Changing rate of serious infections in biologic-exposed rheumatoid arthritis patients. Data from South American registries BIOBADABRASIL and BIOBADASAR.

OBJECTIVE: Most reports on serious infections (SI) in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) are from the USA and Western Europe. Data from other regions are largely missing. We report data from South American countries with different backgrounds and health-care systems but similar registries. METHODS: We merged 2010-2016 data from two registries, BIOBADABRASIL (Brazil) and BIOBADASAR (Argentina), which share the same protocol, online platform and data monitoring process. Patients with active RA were included when they began the first bDMARD or a conventional synthetic DMARD (csDMARD, control group). The SI incidence rate (IR) per 1000 patient/years and adjusted IR ratio (aIRR) were estimated for bDMARDs and csDMARDs. RESULTS: Data were analysed for 3717 RA patients with an exposure of 13,380 patient/years. The 2591 patients treated with bDMARDs (64% tumour necrosis factor-α inhibitors (TNFi)) had a follow-up of 9300 years, and the 1126 treated with csDMARDs had an exposure of 4081 patient/years. The SI IR was 30.54 (CI 27.18-34.30) for all bDMARDs and 5.15 (CI 3.36-7.89) for csDMARDs. The aIRR between the two groups was 2.03 ([1.05, 3.9] p = 0.034) for the first 6 months of treatment but subsequently increased to 8.26 ([4.32, 15.76] p < 0.001). The SI IR for bDMARDs decreased over time in both registries, dropping from 36.59 (28.41-47.12) in 2012 to 7.27 (4.79-11.05) in 2016. CONCLUSION: While SI remains a major concern in South American patients with RA treated with bDMARDs, a favourable trend toward a reduction was observed in the last years.Key Points• New comprehensive data on biologic drugs safety from international collaboration in South America.• First proposal for national registries data merging in South America.• Serious infections remain a major concern in RA patients treated with biologics.• A significant reduction of serious infections in RA patients exposed to biologics was observed over a 7 years period.

[Clinical features of systemic sclerosis and association with antitopoisomerase-1 antibody and centromere pattern of antinuclear antibody]. / Características clínicas da esclerose sistêmica e associação ao anticorpo antitopoisomerase-1 e padrão centrómero do anticorpo antinuclear.

OBJECTIVE: To describe clinical features of patients with systemic sclerosis (SSc) and associate them with antitopoisomerase-1 antibody and centromere pattern of antinuclear antibody. METHODS: We evaluated 50 patients who met SSc screening criteria of the American College of Rheumatology, and classified as limited cutaneous SSc and diffuse cutaneous SSc. Clinical history, physical examination and laboratory tests were evaluated: cutaneous, vascular, gastrointestinal, renal, pulmonary and cardiac involvement, in addition to autoantibodies. The continuous quantitative variables, discrete quantitative and categorical variables were evaluated employing the relevant statistical tests. A P value ≤ 0.05 was considered statistically significant. RESULTS: The authors found that 88% of the patients were women, and 70% of the cases corresponded to the limited cutaneous form. The skin thickening assessed by the modified Rodnan skin score found as minimum of 3, and a maximum of 32, and median of 14. Raynaud's phenomenon was found in 100% of patients, skin ulcers in 56%, esophageal symptoms in 80%, interstitial lung disease in 44%, and increase in right ventricular systolic pressure in18% of the patients. Antinuclear antibodies were found in 80%, the centromere pattern in 34% and antitopoisomerase-1 in 22% of the patients. We found that 88.2% of patients with centromere pattern antinuclear antibody had limited cutaneous SSc, while 72.7% of patients with topoisomerase-1 antibodies had diffuse cutaneous SSc. CONCLUSION: The clinical features of this population of patients with SSc are similar to results in the literature, as well as the association with the autoantibodies evaluated.

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%, respectively; p<0.0001), as well as in those with rheumatic diseases (32 vs. 4%, respectively; p<0.0001), ankylosing spondylitis (45 vs. 4%, respectively; p<0.0001) and psoriatic arthritis (40 vs. 4%, 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%). Approximately 80% of the patients had gastrointestinal symptoms, such as diarrhea (26%), abdominal pain (31%) and weight loss (5%), 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.

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.

Pyomyositis associated with diabetes mellitus and liver cirrhosis.

Pyomyositis is a primary infection of the skeletal muscle, occurring most commonly in tropical countries. Adults who develop the disease have, in most cases, associated comorbidities that compromise the immune system, including diabetes mellitus and liver cirrhosis.

[Systemic lupus erythematosus presenting as autoimmune parotitis and pancreatitis - Case Report]. / Lúpus eritematoso sistêmico manifestando-se como parotidite e pancreatite auto-imune - Relato de caso.

Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease which can present from classical to atypical forms. We discuss the case of a young lady of 29 years-old recently diagnosed with SLE that manifested parotitis and pancreatitis.

[Skin manifestation in systemic sclerosis]. / Manifestações cutâneas na esclerose sistêmica.

OBJECTIVE: To assess cutaneous manifestations in a population of patients with systemic sclerosis (SSc). METHOD: The study population was constituted by 50 patients with a diagnosis of SSc, according to the classification criteria for SSc established by the American College of Rheumatology. According to the criteria proposed by LeRoy and cols., the disease was classified as diffuse SSc, or limited SSc, depending on the extent of skin involvement. Through history and physical exam the following variables were assessed: skin sclerosis, Raynaud's phenomenon, digital pitting scars, ischemic ulcers, telangiectasia, leucomelanoderma, microstomy, calcinosis and pruritus. RESULTS: In the study population, 88% were women, with a mean age of 52.3+/-12.4 years. Limited SSc was the most frequent subset, being present in 70% of the evaluated patients. We found Raynaud's phenomenon in 100% of the patients, telangiectasia in 94%, leucomelanoderma in 38%, pruritus in 50%, calcinosis in 40%, microstomy in 62%, digital scars in 66% and ischemic ulcers in 58%. The modified Rodnan skin score values ranged from 3 to 32, with a median of 14, and percentile 25 of 9 and percentile 75 of 17.75. CONCLUSION: Cutaneous manifestations are very common in ES, being responsible for important limitations on daily activities and stigmatization of patients.

Piomiosite associada ao diabetes mellitus e cirrose hepática / Pyomyositis associated with diabetes mellitus and liver cirrhosis

A piomiosite é uma infecção primária do músculo esquelético mais comum nos países tropicais. Adultos que desenvolvem a doença apresentam, na maioria dos casos, comorbidades associadas que comprometem o sistema imunológico, entre elas diabetes mellitus e cirrose hepática.

Pyomyositis is a primary infection of the skeletal muscle, occurring most commonly in tropical countries. Adults who develop the disease have, in most cases, associated comorbidities that compromise the immune system, including diabetes mellitus and liver cirrhosis.

Silicose e Esclerose Sistêmica – Síndrome de Erasmus: relato de um caso / Silicosis and systemic sclerosis – Erasmus' syndrome: case report

A silicoesclerodermia, descrita inicialmente por Erasmus em 1957, é o resultado da interferência na imunidade celular relacionada à citotoxicidade da sílica, responsável pelas reações auto-imunes e pela formação de imunocomplexos circulantes. Neste relato, os autores descrevem o caso de um homem de 61 anos com antecedentes de exposição à sílica e que desenvolveu Síndrome de Erasmus.

Silicoscleroderma, described by Erasmus in 1957, is the result of cellular immunity interference related to the cytotoxicity of silica, and it is responsible for autoimmune reactions and formation of circulating immunecomplexes. In this text, the authors describe a 61-years-old man with previous exposure to silica, and who developed Erasmus’ syndrome.

Análise descritiva das características demográficas e clínicas de pacientes com artrite reumatóide no estado de São Paulo, Brasil / Descriptive analysis of the demographical and clinical characteristics of the patients with rheumatoid arthritis in the State of São Paulo, Brazil

OBJETIVO: realizar uma análise retrospectiva das características demográficas e clínicas de pacientes com artrite reumatóide (AR), em acompanhamento ambulatorial no Estado de São Paulo, Brasil. MÉTODOS: foram revisados 1.381 prontuários de pacientes com artrite reumatóide, atendidos entre 2002 e 2005. Os prontuários foram transcritos em protocolos padronizados, coletando-se idade, sexo, raça, peso corpóreo, tempo de doença, gravidade da doença, classificação do estado funcional, fator reumatóide, condição social, presença de dor na última consulta, avaliação de progressão radiológica, envolvimento extra-articular, emprego de questionários de Qualidade de Vida ou de Atividade da Doença, tipos de tratamentos e de programa de reabilitação. RESULTADOS: dos 1.381 pacientes, 86 por cento eram mulheres, caucasianas, estavam entre a quarta e quinta década, tempo médio de doença de 7,2 anos e o peso corpóreo médio de 65,6 kg. Uma minoria (5 por cento) foi classificada como grave, e a maioria apresentava classe funcional I e II. As manifestações extra-articulares ocorreram em 23,3 por cento, e o fator reumatóide era positivo em 71 por cento dos pacientes. Somente um terço possuía acompanhamento radiológico e estava trabalhando. O medicamento mais utilizado foi o metotrexato (dose 15-19 mg/semana). Um quarto dos pacientes estava freqüentando programas de reabilitação, e um terço possuía avaliações de qualidade de vida e de atividade da doença. CONCLUSÃO: essa análise proporcionou uma visão parcial dos pacientes brasileiros com AR, identificando pontos importantes em relação às características demográficas e clínicas, os tipos de tratamentos farmacológicos e a pequena utilização de marcadores de doença e questionários de qualidade de vida, bem como a limitação de serviços de reabilitação disponíveis para os pacientes.

