Case Report: Successful treatment of dystrophic epidermolysis bullosa pruriginosa with upadacitinib in a patient with COL7A1, CARD14, and G6PD gene mutations.

Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare subtype of dystrophic epidermolysis bullosa (DEB) characterized by intensely pruritic blisters, prurigo-like nodules, and scarring on the extensor aspects of the extremities. We present a 43-year-old female patient with a 30-year history of recurrent erythematous plaques, nodules, and blisters, which was accompanied by severe pruritus affecting the scalp, back, and extremities. Whole-exome sequencing identified a heterozygous likely pathogenic variant in COL7A1 (c.6760G>A, p.Gly2254Arg), a heterozygous variant of uncertain significance (VUS) in CARD14 (c.2172C>A, p.Tyr724*), and a heterozygous pathogenic variant in G6PD (c.1388G>A, p.Arg463His). Combined with the patient's clinical manifestations, histopathological findings, direct immunofluorescence results, negative results for pemphigus and pemphigoid autoantibodies, genetic testing results, and past medical history, the patient was diagnosed with refractory DEB-Pr and glucose-6-phosphate dehydrogenase (G6PD) deficiency. To the best of our knowledge, the co-occurrence of these three distinct variants in a patient with DEB-Pr has not been previously reported in the literature. Oral upadacitinib (initiated at 15 mg once daily) induced rapid and substantial relief of pruritus as well as improvement of cutaneous lesions. Clinical symptoms continued to improve during subsequent gradual dose tapering, and maintenance therapy with 15 mg once weekly has been administered since month 16 of treatment, with a 7-month follow-up to date. No treatment-related adverse events were observed throughout the entire 22-month follow-up period. This case suggests that Janus kinase (JAK) inhibitors may represent a feasible therapeutic option for patients with similar refractory DEB-Pr.