Characterization of Kikuchi-Fujimoto Disease in Children and Risk Factors Associated with Its Course.

OBJECTIVE: To outline the characteristics of Kikuchi-Fujimoto disease (KFD) in children and analyze factors associated with severe and recurring courses. METHODS: Electronic medical records of children histopathologically diagnosed with KFD at Seoul National University Bundang Hospital from March 2015 to April 2021 were retrospectively reviewed. RESULTS: 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. CONCLUSIONS: 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: Report of a Case with Progression to Lupus Nephritis.

BACKGROUND Kikuchi-Fujimoto disease (KFD) is an enigmatic disease, with a distinctive histopathology and a benign and self-limited course. It is more frequent in young Asian women. Autoimmune diseases are identified as one of its triggers; primarily SLE, which may precede, be concomitant with, or develop after the diagnosis of KFD. Patients with KFD should receive periodic follow-up for several years to detect possible evolution of SLE. The main feature of KFD is lymphadenopathy, and cervical lymph nodes are involved in 50% to 98% of cases. Other symptoms such as fever, fatigue, weight loss, and arthralgias are also reported. Differential diagnosis between KFD and SLE is a challenge. When KFD and SLE coexist, a lymph node biopsy may be diagnostic. Treatment should be symptomatic with analgesics and anti-inflammatories, with complete resolution in 3 to 4 months. Corticosteroids and immunosuppressive therapy are justified only in cases concomitant with SLE. CASE REPORT We report a case of KFD in a 28-year-old woman who was initially negative for anti-nuclear antibodies (ANA) and anti-double-stranded deoxyribonucleic acid antibodies (anti-dsDNA), but who became antibody-positive and presented with lupus nephritis 2 months later. CONCLUSIONS We present a case of a patient with KFD who developed SLE 2 months later; highlighting the importance of recognizing its association and its possible progression to monitor for future development of SLE and provide timely treatment to avoid complications. We also compared the clinical, laboratory, and histological similarities between the 2 entities.

Hemophagocytic Lymphohistiocytosis Associated with Histiocytic Necrotizing Lymphadenitis: A Clinical Study of 13 Children and Literature Review.

OBJECTIVE: To analyze the clinical characteristics and prognosis of pediatric hemophagocytic lymphohistiocytosis (HLH) associated with histiocytic necrotizing lymphadenitis (HNL). STUDY DESIGN: We retrospectively collected the clinical data of all children with HNL-HLH enrolled in Beijing Children's Hospital from 2007 to 2019. The control patients with Epstein-Barr virus-associated HLH and simple HNL (not associated with HLH) were case matched (1:2). The clinical features and prognosis were analyzed by case-control study. Cases of HNL-HLH in the literature were reviewed. RESULTS: The male-to-female ratio of the 13 patients in our center was 9:4. The mean age of the patients at disease onset was 8.1 ± 1.2 years, younger than that of the 16 patients in the literature (P = .017). Clinical presentations, especially rash and splenomegaly, and laboratory examination of HNL-HLH group were statistically different from Epstein-Barr virus-HLH group, simple HNL group, and patients reported in the literature (P < .05). Three patients were treated with immunosuppressive drugs or chemotherapy owing to poor control of HLH. One patient died, and all 12 remaining patients survived, 2 of which developed autoimmune diseases. Kaplan-Meier survival curves showed no statistical difference among the 3 groups (P > .05). CONCLUSIONS: HNL-HLH is more common in school- and preschool-age children. Most patients have a favorable prognosis. Some patients suffer from relapses or develop autoimmune diseases. Prolonged follow-up should be carried out for patients with HNL-HLH.

Clinical Characteristics of Severe Histiocytic Necrotizing Lymphadenitis (Kikuchi-Fujimoto Disease) in Children.

OBJECTIVES: To analyze the clinical characteristics of children with Kikuchi-Fujimoto disease focusing on cases with prolonged fever. STUDY DESIGN: 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. RESULTS: 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). CONCLUSIONS: 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.

Kikuchi-Fujimoto disease: pediatric case report.

