Virtually all patients with this deep form of pemphigus first present with painful, nonhealing ulcerations in the mouth. Blisters are rare (Fig. 23-2), as they rupture soon after forming to leave an ulcerated area (Fig. 23-3). Ulcerations are usually multiple, superficial, and irregular in shape, and arise from mucosa of healthy appearance. Although any surface can be involved, the most common sites are the buccal and labial mucosa, the palate, and the tongue (Fig. 23-4). The ulcers of PV do not heal, in contrast to the oral lesions of aphthous stomatitis or viral infections that heal over days to weeks. Ulcers are also multiple, which differentiates them from an ulcerated tumor, which is single.

Because the disease is rare, PV is not often diagnosed at a first examination, but rather considered only after lesions have been present for weeks to months and the patient has not responded to antibiotic, antifungal, or antiviral therapy. PV should be considered in anyone who has multiple, nonhealing oral ulcers that persist for longer than a month.

The condition progresses over weeks to months with lesions developing on the skin and symptoms indicating nasal and esophageal involvement. Occasionally, such skin lesions are the initial manifestations. They usually begin as small blisters filled with a clear fluid, arising from normal-appearing skin. The blisters are typically flaccid because the overlying epidermis is thin and cannot sustain much pressure. Because they are thin, the blisters rupture in several days, and are replaced by well-demarcated, coin-sized, superficial erosions with a surrounding collar of loose epidermis (Fig. 23-1). Lesions appear most often on the scalp, upper chest, and back and have predilection for the medial portion of the torso rather than the sides. The face and neck are also commonly involved, but any surface covered by stratified squamous epithelium can be affected.

Sites that are often missed on examination include the periungual areas; the pharynx and larynx, indicated by pain on swallowing food and by hoarseness; the nasal cavity, manifested by nasal congestion and morning mucous discharge; and the cervix.

Nikolsky sign: a characteristic mechanical feature of all forms of active and severe pemphigus is the Nikolsky sign, in which firm, sliding pressure on normal-appearing skin causes separation of the epidermis from the underlying dermis. This sign is elicited most easily adjacent to an active lesion.

In this superficial form of pemphigus, there is insufficient overlying tissue to trap fluid and cause blister formation. Lesions typically start with multiple, pruritic, crusted, coin-sized patches on the upper torso, face, and scalp (Fig. 23-5). They arise from healthy-looking skin and are likened to cornflakes. The crusts can be removed easily, leaving superficial erosions. Untreated lesions do not heal, and increase in number over weeks to months. Lesions can become confluent to resemble exfoliative dermatitis in severe cases. Notably, oral involvement in PF is rare, in contrast to that seen in deep PV.

Certain drugs can trigger both PV and PF (Table 23-1). Though uncommon, this possibility should be excluded in all patients with newly diagnosed disease.
The clinical, histological, and immunofluorescence abnormalities of drug-induced and idiopathic pemphigus are similar. The most commonly implicated drugs contain sulfhydryl groups and include penicillamine and the angiotensin-converting enzyme inhibitors, such as captopril. In contrast to other drug-induced eruptions, DIP may not develop for up to several months after initiation of treatment with the offending agent. Most patients with DIP have a good prognosis and clear with adequate therapy and discontinuing of the causative agent.

Diagnosis is based on three independent sets of criteria: clinical features, histology, and immunologic tests.

Pemphigus must be differentiated from the many other conditions that also cause skin blisters or oral ulcers and erosions (Table 23-2) (Figs. 23-6 to 23-10). Blisters arise as a sign of many other autoimmune, genetic, and metabolic diseases:

PNP is sometimes judged as a variant of pemphigus because it is associated with acantholysis and with antibodies against desmoglein 1 and 3; it is usually associated with an occult lymphoproliferative neoplasm (especially B-cell lymphoma/leukemias, thymomas, and Castleman tumors), however, and may be considered a separate disease:

This disease is generally progressive and often fatal within 2 years if associated with a malignant neoplasm. Treatment of the underlying malignancy does not influence the skin disease, although treatment of associated benign neoplasms does lead to resolution of PNP.

Many factors that aggravate pemphigus should be avoided. These include dental work, sun exposure, radiographs, stress, and trauma. Disease flares following dental work are common enough to merit prophylactic administration of 20 mg/d prednisone (in addition to the patient’s normal requirement) for 5 to 7 days, for each dental procedure associated with trauma to the gums. Patients should also be instructed to avoid unnecessary exposure to the sun and to use broad-spectrum sun-protective creams and clothing.

The clinical course of PV is rather unpredictable, but invariably chronic. Several factors direct the clinical outcome: age of onset, severity of disease, response to systemic corticosteroids, and disease progression. Typically, however, bullae and erosions will spread if left untreated (Fig. 23-1). As with burns, these lesions when widespread can be complicated by metabolic disturbances or severe infection and sepsis, which are leading causes of death. Before the advent of systemic corticosteroids, about 75% of patients who developed PV died within a year. With treatment, however, lesions heal with crusting followed by re-epithelialization. There is no scarring, although transient residual hyperpigmentation can occur at sites of former lesions. Most patients with PV eventually enter a phase of partial remission in which they can be maintained, lesion-free, with minimum (<15 mg/d prednisone) doses of corticosteroids, or achieve complete remission in which they are lesion-free and require no therapy. Unfortunately, the immunosuppressive therapy is also a major contributor to the development of infections of the denuded epithelium and the resultant fatal sepsis that often claims the lives of PV patients.

The prognosis of untreated PF is better than that of PV, mostly due to the superficial nature of the lesions, and because of the lower risk of infection, fluid loss, and metabolic disturbance. The treatment, however, is no easier, because the doses of drugs needed to control PF are similar to those used for PV.