Paraneoplastic Pemphigus: Further investigation in the Emergency Department included laboratory findings that consisted of a complete blood count (CBC) with differential and a chemistry panel, both within normal limits. A Dermatology consult was arranged at the time of the initial visit and a skin biopsy was performed. Since the patient appeared well and generally was able to tolerate oral liquid intake, even though there was a component of odynophagia, she was discharged to home on oral corticosteroids (prednisone [1mg/kg every other day]) and a medicated mouthwash (tetracycline [1.5g] and nystatin [3 X 10⁶ units] + hydrocodone [65mg] all mixed into a 500mL elixir of diphenhydramine [12.5mg/5mL]). As there was no evidence of bacterial superinfection of any of her skin lesions, no antibiotics were prescribed. Followup examinations were arranged with both the Dermatology clinic and the patient’s primary care physician.

The skin biopsy results demonstrated prominent interface change at the dermoepidermal junction, with intraepidermal and predominantly subepidermal vesicle and bulla formation. Numerous necrotic keratinocytes were also seen at all levels of the epidermis. Superficial perivascular and interstitial lymphocyte–predominant inflammatory infiltrates were present, including rare eosinophils. The histologic features were interpreted as suggestive of paraneoplastic pemphigus (PNP).

Autoimmune blistering diseases include pemphigus vulgaris, PNP, bullous pemphigoid, cicatricial pemphigoid, dermatitis herpetiformis, and linear immunoglobulin A (IgA) dermatosis. A rare condition, PNP usually has an onset at age 60 years or older and is more common in women than men. This disease is distinct from the classic forms of pemphigus and is characterized by extensive mucocutaneous erosions in the presence of a neoplasm, most often leukemia or lymphoma. Other neoplasms associated with PNP, both malignant and benign, include Waldenström macroglobulinemia, sarcomas, thymomas, and Castleman disease.

Patients with PNP often present with painful oral mucosal erosions accompanied by a generalized cutaneous eruption. The earliest and most common clinical finding in PNP, however, is painful oral erosions. The erosions can occur anywhere in the mouth, including the buccal mucosa, labia, gingiva, and lingual mucosa. The cutaneous eruptions may initially present with erythema but usually develop into bullae and erosions and can assume a wide variety of morphologies, including morbilliform, urticarial, bullous, papulosquamous, or a rash with lesions resembling those of erythema multiforme. Some patients report pruritus or pain over the area of the cutaneous involvement. In addition to oral involvement, biopsy-confirmed PNP has also been reported in the gastrointestinal tract and the respiratory mucosa. Involvement of the respiratory mucosa has been increasingly recognized, manifesting as obstructive lung disease that can progress to bronchiolitis obliterans and lead to significant morbidity and mortality.

On histopathologic examination, PNP appears to be a combination of pemphigus vulgaris and erythema multiforme. The suprabasilar acantholysis seen in pemphigus vulgaris is present, as well as basal cell vacuolation, lymphocytic exocytosis, and dyskeratotic keratinocytes typical of erythema multiforme. Interface dermatitis is frequently found in PNP, both with and without acantholysis. Exocytosis of inflammatory cells into the epidermis is common; the amount and the degree of exocytosis are directly proportional to the degree of dyskeratosis.

Direct immunofluorescence microscopy of the patient’s skin shows deposits of IgG and complement on the surface of the keratinocytes and other similar immunoreactants in the epidermal basement membrane zone to varying degrees. Patients with PNP have IgG autoantibodies against cytoplasmic proteins that are members of the plakin family (eg, desmoplakins I and II, bullous pemphigoid antigen 1, envoplakin, periplakin, and plectin), and against cell-surface proteins that are members of the cadherin family (eg, Dsg3). Immunoprecipitation and immunoblotting are the standard diagnostic tests for PNP because both of these techniques have comparatively higher specificities and sensitivities than indirect immunofluorescence (IDIF) testing. Unfortunately, neither test is widely available; however, they can be performed in some research settings.

Initially, patient care is aimed at treating superinfection, if present. Standard therapy with warm compresses, nonadherent wound dressings, and oral antibiotics is indicated. The administration of a potent immunosuppressive agent is required to decrease blistering, but this therapy can often be ineffective. In general, skin lesions are more responsive to therapy than mucosal lesions. Other therapeutic options include plasmapheresis and immunophoresis. In cases in which a solid neoplasm is the underlying malignancy leading to the rash, curative resection should be attempted when appropriate, but even this may not halt disease progression.

In general, the prognosis of PNP is poor; however, when the disease is associated with benign tumors, the prognosis is somewhat better. The mortality rate when PNP is associated with malignant tumors is estimated at 90%. Nearly all patients with the 2 most common associated tumors, non-Hodgkin lymphoma and chronic lymphocytic lymphoma, have a high mortality within 2 years of diagnosis. PNP is the only form of pemphigus that affects the epithelium of the respiratory mucosa, which manifests clinically as dyspnea in the setting of normal chest radiograph findings and can indicate a progression to bronchiolitis obliterans. The most recent estimates are that approximately one third of deaths from PNP are due to pulmonary insufficiency.



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