Chronic Infections in Fibromyalgia Syndrome: Sources of Morbidity and Illness Progression ImmuneSupport.com 09-30-2002 By Prof. Garth L. Nicolson The Institute for Molecular Medicine 15162 Triton Lane, Huntington Beach, CA 92649-1401 (From "The Fibromyalgia Survivor 2000") Fibromyalgia Syndrome (FMS) is characterized by muscle pain and tenderness at specific sites, but there are also a number of other less specific chronic signs and symptoms. Among these are disabling fatigue, impairments in short-term memory, headaches, gastrointestinal and vision problems and sometimes intermittent low-grade fevers, joint pain and other signs and symptoms. In many patients, the diagnosis of FMS is accompanied by other secondary diagnoses, such as Chronic Fatigue Syndrome (CFS), Rheumatoid Arthritis (RA), Inflammatory Bowel Diseases, and other syndromes, which can also present with overlapping signs and symptoms. This suggests that although the exact causes of these illnesses are not known and may be different in each patient, there are similarities in these conditions that may be important in patient morbidity (sickness) or in illness progression . Instead of concentrating on possible causes of FMS, we have been interested in the progression of chronic illnesses like FMS and in the potential role that chronic infections may play in FMS. The complex signs and symptoms that evolve in many FMS, CFS and RA patients may be due, in part, to systemic chronic infections (bacteria, viruses, fungi). Such infections can follow acute or chronic chemical, environmental or other insults (trauma, chemical exposures, acute viral illness, etc.) that have the potential to suppress the immune system and cause metabolic imbalances . Illness Progression in FMS Patients Illnesses like FMS evolve over time, probably in a multistep process that may require multiple toxic exposures, including infections that could be causative for the illness in a few patients, cofactors for the illness (not causative but important in patient morbidity) in others, or more likely in most patients, opportunistic infections that cause morbidity. Such infections need not be present at the onset of illness to be important. Because of their dysfunctional metabolic and immune systems, many FMS patients may be particularly susceptible to chronic infections that worsen their illness. Of course, illness progression in FMS patients could also be caused by other factors, psychological stress, physical trauma, other illnesses and many other factors . Chronic infections are usually held in check by our immune systems, but they can take hold if they can avoid immune surveillance and penetrate and hide in various tissues and organs, including muscle cells and nerve cells. When such "stealth" viral and bacterial infections occur, they can cause many of the complex signs and symptoms seen in FMS, CFS, RA and GWI, including enhanced immune dysfunction and metabolic imbalances [1, 2]. Changes in environmental responses as well as increased titers to various endogenous viruses that are commonly found to be expressed in these patients have been seen in FMS, CFS and GWI patients. If infectious agents are involved, few can produce the complex chronic signs and symptoms found in these patients. One that can is represented by a small, primitive class of bacteria called mycoplasmas . Mycoplasmas and other bacteria (Chlamydia, Coxiella, Brucella, Borelia, etc.), although not as well known as other agents in causing various diseases, are now considered important emerging pathogens in various chronic illnesses. As chronic illnesses such as FMS, CFS and RA progress, there are a number of accompanying clinical problems, and in some patients show increases in autoimmune signs and symptoms. This suggests that they do not have classical autoimmune diseases but they may have incomplete diagnoses for these diseases. Although it is certainly not proven, this pattern is consistent with certain chronic infections, such as mycoplasmal infections, that penetrate into nerve cells, synovial cells in joints, muscle cells and other cell types. Microorganisms like mycoplasmas can incorporate into their own surface structures pieces of host cell membranes that contain important host membrane antigens that can trigger autoimmune responses , and they can also mimic host cell antigen structures . Thus patients with such infections may respond immunologically to microorganism antigens as well as their own membrane antigens, producing unusual autoimmune signs and symptoms. This could explain why such patients do not