Thursday, May 28, 2009

Knee, Assymptomatic Babesia, Autoimmune neuropathy, Tindamax

Another young woman came into my office with swollen knees. The first doctor she saw, an IDSA doc had no trouble making the diagnosis since Her Lyme ELIZA was positive and she had 13/13 Lyme Western Blot bands present. The ID doctor presented her with 2 options. She could take a 30 day course of Rocephin or she could go on low dose Doxycyline. It was sort of left up to the patient. One has to ponder how these 2 options are interchangeable. Rocephin, a cell wall inhibitor kills only Bb in the spirochete form. Doxy, a protein synthesis inhibitor kills Lyme in the spirochete and the L-form. It always troubles me that the "experts" are unaware of these basic facts. From my perspective it makes more sense to use two antibiotics which can synergistically attack the spirochete and L-form simultaneously. The patient has acute, active synovitis with swollen, inflamed joints. In chronic Lyme arthritis it has been shown that L-forms in the synovial lining are the problem. In acute Lyme arthritis It appears spirochetes are the culprit since such patients typically respond well to only IV Rocephin. In this case IV Rocephin is a reasonable treatment choice. Oral therapy with something like Amoxil and Doxy is also a reasonable option.(There seems to be some controversy about the combination of Amox and Doxy. They are thought to have an adverse interaction. I do not think this is the case. One can use Amox and Biaxin or Ceftin and Doxy if one prefers). The ID docs, as I am oft told, "don't believe in co-infections." This I do not get. I re-tested her. She was positive for Babesia duncani as well. She has no symptoms of Babesiosis.

After 4 weeks of oral combination antibiotic therapy, she came in today about 50% improved. After weighing the options, we decided to go to IV Rocephin for 30 days. Then I looked at the Babesia issue: She is young. She has no symptoms of systemic Lyme disease. She only has knee involvement. Her immune system may be functioning well, at least her CD57 level is normal. In this case I decided to treat Babesia by standard-text book recommendations. I ordered Mepron and Zithromax for only 21 days. Perhaps her immune system could truly eliminate the Babesia but I thought it would be better to treat-prophlactically. After all, chronic Babesiosis when it does occur can be a beast.

I decided to do a little exam of the nervous system. I continue to find that nearly every patient with Lyme disease has some peripheral neuropathy. As with most patients, there was a little stocking/glove loss of pin-prick sensation and a little decrement in vibratory sensation in the feet.

I am now fairly certain that these findings are due to a Lyme induced autoimmune process. Usually the autoimmune process is minor, but it is something that I have learned to keep a close eye one. It can worsen due to Bb infection but it can also worsen as a result of Lyme therapy. I look carefully for symptoms of progressive numbness, tingling and weakness. I examine for a worsening sensory exam. And when I find that previously existent deep tendon reflexes vanish I am particularly concerned.

When I see an increased in autoimmune neuropathy I quickly back off therapy.

I have wondered if some antibiotics have a tendency to cause more autoimmune reactions than others. This is an observation; I cannot back it up with any data.
I have observed that these reactions seem to occur more frequently when Minocin is used early in the course of therapy. I don' think Doxy does it. It seems less common with Amoxil, Rocephin, Biaxin and Zithromax.

So for what it is worth I now avoid Minocin as a first line agent.
On a final note- I am increasingly impressed with the effectiveness of Tindamax.
For example, when a patient responds rapidly to the combination of Amoxil and Biaxin, adding Tindamax a month or two later frequently makes a huge difference.

Thursday, May 21, 2009

Lyme, CHF, Rhabdomyolysis and Crohn's

A 59 year old female visited me for an evaluation for Lyme disease visited me 9 months ago. She had a past medical history of Crohn's disease and celiac disease. She also had a history of congestive heart failure, resolved, 10 years prior to our first meeting. The cause of the CHF had never been determined. In addition, she had a severe history of muscle disease related to the cholesterol medicine Lipitor 6 years back. The lipitor had caused a severe break down of muscle tissue. The disorder is called rhabdomyolysis; this was associated with acute renal failure which has resolved. She reported a history of prednisone use for 18 months for her bowel disease. A previous physician had diagnosed fibromyalgia. At the time of our visit this once high functioning professional was disabled.

