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ID PMID Title PublicationDate abstract
9159535 Testosterone metabolism and cyclosporin A treatment in rheumatoid arthritis. 1997 Apr A constant dose-dependent side-effect in cyclosporin A (CSA)-treated patients is the appearance of hypertrichosis; this occurs in both sexes and suggests an androgenizing activity. To determine the influence of CSA on peripheral androgen metabolism, we evaluated in rheumatoid arthritis (RA) patients treated with low-dose CSA (3.5 mg/kg/day), during a period of 12 months, plasma levels of testosterone (Tes) and of 5alpha-androstane-3alpha, 17beta-diol glucuronide (Adiol-G), an important peripheral Tes metabolite. Clinical and laboratory parameters of RA were also monitored. Furthermore, the metabolism of physiological concentrations of Tes (1 x 10(-8) M) was evaluated in primary cultures of RA synovial macrophages (M phi) in the presence of CSA concentrations close to the pharmacological immunosuppressive doses (100-500 ng/ml). At the final time of observation (12 months), a significant increase in the mean plasma Adiol-G level was observed in patients of both sexes. The increase was evident after 1 month of treatment in male patients (P < 0.01) and after 3 months in female patients (P < 0.05). Almost all the patients experienced the side-effect of a low-degree hypertrichosis after a mean period of 1-2 months. No significant correlations with the laboratory parameters of the disease were observed. Results from in vitro experiments on Tes metabolism by cultured synovial M phi showed at 24 and 48 h, in the presence of CSA, a significantly (P < 0.0001) greater formation of dihydrotestosterone and increased amounts of other Tes metabolites, including androstenedione, androsterone and epiandrosterone, when compared to untreated controls. In conclusion, the appearance of a dose-related hypertrichosis and the increase in plasma androgen metabolites (i.e. Adiol-G) in CSA-treated patients, as well as the hormonal metabolic effects on cultured synovial M phi, should be regarded as possible markers of the influence of CSA on peripheral androgen metabolism at the level of target cells.
11517757 [Tumor necrosis factor-alpha and kidney damage in rheumatoid arthritis]. 2001 AIM: To investigate clinical significance of tumor necrosis factor-alpha (TNF-alpha) and kidney damage in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: 94 patients (84 women and 10 men, mean age 45.2 +/- 11.9 years and the disease duration 7.5 +/- 6.5 years) with RA and 20 donors were examined. In 37(39.4%) and 57(60.6%) patients radiological stages I-II and III-IV, respectively, were determined. TNF-alpha and C-reactive protein (CRP) were measured by ELISA. RESULTS: Serum levels of TNF-alpha in patients with RA appeared significantly higher than in donors (10.9 +/- 22.1 pg/ml vs 0.6 +/- 2.0 pg/ml, p < 0.001). 33 (35.1%) of 94 patients had TNF-alpha levels above 6.6 pg/ml. High serum levels of TNF-alpha correlated significantly with the presence of nephrotic syndrome (r = 0.22, p = 0.03) caused by secondary amyloidosis. There were no correlations between high levels of TNF-alpha and sex, age, disease duration, stages and clinical activity in patients with RA. Positive correlation was found between high levels of TNF-alpha and ESR (r = 0.30, p = 0.003), CRP (r = 0.37, p = 0.0001). CONCLUSION: Thus, TNF-alpha may be involved in pathogenesis of amyloidosis in RA.
9239413 Genetic bias in immune responses to a cassette shared by different microorganisms in patie 1997 Aug 1 Rheumatoid arthritis (RA) is an autoimmune disease associated with HLA-DRbeta1 alleles which contain the QKRAA amino acid sequence in their third hypervariable region(s). The QKRAA sequence is also expressed by several human pathogens. We have shown previously that an Escherichia coli peptide encompassing QKRAA is a target of immune responses in RA patients. Here we address two questions: first, whether QKRAA may function as an "immunological cassette" with similar, RA-associated, immunogenic properties when expressed by other common human pathogens; and second, what is the influence of genetic background in the generation of these responses. We find that early RA patients have enhanced humoral and cellular immune responses to Epstein-Barr virus and Brucella ovis and Lactobacillus lactis antigens which contain the QKRAA sequence. These results suggest that the QKRAA sequence is an antigenic epitope on several different microbial proteins, and that RA patients recognize the immunological cassette on different backgrounds. ANOVA of immune responses to "shared epitope" antigens in monozygotic twin couples shows that, despite significantly elevated responses in affected individuals, a similarity between pairs is retained, thus suggesting a role played either by hereditary or shared environmental factors in the genesis or maintenance of these responses.
