PT  - JOURNAL ARTICLE
AU  - Saper, Vivian E
AU  - Chen, Guangbo
AU  - Deutsch, Gail H
AU  - Guillerman, R Paul
AU  - Birgmeier, Johannes
AU  - Jagadeesh, Karthik
AU  - Canna, Scott
AU  - Schulert, Grant
AU  - Deterding, Robin
AU  - Xu, Jianpeng
AU  - Leung, Ann N
AU  - Bouzoubaa, Layla
AU  - Abulaban, Khalid
AU  - Baszis, Kevin
AU  - Behrens, Edward M
AU  - Birmingham, James
AU  - Casey, Alicia
AU  - Cidon, Michal
AU  - Cron, Randy Q
AU  - De, Aliva
AU  - De Benedetti, Fabrizio
AU  - Ferguson, Ian
AU  - Fishman, Martha P
AU  - Goodman, Steven I
AU  - Graham, T Brent
AU  - Grom, Alexei A
AU  - Haines, Kathleen
AU  - Hazen, Melissa
AU  - Henderson, Lauren A
AU  - Ho, Assunta
AU  - Ibarra, Maria
AU  - Inman, Christi J
AU  - Jerath, Rita
AU  - Khawaja, Khulood
AU  - Kingsbury, Daniel J
AU  - Klein-Gitelman, Marisa
AU  - Lai, Khanh
AU  - Lapidus, Sivia
AU  - Lin, Clara
AU  - Lin, Jenny
AU  - Liptzin, Deborah R
AU  - Milojevic, Diana
AU  - Mombourquette, Joy
AU  - Onel, Karen
AU  - Ozen, Seza
AU  - Perez, Maria
AU  - Phillippi, Kathryn
AU  - Prahalad, Sampath
AU  - Radhakrishna, Suhas
AU  - Reinhardt, Adam
AU  - Riskalla, Mona
AU  - Rosenwasser, Natalie
AU  - Roth, Johannes
AU  - Schneider, Rayfel
AU  - Schonenberg-Meinema, Dieneke
AU  - Shenoi, Susan
AU  - Smith, Judith A
AU  - Sönmez, Hafize Emine
AU  - Stoll, Matthew L
AU  - Towe, Christopher
AU  - Vargas, Sara O
AU  - Vehe, Richard K
AU  - Young, Lisa R
AU  - Yang, Jacqueline
AU  - Desai, Tushar
AU  - Balise, Raymond
AU  - Lu, Ying
AU  - Tian, Lu
AU  - Bejerano, Gill
AU  - Davis, Mark M
AU  - Khatri, Purvesh
AU  - Mellins, Elizabeth D
ED - 
TI  - Emergent high fatality lung disease in systemic juvenile arthritis
AID  - 10.1136/annrheumdis-2019-216040
DP  - 2019 Dec 01
TA  - Annals of the Rheumatic Diseases
PG  - 1722--1731
VI  - 78
IP  - 12
4099  - http://ard.bmj.com/content/78/12/1722.short
4100  - http://ard.bmj.com/content/78/12/1722.full
SO  - Ann Rheum Dis2019 Dec 01; 78
AB  - 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.