Investigators from Cincinnati Children’s Hospital Medical Center (CCHMC), Cincinnati, OH, and Stanford University, Stanford, CA, conducted a prospective study to describe the clinical, immunologic, and pathologic characteristics in children with systemic juvenile idiopathic arthritis (SJIA) who develop lung disease (LD) and to identify risk factors for development of LD in SJIA patients. Study participants were children with SJIA followed at CCHMC who developed LD or patients with SJIA-LD who were referred to CCHMC since 2010. The diagnosis of SJIA in study children was confirmed using specific guidelines, and the presence of LD was determined based on objective findings on physical examination and/or imaging studies. Clinical data, including interleukin-18 (IL-18) levels, imaging findings, development of macrophage activation syndrome (MAS), and history of adverse response to biologic therapeutics to manage SJIA, were abstracted from the medical record of study participants. Lung biopsies were performed as clinically indicated. To identify risk factors for development of LD, study participants were matched 1:2 on age and sex with patients with SJIA without LD who were in the authors’ registry. The medical records of these “controls” were reviewed and clinical features compared to those with LD.
Since 2010, 18 children at CCHMC met criteria for SJIA with LD, including 13 patients referred for further evaluation and 5 patients diagnosed with SJIA at CCHMC who developed LD. During this same period, a total of 74 children were treated for SJIA at CCHMC. At the time of diagnosis, most children with SJIA-LD had only subtle respiratory symptoms, such as mild tachypnea. Of the 18 study patients, 16 had at least one key pulmonary finding on chest CT, including pleural thickening, septal thickening, bronchial wall or peri-bronchial thickening, “tree in-bud” opacities, “ground glass” opacities, or lymphadenopathy. Eight children underwent lung biopsy. Histopathologic findings within the endogenous lipoid pneumonia spectrum and lymphocyte-predominant inflammation were found in all biopsies. Compared to SJIA patients without LD, those with LD were significantly more likely to be diagnosed when they were ≤2 years old (odds ratio [OR], 6.5; 95% CI, 1.73–22.67). SJIA-LD patients were also more likely to have a history of adverse reaction to biologic therapeutics (OR, 13.6; 95% CI, 2.35–67.42), more likely to have a history of MAS (OR, 14.5; 95% CI, 3.35–47.21), and had higher serum IL-18 levels (P=.047) than controls.
The authors conclude that LD in children with SJIA has distinct clinical and immunologic features and is an uncharacterized inflammatory LD.
Dr Higgins has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.
In the past decade, treatment with biologic disease modifying anti-rheumatic drugs (bDMARDs) that block IL-1 and IL-6 has greatly improved outcomes for children with...