSA list is Rocephin. The LLMD list of intravenous therapies for Lyme is expanded, but still limited. Perhaps in jurisdictions which give LLMDs more latitude--- (Connecticut, Rhode Island and California), other IV therapies should be tried.

The incredible wet mount exam: Numerous blood wet mounts of tick borne disease patients have now been studied. Four results have been found repeatedly.

1) Small motile gram negative bacteria, outside the cells are seen frequently. These unknowns may be the BLO, Bartonella like organisms described by other physicians. These bacteria respond to treatment with Bactrim, quinolones like Cipro, Rifampin and other similar drugs.
2) Crescent shaped organisms. These organisms do resemble Toxoplasmosis, which they are not. The seem to respond to therapy based on Malarone.
3) Elongated, larger structures are frequently seen. Very strange. These are thought to be parasites, worms--microfilaria like. These entities seem to respond to Tindamax based regimens. It has been suggested that Ivermectin may be effective but I have little experience here.
4) This is the finding which intrigues me the most at this time. White blood cells are observed with swarms of intracellular organisms. This resembles Ehrlichia or related organisms--but no positive ID has been made. It may be that Zithromax and Rifampin are effective here. I have just begun to do before and after analyses.

In many patients with neuroborreliosis syndromes the contribution of the BLO is very significant and must be considered. I apologize for old entries in which I questioned this issue.
One problem is that many non ill patients also show swarming gram negative bacteria in the blood as seen in some healthy controls. Here, clinical judgement rules the day.

Revisiting an old patient. Two years ago a patient with terrible neuroborreliosis was succesfully treated with a combination of first IV Rocephin followed by the addition of IV Zithromax and finally IV Flagyl. According to his recollections it was the IV Flagyl which helped him dramatically improve. Both oral Flagyl and oral Tindamax had not been helpful. This patient stabilized on long term oral antibiotics. After some time he was "lost to follow up." He stopped all antibiotics.

He has now returned with a full relapse of florid neuroborreliosis. He has been treated the same way. Rocephin during the entire course--Zithromax adding for a second phase of the course --and finally IV Flagyl added to the mix. He has improved with the first two drugs but is only 60% better after three and on half months. Today I ordered the Flagyl. He told me: " Doc, now I am going to turn the corner." I hope so. I have seen this result in other patients as well. The Flagyl is administered as a once daily dose of 500mg.

Lyme-Bartonella-B12-Folic acid and vitamin D

2009-07-28T15:12:00.000-07:00

A 35 year old female was seen by my associate one month ago with complaint of fatigue, malaise joint pain and fatigue. The symptoms had been present for about 2 months. My associate ordered a Lyme Western Blot. Bingo. Three of three IgM bands were present: Lyme disease. Here are some additional result:B12 280, folic acid 5.8, C4a 3200, vitamin D 25-Hydroxy 26, vitamin D 1-25 dihydroxy 75. I saw her 3 weeks ago. Today was our second visit. The symptoms had really been present for the past 6 months or longer. She had experienced fever, swollen lymph nodes, muscle weakness--especially of the arms, profound fatigue, pain in knees-feet-shoulders, total body pain, brain fog and forgetfulness as well as episodes of confusion, depression, word salads, tingling and drenching sweats. The exam showed weakness of the arms and evidence of peripheral neuropathy.

Here is what I think I have learned and how I applied it for this patient. Lyme and Bartonella seem to be co-travellers. It is the combination that causes many of these symptoms, especially the cognitive ones. The swollen glands are a tip off-Bartonella. Soaking sweats do not always equate with Babesia. The low B12 and folic acid are a tip-off. These nutrients are essential for the manufacture of red blood cells. Depletion of these vitamins suggest a bacteria or parasite of red blood cells causing rapid turn over and depletion. Bartonella are present in large numbers whereas Babesia are present in relatively small numbers; these vitamin deficiencies would seem to be the calling card of Bartonellosis.

Vitamin D is a useful parameter. The conversion to active vitamin D in the kidneys occurs because the immune system is attempting to regain equilibrium. This push to the Th2 state away from Th1 occurs because the infection is causing excessive inflammation. As an aside, it doesn't matter if the patient is given supplemental D or not. More vitamin D might provide additional fuel to cool off the rambunctious Th1 response: it is OK to give and may help the patient feel better. Vitamin D toxicity is a non-issue. The only potential issue is hypercalcemia--excessively high levels of calcium in the blood. This is highly unlikely and can be monitored.
Forget the whole Marshall distraction.

I placed the patient on Doxycyline and low dose Cipro. Three weeks later she is doing fabulously.
The Herx was bad for 2 weeks. Now: the fog has lifted, her muscles are strong again and even the night sweats are gone.

The old Doxy plus Cipro was not treating Lyme by two different intracellular mechanisms; it was treating Lyme and Bartonella all along. That is why it has worked so well!

The low dose Cipro seems safe and effective. This patient has allergies to Penicillin and Sulfa.

It is all coming together.

The Untouchables

2009-07-27T14:25:00.000-07:00

My critically ill patient is back in the office. She is literally disintegrating before my eyes, her encephalopathy worse. Confused, hallucinating and delusional-- she is unable to speak. A week ago she was somewhat mobile. Now she is confined to a wheel chair resembling many unfortunate patients I have cared for in nursing homes with end stage Alzheimer's disease: this patient is 47 years old. Another doctor had cared for her for 7 months. She has been under my care for only one month. She needs hospitalization. I have sent other patients to many hospitals over a period of years with poor outcomes. This different University Hospital is reputed to be a bit more friendly. We shall see.

I send her to the hospital with a stack of studies and a hand written summary. She is sero-positive for both Lyme and Ehrlichia--thank God! I have written down the name of a neurologist who is reputed to be "Lyme friendly."

The only way to be admitted to hospitals these days is through the ER, unless you are an "attending" with direct admitting privileges. And even this occurs rarely these days.

The intern is the first to call me: "We don't see anything acutely wrong with patient"--not wanting to admit her to his service.

She is very ill, please admit her.

I am called back by a supercilious second year resident, his boss. "The patient has been the same for a month--there is nothing acute here--we don't want to admit her. The neurologist whose name you wrote down won't be able to see her unless you call him. You should not have sent the patient to the ER: you have given her the erroneous impression that she will be admitted. I don't see any reason for an admission."

"Please admit this patient. She is getting worse. She has a severe progressive encephalitis. She absolutely must be admitted for a work up; she needs a a lumbar puncture. You cannot send this patient home"-- I implore.

"Humf, I will get neurology to see her." The neurologist you have requested will not see her unless you arrange it--here is his beeper number."

I page the doctor: no response.

The gatekeeper--the man who would keep my critically ill patient from admission to the esteemed University Hospital is a "sagacious" 26 year old doctor with a major "...tude."

The patient is crazy of course, the doctor a wack-job. Tick borne disease causing encephalopathy--"whatever". Reluctantly: "I'll see what neurology has to say."

The untouchables: cursed-- damned-- invisible.
At least that how it seems.

Why take the blue pill if the red one works just as well?

Something about chasing a white rabbit down a hole I think.

"I'm sorry-- which pill do we take?"

Bartonella re-visited

2009-07-18T16:06:00.000-07:00

Bartonella is a facultative (difficult to culture), gram negative intracellular bacteria. New strains--known to cause human disease are being discovered on a regular basis. Standard serologic (antibody) tests ordered by physicians for Bartonella test only antibodies against B. henselae and B. quintana. A quick survey of medical literature shows a long list of Bartonella species with exotic sounding names: B. clarrideiae, B. koehlerae, B. vinsoni, B. berkhoffi, B. elizabethe, B. bovis, B. rochalimae, B. melophagi, B. facilliformis and others. The "species PCR Bartonella" test could miss other Bartonella species whose DNA is different. A CDC (Lyme-division) representative, recently said that new species of Bartonella in mice are being discovered on a regular basis. The CDC plans to publish a point-counterpoint piece regarding the significance of Bartonella in human disease.

Could the mystery bacteria seen in blood wet mounts and smears of many tick borne disease patients be yet unclassified forms of Bartonella? I think the answer is YES. These small bacteria stain gram negative and do not culture. Although Bartonella are intracellular organisms--live in cells, Bartonella species can exhibit prolonged bacteremia (bacteria in the blood).

Is the treatment of Bartonella different than that for Lyme? Both Lyme-Borrelia burdorferi and Bartonella are gram negative bacteria. The medical literature claims that both bacteria can for the most part be treated with the same antibiotics: Doxycyline, Biaxin, Zithromax, Rocephin, Levaquin and others. These drugs are bacteriostatic. Only two drugs are reputed to be bactericidal: Gentamycin and Rifampin. The standard medical literature also claims that Bartonella can be treated with short courses of antibiotics (similar to claims for Lyme). The literature indicates that Bartonella can cause brain infection but states that there is only one reported mortality. It is recommended that such cases should be treated more aggressively.

Back to the CDC. Most readers of this BLOG are familiar with the concept of tick borne disease. This concept is foreign to the CDC, despite a web-page which is misleading . The groups which study Lyme and co-infections are separated, even geographically(Colorado versus Georgia). Lyme is linked with spirochete diseases. Ehrlichia/Anaplasmosis are in a Rickettsia group. Babesia is in a parasite/protozoa group and Bartonella is in another group. The CDC admits it has never studied how multiple tick borne infections interact in a single host.

But I digress.

We don't really know what the germs (mystery bugs) are, what their role in disease is and how best to treat them.

A new patient, one who is extremely sick, was recently referred to my practice by one of my difficult patients--who is finally getting better--thanks.

This patient has a long history of chronic Lyme disease with pain and severe encephalopathy. She is only 45 years old but has moderate to severe dementia. Her previous physician, a well known Lyme treating doctor had prescribed a prolonged course of Rocephin--without benefit and essentially informed the patient and family that there was nothing else he could do.

I agreed to take the patient on to see if I could help. Based on experience I know that some patients respond to IV Zithromax even when IV Rocephin has failed. Perhaps this is a manifestation of the "Bartonella" syndrome.
There was a response. Within two weeks her pain was 50% better. Her encephalopathy worsened--a Baronella brain Herx?? At least it was something. These results are contemporaneous with this entry; adjustments in therapy are being made.

Clearly, there are patients who respond better to: Bactrim, IV Zithromax, Rifampin, Cipro, Levaquin and other drugs. LLMDS and their patients will attest to this.

Many patients are clinically diagnosed with the triad of: Lyme-Babesia-Bartonella--frequently on clinical grounds.

If there is a method to my madness I have found that patients respond best when the treatment strategy targets: Lyme then Babesia then Bartonella and then back to Lyme. Of course it may be desirable to use drugs which overlap in their ability to address the collection of infections. And so it goes.

Babesia questions

2009-07-14T05:59:00.000-07:00

For convenience we can divide physicians into two camps: those who follow the IDSA and those who follow ILADS. This is an over-simplification. Many physicians fall in between. I am seeing more infectious disease physicians cross over into the chronic Lyme side of things. Many other physicians are becoming more interested in treating Lyme as a chronic disease and treating it as such. The paradigm has broadened for many of us; chronic Lyme has evolved into chronic tick borne disease. Many patients do not improve or recover, at least not fully, unless other co-infections are treated as well. The treatment of co-infections exposes Lyme aware physicians to increased criticisms by IDSA leaning physicians because the presence of these entities is frequently more difficult to demonstrate than Lyme--Borrelia burdorferi.

Readers must be reminded that in the main, laboratory evidence suggesting the presence of Babesia tells the physician only one thing: the patient has been exposed to Babesia. Here I am referring to serological antibody tests. Other, more convincing tests, for the non-believers, include a blood smear which shows the organisms or a FISH test offered by IgeneX. These tests are not particularly sensitive missing most cases. Serologically, we can test for two strains of Babesia through commercial labs: B. microti and B. duncani. There are numerous other strains of Babesia for which no simple test exists. Clongen lab can perform a Babesia "species" PCR test which is very specific but not all that sensitive. It screens for the presence of Babesia DNA for about 15 species of Babesia.

In routine lab panels described elsewhere, anybodies directed against B. microti and B. duncani or WA1 are routinely obtained. It is always nice to have one's clinical suspicions mirrored in a laboratory test. But like most things Lyme: the diagnosis of Babesiosis is a clinical one.