10817567 Soluble vascular cell adhesion molecule 1 mediation of monocyte chemotaxis in rheumatoid a 2000 May OBJECTIVE: Rheumatoid arthritis (RA) is characterized by infiltration of leukocytes, including monocyte/ macrophages, into synovial tissue (ST), but factors mediating the ingress of these cells are poorly understood. Vascular cell adhesion molecule 1 (VCAM-1) plays an important role in adhesion of leukocytes to the vasculature. This study was undertaken to test the hypothesis that soluble VCAM-1 (sVCAM-1) might mediate chemotaxis of monocytes in RA. METHODS: Chemotaxis assays were performed using a modified Boyden chamber to determine the effects of sVCAM-1 on and the role of very late activation antigen 4 (VLA-4) in peripheral blood (PB) monocyte migration. Synovial fluids (SF) were immunodepleted of sVCAM-1 to identify a role for sVCAM-1 in RA. Immunohistochemistry and flow cytometry analyses were performed to show the expression of VLA-4 in ST, SF, and PB. Tyrosine phosphorylation was studied by Western blot analysis on PB monocyte lysates in the presence of signaling inhibitors. RESULTS: Soluble VCAM-1 induced monocyte migration in the nM range, in a concentration-dependent manner. Anti-VLA-4 significantly inhibited sVCAM-1-induced monocyte migration, suggesting that sVCAM-1 acts in part via a VLA-4-dependent mechanism. In RA SF, incubation with anti-VCAM-1 resulted in a reduction in the ability to induce monocyte migration (mean 28%). VLA-4 immunolocalized to RA ST, SF, or PB, monocytes, macrophages, and lymphocytes. Soluble VCAM-1 stimulated tyrosine phosphorylation in monocytes, and pertussis toxin, chelerythrine chloride, and staurosporine significantly reduced sVCAM-1-mediated monocyte chemotaxis, suggesting that signaling pathways via G proteins and protein kinase C are required for sVCAM-1-mediated monocyte migration. CONCLUSION: These results demonstrate a novel function for sVCAM-1 as a monocyte chemotactic agent in RA and suggest a new potential target for modulating monocyte ingress into inflamed RA ST.
10963074 New therapeutic targets in rheumatoid arthritis. 2000 Gene therapy has the significant advantage of providing targeted and continuous administration of a therapeutic agent within the joint. A number of targets of choice are discussed, including cytokines, metalloproteinase inhibitors and angiogenesis costimulators. Gene transfer can also be used to inhibit intracellular biological cascades (apoptosis, signal transduction, cell differentiation). Preliminary Phase I ex vivo studies have confirmed the feasibility of gene therapy in rheumatoid arthritis. Vectors will have to be improved before in vivo studies are performed.
10628065 Leflunomide for the treatment of rheumatoid arthritis. 1999 Leflunomide treatment appears to offer an alternative to methotrexate and sulfasalazine and is a welcome addition to the therapeutic armamentarium for treating active RA. Leflunomide treatment for more than 12 months results in clinically meaningful improvements in disease-specific measures of physical function. The phase 3 trials have shown leflunomide to be as effective as methotrexate and sulfasalazine and an option for initial DMARD therapy. As with all new agents, the long-term safety and value of leflunomide will be determined by use in the clinic.
11315081 The variance for the disequilibrium coefficient in the individual Hardy-Weinberg test. 1999 Dec It is of interest to detect the deviation from Hardy-Weinberg proportion (HWP) for a particular heterozygote. Hernández and Weir (1989, Biometrics 45, 53-70) suggested a disequilibrium coefficient approach and proposed a 1-d.f. chi2 test. This note derives the appropriate variance under the null hypothesis for performing this individual HWP test. Examples of applying the test to human genetic disease data are presented.
