We report the case of a 31-year-old woman with systemic lupus erythematosus who was found to have oral hairy leukoplakia (OHL). She was on immunosuppressive therapy but was human immunodeficiency virus (HIV)-negative. OHL has been previously reported in HIV-negative patients who were immunosuppressed for other reasons, such as solid organ or hematopoietic stem cell transplantation, hematologic malignancies, or systemic diseases. To the best of our knowledge, this is the first case of OHL in an HIV-negative patient reported in the otolaryngology literature. It adds to the growing list of cases of OHL in HIV-negative patients and serves as a reminder to physicians to include OHL in the differential diagnosis for oral cavity lesions in all immunosuppressed patients. The article also summarizes the current state of knowledge about the pathogenesis of OHL, its relation to the Epstein-Barr virus, and the treatment options.
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