The burden of an ultra-rare inherited skin disorder: Congenital erythropoietic porphyria.

Congenital erythropoietic porphyria (CEP), an ultra-rare metabolic disorder of heme biosynthesis, drastically impacts patients' health-related quality of life (HRQL), but literature is lacking regarding specific domains impacted and psychosocial issues. To understand patient perspectives to inform the development of reliable patient-reported outcomes (PROs) a mixed methods study was conducted with questionnaires and interviews to qualitatively captured symptom descriptions and general concept elicitation of impacts on daily activities. Participants were recruited from around the global via advocacy groups. Nineteen participants were interviewed; 15 adults with CEP and four parents of children with CEP. Most participants were non-Hispanic White, female, and had CEP onset in infancy. The most commonly reported CEP symptoms were skin fragility, scarring, discoloration of the teeth, and blistering, which led to infection, scarring, and disfigurement. All participants reported using many sun-protective methods, however still experienced symptoms. Blister formation and healing processes were unpredictable and blistering was regarded as most burdensome. Most participants experienced chronic pain. Participants uniformly noted that more time in sunlight with less blistering or improved blister healing would improve their quality of life. Key HRQL domains to measure include participants prioritized ability to participate in social roles and activities, pain interference, and social isolation. CEP necessitated significant modifications to daily activities, including employment and education. CEP also introduced stressors on financial security, mental and emotional health, social health, and family dynamics. This information will improve counseling and management for CEP and may be used for future PRO development for disease-modifying therapies in this population. SYNOPSIS: Individuals with CEP have a significantly impacted quality of life to all aspects of daily living regardless of disease severity, with underappreciated symptoms including severe skin fragility and chronic pain, and significant unmet medical needs.