HLA–DRB1*15 and Eosinophilia Are Common Among Patients With Systemic Juvenile Idiopathic Arthritis

Abstract

ObjectiveConcern exists that medications used to treat patients with systemic juvenile idiopathic arthritis (JIA), particularly interleukin (IL)‐1 and IL‐6 blocking agents, might be causing adverse drug reactions and lung disease (systemic JIA‐LD). Carriage of HLA–DRB1*15 has been reported as a risk factor for adverse drug reactions among patients with systemic JIA. We performed a retrospective chart review to evaluate these factors at our center.MethodsWe reviewed the records of 86 subjects with systemic JIA followed for at least 6 months between 1996 and 2022. HLA typing was performed in 23 of the subjects. We compared characteristics of patients with or without eosinophilia. Among patients with HLA typing, we compared clinical characteristics of subjects with or without DRB1*15 and with or without systemic JIA‐LD.ResultsAmong the 23 patients with HLA typing, 74% carried DRB1*15, and 63% of patients without systemic JIA‐LD carried DRB1*15. Seven subjects had systemic JIA‐LD, all of whom carried DRB1*15. Patients with systemic JIA‐LD were younger at the time of diagnosis and more likely to have had macrophage activation syndrome. Exposure to IL‐1 and IL‐6 blockers was common, occurring in 95% of patients. Eosinophilia occurred in 39% of patients with systemic JIA, often before IL‐1 or IL‐6 blockade. Eosinophilia was associated with adverse drug reactions and macrophage activation syndrome. There was 1 death, unrelated to active systemic JIA disease.ConclusionCarriage of DRB1*15 was more common in this cohort of patients with systemic JIA than in the general population. Eosinophilia and systemic JIA‐LD were more common among patients with severe systemic JIA complicated by macrophage activation syndrome.

UnDRESSing Systemic Juvenile Idiopathic Arthritis Lung Disease

“…Likewise, if DRB1*15:01 is the risk allele for such a reaction, carriage rates in the systemic JIA-LD drug-exposed populations should be higher than in the non-systemic JIA-LD population. Articles by Lerman et al (7) and Womba et al (8), included in this issue of Arthritis Care & Research, test these hypotheses using retrospective data and conclude that neither of these predicted observations are true. Lerman and colleagues show that eosinophilia precedes drug therapy in 43% of patients with systemic JIA (7).…”

“…Articles by Lerman et al (7) and Womba et al (8), included in this issue of Arthritis Care & Research, test these hypotheses using retrospective data and conclude that neither of these predicted observations are true. Lerman and colleagues show that eosinophilia precedes drug therapy in 43% of patients with systemic JIA (7). This suggests eosinophilia is a feature of the disease rather than drug reaction.…”

“…Wobma et al find that the MHC haplotype does not statistically associate with eosinophilia (8). Furthermore, Lerman et al show that DRB1*15:01 is enriched in systemic JIA more broadly, perhaps as a risk factor for severe disease, but not necessarily associated with systemic JIA-LD or drug reaction per se (7). Thus, as with eosinophilia, the fact that DRB1*15:01 was originally associated with systemic JIA-LD may simply be due to its association with severe systemic JIA more broadly rather than a lung disease-specific factor.…”