Emergent high fatality lung disease in systemic juvenile arthritis. Issue 12 (27th September 2019)

• Record Type: Journal Article
• Authors: 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;
• Other Names: author non-byline.; Abulaban K author non-byline.; Agbayani R author non-byline.; Akoghlanian S author non-byline.; Anderson E author non-byline.; Andrew M author non-byline.; Badwal B author non-byline.; Barillas-Arias L author non-byline.; Baszis K author non-byline.; Becker M author non-byline.; Bell-Brunson H author non-byline.; Benham H author non-byline.; Benseler S author non-byline.; Beukelman T author non-byline.; Birmingham J author non-byline.; Boncek M author non-byline.; Brunner H author non-byline.; Bryson A author non-byline.; Bukulmez H author non-byline.; Cerracchio L author non-byline.; Chalom E author non-byline.; Chang J author non-byline.; Chowdhury N author non-byline.; Chundru K author non-byline.; Davis T author non-byline.; Dean J author non-byline.; Dedeoglu F author non-byline.; Dempsey V author non-byline.; Dionizovik-Dimanovski M author non-byline.; Dolinsky L author non-byline.; Drew J author non-byline.; Feldman B author non-byline.; Ferguson P author non-byline.; Ferreira B author non-byline.; Fleming C author non-byline.; Franco L author non-byline.; Goh I author non-byline.; Goldsmith D author non-byline.; Gottlieb B author non-byline.; Graham T author non-byline.; Griffin T author non-byline.; Hance M author non-byline.; Helfrich D author non-byline.; Hickey K author non-byline.; Hollander M author non-byline.; Hsu J author non-byline.; Huber A author non-byline.; Hudson A author non-byline.; Hung C author non-byline.; Huttenlocher A author non-byline.; Imundo L author non-byline.; Inman C author non-byline.; Jaquith J author non-byline.; Jerath R author non-byline.; Jones J author non-byline.; Jones S author non-byline.; Jung L author non-byline.; Kahn P author non-byline.; Kingsbury D author non-byline.; Klein K author non-byline.; Klein-Gitelman M author non-byline.; Kramer S author non-byline.; Kufen A author non-byline.; Lapidus S author non-byline.; Latham D author non-byline.; Linehan S author non-byline.; Malla B author non-byline.; Malloy M author non-byline.; Martyniuk A author non-byline.; Mason T author non-byline.; McConnell K author non-byline.; McCurdy D author non-byline.; McKibben K author non-byline.; McMullen-Jackson C author non-byline.; Moore K author non-byline.; Moorthy L author non-byline.; Muscal E author non-byline.; Norris W author non-byline.; Olson J author non-byline.; O'Neil K author non-byline.; Onel K author non-byline.; Phillips K author non-byline.; Ponder L author non-byline.; Prahalad S author non-byline.; Rabinovich C author non-byline.; Rauch S author non-byline.; Ringold S author non-byline.; Riordan M author non-byline.; Roberson S author non-byline.; Robinson A author non-byline.; Rojas E author non-byline.; Rosenkranz M author non-byline.; Rosolowski B author non-byline.; Ruth N author non-byline.; Schikler K author non-byline.; Sepulveda A author non-byline.; Smith C author non-byline.; Stapp H author non-byline.; Stewart K author non-byline.; Syed R author non-byline.; Tangarone A author non-byline.; Tesher M author non-byline.; Thatayatikom A author non-byline.; Vehe R author non-byline.; von Scheven E author non-byline.; Wahezi D author non-byline.; Wang C author non-byline.; Wassink C author non-byline.; Watson M author non-byline.; Watts A author non-byline.; Weiss J author non-byline.;
• Is Part Of: Annals of the rheumatic diseases. Volume 78:Issue 12(2019)
• Page Start: 1722
• Page End: 1731
• Publication Date: 2019-09-27
• Subjects: inflammation -- juvenile idiopathic arthritis -- adult onset still's disease -- DMARDs (biologic) -- treatment; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2019-216040
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Objective: To investigate the characteristics and risk factors of a novel parenchymal lung disease (LD), increasingly detected in systemic juvenile idiopathic arthritis (sJIA). 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.