Parenchymal lung disease reported in systemic juvenile idiopathic arthritis
Acute digital clubbing was one clinical characteristic of a rare and potentially fatal lung disease recently observed in a cohort of patients with systemic juvenile idiopathic arthritis, according to findings published in Annals of the Rheumatic Diseases.
“Initially described in 1897, parenchymal lung disease has never been a feature of Still’s disease,” Vivian Saper, MD, adjunct clinical professor of pediatric rheumatology, allergy, asthma and immunology in the division of human gene therapy at Stanford University School of Medicine, told Healio Pulmonology. “Therefore, the occurrence of lung disease in systemic juvenile idiopathic arthritis is a surprise. Furthermore, the constellation of clinical features, pathology and radiography is distinct from any known connective tissue-associated interstitial lung disease.”
The current multicenter, retrospective study included 61 patients with systemic juvenile idiopathic arthritis.
Results showed that acute erythematous clubbing and frequent anaphylactic reactions to tocilizumab (Actemra, Genentech) were two of several features associated with this lung disease, including serum ferritin elevation and/or significant lymphopenia prior to lung disease detection.
Septal thickening, involving the periphery of multiple lobes with or without ground-glass opacities, was the most commonly reported CT pattern. Pathology findings showed pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia with atypical features, such as regional involvement and concomitant vascular changes, in 23 cases.
Delayed drug hypersensitivity was also evident in a number of cases.
No monogenic defect or causal pulmonary alveolar proteinosis-related or macrophage activation syndrome-related mutations were found after whole-exome sequencing of 20 patients in the cohort. Additionally, macrophage activation syndrome at onset of systemic juvenile idiopathic arthritis was elevated in drug-exposed patients, but showed no associations with lung disease features, according to the findings.
Lung disease risk was elevated in patients with trisomy 21 and young onset of systemic juvenile idiopathic arthritis.
The researchers added that exposure to interleukin-1 (IL-1) and IL-6 inhibitors demonstrated associations with a number of features of the lung disease in 46 patients.
Outcome data showed a 5-year survival rate of 42%.
“We really can’t say yet how to treat or prevent this lung disease in children, with the exception of those with apparent delayed drug hypersensitivity,” Elizabeth Mellins, MD, professor in the department of pediatrics and program in immunology at Stanford University School of Medicine, said in an interview. “We are concerned about the possible association of IL-1 and IL-6 inhibitors with this lung disease, which is a very rare complication, compared to the large group of children who derive great benefit from these drugs. For now, it seems best to manage each child with systemic juvenile idiopathic arthritis and lung disease individually, with the help of a pediatric pulmonologist.”
Rheumatologists treating children with systemic juvenile idiopathic arthritis should look for features associated with drug-related eosinophilic systemic syndrome (DReSS), Saper said.
“In DReSS, the recommendation is withdrawal of the implicated medication,” she said. “We also recommend vigilance about the risk for pneumocystis pneumonia.”– by Rob Volansky
Disclosures: Mellins and Saper report no relevant financial disclosures.