Epidermolysis bullosa

EB Simplex is the most prevalent form. It arises from defects in the proteins found within the epidermis, the outermost layer of the skin. The plane of blister separation is discernible in the uppermost skin layers. The updated classification includes seven genes implicated in EBS. The genes most frequently impacted are KRT5 and KRT14, responsible for encoding keratin 5 and 14 proteins, respectively. Additional genes involved are PLEC (plectin), DST (BP230 or bullous pemphigoid antigen 230), EXPH5 (exophilin 5), KLHL24 (kelch-like protein 24), and CD151 (CD151 protein).

In most cases, EBS is inherited through an autosomal dominant pattern. The emergence of de novo mutations is also feasible and recurrent. While autosomal recessive inheritance is possible, it remains exceedingly rare, with only a few cases documented thus far.

The classic presentation of EBS encompasses:

• Blisters primarily on the palms of the hands and soles of the feet.
• Plantar keratoderma: gradual thickening of the skin on the soles of the feet, which can lead to pain and loss of mobility.
• Nails may become thicker and dystrophic (appearing damaged, discoloured, curved, or misshapen).
• Hair is usually not affected.
• Blisters usually get worse with heat, sweat, humidity, or minor trauma.
• Blisters heal within a few days without leaving permanent scars.
• Mucous membranes are minimally or not affected.
• Blisters may heal with hyperpigmentation (darkening of the skin).

EBS is the most common type of EB, and its main subtypes include:

• Localised EBS (previously known as Weber-Cockayne): Blisters start to appear from birth or infancy, primarily on the hands and feet.
• Intermediate EBS (previously known as Severe Generalised EBS or Köbner EBS): Blisters appear at birth and are generalised but less severe.
• Severe EBS (previously known as Severe Generalized EBS or Dowling-Meara EBS): The skin is notably fragile, and blisters, as well as ulcerated areas on the hands, feet, and nails, are common from birth. Blisters may occur after minor trauma or spontaneously during the neonatal period. Oral mucosa is typically affected in the first months of life, and growth delay is typical. Neonatal complications associated with severe EBS can be potentially life-threatening within the first year of life. Confluent palmoplantar keratoderma (widespread thickening of the skin on the palms and soles) is mainly observed in severe EBS.

All subtypes of EBS, including the less common ones, are summarised in this table: