may lead to serious complications such as blindness and airway compression, early and aggressive treatment initiation may be needed. presentation scarring is a common consequence of mmp that distinguishes this variant from mucosal involvement in bullous pemphigoid, which typically does not scar. reticulated, white striations representing mucosal fibrosis often are present at sites of healed lesions, and functional limitations secondary to scarring may occur. as examples, mmp involving the ocular mucosa can lead to symblepharon, ankyloblepharon, and eventual blindness, and progressive laryngeal and tracheal involvement can result in asphyxiation. oral disease most commonly affecting the mouth, including the buccal mucosa, gingiva, tongue, vermillion lips, and palate. desquamative gingivitis is the most frequent manifestation. the gingiva is erythematous, in which patients usually complaint of bleeding upon brushing. rupturing of oral vesiculobullous lesions leave clean, noninflamed, painless erosions. the vermilion border of the lips is spared, which is typical in pemphigus. hoarseness due to laryngeal involvement can be seen in 8% of cases. a subset of patients have only oral disease, which has a relatively benign course compared with patients with oral cavity and other mucosae and skin involvement. ocular disease the eye is involved in 65% of cases. initially presented with unilateral conjunctivitis (such as burning or excessive tearing), then fibrosis beneath the conjunctival epithelium. shrinkage of the conjunctiva leads to obliteration of the conjunctival sac. symblepharons are fibrous strands connecting the conjunctiva of the lid to the globe. besides, reduced tearing with erosion and neovascularization of the cornea leads to corneal opacification and perforation. scarring of the lid results in entropion (inward turning of the lid) and trichiasis (in-turning of the eyelashes). these conditions ultimately lead to blindness in approximately 20% of cases. it is crucial to go for follow-up because relapse occurs in 22% of those who were in remission and not undergoing therapy. other mucous membranes less common sites that might get involved are nasopharynx, esophagus, and urethra. nasopharyngeal involvement can lead to ulcerations of the septum and airway obstruction which might require tracheostomy. esophageal disease may present with ulcerations, dysphagia, odynophagia, and stenosis. stenosis at urethra, vaginal orifice and rectal have also resulted from chronic inflammation and scarring. skin disease about 25% of patients have cutaneous lesions, with tense vesicles or bullae, mainly on the face, neck, and scalp. healing of erosion is either with or without atrophic scars. cutaneous lesions of mucous membrane pemphigoid presents in 2 subtypes: (1)presents as generalized eruption of tense bullae without scarring (2) presents as localised blisters on an erythematous base, resulting in atrophic scarring. mucous membrane pemphigoid is also associated with malignancy malignancy — mmp with antibodies directed against laminin 332 (previously known as laminin 5 and epiligrin) has been associated with an increased risk for internal malignancy. in a cohort of 35 patients with this type of pemphigoid (diagnosed with immunoprecipitation), 10 (29 percent) developed solid organ malignancies, 7 of which were diagnosed within 14 months after a diagnosis of mmp. occurrences of non-hodgkin lymphoma and cutaneous t cell lymphoma have also been reported in individual patients with anti-laminin 332 mmp. the pathophysiologic relationship of this subtype of mmp to cancer is unknown. however, expression of laminin 332 has been detected in malignant cells, and laminin 332 appears to be capable of promoting tumor cell growth, invasion, and metastasis. the clinical manifestations of mmp in patients with laminin 332 antibodies are similar to the features of mmp with other antibody profiles. therefore, clinical examination cannot reliably distinguish anti-laminin 332 mmp from other forms of mmp. additional studies are necessary to confirm the findings of a retrospective study of 154 patients with mpp that associated the detection of laminin 332 antibodies via a novel enzyme-linked immunosorbent assay (elisa) with a greater likelihood for severe disease. since diagnostic laboratory testing for laminin 332 antibodies is not commercially available, suspicion for laminin 332 primarily is based upon immunofluorescence microscopy findings. although not exclusive to laminin 332 mpp, the detection of antibodies bound to the dermal side of basement membrane zone-split (salt-split) skin suggests the possibility of this diagnosis. until definitive testing for laminin 332 antibodies becomes available, we recommend that patients with mmp in whom serum indirect immunofluorescence (iif) studies reveal antibodies bound to the dermal side of basement membrane zone-split skin undergo age and gender appropriate cancer screening. additional evaluation for malignancy should be performed as indicated based upon a review of symptoms, physical examination, and the results of age-appropriate screening. cause autoantibodies targeted to components of the basement membrane zone have been identified as pathogenic in mucous membrane pemphigoid. antigens include 180-kd bullous pemphigoid antigen (bp180), laminin 332, beta-4-integrin, and other antigens that are not fully discovered are identified against the basement membrane. complication of d- penicillamine therapy may trigger and causes mucous membrane pemphigoid. it also occurs after acute severe ocular inflammation in patients with stevens-johnson syndrome. pathophysiology autoantibodies target the basement membrane zone proteins which are responsible to promote adhesion within the basement membrane zone of the mucosa and the skin. the major basement membrane zone proteins identified include : c-terminus of bp180 bp230 laminin 332(also known as laminin 5 or epiligrin) alpha-6-beta-4 integrin type vii collagen. in contrast to the target of the n-terminus of bp180 that is located in the hemidesmosomes and upper lamina lucida in bullous pemphigoid, the target antigen in mmp is the c-terminus of bp180 which is located in the lower lamina lucida and lamina densa. this results in a deeper separation that is more likely to scar as compared to a more superficial blister that is unlikely to scar in bullous pemphigoid. antibodies to the beta-4 integrin subunit of alpha-6-beta-4 integrin is shown to be associated with ocular disease while oral involvement