Clinical features of histiocytic necrotizing lymphadenitis in children.

Due to its nonspecific clinical characteristics, histiocytic necrotizing lymphadenitis (HNL) is often misdiagnosed as a suppurative cervical lymphadenitis and lymphoma. Thus, this study aimed to investigate the clinical characteristics of HNL in pediatric patients. We retrospectively identified 61 patients with histopathologically confirmed HNL. Clinical and laboratory data, including age, sex, clinical manifestations, laboratory investigations, histological discoveries, treatment, and outcomes, were collected from the medical records to determine associations with extracervical lymph node (LN) involvement. The mean age of patients was 9.7 ± 2.8 years (range, 1.5-14.0 years), and the male-to-female ratio was 2.2:1. The most common systemic symptom was fever in all patients. The median pre-admission and total durations of fever were 13.0 (interquartile range [IQR]: 9.0-22.5 days) and 22.0 days (IQR: 17.0-33.0 days), respectively. Patients with temporary fever (< 2 weeks) had a higher peak temperature and were more likely to undergo LN biopsy after admission than those with a prolonged fever (≥ 2 weeks). Multivariate analysis revealed that peak temperature ≥ 40 °C was significantly associated with a longer fever duration (P = 0.023). Laboratory values showed leukopenia (68.9%), which presented more frequently in solitary cervical LNs than in extracervical LNs (82.4% vs. 52.9%, p = 0.027) in patients with prolonged fever. CONCLUSIONS: HNL is often misdiagnosed in older children with persistent fever and lymphadenopathy, leading to unnecessary diagnostic tests and evaluations, inappropriate antibiotic administration, and mismanagement. A multidisciplinary team, including primary care providers, rheumatologists, and pathologists, can improve patient outcomes by increasing their awareness of this rare condition. WHAT IS KNOWN: • Histiocytic necrotizing lymphadenitis (HNL) is characterized by fever, leukopenia, and neck lymphadenopathy with unknown etiology. • The lack of neutrophils or eosinophils in the histology, immunohistochemistry results help distinguish HNL from infectious causes. Although HNL is a self-limiting disease, antibiotics and steroid treatments were used inappropriately. WHAT IS NEW: • A fever peak ≥ 40 °C was associated with a longer fever duration in HNL patients. Leukopenia presented more frequently in solitary cervical lymph node (LNs) than in extracervical LNs inpatients with prolonged fever. • Steroids are not recommended as a routine treatment, however, in some severe or relapsing cases with persistent symptoms, prednisolone (5 mg twice a day for 2 days) or other steroids (an equivalent dose of prednisolone) responded favorably.

Malaltia de Kikuchi-Fujimoto amb afectació axil·lar / Enfermedad de Kikuchi-Fujimoto con afectación axilar / Kikuchi-Fujimoto disease with axillary involvement

Introducció. La malaltia de Kikuchi-Fujimoto, o limfadenitisnecrosant histiocítica, és una malaltia rara i benigna quesol autolimitar-se.Cas clínic. Pacient de 12 anys amb febre de llarga duradad’origen desconegut i una adenopatia axil·lar. L’anàlisi desang no mostrava alteracions específiques de l’origen etiològic del quadre. L’ecografia a la zona axil·lar va evidenciarun conglomerat adenopàtic de 5x7 cm amb signes inflamatoris. Es va fer una tomografia per emissió de positrons -tomografia computada (PET-TC) que mostrava adenopatiessupra- i infradiafragmàtiques hiperactives amb una taxametabòlica moderada-alta; l’adenopatia axil·lar presentavaun centre no metabòlic, suggestiu de necrosi. El diagnòsticdefinitiu de malaltia de Kikuchi-Fujimoto es va establirmitjançant la biòpsia d’un gangli limfàtic, que també vaconduir a la resolució clínica del quadre.Comentaris. Mitjançant aquest cas s’espera poder millorarla pràctica clínica dels pediatres davant d’un cas de febreamb una adenopatia, en què cal excloure causes més freqüents com malalties infeccioses, inflamatòries, autoimmunitàries o oncològiques, i facilitar-los la comprensió dela malaltia de Kikuchi-Fujimoto, ja que sovint no estan familiaritzats amb el diagnòstic d’aquesta entitat i això condueix a cursos inadequats d’antibiòtics i a un augment deltemps fins al diagnòstic definitiu. Cal remarcar que l’extirpació de l’adenopatia sol establir el diagnòstic i resoldre la clínica. (AU)

