Murphy MJ, Gruenstein D, Wang A, et al. - Findings from this case series indicate effectiveness of Janus kinase (JAK) inhibition for treating persistent erythema multiforme (PEM). In addition, interferon gamma (IFN-γ) and interleukin 15 (IL-15) could represent essential cytokine mediators of the disease.

• A retrospective case series of 4 patients with PEM refractory to multiple treatment approaches finally treated with tofacitinib, 5 to 10 mg, twice daily or upadacitinib, 15 mg, once daily.

• JAK inhibition resulted in marked clinical improvement in all 4 patients.

• Overproduction of IFN-γ and IL-15 in erythema multiforme as well as tofacitinib-induced modulation of both was revealed in RNA sequencing and proteomic assessment in a single patient before and during treatment.

• In these and other PEM cases (total, 12 patients), significant upregulation of IFN-γ and IL-15 was corroborated by RNA in situ hybridization.