Systemic juvenile idiopathic arthritis-related lung disease: Frequency and associated factors

Objective: Recent reports indicate a rising pattern of lung involvement in systemic juvenile idiopathic arthritis (sJIA) characterized by interstitial lung disease (sJIA-LD), distinct from the classical presentation. sJIA-LD is estimated to occur in 5–15% of patients, typically with an insidious onset and a proposed mortality of 10– 15%. Disease severity, treatment-related effects, and genetic factors have been suggested as contributors to its pathogenesis. This study aimed to determine the frequency of sJIA-LD in a large patient cohort, to examine its association with factors such as age at onset, disease activity, treatment history, and genetics, and to contribute the development of a screening algorithm. Materials and Methods: This single-center cross-sectional study included 87 patients followed with an sJIA diagnosis. Patients were considered at risk and underwent thoracic CT imaging if they had any of the following: diagnosis before age 2, Down syndrome, MAS episodes, subclinical MAS, adverse reactions to biologics, decreased lung diffusion capacity, persistent cough, digital clubbing, or suspicious chest radiography. Demographic and clinical data, disease activity, treatment history, KL-6 levels, and HLA-DRB1*15 positivity were compared between patients with CT confirmed sJIA-LD and those with sJIA without lung involvement. Results: Fifteen of 87 patients were diagnosed with sJIA-LD. Digital clubbing (46%) was the most common finding, and more than half of the patients were completely asymptomatic. Thoracic CT most frequently showed subpleural reticulations (53%) and interseptal thickening (73%). A statistically significant association was identified between sJIA-LD and the following: diagnosis before age 2, asymptomatic inflammation, MAS frequency, subclinical MAS, adverse reactions to biologic therapy, canakinumab use, eosinophilia, KL-6 positivity, and HLA-DRB1*15 positivity. HLA-DRB1*15 showed a strong association with sJIA-LD, while high disease activity was the only independent risk factor. Conclusion: The frequency of sJIA-LD in this cohort was 17%, and the condition often remained asymptomatic. Indicators of high disease activity such as asymptomatic inflammation, subclinical MAS, and MAS episode frequency increased the risk of sJIA-LD. HLA-DRB1*15 positivity appears to be a valuable predictor of both biologic drug hypersensitivity and sJIA-LD development. HLA-DRB1*15 typing should be considered at initial diagnosis and especially prior to initiating biologic therapy.