Understanding fibromyalgia and autoimmune diseases
by Nathan Wei, MD, FACP, FACR
Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.
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Information, in part, from the American College of Rheumatology
Fibromyalgia is a chronic disorder characterized by widespread musculoskeletal pain, fatigue, and tenderness in localized areas of the neck, spine, shoulders, and hips called "tender points."
People with this syndrome may also experience sleep disturbances, morning stiffness, irritable bowel syndrome, anxiety, and other symptoms. Available data suggest that the number of persons aged 18 and older in the United States with fibromyalgia is approximately 3.7 million. It primarily occurs in women of childbearing age, but people of all ages may also be affected.
Although the cause of fibromyalgia is unknown, researchers have several theories about the causes or triggers of fibromyalgia. Some scientists believe that the syndrome may be initiated by an injury or trauma. This injury may affect the central nervous system. Fibromyalgia may be associated with changes in muscle metabolism, such as decreased blood flow, causing fatigue and decreased strength. Others believe the syndrome may be triggered by an infectious agent such as a virus in susceptible people, but no such agent has been identified.
Fibromyalgia is not an autoimmune disease, although many people believe it to be. As noted below, there may be some evidence that FM has an autoimmune component to it. Unfortunately, there is not a lot of concrete evidence to support and validate that notion yet.
Fibromyalgia is difficult to diagnose because many of the symptoms mimic those of other diseases. The American College of Rheumatology (ACR) has developed criteria for fibromyalgia that physicians can use in diagnosing the disease. According to ACR criteria, a person is considered to have fibromyalgia if he or she has widespread pain for at least 3 months in combination with tenderness in at least 11 of 18 specific tender point sites.
An example of what may be evidence of the autoimmune tendency for FM was reported in this news release...
NEW ANTIBODIES DISCOVERED IN MANY FIBROMYALGIA PATIENTS
(NEW ORLEANS, February 10, 1999) Autoimmune Technologies, LLC, a New Orleans biotechnology company, today announced that scientists have discovered a new antibody in the blood of many fibromyalgia patients. This research is described in an article entitled "Anti-Polymer Antibody Reactivity in a Subset of Patients with Fibromyalgia Correlates with Severity," which appears in the February 1999 issue of The Journal of Rheumatology, a prominent scientific journal.
Using a patented blood test called the Anti-Polymer Antibody Assay, or APA Assay, researchers found anti-polymer antibodies in approximately one-half of all patients who were diagnosed with fibromyalgia and in more than 60% of the fibromyalgia patients with severe fibromyalgia symptoms. Patients with diseases frequently confused with fibromyalgia, including rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis/scleroderma, had a much lower incidence of these antibodies than did the fibromyalgia patients.
Fibromyalgia syndrome is a chronic pain disorder that affects millions of individuals, primarily women, in many countries throughout the world. The cause or causes of fibromyalgia are currently unknown, but researchers have suggested that trauma, infection, and exposure to environmental factors may all participate in the development of this debilitating illness. Together with widespread pain and tender points in various areas of the body, signs and symptoms include fatigue, sleep disorder, morning stiffness, headache, cognitive problems, and other symptoms. In the United States, some 3% to 5% of adult women meet the strict diagnostic criteria of the American College of Rheumatology for fibromyalgia, but as many as 15% to 20% of adult women may have fibromyalgia-like symptoms.
Fibromyalgia syndrome is often difficult to diagnose, and typically a diagnosis is reached through the time-consuming and expensive process of ruling out other illnesses that have similar symptoms. In addition, many physicians consider fibromyalgia to be the result of aging and other normal body processes and do not regard it as a distinct clinical disorder. The resulting reluctance on the part of some physicians to attribute their patients' symptoms to a specific illness has added considerably to the distress of many fibromyalgia patients. Until now, there has been no laboratory test to help identify fibromyalgia.
"Our results show that there is a unique immunological response in many fibromyalgia patients," said Russell B. Wilson, Ph.D., president of Autoimmune Technologies and lead investigator of the published study. "We hope that these findings will lead to a better understanding of the illness and to the development of treatments for these patients."
It is possible, Dr. Wilson pointed out, that anti-polymer antibodies are associated with one of the several different causes of fibromyalgia, perhaps the cause that tends to produce the most severe symptoms. The published data indicate that this may be the case, although more research will be needed. In addition to serving as a marker for fibromyalgia, he noted, it is also possible that these antibodies are directly involved in initiating or promoting fibromyalgia.
The development of a laboratory test for fibromyalgia was welcomed by experts in the field.
"The fibromyalgia syndrome is common in clinical medicine and in the general community. We also have data on its cost," said I. Jon Russell, M.D., Ph.D., an internationally recognized fibromyalgia investigator and clinician from the University of Texas Health Center at San Antonio. "The direct medical costs of this disorder to the U.S. economy are over $16 billion annually. The findings of this study raise the hopeful prospect that a new test will help us better understand fibromyalgia. Further research is needed to confirm the clinical specificity of the test relative to other painful conditions. In addition, it will be important to determine whether the antibody identified by this test in the blood of people with fibromyalgia is related to the cause of the disorder or simply represents an interesting epiphenomenon," Dr. Russell said.
Associated factors appear in parallel in epiphenomena. If further research shows the production of anti-polymer antibodies to be an epiphenomenon, the antibodies would serve as a laboratory marker for fibromyalgia without playing a direct role in the disease process.
Kristin Thorson is president of The Fibromyalgia Network, a patient self-help organization headquartered in Tucson, Arizona, and president of The American Fibromyalgia Syndrome Association, a charitable organization dedicated to funding research on fibromyalgia and chronic fatigue syndrome. "In the past," Ms. Thorson said, "many health insurance companies and some members of the medical community have argued that fibromyalgia is not real - all because no one had developed a lab marker to indicate otherwise. Now that there is a blood marker that can be shown to correlate with disease severity, there should be no more debate over the existence of fibromyalgia and scientists should be encouraged to research effective therapies for this potentially disabling illness."
Robert M. Bennett, M.D., a physician and scientist who is chairman of the Division of Arthritis and Rheumatic Disease of Oregon Health Sciences University in Portland and a widely published and internationally known expert on fibromyalgia syndrome, said "There are two major problems for most physicians in accepting fibromyalgia. The first is the lack of an easily performed laboratory test. The second is its recalcitrance to therapy. The promise of a potentially useful diagnostic marker is an exciting development in this field. If the sensitivity and specificity of this test can be confirmed by independent laboratories, it could open up an important new research avenue for a condition that compromises the quality of life of five million to ten million U.S. women."
Autoimmune Technologies expects during 1999 to apply to the U.S. Food and Drug Administration for approval of a kit form of the Assay as a diagnostic test. "The reproducibility of the APA Assay has already been independently demonstrated by the National Institute of Public Health and the Environment, or RIVM, in The Netherlands," said Dr. Wilson. "The RIVM has found the APA Assay to give reproducible results and to be useful for the evaluation of the presence of anti-polymer antibodies in human serum. The other confirmatory studies discussed by Drs. Russell and Bennett are already well under way. These studies, together with our research published in The Journal of Rheumatology, will be included in our application to the FDA for approval of the Assay as an in vitro diagnostic test to aid in the diagnosis of fibromyalgia."
Other authors of the article in this month's issue of The Journal of Rheumatology include Dr. Oscar S. Gluck and Dr. John R. P. Tesser of the Arizona Rheumatology Center in Phoenix, Dr. Janet C. Rice of Tulane University School of Public Health and Tropical Medicine, and Dr. Alan J. Bridges of the University of Wisconsin School of Medicine in Madison.
Anti-polymer antibodies were discovered by researchers at Tulane University Medical Center, where the APA Assay was developed. Autoimmune Technologies has licensed the APA Assay from Tulane. An APA Assay kit is not currently in commercial distribution in the U.S., although the Assay is being performed by Autoimmune Technologies as a service to physicians and researchers for investigational use only. A kit form of the APA Assay will be available in the near future in other countries.
The APA Assay is covered by U.S. and European patents, and patents in other countries are pending.
For further information, visit the Autoimmune Technologies Web site at www.autoimmune.com.
So far, this assay has not found widespread use.
Another study also suggested a link between autoimmunity and FM...
Detection of Interleukin 1beta (IL-1beta), IL-6, and Tumor Necrosis Factor-alpha in Skin of Patients with Fibromyalgia
SOUZAN SALEMI, JANINE RETHAGE, UWE WOLLINA, BEAT A. MICHEL, RENATE E. GAY, STEFFEN GAY, and HAIKO SPROTT
Objective. To determine if abnormal collagen metabolism is correlated with neurogenic inflammation, a potential activator of collagen metabolism, in patients with fibromyalgia (FM).
Methods. The presence of inflammatory cytokines, interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)- was investigated in skin tissues by using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Fifty-three skin biopsies from female patients with FM (30-65 years of age) were examined and compared to skin biopsies of 10 age and sex matched healthy controls. Biopsies were obtained from the left deltoid region. Rheumatoid arthritis synovial fibroblasts and tissues were used as positive controls for the expression of cytokines. Total RNA isolated from the tissue samples were reverse transcribed (RT) by random hexamers as the primer for RT followed by PCR amplification using specific primers for IL-1ß, IL-6 or TNF-. Expression of IL-1ß, and TNF- protein was investigated in the skin by immunohistochemistry using specific antibodies (avidin-biotin method).
Results. Positive signals (RT-PCR) were detected in skin tissues of 19/50 (38%) FM patients for IL-1ß, in 14/51 FM patients (27%) for IL-6, and in 17/53 patients (32%) for TNF-. None of the cytokines could be detected in healthy control skin. Immunoreactivity for IL-1ß and TNF- was demonstrated in certain skin tissues of our FM patients.
Conclusion. The detection of cytokines in FM skin indicates the presence of inflammatory foci (neurogenic inflammation) in the skin of certain patients (about 30% of FM patients), suggesting an inflammatory component in the induction of pain. This may explain the response to nonsteroidal antiinflammatory therapy in a subset of FM patients. (J Rheumatol 2003;30:146-50)
From the Center of Experimental Rheumatology, Department of Rheumatology and Institute of Physical Medicine, University Hospital, Zürich, Switzerland and the Department of Dermatology Allergology, Friedrich-Schiller University, Jena, Germany.
Supported in part by the Zurzach foundation, the American Fibromyalgia Syndrome Association (AFSA), and the Albert Böni Foundation.
S. Salemi, PhD; J. Rethage, Msc; B.A. Michel, MD; R.E. Gay, MD; S. Gay, MD, H. Sprott, MD, Center of Experimental Rheumatology, Department of Rheumatology and Institute of Physical Medicine, University Hospital; U. Wollina, MD, Department of Dermatology and Allergology, Friedrich-Schiller University.
Address reprint requests to Dr. H. Sprott, Center of Experimental Rheumatology, Department of Rheumatology and Institute of Physical Medicine, University Hospital, Gloriastrasse 25, CH-8091 Zürich, Switzerland. E-mail: firstname.lastname@example.org
Submitted March 18, 2002; revision accepted May 24, 2002.
Lupus is an autoimmune disease. The presence of auto-antibodies (antibodies against the self) that serve as markers of disease and which also seem to have a role in worsening the disease have been demonstrated and validated. Having an autoimmune disease such as lupus or rheumatoid arthritis increases the likelihood that a person will develop FM; however, it is unlikely that someone will develop an autoimmune disease if they have fibromyalgia.
Treatment of fibromyalgia requires a comprehensive approach. The physician, physical therapist, and others in the medical support system, as well as the patient may all play an active role in the management of fibromyalgia. Studies have shown that aerobic exercise, such as swimming and walking, improves muscle fitness and reduces muscle pain and tenderness. Heat and massage may also give short-term relief. Psychotropic drugs in the antidepressant class may help elevate mood, improve quality of sleep, and relax muscles. Fibromyalgia patients may benefit from a combination of exercise, medication, physical therapy, and relaxation.
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