Emergent high fatality lung disease in systemic juvenile arthritis.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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Saper Vivian E, Chen Guangbo, Deutsch Gail H, Guillerman R Paul, Birgmeier Johannes, Jagadeesh Karthik, Canna Scott, Schulert Grant, Deterding Robin, Xu Jianpeng, Leung Ann N, Bouzoubaa Layla, Abulaban Khalid, Baszis Kevin, Behrens Edward M, Birmingham James, Casey Alicia, Cidon Michal, Cron Randy Q, De Aliva, De Benedetti Fabrizio, Ferguson Ian, Fishman Martha P, Goodman Steven I, Graham T Brent, Grom Alexei A, Haines Kathleen, Hazen Melissa, Henderson Lauren A, Ho Assunta, Ibarra Maria, Inman Christi J, Jerath Rita, Khawaja Khulood, Kingsbury Daniel J, Klein-Gitelman Marisa, Lai Khanh, Lapidus Sivia, Lin Clara, Lin Jenny, Liptzin Deborah R, Milojevic Diana, Mombourquette Joy, Onel Karen, Ozen Seza, Perez Maria, Phillippi Kathryn, Prahalad Sampath, Radhakrishna Suhas, Reinhardt Adam, Riskalla Mona, Rosenwasser Natalie, Roth Johannes, Schneider Rayfel, Schonenberg-Meinema Dieneke, Shenoi Susan, Smith Judith A, Sönmez Hafize Emine, Stoll Matthew L, Towe Christopher, Vargas Sara O, Vehe Richard K, Young Lisa R, Yang Jacqueline, Desai Tushar, Balise Raymond, Lu Ying, Tian Lu, Bejerano Gill, Davis Mark M, Khatri Purvesh, Mellins Elizabeth D, Childhood Arthritis and Rheumatology Research Alliance Registry Investigators
Аннотация
METHODS: In a multicentre retrospective study, 61 cases were investigated using physician-reported clinical information and centralised analyses of radiological, pathological and genetic data.
RESULTS: LD was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the interleukin (IL)-6 inhibitor, tocilizumab. Serum ferritin elevation and/or significant lymphopaenia preceded LD detection. The most prevalent chest CT pattern was septal thickening, involving the periphery of multiple lobes ± ground-glass opacities. The predominant pathology (23 of 36) was pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), with atypical features including regional involvement and concomitant vascular changes. Apparent severe delayed drug hypersensitivity occurred in some cases. The 5-year survival was 42%. Whole exome sequencing (20 of 61) did not identify a novel monogenic defect or likely causal PAP-related or macrophage activation syndrome (MAS)-related mutations. Trisomy 21 and young sJIA onset increased LD risk. Exposure to IL-1 and IL-6 inhibitors (46 of 61) was associated with multiple LD features. By several indicators, severity of sJIA was comparable in drug-exposed subjects and published sJIA cohorts. MAS at sJIA onset was increased in the drug-exposed, but was not associated with LD features.
CONCLUSIONS: A rare, life-threatening lung disease in sJIA is defined by a constellation of unusual clinical characteristics. The pathology, a PAP/ELP variant, suggests macrophage dysfunction. Inhibitor exposure may promote LD, independent of sJIA severity, in a small subset of treated patients. Treatment/prevention strategies are needed.