Paradigm shift

My patients with chronic Lyme disease may suddenly relapse after years of feeling well.

A new mouse study shows not just persistence of Lyme bacteria after 30 days of antibiotic treatment with ceftriaxone but “resurgence” of infection. The authors of the study tell us their findings are controversial and caution us not to change the way we treat patients based on these findings. Of course not.

The study is published in PLOS January 2014.  The levels of bacteria in experimentally treated mice were found to decrease at months 2, 4 and 8 but surge to pretreatment levels at 12 months. The DNA load of bacteria in in the group treated with salt water and the group treated with 30 days of antibiotics was the same at 12 months.  As seen in other studies, the post-treatment spirochetes were “non-cultivable.” They can cannot be cultured in laboratory media. These spirochetes were clearly different from their pre-antibiotic forbearers.  Other mouse studies have demonstrated non-cultivable organisms. It has been suggested that these bacteria are attenuated and do not cause disease. Various metrics performed in this study do not support this thesis. Although these spirochetes do not culture, they transfer to other mice via ticks used in xenodiagnoses. Intact, viable spirochetes were microscopically observed in the same tissues; joints, heart and blood vessels. 

A study published March 11, 2014 looked at stored serum from Lyme patients. PCR for Lyme in patient serum has always been a low yield test.  In 1/12 post treatment blood samples a genetically novel Lyme variant was found; and, in 20 pretreatment samples one Borrelia miyamotoi and two B. burgdorferi were found. These findings are surprising. Perhaps we do not have a good handle on the genetic spectrum of Borrelia species causing Lyme disease syndromes.

According to standard bearers of the disease like Steere, as described in his paper “Diagnosis of Lyme Borreliosis,” --  the 2 tier CDC test is essentially always positive in patients with disseminated disease after 4 weeks;  PCR of synovial fluid in patients with negative serology should not be performed because positive results will be false positives; and usually, patients with objective evidence of dissemination have one or more of the following:  EM rash, atrioventricular cardiac conduction delays, myopericarditis, facial palsy, meningitis and meningioradioradiculoneuritis (Bannsworth’s syndrome).

I think maybe we are talking about two completely different diseases.

In our patients (with Lyme disease) Western Blot testing is neither accurate nor dependable. In our experience IgG bands, especially the 5/10 discussed by Steere are almost never seen. Positive Western Blot responses are primarily IgM in all stages of the disease.  ( Regarding the Steere/CDC two tier test for Lyme It is fascinating to read that the IgM bands are based on Engstrom’s work using B. burgdorferi strain 297, that the IgG bands are based on Dressler’s work with Bb strain N40 and that the antigens in standard FDA approved kits come from yet a third strain of Lyme, Bb B31).  These studies were pre- 1994 and presented at the Dearborne conference.

When I find a positive PCR for Lyme in joint or body fluid it is essentially always a true positive result. The fault with PCR is low sensitivity. 

Aside from different sero-reactions, my patients with late, disseminated disease have: constitutional symptoms like fatigue; neurocognitive and neuropsychological problems; arthralgia (joint pain) with arthritis (inflamed swollen joints) rare; peripheral neuropathy and autonomic neuropathy and usually have none of the above manifestations.  Of course my patients do have arthritis, meningitis, radiculitis, EM and carditis, but these are exceptions, not the rule.  

I think I explain the split personality of the disease. The characterization of the disease from the perspective of academic medicine is based on inherent biases and the need to have something concrete which can be easily characterized and defined.  The other personality of the disease stems from a patient-centered clinical process. Medical practitioners know that disease is frequently not black and white and that it usually forgets to read the text books. 

Those on the academic side are interested in having a debate. They are by nature competitive and feel they have to prove they are correct.  Recently Barbour described the 3 decades long debate and compared the two sides, one his side: all of academia, science, public health authorities – on the other side: a few non-academic practitioners and patient advocacy groups. This is not a valid debate point. Many famous persons and institutions have been wrong throughout history.  And important medical academics like Fallon do in fact disagree with the main view. 

