Complex patient with autoimmunity, humoral deficiency treated with combined modalities.

This 42 year old female a had a history of stable Crohn’s disease, otherwise, she was in excellent health until 2009. Previous to the onset of illness she had been an avid athlete who ran 10 miles several times per week. She lives in a neighborhood known to be Lyme endemic. Her dog has recently been treated for Lyme disease. Her husband had a bull’s eye rash 8 years ago and was successfully treated with a short course of doxycycline. She has no recollection of a prior tick bite, flu-like illness or rash of any kind.

Her colitis flared for no apparent reason. She experienced an unusually difficult exacerbation requiring high dose steroids. As the gastrointestinal symptoms cleared she began to experience joint pain which ultimately became wide spread. Inflammatory bowel diseases, Crohn’s and ulcerative colitis can be associated with “extra-colonic” autoimmune manifestation including inflammatory arthritis.  She saw numerous doctors at both the Mayo Clinic and Johns Hopkins who concurred with this diagnosis. Frustratingly, she did not respond as expected. A wide array of immunosuppressive biological agents including Enbrel and Remicade were prescribed over a two year period; during this time her illness became much worse. She became house bound. She suffered with debilitating fatigue, neurological symptoms including tremors, numbness and tingling, weakness, poor balance and progressive cognitive deficits. She saw a homeopath who diagnosed Lyme disease. She was prescribed a wide array of natural therapies which proved to be ineffective. Another LLMD  treated her with IV Rocephin for three months and she continued to steadily feel worse. It was at this point that I first her in my office.

She was disabled by diffuse joint pain, large, medium and small joints, from head to toe. She was in pain management and taking a high dose of  opiod. She was unable to focus or think clearly. Fatigue was beyond description. Lifting her head from the pillow was a task, taking a shower a massive endeavor. She experieneced constant shortness of breath.  She lost considerable weight and muscle mass. She had constant flulike symptoms with low-grade fevers, chills and night sweats. Neurological symptoms included: numbness and tingling, a loss of balance and a loss of coordination, episodes of frank confusion, progressive memory loss, trouble reading and writing, uncontrollable thoughts, irritability, anxiety and depression.

Her examination was remarkable for joint tenderness without swelling or signs of inflammation and and abnormal neurological examination which showed weakness, asymmetric reflexes and a severe loss of sensation of lower extremities. 

Laboratory testing revealed positive revealed a positive IgeneX WB with IgM 39 and 41 bands. Coinfection panel was negative. Blood smear exam showed active parasitemia. 

Intravenous antibiotics in combination and anti-malarial medication were administered for months; the clinical course waxed and waned; a modicum of  durable improvement was seen after 6 months.

She experienced unusually prolonged and recurrent Herxheimer reactions.

 A sleep study showed an absence of both deep sleep and REM.

She was treated aggressively for Lyme and Babesia.

An EMG/NCV showed no significant peripheral neuropathy. A small fiber biopsy was scheduled but not done.

After 7 months of IV antibiotics low pressure hyperbaric oxygen therapy was started and she began to feel better after a few weeks.

She was tested for immune deficiency. Total IgG was borderline low, 400, IgG subclass 2 was 170, below the normal range, the other IgG subclasses and IgM were normal.

Baseline pneumococcal antibody subtypes were obtained: she had no immunity.

A polyvalent pneumococcal vaccine was administered; four weeks following vaccination peumococcal subtype antibodies were drawn and she had virtually no response.

She was diagnosed with a humoral deficiency and was approved for the use IViG. 

She started IVIG.

After 8 months of treatment she has made good progress towards recovery and continues to improve.

Discussion: 

When this patient was evaluated in a major medical center, a wide range of specialists offered opinions through the lens of their areas of expertise. Infectious diseases. Gastroenterology. Rheumatology. Pulmonology. Pain management. Immunology. Neurology. Psychiatry. And perhaps a few more. She has a multi-system illness which does not fit into the established paradigms; these specialist through the myopia of their specialty  have been indoctrinated to believe nothing here resembles Lyme disease, which they have been taught is a straightforward disease, easily treatable. The lead physician who is responsible for tying together all the disparate opinions believes the same. 

The misinformation fed to these specialists comes from a handful of "experts" who refuse to consider they could be wrong. Their views are reinforced because they function within a community of like-minded colleagues. 





 

Why your doctor does not believe in Lyme disease

In his new book, Dr. Horowitz gently discusses the issue. He talks about a paradigm change. This doesn’t answer the question for patients on a visceral level.

I surveyed some physician friend colleagues asked them if they can think of another disease that has been as divisive as Lyme disease.  They always come up empty-handed.  

Your doctor is being bashed by medical boards, ridiculed by other medical professionals, even shunned and ostracized and generally not having a good time (in some arenas, not globally).

You are angry, infuriated, incensed, bellicose or just pissed off. 

