Paraneoplastic Pemphigus Clinical Presentation

Updated: Feb 07, 2019
  • Author: Lynne J Goldberg, MD; Chief Editor: Dirk M Elston, MD  more...
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Presentation

History

Paraneoplastic pemphigus is usually associated with malignancy, although it can occur in association with benign neoplasms. The most common malignancy associated with paraneoplastic pemphigus is non-Hodgkin lymphoma. [20, 21, 22] Other associated malignancies and conditions include chronic lymphocytic leukemia, Castleman disease, [23, 24, 25, 26] Waldenström macroglobulinemia, [27] thymoma, [24, 28] sarcoma, [28] , lung carcinoma, and malignant melanoma, [16] although this has been challenged. [29] It has been reported in a patient with HIV disease who was found to have intra-abdominal diffuse B-cell lymphoma. [30]

An association reported in 2009 is with systemic mastocytosis, [31] and an atypical case associated with endometrial carcinoma lacking mucosal involvement has been reported. [32] Paraneoplastic pemphigus can coexist with bullous pemphigoid [33] and has been reported to "shift" to pemphigus vulgaris, [34] although this is controversial.

Also see Non-Hodgkin Lymphoma (pediatric focus), Chronic Lymphocytic Leukemia, Waldenstrom Hypergammaglobulinemia, and Thymoma

Patients present with painful oral erosions, often accompanied by a generalized cutaneous eruption. Oral erosions occur early and typically are severe, often involving the lateral tongue and vermilion. The eruption can assume a wide variety of morphologies. A classification system has been suggested, dividing lesions into pemphiguslike, pemphigoidlike, erythema multiforme–like, graft versus host disease–like, and lichen planus–like. Additionally, some patients report pruritus or pain. Cases without mucosal involvement have been reported, especially with the lichen planus –like variant, although these patients lacked autoantibodies. [10]

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Physical Examination

Mucosal findings

The earliest and most constant clinical finding in paraneoplastic pemphigus is painful oral erosions. Of those patients who present with a skin eruption, all go on to develop mucositis at some point during the course of the disease. Some patients only experience oral lesions.

The erosions of paraneoplastic pemphigus can occur anywhere in the mouth, including the buccal, labial, gingival, and lingual mucosae. All surfaces of the oropharynx can be affected. Erosions and subsequent crusting on the vermilion of the lips are typical and similar to that seen in persons with Stevens-Johnson syndrome. In contrast to pemphigus vulgaris, where oral lesions are discrete, oral involvement by paraneoplastic pemphigus tends to be more diffuse. [6] . Paraneoplastic pemphigus also tends to affect the conjunctiva, unlike pemphigus vulgaris, and genital mucosal surfaces can also be affected. Finally, nasal ulcers can occur and may cause epistaxis.

Cutaneous findings

The eruption of paraneoplastic pemphigus is highly variable. Patients may present with diffuse erythema, vesiculobullous lesions, papules, scaly plaques, exfoliative erythroderma, erosions, or ulcerations. The erythema can be macular, urticarial, or targetoid, and it may be polymorphous. Patients may initially present with erythema, and they may subsequently develop bullae and erosions.

Large areas of denudation with a positive Nikolsky sign can occur. Pustules have been reported. The papular lesions may resemble lichen planus, and the oral lesions may also be mistaken for lichen planus. [35] A single patient has been reported with a solitary, pemphigus vegetans–like lesion that arose in a previous bulla. In addition to the pattern of mucosal involvement, clinical features distinguishing paraneoplastic pemphigus from pemphigus vulgaris include involvement of the palms and soles and sparing of the scalp in the former. [6]

A 2012 study on prognostic factors of paraneoplastic pemphigus found the presence of erythema multiforme–like lesions heralded a worse prognosis, especially if there was keratinocyte necrosis on biopsy and severe skin or mucosal involvement. [19]

Extracutaneous findings

Findings outside of the integument occur in approximately one third of patients. Biopsy-confirmed paraneoplastic pemphigus has been reported in the gastrointestinal tract and the respiratory tract mucosa. The latter has been increasingly recognized and is a significant cause of mortality. Pulmonary involvement manifests as obstructive lung disease and progresses to bronchiolitis obliterans and death. Despite its ominous significance, signs of pulmonary involvement are subtle. Patients develop dyspnea, yet chest radiograph findings are normal. However, pulmonary function testing reveals a severe obstructive pattern and decreased diffusion capacity. [36] Ocular involvement ranges from mild conjunctivitis to symblepharon with corneal scarring. [37] Muscle weakness can occur, and some patients develop myasthenia gravis. [38]

Correlation with pathogenesis

It has been suggested that patients with humorally mediated paraneoplastic pemphigus have a pemphigus vulgaris–like appearance, while cell-mediated disease appears more lichenoid. [39] Patients with lichenoid paraneoplastic pemphigus may lack autoantibodies or develop them later in their course. In addition, antibodies to certain antigens may correlate with disease manifestations, as patients without epiplakin antibodies do not develop bronchiolitis obliterans. [8]

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Complications

The main complication of paraneoplastic pemphigus is impaired skin barrier function, which can lead to localized infection, sepsis, and death. Additionally, painful oral and pharyngeal ulceration can interfere with eating, which can compromise nutritional status. Finally, involvement of respiratory tract epithelium can lead to respiratory insufficiency due to bronchiolitis obliterans and can result in death.

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