54 year old woman with memory loss

A 54 year old woman came into my office a month ago for a Lyme evaluation. She had a history of tick bite/rash which had been treated with standard therapy three years ago. This history alone raised my antennae to the possibility of chronic Lyme. Her chief complaint was memory loss. She had no other symptoms typically seen in chronic Lyme patients. She described word retrieval difficulties, inattentiveness, brain fog and mild forgetfullnes. These are the typical symptoms described by many Lyme patients. Her neurological exam showed borderline findings, nothing concrete. Nonetheles, the history was compelling and I prescribed a one month course of Doxycycline pending the results of the diagnostic work up. After one month of therapy no Herx reaction or change in symptoms was noted. Her workup was unusually negative. The brain MRI and SPECT scan were normal. A standard Lyme laboratory profile was negative. A Clongen Western blot showed reactivity only at the 41band- both IgM and IgG. Does this patient have Lyme disease?

It seemed that the answer may be no. After contemplation, I decided to give her a diagnostic challenge. I prescribed Amoxicillin 7.5 grams per day, Biaxin 1 gram per day and Flagyl 1 gm per day for up to 15 days. I asked her to return in two weeks to have the Western Blot redone and to have a blood PCR for Lyme drawn. In addition, I told her that she should come in sooner for these tests if/when she has a significant Herxheimer response. I informed her that if the results were still negative and she did not Herx, I would not be able to establish the Lyme diagnosis.

If not Lyme, what is causing the memory issues? Many patients complain of cognitive changes. These were obviously significant enough to lead patients to seek medical attention. A family history of Alzheimer's disease or dementia is frequently reported, obvious causing greater concern to the patients. It is known that early, mild symptoms, over a period of years, can be traced back in patients who develop Alzheimer's disease.

Psychometric evaluations are expensive and probably of little value. They are only helpful if you have a "premorbid"(before illness) baseline. There is a great deal of variability under the bell shaped curve which could still fall into the normal range. High functioning individuals can easily loose 30-40 IQ points and still score normal on the tests. These tests are expensive and generally not covered by insurance. An evaluation by a neurologist will be unhelpful.
The only useful clinical parameter is the patient's description of symptoms.

No- it is not menopause. Many women I see are convinced that it is normal to experience significant cognitive decline after menopause. This is not true.

Are there other treatable causes? Perhaps not. A survey for other infectious diseases may be worthwile. It is possible that bacteria such as Chlamydia species, Mycoplasma species and viruses such as HHV6 may be playing a role. Alzheimer's disease is characterized as a progressive neurodegenerative disorder of unknown cause. It is known to be associated with inflammation and immune system activation.
If Lyme can cause cognitive dysfunction then it makes sense to consider the possibility of other chronic infections can act in the same way. At this point there is no treatment which can prevent Alzheimer's disease or modify its course. Some drugs are being investigated, including Namenda. Widening the paradigm which stems from experience with Lyme disease, could be applied in such cases, as long as patients understand that this is an experimental approach.

I have ommited the point regarding arguments that can be made with regard to an isolated 41band. However, without other typical Lyme feature, making this connection might be skating on very thin ice.

Prostate Herx

I don't know how common this phenomenon is but it is worth mentioning. A chronic Lyme patient was seen by another physician who changed the antibiotic regimen around.
He started him on Cipro. Some weeks later the patient developed severe lower abdominal pain, severe enough to send him to the emergency room. A workup including a CT of the abdomen and pelvis was negative. On questioning he denied urinary or bowel symptoms. He has had a recent colonoscopy which was negative. The exam showed marked tenderness of the suprapubic area (area over the bladder). A rectal exam revealed a tender prostate. Palpation of the prostate re-created his symptoms.

Many men suffer with chronic prostate symptoms. These include difficulty with urination, bladder- groin pain and even low grade fevers. These symptoms can be relapsing and remitting over a period of years and/or decades.(Symptoms related to benign enlargement of the prostate and prostate cancer typically do not have a pattern of spontaneous improvement and exacerbation). Urologists don't know what to do. It is the bane of their existence. Different terms have been used: non bacterial chronic prostatitis, prostatosis, prostadynia and others. An infectious cause is frequently suspected, but none can be found. Patients frequently get better with long term antibiotics and then relapse when the antibiotics are discontinued. Sometimes patients get worse with antibiotics.

Infections within the prostate are believed to be sequestered- hidden. There may be a prostate blood blood barrier. Bacteria may live in biofilm colonies. Bacteria may hide in deep parts of the tissue which have poor blood flow thus limiting access to the immune system cells. These infections seem to never go away. Although no microbe can be isolated by standard microbiology techniques, many believe that the condition is caused by persistent infection with cell wall deficient bacteria. These would include Chlamydia, Mycoplasma and Lyme species.

Antibiotics can cause a severe localized "Herx" as the bacteria are killed and the immune system reacts. This can go on almost indefinitely. The only way to stop it is to discontinue antibiotics; and then try later with lower doses. Drugs with less prostatic activity may need to be used.

The drugs which have perhaps the greatest effect in the prostate are the quinolones, like Cipro.

In this case the treatment was to stop the antibiotics and use anti-inflammatory medicines. Here is a case where I have found an herbal preparation to very beneficial. The herb Saw Palmetto can be very effective in relieving prostate inflammation.

Lyme has been implicated in other mysterious urinary syndromes including interstitial cystitis. I have seen this syndrome improve with Lyme therapy as well.

Welchol, Questran and neurotoxins?

This one is a bit technical. You can skip to the bottom.
Neuroborreliosis the most common and dreaded syndrome I see in patients with disseminated Lyme disease is amongst the most challenging clinical problems seen.
Some mechanisms of CNS dysfunction have been fairly well demonstrated. Bb can cross the blood brain barrier. The pathogens are greeted by local immune cells including: monocytes, macrophages and dendritic cells. An inflammatory reaction medicated by cytokines and chemokines is initiated. Antibody producing B cells appear in the CSF(spinal fluid) in unexpectedly high numbers. The Bb bacteria seem to enter glial cells(supporting cells) rather than brain neurons. A proliferation of killer T cell(clones) has been shown. The damage to nerve cells seems to be due to cytotoxic(cell killing)side effects of this process. Autoimmune processes via the production of autoantibodies and molecular mimicry have been established in animal models. The third purported cause of Lyme/brain disease involves "neurotoxins." From what I can gather, this seems to be a theoretical idea; there is not much science to support it.

The most frequently mentioned neurotoxin is quinolinic acid. High levels of this toxin have been measured in the spinal fluid of patients with various chronic neurological diseases. There is experimental evidence that macrophages incubated with Bb produce quinolinic acid. Scientific evidence, from my review of the literature, does not support the accumulation of quinolinic acid in the brains, spinal fluid or bile of Lyme patients. If such evidence exists please post it here.

The neurotoxin theory, as it relates to bile acid sequestrants is:
Lipid soluble toxins are postulated to be processed through the liver, then end up in bile, which is recirculated. These toxins are then able to egress back into the blood stream, find their way past the blood brain barrier and cause neurological dysfunction. These toxins have not been identified. Bile binding resins remove these toxins causing an improvement in neurolgical dysfunction.

These ideas stem from theories described by Dr. Shoemaker in Maryland. And have been repeated by Dr. Burrascano in his guidelines.

Standing back, the theory seems dubious at the very least.

In my clinical practice I have tried these drugs: they work! How?

It turns out that Welchol lowers CRP- C-reactive protein, a primary marker for inflammation or immune activation. CRP is a circulating protein which initiates the complement cascade. This a major "effector" mechanism of the immune system.

Rather than removing neurotoxins, Welchol may be removing inflammatory byproducts of the immune response to Lyme infection. This dovetails with my observation that this drug frequently reduces not only brain inflammation, but can frequently improve other immune mediated symptoms like joint pain.

Bottom line: Welchol and Questran help. They remove "something" that is bound to bile, or by some other mechanism. They lower inflammation based on studies which show a reduction in CRP.

Food for thought: Statin drugs like Lipitor also lower CRP. This mechanism in the prevention of heart disease may be more important than the cholesterol lowering effect. Some studies have shown that patients on statins have a lower rate of Alzheimer's disease. Anti-inflammatory effect? "Neuroprotective" effect?

Better news. Coffee is the new wonder drug. It lowers the risk of Parkinson's, Alzheimer's, liver disease and more. It apparently reduces brain inflammation.

Are there specific gender responses in Lyme disease?

This is speculative and not based on any study. Symptomatic Lyme disease appears to be more common in women than men. However, when men develop Lyme disease they are frequently sicker and more difficult to treat. Women have a more robust immune response. In fact, autoimmune disorders are about twice as common in women as men. The flip side of the coin is that men are more susceptible to infection. So when men do finally present with Lyme, it may be more severe and more widely disseminated. Women may have significant symptoms far earlier in the course of the disease, due to reactive immune systems, bringing them to treatment much earlier. Many of my quick responders to treatment are women. A confounding issue is that in general, women utilize health care services to a much greater extent than men. Men tend to ignore symptoms until they are pretty far down the road. This is an observation. I wouldn't hang my hat on it. But is an area of speculation worth looking into at some point.

Memory loss and ADD in a 16 year old girl

I have so many great cases. I can't write about as many as I would like. This case is very alarming to me. I will summarize its salient features. Her treatment for purposes of this discussion started at age 15. She had knee pain since age 11 which was getting worse. She had not sought care for the knee pain. At age 11 she came to the office with mono-articular arthritis of one knee. A Lyme test was CDC positive. She was treated with two weeks of Ceftin- and then lost to follow up.(She was treated based on guidelines as they were understood at that time.) Shortly before the first visit now, she noted a bulls eye rash on her leg. It was noted that she had years of fatigue and neuropathy symptoms. An associate in my office had diagnosed "ADHD" two years prior to this visit and prescribed Adderall with a positive result.

Her standard Lyme WB showed 13/13 positive bands. Her C6 peptide antibody was through the roof. She was treated with 4 months of oral antibiotics without improvement; in fact she got worse. She developed a syndrome of numbness of both legs below the knees. (I have seen this exact syndrome on several other occasions.) She was started on IV Rocephin. She stayed on this for only 30 days. It was stopped when I was out of town because of suspected PIC line infection. The numbness resolved quickly. Her memory improved. It only became clear- after the Rocephin, that she had memory problems. Sometimes you only notice something when it is no longer present. The "ADHD" was better as well. She continued to improve, dramatically on oral antibiotics- but then stopped taking everything. She went off antibiotics for about 5 months and was lost to follow up.

When she returned, finally- two months ago, Her forgetfulness had become "terrible." She had lost all of her cognitive gains. A SPECT scan showed hypoperfusion of the left frontal lobe of the cerebral cortex. She now complained of hot flashes- suggesting a possible Babesia co-infection. She was treated for Babesia and Lyme over the ensuing two months. The joint pain was better. The fatigue was a little better. The memory loss- inattention- brain fog were no better. She was/is having academic difficulties.

My plan is oral antibiotics for another month- if the cognitive deficits are not improved IV therapy will be re-instituted.

I would like to comment on the SPECT scan. It shows changes in regional blood flow patterns in the brain. Blood flow may be decreased in areas of the brain which are metabolically inactive due to toxins or other injury. The areas of the brain which show poor perfusion are diseased in a way which causes them to function poorly.

Classically, neuroborreliosis is associated with poor functioning in the frontal lobes. There may also be diffuse involvement of the temporal or parietal lobes.

The abnormality here is seen in her dominant hemisphere. So of course it would cause cognitive difficulties.

What is the finding in ADD? Frontal lobe dysfunction: the same thing. With straight ADD the abnormal scan corrects with the administration of Ritalin or a similar drug. The problem has to do with a lack of dopamine activation of neuronal pathways to the frontal lobes.

It should not be surprising that what is diagnosed as ADD may in fact be neuroborreliosis. Lyme induced "ADD" may also improve with Ritalin. It just doesn't work as well as with traditional ADD. Many "ADD" patients may be able to stop stimulant medications after successful antimicrobial therapy of their Lyme disease.

She should get better. I lectured her and parents about compliance. Aggressive therapy is critical. The consequences of ineffective therapy, long term, would be grave.

Father and Daughter: Pardigms old and new

A patient I saw today:
This was one of my early cases. I was just learning. The daughter saw me first. She was diagnosed with some form of reactive arthritis by a rheumatologist. She had a borderline rheumatoid factor, borderline ANA and a high CRP and sed rate. She was placed on Methotrexate, a commonly used immune/disease modifying drug. Around that time she began seeing me. I demonstrated evidence of chronic infection, either old or active, with Lyme as well as other bacteria. Ongoing infection could be an explanation for her problems. This could imply an alternative approach to her problems might be helpful. The rheumatologist became aware of this. A cough led to a chest X-ray. Surprise. It showed enlargement of hilar lymph nodes in her thorax. The rheumatologist was alarmed. He knew that Methotrexate(MTX) could be associated with Lymphoma- a type of cancer. He also knew that MTX induced lymphoma could regress when the MTX was stopped. The MTX was stopped. A repeat Chest film was normal. He was relieved: another one pulled out of the fire. The ball was in my court. I treated her for Lyme and chronic Salmonella- something I considered more important at that time. She responded poorly. Antibiotics didn't help. I sent her to another LLMD/rheumatologist. The other physician tried her on everything under the sun, including many alternative medical therapies. She also struck out. The new rheumatologist, as a last resort, suggested the patient try Enbrel, another immune modulating drug. After the close call with MTX my patient said no thank you and returned to me.

The father is another story. The same (first rheumatologist) diagnosed him with rheumatoid arthritis. It was atypical. He was in his 60s and it occurred after an acute viral infection. He had high titers against EBV and a dramatic positive WB for Lyme. He was upset when he realized the rheumatologist made the "wrong" diagnosis. Unlike his daughter, he responded beautifully to anti-Lyme treatment and went into a complete remission. He too had a positive rheumatoid factor test and other markers for autoimmune disease.

My impression is that both father and daughter have the same genetic profile. They share an HLA genetic type which put them at risk for infection-activated autoimmune disease. One had responded well to anti-microbial treatment, the other had not.

Let's get back to the daughter. She has a very high CRP, about 45. Her sed rate is in the same range, about 45. She has persistent joint pain and fatigue. She also has radicular pain of the left upper extremity (pinched nerve pain in the neck), but this could be due to a mechanical problem such as a disc, not Lyme disease.
She has no other neurological symptoms or cognitive symptoms, and no other symptoms of note. She had been on three years of antibiotics and other therapies, with no change in her complaints. She has some other low grade, nagging lab abnormalities: low carnitine, low B12. low folate and vitamin D dysregulation. Her RA factor and ANA remain modestly elevated. If I were not a "Lyme doctor" I would say she has a variant of rheumatoid arthritis. The Enbrel seems appropriate- except that it might give her cancer, and she wasn't willing to risk it.

So what to do? I dazzled her with fancy foot work. I explained the molecular mechanisms of autoimmune disease- various theoretical constructs- Th1 and Th2- I was stalling. It was the end of the day.

Sometimes I just don't have a great answer. So I ended up prescribing a novel combination of antibiotics- maybe I'll (she'll) get lucky. Perhaps not. One out of two isn't bad, is it?

I don't get everyone better. But I never quit trying.

Foot pain, menopause, and tick borne disease

You know, I really am a regular family doctor, although most of the patients I see these days have Lyme and/or related disorders. Lyme follows me around- like a bad penny.
A "regular patient," came into to see me. She is a 53 year old woman followed for diabetes and high cholesterol. The chief complaint recorded on her chart was "foot pain." I noted that she actually had joint pain and tenderness of the 2nd metatarsal-phalangeal joint of the left foot. I quickly noted some loss of vibratory sensation in the feet which was not unusual in a diabetic. Diagnosis: foot/joint pain- etiology (cause) unknown. I prescribed an NSAID.

Not another one I thought. I reluctantly sent off some screening lab tests. She didn't have gout or rheumatoid arthritis, of course not. Her C6 peptide index for Bb was 2.34, a definite positive for Lyme disease. I asked her to return. The NSAID helped a bit. I asked a few questions. I got positives. Fatigue- numbness and tingling- brain fog- night sweats- they were all present. The sweats, fatigue and brain fog were chalked up to menopause. Her last menstrual period had been over one year ago.

Many post menopausal women I see think that menopause causes fatigue and brain fog in addition to sweats and hot flashes which can have a distinct "flu like" flavor.

I explained the diagnosis and started Biaxin, Plaquenil and Mepron. I recommended Artemesia, but she did not take this at first.

One month later everything was better except the sweats which had increased. The foot pain, fatigue, numbness and brain fog were completely gone. No, most patients do not respond so quickly.

Please start the Artemisia/Artemesin. She did.

One month later- today- she saw me. An incident at work led to an ER visit. She had a bout of chest pain with a negative cardiac work-up. The sweating was gone. It went away right after she started the Artemesin.

I explained that the chest pain was common in Lyme patients. Same meds: follow up in 8 weeks.

Menopause versus Babesia. Sometimes it is a tough call. If the hormone replacement therapy is not working as expected- sometimes Mepron/Artemesin works wonders.

Easy one

A 64 year old woman visited me two months ago. She is a mushroom picker and has had multiple tick bites. A classic EM rash in 2005 was treated with 3 weeks of Doxycycline.
She complained of generalized pains, joint pains- especially knees and elbows, numbness and tingling, leg cramps, night time chills and sweats which awakened her, weakness, fatigue and short term memory loss. Lab results from IgeneX revealed the following results.
Lyme Western Blot: IgM 34 band and 66 band. IgG 31 band and 41 band. Babesia duncani IgG titer 1:40- considered a borderline positive. She was treated with Biaxin and Plaquenil for one month. A month later she was dramatically improved. The fatigue, pain, tingling, cramping and memory were mostly improved. She reported a minor short lived Herx.

She was placed on: Biaxin and Plaquenil plus- Malarone 2x per day, Artemesisn (which she never took) and Flagyl 250 mg 2x per day.

Four weeks later, yesterday, she was seen again. The fatigue, sweating and chills, joint pain, tingling, cramping, memory loss, and blurred vision (which was mentioned now for the first time) were 100% better. This robust appearing woman was in full remission after two months of therapy. She told me she was "wowed" by the results. I suspect I was much more "wowed than she was!
Incidentally the chills and sweats- attributed to Babesia went away after one week of Malarone.

I decided to continue the same protocol for another two months and then see her back in the office. I am learning: Don't change horses in mid-stream when you are winning the race.
There are many temptations to change the regimen for this reason or that. It takes some discipline to shut my over-active brain off. Thankfully, I closed my pen and put it away. By the way, I told her to skip the Artemesin.

Neuroborreliosis: another case

Reader seem to like case summaries. Here is one I saw today. This 58 year old man first presented to me 13 months ago. He had typical disseminated Lyme disease with neurborreliosis. He had a normal SPECT scan but the brain MR showed white matter disease. The radiology report indicated that the findings were characteristic of Lyme disease. Western Blots were IgG and IgM positive across the board. The C6 peptide antibody test was off the charts. Oral medications over a 7 month period of time produced up and down results with a positive trend. Persistent symptoms nonetheless included: joint pains, brain fog, memory loss, muscle weakness causing him to drop things, cognitive processing delays and even bouts of confusion, headache, dysphagia (trouble swallowing), poor stamina and other symptoms. IV Rocephin was started 5 months ago. At that point his work performance was poor and he was considering disability. He started getting better, slowly at first. Ups and downs with some disorientation marked the first month. After 8 weeks, his insurance cut him off Rocephin despite extensive documentation provided by me. The patient was determined to continue therapy and payed for treatment out of pocket. After 10 weeks, Levaquin was added. He continued to show improvement. He then reported one very good day! After 14 months Flagyl 500mg per day was added. Five weeks ago he reported two fantastic weeks. He was on Rocephin 2gm daily, Levaquin 500mg daily and Flagyl 500mg daily. The Flagyl was increased to 500mg twice daily. I saw him today after more than one year of therapy. He had been on Rocephin for 5 months. He now reported 5 consecutive fantastic weeks. This man who had seriously considered disability was 100% better. Gone were multiple cognitive complaints, pains, neuropathy, weakness decreased stamina and all the other symptoms noted above. He was back- in full clinical remission. Today we stopped the Rocephin and substituted Omnicef, 600mg per day. Follow up in 8 weeks.

Proposed mechanism of Lyme IgM response

The initial immune response to pathogens occurs through innate responses. Macrophages express pattern recognition receptors which distinguish pathogens from host tissue. They recognize microbial components called pathogen-associated molecular patterns. The innate immune system is more specific than previously thought. It shares certain features with the acquired immune response. These include: cytokines, chemokines, complement activation, phagocytic cells- macrophages and neutrophils, natural killer T cells and natural autoantibodies.

Ordinarily the initial innate response transitions into the acquired immune response which involves captured antigen presentation to lymphocytes leading to antibody production. The initial response releases IgM antibodies. A molecular switching causes the production of blocking IgG antibodies. For this process to occur continued immune stimulation via continued antigen presentation is required.

The Lyme bacteria are quickly put on notice shortly after infection due to the vigorous innate immune response. They quickly gear up to avoid immune destruction. Once they become intracellular or cystic, available antigens for presentation to lymphocytes become increasingly scarce. One can imagine that antibody producing antigens are present only long enough for the acquired immune response to initiate IgM production. At the time that IgG switching should occur, antigen loads may be so low that follow through IgG switching does not occur, or occurs very poorly.

If the germs lacked the ability to morph into antigenically invisible forms, as is the case with extracellular germs, then the full complement of IgG antibodies would be produced.

From time to time the spriochetes reappear from the hidden niches. The same process is repeated. There is an IgM response. The spirochetes in this adverse environment go back into hiding and the antibody producing machinery is shut down once again.

Hence, Lyme always looks like a "new infection" because of these atypical IgM only responses. These ideas may be useful as novel strategies for vaccine development are considered.

Plaquenil alone?

A 70 year old male patient was diagnosed with Lyme disease 6 or 7 months ago. He reported a history of tick bite and rash in 2002. He received a short course of antibiotics at that time. When I saw him initially he complained of knee pain and swelling, fatigue, generalized arthralgia (joint pain), numbness and tingling and an irregular heart beat. He was seropositive by Western Blot. He was treated with Amoxil, Biaxin and Plaquenil. After two weeks he reported that the antibiotics were causing nightmares and insomnia. He attributed this to Biaxin. The regimen was changed to Amoxil and Minocin. The knee pain and other symptoms rapidly improved over the next two weeks. Then one week later he complained of confusion and unsteadiness. I diagnosed a "brain Herx." I added Plaquenil back, as well as Welchol, presumptively to remove "neurotoxins." I also reduced the dose of Amoxicillin and Minocin. He continued to improve rapidly once more with a cessation of neurocognitive symptoms. However three weeks later he had a bout of gastroenteritis and the antibiotics were held for a few days. Like many of my patients, he was "lost to follow up" for a couple of months. The patient stopped the Amoxil and Plaquenil and took only Minocin, on his own which he increased back to the full dose, without consulting with me. He returned to my office after a total of 4 months of treatment stating that he was 85% better. I scolding him for non-compliance: it didn't do any good. I added Flagyl only 250mg twice daily. When he returned a month later he told me that the Flagyl had made him "spacey" so he stopped it after a few days. He was feeling close to normal. Call me! I tried him on Zithromax and Plaquenil about 6 weeks ago. I made the change because he was also complaining of sinusitis. It seemed that there may have been problems with Amoxil, Biaxin and other antibiotics. He came back to see me today. He felt perfectly fine: back to normal for the past four weeks. And by the way, he had only taken the Zithromax for a few days because it upset his stomach. Everything was fine he was taking only Plaquenil. To review: Brain symptoms, joint pain, neuropathy symptoms, palpitations and fatigue were gone. He Had been treated for a little more than 6 months. This was the best he had felt in years. So far the symptoms were not returning.

This is not my typical patient. Most actually do what I say; they take medicines as prescribed and return for follow up as instructed. In his defense, his wife had major surgery during this time frame; personal mitigating circumstances interfered with our process.

When patients go into remission it is unlikely that the Lyme bacteria have been eliminated. Let me insert an additional piece of information. This patient had a fairly strong IgG response on the standard Western Blot: 4/10 bands were reactive.

Patients with IgG responses may have some blocking immunity for intact spirochetes.
Per the immunology text book: symptoms related to intracellular infection relate mostly to the immunologic response to the infection- not the presence of the germs in and of themselves.

One could postulate that 1) The patient had a blocking IgG response to keep the spirochetes in check and 2) The immunomodulating effects of Plaquenil were keeping the lid on a potentially toxic T cell response to the intracellular component. The fact that he responded so favorably with primarily Minocin supports the hypothesis that the main issue in his case related to intracellular disease.

It was clear that cystic forms of the bacteria were still present. However, if they converted to spirochetes or L-forms the above two mechanisms would be in place to keep the disease quiescent.

I decided to leave him on just Plaquenil for the time being to see if this would foster a long term clinical remission. Sure, it doesn't follow any standard paradigm. But I can't argue with success.

Lyme disease for dummies: part one

A lot of the information presented about Lyme disease is full of doctor- speak and goes over the head of many patients. When I find myself telling patients about the disease I frequently find ways of making the concepts more easily understood by a lay person. Not only is the jargon confusing, but many or most of the patients already have brain fog; so its not surprising that they leave the office having no idea what I just said. I suspect that many folks are too polite to tell me that I lost them. They just leave the office affably with prescriptions in hand- hoping I know what I am talking about. When I use the word "dummy" in the title, patients reading this should take no offense.

Lyme disease occurs when a bacteria is delivered into your skin by a tiny tick. The ticks are like scavengers and can also carry a host of other germs in addition to Lyme.
Early Lyme infection associated with a rash is usually easy to treat. Most patients don't recall a tick bite or a rash. Most of the patients I see have chronic symptoms which are thought to be due to persistent Lyme infection, frequently, along with other chronic germs.

Lyme, a spirochete named Borrelia burdorferi (Bb) for short, is a very smart germ.
Humans that look like us have been around for more than 100,000 years. Our immune systems are very smart as well, but they haven't evolved much recently. In fact, we have given our immune systems reasons not to evolve. Hundreds of years ago the major cause of death for most humans was infectious disease. Small Pox and the Plague killed many millions. This would drive the process of natural selection to improve the human immune system. But in recent times, with advent of vaccines and antibiotics, there isn't much to motivate our immune systems to improve. Bacteria and other microorganisms, on the other hand can evolve very quickly. They are smaller, simpler and divide very quickly. The biological blueprint DNA, can readily change to adapt to a hostile environment. Natural selection occurs when random gene mutations make the organism more adaptive. Bacteria, like Lyme, are in a continual process of improving their odds of defeating our immune system as biological processes are refined via DNA mutations. The bacteria develop ways to optimize their chances of survival in an otherwise hostile environment.

Germ versus human. Thus far, it has been a race that we cannot yet win.

So their are numerous tricks that these germs have developed to thwart out bodies defenses against them. What about antibiotics. Don't these wonder drugs of the modern era kill all bacteria? Unfortunately, the answer is no. These germs are so smart that they can "out think" our immune systems and still survive in our bodies despite huge doses of antibiotics. (There are some doctors who disagree with this perspective, but I and the patients I treat will attest to its accuracy).

This doesn't mean all is lost. Our bodies are used to many chronic infections which we carry as relatively harmless parasites. There are effective treatments which can control Lyme and its symptoms and frequently cause a "clinical" remission in which all the symptoms go away. A clinical remission is different than a cure. Some bacteria may remain in the body, but hopefully they are no longer troubling you.

Lyme can disseminate throughout your body and cause a huge array of varying symptoms.
This is perhaps why some have called it the great imitator.

Many doctors do not believe in "chronic Lyme disease" because the symptoms seem so vague and non specific. They might argue that it could be anything. While it is true that Lyme disease can be associated with a long laundry list of symptoms, it is my experience that the vast majority of patients have a constellation- a grouping of similar symptoms. It seems that 90% of patients complain of: fatigue, pain of joints muscles or tendons, numbness and tingling- or pins and needles and brain dysfunction such as trouble recalling words or a sense of "brain fog." In my experience, the symptoms of many of the patients I see are very similar. There may be many other symptoms in individual patients that can be built onto the the core symptoms. But generally, if chronic Lyme is the diagnosis, these core symptoms will also be present. If a non typical symptom is the primary complaint, then I look for something else before considering the diagnosis of Lyme disease.

Many claim that the physical examination of Lyme patients is usually negative. I disagree. Almost 100% of Lyme patients have subtle neurological changes which can be discovered with a careful examination.

Laboratory testing is a very complex topic. The conventional test for Lyme is believed by many- myself included, to be very inadequate. The laboratory evaluation of Lyme patients throws out a wide net. It looks for changes in the immune system and other metabolic markers. It checks for other tick borne co-infections. Ultimately a better Lyme test may need to be done by a special lab with out of pocket cost to the patient.

Lyme disease is complex; this is perhaps an understatement. Disease occurs when the patient is sick (not as obvious as you might think). Illness is associated with an imbalance in the factors which ordinarily support good health and well being. Lyme-Bb is a germ. Simply being infected with the germ does not mean you have Lyme disease. Chronic Lyme infection may be carried as a passive parasite. There are many factors which can tip the balance between health and illness. These include genetic factors and environmental factors. Some infected patients will never develop illness and others will only develop illness after a prolonged period of time. Some patients will develop only mild, barely noticeable symptoms, while others will develop a severe, life threatening and/or disabling disease. These thing are not predictable given the current state of the art. There is never any reason to test persons who have no symptoms.

These disease state itself is caused by a multitude of complex factors. The infection itself is one issue. The immune system's response may be another. Lyme infection is a powerful stimulator of immunological responses. These responses can be associated with inflammation that causes tissue damage; and, the immune system can be over-stimulated to produce autoimmunity. Autoimmunity occurs when the body's immune system mistakes its own tissues for foreign undesirable structures such as those associated with germs. This sort of reaction can make Lyme disease much worse and cause or exacerbate a whole genre of disorders called autoimmune diseases.
Many have also postulated that Lyme symptoms also result from toxins that are released in the struggle between the immune responses and germ.

Patients famously get worse when treatment is started. This is called the Herxheimer reaction. Is is thought that the initial killing of the germs causes an exaggerated immune response and that the inflammation associated with this response makes you feel worse for a period of time- after which you start feeling better!

The treatment of Lyme disease can be a long and difficult process. There is no therapy that works for all patients. Frequently responses are judged based on trial and error. Chronic Lyme disease is a new and controversial entity. For complicated political reasons, many physicians today refute that it exists at all.
The understanding about the mechanisms of the disease are in a state of flux and continual revision. Patience, persistence and creativity are essential ingredients in the successful treatment of Lyme and tick borne diseases.

Coenzyme Q10 and Mepron

A lot of theories seem to float around in the land of Lyme and then become woven into the fabric of the paradigm. DON'T TAKE Q10 IF YOU ARE TREATING BABESIA! Is this right?
First of all, does coenzyme Q10 work? Apparently it does. It is even mentioned in lectures at Harvard as possibly effective for a variety of conditions. It's efficacy in heart failure is pretty well established. It works in the mitochondria of the cell. This is the cell's power house which generates ATP- energy- through the KREBS cycle.
It appears to help cells produce more energy. Patients taking the supplement claim they have increased energy and less fatigue. By the same token, creatine- which I previously discounted- of weight lifter fame, may also improve energy by providing a vehicle for storing ATP.

Atovaquone- Mepron and Malarone also appears to work through a mitochondrial mechanism. It interferes with electron transport- the final stage of the KREBS cycle necessary for cellular energy production. This is considered a possible mechanism of action. It does not involve the coenzyme Q10 pathway. And even if it did, it inhibits an enzymatic conversion in the cell. It's effect would be independent of the amount of Q10 present. And furthermore- there is nothing to suggest that oral Q10 supplements would have any way of getting into bacterial mitochondria.

Q10 and Mepron both have effects in the mitochondria of cells. That is all they have in common. They work on different cellular mechanisms. If Q10 is an effective supplement for Lyme symptoms, then there is no scientific rationale for stopping it when anti-Babesia therapy is prescribed.

I know this contradicts advice I have given patients in the past. But not having the time to research every recommendation, I had taken this on faith. I think it was incorrect advice.

Vitamin D redux

Sometimes you do a better job when you don't know what you are doing. As I started treating Lyme disease my mentor told me that vitamin D was low. It should be checked and replaced. I dutifully checked vitamin D OH 25 and found it to be uniformly low. I immediately started new Lyme patients on high dose pulses of vitamin D. In retrospect they all did well with this approach. Then I learned I wasn't supposed to do this. The patients were vitamin D toxic. When I checked vitamin D dihydroxy 1,25- the active form,I found that sure enough, the patients were really vitamin D toxic! Now I told my patients to withhold D and even consider Benicar. This was based on theory- not practice.

What if I was right the first time?

One huge problem with Lyme patients is that they don't make antibodies against the germ. In technical terms there is a poor humoral response.

What have we (I) learned? Lyme is a Th1 disease associated with a shift away from Th2. This describes a helper T lymphocyte response. (If you don't know what that means you can still follow the gist of this blog). The Th2 response is needed to promote antibody production. These Th1 weighted patients need a push in the Th2 direction to gear up the antibody making machinery. Vitamin D helps with this according to my immunology text.

Maybe high/toxic vitamin D levels are a good thing. Maybe they help (in lingo) up- regulate immunological receptors which would increase antibody production, a major thing that is missing in Lyme patients!

Maybe it is particularly useful to give extra D when antibiotics are first prescribed and a Herx occurs. This might be a critical chance to influence ongoing and future production of antibodies directed against Lyme.

All of the above is wild speculation and based on a logical argument which may be filled with flaws. Really the point is we don't know what we are doing with vitamin D; and, how did a theory from a non physician, about a disease other than Lyme disease, become so influential amongst LLMDS and the Lyme community at large?

Rapid Rocephin Relapse

I have been treated a 30 something year old female for disseminated Lyme and neuroborreliosis for over a year. Most symptoms cleared up with oral meds. The cognitive issues stubbornly refused to budge. This patient interestingly also developed a tremor with features of Parkinson's disease. The Rocephin took a while, but after 8 weeks started showing some very positive effects. Memory, brain fog, word retrieval, cognitive processing speed and tremor all improved. Antibiotic therapy was interrupted because of an unrelated medical problem. She did OK for two weeks; during week 3 off Rocephin she experienced a precipitous decline. All the target symptoms mentioned above rapidly returned. She even developed joint pain which had been absent for months. What happened? I am sure this patient is tired of me thinking out loud every time I see her. Where there is no science, I have to logically figure out the process and make therapy decisions based on working hypotheses.

Obviously we restarted the Rocephin right away- but what else, and why?

I had tried Zithro with the Rocephin earlier in the course but after 6 days it was stopped because of side effects (nausea and vomiting- I think).

Why does the disease reactivate so quickly and so aggressively. It is like I whacked a hornet's nest with a baseball bat. As long as I was batting away the hornets stayed in their nest. As soon as I stopped whacking, they came out madder than Hell.

It can't be a Herx reaction. The meds were removed. A reverse Herx? Of course not.
The spriochetes couldn't have grown and spread that quickly. They are very slow replicators- it takes a long time for them to reproduce and invade new tissues.
Is it due to an inflammatory or autoimmune response? Maybe. It is known that Rocephin has some anti-inflammatory neuroprotective effects. Could removing it quickly cause rebound inflammation and/or autoimmunity? Interesting- doesn't pass the sniff test.

Let me put this phenomenon together with something I recently read. Intracellular bacteria cause minimal pathological effects. That's interesting. Perhaps when the Lyme bacteria convert into L-forms and disappear into the cellular cytoplasm they cause less overt disease/symptoms. This is the opposite of what many Lyme experts have claimed, but maybe they are wrong. Many antibiotics like Biaxin and Zithromax can kill Lyme in both the L-forms and the spirochete forms. One thing we know about Rocephin is that it only kills spirochetes forms, leaving L-forms (intracellular) unscathed.

A picture appeared in my mind. I could imagine Rocephin molecules zipping down the blood stream like speeding cars on the Autobahn. Any Lyme (spirochetes) in the way would be wiped off the road instantly. The Lyme germs would have to respond quickly if they were to survive. Quickly they converted into cysts and L-forms and slipped into cells. The Rocephin would clear the blood stream and its surrounding watershed of cell wall possessing spirochete forms. Lyme in its other forms was safe.

Where does this leave us? Autoimmunity? Rocephin doesn't destroy auto-antibodies. Could there be increased inflammation with cytokines and cellular destruction? This could only occur if Rocephin has a very potent immune suppressing effect like a steroid or immunomodulator like an anti TNF drug. There is nothing in the literature to suggest that Rocephin has such properties. If it had a potent immunomodulating effect then benefits after treatment should occur quickly. Usually, the benefits of Rocephin are not seen for several weeks.

Maybe the signs and symptoms associated with Lyme neroborreliosis are mediated almost entirely by intact- motile spirochetes. Rocephin is strictly clearing these forms from body fluids and tissues.

When you take away the Rocephin what happens? The L-forms and cyst forms (metaphorically) duck there heads out from their hiding places. They put a toe in the water to check the temperature. All clear. Party time for spirochetes. It is the rapid release of spirochetes into tissues and fluids which causes the immune response and clinical disease. That is my best hypothesis. Hopefully you followed the logical chain which got me there.

Wasn't there a study showing that Amoxicillin alone controlled symptoms in chronic Lyme? Yes. Perhaps it has always been about the spirochetes after all. The cysts and L-forms were just put there to make it impossible to kill the bastards (pardon my French).

Getting back to the patient. Not having the luxury of time as I put my thought together in this piece I made an executive decision: I started Rocephin and IV Flagyl. The Flagyl should help one mechanism of escape. Before I take her off Rocephin I will have to close the other door as well. If she couldn't take Zithromax, another anti-L-form therapy will be needed. The possibilites include Biaxin, Doxycyline, Minocycline and Cipro.

Inside the Box

Physicians who treat Lyme disease have been accused of ignoring the proved science and working outside the box. I am at a medical conference for a week. I decided to buy a textbook. This behemoth 1500 page book called: Clinical Immunology- Principals and Practice was published this year- 2008. It appears to be the preeminent text on the subject. It was written for specialists in the field. Leafing through the pages of this tome is enough to give one vertigo. It is full of incredible information written in a language all its own, which is certainly intimidating to a non scientist like myself. Despite this, I have tried to make some sense of its relevance to the disease which is the perpetual obsession of this Blog- Lyme disease, of course.

I will attempt to transfer some relevant information to the reader. I have found that some of my prior comments were erroneous. I hope this will correct the record.
For the most part however, I have found validation of the concepts previously presented to a greater extent than I would have anticipated.

The immune system is magical. The book is broken down into chapters. I suspect that it is impossible to take in the breadth of knowledge presented here in a single glance. The immune system is highly complex, evolved and robust system. Nonetheless: "The vertebrate immune system is a product of eons of evolutionary struggle and their much less rapidly reproducing, and hence less adaptable, hosts." (Rich page 3).

Immune cells have pattern recognition receptors (PPRs). Everything in immunology has annoying acronyms which I sometimes think were put there to keep nosy neophytes, like me out of mix. These receptors on immune cells called T cells are necessary so that the immune system can distinguish things that belong (and not attack them), like your own cells, from things that do not belong like bacterial invaders. I have long suspected that some patients seem to have a natural immunity from developing Lyme disease after infection. Chapter 3, page 48 indicates that certain genes which regulate certain TLRs- Toll like receptors- a type of PPR, confer either susceptibility or resistance to Lyme disease. The incidence of these genetic variations is not mentioned.

The literature about Borrelia burdorgferi, the Lyme germ clearly indicates that it has both intracellular and extracellular forms. Chapter 25 deals with the immunology of intracellular bacteria. On pages 390-391 the authors make it very clear that with rare exception- intracellular bacteria cannot be eradicated from the host. The authors state that the intracellular environment provides a protective niche. Such bacteria are of low toxicity. The extent of disease frequently relates to damage caused by the immune response rather than the infection itself. The primary mode of attack involves the innate immune system rather than the acquired immune system.
One immune cell which "eats" foreign bacteria is called the neutrophil. This is a major actor in the immune system. Page 397, the neutrophils are inactive against intracellular germs, because they are inside cells. Nonetheless, the bacteria may enter the short lived neutrophils and use them as a "Trogan horse." The dying neutrophils containing our buddy (Lyme),as an intracellular germ, is "eaten" by a macrophage, which in a resting state has a long life, low antimicrobial activity and provides a good home for such germs. Many such bacteria live in a phagosome, a structure which would ordinary assist in their elimination, but intracellular bacteria may have the ability to escape into the cytoplasm, the main body of the cell, and enjoy a safe nutrient rich environment. These bacteria have also figured a way to transfer directly from cell to cell without venturing into the dangerous waters of the circulating blood stream. (Page 400). While much is understood about the production of protective antibodies against extracellular bacteria, little is known about (T cell) immunity required to protect against intracellular germs. B cells which produce the protective antibodies for extracellular germs have a minor role here due to the bacteria's "lifestyle." Page 403.

Chapter 26 actually deals with the immune response to spirochetes. So I had to buy the book. It does contain significant factual errors but is still a treasure trove of great information.

The Ixodes tick actively participates in the transmission of Lyme to the host. This is one reason why it is unlikely that other vectors, like mosquitoes transmit the infection. The tick secretes a protein (Salp 15) which inactivates host T cells, helper CD4 cells. Bb latches onto the beneficial protein via the Lyme OspC protein (associated with 23 band on WB), as part of an immune avoidance strategy. (Page 418). Lyme- Bb is a very smart germ. It comes with a daunting array of immune defeating weapons. It has 21 plasmids. These are extra pieces of DNA, not integrated into the nucleus of the organism. It's genomic structure (DNA) is able to recombine with the extra pieces of DNA and change it's structure to thwart the immune resposnes. One surface protein, Ops A is present when the spirochete is living in the tick's gut. It apparently is useful for bacterial attachment in this environment. A tick receptor protein TROSPA is involved. This acronym is frequently encountered. It simply stands for tick receptor outer surface protein A. As soon as mammalian blood, like ours is encountered it reduces OspA by ninety fold and produces OspC- the immune system avoiding protein. A neat trick! (Page 411).

Proteins are not the only structures to which antibodies can be formed. Lipids and carbohydrates can also be immunogenic, cause antibody production. Other spirochetes express lippopolysacharides on their surface. Borrelia is the only member of the spirochete family which does not do this. It does not engage Toll like receptor 4. It is not clear how this effects the overall immune response. It's variable responses to TLRs 2 and 4 is mentioned and this seems to have an effect on limiting immunological responses to Bb. (Page 415)

Lyme has mechanisms to evade the complement system which is a main effector mechanism for the destruction of bacteria. (Page 416)

I seem to have gotten the Th1 and Th2 issue somewhat confused. While the Th1 mechanisms is essential in the control of intracellular infection, The Th2 mechanism is essential for the antibody response of B cells and immunoglobulin switching. The shift towards a Th1 response seen with Lyme infection actually results in more inflammation and less antibody production. (Page 417) Is this because the immune system is confused since it is dealing with both an intracellular and an extracellular infection- my own conjecture.


My last comments relates to statements on page 418. Antibodies against OspB (Band 34) can be thwarted by a mutation of this protein which removes a lysine amino acid.
Lyme can attach to intracellular matrix proteins such as decorin to avoid detection by the immune system. Lyme can acquire host antigens- from our cell, to avoid the immune system. And Lyme can constantly change it's surface proteins giving the immune system a run for its money. Finally, one example is given of how Lyme can recombine genomic DNA and plasmid DNA to alter a specific surface protein antigen.

Believe it or not, this blog has omitted 95% of the arcane details of the immunological mechanisms. I have here tried to offer some simplified information.

This information is right off the pages of the most current text in immunology. Ostensibly it is information with which IDSA members should be intimately familiar with.

Inside the box data would seem to provide biological support for the notion that 14 days of antibiotics would frequently be ineffective against Lyme disease. This contradicts "facts" presented in the 2006 IDSA guidelines.

Lyme and a thrombotic Herxheimer reaction?

A new patient came to see me for chronic Lyme disease. The scenario was classic: history of tick bites, positive lab results and typical symptoms. He was in his late 50's. He had no history of thrombotic or cardiovascular disease. Shortly after starting antibiotic therapy he was admitted to a hospital for a myocardial infarction
(heart attack). During this hospital stay he also develop a blood clot in a leg which broke off and lodged in a lung (pulmonary embolism).

He was tested for medical causes of increased blood clotting- hypercoaguable state.
There are many genetic causes. There are also acquired causes. He tested positive for "lupus circulating anticoagulant"- this an acquired cause with genetic predisposition. His hematologist told him he may have lupus.

Lupus is a clinical disorder with a complex of symptoms and findings. He clearly does not have lupus. Circulating lupus anticoagulant is associated with autoimmune disease such as systemic lupus and other similar disorders. Infection is also a potential cause of this clotting disorder. Lyme is associated with increased autoimmunity as well as increased coagulation due to pro-inflammatory cytokine responses.

Generally antibiotics have anti-inflammatory effects. This is not always the case. For example, treatment recommendations for ulcerative colitis- an inflammatory bowel disorder includes the antibiotics Cipro and Flagyl. On the other hand, the use of antibiotics with the other inflammatory bowel disease- Crohn's disease may provoke a flare- (A pro-inflammatory effect?)

These pro-inflammatory and anti-inflammatory effects are hard to predict. There is the issue of timing and a variable impact on even similar autoimmune disorders. There are many influences which may tip the balance of the immune response.

Herxheimer responses are associated with a pro-inflammatory response. It is necessary to rev up the immune system before treatment can be successful.
It is well established that these effects can be quite negative in the short run. They generally cause no permanent impairments. It is the storm before the quiet.

I must entertain the possibility that this patent's heart attack and pulmonary embolism were directly related to an unexpected Herx. An autoimmune process was triggered which increased blood clotting leading to these two events. Thankfully the patient is no worse for the wear.

I would rather chalk it up to a coincidence. Unfortunately (for me), I don't believe in coincidences.

Novel combinations of Lyme medications

It is hard to predict how patients will respond to antibiotic combinations. As I review records of patients that I have treated over several years, I have noted that Doxycyline in combination with Plaquenil had been very effective. I was using this before I became more "Lyme literate" and discovered that Burrascano and Donta claimed that Plaquenil was only effective with macrolides. I saw a patient yesterday who has had chronic Lyme disease. She presented mostly with fatigue, brain fog and muscle/joint pain. She was in the past diagnosed by a rheumatologist with a mixed connective tissue disorder. She had borderline auto-antibody immune indicators-low level RF and ANA. She was treated with prednisone and methotrexate with a poor response. Her condition devolved into what was called fibromyalgia before I began treating her. I have found that quinolones, particularly Cipro can be very effective for fibromyalgia symptoms. In this case I used Cipro in combination with Amoxicillin. She had a good response. She became 60% better. I then added Flagyl. She "loved" Flagyl. She felt much better. She was perhaps 80% better. This process transpired over about 18 months. She would try off antibiotics and relapses would occur.(Other antibiotics were used but this combo was the most effective consistently) Two months ago the Flagyl wasn't working as well. She was back down to the 60% better level. I tried something different: Amoxil- Cipro(250mg twice daily) and Plaquenil. The Flagyl was stopped. She returned for follow up. Plaquenil was magic. For the first time in decades- she was 100% better. Perhaps this relates to her tendency for autoimmune responses. Nonetheless, this is an example of how experimentation with atypical combinations of Lyme agents can pay off.

Chronic Lyme and poor IgG response

Chronic Lyme patients frequenly have a poor antibody response as seen on a Western Blot. Frequently there is a predominance of IgM bands. IgG responses may be sparse or absent. Patients who test positive according to the national CDC surveillance criteria usually do so by meeting the IgM criteria. This is still seen in patients who have had Lyme disease for many years. IgM antibodies are the "quick and dirty" response of B lyphocyte antibody production. These are churned out early after antigen (Lyme protein) presenation to helper T cells. IgM antibodies are not particularly effective. They are larger and do not bind all that well to target antigen proteins. These antibodies may show less specificity and be more like to induce autoimmune reactions due to molecular mimicry. The same B cells or plasma cells that produce IgM antibodies (immunoglobulins) also produce IgG antibodies. A molecular switch is pulled after the initial period of infection. IgM production is shut down. The B cells or plasma cells now kick into gear manufacturing IgG antibodies. These smaller, more precise antibodies bind better to the target proteins. It takes time for the "antibody factory" to gear up and make these preferred antibodies. This is why the Immune system provides this two punch approach to dealing with germs. These (IgG) antibodies are typically associated with immunity to a particular disease. This is for example the response one would expect to see after an effective vaccine.

With this in mind, I have started paying attention to the balance sheet, as it were. I compare the IgM and IgG responses seen in various patients. Patients with a predominat IgG response fare much better in general. For example, I saw a patient yesterday who had presented with severe symptoms of longstanding disseminated Lyme disease about 18 months ago. He responded remarkably well to treatment, despite an advanced age of 76. Therapy was stopped after one year. He experienced a prompt therapeutic response followed by full remission. Six months later he reports
robust health. I glanced at his Western Blot. He had 7 IgG bands and zero IgM bands. His immune responses to Lyme were appropriate. Unfortunately this is the exception not the rule.

Patients with predominant IgM responses generally do not respond nearly as well to therapy. Therapy is required for a much longer period of time. These patients require more creative combination therapies and attention to co-infection.

It is not essentially a host response issue. Patients make normal IgG antibodies when exposed to other infectious diseases. There is something unique about Lyme disease. Somehow it short circuits the switching of IgM and IgG antibodies.

There is a subset of patients whose immune systems apparently go beserk when exposed to Lyme. Dr. Kilani reports Western Blot strips in which the entire strip, IgG and IgM turn black. He suspects these patients may have autoimmune hyper-reactivity. I have no experience to support or confirm this observation. I will keep a look out.

Babesia Herxheimer reactions?

I haven't seen anything written about this phenomenon. When I learned about the Jarish Herxheimer reaction the literature indicated that it was limited to an exclusive club of microbes. It was associated with syphilis, leptospirosis, relapsing fever, rate bite fever, Lyme disease, anthrax and very few other infections. The reaction was related to two things: 1) the infection was disseminated and 2) the germ antigens, released when the germ was killed, caused an exaggerated immunological response associated with an unusually exuberant cytokine response.

Now the term Herxheimer reaction seems to be associated with a whole host of other infections. My clinical experience confirms that when patients are placed on anti-Babesia therapy they experience massive Herxheimer reactions. The sweating increases. Pain and fatigue increase. Even cognitive dysfunction- brain fog and memory loss increases substantially. These reactions can be much more intense than those associated with initial anti-Borrelia (Lyme) therapies.

