Kikuchi-Fujimoto Disease (KFD), also known as Kikuchi disease or Kikuchi histiocytic necrotizing lymphadenitis, is a rare and self-limiting condition characterized by cervical lymphadenopathy and fever, primarily affecting young Asian adults. The aetiology of KFD remains unknown, although various infectious agents have been suggested as potential triggers. With the emergence of the COVID-19 pandemic, cases of post-COVID-19 KFD and post-COVID-19 vaccine KFD have been reported. In this article, we present the first case of post-COVID-19 KFD in Hong Kong. A 24-year-old man developed fever and painful neck swelling 1 month after recovering from COVID-19. Diagnostic evaluation, including ultrasound-guided fine needle aspiration cytology (FNAC), confirmed the diagnosis of KFD. The patient's symptoms resolved spontaneously with supportive care. This case underscores the importance of considering KFD as a potential differential diagnosis in patients presenting with cervical lymphadenopathy and fever following COVID-19 recovery or vaccination.

To outline the characteristics of Kikuchi-Fujimoto disease (KFD) in children and analyze factors associated with severe and recurring courses.

Electronic medical records of children histopathologically diagnosed with KFD at Seoul National University Bundang Hospital from March 2015 to April 2021 were retrospectively reviewed.

A total of 114 cases (62 males) were identified. The mean patient age was 12.0 ± 3.5 years. Most patients came to medical attention with cervical lymph node enlargement (97.4%) and fever (85%); 62% had a high-grade fever (≥39°C). Prolonged fever (≥14 days) was seen in 44.3% and was associated with a high-grade fever (P = .004). Splenomegaly, oral ulcer, or rash was present in 10.5%, 9.6%, and 15.8%, respectively. Laboratory findings showed leukopenia, anemia, and thrombocytopenia in 74.1%, 49%, and 24%, respectively. Sixty percent of cases had a self-limited course. Antibiotics were initially prescribed in 20%. A corticosteroid was prescribed in 40% of patients and was associated with oral ulcer (P = .045) and anemia (P = .025). Twelve patients (10.5%) had a recurrence with a median interval of 19 months. No risk factor for recurrence was identified in multivariable analysis. Clinical characteristics of KFD were similar between our current and previous studies. However, antibiotics use decreased (P < .001); nonsteroidal anti-inflammatory drugs use increased (P < .001), and, although statistically not significant, corticosteroid treatment also increased.

Over a span of 18 years, the clinical characteristics of KFD did not change. Patients presenting with high-grade fever, oral ulcer, or anemia may benefit from corticosteroid intervention. All patients should be monitored for recurrence.

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.

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.

To analyze the clinical characteristics of children with Kikuchi-Fujimoto disease focusing on cases with prolonged fever.

This was a retrospective study of children diagnosed with Kikuchi-Fujimoto disease from March 2003 to February 2015 in South Korea. Electronic medical records were searched for clinical and laboratory manifestations.

Among 86 histopathologically confirmed cases, the mean age was 13.2 (SD ± 3.1) years, and male to female ratio was 1:1.32. Cervical lymph node enlargement, found in 85 of the patients (99%), was predominantly unilateral in 64 (75%), and involved the cervical lymph node level V in 67 (81%). Fever was present in 76% of the cases, with a median duration of 9 days (IQR 0.25-17.0). Multivariate analysis revealed that a high fever peak ≥ 39.0°C (P = .010) and presentation with ≥ 2 systemic symptoms other than fever (P = .027) were factors that were significantly associated with longer fever duration. As the size of the largest lymph node's short diameter increased, the fever duration increased (P = .015). Leukopenia (P = .022) also had a significant association with a longer fever duration. Patients with sonographic findings of conglomerated enlarged lymph nodes had a longer median duration of fever compared with those with separate enlarged lymph nodes (11 vs 4.5 days, P = .019).

Patients with high fever, more systemic symptoms, leukopenia, and larger lymph nodes with a conglomerated distribution may benefit from early recognition and selective consideration of corticosteroid therapy.

Lymph node or spleen enlargement may be innocent or the first sign of a serious disorder. Lymphadenopathy and splenomegaly can be found in symptomatic or asymptomatic patients. Lymph node enlargement in a single region or multiple sites can be seen in various diseases, including infections, noninfectious inflammatory conditions, or malignancies; a similar differential diagnosis applies to splenomegaly, but splenomegaly can also be caused by vascular abnormalities and hemolysis. Frequently, lymphadenopathy is detected incidentally during screening examinations or imaging procedures. This review focuses on causes of lymphadenopathy and splenomegaly and an appropriate diagnostic approach to patients with lymphadenopathy or splenomegaly.

