Definition:

Epidermolysis bullosa (EB) is defined by mechanical fragility of the skin, it is a group of genetically inherited disorders characterized by the formation of blisters on the skin and mucous membranes, often triggered by minimal trauma or friction, particularly on areas like the hands and feet, in severe cases, blistering can also affect internal organs such as the esophagus, stomach, and respiratory tract, even in the absence of external friction.

It is classified into four major subtypes: EB simplex, junctional EB, dystrophic EB, and Kindler EB, each distinguished by the specific layer of tissue where blistering occurs. Collectively, these subtypes encompass over 30 distinct clinical phenotypes.

Epidemiology:

According to data from the National EB Registry, the estimated prevalence of epidermolysis bullosa (EB) in the U.S. is 11.1 cases per 1 million people, with an incidence of 19.6 per 1 million live births.

The prevalence and incidence for major EB subtypes are as follows: EB simplex (6.0 and 7.9), junctional EB (0.5 and 2.7), dominant dystrophic EB (1.5 and 2.1), and recessive dystrophic EB (1.4 and 3.0) per 1 million population and live births, respectively.

Etiology:

EB results from genetic mutations in proteins essential for skin adhesion. These mutations determine where blistering occurs. For example:

Epidermolysis Bullosa Simplex: Mutations disrupt proteins within the epidermis
Junctional Epidermolysis Bullosa: Mutations affect the dermal-epidermal junction
Dystrophic Epidermolysis Bullosa: Mutations impair structures in the upper dermis

The structural weakness in these layers leads to blister formation even with minor friction or trauma.

Clinical Features:

Clinically, EB manifests as fragile skin prone to blistering and erosions.

Fragile Skin and Blisters: Skin easily blisters and erodes, especially in areas prone to friction. Scarring is minimal in localized EBS but severe in recessive DEB.
Nail and Hair Abnormalities: Dystrophic or missing nails are common, along with scarring alopecia.
Extracutaneous Involvement:
Eye: Repeated eye blistering may cause neovascularization and blindness.
Gastrointestinal: Esophageal strictures, malabsorption, and constipation can develop.
Genitourinary: Blistering may result in urethral or bladder strictures.
Rare Presentations: Some forms of JEB and EBS may present with pyloric atresia at birth.

Approach to Diagnosis of Epidermolysis Bullosa (EB):

Diagnosing EB requires a combination of clinical evaluation and specialized testing. In cases with a known family history, a dermatologist can often make a preliminary diagnosis based on the patient’s symptoms. However, more precise diagnostic tools are often necessary. Skin biopsy with immunofluorescence antigen mapping (IFM) is used to examine newly formed blisters, identifying the defective skin proteins involved. Transmission electron microscopy (TEM) can reveal the ultrastructural level where blistering occurs, although this technique is typically available only in specialized laboratories. With the advancements in genetic testing, next-generation sequencing has become a valuable tool for confirming the diagnosis, pinpointing the exact mutation, and providing genetic counseling for families.

Management:

Currently, there is no cure for EB, and treatment focuses on symptom relief, skin protection, and preventing complications. Key management strategies include:

Daily Care:

Prevent Friction: Use soft clothing, padding, and non-irritating footwear. Handle infants and children with care to prevent skin damage.
Maintain a Cool Environment: Avoid overheating, which can trigger blistering.
Blister Care: Blisters should be drained and dressed by trained professionals using non-adhesive or silicone-based dressings.

Wound Management:

Bathing Solutions: Sodium hypochlorite or acetic acid baths help prevent bacterial infections.
Wound Dressings: Use low-tack silicone dressings or Vaseline®-impregnated gauze to promote healing and prevent trauma during dressing changes.

Medications:

Topical Treatments: Diacerein cream for EBS, and aluminum chloride for managing hyperhidrosis.
Systemic Treatments: Antibiotics for infections and drugs like tetracycline or erythromycin for EBS. Emerging therapies, such as retinoids and losartan, aim to reduce severe complications in DEB.
Innovative Therapies in Research: Therapies such as Gene Therapy and Stem Cell Therapy are being explored to repair defective genes and improve skin integrity.
Specialized Care:Multidisciplinary care teams address complications affecting the esophagus, eyes, and gastrointestinal system.

Written by:

Raneem Alahmadi, Medical Intern.

Revised by:

Naif Alshehri, Medical Intern

Resources:

Bolognia 5th edition

Dermnet