Let's take a look. We are told that Babesia is associated with specific symptoms. These include: recurrent chills and sweats- the sweats are frequently drenching, neck pain and air hunger. We are told that it is a clinical diagnosis and that lab tests are inaccurate and cannot be relied upon. Babesia is a malaria like parasite, and resides in red blood cells. Malaria is associated with a parasitic infection of the red blood cells associated with hemolysis, rupture of the red blood cells. The afflicted individuals experience sever chills, sweats and fevers and are frequently very ill. It is diagnosed when the parasites are observed in the red cells under the microscope. The blood smears for Babesia are generally negative. We are told it is because the parasites infest a very small percent of red blood cells.

PCR tests, antibody tests and a wide variety of special diagnostic assays searching out confirmation of Babesia are usually negative. There is no evidence of ruptured red blood cells. Occasionally antibodies for a Babesia strain may be present. This indicates exposure to the organism- not active infection. If IgM antibodies are present active infection is more likely. For the most part there is no confirmation whatsoever. The standard wisdom (mainstream medicine) is that Babesia is generally a self limited infection which is cleared by the immune system.

Let me play Devil's advocate. Lyme can cause sweats, flu symptoms, breathing problems and pains of all sorts. The same symptoms frequently clear when only Lyme therapy is given. Is Babesia really present at all? Or is a case of the emperor without any clothes. If we have invisible "Bartonella like organisms," perhaps we should have "Babesia like organisms." or Babesia syndrome associated with Lyme disease. Perhaps the anti-Babesia therapy is really killing a form of Lyme via some unsuspected mechanism. If the Babesia organisms are rare and hard to find then why does killing them cause a Herx reaction? Is there any precedent for the treatment of parasitic (piroplastic) infection associated with a described Herxheimer response?
I believe it is important to question all the assumptions of what has now become the new orthodoxy of Lyme literate dogma.

Let's put this argument aside. When I treat patients for Babesia they do have dramatic Herx reactions. The reactions can be disabling and cause serious setbacks.
Patients may Herx with a single dose of Artemesia or Malarone. Frequently Mepron cannot be tolerated due to excessive Herxing. The dose of anti-Babesia therapy must be gradually ramped up based on individual tolerances. One can start with Artemesia/Artemesin or Malarone/Mepron. When the second agent is added it must be done gradually. The clinical response is that the sweating and associated symptoms increase for a period of time and then gradually wane and disappear. It works.

For now I do believe in chronic, persistent Babesiosis, despite the lack of supporting evidence, as part of the Lyme disease complex; but my mind is open to other possibilities.

Lyme: Zebra or Horse?

A new patient waited in exam room one. I fumbled into the room juggling the new chart and my requisite morning coffee. We introduced ourselves. Her serious demeanor dissolved into an ambivalent, nervous smile as I settled in my chair. She found me through a Lyme forum on the net. Several months of symptoms troubled her. Admittedly the symptoms were not severe, but they had persisted for several months. She had sought answers from her primary doctor, her ENT and a neurologist. No one had an answer. She googled her symptoms and did her cyber research. The same diagnoses kept popping up: Lyme and MS. The neurologist at her behest had ordered a second Lyme test- the definitive one- the Western blot. A phone call reassured her that it DEFINITELY was not Lyme- the test proved this. She wasn't convinced. She found me.

Now I was supposed to settle the matter. Always healthy in the past, this attractive young mother of 4 was now saddled with- dizzy spells, tingling in her fingers, tremors, a loss of balance and mild joint pains. She had no real fatigue or cognitive issues. Nonetheless the symptoms were bothersome. After much research and ambivalent contemplation she made a decision- she sat on the exam table across from me.

As always I asked questions, probing her history and related symptoms. I did my exam, the careful neurological exam which has become the cornerstone of my Lyme disease evaluation. I look for subtleties that would be called "WNL" in most exams. This means within normal limits- As interns we claimed it meant "We Never Look." As usual, I found various abnormalities. There was evidence of: cranial nerve dysfunction, upper motor neuron disease, peripheral neuropathy and a subtle tremor suggesting mild Parkinsonian features. I ordered the usually battery of tests to help confirm the diagnosis I suspected at this point.

She didn't know anything about Lyme she said. In reality she was already steeped in the world of Lyme land, with its own language and complex iconoclastic paradigms.

She asked THE question. "Do I always diagnose Lyme disease in patients like her. Do the labs always point me in that direction?"

She had already been to three doctors. I had spent over 20 years considering all the other diagnoses, the usual suspects, until I wandered down the rabbit hole into Lyme land. Here's the odd twist. As a physician I was taught that one must consider common disorders first when making a diagnosis. If a patient had a cough it was likely due to bronchitis, asthma or pneumonia. It probably wasn't Wegeners granulomatosis. Odd ball diagnosis were called Zebras. This came from the oft told metaphor: If you hear hoof beats in Central Park think Horses- not Zebras.

As far as the rest of the Medical world is concerned the diagnosis of Lyme disease as an explanation for her symptoms would clearly constitute a Zebra. And now, in the new reality I inhabit, any diagnosis other than Lyme (think common first) could only be categorized as a Zebra.

Patient response

There are numerous factors which seem to determine how each patient will respond.
If patients are to improve I believe that doctors need to try different approaches. The one size fits all method works poorly. A 43 year old woman was seen several months ago for a second opinion. She was diagnosed with fibromyalgia and CFS. She had been very physically active. She was a personal trainer. Now she was a wreck. She had typical signs and symptoms of disseminated Lyme and neuroborreliosis. Her SPECT showed left frontal lobe hypo perfusion. The brain MRI was normal. Her exam had neurological abnormalities and her labs confirmed exposure to Lyme. She was treated with Ceftin and Minocin. There was a tolerance issue and a bad Herx. She was given a Medrol dose pack and switched to Biaxin and Plaquenil. After two months she felt even worse. We started IV Rocephin. The pain was improving but the cognitive issues were unaffected. Symptoms of sweating in cycles suggested Babesiosis. Mepron and Artemesin were added(the Biaxin and Plaqueil had never been discontinued). The sweating went away but otherwise she felt worse.She only took this regimen for a month. There was a worsening of cognitive functions- more memory loss, and an increase in neuropathic symptoms and pain. She was then treated with only Rocephin: still not better. IV Zithromax was added- then she started to improve. It was the IV Zithromax that was making a difference. The Rocephin was stopped and she continued to improve. When Flagyl was added she again felt worse. The treatment was changed: IV Zithromax. Just Rifampin was added and she was now really improving. She was tired- but able to work. Her cognitive dysfunction was clearing up. Much of her pain was gone. (I had prescribed Levaquin but she didn't take it after looking up its side effects). I saw her today 5 months into treatment. The hangdog look was gone. She agreed to try the Levaquin. I hope it helps.

She had Lyme with neurocognitive deficits and an abnormal SPECT scan.
The only lab data I will add is that she had a high C6 Lyme peptide index and that her blood smear at Clongen showed motile gram negative coccobacilli.

What have I been treating her for?
Do people really have Herx reactions which go on for months?
If a patient Herxes for more than one month I think it is time to change the treatment. The immunological consequences of a prolonged "Herx" can't be good.
Bacteremic. Yes. With what? Has Fry found the answer before Clongen: We shall see.
Babesia- or an immitator like Toxoplasmosis, as exists in immunosupressed HIV patients? This has been suggested as a possibility.
Is there really Bartonella and or Mycoplasm. We don't know.
Why didn't Rocephin work while Zithromax did?
There are lots of questions and still few answers.
As a clinician all I can do is report my clinical results.
Again, one size does not fit all.

Sexual transmission

A single patient who is CDC positive for Lyme, symptomatic and off antibiotics for four months agreed to have his semen tested. An ultrasensitive culture was performed at Clongen labs. Diptheroids, thought to be a contaminant grew. No Borrelia grew in the culture medium. This is only one case. So far there is no evidence to support the theory that LD is sexually transmitted. Quack watch has criticized "LLMDS" for promoting this notion, well....

DNA fingerprinting has been difficult: Clongen still expects a answer soon? Perhaps next week: we shall see.

Towards a unified perspective

As confusing as Lyme disease is for patients; it is more confusing for me. As I became indoctrinated into the world of "Lyme literacy" it became easy to say/think that all the text books(and doctors) are wrong- Lyme is the cause of all the ill's of the world- why can't you blind doctors see that?. If one finds himself in such a manic state he either needs to take a Xanax, or slow down- take a deep breath, and look again. Are all the rheumatologists and neurologists wrong? Have I lost my mind. Can I be so pompous as to believe that only folks who think like me are right and that everyone else is wrong? (Lets leave infectious disease physicians out for the time being.) There are a "zillion" articles and texts which validate the paradigms they work under. Perhaps a more humble approach is needed. Perhaps everyone is a little right (and a little wrong). The more you are a hammer, the more everything around you takes on characteristics of nails.

At the core is the concept of inflammation. Inflammation is primarily an immunological response. The inflammatory process always begins when a foreign protein is introduced to the body. This is called an antigen. The sentries of the immune system, such as macrophages, sniff out the protein that doesn't belong. This leads to a complex process in which the immune system becomes activated. Without this process we could not survive. Not only does the immune system remove germs: its myriad functions include responding to allergens (proteins to which we have allergic responses) and even removing mutated cells, which if left unchecked could develop into cancer. Without this system we would be doomed. The system cannot be too efficient, it has to be quite selective. It has to recognize normal tissues and leave them undisturbed- we know this is not always the case; it even has to recognize "friendly" bacteria and other microbes, such as those that live in our gut. It has to be an awfully "smart" system.


If the immune system operates normally, things are kept in a state of equilibrium. If it is over activated we can become sick. Many checks and balances are in place- there is a delicate balance required for "normal" health. Sometimes, something very small- like an infection, can disturb the natural order and make us ill. I will confine my remarks to the imbalances caused by small micro-organisms known as bacteria.

