Epidermolysis Bullosa: What You Need to Know

Summary and Overview

Epidermolysis bullosa (EB) is a rare inherited disorder causing fragile skin that blisters from minor trauma. It involves mutations in genes essential for skin integrity, affecting layers at the dermal–epidermal junction. Major types include epidermolysis bullosa simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), and Kindler syndrome, each defined by the skin layer affected and genetic defect. Severity ranges from mild localized blistering to severe, life-threatening forms with extensive skin and mucosal damage. Diagnosis relies on clinical evaluation, specialized lab tests, and genetic analysis to guide management. Treatment is mainly supportive—wound care, pain control, infection prevention, and nutrition—with recent FDA-approved gene therapies offering new hope. Multidisciplinary care addresses the complex physical and psychosocial impacts, while patient advocacy groups provide vital support and education.

Causes and Classification

EB results from mutations in over 16 genes encoding proteins crucial for skin cohesion, inherited in autosomal dominant or recessive patterns. The four main types are:

• EBS: Caused by mutations in keratin genes (KRT5, KRT14), leading to intraepidermal blistering; most common form.
• DEB: Caused by COL7A1 mutations affecting type VII collagen anchoring fibrils; blistering occurs below the basement membrane.
• JEB: Involves mutations in basement membrane proteins (LAMA3, LAMB3, LAMC2, COL17A1), causing blistering within the lamina lucida.
• Kindler syndrome: Features mixed cleavage levels, skin fragility, photosensitivity, and was recently added to the EB classification.

Advances in genetic testing have refined classification and enabled better genotype-phenotype correlations.

Clinical Presentation

EB causes fragile skin that blisters and erodes easily, often from birth. Severity and symptoms vary by subtype. EBS typically presents with localized blistering on hands and feet; severe forms involve mucosal surfaces. JEB often includes mucosal lesions and generalized blistering with poor prognosis in severe cases. DEB is marked by blistering beneath the basement membrane, flexion contractures, nail and dental abnormalities, and internal complications like esophageal strictures. Kindler syndrome involves blistering at multiple skin levels, photosensitivity, and extracutaneous features. Additional issues include nail dystrophy, pigmentation changes, and involvement of eyes, gastrointestinal, and genitourinary systems. Diagnosis relies on clinical examination, family history, genetic testing, and skin biopsy.

Diagnosis

Diagnosis begins with clinical assessment of blistering patterns, onset, and mucosal involvement. Genetic testing is the gold standard, identifying mutations in genes linked to EB. When genetic testing is unavailable, skin biopsy with immunofluorescence mapping and electron microscopy helps localize blistering and identify affected proteins. These methods distinguish EB subtypes and differentiate EB from other blistering disorders. Standard microscopy is insufficient. Tools like the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) assist in disease severity assessment and monitoring.

Management and Treatment

There is no cure for EB; management focuses on symptom relief and preventing complications. Essential care includes meticulous wound management, pain control, infection prevention, and nutritional support. Wound care involves daily skin inspection, gentle blister drainage, protective ointments, and specialized dressings. Pain management is critical due to severe discomfort. Nutritional support addresses feeding difficulties from mucosal involvement. Care routines are demanding, often placing substantial burdens on families, necessitating psychosocial support. Recent FDA approvals of gene therapies—prademagene zamikeracel and beremagene geperpavec—target recessive dystrophic EB by correcting genetic defects and improving wound healing. Multidisciplinary teams provide comprehensive care addressing physical and emotional needs.

Emerging Therapies and Research

Innovative treatments include gene therapy, stem cell therapy, and protein replacement aiming to correct underlying defects. Gene therapy has shown success in JEB and RDEB by introducing functional genes via ex vivo modified epidermal stem cells or in vivo approaches recently FDA-approved. Gene editing techniques like CRISPR/Cas9 enable precise mutation correction in key genes such as COL7A1. Stem cell therapy uses genetically modified induced pluripotent stem cells to promote skin regeneration. Protein therapy delivers missing structural proteins directly to skin. Natural gene replacement via revertant mosaicism grafting shows promise, especially in junctional EB. Ongoing clinical trials focus on improving safety, efficacy, and durability of these therapies.

Living with EB and Patient Support

EB affects daily life profoundly, causing persistent blistering, wounds, and complications beyond the skin, including vision and swallowing difficulties. Care demands are high, often impacting family dynamics and requiring psychological support to manage emotional burdens. Home nursing programs improve quality of life by enhancing wound care and reducing hospitalizations. Patient advocacy organizations like DEBRA International provide education, psychosocial support, networking, and public awareness efforts. They also advocate for patient needs at policy levels. Access to comprehensive care and support services is vital to improve outcomes and quality of life for individuals with EB and their families.

The content is provided by Jordan Fields, Scopewires