A Case of Systemic Lupus Erythematosus Initially Presenting With Generalized Lymphadenopathy: A Diagnostic Challenge

Lymphadenopathy (LAD) can emerge as an initial manifestation of systemic lupus erythematosus (SLE); however, establishing an accurate differential diagnosis remains challenging due to the wide spectrum of infectious, malignant, and autoimmune conditions associated with this presentation. We report the case of a 47-year-old man admitted with a two-month history of persistent fever (approximately 38 °C), night sweats, chills, and diffuse generalized lymphadenopathy. Physical examination revealed enlarged, mobile, non-tender, soft cervical, axillary, and inguinal lymph nodes measuring approximately 2-3 cm in diameter, along with hepatomegaly and splenomegaly. An extensive diagnostic workup was initially undertaken to exclude malignant and infectious causes. Two weeks after admission, the patient developed inflammatory arthritis, hemolytic anemia, severe thrombocytopenia, leukopenia, and lymphopenia. Given the evolving clinical findings, SLE was suspected, and comprehensive lupus-specific serological testing confirmed the diagnosis. The patient fulfilled the 2019 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for SLE based on immunological abnormalities and multisystem involvement. Treatment with high-dose corticosteroids, intravenous immunoglobulin, and immunosuppressive therapy led to significant clinical improvement. This case underscores that extensive generalized LAD may represent an initial presentation of SLE and should be included in the differential diagnosis of patients presenting with LAD and constitutional symptoms.