Mucous membrane pemphigoid (syn. cicatricial pemphigoid)

Mucous membrane pemphigoid (MMP) is a chronic, immunobullous condition of the mucosa that may involve the skin, and usually results in permanent scarring of the affected area, particularly the conjunctiva. This entity includes patients formerly diagnosed as oral pemphigoid and some cases of linear IgA disease and epidermolysis bullosa acquisita.

Considerable variability exists in the clinical presentation of MMP, affected sites include the oral cavity, conjunctiva, nasopharynx, larynx, oesophagus, genitourinary tract, and anus. The skin is involved in approximately one-quarter of patients, often limited to the head, neck, and upper torso regions. Pathologically MMP is characterised by the presence of subepidermal blisters, with various basement membrane zone components as targets of the autoantibodies.

This chapter is set out as follows:

• MMP is an immunobullous condition

• The immunobullous conditions are characterised by pathogenic autoantibodies directed at target antigens whose function is either cell-to-cell adhesion within the epidermis or adhesion of stratified squamous epithelium to the dermis or mesencyme. The target antigens involved are components of desmosomes or the functional unit of the basement membrane zone known as the adhesion complex

• In MMP, IgG and less commonly IgA autoantibodies are directed against varies basement membrane zone antigens including bullous pemphigoid antigens BP180 and BP230, along with laminin 5, laminin 6 and the β4-integrin subunit

• MMP is predominantly a disease of late-middle to old age with a peak incidence at around 70 years. However, childhood cases have been reported

• It is twice as common in women than men

Blood tests - indirect immunofluorescence (reference: Rook's Textbook of Dermatology)

• A request for skin antibodies covers both pemphigoid (skin basement membrane) and pemphigus (skin desmosome) antibodies. In MMP, the result is often negative, however, a minority will be positive for circulating pemphigoid antibodies 

Skin biopsies (reference: Rook's Textbook of Dermatology)

• In order to take the biopsies correctly refer to the section on investigations in the chapter Bullous pemphigoid - of course depending on the site of blisters, other specialist departments may need to be involved. Two samples are needed:
• Histology of a blister reveals a subepidermal blister with a variable inflammatory cell infiltrate 
• Direct immunofluorescence (DIF) of peri-lesional mucosa or skin is essential for diagnosis, and reveals linear deposition of IgG, C3, or less commonly IgA along the basement membrane zone

• In cases of clinical diagnostic uncertainty the use of salt-split skin immunofluorescence studies can be useful in differentiating between MMP and bullous pemphigoid - the skin biopsy sample is placed in 1 mol/L salt prior to performing the immunofluorescence studies, which causes cleavage through the lamina lucida. Examination of the salt-split skin reveals IgG on the blister floor (dermal side of split skin) in MMF, while, in bullous pemphigoid the IgG can be found in blister roof (epidermal side of split skin) 

• Patients suspected of having MMP should be referred urgently to an appropriate specialist in Secondary Care 

• MMP is a chronic, progressive disease that often responds poorly to treatment. Spontaneous resolution is rare. Some patients may experience long remissions with intermittent exacerbations

• A multidisciplinary approach is essential in the management of MMP. Early recognition and treatment may decrease disease-related complications. In a patient who presents with involvement of one site, a thorough review of symptoms highlighting other potential areas of involvement should be obtained. The choice of agents for treatment of MMP is based upon the sites of involvement, clinical severity, and disease progression