10943859 Soluble complement receptor 1 (CD35) delivered by retrovirally infected syngeneic cells or 2000 Aug OBJECTIVE: The complement system is important in the development of autoimmune inflammation, including rheumatoid arthritis (RA) and collagen-induced arthritis (CIA). Complement receptor 1 (CR1) is involved in regulation of complement activity. Studies on models of autoimmunity have demonstrated that soluble CR1 (sCR1) is a potent therapeutic agent. The present study was thus undertaken to investigate the feasibility of antiinflammatory gene therapy to prevent CIA by delivery of genes encoding truncated sCR1 (tsCR1) and dimeric tsCR1-Ig. METHODS: Syngeneic fibroblasts or arthritogenic splenocytes, engineered to express tsCR1 using retrovirus-mediated gene transfer, were injected into DBA/1 recipients that had been immunized with bovine type II collagen (CII). In separate experiments, naked DNA containing tsCR1 and tsCR1-Ig genes was injected intramuscularly into the immunized animals. The clinical development of arthritis was monitored, anti-CII levels measured, and antigenic T cell response studied. Affinity-purified tsCR1-Ig was assayed for its inhibitory effect on the alternative complement pathway in mouse serum. RESULTS: Treatment of CII-immunized mice with the tsCR1-expressing cells inhibited development of CIA, reduced anti-CII antibody levels, and inhibited T cell response to CII in vitro. Intramuscular injections of DNA encoding the CR1 genes prevented the progression of disease. Furthermore, compared with full-length sCR1, purified tsCR1-Ig was more active in inhibiting the murine alternative complement pathway. CONCLUSION: Our findings demonstrated that tsCR1 and tsCR1-Ig, when delivered via gene therapy, had a beneficial effect on autoimmune inflammation. These results indicate that targeting the complement system in RA patients may be of clinical importance.
10402081 Oral carriage of staphylococci in patients with rheumatoid arthritis. 1999 Jun OBJECTIVE: To determine the prevalence of oral staphylococcal carriage in patients with rheumatoid arthritis compared with healthy controls. METHODS: Fifty healthy adults, 25 healthy elderly volunteers and 25 patients with rheumatoid arthritis were studied. An oral rinse, tongue swab and nasal swab were collected for culture on blood agar and a range of selective agars. Isolates of staphylococci were identified and antibiotic sensitivity profiles determined by standard methods. RESULTS: Staphylococci were isolated from the mouths of 94% of the healthy adults, 24% of whom carried Staphylococcus aureus. All the healthy elderly carried oral staphylococci and 36% were colonized with S. aureus. Staphylococci were isolated from 96% of the rheumatoid arthritis patients and this group had the highest carriage rate of S. aureus (56%), significantly higher than the healthy adults (P < 0.05). In all three groups, Staphylococcus epidermidis was isolated from the mouths of > 80%. No methicillin-resistant strains of S. aureus were isolated. CONCLUSION: Oral carriage of S. aureus appears to be common in patients with rheumatoid arthritis and studies of the mouth as a source of infection in septic arthritis would be merited.
11001378 New and future drug therapies for rheumatoid arthritis. 2000 Jun Several new drugs have recently been introduced for the treatment of rheumatoid arthritis (RA). These include the cyclooxygenase-2 inhibitor, celecoxib, the anti-tumour necrosis factor agents, etanercept and infliximab, and the new disease-modifying anti-rheumatic drug (DMARD), leflunomide. In clinical trials, celecoxib has been shown to be effective for palliation of the signs and symptoms of RA and to have fewer gastrointestinal side-effects than conventional non-steroidal anti-inflammatory drugs. Etanercept and infliximab are indicated for reduction of the signs and symptoms of RA in patients who have failed to respond adequately to previous DMARDs. The clinical success rate in etanercept-treated patients is significantly better than in placebo-treated patients for up to 18 months. Leflunomide is a DMARD with a novel mechanism of action that has been approved as a first-line treatment for RA. Treatment with leflunomide results in significantly greater improvement of the signs and symptoms of RA than placebo for up to 2 yr and slows radiographically assessed disease progression. Agents are currently in development that will be targeted against components of the immune activation and co-stimulatory pathways. These include antibodies directed against the interleukin-2 receptor and blockers of the CD28 and CD40 co-stimulatory pathways. Continuing research into the pathogenesis of RA will undoubtedly identify even more effective therapeutic approaches for the management of this disease in the future.
