Skip to main content

Cytokine Inhibitor Lung Disease in Still's Linked to HLA-DRB1 Alleles

Pulmonary complications in the setting of Still's disease (both juvenile and adult) has seldom but consistently been reported, including reports of pneumonitis, pulmonary hypertension and a severe or fatal lung disease, often associated with hypersensitivity to anticytokine therapy.  A multicenter study reports that drug hypersensitivity and pulmonary reactions in Still's patients receiving IL-1 or IL-6 inhibitors is strongly associated with HLA-DRB1*15 haplotypes.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe, delayed hypersensitivity reaction that has been shown to occur in a minority of Still’s disease patients with atypical lung disease while taking inhibitors of interleukin 1 (IL-1) or IL-6.  The genetics associated with Still’s disease with DRESS was compared to those patients who were drug-tolerant with Still’s.

Class II MHC (HLA) alleles were assessed in study Still’s disease patiehs with cytokine inhibitor-related DRESS (n=64) and drug-tolerant Still’s controls (n=30). They also haplotyped 94/131 for HLA. European Still’s-DRESS cases against ancestry matched a Childhood Consortium of pediatric Still’s (INCHARGE) cases (n=550) and compared for HLA allele frequencies.

Still’s-DRESS had eosinophilia (89%), AST-ALT elevation (75%), non-evanescent rash (95%; 88% involving face) and more cases of macrophage activation syndrome (MAS) during treatment (64% vs 3%).  These patients also had significantly more HLA-DRB1*15 haplotypes than did the INCHARGE Still’s controls (p=7.5×10-13), ancestry-matched controls (p=6.3×10−10). 

HLA typing and vigilance for serious lung reactions to these drugs may be warranted.

stillsNow cTA

ADD THE FIRST COMMENT

If you are a health practitioner, you may to comment.

Due to the nature of these comment forums, only health practitioners are allowed to comment at this time.

Disclosures
The author has no conflicts of interest to disclose related to this subject