Patients with pemphigus vulgaris (PV) are seen to initially suffer from oral erosions and then successively develop cutaneous involvement. Mucous membrane erosions precede cutaneous expressions of the disease and often result in a lengthened course of misdiagnosis with illnesses such as aphthous ulceration [1]. As seen in some cases of PV, painful oral ulceration may appear to be the only indicator of the disease. Common mucosal surfaces that are involved in the manifestation of the disease include the gingiva, soft and hard palate, floor of the mouth, tongue, esophagus, oropharynx, nasal, larynx, urethra, vulva, and cervix [1, 2]. Conjunctiva involvement is less frequently observed in PV. PV patients also demonstrate dysphagia accompanied with weight loss [2].

Oral involvement remains isolated for months before the occurrence of cutaneous lesions that could be localized or generalized. Commonly involved skin lesions occur on the trunk, groins, axillae, scalp, face, and various pressure points of the body [1]. These sites develop flaccid blisters that amalgamate and eventually rupture resulting in agonizing erosions. The addition of new blisters to adjacent skin upon slight pressure (direct Nikolsky) and shearing of the skin as a result of rubbing on normal skin (indirect Nikolsky) may be a suggestive sign of PV but not a 100% reliable diagnosis [1]. Other clinical manifestations are nail dystrophy, paronychia, subungual hematomas, and neonatal pemphigus vulgaris [1]. Additionally, association of the periungual areas can contribute to chronic perionyxis, onychomadesis, onychoschizia, and onycholysis [2]. Skin lesions are also predominantly found on areas with scars and radiotherapy.

There are three major and two minor criteria for the diagnosis of PV (Fig. 6.1). The three major criteria consist of the clinical picture, biopsy /histopathology, and direct immunofluorescence (DIF) . First, the dermatologist performs a comprehensive physical exam of the patient, paying close attention to clinical factors such as nonscarring, fragile vesicles, and bullae involving the mucosae and varying degree of cutaneous involvement [1]. Second, a biopsy of the most recent untreated lesional and perilesional skin is executed. Hematoxylin and eosin (H+E) analysis is conducted to differentiate the existence and degree of blistering or acantholysis. H+E analysis is best performed from tissues that can be sent for direct immunofluorescence testing to determine the presence of autoantibodies within the epidermis. Although PV lesions are typically paucicellular, the density, type, and amount of inflammatory infiltrate—particularly eosinophils—can contribute to determining a diagnosis of PV [1]. Individuals suffering from isolated mucosal disease must have the H+E and direct immunofluorescence executed on the lesional and perilesional biopsies to confirm for PV. Third, if the DIF shows deposition of immunoglobulin G (IgG) and (complement component 3) C3 on the epithelial cell surface, it is strongly indicative of PV. The two minor criteria consist of indirect immunofluorescence (IF) and enzyme-linked immunosorbent assay (ELISA) . Using IF, we also look for deposition of IgG and C3 on the epithelial cell surface, as it is strongly indicative of PV. The ELISA test can be utilized to measure the amount of anti-desmoglein 3 and 1 autoantibodies in the blood. These values are in general, but not perfectly aligned with the level of disease activity [1].