Patients new to this world all ask same question .Why?

There is a war going on. Years ago, I had a conversation with an infectious diseases specialist I thought it was collegial; at the end of the discussion I said “I guess we’ll just have to agree to disagree.” She said no we won’t and proceeded to report me to the Medical Board. Doctors don’t usually report their colleagues to Medical Boards. Most follow the rule, “people who live in glass houses shouldn’t throw stones”

Phenomenologically, Dr. Steere and is infectious diseases specialist saw a Lyme as a vectorborne illness causing joint pain or rash: something straightforward. Something easy to treat.

Phenomenologically, Dr. Burrascano and primary care colleagues, saw patients in Lyme endemic areas as poly-symptomatic; patients had every symptom in the book.

Dr. Steere, Dr. Burrascano, myself and likely all the physicians I can think of were taught that there is no disease that causes so many disparate symptoms. These has a “positive review of systems,” meaning they has a psychiatric disorder. Easy one.  

Lyme breaks the mold.

Dr. Burrascano and others thought all these patients cannot be crazy; something else is going on. The cohort of sick patients lived in rural areas known to have a lot of Lyme, they enjoyed outdoor activities, they had a history of previously treated Lyme disease, they had a history of tick bites, the had a history of rashes and summer flus, or they just had an insidious, progressive disease. 

First impressions are important. Dr. Steere’s first impression was that Lyme causes joint pain and is easy to treat.

Dr. Burrascano’s first impression was that these were very sick patients, commonly referred to a “train wrecks.” These patients got better when given antibiotics; symptoms returned when antibiotics were stopped; symptoms got better again antibiotics were restarted. The first impression was that Lyme is a complex multi-system disease which is hard to treat.

These two groups were describing something entirely different, something universes apart. Both were called Lyme disease. 

The war began. Steere  was reported to a Medical Board. Burrascano was doomed. Once the war broke out the truth didn’t matter. Since Steere and his colleagues are associated with Ivy League institutions they won the battle. They have created educational programs for doctors espousing their point of view point and ridiculing the views of the other camp.

I hop the answer to the big question is contained in the above narrative. 

In this war I see the IDSA crowd is calling lymies and their doctors crazy and “antiscience.”  Lymies believe the IDSA crowd is involved in some vast conspiracy. Get a grip.

It comes down to stubbornness, hubris and ego. They call me “antiscience.” A friend once told me: “watch what they call you; that is what they are.”

Biofilms and Quorum Sensing

There is a lot of confusion about biofilms and Lyme disease.  I have frequently heard from patients that a “biofilm-buster” is needed. Biofilms consistent of colonies of microorganisms who live within the confines of a protective membrane made of mucopolysaccharides with odd pieces of DNA. These molecules are long chain sugars. We know that biofilms provide a protective niche permitting the survival of Lyme spirochetes and many other bacteria. Most of what we know about biofilms is derived from in-vitro, test tube studies which focus on surface infections, for example, diabetic wounds and cytstic fibrosis. Most of this research has focused on Pseudomonas, a notoriously stubborn pathogen associated with these diseases. We have precious little information about Lyme biofilms.

Biofilms comprised of Pseudmonas aeruginosa have experimentally been treated with a number of topical agents, like xylitol, with some success. Ammons found that lactoferrin has biofilm activity for surface Pseudomonas. How well does this translate? One mechanism of action is the chelation of iron. While this may work with Pseudomonas it may not work with Lyme (even topically), because these spirochetes use manganese in lieu of iron. Other agents, like stevia, have had some success treating Lyme biofilm-like colonies but these finding are from test tube studies and likely do not apply to systemic infection.

Proteolytic enzymes have been widely touted as ‘biofilm-busters.” This has never made sense to me since biofilms do not contain protein.  

Yeast have biofilms. Cremer et al, current Antimicrobial Agents Chemotherapy, screened 1600 drugs/agents and found that Artemisinins were synergistic with miconazole for the treatment of Candida albicans biofilm related infection. This synergy did not occur with several other anti-fungal drugs studied. I am sure many readers have personal experience with stubborn Candida biofilms on their tongues. This highlights the fact that drugs used for a single purpose (artemisinin for Babesia) may help in unexpected ways (Candida).  

The recent study from Hopkins about Lyme persisters and the original studies of Sapi are at odds with one another. The Hopkins study lumps cysts or round bodied forms together with biofilm-like colonies calling them stationary phase bacteria. Sapi considers cyst or round body forms and biofilm forms to be two separate entities. Hopkins reports that doxycycline, amoxicillin and Flagyl have no effect on stationary forms. Sapi found amoxicillin and Flagyl have anti-cyst effects and that Tindamax works well against cysts and also kills spirochetes within biofilms. More study is needed.

