Emergent high fatality lung disease in systemic juvenile arthritis.
DOI: 10.1136/annrheumdis-2019-216040; PMCID: PMC7065839
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.
Annals of the rheumatic diseases
Arthritis, Juvenile; Biopsy; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Incidence; Infant; Lung; Lung Diseases; Male; Prognosis; Retrospective Studies; Survival Rate; Tomography, X-Ray Computed; United States
DMARDs (biologic); adult onset still's disease; inflammation; juvenile idiopathic arthritis; treatment
Saper VE, Chen G, Deutsch GH, et al. Emergent high fatality lung disease in systemic juvenile arthritis. Ann Rheum Dis. 2019;78(12):1722-1731. doi:10.1136/annrheumdis-2019-216040