Rastreamento da infecção latente por tuberculose em pacientes com artrite idiopática juvenil previamente à terapia anti‐TNF em um país de alto risco para tuberculose

ResumoObjetivoAvaliar, em um país endêmico, a eficácia em longo prazo do rastreamento à procura de infecção latente por tuberculose (ILTB) e profilaxia primária em pacientes com AIJ em uso de bloqueadores do TNF.MétodosTrata‐se de uma coorte retrospectiva que incluiu pacientes com AIJ elegíveis para a terapia anti‐TNF. Os pacientes foram rastreados à procura de ILTB previamente ao uso de anti‐TNF por meio do teste tuberculínico (TT), radiografia de tórax e história de exposição à TB. Os indivíduos foram acompanhados regularmente em intervalos de dois meses.ResultadosIncluíram‐se 69 pacientes com AIJ com idade atual de 17,4±5,8 anos, com média de duração da doença de 5±4,9 anos; 47 pacientes receberam um único anti‐TNF, enquanto 22 foram transferidos para outro anti‐TNF uma ou duas vezes: 57 foram tratados com etanercepte, 33 com adalimumabe e três com infliximabe. O rastreamento à procura de ILTB foi positivo em três pacientes: um era TT positivo e tinha história de exposição à TB e dois apenas eram TT positivo. Não foi diagnosticado caso de TB ativa durante o período de estudo (mediana de seguimento de 3,8 anos).ConclusãoA avaliação em longo prazo revelou que o rastreamento à procura de ILTB e a profilaxia primária antes do tratamento com anti‐TNF foram eficazes em um país de alto risco para TB e o TT foi o parâmetro mais sensível para identificar esses pacientes.AbstractObjectivesTo evaluate, in an endemic country, the long‐term efficacy of latent tuberculosis infection (LTBI) screening and primary prophylaxis in patients with JIA receiving TNF blockers.MethodsThis was a retrospective cohort that included JIA patients eligible to anti‐TNF therapy. Patients were screened for LTBI prior to anti‐TNF using tuberculin skin test (TST), chest X‐ray and history of exposure to TB. Subjects were regularly followed at 2‐month intervals.ResultsSixty‐nine JIA patients with current age of 17.4±5.8 years, mean disease duration of 5.0±4.9 years were included. Forty‐seven patients received a single anti‐TNF, while 22 patients switched to another anti‐TNF once or twice: 57 were treated with etanercepte, 33 patients with adalimumab and 3 infliximab. LTBI screening was positive in three patients: one had TST‐positive and history of TB exposure and two had solely TST‐positive. No active TB was diagnosed during the study period (median of follow‐up was 3.8 years).ConclusionLong‐term evaluation revealed that LTBI screening and primary prophylaxis before anti‐TNF treatment was effective in a high‐risk country and TST was the most sensitive parameter to identify these patients

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&gt;0.05). Rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis disease activity parameters were comparable in both groups (p&gt;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.FAPESPCNPQFederico FoundationWyet

a Portuguese and Brazilian collaborative analysis

OBJECTIVE: To investigate the relationship between body mass index (BMI) and disease activity in patients with Juvenile Idiopathic Arthritis (JIA). METHODS: Patients with JIA, aged ≤18 years, registered at the Rheumatic Diseases Portuguese Register (Reuma.pt) in Portugal and Brazil were included. Age- and sex-specific BMI percentiles were calculated based on WHO growth standard charts and categorized into underweight (P 97). Disease activity was assessed by Juvenile Arthritis Disease Activity Score (JADAS-27). Uni- and multivariate analyses were performed. RESULTS: A total of 275 patients were included. The prevalence of underweight, normal weight, overweight and obesity was 6.9%, 67.3%, 15.3% and 10.5%, respectively. Underweight patients had significantly higher number of active joints (p <0.001), patient's/parent's global assessment of disease activity (PGA) (p=0.020), physician's global assessment of disease activity (PhGA) (p <0.001), erythrocyte sedimentation rate (ESR) (p=0.032) and overall higher JADAS-27 (p <0.001), compared to patients with normal weight, overweight and obesity. In the multivariate regression, underweight persisted significantly associated with higher disease activity, compared to normal weight (B=-9.430, p <0.001), overweight (B=-9.295, p=0.001) and obesity (B=-9.120, p=0.001), when adjusted for age, gender, country, ethnicity, JIA category and therapies used. The diagnosis of RF- (B=3.653, p=0.006) or RF+ polyarticular JIA (B=5.287, p=0.024), the absence of DMARD therapy (B=5.542, p <0.001) and the use of oral GC (B=4.984, p=0.002) were also associated with higher JADAS-27. CONCLUSION: We found an independent association between underweight and higher disease activity in patients with JIA. Further studies are needed to understand the underlying mechanisms of this association.publishersversionpublishe

