Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBV-MCU) is an indolent, self-limited, and localized entity distinct from other EBV-associated disorders. It occurs exclusively in patients with immunodeficiency states, including primary immune disorders, AIDS, age-related immunosenescence, post-transplantation states, and iatrogenic immunosuppression. In the latter context, associated immunomodulating agents include methotrexate, cyclosporin, cyclophosphamide, tacrolimus, azathioprine, mycophenolate, tumor necrosis factor (TNF)-alpha inhibitors, and topical glucocorticoids.

EBV-MCU has a slight female predominance and a reported median patient age of 66.4 years. Mucosal ulcers are the most common lesions in EBV-MCU, and the vast majority occur in the oropharyngeal mucosa. Symptoms include odynophagia and secondary anorexia. Involvement of the gastrointestinal (GI) tract is also documented, with ulcers identified within the esophagus, ileocolic region, and anorectal mucosa. Cutaneous ulcers have been reported in labial skin, as well as on the chest and arms. The majority of cases present with a solitary ulcer; however, instances of multifocal disease have been reported.

EBV-MCU typically produces a waxing and waning clinical course, and exacerbations may be seen when maintaining or increasing immunomodulating agents in the context of iatrogenic immunosuppression.

The exact pathophysiology is unclear. Immunodeficiency states in patients with latent EBV infection are postulated to shrink the EBV-sensitized T-lymphocyte repertoire, leading to a local EBV-driven lymphoproliferative response with preserved systemic viral dormancy.