Dermatology has a long-standing affinity for acronyms. From AGEP (acute generalized exanthematous pustulosis) to XP (xeroderma pigmentosum), acronyms have become a part of our dermatology lexicon, perhaps occasionally to the consternation of our colleagues in other specialties. In this issue, Brau-Javier et al1 describe a patient with a severe pustular skin disease called “DIRA ” —an acronym for “deficiency of the interleukin 1 (IL-1) receptor antagonist, ” which we first described in 9 pediatric patients in 2009.2 As its name suggests, DIRA is a new autoinflammatory disease linked to activation of the IL-1 pathway (Figure), joining the ranks of other IL-1 –associated conditions with a prominent dermatologic component, foremost the cryopyrin-associated periodic fever syndromes (CAPS) —familial cold –induced autoinflammatory syndrome (FCAS), Muckle-Wells syndrome, and neonatal-onset multisystem inflammatory disease (NOMID).3
Figure. The pathogenesis of DIRA (deficiency of the interleukin 1 [IL-1] receptor [IL-1R] antagonist) and DITRA (deficiency of the IL-36 receptor [IL-36R] antagonist). Loss of the IL-1R antagonist leads to unopposed proinflammatory signaling by IL-1 α and IL-1 β in patients with DIRA. In DITRA, loss of the IL-36R antagonist results in analogous unchecked signaling by IL-36 α, IL-36 β, and IL-36 γ at the IL-36R (right panel). Patients with DIRA from Puerto Rico harbor a genomic deletion in both the IL-1R antagonist (left panel) and IL-36R antagonist (center panel). Because the IL-36 proinflammatory signaling isoforms are also deleted, a functional consequence of loss of the IL-36R antagonist in Puerto Rican patients with DIRA is unlikely.
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