Paraneoplastic pemphigus (PNP) typically affects middle-age patients but it can rarely occur in children. There is no racial or ethnic predilection and the incidence is equal in males and females.
The most constant clinical feature of this disorder is intractable stomatitis consisting of erosions and ulceration of all surfaces of the oropharynx, including the lips. In fact, this may be the only disease manifestation. Other mucous membranes such as the conjunctival, esophageal, laryngeal, tracheobronchial, nasopharyngeal, oropharyngeal, vaginal, and penile mucosa may be involved. Cutaneous lesions are varied and can include tense bullae resembling bullous pemphigoid, erosions resembling pemphigus vulgaris, target lesions resembling erythema multiforme, lichenoid lesions resembling lichen planus, or arcuate/bullous lesions resembling linear IgA dermatosis. Involvment of the palms and soles with bullae and lichenoid lesions is common and helps to distinguish PNP from other disorders. PNP is associated with either benign or malignant neoplasms in all cases. Non-hodgkin’s lymphoma is the most commonly associated tumor.
Histopathologic exam demonstrates features of both pemphigus vulgaris and erythema multiforme with suprabasilar acantholysis, basal cell vacuolization, dyskeratotic keratinocytes, and a lichenoid or perivascular mononuclear cell dermal infiltrate. Direct immunofluorescence is positive for intercellular IgG as well as intercellular C3 and granular/linear C3 along the basement membrane zone. Indirect immunofluorescence typically demonstrates circulating IgG that binds to both stratified and nonstratified squamous epithelium. This is in contrast to pemphigus vulgaris in which indirect immunofluorescence is positive only on stratified squamous epithelium or mucosal substrates. Thus, to distinguish PNP form PV or PF, one must use both types of epithelia as substrates.
PNP is an acquired autoimmune disorder that occurs secondary to the formation of IgG antibodies that interact with three different types of antigenic targets. These include 1) the plakin proteins (cytoplasmic plaque proteins that link the keratin intermediate filaments to the cell surface), 2) a 170 kDa transmembrane protein, and 3) desmogleins 1 and 3. These autoantibodies may be detected by immunochemical techniques such as immunoprecipitation.
Patients with benign tumors that have been surgically excised typically improve substantially or clear completely. In contrast, patients with malignant neoplasms tend to follow a rapidly progressive and invariably fatal course.