I think biases within the academic world are very important. For example:  “Germs are killed by antibiotics – end of story.”  Barbour elicits the image from “The Terminator” movie where a robot is turned to molten metal and magically resurrects itself as analogous to our thinking about Lyme bacteria suggesting we are imbuing the spirochetes with supernatural properties.  He proffers the concept that the remains of dead Lyme bacteria may trigger a post-Lyme syndrome. The science is saying something else. 

I suspect Lyme spirochetes are not entirely unique in their response to antibiotics. Many microbes are never completely destroyed by antibiotics and may contribute to chronic illness in some manner. This may apply to mycoplasmas and chlamydias for example. 

Academic medicine should take notice. Something unique and very significant is going on when patient groups are able to get laws changed in opposition to their unyielding views. The prevailing paradigm is changing.  New thinking requires the experts to set aside their egos and preconceived notions and take a fresh look at the problem with new eyes.

Babesia only

This 53-year-old male, formerly a serious athlete, has been sidelined since 2000 with a primary diagnosis of chronic fatigue syndrome. He suffered dehydration and hyponatremia, low sodium, after running a marathon, and has never been well since. His symptoms have included: severe fatigue, muscle pains, tendinitis and joint pains. Over many years he experienced significant ups and downs with reliable exacerbation every 4 to 6 weeks. During these episodes he had more fatigue and achiness, and felt more flu-like. He has never had any significant fevers, night sweats or air hunger.

He lives in an area were Lyme disease is endemic and spends much time outdoors. He has no recollection of any tick bites or EM rash. Testing for Lyme disease has been negative.  Co-infection testing has been negative except for a blood smear examination which showed the presence of intra-erythrocytic organisms compatible with Babesia species.

He has been treated specifically for Babesia and has improved dramatically over a 7 month course. Recently hyperbaric oxygen therapy was added and he has done even better. Of course antibiotics in Babesia programs also kill Lyme. 

People sometimes ask me: can you just have Babesia? In theory yes.   Infected Ixodes scapularis ticks can pick up an unpredictable “grab bag” of germs.  Any one tick will be infected with varied combinations of:  Babesia, Anaplasma, Rickettsia species, Mycoplasma species, Bartonella species, Lyme – a variety of strains, others?  Some ticks will be infected only with Babesia.  

Some suggest that hyperbaric therapy “feeds” Babesia, making it worse. This is not true. 

Recurring flu-like symptoms, ostensibly the calling card of Babesia have been gone for months. The cyclical exacerbations are gone.  He still suffers with fatigue but his pain is almost completely gone. He was recently able to participate in a sporting event without the severe consequences (utter exhaustion and horrible muscle pains) he has become accustomed to – and this is great.  

An inconvenient truth

The CDC has replaced the term post Lyme disease with post treatment Lyme disease syndrome and admit on its website that the cause of the syndrome is not known. The CDC says the cause of the syndrome is unknown but acknowledges research shows persistence in animals. The CDC claims that studies show no benefit from prolonged antibiotic therapy and that patients with this syndrome eventually get better without further care; both of these statements are wrong. Substantial, contemporary literature disputes the first claim and nothing supports the latter claim. The piece (CDC web page) dredges up the notion that patients who do not get better with 2-4 weeks of therapy have an "autoimmune" disease comparable to three other bacteria which cause the same sort of thing. Strep throat - rheumatic fever; chlamydia - the STD variety- Reiter's syndrome; and Campylobacter, a gut bug- Guillain-Barre syndrome. None of these other germs is anything like Lyme disease: the analogies are poorly drawn. These other bacteria cause localized infection: throat, genitals, colon: Lyme is a widely disseminating multisystem bacteria. Reiter's syndrome is an obsolete term now replaced with reactive arthritis.(at least use the correct mainstream terminology). I do not dispute that a variety of microorganisms cause autoimmune disease. But the existence of an autoimmune phenomenon does not preclude the role of chronic, persisting infection. Chlamydias are small intracellular organisms which do not clear easily. Latest research, 2010:

Controversial Treatment Approach Could Lead to a Cure

Keywords for this press release: reactive arthritis, Chlamydia-induced reactive arthritis, Reiter's syndrome, chronic ReA, Chlamydia trachomatis bacterium, antibiotic treatment, chlamydial gene transcription, heat-shock proteins, chlamydial protein synthesis, antibiotic combinations, doxycycline, azithromycin, rifampin

Researchers from University of South Florida College of Medicine found a combination of antibiotics to be an effective treatment for Chlamydia-induced reactive arthritis, a major step forward in the management, and possibly cure, of this disease. Results of this study are published in the May issue of Arthritis & Rheumatism, a journal of the American College of Rheumatology.

