Lyme disease tests: New and Old

Diagnostic testing

Testing may be difficult when the standard diagnostic test fails. The gold standard, the identification of the organism by DNA or culture is frequently not feasible or available. Several antibody tests have been developed which may be helpful, but these tests have a low sensitivity, missing many cases. As an adjunct, a newer technology involves lymphocyte stimulation.  When cells (T lymphocytes) are exposed to proteins derived from the pathogen, cell mediated responses such as the release of gamma interferon can be measured indicating prior exposure to the pathogen. This test may have limitations and likely should only be used adjunctively.

Of course, we are talking about diagnostic procedures for Mycobacterium (tuberculosis).

Let’s talk about Lyme.

Testing for Lyme remains problematic.  Tests have been inaccurate, unreliable and at times and prohibitively expensive. 

We depend on clinical diagnosis. But sometimes we are not sure.

All currently available tests have pros and cons.

A lot of labs are suddenly getting into the Lyme testing business.  Many tests are in development.

The Western Blot remains the first line test.  It is important that a Western Blot be ordered, not just an ELISA with reflex to Western Blot. The ELISA is not dependable. An alternative ELISA, the C6 peptide may be ordered. Usually negative, sometimes it is positive when other tests are not.   A C6 from LabCorp/Quest is not adequate, a numerical value, available from various reference laboratories is needed. (MDL, IgeneX, many others).  In my experience, values under the lab recommended positive cutoff may indicate exposure to Lyme.

PCR (polymerase chain reaction) is a test which measures the presence of specific DNA.  Most consider this the gold standard.  DNA testing for Lyme also has a low sensitivity and misses most cases. The only specimen available to test is usually blood. Lyme is a tissue pathogen and may be present in the blood in very small numbers. This is different from viral illnesses such as HIV and Hepatitis C where large numbers of viral particles are present in the blood.  Many clinical labs are working on ways to improve the sensitivity of the test.  Urine may be a better place to look.  Lyme lives in the bladder and is shed in urine. One such test is offered by Quest. So far I have not found any positives. Other clinical labs may have better results.

This is not to be confused with the antigen capture test or the nanotechnology test, which also looks at urine samples.

The Nanotrap captures tiny amounts of proteins found on the surface of the Lyme bacteria. The test so far only measures outer surface protein A, or OspA.  This protein corresponds with the 31 band of the Western Blot.  Remember, Lyme is a clever “shape shifter.” This protein is expressed when the spirochete is attached to the gut of the tick. After infection, this protein disappears (downregulated) and Osp C (upregulated) takes its place. So, the current test is really only helpful for acute Lyme and -- maybe late-stage Lyme. After many months of infection, this protein (OspA) may reappear. The test as it sits is not clinically useful for most patients.

The scientists at the Center for Applied Proteonomics and Molecular Medicine, George Mason University, new to the field, were shocked that the so-called experts in the field insisted that chronic Lyme is not real.  To get "proof of concept" and the blessing of the IDSA, ILADS and the CDC, the new test was designed to detect only acute Lyme. The CDC admits that current testing (two tier test) for acute Lyme is flawed, and THERE IS AN X-PRIZE award for the first lab to develop an accurate acute Lyme test!  

Now there is general proof of concept. An improved test, said to come out soon, will look for many proteins, including OspC.   The improved test may be extremely helpful for the diagnosis of all stages of Lyme disease.  

A culture test from ALS is available. After being slammed by the CDC, the lab is actively engaged in studies to achieve FDA clearance.  The blood culture test has two drawbacks: cost and the patient must be off antibiotics for 2 months before the test is performed. Otherwise, it may be a very good test. At first I was concerned that the test found Borrelia species rather than B. burgdorferi. This may be an advantage rather than a disadvantage because Lyme disease is a borreliosis comprised of an expanding menu of species and strains.

Another test, Lymphocyte transformation test, is available from Pharmasan and others. This test measures a different kind of immune response.  It is based on FDA approved, commercially available TB tests.  The test measures the innate immune response. An initial response which predates acquired immune responses which lead to antibody production. Immune cells patrolling our blood and tissues have the ability to recognize patterns which shouldn't be there (Pattern Recognition Receptors). Killer T cell lymphocytes are the first line of defense. Killer T cells attack offending antigen (Lyme) and turn on other immune responses including the production of cytokines, modulators of immune regulation.  When this reaction occurs it leaves behind permanent T memory cells. These memory cells, when exposed to Lyme antigens react by releasing gamma interferon, a potent cytokine.  This reaction can be measured.  This test may be considered a complement to other tests, such as the Western Blot test. It is somewhat costly.

From a cost perspective, in my experience, it is best to start with a Western Blot (MDL) which provides images and alternative diagnostic criteria.

A fair question might be: since the Western Blot only shows exposure to Lyme, not the presence of actual infection, shouldn’t a test that directly measures Lyme infection be done, to prove that Lyme is there?

Here is my answer:  Since Lyme persists in mice, dogs and monkeys and test tubes and the test subject has symptoms compatible with Lyme disease, it is reasonable to conclude active infection is present. Further testing is not needed.  Additional tests may have false negative results only adding a layer of unneeded confusion. The goal of therapy is remission of symptoms, not eradication of organisms.

At the end of the day, in many cases, the diagnosis of Lyme disease is clinical and the role of lab testing adjunctive only.

Alpha gal allergy (meat allergy) and lone star ticks

A 40-year-old patient developed a meat allergy after a tick bite.  This condition has been reported in association of lone star tick bites.  She previously lived in a rural part of South Eastern Virginia and actively engaged in gardening and she had two dogs. Over a period of years, she had numerous tick bites. On one occasion she developed a bull’s eye rash after a tick bite and was treated for Lyme disease. It was after this she noticed a reaction to dairy products, causing hives. She had acquired the tick-bite meat allergy syndrome.  She was a long time vegan. One would have thought “meat allergy” wouldn’t be a problem. It was. Dairy was surprisingly an issue. She found that she was sensitive to trace amounts of meat. For example, she reacted to vegan food prepared in restaurants that also served meat. She became sensitive to leather shoes and leather belts. She began to have hives daily. Nothing could control the reactions.  She became progressively sensitive to a wide array of inciting agents. Chemicals, other foods, environmental changes (change in temperature), non-specific scents would cause reactions. Hives were a daily affair, recurring several times. The hives were severe covering large swaths of skin, itching like mad. The hives were minimally controlled with high doses of antihistamines. She had several scary anaphylactic reactions and carried an epi-pen at all times. The illness was progressive and frightening. In addition to allergic manifestations she suffered with: chronic fatigue, migratory joint pain, numbness and tingling and brain fog.  

She tested positive for alpha gal antibodies.  Alpha gal is short of galactose-alpha-1,3 galactose. Alpha gal is a carbohydrate not found in our bodies but present in other mammals we ingest, i.e. cows and pigs.  A protein in lone star tick saliva promotes the production of antibodies against the foreign carbohydrate leading to the disorder.