9133934 Methods to score vertebral deformities in patients with rheumatoid arthritis. 1997 Feb The objective was to compare four different scoring methods for vertebral deformities: the semiquantitative Kleerekoper score and three quantitative scores (according to Minne, Melton and Raymakers) in patients with rheumatoid arthritis (RA). Lateral radiographs of the thoracic and lumbar vertebral column were scored in 52 RA patients treated with corticosteroids (Cs) and 52 RA patients not Cs treated (matched for age and gender). Clinically manifest vertebral fractures were defined as a vertebral deformity leading to the prescription of therapy: bedrest and/or analgesies. The number of Cs-treated RA patients with vertebral deformities was only increased according to the Kleerekoper score (relative risk 2.31; 95% confidence interval 1.36-3.90). The total number of vertebral deformities was increased in Cs-treated RA patients according to the method of Kleerekoper. Minne and Raymakers, but not according to Melton. The Spinal Deformity Index was increased in the Cs-treated RA patients according to Minne (P < 0.05), but not according to Raymakers. In both patient groups, the number of patients with clinically manifest vertebral fractures was much lower than that of vertebral deformities, e.g. in the Cs-treated patients 13% vs 35.79% (depending on the scoring method used). All eight patients with clinically manifest vertebral fractures had severe height loss (25% or more) in at least one vertebra. Vertebral deformities seem to occur more often in Cs-treated patients than in those not Cs-treated. However, differences exist in the number of patients with vertebral deformities and in the total number of vertebral deformities between different scoring methods. This emphasizes the need for a gold standard or consensus for defining vertebral deformities, in which, in our opinion, a Spinal Deformity Index has to be included. Clinically manifest vertebral fractures are predominantly characterized by severe vertebral deformities on X-rays.
9972980 Interleukin 8 and monocyte chemoattractant protein-1 in patients with juvenile rheumatoid 1999 Feb OBJECTIVE: To measure serum and synovial fluid (SF) levels of interleukin 8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in patients with juvenile rheumatoid arthritis (JRA) and to compare them with adult rheumatoid factor-positive rheumatoid arthritis (RA). METHODS: IL-8 and MCP-1 were measured by immunoassay (1) in sera obtained from 55 children with JRA and from 16 adults with RA, and (2) in SF obtained from 30 children with JRA and 11 adults with RA. RESULTS: Patients with active systemic JRA had serum levels of IL-8 and MCP-1 higher than in controls (p<0.01) and in patients with active polyarticular or pauciarticular JRA (p<0.05). In patients with RA serum MCP-1 levels were higher than in patients with the 3 JRA onset types, while no difference was found for IL-8 levels. Patients with systemic JRA and with current systemic features had serum levels of IL-8 and MCP-1 higher (p = 0.03 and p = 0.04, respectively) than patients in which systemic features had subsided. No significant differences in SF IL-8 or MCP-1 levels were found among the 3 JRA onset types or adults with RA. In patients with JRA SF leukocyte counts were correlated with SF IL-8 levels (p = 0.002), but not with MCP-1 levels. Moreover, SF levels of both IL-8 and MCP-1 were correlated with those of IL-1beta (p<0.001) and IL-6 (p<0.01), but not with those of TNF-alpha. CONCLUSION: Elevated serum levels of IL-8 and MCP-1 in patients with systemic JRA with current systemic features at sampling suggest systemic production of the 2 chemokines during systemic phases of the disease. Similar SF levels of IL-8 and MCP-1 among the 3 JRA onset-types and RA suggest comparable local production of the 2 chemokines.
9361155 Methotrexate use in rheumatoid arthritis. 1997 Nov To overstate the importance of methotrexate in the contemporary management of rheumatoid arthritis would be difficult. It has achieved this distinction because of its efficacy and tolerability. This article reviews the data on the efficacy and toxicity of methotrexate, discusses caveats for clinical use, examines the use of methotrexate in combination therapy, and speculates on the future use of methotrexate in rheumatoid arthritis.
9159537 Body composition in rheumatoid arthritis. 1997 Apr The objectives were to assess bone mineral density (BMD) at different body sites in rheumatoid arthritis (RA) patients related to disease severity parameters, disease duration and corticosteroid intake, and to look for body composition measurements as lean body mass (LBM) and per cent fat as possible prognostic factors in RA. Body composition values were measured cross-sectionally in 89 RA patients and compared with 157 controls. Patients were divided into males and postmenopausal females, ever steroid treated and never steroid treated. BMD values of all body sites were significantly lower compared to normals in all subgroups, except for the lumbar spine (L2 L4) in all postmenopausal women and males never treated with steroids. There was also no clear BMD decrease in the arms of male RA patients. LBM was significantly lower in all body parts compared to controls, whereas the fat distribution ratio (FDR) showed a clear shift to abdominal in all patients. These are parameters of chronic illness and a predictor of cardiovascular disease, respectively. BMD data confirm our previous data in different patient groups (low at appendicular sites, normal lumbar BMD), but no clear influence of disease severity and steroid intake could be found. Body composition data, as LBM and FDR, are also altered in RA patients: decreased LMB and more central FDR. Their usefulness as prognostic markers in early RA patients needs to be clarified prospectively in these patient groups.
