Emergent high fatality lung disease in systemic juvenile arthritis

Childhood Arthritis and Rheumatology Research Alliance Registry Investigators

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1722-1731
Number of pages10
JournalAnnals of the Rheumatic Diseases
Volume78
Issue number12
DOIs
Publication statusPublished - Dec 2019

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    Childhood Arthritis and Rheumatology Research Alliance Registry Investigators (2019). Emergent high fatality lung disease in systemic juvenile arthritis. Annals of the Rheumatic Diseases, 78(12), 1722-1731. https://doi.org/10.1136/annrheumdis-2019-216040