Thursday, February 28, 2013

Go to church

This 37 year old office manager says she hasn't felt well for half her life; and she's pretty angry about it; and for good reason.

She believes she has been sick 1/2 her life. She had mono when she was 15 and says she never completely recovered. She continued to have chronic fatigue, punctuated by bouts of  fever, malaise and flulike symptoms. Her doctors said she was healthy. She knew little to nothing about Lyme disease during those years.  In March 2009 she went to her family doctor with a small tick imbedded in her back and asked him to remove it. He immediately told her that this small dark tick was not a Lyme tick. She was taken aback; the thought of Lyme disease had not occurred to her. She got sicker than usual: more fatigue and dizziness. One month later she returned to the same doctor. Three weeks after the last visit she found a tick attached to her thigh and now she had a rash. The doctor opined that the rash was too soon for Lyme disease. He prescribed one week of doxycycline to cover his bases.  He ordered a Lyme test which was negative, confirming his original impression.

Then she became much sicker:  fevers and malaise, joint pains and swelling, increased fatigue and cognitive problems. Her doctor told her that nothing was wrong, it was a spiritual issue, and that she should go to church.

Over time she had the kind of fatigue that makes it hard to lift your head from a pillow. She developed psychological symptoms: irritability, mood swings with emotional lability, an inability to focus or get much done. With increasing memory loss she had confusion and disorientation. Anxiety, and then panic attacks became prominent. Other physical symptoms intensified:  night sweats and fevers, headaches, tingling sensation, a feeling of bugs crawling under her skin, weakness making it hard to walk at times, generalized pain with more joint pains with swelling, chills, insomnia, weight loss, cold intolerance, blurred vision and other strange changes in vision, ringing in the ears, painful and swollen glands, air hunger and more.  She seemed to have everything on the expansive list of  possible Lyme symptoms.

Her family doctor reaffirmed his prior diagnosis: there was nothing wrong. He repeated blood work including a Lyme test - everything was normal.

She came to the diagnosis of Lyme on her own, as so often happens; then she came in to see me.

After 18 months of intensive treatment for Lyme disease and coinfections, she has improved tremendously. Her life is back.

Fantastic news. A pending bill in Virginia will require all doctors to inform patients about the pitfalls of the test whenever they order a Lyme. Hopefully this will inform doctors as much as it does patients.

Wednesday, February 27, 2013

Virulent Lyme strains and another look at biofilms

I have recently seen two young men, in previous robust health, who have been stricken with subacute progressive Lyme disease with both neurological and` musculoskeletal manifestation. These patients had been athletes in tip-top shape. Now suddenly plagued by weakness, fatigue and cognitive issues are fully disabled. The question then comes up: why did these two become so sick. This continues to be a vexing issue.

A study published in the New England Journal of Medicine this past fall finally put to bed the debate. Not. There is no chronic Lyme according to Dr. Steere. Study subjects had discrete bouts of stage 1 LD with rash and had recovered between each discrete episode. Multiple strains of Lyme were found with separate infections. It was then suggested that chronic Lyme is a product of new infection, not relapse from the original  infection.

I think most doctors are in agreement that Lyme disease can be cured when caught in the early stages with an EM rash. What this study does show is that there are a multitude of Lyme strains present in the same geographical local - the same cohort of ticks.

These various strains have difference virulence factors and predilections to cause on sort of disease over another. I suspect these two men became so ill because they were unlucky enough to be a victim of the wrong tick, one harboring a very nasty variation of Borrelia burdorferi.

In one case, the young man had already received standard care with 28 day of intravenous Rocephin. The ID specialist said there was nothing else to be done and that he might be disabled for the rest of his life. This will not happen Mr. IDSA.

There arises confusion about what is chronic Lyme disease. The IDSA  defines it to be symptoms which recur after a properly treated bout of acute Lyme. But is not what we are talking about. We are talking about disseminated bacterial organisms which persist despite antibiotic therapy and continue to make the patient ill. These patients are hard to treat, but treatment can make them better.

The topic of biofilms came up in my office today, as it frequently does. There seems to be a lot of misunderstanding here. It turns out that bacteria are social creatures. They frequently form aggregates sealed off in a weird mix of muccopolysacchrides and pieces of DNA. The bacteria in these walled off areas seem to have an uncanny intelligence, communicating with one another by quorum sensing.  Organisms in biofilms may be a 1000 times (or more) resistant to antibiotics compared with singular organisms. The biofilms disperse organisms from time to time which then set up new colonies.

Lyme is not unique. About 80% of human infections are associated with biofilms. Biofilms are omnipresent. They are the slime adherent to the inside of your pipes and hoses. They are the plaque on your teeth. Chronic sinusitis may never clear until the biofilms are surgically removed.

Biofilms have efflux pumps which pump out antibiotics. They clearly contribute to the chronicity of the disease, to what extent is not clear.

Patients have frequently asked me if they have cystic forms of the spirochetes? Everyone does, it goes with the territory. Likewise, everyone has biofilms.

There seems to be a mistaken notion that biofilms can be degraded with proteolytic enzymes like nattokinase. Since biofilms are not protein based this does not make sense.

I have thought there is no specific way of  treating biofilms. I have felt that antibiotics like Tindamax which have better biofilm penetration, finding the right antibiotics, ones that work synergistically and using IV antibiotics to better saturate tissues were the way to go.

It does seem that dispersement of biofilms is a desired goal since bacteria are much easier to kill in free planktonic state. There are a couple of enzymes which facilitate this process but they are not available for clinical use. It has also been found that nitric acid, an important molecule, may facilitates the dispersal of biofilms. Apparently the best promoter of nitric acid is the amino acid arginine which can be taken as a supplement.

Thursday, February 21, 2013

Brittany's Babesia

My patient, Brittany's story was recently featured in the Animal Planet's "Monsters Inside Me." The producer told me he would shoot me a copy of the episode before it aired so I could correct mistakes. This did not happen. Brittany did not test positive for B. microti as stated; she tested positive for B. duncani, also known as WA1. This is the west coast species and not supposed to be here. One of my patient documents his experience with two Johns Hopkins infectious disease doctors on youtube,  regarding his B. duncani infection. In his case, B. duncani was proved not only by an antibody test but also positive by gold standard RNA and DNA tests, FISH and PCR. The ID doctors did not know what he was talking about and one offered to call a psychiatrist.

Here is an interesting tidbit fro a study published by the American Society of Microbiology, Clinical Vaccine and Immunology, November 2010.

They looked at "clinical specimens," sera sent for diagnostic purposes and random sera of donated blood, from different geographic regions of the United States, including my state of Maryland in the years, 2008, 2009.

It turns out that B. duncani was widely distributed across the US. Seropositivity for B. duncani was 27% of clinical specimens and 2% of blood donor specimens. B. microti was found only in 0.4% of donor specimens. If my math is any good B. duncani was 500% more prevalent than B. microti nation-wide.

The potential ramification of these findings can be considered. Two percent of blood donors tested positive for exposure to B. duncani. Since blood donors are generally healthy people and other species of Babesia were not tested for  -  the percent of Americans exposed to Babesia could be a number much greater than 2%.  The CDC recognizes that three other species of Babesia: CA1, MO1 and divergens can cause human disease in this country. And many LLMDS believe that numerous unknown Babesias may cause human disease. There are over 100 known species of Babesia associated with animal disease.

If 2% of Americans test positive for Babesia, then about 6 million Americans test positive. This number could be very conservative since is looks at healthy adults and does not include other species. Three additional species are recognized by the CDC : MO1, CA1 and B divergens to cause human disease in the US. And many LLMDS think scores of other Babesia species may be involved in human disease. Not unreasonable: over 100 species are known to cause animal disease.

If only a small fraction of Lyme patients test positive for Babesia, my experience, then one could guess that the number of Lyme infected individuals is 6 million times a larger number.

But I guess you already knew this.

Tuesday, February 12, 2013

Another look at gluten

I have long thought that gluten free diets are way over-prescribed for Lyme patients. Celiac disease, the most extreme form of gluten intolerance is relatively rare. Wheat, the primary source of gluten, was the first  grain cultivated by our ancestors dating back more than 10,000 years. We have be eating a lot of guten for thousands of years, I have been interested in the "island where people forget to die," a small Greek island with  more men per-capita living over the age of 100 than any place else on earth  -  and coarse bread is a staple in their diet. But perhaps my logic is a bit flawed. Gluten intolerance is part of the spectrum of autoimmune diseases. The incidence of  autoimmune diseases is climbing, including celiac disease. It seems mainstream science is catching up to what many "holistic" practitioners already knew. Gluten sensitivity is a real disorder, apart from celiac disease, per researches from the University of Maryland.  There is no reliable diagnostic test for the disorder. Saliva samples and stool samples for anti-gliadin antibodies may be helpful but  may also over-call the diagnosis. There may be other clues: the presence of markers for autoimmunity such as a slightly elevated ANA, B12 or folic acid deficiencies may suggest a  maladsorption issue. I think all minimal or borderline abnormalities on a standard celiac disease panel should be considered. Classic celiac disease with significant gastrointestinal symptoms or the characteristic, dermatitis herpetiformis rash may be completely absent. Patients may experience fatigue, chronic fatigue syndrome, generalized pain, fibromyalgia, brain fog or peripheral neuropathy. As mentioned in my last post, gluten sensitivity should always be considered in chronic fatigue syndrome, known to be associated with immuno-dysregulation. A celiac test, for what its worth, is always included in my initial workup of new patients.

A young woman recently came to see me with complaints compatible with chronic Lyme. On closer questioning she admitted that a gluten free diets had resolved nearly all of her symptoms. As I tried to figure out what to do her sagacious father suggested she stay on a gluten free diet to find out what symptoms, if any, remained. Great idea.

That having been said, I still think that most Lyme patients do not need a gluten free diet. It is required for a relatively small percent of patients and it is an onerous undertaking.

There are genetic factors which predispose patients to have the illness, HLA types, DQ2 and DQ8 may be checked. Ultimately, in many cases,  the only way to know if the diet will help is to try it for 8-12 weeks.

There remains the question of whether Lyme causes gluten problems. The answer is, I don't know, maybe. There is evidence that infections may precipitate the appearance of celiac disease, the frequency or which increases with age.

Chronic fatigue syndrome, Lyme, Babesia, and Adrenal fatigue

I have been treating this patient for a few months. This 42 year old female came to see me for a Lyme evaluation.  Lyme didn't seem likely, but since her husband suffers with chronic Lyme disease she decided to check out this possibility. Her chief complaint was fatigue. She carried the diagnosis of chronic fatigue syndrome.

She feels she has been tired her entire life, at least since age 19. At age 20 she was diagnosed with depression. Various antidepressants were prescribed with minimal benefit. A sleep study(polysomnogram)  was negative. The MSLT, multiple sleep latency test was slight abnormal but did not meet the criteria for narcolepsy. She has been  treated with 600 mg of Nuvigil( a very high dose), without any benefit - this is unusual. Her symptoms had become significantly worse over the last year. She had episodes of profound fatigue and perhaps weakness of her legs. At  times it was  difficult for her to get out of bed in the morning. Other symptoms included: mild brain fog, rare knee pain and some numbness and tingling. She had a history of night sweats which stopped one year ago. She had persistent loose stools, short of diarrhea. She has been seeing a psychiatrist for years. Recently anxiety has become worse along with  panic attacks. She complained of the inability to accomplish tasks, difficulty handling stress, and indecisiveness.

Lab tests showed serological positivity to Babesia microti and Lyme. In addition, there was evidence of adrenal dysfunction. The ACTH level was very high, 98, while the cortisol level was 14, within the normal range.

In addition to chronic Lyme disease I felt she suffered with adrenal fatigue. The diagnosis is associated with dysfunction of the hypothalamic's-pituitary-adrenal axis. The ACTH level should not have been elevated in the face of a normal cortisol level.

Her treatment then included: typical antibiotics  -  plus Cortef. After only 6 weeks she claimed that "this  was the best she had felt in years!"  She states she now feels normal. Gone were fatigue and cognitive symptoms.She was incredulous, as were her psychiatrist and sleep specialist. Side effects of therapy included, nausea and constipation -  surprisingly, rather than diarrhea.

In patients who have been chronically ill for years or even decades, adrenal fatigue must be considered along with other potential causes. Patients with chronic fatigue syndrome should always have sleep studies including the MSLT  and be evaluated for gluten sensitivity, thyroid disease, and a variety of other disorders.

Sunday, February 10, 2013


Lyme patients have a higher prevalence of other autoimmune diseases. Generally with autoimmune disorders there is a genetic predisposition; but specific infections, Lyme included, may trip the autoimmune switch. One frequent, Lyme associated disorder is  hypothyroidism. The diagnosis is frequently used interchangeably with Hashimoto's disease. The hallmark is the presence of the thyroid antibody TPO, thyroid peroxidase. Most physicians screen for hypothyroidism by checking TSH levels. I have found this to be inadequate. I also order thyroid antibodies whose presence may precede "chemical hypothyroidism." Symptoms may occur despite normal TSH levels. There is debate about what is the optimal TSH. I believe the optimal TSH level is less than 2 rather than the conventional 4. Patients are confused because higher levels correspond to lower thyroid levels and lower number correspond to higher thyroid levels. TSH does not measure thyroid levels. It measures a pituitary hormone which stimulates the output of thyroid hormone. It is a much more sensitive marker than the direct measurement of the thyroid hormones, T3 and T4. In other words, the TSH is inversely related to thyroid level.

Traditionally, thyroid supplementation is with T4 only products like Synthroid. T4 is inactive and converted to T3, the active hormone, peripherally, in blood and organs. I believe the solo T4 therapy is frequently be sub-optimal. Since the thyroid gland secretes both T3 and T4 combination therapy with the two more closely simulates normal physiology. Armour thyroid is a combination product  derived from desiccated pig hormone may be used. Alternatively, synthetic T4 and T3 can be combined. T3 is commercially available as Cytomel.  T3 is 4 times more potent than T4 so the two should not be taken in equal proportion. T3 appears to be more energizing and perhaps more active in the brain and central nervous system. T3 supplementation is problematic because of its short half life. The dose may be divided into small fragments taken at least twice daily. Another option is to have T3 compounded into a slow release capsule.

Thyroid supplementation is sometimes used even when a patient is "euthyroid" with normal thyroid levels. Depression is a common feature shared by many Lyme sufferers. T3 has long been known to work as an antidepressant booster when combined with other antidepressants.

Monday, February 4, 2013

Cocktails (of antibiotics)

Doctors treating chronic Lyme disease with long-term antibiotics certainly have a lot of different approaches.  Some physicians pulse antibiotics: drug A is taken for X days and held for Y days and the cycle repeats.  Some doctors use antibiotics continuously.  Some use a single antibiotic agent and others use multiple antibiotics. Some physicians prescribe a complex recipe: take A on Monday and Wednesday, take B on Friday and Tuesdays, Take C on Saturday, skip Sunday, but combine C and D alternate Sundays etc.  Patients are left wondering, what is the best approach?  Doctors base their choices on theories and clinical experience. Nobody knows the right answer. But I will share my biases.

When antibiotics are pulsed research shows that resistant forms of bacteria are more likely to develop. Combinations of antibiotics reduce the likelihood of resistance. In addition, for reasons unknown, a combination of medicine may change the resistance characteristics of a bacteria. For example, when Cipro is added to minocycline it has been observed that a heretofore minocycline resistant bacteria  may become sensitive to minocin. In other words, the minocycline was unable to kill the microbe until Cipro was added to the mix.

Mathematical models and studies (although others disagree) have shown that the use of two synergistic antibiotics reduces the likelihood of the emergence of  antibiotic resistant strains.

We are unable to assess the antibiotic resistance patterns of Lyme spirochetes but we know they posses the genetic wherewithal to create multi-drug resistance.

When dealing with such a notoriously difficult to treat organism. It has been found that two combined antibiotics kill more germs than either taken alone. This also applies to a strategy of alternating the two antibiotics. In other words, it is more effective to take A and B together for 30 days than to take A for 15 days and B for 15 days.

It is commonly known that drugs like Zithromax are added to Mepron to avoid the development of resistance in the treatment of Babesia. It is also commonly known that Rifampin should never be used as a single agent to prevent the quick onset of resistance to this agent.

Literature and clinical experience supports the idea of bathing tissues in a constant concentration of an antimicrobial. For example, intramuscular penicillin (ouch) works - even though the amount(milligrams) of drug delivered per injection  is low because there is a steady concentration of antibiotic bathing the  target tissues. A slow intravenous infusion of an antibiotic over hours has been shown in one study to work better than infusion of the same drug over a shorter period of time.

I prefer to use antibiotics in combination. I have found it works; anyway it is less confusing  than some other treatment protocols. In addition to clinical experience, there is some science to support this approach.

Another concept has been suggested. And this has  always made sense to me. We know that antibiotics are unable to kill all the spirochetes (or other organisms). Our goal is to get  patients into remission. We think than happens because the immune system "learns" how to control the parasites. Dead bacteria released into the circulation allow the body's defenses the opportunity to become better at controlling the unwanted spirochetes. In other words, a type of self vaccination occurs when organisms are continually killed.  It has been suggested that pulsing is a more effective way to accomplish this task. I do not understand this reasoning  but maybe I am missing something.

Sunday, February 3, 2013

CVID and Lyme

My 25 year old patient is a  liberal arts major at a small, prestigious college. He has missed multiple semesters from college because of Lyme associated cognitive problems. He seems brilliant to me. We converse about a variety of topics in literature and philosophy in a way which seems fluid and cogent. He shares a problem with so many Lyme patients. On the outside he looks OK, but observers don't know what its like inside his brain. He complains of executive dysfunction, difficulty concentrating and difficulty connecting thoughts. Reading, comprehension, and writing can all be difficult. Invisible psychiatric symptoms, mood swings, irritability and anxiety co-exist when things are bad. But - he has been stable for the last 8 months except when I try to wean him off antibiotics. The only thing that works is quadruple antibiotics, two for Lyme and two for bartonella syndrome. If I take away any one of the 4 and symptoms return quickly. A recent cold set him back for a month. He seems he holds on only by a tenuous thread. But there is something else going on, a pattern I have seen repeated in many other patients.

I ask him question of life before Lyme. He has a history of chronic, recurrent, difficult to resolve sinus infections and bronchitis.

I ordered another test: an immunoglobulin profile. Total levels of IgG, IgM, IgA, IgD and IgG. IgG subclasses 1-4.

There are deficiencies of IgG, IgM and several IgG subclasses.

I ordered a pneumonia vaccine, 23 strains, measure immune responses in 3 weeks. There is minimal IgG antibody response in 13 strains within the vaccine.

The patient has CVID - common variable immune deficiency syndrome(s), a collection of genetically predisposed, acquired disorders. This may explain much of what has been going on with this patient.

Other patients have responded to IVIG or especially the newer subcutaneous form he is scheduled to start as soon as possible.

Hopefully this will be a game changer.


The diagnosis of chronic Lyme disease is more often than not accompanied by a subjective complain of numbess and tingling, often accompanied by weakness, dizzininess, loss of balance and other neurological complaints. The examination frequently demonstrates a lack of sensation to vibration, pin-prick or temperature in a distal, "stocking/glove" distribution, as well as muscle weakness. The workup for this scenario should include "electro-diagnostic" testing (EMG/NCV - electromyogram and nerve conduction velocity testing), which can demonstrate the presence of a peripheral neuropathy, axonal or demyelinating. If this is negative, a skin biopsy may show the presence of a small fiber neuropathy. These findings may be of profound clinical consequences.

Numerous patients come to mind. One patient, a 55 year old dog groomer came in for the treatment of chronic Lyme disease. He had been sick for years and only getting sicker. His major initail concerns were, progressive fatigue, overall aching of both muscles and joints and increasing forgetfulness/brain fog. He was not significantly bothered by the lack of sensation in both legs. I was. I ordered an EMG.

The EMG revealed a severe peripheral neuropathy.

Because of this, the insurance company approved the use of IVIG, an intravenous blood product consisting of concentrated iG antibodies from a large pool of donors. Without insurance approval for the "right" diagnosis, the cost of this treatment is prohibitive.

After a year of treatment with up and down results. He came into the office recently having now been on IVIG for several months,

"knock on wood," he said.  He felt terrific. The fatigue was dramatically better; the pains were nearly gone, and the cognitive dysfunction had greatly improved. Sensation was returning to his feet.

Like all therapies, IVIG, carries with it serious risks, including the possibility of severe allergic reactions.  Patients with IgA deficiency must recevie a special product.

But these kinds of results have been reproduced in many of my patients.