10914426 Muscle involvement in rheumatoid arthritis: an ultrastructural study. 2000 May An electron microscopic investigation has been carried out on muscle bioptic samples from patients affected by rheumatoid arthritis (RA). This study was undertaken to seek further ultrastructural alterations affecting striated muscles in RA pathology. Bioptic samples were collected on a total of 30 surgical interventions of hip (10), knee (8), and foot (12). This yielded three muscle types: gluteus maximus, vastus lateralis, and extensor digitorum communis. Muscle samples from 12 patients with no RA stigmata, selected to match RA patients by age and gender, constituted the control group. Tissue samples were prepared both for conventional histochemical methods and according to conventional electron microscopic procedures, including morphometric analysis. Although to a different extent in each sample, in muscles from RA vs. controls the authors observed the simultaneous presence of discrete muscular alterations such as wider separation of myofibrils, myelin figures, dilated sarcotubular system, pleomorphic mitochondria, myofibril flaking, and lipofuscin deposition in the subsarcolemmal region. In addition to a progressive atrophy, the above findings are suggestive of rheumatoid myositis and lend further support to the still poorly documented presence of an idiopathic inflammatory myopathy and inclusion body myositis associated with RA.
10461474 Serum YKL-40 concentrations in patients with rheumatoid arthritis: relation to disease act 1999 Jul OBJECTIVE: YKL-40, also called human cartilage glycoprotein-39, is secreted by chondrocytes, synovial cells, macrophages and neutrophils. Studies have shown that YKL-40 is an autoantigen in rheumatoid arthritis (RA). We evaluated whether serum YKL-40 was related to disease activity in patients with RA. METHODS: Serum YKL-40 was determined by radioimmunoassay in 156 patients with RA during a 1 yr longitudinal study. RESULTS: Serum YKL-40 was increased in 54% of the patients with clinically active disease. Patients with clinically active disease initially who became inactive after 12 months had a significant decrease in serum YKL-40 (-30%, P < 0.002) and patients who changed from inactive to active disease had an increase in serum YKL-40. Patients who remained active had unchanged serum YKL-40 during the study. Serum YKL-40 decreased rapidly (-24% after 7 days, P < 0.01) during prednisolone therapy, and more slowly in patients treated with methotrexate only (-15% after 60 days, P < 0.01). Patients with early RA (disease duration < 3 yr, n = 50) and a persistently elevated serum YKL-40 were at risk of radiological disease progression as determined by Larsen score. CONCLUSION: Serum YKL-40 varies according to disease activity in RA, but provides in some respect information different from conventional markers. Our previous studies are consistent with a local release of YKL-40 in the arthritic joint followed by a secondary increase in serum YKL-40. YKL-40 may prove to be a new tool for the study of disease activity and pathophysiology of RA.
11407088 Vascular endothelial growth factor levels in the serum and synovial fluid of patients with 2001 May OBJECTIVE: To determine the vascular endothelial growth factor (VEGF) concentrations in serum and synovial fluid (SF) from patients with rheumatoid arthritis (RA) and to search for relationships between VEGF levels and clinical and laboratory variables. METHODS: We measured VEGF levels using an enzyme-linked immunosorbent assay. Serum samples were obtained from 99 RA patients, 49 osteoarthritis (OA) patients, and 80 normal controls. Paired samples of serum and SF were collected from 32 patients with RA and 15 with OA. RESULTS: The mean serum VEGF concentration was 590.1 pg/ml for RA patients, 286.7 pg/ml for OA patients, and 265.8 pg/ml in controls. The serum VEGF concentration was significantly higher in the RA patients than in the OA patients or the controls (both p < 0.001). Furthermore, the VEGF levels in SF from RA patients were significantly higher than in SF from OA patients (p = 0.017). However, there was no correlation between VEGF levels in serum and SF from the same RA patients. The serum VEGF concentration was correlated with the ESR, serum CRP concentration, serum rheumatoid factor, number of tender and swollen joints, Modified Health Assessment Questionnaire, and patient and physician global assessments of disease activity in RA patients. CONCLUSION: These results suggest that VEGF level is related to RA disease activity, suggesting that VEGF may play some role in the pathogenesis of RA.
