Bullous Dermatoses (Blisters and Bullae)

Hereditary epidermolysis bullosa (EB) is an umbrella term which covers a group of rare inherited conditions with disturbance of the coherence of the epidermis, causing blisters to form after trauma. See related article Epidermolysis Bullosa. It varies from very mild to severely mutilating and even lethal. Several nomenclature systems for these conditions have been proposed, the latest being as follows:

• EB simplex
• Junctional EB
• Dystrophic EB
• Hemidesmosomal EB

Familial benign pemphigus is also known as benign chronic pemphigus or Hailey-Hailey disease.¹ See separate article Benign Chronic Pemphigus. It is an autosomal dominant condition of limited penetrance. It usually presents in late teens or early adulthood but it may not present until the 30s or 40s. It presents as an inflamed erosive, oozing condition with crusts on the nape of the neck, axillae, under the breasts, inguinal folds and scrotum with cracks and fissures. There may be longitudinal white bands on the nails in 70%.²

Pemphigus vulgaris (PV) is a serious, autoimmune disease affecting the skin and mucous membranes. See related article Pemphigus. It is derived from the Greek word pemphix meaning bubble or blister. A number of variations of the disease have been described, including drug-induced pemphigus and IgA pemphigus. The best known drugs to induce it are penicillamine and captopril but rifampicin and emotional stress have been implicated. Pemphigus is a rare disease with an incidence between 0.5 and 3 cases per 100,000.

• Age of onset is usually between 40 and 60 years but it can occur much younger, especially in Indian patients.³
• It presents with oral lesions in 50 to 70% and almost all have some mucosal lesions. Mucosal lesions may be the only feature but on average they precede skin lesions by 5 months.
• Other mucous membranes to be involved include the conjunctiva, oesophagus, labia, vagina, cervix, penis, urethra and anus.

Lesions on the back are common in patients confined to bed.
This large area of skin loss will cause problems with fluid loss, temperature homeostasis and as a portal of infection.

This is a rare bullous disease of pregnancy that affects about 1 person in 2 million per year. It is autoimmune in origin. See separate article Pemphigoid Gestationis.

• Lesions may appear any time during pregnancy but they most commonly develop during the second and third trimesters.⁴
• There is sudden onset of extremely pruritic urticarial papules and blisters on the abdomen and trunk. Pruritus is severe and unrelenting.
• Lesions start with erythematous urticarial patches and plaques around the umbilicus. They progress to tense vesicles and blisters. Sometimes urticarial plaques may never develop blisters. They differ from true urticaria because they are relatively fixed in nature.
• The rash spreads peripherally, often sparing the face, palms and soles. Mucosal lesions occur in fewer than 20% of cases.
• Symptoms usually subside at delivery but dramatic flares can occur immediately postpartum.
• It usually resolves within weeks to months after delivery and possibly quicker with breast-feeding. Disease persisting for years after delivery has been reported.
• It may recur with the resumption of menstruation, use of oral contraception and subsequent pregnancies. This is unaffected by a change in partner.⁴

Bullous pemphigoid (BP) is a rare, chronic, autoimmune, subepidermal, blistering skin disease that rarely involves mucous membranes. See separate article Bullous Pemphigoid. It mainly affects people aged over 60 years, with an average age onset of 65 years. It has been reported to follow chronic skin diseases such as lichen planus and psoriasis. It can also follow ultraviolet and X-ray irradiation, vaccination in children⁵ and after some drugs. The most noted are furosemide, captopril, ibuprofen and other NSAIDs, and penicillamine.

• It usually starts with a prodromal urticarial or papular lesion that heralds, by weeks or months, the sudden appearance of bullae that are large, tense, oval and containing serum or blood-stained fluid. They usually collapse and form a crust.
• They are mainly in the axillae, medial aspect of thighs, groin, abdomen, flexor aspects of forearms and lower legs.
• Biopsy and direct immunofluoresence usually confirm the diagnosis.

This refers to a group of rare chronic autoimmune blistering diseases affecting mainly mucous membranes (including the conjunctiva). See separate article Cicatricial pemphigoid for more details.

Dermatitis herpetiformis (DH) is a chronic, recurrent disorder associated with a gluten-sensitive enteropathy as in coeliac disease but it affects an older age group and 90% have no gastrointestinal (GI) symptoms. See separate article Dermatitis Herpetiformis, which is much more extensive.

• Skin lesions are extremely itchy and groups of vesicles appear most frequently on extensor surfaces. There is burning, stinging and intense pruritus, often before new lesions appear.
• Erythematous vesicles appear in a typical pattern. They are symmetrical over the extensor surfaces, including elbows, knees, buttocks, shoulders and the nuchal area.
• Erythematous papules and plaques of urticaria occur less frequently, whilst bullae are rare.
• There may be crusts or erosions if there are no vesicles.
• Patients often complain of stinging or burning of the skin before the appearance of new lesions.
• Oral mucosa, palms and soles are rarely involved.

This is a bullous disorder of autoimmune aetiology. Annual incidence is 1 case per 250,000. It is usually triggered by infection or drugs.⁶

The features of Stevens-Johnson syndrome can range from mild skin and mucous membrane blisters to a severe, sometimes fatal systemic disorder. See separate article Stevens-Johnson Syndrome. Causes include:

• Infection.
• Immunisation: associated with immunisation, e.g. measles, hepatitis B.
• Drug-induced: many drugs have been implicated, e.g. penicillins, sulphonamides, phenytoin, carbamazepine, non-steroidal anti-inflammatory drugs, anti-malarials and allopurinol.
• Cocaine use.
• Radiation therapy for cancer.
• Malignancy: various carcinomas and lymphomas have been associated.
• Idiopathic: in 25-50% of cases.

See individual records for specific investigations. Tests are likely to include:

• Histological analysis of a skin biopsy to exclude other causes of blistering.
• Bacterial culture.
• Electron microscopy of a fresh blister biopsy, which may assist diagnosis.
• Immunofluorescent microscopy.
• DNA mutation analysis.

See individual records for specific management.

Treatment is likely to involve steroids, immunosuppressant drugs, antibiotics or a combination of all three.