Kikuchi-Fujimoto disease with hemophagocytic lymphohistiocytosis in children: a seven-patient case series

Background Kikuchi-Fujimoto disease, also known as histiocytic necrotizing lymphadenitis (HNL), is typically self-limited but may be complicated by hemophagocytic lymphohistiocytosis (HLH) and may coexist with autoimmune disease, particularly systemic lupus erythematosus (SLE). Pediatric HNL-HLH is rare, and detailed data on pathology, HLH-2004 criteria, immune profiles, acute-care requirements, and subsequent autoimmune diagnoses remain limited. Methods We retrospectively reviewed children with biopsy-confirmed HNL who fulfilled at least five of eight HLH-2004 criteria at Guangzhou Women and Children’s Medical Center from January 2020 to December 2025. We summarized patient-level clinical, laboratory, immunological, pathological, treatment, acute-outcome, and follow-up data. Results Seven children were included (four boys; median age, 7 years; range, 1–13 years). Three patients met seven HLH-2004 criteria, two met six, and two met five. Fever, ≥2-lineage cytopenia, hyperferritinemia, and hypertriglyceridemia and/or hypofibrinogenemia occurred in all patients. Antinuclear antibody was positive in three patients, and complement C3 and/or C4 levels were low in four. Admission peripheral-blood natural killer (NK)-cell proportions were below the local reference range in five patients (range, 1.11%–9.83%). Four patients required pediatric intensive care, and three underwent plasma exchange. At discharge, complete remission was documented in six patients and partial remission in one; no in-hospital deaths occurred. Six patients had post-discharge follow-up (median, 23.5 months; range, 7–73 months), with no documented HLH recurrence. SLE was diagnosed in three patients during the index hospitalization, at 6, 11, and approximately 92 days after admission. Conclusion This seven-patient series documents intensive-care requirements in four children with HNL-HLH and clinical SLE diagnoses in three during the index hospitalization. These observations highlight the importance of pathological confirmation, assessment of hyperinflammatory severity, and rheumatologic follow-up when autoimmune features are present. Larger multicenter studies are needed to clarify the prognostic and therapeutic implications of immune-profile abnormalities.