A systematic literature review of the disease burden in patients with recessive dystrophic epidermolysis bullosa

Abstract

Background/objective Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic collagen disorder characterized by skin fragility leading to blistering, wounds, and scarring. There are currently no approved curative therapies. The objective of this manuscript is to provide a comprehensive literature review of the disease burden caused by RDEB. Methods A systematic literature review was conducted in MEDLINE and Embase in accordance with PRISMA guidelines. Observational and interventional studies on the economic, clinical, or humanistic burden of RDEB were included. Results Sixty-five studies were included in the review. Patients had considerable wound burden, with 60% reporting wounds covering more than 30% of their body. Increases in pain and itch were seen with larger wound size. Chronic wounds were larger and more painful than recurrent wounds. Commonly reported symptoms and complications included lesions and blistering, anemia, nail dystrophy and loss, milia, infections, musculoskeletal contractures, strictures or stenoses, constipation, malnutrition/nutritional problems, pseudosyndactyly, ocular manifestations, and dental caries. Many patients underwent esophageal dilation (29–74%; median dilations, 2–6) and gastrostomy tube placement (8–58%). In the severely affected population, risk of squamous cell carcinoma (SCC) was 76% and mortality from SCC reached 84% by age 40. Patients with RDEB experienced worsened quality of life (QOL), decreased functioning and social activities, and increased pain and itch when compared to other EB subtypes, other skin diseases, and the general population. Families of patients reported experiencing high rates of burden including financial burden (50–54%) and negative impact on private life (79%). Direct medical costs were high, though reported in few studies; annual payer-borne total medical costs in Ireland were $84,534 and annual patient-borne medical costs in Korea were $7392. Estimated annual US costs for wound dressings ranged from $4000 to $245,000. Patients spent considerable time changing dressings: often daily (13–54% of patients) with up to three hours per change (15–40%). Conclusion Patients with RDEB and their families/caregivers experience significant economic, humanistic, and clinical burden. Further research is needed to better understand the costs of disease, how the burden of disease changes over the patient lifetime and to better characterize QOL impact, and how RDEB compares with other chronic, debilitating disorders.

Multidisciplinary care for patients with epidermolysis bullosa from birth to adolescence: experience of one Italian reference center

“…Clinical practice guidelines for the management of cutaneous SCC and epidemiological data on adult EB patients with SCC have been published [ 15 – 17 ]. However, only few case reports on paediatric EB patients with SCC have been reported [ 18 , 19 ]. In our population one girl with RDEB, chronic wounds appeared at 11 years of age and she died at 16.…”

Impact of low-dose calcipotriol ointment on wound healing, pruritus and pain in patients with dystrophic epidermolysis bullosa: A randomized, double-blind, placebo-controlled trial

“…Itch and pain rank highest among EB-associated morbidities that significantly decrease patient quality of life [ 9 , 13 ]. With regard to the analgesic potential of calcipotriol, our results remain inconclusive and elusive with patients reporting a statistically significant benefit at day 14 with placebo, but no difference between placebo and verum at day 28.…”

In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial

“…C7 defects impair dermal–epidermal cohesion and produce lifelong widespread painful blistering and fibrosis starting at birth, accompanied by scarring, susceptibility to infection and a predisposition to skin cancer 5 , 6 . This disease is extremely burdensome to patients 7 , however, no approved corrective therapies for RDEB currently exist.…”