Severe delayed hypersensitivity reactions to IL-1 and IL-6 inhibitors link to common HLA-DRB1*15 alleles.
Publication/Presentation Date
3-1-2022
Abstract
OBJECTIVES: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, delayed hypersensitivity reaction (DHR). We observed DRESS to inhibitors of interleukin 1 (IL-1) or IL-6 in a small group of patients with Still's disease with atypical lung disease. We sought to characterise features of patients with Still's disease with DRESS compared with drug-tolerant Still's controls. We analysed human leucocyte antigen (HLA) alleles for association to inhibitor-related DHR, including in a small Kawasaki disease (KD) cohort.
METHODS: In a case/control study, we collected a multicentre series of patients with Still's disease with features of inhibitor-related DRESS (n=66) and drug-tolerant Still's controls (n=65). We retrospectively analysed clinical data from all Still's subjects and typed 94/131 for HLA. European Still's-DRESS cases were ancestry matched to International Childhood Arthritis Genetics Consortium paediatric Still's cases (n=550) and compared for HLA allele frequencies. HLA association also was analysed using Still's-DRESS cases (n=64) compared with drug-tolerant Still's controls (n=30). KD subjects (n=19) were similarly studied.
RESULTS: Still's-DRESS features included eosinophilia (89%), AST-ALT elevation (75%) and non-evanescent rash (95%; 88% involving face). Macrophage activation syndrome during treatment was frequent in Still's-DRESS (64%) versus drug-tolerant Still's (3%; p=1.2×10
CONCLUSIONS: DRESS-type reactions occur among patients treated with IL-1/IL-6 inhibitors and strongly associate with common HLA-DRB1*15 haplotypes. Consideration of preprescription HLA typing and vigilance for serious reactions to these drugs are warranted.
Volume
81
Issue
3
First Page
406
Last Page
415
ISSN
1468-2060
Published In/Presented At
Saper, V. E., Ombrello, M. J., Tremoulet, A. H., Montero-Martin, G., Prahalad, S., Canna, S., Shimizu, C., Deutsch, G., Tan, S. Y., Remmers, E. F., Monos, D., Hahn, T., Phadke, O. K., Cassidy, E., Ferguson, I., Mallajosyula, V., Xu, J., Rosa Duque, J. S., Chua, G. T., Ghosh, D., … INCHARGE Consortium (2022). Severe delayed hypersensitivity reactions to IL-1 and IL-6 inhibitors link to common HLA-DRB1*15 alleles. Annals of the rheumatic diseases, 81(3), 406–415. https://doi.org/10.1136/annrheumdis-2021-220578
Disciplines
Medicine and Health Sciences | Pediatrics
PubMedID
34789453
Department(s)
Department of Pediatrics
Document Type
Article