An explanation of Tindamax’s greater effect against biofilms may be due to disruption of quorum sensing: a process by which bacteria within the biofilm communicate with each other by molecular signaling (very complicated stuff). In Pseudomonas models a number of antibiotics have been shown to interfere with quorum sensing and associated virulence factors.

Experimentally, these have included: Zithromax, Flagyl, Tindamax and Cipro. 

The take-away point is that the best biofilm-buster might be a specific antibiotic or combination of antibiotics.

Cyst forms, round body forms, L-forms, biofilms forms: now we have a new buzz word to add to the list, quorum sensing (QS).

I think parsing ‘Lyme” into these parts and trying to tailor therapy for each one is generally not helpful. These notions are helpful in a general sense only; patients respond differently, unpredictably. Experience remains our best teacher. Theory is no substitute for that which is tried and true.

Correction to below

After asking Labcorp rep, they still perform Lyme WB, at least upon my request, without ELISA or EIA.  Please note.

Labcorp and the Lyme Western Blot

As many are aware, Labcorp will no longer allow physicians to order Western Blots for Lyme disease. The only test available is the ELISA with reflex to Western Blot if positive.

They have also taken away the C6 peptide.  The results are presented as only negative if less than 0.91.

These changes are not going to get Labcorp any more business.  What motivated the change?

One can only guess that someone affiliated with the IDSA influenced the policy change. In the past, when the Western Blot was ordered, the laboratory informed us the ELISA test should be ordered as well. Should be? According to whom?

Some ID doctors are inappropriately applying the HIV testing paradigm in the case of Lyme testing. When testing for HIV it is crucial to do the ELISA first because it is possible to have a positive Western Blot and a negative ELISA rendering a negative test.  Luckily with HIV there are other, better,  confirmatory tests available.

There is no evidence the same applies with Lyme testing.  The IDSA has claimed there are a lot of false positive Lyme Western Blots because of cross reactivity.  This claim remains largely unreferenced.  I recently saw a patient with a history of syphilis, RPR positive. The Lyme Western Blot was entirely negative. Many patients test positive for rheumatoid arthritis and Epstein Barr Virus and have negative Western Blots. (these are the common scenarios said to cause false positive tests). The ELISA is known to have many false negatives. Skipping this test and going to the Western Blot increases the sensitivity of the test.  If there is some decrease in specificity it would seem to be minimal at best.  In other words, patients are more likely to get an accurate result when the physician orders the Western Blot directly and skips the ELISA.

The CDC still states that Western Blot testing should only be done when the ELISA is first positive. The Website states that IgM results found after the first 4-6 weeks are likely false positive unless 5/10 IgG bands appears at that time. These facts are referenced back to findings from 1994-95. As you may recall this finding was based on an assay using the discarded N40 strain of Lyme and B31 has become the standard strain.

1) These results are based on a meeting which occurred 20 years ago. When the testing remains so controversial why hasn't there been a more recent reassessment?

2) At best this is revisionist history. The test was developed for surveillance (an epidemiology or research tool) not for diagnosis.  How a test developed for an entirely different purpose (monitoring the relative number of cases in different locations over time) morphed into a bullet proof test for diagnosis of Lyme disease is far beyond my ability to comprehend. 

Why are we going backwards. Why is there a problem with giving physicians and their patients more information?

The CDC stubbornly says on their website that there are no borderline positive tests. There is an absolute requirement to have 5/10 bands because at least this many always shows up.  According to the logic presented by the CDC the finding of a positive ELISA followed by the appearance of 4 IgG Western Blot bands is absolutely, 100% negative for Lyme.

One would like to know who wrote this tripe.

The long arm of the IDSA has managed to promote its agenda by manipulating the CDC and now Labcorp.

I caught Ben Beard, the chief of the bacteria section (Lyme included)  of vector borne diseases for CDC off balance when I had the opportunity to meet with him along with members of Nat Cap Lyme some years ago. Dr. Beard was flustered when I pointed out the contradictions in the CDC pronouncements especially about the appropriate use of the two tiered Lyme test.

When I asked him if the CDC wasn't speaking out of both sides of its mouth on the topic he hemmed and hawed and then ultimately responded "well, that's the party line."

What party was he referring to? Democrats? Republicans? Perhaps the IDSA vs ILADS. Dr. Beard's s comment to me was an admission that politics have trumped reason, logic and science. The IDSA has extended its mandate. They are no longer a professional society for infectious disease physicians. They are in fact a political party. Triumphantly they can say, Labcorp: Welcome to the party!  As with all political parties, the truth is frequently abandoned when its application leads to undesired results.

In the wake of emerging science and changes in the very nature of the pathogens responsible for Lyme disease this discussion is becoming more and more a moot point.

Its a win for:  Quest, Clongen, IgeneX, Stony Brook and a few others.  Lyme patients who are insured by health insurance companies that insist Labcorp be used should complain and lobby for a change to another lab.  As they say: vote with your feet.

