Disseminated Herpes Simplex Virus Infection Presenting With Cytopenias in a Patient With Untreated Rheumatoid Arthritis.

Background: Disseminated herpes simplex virus (HSV) infection is an uncommon but serious condition, typically seen in immunocompromised hosts. Cytopenias, including neutropenia and thrombocytopenia, are rare manifestations, particularly in patients not actively receiving immunosuppressive therapy. Case Presentation: We report a 75-year-old female with a history of rheumatoid arthritis (RA), previously on methotrexate and low-dose prednisone, who presented with painful oral and genital ulcers, mucositis, and rapidly progressive bicytopenia (neutropenia and thrombocytopenia). Her recent brief reinitiation of methotrexate prompted evaluation for drug-induced cytopenias; however, methotrexate levels were undetectable. Extensive infectious, nutritional, rheumatologic, and hematologic workup revealed HSV positivity from oral and inguinal ulcers. Bone marrow biopsy showed no evidence of hematologic malignancy or aplasia. She was treated with intravenous acyclovir, leading to clinical improvement and recovery of blood counts. Discussion: This case highlights the diagnostic complexity of cytopenias in patients with autoimmune diseases. While methotrexate toxicity and Felty's syndrome were initially considered, the clinical trajectory and lack of supportive findings redirected focus to infectious causes. Disseminated HSV infection causing cytopenias is rare and often overlooked in immunocompetent or intermittently immunosuppressed patients. In this patient, immune dysregulation due to underlying RA and advanced age likely contributed to HSV dissemination and bone marrow suppression. Conclusion: Clinicians should maintain a high index of suspicion for disseminated HSV in patients with autoimmune diseases presenting with mucocutaneous lesions and cytopenias, even in the absence of significant immunosuppressive therapy. Prompt recognition and antiviral therapy are critical to prevent complications and improve outcomes.