Introducción. La enfermedad de Kikuchi-Fujimoto, o linfadenitisnecrotizante histiocítica, es una enfermedad rara y benigna quesuele autolimitarse.Caso clínico. Niño de 12 años con fiebre de larga duración deorigen desconocido y una adenopatía axilar. El análisis de sangreno mostraba alteraciones específicas del origen etiológico delcuadro. La ecografía a nivel axilar evidenció un conglomeradoadenopático de 5x7 cm con signos inflamatorios. Se realizó unatomografía de positrones - tomografía computarizada (PET-TC)que mostraba adenopatías supra e infradiafragmáticas vas con una tasa metabólica moderada-alta; la adenopatía axilarpresentaba un centro no metabólico, sugestivo de necrosis. Eldiagnóstico definitivo de enfermedad de Kikuchi-Fujimoto se estableció mediante la biopsia de un ganglio linfático, que tambiéncondujo a la resolución clínica del cuadro.Comentarios. Mediante este caso, se espera poder mejorar la práctica clínica de los pediatras frente a un caso de fiebre con unaadenopatía, donde se tienen que excluir causas más frecuentescomo enfermedades infecciosas, inflamatorias, autoinmunes u oncológicas, y facilitarles comprensión de la enfermedad de KikuchiFujimoto, ya que a menudo no están familiarizado con el diagnóstico de esta entidad y ello conduce a cursos inadecuados deantibióticos y un aumento del tiempo hasta el diagnóstico definitivo. Remarcar que la extirpación de la adenopatía suele establecerel diagnóstico y resuelve la clínica. (AU)

Introduction. Kikuchi-Fujimoto disease, or histiocytic necrotizinglymphadenitis, is a rare and benign self-limited disease.Case report. 12-year-old child with long-lasting fever of unknownorigin and one axillary adenopathy. The blood tests failed to identify the etiological origin of the condition. Axillary ultrasoundshowed a 5x7 cm adenopathy conglomerate with inflammatorysigns. A PET-CT was performed reporting hyperactive supra andinfradiaphragmatic adenopathies with a moderate-high metabolicrate; the axillary adenopathy presented a non-metabolic center,suggestive of necrosis. The definitive diagnosis of Kikuchi-Fujimoto disease was established by biopsy of a lymph node, whichalso led to the clinical resolution of the condition.Comments. Through this case, we aimed at improving the clinicalpractice of pediatricians in the presence of a case of fever with anadenopathy, where more frequent causes such as infectious, inflammatory, autoimmune, or oncologic diseases should be excluded; and to provide a better understanding of Kikuchi-Fujimotodisease, as the diagnosis of this entity is often unfamiliar, whichleads to inappropriate courses of antibiotics and increased timebefore final diagnosis. The excision of the adenopathy usually establishes the diagnosis and resolves the symptoms. (AU)

Baffled with fever and lymphadenopathy: neither infection nor malignancy, think Kikuchi disease.

Kikuchi disease is a rare, benign condition of unknown aetiology, which usually involves young women and is characterised by cervical lymphadenopathy and fever. Herein, we are reporting a case of a young Asian woman, who presented with fever and lymphadenopathy raising possibility of either infection or malignancy but after appropriate clinical investigations including lymph node biopsy, it turned out to be Kikuchi disease. She made an uneventful complete recovery with only symptomatic treatment.

Kikuchi's disease with hemophagocytic lymphohistiocytosis: A case report and literature review.

INTRODUCTION: Kikuchi's disease (KD) is a rare form of necrotizing lymphadenitis that rarely occurs in association with hemophagocytic lymphohistiocytosis (HLH) in children. PATIENT CONCERNS: We report the case of a 4-year-5-month-old boy who suffered from fever, cervical lymphadenopathy, pancytopenia, hypertriglyceridemia, splenomegaly, low NK cell activity. DIAGNOSES: A diagnosis of KD with HLH was made based on the results of biopsy of cervical lymph node and HLH-2004 trial guidelines. INTERVENTIONS: The patient was treated with corticosteroids, cyclosporine, etoposide, continuous hemodiafiltration (HDF), and plasma exchange (PE). OUTCOMES: He showed a complete response to therapy, and his condition gradually improved. He was discharged on day 45 after admission due to his good recovery status. CONCLUSION: HLH can be associated with KD, especially in childhood, and may have an aggressive clinical course. Continuous HDF and PE and chemotherapy should be reserved for those patients who fail to respond to IVIG and corticosteroids.