Alpha gal allergy is not a benign disorder.  Despite claims to the contrary, patients may become sensitive to many other foods, including dairy, eggs and poultry.  In the case of this patient, she became reactive to foods high in histamine and histamine promoters (such as tomatoes, eggplants, strawberries etc.).  She developed a generalized, systemic mast cell disorder. To the best of my knowledge, this has not been described in literature.

When I first met her, several months ago, she had acquiesced to the notion that hives would always be with her.

But we got her better.  

Treatment has included: therapy for mast cell activation disorder and long-term antibiotics. The former daily hives now occur once monthly at most.

Mast cell programs have previously been described.  A low histamine or mastocytosis diet is required.  In addition, high doses of antihistamines: H1 and H2 blockers, Singulair (leukotriene blocker) and cromolyn (mast cell inhibitor) have effectively controlled her symptoms.

Long-term antibiotics have been very helpful, controlling fatigue, numbness and tingling, joint pain and brain fog.  We she came to see me she was only worried about alpha gal not realizing how much persistent Lyme was affected her.

This disorder is associated only with bites from lone star ticks (perhaps chiggers) but not deer ticks.

Yet another reason to avoid tick bites at all (reasonable) costs.

Unsuspected high level parasitemia (babesiosis)

 Everything I said in the last post needs to be taken with a grain of salt. 

A 40 year old patient from Texas recently presented to my office with:  fatigue, headache, crawling sensations, shooting ear pain, feeling hot, hearing loss, lack of endurance, poor sleep, sound sensitivity, brain fog, swelling of lymph nodes, irritability and other strange sounding symptoms.

She denies ever experiencing: night sweats, air hunger, fevers, depression, mood changes or tearfulness.

She had previously tested positive for Lyme antibodies.

This patient's Giemsa stained blood smear shows a high level of parasitemia. (High levels of Babesia in the blood).

 

Babesia antibodies were not present. Only B. microti and B. duncani tests are available.  LabCorp is offering the B. duncani or WA1 antibody test again.  Direct examination of freshly prepared stained blood smear remains the gold standard for the identification of the organisms. Other, high tech modalities may be limited, especially when the particular species is unknown. These other tests may include: PCR and FISH.

Some patterns of disease are frequently observed, but the disease as a whole, remains quite unpredictable.

A coinfection cannot be excluded based on history alone. On the flip side, a negative blood test does not exclude the presence of coinfection. In this case Babesia. All available Babesia tests are imperfect.

One of the many challenges.

The Swiss Agent

From STAT we learn that Willie Burgdorfer, the Swiss microbiologist who discovered the Lyme bacterium also discovered a long discarded something else. The mysterious sounding Swiss Agent. Sleuthing the mysteries and controversies surrounding Lyme, modern day researchers have uncovered 40-year-old papers which denote the discovery of the Swiss Agent bacterium. In a note to himself, Burgdorfer asked himself: “I wondered why somebody didn’t do something.”  “Then I realized that I am somebody.”  The agent is known by science to be Rickettsia Helvetica. The organism is purported to cause a Lyme-like illness. The primary investigator at the CDC told the author that molecular biology methods will uncover the germ but the process will take several years. * (Their priorities are clear).  Infection with the agent and associated illness is better known in Europe. It is said to cause debilitating symptoms including: fatigue, headaches, muscle weakness, meningitis, facial paralysis and (sarcoidosis?). I am not vouching for the veracity of this statement.

The paper lays bare, in the starkest terms, the gist of the issues central to the Lyme wars, naming names.

Rickettsia are a genus of tiny, gram negative, obligate intracellular bacteria. Intracellular bacteria are notoriously difficult to eradicate. The best known disease caused by Rickettsia is the redundant sounding Rickettsia rickettsii which causes Rocky Mountain Spotted Fever. RMSF is one of the most severe and potentially devastating tickborne illnesses and thankfully is rare. Many of my patients test borderline positive for RMSF and I have long considered this evidence an unknown cross-reacting species of Rickettsia.

These germs are primarily treated with doxycycline. This is another reason why doxycycline should always be incorporated into the treatment of patients with tickborne illness, at least early on, unless there is a compelling reason not to do so.

I suspect this exotic sounding germ: The Swiss Agent – is a relatively minor and fairly benign coinfection. 

We do not need another explanation for the chronicity of Lyme. The evidence, both clinically and in the laboratory is clear.

The article states the IDSA position is that Lyme is characterized by a bull’s eye rash and “pinpoint” lab test and cured with 2-4 weeks of antibiotics. Really?

The Lyme syndrome is consistently a product of Lyme (borreliosis), babesiosis and bartonellosis. The exact species of which is more often than not, an unknown.

A simple categorization based on stereotypic symptoms is more common than I would have once thought.

Babesiosis: recurring flulike symptoms, night sweats (or day sweats), air hunger, low grade fevers – usually in the late afternoon and depression with inexplicable sudden tearfulness (even in macho men).

Bartonellosis: Pain in non-joint regions (tendons, muscles, plantar fascia or bottom of feet, “shin splints,” neck pain, headaches and occasion characteristic rash. Other symptoms such as those of interstitial cystitis are also relatively common.  Rather than depression, these patients complain of anxiety, irritability, anger, (Lyme rage) and other psychiatric symptoms.

Lyme: Everything else.  Fatigue (all 3), Exhaustion, poor sleep, migratory joint pain, cognitive dysfunction with brain fog, trouble finding words, trouble thinking clearly, episodic confusion, getting lost etc., weakness, numbness and tingling and usually others symptoms suggesting broader multisystem connections, for example: floaters, ringing in the ears, racing heart, change in bowel/bladder function and others.

Sound familiar?

Patients will have visited many doctors and been told: they don’t have Lyme, they have fibromyalgia or chronic fatigue, they need to see a psychiatrist.

Optimal treatment options are becoming clearer over time.  I know longer write about the details of therapy.  Treatment needs to ultimately cover Lyme and Lyme persisters and the two other prominent coinfections, comprising the “nuclear triad.”

Appointments in my office are currently available. Our hyperbaric oxygen therapy at 1.6 ATA (20 feet underwater) is currently underutilized and “on sale.”

Lyme - ALS and the practice of medicine

This 54-year-old female is happy. Rightfully so.  She has been pulled from the grave.

5 months ago she was handed a death sentence, ALS (Lou Gehrig’s disease), the worst kind at that.  She found she suddenly had trouble speaking, becoming hoarse then losing the ability to talk. Shortly thereafter she found it hard to swallow. She lost weight. She developed weakness of the right upper and left lower extremities. She went to a neurology clinic at a famous tertiary care center.  She was diagnosed with bulbar ALS, a most severe and deadly form. The expectation was that she would need a feeding tube followed by ventilator. The doctors at the clinic continued to follow her downhill course over a three-month period. An EMG test showed the expected motor neuron denervation.  The patient reported an ultrasound exam of superficial nerves showed nerve swelling rather than atrophy as expected.   Scratching collective heads, the neurology team decided to do a lumbar puncture. Lyme was considered. The endorsed DNA/PCR test was negative.  One of her doctors ordered a non-sanctioned test:  Lyme Western Blot antibodies in the CSF. The result was positive. A blood test for Lyme (ELISA first) was negative.  Nonetheless, she was referred to an ID doctor who was sufficiently impressed to prescribed IV Rocephin. After 2 weeks routine monitoring showed an elevation of the kidney function tests, BUN and creatinine and antibiotics were discontinued, despite the fact that she had already responded favorably to the 2-week course of treatment.  She told me her neurologists, expecting rapid deterioration, were recently surprised to see her walk into their office under her own power.
This was the point at which I met her.

When I first met her (6 weeks ago) she could barely eke out a few unintelligible vocalizations.    She coughed constantly (due to aspiration secondary to inability to swallow I suspected).  She had other limb weakness and joint pain and swelling.

She had lost 15 pounds and was clinically dehydrated, not in renal failure. Patients with neurological dysphagia (impaired swallowing) have trouble swallowing “thin” water.  Per my recommendation, with the addition of thickener to fluids, she was able to hydrate well and the kidney tests normalized.

After 6 weeks of IV antibiotics, our second visit, she spoke with me with a very hoarse, gravelly but also very intelligible voice. She was no longer coughing. She was getting stronger and becoming more active day by day.

During examinations she evinced typical neurological signs associated with ALS, including:  hyperreflexia, weakness and abnormal reflexes (Hoffman and Babinsky).

Her illness also encompassed my other typical Lyme features:   Brain fog, joint pain, night sweats and air hunger.  These symptoms were in various stages of getting better.

Lab results: Positive Lyme Western Blot IgG, 8/10 bands MDL, Giemsa blood smear positive for parasites (presumptive Babesia).

More of the story unraveled.  She lives in the country near Frederick Maryland.  She loves to garden.  She also is an avid camper in Southern Maryland.  She recalls finding a red patch on her right forearm 2 years which went away with the application of cortisone, given the diagnosis eczema.

She went back to the original neurology clinic and was told that she should only get 28 days of Rocephin based on CDC guidelines.  She also patient sought the opinion of another University based neurologist who said keep treating for Lyme.

Motor neuron disease or ALS is a known, albeit extremely rare manifestation of neurological Lyme disease.

Of course there are no guidelines for the management of Lyme induced ALS.  I suspect the tertiary care specialists (recommending antibiotics be stopped) were extrapolating from obsolete IDSA guidelines, predicated on the belief that Borrelia spirochetes do not persist after antibiotic therapy, a thesis that has been thoroughly discredited and longer the dogma of mainstream thinking.

This must stop.  Lives are at stake.

Health care professionals need to know what Lyme is and what the practice of medicine is.

Lyme is a new and emerging disease, an epidemic of epic proportion with the potential to kill and maim.  The clinical manifestations of the disease are protean.  The extent and severity of the disease has not been recognized by the medical profession and public health officials.  Progress towards a better understanding of the illness has been mired in war of ideas (driven by egos of certain individuals in the academic medical community). Very little research has been done and we sadly know very little about this new disease which reared its ugly head 40 years ago. In a general sense we do not know the optimal therapies for the management of the illness. We know even less about specific variations of therapy which may be optimally effective for the widely divergent clinical presentations of illness.

The practice of medicine is the application of the current iteration of the healing arts as they have evolved over hundreds of years. Today's doctors are better informed (much more is known) than their forbearers of years gone by. By the same token, doctors must be cognizant of the certainty that their future replacements will see them in the same light. The practice of medicine is based on a complex synthesis of science, fact, experience, educated guesses, empiricism, judgement and perhaps philosophy, prescribed by a thoughtful (hopefully intelligent) physician who is committed to his  creed and solemn responsibility. My dad (a surgeon) always said medicine is a calling, not a job. A bit preachy, but true.

Lyme patients frequently suffer a slow, smoldering sort of death with a quality of life comparable to that of terminal cancer patients.

Contemporary notions of medicine, created by institutions and corporations demand tangible metrics by which physicians be judged.  This may or may not work.  Currently the wrong metric is being applied, i.e. following guidelines.  This is bean counting.  What is important? the patients - of course. This may not be obvious to the institutions that oversee medicine.  The primary metric that should be followed is patient outcomes. This is the only useful measure, when the disease, as is the case with Lyme, is complex and poorly understood.

The "system" should learn from doctors who make their patients better, not condemn them, as is frequently the case.

What do you do when you are bitten by a tick?

What do you do when you are bitten by a tick?

A patient pulled a tick off a thigh 10 months ago. He watched for a rash or other symptoms.  Nothing happened and the incident was quickly of sight, out of his mind.  Three to four months later he started to generally feel crummy, tired and achy.  He thought he was just run down, probably just stress at work and at home. He was confident things would soon clear. But they didn’t. The fatigue turned into bone crushing exhaustion. He found he was losing his mental edge. This former marathon runner was finding it hard to get out of bed; his ability to think clearly and his short term memory were increasingly impaired. He scheduled a routine physical with his family doctor and requested a Lyme test. His doctor informed him that everything looked good except the Lyme test which was positive. The GP ordered 3 weeks of doxycycline. The treatment did not help at all.  He returned to his family doc who said he was not surprised the treatment failed but there was nothing more he could do. The doc said that the 3-week therapy was all the CDC would allow. After cajoling, the primary care physician agreed to prescribe an additional 2-week course of doxy but warned it would not help. The prediction came true.

I saw the patient a couple of weeks ago as he weakly limped into my office having trouble getting onto the examination table. He admitted to increasing confusion and bouts of disorientation.

Where did the notion that the CDC only allows 3 weeks of doxycycline come from? How did the prescient physician know another 2 weeks of doxy was not going to help?

The CDC links with its strategic partner, the IDSA.  The IDSA wrote guidelines 10 years ago which it still apparently clings to.  Let’s see – the spirochete responsible for Lyme disease was discovered in 1982: for all intents and purposes the disease we know is 34 years old. Therefore, guidelines written 10 years ago were penned without the benefit of knowledge garnered during the entire last third of the disease’s life.

The guidelines include “facts” which we now know to be clearly incorrect. For example, the documents states there is no scientific plausibility for the notion that post-Lyme syndrome is due to persistence of organisms. The last NIH sponsored study by Fallon which suggests organisms persist was not published until 2007. The lead author believes in persistence. Animal studies in mice, dogs and primates support persistence. Test tube studies support persistence. Even a xenodiagnoses study recently showed that pristine ticks can acquire Lyme infection from humans with early Lyme previously treated by CDC guidelines. Most of this evidence was not available in 2006.

The IDSA guidelines do not discuss a clinical scenario like the one discussed in the patient’s history. The guidelines strangely discuss acrodermatitis and lymphocytoma, rare conditions known only to exist in Europe caused by species of Borrelia not found in North America. The guidelines, written with a didactic, professorial flare, were out of touch will the realities of clinical Lyme disease in America at the time they were written.

The guidelines do make a distinction between early Lyme and late stage Lyme, especially when it involves the central nervous system.

The patient’s clinical course most closely resembles the late stage, central nervous system involvement type.  The guidelines recommend that 3-4 weeks of intravenous Rocephin be considered (along with a spinal tap).  The 21 days of doxycycline is not what the guidelines recommended for the patient. The family doctor was confused. (who wouldn’t be?)  The guidelines state that only partial resolution of symptoms should be expected and that the impulse to prescribe longer courses of therapy be stifled. This reasoning should be questioned in the face of clear and convincing evidence of Lyme persistence.

To summarize: The family doctor mistakenly thought that the CDC would only allow a 3-week course of doxycycline and the doctor knew that treatment was destined to fail, even when extended by a couple of weeks. I assume this understanding was the result of years of clinical experience. (The CDC does not have the authority to control a doctor's prescriptions). The IDSA guidelines, linked to the CDC, probably recommended a course of intravenous therapy for this patient, not the 3 weeks of doxycycline. What is clear is that the obsolete documented warned doctors the therapy would not work (only be partially effective).

Actually the IDSA guidelines were deleted from the United States DHHS guidelines clearinghouse because they are more than 10 years old. The only listed, vetted and currently active guidelines are those written by ILADS.

Unfortunately, the CDC, IDSA and the institutions of American Medicine do not recognize ILADS. 

From the perspective of mainstream medicine these guidelines do not exist. In the absence of guidelines, the system tells us answers must come from the appropriate vetted experts:  Board Certified Infectious disease specialist.

Doctors call LLMDs do not exist according to mainstream medicine.

The Lyme paradigm war has been raging for decades and shows few signs of letting up any time soon.

This patient in fact saw an Infectious Diseases expert before seeing me.  The expert said the patient never had Lyme disease in the first place because the test results showed IgM antibodies not IgG antibodies. This misconception is discussed elsewhere in my blogs, somewhat exhaustively.  The patient disagreed with the assessment, as do I.

The system predictably got it wrong for a number of reasons, not within the scope of this discussion.

A recent book written by Afrin implores us to “Never Bet Against Occam.” The theorem informs us that the solution (correct hypothesis) to a problem is generally the simplest one: the one requiring the fewest number of assumptions.

The expert made a bad bet.

The patient was bitten by a tick and got sick. Occam informs us the patient has Lyme disease or something that looks and acts a whole lot like it.

This brings us back to the original question. What do you do if you are bitten by a tick?

The answer has to be to take antibiotics for some duration, in hopes of preventing something like the disaster that befell this patient.  The correct regimen is unknown and is a matter of discussion and opinion. But, the correct answer to the question is NOT:  do nothing and wait to see if a rash appears.

A long, difficult journey likely awaits the unfortunate patient who, largely based on widely disseminated misinformation, made the wrong choice. 

Patterns

Patients suffering with Lyme disease and related ailments are frequently discarded and disenfranchised by a medical system which disavows the reality of their illness. Patients so suffering have a myriad of complaints and symptoms which may appear bewildering to the modern doctor allowed 6 minutes by managed care or to the super-subspecialist who views them through a narrow lens. The would be/should be diagnostician comes to the bedside of the sufferer with a suitcase of suppositions and biases. From the start, doctors these days seem possessed by an annoying compulsion to make a diagnosis as quickly as possible and deliver the news to the patient as soon as possible, preferably by the end of an initial 6-minute encounter. Today’s healers, along with their patients, cling to a belief that clinical diagnoses can be supported by technology of one sort or another. To the extent that a patient’s history can provide an underpinning of diagnosis, medical clinicians expect a narrative that makes sense within the context of a particular frame of reference. That frame of reference is largely based on mainstream notions of disease.

Within that culture (mainstream medicine) chronic Lyme disease is nonexistent fiction except in the minds of confused patients of who spend too much time on the internet or in the minds of  charlatans (Lyme doctors), poised to take advantage of long-suffering souls or who are at best well-meaning but poor clinicians chasing treatments based on an ill-conceived diagnosis “du jour.” Before the 6-minute doctor walks into the patient exam room the prospect of a diagnosis of chronic Lyme is nil.

The early focus is on the patient history. Patients present with a hodgepodge of incoherent symptoms as perceived by our doctors. Doctors, who are taught to look for patterns seen none at first blush. When a doctor sees a patient the gears in his mind are spinning (if he’s had his coffee), looking for connections with the quick assemblage of possibilities, the differential diagnosis. Of course doctors can only diagnose what they know. And doctors are taught that is much more likely for a common disorder to present in an unexpected way than for a rare disorder to present itself in the context of the same confusing patient presentation.

With this said, most clinicians think about the same diagnostic possibilities: depression, somatization disorders (psychosomatic), fibromyalgia, chronic fatigue syndrome and autoimmune syndromes. Pieces of the story which may not comport with the chosen diagnosis are conveniently excised. The clinician having quickly formed an impression, even within the context of a brief encounter, shares the presumptive diagnosis with the patient and makes a referral or writes a prescription on this basis.

Today, the more enlightened mainstreamers understand the concept of post-Lyme or post treatment Lyme syndrome. Still, this disorder is described within the context of clearly established early Lyme, previously treated with persisting symptoms. The description of the syndrome is fairly limited: fatigue, brain fog, aches and pains, numbness and tingling and perhaps a few other symptoms. But this diagnosis is made reluctantly. The diagnostician, generally a biased infectious disease specialist, demands evidence of a tick bite, perhaps a rash and “dependable” affirming laboratory findings. Should the diagnosis be made – grudgingly, there is no offer of treatment. Instead patients are told they will generally improve over time, or not -- no further thought given as the specialist moves on to the next patient.

Most infectious disease experts spout that Lyme doctors erroneously make the diagnosis, more often than not, in the absence of evidence of a tick bite or a positive blood report. Not only is chronic Lyme the wrong diagnosis, but the patient is said to have never have had Lyme at all.

The process described above occurs with regularity and predictability. Of course patients, the sick and the uninitiated, have no idea what lies in store when they dial the family doctor’s office to schedule an appointment.

The fight over Lyme has been ongoing since the disease was first named in 1977. Polly Murray, the first diagnosed patient, who shared her woes with a famed doctor at Yale was a bit put off when a new disease, “Lyme disease”, was announced to the world, because it was described as a disorder characterized by joint pain. What about all the other symptoms which had been going on and on for years? She was told: No disease causes all of those symptoms. This oft mentioned refrain has been thematic until the present.  No disease can cause all of those symptoms. Doctors do look for recognizable patterns of symptoms. This is why chronic Lyme symptoms are easily subsumed by the diagnosis of chronic fatigue syndrome or fibromyalgia. The shoe fits – more or less. In 1977 even these categorizations of illness were decades off in the future.

Previously the best fit was psychosomatic disorder. As I was taught, a positive review of symptoms (positive symptoms in so many, unrelated domains), is itself evidence of a psychiatric basis for all of the complaints. Again, we have to go back to the idea that doctors only diagnose that which they know.

But there are diseases which cause seemingly unusual constellations of symptoms. In her book, Polly Murray somewhat poignantly tells the story of one physician who carefully listed to her and said: He believed there was something physically wrong (validating) but medicine did not yet have the tools to understand, diagnose or treat the disorder and he hoped that at some future date things would change. Why is this poignant?  Doctors feel annoyingly compelled to make a call, provide a diagnosis, a label. The “I don’t know” diagnosis is rarely employed. Unfortunately, once a patient is so labeled, the diagnosis, frequently one with negative connotations, becomes indelibly tattooed to the patient’s forehead, prominently displayed when the patients seeks opinions from subsequent medical practitioners.

