SG14 JAK of all trades: successful use of upadacitinib in treatment of epidermolysis bullosa pruriginosa

Abstract

We present the case of a 33-year-old man with epidermolysis bullosa (EB) pruriginosa secondary to a COL7A1 heterozygous point mutation at c6109G>A exon 73. His background was significant for an atopic predisposition, with a childhood history of allergic rhinitis and asthma, but not atopic dermatitis. EB pruriginosa is a rare subtype of dystrophic EB caused by mutations in the COL7A1 gene. It has a distinct phenotype characterized by progressive recalcitrant linear cord-like lichenoid changes and pruriginous nodules over the extensor surfaces of the lower limbs. Quality of life is greatly diminished by profound pruritus and consequent blistering and scarring. There is renewed interest in repurposing existing anti-inflammatory therapeutics for the treatment of EB; Janus kinase (JAK) inhibitors have emerged as promising candidates, with transcriptomic studies demonstrating altered JAK–signal transducer and activator of transcription signalling and T helper 2 responses. However, clinical evidence is limited, with reports of use of tofacitinib (JAK1/3 inhibitor), baricitinib (JAK1/2 inhibitor) and upadacitinib (JAK1 inhibitor) showing varying efficacy. Upadacitinib is currently approved in England for the treatment of atopic eczema, rheumatoid arthritis, ankylosing spondylitis and inflammatory bowel disease. Studies highlight the brisk amelioration of itch in atopic dermatitis. Following prescreening and risk counselling, upadacitinib was initiated at 15 mg once daily. Marked clinical improvement was noted at 12 weeks with flattening lichenoid plaques and reduced blistering. The visual analogue scale itch score improved from 8 out of 10 to 3 out of 10. Epidermolysis Bullosa Disease Activity and Scarring Index improved from 21 (activity score 7, damage score 14) to 17 (activity 4, damage 13), and Quality of Life Evaluation in Epidermolysis Bullosa improved from 32 to 20. Dosing was increased to 30 mg once daily with continued improvement, and no infective, thrombotic or oncogenic sequelae were noted at 24 weeks. This case report adds to the small but growing body of evidence that selective JAK1 inhibitors are a safe, effective and well-tolerated treatment for EB pruriginosa.