Social impact of disease parameters and damage accrual in patients with juvenile-onset systemic Lupus Erythematosus: a multicenter cross-sectional study

Objectives: To describe the frequency and investigate potential associations of unemployment, need of financial assistance and health-related quality of life in adult patients with Juvenile-onset Systemic Lupus Erythematosus (JSLE). Methods: In this multicenter cross-sectional study including JSLE adult patients, questionnaires were applied evaluating demographic characteristics, medical history, treatment, government financial assistance and work status, quality of life, economic classification, disease activity and damage accrual. Results: Sixty-nine JSLE patients from two Brazilian tertiary centers were included in this study. Twenty-eight (40.6%) patients were unemployed and 16 (23.2%) were receiving financial assistance or retirement. Work unemployment was associated only with higher damage scores (OR 1.95, 95% CI 1.14 to 3.35, p = 0.015), while the need of financial&nbsp; assistance was associated with higher damage scores (OR 1.83, 95% CI 1.02 to 3.27, p = 0.042), longer disease duration (OR 1.15, 95% CI 1.01 to 1.32, p = 0.043) and worse economic score (OR 0.87, 95% CI 0.76 to 0.99, p = 0.036). Emotional health, body image perception and pain were the most compromised domains of quality of life but showed no correlation with disease parameters. Disease activity, on the other hand, was inversely associated with symptoms scores (ρ = -0.34, p = 0.004) and scores of adverse effects of medications (ρ = -0.27, p = 0.024). Conclusion: JSLE is a disease with severe outcomes and high social burden that profoundly impact patients during adulthood. Damage accrual is the main risk factor for both unemployment and need of financial assistance and its prevention must be central in the management of JSLE patients

Macrophage Activation Syndrome Associated with Etanercept in a Child with Systemic Onset juvenile Idiopathic Arthritis

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - FAPESP[06/61303-7]CNPq Conselho Nacional de Desenvolvimento Cientifico e Tecnologico[305468/2006-5]CNPq Conselho Nacional de Desenvolvimento Cientifico e Tecnologico[300248/2008-3]Federico Foundatio

Late response to anti-TNF-alpha therapy in refractory mucocutaneous lesions of Beh double dagger et`s disease

Beh double dagger et`s disease (BD) is a multisystem chronic inflammatory disorder characterized by oral and genital ulceration and ocular involvement. Recurrent oral and genital ulcers are the most common symptoms of BD and occur in more than 80% of patients. The treatments of these disease manifestations include colchicine, corticosteroids and immunosuppressive drugs in severe cases. Anti-TNF-alpha therapy may be useful in refractory severe BD, particularly for ocular, central nervous system, gastrointestinal and refractory mucocutaneous lesions. During a 2-year period, 280 patients suffering from rheumatic diseases received anti-TNF-alpha agents at the infusion center of our University Hospital. Two patients (0.7%) presented BD; one of them had celiac disease as well, with recalcitrant mucocutaneous lesions that were not responsive to immunosuppressive drugs. We reported those patients who were successfully treated with infliximab and adalimumab, despite their late response.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, FAPESP[06/61303-7]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, CNPQ[300248/2008-3]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, CNPQ[305468/2006-5]Federico Foundatio

Latent tuberculosis infection screening in juvenile idiopathic arthritis patients preceding anti-TNF therapy in a tuberculosis high-risk country

Abstract Objectives: To evaluate, in an endemic country, the long-term efficacy of latent tuberculosis infection (LTBI) screening and primary prophylaxis in patients with JIA receiving TNF blockers. Methods: This was a retrospective cohort that included JIA patients eligible to anti-TNF therapy. Patients were screened for LTBI prior to anti-TNF using tuberculin skin test (TST), chest X-ray and history of exposure to TB. Subjects were regularly followed at 2-month intervals. Results: Sixty-nine JIA patients with current age of 17.4 ± 5.8 years, mean disease duration of 5.0 ± 4.9 years were included. Forty-seven patients received a single anti-TNF, while 22 patients switched to another anti-TNF once or twice: 57 were treated with etanercepte, 33 patients with adalimumab and 3 infliximab. LTBI screening was positive in three patients: one had TST-positive and history of TB exposure and two had solely TST-positive. No active TB was diagnosed during the study period (median of follow-up was 3.8 years). Conclusion: Long-term evaluation revealed that LTBI screening and primary prophylaxis before anti-TNF treatment was effective in a high-risk country and TST was the most sensitive parameter to identify these patients

PENILE AND SCROTUM SWELLING IN JUVENILE DERMATOMYOSITIS

Edema is a well-known feature of juvenile dermatomyositis (JDM). However, to our knowledge localized penile and scrotum swelling was not previously reported. During a 27-year period, 5,506 patients were followed up at the Pediatric Rheumatology Unit of our University Hospital and 157 patients (2.9%) had JDM. One of them (0.6%) had concomitant localized penile and scrotum swelling. He had severe disease activity since he was 7-year-old, manifested by diffuse cutaneous vasculitis, recurrent localized edema (limbs or face) and only one episode of generalized edema. At the age of 10, he presented edema of the genitalia associated with mild skin erythema. Penis, scrotum and testicular ultrasound as well as magnetic resonance imaging showed skin edema without testicular involvement. He was taking prednisone, methotrexate, cyclosporin, hydroxychloroquine and thalidomide. Improvement of skin rash, penile and scrotum swelling was noticed only with rituximab therapy. No adverse event was observed during anti-CD20 infusions and after six months of follow up. Penile and scrotum edema was a rare manifestation of JDM which improved with anti-CD20 monoclonal antibody treatment.FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)[08/58238]FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)[2009/51897-5]CNPQ[300248/2008-3]Federico Foundatio

Pandemic unadjuvanted influenza A (H1N1) vaccine in dermatomyositis and polymyositis: Immunogenicity independent of therapy and no harmful effect in disease

The goal of the present study was to evaluate the influence of the influenza A H1N1/2009 vaccine on dermatomyositis/polymyositis (DM/PM) disease parameters and the potential deleterious effect of therapy on immune response. Thirty-seven DM and 21 PM patients (Bohan and Peter's criteria) were gender- and age-matched to 116 healthy controls. Seroprotection, seroconversion, the geometric mean titers (GMTs) and the factor increase (FI) in the GMTs were calculated. Disease safety was determined from a muscle enzyme analysis and the DM/PM scores [patient's visual analog scale (VAS), physician's VAS, manual muscle strength (MMT-8)] evaluated pre- and post-vaccination. The mean age (43.1 +/- 9.9 vs. 43.8 +/- 8.4 years, p = 0.607) and gender distribution (p = 1.00) were comparable between the patients and controls. After 21 days, seroconversion (p = 0.394), seroprotection (p = 0.08), GMT (p = 0.573) and the FI in the GMT (p = 0.496) were similar in both groups. The disease and muscle parameters remained stable throughout the study, including the creatine kinase (p = 0.20) and aldolase levels (p = 0.98), the physicians' VAS (p = 1.00), the patients' VAS (p = 1.00) and the MMT-8 (p = 1.00). Regarding the influence of treatment, the seroconversion rates were comparable between the controls and patients undergoing treatment with glucocorticoid (GC) (p = 0.969), GC &gt;0.5 mg/kg/day (p = 0.395) and GC + immunosuppressors (p = 0.285). Vaccine-related adverse events were mild and similar in the DM/PM and control groups (p &gt; 0.05). Our data support the administration of the pandemic influenza A H1N1/2009 vaccination in DM/PM, as we found no short-term harmful effects related to the disease itself and adequate immunogenicity in spite of therapy. Further studies are necessary to identify any long-term adverse effects in patients with these diseases.(c) 2012 Elsevier Ltd. All rights reserved