Mycoplasma’s Role in Rheumatoid Arthritis (RA) and Other Autoimmune Disorders
© 2004 Katherine Poehlmann, Ph.D.
The Inflammation Process
Symptoms of pain, swelling, warmth, and redness associated with impact trauma or muscle damage are usually beneficial. Cells of the immune system are attracted to the injured area where they fight any infection, then clear away the debris in preparation for tissue regrowth and repair.
Chemicals such as cytokines and prostaglandins work in concert to control the infection process, and are released in an orderly and self-limiting manner. When the process does not stop at the appropriate time, the immune system continues to fight in an active and destructive state. The constant activity leads to chronic fatigue, a diminished energy level, curtailed oxygen transport, increased interferon activity, and an overworked thyroid leading to exhaustion. Mycoplasma grows best when the thyroid is in hypo state, i.e., when it is minimally active.
Many of the natural chemicals and destructive enzymes generated by the immune system can, over time, cause damage to cartilage. The drugs prescribed to relieve RA pain are in fact trying to inhibit this natural chemical overproduction but they do not remove the root cause of the inflammation.
All RA forms have an inflammatory component and show evidence of connective/synovial tissue damage. These are indicators of a process resembling the autoimmune reaction where the body inexplicably attacks its own cells. In RA, the reaction is actually the body’s natural allergic response to an infection in the connective tissues. This battle is the cause of the inflammation, pain, and disfiguring effects of RA since the disease agent is connected to the cell by various forms of comingling of foreign and host DNA. When the disease agent is removed, the attack stops.
The autoimmune theory has become so entrenched in American medical school teaching that other options have not been considered until very recently. With PCR analysis of synovial fluid it is possible to detect the genetic material of the mycoplasmal microorganisms, L-forms, and other agents triggering rheumatoid arthritis and reactive arthritis. Much of the research is originating outside the United States, but American scientists are now starting to explore the possibility of bacterial infection in RA, confirming the findings of Dr. Thomas McPherson Brown.
Mere fragments of mycoplasma are sufficient to create a powerful antigenic reaction in the joints that causes the body to produce antibodies to counter it. The antibody reaction may be mainly against a “host antigen” carried on the mycoplasmal membrane. It may be a reaction to a hybrid antigenic molecule formed by a comingling of invader surface shape with toxins or food molecule shapes.
Patients with other diagnoses, such as Lyme Disease or Fibromyalgia, who test positive for Mycoplasma or Chlamydia strains or other bacteria and nanobacteria also exhibit RA indicators and symptoms.
Mycoplasma’s Role in Autoimmune Disorders
Mycoplasmas and bacterial L-forms are resident, in vivo parasitic “invaders” that become active from time to time to obtain nutrients, expel wastes, breed, and migrate in and out of the body to form new colonies. These actions precipitate an allergic reaction that appears to be an autoimmune disorder since no external cause for the reaction is detected by routine testing methods. In vitro cultures are slow and usually fail to detect mycoplasmas and L-forms.
Mycoplasmas exhibit cloaking behavior in several ways: cell shape modification, infiltration of T-cells, and mimicry of normal cells.
Mycoplasmas and L-Forms
We carry mycoplasmas and L-forms with us as remnants of childhood infections such as pneumonia, strep throat, bronchitis, rheumatic fever, or other early illnesses. Microorganisms such as mycoplasmas often lie dormant, waiting for conditions to be favorable for propagation. This could explain conditions such as rheumatoid arthritis, Chronic Fatigue Syndrome (CFS), or Gulf War Illness, which seem to strike suddenly. There are possible viral co-factors such as herpes simplex or strep pneumonia that can form deadly combinations.
Chronic pneumonia is a good prototype for what happens when a mycoplasma infection becomes fixed around a certain area. Nodules of granulation material—inflamed tissues that surround the infectious organism for months—produce the characteristic cough of the disease. A similar phenomenon happens around the RA sufferer’s joints. During the inflammation reaction, the body responds by moving calcium to the site, forming nodules—dry, gritty, calcium hydroxyapatite crystals—that clump around the invading microbes.
The body must be trained to defend itself with minimal help from external agents such as antibiotics. This is the reason for very low antibiotic dosage over a period of weeks or months recommended by Dr. Brown. In parallel, one must take steps to strengthen the immune system through diet, exercise, and other healthy lifestyle changes.
Other contributing factors to poor health can be traced to specific systems: e.g., diabetes to the circulatory system, thyroid problems to the endocrine system, and so forth. Working together with a specialist in these areas will hasten recovery.
In time, it is possible to wean oneself away from antibiotics.
The Puzzle of RA Flare-Ups
One of the enduring puzzles of so-called autoimmune disorders is that they all go through cycles of exacerbation and remission. Hundreds of experiments on animals have proved that mycoplasmas are important cofactors in arthritis and other chronic rheumatic disorders and that the tetracycline family of antibiotics suppresses mycoplasmal infections. Immune system control mechanisms appear to be cyclic in nature due to time lags in other regulatory processes (digestion, sleep cycle, etc.)
Mycoplasmas are capable of long-term intercellular in vivo survival and slow, intracellular replication, so they may be resident and waiting for some trauma or barometric pressure changes to activate them when the host’s immune system has moderated its operation. Thus the progression of the infection is cyclical, with waves of reemergence followed by withdrawal to less detectable forms.
Therefore, when mycoplasmas act as antigenic substances, triggering internal allergic responses, they release toxins intermittently to a sensitized area, subsiding and then reappearing. Antibodies move through the body via white blood cells and platelets, and it is through this means that RA migrates from shoulder to hand to knee as the antibodies launch counterattacks against local antigens and toxins. The antibodies move on to new battlefields whenever migrating pathogens like mycoplasmas flare up.
This type of ebb and flow explains the types of flare-ups that RA sufferers describe.
The apparent causal relationship between changes in the weather and RA pain can be explained. Clinical evidence shows that two environmental factors can cause flare-ups: (1) a sudden drop in barometric pressure and (2) the presence of high humidity in conjunction with this drop. The aches and pains correspond to a sudden release of antigens to a sensitized area, confirming Dr. Brown’s theory that migrating or shape-changing mycoplasmas act as antigenic triggers. As the microorganisms migrate out of the body they stimulate respiratory distress, thus broadcasting their seeds via effluvia (e.g., sneezing) to other mammalian hosts.
Trauma to joints and tendons may cause structural changes, further reducing oxygen transport and limiting removal of fluids and wastes in the region of the injury. The lack of oxygen in the traumatized area increases pressure and swelling. The usual treatment is anti-inflammatory drugs. For the COX-2 enzyme to work, the body needs sufficient copper and zinc. Hyaluronidase enzymes are destructive and facilitate bacterial reproduction. Vitamin C thwarts hyaluronidase
Mycoplasma are borderline anaerobes. That is, they are sensitive to changes in barometric pressure. They move about the body in search of more comfortable places to reside. This movement triggers the inflammation response from the immune system. Hyperbaric oxygen treatments force oxygen into compromised cells and tissue, thus allowing the infection-fighting function of white blood cells to proceed.
Aerobic exercise, deep breathing, use of a slant board are recommended. DMSO and other topical salves help improve circulation to the affected areas. Coenzyme Q10 and anti-oxidant vitamins are worthwhile supplements.
Dr. Brown’s research showed that when tetracycline is used to suppress the defensive envelope the organism builds around itself, the body’s own disease-fighting capability can combat it effectively and the RA is eventually driven into remission. Tetracycline antibiotics are among the few that are effective against virtually all species of mycoplasmas, with relatively low toxicity and few side effects. Physicians have used oxytetracycline long term for decades to treat adolescent acne with minimal adverse effects.
Test results from individuals suffering from arthritis who participate in double-blind tests with tetracyclines are not typically interpreted correctly because these tests are designed to look for a rapid linear response within a six-month period. Some chronic disease conditions do not react to a long-term, low-dose antibiotic treatment in such a short amount of time. Some conditions may require years, often because other co-factors are present and not corrected.
These antibiotics are so effective in suppressing mycoplasmas in RA that a reaction called the Jarisch-Herxheimer effect develops on initial use.
The Jarisch-Herxheimer Reaction
The fact that tetracycline causes the Jarisch-Herxheimer reaction demonstrates the presence of infection. There may be more to it than that. The reaction manifests itself as a worsening of existing symptoms. It is caused by the rapid death of a colony of parasitic microorganisms releasing their internal toxic contents in situ. With precise testing for mycoplasmal microorganisms and L-forms, perhaps by PCR or biochip methods, it may be possible to trace the origin of the infection and to see the relationship, for instance, between folic acid and fat-molecule destruction.
According to Dr. Brown, with a bacterial allergy the mycoplasma creates a barrier around itself that keeps the immune system’s natural disease-fighting antibodies at bay. Tetracycline works by suppressing this barrier, the mycoplasma’s means of defense. Research is underway to determine exactly what consitutes this barrier: toxins, lipids, or enzymes.