Doctors have a hard time understanding their world in proper perspective. Like others, they are caught up in the moment. Their professional world occupies a point in space in time. Things are ever changing.  Knowledge is ever increasing. The truths of medicine and science are always a moving target, always outside our grasp. The current state of the art will invariably be proved wrong. The current paradigm will be inevitably replaced by a new one as any student of history clearly knows.

This brings us to issues of the Lyme patient and the Lyme doctor. Lyme patients more often than not present with patterns of symptoms that are seen over and over again.  The symptoms are neither random nor manifestations of a modern epidemic of madness.  Lyme patients may complain of fatigue, disturbances of energy and sleep, pains which move about, strange sensations, numbness and tingling, cognitive changes and others. Those with Babesia may consistently have flulike symptoms, night sweats, air hunger and emotional changes. Those with Bartonella may have certain rashes, heel and shin pain, other sorts of muscle pains and specific psychological symptoms etc.

The Lyme doctor differs from his colleagues because he resides in a world of other possibilities. One in which Lyme is placed highly in the ranks of differential diagnoses. He is someone who knows that the problems of Lyme, diagnosis and treatment are far from worked out. Her certainly understands that current technology does not give us the answers.

But I think the Lyme doctor is one who puts his patients above all else. He tries to cobble together that which is known with that which is suspected and go out on a limb, offering treatments which may help the Lyme sufferer, at the same time avoiding harm, such treatments based on science and various clinical resources, but outside the standards offered by the narrow prescriptions of the accepted paradigm of the day. Speaking for myself, the Lyme doctor is one who uses the tools handed him by the profession but in some unique ways, caring more about his patient’s welfare than his own or what his colleagues may think of him. The Lyme doctors allows himself the luxury of critical thinking in a day when that particular commodity is eschewed, in favor of guidelines, the product of our institutions. The danger of thinking for yourself is that you might get it wrong. Powerful forces say you are. But clinical experience tells us we have it right, so we persevere, and thousands of lives are on the line.  

The Lyme brain and nootropics

Cognitive impairment is one of the most disabling symptoms seen in patients with Lyme disease.  The symptoms can be quite subjective. The symptoms can be very disconcerting and at times disabling. The complaint is almost universally overlooked by general physicians and neurologist. After all, there is no evidence of dementia.  Many patients will pass neurocognitive testing, rarely offered and quite expensive. SPECT scans, infrequently performed, may or may not be abnormal and when abnormal brushed off as nonspecific. But as a patient recently shared with me, before Lyme she performed great at a high level job requiring timely completion of complex intellectual tasks; she can still get the job done but it takes 3 times as long. On this basis it is no longer financially viable for her to continue the consulting work and she is applying for disability. Doctors tell their patients: its normal to be a little slower after 50, it is natural for math skills to slip a bit.  Increased difficulty with word retrieval is par for the course with middle age.  Maybe to some extent this is true, but Lyme patients experience something qualitatively – and quantitatively different.  Mainstream medicine with its black and white world view is deaf and blind to the complaints of Lyme sufferers who may: get lost, confused, space out and put their cell phones in the fridge. If it is not Alzheimer’s disease, frontotemporal dementia, Lewy body disease, a brain tumor, a subdural hematoma, hydrocephalus, a prion disease or a few other conditions patient are told there is nothing to worry about. We know differently.  Of course the same Lyme patients complaining of brain fog also complain of fatigue. Frequently the two are intimately connected and it is hard to separate cognitive issues related to fatigue from those that exist independently. The question then is: what, if anything can be done? 

Clearly if we are dealing with germs in the brain we need to use antimicrobial agents which are powerful, able to penetrate into the brain and able to target the specific organisms of concern.  Typically, the focus is on spirochetes, pleomorphic variants, blood parasites, bacteria in blood vessels, biofilms and perhaps other organisms, like worms.

What else?  How do we make the brain work better?

Drugs that make the brain work better are called nootropics. The best known are stimulants.  Drugs like Provigil help with wakefulness. Clearly treating fatigue may help. Drugs like Ritalin, Adderall help with focus, attention and task performance. These drugs impact the neurotransmitter dopamine and are particularly active in the frontal lobe, executive function area of the brain.

Drugs like Namenda, commonly used in Alzheimer’s disease, negate excessive activity of the neurotransmitter glutamic acid caused by brain inflammation and related neurotoxins. Patients on this drug frequently find they are able to think more clearly.

Cholinergic drugs promote the activity of acetylcholine, a neurotransmitter involved with memory and other cognitive functions.  Rather than a prescription drug, I have found the supplement Procera (or similar) to positively impact cognition.

Do bile acid binders, cholestyramine and Welchol help?  In some patients the answer seems to be yes. I am not sure why.  Toxins?  I don’t think so. The prototypic neurotoxin, QUIN does not cross the blood brain barrier well, hence the use of drugs like Namenda. However, bile acids and cholesterol, both of which are lowered with bile acid sequestrants have signaling effects in the brain.

Glutathione may help, but only IV.  It may reduce the burden of free radicles, reactive species causing oxidative stress, negatively impacting function of neurons. In addition, mitochondrial dysfunction is directly connected to oxidative stress. Alleviated the latter promotes function of the former. Mitochondria in brain cells are essential for the production of energy.

Ketone bodies?  Some patients experience incredible improvements on an Atkins like diet. A ketogenic diet changes the brains fuel from primarily to glucose to primarily ketone bodies. This may result in neuroprotection, decreased brain inflammation, decreased oxidative stress and better mitochondria function.  Perhaps ketone supplements help as well.

Hyperbaric oxygen therapy.  For practical reasons most patients only have access to home units with offer a low pressure. A new unit can be purchased for as little as 5500 dollars. Patients who do the best spend 2 hours or more per day in the chamber. The treatment reduces oxidative stress, promotes glutathione and has been specifically shown to improve neuroplasticity with reversal of abnormal SPECT scan patterns.

Food for thought

( Nothing here should be construed as specific medical advice)

Babesiosis: species unknown.

This image is a copy (colors modified) of a Giemsa blood smear obtained from the blood of a 40 year old female 3 years of persisting low grade fever despite appropriate antimicrobial therapy.

Parasites seen within red blood cells assume a variety of shapes and configurations

Human Babesiosis, infection with B. microti was reported first in the 1960s. B. microti is still around, but most cases of human babesiosis are caused by another parasite(s) Three other species of Babesia are recognized by the CDC as known causes of human babesiosis in the US: B. microti, WA1 (B. duncani), MO1 and CA1. These parasites are nastier and are much more common (at least WA1). One study in 2011 found that 2% of the general population tests positive for B. duncani. Over 100 species of Babesia are known, many of which are known to cause animal disease only. Deer ticks and lone star ticks carrier many unknown Babesia species. In Europe B. divergens is a recognized cause of human babesiosis and considered more severe than human disease with B. microti.  This bovine parasite made the jump from cattle to humans proving the notion that such shifts occur in nature.