Her complaints included: nausea, fatigue, back and neck pain, blurred vision, diffuse body pains, sensitivity to sound and light, diffuse joint pains, pins and needles, rashes, fatigue, palpitations, sweats and severe cognitive issues. Her cognitive problems included poor focus, slow cognitive processing, short term memory loss, word retrieval problems and bouts of confusion and disorientation.

Her physical exam showed multiple abnormalities involving the nervous system. These included changes in cranial nerves, sensory nerves and upper motor neurons.

Her initial lab tests showed: mild anemia, a Lyme C6 peptide index of 0.27 and a single positive Bb WB band IgG 41. The results were otherwise unremarkable.

The controversies about Lyme disease were discussed with the patient. She was given informed consent. She wanted treatment without any further defining laboratory tests.

She has been on a program of typical oral Lyme medications. These have included: Zithro, Mepron, Amoxil, Minocin, Biaxin, Tindamax and Rifampin.

In her particular case Rifampin has been particularly helpful for reasons that are not clear to me. In general this is consistent with my experience that different antimicrobials work better with individual patients.

To date her improvement has been dramatic. The symptoms which had previously been attributed to Crohn's disease are completely absent. Her muscle and joint pains are nearly gone. She does admit to very slight joint pain at times and sensitivity of her skin. Her energy level is almost normal. All cognitive problems have resolved. The palpitations are gone. The sweats are gone. She is functionally normally and now returning to work in her professional capacity.

Comments: 1) Cardimyopathy- the undiagnosed heart failure could be caused by Lyme carditis. 2) Lyme can cause symptoms of inflammatory bowels disease or cause exacerbations. In this case Lyme therapy has for the time being caused a remission of Crohn's disease. 3) This is the most controversial point: Lyme has been demonstrated to exist in muscle tissues and causes myositis. It has been my observation that some patients who develop muscle pain related to statins(cholesterol medications) can later tolerate the drugs when Lyme has been treated. The reasoning here is that it is the double insult to the muscles of Lyme and the drug that causes the symptoms. When one factor is removed(Lyme) the drug becomes tolerable. Given this patient's history I would never recommend that she try taking this class of medication again. She tolerates Welchol well, which as has been pointed out, also frequently provides benefits to patients treated for Lyme disease.

Thursday, May 14, 2009

Wellness, Illness and Lyme

Wellness and Illness exist on a continuum. We all have a balance sheet of sorts which relates to our status on this scale. On the wellness side we have: favorable genes and environment, happiness, laughter, low stress, good mental health and self esteem, fulfillment of career-relationships-family, positive nutrition, exercise, healthy sexuality, music, dance, intellectual curiosity, reading, writing, hobbies and other things which make us well rounded. A person on this side of the health continuum feels well and energetic, sleeps well and is devoid of pain. (I think you also need a surplus of money and time).

On the other side of the balance sheet we have pretty much the opposite of all these positives. You can go down the list. The negative side of the balance sheet also tends to include many chronic illness and negative factors; some are of our own making and others are just the result of bad luck. These include: unfavorable socioeconomic status, unfortunate genes and environmental factors, smoking, drinking, substance abuse, an abusive diet, migraine or headache disorders, heart disease, diabetes and other endocrine disorders, asthma and allergic disorders, gastrointestinal disorders, autoimmune disorders, pain syndromes, malignant disorders and much more. Those living of this side of the spectrum experience life quite differently. Every day may be a struggle fraught with an array of challenges and discomforts. These folks are in pain. They sleep poorly- have mental health issues, and experience subjective and objective signs of a lack of good health or illness.

There are always unexpected factors and influences, such as illness, accidents or personal tragedy, which can precipitously change one's status. An individual experiencing all the benefits associated with column A can quickly find themselves experiencing a predominant column B status.

Sometimes it appears humans are incredibly resilient while at other times it appears we are delicate and tenuous. Of course most of do not live in either of the extremes of the continuum described. We reside somewhere in the middle of two,(I hope). Those of us closer to the the health side (column A) may at times be be better equipped to handle a new negative challenge than those who resides predominantly in column B. But this is not always the case: Enter the unpredictable world of infectious diseases.

