What are Blistering Diseases?
Structure of the Skin
Inherited Blistering Diseases
Auto-Immune Blistering Diseases

Auto-Immune Blistering Diseases

What are auto-immune diseases?

Auto-immune diseases are caused when the immune system starts attacking the patient's own body. The immune system is very complex, and the underlying mechanism of auto-immunity is not well understood.

Auto-immune blistering diseases are a group of auto-immune diseases which affect the skin, although auto-immune diseases occur in many other systems of the body. For example, inflammatory bowel disease (ulcerative colitis and crohn's disease) are auto-immune diseases of the intestine, and multiple sclerosis is an auto-immune disease which affects the nervous system.

In auto-immune blistering diseases, the body makes antibodies against the adhesion proteins in the skin. Different proteins are affected in different types of diseases.

Pemphigus

Pemphigus is rare, with about 1 new case / 1 000 000 people / year. There are 3 types: pemphigus vulgaris, pemphigus foliaceus and paraneoplastic pemphigus.

Pemphigus vulgaris

Pemphigus vulgaris accounts for 80% of cases of pemphigus. It is caused by auto-antibodies against adhesion proteins in the epidermis (desmoglein 1 and 3). It is characterised by fragile blisters on the skin and mucosa.

Pemphigus foliaceus

Pemphigus foliaceus accounts for 20% of cases of pemphigus. It is caused by auto-antibodies against desmoglein 1 only, and only affects the skin.

Paraneoplastic pemphigus

Paraneoplastic pemphigus is rare. It is associated with cancer elsewhere in the body. Mucosa is generally severely affected.

Bullous pemphigoid

Bullous pemphigoid had an incidence of about 10 / 1 000 000 people / year. It is more common in people over 50 years. It is caused by auto-antibodies against adhesion proteins in the basement membrane (BP180 and BP230). It causes large tense blisters on the skin.

Mucous membrane pemphigoid

Mucous membrane pemphigoid (also called cicatricial pemphigoid) is rare. It particularly causes blisters in the mouth and around the eyes. It can also affect the nose, throat, oesophagus, genitalia and rectum. Skin involvement occurs in some patients. A number of auto-antibodies can be found in mucous membrane pemphigoid, including BP230, collagen 7, integrin b4, LAD antigen and laminin a3.

Epidermolysis bullosa acquisita

Epidermolysis bullosa acquisita is characterised by chronic widespread blistering at sites of trauma. The skin is fragile, and blisters heal leaving prominent scarring. The mucosa, including the oesophagus can be affected. It is caused by auto-antibodies against collagen 7 in the dermis.

Linear IgA bullous disease

Linear IgA bullous disease (also called chronic bullous disease of childhood in children) is rare with approximately 1 new case per 2 000 000 people per year. It causes characteristic annular lesions with blisters at the edge on skin and mucosa. It is caused by IgA antibodies against the basement membrane zone.

Bullous lupus

Systemic lupus erythematosus is an auto-immune disease which effects multiple systems in the body, and can effect the skin in a variety of ways. In bullous lupus blisters occur especially on sun exposed skin. For more information on lupus, see www.lupus.com.au.

Dermatitis herpetiformis

Dermatitis herpetiformis occurs in association with coeliac disease. Coeliac disease is caused by sensitivity to gluten (found in wheat) and causes diarrhoea. Dermatitis herpetiformis causes very itchy small blisters, especially on the arms, legs and back.

Diagnosis

There are 3 main tests used to help confirm the diagnosis.

Histopathology
A skin biopsy is normally taken from a fresh blister. Under a microscope, the location of the blister within the skin can be seen.



Direct immunofluorescence
A skin biopsy is also taken for direct immunofluorescence. This looks for the presence of antibodies in the skin.



Indirect immunofluorescence
A blood sample is taken to look for antibodies circulating in the blood.

ELISA and Immunoblotting
These tests are more sensitive ways of looking for antibodies in the blood. They are mainly used for research and are not available in Australia.

Treatment

The aim of treatment in auto-immune blistering diseases is to suppress blister formation. There is no definitive cure, but blistering can normally be controlled. This is done with a variety of medications which suppress the immune system.

Corticosteroids are the cornerstone of treatment for auto-immune blistering diseases. They are generally used in combination with an immunosuppressant (such as azathioprine, cyclosporin, cyclophosphamide, methotrexate or mycophenolate). Other treatments include anti-inflammatory antibiotics (such as minomycin and tetracycline), dapsone, and intravenous immunoglobulin (IVIG).

For more information, see the patient information leaflets prepared by the British Association of Dermatologists.