OVERVIEW

What is epidermolysis bullosa?

Epidermolysis bullosa (EB) is a chronic, non-inflammatory blistering disorder characterized by skin and mucosal susceptibility to mechanical damage, leading to blister formation. Its hallmark is significant mechanical fragility of epithelial tissues, causing blisters and erosions after minor trauma.

It is generally classified into two types: hereditary (congenital) and acquired (epidermolysis bullosa acquisita, EBA).

Currently, there is no effective treatment, and meticulous care to avoid infection is crucial.

What are the types of epidermolysis bullosa?

• Hereditary epidermolysis bullosa is a group of inherited skin disorders characterized by blistering of the skin and mucous membranes after minor trauma. Based on the blister location under transmission electron microscopy, it is divided into three types:

  • Epidermolysis bullosa simplex (EBS): Blisters or clefts occur within the epidermis.
  • Junctional epidermolysis bullosa (JEB): Blisters form within the lamina lucida of the basement membrane zone.
  • Dystrophic epidermolysis bullosa (DEB), also known as dermolytic EB: Blisters or clefts occur below the dense plate of the basement membrane zone.

• Acquired epidermolysis bullosa (EBA) is an autoimmune disorder. The cause is unknown, but studies suggest an association with anti-type VII collagen antibodies and HLA-DR2 positivity.

Is epidermolysis bullosa common?

The incidence of hereditary epidermolysis bullosa is approximately 1 in 50,000. Currently, there is no reported incidence rate for acquired epidermolysis bullosa.

What are the age-related characteristics of epidermolysis bullosa?

• Hereditary epidermolysis bullosa typically manifests in infancy. EBS has a relatively better prognosis, while JEB and DEB have poorer outcomes.
• Acquired epidermolysis bullosa mostly occurs in elderly individuals.

SYMPTOMS

What are the manifestations of epidermolysis bullosa?

The common feature of all types of epidermolysis bullosa is increased skin fragility, where blisters or bullae appear on the skin and mucous membranes after minor friction.

Lesions often occur in friction-prone areas such as the hands, feet, elbows, knees, and buttocks, but may also spread throughout the body. Some cases are accompanied by scarring, atrophy, nail dystrophy, or extracutaneous manifestations, and severe cases may lead to disability or death.

• Hereditary (congenital) epidermolysis bullosa:

1. Epidermolysis bullosa simplex (EBS):

   • Mostly autosomal dominant inheritance, the mildest form, usually without scarring after healing. Symptoms typically appear within the first year of life.
   • Blisters often occur after pressure or mechanical trauma. Before blisters appear, the affected skin may show mild erythema, itching, or a burning sensation, followed by the formation of tense, clear blisters (occasionally blood blisters). Ruptured blisters form erosions but heal easily.
   • No scarring occurs in the absence of infection. Common sites include exposed areas, hands, feet, knees, elbows, and neck, with hands and feet being the most frequent.
   • About 2% of patients may have mild involvement of oral, genital, or perianal mucosa. Physical development is generally normal.

2. Junctional epidermolysis bullosa (JEB):

   • Rare, autosomal recessive inheritance. Widespread blisters, bullae, erosions, and crusting are present at birth, leaving atrophic scars after healing. Oral mucosal erosions, ulcers, and scarring often lead to difficulty opening the mouth.
   • Patients generally have poor health, growth retardation, and severe anemia. Prognosis is poor, with most patients dying before the age of 2.

3. Dystrophic epidermolysis bullosa (DEB): Divided into autosomal dominant and recessive forms.

   • Dominant DEB appears in infancy or childhood. Lesions heal slowly, leaving atrophic or hypertrophic scars, commonly on the limbs. Epidermal cysts and milia are frequent, with mucosal involvement in a few cases.
   • Recessive DEB is more severe, with generalized blisters, bullae, and erosions (sometimes hemorrhagic) present at birth. Nikolsky sign (+). Slow healing leads to atrophic scars and milia. Severe scarring often causes flexion contractures in joints (knees, elbows, wrists, ankles), impairing function. Mucosal involvement is common, with recurrent esophageal bullae being the most severe.
   • Esophageal lesions begin in early childhood but worsen in adulthood, causing dysphagia and often leading to aspiration pneumonia. Extensive erosions may result in fluid and protein loss. Most patients die in childhood or adolescence due to secondary infections, sepsis, pneumonia, or malnutrition.

• Epidermolysis bullosa acquisita (EBA): Mostly occurs in the elderly. Lesions appear on trauma-prone areas like fingers, feet, and the sides of elbows/knees. Non-inflammatory blisters, bullae, and erosions form, leaving atrophic scars and milia after healing. Some patients have hair, nail, or mucosal involvement.