10493664 Increased HLA-DR and CD44 antigen expression in the gut: evidence of extraarticular immuno 1999 Sep OBJECTIVE: To examine the gastrointestinal (GI) immune system in rheumatoid arthritis (RA) for evidence of activation. METHODS: Duodenal biopsies from 25 patients with RA were obtained by endoscopy. Single cell suspensions from the epithelial layer and lamina propria were prepared. Flow cytometry was used to examine the expression of CD4, CD8, T cell receptor-gammadelta (TCR-gammadelta), TCR-alphabeta, HLA-DR, CD44, and interleukin 2 receptor on gut T lymphocytes. Fifteen disease control (DC) individuals and 6 patients with osteoarthritis (OA) taking longterm nonsteroidal antiinflammatory drug (NSAID) therapy were also investigated. Peripheral blood T lymphocytes from all individuals were examined for the expression of these surface molecules. RESULTS: HLA-DR expression was significantly increased on intraepithelial lymphocytes (IEL) and enterocytes from patients with RA (n = 13) compared with the 2 control groups (p<0.01). Immunohistochemistry also revealed increased expression of HLA-DR on enterocytes from patients with RA. RA IEL (n = 6) expressed significantly higher levels of CD44 (p<0.02). In the lamina propria, a small but significant gammadelta T lymphocyte population (mean 5.5%, range 2-12%) was detected in rheumatoid factor positive RA patients (n = 8) compared with RF negative RA patients (n = 8, mean 2%, range 0.4-6%; p<0.01) and the disease control group (n = 15, mean 2%, range 0.5-5%; p<0.01). None of these changes were detectable in peripheral blood lymphocytes from patients with RA. CONCLUSION: This study demonstrates evidence of activation of specific components of the GI immune system in RA. Peripheral blood T lymphocytes from patients with RA did not show increased expression of activation markers, suggesting that changes in the RA GI tract are not systemic but localized. Moreover, these changes appear to be independent of NSAID therapy.
9272304 Development of arthritis and hypothyroidism during alpha-interferon therapy for chronic he 1997 Jul Alpha-interferon (alpha-IFN) therapy may induce, reveal or exacerbate various autoimmune-related disorders. The most common is the development of autoantibodies, while clinically overt autoimmune diseases are rare. We describe a 49-year-old woman who developed seronegative rheumatoid-like arthritis and autoimmune hypothyroidism after 7 months of human lymphoblastoid alpha-IFN therapy given for hepatitis C virus-related chronic active hepatitis (CAH-HCV). There was no family or personal history of autoimmune, thyroid or articular diseases. Our patient required continuous therapy for arthritis and hypothyroidism despite discontinuation of alpha-IFN. This suggests that alpha-IFN therapy may induce the contemporary appearance of two different persistent autoimmune-related diseases in the same patient. However, chronic HCV infection may play an important adjuvant role in the development of these diseases.
9376995 Fibromyalgia-associated hepatitis C virus infection. 1997 Sep The objective was to determine whether there might be an association between hepatitis C virus (HCV) chronic infection and fibromyalgia (FM). We determined the prevalence of HCV infection in 112 FM patients, in comparison with matched rheumatoid arthritis (RA) patients from the out-patient clinic of a teaching tertiary care general hospital. Furthermore, we looked for evidence of FM in 58 patients diagnosed with chronic hepatitis due to HCV, compared with matched surgery clinic patients, HCV antibodies were determined by enzyme-linked immunosorbent assay (ELISA) and recombinant immunoblot assay (RIBA). Serum RNA of HCV (HCV-RNA) was determined by polymerase chain reaction. In the group of FM patients, HCV antibodies were found by ELISA in 17 (15.2%) patients and in six (5.3%) of the RA controls (P < 0.05). RIBA was positive in 16 and indeterminate in one of the FM patients. Serum HCV-RNA was found in 13 of these FM patients. In eight (47%) FM patients, alanine aminotransferase (ALT) was normal, although HCV-RNA was detected in four (50%) of them. In the group of patients with chronic hepatitis due to HCV, all patients had HCV antibodies and the presence of HCV-RNA in serum. Within these patients, 31 (53%) had diffuse musculoskeletal pain, while six (10%) fulfilled FM diagnostic criteria. In the control group, 13/58 (22%) had diffuse musculoskeletal pain (P < 0.001), whereas only one female patient (1.7%) fulfilled FM criteria (P < 0.05). Serum ALT was 51.7 +/- 38.4 in FM patients, whereas it was 122 +/- 76.3 in patients with HCV chronic hepatitis but without FM (P < 0.001). There were no statistical differences in autoimmune markers between patients with and without FM. These data suggest that there exists an association between FM and active HCV infection in some of our patients. FM is not associated with liver damage or autoimmune markers in these patients. HCV infection should be considered in FM patients even though ALT elevations were absent.