Intestinal microsporidiosis: a hidden risk in rheumatic disease patients undergoing anti-tumor necrosis factor therapy combined with disease-modifying anti-rheumatic drugs?

OBJECTIVE: Immunosuppressed patients are at risk of microsporidiosis, and this parasitosis has an increased rate of dissemination in this population. Our objective was to evaluate the presence of microsporidiosis and other intestinal parasites in rheumatic disease patients undergoing anti-tumor necrosis factor/disease-modifying anti-rheumatic drug treatment. METHODS: Ninety-eight patients (47 with rheumatoid arthritis, 31 with ankylosing spondylitis and 11 with psoriatic arthritis) and 92 healthy control patients were enrolled in the study. Three stool samples and cultures were collected from each subject. RESULTS: The frequency of microsporidia was significantly higher in rheumatic disease patients than in control subjects (36 vs. 4 percent, respectively; p<0.0001), as well as in those with rheumatic diseases (32 vs. 4 percent, respectively; p<0.0001), ankylosing spondylitis (45 vs. 4 percent, respectively; p<0.0001) and psoriatic arthritis (40 vs. 4 percent, respectively; p<0.0001), despite a similar social-economic class distribution in both the patient and control groups (p = 0.1153). Of note, concomitant fecal leukocytes were observed in the majority of the microsporidia-positive patients (79.5 percent). Approximately 80 percent of the patients had gastrointestinal symptoms, such as diarrhea (26 percent), abdominal pain (31 percent) and weight loss (5 percent), although the frequencies of these symptoms were comparable in patients with and without this infection (p>0.05). Rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis disease activity parameters were comparable in both groups (p>0.05). The duration of anti-tumor necrosis factor/disease-modifying anti-rheumatic drugs and glucocorticoid use were also similar in both groups. CONCLUSION: We have documented that microsporidiosis with intestinal mucosa disruption is frequent in patients undergoing concomitant anti-tumor necrosis factor/disease-modifying anti-rheumatic drug therapy. Impaired host defenses due to the combination of the underlying disease and the immunosuppressive therapy is the most likely explanation for this finding, and this increased susceptibility reinforces the need for the investigation of microsporidia and implementation of treatment strategies in this population.

Pesquisa de autoanticorpos em pacientes com artrite psoriásica sob terapia anti-TNFα / Autoantibodies in patients with psoriatic arthritis on anti-TNFα therapy

INTRODUÇÃO: A terapia imunobiológica anti-TNFα tem-se mostrado efetiva no tratamento de pacientes com artrite psoriásica (APs) refratária. No entanto, não está bem definido o risco de desenvolvimento de autoanticorpos comumente encontrados nas doenças reumatológicas em pacientes com APs na vigência desse tratamento. OBJETIVO: avaliar a indução de autoanticorpos específicos durante a terapia anti-TNFα em pacientes com APs. PACIENTES E MÉTODOS: Foram analisadas amostras de soro de 23 pacientes com APs (mulheres: 61 por cento, idade: 45,04 ± 12,68 anos, quadro poliarticular: 69,6 por cento, duração da doença: 13,3 ± 7,7 anos, infliximabe: 82,60 por cento) obtidas imediatamente antes (basal) e cerca de um ano após a introdução da terapia anti-TNF (última amostra) (385 ± 131,45 dias). A pesquisa incluiu a detecção de anticorpos antinucleares (ANA) e anticorpos para dsDNA (imunofluorescência indireta em células Hep-2 e em Crithidia luciliae, respectivamente); RNP e Sm (hemaglutinação passiva); Ro/SS-A e/ou La/SS-B, cromatina, histona, peptídeo citrulinado (CCP) e cardiolipina (ELISA). RESULTADOS: A pesquisa basal de ANA revelou positividade em 47,8 por cento dos pacientes, com predomínio do padrão nuclear homogêneo (81,8 por cento). Todas as amostras de soro testadas foram negativas para fator reumatoide e anticorpos anticardiolipina, RNP, Sm, Ro/SS-A, La/SS-B, histona e dsDNA, enquanto dois pacientes apresentaram positividade para anticromatina e um para anti-CCP. Todas as amostras de ANA positivas no tempo basal, exceto uma, mantiveram essa reatividade após a introdução da terapia anti-TNF. Reatividade "de novo" ANA foi observada em quatro dos pacientes originalmente negativos (33,3 por cento). Anticorpos anti-Ro/SS-A, La/SS-B, cardiolipina, histona, dsDNA e fator reumatoide foram sistematicamente negativos em todas as amostras finais de soro testadas e positividade anticromatina foi detectada em outros três...

INTRODUCTION: Anti-TNFα therapy has been effective in the treatment of patients with refractory psoriatic arthritis (PSA). However, the risk of developing autoantibodies commonly found in rheumatic diseases in PSA patients undergoing this therapy is not clear. OBJECTIVE: To evaluate the induction of specific autoantibodies after anti-TNFα therapy in PSA patients. PATIENTS AND METHODS: Serum samples from 23 PSA patients (women: 61 percent, age: 45.04 ± 12.68 years, polyarticular: 69.6 percent, disease duration: 13.3 ± 7.7 years, infliximab: 82.60 percent) obtained immediately before (baseline) and approximately one year after the introduction of anti-TNF therapy (last sample) (385 ± 131.45 days), were analyzed. The analysis included detection of antinuclear antibodies (ANA) and anti-dsDNA antibodies (indirect immunofluorescence on Hep-2 cells and Crithidia luciliae, respectively); anti-RNP and anti-Sm (passive hemagglutination); and anti-Ro/ SS-A and/or anti-La/SS-B, anti-chromatin, anti-histones, anti-citrullinated peptide (CCP), and anti-cardiolipin (ELISA) antibodies. RESULTS: At baseline, ANA was positive in 47.8 percent of patients, with predominance of homogeneous nuclear pattern (81.8 percent). All baseline serum samples were negative for rheumatoid factor and antibodies to cardiolipin, RNP, Sm, Ro/SS-A, anti-La/SS-B, anti-histone, and anti-dsDNA antibodies, while two patients were positive for anti-chromatin and one for anti-CCP. All ANA-positive samples at baseline, except for one, remained positive after the introduction of anti-TNF therapy; however, de novo ANA reactivity was observed in four originally negative patients (33.3 percent). Anti-Ro/SS-A, La/SS-B, cardiolipin, histones, dsDNA, and rheumatoid factor antibodies remained negative in all final serum samples tested, and anti-chromatin positivity was detected in three other patients. CONCLUSION: Our findings have shown that anti-TNF therapy induced ANA positivity...

Complicações imediatas de 3.555 aplicações de agentes anti-TNFα / Immediate complications of 3, 555 injections of anti-TNFα

OBJETIVO: Avaliar as complicações imediatas da aplicação de agentes anti-TNFα no Centro de Dispensação de Medicação deAlto Custo do HC-FMUSP. PACIENTES E MÉTODOS: Foram incluídos todos os pacientes que receberam agentes anti-TNFα entre agosto/2007 e março/2009.As complicações imediatas (até 1 hora após o término da aplicação) foram classificadas em leves (cefaleia, rash, tontura, prurido, náuseas), moderadas (febre, urticária, palpitação, dor torácica, dispneia, variação da pressão arterial de 20 a 40 mmHg) ou graves (febre com calafrios, dispneia com sibilância, variação da pressão arterial > 40 mmHg). RESULTADOS: Foram avaliados 242 pacientes: 94 (39 por cento) com artrite reumatoide, 64 (26 por cento) com espondilite anquilosante, 32 (13 por cento) com artrite psoriásica, 26 (11 por cento) com artrite idiopática juvenil e 27 (11 por cento) com outros diagnósticos. O número total de aplicações foi de 3.555, sendo 992 (28 por cento) de adalimumabe, 1.546 (43 por cento) de etanercepte e 1.017 (29 por cento) de infliximabe. Complicações imediatas foram observadas em 39/242 (16 por cento) pacientes. As complicações ocorreram em 45/3.555 (1,2 por cento) aplicações. Estas foram mais frequentes com infliximabe comparado com adalimumabe (3,7 por cento vs. 0,5 por cento, P < 0,0001), e com etanercepte (3,7 por cento vs. 0,25 por cento, P < 0,0001). As complicações foram: leves 14/45 (31 por cento), moderadas 21/45 (47 por cento) e graves 10/45 (22 por cento); ocorreram principalmente nos primeiros seis meses de tratamento (56 por cento) e nas aplicações endovenosas, predominantemente na primeira hora de infusão (76 por cento). CONCLUSÃO: As reações agudas, apesar de raras, são potencialmente graves e ocorrem principalmente nas primeiras aplicações tanto no uso de medicações endovenosas como de subcutâneas...

OBJECTIVE: To evaluate the immediate complications of anti-TNFα drugs at the "Center for Dispensation of High Cost Medications" of HC-FMUSP. PATIENTS AND METHODS: All patients who received anti-TNFα agents between August 2007 and March 2009 were included in this study. Immediate complications (up to 1 hour after the injection) were classified as mild (headache, rash, dizziness, itching, nausea), moderate (fever, urticaria, palpitation, chest pain, dyspnea, blood pressure variations between 20 and 40 mmHg), or severe (fever with chills, dyspnea with wheezing, variations in blood pressure > 40 mmHg). RESULTS: Two hundred and forty-two patients were evaluated: 94 (39 percent) with rheumatoid arthritis, 64 (26 percent) with ankylosing spondylitis, 32 (13 percent) with psoriatic arthritis, 26 (11 percent) with juvenile idiopathic arthritis; and 27 (11 percent) with other diagnoses. A total of 3,555 injections were administered: 992 (28 percent) adalimumab, 1,546 (43 percent) etanercept, and 1,017 (29 percent) infliximab. Immediate adverse events were observed in 39/242 (16 percent) patients. Injectionrelated complications were observed in 46/3,555 (1.2 percent) injections. They were more common with infliximab than adalimumab (3.7 percent vs. 0.5 percent, P < 0.0001) and etanercept (3.7 percent vs. 0.25 percent, P < 0.0001). Complications were classified as mild 14/45 (31 percent), moderate 21/45 (47 percent), and severe 10/45 (22 percent), and occurred mainly in the first six months of treatment (56 percent) and after intravenous injections, especially (76 percent) in the first hour. CONCLUSION: Although rare, acute reactions can be severe, being observed more commonly after the initial injections, both intravenous and subcutaneous...