Epidermolysis bullosa

The epidermis and the dermis (the innermost layer of the skin) are separated by a structure known as the basement membrane. This membrane plays a crucial role in maintaining the connection between the epidermis and dermis. The point at which blisters form is within this region. Seven genes associated with JEB have been identified. Among these, the most common ones encode the same protein, laminin-332, and these are the LAMA3, LAMB3, and LAMC2 genes. The other genes implicated include COL17A1 (Collagen 17), ITGB4 (integrin β4), ITGA6 (integrin α6), and ITGA3 (integrin α3).

JEB follows an autosomal recessive inheritance pattern. The classic presentation of JEB includes:

• Blisters/erosions.
• Dystrophic nails: the presence of rough and thickened fingernails or toenails.
• Atrophic scarring: indentations in the skin due to thinning of the epidermis or dermis.
• Granulation tissue (tissue formed in the early stages of healing) is evident around the mouth and nasal passages.
• Scalp abnormalities: blisters on the scalp and/or scarring alopecia (areas of scar tissue where hair does not grow).
• Respiratory tract involvement: can be present in severely affected individuals.
• Anaemia: reduced quantity of red blood cells and haemoglobin. It is more common in individuals with severe presentations.
• Delayed growth and malnutrition.
• Blisters and erosions in the mouth.
• Enamel hypoplasia: underdeveloped enamel on teeth.
• Excessive dental cavities due to enamel defects.
• Gastrointestinal tract complications (blisters in the mouth, oesophagus, and/or anal margins).
• Ocular complications.

The primary subtypes of JEB are as follows:

• Intermediate JEB (previously referred to as Intermediate Generalized JEB or non-Herlitz JEB): Blisters are widespread but less severe, and chronic granulation tissue usually does not form (though it can occur in chronic wounds). In adulthood, squamous cell carcinoma may appear. Nails are often lost or may become thick and dystrophic.
• Severe JEB (formerly known as Severe Generalised JEB or Herlitz JEB): During the initial weeks of life, blisters commonly emerge on the elbows, buttocks, and around the nails. In the ensuing months, wounds can become chronic, some delicate, accompanied by granulation tissue that frequently affects the face, ears, and fingertips of the hands and feet. The larynx mucosa is affected by blisters, erosions, granulation tissue, and scarring. This can lead to airway obstruction, posing a significant health risk. All nails are usually lost within the first months of life. Severe JEB typically leads to mortality within the initial two years of life due to developmental delays, respiratory complications, or sepsis.

An overview of all JEB types, including the less common ones, is provided in the subsequent table: