Immune dysfunction and antibiotics

Clongen reports many unusual organisms seen swimming around in a drop of blood taken from many of the most ill, chronically afflicted patients. Why? I believe these patients are immunologically compromised. People of the ILADS/chronic Lyme disease community, have long claimed that Lyme disease infection (Borrelia spirochetes) is immunosupressive: this, it is argued, why co-infections, erstwhile opportunists, are able to easily grab a foothold. As one of my patients pointed out to me, there exists research showing a mechanism by which this might occur. Wooten and others have shown that Borrelia infection can lower a specific cytokine ( a mediator of normal immune function), IL 10. This weakens the ability of the immune system to fight or contain certain infections. If one microbe can do this, it is plausible that many others can do so as well, through various mechanisms. For example, XRMV, has been linked to Chronic Fatigue Syndrome. Not CFS. The proper nomenclature is CFIDS (Chronic Fatigue Immunodeficiency Syndrome) because the syndrome is believed to be associated with a yet understood, dysfunction within the immune system

The epidemic of CFS started suddenly in the mid 1980s. The Medical community at first thought it might be caused by Epstein Barr Virus, but ultimately decided the cause was unknown. The CDC was concerned about this new epidemic because they developed a case definition for the disorder, first in 1988, then revised in 1994.

Please visit the CDC website and print out their Case definition of CFS. Compare this to the ILADS published expanded definition of chronic Lyme disease. They match, nearly to a T.

Fibromyalgia arrived on the scene around the same time. For the longest time, most physicians refused to consider it a "real disease." Ultimately, The American Academy of Rheumatology published a case definition, in essence, pronouncing Fibromyalgia a genuine disease.

Fibromyalgia shares many features with chronic Lyme disease and CFS. Even the terminology sounds familiar. Instead of having Brain fog - Patients have "fibro-fog."

Let me turn the table a bit more. Pain - and I will introduce a new variable, Migraines: why does it hurt. Pain occurs when sensory fibers are stimulated, carrying a message to the brain/pain center causing the subjective feeling of pain.

Why Migraines? At first doctors thought it was a vascular disorder caused by constriction and dilation of blood vessels. Then, it was understood to be a brain disorder. Abnormal brain function can be imaged associated with migraines. Now - Botox injections can treat migraines. What is going on here?

Botox paralyzes nerves, relaxes muscles. This decompresses some nerves.

Inflamed, architecturally changed muscle tissue, impinges on nerves which too may be damaged and inflamed, perhaps exacerbated by autoimmune damage of tissues.

A lot of patients with migraines also have fibromyalgia, associated with tight muscles in the back of the neck. It is now understood that pressure applied to tiny nerve fibers, compressed by local abnormal muscles initiates the cascade. Messages are sent to the brain leading to abnormal brain function and then changes in blood vessels. The vessels constrict and then dilate, pressing on nerves. This is why migraines have a pounding quality. The vessels dilate more when the heart contracts. Fibro muscles irritate nerves but in a different way. The same can be said for Lyme patients.

Stardard medical thinking holds that painful conditions like fibro and irritable bowel syndrome are due to overly sensitive nerves. This thinking seems to have a psycho-somatic slant. These sorts of biases need to be replaced with a better understanding of the science and a respect for the suffering of the patients, rather than blaming the patient - as if in some way, the patient is responsible for the illness.

This thinking is fueled by observations that certain illnesses are more prevalent in women - the implication: women are prone to hysteria and psycho-somatic problems. In fact women have more robust immune responses than men and are twice as likely to experience autoimmune disease. This is where we need to look.

Let's go back to the first paragraph. Sick patient have germs in the blood; parasites bacteria, unknowns. The immune system is to some measure broken. These germs should be contained in a box, somewhere else, by a competent immune system.

Perhaps an initial infection: Lyme, Mycoplasm or something else, initiates the process seen in our: chronic Lyme, CFS, fibro, chronic pain syndromes, migraine, IBS, chronic pelvic pain, IC and other patients. The smart, offending germs are in some way programmed to disrupt normal immunological functions(as is known to be the case with Borrelia) causing a wide range of downstream sequelae.

Some antidepressants, Cymbalta, Elavil disrupt the neuronal messages sent to the pain center, or in some way alter the perception of pain in the brain. The same is true for anticonvulsants like Neurontin, Lyrica. They may help some. But they do not get at the root of the cause.

Sometimes - antimicrobials, of various sorts, (from doxycycline to Tindamax to Malarone) work much better for these patients.

Immune compromise, mediated by one infection ( not to discount the role of genetics, stress and other factors) can "activate" heretofore quiescent germs. This explains why patients relapsing with Lyme often experience a rip-roaring relapse of a previously controlled co-infections, like Babesia.

The process may be associated with multiple breakdowns of normal imune function. For example: cytokines become dysregulated, T cell and B cells malfunction, autoantibodies are made. Autoantibodies, the cause of autoimmune disorders, play a huge role in the disease complex.

Bottom line: sometimes it is best not to worry what it is: are bands present or not? Is it fibro or CFS. Not to say you should stop trying to figuring it out.

