When fever lingers, think beyond the usual: Consider Kikuchi-Fujimoto disease

Anne Prewina Gurushekar¹, Kausalya²

¹Consultant Pediatrician, Kauvery Hospital, Tirunelveli, Tamil Nadu

²Duty Medical Officer, Kauvery Hospital, Tirunelveli, Tamil Nadu

Introduction

Kikuchi-Fujimoto Disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare, self-limiting, and enigmatic inflammatory condition most often seen in young adults, particularly women of Asian descent. Its exact pathogenesis remains unclear, though it is generally believed to involve an exaggerated T-cell–mediated immune response to an unidentified antigen, often viral in origin. Pediatric cases are especially rare and frequently underdiagnosed, making early detection difficult and misdiagnosis common.

Case Presentation

A previously healthy 5-year-old boy presented with a 20-day history of continuous high-grade fever and gradually enlarging, painful lymph nodes in the neck and inguinal regions. Prior treatment at multiple hospitals with oral antibiotics (amoxicillin-clavulanate and cefpodoxime) showed no clinical response. There was no history of fatigue, weight loss, or reduced appetite.

Three years earlier, he had a similar episode of generalized lymphadenopathy and fever that resolved over two months with antibiotics.

The child had no significant birth, past medical, or surgical history, and there was no family history of autoimmune or lymphoproliferative disorders.

On examination, he was alert and active. Multiple bilateral jugulodigastric lymph nodes were palpable, the largest measuring 2 × 1 cm on the right, and were tender. Inguinal lymphadenopathy (2 × 1.5 cm, bilateral) and bilateral axillary nodes were also palpable. Hepatomegaly was noted, while cardiovascular, respiratory, and neurological examinations were normal.

Laboratory investigations revealed leukocytosis with lymphocytosis and monocytosis. CRP was elevated. Peripheral smear showed normocytic, normochromic red cells. Mantoux test, Monospot test, and Gene Xpert for tuberculosis were negative. Brucella IgM was negative, though IgG was positive; blood cultures showed no growth. The child received intravenous ceftriaxone during admission without improvement.

Neck ultrasound revealed multiple necrotic cervical lymph nodes at bilateral levels Ib, II, and III, the largest being 2.0 × 1.1 cm, with loss of the fatty hilum. Abdominal ultrasound showed moderate hepatosplenomegaly without intra-abdominal lymphadenopathy. FNAC performed externally revealed scattered epithelioid cells, a polymorphous lymphoid population, and a necrotic background.

Given the persistent fever and imaging results, differential diagnoses included tuberculous lymphadenitis, Kikuchi-Fujimoto Disease, non-Hodgkin lymphoma and systemic lupus erythematosus (SLE).

Although excision biopsy was advised repeatedly, the parents were hesitant as they felt it to be invasive.

However, with the fever persisting for almost a month, the biopsy was eventually performed. Histopathological examination revealed focal necrosis surrounded by crescentic histiocytes, plasmacytoid monocytes, and karyorrhectic debris, with absence of neutrophils—findings diagnostic of Kikuchi-Fujimoto Disease.

Just as oral corticosteroids were being considered in view of systemic involvement, the fever resolved spontaneously by day 40. ANA panel and HLH workup were both negative.

At discharge, the child was afebrile, hemodynamically stable, and in excellent general condition. He remains well on follow-up.

Discussion

KFD is a globally rare condition, though more frequently seen in Asia. A study by Kim et al. identified 733 cases worldwide from 2001–2012, including only 140 pediatric patients.

It is even more uncommon in children under 10 years of age and is more prevalent in females.

Histopathological confirmation plays a critical role in diagnosing chronic lymphadenopathy. Early excision biopsy can prevent unnecessary antibiotic use and delays in diagnosis.

The child’s history of a similar episode three years’ prior raises the possibility of a previously undiagnosed or recurrent KFD episode. While recurrence is rare (up to 4%), it is usually mild.

Importantly, KFD is known to be associated with autoimmune conditions, particularly SLE, necessitating thorough evaluation for autoimmune markers.

References

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Jagadeesan S, Rani S, Porwal YC, Patel P. Lupus and Kikuchi-Fujimoto Disease: A Combination for Catastrophe. Cureus. 2022 Jul 28;14(7):e27423. doi: 10.7759/cureus.27423. PMID: 36051719; PMCID: PMC9420304.
Hutchinson CB, Wang E. Kikuchi-Fujimoto disease. Arch Pathol Lab Med. 2010 Feb;134(2):289-93. doi: 10.5858/134.2.289. PMID: 20121621.
Kim TY, Ha KS, Kim Y, Lee J, Lee K, Lee J. Characteristics of Kikuchi-Fujimoto disease in children compared with adults. Eur J Pediatr. 2014 Jan;173(1):111-6. doi: 10.1007/s00431-013-2131-3. Epub 2013 Aug 17. PMID: 23955486.
Kottarathil MS, D’Cruze L, Sundaram S, Kalantri SH, Malik A. Spectrum of Kikuchi-Fujimoto Disease: A 10-Year Study in a Tertiary Care Centre in South India. Cureus. 2024 Sep 21;16(9):e69888. doi: 10.7759/cureus.69888. PMID: 39439650; PMCID: PMC11494157.
Inamo Y. The Difficulty of Diagnosing Kikuchi-Fujimoto Disease in Infants and Children Under Six Years Old: Case Report and Literature Review. Cureus. 2020 Mar 24;12(3):e7383. doi: 10.7759/cureus.7383. PMID: 32337111; PMCID: PMC7179985.

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When fever lingers, think beyond the usual: Consider Kikuchi-Fujimoto disease