Affiliations

Advocate Children's Hospital

Abstract

Introduction/Background:

Fever of unknown origin (FUO) is a common pediatric presentation with a broad infectious and noninfectious differential. Histiocytic necrotizing lymphadenitis (HNL), also known as Kikuchi-Fujimoto disease (KFD), is a rare, self-limited condition characterized by prolonged fever and cervical lymphadenopathy. Diagnosis is often delayed due to nonspecific findings, with definitive confirmation requiring histopathologic evaluation. We describe a case of FUO and cervical lymphadenopathy ultimately diagnosed as HNL.

Description:

A 14-year-old female presented with one month of neck pain, tender cervical lymphadenopathy, and fevers. Initial outpatient treatment with amoxicillin-clavulanate did not result in improvement. Reevaluation demonstrated leukopenia and neutropenia, prompting hospital admission. On admission, the patient was well appearing, with examination notable for cervical lymphadenopathy. Infectious Disease, ENT, Hematology/Oncology, and Rheumatology were consulted. Extensive infectious evaluation-including blood cultures and testing for EBV, CMV, Bartonella, toxoplasmosis, parvovirus, HHV-6, tuberculosis, and Lyme disease-was negative. Evaluation for oncologic and rheumatologic processes, including hemophagocytic lymphohistiocytosis, was unremarkable aside from an elevated ANA. Abdominal and cervical imaging demonstrated multiple enlarged supraclavicular lymph nodes without abscess. The patient experienced intermittent fevers managed symptomatically without further antibiotics. Given improvement in leukopenia and neutropenia and overall clinical stability, she was discharged with outpatient follow-up. An outpatient cervical excisional lymph node biopsy confirmed HNL. Total fever duration was 23 days. She continues to do well under rheumatology care.

Discussion:Although generally benign and self-limited, HNL can recur and be associated with the development of systemic lupus erythematosus, necessitating longitudinal care. This case highlights the diagnostic challenges of HNL due to nonspecific features and overlap with serious etiologies such as lymphoma. Increased recognition of HNL as a cause of FUO may reduce unnecessary testing and delays in diagnosis.

Presentation Notes

Presented at Scientific Day; May 20, 2026; Milwaukee, WI.

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May 20th, 12:00 AM

The Node Knows: Histopathology as the Key to Fever of Unknown Origin in an Adolescent

Introduction/Background:

Fever of unknown origin (FUO) is a common pediatric presentation with a broad infectious and noninfectious differential. Histiocytic necrotizing lymphadenitis (HNL), also known as Kikuchi-Fujimoto disease (KFD), is a rare, self-limited condition characterized by prolonged fever and cervical lymphadenopathy. Diagnosis is often delayed due to nonspecific findings, with definitive confirmation requiring histopathologic evaluation. We describe a case of FUO and cervical lymphadenopathy ultimately diagnosed as HNL.

Description:

A 14-year-old female presented with one month of neck pain, tender cervical lymphadenopathy, and fevers. Initial outpatient treatment with amoxicillin-clavulanate did not result in improvement. Reevaluation demonstrated leukopenia and neutropenia, prompting hospital admission. On admission, the patient was well appearing, with examination notable for cervical lymphadenopathy. Infectious Disease, ENT, Hematology/Oncology, and Rheumatology were consulted. Extensive infectious evaluation-including blood cultures and testing for EBV, CMV, Bartonella, toxoplasmosis, parvovirus, HHV-6, tuberculosis, and Lyme disease-was negative. Evaluation for oncologic and rheumatologic processes, including hemophagocytic lymphohistiocytosis, was unremarkable aside from an elevated ANA. Abdominal and cervical imaging demonstrated multiple enlarged supraclavicular lymph nodes without abscess. The patient experienced intermittent fevers managed symptomatically without further antibiotics. Given improvement in leukopenia and neutropenia and overall clinical stability, she was discharged with outpatient follow-up. An outpatient cervical excisional lymph node biopsy confirmed HNL. Total fever duration was 23 days. She continues to do well under rheumatology care.

Discussion:Although generally benign and self-limited, HNL can recur and be associated with the development of systemic lupus erythematosus, necessitating longitudinal care. This case highlights the diagnostic challenges of HNL due to nonspecific features and overlap with serious etiologies such as lymphoma. Increased recognition of HNL as a cause of FUO may reduce unnecessary testing and delays in diagnosis.

 

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