Customize your JAMA Network experience by selecting one or more topics from the list below.
Pemphigus vulgaris (PV) is a rare immunobullous disorder characterized by acantholysis and intraepithelial blister formation involving the skin and mucous membranes. Esophageal involvement in pemphigus is relatively common yet often underrecognized.1 We present images in a case report of endoscope-induced esophagitis dissecans superficialis (EDS) in a patient with PV with gastrointestinal symptoms and absence of cutaneous disease.
A woman in her 50s with a 6-month history of oral ulcers was evaluated in the outpatient dermatology clinic. She also complained of dysphagia, odynophagia, bloating, nausea, food aversion, and weight loss. On examination, there were 2 small oral erosions involving the left posterior buccal mucosa with no other associated skin findings. She was referred to gastroenterology for esophagogastroduodenoscopy (EGD), which showed a normal-appearing esophagus and stomach except for epithelial sloughing resulting from minor endoscopic pressure—a finding consistent with EDS (Figure 1).
Esophageal mucosal sloughing (esophagitis dissecans superficialis) resulted from minor endoscopic instrument pressure, a mucosal finding analogous to Nikolsky sign in skin.
Histopathological examination of esophageal biopsy specimens demonstrated separation of the mucosa from submucosal layer with suprabasal epithelial acantholysis and retained basal keratinocytes along the submucosal surface imparting a characteristic “tombstone” appearance. Direct immunofluorescence (DIF) examination revealed strong netlike IgG cell surface antibody staining (Figure 2), including IgG4, and C3 cell surface reactivity. Serological testing for desmoglein 1 and 3 antibodies by enzyme linked immunosorbent assay showed an increased IgG desmoglein 3 antibody level (63 U/mL). Together, these findings were consistent with a diagnosis of PV. Treatment with oral prednisone, 40 mg/d, and mycophenolate mofetil, 1500 mg twice daily, was initiated.
Direct immunofluorescence of the distal esophageal mucosa shows prominent IgG epithelial cell surface staining of cells in the lower epithelium involving basal cells (original magnification ×40).
Pemphigus is an immune-mediated disease in which binding of autoantibodies to desmoglein 1 and/or desmoglein 3 induces acantholysis with blistering of mucous membranes and skin. Desmoglein 3 is predominantly expressed throughout mucous membrane epithelium, and IgG desmoglein 3 antibodies predominate in patients with PV and mucosal involvement. Oral lesions develop in 90% of patients with PV and precede the development of skin lesions in 70% of cases.2
Involvement of the esophagus in PV results in significant morbidity, but the prevalence of esophageal involvement is unclear.2 In a study of 28 consecutive patients with PV who underwent upper endoscopy, 19 (68%) of the patients had endoscopic evidence of PV (eg, ulcers, erosions, or blisters).1 The authors reported a strong correlation between esophageal symptoms and endoscopic findings, and all 28 patients had positive DIF findings of pemphigus. Importantly, no procedural or biopsy-related complications were observed. The percentage of patients with PV and esophageal involvement ranges between 42% and 87.5% in other studies.3,4 Larger studies are necessary to determine the prevalence of esophageal involvement in the PV population.
Esophageal involvement in PV is associated with EDS, or “sloughing esophagitis,” first termed in 1892 to describe sloughing of the mucosal layer of the esophagus.5 Kaplan et al6 described the first case of EDS in a patient with PV and positive DIF findings. Although the cause of EDS is unknown, it often is triggered by immune-mediated or physical factors—a finding analogous to Nikolsky sign. We describe a patient with PV with esophageal involvement and induction of EDS by instrumentation during endoscopy, thus highlighting the importance of discussing this consideration with gastroenterologists prior to endoscopic evaluation.
In summary, esophageal involvement occurs in patients with PV, who often present with nonspecific gastrointestinal symptoms. Clinicians should have a low threshold for endoscopic examination referral of patients for whom there is suspicion of immunobullous disease. Suitable tissue handling (ie, Michel’s medium for biopsy transport of specimens for DIF examination) should be discussed with the endoscopist in advance. This case underscores the important role endoscopy plays in establishing a diagnosis, providing direct visualization of the esophagus and facilitating biopsy for histopathologic and DIF analyses.
Corresponding Author: Kristin M. Leiferman, MD, Department of Dermatology, University of Utah, 30 N 1900 E, Room 4A330, School of Medicine, Salt Lake City, UT 84132 (Kristin.Leiferman@hsc.utah.edu).
Published Online: May 4, 2016. doi:10.1001/jamadermatol.2016.1007.
Conflict of Interest Disclosures: None reported.
Additional Contributions: We would like to thank the staff of the University of Utah Department of Dermatology, Dermatopathology, and Immunodermatology Laboratories for their technical assistance in preparing the patient tissue specimens for microscopic evaluation. They received no compensation for their contributions but for that received in the normal course of their employment.
Braunberger T, Hawkes JE, Clarke JT, Boynton KK, Leiferman KM. Esophagitis Dissecans Superficialis Endoscopically Induced in a Patient With Pemphigus Vulgaris and Gastrointestinal Complaints. JAMA Dermatol. 2016;152(8):948–950. doi:10.1001/jamadermatol.2016.1007
Create a personal account or sign in to: