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.