Kikuchi-Fujimoto Disease: A Rare Condition Mimicking Sepsis

Case Report Iranian Journal of Otorhinolaryngology, Vol.37(3), Serial No.140, May-2025 Kikuchi-Fujimoto Disease: A Rare Condition Mimicking Sepsis * Sethu Thakachy Subha1, Naseeha Roslan Ainur1, Mohd Ali Razana2 Abstract Introduction: Kikuchi-Fujimoto disease is a self-limited disease which is also known as histiocytic necrotizing lymphadenitis. The Kikuchi-Fujimoto disease is a rare cause of cervical lymphadenopathy, with or without systemic signs, such as fever, leukopenia, and skin rashes. Case Report: We presented a case of Kikuchi-Fujimoto disease in a 29-year-old female mimicking sepsis after a COVID-19 infection. Clinical examination revealed stable vitals and multiple diffuse non-tender bilateral cervical and axillary lymph adenopathy with hepatosplenomegaly. The patient’s blood parameters showed leukopenia, raised erythrocyte sedimentation rate, lactate dehydrogenase, microcytic hypochromic anemia with normal renal and liver function tests. The patient was treated with broad spectrum intravenous antibiotics and subcutaneous neupogen with a clinical suspicion of sepsis. The patient then underwent a CT scan which validated the clinical findings. Although the fever subsided, a persistent cervical lymphadenopathy was observed and the biopsy confirmed it to be necrotising lymph adenitis secondary to Kikuchi-Fujimoto disease. This patient has been regularly monitored and has shown resolution of cervical lymphadenopathy. Conclusion: Clinicians should suspect Kikuchi-Fujimoto disease when patients present with persistent cervical lymphadenopathy unresponsive to initial medical treatment. Lymph node biopsy should be undertaken to rule out Kikuchi-Fujimoto disease and prevent these patients from extensive diagnostic procedures and inappropriate treatment modalities. Keywords: Fever, Kikuchi-Fujimoto disease, lymphadenopathy, Necrotizing Lymphadenitis, sepsis Received date: 19 Aug 2024 Accepted date: 06 Feb 2025 *Please cite this article; Subha ST, Ainur NR, Razana MA. Kikuchi-Fujimoto Disease: A Rare Condition Mimicking Sepsis Iran J Otorhinolaryngol. 2025:37(3):161-164. Doi: 10.22038/ijorl.2025.82006.3754 1Department of Otorhinolaryngology, Hospital Sultan Abdul Aziz Shah, Faculty of Medicine & Health Sciences University Putra Malaysia, Malaysia. 2Department of Pathology, Hospital Sultan Abdul Aziz Shah, Faculty of Medicine & Health Sciences University Putra Malaysia, Malaysia. *Corresponding author: Department of Otorhinolaryngology, Hospital Sultan Abdul Aziz Shah, Faculty of Medicine & Health Sciences University Putra Malaysia. E-mail: , 161 Subha ST, et al Introduction Kikuchi-Fujimoto disease predominately occurs in young adult female patients (1). Various studies have shown that cervical lymphadenopathy with fever as the most common clinical manifestation of KikuchiFujimoto disease (2,3). Other clinical symptoms include headache, vomiting, malaise, weight loss, arthralgia, and skin rashes (2). The aetiology of Kikuchi disease is unknown but infective and autoimmune conditions have been described as causative factors (2). A few case reports have also described Kikuchi disease as triggered or occurring along with COVID-19 and post-vaccination (4,5). Some previous studies have also reported a complex association between Kikuchi-Fujimoto Disease and systemic lupus erythematosus (6-8). Clinicians are not familiar with the Kikuchi-Fujimoto disease and this report highlights that a timely diagnosis of this self-limiting entity is crucial. and anti-extractable nuclear antigens (ENA) were performed, and all of them revealed negative results. A computed tomography of the brain, thorax, abdomen revealed diffuse cervical (Figure 1) and axillary lymphadenopathy with hepatosplenomegaly. Meanwhile, a biopsy of the neck node was performed and histopathology confirmed necrotising lymphadenitis secondary to Kikuchi’s disease, as shown in Figures 2, 3, 4, and 5. A written informed consent for publication was obtained from the patient. The patient remained well during the follow-up. Case Report A 29-year-old female presented with a onemonth intermittent fever, headache, and neck lumps. Her headache was nonspecific with no temporal pattern. The patient had a history of COVID-19 infection two weeks prior to the onset of the symptoms. A clinical examination showed stable vitals and multiple diffuse nontender bilateral cervical and axillary lymph adenopathy and hepatosplenomegaly. The examination of the central nervous, cardiovascular, and respiratory systems was normal. Laboratory tests showed bicytopenia (white cell count-2.18 x 109/L), increased erythrocyte sedimentation rate, (65mm/hour), raised lactate dehydrogenase, and microcytic hypochromic anaemia with normal renal and liver function tests. The patient was initially treated for neutropenic sepsis with broadspectrum antibiotics and subcutaneous neupogen. Blood and urine cultures remained negative. The patient’s fever had settled but the neck nodes persisted and were further investigated for lymphoma and autoimmune diseases. Assessments of antibodies against human immunodeficiency virus and hepatitis B and C, chest radiography, and electrocardiography were unremarkable. The antinuclear antibody test was positive. Further serological tests including rheumatoid factor, anti-double-stranded-DNA antibodies (dsDNA), Fig 1. Contrast enhanced CT scan shows multiple lymph nodes with heterogenous enhancement on both sides of the neck with no necrotic component and some of them are matted. Fig 2. Photomicrograph of surgical specimen from lymph node shows amorphous necrotic debris and karyorrhectic nuclear dust (Hematoxylin-eosin stain, x 100 magnification). Fig 3. Photomicrograph of surgical specimen from lymph node shows partial involvement by irregularly shaped, pale areas containing eosinophilic granular material, and abundant karyorrhectic debris (nuclear dust) surrounded by mononuclear histiocyt 162 Iranian Journal of Otorhinolaryngology, Vol. 37(3), Serial No.140, May-2025 Kikuchi-Fujimoto Disease Fig 4. Photomicrograph of surgical specimen from lymph node shows pale areas and mottled or starry sky (upper part) appearance due to small lymphocytes admixed with immunoblasts. (Hematoxylin-eosin stain, x 40 magnification) Fig 5. Photomicrograph of surgical specimen from lymph node shows central karyorrhectic debris with small lymphocytes, mononuclear histiocytes and plasmacytoid dendritic cells. No neutrophils. (Hematoxylin-eosin, x 200 magnification) Discussion Kikuchi-Fujimoto disease (KFD) was first described in 1972 by Kikuchi and Fujimoto in Japan (2). A review of related literature review revealed that COVID-19 infection and vaccination have triggered the Kikuchi-Fujimoto disease and other autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, vasculitis, multisystem inflammatory syndrome in children and adults, and antiphospholipid syndrome (3,4,5,9). Although various viruses have (...truncated)