Autoimmune Bullous Diseases
Bullous pemphigoid (BP)
Bullous pemphigoid (BP) is the most common form of autoimmune bullous dermatosis.
It affects primarily the elderly but it has also been described in children. The disease is characterized clinically by tight, often large, bullae with a clear content, developing primarily on the edge of erythematous plaques. Intense itching is common. The infantile form occurs within the first year after birth and presents as bullous lesions on erythematous skin or on normal acral skin.
It has an estimated prevalence of 1/40,000 (and an annual incidence of 1/150,000 cases in France and Germany).
Mucous membrane pemphigoid
Mucous membrane pemphigoid is a bullous dermatosis characterised clinically by blistering of the mucous membranes followed by scarring, and immunologically by IgG, IgA and/or C3 deposits on the epidermal basement membrane.
The average age of onset is 60-70 years and the disease appears to be more common in women than in men. Mucous membrane pemphigoid is a chronic disease with periods of more rapid evolution. The disease manifests as fragile bullous lesions that give way to superficial erosions. The principle sites affected are the oral (80-90% of cases), ocular (50-70% of cases), pharyngolaryngeal (8-20% of cases), genital (15% of cases) and oesophageal mucous membranes. Some forms affect only one mucosal membrane, in particular the buccal (erosive gingivitis) or ocular mucosae. An exclusively cutaneous form has also been observed in some cases. The ocular manifestations are initially inflammatory but then lead to retractile scarring of the conjunctive membrane, associated with corneal metaplasia resulting in vision loss.
The prevalence is unknown.
Epidermolysis bullosa acquisita (EBA)
Epidermolysis bullosa acquisita (EBA) is a subepidermal bullous dermatosis of autoimmune origin that was named as a result of its resemblance to hereditary forms of epidermolysis bullosa (HEB), most notably dystrophic HEB. The disease manifests in two clinical forms: a classical form and an inflammatory form. In the classical form, onset occurs in adulthood and the bullae may be soft, tense or haemorrhagic, located on otherwise healthy skin. Lesions are usually triggered by minor trauma and are mainly localised to sites that are easily injured. Involvement of the mucous membranes, hair and nails is frequent. The inflammatory form was recognised more recently and resembles bullous pemphigoid with bullae developing on erythematous skin lesions, plaques without bullous eruptions and diffuse lesions that are not limited to trauma-prone sites. The disease manifests during childhood. EBA is present in association with another disease (most notably Crohn’s disease, haemorrhagic rectocolitis or diabetes mellitus) in 10-50% of cases. The nosological boundaries between EBA and bullous systemic lupus erythematosus (see this term) remain under debate.The prevalence is unknown but the incidence is estimated at 1 in 96,200 new cases per year.
Dermatitis herpetiformis (DH)
Dermatitis herpetiformis (DH) is a chronic autoimmune subepidermal bullous disease characterized by grouped pruritic lesions such as papules, urticarial plaques, erythema, and herpetiform vesiculae, with a predominantly symmetrical distribution on extensor surfaces of the elbows (90%), knees (30%), shoulders, buttocks, sacral region, and face of children and adults. Erosions, excoriations and hyperpigmentation usually follow. DH may also appear as a consequence of gluten intolerance.
Pemphigus is a group of chronic autoimmune skin diseases characterised by blisters formation on the outer layer of the skin and the mucous membranes. Three clinical forms have been characterised, of which paraneoplastic pemphigus is extremely rare.
- Paraneoplastic pemphigus occurs in a background of suspected or proven neoplasia. The associated cancers are mostly lymphomas, chronic lymphoid leukaemia and in some cases, Kaposi sarcoma, thymomas, carcinomas, and poorly differentiated sarcomas. The disease almost always begins with severe diffuse blisters (bullae) in the mouth, on the lips and on the oesophagus. Eyes are frequently involved. Skin lesions vary and can be misleading, presenting as bullous lichenoid lesions, evocative of urticaria or polymorphous erythema. Lungs can also be involved (in 30% to 40% of cases), as well as the gastrointestinal tract.
- Pemphigus vulgaris is the most frequent (75%) Onset occurs on average at 50-60 years, although childhood onset forms have been described. The disease begins with blisters (bullae) in the mouth, which are often mistaken for aphtae. The blisters are flaccid and are easily broken, leading to often painful lesions or erosions. Blistering can also affect the oesophagus, rectum, nose or the lining of the eyelids. Skin lesions appear several weeks or several months after the onset of mucosal erosions. Nikolsky’s sign can appear on perilesional skin or, in some cases, even on healthy skin. Pemphigus vegetans is a clinical variant characterised by intertriginous lesions developing into vegetating plaques.
- Superficial pemphigus is a rare, autoimmune, bullous skin disease characterized clinically by multiple flaccid blisters, typically occurring on the face, scalp, trunk and extremities, which rapidly evolve into scaly, crusted, pruritic skin erosions. Histopathologically, superficial acantolytic blisters, as well as intercellular deposits of IgG autoantibodies directed against desmoglein 1 (and occasionally against desmoglein 3) in the upper epidermis, are observed.
Pemphigoid gestationis is a rare skin blistering disorder that occurs in women. It usually presents in mid to late pregnancy (13 to 40 weeks gestation, known as the second and third trimesters) with an itchy rash that develops into blisters. It may recur in subsequent pregnancies and occasionally recurs in women who go on to take oral contraceptive therapy or during menstruation when their periods restart after pregnancy.
Pemphigoid gestationis is an auto-immune blistering disease. This means that the mother’s immune system starts reacting against her own skin causing the skin to split and form blisters. Current knowledge suggests that some very small parts of the placenta tissue enters the mother’s blood stream and causes her immune system to activate producing antibodies which attack the skin.
Linear IgA disease
Linear IgA disease is a very rare blistering condition of the skin in adults. A similar condition affecting children is known as Chronic Bullous Disease of Childhood (CBDC). The condition is called ‘Linear IgA disease’ because a type of protein called immunoglobulin A (IgA) can be seen deposited under the outer layer of the skin (the epidermis) in a line (linear) when a small sample of skin biopsy is prepared specially and examined under the microscope. Often no cause can be identified. Sometimes, infections and occasionally medicines may trigger linear IgA disease. The disease is thought to be related to the immune system (IgA protein) attacking structures in the skin layers (i.e. it is an autoimmune disease). When these structures are damaged, the skin blisters may form.