OBJECTIVE: to perform a retrospective analysis of clinical and demographic characteristics of rheumatoid arthritis (RA) patients followed in outpatient clinics in the State of São Paulo, Brazil. METHODS: 1.381 medical records of rheumatoid arthritis patients were reviewed in the period between 2002 and 2005. These data were analyzed using a standardized form, based on the following parameters: sex, age, race, weight, follow-up time, disease progression, functional status, rheumatoid factor positivity, social status, pain in the last visit, radiologic progression, extra-articular manifestations, quantitative assessment of functional status and disease active score (DAS), pharmacological treatment, and physical therapy. RESULTS: 86 percent were female Caucasians. Age of disease onset varied between the forth and fifth decades. Mean follow-up was 7.2 years and mean body weight was 65.6 kg. Less than 5 percent of the patients were classified as severe and the majority of the patients presented functional class I and II. Extra-articular manifestations were observed in 23.3 percent and the rheumatoid factor was positive in 71 percent. Only 33 percent of the patients had radiological evaluation and were working regularly. Methotrexate was the most common medication (15-19 mg/week). Only 25 percent of these patients were attending physical therapy and 30 percent had quantitative assessment of functional status and DAS. CONCLUSION: this analysis provided a partial analysis of the RA Brazilian population, identified demographic and clinical characteristics, the therapeutic drugs used, and the difficulty of the patients in attending rehabilitation services.

Trombose de veia jugular em paciente com anticorpo anticardiolipina e lúpus eritematoso sistêmico / Thrombosis in jugular vein in patient with anticardiolipin antibody and systemic lupus erythematosus

Os autores relatam o caso de uma paciente com 19 anos de idade, portadora de lúpus eritematoso sistêmico, que apresentou edema súbito e progressivo em membro supeior esquerdo e dor e circulação colateral visível em região supraclavicular esquerda. Foi realizado diangóstico de trombose venosa em veia jugular externa esquerda por meio do dúplex scan. Nos exames laboratoriais, evidenciou-se a presença de anticorpo anticardiolipina

Pinçamento aorto-mesentérico associado a esclerose sistêmica progressiva / Aortomesenteric duodenal compression in association with progressive systemic sclerosis

Os autores apresentam o caso de uma paciente de 48 anos de idade com quadro de pinçamento aorto-mesentérico como complicação de esclerose sistêmica progressiva forma CREST. A paciente preencheu todos os critérios diagnósticos para a patologia de base e durante a evolução do caso, já com dismotilidade esofágica e síndrome desabsotiva, e após emagrecimento acentuado e rápido, apresentou quadro de abdome agudo em decorrência de pinçamento aorto-mesentérico. Chama-se atenção apra raridade desta complicação, e ainda pela alta morbidade causada pelo comprometimento sistêmico da Esclerose Sistêmica Progressiva (E.S.P.).

Poliarterite nodosa: registro de um caso com estudo angiográfico / Polyarteritis nodosa: report of a case with angiographic study

O caso de poliarterite nodosa (PAN) em paciente de 54 anos de idade é relatado. O quadro clínico evidenciava polineuropatia sensitivo-motora clássica de 6 meses de evoluçäo, associado a emagrecimento acentuado, adinamia artralgia, mialgia, taquicardia, febre e hipertensäo arterial. Os exames complementares iniciais revelaram leucocitose, VHS elevado, HBAg positiva e pesquisa de crioglobulinas positiva. O estudo angiográfico visceral na circulaçäo renal e hepática revelou presença de inúmeros aneurismas sendo o diagnóstico confirmado. O paciente evoluiu para óbito após cerca de duas semanas. É feita breve revisäo sobre PAN, salientando-se a importância da detecçäo de HBAg na etiopatogênese e do estudo angiográfico para o diagnóstico