Granuloma annulare (GA) is an inflammatory skin disorder. While localized GA is often self-resolving, generalized GA is often recalcitrant to treatments. There are no targeted treatments for GA, largely due to lack of mechanistic understanding. Recently TNF antagonism showed promise in GA, suggesting an underlying immune pathogenesis.
To elucidate the immune pathogenesis and identify potential therapeutic targets for GA.
Lesional and non-lesional skin biopsies were obtained from GA patients and evaluated for a large array of inflammatory markers in comparison to inflammatory markers from normal skin of healthy individuals.
We found differential expression of many inflammatory genes compared to normal skin. These genes were associated with Th1/innate immunity (TNFα, IL-1β, IL-12/23p40, STAT1, CXCL9/CXCL10), JAK-signaling, and Th2 (IL-4, IL-31, CCL17, CCL18; p<0.05). Unexpectedly, IL-4 showed significant upregulation in GA lesional skin versus control skin (15,600-fold change).
Limited sample size.
Our findings shed light on the inflammatory pathways of GA, supporting the notion that immune mechanisms could be driving disease, as suggested by the promising data of TNFα inhibitors in GA. The significant JAK and particularly Th2 signaling in GA advocates for the investigation of specific JAK and Th2-targeted drug therapy.

Copyright © 2019. Published by Elsevier Inc.