Pemphigus vulgaris: an acquired blistering disease. (Case Report).

Abstract

Pemphigus vulgaris is one of a group of autoinunune disorders that are caused by autoantibodies against the desmoglein adhesion molecules of squamous epithelial cells. It is a rare form of immune dysfunction that can prove vexing to the patient and physician, but it has distinct clinical and histologic findings. We report a case of a patient with the autoimmune blistering disease pemphigus vulgaris localized to the oral cavity and discuss the important clinical, immunopathologic, and therapeutic factors of this disease. This case report highlights the unusual nature of pemphigus vulgaris, the modalities used in its diagnosis, and effectiveness of therapy. Pemphigus vulgaris is an uncommon disease blistering disorder due to desmoglein autoantibodies, whose presentation can be alarming and puzzling to the clinician. Awareness of the disease's presentation and mechanism will allow for an efficient diagnostic evaluation and timely treatment.

Key Words: desmoglein, paraneoplastic pemphigus, pemphigus, pemphigus foliaceous, pemphigus vulgaris

Pemphigus vulgaris (PV) is one of a group of unique, related blistering disorders that includes pemphigus foliaceous (PF) and paraneoplastic pemphigus (PNP). The incidence of PV in the United States is estimated at 0.42 per 100,000. (2) They are histologically characterized by suprabasilar acantholysis and immunopathologically characterized by autoantibodies to desmosomal cadherins. (1) In PF the autoantibody is to desmoglein 1 (Dsgl), in PV to desmoglein 3 (Dsg3). (3) The mechanism that initiates the formation of anti-DSG antibodies is unknown, but may be induced by medications, such as D-penicillamine, and may resolve once the inciting medication is withdrawn. In the past, untreated pemphigus had a very high mortality rate. (2,4,5) Therapy aimed at immunosuppression has reduced the mortality to 5 to 15%. Specifically, therapy with steroids has been the most significant factor in reducing the mortality of this disease, often in conjunction with other immunosuppressants such as cyclophosphamide, azathioprine , and mycophenolate as well as plasmapheresis. (2,4,5)

Discussion

As stated earlier, PV is one of a group of related blistering diseases. PV is the most common of this family, predominately seen in middle-aged and elderly Jewish patients. Characterized by the formation of flaccid blisters and erosions of the skin, the scalp is commonly involved, and oral cavity involvement is almost always present. Infants born to mothers with active PV may have similar lesions during the first few weeks of life due to persistent circulating maternal antibodies. Serum from PV patients, when tested on monkey esophagus using indirect immunofluorescent methods, will show antikeratinocyte IgG antibodies. Generally, they are antibodies to Dsg3. (1)

PE usually affects those of the same age group, and the lesions form scaling and crusting plaques on the trunk. Its endemic form in Brazil is referred to as Fogo Selvagem. (3) Oral lesions are uncommon, as are intact blisters. Serum from PV patients, when tested on guinea pig esophagus using indirect immunofluorescent methods, will show antikeratinocyte IgG antibodies to Dsg1. (1) In an interesting clue to possible environmental triggers in the endemic form of PF, anti-Dsg1 antibodies can be found in some healthy Brazilian control individuals. (3)

PNP occurs in patients with neoplastic illness, such as B-cell lymphomas, leukemias, and thymomas. They present with extensive, recalcitrant oral and skin lesions, and on immunofluorescence, have antibodies to monkey esophageal keratinocytes, heart, lung, and other desmosomes. A highly aggressive form of pemphigus, it is resistant to present therapies, often causing death via pulmonary complications. (3)

Therapy for PV and PF has markedly reduced their morbidity and mortality, though the mortality of PNP is still about 95%. (5) Current therapy involves the use of combinations of steroids (topical, oral, and IV), antimetabolites, and cytotoxic medications. 1-5 Unresponsive patients may be further treated with plasmaphoresis or immunophoresis. These medical regimens suffer from significant toxicity and morbidity, as well as significant expense. Patients and their physicians should be aware that injudicious use of these therapies can be worse than the disease. (5)

Accepted December 3, 2002.

References

(1.) Udey MG, Stanley JR. Pemphigus: Diseases of antidesmosomal autoimmunity. JAMA 1999;282:572-576.

(2.) Enk AH, Knop J. Mycophenolate is effective in the treatment of pemphigus vulgaris. Arch Dermatol 1999;135:54-56.

(3.) Anhalt GJ, Diaz LA. Prospects for autoimmune disease: Research advances in pemphigus. JAMA 2001;285:652-654.

(4.) Fleischli ME, Valek RH, Pandya AG. Pulse intravenous cyclophosphamide therapy in pemphigus. Arch Dermatol 1999;135:57-61.

(5.) Stanley JR. Therapy of pemphigus vulgaris. Arch Dermatol 1999;135:76-78.

RELATED ARTICLE: Key Points

* Pemphigus vulgaris is one of a group of related blistering diseases.

* This case report highlights the unusual nature of pemphigus vulgaris, the modalities used in its diagnosis, and the effectiveness of therapy.

* Awareness of the disease's presentation and mechanism allows for an efficient diagnostic evaluation and timely treatment.

Case Report

A 30-year-old black man presented with a 2-month complaint of pharyngitis and halitosis. He denied odynophagia, dysphagia, globus sensation, tonsillitis, herpes simplex or HIV infection, or recent therapy with antibiotics. He had been treated in the past for esophageal reflux, and was presently taking Prilosec. He denied use of tobacco products, occasionally consumed ethanol, and had no known drug or food allergies. He was an enlisted military service member, had not traveled outside his local area recently, and until recently was in good health. On oral examination he had superficial irregular ulcerations of the buccal mucosa covered by a fibrin clot (Fig. 1). There was no ocular, nasal, skin, nail, or genitourinary involvement. Laboratory testing included FTA-ABS, basic serum metabolic panel with liver function tests, urinalysis, complete blood count with differential, and herpes simplex titers were normal. His most recent HIV test was negative as well. Biopsy revealed chronically inflamed squamous mucosa with the distinct diagnostic pattern of suprabasilar splitting of the epidermis (Fig. 2, 3, 4).

From the Department of Otolaryngology-Head and Neck Surgery, Naval Medical Center, Portsmouth, VA, and the Department of Otolaryngology-Head and Neck Surgery, Naval Medical Center, Bethesda, MD.

Presented as a poster at the 95th Annual Scientific Assembly of the Southern Medical Society Meeting, Nashville, TN, November 8, 2001.

The authors are military service members. This work was prepared as part of their official duties. Title 17 U.S.C. 105 provides that copyright protection under this title is not available for any work of the United States Government. Title 17 U.S.C. 101 defines a United States Government work as a work prepared by a military service member or employee of the United States Government as part of that person's official duties. The views expressed are those of the authors and do not reflect the official policy or position of the Department of the Navy, the Department of Defense, or the United States Government.

Reprint requests to LCDR Kirby J. Scou, Department of Otolaryngology- Head and Neck Surgery, Naval Medical Center Portsmouth, Charette Health Care Center, 27 Effingham Street, Portsmouth, VA 23708-5000. Email: [e-mail]

Copyright [c] 2003 by The Southern Medical Association 0038-4348/03/9606-0618