Someone ranking high on the health side, may have a better immune system and fend off a typical case of pneumonia with relative ease. Influenza may be another matter. It turns out that the H1N1 strain of flu, last seen 91 years ago, caused the highest mortality and morbidity in those who would appear to be the healthiest, namely 20 to 40 year olds. In fact it was their excellent health that likely led to the disastrous outcomes. Their perfectly tuned immune responses actually became their Achilles heel. Hyper-responsiveness of the immune system led to an outpouring of pro-inflammatory cytokines. These are the chemical mediators which direct the activity of our immune system. Readers of this BLOG should be familiar with cytokines; these are the molecules responsible for Herxheimer reactions so frequently experienced with Lyme therapy. The overactive responses, called a cytokine storm, could be thought of as a Herx reaction on steroids, and could overwhelm the infected host and lead to organ failure.

Other insults to our health are much less predictable; I am thinking of Lyme disease.

Today I saw a woman who cannot comprehend how Lyme disease could have made her so ill. After all, she has done everything to promote the best possible health. She is committed to exercise, yoga, a vegetarian balanced diet, healthy relations, laughter and all the other positives noted in the column associated with good health. In fact her professional life centers around teaching others these concepts. The germ still prevailed. She has neuroborreliosis associated with significant cognitive deficits. Her brain MRI and SPECT scans confirm this. Against her innate judgment she has accepted the reality of a long and intensive treatment course of antimicrobial therapy.

Health and illness can exist on a balance beam. Sometimes all it takes is one factor, like Lyme disease, to act as the hair that broke the camels back. The weight of that hair varies for each individual.

Tuesday, May 12, 2009

Spirochete Associated Immune Dysregulation- A new paradigm

The other day a patient a seemingly simple question: "Doctor, why is my case of Lyme disease so mild." Perhaps the answer to this question can lead us down the path of understanding Lyme disease.

The standard(LLMD)paradigms would suggest that the Lyme disease syndrome is the product of a multi-pathogen state. The co-infections, including Bartonella and Babesia are additional tick borne pathogens which contribute to the character and severity of the illness. But is this right? Perhaps not. What I have seen in very ill patients, consistently, is the presence of other, to date unrecognized "germs," swimming in the blood of such patients, undeterred- in the face of large and prolonged courses of antibiotics. Some of these organisms for example look like Toxoplasmosis. The existence of "Toxo like organisms" has been touched on in medical literature. Others are small gram negative bacteria which resemble Bartonella but are not Bartonella. In fact such "mystery bacteria" resembles hundreds of other bacteria which might stain in the same way. There exists a plethora of bacteria which share a similar morphology; for now, these are unknowns. Are these blood organisms seen in Lyme patients really tick borne pathogens?. Perhaps not. I propose that these anomalous bugs are pre-existing endogenous organisms, normally contained by the host immune system- prior to the onset of the illness- until the genie is let out of the bag.

Before chronic Lyme, or post-Lyme as some like to call it there was chronic fatigue syndrome. CFS became CFIDS: chronic fatigue and immunodeficiency syndrome. It has been pointed out by numerous observers that the two syndromes have much in common. The CDC has defined criteria for the syndrome. It usually starts after a "flu like illness." It has a new onset: it is not lifelong. It is associated with fatigue not relieved with rest. It is associated with: impaired memory or concentration, unrefreshing sleep, muscle pain, joint pain, headaches, sore throat and tender lymph nodes. Many other symptoms may occur as well. It is characterized by impaired immune responses. It is understood to be a "multi-system" disease. Its cause is not understood and it has a poor prognosis. Does this sound familiar?

Let us shift gears to chronic Toxoplasmosis. The seroprevalence of Toxoplasmosis is incredibly high. Most of the world's population is colonized by this parasite and they are ostensibly asymptomatic. It is thought that the "normal" immune system keeps it in check. Numerous symptoms may be associated with chronic Toxo. These include: fever, malaise, swollen lymph glands, eye symptoms and more. In immunocompromised patients, including the population with AIDS, symptoms include: fever, chills, skin rash, brain symptoms, heart and lung symptoms, confusion, headache, tremor, muscle weakness and more.

The existence of immunosuppression is one hall mark of Lyme disease or what is now called tick borne disease. I have repeatedly spoken of the "opportunistic" nature of co-infections. Evidence of immune compromise is regularly seen seen in patient lab studies. Many patients have low white blood cell counts with low neutrophils and increased lymphocytes. Patients may have low levels of natural killer T cells per the CD57 test. Patients have alterations in vitamin D suggesting a shift in helper cell Th1 and Th2 responses. These patients have a compromised immune system. This compromise is specific and limited. It does not lead to the full blown immunological defects seen in certain inherited disorders or acquired disorders like AIDS. It appears this subtlety has made it difficult for skeptics to appreciates its very existence.

Whereas some point to the Lyme spirochete as the culprit which initiates the cascade leading to immune dysfunction, other advocates point to CPN, Mycoplasma, yeast and other agents as the inciting cause. The disease may go by many names including CFIDS and fibromyalgia.

There are common threads. These chronically ill patients suffer with varying degrees of immunosuppression. The syndromes and their attendant symptoms overlap. Previously innocuous germs perhaps become interwoven into the fabric of a systemic, multi-system disease process. These germs may include: CPN, Mycoplasmas, Toxo like organisms, gram negative bacteria- or Bartonella like organisms if you like, yet unspecified "others" and perhaps a host of viruses including EBV, CMV and HHV6. In many cases the Lyme germ, Borrelia burdorferi may also be an innocent bystander, until something tips the immunological balance in favor of the disease process.

There may be an interplay behind the germs and other environmental factors. Certainly non-infectious proteins such as gluten can trigger abnormal immunological responses. Host factors such as exposure to toxins and stress may very well play an important role in some cases.

But this cannot be the whole story. Per the title of this piece, we are dealing with not only immune suppression, but immune dysregulation. Patients with this disease syndrome suffer with immune consequences impacting both sides of the immunological continuum. We have immunosuppression. On the flip side there is immune system over-activation, leading to the myriad of complex autoimmune responses which complicate the course of the illness more often than not.

Lyme and related organisms have clearly been implicated in a wide host of autoimmune syndromes ranging from inflammatory arthritis to MS and CIDP.

The spirochete dysregulates the immune system at both ends of the spectrum simultaneously- a nasty trick. It creates an environment ideal for opportunistic pathogens while at the same time it contributes to the destruction of erstwhile healthy tissues via an autoimmune process.

Perhaps chronic Lyme disease, fibromyalgia, CFIDS and other related disorders could potentially be combined into a new rubric, forming the foundation of an entirely new class of medical disease.

To get back to the patient's question: why are some people ill while others are not? The answer comes down to an understanding how a complex array of variables interact. As always these include genetic and environmental factors. The end result is seen in each patient's unique clinical syndrome.

Monday, May 11, 2009

Lyme Disease While I Stand On One Foot

A 46 year old female came into my office today looking for help. She was referred by a friend but really didn't know much about Lyme disease. Two years ago she noticed a tick bite behind a knee. Her physician told her to watch the area: no treatment was required unless she developed a bulls eye rash. This never occurred so she received no therapy. Over the months she got sick and sicker with a variety of ailments. She developed gallbladder problems. Removal of the diseased organ did not improve things. She had constant symptoms of diarrhea, bloating and nausea. She developed headaches, vertigo and palpitations. She saw a neurologists- no help; an ENT specialist- no help; a cardiologist- no help. It was finally her gynecologist who suggested that she be tested for Lyme disease. The test was positive(I don't have the results). Her primary doctor prescribed 2 weeks of Doxycyline- should be cured: she wasn't. An infectious disease specialist prescribed "blue pills"(probably Ceftin) for 3-4 weeks with any change. She brow beat the ID specialist after doing a little research of her own, into prescribing Rocephin because she was no better. He reluctantly agreed to prescribe Rocephin for the "magic" 28 days, which was of no help. Enough he said. The ID specialist even consulted with another colleague. Both concurred: she was cured. The ID specialist said that co-infections do not exist. Even if they do- the Doxycyline and Rochephin had already killed everything. She did not have Lyme disease. Her primary physician recommended that she see more specialist at a University hospital. She does not have Lyme disease.

Her current symptoms are: severe fatigue- incapacitating, brain fog with horrible memory loss, sleep problems, headaches, neck pains, shaking, joint pains of knees shoulders and more, muscle pain, palpitations, neck pain, hot flashes and persistent vertigo. Does any of this sound familiar?

Her neurological exam revealed a treasure trove of pathology. She had cranial nerve dysfunction, sensory disturbances, weakness on one side, a positive Babinsky showing upper motor neuron disease a positive Romberg and more.

The question then became: how was a going to tell her everything I needed to tell her about Lyme disease. There is a famous parable from Jewish folklore. A non believer was reported to have asked the famous Rabbi- Rabbi Akiba, to tell him everything about being Jewish while he stood on one foot. The wise sage, as the story goes said: "Treat your fellow man as you yourself would wish to be treated; the rest is commentary, now go learn." So in essence my goal was the same. I needed to tell her everything she needed to know about Lyme disease while she stood on one foot. Unfortunately, I could not be quite as terse as the famous Rabbi.

Here is the outline of how I proceed with such a patient. First she was informed about the raging controversy. Second she was told about the 3 different morphologies of the Bb bacteria and something about its ability to persist in the host after prolonged bouts of antibiotics. The she was informed about the potential for co-infections and the fact that these opportunistic pathogens may play a role in her illness. She further instructed that mysterious co-infections exist in many patients treated for tick borne illness- which is replacing the term Lyme disease. As an aside, just last week, it was announced that a group sequencing the genone of Ixodes scapularis, the tick which carries Lyme disease, uncovered a novel strain of Rickettsia, a relative of Rocky Mountain Spotted Fever.

She was told that the treatment for Lyme and related disorders is frequently long and complex and based on trial and error. Herxheimer reactions are common and may be a good sign.

She was told about the use of laboratory tests and their role in the diagnosis and management of Lyme and tick borne disease. Here is what I order for this patient: CBC, Chem panel, TSH(thyroid test), vitamin B12 and folic acid, vitamin D- 2 forms, CD57, sed rate, CRP, Ehrlichia antibodies, Bartonella antibodies, Babesia microti and WA1 antibodies, ANA, RF, C3a, C3b and a repeat Lyme Western Blot since I do not have the results. All of these tests can be done through the patient's insurance at Labcorp. The purpose for all of these tests was, in a general sense, was explained to the patient as well. The use of specialty labs such as IgeneX and Clongen was also briefly touched on.

Because of cognitive complaints I also order a SPECT scan- she has already had a brain MRI. The reason for this was explained.

Then I explained to the patient why I would not recommend that she see further specialist at this time. I tell her that if she wishes treatment from me I require that she sign an informed consent form. I briefly touch on the politics which have made such forms mandatory.

Normally I await the results of all the tests before a begin therapy I explain to her. But I tell her I am already convinced she has chronic Lyme disease. The history fits. The physical fits. The negative brain MRI fits. The history of a positive Lyme test fits. In her particular case I am comfortable with starting treatment today.

Now I need to explain therapy options to the patient. First of all, I confess I was a little surprised that she had not benefits from the Rocephin, but on the other hand, in many cases clinical improvement is not seen for more than 8 weeks. At this point I recommend going back to oral therapy since the PIC line is no longer in place. Because we are entering the warmer months I avoid Doxycyline. I tell her that I have good success combining antibiotics. I recommend Amoxicillin 3 grams per day plus Biaxin one gram per day. I also recommend two types of probiotics: one is Acidophilus based and other is Saccromyses based. I warn her about potential side effects including: allergic reactions, diarrhea and yeast infections. I ask her to return for follow up in 4 weeks. I explain all of these things in some detail.

She then asks what to expect. Will she better or worse? How long will therapy take? If I don't know can I give an estimate? I then try to field these important and complex questions in the few minutes left in our visit.

Read I say. Become informed. See Under Our Skin. Read Cure Unknown. Visit the ILADS website. Read some of my literature- perhaps part of my blog.(The rest is

That's Lyme disease- while you stand on one foot.

I wish it were that easy.

Friday, May 8, 2009

Management of Lyme epi-phenomena: Ischemic colits?

Frequently, in the management of the very ill patient, with advanced Lyme and tick borne disease, it is the management of the epi-phenomena that become most challenging. Treating the infectious components of the illness can be relatively simple when compared with the management of other, side medical issues, which can require a great deal of caution, thought and general medical experience.

In this post, rather than addressing the complex choices of antimicrobial therapy, I have chosen to discuss therapeutic considerations which do not directly deal with treating infection per say.

I will review some of these issues as seen in one patient. This patient presented with advanced partially treated systemic Lyme disease with neuroborreliosis. She had fared well with previous courses of IV antibiotics which seemed to be indicated at the start. She unexpectedly experienced frank psychosis associated with new auditory hallucinations. This is considered a "psychiatric Herx" by many. The management of Herx reactions in general is quite problematic. The approach of most physicians is to stop the antibiotics for several days and then gradually ramp up the dose. In this case, after a careful discussion with the patient, I decided to instead try a tapering course of oral prednisone. It was not very effective so I went to plan B: a lower dose of antibiotics. I was rapidly able to get back up to speed with the prior dose of antibiotics. Her neuro-psychiatric symptoms stabilized and then improved.

This patient has had a prominent problem with body jerking. It appears unusual and some doctors have diagnosed these seemingly bizarre movements to be "pseudoseizures.," considered psychosomatic. I believe many such patients have atypical myoclonus, a well known form of partial epilepsy. This clinical syndrome varies in degree and presentation in many such patients. The anticonvulsant drug Neurontin was tried and had minimal benefit. I then tried the anticonvulsant and anti-anxiety drug Klonopin; it has been remarkably effective in controlling this manifestation of the illness. This one intervention has been very comforting for this patient.

The patient has had severe blood pressure fluctuations, with extreme high and low readings which her cardiologist has been unable to manage. Her therapy had included a beta blocker and a calcium channel blocker for hypertension, but these were ineffective. I changed her to an angiotensin receptor blocker, Benicar, which is also reputed to have beneficial effects in Lyme patients. These fluctuations in blood pressure are generally thought to be due to "dysautotnomia." This refers to neuropathy which affects the autonomic nervous system. This is comprised of the sympathetic and the parasympathetic systems which control many autonomic, which I think of as automatic, functions in the body, including blood pressure regulation.
This story became more complex as you will see.

The patient was admitted to the hospital with acute abdominal pain and bloody diarrhea. Her work up in the hospital revealed ischemic colitis. This is a relatively uncommon disorder which I have only seen in elderly patients who have blockages and or clots of the arteries which supply blood to the bowel. The treating physicians were baffled by this patient's disease presentation. The patient reported to me that the episode was preceded by a period of very low blood pressure. Hypotension, or low blood pressure, can cause a lack of blood flow or perfusion to vital organs. The regulation of blood flow to the gut is in part controlled by the autonomic nervous system. One can then construct a scenario in which these two factors acting in concert caused the ischemic colitis.

With this resolved, it became apparent that management of her blood pressure was crucial. In this relatively young female with an otherwise healthy cardiovascular system, I felt that the risk of episodes of very high blood pressure was much less than the risk of low blood pressure. I considered the possibility that endocrine dysfunction, especially with respect to adrenal functioning could be contributing to blood pressure dysregulation. This effect has been well documented to occur in very ill LD patients. The adrenal gland makes two hormones which may effect blood pressure. These are cortisol and especially aldosterone. I supplemented the patient with Cortef (cortisol like) and Florinef (aldosterone like). I stopped all previous blood pressure medications. For high BP readings I started Catapres. This is a centrally acting alpha agonist which is quite effective and fairly short lived in effect. This seems to be working. To provide further context- the high BP readings, systolic, have been over 200 and the lows have been down to 80.

