Emergent high fatality lung disease in systemic juvenile arthritis

Childhood arthritis and Rheumatology Research alliance Registry investigators

Research output: Contribution to journalArticle

10 Scopus citations

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 (US)
Pages (from-to)1722-1731
Number of pages10
JournalAnnals of the Rheumatic Diseases
Volume78
Issue number12
DOIs
StatePublished - Jan 1 2019

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Keywords

  • DMARDs (biologic)
  • adult onset still's disease
  • inflammation
  • juvenile idiopathic arthritis
  • treatment

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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