Emergent high fatality lung disease in systemic juvenile arthritis

Title

Emergent high fatality lung disease in systemic juvenile arthritis

Creator

Saper Vivian E; Chen Guangbo; Deutsch Gail H; Guillerman R Paul; Birgmeier Johannes; Jagadeesh Karthik; Canna Scott; Schulert Grant; Deterding Robin; Xu Jianpeng; Leung Ann N; Bouzoubaa Layla; Abulaban Khalid; Baszis Kevin; Behrens Edward M; Birmingham James; Casey Alicia; Cidon Michal; Cron Randy Q; De Aliva; De Benedetti Fabrizio; Ferguson Ian; Fishman Martha P; Goodman Steven I; Graham T Brent; Grom Alexei A; Haines Kathleen; Hazen Melissa; Henderson Lauren A; Ho Assunta; Ibarra Maria; Inman Christi J; Jerath Rita; Khawaja Khulood; Kingsbury Daniel J; Klein-Gitelman Marisa; Lai Khanh; Lapidus Sivia; Lin Clara; Lin Jenny; Liptzin Deborah R; Milojevic Diana; Mombourquette Joy; Onel Karen; Ozen Seza; Perez Maria; Phillippi Kathryn; Prahalad Sampath; Radhakrishna Suhas; Reinhardt Adam; Riskalla Mona; Rosenwasser Natalie; Roth Johannes; Schneider Rayfel; Schonenberg-Meinema Dieneke; Shenoi Susan; Smith Judith A; Sönmez Hafize Emine; Stoll Matthew L; Towe Christopher; Vargas Sara O; Vehe Richard K; Young Lisa R; Yang Jacqueline; Desai Tushar; Balise Raymond; Lu Ying; Tian Lu; Bejerano Gill; Davis Mark M; Khatri Purvesh; Mellins Elizabeth D; Childhood Arthritis and Rheumatology Research Alliance Registry Investigators

Publisher

Annals Of The Rheumatic Diseases

Date

2019
2019-12

Description

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.

Subject

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

Identifier

PMID: 31562126

Format

Journal Article

Search for Full-text

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Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

1722-1731

Issue

12

Volume

78

ISSN

1468-2060

Tags

Citation

Saper Vivian E; Chen Guangbo; Deutsch Gail H; Guillerman R Paul; Birgmeier Johannes; Jagadeesh Karthik; Canna Scott; Schulert Grant; Deterding Robin; Xu Jianpeng; Leung Ann N; Bouzoubaa Layla; Abulaban Khalid; Baszis Kevin; Behrens Edward M; Birmingham James; Casey Alicia; Cidon Michal; Cron Randy Q; De Aliva; De Benedetti Fabrizio; Ferguson Ian; Fishman Martha P; Goodman Steven I; Graham T Brent; Grom Alexei A; Haines Kathleen; Hazen Melissa; Henderson Lauren A; Ho Assunta; Ibarra Maria; Inman Christi J; Jerath Rita; Khawaja Khulood; Kingsbury Daniel J; Klein-Gitelman Marisa; Lai Khanh; Lapidus Sivia; Lin Clara; Lin Jenny; Liptzin Deborah R; Milojevic Diana; Mombourquette Joy; Onel Karen; Ozen Seza; Perez Maria; Phillippi Kathryn; Prahalad Sampath; Radhakrishna Suhas; Reinhardt Adam; Riskalla Mona; Rosenwasser Natalie; Roth Johannes; Schneider Rayfel; Schonenberg-Meinema Dieneke; Shenoi Susan; Smith Judith A; Sönmez Hafize Emine; Stoll Matthew L; Towe Christopher; Vargas Sara O; Vehe Richard K; Young Lisa R; Yang Jacqueline; Desai Tushar; Balise Raymond; Lu Ying; Tian Lu; Bejerano Gill; Davis Mark M; Khatri Purvesh; Mellins Elizabeth D; Childhood Arthritis and Rheumatology Research Alliance Registry Investigators, “Emergent high fatality lung disease in systemic juvenile arthritis,” NEOMED Bibliography Database, accessed January 27, 2021, https://neomed.omeka.net/items/show/10816.

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