We introduce a 16-year-old female who presented with tender cervical lymphadenopathy, prolonged fever, and hypothyroidism. After excluding common causes of fever of unknown origin, a surgical biopsy of cervical lymph nodes revealed Kikuchi-Fujimoto disease. The patient showed improvement with a short-term course of NSAIDs. An increased titre of thyroperoxidase antibody led to a diagnosis of Hashimoto\'s thyroiditis during stable condition. This report underscores the importance of considering Kikuchi-Fujimoto disease in the differential diagnosis of prolonged fever of unknown origin with lymphadenopathy and highlights the association with Hashimoto\'s thyroiditis, advocating for vigilance regarding hypothyroidism in long-term follow-up after Kikuchi-Fujimoto disease recovery.

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare condition characterized by benign localized lymphadenopathy and clinical symptoms such as fever, sore throat, odynophagia, and leukopenia. Though the etiology of KFD is unknown, this condition is similar to viral infection, including increased infiltration of activated plasmacytoid dendritic cells. KFD exhibits three histological phases that reflect its progression status: proliferative, necrotic, and xanthomatous lesions. The expression loss of pan T-cell markers, such as CD2, CD5, and CD7, of infiltrating T-cells is observed in KFD cases, complicating the distinction from T-cell lymphoma. However, reports on the loss of their expression in KFD have been limited. Furthermore, the precise population of the T-cell subset in KFD is still unclear. Here, we focused on surface markers and transcription factors for T-cell differentiation and analyzed them immunohistochemically in 46 KFD cases. We observed diminished CD5 expression of CD8-positive (CD5dim CD8+) T-cells in the proliferative lesion of KFD cases. Furthermore, these CD5dim CD8+ T-cells expressed T-BET, a master regulator of type 1 helper T-cells. The upregulation of T-BET and downregulation of CD5 in CD8+ T-cells causes dysregulated activation and proliferation of CD8+ T-cells, potentially contributing to the unique histopathological features of KFD. Recognizing the frequent infiltration of T-BET-positive CD5dim CD8+ T-cells in KFD is important for distinguishing it from mature T-cell lymphoma. Our findings suggest that the immune response in KFD shares similarities with viral infections and highlight the importance of characterizing T-BET-positive CD5dim CD8+ T-cell populations for understanding KFD pathogenesis.

Kikuchi-Fujimoto disease (KFD) is a benign, self-limiting histiocytic necrotizing lymphadenitis systemic disorder with unknown etiology. KFD has been known for half a century, but difficulties in distinguishing it remain. Its diagnostic significance is related to the increasing prevalence of KFD with autoimmune diseases in various timeframes. Systemic lupus erythematosus (SLE) is the most prevalent autoimmune connective tissue disease (AICTD) appearing alongside KFD. An 18-year-old female presented with acute muscle weakness, shortness of breath, fever, and significant weight loss for 5 months before admission. Pain and morning joint stiffness had been felt for 9 months. One year ago, she lumped her right neck and was diagnosed with KFD from the excision biopsy and immunohistochemical staining (CD68). Creatine-kinase enzymes and C-Reactive protein were elevated with a high anti-Ku and anti-Jo-1 negative level. There was a low level of complements, high anti-nuclear antibody titer, with positive anti-SS-A. Sialometry and Schirmer test showed reduced salivary and lacrimal gland production. We diagnosed this patient as having an overlap syndrome preceded by KFD. The AICTD involved was Sjögren\'s syndrome and SLE. Although KFD is considered a self-limiting disease, its occurrence should be noticed regarding the possibility of other autoimmune conditions. KFD usually coincides with AICTD, although it could also precede or occur afterward. This case is reported to raise awareness of the overlap syndrome preceded by KFD.

OBJECTIVE: To characterize the clinical features and to identify the predictors of recurrence of histiocytic necrotizing lymphadenitis (HNL) in Chinese children.
METHODS: This study retrospectively analyzed the clinical characteristics, laboratory and pathological findings, and recurrence status of children diagnosed with HNL at a single center in China from January 2018 to May 2023. Logistic regression analysis was employed to identify predictors of HNL recurrence.
RESULTS: 181 Chinese children with histopathologically confirmed HNL were enrolled (121 males and 60 females). The mean age was 9.3 ± 2.9 years. The most prominent clinical features were fever (98.9%) and cervical lymphadenopathy (98.3%). Aseptic meningitis was the most frequent complication (38.5%), while hemophagocytic lymphohistiocytosis and autoimmune disease were rare (1.7% and 1.2%, respectively). Recurrence occurred in 12.7% of patients. Erythrocyte sedimentation rate (> 30 mm/h) was the significant predictors of HNL recurrence, with odds ratios of 6.107, respectively.
CONCLUSIONS: Our study demonstrates that fever and cervical lymphadenopathy are the most frequent clinical manifestations of HNL in Chinese children, which often coexist with aseptic meningitis. HNL patients with risk factors require follow-up for recurrence.

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare, benign, and self-limiting condition characterized by lymph node inflammation. While KFD is rarely associated with ocular manifestations, our case report highlights bilateral optic neuritis in a 13-year-old male patient with KFD. We also provide a comprehensive review of similar cases in the literature.

