Yannan Huang, UCCOM MS2 (medical student); Shima Yasin MD, Rheumatology; Christopher Towe MD, Pulmonary Medicine; Grant Schulert MD PhD, Rheumatology (PI)

Introduction: Systemic juvenile idiopathic arthritis (SJIA) is a chronic autoinflammatory disease of childhood, representing 10-15% of the total JIA population. Complications of SJIA include macrophage activation syndrome (MAS), a serious and often life-threatening episode of hyperinflammation, as well as a previously uncharacterized, and only recently recognized, inflammatory lung disease (SJIA-LD). The high morbidity and mortality of the SJIA-LD disease course, which currently affects as many as 1 in 20 SJIA patients, warrants the need for further evaluation of the prognostic predictors, treatment, and long-term outcomes for these patients.

Methods: A prospective cohort of 34 SJIA patients were identified at the time of lung disease detection or referral to CCHMC for consultation or second opinion. Patients were then categorized as having suspected, probable, or definite SJIA-LD based on objective findings as seen on clinical exam, chest imaging, and tissue biopsy. Clinical data and imaging were abstracted from patient medical records. Overall survival and free survival free of supplemental oxygen were analyzed using Kaplan-Meier curves.

Results: Of the total 34 patients, 6 were identified as having suspected SJIA-LD, 16 were identified as having probable SJIA-LD, and 13 were identified as having definite (biopsy-confirmed) SJIA-LD. The median age of SJIA patients at lung disease diagnosis was 3.6 years. Predominant clinical features of SJIA-LD, present in over half of the patients, included clubbing of fingers and/or toes (76%) dyspnea on exertion (65%), and cough (56%), followed by the need for home oxygen supplementation (47%) and tachypnea (47%). Medications for SJIA treatment post lung disease diagnosis, showed an overall decrease in the proportion of patients using biologics (anakinra, tocilizumab, canakinumab), while other forms of immunosuppressive or immunomodulating therapy showed either no significant difference (methotrexate, cyclosporine, corticosteroids, and tacrolimus), or an increase in use (tofacitinib). The only common feature on chest CT seen in the majority of patients was septal thickening (64.7%). However, among patients who required at home oxygen supplementation (16/34), predominant features included tree-in-bud opacities, ground-glass opacities, and pulmonary artery enlargement. While the overall survival 500 days post lung disease diagnosis is ~90%, only 67% remained free of supplemental oxygen.

Conclusion: Clubbing of fingers and/toes, dyspnea on exertion, and cough are predominant clinical findings in SJIA-LD that can serve as diagnostic measures for SJIA patients in whom lung disease is suspected. Additionally, on chest CT, features of ground-glass opacities, tree-in-bud, and PA enlargement are common in patients later requiring O2 supplementation, a prognostic indictor for worsening lung disease. Given that the increased incidence of lung disease in SJIA patients parallels the increased usage of biologics, an overall decreased use of biologics for SJIA treatment post lung disease diagnosis reflects physician precaution against further potential disease progression. Compared to earlier studies with reported mortality rates of greater than 50% less than a year after diagnosis, our study found a much higher overall survival probability but with a steady increase in the proportion of patients requiring home oxygen within the first 500 days.

Keywords/Tags: SJIA, lung disease, pediatrics, SMURRF