Details

Autor(en) / Beteiligte

• Saper, Vivian E
• Ombrello, Michael J
• Tremoulet, Adriana H
• Montero-Martin, Gonzalo
• Prahalad, Sampath
• Canna, Scott
• Shimizu, Chisato
• Deutsch, Gail
• Tan, Serena Y
• Remmers, Elaine F
• Monos, Dimitri
• Hahn, Timothy
• Phadke, Omkar K
• Cassidy, Elaine
• Ferguson, Ian
• Mallajosyula, Vamsee
• Xu, Jianpeng
• Rosa Duque, Jaime S
• Chua, Gilbert T
• Ghosh, Debopam
• Szymanski, Ann Marie
• Rubin, Danielle
• Burns, Jane C
• Tian, Lu
• Fernandez-Vina, Marcelo A
• Mellins, Elizabeth D
• Hollenbach, Jill A
• Aziz, Rabheh Abdul
• Berard, Roberta
• Bingham, Catherine A
• Bonaparth, Alexis D
• Casey, Alicia
• Collins, Kathleen P
• Cidon, Michal
• Goodman, Steven I
• Grom, Alexei A
• Hazen, Melissa
• Hoftman, Alice
• Ibarra, Maria
• Jerath, Rita
• Kingsbury, Daniel J
• Klein-Gitelman, Marisa S
• Lai, Khanh
• Lapidus, Sivia
• Mendoza-Londono, Roberto
• Onel, Karen
• Perez, Maria
• Radhakrishna, Suhas M
• Reinhardt, Adam
• Riskalla, Mona
• Roth, Johannes
• Rosenwasser, Natalie
• Saad, Nadine
• Schulert, Grant S
• Shenoi, Susan
• Smith, Judith A
• Soep, Jennifer
• Stingl, Cory
• Stoll, Matthew L
• Tesher, Melissa
• Whitehead, Benjamin
• Zemel, Lawrence
• Anton, Jordi
• Bohnsack, John F
• Cobb, Joanna
• Demirkaya, Erkan
• Foell, Dirk
• Gattorno, Marco
• Grom, Alexei
• Hilario, Maria Odete
• Ilowite, Norman T
• Haas, Johannes-Peter
• Hinks, Anne
• Kastner, Daniel L
• Langfeld, Carl D
• Martini, Alberto
• Minden, Kirsten
• Oliveira, Sheila
• Özen, Seza
• Rosen-Wolff, Angela
• Rosenberg, Alan
• Russo, Ricardo
• Signa, Sara
• Tachmazidou, Ioanna
• Tenbrock, Klaus
• Thompson, Susan
• Thomson, Wendy
• Wedderburn, Lucy R
• Woo, Patricia
• Yeung, Rae S M
• Zeft, Andrew S
• Len, Claudio

Titel

Severe delayed hypersensitivity reactions to IL-1 and IL-6 inhibitors link to common HLA-DRB115 alleles

Ist Teil von

• Annals of the rheumatic diseases, 2022-03, Vol.81 (3), p.406-415

Ort / Verlag

England: BMJ Publishing Group Ltd and European League Against Rheumatism

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• ObjectivesDrug 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.MethodsIn 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.ResultsStill’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=1.2×10−14). We found striking enrichment for HLA-DRB1*15 haplotypes in Still’s-DRESS cases versus INCHARGE Still’s controls (p=7.5×10-13) and versus self-identified, ancestry-matched Still’s controls (p=6.3×10−10). In the KD cohort, DRB1*15:01 was present only in those with suspected anakinra reactions.ConclusionsDRESS-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.