Strep throat. An aerobic gram positive cocci which replicates every 20 minutes and infects superficial throat structures and tonsils is very different from an anerobic, pleomorphic, blood-brain crossing spirochete. Thankfully we rarely see rheumatic fever anymore, but patients with recurring disease were frequently treated with long term penicillin therapy including Bicillin injections. A significant percent of the population is permanently colonized with strep and remain so no matter how many courses of amoxicillin they take.  PANDAS is a more contemporary issue in this same vein. 

Guillain-Barre. An awful syndrome. Can be caused by flu vaccines, Lyme disease and many other infections. This is apples and oranges.

Patients with post-treatment Lyme have a disease so complex and varied that it can make your brain stop working or cause your heart to stop.

Nothing else is like this.  Lyme spirochetes disseminate widely, easily cross into the brain and infect a host of tissues. These other syndromes are not comparable. The CDC piece is dismissive, essentially saying: autoimmune disorders occur in the aftermath of other infections so there is nothing special about this post-treatment Lyme syndrome which is relatively rare and gets better by itself anyhow.

Assertions that a few weeks of doxycycline kill all Lyme spirochetes have no basis in fact or science.

Antibiotics are not that effective. If they were we would die every time we took them. It is impossible to eradicate all the flora in our gut with any course of antibiotics, thankfully. Otherwise our immune systems would be fatally wounded.  I do not believe we ever eradicate all dental spirochetes protected by biofilms with courses of antibiotics. How then are we going to eradicate Borrelia spirochetes, demonstrating the best survival skills of any organism on the planet.  Spirochetes persist in mice, dogs, monkeys and people. It is an inconvenient truth.

Bile acid sequestrants, mold, toxins and Lyme

My patient after 5 years of antibiotic treatment had been in a fairly remitted state. And then she was exposed to toxic mold and the entire Lyme syndrome became activated.  She experienced recurrent fatigue, pains, cognitive dysfunction, mood swings with emotional ups and downs, along with night sweats and other symptoms had taken multiple naturopathic therapies for detoxification which had not helped much.  We started Welchol, which had been helpful in the past and which was very effective right away. A urine test sent to Realtime laboratories showed the presence of mycotoxins. The concept is that even though the home mold issue had been remediated, mold persisted in her sinuses elaborating toxins. The treatment for this was intranasal antifungal therapy, intraconazole, combined with BEG, to treat bacteria and also break down biofilms. Topically EDTA works here to degrade biofilms mucopolysaccharide strands held together by calcium which is in turn chelated by this agent. Other aspects of her illness, including:   neuro-Lyme, Babesia and Bartonella were also addressed independently.  The addition of glutathione and methy b12 and methylfolate may promote detoxification and seem to be helpful.

Bile acid sequestrants, (BAS) primarily cholestyramine and Welchol have become popularized for their putative role in the removal of toxins. In the past, I implied, or stated that these agents remove neurotoxins. This statement cannot be supported. I do not believe they remove quinolinic acid.

QUIN, quinolinic acid is the major neurotoxin associated with Lyme neuroborreliosis and possibly many other neuro-inflammatory diseases: HIV dementia, Parkinson’s disease, motor neuron diseases, Huntinington’s disease, MS and psychiatric disorders.  It is produced and released by infiltrating macrophages and activated by glial cells. The concentration of QUIN in cerebrospinal fluid may correlate with the severity of these illnesses. QUIN serum concentration was recently shown to be associated with increased hepatic encephalopathy seen in patients with cirrhosis of the liver.  QUIN, an NMDA agonist, acts as a neurotoxin, gliotoxin,, proinflammatory mediator, prooxidant molecule and may alter the integrity of the BBB.

Many exogenous toxins have negative effects on the brain and central nervous system.

