Esophageal Pemphigus Vulgaris

The term “pemphigus” refers to a group of autoimmune blistering diseases of the skin and mucous membranes characterized histologically by intradermal blisters and immunopathologically by the detection of in vivo bound and circulating immunoglobulin (Ig)G antibodies directed against the cell surface of keratinocytes. Although pemphigus vulgaris (PV), pemphigus foliaceus, and paraneoplastic pemphigus make up the three primary subgroups of pemphigus, PV accounts for approximately 70% of pemphigus cases.^1–4

Blisters in PV are associated with the binding of IgG autoantibodies to keratinocyte cell surface molecules. Tese intercellular or PV antibodies bind to keratinocyte desmosomes and desmosome-free areas of the keratinocyte cell membrane, resulting in a loss of cell-cell adhesion, a process termed “acantholysis.”^1,5

The incidence of PV varies from 0.5 to 3.2 cases per 100,000, with an approximately equal male-to-female ratio.⁶ PV is a potentially life-threatening disease, with a mortality rate of approximately 5–15%. Complications secondary to the use of high-dose corticosteroids contribute to the mortality rate. Morbidity and mortality are related to the extent of disease, the maximum dose of systemic steroids required, and the presence of other diseases. Prognosis is worse in older patients with extensive disease.^1,6

Symptomatic involvement of stratified squamous epithelial mucosa, especially the oral mucosa, is observed in nearly all subjects during the course of the disease and in approximately 50% of cases at onset. The pharyngo-laryngeal, genital, anorectal, and conjunctival mucosa are less commonly involved.⁷

Esophageal involvement is rarely reported or discussed in the literature,⁸ perhaps due to its lack of detection or misdiagnosis and subsequent treatment with an inappropriate reduction of steroid dosage. The lack of esophageal PV reports may also be partially due to the low prevalence of PV activity at this site, or possibly, the initial examination's failure to focus on the esophagus.

Odynophagia and dysphagia are the usual complaints in patients with esophageal pemphigus, as well as in herpetic esophagitis or candidiasis of the esophagus. Bleeding from esophageal pemphigus appears to be quite rare. The usual clinical manifestations of esophageal PV include blisters, erosions, and erythema. Esophagoscopy together with brush cytology, biopsy, and direct and indirect immunofluorescence are the most definitive methods of diagnosis.^7,9

It is likely that asymptomatic esophageal involvement is more prevalent than previously recognized. Since 1970, only approximately 60 cases of esophageal pemphigus have been reported in the literature, although in 1892 Rosenberg had already coined the phrase “esophagitis dis-secans superficialis” in reference to healthy subjects with esophageal sloughing, and in 1935 Patterson first documented esophageal involvement in pemphigus. In only very few cases have the subjects dramatically sloughed the entire mucosal lining of the esophagus.^9,10

Systemic corticosteroid therapy is effective at reducing or eliminating the clinical manifestations of PV, with as high as 400 mg of prednisone being administrated daily for patients with severe involvement. Topical corticosteroids can be used as an adjunct therapy if the bullae are confined to oral mucosa. Oral or intravenous administration of cyclophosphamide, azathioprine, cyclosporine, and methotrexate may allow the reduction of corticosteroid dosage. Even with immunosuppressive therapy, up to 10% of patients die from their disease, because of electrolyte loss, wound infection, or treatment complications.¹¹

The case reported by Houghton and colleagues is interesting for several reasons.¹² First, the patient presented twice with an uncommon symptom, hematemesis, although odynophagia was noted initially, and in the first episode, bleeding occurred while the patient was under proper treatment. The course of the disease was atypical, as was the relative oral mucosa sparing.

Second, the patient's esophagogastroduodenoscopy revealed circumferential erythema and excoriation involving almost the entire esophagus, from 2 cm below the upper esophageal sphincter to the gastroesophageal junction. This description, along with the accompanying figures, is very similar to the esophagitis dissecans superficialis mentioned above. It is very rare for PV to affect the entire esophagus, resulting in complete sloughing of the mucous membrane.

Third, the bleeding was caused by a distal esophageal ulcer. A gastroesophageal junction ulcer is an unusual endoscopic feature of PV. Typically, it can be found in patients who take alendronate or have gastroesophageal reflux disease.¹³ Interestingly, alendronate has been reported to be associated with esophagitis dissecans superficialis. Despite the lack of evidence shown by the histologic examination for specific alendronate-associated injury (polarizable crystalline foreign material, which occurs in 60% of cases, and multinucleated giant cells, which occur in 30% of cases), it is conceivable that the concomitant use of this medication with alendronate resulted in synergistic damaging effects. The PV esophagus may be regarded as a site predisposed to pill-induced injury, supporting the consideration for the reintroduc-tion of alendronate.

Fourth, hemostasis was achieved by the application of endoclips.

In summary, the case reported by Houghton and associates is an extremely unusual instance of PV that involved the entire esophagus with relative sparing of oral mucosa, presented as hematemesis due to a bleeding gastroesophageal junction ulcer, and was successfully treated medically and endoscopically.