Many clinical signs and symptoms have been ascribed to Babesiosis. In my practice the primary symptom is sweating. Patients have night sweats, sweats after a hot shower, day sweats or chills and flu like symptoms which recur cyclically. A secondary feature is muscle pains in preference to joint pain.

Another helpful test is the evaluation of a wet mount slide. Many patients show a crescent shaped organism which resembles Toxoplasmosis. I do not believe this organism is Toxo: many patients with the organism have negative serology (antibodies) directed against Toxo. I will explain why I mention this finding in connection with Babesiosis in a moment.

The standard treatment for Babesiosis has been Mepron, usually combined with Zithromax.
Mepron is a yellow liquid which is unpleasant tasting and very expensive. It contains a single ingredient: Atovaquone. Malarone, on the other hand, contains two anti-parasite ingredients: Atovaquone and Proguanil. Malarone is a less expensive, convenient tablet.

Malarone seems to address this crescent shaped parasite whereas Mepron does not. It is my suspicion that this other, yet unknown parasite, is responsible for much muscle pain, including that associated with fibromyalgia syndromes.

Even though the dose of Atovaquone in Malarone is only 1/3 of that present in Mepron, I have found it is effective for Babesia symptoms. My experience has informed me that it is the length of therapy, not the dose of Atovaquone which helps ameliorate Babesia related symptoms and presumably infection. Anti-Babesia or parasite therapy can be augmented by adding the herbal medicine, Artemsin, usually 200mg twice daily.

So yes, there are more positive serologies for B. duncani than B. microti here on the east coast which contrasts with the views of local health officials, still, the diagnosis of this syndrome is made strictly on clinical grounds. There exists a subset of patients with antibodies to Babesia who never exhibit symptoms of this infection. Most of these patients improve even though this specific co-infection has not been treated. Presumably, in these cases, the infection was mild and eliminated by a well functioning immune system. Even so, the presence of these antibodies can be used to substantiate the diagnosis of chronic Lyme in patients who are Lyme seronegative: where there is smoke there is usually fire.

A basic rule of thumb which has served me well for over 25 years of medical practice still holds: treat the patient, not the labs.

Another comment: Zithromax is not very is not very effective against Lyme disease; its cousin macrolide Biaxin is. Biaxin is frequently avoided when antibiotics are combined because of its it "sloppy" tendency to cause adverse drug to drug interactions: it doesn't play well with others.

Biaxin may reduce blood levels of Atovaquone by 40%. Still, in patients where the treatment of Lyme is imperative along with the treatment of Babesia, this combination has still been effective in many patients.

Another, quite effective drug can be mixed with Malarone for Lyme disease: Cleocin. But this drug carries its own unique risks, especially C. diff colitis, the nemesis of physicians treating chronic Lyme and related disorders. As always the need for probiotics can not be stressed enough. I prefer the combination of Sacchromyces with an Acidophilus mix.

Ambien and a bump to the head with surprising consequences

2009-07-08T05:41:00.000-07:00

A 42 year old female was in good health until she took an Ambien one night to help with some insomnia. Apparently she got up during sleep (sleep walking), went into the kitchen, and began to cook a meal. She then proceeded to fall down and bang her head. She presented to my office with a headache, some dizziness and severe pain and swelling in her lower extremities. Her calf muscles were extremely swollen and tender. I was concerned that she might have a subdural hematoma ( a clot in the skull) or rhabdomyolysis, a condition of muscle breakdown after injury which can lead to kidney failure. I sent her to the ER for a work up. The results were negative.

She came back in a day later. Her calf muscles were increasingly tight, swollen and painful. I was worried about a DVT (a blood clot). I sent her for a duplex (ultrasound) study to exclude this. It was negative. The pain was increasing in intensity. Narcotics, at a fairly high dose were needed to control the pain. The Percocet was not working; she returned with tears streaming down her face. She did not have myositis--inflammation of the muscles because the muscle enzyme CPK or CK was normal. Did she has some sort of myopathy? I ran some blood tests for an autoimmune disease. Oddly, her rheumatoid factor was elevated at 285. New symptoms appeared: there was now a tremor of her arms. I started a tapering dose of steroids. It was of no help.

A neurological exam was performed. Deep tendon reflexes were absent across the board. Pin prick sensation was decreased in a stocking/glove pattern affecting all limbs. Vibratory sensation was minimal in the feet. A tick borne disease panel was ordered.

The results: Lyme ELISA IgM 0.91--equivocal range, Lyme WB 41 IgM and IgG bands, Babesia WA1 antibody elevated 1:256, C6 peptide 0.2, CD57 63. Did she in fact have tick borne illness? Had trauma activated a latent tick borne infection leading to an autoimmune syndrome with progressive symptoms in a previously well individual? That was my thinking.

And her symptoms were progressive--rapidly. She developed uncontrolled rhythmic seizure like jerking of her arms. This was associated with uncontrolled vocalizations typical of Tourettes syndrome. The pain and muscle swelling continued to be severe and difficult to manage. She developed night sweats. None of these symptoms existed prior to her traumatic injury.

Treatment for Lyme and Babesia with typical antimicrobials over a 2 month period has been successful. The neuro symptoms--the seizures and Tourettes resolved. The pain and swelling has lessened. She is now returning to work half time, a feat which would have been unimaginable a few weeks ago.

This is the clinical vingette.

These are my thoughts--conjectures.

There are a large number of patients who harbor Lyme (Bb) and its associated co-infections without clinical illness. These parasitic entities are contained by the host and its immune system.
The healthy state can be quite tenuous. Many things can unleash the ticking bomb: intercurrent infection, stress or even physical trauma.

The percent of individuals in endemic areas who are assymptomatic carriers of TBD may be much higher than suspected, given my suspicion that the vast majority of infected individuals exhibit no symptoms of disease.

A positive Lyme ELISA test should not be discounted when the second tier--the Western Blot is negative. Any positive result for Lyme: ELISA, Western Blot or C6 peptide should be considered as potential evidence of the disease.

Positive tests for Babesia WA1 or Babesia duncani have become extremely common, much more so than B. microti. There has to date been no acknowledgement of this change in distribution of this parasite from the west coast to the east coast by health departments.

There are better sleeping medications than Ambien.

Lyme disease and female hysteria

2009-06-19T12:11:00.000-07:00

I offer this piece after reading only the abstract of a recently published article. There may be inaccuracies because I have not read the entire piece. Feel free to post corrections.

A syllogism is a form of logical thinking which I learned about in college. Syllogisms are frequently twisted into false logic causing spurious or misleading conclusions. To say( 1) more women have Lyme disease(which is vague) then (2)more women also have depression(which is also vague) THEREFORE women who have Lyme disease likely have depression- is like saying: fire hydrants are red: you are red: therefore you are likely a fire hydrant. This is the sort of logic evinced in a recent article published by prominent anti-Lyme IDSA figures in the Journal of Women's Health. I can understand why women take umbrage with these remarks.

Not only is the logic false, but the implications are insulting to many health care professionals and professional health care organizations. If "Chronic Lyme disease" is a vaguely defined term that has been applied to patients with prolonged subjective symptoms..." The same cannot be said for fibromyalgia, chronic fatigue or depression.

Fibromyalgia is not vague. It is a syndrome which has been clearly described by the American Association of Rheumatology. It is defined by very specific symptoms combined with very specific physical findings. Chronic fatigue syndrome is not vague. It has been very clearly defined. This definition can be viewed in CDC published literature. Depression is certainly not vague. The psychiatric community has meticulously defined this disorder, and its subtypes, in a book called the DMS4.

There are clear cultural differences between men and women. Men are infrequent users of the health care system. Men are less likely to complain of symptoms. Culturally men are taught to be stoic, to not complain and ignore symptoms until they are very advanced.

Their are indeed biological differences between men and women as well. Women are twice as like to suffer with autoimmune diseases as men. Most physicians who treat chronic Lyme disease are well aware of the strong autoimmune component of Lyme disease. Women also live longer than men and are less likely to succumb to severe infectious illnesses. These differences are real.

Are diseases like depression really more common amongst women? We know that women are more likely to seek professional help for depression. MEN ARE FOUR TIMES MORE LIKELY TO SUCCESSFULLY COMMIT SUICIDE. Which gender is more depressed? Men are more likely to suffer with alcoholism, drug addiction and commit acts of violence. These are well known surrogates of depression and other mental illnesses.

The word "hysteria" is derived from an ancient Greek medical concept. It was a female disease related to a disturbance of the uterus. Hysteria has become synonymous with the terms "psychosomatic" and "psychogenic." Sadly, many physicians today are still influenced by this ancient, unwarranted prejudice.

One might conclude that the authors have lumped together these so called female predominant disorders because the underlying beliefs of the authors, like many others in the medical community, is that these "new age" illness are a phony-psychosomatic- manifestation of hysteria- as described by the ancient Greeks.

Why conclude that so called chronic Lyme patients have been misdiagnosed and really have these other syndromes? What evidence is there to back up this conclusion? Perhaps it is the other way around. Typically, chronic Lyme patients do not neatly fit into the syndromes of fibromyalgia or chronic fatigue syndrome. Unfortunately may cynical physicians, who fail to accept the reality of these illness, have used these clinical disorders as a "waste basket" for Lyme patients when in fact no clear diagnosis has been established--at least according to their paradigm.

This sort of thinking seems dismissive and anachronistic with regard to the suffering of so many chronic Lyme sufferers. And as stated at the outset, the logical argument marshaled here is questionable at the very least.

One has to question the motives of the authors: Are they trying to promote a scientific understanding of a disease or are they publishing pabulum in an effort to promote their pre-existing, crumbling paradigm?

I think its time for a change. Don't you?

The accidental patient

2009-06-15T11:43:00.001-07:00

I just saw a 32 year old female. This is the patient that I dread to see. She saw my associate for a routine physical. My associate does not treat Lyme disease. The patient complained of severe brain fog, memory loss, inattention and confusion. These alarming symptoms had been increasing over a period of several years. She even told my associate that she felt like she was developing Alzheimer's disease--at age 32. My associate ordered a few lab tests; she threw in a Lyme WB. The results: IgG 41 and 39 bands present. This meets the IgeneX criteria for a positive Lyme test. According to IgeneX the presence of these two bands indicates Lyme exposure with specificity of 96%. Of course IgeneX is looking at their own assay; there is no real basis for transposing this data to WBs obtained elsewhere, even though his may seem logical.The patient researched her symptoms on the Internet. Lyme disease frequently popped up on her browser. She is confused. Does she have Lyme disease? If so, how is it treated. Internet sources inform her that treatment ranges from 28 days to lifelong. How is a medical consumer to make sense of this and other contradiction? Throw more in the mix: She is trying to get pregnant, now what? Can Lyme be passed to the fetus? She has read this on line. On the other hand, aren't antibiotics dangerous to a developing fetus and just dangerous in general.

My exam showed peripheral neuropathy: nothing else concrete.

Cognitive problems are difficult to prove. For the most part the patient's subjective report of symptoms is all you really have to go on. Neuro-psychological testing can be ordered but these tests are nearly impossible to interpret without a before and after. By the time patients present we only have the "after." The tests are expensive, time consuming and rarely covered by insurance companies. What then?

A brain MRI and brain SPECT scan are good starting point. They may be normal or abnormal.
If the brain MRI shows white matter changes a neurologist might to chalk it up to migraine , early MS or vasculitis. A rheumatologist will likely concur: vasculitis. A psychiatrist might suggest depression.

Further Lyme WBs may be positive or negative. Co-infection testing may be positive or negative. From the perspective of other physicians I have found that little credence is given to these results even when they are positive.

This young woman with very troubling symptoms showed up on my schedule for 15 minutes to review "lab results." If not for the 39 band on a WB she probably would never have seen me.
It became my job to introduce her to a medical parallel universe, within the allotted time.

Being an "LLMD," if that is what I am- can sometimes feel like a curse. Ignorance is bliss. But I became a doctor to help people- that is who I am- that is what I do.

How do this tell this young woman that she is lucky she came to see me on this day?- it sounds arrogant, even to me. She may see countless other physicians who will conclude that she definitely does not have Lyme disease. As an "erstwhile" neurologists friend once quipped: "Why is it that you know something that no one else knows?" Why indeed.

I am amongst the very few that believe in chronic Lyme or for that matter the existence of neuroborreliosis it seems. I get no support from local colleagues or local medical institutions held in high esteem who believe my views are incorrect and misguided. Furthermore, they point to the dangers of long term antibiotic therapy for a non-existent illness.

I have but 15 minutes to inform and instruct her. All I can do is order the tests outlined below and give her a lot of reading material. I can ask her to watch Under Our Skin--which my patients tell me is now difficult to find. I direct her to "Cure Unknown" and the ILADS website.
My blog is not a good starting point. It is generally only helpful for those already steeped in the Lyme debacle.

I do not know if she will follow through with any of my recommendations. Lyme patient's with cognitive deficits have trouble reading and processing to start with.

And then there is the problem with family members. They dismiss the diagnosis of Lyme disease and frequently ridicule it. It doesn't exist. They disparage the treating doctor(s) and offer no validation of the patient's suffering or pain. This may lead to depression and feelings of alienation and hopelessness. The high fees charged by many physicians further reduces their credibility in the minds of many.

No this is not the patient I want to see. Not today. Perhaps selfishly I would rather see the patient who has already seen 40 other doctors, those who know more about the nuances of Lyme than I do. If I charged high fees the uninitiated would be weeded out: life would be so much easier.

Treating such patients(the one described here) is a risky business. It is not insurance companies who have "turned me in," contrary to public belief. No, it is my colleagues, members of the IDSA, who have been anxious to report me to the Medical Board.

The anger which I once had is gone. It is pointless and emotionally draining. As the smoke has cleared I am overcome with a new found sense of humility. After all- who I am really- a lone voice shouting into an empty wind only to hear the echo of my own voice.

I put myself into the patient's shoes. How can this one doctor have special knowledge about my illness? It admittedly does not meet the sniff test. She may ultimately see an assortment of specialist who may politely or not so politely tell her that I am a quack- or just wrong at best. Although it is not Lyme disease, no diagnosis will be found. Perhaps years later she will come back with a progressive, mustisystem illness- perhaps with an infected child. Or maybe, after looking into the matter she will decide to return for me to treat her. Time will tell. I cannot control the decisions of others. I can only control my own decisions.

I have no confidence that the IDSA "review" of its guidelines will bring us any closer to the truth.
The public debate in DC is set to occur this July. ILADS is armed with great speakers and a plethora of facts and published scientific studies. But ultimately the IDSA will be passing judgment on itself. How can the accused party fairly judge itself? This runs contrary to human nature.

The light of truth will eventually shine on this national disgrace known as Lyme disease. How long this will take? Nobody knows. We do our best and sail on through the still stormy seas.

I love being a doctor, I always have. Still--some days I wish I were a fisherman, sailing into challenging whimsical ,unpredictable seas-seeking elusive tuna or other prizes.

Perhaps this is what I do after all.

My basic panel of tests ordered for the evaluation of suspected tick borne disease

2009-06-15T05:57:00.000-07:00

The diagnosis of Lyme disease is made on clinical grounds. Nonetheless, these are routine test- I suppose standard tests, ordered for many of my patients suspected of having tick borne illness-
CBC
Chem panel-CMP
Sed rate
CRP
C3a and C4a
B12 and folic acid
Vitamin D: hydroxy 25 and didroxy 1,25
CD57- if covered by insurance
ANA
Rheumatoid factor
Bartonella antibody panel
RPR- HIV and hepatitis screen where appropriate
Babesia antibody panel: microti and WA1- although the name has been changed to duncani, Labcorp and Quest only know it by this name
Ehrilchia antibody panel plus Anaplasmosis
Lyme ELIZA C6 peptide index
Lyme Western Blot: 14IgM and 14 IgG bands- if the patient cannot afford the test I will first obtain the 13 blot test- I still get many positives
Wet mount examination of patient's blood
Only the expanded Lyme Western Blot and the Wet mount need to be performed by specialty labs

If further co-infection testing is required then Babesia species and Bartonella species by PCR may be obtained. A FISH test exists for Babesia- I have not generally ordered this test

Mycoplasm fermentans is a tick borne organism. It can only be demonstrated by PCR. An antibiotic active against Mycoplasm species should be given first to increase yield. Alternatively, a Mycoplasma species PCR may be ordered- this has a higher yield. It may demonstrate the presence of non-tick borne tissue organisms. I do not generally order this test

Another other non tick borne organism which I sometimes test for is Chlamydia pneumonia. This is an antibody test. PCR is also available- but is rarely positive

Fluids such as synovial fluid are tested for Lyme antibodies, C6 peptide index and Lyme PCR

Testing for viruses, such as EBV does not change my therapy- these tests only cause confusion- so I do not order them

Patients with fatigue- nearly everyone, gets a sleep study- sleep disorders are incredibly common in this group of patients

Patients with cognitve issues get brain MRI and SPECT scan

This is my basic set of tests for many patients

Localized Herx: knee

2009-06-15T05:39:00.000-07:00

A patient presented to me with an acute swollen knee. She had been healthy until another physician prescribed a course of Cipro for a urinary tract infection.
She had typical mono-articular arthritis: arthritis of a single joint. The knee was swollen, red an hot with a large effusion. The patient tested positive for Lyme disease and was successfully treated.

This- I think may demonstrate the concept which I alluded to in the response to my last entry. First of all many ostensibly healthy persons are infected with sub-clinical Lyme. Something- many things, can set off the disease. Second, Herxes can be very localized, presenting in a specific area.

Many thinking in this case was that the Lyme organisms were present in the synovial tissues of this patent's knees. Cipro, a quinolone, was able to have exceptional penetration in to these tissues. As a result, this localized Herx occurred in the patient's knee. Post-quinolone treatment relied on less potent antibiotic, which have less penetration into synovial tissues. These tissues are minimally penetrated by most other antibiotics.Therapy with Amoxil and Biaxin, over time, was successful:swelling and arthritis gradually improved.

It is pure conjecture. I simply ask the question: could tendon rupture seen with quinolones represent a similar reaction?

Cipro for Lyme: Back to the future

2009-06-10T06:06:00.000-07:00

A 60 year old female came to my office over one year ago. She had been struggling with fibromyalgia, ulcerative colitis and depression for decades. She provided a multi-page list of symptoms. The highlights were: fatigue, pain, loss of sensations, symptoms related to special senses--hearing-vision, AND rather profound cognitive deficits. She was on a list of nutritional supplements which filled a full page. She had been a highly functional professional in the past. She suspected she might have chronic Lyme disease; this diagnosis had never been made.

She brought sheaves of lab work which was unhelpful. I found her to have an elevated rheumatoid factor-(174)-normal less then 14. Her white blood cell count was minimally depressed, 3.7. Her CD57 was slightly depressed, 50. Special Clongen labs showed positive 39 and 23 Western Blot bands. A wet mount exam showed round extracellular bacteria.

The initial physical exam revealed a fairly profound peripheral neuropathy.

Her treatment was complex; she was prescribed a number of antibiotic combinations.
I will not discuss all the antibiotics she has taken over time, except to say that she was aggressively treated for the known co-infections.

One drug which has been particularly efficacious is Cipro. When this was discontinued she has back-pedaled everytime: symptoms which had improved return.

When I started treating chronic Lyme in a serious way, several years ago, I was sent a paper written by Dr. Jemsek. He described a Lyme regimen in which he used Cipro with Doxycyline. He stated that the two drugs worked via an intracellular mechanism and were synergistic.

After reading this I jumped on the Cipro train. Old data on MICs(minimal inhibitory concentrations), showed that Cipro was reasonably active against Bb.

I used Doxy and Cipro and then began switching to Cipro and Amoxicillin.

Doxycyline works by inhibiting protein synthesis within bacteria. Cipro works by inhibiting DNA gyrase necessary for DNA synthesis. Rather than using two intracellular antibiotics I combined a cell wall inhibitor with an intracellular antibiotic with the belief that this might be more effective. This sort of thinking was espoused by many LLMDS if not this particular combination.

In those days I wasn't giving Bartonella much thought, but it is well known that Cipro has activity against Bartonella.

I had years of experience with Cipro prior to launching into the the waters of Lyme. The tendon rupture issue is much exaggerated in my experience. What I know about Cipro is that it is a very powerful antibiotic. It has been claimed that oral Cipro can provide tissue antibiotic levels rivaling that of IV antibiotics. Cipro is one of the few antibiotics able to cross the prostate/blood barrier. Very high tissue concentrations--in many organs, are achieved with oral doses.

As I look back at charts of patients treated with Cipro I find that many had excellent responses. Then I stopped using Cipro for the most part: it was not an LLMD recommended drug.

As of late I am using the drug more. It provides high tissue concentrations, is active against Bb- and also works for Bartonella-or Bartonella syndrome.

I start low: 250 mg daily-- and then increase to 250mg twice daily. This relatively low dose is frequently effective. Patients are warned about tendon/muscle pain. I generally institute it when these pains have already been controlled by other antibiotics. I have never seen a tendon rupture.

As aside, Cipro is also active against Mycoplasmas and Chlamydia pneumonia.

It works.

The murky world of Western Blots

2009-06-05T16:38:00.000-07:00

Lyme Western Blots can be quite different.
Some labs make their own kits while other labs buy commercially prepared kits.
The "mill labs" Labcorp and Quest simply report whether or not bands are present or not. Other labs grade Blot/band responses.

Specialty labs typically grade bands on a scale of 1 to 4 and may also use the indeterminate designation. These results are manually read by the person performing the test.

The dark line or blot seen on the patient strip (blot) are visually compared to the control strip. The ratings are subjective and may very from one observer to the next.
The human eye unfortunately is not all that reliable.

I recently looked at some blot results with Dr. K. He has used both manual blot and computerized blot technologies.

He offers state of the art computerized WB results.
Here the computer digitizes the the images seen on the Western Blot strip. The computer counts the pixels and compares the intensity of the patient test reaction with that of the control. To my eye, patient bands may appear equal to the control reaction but may be read negative by the computer.

He uses the "Mayo Clinic" methods. Bands are reported as positive only if the pixelated blot/band is 90% of the control. The report indicates a percent reading as it relates to images present on the control strip. For example, an IgG 41 band might be reported as 300%, this means it has 3X as many pixels as the control band as read by the computer software.

This technology which should be more accurate in fact tends to show less positive bands than manual WB results. This is because the human eye tends to see bands as being more intense than perhaps they actually are. We are biased to see positive bands. However-- since WB have always been performed manually one could question the validity of the computer generated reports.

A strip for one of my patient's recently showed a 34 band with a reading of 85%. Although this is 5% less than the Mayo Clinic criteria, it is pretty clear to me that this is a positive band.

When I look at strips I frequently see weak bands at key locations which are reported as negative. This is based on the set-point of the software. Truly "negative" bands(in my opinion) show no reactivity at all- the strip is blank. Any bands which are visible, even if they are a low percent of the control need to be considered, especially when they are present at critical locations. When physicians are presented with the actual strips it provides more information. Information is always a good thing.

IgeneX makes it own kits and interprets the results manually.
Clongen uses commercial kits, which are CDC approved( I don't know if this is good or bad) and offers both manual and computerized interpretations if requested.

The mill labs only report if bands are present. They do not indicate their cut-off points or methodology.

When WBs are sent to three labs at the same time different results are obtained quite frequently.

As you can see the world of Lyme Western Blots is murky like everything else Lyme; so--what else is new?

Interstital Cystitis and Lyme- preliminay report

2009-06-03T06:35:00.000-07:00

I would like to comment briefly about this disorder and its potential relationship to Lyme disease. I have been treating at least one patient who has reported an excellent response to treatment. Willie burdorferf, the microbiologist who discovered the Lyme spirochete reported in 1988 that Borrelia burdorferi, the bacteria which bears his name was found consistently in the urinary bladders of mice.
A great deal of research has supported the notion that Bb widely disseminates into many organs. The co-existence of urinary tract disorders in patients with Lyme disease is well documented. There is evidence that Lyme has been found in stomach, colon and gallbladder biopsy samples. To the best of My knowledge no studies have been undertaken to examine bladder tissue samples for the presence of Lyme. At least one study has demonstrated positive Lyme PCR in genital secretions. This may represent contamination from the urinary tract. PCR tests for genitourinary STDs, Chlamydia and gonorrhea, from urine samples have existed for years(this demonstrates that urine contamination from other sources is frequently present). Positive Lyme PCRs have been obtained from urine specimens. Overall, a body of evidence suggests that Lyme can- may reside in the urinary bladder.

Interstitial cystitis is a fairly common disorder. It occurs more commonly in women. It's name is derived from the minimal pathological changes seen in bladder biopsies.
It is associated with symptoms which at times are crippling. Such symptoms may include: pain in various locations, frequency, pelvic pain, bloating and other related symptoms. IC(interstitial cystitis) patients are thought to have a higher incidence of fibromyalgia and chronic fatigue syndrome.
The standard thinking is that the cause is unknown; although it is said not be due to infection and not respond to antibiotics.

These symptoms overlap with several other disorders: chronic pelvic pain of unknown cause, chronic prostatis or prostatosis in men and chronic urethral or para-urethral syndrome seen in women.

Standard urinary tract infections are caused by bacteria that normally live in the colon. Examples include: E. coli and enterococcus. These are classic gram negative and gram positive bacteria. They can be easily grown in standard culture medium. standard antibiotics only treat gram negative bacteria- such as Bactrim.

Lyme is very difficult to grow in culture media, even by expert hands. And- if it is found only in the bladder wall, such cultures will be useless.
Other L-form bacteria have also been implicated in these syndromes, including: Chlamydia and Mycoplasm species. These too are very difficult to culture.

Physicians typically prescribe antibiotics for 7 to 14 days for urinary tract infections. Experience with Lyme disease shows that short courses of antibiotics are not effective. Only in prostate infections have longer courses of antibiotics been used. Physicians are aware of the prostate-blood barrier and bacterial sequestration within the gland. Antibiotic courses up to 90 days have been used- with some success and frequent relapse.

My patient has established IC. She also tests positive for LD by Western Blot and has a variety of other symptom commonly associated with Lyme disease. She had been miserable for two years with a horrendous quality of life. Experts in IC had been unable to help her.

She has been treated with the usual Lyme antibiotic combinations. The combination of Biaxin with Plaquenil was incredibly effective for the IC symptoms and life altering.

My thoughts are that IC and related conditions are caused by L-form infection of perhaps Bb and other L-form bacteria. Biaxin is not an antibiotic used for urinary tract infections in the typical sense. Minocin has also shown some promise. Cipro has been used for both Lyme and urinary tract infections, but I have noticed a very significant "bladder herx" when patients have been treated with it. Perhaps it can be tolerated later in the course of therapy.

I have seen evidence that IC and related syndromes respond to antibiotics. Long term antibiotics are required- patients need to realized that symptoms will not improve over-night.

Lyme disease should be considered in these patients. This is a work in progress. I cannot claim a lot of experience here. However- my patient has reported that other IC patients, with whom she communicates, have also experienced improvement with the combination of Biaxin and Plaquenil.

Life after Rocephin

2009-06-02T15:08:00.000-07:00

What happens after you stop Rocephin? From the Fallon study we know that all cognitive gains achieved after a 10 week course of Rocephin are quickly lost.
Many patients find themselves in the post-Rocephin boat. I will briefly describe the clinical course of one of those patients whom I saw today for a follow up visit. This 57 year old female in many ways is a typical patient with neuroborreliosis. After an acute illness with Lyme disease 3 years ago she subsequently developed progressive cognitive deficits. She experienced memory loss- both short term and long term, difficulty with concentration, poor attention and slow processing. Along with this she had bouts of confusion and disorientation. I picked her up as a new patient 3 months ago. She had been on 4 months of Rocephin and experienced a terrific clinical response. She was afraid of stopping the Rocephin. She had regained at least 70% of lost cognitive functioning. I told her that she could not stay on Rocephin forever and that in my experience Rocephin gains can be sustained with oral antibiotics once the plug is pulled. To reassure her I also let her know that Rocephin could always be restarted.

Here is my thinking. The primary antibiotic which was so effective, Rocephin or ceftriaxone is a third generation cephalosporin. The oral Lyme medicine which most closely resembles Rocephin- a third generation cephalosporin is Omnicef; so I chose this drug. In my experience Amoxicillin would probably have been equally effective.
To boost the blood concentration, and hopefully the effects of Omnicef, I added Benemid or probenicid. This drugs inhibits renal excretion of penicillins and cephalosporins- increasing the blood/brain concentration. In addition I thought that adding additional-synergistic antibiotics, known to pass the blood brain barrier and improve cognition made sense. So I added Minocin and then Tindamax to the regimen.

Now three months off Rocephin she has continued to improve each month. Her level of cognitive functioning is up to 80 to 90 percent of normal.

There have been no published scientific studies to support these findings. However, my impression at this time is that 1) It may be necessary to use Rocephin for significant cognitive dysfunction and that 2) those improvements can be sustained- if not augmented with the use of appropriate oral antibiotics. The duration of therapy cannot be predicted ahead of time; but an open ended approach makes sense as the patient improves. And beyond this some sort of maintenance therapy may be required.

The Lyme Western Blot revisited

2009-06-01T14:29:00.000-07:00

I get a lot of questions about Western Blot test results: Do I have Lyme?
The disease cannot be diagnosed by a blood test. The Western Blot test is one tool used to demonstrate that a patient has been exposed to Borrelia burdorferi. Period.
Testing for Lyme antibodies is much more complicated than testing for most other germs. Antibodies directed against most bacteria and viruses are determined by ELISA or IFA technology, and that it all that is generally required. The Western Blot was supposed to be a confirmation test used to validate a positive ELISA in the case of Lyme disease. Many of us who treat Lyme have found this to be inaccurate. The only other disease that I am aware of that uses this two tier approach is HIV. Some patients who test positive for HIV by the ELISA method are negative by the Western Blot method. These patients are false positive; they do not have HIV. Some patients who test positive by the WB method are ELISA negative and also do not have HIV. For the HIV test to provide accurate result the ELISA must be done first before the WB.

What is true for HIV testing is not true for Lyme testing. Nonetheless, many physicians cling steadfastly to this incorrect line of thinking.

A test is considered sensitive when it picks up all, or nearly all positive cases. Frequently, tests with high sensitivity also include some false positives. When this occurs the test is considered sensitive but not specific. A test is considered specific when a positive result is very accurate and can be relied upon for a diagnosis.

For many reasons, which have been discussed elsewhere, it has been shown that the current Lyme ELISA test is not sensitive. In other words it has many false negatives. This is why most physicians who treat a lot of Lyme disease skip the ELISA test and go right to the WB test.

It has been well established that seronegative(no antibodies) Lyme disease exists. One could debate how frequently this occurs, but in my experience it is quite frequent. This knowledge influences the interpretation of WB bands as will be discussed.

The spirochete has a lot of targets for antibody production. Areas on a germ which elicit the production of antibodies are called antigens. Antigenic regions on the bacteria are associated with the production of unique antibodies which target that specific antigenic region of the bacteria. In the WB test these are seen as bands which appear on the blot.

What is CDC positive? People are very confused about this. The CDC criteria for evaluating Lyme WB bands was created in 1994. Its purpose was epidemiological surveillance. It was never intended for use as or validated for use as a diagnostic tool. Those of us who look at Western Blots do our best to interpret the results based on our knowledge of what the bands represent. Since many patients are seronegative, the diagnosis of Lyme may be suggested when very few bands appear.

What is the IgeneX criteria? IgeneX has developed internal criteria which it reports as evidence of exposure to Bb. Basically if a patient shows two specific bands(in the same antibody class) the test is reported as positive.

The most commonly seen band is the 41 band. Most consider it sensitive but feel that it lacks specificity. I think the jury is still out on this one. It is not yet clear to me whether or not the presence of only this band can be used as supporting evidence of exposure to Bb. I don't think there are as many false positives as has been suggested by other authors. Both the CDC and IgeneX consider this band to be quite specific.

There are no standardized criteria for a positive Lyme Western Blot. This means that your doctor many interpret the results quite differently from other doctors. This includes LLMDS.

What we do know is that some of the bands are not very specific for Bb. I, like IgeneX tend to discount non-specific bands when viewing a report. When highly specific bands appear it is unlikely that their presence represents anything other than Bb exposure. Based on this thinking, many doctors may feel comfortable concluding that the test for Lyme is positive if few of these specific markers are identified on the WB test.

The very specific bands include: 93(region) 41,39,34,31 and 23. Some authors include the 18 band.

Whereas IgeneX will only call the test positive if the two specific WB bands are found in the same subclass of antibodies, IgG or IgM, this designation seems arbitrary and is of less importance to me. For example, If a patient has an IgG 93 band and IgM 23 band I feel comfortable that the patient result shows evidence of Lyme exposure.

In fact, the presence of a single, highly specific band(with the exception of the 41 band) may be taken as evidence that the patient has been exposed to Bb - a positive result. Again, it must be emphasized that there are no universally agreed upon criteria for the assessment of a positive or negative WB. Doctors who treat Lyme may all interpret these results through the lens of their own beliefs and experience and report differing conclusions.

The question then(at least regarding WB tests) is not doctor, do I have Lyme?
The question is, doctor is my Lyme test positive. First off, patients frequently ask: am I CDC positive. I then have to go through the process of explaining why this is not important. Ultimately I can only present patients with my interpretation of the results. This can end up being a bit unsatisfactory for the patient. Unfortunately, as is the case with most things "Lyme," answers to questions are frequently fuzzy. In the example given above, the 93 IgG and the 23 IgM are present. I would interpret this as positive result. There is no text or standard resource which patients can use to validate my interpretation. Ultimately it may come down to the doctor - patient relationship, and a patients comfort level with their doctor's interpretation. Patients should be aware of these complexities when requesting results from their doctor.

This is where the art of medicine trumps the science of medicine once more.

Knee, Assymptomatic Babesia, Autoimmune neuropathy, Tindamax

2009-05-28T17:26:00.000-07:00

Another young woman came into my office with swollen knees. The first doctor she saw, an IDSA doc had no trouble making the diagnosis since Her Lyme ELIZA was positive and she had 13/13 Lyme Western Blot bands present. The ID doctor presented her with 2 options. She could take a 30 day course of Rocephin or she could go on low dose Doxycyline. It was sort of left up to the patient. One has to ponder how these 2 options are interchangeable. Rocephin, a cell wall inhibitor kills only Bb in the spirochete form. Doxy, a protein synthesis inhibitor kills Lyme in the spirochete and the L-form. It always troubles me that the "experts" are unaware of these basic facts. From my perspective it makes more sense to use two antibiotics which can synergistically attack the spirochete and L-form simultaneously. The patient has acute, active synovitis with swollen, inflamed joints. In chronic Lyme arthritis it has been shown that L-forms in the synovial lining are the problem. In acute Lyme arthritis It appears spirochetes are the culprit since such patients typically respond well to only IV Rocephin. In this case IV Rocephin is a reasonable treatment choice. Oral therapy with something like Amoxil and Doxy is also a reasonable option.(There seems to be some controversy about the combination of Amox and Doxy. They are thought to have an adverse interaction. I do not think this is the case. One can use Amox and Biaxin or Ceftin and Doxy if one prefers). The ID docs, as I am oft told, "don't believe in co-infections." This I do not get. I re-tested her. She was positive for Babesia duncani as well. She has no symptoms of Babesiosis.

After 4 weeks of oral combination antibiotic therapy, she came in today about 50% improved. After weighing the options, we decided to go to IV Rocephin for 30 days. Then I looked at the Babesia issue: She is young. She has no symptoms of systemic Lyme disease. She only has knee involvement. Her immune system may be functioning well, at least her CD57 level is normal. In this case I decided to treat Babesia by standard-text book recommendations. I ordered Mepron and Zithromax for only 21 days. Perhaps her immune system could truly eliminate the Babesia but I thought it would be better to treat-prophlactically. After all, chronic Babesiosis when it does occur can be a beast.

I decided to do a little exam of the nervous system. I continue to find that nearly every patient with Lyme disease has some peripheral neuropathy. As with most patients, there was a little stocking/glove loss of pin-prick sensation and a little decrement in vibratory sensation in the feet.

I am now fairly certain that these findings are due to a Lyme induced autoimmune process. Usually the autoimmune process is minor, but it is something that I have learned to keep a close eye one. It can worsen due to Bb infection but it can also worsen as a result of Lyme therapy. I look carefully for symptoms of progressive numbness, tingling and weakness. I examine for a worsening sensory exam. And when I find that previously existent deep tendon reflexes vanish I am particularly concerned.

When I see an increased in autoimmune neuropathy I quickly back off therapy.

I have wondered if some antibiotics have a tendency to cause more autoimmune reactions than others. This is an observation; I cannot back it up with any data.
I have observed that these reactions seem to occur more frequently when Minocin is used early in the course of therapy. I don' think Doxy does it. It seems less common with Amoxil, Rocephin, Biaxin and Zithromax.

So for what it is worth I now avoid Minocin as a first line agent.
On a final note- I am increasingly impressed with the effectiveness of Tindamax.
For example, when a patient responds rapidly to the combination of Amoxil and Biaxin, adding Tindamax a month or two later frequently makes a huge difference.

Lyme, CHF, Rhabdomyolysis and Crohn's

2009-05-21T15:08:00.000-07:00

A 59 year old female visited me for an evaluation for Lyme disease visited me 9 months ago. She had a past medical history of Crohn's disease and celiac disease. She also had a history of congestive heart failure, resolved, 10 years prior to our first meeting. The cause of the CHF had never been determined. In addition, she had a severe history of muscle disease related to the cholesterol medicine Lipitor 6 years back. The lipitor had caused a severe break down of muscle tissue. The disorder is called rhabdomyolysis; this was associated with acute renal failure which has resolved. She reported a history of prednisone use for 18 months for her bowel disease. A previous physician had diagnosed fibromyalgia. At the time of our visit this once high functioning professional was disabled.

Her complaints included: nausea, fatigue, back and neck pain, blurred vision, diffuse body pains, sensitivity to sound and light, diffuse joint pains, pins and needles, rashes, fatigue, palpitations, sweats and severe cognitive issues. Her cognitive problems included poor focus, slow cognitive processing, short term memory loss, word retrieval problems and bouts of confusion and disorientation.

Her physical exam showed multiple abnormalities involving the nervous system. These included changes in cranial nerves, sensory nerves and upper motor neurons.

Her initial lab tests showed: mild anemia, a Lyme C6 peptide index of 0.27 and a single positive Bb WB band IgG 41. The results were otherwise unremarkable.

The controversies about Lyme disease were discussed with the patient. She was given informed consent. She wanted treatment without any further defining laboratory tests.

She has been on a program of typical oral Lyme medications. These have included: Zithro, Mepron, Amoxil, Minocin, Biaxin, Tindamax and Rifampin.

In her particular case Rifampin has been particularly helpful for reasons that are not clear to me. In general this is consistent with my experience that different antimicrobials work better with individual patients.

To date her improvement has been dramatic. The symptoms which had previously been attributed to Crohn's disease are completely absent. Her muscle and joint pains are nearly gone. She does admit to very slight joint pain at times and sensitivity of her skin. Her energy level is almost normal. All cognitive problems have resolved. The palpitations are gone. The sweats are gone. She is functionally normally and now returning to work in her professional capacity.

Comments: 1) Cardimyopathy- the undiagnosed heart failure could be caused by Lyme carditis. 2) Lyme can cause symptoms of inflammatory bowels disease or cause exacerbations. In this case Lyme therapy has for the time being caused a remission of Crohn's disease. 3) This is the most controversial point: Lyme has been demonstrated to exist in muscle tissues and causes myositis. It has been my observation that some patients who develop muscle pain related to statins(cholesterol medications) can later tolerate the drugs when Lyme has been treated. The reasoning here is that it is the double insult to the muscles of Lyme and the drug that causes the symptoms. When one factor is removed(Lyme) the drug becomes tolerable. Given this patient's history I would never recommend that she try taking this class of medication again. She tolerates Welchol well, which as has been pointed out, also frequently provides benefits to patients treated for Lyme disease.

Wellness, Illness and Lyme

2009-05-14T15:31:00.000-07:00

Wellness and Illness exist on a continuum. We all have a balance sheet of sorts which relates to our status on this scale. On the wellness side we have: favorable genes and environment, happiness, laughter, low stress, good mental health and self esteem, fulfillment of career-relationships-family, positive nutrition, exercise, healthy sexuality, music, dance, intellectual curiosity, reading, writing, hobbies and other things which make us well rounded. A person on this side of the health continuum feels well and energetic, sleeps well and is devoid of pain. (I think you also need a surplus of money and time).

On the other side of the balance sheet we have pretty much the opposite of all these positives. You can go down the list. The negative side of the balance sheet also tends to include many chronic illness and negative factors; some are of our own making and others are just the result of bad luck. These include: unfavorable socioeconomic status, unfortunate genes and environmental factors, smoking, drinking, substance abuse, an abusive diet, migraine or headache disorders, heart disease, diabetes and other endocrine disorders, asthma and allergic disorders, gastrointestinal disorders, autoimmune disorders, pain syndromes, malignant disorders and much more. Those living of this side of the spectrum experience life quite differently. Every day may be a struggle fraught with an array of challenges and discomforts. These folks are in pain. They sleep poorly- have mental health issues, and experience subjective and objective signs of a lack of good health or illness.

There are always unexpected factors and influences, such as illness, accidents or personal tragedy, which can precipitously change one's status. An individual experiencing all the benefits associated with column A can quickly find themselves experiencing a predominant column B status.

Sometimes it appears humans are incredibly resilient while at other times it appears we are delicate and tenuous. Of course most of do not live in either of the extremes of the continuum described. We reside somewhere in the middle of two,(I hope). Those of us closer to the the health side (column A) may at times be be better equipped to handle a new negative challenge than those who resides predominantly in column B. But this is not always the case: Enter the unpredictable world of infectious diseases.

Someone ranking high on the health side, may have a better immune system and fend off a typical case of pneumonia with relative ease. Influenza may be another matter. It turns out that the H1N1 strain of flu, last seen 91 years ago, caused the highest mortality and morbidity in those who would appear to be the healthiest, namely 20 to 40 year olds. In fact it was their excellent health that likely led to the disastrous outcomes. Their perfectly tuned immune responses actually became their Achilles heel. Hyper-responsiveness of the immune system led to an outpouring of pro-inflammatory cytokines. These are the chemical mediators which direct the activity of our immune system. Readers of this BLOG should be familiar with cytokines; these are the molecules responsible for Herxheimer reactions so frequently experienced with Lyme therapy. The overactive responses, called a cytokine storm, could be thought of as a Herx reaction on steroids, and could overwhelm the infected host and lead to organ failure.

Other insults to our health are much less predictable; I am thinking of Lyme disease.

Today I saw a woman who cannot comprehend how Lyme disease could have made her so ill. After all, she has done everything to promote the best possible health. She is committed to exercise, yoga, a vegetarian balanced diet, healthy relations, laughter and all the other positives noted in the column associated with good health. In fact her professional life centers around teaching others these concepts. The germ still prevailed. She has neuroborreliosis associated with significant cognitive deficits. Her brain MRI and SPECT scans confirm this. Against her innate judgment she has accepted the reality of a long and intensive treatment course of antimicrobial therapy.

Health and illness can exist on a balance beam. Sometimes all it takes is one factor, like Lyme disease, to act as the hair that broke the camels back. The weight of that hair varies for each individual.

Spirochete Associated Immune Dysregulation- A new paradigm

2009-05-12T09:31:00.000-07:00

The other day a patient a seemingly simple question: "Doctor, why is my case of Lyme disease so mild." Perhaps the answer to this question can lead us down the path of understanding Lyme disease.

The standard(LLMD)paradigms would suggest that the Lyme disease syndrome is the product of a multi-pathogen state. The co-infections, including Bartonella and Babesia are additional tick borne pathogens which contribute to the character and severity of the illness. But is this right? Perhaps not. What I have seen in very ill patients, consistently, is the presence of other, to date unrecognized "germs," swimming in the blood of such patients, undeterred- in the face of large and prolonged courses of antibiotics. Some of these organisms for example look like Toxoplasmosis. The existence of "Toxo like organisms" has been touched on in medical literature. Others are small gram negative bacteria which resemble Bartonella but are not Bartonella. In fact such "mystery bacteria" resembles hundreds of other bacteria which might stain in the same way. There exists a plethora of bacteria which share a similar morphology; for now, these are unknowns. Are these blood organisms seen in Lyme patients really tick borne pathogens?. Perhaps not. I propose that these anomalous bugs are pre-existing endogenous organisms, normally contained by the host immune system- prior to the onset of the illness- until the genie is let out of the bag.

Before chronic Lyme, or post-Lyme as some like to call it there was chronic fatigue syndrome. CFS became CFIDS: chronic fatigue and immunodeficiency syndrome. It has been pointed out by numerous observers that the two syndromes have much in common. The CDC has defined criteria for the syndrome. It usually starts after a "flu like illness." It has a new onset: it is not lifelong. It is associated with fatigue not relieved with rest. It is associated with: impaired memory or concentration, unrefreshing sleep, muscle pain, joint pain, headaches, sore throat and tender lymph nodes. Many other symptoms may occur as well. It is characterized by impaired immune responses. It is understood to be a "multi-system" disease. Its cause is not understood and it has a poor prognosis. Does this sound familiar?

Let us shift gears to chronic Toxoplasmosis. The seroprevalence of Toxoplasmosis is incredibly high. Most of the world's population is colonized by this parasite and they are ostensibly asymptomatic. It is thought that the "normal" immune system keeps it in check. Numerous symptoms may be associated with chronic Toxo. These include: fever, malaise, swollen lymph glands, eye symptoms and more. In immunocompromised patients, including the population with AIDS, symptoms include: fever, chills, skin rash, brain symptoms, heart and lung symptoms, confusion, headache, tremor, muscle weakness and more.

The existence of immunosuppression is one hall mark of Lyme disease or what is now called tick borne disease. I have repeatedly spoken of the "opportunistic" nature of co-infections. Evidence of immune compromise is regularly seen seen in patient lab studies. Many patients have low white blood cell counts with low neutrophils and increased lymphocytes. Patients may have low levels of natural killer T cells per the CD57 test. Patients have alterations in vitamin D suggesting a shift in helper cell Th1 and Th2 responses. These patients have a compromised immune system. This compromise is specific and limited. It does not lead to the full blown immunological defects seen in certain inherited disorders or acquired disorders like AIDS. It appears this subtlety has made it difficult for skeptics to appreciates its very existence.

Whereas some point to the Lyme spirochete as the culprit which initiates the cascade leading to immune dysfunction, other advocates point to CPN, Mycoplasma, yeast and other agents as the inciting cause. The disease may go by many names including CFIDS and fibromyalgia.

There are common threads. These chronically ill patients suffer with varying degrees of immunosuppression. The syndromes and their attendant symptoms overlap. Previously innocuous germs perhaps become interwoven into the fabric of a systemic, multi-system disease process. These germs may include: CPN, Mycoplasmas, Toxo like organisms, gram negative bacteria- or Bartonella like organisms if you like, yet unspecified "others" and perhaps a host of viruses including EBV, CMV and HHV6. In many cases the Lyme germ, Borrelia burdorferi may also be an innocent bystander, until something tips the immunological balance in favor of the disease process.

There may be an interplay behind the germs and other environmental factors. Certainly non-infectious proteins such as gluten can trigger abnormal immunological responses. Host factors such as exposure to toxins and stress may very well play an important role in some cases.

But this cannot be the whole story. Per the title of this piece, we are dealing with not only immune suppression, but immune dysregulation. Patients with this disease syndrome suffer with immune consequences impacting both sides of the immunological continuum. We have immunosuppression. On the flip side there is immune system over-activation, leading to the myriad of complex autoimmune responses which complicate the course of the illness more often than not.

Lyme and related organisms have clearly been implicated in a wide host of autoimmune syndromes ranging from inflammatory arthritis to MS and CIDP.

The spirochete dysregulates the immune system at both ends of the spectrum simultaneously- a nasty trick. It creates an environment ideal for opportunistic pathogens while at the same time it contributes to the destruction of erstwhile healthy tissues via an autoimmune process.

Perhaps chronic Lyme disease, fibromyalgia, CFIDS and other related disorders could potentially be combined into a new rubric, forming the foundation of an entirely new class of medical disease.

To get back to the patient's question: why are some people ill while others are not? The answer comes down to an understanding how a complex array of variables interact. As always these include genetic and environmental factors. The end result is seen in each patient's unique clinical syndrome.

Lyme Disease While I Stand On One Foot

2009-05-11T14:34:00.000-07:00

A 46 year old female came into my office today looking for help. She was referred by a friend but really didn't know much about Lyme disease. Two years ago she noticed a tick bite behind a knee. Her physician told her to watch the area: no treatment was required unless she developed a bulls eye rash. This never occurred so she received no therapy. Over the months she got sick and sicker with a variety of ailments. She developed gallbladder problems. Removal of the diseased organ did not improve things. She had constant symptoms of diarrhea, bloating and nausea. She developed headaches, vertigo and palpitations. She saw a neurologists- no help; an ENT specialist- no help; a cardiologist- no help. It was finally her gynecologist who suggested that she be tested for Lyme disease. The test was positive(I don't have the results). Her primary doctor prescribed 2 weeks of Doxycyline- should be cured: she wasn't. An infectious disease specialist prescribed "blue pills"(probably Ceftin) for 3-4 weeks with any change. She brow beat the ID specialist after doing a little research of her own, into prescribing Rocephin because she was no better. He reluctantly agreed to prescribe Rocephin for the "magic" 28 days, which was of no help. Enough he said. The ID specialist even consulted with another colleague. Both concurred: she was cured. The ID specialist said that co-infections do not exist. Even if they do- the Doxycyline and Rochephin had already killed everything. She did not have Lyme disease. Her primary physician recommended that she see more specialist at a University hospital. She does not have Lyme disease.

Her current symptoms are: severe fatigue- incapacitating, brain fog with horrible memory loss, sleep problems, headaches, neck pains, shaking, joint pains of knees shoulders and more, muscle pain, palpitations, neck pain, hot flashes and persistent vertigo. Does any of this sound familiar?

Her neurological exam revealed a treasure trove of pathology. She had cranial nerve dysfunction, sensory disturbances, weakness on one side, a positive Babinsky showing upper motor neuron disease a positive Romberg and more.

The question then became: how was a going to tell her everything I needed to tell her about Lyme disease. There is a famous parable from Jewish folklore. A non believer was reported to have asked the famous Rabbi- Rabbi Akiba, to tell him everything about being Jewish while he stood on one foot. The wise sage, as the story goes said: "Treat your fellow man as you yourself would wish to be treated; the rest is commentary, now go learn." So in essence my goal was the same. I needed to tell her everything she needed to know about Lyme disease while she stood on one foot. Unfortunately, I could not be quite as terse as the famous Rabbi.

Here is the outline of how I proceed with such a patient. First she was informed about the raging controversy. Second she was told about the 3 different morphologies of the Bb bacteria and something about its ability to persist in the host after prolonged bouts of antibiotics. The she was informed about the potential for co-infections and the fact that these opportunistic pathogens may play a role in her illness. She further instructed that mysterious co-infections exist in many patients treated for tick borne illness- which is replacing the term Lyme disease. As an aside, just last week, it was announced that a group sequencing the genone of Ixodes scapularis, the tick which carries Lyme disease, uncovered a novel strain of Rickettsia, a relative of Rocky Mountain Spotted Fever.

She was told that the treatment for Lyme and related disorders is frequently long and complex and based on trial and error. Herxheimer reactions are common and may be a good sign.

She was told about the use of laboratory tests and their role in the diagnosis and management of Lyme and tick borne disease. Here is what I order for this patient: CBC, Chem panel, TSH(thyroid test), vitamin B12 and folic acid, vitamin D- 2 forms, CD57, sed rate, CRP, Ehrlichia antibodies, Bartonella antibodies, Babesia microti and WA1 antibodies, ANA, RF, C3a, C3b and a repeat Lyme Western Blot since I do not have the results. All of these tests can be done through the patient's insurance at Labcorp. The purpose for all of these tests was, in a general sense, was explained to the patient as well. The use of specialty labs such as IgeneX and Clongen was also briefly touched on.

Because of cognitive complaints I also order a SPECT scan- she has already had a brain MRI. The reason for this was explained.

Then I explained to the patient why I would not recommend that she see further specialist at this time. I tell her that if she wishes treatment from me I require that she sign an informed consent form. I briefly touch on the politics which have made such forms mandatory.

Normally I await the results of all the tests before a begin therapy I explain to her. But I tell her I am already convinced she has chronic Lyme disease. The history fits. The physical fits. The negative brain MRI fits. The history of a positive Lyme test fits. In her particular case I am comfortable with starting treatment today.

Now I need to explain therapy options to the patient. First of all, I confess I was a little surprised that she had not benefits from the Rocephin, but on the other hand, in many cases clinical improvement is not seen for more than 8 weeks. At this point I recommend going back to oral therapy since the PIC line is no longer in place. Because we are entering the warmer months I avoid Doxycyline. I tell her that I have good success combining antibiotics. I recommend Amoxicillin 3 grams per day plus Biaxin one gram per day. I also recommend two types of probiotics: one is Acidophilus based and other is Saccromyses based. I warn her about potential side effects including: allergic reactions, diarrhea and yeast infections. I ask her to return for follow up in 4 weeks. I explain all of these things in some detail.

She then asks what to expect. Will she better or worse? How long will therapy take? If I don't know can I give an estimate? I then try to field these important and complex questions in the few minutes left in our visit.

Read I say. Become informed. See Under Our Skin. Read Cure Unknown. Visit the ILADS website. Read some of my literature- perhaps part of my blog.(The rest is
commentary).

That's Lyme disease- while you stand on one foot.

I wish it were that easy.

Management of Lyme epi-phenomena: Ischemic colits?

2009-05-08T06:20:00.000-07:00

Frequently, in the management of the very ill patient, with advanced Lyme and tick borne disease, it is the management of the epi-phenomena that become most challenging. Treating the infectious components of the illness can be relatively simple when compared with the management of other, side medical issues, which can require a great deal of caution, thought and general medical experience.

In this post, rather than addressing the complex choices of antimicrobial therapy, I have chosen to discuss therapeutic considerations which do not directly deal with treating infection per say.

I will review some of these issues as seen in one patient. This patient presented with advanced partially treated systemic Lyme disease with neuroborreliosis. She had fared well with previous courses of IV antibiotics which seemed to be indicated at the start. She unexpectedly experienced frank psychosis associated with new auditory hallucinations. This is considered a "psychiatric Herx" by many. The management of Herx reactions in general is quite problematic. The approach of most physicians is to stop the antibiotics for several days and then gradually ramp up the dose. In this case, after a careful discussion with the patient, I decided to instead try a tapering course of oral prednisone. It was not very effective so I went to plan B: a lower dose of antibiotics. I was rapidly able to get back up to speed with the prior dose of antibiotics. Her neuro-psychiatric symptoms stabilized and then improved.

This patient has had a prominent problem with body jerking. It appears unusual and some doctors have diagnosed these seemingly bizarre movements to be "pseudoseizures.," considered psychosomatic. I believe many such patients have atypical myoclonus, a well known form of partial epilepsy. This clinical syndrome varies in degree and presentation in many such patients. The anticonvulsant drug Neurontin was tried and had minimal benefit. I then tried the anticonvulsant and anti-anxiety drug Klonopin; it has been remarkably effective in controlling this manifestation of the illness. This one intervention has been very comforting for this patient.

The patient has had severe blood pressure fluctuations, with extreme high and low readings which her cardiologist has been unable to manage. Her therapy had included a beta blocker and a calcium channel blocker for hypertension, but these were ineffective. I changed her to an angiotensin receptor blocker, Benicar, which is also reputed to have beneficial effects in Lyme patients. These fluctuations in blood pressure are generally thought to be due to "dysautotnomia." This refers to neuropathy which affects the autonomic nervous system. This is comprised of the sympathetic and the parasympathetic systems which control many autonomic, which I think of as automatic, functions in the body, including blood pressure regulation.
This story became more complex as you will see.

The patient was admitted to the hospital with acute abdominal pain and bloody diarrhea. Her work up in the hospital revealed ischemic colitis. This is a relatively uncommon disorder which I have only seen in elderly patients who have blockages and or clots of the arteries which supply blood to the bowel. The treating physicians were baffled by this patient's disease presentation. The patient reported to me that the episode was preceded by a period of very low blood pressure. Hypotension, or low blood pressure, can cause a lack of blood flow or perfusion to vital organs. The regulation of blood flow to the gut is in part controlled by the autonomic nervous system. One can then construct a scenario in which these two factors acting in concert caused the ischemic colitis.

With this resolved, it became apparent that management of her blood pressure was crucial. In this relatively young female with an otherwise healthy cardiovascular system, I felt that the risk of episodes of very high blood pressure was much less than the risk of low blood pressure. I considered the possibility that endocrine dysfunction, especially with respect to adrenal functioning could be contributing to blood pressure dysregulation. This effect has been well documented to occur in very ill LD patients. The adrenal gland makes two hormones which may effect blood pressure. These are cortisol and especially aldosterone. I supplemented the patient with Cortef (cortisol like) and Florinef (aldosterone like). I stopped all previous blood pressure medications. For high BP readings I started Catapres. This is a centrally acting alpha agonist which is quite effective and fairly short lived in effect. This seems to be working. To provide further context- the high BP readings, systolic, have been over 200 and the lows have been down to 80.

For colitis I have also added Asacol, a local bowel anti-inflammatory. Many LD patients have colitis like symptoms. Usually this is manifested by diarrhea, vague gastrointestinal discomfort and bloating. These symptoms frequently disappear with antibiotics, even though one would expect these symptoms to result from antibiotic therapy. Many Lyme patients have microscopic or collagenous colitis diagnosed from colonoscopy biopsies. Clongen reports many positive Lyme PCRs obtained via colon biopsy specimens. I have also added Questran- an interesting agent in this context. It is well know to control diarrhea; it is also associated with the removal of fat soluble toxins filtered through the liver and a reduction in inflammation measured by CRP levels. The addition of this agent appears to have afforded additional benefits. If there was an atherosclerotic component to the ischemic colitis in this patient with moderately elevated cholesterol, it's primary purpose as a cholesterol lowering drug should offer further benefits.

Neuropathic pains, as seen in this patient and many others, frequently improve with anticonvulsants like Neurontin or Tegretol combined with antidepressants like low dose Elavil or Cymbalta, as has been the case with this patient.

Despite all these ups and downs which I have called Lyme related epi-phenomena, this patients overall response to treatment has been dramatically positive.

Hammer and a different nail: Brucellosis??

2009-05-07T14:45:00.000-07:00

In 2005 a 39 year old female developed tingling and weakness of the right leg. She subsequently developed an unusual burning pain of the left flank. Weakness spread to both legs followed by the onset of fatigue. A community neurologist diagnosed MS. She went to NIH for further evaluation. Three lesions were seen in the brain MRI and she was begun on MS therapy with Avonex. Despite therapy the burning sensations persisted and were quite severe and difficult to manage. She went on to develop tachycardia and anxiety. She required treatment with beta blockers, anti-anxiety drugs and analgesics. This was a year into her syndrome. She subsequently developed ringing in the ears(tinnitus). MS flare ups with burning and weakness were treated with IV steroids with some improvement. A Lyme WB showed a 41 band and she was briefly treated with doxycycline with no improvement. Now, nearly 2 years into the illness, she developed cholecystitis. Symptoms of leg weakness, burning and tremors worsened. The brain MRI was stable. The MS therapy was ineffective. Over several months she developed memory loss and increasing fatigue. Courses of IV steroids prescribed by neurologists seemed to exacerbate things. I convinced her to have an evaluation to exclude LD. The WB showed a nonspecific banding pattern and the urine antigen capture test was negative. Over the next year she became more profoundly tired. I thought everything fit with Lyme. I was determined to prove she had Lyme disease. I was unable to do so. Despite negative test results, more antibiotics were tried without much improvement. She progressed to develop diffuse joint pains.

Then she had an episode of profound weakness and went to the hospital ER. A serological test for Brucellosis was positive, but she was told it was a false positive. She developed cranial nerve signs and had persistent, worsening signs of peripheral neuropathy Two years ago I put her on Doxy and Rifampin, therapies for Brucellosis. She then moved out of state and was lost to follow up. Recently she came back to the area. She is still being treated for MS. She recalls that the antibiotics helped but she only took them for several weeks. Now, at age 43, she has weakness, migraines and profound fatigue. She has been hospitalized for MS exacerbations and treated with steroids on several occasions. She has developed progressive neurological impairments typically associated with MS. Her anxiety has increased and she takes tranquilizers at an increased dose.

A Brucella IgM antibody by EIA, obtained a few days ago shows a positive IgM. The IgG is negative.

A quick review of literature shows that the debate regarding chronic Brucellosis has been ongoing for decades, before anyone had heard the words Lyme disease.

It turns out that chronic Brucellosis has been thought to be associated with non specific symptoms including: joint pain, muscle pain, neurological disease and neuro-psychiatric symptoms. Brucella is a small, inracellular gram negative bacteria. Like other such organisms, it has mechanisms for eluding the innate and acquired immune defenses. According to Harrison's textbook of medicine, significant neurological disease requires 6 to 12 months of antibiotics, typically with Rocephin. But of course, the existence of chronic, post treatment Brucellosis is controversial. It is suggested that malingering, obesity and alcohol abuse need to be excluded.

This patient is not native to the US. She grew up in a part of the world where Brucella is known to be endemic.

Sounds a bit like Lyme before Lyme.

Gout , Lyme or Both?

2009-05-05T17:00:00.000-07:00

A middle aged man came into the office with acute pain, swelling, warmth and redness of a knee. He had no other symptoms to suggest chronic Lyme disease. Past experience, as well as all major texts indicated that that gout was the most likely culprit. The patient was treated with typical gout therapy: Indocin and Colchicine. Blood was sent to help sort out the usual suspects which may cause "acute mono-articular arthritis."

His uric acid acid level was quite high- 9.6- definitely compatible with the gout diagnosis. But the diagnosis was a bit messy. His serum Lyme WB by Labcorp showed IgG bands present at the 30 and 41 positions. And then, one week later the patient came back for a follow up visit. The gout therapy had not worked. The knee was a little better but now there was swelling of the great toe, the metatarsal phalangeal joint. This is the classic finding of gout. I aspirated the fluid. I only obtained a few CCs of blood tinged fluid. I sent the fluid for Lyme Western Blots. The results: 6 IgG bands present and 2 IgM bands present.

Now the therapy was converted to antibiotics rather than anti-inflammatory agents.
The patient could be unlucky enough to have both Lyme arthritis and gouty arthritis. The only way to confirm gout is to analyze the joint fluid for the presence of uric acid crystals. Unfortunately this test was not performed.

I could imagine that gout triggered Lyme or the other way around. This is the second case I have seen with the same presentation.

Leg numbness and loss of balance

2009-05-04T13:59:00.000-07:00

A 60 something year old gentleman consulted me for complaints of progressive leg numbness and loss of balance. He lives in a rural, wooded area and was concerned about the possibility of Lyme disease. He was accompanied by his wife who had heard of my interest in tick borne illness. The patient had visited his primary care physician and a neurologist without a diagnosis. His symptoms had been progressive over a period of years. He claimed that he could no longer feel his legs and that he was falling over at times. Perhaps he was a bit weaker as well. He denied any changes in memory or cognitive functioning. He denied any pains. He denied any unusual fatigue.

He looked generally well and high spirited.
His physical exam- neurologically, was quite abnormal.
His mental status was basically normal although at times he struggled to find words.
His cranial nerves were normal. The motor exam was normal. Deep tendon reflexes were diminished. Finger to nose testing was slow and imprecise. His sensory exam was highly abnormal. He had a complete absence of the ability to feel vibration in his feet, knees and hands. He had minimal ability to detect vibration on his elbows. He had a loss of hot and cold discrimination in his lower extremities. He had absent position sense in his feet- he could not discriminate if his big toe was up or down. He passed the Romberg test, but was a bit wobbly. His gait was abnormal- it was broad based with a "bowlegged" appearance.

His exam was not consistent with what I have seen in scores of Lyme patients. I have never seen diminished vibratory sense to that extent. I have never seen a loss of position sense and hot and cold discrimination in my Lyme patients. And his gait was not typical of what I had seen in Lyme patients.

He was not suffering from Lyme disease. In fact I immediately suspected the correct diagnosis. A key to making the diagnosis was a piece of standard medical history which I have omitted until now. I asked him if he drank alcohol- if so how much.
He reported that he drank 6 beers daily along with 6 little cigars. In medical school I was taught, somewhat facetiously, to triple patient reported alcohol consumption. This is a bit of an exaggeration. Nonetheless, it was clear to me that the extensive neurological abnormalities were entirely consistent with long term alcohol abuse. Alcohol can cause injury to the cerebellum causing a loss of balance with a broad based gait. It can cause the severe sensory deficits described due to injury to specific posterior column nerve tracts. There are other causes of these abnormalities but I did not think he had Lyme disease.

A complete neurological workup was ordered, including EMG and NCV. Brain MRI and PET scans were ordered to evaluate brain function and anatomy. Routine lab tests included a test for syphilis and vitamin B1- thiamine- low in alcoholism. The patient reported that he did not know that he was an alcoholic and that previous physicians had not made this diagnosis.

Not everything neurological is Lyme: clearly not. In this case the diagnosis was fairly straightforward. Interestingly, some studies have shown that these neurological deficits can improve with abstinence. We shall see.

Lyme and the Brain: The science and the art

2009-04-28T17:06:00.000-07:00

Lyme and its effects on the brain can be unpredictable and challenging to treat.

This 39 year old female has been treated for chronic CNS TBD for over two years. Her sentinel complaints were Menier's disease and muscle twitches, joint pain and muscle pain. Her cognitive problems had been progressive over a period of several years. When asked, she admitted to significant memory issues, word retrieval problems and episodes of confusion. She began to have difficulties functioning as a high level manager. She was treated with a wide assortment of oral antibiotic combinations. After several months the symptoms associated with Menier's disease dissipated. Unfortunately, a year and one half into therapy she began to experience involuntary movements. Her cognitive deficits were unchanged. My impression was that she was developing a Parkinson's like syndrome. A neurologist found nothing amiss. A course of IV Rocephin was started 18 months into treatment. Her neurocogitve symptoms stubbornly hung on. I considered her treatment resistant. She did improve on many fronts: She has more energy; she no longer sweats; her pains are gone; her muscle twitches are gone; but- she still has muscle stiffness and rigidity. Nonetheless, the very significant cognitive deficits persist. Her exam still shows mild stigmata of a Parkinson's syndrome, but to a much lesser extent.

The MRI and SPECT scan of the brain were normal. Her Lyme WB only seroconverted after months of therapy. Despite an exhaustive search for co-infections by both serology and PCR nothing was uncovered. Her wet mount showed no organisms. She was empirically treated for all potential co-infections with combination antimicrobial therapy. Various symptoms did improve along the way, but not those related to her cognition.

She was recently presented to me a thorough neuropsychological evaluation which she obtained independently.The psychologist found: left hemispheric abnormalities, impaired prose recall, severely impaired verbal list-learning/memory, impaired letter and semantic fluency and frontal-executive dysfunction with attention difficulties. It was suggested that such abnormalities could be due to Lyme disease.

Recently two drugs which in the past caused intolerable CNS Herx responses are now tolerable and seem to be helping. She reports these drugs make her feel human again. I don't really know what this means but it sound like a good thing. These drugs include Minocin and Levaquin. Ritalin just been added because it should improve fronto-executive dysfunction.

Why are these two antibiotics more effective than others? I do not know. One general principal seems to be: If a drug makes you Herx then it must be killing something that has otherwise survived the onslaught of antibiotics. Of course this logic is crude and may be entirely incorrect. Like other physicians who treat these vexing patients I sometimes invent plausible, common sense explanations for observed phenomena.

I do think one should consider the non-antimicrobial effects of antibiotics. In this patient beta-Lactams, Rocephin and oral Amoxil and Omnicef, which ostensibly confer benefits related to gluatmate toxicity showed no demonstrable benefits. OK- she doesn't have gluatmate toxicity?

Does Minocin offer some unique benefit for this patient with its putative effects on nitric oxide and 5-Lipooxygynase? Does Levaquin offer benefits due to immunmodulatory effects pertaining to inflammatory cytokines? Or is it just killing "something" left over. Let me insert that previous courses of the same drugs were not so helpful in the past.

The Parkinson's features of this case have largely resolved. Again, I do not know why. The neurocognive features stubbornly remain despite my dogged efforts to make them better.

Will this patient improve over time? Will brain function gradually return after years of therapy as described by other patients- or will she be left with residual neurological symptoms which can only be treated symptomatically.

These are questions I cannot answer. I am hoping that time will tell.
This is all within the domain art of medicine and far outside the domain of the science of medicine. Hopefully the medical profession as a whole will recognize that much of what is called the practice of medicine will continue to reside within a gray, uncertain and foggy realm for the foreseeable future. While it is incumbent on every physician to "first do no harm," it is also incumbent on physicians to make every effort to heal and help our patients.

Neuroprotection: Let the doctor speak!

2009-04-21T15:03:00.000-07:00

Last night I heard a doctor try to tell Diane Rehm about neuroprotection. She cut him off. I think we should have heard him out.

Again we hear that there is no "evidence" to support chronic Lyme. There is no evidence to support the use of prolonged antibiotic therapy in patients with persistent Lyme related symptoms. Such are the proclamations made by "experts" who have evaluated the results of 3 NIH sponsored studies. These clinical studies sponsored by the NIH have been woefully misinterpreted. At any rate, none of these studies claim that the Lyme organisms have been eradicated or provide any scientific evidence to support this contention.

Then, when naysayers admit that such therapies seem to help patients, they claim it is due to other, non-specific effects of antibiotics.(Let the doctor speak) After all there are no germs to be killed. Based on what science have such experts concluded that there are no germs to be killed? Sounds like a bait and switch tactic to me.

How can the deniers have it both ways? Do the drugs help or don't they?

Beta-Lactam antibiotics may indeed offer neuroprotection. Included here are drugs in the penicillin family and the cephalosporin family. Animal studies have shown that Rocephin has neuroprotective properties in animal models. These drugs upregulate a molecule called GLT1 which in turn inhibits gluatamate. Glutamate is the principal "excitatory" neurotransmitter in the nervous system. Inflammation of the nervous system, both acute and chronic is associated with "glutamine toxicity." It is thought that drugs such as Rocephin may provide clinical benefits for a wide array of neurological disorders. For example,Rocephin has been shown to improve the clinical course of ALS in the mouse model.

Minocyline is reported to have neuroprotective effects due to inhibition of 5-lipoxygenases, a pro-inflammatory enzyme associated with the aging brain.

Antibiotics are reported to have anti-inflammatory properties independent of their germ killing effects. Some medical literature suggests that tetracycalines are inti-inflammatory because they inhibit nitric oxide. Cipro decreases inflammatory cytokines including: TNF-alpha, IL-6 and others. Erythromycins are said to inhibit cytokine production. And so on.

Naysayers, who deny chronic Lyme say patients improve because of these non-specific effects. Does this argument hold any water? NO!

Let us consider the use of Rocephin in a "neuroborreliosis" patient. This individual has an encephalopathy characterized by significant mental status changes. The brain MRI may be normal or abnormal. The SPECT/PET scan may be normal or abnormal. Something has caused a severe acquired brain disorder. If it is not Lyme disease they what else is it pray tell? After treatment with Rocephin the patients improves, perhaps to the point of baseline health. Here is a fantastic medical success story. Why would any physician be unhappy with the result for this patient regardless of one's beliefs?

My suspicion is that the neuroprotective effects may be playing a significant role. The primary effect of the drug however is to combat spirochetes in the brain.

The same arguments can be made down the line. If antibiotics have additional effects which benefit our patients great, what a plus!

None of this information "proves" that chronic Lyme is not real. The points are interesting but are not scientific evidence that chronic Lyme is not real. In fact they are irrelevant distractions from the debate at hand.

We know that chronic, persistent Lyme disease is real. Lyme hides in niches which cannot be accessed by the immune system. Bb binds to proteins in the intracellular matrix such as decorin. Bb can acquire antigen markers from host endothelial cells to camouflage itself. Bb can enter fibroblasts, an intracellular protected niche. Bb can enter immune privileged areas such as the brain where the immune responses are limited. It can morph into intracellular forms which cannot be accessed by the acquired immune responses. In this arena only primitive, innate immune responses are active; it has been established that such responses are unable to sterilize the cells of such organisms. Lyme spirochetes can morph into a cystic form not destroyed by immune responses. Bb can rearrange the structure of surface antigens by recombination with plasmids. All of these assertions are very well documented in peer reviewed literature and texts.

Animal models and human models have both demonstrated the persistence of the organism after large courses of antibiotic therapy in various tissues. This too is well documented in peer reviewed literature.

Patients with chronic Lyme have been shown to have consistent, reproducible clinical syndromes associated with characteristic physical and laboratory findings.

I treat these patient in my office every day, and for the most part they all get better.

Some of sickest patients I have encountered in my now lengthy medical career seem to be caught between the cracks of a dysfunctional medical system, the byproduct of misguided politics, and a stubborn refusal to really consider all the evidence.

Please let the doctor speak.

Lyme literacy is spreading to the psychiatric community

2009-04-20T15:32:00.000-07:00

A 52 year old female came to my office for the first visit one year ago. She had a history of a purplish blotch on her leg which she acquired while horse back riding 5 years ago. She subsequently developed a severe painful neuropathy associated with crippling pain and weakness of her limbs. An evaluation at John's Hopkins was negative. A rheumatologist later diagnosed fibromyalgia. At the time of our first visit she had been on social security disability for several years, mostly for pain. In 2006 a diagnoses of Lyme disease had been made and she received 6 weeks of Rocephin. Any benefits were apparently short lived. Her chief complaint related to our first visit was neurocognitive impairments. She complained of memory loss, anxiety, depression, panic attacks and episodes of frank confusion. She had a normal MRI and SPECT scan. Over the subsequent year she has been on several regiments of oral antibiotics. The treatment has been interrupted at times due to compliance issues. Because of her neurocognitive symptoms I have recommended further courses of IV Rocephin and she has been reluctant. During this period of time she has been followed by pain management specialists and mental health professionals. I am delighted to have in my procession a detailed consultation from a psychiatrist, a consultant who specializes in psychopharmacology. The note reviews her complex history. It outlines the history of all her medications- a long list, and includes the antibiotics she has taken over a period of months including: Omnicef with Benemid, Tindamax, and Minocin.

The consulting psychiatrist notes that CNS Lyme has been inadequately treated. (The history documents more than 9 months of oral antibiotics). He states that the CNS Lyme should be definitively and exhaustively treated. In his experience with a previous patient, improvement only occurred with 3 months of intravenous antibiotic therapy.

I thought the consult was brilliant.
Sometimes it is nice not to be alone.

I have to go home and listen to the Diane Rehm show which aired today.

Lyme and Bartonella: A Tale of Two Herxes

2009-04-15T19:06:00.000-07:00

I recently saw a young woman now in college, with a long and complex history of Lyme and tick borne illness. She had been treated by another physician for 5 years with an arsenal of oral antibiotics. Her lab work in the past revealed positives results of one kind or the other for Lyme, Babesia, Ehrlichia and Bartonella. The oral medications had targeted all of these specific microbes. She had previously refused any IV antibiotics despite her physician's recommendations. She has many disabling symptoms including, muscle and joint pains, weakness and neuropathy and especially cognitive dysfunction. The issue of greatest concern was tick borne encephalopathy, usually called neuroborreliosis. As you will see, there is a reason why I use the former name. Let me interject here- this patient was quite assertive about directing her own care. She was on spring break so she wanted to go through any necessary Herx to correspond with her calendar. For encephalopathy I generalize recommend a course of IV Rocephin over a period of 12 weeks on average. At times I add a second agent, but generally only after the Herx occurs and a stable clinical response has been established over time. This young woman had dark purple stretch marks- striae, on her trunk. She also had classic Bartonellosis which has been rare in my practice.

After starting Rocephin she Herxed for about a week and then really began feeling very well. Her cognitive functions were the best they had been in years. But, as I said, she wanted to push the envelop and get all the Herxing over at one time to accommodate to her time table. The Rocephin Herx occurred two weeks ago so she had only one week of feeling great. I reluctantly agreed to add Zithromax. The insurance would not approve IV Zithromax so it was prescribed by mouth.

The response was rapid, dramatic and not for the better. She took a quick nose dive. The fatigue was severe. The brain fog and memory loss were much worse. She had mild sweats and oddly- the striae had increased in hue and size.

As of this writing she and I am negotiating with my patient how to best handle the situation. She wants to let the Herx rage while I am inclined to back off the Zithromax for the time being.

The point of interest to me is that in this patient, with seropositive Bartonella and the classic striae as described in the literature, experienced a dramatic Herx with Zithromax. This may be evidence that classic Bartonella does in fact respond very well to Zithromax. This may lend further credence to the thinking that those co-infection syndromes which respond only to quinolones, Zithromax with Bactrim, or Zithromax with Rifampin may not be closely related to Bartonella.

In point of fact the "mystery" bacteria seen on wet mounts do not behave like Bartonella species. Bartonella is an intracellular bacteria and should be found predominantly in red blood cells. These other organisms are entirely extracellular.

The question is then, why did treating Bartonella cause such a severe brain Herx. An argument could be made that Baronella had crossed the blood brain barrier and that Bartonella brain infection was a major component in the patient's encephalopathy.

There is a weakness in this argument. The encephalopathy was clearing up very well with only Rocephin. I suspect that a longer course of only Rocephin would have had an excellent clinical result. This suggest that Lyme, not Bartonella was the cause of encephalopathy. The rapid killing of Bartonella may have led to an influx or neurotoxins or inflammatory cytokines which led to the dramatic "brain Herx" or worsening of cognitive symptoms. This seems to make more sense to me.

It may be appropriate to call the clinical scenario tick borne encephalopathy rather than neuroborreliosis, since it is not known if the brain symptoms are due simply to Lyme infection or also due to co-infection.

I am aware that well documented cased of Bartonella infecting brain tissue exist, but they are rare.

The topic is certainly up for debate. I am only sharing my thoughts at this time as I am trying to understand the process as it is unfolding in this patient.

Bartonella like organism first- Lyme second

2009-04-13T14:26:00.000-07:00

This is a follow up on the 20 year old female who saw me in late march. She has been sick for over 14 months. She presented with a bulls eye rash and was treated with Doxy for 4 weeks. Headaches, shaking chills, joint paints and nausea and vomiting. She was told it wasn't Lyme. She managed to convince doctors to prescribe two more courses of Doxy, each prescribed for only 2 weeks with minimal improvements. She limped along for the next 9 months before seeing me. Her presenting complaints included: neck pain with swollen glands, headaches, joint pains, fevers, cognitive dysfunction and severe fatigue. She had become very forgetful and developed a stutter. The pain in her knees, shoulders, hips and neck was severe. She complained of sweats, blotchy rashes, sleep problems, irritability and depression. Her physical exam showed no rash but a grossly abnormal neurological exam. Findings included: upper motor neuron signs, lower motor neuron signs and evidence of a sensory peripheral neuropathy.

Following my usual rule: Lyme first. I prescribed Omnicef, Benemid and Minocin.

Within two weeks she was dramatically better. The Herx had lasted only a few days. She was free of fatigue, headaches, pains and sweats. The majority of her cognitive issues had improved. It was quite remarkable. The fly in the ointment was that she was experiencing intolerable heartburn. The Minocin I thought. I continued the Omnicef, superchared with Benemid and substituted Zithromax for Minocin.

Today, just 2 weeks later, all the gains were gone. Focusing on her chief complaint it was clear that the neck pain and swollen glands were a prominent feature of her syndrome. She was thrilled that she had experienced one great week for the first time in a year, but it was gone as quickly as it came. Now I looked at a new finding on her upper back. There were two small 2 cm red streaks about a scapula.

OK- what's going on?

Clearly blasts of anti-Lyme therapy were not helping. She seemed to have the Bartonella like syndrome described in the playbook of many other notable LLMDS. In this case Lyme was playing only a bit part in the scenario. Her Bartonella serology was negative. A "species" Bartonella PCR would be nice as would a blood wet mount. These tests had not been obtained due to financial constraints. In my mind's eye I could see swarms of tiny gram negative bacteria coursing through her blood and organs wreaking all sorts of havoc. I can't say if these organisms are actually a form of Bartonella or a "mystery bug."

Lyme just doesn't respond that quickly to any antibiotic therapy.The same is true for Babesia and other parasitic diseases. Minocin has exhibited the ability to suppress these small gram negative bacteria in some of my patients but not eliminate them. Other recent clinical experience has shown that Zithromax, which should have activity against Bartonella species, does not work here by itself. BUT, the combination of Zithromax with Bactrim has shown success in suppressing the small gram negative bacteria.

I considered other therapy options: Rifampin and Zithromax or switching to a quinolone- either Cipro or Levaquin; but I decided to try the Bactrim and Zithromax combo.

Several other doctors had told her she did not have Lyme disease (she was Western Blot positive for Bb). Confused by my contorted explanations and our discussion of treatment options, she asked me: "Doctor,do I have Lyme disease?" "Yes." I replied- "you definitely have Lyme disease, I just don't think that Lyme is causing your symptoms right now." "Thank goodness," she responded- "I was afraid I was just crazy."

Wet Mounts

2009-04-07T16:10:00.000-07:00

The analysis of a blood wet mount has become part of the routine evaluation of patients presenting with an evaluation for TBD. Positive results are seen in 70 to 80% of patients. So far we do not know what the organisms are. Many patients have large numbers of small motile bacteria which stain gram negative. Other distinct and separate morphologies are also frequently seen. Some of these organisms are tear drop and crescent shaped and resemble Toxoplasmosis. Others appear as rods. It is important that researches be found who will take these anomalies seriously and help solve these mysteries. According to conventional medical knowledge,It is not normal for us to have bacteria and parasites freely swimming in our blood. Transient bacteremia occurs when we brush our teeth, but the normal immune system quickly eliminates the organisms. The blood should appear as a sterile fluid under normal circumstances. Well known blood borne pathogens such as HIV and Hepatitis C are viruses and cannot be seen with the light microscope.

Perhaps some of these organisms are normal residents of the human body. It is unknown. Perhaps these microbes appear in the blood in large numbers when immune suppression is present as may occur with Lyme disease.

It is not scientific- but my clinical experience indicates that the sickest TBD patients usually have the highest loads of these organisms- AND they usually have mixed morphologies, some resembling bacteria and other resembling parasites. Patients with the protozoa type morphologies are usually the sickest.

Ultimately the identity of these organisms will be disclosed. It is yet to be known how these results will play into the management of patients with tick borne illness- or other illness for that matter. Do these organisms represent a new set of previously unknown tick borne co-infections? Will it be shown that they are normal human flora? Will they be used as a marker of disease activity or will they require specific, targeted therapies? For now I can only offers clinical impressions which may or may not have validity as the science is unraveled.

The amazing thing about this part of the puzzle is that these findings are as clear as the tip of your nose. You don't need sophisticated Western Blot or PCR technology.
There can be no debate whether an adequate course of a particular antibiotic has eradicated a particular blood wet mount organism. These organisms appear right under your eyes.

All you need is a drop of blood and a standard light microscope set at 1000 power.

There are many patients will a complex multi-system disorder associated with Lyme disease and other tick borne infections. Many, if not most of these patients have blood organisms which remain unidentified. These patients as a whole respond to antimicrobial therapy of various sorts. As clinicians we do our best, but we need help.

We need scientists: parasitologists, microbiologists, molecular biologists, experts in DNA sequencing at high powered universities and research centers who have the expertise to solve the riddle. What are these mystery bugs and what role do they play in the course of human disease?