Effect of methotrexate and anti-TNF on Epstein-Barr virus T-cell response and viral load in patients with rheumatoid arthritis or spondylarthropathies.

INTRODUCTION: There is a suspicion of increased risk of Epstein-Barr virus (EBV)-associated lymphoproliferations in patients with inflammatory arthritides receiving immunosuppressive drugs. We investigated the EBV load and EBV-specific T-cell response in patients treated with methotrexate (MTX) or anti-TNF therapy. METHODS: Data for patients with rheumatoid arthritis (RA) (n = 58) or spondylarthropathy (SpA) (n = 28) were analyzed at baseline in comparison with controls (n = 22) and after 3 months of MTX or anti-TNF therapy for EBV load and EBV-specific IFNgamma-producing T cells in response to EBV latent-cycle and lytic-cycle peptides. RESULTS: The EBV load and the number of IFNgamma-producing T-cells after peptide stimulation were not significantly different between groups at baseline (P = 0.61 and P = 0.89, respectively). The EBV load was not significantly modified by treatment, for RA with MTX (P = 0.74) or anti-TNF therapy (P = 0.94) or for SpA with anti-TNF therapy (P = 1.00). The number of EBV-specific T cells was not significantly modified by treatment, for RA with MTX (P = 0.58) or anti-TNF drugs (P = 0.19) or for SpA with anti-TNF therapy (P = 0.39). For all patients, the EBV load and EBV-specific T cells were significantly correlated (P = 0.017; R = 0.21). For most patients, short-term exposure (3 months) to MTX or anti-TNF did not alter the EBV load or EBV-specific T-cell response but two patients had discordant evolution. CONCLUSIONS: These data are reassuring and suggest there is no short-term defect in EBV-immune surveillance in patients receiving MTX or anti-TNF drugs. However, in these patients, long term follow-up of EBV-specific T-cell response is necessary and the role of non-EBV-related mechanisms of lymphomagenesis is not excluded.

Spondyloarthropathy and chronic B hepatitis. Effect of anti-TNF therapy.

UNLABELLED: Several cases of TNF antagonist-related reactivation of hepatitis B have been reported. Here, we describe 4 cases in patients with spondyloarthropathies. Long-term monitoring of the hepatitis B virus (HBV) load is in order in HBV-positive patients treated with TNF antagonists. CASE REPORTS: There were 3 men and 1 woman, aged 30-40 years. Follow-up ranged from 1 to 5 years. In 2 patients, the HBV infection was not discovered until the pre-TNF antagonist therapy workup. A viral load increase was noted after a TNF antagonist was added to methotrexate in 2 patients, whose viral load values returned to baseline after the introduction of the antiviral agent lamivudine. Lamivudine was started at the same time as the TNF antagonist in the other 2 patients, whose viral loads remained undetectable. Escape phenomenon requiring a switch to another antiviral agent was required in 1 patient after more than 4 years of treatment with 3 TNF antagonists. CONCLUSION: These 4 case reports illustrate the challenges raised by latent HBV infection in patients who require TNF antagonist therapy. They support routine HBV testing before treatment initiation, followed in HBV-positive patients by viral load monitoring. Antiviral therapy can be used preventively and should be given if the viral load increases under TNF antagonist therapy. In patients on antiviral therapy, viral load monitoring should be continued, given the risk of escape phenomenon after several years.

Soft tissue rheumatic lesions and HIV infection in Zambians.

OBJECTIVE: To explore the relationship between human immunodeficiency virus (HIV) infection and soft tissue rheumatic lesions in HIV-positive black Zambians. METHODS: We performed a prospective study of all patients over 18 years of age attending a rheumatic clinic in a teaching hospital. All patients underwent routine blood tests, and radiographs were performed when indicated. HIV status was determined by ELISA, and clinical staging was determined by World Health Organization criteria. Patients with isolated sacroiliac pain, enthesitis, or a soft tissue lesion were selected for analysis. For HIV-positive patients, only those in clinical stage 1 (asymptomatic or persistent generalized lymphadenopathy) were selected. RESULTS: Our study cohort comprised 120 patients (41 men, 79 women, age 23-70 yrs). Diagnosis and number (% HIV positive) were distributed as follows: sacroiliitis, 14 (100%); heel pain, 14 (100%); costochondritis, 3 (100%); polyenthesitis (> or = 4 sites), 20 (100%); carpal tunnel syndrome, 8 (63%); rotator cuff syndrome, 18 (30%); tendinitis, 8 (25%); sciatica/cervical spondylosis, 12 (16%); sacroiliac strain, 7 (0%); and de Quervain's tenosynovitis, 16 (0%). HIV seroprevalence was 54% overall, 74% in those under 45 years of age, and 17% in those over 45 years of age. Population prevalence of HIV in Lusaka is about 30% in the 30-40-year age range. Mean erythrocyte sedimentation rate (ESR) in 65 patients positive for HIV was 80 mm/h and in 55 patients negative for HIV, 18 mm/h. Within each subgroup the mean ESR was significantly higher in HIV-positive patients. CONCLUSION: A young age and a raised ESR are both good indications of HIV infection in Zambian patients with soft tissue lesions. Enthesitis is a distinct HIV-related phenomenon, either an early form or a forme fruste of HIV-related spondyloarthropathy.

Safety of anti-TNF-alpha therapy in rheumatoid arthritis and spondylarthropathies with concurrent B or C chronic hepatitis.

OBJECTIVE: To assess the safety of anti-tumour necrosis factor (TNF)-alpha therapy in patients with rheumatoid arthritis (RA) or spondylarthropathies (SA) and concurrent chronic hepatitis B or C. METHODS: Records concerning 480 outpatients attending the Rheumatology Department of the University Hospital of Nice (France) for RA or SA were retrospectively reviewed for the duration of disease, treatment, serological status and biological data. RESULTS: Six relevant cases were identified: two of RA with chronic hepatitis B; one of SA with chronic hepatitis B and three of RA with chronic hepatitis C. Five patients had received etanercept and one infliximab; two had been given adalimumab after an unsuccessful trial of etanercept. Patients with concurrent chronic hepatitis B were also given lamivudine. In none of the cases had changes in serum aminotransferases or viral load been reported. CONCLUSION: The use of anti-TNF-alpha therapy (plus lamivudine in the presence of concurrent underlying hepatitis B viral infection) appeared to be safe in that it had no effect on serum aminotransferases and/or viral load. However, repeated monitoring is necessary throughout the treatment period.

Hepatitis C virus seroprevalence and genotypes in patients with diffuse connective tissue diseases and spondyloarthropathies.

Many extrahepatic manifestations, including rheumatic diseases, have been reported to be associated with hepatitis C virus (HCV) infection. In order to investigate the prevalence of HCV infection among patients with rheumatic diseases, in the present study we interviewed 367 patients and tested their blood samples for HCV antibodies (anti-HCV) by an enzyme-linked immunosorbent assay. Anti-HCV-reactive samples were retested for confirmation by a line immunoassay and also for HCV RNA detection by the polymerase chain reaction. HCV RNA-positive samples were genotyped by INNO-LIPA. An overall HCV infection prevalence of 1.9% (7/367) was found. Of the 7 HCV-infected patients, 4 had systemic lupus erythematosus and 3 rheumatoid arthritis, resulting in positivity rates of 2.3 and 3.4%, respectively. HCV RNA genotyping revealed the presence of subtypes 1a (57.1%), 1b (28.6%) and 3a (14.3%). The clinical course was favorable for all HCV-infected patients, except one, who died due to renal insufficiency related to lupus nephritis. These results demonstrate a low HCV infection prevalence among the population studied. In the few positive cases, we observed no adverse influence of this infection on the clinical evolution of the rheumatic disease.

Arthritis in association with human immunodeficiency virus infection in Black African children: causal or coincidental?

OBJECTIVES: To compare human immunodeficiency virus (HIV)-infected and HIV-uninfected children with arthritis of unknown origin to determine whether the association between HIV infection and arthritis is causal or coincidental. METHOD: Retrospective review of 132 children with arthritis who were tested for HIV infection. RESULTS: Thirty-five (27%) of the children were HIV infected and the male to female ratio was 2.5:1 (P = 0.02). Arthritis was the presenting feature of HIV infection in 78% of these children. The remaining 97 (73%) were diagnosed as having juvenile idiopathic arthritis. 'Spondyloarthropathy-like' features were found in 34% of HIV-infected children compared with 5% of uninfected children. CONCLUSION: The high prevalence of HIV infection in 27% of children, the predominance of males and the increased prevalence of 'spondyloarthropathy-like' features, supports a causal relationship between HIV infection and arthritis.