PC1193: Fever, Fatigue and Ferritin of Forty-thousand

Introduction: Inflammatory diseases are conditions that are difficult to diagnose. They present with non-specific symptoms that may mimic viral or autoimmune conditions.

Case Description: We present the case of a 9-year-old male who presents with 8 days of fatigue and fever. Prior to admission he was treated unsuccessfully for streptococcal pharyngitis and admitted due to continued fever as well as findings of pleural and pericardial effusions on chest x-ray. On presentation he was found to have right cervical and bilateral inguinal lymphadenopathy. His lung exam was normal and there was no rash, hepatosplenomegaly or pedal edema.

He had leukocytosis (21.53x103/mcL) with elevated inflammatory markers including ESR (81mm/h) and CRP (25mg/dL) and Ferritin (9290 ng/mL). His Covid IgG was negative. Based on his elevated BNP, D-dimer, and Fibrinogen, he was treated with Intravenous Immunoglobulin (IVIG) for atypical Kawasaki Disease and/or MIS-C. He failed two rounds of IVIG and steroid therapy. Given his persistent elevation in ferritin (>40,000) and fever, a detailed workup was completed for Systemic Juvenile Idiopathic Arthritis, Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS) and malignancy. Laboratory workup showed elevated Triglycerides, absent NK activity and elevated IL2 receptor, IL-18 and CXCL9. His PET scan revealed hypermetabolic activity in cervical, axillary, inguinal, and splenic lymph nodes with mild pleural and pericardial effusion. On meeting the HLH criteria, Anakinra was started which showed significant improvement and the patient's fever subsided after 26 days. His final diagnosis was confirmed on lymph node biopsy-Hemophagocytic Lymphohistiocytosis secondary to Kikuchi-Fujimoto Disease

Discussion: Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare self limiting idiopathic inflammatory disease. It’s prevalence is higher in females and people of Asian and East European descent. The etiology of KFD is unknown although the Epstein-Barr virus (EBV), human herpesvirus types 6, 7, and 8, herpes simplex virus, and HIV, have been suggested as possible inciting agents.The overall prognosis is favorable with a benign course although potential association with sJIA and SLE has been reported. Our patient had elevated CXCL9 and IL18 which have genetic predisposition to sJIA therefore, he will need long term follow up with Rheumatology.

Conclusion: KFD presents with a constellation of non-specific symptoms that mimic many viral and autoimmune conditions making it challenging to diagnose. A high index of suspicion is needed when performing a workup for rheumatological disease.