Pyoderma Gangrenosum Associated With Iatrogenic Interleukin 17A Blockade: A Report of Two Cases and a Review of the Literature.

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. [ABSTRACT FROM AUTHOR]