Are staunch supporters of the IDSA admitting they might have been wrong all along?

A paper from the Department of Molecular Biology and Immunology from Johns Hopkins is quite remarkable, especially since Paul Auwaerter is one of the authors.  The paper presents ideas which are a complete turnaround from the previous orthodoxy promoted by this institution and this author in particular.  The entity in question is called PTLSD, post-treatment Lyme disease syndrome by the authors. The authors state they do not know the cause of the syndrome. They concede that up to 1/5 of the patients treated for Lyme disease by IDSA standards have persisting or lingering symptoms.

The authors state recruitment for clinical trials has been difficult. Why?  The only patients accepted into the studies were treated for early, classic Lyme and subsequently developed the famous 5/10 CDC IgG bands. Findings these patients is like finding a needle in a haystack.  Recent peer-reviewed literature suggests that patients with chronic symptoms tend to have poor IgM responses and never develop IgG responses. The patients we see in our clinical practices rarely have CDC positive IgG responses. Chronic Lyme studies recruit a small cohort of patients likely to be healthier than the vast majority of chronic patients.

Let me digress.  The IDSA and CDC keep insisting that patients with chronic Lyme develop 5/10 IgG bands in virtually every case. Repeating something over and over again does not make it true.

The 5/10 come from a paper written by Dressler in 1993, one year before the ill-fated Dearborn conference. This is the same Dressler that suggested IgM criteria should be 2/8 bands (sounds an awful lot like IgeneX criteria). The criteria was dismissed because Dressler’s research was based on the N40 strain of B. burgdorferi, not the B31 which has become the standard. Therefore, the “flawed” IgM standard was dismissed. Somehow, the “flawed” IgG criteria based on the same discarded strain of Lyme was allowed to become the standard and this has never changed.

The authors list possible causes of the syndrome:  autoimmune, persisting debris (dead germs) or persisting infection. Only the persistent infection hypothesis is called “controversial,” even though this is the only hypothesis backed by fact.

It is silly to have a discussion about whether animals have chronic Lyme symptoms. The authors state: “a number of prospective, randomized clinical studies demonstrated no significant beneficial effect of additional antibiotic therapy… and no evidence of presence of B. burgdorferi in patients with long-term symptoms.” 

How do they define “significant?”  Patients showed improvements in fatigue, pain and quality of life issues and Dr. Fallon the last author of the famous NIH sponsored studies believes that additional antibiotic therapy helps because there is persisting infection.  The authors claim there is no evidence of presence of B. Burdorferi. There certainly is no evidence that the spirochete is gone. The authors also note that some studies showed a decrease in fatigue. The authors seem to be arguing amongst themselves.

The authors are intrigued by the fact that one patient who had been treated for Lyme gave the germ to a tick allowed to feed on his blood.  This test seem just wrong to me.  Why wasn’t a PCR done of the patient’s blood at the same time? This procedure makes a lot more sense to me. Anyway, I am glad the authors are intrigued.

The authors concede that recent literature demonstrates the persistence of infection in mice.

This is where it gets weird. The authors talk about 3 morphological forms: spirochete, L-form, and cyst. I am I reading this right? This sounds like the ILADS’ pabulum which the same sources have spent a lot of resources on, even in recent months, discrediting.

Without this apparent change of face there would be reason to do this research or publish this paper.

These authors discuss two stages in the life cycle of Lyme: the rapid growth phase and the stationary phase. These authors commit blasphemy. The cross one more line and talk about “biofilm-like aggregates.”

In the test tube, the researchers found there are always persisters.

The purpose of the study was to show the researchers had developed a tool to help identify antimicrobials which may better able to eliminate persisters.

“Our findings may have implications for the development of a more effective treatment for Lyme disease and for the relief of long-term symptoms that afflict some Lyme disease patients.”

I am getting confused.  Was this study written by IDSA proponents or backers of the ILADS’ way of thinking?

Even in a test tube. No antimicrobial was found that could kill all the persisters.  That should be like “shooting fish in a barrel.”

In a real human being things are a bit more complex. The germs hide on the inside and outside of cells. The germs penetrate deep tissues like cartilage with minimal blood flow. The spirochetes invade a panoply of host tissues, all with different characteristics:  brain, nerves, joints, cartilage, tendon, heart, colon and numerous others.

Based on these few facts it seems outlandish to believe that a short course of IDSA sanctioned therapy is likely to eradicate all of the spirochetes.

Novel drugs like: clofazimine, daptomycin, cefoperazone, carbomycin are the best drugs for killing cysts.

Let’s not rush in – please.  Flagyl is said to have no anti-cyst activity, contradicting other work which proves the opposite. Most of these drugs are highly specialized, too potent and should likely not be used.

It seems that the science is catching up with ILADS, leaving the IDSA in it's wake.