Kikuchi-Fujimoto Disease Research Articles

Kikuchi–Fujimoto Disease: A Case Series and Review of the Literature

Kikuchi–Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare, self-limiting disorder characterized by fever typically lasting for 1 week up to 1 month and painful necrotizing lymphadenopathy, primarily affecting young adults of Asian ancestry. Although the exact cause remains unclear, infectious and autoimmune mechanisms have been implicated in the pathogenesis of the disease. In this case series, we aim to describe the histopathological features of KFD over a ten-year period at Mount Sinai Medical Center of Florida, and review the current understanding of its pathogenesis, clinical presentation, diagnosis, and management. A retrospective review of our pathology database between January 2013 and May 2024 was performed to identify patients diagnosed with KFD at our institution. Eight cases of KFD were identified, with a mean age of 35 years (range 24–49) and slight male predilection (5:3). Three patients exhibited leukopenia, and two had concurrent HIV infection. One patient developed systemic lupus erythematosus (SLE), and another developed IgA nephropathy during follow-up. Histopathological examination revealed the characteristic features of KFD, including lymph node architectural effacement, histiocytic infiltration, and necrosis. In conclusion, KFD remains a diagnostic challenge due to its overlapping clinical features with other infectious and autoimmune diseases, particularly SLE. While most cases resolve spontaneously, long-term follow-up is warranted due to the potential for recurrence and autoimmune associations.

Kikuchi lymphadenitis, a rare case: an overview of its clinical presentation, diagnostic challenges, and therapeutic approaches

Kikuchi-Fujimoto Disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare, self-limiting condition typically presenting with lymphadenopathy and fever. The etiology remains unclear, but it is thought to be associated with viral infections and autoimmune processes. We report a case of a female who presented with cervical lymphadenopathy. An excisional biopsy of the lymph node was performed, showing characteristic histopathological features of KFD. Based on the clinical presentation and histopathological findings, a diagnosis of Kikuchi-Fujimoto disease was made. The patient was managed with supportive care, including antipyretics and Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). No antibiotics or corticosteroids were administered. The patient's symptoms gradually resolved over a period. Follow-up at three months revealed the resolution of symptoms with no recurrence. The patient remained asymptomatic at subsequent visits. KFD should be considered in young patients presenting with fever and lymphadenopathy. Diagnosis is confirmed through lymph node biopsy demonstrating characteristic histopathological features. The disease typically follows a benign course with spontaneous resolution, and management is primarily supportive.

A Case of Necrotizing Lymphadenitis Misdiagnosed as a Neck Abscess.

Histiocytic necrotizing lymphadenitis (HNL), also known as Kikuchi disease, is a relatively rare sub-acute necrotic localized lymphadenitis. This benign, self-limiting condition is characterized by fever, painful lymphadenopathy, skin rash, and other systemic symptoms. Due to its nonspecific presentation, unclear etiology, and pathogenesis, HNL has a low incidence rate in clinical practice. Insufficient awareness among clinicians and pathologists can easily lead to misdiagnosis. This article reported a 27-year-old female patient who was admitted to the hospital with fever, neck pain, and enlarged lymph nodes in the neck. There were no special medical or personal histories, and postoperative pathology confirmed tissue necrotizing lymphadenitis. After treatment with steroids and symptomatic therapy, she recovered and was discharged from the hospital. Follow-up to date has shown no recurrence.

Kikuchi-Fujimoto Disease Presenting as Autoimmune Limbic Encephalitis: A Case Report with Review of Literature.

Kikuchi-Fujimoto disease (KFD) is a rare benign condition associated with fever and lymphadenopathy and was first described by Kikuchi and Fujimoto independently in 1972 as histiocytic necrotizing lymphadenitis. The diagnosis is made by histopathology with immunohistochemistry. Limbic encephalitis is an extremely rare presentation of this uncommon disease, which has been described mainly in children. Available evidence is sparse in the form of case reports and case series in the form of 10 cases published till date. We report a case of an adult female with KFD with autoimmune limbic encephalitis, who had complete clinical and radiologic recovery with treatment, and a literature review of all the cases published till date.

Systemic Juvenile Idiopathic Arthritis and arthralgia - can it be diagnosed early within the window period? – An observation of serum biomarkers and analysis with other differential conditions in children

Background: Systemic juvenile idiopathic arthritis (sJIA)is a cause of persisting arthralgia which is often missed. Diagnosing sJIA can be challenging, especially when overt arthritis is absent at presentation, highlighting the need for a diagnostic biomarker. Few recent studies have assessed potential biomarkers for sJIA, however, there is no consensus in detecting early. We conducted a study evaluating serum IL-1, IL-6, IL-18, S100A8, and S100A9 as potential diagnostic markers to distinguish sJIA from other conditions presenting as joint pain in children. Methods: A prospective study was conducted in our institute from May-2019 to October-2020 in children under 16 years, who had persisting arthralgia. Serum concentrations of IL-1, IL-6, IL-18, S100A9, and S100A8 were determined using ELISA kits. Receiver operating curve (ROC) analysis was used to determine the cut-off values for IL-1, IL-6, IL-18, S100A8, and S100A9 for differentiating sJIA from other causes of joint pain and fever. Results- Out of 47 children who presented with joint pain and fever 19 of them were eventually diagnosed with sJIA. In the other 28 children, arthralgia and fever was attributed to conditions other than sJIA (non-sJIA). The non-sJIA group comprised children with acute lymphoblastic leukemia, hemophagocytic histiocytosis, systemic lupus erythematosus, Kawasaki disease, Kikuchi disease, and inflammatory bowel disease. Serum levels of IL-18, S100A8, and S100A9 were significantly higher in patients with sJIA compared to the non-sJIA group (p<0.05). The area under the curve (AUC) was significant for IL-18(77.9%), S100A8 (74.9%), and S100A9(71.2%). A serum IL-18 cut-off level of > 2030.45 pg/ml was useful for differentiating between sJIA and other diseases with a sensitivity of 66.67% and specificity of 75.86% for the diagnosis of sJIA. Conclusion- Serum IL-18, S100A8, and S100A9 can be useful in differentiating sJIA early from other causes of persisting arthralgia in children provided with appropriate identification of symptomatology and suspicion.

Spectrum of Kikuchi-Fujimoto Disease: A 10-Year Study in a Tertiary Care Centre in South India.

Background Kikuchi-Fujimoto disease (KFD) is a benign lesion of the lymph nodes predominantly seen in younger women and is a condition associated with a good prognosis due to its indolent nature. Since KFD is chiefly a diagnosis of exclusion, it is liable to a higher degree of misdiagnosis. Aim In our study, we attempt to document and analyse the demographic, clinical, and pathological spectrum of cases diagnosed as KFD in a South Indian tertiary care centre over a period of 10 years. Methodology This study was conducted in a retrospective observational manner. Descriptive statistics, including simple frequency and percentage, were used to analyse and summarise the collected data. Results Among the 44 cases obtained, 36 patients were female and eight were males, with an age range of eight to 70 years. The mean age of the affected population was 26 years. Fever was a presenting complaint in 63.6% of cases, and 100% of the cases had lymphadenopathy, chiefly affecting the posterior cervical group of nodes (32/44 cases). Multiple lymph node groups were involved in 22 cases. Most of the nodes were larger than 1 cm in their greatest dimension. On analysis of peripheral smears, 43.2% of patients showed leukopenia. Anti-nuclear antibody (ANA) analysis showed a positive status among two patients, simultaneously establishing the diagnosis of systemic lupus erythematosus (SLE). A history of treated tuberculosis was present in four patients, and one patient had a history of non-compliance with TB treatment. Two patients had recently been diagnosed with TB and were on treatment. The involved nodes were subjected to fine-needle aspiration studies in 13 patients; 12/13 cases showed reactive lymphadenitis, while one case had atypical lymphoid cells. The involved nodes of all the patients were excised and sent for histopathological analysis. The diagnosis of KFD was confirmed on the biopsy. Conclusion In this study, we note the clinical presentations of all the patients diagnosed with KFD and elaborate on the investigations that were employed to verify the diagnosis via exclusion that enabled differentiation of KFD from its close mimickers, which have specific treatment. Keeping this entity in mind is essential in order to prevent overdiagnosis, as most often this condition resolves spontaneously, and in occasional cases, symptomatic treatment is sufficient for its management.

Kikuchi–Fujimoto disease and primary Sjögren’s syndrome coexisting: A case-based literature review

ABSTRACT Kikuchi–Fujimoto Disease (KFD), also known as Kikuchi histiocytic necrotising lymphadenitis, is an extremely rare and benign condition that mostly affects young women. It is characterised by lymph node involvement with a predilection for the cervical region, commonly presenting with tender lymphadenopathy and a low-grade fever. The diagnosis requires excisional lymph node biopsy with immunohistochemical analysis. KFD is mostly self-limiting within a few weeks to months, with only some patients requiring symptomatic relief with non-steroidal anti-inflammatory drugs or corticosteroids, and a minority developing recurrent episodes of the disease. Importantly, it has been reported in association with systemic lupus erythematosus and, to a lesser extent, other immune-mediated inflammatory rheumatic diseases, such as Sjögren’s syndrome, whose clinical presentation itself may include lymphadenopathy. In this paper, we present an unusual case of a woman with primary Sjögren syndrome (pSS) and a past medical history relevant for lymphoma, sarcoidosis, and thymoma, who later developed KFD, a particularly challenging diagnosis in this setting. We then performed a literature review of the association between KFD and pSS, gathering a total of 13 patients, and focusing epidemiological, clinical, and laboratory data.

Kikuchi-Fujimoto disease co-occuring with Hashimoto thyroiditis: A case report and literature review.

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 with Subsequent Meningoencephalitis Insights into Rare Complications – A Case Report

Kikuchi-Fujimoto Disease with Subsequent Meningoencephalitis Insights into Rare Complications – A Case Report

Kikuchi-Fujimoto disease: rare but worth remembering: a case study.

Kikuchi-Fujimoto disease: rare but worth remembering: a case study.

Think beyond TB lymphadenitis - Kikuchi fujimoto lymphadenitis

Kikuchi-Fujimoto disease (KFD) is an extremely unusual lymphadenopathy that typically affects females between the ages of 20 and 40, but the aetiology is still unclear. A 28-year-old female presented with right-sided cervical lymph nodes, but there was no history of fever, anorexia, or loss of appetite. Ultrasonography of the patient's neck revealed bilateral cervical lymphadenopathy. Both the acid-fast bacilli smear and GeneXpert tests returned negative results. Histopathology revealed the presence of lymphocytes and histiocytes mixed with karyorrhectic debris. Immunohistochemistry markers support the diagnosis of Kikuchi-Fujimoto lymphadenitis. This case demonstrates that early recognition of KFD reduces unnecessary evaluations and treatments and patient suffering. KFD is a self-limiting disease that requires a systematic approach for a diagnosis; once the diagnosis is made and confirmed by techniques such as immunohistochemistry, symptomatic treatment alone would suffice in the majority of cases. The commonest presentation is an acute or subacute febrile illness associated with cervical lymphadenopathy.

Lateral rectus palsy as the first presentation of Kikuchi Fujimoto’s disease

Kikuchi Fujimoto’s Disease (KFD) or histiocytic necrotising lymphadenitis is recognised as a disease with a benign and indolent course. The common clinical symptoms of KFD include fever, headache, arthralgia and cervical lymphadenopathy. The diagnosis is based on clinical grounds and histological findings of lymph node biopsy. Kikuchi disease presenting with neurological manifestations is seldom seen. Out of all reported neurological manifestations, aseptic meningitis, brainstem encephalitis and cerebellar ataxia are common. We report a case of a 16 year old girl presenting with right sided lateral rectus palsy as the first presentation of KFD.

Using T2-weighted magnetic resonance imaging-derived radiomics to classify cervical lymphadenopathy in children

BackgroundCervical lymphadenopathy is common in children and has diverse causes varying from benign to malignant, their similar manifestations making differential diagnosis difficult.ObjectiveThis study aimed to investigate whether radiomic models using conventional magnetic resonance imaging (MRI) could classify pediatric cervical lymphadenopathy.MethodsA total of 419 cervical lymph nodes from 146 patients, and encompassing four common etiologies (Kikuchi disease, reactive hyperplasia, suppurative lymphadenitis and malignancy), were randomly divided into training and testing sets in a ratio of 7:3. For each lymph node, 1,218 features were extracted from T2-weighted images. Then, the least absolute shrinkage and selection operator (LASSO) models were used to select the most relevant ones. Two models were built using a support vector machine classifier, one was to classify benign and malignant lymph nodes and the other further distinguished four different diseases. The performance was assessed by receiver operating characteristic curves and decision curve analysis.ResultsBy LASSO, 20 features were selected to construct a model to distinguish benign and malignant lymph nodes, which achieved an area under the curve (AUC) of 0.89 and 0.80 in the training and testing sets, respectively. Sixteen features were selected to construct a model to distinguish four different cervical lymphadenopathies. For each etiology, Kikuchi disease, reactive hyperplasia, suppurative lymphadenitis, and malignancy, an AUC of 0.97, 0.91, 0.88, and 0.87 was achieved in the training set, and an AUC of 0.96, 0.80, 0.82, and 0.82 was achieved in the testing set, respectively.ConclusionMRI-derived radiomic analysis provides a promising non-invasive approach for distinguishing causes of cervical lymphadenopathy in children.Graphical

Clinical features and recurrence predictors of histiocytic necrotizing lymphadenitis in Chinese children

ObjectivesTo characterize the clinical features and to identify the predictors of recurrence of histiocytic necrotizing lymphadenitis (HNL) in Chinese children.Study designThis 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.Results181 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.ConclusionOur 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 disease complicated with aseptic meningitis following COVID-19 Vaccination: a case report

BackgroundKikuchi Fujimoto disease is a rare self-limiting disorder mainly affecting young Asian females. The typical presentation is unexplained fever with associated cervical lymphadenopathy. It can mimic many sinister diseases such as lymphoma, tuberculosis, and systemic lupus erythematosus. Aseptic meningitis due to Kikuchi disease is extremely rare, and majority were reported from Japan. There have been no published cases of aseptic meningitis due to Kikuchi disease in Sri Lanka.Case presentationA 29 years old Sri Lankan female presented with a prolonged fever for three weeks with an associated headache for five days duration. She developed painful cervical lymphadenopathy during the hospital stay. She has been previously well and had been vaccinated against COVID-19 six weeks before. Her lumbar puncture showed lymphocytic pleocytosis with marginally elevated protein levels and reduced ratio of serum to CSF sugar. Lymph node biopsy was consistent with necrotizing lymphadenitis. She was subsequently diagnosed with Kikuchi disease complicated with aseptic meningitis. She responded to corticosteroids well and had an uneventful recovery.ConclusionKikuchi disease is a rare self-limiting disorder that can be complicated with aseptic meningitis on infrequent occasions. Other conditions such as tuberculosis, lymphoma, systemic lupus erythematosus, and adult-onset Still’s disease should be considered as differential diagnoses. Knowledge of Kikuchi disease and its complications will prevent unnecessary investigations which delay the early diagnosis and treatment.

Pyrexia of unknown origin with lymphadenopathy - An uncommon diagnosis

Kikuchi disease or histiocytic necrotizing lymphadenitis is a benign and self-limited disorder characterized by tender regional cervical lymphadenopathy. We report a case of a 4-year 5-month old female presenting with fever and lymphadenopathy for 2 months. All infective and inflammatory cause of pyrexia of unknown origin was negative. Lymph node histopathology showed features of Kikuchi’s disease.

Serum Soluble IL-2 Receptors Are Elevated in Febrile Illnesses and Useful for Differentiating Clinically Similar Malignant Lymphomas from Kikuchi Disease: A Cross-Sectional Study.

Background: The use of serum soluble interleukin 2 receptor (sIL-2R) for the diagnosis of febrile illnesses has not been examined. In this study, febrile patients were classified according to etiology and disease, and serum sIL-2R levels were evaluated. We determined whether serum sIL-2R is a useful marker for differentiating between malignant lymphoma (ML) and non-ML patients and between patients with ML and Kikuchi disease, which present similar clinical manifestations. Methods: This study was a cross-sectional study and included 344 patients with uncomplicated hemophagocytic syndrome, who had a fever of 38 °C or higher within 1 week of admission to our institution. Patient serum sIL-2R was measured, and the serum sIL-2R values are shown as median and IQR. Results: Serum sIL-2R increased above the upper reference limit in all disease groups with fever. The serum sIL-2R level in ML patients (n = 13) was 4760 (2120-6730) U/mL and significantly higher (p < 0.001) than the level of 998 (640-1625) U/mL in non-ML patients (n = 331). The serum sIL-2R level in ML patients (n = 13) was also significantly higher (p < 0.001) compared with that in patients with Kikuchi disease (n = 20; 705 (538-1091) U/mL). Conclusions: Serum sIL-2R tends to exceed the upper reference limit in patients with febrile illnesses. We conclude that the measurement of serum sIL-2R is useful for differentiating ML from non-ML and ML from Kikuchi disease.

Kikuchi-Fujimoto Disease: A Rare Lymphadenitis with Diagnostic Challenges and Treatment Considerations

Kikuchi-Fujimoto disease (KFD) is a rare form of lymphadenitis that primarily affects young women in Japan and other parts of Asia. It is caused by unknown agents, possibly viruses that trigger an autoimmune response in genetically susceptible individuals. KFD is often misdiagnosed due to its resemblance to other benign and malignant conditions, including SLE-related lymphadenitis and lymphoma. Diagnosis of KFD requires a lymph node biopsy, which reveals characteristic features such as histiocytic necrotizing lymphadenitis. Additional diagnostic tests, including skin biopsy, MRI, and cerebrospinal fluid analysis, can aid in confirming the diagnosis. KFD is self-limiting, and most patients recover within a few months with symptomatic treatment. However, early intervention with corticosteroids and hydroxychloroquine is crucial for effective management, particularly in cases with extra-nodal involvement or neurological symptoms. Lymph node removal can also be an effective therapeutic measure, and Hemophagocytic lymphohistiocytosis (HLH), a potential complication of KFD, is managed with a combination of immunoglobulins and steroids. While KFD is a benign condition, its diagnosis and treatment can be challenging, requiring close monitoring and follow-up.

Kikuchi-Fujimoto disease: A rare case of pyrexia of unknown origin

A young male was referred to a clinician for a complaint of fever of short duration with non-specific joint pain and treated for 1 week but after some time again presented with the same complaints with severe epigastric tenderness and vomiting. There was no past medical history before this episode. When cervical lymph node biopsy was performed gave us the diagnosis of histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease). A rare form of necrotizing lymphadenitis is an uncommon, benign, self-limiting disorder of obscure etiology. It affects mostly young adults of both genders. Clinically, it presents with fever and lymphadenopathy of a firm to rubbery consistency frequently involving cervical lymph nodes while weight loss, splenomegaly, and leukopenia in severely ill patients.

Kikuchi-Fujimoto disease, simultaneously diagnosed with systemic lupus erythematosus in an Arabic female: an agonizing combination.

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare, benign condition affecting young Oriental-Asian females. It is characterized by fever and tender cervical lymphadenopathy with an unclear aetiology, and in most longitudinal reviews, KFD occurs before systemic lupus erythematosus (SLE). Herein, the case of a 28-year-old Kuwaiti female without any relevant past medical history, who was simultaneously diagnosed with KFD and SLE following an Ebstein-Barr virus infection, is reported. The patient was treated with oral prednisolone, hydroxychloroquine, cyclosporin, and belimumab and her response was clinically and biochemically favourable. Although KFD is prevalent in Asian populations, it may affect all races. Early diagnosis of KFD is difficult, particularly when simultaneously diagnosed with SLE, but crucial to preventing inappropriate therapy. Clinicians need to know about this rare disease, especially when patients present with fever and swollen lymph nodes, due to a risk of misdiagnosis with tuberculosis or lymphoma, as these are more often thought to be the cause of such symptoms.