BAS have been shown to help removal of toxins from mold and some bacteria. There is no narrative to support the contention that Lyme is a biotoxin disease or that BAS removes these unsubstantiated toxins. 

BASs remove stuff. 

Bile acids are produced by the liver and circulated through the small bowel to assist in the digestion of fat, emulsification. BAS remove these substances – and other things. For example, thyroid hormone. Recent studies point to the usefulness of these agents for thyrotoxicosis. BAS also remove toxins associated with C. diff colitis. BAS have other effects which are not well understood. Their primary purpose is to lower cholesterol. Bile acids are derived from cholesterol; when they are taken away -  the liver makes new bile acids from circulating serum cholesterol therefore lowering serum cholesterol levels.  For reasons not understood, BAS also lower blood sugar. The BAS, as previously stated, has been shown to lower CRP levels, an indicator of lowered inflammation by way of complement activation. 

BAS may cause decreased adsorption of some drugs, (not most). Penicillin and tetracycline are on the list. There is a concern about fat soluble vitamins, not proved. 

Activated charcoal is also reported to remove mycotoxins. Charcoal is known as the universal antidote for poisoning; I am afraid it also indiscreetly removes drugs you want to keep on board.

As more adverse information about statin drugs comes out:  raise blood sugar, cause cognitive difficulties, cause muscle inflammation and liver inflammation --  in general, I would argue that BAS should be considered in lieu of the more toxic agents. Pharmaceutical representatives quickly point out that “data” only supports the use of statins to prevent cardiovascular disease. Older studies with cholestyramine showed similar results: new studies will never be done with these drugs because of economics. But I digress.

Anti-science

I must confess, there truly is a problem with anti-science in this country. But the IDSA has it backwards. Truths are easily ignored/denied when politically convenient.

Scientist, such as those who deny the reality of global climate change, readily discard science when it suits their politics.

Persistence of Lyme? recent literature:

1) Persistence of Borrelia burgdorferi in Rhesus Macaques,  Jan 2012, Embers et al. Tulane University.
 2) Two previous studies in mice and one in dogs prove persistence of the organism.  See Columbia University Lyme Research Center, Editorial Fallon.

OK that's animals, People?

1) Brian Fallon, A Reappraisal of the US Clinical Trials of Post-Treatment Lyme Disease Syndrome. Conclusion: Repeat use of antibiotics helps: i.e. Lyme persists in humans.
2) Bio-statistical review of the 4 studies NIH sponsored studies: Delong, Brown University, Nov 2012: Re-treatment can be beneficial: i.e. Lyme persists in humans.

The basis of the entirety of the IDSA arguments is being called into question by heavy hitters in the world of academic scientific research.

Politics? Study 2010, Johnson, Stricker, in Philosophy, Ethics and Humanities in Medicine, The IDSA panel:

a) 40% of panel members had financial conflicts of interest
b) Since the level of evidence was poor many guidelines based on subjective expert opinion, 38/71.
c) IDSA guidelines published in IDSA journal, calls into question bias of "peer review process."
d) Failure to acknowledge legitimate controversy
e) Guidelines restrict the use of clinical judgement and fail to offer alternative treatments.
f) IDSA panel comprised of academic researchers, not practitioners with clinical experience.

Science is a systemic process which seeks out truths about the world and universe around us. Here are examples of truth uncovered by the very process held sacrosanct by the IDSA. Does science matter to those whose opinions are cast in stone and predicated on politics?  Those who deny global climate change will not change their views until a glacier from a new ice age lands on their house. What will it take to change the mind of those who truly believe that 3 weeks of doxycycline cures patients with long-term Lyme disease? 


There is absolutely a problem with anti-science in America.

Unnecessary neck surgery

After 3 years of therapy my 60 year old patient feels well enough for a trial off antibiotics. During this recent visit I explored the topic:  when do you think you started having symptoms of Lyme disease?

She thinks it started 5 years ago with neck pain and a "pinched nerve."

Twenty percent of patients visiting their primary care physicians have chief complaints considered orthopedic.  One of the more common complaints is neck pain or shoulder pain.  Many of these patients also complain of symptoms which radiate into an arm. This is typically diagnosed as cervical radiculitis or cervical radiculopathy, also known as a pinched nerve in the neck. Large nerve branches called radicals, exit at intervals from the spinal cord between the cervical vertebral bodies. Vertebrae are numbered based on location. If a nerve root exists between the second and third vertebrae in the neck, called C2 and C3 the the corresponding nerve root would be C3. Almost all pinched nerves in the neck occur at the space between C5 and C6, causing C6 nerve root symptoms or between C6-7 leading to C7 nerve root problems. When these nerves are "pinched" symptoms referable to the sensory and motor functions of the particular nerve will typically be seen:  weakness, decreased sensation and loss of the relevant deep tendon reflexes. This is a diagnosis that any 3rd year medical student can easily make.

Doctors today rely more heavily on tests to make or confirm diagnoses. An MRI of the neck is typically ordered. A bulging or herniated disc or a bone spur will be seen in the corresponded area and the diagnosis is made. Simple. In some cases if more information is desired an EMG/NCV will be ordered.

Busy doctors frequently make a quick jump: neck pain to MRI. A diagnosis is made.

My patient with severe neck pain had been followed by her neurosurgeon for over a year.  The patient had been treated with a year of physical therapy and 3 epidural steroid injections all of which only intensified the pain. Her doctor said the finding on the MRI could not support surgical intervention and she should continue conservative measures.  On a subsequent follow-up visit her usual doctor was away and she saw a stand-in. He quickly proclaimed he could fix her pain with an operation. Desperate for relief she agreed to an operation. One surgery led to another. She's got the scars to prove it but her pain did not improve one iota.

Google cervical radiculitis or radiculopathy.  You will find the cause is a disc problem or a bone spur.  You will see that various therapies are available including surgical ones.

Lets go back to the test. MRI of the spine. Studies have been done in asymptomatic folks in the general population. At age 20 15% of folks have disc disease. By age 60 a striking 85-90% of asymptomatic individuals have disc disease in their neck according to MRI findings.

Lets go back to google. Now search Lyme radiculitis or radiculopathy and the connection will clearly appear.  If you had used the search word radiculo-neuropathy to start with Lyme would have immediately popped up.

These conditions looks like the same problem. With Lyme (and other infections) pain does not occur because the nerve is pinched but because the nerve is inflamed by the infection. In many cases there is a combination of the two. The nerve, a little pinched, asymptomatic, becomes very symptomatic when the nerve is inflamed by infection.

In the case of this particular patient she also had a "pinced nerve" in her back as well causing sciatica which worsened with a year of physical therapy and cortisone shots.

In her case both the neck and back pain completely went away with a course of antibiotics.

Radiculoneuropathy is a well known complication of Lyme disease described early on with Bell's Palsy and considered a form of neuroborreliosis in the literature.

An IDSA thinking neurologist recently published a paper which stated there are only three neurological manifestations of Lyme disease: meningitis, cranial neuritis like Bell's Palsy and radiculoneuritis.  His main point was discredit the notion that Lyme is associated with other neurological diseases like MS and ALS as frequently discussed by ILADS types.

My patient's warning:  Think twice before you undergo the knife for a pinched nerve in your neck. 

Lyme war: hotter than ever

The war over Lyme disease is perhaps only getting hotter. Numerous articles have been published in the last couple of years; many have been editorial in nature and have strongly touted the IDSA point of view. A piece written by Paul Auwaerter in 2012 published in “Transactions of the American Clinical and Climatological Association” is exemplary of this trend. Some important and relevant issues are covered in this pseudo-erudite, sarcastic editorial  -- masquerading in the guise of academic medical evidence.  Here the IDSA is strongly pressing its case while deriding phony LLMDS who mendaciously contend they are the only ones who truly understand the disease.  I personally do not like the term LLMD because both sides are generally very literate with regard to Lyme disease literature. Naturally each side cherry pick the data which supports their a-priori view. Of course I believe their viewpoint is dangerously wrong.

