Emergent high fatality lung disease in systemic juvenile arthritis.
Ann Rheum Dis
; 78(12): 1722-1731, 2019 12.
Article
en En
| MEDLINE
| ID: mdl-31562126
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.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Artritis Juvenil
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Pulmón
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Enfermedades Pulmonares
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
/
Incidence_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Límite:
Child
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Child, preschool
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Female
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Humans
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Infant
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Male
País/Región como asunto:
America do norte
Idioma:
En
Revista:
Ann Rheum Dis
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos