RT Journal Article
SR Electronic
T1 Emergent high fatality lung disease in systemic juvenile arthritis
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 1722
OP 1731
DO 10.1136/annrheumdis-2019-216040
VO 78
IS 12
A1 Vivian E Saper
A1 Guangbo Chen
A1 Gail H Deutsch
A1 R Paul Guillerman
A1 Johannes Birgmeier
A1 Karthik Jagadeesh
A1 Scott Canna
A1 Grant Schulert
A1 Robin Deterding
A1 Jianpeng Xu
A1 Ann N Leung
A1 Layla Bouzoubaa
A1 Khalid Abulaban
A1 Kevin Baszis
A1 Edward M Behrens
A1 James Birmingham
A1 Alicia Casey
A1 Michal Cidon
A1 Randy Q Cron
A1 Aliva De
A1 Fabrizio De Benedetti
A1 Ian Ferguson
A1 Martha P Fishman
A1 Steven I Goodman
A1 T Brent Graham
A1 Alexei A Grom
A1 Kathleen Haines
A1 Melissa Hazen
A1 Lauren A Henderson
A1 Assunta Ho
A1 Maria Ibarra
A1 Christi J Inman
A1 Rita Jerath
A1 Khulood Khawaja
A1 Daniel J Kingsbury
A1 Marisa Klein-Gitelman
A1 Khanh Lai
A1 Sivia Lapidus
A1 Clara Lin
A1 Jenny Lin
A1 Deborah R Liptzin
A1 Diana Milojevic
A1 Joy Mombourquette
A1 Karen Onel
A1 Seza Ozen
A1 Maria Perez
A1 Kathryn Phillippi
A1 Sampath Prahalad
A1 Suhas Radhakrishna
A1 Adam Reinhardt
A1 Mona Riskalla
A1 Natalie Rosenwasser
A1 Johannes Roth
A1 Rayfel Schneider
A1 Dieneke Schonenberg-Meinema
A1 Susan Shenoi
A1 Judith A Smith
A1 Hafize Emine Sönmez
A1 Matthew L Stoll
A1 Christopher Towe
A1 Sara O Vargas
A1 Richard K Vehe
A1 Lisa R Young
A1 Jacqueline Yang
A1 Tushar Desai
A1 Raymond Balise
A1 Ying Lu
A1 Lu Tian
A1 Gill Bejerano
A1 Mark M Davis
A1 Purvesh Khatri
A1 Elizabeth D Mellins
A1 ,
YR 2019
UL http://ard.bmj.com/content/78/12/1722.abstract
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.