What are the complications of epidermolysis bullosa?

• 50%–80% of dystrophic epidermolysis bullosa patients develop squamous cell carcinoma in chronic erosive areas, which is prone to invasion and metastasis.
• Junctional epidermolysis bullosa often involves tracheal blisters, stenosis, or obstruction. Growth retardation and severe anemia are common. Death is usually caused by sepsis, multi-organ failure, or malnutrition.

CAUSES

What are the causes of epidermolysis bullosa?

• Epidermolysis bullosa acquisita (EBA) is an autoimmune disease. The exact cause is unknown, but studies suggest it is associated with the production of type VII collagen antibodies and HLA-DR2 positivity.
• Hereditary epidermolysis bullosa results from gene mutations encoding structural proteins of the epidermis and basement membrane zone, leading to impaired synthesis or abnormal structure of these proteins, which causes blister formation at different anatomical sites.
  • EBS is linked to mutations in the genes encoding keratin 5 and 14;
  • JEB is associated with mutations in genes encoding laminin 5, type XVII collagen (BPAG2), and other components;
  • DEB is caused by mutations in the gene (COL7A1) encoding type VII collagen.

DIAGNOSIS

How is epidermolysis bullosa diagnosed?

Doctors typically diagnose it without difficulty based on characteristic medical history, family history, clinical manifestations (skin lesions), histopathological findings, and transmission electron microscopy. Genetic testing may sometimes be required.

What tests do patients with epidermolysis bullosa need?

• Histopathology: Microscopic examination may reveal edema and liquefaction degeneration of basal cells, subepidermal blisters, and occasional inflammatory cell infiltration in the blisters and superficial dermis.

• Transmission electron microscopy can further determine the precise location of the blisters.

• Peripheral blood tests: In cases of anemia, red blood cell count and hemoglobin levels may decrease. With concurrent infection, white blood cell and neutrophil counts may rise significantly. Severe infections with electrolyte imbalances require blood electrolyte, pH, liver/kidney function, and immunofluorescence antigen localization tests. For infections, secretion culture and drug sensitivity tests are also performed.

• Severe cases may require chest X-rays, electrocardiograms, and ultrasounds.

What conditions should epidermolysis bullosa be differentiated from?

EB must be distinguished from various autoimmune, infectious blistering disorders, and drug-induced blistering diseases, such as bullous pemphigoid and pemphigus.

TREATMENT

Which department should I visit for epidermolysis bullosa?

Dermatology, Pediatrics, Emergency Department.

Does epidermolysis bullosa require hospitalization?

Hospitalization is recommended to identify the cause, complete examinations to determine the type and treatment plan. Patients with infections should be hospitalized promptly for anti-infection therapy.

How is epidermolysis bullosa treated?

There is currently no effective cure. The principle is meticulous care, protecting the affected areas, avoiding trauma, friction, and heat, and preventing secondary infections.

• Infection prevention and management:
  • Cover epidermolysis bullosa (EB) wounds with non-adhesive silicone dressings, absorbent foam dressings, or non-adhesive silicone tape.
  • For wounds with severe bacterial colonization, diluted bleach baths or wet dressings, topical antiseptics, and topical antibiotics can be used to reduce bacterial load.
  • Wounds with confirmed infections often require systemic antibiotics.
• Pain management: Pain control is a crucial aspect of EB treatment.
  • For mild to moderate pain, analgesics (e.g., paracetamol, acetaminophen) can be used alone or combined with NSAIDs.
  • Severe pain may require opioids or anti-anxiety medications.
• Nutritional support: All patients with severe EB experience nutritional impairment and require support.
  • Anemic patients need iron supplementation, with or without erythropoietin.
  • Patients with osteopenia or osteoporosis should receive calcium and vitamin D supplementation.
• Recent reports from abroad mention bone marrow transplantation as a treatment.

DIET & LIFESTYLE

What should patients with epidermolysis bullosa pay attention to in their diet?

There are no specific dietary restrictions, but it is recommended to maintain a regular and light diet, avoiding spicy, greasy, and irritating foods.

What should patients with epidermolysis bullosa pay attention to in daily life?

• Maintain a regular daily routine, avoid excessive fatigue, and engage in appropriate exercise. Avoid stressful conditions such as infections.
• Follow a light and regular diet, avoiding irritating or allergenic foods.

PREVENTION

Can Epidermolysis Bullosa Be Prevented?

There are currently no effective preventive measures for this disease. Early detection and diagnosis are key to its management. Preventing infections can help reduce complications.