Natural antibiotic or antibacterial substances such as immune system-enhancing herbs and tonics may also produce a Jarisch-Herxheimer effect. As soon as this “allergic reaction” is noted, the individual should stop intake of the substance because the body’s immune system needs time to train itself to deal with the infection and become stronger.
Dr. Mercola has found that those of his patients who follow strictly prescribed nutritional guidelines rarely experience a Jarisch-Herxheimer reaction. Supplements of vitamins C and B6 are helpful in countering the body’s excessive histamine production during the course of the reaction.
This treatment method may seem counterintuitive, but it follows standard allergen immunization principles. The Jarisch-Herxheimer effect to some extent indicates success, but it cannot be endured for long without considerable discomfort, so treatment should be temporarily suspended or dosage reduced. Periodic resumption should be tried until the person gradually becomes immunized to the allergy trigger. The allergic reaction diminishes as the population of the invading organism is driven to manageable levels.
Cortisone or other corticosteroids or antihistamines may be used in conjunction with tetracyclines to permit higher doses of the antibiotic with acceptable levels of allergic reaction.
Some RA Success Stories
Test results from individuals suffering from arthritis who participate in double-blind tests with tetracyclines are not typically interpreted correctly because these tests are designed to look for a rapid linear response within a six-month period. Some chronic disease conditions do not react to a long-term, low-dose antibiotic treatment in such a short amount of time. Some conditions may require years. When the treatment is discontinued, a relapse occurs. These antibiotics are so effective in suppressing mycoplasmas that a reaction called the Jarisch-Herxheimer effect develops.
One 1995 study showed that RA may be caused by, exacerbated by, or have relapses triggered by a persistent infection of Mycoplasma or Chlamydia. Treatments with minocycline have shown positive results. This study is significant because it was conducted over the course of nearly a year. Some of the 219 participants were as young as 18 years of age. The improvement associated with the minocycline treatment suggests that a longer, protracted infection such as that caused by mycoplasmas contributes to RA. Another minocycline study showed as much as 50 percent improvement for 65 percent of the test subjects.
Dr. Gabe Mirkin notes that five significant controlled studies show that minocycline drops the rheumatoid factor towards zero and helps both to alleviate pain and to retard cartilage destruction in rheumatoid arthritis patients. In his August 1999 newsletter, Dr. Mirkin cites a study showing that more than half of RA sufferers are infected with mycoplasma. He has treated his patients successfully with minocycline.
Dr. A. Robert Franco, head of the Arthritis Center of Riverside, CA, has treated over 1,000 RA patients successfully with Dr. Brown’s antibiotic regimen since 1988.
A summary of reported statistics shows 30-40% probability of complete remission using Dr. Brown’s treatment, and 70-80% probability of significant reduction of symptoms. That’s the good news.
The Bad News
The featured presentation at the American Academy of Rheumatology in 1997 demonstrated that minocycline is the safest and least costly drug for RA, and is also the most effective when given prior to extensive cartilage damage has occurred. Dr. Mirkin deplores the fact that despite hundreds of papers showing that hundreds of different infections cause arthritis, most rheumatologists continue to treat RA with immunosuppressing drugs because they consider RA to be an autoimmune disease. According to Dr. Mirkin, these dangerously toxic drugs shorten the patient’s life by an estimated ten years and increase cancer risk six fold. The drugs are highly expensive, and merely dull pain rather than target the infection.
When antigens and antibodies clash, the result is destruction of cells and a sudden release of toxins, which are composed of a variety of diverse components—proteolytic enzymes, kinins, kallikreins, histamines, hydrogen peroxide, and other irritants. The result of the struggle is pain and inflammation.
As the mycoplasma antigen migrates to a new area, the antibodies follow it to this new combat zone, leaving the former battlefield to rest and heal, but the toxins released by the antigen-antibody conflict are often trapped in pockets of the bursa and are not promptly expelled through the various elimination organs of the body.
These trapped toxins can create a mass of fluid or scar tissue that can bring pressure to bear upon the joints when blood vessels expand. Gravity assists in trapping toxins in the lower-extremity joints of the knees and feet. Excess weight and ill-fitting shoes, especially high heels, will exacerbate the pressure and pain on these swollen, irritated tissues.
Clearance of bacteria from soft tissues appears to be of low priority importance as a host-defense mechanism during soft-tissue infection. It may be that this is the reason mycoplasmas are able to establish a foothold early and have time to adapt to later assault by antibiotics.
Neutralizing Harmful Toxins and Enzymes
In those cases where the particular pathogen is unknown or in doubt, it is more effective to target and neutralize the irritants as a first step, without identifying the organism producing them.
OTC anti-inflammatories and antihistamines can help. Sports doctors treat injured athletes with beneficial enzymes like bromelain and papain.
Other benign ways to expel these accumulated toxins are localized massage, herbs that stimulate circulation and eliminate toxins, increased water intake, and daily low-impact aerobic exercise followed by elevation of the lower legs to above-heart level several times per day using a slant board. The toxins will be loosened and drain into the bloodstream to be eliminated by the kidneys, skin, and lymphatic system.
Topical application of DMSO may also be helpful in reducing pain and swelling, in combination with topical oil of wintergreen (methyl salicylate) -- like liquid aspirin.
One aspect of RA allergic flare-up appears to be related to certain toxins, for example, salmonella toxin, where studies have found arthritis-causing genetic marker HLA-B27. In some instances, a defective HLA-B27 gene generates a molecule with a structural weakness causing it to fold up and become useless.
HLA-B27 is found on the surface of white blood cells of about eight percent of the population. More than 50 percent of adults who have rheumatoid arthritis also have the inherited marker HLA-DR4. Having this marker increases one's risk of developing RA four fold. Furthermore, research indicates that these genetic markers may predispose individuals to contract arthritis after particular infections, such as gastrointestinal infections, urinary tract infections, or diarrheal food poisoning. The linked cluster of genes, HLA-D4, occurs more frequently in people with RA
Clues might be found in the toxin or enzyme generated by the microbe, e.g., the correlations listed in the IBM Bio-Dictionary Annotation between Mycoplasma pneumonia and the COX-2 enzyme. Some of these destructive enzymes are collagenase, hyaluronidase, and penicillinase.
An allergic response, whether to an internal or external substance, is really a stimulation of the immune system to develop a specific antibody, immunoglobulin E (IgE). The IgE antibodies attach themselves to mast cells to prepare to ward off the invaders. As the offending substance (e.g., ragweed pollen) enters the body, it bumps against these primed mast cells and sets off their histamine chemicals. Destructive H2O2 is also released.
Mycoplasmas’ behavior is cyclic in nature. They often persist in metabolically inactive states where a few are released from cells, followed by more active states where many are released. Whatever the trigger, over a period of months or years the body creates fixed-tissue antibodies that are poised and ready to react to the released toxins whenever and wherever they appear. The body thus learns to react to mycoplasmas in the same way it learns to react to a substance like poison ivy. Antibody reactions alone cannot suppress mycoplasmal infections. This may be why efforts to develop vaccines against mycoplasmas have not been successful.
Over-the-counter (OTC) antihistamines such as chlorophineramine maleate have been shown to reduce the severity of rheumatoid arthritis attacks by mitigating joint pain.
However, one should not rush to swallow antihistamines at the first sign of sneezing. Instead, one should find ways to avoid allergens from animals, dust mites, molds, grasses, detergents, and foods by identifying the circumstances under which allergies strike, then removing the offending agent. The process may be as simple as cleaning furnace filters or installing electrostatic air cleaners in the home or office to keep dust levels to a minimum.
Food allergies are especially important. Reactions can be delayed as long as 72 hours. Testing can be a worthwhile investment. RA symptoms can result from Candida overgrowth. Bacteria thrive in a sugary environment. Diabetics are at risk to developing infections, and people with bacterial infections are at risk for diabetes.
Thyroid Health is Vital
Many of these symptoms apply to MS in particular, but some are experienced in a wide variety of autoimmune disorders. They are the classic set of symptoms for thyroid dysfunction, which has been shown to be linked to mycoplasma infection.
One of two types of antibodies—thyroperoxidase or thyroglobulin—is found in nearly all patients with hypothyroidism (Hashimoto’s thyroiditis) and in approximately 50 percent of those with hyperthyroidism (Grave’s Disease).
According to the Thyroid Society, twenty million Americans have some form of thyroid dysfunction but many are undiagnosed or misdiagnosed. The thyroid gland controls the body’s metabolism by producing hormones that regulate energy, control heart rate and body weight, and determine how the body uses nutrients. Thyroid test results, therefore, can be a valuable indicator of nutritional balance and efficient use of hormones. An endocrinologist should be consulted.
Since disease often begins when the immune system is dysfunctional or weakened, a nutritional analysis should be a starting point.
Tests for Microbial Infection
The principal tests helpful in diagnosing microbial infections are: Polymerase Chain Reaction (PCR), Tetracycline (as a probe), Erythrocyte Sedimentation Rate (ESR), Interferons, Rheumatoid Factor (R-factor), Neutrophil Testing, Joint Scan, Genetic Markers, Antibody tests.
All laboratory test results must of course be interpreted in the context of the patient’s overall health. Other factors influencing test results may be drugs the patient is taking, foods ingested before the test, how strictly the patient followed pretest instructions (e.g., fasting), and variations in laboratory procedures and techniques.
Some fundamental questions arise concerning the reliability of any diagnostic test involving organic samples, which may be collected exactly according to procedure at the doctor’s office, but may suffer damage in transit to the lab. Sensitivity to time, temperature, humidity, altitude, and other factors may influence test results by altering the sample before the lab technician begins to examine it. False positives or out-of-range values may result. Several tests may be required to obtain an average. Internet resources can help interpret test results and augment the physician’s assessment.
Many CFS and Fibromyalgia patients have a systemic cytomeglovirus infection. Dr. Garth Nicolson recommends testing for this infection in any instance of autoimmune illness.
Dr. Brown and his associates accumulated significant evidence that mycoplasmas and their L-forms were at the root of RA. They discovered that tetracyclines were a group of antibiotics that could kill or radically suppress mycoplasma and L-form growth. They also found that tetracyclines could help RA conditions to improve when administered in a low, controlled dose over a long period (months to years), depending on the severity of the condition and whether there were other bacterial complications adding to the sensitizing process. In these cases other antibiotics could treat the other bacteria. This approach will gradually bring the infection(s) to within manageable bounds.
Large doses of Vitamin C (3-5 grams daily) will thwart destructive enzymes like hyaluronidase that destroy connective tissue
Gentle aerobic exercise daily will oxygenate cells and flush toxins from the body. Use a slant board (ten minutes twice per day). Drink 8 glasses of pure water daily (2 sports bottles)
The right nutrition is essential for a healthy body. “We are what we assimilate.” Cells take in useful nutrients and begin the repair process, then discharge waste chemicals. Toxins are naturally excreted if circulation is good (blood and lymph), immune system in strong, endocrine functions are working effectively.
Dr. Poehlmann is the author of Rheumatoid Arthritis: The Infection Connection, available on Amazon.com and at major bookstores, or click here to order now.
 The autoimmune theory is underscored repeatedly in immunology textbooks and also in the publication of the Arthritis Foundation. E.g., Purpura, Mary, “One Person’s Stress is Another Person’s Challenge.” Arthritis Today, March/April 1997, and also Dinsmoor, Robert and Kahn, Cynthia, “Smart Drugs.” Arthritis Today, January/February 1996.
 See www.rheumatic.org for paper citations, case studies, laboratory results, abstracts, and so forth. An impressive paper by Dr. Joseph M. Mercola, “Protocol for Using Antibiotics in the Treatment of Rheumatic Diseases,” can be found at www.mercola.com. The paper was presented at the 31st Annual Meeting of the American Academy of Environmental Medicine in Boston, MA in October 1996. Dr. Mercola lauds Dr. Brown’s pioneering work in mycoplasma research and tetracycline treatment.
 Tilly, B.C.; Alarcon, G.S.; Heyse, S.P.; et al “Minocycline in Rheumatoid Arthritis: a 48-week, Double-Blind, Placebo-Controlled Trial.” Ann Int Med 1995;122:147-148.
 O’Dell, J.R.; Paulsen, G.; Haire, C.E.; et al. “Treatment of Early Seropositive Rheumatoid Arthritis with Minocycline: Four-year Followup of a Double-blind, Placebo-controlled Trial.” Arthritis and Rheumatology 1999;42:1691-1695.
 Mirkin, Dr. Gabe. “Mirkin Report for Healthier Living.” August 1999.
 Rheumatology 1999;38(6): 504-509
 See www.thearthritiscenter.com/arthritis_info.htm#Anchor-Infections-11481. This is an excellent and comprehensive website. The Arthritis Center is located at 4000 14th Street, Suite 511, Riverside, CA 92501. Phone: (909) 788-0850.
 O’Dell, et al. “Minocycline Therapy for Early Rheumatoid Arthritis Continued Efficacy at Three Years.” Annual meeting of the American College of Rheumatology. November 9, 1997.
 Mirkin, Dr. Gabe. “Mirkin Report for Healthier Living.” August 1999.
 These and other tests are described in detail in chapter 6 of Rheumatoid Arthritis: The Infection Connection by Katherine M. Poehlmann, Ph.D. Satori Press, 2002.