have all of the clinical characteristics expected in these usually rare autoimmune diseases. Microorganisms Can Cause Morbidity in FMS Patients Microorganisms like Mycoplasmas are not considered important human pathogens when they are found at superficial sites, such as the oral cavity or gut, but some species, such as M. fermentans, M. penetrans, M. pneumoniae, M. genitalium, M. pirum and M. hominis, among others, have the capacity to penetrate into the blood circulation and colonize various tissues, and these cell-penetrating microorganisms have been closely associated with various human diseases [1, 3]. Do such infectious agents actually cause FMS, CFS or RA? Probably not on their own, but some bacteria and viruses appear to be an important element in causing chronic illness progression, patient morbidity, or exacerbating the major signs and symptoms seen in patients with chronic illnesses. We have found that ~70% of FMS, ~60% of CFS and ~50% of RA and Gulf War Illness patients have mycoplasmal blood infections that can explain many of the chronic signs and symptoms found in these patients. In the majority of FMS and CFS patients we have found multiple pathogenic mycoplasmas in their white blood cells but these infections are only found in 0-9% of controls [1, 4]. Interestingly, the majority of CFS and FMS patients had multiple mycoplasmal infections but none were found in controls ; however, single infections are found in some nonsymptomatic subjects (0-9%). The tests that we use to identify mycoplasmal infections, Forensic Polymerase Chain Reaction, are very sensitive and highly specific. These tests are a dramatic improvement over the relatively insensitive serum antibody and other tests that have been used to assay for systemic infections. New Treatments for FMS and other Chronic Illnesses When microorganism infections are identified in the blood of patients, they should be treated as medical not psychiatric patients, just like any other patients with blood infections. This does not mean that psychological or psychiatric problems are not important in chronic illness patients. But if such infections are important in these disorders, then appropriate treatments with antibiotics or other medications that suppress chronic infections should result in improvement and even recovery. This is exactly what has been found [1, 2]. The majority of patients with confirmed pathogenic mycoplasmal infections eventually recover from 50-100% of their premorbid health on therapies that are directed specifically against their chronic infections not against possible psychological problems . The recommended treatment for confirmed mycoplasmal blood infections is long-term antibiotic therapy, usually multiple 6-week cycles of doxycycline (200-300 mg/day), ciprofloxacin or Cipro (1,500 mg/day), azithromycin or Zithromax (500 mg/day) or clarithromycin or Biaxin (750-1,000 mg/day). Multiple cycles are required, because few patients recover after only a few cycles, possibly because of the intracellular locations of the infections, the slow-growing nature of these microorganisms and their inherent insensitivity to antibiotics. We now recommend that patients who have been diagnosed with blood infections receive continuous oral antibiotics for at least 6 months before using the 6-week cycles of treatment. Although patients starting such therapy usually have Herxheimer reactions and feel initially worse due to die-off or release of toxic materials from damaged microorganisms, they eventually stabilize within days to a few weeks and then slowly begin to recover. Unfortunately, the treatment requires long-term therapy, and recovery is usually very slow. Patients that have been sick for many years are unlikely to recover within a year of therapy . The clinical responses that are seen are not due to placebo effects, because administration of some antibiotics, such as penicillins, resulted in patients becoming more not less symptomatic. In addition, they are not due to immunosuppressive effects of some of the antibiotics, because other antibiotics that do not cause immune suppression are also effective but only if they suppress the chronic infections. If they don’t have these infections, then antibiotics should not work . Some patients recover to a certain point and then fail to continue to respond to the recommended antibiotics, suggesting that other problems, such as viral infections, environmental exposures and other toxic events, and even stress, also play an important role in these illnesses, and may even play a predominant role in some patients. What results have been obtained with antibiotics for chronic illnesses like FMS? Although a majority of patients diagnosed with chronic blood infections appear to benefit from antibiotic therapy, many patients respond and have some alleviation of most signs and symptoms but do not fully recover. A 3-year follow-up of antibiotic therapy in Northern California indicates that a majority (~80%) of FMS/CFS) patients from Shasta County that were confirmed with mycoplasmal infections recovered from 50-100% of their pre-illness health within this time period, and even some patients who did not test positive showed benefit from antibiotics, suggesting other bacterial infections. Similar to other therapies for chronic illnesses, not every patient benefited from antibiotic therapy, and the time required for recovery was quite variable in different patients . In some patients oxygen therapy has proved useful. Oxygen suppresses the anaerobic chronic infections like mycoplasmas. In addition to antibiotics, patients must take vitamins, minerals, immune enhancement and other supplements to help boost immunity. . For example, these patients are often depleted in vitamins B complex, C and E, among others, and certain minerals . Amino acids, fish oils, probiotic bacteria (Lactobacillus acidophillus) and a number of natural remedies have proven useful during therapy . Complex Causes of Chronic Illnesses Do chronic infections explain illnesses like FMS? It is unlikely that there is only one or even a few explanations for complex chronic illnesses like FMS or CFS. Rather, these illnesses are probably due to a combination of multiple toxic exposures, chemical and biological, in combination with genetic susceptibility (immune systems and/or detoxification systems, cellular metabolism) that determines whether a person becomes chronically ill. These considerations probably also play an important role in determining who will recover to various extents on different types of therapy. In addition, recovery can be complicated by patients’ over-dependence on drugs, such as certain antidepressants or other drugs that can suppress portions of the immune system. Interestingly, those patients that slowly recover after several cycles of antibiotics are generally less environmentally sensitive, suggesting that their immune systems may be returning to pre-illness states. If such patients had illnesses that were solely caused by psychological or psychiatric problems or by environmental or chemical exposures, they should not respond to the recommended antibiotics and recover their health. In addition, if such treatments were just reducing the autoimmune responses, then patients should not maintain recovery after the treatments are discontinued. For Further Information The Institute for Molecular Medicine can test patients for evidence of mycoplasmal and other infections (Chlamydia, Borrelia, HHV-6, CMV) of the types that worsen human diseases like FMS, CFS, RA and Gulf War Illness. Blood samples can be sent to the Institute for Molecular Medicine’s new certified reference laboratory, International Molecular Diagnostics, Inc. for mycoplasma and other testing (Tel: 714-799-7177). The Institute’s website for further information is: www.immed.org. International Molecular Diagnostics, Inc. website is www.imd-lab.com. Contact: Prof. Garth L. Nicolson The Institute for Molecular Medicine 15162 Triton Lane Huntington Beach, CA 92649-1401 Tel: 714-903-2900 Fax: 714-379-2082; email: email@example.com References 1. Nicolson, G.L., Nasralla, M, Hier, J., Erwin, R., Nicolson, N.L. and Ngwenya, R. Mycoplasmal infections in chronic illnesses: Fibromyalgia and Chronic Fatigue Syndromes, Gulf War Illness, HIV-AIDS and Rheumatoid Arthritis. Med. Sentinel 1999; 4:172-176. 2. Nicolson, G.L. The role of microorganism infections in chronic illnesses: support for antibiotic regimens. CFIDS Chronicle 1999; 12(3):19-21. 3. Baseman, J.B. and Tully, J.G. Mycoplasmas: Sophisticated, reemerging, and burdened by their notoriety. Emerg. Infect. Dis. 1997; 3:21-32. 4. Nasralla, M., Haier, J. and Nicolson, G.L. Multiple mycoplasmal infections detected in blood of Chronic Fatigue and Fibromyalgia Syndrome patients. Eur. J. Clin. Microbiol. Infect. Dis. 1999; in press. 5. Nicolson, G.L. Considerations when undergoing treatment for chronic infections found in Chronic Fatigue Syndrome, Fibromyalgia Syndrome and Gulf War Illnesses. (Part 1). Antibiotics Recommended when indicated for treatment of Gulf War Illness/CFIDS/FMS (Part 2). Intern. J. Med. 1998; 1:115-117, 123-128.