**4. Mucous membrane pemphigoid**

Mucous membrane pemphigoid (MMP) also known as cicatricial pemphigoid, is a rare subepidermal blistering disease with highly variable clinical heterogeneity and

#### *Skin Blister Formation and Subepidermal Bullous Disorders DOI: http://dx.doi.org/10.5772/intechopen.110472*

potential diagnostic delays. It predominantly affects the mucous membranes and, up to 30% of patients may also have skin involvement [37, 40, 41]. The disease most frequently involves the oral mucosa (85% of patients), followed by ocular conjunctiva (65%), nasopharynx, larynx, anogenital region, and esophagus involvement can be seen and results in mucosal blistering, ulceration, and subsequent scarring [41, 42]. The disorder if not recognized and treated early and aggressively in some cases, often may cause blindness, esophageal strictures, and even difficulty speaking and breathing [17, 22]. MMP mainly occurs in the elderly population, commonly observed between 60 and 80 years of age and seen in women more often than men [37, 42].

Certain HLA types like HLA DRB1\*1503 have been associated with an increased risk of developing MMP [17, 22]. Autoantibodies against different antigens of the basement membrane zone, such as BP180, BP230, integrin subunits α6/β4, laminin-332 (also called epiligrin and laminin-5), laminin-6, and type VII collagen has been blamed for dermo-epidermal separation and blister formation in MMP [40, 42]. Generally, MMP has been classified into three types based on the antigenic target classic MMP (BP180); ocular MMP (α6β4 integrin); and anti-laminin 332 MMP (laminin 332) [18].

In the clinic, there are vesiculobullous lesions in all cases, but in contrast to BP oral involvement is in up to 85% of cases. The most commonly involved sites are the head and upper body and clinical evidence of scarring can clue in the diagnosis of MMP [18]. Healing of the lesions of the disease with scarring is an important cause of morbidity. Clinically, irreversible damage specific to the location of the lesions can be seen. Therefore, early diagnosis and effective treatment of the disease are important. Complications related to the eyes are very important as the eyes are the most frequently involved area. There may be non-specific conjunctivitis, as well as complications such as lagophthalmos, entropion, trichiasis, keratitis, glaucoma, and even blindness [43]. The most common finding of oral mucosal MMP is desquamative gingivitis. Ulcers and erosions due to the opening of bullae may also be seen. Patients complain of bleeding, pain, and dysphagia. As a result of oral mucosal involvement, speech and feeding difficulties may occur. Organ-specific complications can also be seen due to the involvement of other mucosal tissues [40, 44].

Diagnosis is made by clinical correlation with histopathologic, immunopathologic, and serologic findings [18]. Histology typically demonstrates the subepithelial split with or without significant mixed inflammatory infiltrates (predominantly neutrophilic and lymphocytic and variable eosinophilic) and lamellar fibrosis in the upper dermis [18, 45]. Lamellar fibrosis that can be seen underneath the subepidermal bullae is characteristic but is not always present. If it is, it can help distinguish MMP from other subepidermal blistering dermatoses [18]. In DIF examination, the linear deposition of IgG, IgA, or C3 along the BMZ is seen [45, 46]. As in BP, salt-split skin DIF shows epidermal staining in MMP except in anti-laminin 332 type [18, 41]. ELISA for the C-terminal domain of BP180, and laminin 332 MMP is not widely available so the benefit of serologic testing is limited for MMP diagnosis [18].

The choice of treatment depends on the severity of the disease and the patient's response to previous treatments. As in other chronic diseases, the patient's age, comorbid conditions, drug use, and severity of the disease are effective in the choice of treatment. In addition, a multidisciplinary approach and careful clinical examination are important in treatment because of irreversible tissue damage due to the disease [42].

In the choice of treatment, patients are evaluated as low and high risk. The "low-risk" patients are those with involvement of oral mucosa and/or skin. Patients with involvement of the ocular, nasopharyngeal, esophageal, laryngeal, and genital mucosa are considered "high-risk" patients [37].

Topical agents are the first line of treatment in low-risk patients. Topical or intralesional corticosteroids can be used. Topical tacrolimus can also be used for treatment, but topical steroids are more effective. When patients do not respond to topical treatments or in case of partial response to these treatments, systemic treatments should be started. Dapsone 50–200 mg/day and/or prednisone 0.5–1.0 mg/kg/day, tetracycline 1–2 g/day, and doxycycline 100 mg/day are the preferred agents in systemic therapy. In high-risk patients and low-risk patients who have a partial response to treatment, treatment should be more aggressive, and systemic therapy should be preferred primarily. Prednisone 1–2 mg/kg/day treatment can be used as the first choice for these patients. With or without prednisone treatment, depending on the patient's response to treatment; methylprednisolone 500 mg–1 g/day - 3 days (pulsed steroid therapy) or cyclophosphamide 1 g + dexamethasone 100 mg/day every 28/28 days or IV Immunoglobulin 2 g/kg/cycle and/or rituximab 375 mg/m2/week can be preferred. Also, azathioprine 1–3 mg/kg/day, mycophenolate mofetil 2–3 g/day, methotrexate 10–17.5 mg/week, and cyclophosphamide 1–2 mg/kg/day are also agents that can be used in the treatment [18, 37, 38, 42].
