Fibromyalgia and Hepatitis C: Is There an Association?


Synopsis: Serologic evidence of hepatitis C infection was reported to be more than six times more prevalent in patients with fibromyalgia than in an age- and sex-matched group of patients with rheumatoid arthritis.

Source: Rivera J, et al. Fibromyalgia-associated hepatitis C virus infection. Br J Rheumatol 1997;36:981-985.

What causes fibromyalgia? many patients and their physicians are anxious, if not quite dying, to know. Rivera and colleagues have not provided a definitive answer to that perplexing question, but they have reported evidence that supports an association between hepatitis C virus (HCV) infection and fibromyalgia. They present two case control studies, the first of which compared a group of patients who received a diagnosis of fibromyalgia while attending a rheumatology clinic at a tertiary care hospital with a gender- and age-matched group of patients with rheumatoid arthritis (RA) at the same center. Both groups had HCV screening enzyme linked immuno-adsorbent assays (ELISA) which, if positive, were followed by confirmatory recombinant immunoblot assay (RIBA) and polymerase chain reaction (PCR) assays for HCV ribonucleic acid (RNA). Of the 112 patients in the fibromyalgia group, 15.2% had a positive HCV ELISA, while only 5.3% of the 112 with RA had a positive ELISA for HCV. In the fibromyalgia group, 93% of those with a positive ELISA had a positive RIBA, and 76% had positive PCR for HCV RNA. In the RA group, false-positive ELISA for HCV were more common, with 66% having confirmatory positive RIBAs, while only 33% of those with RA who were ELISA-positive had a positive PCR for HCV RNA. The difference in the prevalence of active HCV infection as indicated by PCR was 11.6% for fibromyalgia vs. 1.8% for RA and was statistically significant at the P < 0.01 level.

In the second case-control study, a group of 32 patients with documented HCV infection, who were being considered for interferon alpha treatment, were compared with a group of gender- and age-matched controls selected from patients awaiting elective surgery. Although 53% of those with HCV reported generalized arthralgia, only six (18.7%) met American College of Rheumatology criteria for fibromyalgia. The control group had only one patient (3.1%) who met fibromyalgia criteria. The difference between these two groups was statistically significant at the P < 0.001 level.


The idea that a chronic infection with HCV is linked to fibromyalgia in some causative fashion is attractive, but there are some methodological issues with the study by Rivera et al that make me hesitate to agree that the association is proven. The most important of these issues is that the examinations for tender points, upon which the diagnosis of fibromyalgia is largely based, were made by one examiner, and it is not stated in the methods section of the article that he was blinded to the HCV serologic test results. If he were aware of the HCV status of the subjects, there is a possibility of unintentional bias, since determination of tender points by palpation is more of a qualitative determination than a truly quantitative measure. Another issue is that in the group with fibromyalgia and evidence of HCV infection, roughly half the patients had abnormal transaminase enzyme levels. Although hepatitis is not specifically an exclusion criterion for fibromyalgia, it is often associated with arthralgia and myalgia. I would be hesitant about making a diagnosis of fibromyalgia in a patient with elevated hepatic enzymes. Finally, the only currently available treatment for HCV infection, interferon alpha, is associated with a high rate of post-treatment relapse, and there is no evidence of which I am aware that even successful treatment, with clearance of HCV RNA as determined by PCR, has any effect on fibromyalgia symptoms. However, if the findings of Rivera and colleagues are confirmed, screening for HCV infection in patients with fibromyalgia, even those with normal transaminase enzyme levels, may be prudent, since more effective therapy for HCV may be available in the future. Identifying patients who have been exposed to HCV may also identify patients whose behavior puts them at risk for other infectious diseases, such as hepatitis B and HIV, for which immunization, counseling, and antiviral therapy may be helpful to prevent or treat these other potentially fatal illnesses. (Dr. Greene is an Instructor in Medicine, Harvard Medical School; Chief, Rheumatology Section, Brockton/W. Roxbury VA Hospital.)

Evidence of active hepatitis C infection was indicated by detection of hepatitis C ribonucleic acid by polymerase chain reaction in what percentage of patients with fibromyalgia?

a. 1.8 %

b. 5.2 %

c. 11.6%

d. 18.7%

e. 19.1%