Rheumatoid Arthritis: Silva C

Fonseca JE, Canhão H, Silva C, Miguel C, Mediavilla MJ, Teixeira A, Castelão W, Nero P, Bernardes M, Bernardo A, Mariz E, Godinho F, Santos MJ, Bogas M, Oliveira M, Saavedra MJ, Barcelos A, Cruz M, Santos RA, Maurício L, Rodrigues M, Figueiredo G, Quintal A, Patto JV, Malcata A, da Silva JC, Araújo D, Ventura F, Branco J, Queiroz MV, Anonymous00300. · Serviço de Reumatologia, Hospital de Santa Maria. · Acta Reumatol Port. · Pubmed #17094336 links to  free full text

Abstract: In Portugal, 13 cases of tuberculosis (TB) were reported, in the period between 1999 and 2005, in 960 patients exposed to anti-TNFalpha treatment (1.35%), 8 females and 5 males. Mean age was 46.7 +/- 13.8 years. 9 patients had rheumatoid arthritis (RA), in 639 exposed patients (1.4%), 3 had ankylosing spondylitis (AS), in 200 exposed patients (1.5%) and 1 had psoriatic arthritis (PA), in 101 exposed patients (1%). The anti-TNFa used was in 8 cases infliximab (in 456 patients exposed, 1.5%), in 4 adalimumab (in 171 patients exposed, 2.3%) and in 1 etanercept (in 333 exposed, 0.3%). Treatment with a biological agent was started 11.1 +/- 8.7 months (min 3 and max 50) before TB onset. Tuberculin skin test (TST) was performed in 9 out of the 13 patients (the other 4 had started biological therapy before 2002). In 3 cases the TST response was 0 mm, in 3 less than 10 mm, in one was 14 mm and in two 20 mm. In the 3 cases with a TST response superior to 10 mm, isoniazid treatment 300 mg/d was prescribed, during 9 months. The time between first symptoms and TB diagnosis was 2.6 +/- 2.9 months. TB involvement was pulmonary in 6 patients, lymph node disease in 2, peritoneal and pulmonary in 2, osteoarticular in one case, lymph node disease and splenic in another and miliar TB in the last case. One death was reported; all of the other cases had a good outcome after anti-TB treatment. In two cases (one treated with adalimumab and the other with infliximab), paradoxical response to treatment occurred. None of the patients has restarted biological therapy after TB treatment.

Padyukov L, Silva C, Stolt P, Alfredsson L, Klareskog L. · Karolinska Institutet, Stockholm, Sweden, and Mechnikov Research Institute, Stockholm, Sweden. · Arthritis Rheum. · Pubmed #15476204 links to  free full text

Abstract: OBJECTIVE: The main genetic risk factor for rheumatoid arthritis (RA) is the shared epitope (SE) of HLA-DR, while smoking is an important environmental risk factor. We studied a potential gene-environment interaction between SE genes and smoking in the etiology of the 2 major subgroups of RA: rheumatoid factor (RF)-seropositive and RF-seronegative disease. METHODS: A population-based case-control study involving incident cases of RF-seropositive and RF-seronegative RA (858 cases and 1,048 controls) was performed in Sweden. Cases and controls were classified according to their cigarette smoking status and HLA-DRB1 genotypes. The relative risk of developing RA was calculated for different gene/smoking combinations and was compared with the relative risk in never smokers without SE genes. RESULTS: The relative risk of RF-seropositive RA was 2.8 (95% confidence interval [95% CI] 1.6-4.8) in never smokers with SE genes, 2.4 (95% CI 1.3-4.6) in current smokers without SE genes, and 7.5 (95% CI 4.2-13.1) in current smokers with SE genes. Smokers carrying double SE genes displayed a relative risk of RF-seropositive RA of 15.7 (95% CI 7.2-34.2). The interaction between smoking and SE genes was significant, as measured by the attributable proportion due to interaction, which was 0.4 (95% CI 0.2-0.7) for smoking and any SE, and 0.6 (95% CI 0.4-0.9) for smoking and a double SE. Neither smoking nor SE genes nor the combination of these factors increased the risk of developing RF-seronegative RA. CONCLUSION: The disease risk of RF-seropositive RA associated with one of the classic genetic risk factors for immune-mediated diseases (the SE of HLA-DR) is strongly influenced by the presence of an environmental factor (smoking) in the population at risk.