PA12 A case of pustular psoriasis in epidermolytic ichthyosis: coincidence or common pathway?

Abstract

Abstract An 8-year-old boy with epidermolytic ichthyosis (EI) due to a heterozygous KRT1 mutation presented with a striking bullous skin eruption. Microbiological swabs were sent, and oral antibiotics were prescribed for suspected bullous impetigo. He deteriorated clinically, developing a fever and more extensive pustular rash reminiscent of generalized pustular psoriasis (GPP). Skin biopsies from two distinct cutaneous sites revealed histology strongly supportive of pustular psoriasis. Oral ciclosporin was commenced in addition to intensive topical emollient therapy. Following widespread desquamation, the pustular eruption fully resolved. Recurrence upon weaning of ciclosporin necessitated the introduction of ustekinumab. The rash remains controlled on this therapy. The EI is caused by heterozygous mutations in KRT1 or KRT10, and presents at birth with erythroderma and widespread skin denudation. The erythema and skin fragility abate in early childhood, giving way to prominent hyperkeratosis. Severe palmoplantar keratoderma is seen in those with KRT1 mutations. The GPP is a rare but life-threatening condition characterized by sterile pustules with or without systemic involvement. Interleukin (IL)-36-mediated inflammatory signalling plays a pathogenic role, as evidenced by loss of function mutations in IL36RN, which encodes an IL-36 receptor antagonist (Marrakchi S, Guigue P, Renshaw BR et al. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med 2011; 365:620–8), and the efficacy of IL-36 receptor inhibitor spesolimab in a recent phase II trial. Both EI and GPP are rare, and the confluence of these entities in this case is striking. Four other cases in the literature describe a GPP-like eruption in patients with congenital ichthyoses. The coexistence of these conditions might be explained by their immunological profiles. Studies of the skin of patients with congenital ichthyoses have shown immune dysregulation with T helper 17/IL-23 skewing, and upregulation of associated inflammatory cytokines, including IL-36γ. The latter encodes for an IL-36 receptor agonist (Paller AS, Renert-Yuval Y, Suprun M et al. An IL-17-dominant immune profile is shared across the major orphan forms of ichthyosis. J Allergy Clin Immunol 2017; 139:152–65). Thus, increased IL-36 receptor agonist activity in congenital ichthyosis could theoretically lead to GPP in genetically predisposed individuals with already upregulated IL-36 receptor-mediated signalling.