is suggested to be linked with antibody reaction towards the alpha-6 subunit. besides, mmp with antibody reaction against laminin 332 has an association with an increased risk for internal malignancy. similar to bullous pemphigoid, other factors such as genetic factors, environmental exposures and the phenomenon of epitope spreading potentially result in mmp. multiple studies have also reported an association of hla-dqb1*0301 with mpp. diagnosis diagnosis of bullous pemphigoid includes clinical assessment, skin biopsy for histopathology and direct immunofluorescence, indirect immunofluorescence and elisa test. among all, direct immunofluorescence is the gold standard for diagnosis of mucous membrane pemphigoid. clinical assessment presence of tense blisters and erosions that occur on skin without another identifiable cause. desquamative gingivitis or mucositis involving oral, ocular, nasal, genital, anal, pharyngeal, laryngeal, and/or esophageal mucosae presence of pruritic eczematous eruptions, or urticarial plaques without identifiable cause. patient's age over 60 years old. histopathology lesional tissue, preferably of an intact vesicle or the edge of an intact bulla is obtained using punch biopsy for haemotoxylin and eosin (h&e) staining. the findings are sub-epidermal blister with dermal infiltrated with lymphocytes, neutrophils and eosinophils. additional findings include sub-epidermal fibrosis which is consistent with the scarring nature of mucous membrane pemphigoid in older lesions and plasma cell infiltration. direct immunofluorescence studies direct immunofluorescence (dif) studies involves directly detecting tissue bound antibodies. biopsy specimens for dif should be taken from perilesional skin instead of lesional skin for h&e histopathologic evaluation. linear band of igg and c3 deposits are found along the basement membrane. occasionally, linear deposition of iga at the basement membrane zone can also be seen. multiple and repeated biopsies increase the sensitivity of dif studies to diagnose mmp. indirect immunofluorescence indirect immunofluorescence is used to detect circulating antibodies targeting the antigens at the basement membrane zone in patients with pemphigoid. in early studies using routine techniques, only one third of patient with mpp were being tested positive. circulating igg and iga antibodies are found in patient's serum. to increase the likelihood of detecting circulating antibodies, human basement membrane zone-split skin and/or concentrated serum should be used. antigen-specific serologic testing autoantibodies directed against a variety of antigens, including bp180, bp230, laminin 332, and type vii collagen may be detected. however, this test could not be used as the only diagnostic tool for testing as elisa testing has limited sensitivity. treatment the factors that determine the type of therapy used for mucous membrane pemphigoid are: site(s) of involvement, severity of disease, rate of progression. oral mucosa is the most common site being affected in mucous membrane pemphigoid. for the mild oral mucosa lesion, high potency topical steroids such as 0.05% clobetasol propionate is used. patients are instructed to apply the ointment or gel 2-3 times a day after drying the oral mucosa to enhance the adherence of mediation to oral mucosa. patients are instructed to avoid drinking or eating for at least 30 minutes after application. dental tray can also be fabricated to help in the application of topical steroids to lesional sites under occlusion for patients with gingival involvement. furthermore, topical tacrolimus, a calcineurin inhibitor, has also shown to be effective to control the disease, including some patients who failed to respond well to topical corticosteroids. topical tacrolimus 0.1% ointment is applied two to three times a day and tapered after improvement in healing of pemphigoid. another method is to use intralesional corticosteroids (triamcinolone acetonide, dilution of 5 to 10 mg/ml; repeated every 2–4 weeks). intralesional therapy is used when the patient does not respond to local therapies. for moderate to severe disease (including the ones involving ocular, nasopharyngeal, or anogenital mucosa) and patient who did not respond to local therapy adequately, systemic agents should be used. systemic corticosteroids and dapsone are used in such cases. the dose of dapsone ranges from 50 to 200 mg daily. dapsone is shown to be effective in treating mucous membrane pemphigoid that does not respond to systemic corticosteroids. whereas for systemic corticosteroids, 0.25 to 0.5 mg/kg of prednisolone is prescribed per day (twice-daily dosage is used during the acute stage and change to a single daily morning dose after new blister formation stops). thereafter, the dosage of prednisolone is slowly tapered over the months in combination with topical therapy or glucocorticoid-sparing agent (e.g., dapsone, azathioprine). patients with severe mucous membrane pemphigoid that cannot be controlled by the intervention above and would need aggressive immunosuppressive regimens and biologic therapies to control the lesions. azathioprine or cyclosphosphamide are the choices of immunosuppressive drugs that can be used. sometimes, immunosuppressive agents and prednisolone can be combined if dapsone fails to improve the condition. lastly, in patients who do not respond to the conventional therapy, rituximab may be an option. there is insufficient evidence that cyclophosphamide combined with corticosteriods are effective in treating mucous membrane pemphigoid. other than that, oral hygiene instructions should be given to patients as oral care is a critical part in treating mucous membrane pemphigoid. before meals, patients are advised to rinse with hydrogen peroxide (diluted with water to a concentration of 1:4 or 1:6) and diphenhydramine to reduce the pain. patient would then rinse with hydrogen peroxide to remove food particles and debris and later rinse with dexamethasone for anti-inflammatory effect. hydrogen peroxide, elixir of dexamethasone and elixir of diphenhydramine are each diluted with water to a concentration of 1:4 or 1:6 and are instructed not to swallow in the end. epidemiology mmp mainly affect the elderly population of ages between 60 and 80 years and rarely children. women are affected twice as frequently than in men. there is no known racial or geographic predilection, but several studies have suggested that there is an association of specific immunogenetic haplotype hla-dqb1*0301 with mmp.