Epidermolysis Bullosa Pruriginosa Treated With Upadacitinib

Abstract

This case series measured the results of using upadacitinib for moderate or severe cases of epidermolysis bullosa pruriginosa.

Epidermolysis bullosa pruriginosa (EBP; OMIM 604129) is a rare, distinct clinical subtype of dystrophic epidermolysis bullosa caused by mutations in the COL7A1 gene. EBP is characterized by skin fragility, blistering, intense pruritus, prurigo-like lichenified lesions, and hypertrophic scarring mainly distributed on the extensor extremities. Traditional treatment, including topical steroids or tacrolimus, antihistamines, thalidomide, and immunosuppressants, often yields high rates of therapeutic failure or disease recurrence. Upadacitinib, an oral selective Janus kinase 1 (JAK-1) inhibitor, has shown great efficacy for the treatment of atopic dermatitis and chronic prurigo,¹ indicating a potential effect for other pruritic dermatoses. Herein, we describe the use of upadacitinib in moderate or severe recalcitrant cases of EBP.

Methods

This study was approved by the Clinical Research Ethics Committee of Dermatology Hospital, Southern Medical University, and written informed consent was obtained from all patients. Patients who received a clinical and molecular diagnosis of EBP from August 2022 to December 2023 were recruited. Female patients of childbearing age without reliable contraception were excluded because JAK-1 inhibitors are contraindicated during pregnancy. Tuberculosis and viral hepatitis were confirmed to be negative before treatment. Upadacitinib, 15 mg once daily, was started for at least 12 weeks for each patient and then was tapered gradually. Cutaneous manifestations were evaluated using the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI). The self-reported effect was assessed by pruritus intensity on a 0- to 10-point visual analog scale (VAS) and the Dermatology Life Quality Index/Children’s Dermatology Life Quality Index. Complete blood counts, routine biochemistry tests, lipid profiles, and creatine kinase levels were monitored before and after treatment. The mean and standard deviation in this article were calculated using statistical software SPSS.

Results

Four patients (1 woman and 3 men; mean [SD] age, 20.50 [10.47] years) with EBP were recruited in the study. Genetic testing showed heterozygous variants in the COL7A1 gene: c.8786G>T (p.Cys2929Phe)/c.2992 + 2T>G (p.?), c.5440C>T(p.Arg1814Cys), c.5747G>A (p.Gly1916Glu)/c.2392G>A (p.Gly798Arg), and c.676C>T (p.Arg226*)/c.4342G>C (p. Gly1448Arg) in patients 1 to 4, respectively. All 4 patients presented with moderate to severe clinical severity of EBP with a basal EBDASI score above 42 before upadacitinib treatment (Figure 1). A rapid response to treatment for pruritus was observed, as the mean (SD) VAS score at the baseline was 8.25 (1.71) and decreased to 1.75 (0.96) at 2 weeks (Figure 2). During the follow-up period, the VAS score for all 4 patients remained at low levels (≤1), reflecting the long-term effectiveness for pruritus. In parallel, the mean (SD) Dermatology Life Quality Index score initially measured at 11.75 (7.27) decreased to 1.50 (1.00) at week 24. There was a marked improvement in lesion severity assessed through the mean (SD) EBDASI score from 61.50 (16.78) to 41.75 (12.28) after 24 weeks of therapy. No evident adverse events were reported, all patients were still receiving JAK-1 inhibitor treatment, and clinical efficacy continued over 52 weeks of continuous treatment.

Figure 1. Clinical Images of Patients With Epidermolysis Bullosa Pruriginosa Before and After Upadacitinib Treatment.

Figure 2. Clinical Scale Scores for 4 Patients.

DLQI/CDLQI indicates Dermatology Life Quality Index/Children’s DLQI; EBDASI, Epidermolysis Bullosa Disease Activity and Scarring Index; and VAS, visual analog scale.

Discussion

Until now, the pathophysiology underlying the unique clinical profiles of EBP has not been fully elucidated. Recent research confirms an increase in a subset of circulating type 2 helper T (T_H2) cells² and predominant T_H2 activation signaling in the lesional skin of patients with EBP.³ Separately, dupilumab, an IL-4 receptor alpha monoclonal antibody, showed efficacy in the treatment of EBP cases,⁴ also indicating the skewed T_H2 immunity in EBP. Additionally, previous studies have documented single cases of patients with EBP treated with either baricitinib or upadacitinib.^5,6 Here, we performed the observational study of EBP case series treated with upadacitinib, which was effective as evidenced by the rapid and sustained improvement in pruritus and skin lesions. Further clinical studies with more EBP cases are warranted to confirm or compare the long-term efficacy and safety of JAK-1 inhibitors for EBP. Study limitations included a small sample size and the absence of a parallel control group.

Supplement.

Data Sharing Statement