For colitis I have also added Asacol, a local bowel anti-inflammatory. Many LD patients have colitis like symptoms. Usually this is manifested by diarrhea, vague gastrointestinal discomfort and bloating. These symptoms frequently disappear with antibiotics, even though one would expect these symptoms to result from antibiotic therapy. Many Lyme patients have microscopic or collagenous colitis diagnosed from colonoscopy biopsies. Clongen reports many positive Lyme PCRs obtained via colon biopsy specimens. I have also added Questran- an interesting agent in this context. It is well know to control diarrhea; it is also associated with the removal of fat soluble toxins filtered through the liver and a reduction in inflammation measured by CRP levels. The addition of this agent appears to have afforded additional benefits. If there was an atherosclerotic component to the ischemic colitis in this patient with moderately elevated cholesterol, it's primary purpose as a cholesterol lowering drug should offer further benefits.

Neuropathic pains, as seen in this patient and many others, frequently improve with anticonvulsants like Neurontin or Tegretol combined with antidepressants like low dose Elavil or Cymbalta, as has been the case with this patient.

Despite all these ups and downs which I have called Lyme related epi-phenomena, this patients overall response to treatment has been dramatically positive.

Thursday, May 7, 2009

Hammer and a different nail: Brucellosis??

In 2005 a 39 year old female developed tingling and weakness of the right leg. She subsequently developed an unusual burning pain of the left flank. Weakness spread to both legs followed by the onset of fatigue. A community neurologist diagnosed MS. She went to NIH for further evaluation. Three lesions were seen in the brain MRI and she was begun on MS therapy with Avonex. Despite therapy the burning sensations persisted and were quite severe and difficult to manage. She went on to develop tachycardia and anxiety. She required treatment with beta blockers, anti-anxiety drugs and analgesics. This was a year into her syndrome. She subsequently developed ringing in the ears(tinnitus). MS flare ups with burning and weakness were treated with IV steroids with some improvement. A Lyme WB showed a 41 band and she was briefly treated with doxycycline with no improvement. Now, nearly 2 years into the illness, she developed cholecystitis. Symptoms of leg weakness, burning and tremors worsened. The brain MRI was stable. The MS therapy was ineffective. Over several months she developed memory loss and increasing fatigue. Courses of IV steroids prescribed by neurologists seemed to exacerbate things. I convinced her to have an evaluation to exclude LD. The WB showed a nonspecific banding pattern and the urine antigen capture test was negative. Over the next year she became more profoundly tired. I thought everything fit with Lyme. I was determined to prove she had Lyme disease. I was unable to do so. Despite negative test results, more antibiotics were tried without much improvement. She progressed to develop diffuse joint pains.

Then she had an episode of profound weakness and went to the hospital ER. A serological test for Brucellosis was positive, but she was told it was a false positive. She developed cranial nerve signs and had persistent, worsening signs of peripheral neuropathy Two years ago I put her on Doxy and Rifampin, therapies for Brucellosis. She then moved out of state and was lost to follow up. Recently she came back to the area. She is still being treated for MS. She recalls that the antibiotics helped but she only took them for several weeks. Now, at age 43, she has weakness, migraines and profound fatigue. She has been hospitalized for MS exacerbations and treated with steroids on several occasions. She has developed progressive neurological impairments typically associated with MS. Her anxiety has increased and she takes tranquilizers at an increased dose.

A Brucella IgM antibody by EIA, obtained a few days ago shows a positive IgM. The IgG is negative.

A quick review of literature shows that the debate regarding chronic Brucellosis has been ongoing for decades, before anyone had heard the words Lyme disease.

It turns out that chronic Brucellosis has been thought to be associated with non specific symptoms including: joint pain, muscle pain, neurological disease and neuro-psychiatric symptoms. Brucella is a small, inracellular gram negative bacteria. Like other such organisms, it has mechanisms for eluding the innate and acquired immune defenses. According to Harrison's textbook of medicine, significant neurological disease requires 6 to 12 months of antibiotics, typically with Rocephin. But of course, the existence of chronic, post treatment Brucellosis is controversial. It is suggested that malingering, obesity and alcohol abuse need to be excluded.

This patient is not native to the US. She grew up in a part of the world where Brucella is known to be endemic.

Sounds a bit like Lyme before Lyme.

Tuesday, May 5, 2009

Gout , Lyme or Both?

A middle aged man came into the office with acute pain, swelling, warmth and redness of a knee. He had no other symptoms to suggest chronic Lyme disease. Past experience, as well as all major texts indicated that that gout was the most likely culprit. The patient was treated with typical gout therapy: Indocin and Colchicine. Blood was sent to help sort out the usual suspects which may cause "acute mono-articular arthritis."

His uric acid acid level was quite high- 9.6- definitely compatible with the gout diagnosis. But the diagnosis was a bit messy. His serum Lyme WB by Labcorp showed IgG bands present at the 30 and 41 positions. And then, one week later the patient came back for a follow up visit. The gout therapy had not worked. The knee was a little better but now there was swelling of the great toe, the metatarsal phalangeal joint. This is the classic finding of gout. I aspirated the fluid. I only obtained a few CCs of blood tinged fluid. I sent the fluid for Lyme Western Blots. The results: 6 IgG bands present and 2 IgM bands present.

Now the therapy was converted to antibiotics rather than anti-inflammatory agents.
The patient could be unlucky enough to have both Lyme arthritis and gouty arthritis. The only way to confirm gout is to analyze the joint fluid for the presence of uric acid crystals. Unfortunately this test was not performed.

I could imagine that gout triggered Lyme or the other way around. This is the second case I have seen with the same presentation.

Monday, May 4, 2009

Leg numbness and loss of balance

A 60 something year old gentleman consulted me for complaints of progressive leg numbness and loss of balance. He lives in a rural, wooded area and was concerned about the possibility of Lyme disease. He was accompanied by his wife who had heard of my interest in tick borne illness. The patient had visited his primary care physician and a neurologist without a diagnosis. His symptoms had been progressive over a period of years. He claimed that he could no longer feel his legs and that he was falling over at times. Perhaps he was a bit weaker as well. He denied any changes in memory or cognitive functioning. He denied any pains. He denied any unusual fatigue.

He looked generally well and high spirited.
His physical exam- neurologically, was quite abnormal.
His mental status was basically normal although at times he struggled to find words.
His cranial nerves were normal. The motor exam was normal. Deep tendon reflexes were diminished. Finger to nose testing was slow and imprecise. His sensory exam was highly abnormal. He had a complete absence of the ability to feel vibration in his feet, knees and hands. He had minimal ability to detect vibration on his elbows. He had a loss of hot and cold discrimination in his lower extremities. He had absent position sense in his feet- he could not discriminate if his big toe was up or down. He passed the Romberg test, but was a bit wobbly. His gait was abnormal- it was broad based with a "bowlegged" appearance.

His exam was not consistent with what I have seen in scores of Lyme patients. I have never seen diminished vibratory sense to that extent. I have never seen a loss of position sense and hot and cold discrimination in my Lyme patients. And his gait was not typical of what I had seen in Lyme patients.

He was not suffering from Lyme disease. In fact I immediately suspected the correct diagnosis. A key to making the diagnosis was a piece of standard medical history which I have omitted until now. I asked him if he drank alcohol- if so how much.
He reported that he drank 6 beers daily along with 6 little cigars. In medical school I was taught, somewhat facetiously, to triple patient reported alcohol consumption. This is a bit of an exaggeration. Nonetheless, it was clear to me that the extensive neurological abnormalities were entirely consistent with long term alcohol abuse. Alcohol can cause injury to the cerebellum causing a loss of balance with a broad based gait. It can cause the severe sensory deficits described due to injury to specific posterior column nerve tracts. There are other causes of these abnormalities but I did not think he had Lyme disease.

A complete neurological workup was ordered, including EMG and NCV. Brain MRI and PET scans were ordered to evaluate brain function and anatomy. Routine lab tests included a test for syphilis and vitamin B1- thiamine- low in alcoholism. The patient reported that he did not know that he was an alcoholic and that previous physicians had not made this diagnosis.

Not everything neurological is Lyme: clearly not. In this case the diagnosis was fairly straightforward. Interestingly, some studies have shown that these neurological deficits can improve with abstinence. We shall see.