The Kikuchi-Fujimoto disease is a rare disease that occurs mostly in young adults, although some cases have been reported in children. It is usually characterized by fever and cervical lymphadenopathy. The etiology of the disease remains unknown. Its course is usually benign and self-limited. It has special histopathological features that allow the differential diagnosis with other entities, which from a clinical point of view can be very complicated. We report a 9 years 11 months old girl with lymphadenopathy and fever with five months evolution, which is the longest evolution among the cases reviewed by the authors in world literature. Given that the presentation of this disease in children is very rare, we estimate that the knowledge of this disease is relevant and pediatricians must consider it in the differential diagnosis of fever of unknown origin in children.

La enfermedad de Kikuchi-Fujimoto es una entidad rara que se presenta principalmente en adultos jóvenes, aunque se han descrito algunos casos en la edad pediátrica. Se caracteriza por adenopatías generalmente cervicales y fiebre. La etiología de la enfermedad permanece desconocida. Su curso es generalmente benigno y autolimitado. Tiene características histopatológicas especiales que permiten el diagnóstico diferencial con otras entidades, lo que desde el punto de vista clínico puede ser muy complicado. Presentamos el caso de una niña de nueve años y 11 meses que cursó con adenopatías y fiebre de cinco meses de evolución. Este tiempo es el más prolongado entre los casos revisados por los autores en la literatura mundial (búsqueda en PubMed y SciELO por “Kikuchi-Fujimoto Disease”, “histiocytic necrotizing lymphadenitis”). Dado que la presentación de esta enfermedad en la edad pediátrica es muy rara, estimamos pertinente su conocimiento y consideración en el diagnóstico diferencial de la fiebre de origen desconocido en niños.

Kikuchi disease in Connecticut.

Kikuchi disease is a self-limited disorder of unknown etiology characterized by focal painful lymphadenitis, fever, and weight loss that can be mistaken for malignancy. Diagnosis is established by node biopsy. Kikuchi disease is endemic in Asia; 10 cases have been reported in the US to date. We report 3 cases and review other US cases.

Enfermedad de Kikuchi-Fujimoto: a propósito de un caso

La enfermedad de Kikuchi Fujimoto es una forma infrecuente de linfadenitis. En la actual provincia de Mayabeque antes provincia de La Habana no se recoge ningún caso con el referido diagnóstico. Se comunica una paciente femenina de 25 años, color de la piel negra, con diagnóstico de enfermedad de Kikuchi-Fujimoto, que presentaba adenopatías predominantemente en región cervical izquierda. Se realizaron estudios de hematología general, serología viral, exéresis y biopsia del ganglio. La biopsia ganglionar mostró abundantes histiocitos, inmunoblasblos, necrosis celular con polvo nuclear y cariorrexis, así como ausencia de neutrófilos y eosinófilos. Evolucionó favorablemente y actualmente se sigue en consulta de hematología (AU)

Kikuchi-Fujimoto disease is a rare form of lymphadenitis. In the current province of Mayabeque formerly Havana Province no cases have been taken up with the referred diagnosis. It is communicated a female patient of 25 years old, black skin color, diagnosed with Kikuchi-Fujimoto disease, who predominantly presented adenopathies in the left cervical region. Studies of general hematology, viral serology, exeresis and ganglion biopsy were performed. ganglionar biopsy showed abundant histiocytes, immunoblasts, cell necrosis with nuclear dust and karyorrhexis, as well as absence of neutrophils and eosinophils. The patient progressed favorably and is currently being monitored in hematology consultation (AU)

[Histiocytic necrotizing lymphadenitis: report of 3 cases]. / Linfadenitis necrotizante histiocitaria: comunicación de 3 casos.

Histiocytic necrotizing lymphadenitis (also known as Kikuchi-Fujimoto's disease) is an uncommon, benign and self-limiting lymph disease. We report three patients aged 14, 22 and 50 years, who presented with fever and cervical lymphadenopathy, accompanied by skin lesions and joint pain in two of the three cases. One of the patient's sister suffered from histiocytic necrotizing lymphadenitis. Laboratory abnormalities varied and findings included leucopenia, relative neutrophilia, elevated C reactive protein, erythrocyte sedimentation rate and ferritin. Basic laboratory screening tests were performed on all patients to rule out autoimmune and infectious diseases. Lymph node biopsy and subsequent pathological examination were essential to establish the diagnosis. All patients received antibiotics at some point of their hospital stay. Two patients required glucocorticoid treatment, while the remaining case experienced a spontaneous recovery. Its pathogenesis is still unknown, but clinical and histopathological studies suggest a connection with autoimmune diseases. There is no established treatment, but apparently the disease responds to the administration of glucocorticoids.

Linfadenitis necrotizante histiocitaria: Comunicación de 3 casos / Histiocytic necrotizing lymphadenitis: report of 3 cases

Histiocytic necrotizing lymphadenitis (also known as Kikuchi-Fujimoto's disease) is an uncommon, benign and self-limiting lymph disease. We report three patients aged 14, 22 and 50 years, who presented with fever and cervical lymphadenopathy, accompanied by skin lesions and joint pain in two of the three cases. One of the patient's sister suffered from histiocytic necrotizing lymphadenitis. Laboratory abnormalities varied and findings included leucopenia, relative neutrophilia, elevated C reactive protein, erythrocyte sedimentation rate and ferritin. Basic laboratory screening tests were performed on all patients to rule out autoimmune and infectious diseases. Lymph node biopsy and subsequent pathological examination were essential to establish the diagnosis. All patients received antibiotics at some point of their hospital stay. Two patients required glucocorticoid treatment, while the remaining case experienced a spontaneous recovery. Its pathogenesis is still unknown, but clinical and histopathological studies suggest a connection with autoimmune diseases. There is no established treatment, but apparently the disease responds to the administration of glucocorticoids.

Enfermedad de Kikuchi-Fujimoto: a propósito de un caso / Kikuchi-Fujimoto disease: A propos of a case

La enfermedad de Kikuchi Fujimoto es una forma infrecuente de linfadenitis. En la actual provincia de Mayabeque antes provincia de La Habana no se recoge ningún caso con el referido diagnóstico. Se comunica una paciente femenina de 25 años, color de la piel negra, con diagnóstico de enfermedad de Kikuchi-Fujimoto, que presentaba adenopatías predominantemente en región cervical izquierda. Se realizaron estudios de hematología general, serología viral, exéresis y biopsia del ganglio. La biopsia ganglionar mostró abundantes histiocitos, inmunoblasblos, necrosis celular con polvo nuclear y cariorrexis, así como ausencia de neutrófilos y eosinófilos. Evolucionó favorablemente y actualmente se sigue en consulta de hematología

Kikuchi-Fujimoto disease is a rare form of lymphadenitis. In the current province of Mayabeque formerly Havana Province no cases have been taken up with the referred diagnosis. It is communicated a female patient of 25 years old, black skin color, diagnosed with Kikuchi-Fujimoto disease, who predominantly presented adenopathies in the left cervical region. Studies of general hematology, viral serology, exeresis and ganglion biopsy were performed. ganglionar biopsy showed abundant histiocytes, immunoblasts, cell necrosis with nuclear dust and karyorrhexis, as well as absence of neutrophils and eosinophils. The patient progressed favorably and is currently being monitored in hematology consultation

Enfermedad de Kikuchi-Fujimoto / Kikuchi-Fujimoto’s disease

La Enfermedad de Kikuchi-Fujimoto, también llamada Linfadenitis Histiocítica Necrosante, es un sindrome benigno y autolimitado descubierto por primera vez en 1972 por Kikuchi y por Fujimoto, dos patólogos japoneses. Es una enfermedad principalmente descrita en mujeres jóvenes hasta los 40 años de edad que se ha encontrado en todos los grupos étnicos y que puede presentarse en una proporción menor en hombres. La etiología es desconocida, aunque se ha asociado a ciertos microorganismos, y son las infecciones junto con el linfoma los principales diagnósticos diferenciales de esta enfermedad, caracterizada por linfadenopatía cervical con dolor, fiebre leve y síntomas sistémicos. El estudio histopatológico de los ganglios linfáticos permite diferenciar esta enfermedad de otras más graves, aunque es indistinguible histológicamente del Lupus Eritematoso Sistémico con el cual puede presentarse concomitantemente.

Kikuchi-Fujimoto’s disease, also called Histiocytic Necrotizing Lymphadenitis is a benign, self-limited syndrome. It is a disease mainly described in young women under 40 years of age, it has been found in all ethnic groups and may occur in a lesser extent in men. The etiology is not known, although it has been associated with some microorganisms. The differential diagnoses of this disease are infections and lymphoma. This disease is, characterized by cervical lymphadenopathy with pain, mildfever and systemic symptoms. Histopathological study of lymphnodes differentiate this disease from others more serious, although histologically it’s indistinguishable of Systemic Lupus Erythematosus with which can occur concomitantly.

Kikuchi-Fujimoto disease: an unusual association with acute renal failure

Kikuchi-Fujimoto disease, also known as histiocytic necrotizing lymphadenitis of unknown etiopathogenesis, is a self-limited disease which frequently appears as feverish lymphadenomegaly, thus creating the need for differential diagnosis with lymphoma, systemic lupus erythematosus (SLE), infectious mononucleosis, cat-scratch disease, and toxoplasmosis with lymphonodal impairment. However, there are cases in which it may evolve with complications such as aseptic meningitis, cerebellar ataxia, and aseptic myocarditis. We are presenting a case of a 24-year-old man who had an initial picture of arthralgia, evening fever and adenomegaly. Kikuchi disease was diagnosed through lymph node biopsy with immunohistochemistry and evolves with severe systemic manifestations, such as pericarditis with cardiac tamponade, pneumonitis, hepatitis, and acute kidney failure - the latter has not been reported in literature yet. There was significant improvement of the clinical picture with prednisone.

[Kikuchi-Fujimoto disease: pediatric case presentation]. / Enfermedad de Kikuchi-Fujimoto: presentación de un caso pediátrico.

Kikuchi-Fujimoto disease or histiocytic necrotizing lymphadenitis is a rare, benign condition, usually self-limited to a six-month period. Classic clinical presentation is characterized by cervical lymphadenopathy, leukopenia and prolonged fever. It affects principally young, Asiatic adult women, although a few cases in the pediatric population have been reported. This disease frequently mimics tuberculous lymphadenitis, malign lymphoma, systemic lupus erythematosus and other benign and malignant conditions. The etiology is unknown, although a viral or autoimmune pathogenesis has been suggested. Laboratory investigations are usually unremarkable, and the most frequent findings are leukopenia, elevated erythrocyte sedimentation rate, anemia and positive antinuclear antibodies. To make an accurate diagnosis, histopathological studies are required. To avoid the use of antibiotics (which have no effect), early diagnosis is necessary. Herein the case of a 10 years old girl is described that presented with high, prolonged fever and marked cervical lymphadenopathy secondary to Kikuchi-Fujimoto disease.

Kikuchi-Fujimoto disease: an unusual association with acute renal failure.

Kikuchi-Fujimoto disease, also known as histiocytic necrotizing lymphadenitis of unknown etiopathogenesis, is a self-limited disease which frequently appears as feverish lymphadenomegaly, thus creating the need for differential diagnosis with lymphoma, systemic lupus erythematosus (SLE), infectious mononucleosis, cat-scratch disease, and toxoplasmosis with lymphonodal impairment. However, there are cases in which it may evolve with complications such as aseptic meningitis, cerebellar ataxia, and aseptic myocarditis. We are presenting a case of a 24-year-old man who had an initial picture of arthralgia, evening fever and adenomegaly. Kikuchi disease was diagnosed through lymph node biopsy with immunohistochemistry and evolves with severe systemic manifestations, such as pericarditis with cardiac tamponade, pneumonitis, hepatitis, and acute kidney failure - the latter has not been reported in literature yet. There was significant improvement of the clinical picture with prednisone.

[Kikuchi-Fujimoto disease: case report]. / Enfermedad de Kikuchi-Fujimoto: Presentación de un caso clínico.

Kikuchi-Fujimoto disease is a self-limited condition of young adults, that usually involves the cervical lymph nodes and is associated with persistent hyperthermia. Diagnosis is based on characteristic pathologic findings, that allows the differential diagnosis with other similar clinical conditions. We report one case of Kikuchi-Fujimoto disease in a 12 year old girl and review the world literature.

Enfermedad de Kikuchi-Fujimoto: presentación de un caso clínico / Kikuchi-Fujimoto disease: case report

La enfermedad de Kikuchi-Fujimoto es una enfermedad de los ganglios linfáticos, habitualmente benigna y autolimitada, que afecta principalmente a adultos jóvenes y se caracteriza poradenopatías (en general cervicales) e hipertermia persistente. Debe diferenciarse de otras causas, infecciosas o tumorales, que cursan con cuadro clínico similar. Su diagnóstico es anatomopatológico (linfadenitis necrotizante histiocitaria) y su tratamiento sintomático. Se presenta un caso clínico de enfermedad de Kikuchi-Fujimotoen una niña de 12 años y se revisa la bibliografía mundial.