Babesia are malaria-like. They are pleopmorphic one cell protozoans, eurcaryotes (defined nucleus) which parasitize host red blood cells. The parasites have a complex life cycle. Sexual reproduction occurs in ticks (genetic material exchanged) and only asexual reproduction occurs in the host.  As with malaria, both genuses (Plasmodium vs Babesia)  have the habit of rapidly becoming drug resistant. Malaria is widely recognized and considered one the most serious public health threats globally. Malaria  infects 1/3 of the world's population, frequently announces it presence with acute high fevers and shaking chills and kills more than 600,000 yearly. Babesia is less lethal and more subtle. The incidence of infection and with which species is unknown and the subject remains uninvestigated. Guilt by association.  Babesia shares a common fate with its accompanying Lyme: dismissed and ignored by mainstream medicine. Babesia symptoms are nonspecific -- but not really. Remarkably, the symptoms of night sweats, sometimes fevers, air hunger, depression with weepiness (and others) are dependably seen. Babesia should be suspected with persisting low grade fevers. Most patients are diagnosed clinically because laboratory testing is unreliable, unavailable and expensive. Nonetheless, my policy is to test -- even in the absence of typical symptoms. Results are sometimes surprising.  For example, I recently found parasites in the blood cells of a man suffering with early onset dementia and all other tests were negative or ambiguous.

Antibody testing for B. microti is widely available. Unfortunately this is the rarer and milder version of the parasite. Testing for WA1 antibodies had suddenly become much more difficult. IFA (immunoflorescent antibody) testing has been more popular than the classic ELISA test. Similar information is obtained. Positive reactions are tagged with molecules that literally glow in the dark when viewed under a special microscope. The FISH (florescent in-situ hybridization) test offered by IgeneX is another option. Here the genetic structure of the parasites are tagged making the whole parasites glow in the dark. The test may not work for organisms of unknown genetic makeup. PCR tests pull out the parasites with a probe of primer DNA which binds the parasites and makes many copies. PCR also only works when the genetic structure of the parasites are known ahead of time.

I think the first line test is a blood smear. You don't have to know the species or DNA ahead of time. This does require a CLIA certified blood parasitology lab. The limiting factor is that the samples need to be prepared immediately otherwise parasites rapidly degrade and become more difficult to find.

My 40 year old patient has suffered with chronic fatigue syndrome and disabling chronic pain. Prominent symptoms include depression, headaches, joint/muscle pain and cognitive impairment. Her quality of life has been very poor. Symptoms have tenacious in the face of aggressive treatment. Standard antibody tests for B. microti and B. duncani have been negative. Two prior blood smears, a year apart were negative. Recently we found the above result. An active area of red blood cell parasites is clearly seen. Without PCR the result cannot be speciated. But since she suffers with tickborne illness and she has not travelled outside the US it is a pretty good bet she has babesiosis. Armed with this new finding, I ramped up the doses of anti-Babesia therapy beyond standard doses and combined several drugs in cocktail fashion. Finally, after years, the fevers are gone.

A vexing problem is that Babesia species, knowns and unknowns, have become increasingly difficult to treat because of widespread drug resistance. Creative, complex drug cocktails are increasingly becoming necessary to treat this frequently virulent and persistent pathogen.

Western Blot are frequently equivocal.

The results shown above are quite clear.

I am consistently able to find evidence of Babesia-like parasites in about 25% of my patients. In patients with soaking night the incidence is much greater. (I can only tests patients seen in my practice).

I suspect most of the unknowns are WA1. I have found that patients may seroconvert after treatment.

Babesia talk, all are welcome, space limited

ANNOUNCEMENT





I HAVE DECIDED TO OFFER A SERIES OF TALKS FOR PATIENTS AND OTHERS


PLACE: MY OFFICE, DOWNSTAIRS CONFERENCE ROOM
               15245 SHADY GROVE ROAD, ROCKVILLE, MD  (NORTH ENTRANCE)


DATE:  THURSDAY MARCH 24, 2016

TIME: 7PM

PLEASE CALL OFFICE TO RSVP, SEATING LIMITED,  301 528 7111


I will cover clinical features, diagnosis and treatment. I will be showing some slides of blood smears and discus the use of blood parasitology in making the diagnosis.


Unfortunately, one of the best tools for diagnosing babesiosis has suddenly been pulled from both LabCorp and Quest. The WA1 or B. duncani antibody test.  The B. microti test which is still offered although not as helpful. The vast majority of positive results, for years, have been B. duncani, the much more prevalent species. In 2011 a study found B. duncani in 2% of the general population and B. microti in 0.4% of the US population. B. duncani has a wide geographic presence, consistently seen along side Lyme in every locale. At this point I am only able to send this test to IgeneX for this valuable test.  It is available through a few other reference labs at a higher cost.

The withdrawal of the "WA1" test was  sudden and unexpected and without explanation. This is a real set back.

Western Blots in perspective

Doctor, can you help me understand my Lyme test, Western Blot?

Many patients spend a lot of time on the internet in efforts to understand the significance of mysterious numbered bands. What does it all mean?

As a starting point: lower your expectations. Lyme Western Blots, like all Lyme tests, lack accuracy and should be taken with a grain of salt.

A Western Blot is a second test, (IDSA/CDC)  a confirmatory test, used to confirm positive results from the initial test an ELISA - according to the IDSA/CDC. The CDC requires the second test because they believe the ELISA is inaccurate, leading to too many false positives, whereas, those in the ILADS camp believe the opposite. On the other side it if felt the ELISA test in nearly completely worthless because of false negative: it misses the majority of cases. Therefore the ELISA is skipped and the Western Blot is ordered directly. In addition, the Western Blot, although more helpful, is still inaccurate in many cases.

The two views are so divergent that mutual understanding and compromise, for the present time, is impossible.

For purposes of this discussion, all of these tests attempt to measure an immune response mounted by a patient who has been exposed to Lyme, or Borrelia burgdorferi. These tests look for antibodies made by an infected person's immune system. These antibodies are tiny proteins, also called immunoglobulins.

These discrepancies are rooted in the early days of the disease. The Lyme bacteria first described in 1982. Soon thereafter scientist went to work developing new diagnostic tests.  Lyme, viewed as a new and emerging disease was thought to be rare and geographically confined. This assumption may have lead to problems with test development from the outset.

The Lyme tests observe reactions between antibodies (from found in patient's blood) and antigens  derived from the Lyme spirochete. This sounds straightforward but it isn't. When a Lyme patient's blood is combined with chopped up pieces of Lyme, an antigen--antibody reactions occur which may be seen as clumping. Many antibodies, ( and there are many thousands), unrelated to Lyme, may still adhere to antigen in the laboratory. This is the nonspecific reactivity or background noise that always occurs with such tests. Scientist are charged with the task of removing the nonspecific clumping, leaving behind the true Lyme-antibody clumping. Not so easy. This call is something of an educated guess. The decision as where to set the bar is made by a committee of experts. To do a good job the experts have to know who has the disease. The experts need control sample taken from truly non-infected persons. If the disease is rampant and difficult to diagnosis and if many control samples are from non-symptomatic persons infected with Lyme the test will perform poorly - or not at all.

