Epidermolysis bullosa

Attributed to abnormalities in a singular protein, type VII collagen (encoded by the COL7A1 gene), this disorder is characterised by its pivotal role in anchoring the epidermis to the dermis through anchoring fibrils. As this essential protein resides in the more profound layers of the skin, blisters materialise at deeper levels. Consequently, these blisters exhibit a prolonged healing process and often result in scarring upon recovery.

Inheritance of DEB can manifest in either an autosomal dominant or recessive pattern. The hallmark presentation of DEB comprises:

• Generalised or localised blisters.
• Absent or dystrophic nails: presence of rough, thickened, deformed, or even missing fingernails or toenails.
• Milia: small whitish cysts on the skin.
• Atrophic scarring: indentations in the skin due to thinning of the epidermis or dermis.
• Anaemia: reduced quantity of red blood cells and haemoglobin. It is more common in individuals with a severe presentation.
• Delayed growth, which is also more common in severely affected individuals.
• Problems with the tissue inside the mouth.
• Ocular complications are more common in individuals with a severe presentation.
• Gastrointestinal tract complications: may include blisters in the mouth, oesophagus, and/or anal margins.
• Pseudosyndactyly: fusion of fingers and toes. This manifestation is more common in severely affected individuals.

The main subtypes of EBD are as follows:

1. Dominant Localised EBD (formerly including acral EBD, pretibial EBD, and EBD limited to nails): Skin fragility becomes apparent from birth or early childhood, primarily affecting specific areas such as fingers, toes, and nails. Sometimes only nails are impacted, progressing to dystrophic nails and potential loss, particularly in the toenails. Occasional blistering and scarring may arise on the skin overlying the shins, though these symptoms might not manifest until late childhood or adulthood. The risk of developing squamous cell carcinoma is less pronounced than in severe recessive EBD and typically emerges in late adulthood.
2. Intermediate Dominant EBD (formerly recognised as generalised EBD) and Intermediate Recessive EBD (previously known as intermediate generalised recessive EBD or non-Hallopeau-Siemens EBD): Distinguishing between the two subtypes exclusively based on symptoms can be challenging, although the recessive form tends to be more severe. Skin fragility is more widespread from birth and early childhood, commonly affecting areas adjacent to bones such as elbows, knees, ankles, hands, and feet. Compared to intermediate dominant EBD, intermediate recessive EBD more frequently presents joint contractures that restrict full extension, along with abnormal thickening (keratoderma) in the fingers and partial interdigital fusion. The risk of squamous cell carcinoma development is not as elevated as in severe recessive EBD and generally arises in late adulthood. Nutritional challenges are frequent due to blister formation in the oesophagus, impacting food intake and absorption, while increased metabolic demands may result from chronic wounds, infections, and inflammation.
3. Severe Recessive EBD (formerly known as severe generalised recessive EBD or Hallopeau-Siemens EBD): Blisters manifest throughout the entire body from birth, and skin fragility is evident even with minor trauma. Chronic wounds are frequent occurrences. Blistering during childhood is more pronounced in areas with prominent bones, leading to extensive scarring that can culminate in joint contractures, hindering complete extension. These contractures, along with progressive pseudo syndactyly (fusion of fingers and toes) and resorption of the terminal bone in fingers and toes, contribute to the formation of hands and feet resembling mittens. Aggressive squamous cell carcinoma development is highly prevalent and a frequent cause of mortality. Its incidence increases from adolescence onward, often appearing in regions of recurring wound and scar formation. Progressive scarring can result in microstomia (mouth contracture) and ankyloglossia (reduced tongue movement).

All EBD subtypes, including the less common variations, are summarised in this table: