by Seniat Woldegiorgis, M.D., and Robert A. Swerlick, M.D., Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia

The purpose of this study was to review the course and management of pemphigus treated at a tertiary care center in the southeastern United States. Thirty (30) patients seen at the Emory Clinic from January 1992 to July 1999, participated in the study - 21 cases of PV and 9 cases of PF. There were 15 women and 15 men. PV was diagnosed in 12 women and 9 men, and PF was diagnosed in 3 women and 6 men. In the PV group, the mean age at onset was 50 (range, 30 to 72). The mean age of onset for PF was 52. The most common presentations were pain, sore throat and pruritus (itching).

A major concern of our findings was the delay of diagnosis associated with pemphigus. We observed that the average delay in diagnosis, in general, was six months, but with specific individuals the delay ranged up to 30 months. Although exact figures were not able to be collected, a number of patients required evaluations by three or more clinicians before they were accurately diagnosed. It is clear that a greater awareness of pemphigus and its manifestations would clearly benefit patients.

Conventional histology, particularly of chronically ulcerated lesions of the skin and mucosa, may yield findings that are nonspecific or, at best, supportive but not diagnostic of pemphigus. Immunoflourescence studies are ideally suited to making a specific diagnosis. In more than 95% of our patient population, immunoflouresence microscopy provided a diagnosis requiring only a serum sample.

Pemphigus is considered a potentially life-threatening disease. Before corticosteroids, mortality approached 100%. With steroid therapy, the rates markedly decreased. However, complications from the disease and its therapy are still extensive. Hospitalization was required in 47% of patients. We emphasize tapering of aggressive treatment as soon as possible. High doses of oral prednisone is consistently associated with significant weight gain, hypertension, and glucose intolerance. Avascular necrosis of the hip requiring total hip replacement occurred in two patients. They were both 42 years old and had no predisposing factors other than prednisone therapy. The first patient had taken a total of 19,800 mg of prednisone over a 29-month period. The second patient had taken 1,100 mg over 7 months before avasular necrosis developed.

Although used often, corticosteroid-sparing cytotoxic agents such as azathioprine or cyclophosamide have not been supported by controlled trials. Retrospective analysis of previous series is complicated by the bias to treat patients with more severe disease or coexisting conditions that make treatment with corticosteroids difficult. Despite this controversy, we believe early treatment with steroid-sparing agents is frequently justified because of the consistent morbidity associated with the prolonged high doses of corticosteroids that are required to control severe disease if used alone. 93% required adjuvant therapy.

A common complication of immunosuppressive therapy in pemphigus patients is secondary infection. In long-term corticosteroid use, oral condidiasis is well recognized and was the most common infection observed in our patient population. An additional, and common complication was the development of herpetic gingivostomatitis (HSV) (inflammation of the gums and other mucous membranes associated with the herpes virus). In 5 patients, viral cultures confirmed HSV infection, and in 2 the clinical appearance and response to antiviral therapy strongly suggested HSV stomatitis (gum and mucous membrane inflammation). The clinical presentation was generally abrupt worsening of stomatitis associated with severe pain that failed to respond to increased doses of corticosteroids. All these patients were successfully treated with oral famciclovir or valacyclovir. However, some required doses generally necessary for varicella-zoster (shingles and chicken pox) virus. We found that HSV frequently caused pemphigus complications, in spite of some case reports that suggest HSV will only cause problems occasionally. It is important to have high clinical suspicion in patients who are taking systemic corticosteroids and immunosuppressive drugs and who have lesions that do not clear with the standard therapies.

In summary, pemphigus affects patients from a variety of ethnic backgrounds living in the southeastern United States. Prompt and aggressive therapy is associated with good outcome, though the treatment is associated with significant morbidity. A greater awareness of this disorder by the general medical community will benefit this patient population by decreasing the significant diagnostic delay. Practitioners should consider the diagnosis of pemphigus in patients who have persistent stomatitis and/or a generalized erosive or crusted skin eruption and should refer such patients for evaluation by a dermatologist or an oral surgeon.

Key Points

• Pemphigus occurs equally in men and women, and it affects multiple ethnic groups.
• Diagnosis was delayed an average of 4.5 months to 6 months, depending on the variant. Diagnostic delay results in a delay in administration of appropriate treatment.
• Hospitalization was necessary in 47% of our patients.
• Thirty-three percent of our patients had a clinical or total remission.