Systemic Lupus Erythematosus Masquerading as Non-Hodgkin Lymphoma

Introduction: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with diverse clinical manifestations, often involving multiple organs. Non-Hodgkin lymphoma (NHL) has been observed in SLE patients, typically as a long-term effect of immunosuppressive therapy. This case presents a scenario where NHL pre-dates and complicates the diagnosis of SLE. Case Description: A 41-year-old male with a history of NHL treated with R-CHOP in 2021 presented with one month of fever, weight loss, and generalized weakness. Suspected lymphoma recurrence prompted further evaluation. Vitals were notable for temperature 100.6°F, BP 117/77 mmHg, and HR 115 bpm. Exam revealed painless right axillary lymphadenopathy. Labs showed leukopenia (1.78 K/µL), hyperferritinemia (7529 ng/mL), transaminitis (AST 185 U/L, ALT 337 U/L), and hypertriglyceridemia (277 mg/dL), raising concern for hemophagocytic lymphohistiocytosis (HLH). PET scan revealed extensive lymphadenopathy. Right axillary lymph node biopsy demonstrated reactive changes without malignancy. Bone marrow biopsy excluded HLH. Infectious work-up was negative. Autoimmune testing showed ANA 1:40, elevated anti-Smith antibodies (6.4 AI), low complement levels (C3 34 mg/dL, C4 8 mg/dL), with negative anti-dsDNA, SSA/SSB, and RNP. The patient developed acute kidney injury and nephrotic-range proteinuria. Renal biopsy revealed lupus nephritis class V with features of class III. He was treated with IV methylprednisolone, mycophenolate mofetil, and hydroxychloroquine. Discussion: This case presents a diagnostic challenge: was the patient's initial NHL diagnosis in 2021 accurate, or was it an early manifestation of SLE? It is possible the lymphoma diagnosis was a misinterpretation of SLE-related lymphadenopathy. The R-CHOP treatment for NHL may have inadvertently controlled aspects of SLE, maintaining remission but with side effects. This case emphasizes the need for a broad differential diagnosis, especially in patients with a history of lymphoma and nonspecific symptoms such as fever, weight loss, and lymphadenopathy. It also highlights the diagnostic challenges of overlapping autoimmune and hematologic conditions, underscoring the need for comprehensive evaluation in complex cases.