When undesirable germs (we are speaking of bacteria here) enter the body the macrophages "gobble" them up. They are processed through the lens of histocompatibility complexes and presented to cells called helper T cell lymphocytes. These T cells somehow "read" the proteins on the surface of these antigens and transmit the information to B cell lymphocytes. These B cells quickly get to work, becoming factory which makes antibodies- special proteins called immunoglobulins, which are able to attach to germs and mark them for destruction. A vigorous response may be needed with alarm bells rung. The B cells can morph into monocytes which are even better antibody (immunoglobulin) factories. Quickly the macrophages and other immune cells crank out other immune system proteins called cytokines, which mobilize the natural immune processes. The cytokines are messenger proteins known as hormones. One can visualize the cytokines as traffic cops frantically directing speeding traffic coming from all directions-performed with pinpoint precision. While this process occurs at "light speed," A complex symphony of players melds into one. The complement system is activated. Special proteins are produced through a complex cascade which also directly attack the offending bacteria. Special proteins are released in very specific ways. Some of these are called: chemokines, bradykin, interleukins, tumor necrosis factor and interferons ( the last three are considered cytokines) and many other molecules. At this time more than 100 distinct cytokines have been discovered. So call "acute phase reactants" are released. These include C-reactive protein of which many of us are familiar. Then granulocytes move in. These are the big guns which gobble up and digest those doomed germs or antigens which have been marked for destruction. In the process granuals are released shedding other inflammatory proteins such as histamine, prostaglandins and leukotriones. The inflammatory process affects many tissues. For example, it affects the lining of the blood vessels, the endothelium, leading to the leaking of fluids (serum) into the surrounding areas. Nitrous oxide is released which promotes an inflammatory response. There is an increase in the clotting pathways of blood proteins. Of course the story is much more complex than this.

Since perhaps millions of pages have been written about the above topic, keep in mind that this represents a vast oversimplification, and that the author is a simple country doctor- trying hard to make sense of a disease many of my colleagues insist does not exist.

How are all these proteins made? They are made in cellular structures called ribosomes of which you have heard much. The ribosomes in our cells, (eucariotic) are quite different from those in bacteria, (procariotic). Antibiotics know which ones to attack. Protein synthesis in each case is directed by RNA, which comes directly from DNA, the blueprint for everything that transpires in our bodies.

Like everything in the universe: the immune system if not infallible. Sometimes mistakes are made.

Let us turn our attention to what rheumatologist know. They actually know quite a lot. They know that variations in histocompatibility complexes, genetically mediated, are associated with various illnesses. These genes have names like: DR and DQ. Small mutations in these genes are associated with differing autoimmune diseases.
Numerous auto-antibodies have been discovered. Theses include rheumatoid factor, ANA, Anti-Sm, Anti-RPN, Anti-Ro, Anti-La and numerous others. These antibodies have special relevance with regard to well characterized rheumatological disorders. Autoimmune disorders are defined based on various clinical and laboratory criteria. There is a great deal of overlap. Symptoms from column A and antibodies from column B are combined in various complex ways to make the diagnosis. Lupus, rheumatoid arthritis and scleroderma constitue only a small fraction of these varied autoimmune disorders. Sometimes these disorders are broken down into those which respond to steroids and those which do not. Rheumatologists and rheumatological literature prominently claims that these disorders are of unknown cause.
Now let us take a look at what rheumatologists have forgotten.

Rheumatic fever is a autoimmune rheumatolgical disorder. It occurs after a Streptoccal infection, usually in the throat (pharyx). It occurs some time after the initial infection. It is an autoimmune disorder because it affects organs which are distant from the site of infection. Typically in affects the skin, the joints, the heart, the kidneys and the brain. Although early treatment generally prevents its occurrence, it can occur despite the lack of signs of ongoing Strep infection (the infections may be considered occult) Recurrent or persistent infection is associated with a relapse of the disease. In some cases indefinite use of antibiotics is recommended to prevent recurrence of the disease.

Another disease associated with Strep infection goes by the name PANDAS. This is an autoimmune disorder affecting the brains of children. It is associated with occult Strep infection. The sufferers have psychiatric symptoms including obsessive compulsive disorder and tics(not ticks). Patients can frequently be taken off psychotropic medication and successfully treated with antibiotics.

Many disorders diagnosed by rheumatologists are called reactive. They follow an infection. The paradigm is that the infection has resolved but that an autoimmune disorder, triggered by the infection remains. Rheumatologic sources point to evidence that continued antibiotic therapy does not influence the outcome. What have they forgotten?

Continued antibiotic therapy does influence the course of rheumatic fever and PANDAS.
Let us consider a little microbiology. Strep is an easy germ to kill. It has no known ability to develop resistance to antibiotics; it replicates quickly and it does not form spores.

How about rheumatoid arthritis? Studies have demonstrated M. fermantans in the synovial fluid of patients with RA. This has been confirmed by 16S rDNA. Viable organisms have also been demonstrated in the synovial tissues. Treatment with antibiotics hasn't helped- or has it. Numerous studies show that Doxycyline and Minocyline are in fact effective drugs for RA. I have observed that rheumatologists tend to avoid these drugs preferring agents which are much more toxic in my opinion.
And unlike the case with Strep- Mycoplasmas are very difficult to eradicate.

Inflammation is bad- so we are constantly told. It in the media all the time. C-reactive protein is a stronger indicator of heart attack risk than cholesterol measurements. Chlamydia pneumonia and other bacteria have been shown to be present in atherosclerotic plaques inside the walls of arteries which can rupture and lead to heart attack and stroke. Some studies have been with drugs like Doxycyline. Is this going to work? Stratton has shown that this organism is very resistant to eradication and that complex multi-drug regimens are needed.

Let us go full circle. Why are people sick who have contracted Lyme disease? We know the causative germ is invasive and nearly impossible to eradicate. We know patients have co-infections which aggravate the disease. Still, some folks who are infected remain relatively unaffected. They are mildly ill or altogether well. The immune response must be a key part of this mystery. For example, the most commonly measured autoimmune antibody is the rheumatoid factor. This is an IgM antibody directed against IgG antibodies. IgM antibodies represent the acute response to an infection. They are made quickly but are not all that effective. In general, they should be supplanted by the more effective, second phase IgG antibodies. Some physicians are troubled by the fact that so called chronic Lyme patients primarily have an IgM response, not an IgG response. If the disease were chronic they reason, one should see IgG responses in the blood. (Actually it turns out that patients who have a robust IgG response to Lyme infection are healthier and respond better to treatment). Is this logical? IgG responses indicate a full immunological/antibody response. These responses are seen in patients who are no longer ill but are in fact recovering from an infectious disease. These are smaller antibodies which bind better to the target sites. So this is not the response one would expect to see in patients with chronic Lyme disease- if such an entity does indeed exist? If the infection is active one would expect IgM antibodies- there is active inflammation. Is this not analagous to the phenomenon which observed with rheumatoid arthritis? Remember, the rheumatoid factor is an IgM antibody. The sickest Lyme patients in fact never have a good IgG response. For some reason the sickest patients are unable to mount a protective immune response. Such patients may suffer and endless cycle of infection and inflammation which becomes very difficult to treat.

And what do we see in chronic Lyme patients? They have an increased incidence of autoimmune antibodies. They have elevated CRP and sed rates. They have elevated complement levels including C3a, C3b and C4a. They have increased circulating immune complexes. They have increased levels of cytokines. They experience inflammatory hematologic abnormalities: the white blood cell count is low. An increased, lymphocyte response may be present, platelet levels may be decreased and abnormalities of blood coagulation may be seen. Alterations in vitamin B12, folic acid and vitamin D may correspond to an active inflammatory process.

Is it post Lyme syndrome? Are the germs gone and we are simply seeing an autoimmune disorder as suggested by the IDSA? This begs the question: What are autoimmune disorders? We have seen evidence that they are in fact promoted by ongoing infection. Autoimmune disorders occur because auto-antibodies are produced. Antibodies are produced when macrophages are activated by foreign proteins. For some yet unexplained reason, sometimes auto-antibodies are produced rather than normal antibodies which would target the offending antigen(protein). The distaff argument then becomes, auto-antibodies are produced because memory cells are activated. When B cells and plasma cells "learn" how to make a particular antibody memory cells are created. These cells "remember" how to make the antibodies and quickly kick into gear when the offending antibody is present. This is why vaccines work. However, there is no reason to believe that these memory cells make antibodies spontaneously. It makes sense that the process is triggered by new antigen exposure. This would explain for example, why rheumatic fever flares up with new exposure to Streptococcal bacteria. The immune system is activated by continued exposure to antigen. In Lyme disease, this dovetails with the observation that IgM antibodies predominate. The immune pump is constantly being primed. I would suggest that a theory of autoimmune disease should include the notion of repeated antigenic stimulation and therefore persistent infection. There is good experimental evidence that patients with "autoimmune" disease, such as rheumatoid arthritis, do in fact show persistent infection.

What do rheumatologist do with their patients? They use steroids. These medications are immunosuppressive. They damp down the entire immune cascade. They reduce activity of macrophages, lymphocytes, granulocytes and cytokines. Patients certainly feel better. The underlying infections may be unchecked with an undesirable effect.
Patients with Lyme who are pregnant feel better. Pregnancy is associated with an immunsuppressed state. After delivery the patients generally have severe relapses as the immune system returns to baseline. Rheumatologists typically prescribe a wide array of immune suppressing drugs. These medications have serious side effects such as life threatening infections and cancers. Concerns regarding the overuse of antibiotics seem less significant in this context.

Are antibiotics bad? Readers of my blog seem very preoccupied with this question.
Antibiotics are neither good nor bad. They are very useful tools essential to the treatment of disorders such as chronic Lyme disease.
A second question is: are alternative and complementary therapies bad? I am concerned about this issue. Many patients who use such therapies claim they help; however, the same patients speak about chronic suffering- the implication: Lyme disease cannot be cured. I am concerned that a focus on these therapies can deprive patients of more effective therapies which offer improvement and a high likelihood of long term remission.

Severe Lyme disease is very bad and must be treated with the most effective tools at our disposal.

Are there ways to make the immune system work better? This question is oft raised. At this time there are no great answers. But perhaps there may be some clues. The relaxation response improves immune function. Exercise improves immune function. A positive mental attitude improves immune function. Correction of sleep disturbances, especially sleep apnea improves immune function. Not being obese improves immune function. Certain diets may improve immune function. Gluten sensitivity and food allergies may stress the immune system and compound the effects of Lyme disease. It is possible that a stressed immune system may experience a tipping point. Removing some of those stressors may allow for quicker overall healing.

