The most constant clinical feature of the disease is the presence of intractable stomatitis (Figs. 55-2A and 55-2B). It is the earliest presenting sign and the one feature that persists throughout the course of the disease, even after treatment and is extremely resistant to therapy. This finding is so consistent that in its absence, PNP should not be considered in the differential diagnosis.
A. Extensive erosions involving the vermillion of the lips in a patient presenting with paraneoplastic pemphigus and an occult lymphoma. The characteristic severe stomatitis, accompanied by polymorphous cutaneous lesions, is the most consistent feature of the disease. B. Painful ulcerations tend to localize to the lateral border of the tongue. C. Lesions of the trunk from the same patient pictured in A. Erythematous macules and papules coalesce and become erosive on the upper chest as the cutaneous lesions evolve. D. Lesions from the forearm of the same patient. These lesions clinically resemble erythema multiforme, but biopsy shows a mix of individual cell necrosis, interface change, and acantholysis.
This stomatitis consists of erosions and ulcerations that can affect all surfaces of the oropharynx. The lesions differ from those seen in pemphigus vulgaris in that they show more necrosis and lichenoid change. They also preferentially localize to the lateral borders of the tongue, and characteristically extend onto and involve the vermilion of the lips. Occasionally, oral lesions are the only manifestation of the disease.
The cutaneous lesions of PNP are quite variable, and different morphologies may occur in an individual patient according to the stage of the disease (see Fig. 55-2C and 55-2D). The initial patients reported with the syndrome had episodes of waves of blistering affecting the upper trunk, head and neck, and proximal extremities. These lesions consisted of blisters that ruptured easily, leaving erosions. The blisters on the extremities were sometimes quite tense, resembling those seen in bullous pemphigoid, or they had surrounding erythema, clinically resembling erythema multiforme (see Fig. 55-2D). On the upper chest and back, confluent erosive lesions can develop, producing a picture resembling TEN. The similarity of the mucocutaneous features to erythema multiforme and TEN explains why this is the most common differential diagnosis for PNP. However, it is important to note that erythema multiforme and TEN are self-limited events that evolve and resolve over several weeks, whereas PNP is a relentlessly progressive and evolves continuously over months.
Cutaneous lichenoid eruptions are very common, and they may be the only cutaneous signs of the disease, or may develop in lesions that had previously been blistered. When cutaneous lichenoid lesions are present, severe stomatitis is also invariably present. In the chronic form of the disease and after treatment, this lichenoid eruption may predominate over blistering on the cutaneous surface. The common presence of both blisters and lichenoid lesions affecting the palms and the soles as well as the paronychial tissues helps to distinguish PNP from pemphigus vulgaris, in which acral and paronychial lesions are uncommon.
There are a small number of patients who appear to have PNP but who do not have demonstrable circulating autoantibodies.11 These patients tend to have predominantly lichenoid skin and mucosal lesions, but behave in every other way like antibody-positive patients. They have the same underlying neoplasms, and frequently develop bronchiolitis obliterans. Because the definition of the disease relies so heavily on demonstration of the specific autoantibody markers, further study is required to determine the exact classification of what is presently termed the lichenoid variant of PNP.
The disease has also been identified in a horse and two dogs. In animal species, the disease is associated with the same neoplasms and has the same clinical outcomes.12
Related Clinical Findings
PNP is the only form of pemphigus that involves nonstratified squamous epithelium. Approximately 30%–40% of cases develop pulmonary injury, often with a fatal outcome.13 The earliest symptoms are progressive dyspnea associated initially with an absence of findings on chest radiography. Pulmonary function studies show airflow obstruction in large and small airways. Inflammation of the large airways evolves and is evidenced by endoscopic biopsy showing acantholysis of bronchial respiratory epithelium. Pulmonary function deteriorates in most cases despite immunosuppressive therapy, and radiologic, histologic, and functional changes characteristic of bronchiolitis obliterans develop.