Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the Pemphigus Vulgaris article more useful, or one of our other health articles.
Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.
Hereditary epidermolysis bullosa
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 the separate related Epidermolysis Bullosa article. 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
Familial benign pemphigus is also known as benign chronic pemphigus or Hailey-Hailey disease. See the separate Familial Benign Pemphigus article.
- It is a rare autosomal dominant condition of limited penetrance caused by loss of function mutation in the ATP2C1 gene.
- It usually presents in the third or fourth decade, although it can occur at any age.
- Heat, sweating and friction often exacerbate the disease, and most patients have worse symptoms during summer.
- It is characterised clinically by a recurrent eruption of vesicles and bullae at the sites of friction and intertriginous areas.
- There may be longitudinal white bands on the nails of patients.
Pemphigus vulgaris (PV) is a rare but life-threatening, autoimmune disease affecting the skin and mucous membranes. See the separate related Pemphigus article. 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.
- PV is caused by circulating antibodies to desmosomes (important adhesion proteins linking cells together). Disruption of these intercellular connections results in a loss of cohesion between cells (acantholysis).
- It presents with oral lesions in 50-70% and almost all have some mucosal lesions. Mucosal lesions may be the only feature but on average they precede skin lesions by five months.
- Multiple blisters develop that easily rupture, leaving behind painful sloughing eroded areas of mucosa and/or skin.
- 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.
- Diagnosis is made on the basis of the presence of a subepidermal vesicle on routine histological examination and of linear deposition of complement along the basement membrane zone of perilesional skin.
- Lesions may appear any time during pregnancy but they most commonly develop during the second and third trimesters.
- 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.
- 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 breastfeeding.
- It may recur with the resumption of menstruation, use of oral contraception and with subsequent pregnancies. This is unaffected by a change in partner.
Bullous pemphigoid (BP) is not only the most common disorder within the pemphigoid group, but also represents the most frequent autoimmune blistering disease in general. It is a rare, chronic, autoimmune, subepidermal, blistering skin disease that rarely involves mucous membranes. See the separate Bullous Pemphigoid article.
- It mainly affects people aged over 60 years.
- It is an organ-specific condition which may be associated with many different disorders (immune, neurological, psychiatric, hematological, pulmonary, and cardiovascular), as well as with different types of malignancies.
- 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 the 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 the separate Cicatricial Pemphigoid article for more details.
Dermatitis herpetiformis (DH) is a chronic, polymorphic, pruritic skin disease that develops mostly in patients with latent gluten-sensitive enteropathy. DH patients usually present with skin manifestations only and are not aware of the underlying small-bowel problems. See the separate Dermatitis Herpetiformis article.
- 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.
- Contrary to the other bullous disorders, there are no circulating autoantibodies binding to the cutaneous basement membrane components or to other adherent structures of the skin, but patients have gluten-induced IgA autoantibodies against transglutaminase.
Linear IgA dermatosis
This is a bullous disorder of autoimmune aetiology. Annual incidence is 1 case per 250,000. It is usually triggered by infection or drugs.
The features of Stevens-Johnson syndrome can range from mild skin and mucous membrane blisters to a severe, sometimes fatal, systemic disorder. See the separate Stevens-Johnson Syndrome article. Drugs including allopurinol, antibiotics, anticonvulsants and non-steroidal anti-inflammatory drugs (NSAIDs) of the oxicam type are the main cause of Stevens-Johnson syndrome. Other causes include:
- Immunisation: associated with immunisation - eg, measles, hepatitis B.
- Cocaine use.
- Radiation therapy for cancer.
- Malignancy: various carcinomas and lymphomas have been associated.
See the individual separate articles 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 the individual separate articles for specific management.
Treatment is likely to involve steroids, immunosuppressant drugs, antibiotics or a combination of all three. Newer therapeutic agents which target-specific pathogenic steps linked with inflammation are being developed.
Further reading and references
Epidermolysis bullosa; DermNet NZ
Pemphigus vulgaris; DermNet NZ
Dermatitis herpetiformis; DermNet NZ
Sardy M, Ruzicka T; Successful therapy of refractory Hailey-Hailey disease with oral alitretinoin. Br J Dermatol. 2013 Aug 12. doi: 10.1111/bjd.12582.
Tchernev G, Cardoso JC; Familial benign chronic pemphigus (Hailey-Hailey Disease): use of topical immunomodulators as a modern treatment option. Rev Med Chil. 2011 May139(5):633-7. doi: /S0034-98872011000500011. Epub 2011 Sep 16.
Vinall C, Stevens L, McArdle P; Pemphigus vulgaris: a multidisciplinary approach to management. BMJ Case Rep. 2013 Dec 162013. pii: bcr2013200479. doi: 10.1136/bcr-2013-200479.
Lipozencic J, Ljubojevic S, Bukvic-Mokos Z; Pemphigoid gestationis. Clin Dermatol. 2012 Jan-Feb30(1):51-5. doi: 10.1016/j.clindermatol.2011.03.009.
Lo Schiavo A, Ruocco E, Brancaccio G, et al; Bullous pemphigoid: etiology, pathogenesis, and inducing factors: facts and controversies. Clin Dermatol. 2013 Jul-Aug31(4):391-9. doi: 10.1016/j.clindermatol.2013.01.006.
Ruocco E, Wolf R, Caccavale S, et al; Bullous pemphigoid: associations and management guidelines: facts and controversies. Clin Dermatol. 2013 Jul-Aug31(4):400-12. doi: 10.1016/j.clindermatol.2013.01.007.
Nakajima K; Recent advances in dermatitis herpetiformis. Clin Dev Immunol. 20122012:914162. doi: 10.1155/2012/914162. Epub 2012 Jul 2.
Karpati S; Dermatitis herpetiformis. Clin Dermatol. 2012 Jan30(1):56-9. doi: 10.1016/j.clindermatol.2011.03.010.
Harr T, French LE; Stevens-Johnson syndrome and toxic epidermal necrolysis. Chem Immunol Allergy. 201297:149-66. Epub 2012 May 3.