Expanding the Potential of Monoclonal Antibodies against IL-4 and IL-13 in Genodermatoses: Efficacy and Safety of Dupilumab in Epidermolysis Bullosa and Ichthyosis

.Background: Epidermolysis bullosa and ichthyosis are rare genetic skin disorders. Epidermolysis bullosa is characterized by extreme skin fragility, leading to blistering and erosions from minor trauma. In contrast, ichthyosis is typified by hyperkeratosis, resulting in widespread scaling and thickening of the skin. Both conditions are genetically heterogeneous and vary widely in severity and clinical presentation. Despite advances in understanding the genetic underpinnings of these disorders, effective treatments remain limited, and patients often suffer from significant morbidity, including recurrent infections, impaired mobility, and psychosocial distress. Although molecular mechanisms and potential therapeutic targets are increasingly known, significant gaps remain in translating these findings into clinical practice. Study aims: The present study aims to: (i) collect statistical and epidemiological data on individuals affected by epidermolysis bullosa and ichthyosis who require treatment with biological drugs; (ii) assess the impact of epidermolysis bullosa and ichthyosis in terms of pain and itch among affected individuals, as well as quality of life in both patients and their families; (iii) investigate the impact of Dupilumab on pain, itch and quality of life. Methods: This longitudinal observational monocentric study considered a cohort (n=8) of patients with EB (n=5) and ichthyosis (n=3), referred to the Dermatology Clinic of the University Hospital of Padua. Patients previously treated exclusively with topical therapies were treated with Dupilumab according to the dosage recommended in the prescribing information for the treatment of atopic dermatitis. Patients over 16 years old were administered the Dermatology Life Quality Index questionnaire and the disease-specific questionnaire (Quality of Life-EB or Ichthyosis-Quality of Life), and they indicated their pain and itch level on the specific Numeric Rating Scales. In patients younger than 16 years old, the children’s versions of the Dermatology Life Quality Index and the Numeric Rating Scales were used; for patients under 16 years, disease-specific questionnaires were administered to the patients’ caregivers to assess the family burden of the disease (Epidermolysis Bullosa-Burden of Disease or Family Burden-Ichthyosis). The data were collected at baseline, every three months during the first year, and every six months after that for 24 months. Results: After 24 months of treatment, the cohort of patients with epidermolysis bullosa exhibited a reduction in mean DLQI scores from 16 to 7, in NRS pain scores from 7.75 to 4, in NRS itch scores from 8.5 to 4, and in EB-BoD scores from 45.33 to 43. Conversely, there was an increase in QOL-EB scores from 47 to 58. During the same period, the cohort of patients with ichthyosis showed a reduction in mean DLQI scores from 16 to 2, in NRS pain scores from 6.67 to 1, in NRS itch scores from 8.33 to 2, in I-QoL scores from 89 to 40, and in FB-Ichthyosis scores from 47.7 to 33. Conclusions: Dupilumab has proven to be an effective and safe drug in the treatment of epidermolysis bullosa and ichthyosis in this small cohort. While limited in sample size, the data collected in this study suggest a potential early and prolonged effect of Dupilumab, possibly mediated through its impact on resident T cells in the skin, as previously observed in atopic dermatitis. These findings underscore the importance of further investigation in larger-scale studies to validate and expand upon these initial observations.