Stevens-Johnson syndrome and toxic epidermal necrolysis in childhood-onset systemic lupus erythematosus patients: a multicenter study

Objective: To assess Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in a large population of childhood-onset systemic lupus erythematosus (cSLE) patients. Methods: Multicenter study including 852 cSLE patients followed in Pediatric Rheumatology centers in Sao Paulo, Brazil. SJS was defined as epidermal detachment below 10% of body surface area (BSA), overlap SJS-TEN 10-30% and TEN greater than 30% of BSA. Results: SJS and TEN were observed in 5/852 (0.6%) cSLE female patients, three patients were classified as SJS and two patients were classified as overlap SJS-TENTEN was not observed. The mean duration of SJS and overlap SJS-TEN was 15 days (range 7-22) and antibio tics induced four cases. Regarding extra-cutaneous manifestations, hepatomegaly was observed in two cSLE patients, nephritis in two and neuropsychiatric involvement and conjunctivitis were observed respectively in one patient. Hematological involvement included lymphopenia in four, leucopenia in three and thrombocytopenia in two patients. The mean SLEDAI-2K score was 14.8 (range 6-30). Laboratory analysis showed low C3, C4 and/or CH50 in two patients and the presence of anti-dsDNA autoantibody in two patients. One patient had lupus anticoagulant and another one had anticardiolipin IgG. All patients were treated with steroids and four needed additional treatment such as intravenous immunoglobulin in two patients, hydroxychloroquine and azathioprine in two and intravenous cyclophosphamide in one patient. Sepsis was observed in three cSLE patients. Two patients required intensive care and death was observed in one patient. Conclusion: Our study identified SJS and overlap SJS-TEN as rare manifestations of active cSLE associated with severe multisystemic disease, with potentially lethal outcome.Conselho Nacional de Desenvolvimento Cientifico e TecnologicoFederico FoundationNucleo de Apoio a Pesquisa "Saude da Crianca e do Adolescente" of USP (NAP-CriAd)Univ Fed Sao Paulo, Pediat Rheumatol Unit, Sao Paulo, SP, BrazilUniv Sao Paulo, Pediat Rheumatol Unit, Fac Med, Sao Paulo, BrazilUniv Sao Paulo, Div Rheumatol, Fac Med, Sao Paulo, BrazilSao Paulo State Univ UNESP, Fac Med Botucatu, Pediat Rheumatol Div, Botucatu, SP, BrazilHosp Infantil Darcy Vargas, Pediat Rheumatol Unit, Sao Paulo, BrazilUniv Fed Sao Paulo, Pediat Rheumatol Unit, Sao Paulo, SP, BrazilCNPq: 303422/2015-7CNPq: 301805/2013-0CNPq: 305068/2014-8CNPq: 301479/2015CNPq: 303752/2015-7Federico FoundationNAP-CriAd-USPWeb of Scienc

Chronic spontaneous urticaria: a survey of 852 cases of childhood-onset systemic Lupus Erythematosus

Data regarding the prevalence of chronic spontaneous urticaria (CSU) in childhood-onset systemic lupus erythematosus (cSLE) patients and possible associated factors are limited to a few case reports. The objectives of this study were to assess CSU in a large cSLE population, in order to evaluate the demographic data, clinical manifestations, disease activity/damage, laboratory abnormalities and treatment. A retrospective multicenter cohort study (Brazilian cSLE group) was performed in 10 Pediatric Rheumatology services and included 852 cSLE patients. CSU was diagnosed according to the guidelines of the European Academy of Allergy and Clinical Immunology, the Global Allergy and Asthma European Network, the European Dermatology Forum and the World Allergy Organization. Patients with CSU (evaluated at urticaria diagnosis) and patients without CSU (evaluated at the last visit) were assessed for lupus clinical/laboratory features and treatment. CSU was observed in 10/852 cSLE patients (1.17%). The median of cSLE duration at urticaria diagnosis was 0 (-3 to 5) years. Comparison of cSLE patients with and without CSU revealed a greater frequency of constitutional symptoms (40 vs. 8%, p = 0.006), reticuloendothelial system involvement (30 vs. 3%, p = 0.003), mucocutaneous (90 vs. 28%, p < 0.0001) and musculoskeletal manifestations (50 vs. 6%, p < 0.0001) and methylprednisolone pulse therapy use (60 vs. 9%, p < 0.0001) in the former group. The frequency of immunosuppressive treatment was lower in patients with CSU (p = 0.018). The median SLE Disease Activity Index 2000 (12 vs. 2, p < 0.0001) and erythrocyte sedimentation rate (40 vs. 19 mm/1st hour, p = 0.024), was higher in patients with CSU. To our knowledge, this is the first study with evidence that CSU may be linked to cSLE. We also demonstrated that this particular skin manifestation occurs predominantly at disease onset and is associated with lupus moderate/high disease activity without major organ involvement1673186192CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ301805/2013-0; 2009/51897-5; 302724/2011-

Defining remission in childhood-onset lupus:PReS-endorsed consensus definitions by an international task force

Objective: To derive childhood-onset SLE (cSLE) specific remission definitions for future treat-to-target (T2T) trials, observational studies, and clinical practice. Methods: The cSLE International T2T Task Force conducted Delphi surveys exploring paediatric perspectives on adult-onset SLE remission targets. A modified nominal group technique was used to discuss, refine, and agree on the cSLE remission target criteria.Results: The Task Force proposed two definitions of remission: ‘cSLE clinical remission on steroids (cCR)’ and ‘cSLE clinical remission off steroids (cCR-0)’. The common criteria are: (1) Clinical-SLEDAI-2 K = 0; (2) PGA score &lt; 0.5 (0–3 scale); (4) stable antimalarials, immunosuppressive, and biologic therapy (changes due to side-effects, adherence, weight, or when building up to target dose allowed). Criterion (3) in cCR is the prednisolone dose ≤0.1 mg/kg/day (maximum 5 mg/day), whereas in cCR-0 it is zero. Conclusions: cSLE definitions of remission have been proposed, maintaining sufficient alignment with the adult-SLE definition to facilitate life-course research.</p

Efficacy of a 7-day course of furazolidone, levofloxacin, and lansoprazole after failed Helicobacter pylori eradication

<p>Abstract</p> <p>Background</p> <p>Increasing resistance to clarithromycin and nitroimidazole is the main cause of failure in the <it>Helicobacter pylori </it>eradication. The ideal retreatment regimen remains unclear, especially in developing countries, where the infection presents high prevalence and resistance to antibiotics. The study aimed at determining the efficacy, compliance and adverse effects of a regimen that included furazolidone, levofloxacin and lansoprazole in patients with persistent <it>Helicobacter pylori </it>infection, who had failed to respond to at least one prior eradication treatment regimen.</p> <p>Methods</p> <p>This study included 48 patients with peptic ulcer disease. <it>Helicobacter pylori </it>infection was confirmed by a rapid urease test and histological examination of samples obtained from the antrum and corpus during endoscopy. The eradication therapy consisted of a 7-day twice daily oral administration of lansoprazole 30 mg, furazolidone 200 mg and levofloxacin 250 mg. Therapeutic success was confirmed by a negative rapid urease test, histological examination and 14C- urea breath test, performed 12 weeks after treatment completion. The Chi-square method was used for comparisons among eradication rates, previous treatments and previous furazolidone use.</p> <p>Results</p> <p>Only one of the 48 patients failed to take all medications, which was due to adverse effects (vomiting). Per-protocol and intention-to-treat eradication rates were 89% (95% CI- 89%–99%) and 88% (88–92%), respectively. Mild and moderate adverse effects were reported by 41 patients (85%). For patients with one previous treatment failure, the eradication rate was 100%. Compared to furazolidone-naïve patients, eradication rates were lower in those who had failed prior furazolidone-containing regimen(s) (74% vs. 100%, p = 0.002).</p> <p>Conclusion</p> <p>An empiric salvage-regimen including levofloxacin, furazolidone and lansoprazole is very effective in the eradication of <it>Helicobacter pylori</it>, particularly in patients that have failed one prior eradication therapy.</p

Opportunistic infections in immunosuppressed patients with juvenile idiopathic arthritis: analysis by the Pharmachild Safety Adjudication Committee

Background To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee (SAC). Methods The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI. Results A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) were adjudicated as infections, of them 603/682 (88.4%) as common and 119/682 (17.4%) as OI by the SAC. Matching these 119 opportunistic events with the provisional list, 106 were confirmed by the SAC as OI, and among them infections by herpes viruses were the most frequent (68%), followed by tuberculosis (27.4%). The remaining events were divided in the groups of non-OI and possible/patient and/or pathogen-related OI. Conclusions We found a significant number of OI in JIA patients on immunosuppressive therapy. The proposed list of OI, created by consensus and validated in the Pharmachild cohort, could facilitate comparison among future pharmacovigilance studies

2016 American College of Rheumatology/European League Against Rheumatism Criteria for Minimal, Moderate, and Major Clinical Response in Juvenile Dermatomyositis An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative

To develop response criteria for juvenile dermatomyositis (DM). We analysed the performance of 312 definitions that used core set measures from either the International Myositis Assessment and Clinical Studies Group (IMACS) or the Paediatric Rheumatology International Trials Organisation (PRINTO) and were derived from natural history data and a conjoint analysis survey. They were further validated using data from the PRINTO trial of prednisone alone compared to prednisone with methotrexate or cyclosporine and the Rituximab in Myositis (RIM) trial. At a consensus conference, experts considered 14 top candidate criteria based on their performance characteristics and clinical face validity, using nominal group technique. Consensus was reached for a conjoint analysis-based continuous model with a total improvement score of 0-100, using absolute per cent change in core set measures of minimal (>= 30), moderate (>= 45), and major (>= 70) improvement. The same criteria were chosen for adult DM/polymyositis, with differing thresholds for improvement. The sensitivity and specificity were 89% and 91-98% for minimal improvement, 92-94% and 94-99% for moderate improvement, and 91-98% and 85-86% for major improvement, respectively, in juvenile DM patient cohorts using the IMACS and PRINTO core set measures. These criteria were validated in the PRINTO trial for differentiating between treatment arms for minimal and moderate improvement (p= 0.009-0.057) and in the RIM trial for significantly differentiating the physician's rating for improvement (p< 0.006). The response criteria for juvenile DM consisted of a conjoint analysis-based model using a continuous improvement score based on absolute per cent change in core set measures, with thresholds for minimal, moderate, and major improvement