It is asserted that chronic Lyme disease is the diagnosis of the day, the soup du jour,  used to fill in a vacuum, to explain chronic maladies poorly understood by medical science. In typical fashion, chronic fatigue syndrome and fibromyalgia are trudged out as disorders erroneously attributed to Lyme disease. Lyme and other infectious diseases before it have been erroneously posited to fill the vacuum of poorly understood chronic illness according to the author. An historical list, ostensibly discredited, of infectious agents previously used for the same purpose are said to include: brucellosis, Epstein-Barr virus, candidiasis, toxic mold and others. The assumption here is that chronic Lyme disease will be replaced with some other entity in the future when the next best thing comes along.

The author states that the LLMDs and their community have created a phony world of bad doctors, bad research, poor publications and meetings to promulgate cockamamie theories and that a thin veneer of pseudoscience is used to unfairly and unwisely promote political agendas. Physicians who stand outside the narrow paradigms of the IDSA are labeled as unethical

The assumptions of the IDSA have been challenged as of late. This is nothing new. In "Contemporary Clinical Trials" in 2012, Delong published a biostatistical review of four clinical trials,(the cornerstone of the IDSA worldview) which clearly refutes the conclusions drawn by the IDSA from these studies. The new analysis shows there is evidence of beneficial effects of the treatments given in the studies.

This assessment was of course later challenged by the cadre of: Klempner, Baker, Shapiro, Marques, Dattwyler, Halperin and Wormser who not surprisingly, vehemently disagreed.

The most recent of the 4 studies was published in "Neurology" in 2008. Patients were treated with 10 weeks of intravenous ceftriaxone. Evaluation of the subjects at 12 week showed significant improvement in neuro-cognitive function and improvements in quality of life measures including fatigue, pain and impaired physical functioning. At 24 weeks the cognitive improvements were not sustained but the improvements in physical functioning were.

Apparently, Dr. Fallon, the lead investigator of the above mentioned study  is not enamored with the way these study results are being bandied about.  In "Open Neurology Journal" in 2012 he states that posttreatment Lyme disease improvements in patient outcomes were demonstrated in 2/4 of the NIH sponsored studies. He concludes:  “While repeated intravenous therapy can be effective, safer modes of delivery are needed.”

The IDSA continues to maintain that two-tier testing for Lyme disease is accurate. This is an important part of the narrative repeatedly used to prove patients do not have Lyme disease. In the "European Journal of Clinical Microbiology and Infectious Disease" in 2011, Ang et al tested 8 different ELISA systems and 5 immunoblots and found no consensus whatsoever amongst these various IDSA endorsed and FDA approved tests. This precious test, promoted to the hilt,  is not accurate.

The counter paradigm regarding Lyme disease is in fact steeped in science. Animal studies in mice, dogs and primates have shown that established Lyme cannot be fully eradicated from the host. Many unique, survival enhancing properties of the microbe in-vitro and in-vivo, have been well described in medical and scientific, peer-reviewed literature now over a period of decades. The assertion that groups like ILADS manufacture evidence is fabricated from whole cloth.

IDSA proponents  believe that notions of chronic Lyme disease reflect some type of mass hysteria fueled by bad science and the internet.  A frequent mantra oft repeated to my patients has been:  "if you only did not read the internet everything would be fine." If only it were true.  Lyme patients are misdiagnosed, disenfranchised, marginalized and dismissed by a medical system which is all to quick to labels them as crazy rather than sick.  The diagnosis of Munchausen's by proxy was used by a hospital in an effort to legally remove a sick child from loving parents. (This occurred to a patient I have evaluated).

Lyme disease is not a fad as the editorial states. Unfortunately it is here to stay. The epidemic has been increasing in prevalence and severity since the 1970s.

The treatment of patients suffering with this unseen plaque is challenging. Each case is different. Multiple factors influence the presentation of the disease. The scope of the illness ranges from mild to deadly.  Some factors seem random. Others are environmental or genetic. There are variant strains of Lyme which may play out differently. The contribution of co-infections with Babesia and other bacteria plays an enormous role.

Lyme war:
 
On one side, the fight is largely political. On the other it is largely professional. Well respected "experts" - the names mentioned above, and others, are using the full weight of regulatory authorities, prominently Medical Boards or other quality review organizations such as those working for health insurance companies, over whom they have much influence, to eliminate their adversaries:  physicians who do not agree with or practice by their standards.

Unfortunately we cannot have a civil disagreement about two paradigms and two standards of care. No. And that really stinks.