It comes down to this: either the illness responds to anti-microbial agent or it doesn't.

This begs the question: which antibiotics/anti-malarials or anti-parastic agents. If you don't pick the right ones you won't know if the illness is anti-microbial responsive.

That's the tricky part. That's what you pay us to figure out.

B12

How important is vitamin B12?

For years doctors gave patients injections of that red liquid in their hips for low energy.
Patients left the office feeling energized with an increased sense of well being.

The practice has been eschewed by conscientious doctors in more recent decades: no scientific rationale - just a placebo effect. The elixir is red - red placebos work best. In evidence based medicine, B12 deficiency may be due to maladsorption or an autoimmune disorder. Blood levels are only low when less than 211. Other countries, including Japan have set the bar for normalcy higher - 500 or more. This is quite a difference.

B12 does many things in the body -- in conjunction with folic acid. It helps regulate the production of red blood cells and DNA synthesis. It facilitates the synthesis of myelin, the protective covering around nerves, and it likely has many other functions which are enumerated in a variety of published sources.

Lower B12 levels, less than 500 have been associated with a variety of neuro-psychiatric disorders, inclusive of cognitive dysfunction. B12 supplementation has helped with neuropathies of various sorts despite normal blood levels according to American standards. Neurologists who discount Lyme as a possible cause of peripheral neuropathy readily recommend generous supplementation with B vitamins.

Commercially, B12 is available as cyanocobalamin, an inactive form. It must be converted into one of two active forms, including methylcobalamine. Many clinicians feel that that the expensive methylcobalamine is the only clinically effective form of the vitamin. Based on my survey of the literature the jury is out on this one.

Patients with neuropathy, cognitive issues and perhaps many other issues may benefit from supplementation. Most of my patients have B12 levels which average around 350. This water soluble vitamin has no toxicity. B12 must be given with folic acid. If oral supplementation is ineffective the old "placebo" (B12 shots) can't hurt.

Gluten

A very sick Lyme, a middle age male with: Babesia/ neuroborreliosis/abnormal SPECT scan is now feeling normal off antibiotics after 2 years of treatment. He also has "gluten sensitvity." Two children and a sister have celiac disease. He has tested negative for celiac. His TtG Iga is negative (supposedly an accurate screening test). Two gastric biopsies, the "gold standard" for celiac were negative. Nonetheless, tiny amounts of gluten cause symptoms: pains, fatigue, rash, neuropathy, and gastrointestinal symptoms, including GERD. Gluten free diets are difficult. Food advertised as gluten free may contain trace amounts of gluten and rapidly set off symptoms. Conclusion: gluten sensitivity exists along a continuum. Standard tests only reveal gross disease with macroscopic loss of intestinal villae. Other patients may have ultra-microscpic changes, not observed with standard tests. In predisposed individuals, gluten causes extreme immune reactivity. These symptoms must be teased out from those of Lyme

Co-morbidity

I had a recent conversation with a patient. I told her we need to sort out other co-morbidities. Co-infections? No. This was a new term for this very Lyme literate patient. I was not saying the patient did not have Lyme disease. Not at all. Patients with Lyme disease frequently have a variety of other medical problems which contribute to their illness to varying extents. And, in some cases, it is not Lyme which is making the patient ill, regardless of what the Western Blot says: if the signs and symptoms do not fit -- Lyme may not be the primary issue. Or, perhaps Lyme's contribution to the illness is minor. For example:

Fatigue--profound fatigue, is almost invariably a prominent symptom. What else causes this? Other causes include hypothyroidism, B12 deficiency, anemia, depression and insomnia. After these are excluded, my patients are sent for sleep studies. Sleep disorders are a major cause of fatigue. Lyme patients have higher rates of sleep disorders compared to the general population. Patients may have obstructive sleep apnea (OSA) or central sleep apnea, a brain disease. Sleep apnea is associated with numerous other medical disorders: cardiovascular disease, diabetes and others. Sleep apnea is also associated with neuro-cognitive dysfunction -- sound familiar? And sleep apnea is associated with alterations of immune function. Specifically, high levels of inflammatory cytokines, TNF alpha, interleukins have been measured in these patients. Sleep apnea is a significant co-morbidity which interfers with the healing process.

Oher sleep orders are common as well. Restless leg syndrome is a common cause of poor quality, non-restorative sleep. This condition may be respond to supplementation with high doses of iron, sometimes intravenously, based on ferritin levels (it is not clear why these patients have profound depletion of iron). This movement disorder shares common features with Parkinson's disease, a movement disorder mediated by dopamine deficiency in the basal ganglia, a deep area of the brain. Both disorders are treated with dopamine agonists such as Mirapex. This should not be confused with cortical brain dysfunction--loss of executive dysfunction--related to insufficient dopamine activity in the cerebral cortex. This is treated with dopamine agonists such as stimulants which work in these areas of the brain.

A second sleep test, an MSLT can evaluate for narcolepsy and other disorders. Narcolepsy has been considered a disorder of arousal but is now understood to be a disorder of sleep. This may be effectively treated with Xyrem, a drug which is safe but suffers a bad reputation.

Sleep disorders: a common co-morbidity, cause fatigue and cognitive impairments, as well as mood changes and irritability. Not to say I don't start Lyme therapy early in the process - I must also fix the "non-Lyme" to see what remains.

This is but one example of numerous potential co-morbidities.

Patients may have: rare genetic disorders, rare metabolic disorders - or acquired mutisytem-disorders. One of my patient suffers with stiff man syndrome. This is a rare autoimmune disease caused by destruction of a GABA precursor. Another suffers with a toxic yeast syndrome which mimics chronic Lyme. Neuro-cognitive changes and new onset headaches may be caused a brain tumors or other cancers. It is know that Lyme may be associated with brain tumors.

Medical texts are ripe with esoteric diseases: mystery diagnoses. These are the patients that seek our help. It is not always Lyme.

Text book

A new patient walked in: a youthful 29 year old female. She wasn't feeling as good as she looked. She suffered with diffuse, migratory muscle and joint pain. She had tingling in her hands, shortness of breath, night sweats, headaches and pain on the soles of her feet. Her brain was foggy: poor concentration, focus and slow processing. She asked me if I thought she might have Lyme disease. I replied: "My G-d, you are right out of the textbook." Then I realized: " Well no, there actually is no text book." One has to be written.

She had a tick bite, a small "seed" tick, 2 years ago. It was accompanied by a red rash, maybe 5cm in size based on her description. "It wasn't a bulls eye."

She saw her family doctor. He told her she was just getting old (29?), that's why she had the symptoms. I asked how old the doctor was. Ancient. She talked her doctor into ordering a Lyme test. The Western Blot showed 28 and 41 bands only. Not Lyme disease.

Her family doctor referred her to: a rheumatologist, a neurologist and an infectious disease specialist. She figured it must be one disease -- she only needed one doctor. Smart girl. An Internet search led her to Lyme disease and then to me.

Doxy failure

14 months ago, a 47 year old male first consulted with me. His illness started after a physical injury sustained working in his garden. He first developed low back pain -- diagnosed as a strain. He went on to develop knee pain, fevers to 102, a red streaky rash on his abdomen, sweating and color changes in his fingers. He went to the ER: he had been ill for 3 weeks. A two tier, CDC surveillance test was positive for Lyme. He was treated with 3 weeks of Doxycyline and felt better. His past medical history is positive for Chrohn's disease.

Three month later he developed recurrent, progressive symptoms -- muscle pain -- increasing joint pain -- profound fatigue, and, drenching night sweats. New neurological symptoms appeared: numbness and tingling, memory loss and cognitive dysfunction.

He presented to me for further care. A 13 band WB showed 3/3 IgM bands. Non diagnostic Bb IgG WB bands were present. He was seronegative for Babesia microti/duncani. He was treated for chronic Lyme disease and Babesiosis, diagnosed clinically.

After many months of antibiotic therapy his disease is in remission, still on antibiotics.

Additional data: C6 peptide ELISA had been 6.41 initially and is n0w 2.3. C4a levels have been elevated. CD 57 levels have been normal. A wet mount showed no bacteria.

His previously active inflammatory bowel disease is now quiescent. A recent colonoscopy was normal.

Three weeks of Doxy for acute Lyme failed. This may be more frequent that commonly held. It has been suggested by some that this is due to co-infections. I am not sure. The average person, with an intact immune system, should be able to throw off both Babesia and Bartonella.

Perhaps in some cases, Lyme is able to sequester itself quickly. Other explanations may be offered. Perhaps in some, already-infected asymptomatic patients, clinical Lyme is triggered by a new infection. The other possibility is a bit more frightening. Perhaps strains of Lyme are now resistance to Doxy. This could explain some Doxy failures with response to other treatments, such as Amox/Biaxin. This patient did respond to Doxy at first. But, partial resistance is know to occur with other bacteria. This is all thinking out loud conjecture.

Lyme disease is associated with a multitude of autoimmune diseases. Crohn's and ulcerative colitis are both autoimmune diseases. Coincidence?

Lyme Rage

A 36 year old female was treated for severe Lyme disease and neuroborreliosis. A course of IV antibiotics was successful 2 years ago. I explained to her the need for maintenance therapy. She took oral antibiotics for a few months, but tiring of the medicines, she sought alternatives, such as A Rife machine. She had been treated for Lyme, Babesia and Bartonella. Her case had been well documented: abnormal MRI, abnormal SPECT scan and multiple positive Western Blot Lyme bands. The aches and pains returned, slowly. The mental confusion returned, slowly. She returned for further treatment 6 months ago. This happy-go-lucky soul had turned into someone else. She was was filled with unbridled rage. She told me she literally felt like killing someone. She was just waiting for that someone to cross her path so she could act out her rage. She meant business.

Several months into therapy she returned to her normal self. The anger disappeared gradually, and then it was gone--after treatment with a second course of IV therapy. Now, several months off IVs, she is largely symptom free, the disease controlled with oral antibiotics. The smile has returned to her face. She is once again a kind and gentle soul.