Epidermolysis Bullosa

Epidermolysis bullosa (EB) is a group of inherited mechanobullous disorders with skin and mucosal fragility due to mutations in genes encoding proteins of the dermoepidermal junction.

• Incidence is about 1 in 17,000 to 50,000 births. Four main types according to blister cleavage level:
  • EB simplex (EBS): intraepidermal (KRT5, KRT14), mostly dominant.
  • Junctional EB (JEB): lamina lucida (LAMA3, LAMB3, LAMC2, COL17A1, ITGA6/B4); Herlitz variant lethal in infancy.
  • Dystrophic EB (DEB): below lamina densa (COL7A1), dominant (DDEB) or recessive (RDEB).
  • Kindler syndrome (FERMT1): mixed levels.
• RDEB severe generalised carries a lifetime risk of aggressive cutaneous squamous cell carcinoma of 70 to 90% by age 55, and is the leading cause of death.
• Other complications: anaemia, malnutrition, oesophageal strictures, pseudosyndactyly, contractures, ocular erosions, dental caries, renal disease, cardiomyopathy, and osteoporosis.

• Blisters and erosions from minor trauma, healing with scars (DEB, JEB) or without scarring (EBS), milia, nail dystrophy or loss, and dyspigmentation.
• EBS: acral blistering, worsening with heat; palmoplantar keratoderma.
• JEB Herlitz: perioral and periorificial granulation tissue, hoarse cry, airway stenosis, failure to thrive.
• RDEB: severe mucosal and gastrointestinal involvement, mitten deformities, and chronic non-healing wounds.
• Pain, itch, and sepsis are major problems.

• Skin biopsy of a freshly induced blister for immunofluorescence antigen mapping and transmission electron microscopy.
• Genetic testing with next generation sequencing panels; prenatal and preimplantation diagnosis.
• Baseline: FBC, ferritin, albumin, zinc, vitamin D, renal function; echocardiography in RDEB.
• Biopsy any non-healing wound for squamous cell carcinoma.
• Exclude epidermolysis bullosa acquisita, bullous impetigo, staphylococcal scalded skin syndrome, congenital infections, and bullous pemphigoid.

• Multidisciplinary care in a specialist centre: dermatology, nutrition, wound care, pain, dentistry, gastroenterology, ophthalmology, and genetic counselling.
• Wound care: avoid adhesives; use soft silicone or non-adherent foam dressings; lance large blisters with a sterile needle but leave the roof intact; bathe with diluted antiseptics; treat infection promptly with topical or systemic antibiotics guided by cultures.
• Disease modifying therapy:
  • Topical beremagene geperpavec (B-VEC, HSV-1 vector gene therapy delivering COL7A1) for DEB wounds.
  • Prademagene zamikeracel (EB-101) autologous gene corrected keratinocyte sheets for RDEB wounds.
  • Birch triterpenes gel 10% to accelerate wound healing in JEB and DEB.
  • Allogeneic haematopoietic cell transplantation and mesenchymal stem cell infusions are experimental.
• Nutrition: high calorie, protein rich diet, gastrostomy if needed; iron IV when oral not tolerated; zinc, selenium, vitamin D, and calcium; oesophageal balloon dilatation for strictures.
• Pain management: paracetamol, gabapentin, topical lidocaine, and opioids as required (procedural pain).
• Surveillance for SCC from adolescence in RDEB (clinical every 3 to 6 months; biopsy suspicious wounds), hand surgery for pseudosyndactyly, dental care, and psychosocial support.