What about vitamins and supplements? I am not convinced, sorry. Vitamin A deficiency can cause a decrement in immune responses- but do not take this- it is fat soluble and can be toxic. What about vitamin D. Lately I have given this some thought. In the past I have espoused the belief that vitamin D dysregulation is a pathogen induced process which increases the survival of intracellular pathogens. This theory came from my reading of Marshall's theories. Perhaps this is completely wrong. Another possibility is that vitamin D levels are raised not by the bacteria, but by the host. Perhaps this is an adaptive response to damp down an exuberant immune response which the host senses is causing harm to our bodies. I will stop criticizing doctors who give LD patients D. For now I don't know, and I will leave this topic alone.

All of these ramblings- and not once have I mentioned the helper cell Th1 versus Th2 controversy. This issue has received too much press. The same can be said for the natural killer T cell issue. These immune cells are probably down regulated by a cytokine response. But I have not found the CD57 marker to offer clinical benefit.

Let me finally return to the title of this entry: Towards a unified perspective.
Rheumatologists are right in their characterization of autoimmune disorders. They claim that the cause of such disorders remains unknown. I am simply suggesting that one can take the process back a notch, and posit that the precipitating causes are infection(s), of which Borrelia burdorferi- the Lyme bacteria may be one. And to the neurologists who asked me: "Are you trying to tell me the patient has Lyme disease, not MS." My response would be the same. MS is a well characterized autoimmune disorder associated with destruction of the protective myelin sheath of neurons. You say it is of unknown cause. I am simply offering a theory which provides an explanation of the underlying cause. Such an explanation may also offer therapeutic considerations. So you see- we can all agree, can't we?
As I said early on- I am omitting infectious disease specialists for the time being.

Odds and Ends

I don't use alternative therapies. Sometimes C.diff and other issues make standard therapy impractical. Patients can try protocols described by Buhner, Coweden and others. I have not found such therapies to be terribly effective in my patients. Salt and C: I don't use it. Anecdotal reports of its efficacy exist. This dove tails with one of the weirder aspects of the disease. Some patients with Lyme claims to see worms in their stool. It has been suggested that this is an unknown microfilaria species. Patients have in fact brought me stool specimens with visible worms. Labs have not IDed the organisms . The first thing the Willie Burdorfer saw in tick guts was worms. I don't know if this species has been characterized. High levels of Na in the gut may have an osmotic effect and act as a de-wormer as has been suggested by some. For such patient, Ivermectin has been tried. Sometimes it seems to help- I am reluctant to recommend this therapy at this time. Dr. Stricker who treat many Morgellons patients uses this anti-parasitic medication with some success. There is some connection between Morgellons and Lyme disease. This is outside my comfort zone.

My expertise(if I have any) has accrued over time. The combinations of drugs I used two years ago were more empiric then systematic. My approaches now are more regimented. I am not sure this has improved the results. For example, when I first read about LD treatments, I noted that Jemsek reported success with Cipro and Doxy. It didn't occur to me that I might also be treating "Bartonella." I used Rifampin because many patients reported that it had been effective; maybe this too was treating something other than Borrelia. The treatments were more hodgepodge. So when I review the cases of patients I have treated over time it may reflect an evolution in my general approach. It is still evolving.

IVIG sound great: I can't prescribe it because of standard of care limitations.

Invanz is a 24 hour drug with a broad spectrum of coverage. There are variable responses of drugs within the same class. I mentioned it based on one anecdote. It might be a great addition to the available arsenal. Most antibiotics require more complex dosing strategies. Unfortunately we have no data regarding the use of many antibiotics including this one.

Whether patients get very ill probably depends on a host of factors. Some strains of Bb may be more pathogenic. The mix of co-infections varies. Individual immunological responses based on genetics may play a large role. Some of this may be medicated by major histocompatibility molecules(genetically determined). Some patients only have IgM responses which made bode poorly versus those patients who develop a robust IgG response. So far we cannot do much about individual genetic based immune responses, but such things may have prognostic and or treatment value.

Ivanz- who knew

A new Lyme med?

This 48 year old female was not one of my best success stories. Despite this, I had helped her a great deal. Two years ago she came to me a train wreck. She had incapacitating total body pain, cognitive impairments and abdominal pain. She had seen rheumatologist who had treated her with immunomodulators including gold and prednisone. Nothing had helped. Antibiotics had caused strange reactions- numbness and tingling in her mouth. Numerous doctors had no idea what was causing her abdominal pain and myriad other symptoms. She had been sick for over 20 years and was at the end of her rope.
The abdominal pain was easy. I have found that gastroenterologists and surgeons make this same mistake over and over again. She had classic right upper quadrant abdominal pain with a tender gallbladder(positive Murphy sign). She had had numerous CT scans and ultrasounds which were negative. Her HIDA biliary scan was normal. The CCK injection given during the test reproduced her symptoms. This is key. If hormonal stimulation of the gallbladder reproduces the pain- the gallbladder is diseased. A clinical rule which has served me well over the years is simple: Treat the patient, not the labs or ancillary tests. The first surgeon I sent her to refused to consider surgery. She was an obvious hypochondriac. Besides, the GI specialists didn't think she had gallbladder disease: IBS. The second surgeon performed a laparoscopic cholecystectomy. Bingo. Path showed chronic cholecystitis.
In my experience, Lyme frequently causes gallbladder disease. She felt better and was impressed right off the bat that I had figured out one of the mysteries. Her labs made TBD a no brainer. She had positive Babesia serology from Labcorp. We began a long odyssey of treatment. There were ups and downs. Antibiotic side effects and intolerance led to long periods of no treatment. Symptoms invariably relapsed. The fibromyalgia and joint pains were somewhat refractory to therapy. Her cognitive improvements were steady. She suffered with bouts of serious depression which complicated her care. Along the way she had two courses of IV Rocephin. They were not as effective as I hoped they would be. Recently she came into my office very concerned. She told me that she had been coughing for two months- she smokes 2 packs per day- she knew that she had lung cancer. My intuition- its not cancer. The Chest Xray showed a mass. She was a wreck. I pointed out that it might be an infection. I ordered the CT, PET and a needle biopsy. The results were non-specific inflammation. No signs of cancer. It looked like a lung abscess. I thought it might be related to Bartonella. I started her on Cleocin and Levaquin. She collapsed in what looked like the mother of all Herxes. She was admitted to the hospital. She saw all the king's horses and all the king's men. They ultimately decided it was indeed a lung abscess. They were unable to identify a causative pathogen. The infectious disease doctor started her on Invanz. Its a new beta lactam antibiotic given once daily. It seems to kill everything that has a cell wall: gram positives, gram negatives and anerobes.
She was in the hospital for 6 days. Something magical happened. I saw her today. She was more bright and chipper than I had ever seen. There was almost a glow of wellness about her. This is the best she had felt in 20 years!. Virtually all of her symptoms had vanished.
Could this drug be a magic bullet that wipes out Lyme and the mystery bacteria crawling around in the bloodstreams of my patients?
Perhaps some other LLMDS should look at this and give it a try. I am trying to avoid more controversial therapies at the moment. This new antibiotics was only approved in the beginning of 2007.

PS: If it appears that I only write about my success stories it is because the other patients are a work in progress. I never give up- and neither do my patients.

17 month review

A 46 year old woman first came to me about 17 months ago. She had a history Lyme disease about 7 years before our first encounter. She had been treated with a three week course of Doxycycline. Her doctors over the years had diagnosed fibromyalgia, chronic fatigue syndrome and memory loss of unknown cause. She also had a history of unspecified colitis dating back 5 years. She was referred to me by a friend. On that occasion her symptoms included: headaches- severe, diffuse total body pain- severe, blurred vision, decreased hearing, memory loss, episodes of weakness and tingling of the extremities. She reported a prior history of Clostridia difficile colitis and an allergic reaction to Flagyl. This was reported to be a serum sickness like reaction and had caused a neurological reaction- some sort of muscle weakness. Her labs showed CDC positive Lyme antibodies. She was started on Ketek with probiotics. She had a massive Herx response. Plaquenil was added. She developed a urinary tract infection which led her to the hospital. Levaquin was given. Two months into treatment she saw improvements. Her hearing had improved. Her mental acuity was better. Her pain had decreased. A month later there was trouble. She developed some abdominal cramping, diarrhea and blood. She had chills. There was marked cognitive improvement. I was worried about C. diff and I knew she had a history of colitis. I had to stop antibiotics. With nothing else to offer, herbal therapy was recommended. One month later she was mostly better GI wise. The Lyme symptoms had neither worsened or improved. Asacol was started for colitic symptoms.
I was going through my experimental "CAM" phase. I even tried the vit C and Na protocol. It may have helped a "smidgen." Three months later I bit the bullet. Ramping up the probiotics she started Zithromax and Rifampin. No diarrhea. A herx: fatigue, increased numbness and now orthostatic dizziness. Adrenal insufficiency? I started low dose cortef, 5mg twice daily. Her insurance wouldn't cover Zithro and we switched to Biaxin. Now 5 months into treatment things were gradually improving. She had crawling sensations- saw worms in her stool and had small fibers extruding from her skin.(I have a patient with severe Morgellons- I didn't want to think about this). I added low dose Cipro and gave her a couple doses of Ivermectin. These weird things improved. I switched gears and put her on Minocin. We were 7 months in. The cortef had been a success and was stopped. A strange pruritic rash improved with antihistamines. A stool test for gluten sensitivity was suggested. She couldn't afford it, so she tried an empirical gluten free diet. Colitis symptoms improved. The original symptoms were about 50% better. 9 months in her antibiotics were ramped up again: Amoxil 3gm per day and Zithromax 500mg per day. It worked. She made steady progress. Plaquenil and Questran were used as well. Vitamin D was avoided and Benicar was added to balance out high levels of vit D dihydroxy 1,25. This helped as well. About 15 months in she was 85% better. I did elicit a history of sweats. I reviewed her chart and realized she had not been treated for Babesia. Two months into Zithro, Mepron, Tidamax (which she tolerates well) and Atemensisn she is 95% better. Admittedly I did some things along the way which I might be hesitant to try now. We were able to get past C. diff and plug away. Her colitis is in remission. Her memory and cognition are normal. Her pain is gone. She exercises and functions normally. She is a new person. We are not quite done yet. It is looking good.