Pyoderma Gangrenosum Associated With Iatrogenic Interleukin 17A Blockade: A Report of Two Cases and a Review of the Literature.
Academic Article
Overview
abstract
Pyoderma gangrenosum (PG) is a rare necrotizing neutrophilic dermatosis driven by monokines and cytokines elaborated by monocytes and autoreactive T cells, respectively. Th1-mediated autoimmune disorders and myeloproliferative disease are among the potential disease associations. More recently, certain medications were implicated, including TNF-alpha inhibitors, rituximab, and IL-17A inhibitors, such as secukinumab, where the development of PG is held to represent a cutaneous immune adverse effect. We present two patients who developed an autoinflammatory syndrome resembling PG in the setting of drug therapy with agents exhibiting an IL-17A inhibitory effect. The drugs were erunumab in one and secukinumab in the other. One patient received the anti-calcitonin gene-related peptide targeted therapy, erenumab, for migraine prophylaxis. While this drug has not been previously implicated in the development of PG, it can cause IL-17A blockade. The other patient was on secukinumab, a monoclonal antibody that selectively targets IL-17A. We documented a microenvironment enriched in IL-17A, emphasizing that the blockade impacts the functionality of the receptor as opposed to a quantitative reduction in IL-17A production by T cells. Qualitative functional IL-17A blockade could result in a paradoxical increase in IL-23, a pro-inflammatory cytokine that may contribute to the influx of neutrophils pathogenetically implicated in PG.