We describe a rare case of intramammary and axillary lymphadenopathy caused by Kikuchi-Fujimoto disease (KFD). A 30-year-old woman presented with enlarged axillary lymph nodes and a right breast mass with tenderness. Computed tomography, ultrasonography, F-2-deoxy-fluoro-D-glucose positron emission tomography and fine-needle aspiration cytology were performed, and malignant lymphoma (ML) was suspected. Histological diagnosis of a needle biopsy and surgical specimen showed histiocytic necrotizing lymphadenitis. It is important to differentiate KFD from ML because of differences in treatment choice and clinical outcome.

Lymphadenopathy of the head and neck region is a common finding in children and a very common reason to image the craniocervical region. Enlarged lymph nodes are commonly palpated by the pediatrician in the office and commonly imaged by the pediatric radiologist. The difficult task of the clinician is to determine whether the adenopathy is acute (<3 weeks) or chronic (>6 weeks) and when imaging is indicated. In children, radiation is always a consideration when choosing an imaging modality; thus, US is usually the first imaging study at our institution, and CT the second option, usually reserved for the very ill child or for when there is a high index of suspicion for malignancy. We present the normal anatomy of head and neck lymph nodes and the US, CT, and MRI appearances in normal and pathologic states to help clinicians generate a reasonable differential diagnosis and prevent unnecessary procedures.

Kikuchi-Fujimoto disease (KFD) is a rare and benign disease that typically affects the cervical lymph nodes. Its aetiology is unknown and a role of the autoimmune system in the pathogenesis is hypothesized. This self-limiting disease is often confused with malignancies. No specific management is generally required but long-term follow-up should be planned despite the low risk of recurrence, as recurrences have been described many years after the first episode and there is a high risk of development of an autoimmune disease or even lymphoma. We review the clinical and histological features of KFD and report an unusual case presenting with cervical and supraclavicular lymphadenopathy, and persistent fever.

Kikuchi-Fujimoto disease (KFD), first described independently by Kikuchi and Fujimoto in 1972, is a subacute necrotizing lymphadenitis of unknown cause. Although most frequent in young Asian women, KFD has a worldwide distribution. Clinically, KFD is characterized by lymphadenitis of one or more lymph nodes, predominantly in the posterior cervical region, fever, and leukopenia in up to 50% of cases. Extranodal manifestations can occur, especially skin lesions and aseptic meningitides. Diagnosis is usually confirmed by analysis of samples from an excisional biopsy of the affected nodes. Histologically, the lesions affect the cortical and paracortical areas of the node. Characteristic features include focal necrosis predominantly in the paracortical region with abundant karyorrhectic debris and atypical mononuclear cells around the necrotic zone (crescent-shaped histiocytes, plasmacytoid monocytes, and small lymphocytes and immunoblasts, mostly CD3(+)/CD8(+)), most often with an intact lymph node capsule, an absence of neutrophils, and a paucity of plasma cells. KFD has been classified into three histological subtypes and is thought to progress from the proliferative type (> 50%) to the necrotizing type (30%) and finally resolve into the xanthomatous type (< 20%). Differential diagnoses should include malignant lymphoma, infectious diseases such as toxoplasmatic lymphadenitis, tuberculous lymphadenitis and cat scratch disease, and systemic lupus erythematosus (SLE). The cause of KFD is unknown: a viral infection has been suggested, but not demonstrated, possibly involving human herpes virus 8 or Epstein-Barr virus. Apoptotic cell death plays a role: proliferating CD8(+) T-lymphocytes act as both killers and victims in the apoptotic process via Fas and perforin pathways. The course is usually benign with resolution in a few months with the use of antiinflammatory drugs. Regular follow-up is required because SLE may develop several years after the onset of Kikuchi-Fujimoto disease.

We present a case of Kikuchi's disease causing meningitis associated with fever and treated successfully with corticosteroids alone. This is considered to be rare but provides an instructive example of how the diagnosis may be confused with that of tuberculous meningitis and highlights the importance of histopathological analysis.

Despite the efforts for control and eradication of tuberculosis, new cases of the disease are diagnosed daily. The diagnosis of tuberculosis is easily made when the classical features of pulmonary necrotizing granulomatous inflammation are seen. However, extrapulmonary lesions may clinically and radiographically mimic a neoplastic process, and this may lead to misdiagnosis and delay in treatment. We studied 6 patients by aspiration biopsy, all recent immigrants and immunocompetent, who presented with weight loss and fatigue. Of these, 5 patients had a mass. One patient presented with a lytic lesion of bone. In all cases the clinical diagnosis was neoplasia. In all aspirates, the smears showed necrotic debris with neutrophils. No neoplastic cells or granulomas were seen. All cases were signed out descriptively with no specific diagnosis. A search for acid-fast organisms leading to the correct diagnosis of tuberculosis was prompted by clinical investigations that revealed pulmonary lesions, or by repeat aspiration biopsy, which showed granulomatous inflammation. Tuberculosis when present in atypical forms is still a challenging diagnosis. The finding of necrotic debris in a needle biopsy without the clinical signs of an abscess should prompt a search for acid-fast bacilli, since the correct diagnosis will eliminate a needless surgical procedure and will lead to timely and appropriate therapy.

The purpose of this study was to evaluate the cytologic features of Kikuchi's lymphadenitis (KL). Smears from 10 patients with histologically proven KL were reviewed. In all cases, fine-needle aspiration (FNA) was performed prior to biopsy. To assess the validity of morphologic recognition, a blinded study, including smears from non-Hodgkin's lymphomas, nonspecific, and mycobacterial lymphadenitis was performed. At least 5 cases showed characteristic cytologic findings that permitted their specific recognition. A polymorphous lymphoid population with abundant karyorrhectic debris and histiocytes, many of which showed a small size and eccentrically placed, crescent nuclei, were characteristic features of KL. The remaining 5 cases failed to show typical findings and were indistinguishable from other nonspecific, reactive lymphadenopathies. When typical cytologic findings are present in an adequate clinical context (cervical nodes in young patients), a precise diagnosis is possible, avoiding unnecessary biopsies.

The authors describe two children with Kikuchi necrotizing lymphadenitis, the main manifestations of which were cervical lymphadenopathy, fatigue, and fever. The diagnosis was based on histopathologic findings after open biopsy. Results of serologic studies, immunoperoxidase staining for Epstein-Barr virus (EBV) latent membrane protein, in situ hybridization for Epstein-Barr encoded RNAs, and polymerase chain reaction amplification of EBV Epstein-Barr nuclear antigen-1 (EBNA) DNA suggested that EBV was the causative agent in both patients. The disease was mild and subsided after complete surgical resection in one patient, with a follow-up of 1 year. In the other patient, a short course of corticosteroids led to complete clinical remission within 2 months, but the child still has biologic signs of persistent EBV infection. He experienced relapse with a large cervical mass and fever 28 months after the initial onset. Histologic findings were identical to those at initial presentation. Symptoms again resolved spontaneously within 2 weeks, but the follow-up was short (12 mos) and the child's EBNA antibodies are still absent. No evidence of immunodeficiency was found in either child. The cause of Kikuchi disease is unknown, but a viral or postviral hyperimmune reaction has been proposed. Malignant lymphoma and systemic lupus erythematosus are differential diagnoses. Early recognition of Kikuchi disease minimizes potentially harmful and unnecessary investigations and treatments. These findings add Kikuchi disease to the protean manifestations of chronic EBV infection.

Histiocytic necrotizing lymphadenitis or Kikuchi-Fujimoto disease is a rare entity, and even more rarely, it is associated with other diseases. In a few cases, the condition is associated with cutaneous lupus erythematosus (CLE). Histiocytic necrotizing lymphadenitis predominantly affects young women, who present with solitary or multiple cervical lymphadenopathy accompanied by symptoms such as fever, weight loss, sweating, or, in exceptional cases, hepatosplenomegaly. Laboratory examinations show normal or nonspecific results. The disease is of unknown origin, although a viral origin has been suggested, with the suspected agents including Epstein-Barr virus, herpesvirus type 6, and cytomegalovirus (CMV). Although the first and most of the more recent cases have been reported in Oriental patients, the disease has a wide geographic distribution. The clinical evolution is favorable, with spontaneous remission in less than 4 months in almost all cases. We present a case of a 37-year-old woman from Peru who presented with cervical adenopathies on two occasions. Biopsy of a lymph node revealed a histopathologic picture compatible with Kikuchi-Fujimoto histiocytic necrotizing lymphadenitis. The adenopathy disappeared in a few months. A year later, she presented with a maculopapular rash in the nasal and malar regions. The results of the skin biopsy and immunofluorescence examination were compatible with chronic CLE. The results of the serology testing for CMV were positive. Treatment with chloroquine was initiated, with almost complete recovery by 5 months. No manifestations of systemic lupus erythematosus have occurred since. The epidemiologic, clinical, and anatomopathologic aspects as well as the differential diagnosis of this entity are reviewed.

Kikuchi's disease (KD), or histiocytic necrotizing lymphadenitis, was initially described in Japan in 1972. In the following years, several series of cases involving patients of different ages, races, and geographic origins were reported, but pediatric reports have been rare. The etiology of KD is unknown, although a viral or autoimmune hypothesis has been suggested. The most frequent clinical manifestation consists of local or generalized adenopathy, although in some cases, it is associated with more general symptoms, multiorganic involvement, and diverse analytic changes (leukopenia, elevated erythrocyte sedimentation rate, and C-reactive protein, as well as an increase of transaminases and serum lactic dehydrogenase). Diagnosis is based on characteristic pathologic findings that permit differentiation of this disease from lymphoma, systemic lupus erythematosus, and infectious lymphadenopathies. We present here the case of a 14-year-old boy who presented with severe systemic manifestations and transient fulminant hepatic failure in response to treatment with antituberculosis drugs. Kikuchi's disease, lymphadenitis, liver failure, antituberculosis drugs.

Spontaneous, suppurative-necrotizing changes associated with Hodgkin's disease (HD) are not infrequent. They are mostly observed in the nodular sclerosis variant of HD and can cause an erroneous histologic diagnosis of suppurative lymphadenitis. Few cytologic reports describing this presentation of HD are available. We describe 5 cases of HD that showed cytologic abscess-like smears dominated by a massive neutrophilic infiltrate and necrosis. Since therapy can induce similar changes, this study did not include patients with known HD. In 2 cases erroneously diagnosed as suppurative lymphadenitis, the presence of neoplastic cells was minimal and only detected after revision. A third case was misdiagnosed as abscessified metastasic carcinoma. Two cases were correctly identified as HD, although in one, the possibility of anaplastic large-cell lymphoma could not be ruled out. In conclusion, necrosis and massive neutrophilic infiltrates can occur spontaneously and can be prominent findings in smears from patients with HD, mainly the nodular sclerosis variant. The cytopathologist should always consider this possibility in the presence of an abscessified, suppurative, lymphadenitis-like aspirate. A detailed search for the characteristic neoplastic cells of HD is mandatory in these cases.

PURPOSE. A 32-year-old Saudi female presented with typical Kikuchi-Fujimoto disease, i.e., fever, cervical lymphadenitis and leukopenia, but there was also painful upper eyelid swelling with pain on upgaze. METHODS. A connective tissue disease and lymphoma workup were unremarkable, as were antibody titers to Apifia felis and Bartonella henselae. RESULTS. Orbital computed tomography showed significant lacrimal gland enlargement. Cervical node biopsy revealed necrotizing lymphadenitis. CONCLUSION. Concomitant lacrimal gland inflammation and cervical lymphadenopathy may be a benign self-limited disease.

We present a unique case of fine-needle aspiration (FNA) from a lymph node with subsequent histologic diagnosis of tumor of plasmacytoid monocytes (PMs). The patient had an associated myeloproliferative disease which terminated into an acute myelomonocytic leukemia. In a 95% ethanol-fixed, hematoxylin-eosin (H&E)-stained smear, the tumor cells appeared monomorphic, medium size, with oval to indented nuclei, finely stippled chromatin, and small nucleoli; the cytoplasm was scanty and slightly eccentric. The cytologic picture suggested some subtypes of small-cell non-Hodgkin's lymphomas or a leukemic infiltration. In the FNA specimen, the cells appeared immunocytochemically negative for some B- and T-cell markers (MB2, L26, LN1, and UCHL1) and strongly positive to KP1, a known histyocyte-macrophage and myeloid marker. The FNA differentiated diagnoses are discussed.

A 37 year old male with a poorly differentiated carcinoma of the stomach presented with cervical lymphadenopathy. It was clinically thought to be a metastatic carcinoma, but on biopsy, it exhibited features of Kikuchi's lymphadenitis. Distinguishing the signet ring histiocytes seen in Kikuchi's disease from signet ring carcinoma cells can be a diagnostic problem. To our knowledge this is the first reported case of an association of Kikuchi's disease and carcinoma.