Kikuchi-Fujimoto disease (KFD) is a self-limiting inflammatory condition primarily affecting young and pediatric patients of Asian descent. This systematic review aims to consolidate current knowledge on the neurological manifestations associated with KFD.

The present review followed the PRISMA guidelines and was registered on PROSPERO (CRD42024579757). PubMed, Scopus and CINAHL Ultimate were searched to identify relevant studies. We included case reports and case series detailing neurological manifestations and complications of KFD of any age/gender.

The initial search identified 456 articles out of which seventy-five case reports and series were included, encompassing a total of 81 cases. The median age of the patients was 23 years (IQR: 15-30). Patients most frequently presented with fever, headache and signs of meningeal irritation. Most patients diagnosed with KFD showed signs of neurological complications at the initial presentation. Meningitis (commonly aseptic meningitis) was the most frequently reported neurological complication followed by encephalitis, encephalopathy and neuro-ophthalmological complications. All patients had lymphadenopathy and showed the characteristic histopathological picture for KFD on biopsy. Steroids and immunosuppressive agents remained the treatment of choice. Complication and symptom specific treatment for neurological findings was provided wherever deemed necessary. Almost every study reported an improvement in neurological complications post treatment.

Neurological manifestations and complications associated with KFD are diverse and have a significant impact on patients. The complications associated with KFD need to be promptly recognized and evaluated by clinicians. Further investigation into the long-term effects and treatment strategies for KFD is warranted.

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.

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.

To develop a scheme for distinguishing Kikuchi-Fujimoto disease (KFD) from lymphoma in patients presenting enlarged lymph nodes (LNs) predominantly on the upper side of the diaphragm. From November 2015 to August 2023, 32 KFD patients and 38 lymphoma patients were pathologically confirmed and enrolled in this retrospectively study. Clinical and 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) features were collected. When comparing those PET/CT parameters, we set 5 models with different research objects: (1) all affected LNs; (2) the 5 largest affected LNs in terms of maximum diameter; (3) the 5 largest affected LNs in terms of maximum standard uptake values (SUVmax); (4) the largest affected LNs in terms of maximum diameter; (5) the largest affected LNs in terms of SUVmax. Compared to lymphoma patients, KFD patients were younger; and with higher incidence of fever, arthralgia, abnormal serum white blood cell, lactate dehydrogenase (LDH) and splenomegaly; lower incidence of affected LNs perinodal infiltration, necrosis and conglomeration; more affected LNs in Head and Neck nodes (particularly in level II) and Axillary in KFD (P ˂ .05). PET/CT parameters presented as various difference in each model. Finally, 11 clinical and PET/CT features (age ≤ 34, with fever, arthralgia, abnormal white blood cell, abnormal LDH, and without node necrosis and node conglomeration have a score of 2 each; splenomegaly, perinodal infiltration, median maximum diameter ≤ 20.5 and median SUVmax ≤ 7.1 of affected LNs in model 2 have score of 1 each) were selected as scheme items for distinguishing KFD from lymphoma. Individuals who have a total score > 8, meet the criteria for KFD. Sensitivity and specificity were high: 86.8% (95% CI: 71.9%, 95.5%) and 96.9% (95% CI: 83.7%, 99.5%), AUC = 0.975 (95% CI: 90.5%, 99.6%), respectively. It can effectively distinguish KFD from lymphoma by clinical and PET/CT parameters.

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, leucopenia, and elevated erythrocyte sedimentation rate feature in severely affected patients. Cutaneous involvement occurs in about 30%-40% of cases as facial erythema and nonspecific erythematous papules, plaques, acneiform or morbilliform lesions of great histologic heterogeneity. Both Kikuchi-Fujimoto disease and systemic lupus erythematosus share an obscure and complex relationship as systemic lupus erythematosus may occasionally precede, develop subsequently, or sometimes be associated concurrently with Kikuchi-Fujimoto disease. It is often mistaken for non-Hodgkin lymphoma while lupus lymphadenitis, cat-scratch disease, Sweet's syndrome, Still's disease, drug eruptions, infectious mononucleosis, and viral or tubercular lymphadenitis are other common differentials. Fine needle aspiration cytology mostly has features of nonspecific reactive lymphadenitis and immunohistochemistry studies usually show variable features of uncertain diagnostic value. Since its diagnosis is exclusively from histopathology, it needs to be evaluated more carefully; an early lymph node biopsy will obviate the need for unnecessary investigations and therapeutic trials. Its treatment with systemic corticosteroids, hydroxychloroquine, or antimicrobial agents mostly remains empirical. The article reviews clinicoepidemiological, diagnostic, and management aspects of KFD from the perspective of practicing clinicians.

Summarized the incidence of bleeding after ultrasound-guided coarse needle biopsy (US-CNB) of benign cervical lymph nodes.

We retrospectively examined the clinical and follow-up records of 590 patients with benign cervical lymph node disease who underwent US-CNB at our hospital during February 2015-July 2022 and were confirmed to have the disease by CNB and surgical pathology. The number of cases, types of diseases, and degree of bleeding of all patients with bleeding after US-CNB were statistically analyzed.

Of the 590 patients, bleeding was noted in 44 cases(7.46%), and the infectious lymph node bleeding rate was 9.48%. Infectious lymph nodes were more likely to bleed than noninfectious lymph nodes after CNB, ,x² = 8.771; P = 0.003, Lymph nodes with pus were more likely to bleed than solid lymph nodes after CNB, x² = 4.414; P = 0.036,.

The bleeding of all patients after CNB was minor bleeding. Infected lymph nodes bleed more frequently than noninfected lymph nodes. Lymph nodes with mobility and a large pus cavity, are more likely to bleed after CNB.

Kikuchi-Fujimoto disease (KFD) is a rare, benign, and self-limited disease, characterized by cervical lymphadenopathy and fever. Herein, we analyzed the differences in its clinical manifestations and risk factors for recurrence between children and adults.

We retrospectively reviewed the medical records of patients diagnosed with KFD at a tertiary referral hospital between 2005 and 2019. Patients were divided into two groups based on their age: children (<19 years) and adults (≥19 years).

During the 14-year study period, 127 patients were diagnosed with KFD. Among these, 34 (26.8%) were children and 93 (73.2%) were adults. The fever duration was longer and the frequency of myalgia was higher in adults than in children; however, no other significant symptomatic differences were noted between the two groups. Lymph node evaluation was mainly performed using ultrasound in children (61.8%) and computed tomography in adults (78.5%). Moreover, the frequency of antibiotic use was higher in children than in adults (76.5% vs 54.8%, P = 0.027). In adults, multivariable logistic regression analysis revealed anti-nuclear antibody (ANA) positivity (titer ≥1:80) as a risk factor for recurrence (odds ratio: 7.813; 95% confidence interval = 1.818-33.333; P = 0.006).

The clinical features of KFD in children and adults were similar; however, the preferred imaging study and frequency of antibiotic use differed significantly between the two groups. Furthermore, in adults, ANA positivity was associated with KFD recurrence. Thus, patients with KFD who present with ANA positivity at diagnosis will benefit from a regular follow-up for monitoring KFD recurrence.

Neck contrast-enhanced CT (CECT) is a routine tool used to evaluate patients with cervical lymphadenopathy. This study aimed to evaluate the ability of convolutional neural networks (CNNs) to classify Kikuchi-Fujimoto's disease (KD) and cervical tuberculous lymphadenitis (CTL) on neck CECT in patients with benign cervical lymphadenopathy. A retrospective analysis of consecutive patients with biopsy-confirmed KD and CTL in a single center, from January 2012 to June 2020 was performed. This study included 198 patients of whom 125 patients (mean age, 25.1 years ± 8.7, 31 men) had KD and 73 patients (mean age, 41.0 years ± 16.8, 34 men) had CTL. A neuroradiologist manually labelled the enlarged lymph nodes on the CECT images. Using these labels as the reference standard, a CNNs was developed to classify the findings as KD or CTL. The CT images were divided into training (70%), validation (10%), and test (20%) subsets. As a supervised augmentation method, the Cut&Remain method was applied to improve performance. The best area under the receiver operating characteristic curve for classifying KD from CTL for the test set was 0.91. This study shows that the differentiation of KD from CTL on neck CECT using a CNNs is feasible with high diagnostic performance.

To investigate ultrasound (US) features of enlarged cervical lymph nodes (LNs) to differentiate between Kikuchi disease (KD) and other common types of infectious lymphadenitis in an East Asian pediatric patient population.

A total of 142 pediatric patients with KD and 45 patients with infectious lymphadenitis (suppurative lymphadenitis [n = 29], nontuberculous mycobacterial lymphadenitis [n = 9], and tuberculous lymphadenitis [n = 7]) were included. The clinical characteristics, laboratory results, and US features of LNs were reviewed. The area under the curve (AUC) from a receiver operating characteristic curve analysis was used as a diagnostic accuracy measure.

A multiple clustered adjacent pattern, bilaterality, an even size, posterior neck involvement, no enlargement, an elongated-to-ovoid shape, homogeneous hypoechogenicity, a well-defined margin, presence of an echogenic fatty hilum, no intranodal gross necrosis, increased perinodal fat echogenicity, and no increased echogenicity of the adjacent sternocleidomastoid muscle were significant US features of the affected LNs to discriminate KD from infectious lymphadenitis (P < .05). Homogeneous hypoechogenicity in KD showed the highest AUC (0.930) as a single variable (95% confidence interval, 0.88-0.96). The AUCs were increased in 3 combination models with 2 US features: homogeneous echogenicity and 1 of 3 other US features (increased perinodal fat echogenicity, 0.935; number of affected LNs, 0.947; and LN shape, 0.949).

Homogeneous hypoechogenicity of LNs was a significant US feature with the highest diagnostic accuracy in differentiating KD from common infectious lymphadenitis on a univariate analysis. In the combination model, US features of an elongated-to-ovoid shape and homogeneous hypoechogenicity showed the highest diagnostic accuracy.

Kikuchi-Fujimoto disease (KFD) is an extremely rare disease, and although it is reported to have a worldwide distribution, young Asian women are most likely to be affected. Although this disease is generally benign and self-limiting, distinguishing it from other diseases that cause lymphadenopathy (e.g., leukemia, lymphoma, and infectious diseases) is challenging. A lymph node biopsy is a definitive diagnostic technique for KFD and only requires skillful pathologists. There are no specific symptoms or laboratory tests for KFD, and more than 50% of KFD patients have suffered from being misdiagnosed with lymphoma, which leads to improper treatment. In this study, lymph node tissue samples from KFD patients were used to reveal their exomes and transcriptomes using a high-throughput nucleotide sequencer. Fourteen single nucleotide polymorphisms (SNPs) were identified as candidate KFD markers and were compared with a healthy lymph node exome dataset. The mutation of these genes caused disruptive impact in the proteins. Several SNPs associated with KFD involve genes related to human cancers, olfaction, and osteoblast differentiation. According to the transcriptome data, there were 238 up-regulated and 1,519 down-regulated genes. RANBP2-like and ribosomal protein L13 were the most up-regulated and down-regulated genes in KFD patients, respectively. The altered gene expression involved in the human immune system, chromatin remodeling, and gene transcription. A comparison of KFD and healthy datasets of exomes and transcriptomes may allow further insights into the KFD phenotype. The results may also facilitate future KFD diagnosis and treatment.

To assess the correlation between inguinal lymph node characteristics and ipsilateral limb amputation rates in patients with ischemic foot ulcers after a successful endovascular treatment.

A retrospective review of patients who were endovascularly treated for ischemic foot ulcers between January 2015 and May 2017. Technical success was defined as arterial recanalization with stenosis less than 30 % and ankle brachial index improvement by > 0.2 after 24 h. Unilateral lymph node size, contrast enhancement, necrosis, and perinodular fat stranding were assessed on pre-procedural CTA. Primary endpoints were amputation and sepsis within 12 months following treatment. The relationship between lymph node characteristics and limb amputation and septic shock were examined.

Endovascular treatment of 202 limbs in 202 patients (135 males; median age 72.8 years [42.2-93.7]) was technically successful. Forty-two (20.8 %) patients underwent amputation, six (3 %) patients had septic shock. There was a significant difference in lymph node sizes between the amputated and the non-amputated limbs (P = 0.000). Lymph node characteristics (size, enhancement, necrosis, and perinodular fat stranding) were significantly related to amputation (P < 0.001). Patients with perinodular fat stranding or increased node size were 5.940 and 1.109 times more likely to undergo limb amputation, respectively. Lymph node characteristics were also significantly related to septic shock (P < 0.05).

Certain lymph node characteristics are associated with amputation in patients with ischemic foot ulcers, after a technically successful endovascular treatment of the limb. Large lymph node size and perinodular fat stranding are predictive of limb amputation.

Kikuchi-Fujimoto disease (KFD) and systemic lupus erythematosus (SLE) are benign entities with histologic features that raise concern about malignancy and infection. We searched for a histology-independent KFD/SLE signature relying on only immunophenotype and basic clinical characteristics.

A histology-independent KFD/SLE signature was generated using 975 excised lymph nodes with flow immunophenotyping, including 16 cases of KFD/SLE. This signature was then evaluated in 1,198 fine-needle aspiration (FNA) specimens.

The top flow cytometry discriminant for KFD/SLE was uniform CD38+ expression on CD19+ events. Immunohistochemistry demonstrated nodules of IgD+, IgM- B cells surrounding necrotizing and activated T-cell areas. A signature combining 6 flow cytometry criteria with age and sample site had a positive predictive value of 88% for KFD/SLE, which had a prevalence of 1.6%. All 4 signature-positive FNA cases with follow-up excision were KFD/SLE. At a second institution, 4 of 5 KFD/SLE cases passed the top discriminant.

A flow cytometry signature combined with age and biopsy site identifies KFD/SLE independent of histology, suggesting a shared immune composition and independently confirming that KFD/SLE represents a distinct entity. Unexpectedly, an IgD+CD38+ small B-cell population is a distinctive feature of KFD/SLE, suggesting a possible pathologic role for anergic/autoreactive B cells.

Cervical lymphadenopathy is among the cardinal manifestations of Kikuchi disease (KD). The incidences and locations of extra-cervical lymph nodes (LNs) involvement in KD have not been comprehensively reported.

From 2003 to 2016, 60 patients with pathologically confirmed KD and with computed tomography and/or whole-body inflammation scans at diagnosis were retrospectively identified. The locations, sizes and characteristics of all affected LNs were analyzed by extensive review of the image studies. The clinical and laboratory parameters were abstracted from medical records and the associations with extra-cervical LNs involvement were identified.

Female accounted for 35 (58.3%) patients and the median age of all patients was 21.3 years (ranges, 3-64 years). Of 59 patients with evaluable neck images, 42 (71.2%) and 16 (27.1%) patients presented with unilateral and bilateral nodal involvement, respectively, with the most common locations at level II, III and IV by Som's classification. The largest LNs appeared most commonly in level II. The incidences of extra-cervical lymphadenopathy in abdomen, pelvis, inguina, axilla and mediastinum with available images were respectively 52.9% (9/17), 47.1% (8/17), 41.2% (7/17), 30.6% (11/36) and 14.3% (8/56). When compared to cases with solitary cervical lymphadenopathy, the cases with extra-cervical lymphadenopathy had significantly greater incidences of bilateral cervical lymphadenopathy (P = .0379) and leukopenia (P = .0173).

Unilateral cervical lymphadenopathy was the most frequent form of LNs involvement of KD. Extra-cervical lymphadenopathy was not uncommon and was associated with the appearance of bilateral distribution of cervical LNs and leukopenia.

To investigate the diagnostic utility of fine needle aspiration (FNA) smear, cell block (CB), flow cytometry (FC) and tuberculosis polymerase chain reaction (Tb-PCR) analysis for Kikuchi's disease (KD).

A total of 173 FNA biopsy samples were collected using a Youyi aspirator. KD was diagnosed by FNA smear, with or without, CB, FC and Tb-PCR.

Out of 173 patients, 131 (75.7%) were female and 126 (72.8%) aged 21-40 years. Of these, 171 patients (98.8%) presented with painful enlarged cervical lymph nodes. All cytological samples identified intracellular apoptotic debris embedded in the cytoplasm of crescentic and phagocytic macrophages. In 24 cell-blocks (CBs), clusters of CD123 positive plasmacytoid monocytes were observed in KD. FC and CBs showed non-specific lymphoid hyperplasia in nine cases with suspicious lymphoma. Tb-PCR was negative in five cases with suspicion of tuberculosis.

In summary, FNA biopsy is a fast, reliable, and relatively inexpensive diagnosis tool for KD. CB preparation is an important adjunct method for the diagnosis of KD.

Histiocytic necrotizing lymphadenitis is an uncommon autoimmune condition characterized by fever, leukopenia, and neck swelling. Diagnostic imaging, including ultrasound and CT, typically demonstrates conglomerates of enlarged cervical lymph nodes with hypervascular cortices and areas of necrosis. Ultimately, the diagnosis is confirmed with the histopathologic findings of paracortical coagulative necrosis with karyorrhectic debris, abundant histiocytes, and absence of neutrophils. Other potential etiologies, such as other causes of infectious lymphadenitis, tuberculosis, lymphoma, and systemic lupus erythematosus, must be excluded. These features are exemplified in this sine qua non radiology-pathology correlation article.