Kikuchi-Fujimoto disease (KFD) is a benign, self-limiting illness that can progress to systemic lupus erythematosus (SLE) in approximately 30% of cases. Neurological injuries can occur in both diseases, albeit with distinct presentations. Venous sinus thrombosis is a serious cerebrovascular complication in patients with neuropsychiatric SLE but is rarely observed in patients with KFD. The involvement of various antibodies, particularly antiphospholipid antibodies, can cause vascular endothelial cell injury, resulting in focal cerebral ischemia and intracranial vascular embolism in SLE. However, there are cases in which thrombotic pathology occurs without antiphospholipid antibody positivity, attributed to vascular lesions. In this report, we present a case of KFD and lupus encephalopathy featuring cerebral venous sinus thrombosis, despite the patient being negative for antiphospholipid antibody. We also conducted a comparative analysis of C3 and C4 levels in cerebrospinal fluid (CSF) and peripheral blood, along with the protein ratio in CSF and serum, to elucidate the pathological changes and characteristics of lupus encephalopathy.

Kikuchi-Fujimoto disease (KFD) is a benign and self-limited disorder that usually presents with regional cervical lymphadenopathy and fever. We report a case of a 12-year-old female who complained of fever, night sweating, significant weight loss, and tender right cervical lymph node enlargement for 2 months. A full workup including laboratory tests and imaging studies, an excisional biopsy, and histopathological analysis were done, and the diagnosis of KFD was confirmed. The patient was treated with analgesia and oral prednisolone, resulting in good improvement. A high degree of clinical suspicion is imperative for physicians, given the rarity of the disease and the associated diagnostic challenges.

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare benign condition characterized by cervical lymphadenopathy and constitutional symptoms mimicking tuberculosis. We present the case of a 22-year-old male who presented with fever, dry cough, loss of appetite, multiple joint pains for 15 days, and loss of weight for one month. Physical examination revealed palpable cervical, occipital, axillary, and inguinal lymphadenopathy, and laboratory investigations were within normal limits except for raised erythrocyte sedimentation rate (ESR). Contrast-enhanced computed tomography (CECT) showed mediastinal lymphadenopathy with no pleuroparenchymal abnormality of the lung. Excision biopsy of a cervical lymph node confirmed necrotizing lymphadenitis consistent with KFD. The patient was treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, resulting in the resolution of symptoms and regression of lymphadenopathy. This case signifies the importance of considering KFD in the differential diagnosis of lymphadenopathy and highlights the significance of histopathological evaluation for accurate diagnosis and management guidance.

BACKGROUND: Histiocytic necrotizing lymphadenitis (HNL) is a self-limited inflammatory disease of unknown pathogenesis. A very small fraction of patients with HNL could develop hemophagocytic lymphohistiocytosis (HLH), a hyperinflammatory disorder. These patients are diagnosed as HNL with HLH (HNL-HLH). HNL-HLH in the pediatric population has been systemically studied, however, the clinical, laboratory, and radiological features and outcomes of adult patients with HNL-HLH remain to be explored. We aimed to explore the clinical, laboratory, and radiological features and outcomes of adult patients with HNL-HLH.
METHODS: We collected the clinical data of patients with HNL-HLH admitted to the First Affiliated Hospital of Nanjing Medical University from October 2010 to June 2015. All the patients underwent lymph node biopsy and have a pathological diagnosis of HNL. The age, gender, clinical presentation, lymph node signs, laboratory findings and imaging data, and pathological findings of the patients were collected.
RESULTS: In this study, we reported five adult patients with HNL-HLH. All five patients showed enlarged lymph nodes and prolonged fever. Laboratory findings were consistent with the diagnosis of HLH. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) showed enlarged lymph nodes with increased FDG uptake and splenic hypermetabolism could be present. All the patients responded well to corticosteroids and had a good prognosis. Two of the five patients were diagnosed with systemic lupus erythematosus during the follow-up.
CONCLUSIONS: Our study demonstrated that adult patients with HNL-HLH showed distinct clinical, laboratory, and radiological features. And the prognosis is good and patients could be managed with steroids and supportive care.

The inflammatory response to viral infection is an important component of the antiviral response, a process that involves the activation and proliferation of CD8+ T, CD4+ T, and dendritic cells; thus, viral infection disrupts the immune homeostasis of the organism, leading to an increased release of inflammatory factors. Kikuchi-Fujimoto disease (KFD) is an inflammatory self-limited disorder of unknown etiology, and it is generally believed that the pathogenesis of this disease includes two aspects: viral infection and autoimmune response. Various immune cells, such as CD8+ T lymphocytes, CD4+ T lymphocytes, and CD123+ plasmacytoid dendritic cells, as well as the cytokines they induce and secrete, such as interferons, interleukins, and tumor necrosis factors, play a crucial role in the pathogenesis of KFD. In this article, we present a case study of a young female patient from China who exhibited typical symptoms of lymph node inflammation and fever. The diagnosis of KFD was confirmed through a lymph node biopsy. She presented with elevated ESR, IL-6, and IFN-γ. Viral markers showed elevated IgG and IgM of cytomegalovirus (CMV) and elevated IgG of Epstein-Barr virus (EBV), while changes occurred in the CD4+ T and CD8+ T cell counts. Eventually, the patient achieved disease relief through steroid treatment. Based on these findings, we conducted a comprehensive review of the involvement of viral infection-induced inflammatory response processes and autoimmunity in the pathogenesis of Kikuchi-Fujimoto disease.