The scientist working on the tests found that many supposed negative control groups reacted strongly to the ELISA. This was unexpected and surprising. It was assumed that there was something unique about Lyme antigens leading them to elicit such a high degree of nonspecific, therefore falsely positive, ELISA reactivity. The notion that the high degree of reactivity might be due to a high incidence of infection in the community was not considered. Scratching their collective beards, the test developing scientist decided a second level of testing was needed to confirm the diagnosis. The Western Blot.

The Western Blot is used clinically for only one other infection I am aware of: HIV. This should raise a red flag.

A Western Blot is more sophisticated. Homogenized Lyme bacteria can be placed on a special strips and passed through an electric current. This process separates out the Lyme antigens based by their respective weights. The heaviest proteins (antigens) migrate to the bottom of the strip, the lightest stay on the top. When these strips are incubated with patient serum, lines form on the strip, representing individual antigen-antibody reactions called bands. From the start there was confusion about the correct use of this second tier test.

In the early 1990s it was clear to Lyme researchers that Lyme testing was disaster. Labs used different techniques and got very different results. A conference was set up in Dearborn Michigan in 1994. Researchers, lab directors and the CDC showed up. The goal was to come up with a standard metric so that labs everywhere would be reading from the same sheet of music when discussing Lyme test results. Lyme Western Blots are divided two tests. Two distinct classes of immunoglobulins (antibodies) are produced by our immune system in response to infection: IgM and IgG.  Western Blot criteria for these two classes of antibodies were discussed at the meeting. One group (Dressler) presented an IgM criteria of 2/8 bands for a positive result.  A second group, (Krupp) suggested a criteria of 2/4. Quite different. Each lab had used a different strain. N40 and B31 respectively. The researchers threw out the N40 test because of poor 39 band reactivity. It was agreed to use the 2/4 criteria. One of the 4 bands (37) was discarded at the last moment so the adopted criteria became the well known 2/3.  Strangely, IgG criteria for positivity, the well known 5/10, came from Dressler's research. In other words, one strain was used for IgM criteria and another for IgG criteria. Certain key bands were intentionally overlooked because of impact on the long discarded Lyme vaccine.

The researchers had one agenda, the CDC another. The researchers sought a uniform, consistent standard so they could reasonably communicate with each other. The CDC wanted a surveillance standard: a test that they could use to track the disease in different locations over time.

The conference never pretended to be in the business of finding an accurate diagnostic test for Lyme: rather a standard for research purposes only. The test that resulted from this meeting can be fairly called a CDC surveillance test. This test continues to be used erroneously for purposes of diagnosis. To makes matters worse, many clinicians believe the test can be used to reliably diagnose the disease. 

The Lyme bacteria possess numerous surface structures against which antibodies can be made. Bands show up if a particular antibody directed against a particular antigen is present in the serum in adequate numbers.

Multiple labs use different bands and different numbers of bands. Here I will get a total by adding IgM and IgG results together.

CDC tests looks at 13 total bands
IgeneX test looks at 28 total bands
Stony Brook test looks at 52 different bands.

In theory IgM bands precede IgG bands. IgM bands are associated with new infection. IgG bands are associated with older infection. Not always.  An effort to apply this principal to Lyme bands has led to endless confusion. In the case of Lyme the rule does not apply.  Lyme infection leads to strange antibody responses. IgM and IgG are jumbled up. The presence of one or the other or both usually has no special meaning.

As alluded to, some antibody responses are nonspecific (background responses) and some are very specific. Some are somewhat specific. For example the 41 band represents a spirochete infection but is not highly specific for Lyme. Some highly specific bands include: 23-25, 31, 34. 37, 39, 66, 83-93. Whether or not bands are reported positive or not varies from lab to lab. Some labs use computers and measures pixels. With this configuration a band is reported positive if it has at least 60% the pixels of control strip. Other labs do the eyeball test. An IND from IgeneX means a reaction, less than the positive cut off point was present. The word indeterminate from Stony Brook means something completely different. It means that at least one of the CDC bands is present.

These test results may or may not be helpful. Western blot results are a lot more helpful when clearly positive. Each clinician may interpret results differently because there is no standard, widely accepted criteria. Based on the state of the art and limitations of the test it should stay that way for now.

The diagnosis of Lyme is clinical. The Western Blot is a tool which may or may not be helpful.

Borreliosis, new and emerging species

A 38-year-old male sought my attention this week because of strange neurological symptoms in the aftermath of a tick bite. He lives in a small town around Richmond VA.  He has had a lot of tick bites over a period of years, ticks of various sizes. He and his family love to hike, camp and generally spend a lot of time in wooded area. In the early Spring of 2015 he found a tick on his calf which he removed. Within days, he developed a red expanding rash on his upper thigh. The rash encompassed the entire anterior portion of the upper thigh. He never developed a bull’s eye rash. The rash was consistently red. The lymph nodes in the groin become swollen and slightly tender. Within days of the tick bite, he developed an array of symptoms: fast heartbeat, anxiety, headache, tingling sensations, poor concentration and others. He went to the ER at the local hospital. He was diagnosed with panic attack and cellulitis (infection of tissues under the skin). Lyme disease was dismissed as a possible explanation. Nonetheless, he was prescribed a week of doxycycline for the cellulitis. He did not improve. He experienced progressive symptoms: neck pain, back pain, muscle twitches, strange vibrations, electrical shooting pains, tingling sensations, zapping sensations. He had a strange feeling of heaviness. He eyes become very sensitive to light. He developed tinnitus (ringing) in both ears and he became very sensitive to loud sounds. He noticed poor endurance and fatigue. It became hard to fall asleep. His cognition felt foggy. Memory was not as good. He had episodes of spacing out and concentration and focus has been a problem.

He went to his family doctor after a couple of months of misery. He was quickly evaluated. A few blood tests were done. The patient was invited back to the doctor’s office after several days and told he had a post-viral syndrome because EBV (Epstein Barr Virus) titers were high. Lyme antibodies were negative. The doctor recommended he wait it out. Things would improve. They didn’t.

In July 2015 he talked his doctor into ordering a whole set of tickborne disease tests at IgeneX. He was told the results were negative. He found a local holistic doctor who prescribed a month of 2 antibiotics and natural therapies. He felt worse. Two doctors now had reviewed the IgeneX reports and read them as negative.

It is only now that he seeks my help.

At this point the reader might be thinking the Western Blot results were somehow positive. This would be incorrect. Two doctors had not looked very carefully at the report. The PCR test for Lyme DNA was positive. IgeneX notes that the test is not specific for Borrelia burdorferi but may also pick other forms of Lyme, including B. andersonii, a contender for STARI.

News Flash. As I have been saying, there are other, mostly unknown species of Lyme. Just this week it was announced: new Lyme organisms discovered by researchers at the Mayo Clinic, modestly named, B. mayonii.

I believe this patient is infected with a variant Lyme strain. Therefore, the minimal reactivity on the Western Blot test would be expected.  The positive PCR was a stroke of luck. Likely vector: lone star tick;  likely pathogen alternative form of borrelia, not B burdorferi.

