Fibromyalgia- is there an infectious connection?
Fibromyalgia (FM) is a commonly misunderstood, sometimes misdiagnosed rheumatic disease. The main symptoms are achiness, pain (more in the muscles than in the joints), stiffness, fatigue, accompanied by headaches, depression, sleep disorders, Raynaud's and irritable bowel syndrome. The sites of pain are located in specific areas call-ed tender or trigger points.
The painful tender points are located where the ligament attaches the muscle to the bone. There are 18 tender point locations. Sensitivity at 11 points defines a diagnosis of fibromyalgia. FM is not life threatening nor does it cause physical deformities. Many lab tests are within normal range. In fact, most patients look extremely well and fit, making it difficult to account for the degree of clinical suffering they are experiencing, yet 10-30% of fibromyalgia patients are disabled to some degree because of their disease symptoms.
It is 9 times more common among women than men, usually between the ages of 40 and 60, is more common in Caucasians than other races, and is the second or third most common disorder treated by rheumatologists.
Potential Pathogens As is the case of most forms of "arthritis," no known cause has been established, but a number of possibilities are mentioned in the medical literature. Like many forms of arthritis, the cause of FM is probably not limited to one single factor. 55% of patients identify a "flu-like" or viral type illness, 33% physical trauma/injury and 14% emotional stress as a precursor to the onset of symptoms. The connection of FM to infections is well documented in the literature, especially in relation to Lyme disease, mycoplasma, Chlamydia pneumoniae., Hepatitis C, Parvovirus B19, HIV, and Epstein-Barr. It is believed as many as 25-40% of long-term Lyme patients develop fibromyalgia-like symptoms, particularly pain and fatigue; as many as 25% of HIV patients, 57% of RA patients and 24% of Psoriatic Arthritis patients also have FM symptoms. A 1993 Annals of Internal Medicine article (Lightfoot et al) found 10% of patients with Lyme Disease would have arth-ritis develop as a result of the spirochete infection. Because this organism (like mycoplasma) is difficult to culture, the diagnoses is based on the occurrence of (1) one or more of the classical features and (2) serum antibodies to the etiologic spirochete after the first 4 to 6 weeks of illness.
Some Lyme/FM patients do not respond to courses of antibiotics, causing researchers to dismiss the possibility of an organism as a trigger for the disease and antibiotics as a therapy. This might be a misleading assumption as explained by Garth Nicholson, PhD, in a recent article (Environmental Phys, 1997). "Are chronic, systemic mycoplasmal infections the answer to CFS, FMS, GWI* and other disorders? Of course not! This is likely to be an appropriate explanation for a rather large subset of CFS, FMS, GWI* and some arthritis patients, but certainly not every patient will have the same chronic infections. Some patients may have chemical exposures or other environmental problems as the underlying reason for their chronic signs and symptoms. In these patients, antibiotics should have no effect whatsoever."
Nicholson has found mycoplasma infections in approximately one half of patients with FM as well as arthritis. "The identification of mycoplasma infections in the leukocyte blood fractions of a rather large subset of CFS, FMS and arthritis patients suggests that mycoplasmas, and probably other chronic infections as well, may be an important source of morbidity in these patients. If such infections are important in these disorders, then appropriate treatment with antibiotics should result in improvement and even recovery. This is exactly what has been found." (Nicholson JAMA 1995). "Only antibiotics that are effective against the pathogenic mycoplasmas result in recovery, and some antibiotics, such as penicillins, can worsen the condition." (Nicholson, 1996, & 1997.)
Goldenberg suggests two possibilities for an infectious cause:
1) the infectious agent would either directly invade tissues such as the joints or central nervous system or
2) "trigger" factors that would cause the chronic myalgias, fatigue, headaches, sleep disturbances, and mood disturbances... Infectious agents are capable of activating cytokines which may in turn cause severe myalgias, fatigue, and neurocognitive disturbances... The potential role of a microbial agent as a trigger to fibromyalgia remains tenable. Antibodies to Chlamydia pneumoniae have been found in 78.3% of FM patients tested or 67.4% for unselected rheumatic patients.
These high numbers point to a possible connection between Chlamydia pneumoniae and fibromyalgia. In a Spanish study, Rivera et al found 15% of 112 FM patients had Hepatitis C viral Infection (HCV), and among HCV patients, 10% had FM. The incidence of FM in the control group was less than 2%; the prevalence of FM in the general population was 2%. "The presence of active infection by HCV is more likely to trigger FM than the stress and anxiety produced by the disease." (Rivera et al, 1997)
Other researchers have described HCV infection as a trigger for autoimmune disorders (Pawlotsky 1994 & Agnello 1992). "In the remaining 85%, other known and unknown viruses that can produce chronic infections, could be responsible for FM symptoms. We think the presence of such viruses should be sought in patients with FM symptoms." (Rivera et al, 1997) Parvovirus B19 infection as a trigger for autoimmune disorders (Pawlotsky 1994 & Agnello 1992). "In the remaining 85%, other known and unknown viruses that can produce chronic infections, could be responsible for FM symptoms. We think the presence of such viruses should be sought in patients with FM symptoms." (Rivera et al, 1997) Parvovirus B19 has been implicated as a cause in cases of chronic arthritis and may mimic rheumatoid arthritis.
Berg et al identified patients with established FM who had symptoms consistent with recent or distant B19 infection. In fact, 30-60% of the general population test positive for Parvovirus B19, and the incidence increases with age.
The timing of testing for PV B19 appears to be critical. Testing too early or too late will yield negative results. 25% of HIV patients experience fibromyalgia symptoms, adding additional discomfort and anxiety.
Epstein Barr Virus (EBV) has been considered a possible cause of FM or CFS because of similarity of symptoms, but so far, a connection has not been proven. Most observers currently believe that no single infectious agent is likely to be the cause of CFS (or FM). Yet it has been shown that chronic persistent viruses may often be reactivated during this illness. Is this merely an epiphenomenon? Or, once reactivated, do these viruses go on to produce many of the symptoms of the disease? And what reactivates these viruses? If it is some defect in immunologic containment, what causes the defect? Could it be stress? genetics? infection with other viruses?
In the view of Komaroff et al, it is reasonable to speculate that all these factors are capable triggers, with different factors playing different roles in different individuals.
COMMON FM SYMPTOMS chronic, widespread pain - most fatigue - 70-90% morning stiffness - 80% migraine headaches - 50% depression - 25-50% sleep disturbances - 70% anxiety - 25% Raynaud's-like syndrome - 33% numbness, tingling - 75% irritable bowel syndrome - 50% positive ANA - 10%
ORGANISMS THAT MIGHT BE CONNECTED TO FM Borellia borgdorferi (Lyme) Hepatitis C Epstein-Barr Virus Mycoplasma Chlamydia pneumoniae Parvovirus B19 HIV References AM Berg, SJ Naides, RW Simms, Established Fibromyalgia Syndrome and Pravovirus B19 Infection, J Rhu, 1993; 20: 1941-1943. D Buchwald, DL Goldenberg, JL Sullivan, AL Komaroff, The "Chronic Active Epstein-Barr Virus Infection" Symdrome and Primary Fibromyalgia, Arth & Rhu, 1987; 30:10, 1132-1136. D Buskila, DD Gladman, P Langevitz, S Urowitz, HA Smythe, Fibromyalgia in Human Immunodeficiency Virus Infection, J Rhu, 1990; 17:9, 1202-1206. XJ Caro, Is There an Immunologic Component to the Fibrositis Syndrome? Rhu Dis Cl N Am, 1989; 15:1, 169-186. B Freundlich, L Leventhal, The Fibromyalgia Syndrome, Primer on the Rheumatic Diseases, Arthritis Found, 1993; 247-249. DL Goldenberg, Fibromyalgia and Related Syndromes, Textbook of Rheumatology, R Klipple ed, Mosby, 4.15.1-10. DL Goldenberg, Fibromyalgia and other Chronic Fatigue Syndromes: Is There Evidence for a Chronic Viral Disease? Seminars in Arth & Rheum, 1988; 18: 111-120. DL Goldenberg, Do Infections Trigger Fibromyalgia? Arth & Rhu, 1993; 36: 1489-92. DL Goldenberg, Fibromyalgia and Its Relation to Chronic Fatigue Syndrome, Viral Illness and Immune Abnormalities, J Rhu, 1989; 16 (suppl 19); 91-93. VM Hsu, SJ Patella, LH Sigal, "Chronic Lyme Disease" as the Incorrect Diagnosis in Patients with Fibromyalgia, Arth & Rheum, 1993; 36:11, 1493-1500. AL Komaroff, DL Goldenberg, Chronic Fatigue Syndrome: Definition, Current Studies and Lessons for Fibromyalgia Research, J Rhu, 1989; 16 (suppl 19), 23-27. JM Krueger L Johannsen, Bacterial Products, Cytokines and Sleep, J Rhu, 1989; (Suppl 19) 16; 52-57. P Langevitz, D Buskila, Studying Tenderness - A Clue to Understanding Fibreomyalgia, Isr J Med Sci, 1992; 28:" 41-42. LJ Leventhal, SJ Naides, B Freundlich, Fibromyalgia and Parvovirus Infections, Arth & Rhu 1991; 34: 1319-1324. RW Lightfoot, BJ Luft, DW Rahn, AC Steere, LH Sigal, DC Zoschke, P Gardner, MC Britton, RL Kaufman, Empiric Parenteral Antibiotic Treatment of Patients with Fibromyalgia and Fatigue and a Positive Serologic Result for Lyme-disease, Ann Int Med, 1993; 119: 503-509. I Machtey, Chlamydia pneumoniae antibodies in Myalgia of Unknown Cause (including Fibromyalgia), Br J Rheum, 36:10, letter, 1134. GL Nicholson, New Treatments for Chronis Infections Found in CFS, Fibromyalgia Syndrome and Gulf War Illness, Environmental Physician, Fall 1997, 13-14. GL Nicholson, Doxycycline Treatment and Desert Storm, JAMA 1995; 273: 618-619. GL Nicholson, NL Nicholson, Diagnosis and Treatment of Mycoplasmal Infections in Persian Gulf War Illness - CFIDS patients, Int. J Occup Med Immunol Tox 1996; 5: 69-78. GL Nicholson, NL Nicholson, M Nasralla, Mycoplasmal Infections and Chronic /Fatigue Illness (Gulf War Illness) Associated with Deployment to Operation Desert Storm, Int J Med, 1997 (in press) J Rivera, A De Degio, M Trinchet, AG Monforte, Fibromyalgia-associated Hepatitis C Virus Infection, Br J Rheum, 1997; 36:9; 981-985. *CFS - chronic fatigue syndrome; FMS - fibromyalgia syndrome, GWI - Gulf War illness