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.
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. Patients 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.