The diagnosis for this patient could be called Lyme disease. Borreliosis is a better term as it announces the fact that essentially the same illness can be caused by other Borrelia species.

By the way: Check out Fitzpatrick’s color atlas of dermatology. All of the images of EM rash are red patches, just like the patient had. None are bull’s eye.

Not your father's Lyme disease

Lone star ticks, (Amblyoma americanum). are taking over. They now comprise more than 80% of the small black legged, hard bodied ticks found in the D.C metro area and elsewhere. These guys are very aggressive. They may be hard to distinguish from their deer tick (Ixodes scapularis) colleagues. Adult females are easy to spot: white spot on top. The shape and coloration is somewhat different. Take a careful look with a magnifying glass and compare to pix on google images. The CDC party line is: Lone stars do not transmit Lyme; they transmit STARI which is a mild disease and easy to treat. The CDC website states it is unknown wich bacteria causes the syndrome. The CDC website says Borrelia lonstari was a suspect but “further research” showed this not to be the case. This “definitive” research is the product of a small study published by Gary Wormser (name familiar) in 2005. Thirty EM rashes were examined for B. burdorferi (classic Lyme) and B. lonestari. Wormser did not find the genetic signature of B. burgdorferi or B. lonstari (or any Borrelia species) Therefore, the case is closed. Incidentally, all cases were from the Cape Girardeau are of Missouri (along the Mississippi river). I leave it to the reader to make sense of this research.  It is said that an inhibitor in lone star tick saliva makes them an inhospitable host for B. burdorferi. Perhaps. Nonethess, multiple studies have shown that B. burdorferi can be found in lone stars.  A patient in my practice with PCR (blood) proven B. lonestari was amongst the sickest patients I have seen. The only lab that I know of that does this test is Clongen. What about Western Blots? This patient was negative except for band 41 at two reference labs.

The Western Blot (as we currently know it) may soon be obsolete as the mix of Borrelia pathogens changes. Clongen found many Babesia organisms in these ticks, species unknown. Laboratory testing for unknown species of Babesia is impossible, except for fresh, properly stained blood smears. Bartonella is already a complete mystery: I say no more here.

Diverse ticks (Ixodes species) around the globe are known to transmit Borrelia species causing a Lyme-like illness, referred to as Borrelia burgdorferi sensu lato. Rapid changes are occurring in the US. The spirochetes live in an expanded reservoir, beyond white footed mice; the species are different; the strains are different and of course the vectors are different.

The coinfections are different and may be complete unknowns.

Here are a few clues: Ehrichia antibodies equal lone star tick. Only Anaplasma in deer ticks. RMSF antibodies show up a lot. I am not sure what this means. Cross reacting Rickettsia sp?  RMSF occurs only in lone stars not deer ticks. Meat allergies (anti-gal) only from lone stars: can be devastating.

The Lyme disease and associated tickborne pathogens paradigm is changing dramatically and very quickly. Be cognizant as we move forward.

A 70 year old man with a decade of night sweats, neuropathy and elevated muscle enzymes

A 70-year-old male believes he has had Lyme disease for over 10 years, first diagnosed 3 years ago.

He recalls a tick bite 10 years ago which led to chronic symptoms, mild enough to be ignored.

Four years ago he was admitted to a hospital with acute neurological manifestations. Primarily he complained of poor balance and difficulty walking.

An EMG was positive for neuropathy. A brain PET (nuclear scan) showed diffuse but non-diagnostic abnormalities.

Despite this scan he remained cognitively sharp and still teaches high level math.

The diagnosis of Lyme was made 3years ago. Prior therapy with Omnicef, Zithromax and Mepron had been unhelpful.

He has numerous concomitant chronic disorders any of which may cause neuropathy: well controlled type 2 diabetes, pernicious anemia, hypothyroidism and MUGUS.

Features of his illness include: daily night sweats for over 10 years after the tick bite and persistently elevated muscle enzymes (CPK), unexplained.   

He had been already treated for more than 2 years: I have been treating him for only 3 months.

He improved fairly quickly with a doxycycline based cocktail.  Then Rifampin was added.

He reports that this is the first time he has not had night sweats in 10 years. Muscle enzymes normalized, first time in 4 years, and, neuropathy symptoms have improved and he is walking better.

This response was far beyond my most optimistic expectations.

Discussion:

Neuropathy: from the perspective of neurologists (in general) his neuropathy would most likely be due to diabetes. All of his “mainstream” illnesses are associated with neuropathy. Never count Lyme out – or perhaps Bartonella in this case. It takes a long time for neuropathy to improve. Symptomatic relief may have more to do with Benfotiamine, a product related to vitamin B1 I suggested he try.

Night sweats: His lab workup for Babesia was negative (including freshly stained blood smear). He had none of the other symptoms which are classically associated with Babesia infection, including air hunger and depression. Rifampin does improve eradication of Lyme persisters when added to other antibiotics but I think the response to Rifampin leads us to Bartonella. There are a host of new and emerging species of Bartonella seen association with tickborne illness.

Muscle enzymes: It is well documented that Lyme can directly infect muscle tissue and elevate muscle enzymes. Bartonella? Bartonella infection causes vasculitis. The bacteria reside within he endothelial cells which line blood vessels. The strange rashes that accompany the infection are a manifestation of inflamed blood vessels. Other causes of vasculitis (medical literature) may cause low grade fevers, night sweats and muscle abnormalities.

PET and SPECT scans may have limited value and be nonspecific. Results should be interpreted in this vane. Cerebral vasculitis may be a consideration.

No response: to Omnicef, Zithromax and Mepron. Additional clues that Lyme and Babesia may not be the most important players. Always start with doxycycline unless there is a compelling reason for not doing so. Doxy is a necessary component of the 3 drug regiment which killed Lyme in Dr. Zhang’s test tubes. It is perhaps the best anti-spirochete Lyme drug. Doxy treats numerous coinfections and doxy is very handy when 3 drug “cocktails” are concocted for Lyme patients. This patient had already experienced considerable relief from a doxy based cocktail before Rifampin was added.

Lyme is ever confusing and at times surprising. For me it is important to attempt to work out the mechanisms (pathophysiology) of symptoms in each patient which provides a basis for treatment going forward.

Are my hypotheses correct? It provides me with a narrative. Of course I am only making educated guesses.  Research one way or the other which could help us understand what is going on with this patient is not in the pre-contemplative stage. Nowhere near it.

Lyme is a tragic disease.

The CDC admits there are at least 300,000 new cases a year. There are a lot more. Most cases are missed or misdiagnosed.

The manifestation of this chameleon diseases are protean.

The disease threatens the premises which hold together the gestalt understanding of human disease. An acceptance of these mind bending notions would require serious revisions of uncountable chapters in medical textbooks.

In a sense this may be what the paradigm war is about. It is not about whether Lyme persists or how long patients should be treated etc. It is about a fundamental rethinking of disease with a new found appreciation of the contribution of microorganisms.

This notion both daunting and scary.

Come, gather round people wherever you roam
And admit that the waters around you have grown
And accept it that soon you'll be drenched to the bone
If your time to you is worth saving
Then you'd better start swimming or you'll sink like a stone
For the times, they are a changing

Bob Dylan