Rheumatology
From a rheumatologic perspective, all patients in our cohort had active sJIA disease; 89% of participants had a history of macrophage activation syndrome (MAS), with 33% having MAS recently before their diagnosis of sJIA-LD. History of MAS, particularly recurrent episodes of MAS, is also a common finding in other sJIA-LD cohorts2, 6, 10. Our patients showed elevations in inflammatory cytokines, specifically IL-18, which has also been seen in other studies. IL-18 elevation has been implicated as a marker of sJIA disease activity, development of MAS, and in sJIA patients with pulmonary alveolar proteinosis 12,13. Other laboratory trends include a prodrome of lymphopenia, ferritin, and peripheral eosinophilia 9. These trends hint at sJIA-LD’s underlying pathophysiology, but further investigation is needed. Common clinical features identified in previous cohorts included lymphadenopathy and hepatosplenomegaly 6, 10. However, these were not identified in our patient population.
Saper, et al. identified several patients with delayed drug hypersensitivity in their case series 9. They noted a high frequency of anaphylactic reactions to the interleukin (IL)-6 inhibitor, tocilizumab. In a cohort of 25 cases, 68% of patients were taking a biologic disease-modifying antirheumatic drugs; two subsequent cohorts likewise observed a higher number of adverse effects related to anti-cytokine drugs 6, 9, 10. As previously mentioned, all patients in our case series were treated with anakinra (an IL-1 inhibitor). Five patients also received IL-6 inhibitor tocilizumab; one patient received IL-1β inhibitor canakinumab. In our case series, one of the four patients treated with tocilizumab developed confirmed DRESS. No other treatment was associated with DRESS. No patients developed anaphylaxis following use of tocilizumab.
Interestingly, five out of nine patients initially presented with symptoms concerning Kawasaki disease. This highlights the importance of keeping sJIA on the initial differential and completing early evaluation if other aspects of the clinical course are not consistent with Kawasaki disease. There is no current evidence that treatment for Kawasaki disease (such as steroids, IVIG, and infliximab) precipitates interstitial lung disease.