[Efficacy of medicinal penetration on acupoint as adjunctive therapy on histiocytic necrotizing lymphadenitis of heat-toxin syndrome: a randomized controlled trial].

OBJECTIVE: To evaluate the clinical efficacy of medicinal penetration on acupoint combined with medication for histiocytic necrotizing lymphadenitis (HNL) of heat-toxin syndrome, and to explore the methods of improving the clinical effect. METHODS: A total of 72 cases with HNL with heat-toxin syndrome were randomly divided into an observation group and a control group, 36 cases in each group. The patients in the control group were treated with oral administration of prednisone tablets for 40 days (first 5 days: 10 mg, three times a day; since then, reduced by 5 mg every 7 days). In the observation group, on the basis of the medication in the control group, the patients were treated with acupoint application and ultrasonic drug penetration therapy, once a day for 14 days. The acupoints of Waiguan (TE 5), Fengchi (GB 20) of affected side and ashi points were selected. The changes of target lymph node swelling, visual analogue score (VAS), axillary temperature and total score of symptoms and signs were evaluated before treatment and 7, 14, 28 and 40 d into treatment; the changes of white blood cell (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and lactic dehydrogenase (LDH) were evaluated on 14 d and 40 d into treatment; the patients were followed-up for half a year. RESULTS: ① Fourteen days into treatment, the clinical cured rate in the observation group was 38.9% (14/36), which was superior to 16.7% (6/36) in the control group (P<0.01); the clinical cured rates were both 100% in the two groups on 40 d into treatment. ② The VAS score, axillary temperature and the total score 7 d into treatment, as well as node swelling, VAS score, axillary temperature and the total score 14, 28 and 40 d into treatment in the two groups were significantly improved (P<0.01); the total score and VAS score of 7 d into treatment, target lymph node swelling, VAS score and total score of 14 d into treatment in the observation group were significantly improved than those in the control group (P<0.01). ③ Compared before treatment, WBC, CRP, ESR in the two groups were significantly improved 14 d and 40 d into treatment (P<0.01), and LDH in the two groups were decreased 40 d into treatment (P<0.01), but there was no significant difference between the two groups (P>0.05). ④ The recurrence rate in the observation group was 5.6% (2/36), which was similar to 16.7% (6/36) in the control group (P>0.05). CONCLUSION: The medicinal penetration on acupoint as adjunctive treatment could effectively relieve the discomfort symptoms of HNL patients with syndrome of heat and toxin, improve the clinical cured rate, and provide the research direction for shortening the course of medication.

Evaluation of macrophage activation syndrome in hospitalised patients with Kikuchi-Fujimoto disease based on the 2016 EULAR/ACR/PRINTO classification criteria.

BACKGROUND: To evaluate the impact of macrophage activation syndrome (MAS) on clinical features in patients with Kikuchi-Fujimoto disease (KFD) and to compare the features of MAS in KFD with those of adult-onset Still's disease (AOSD) and systemic lupus erythematosus (SLE). METHODS: The medical records of febrile patients hospitalised with KFD between November 2005 and April 2017 were reviewed. Patients fulfilling the 2016 classification criteria for MAS were classified as having MAS. Clinical and laboratory features of patients with KFD with and without MAS were evaluated. Poor hospitalisation outcomes were defined as intensive care unit admission or in-hospital mortality. The treatment outcomes of MAS in KFD, AOSD, and SLE were also compared. RESULTS: Among 78 patients hospitalised with KFD, 24 (30.8%) patients had MAS during admission. Patients with KFD and MAS more frequently required glucocorticoid treatment (66.7% vs 40.7%, p = 0.036) and had longer hospital stays than patients with KFD without MAS (12.5 vs 8.5 days, p<0.001). In addition, patients with MAS had worse hospitalisation outcomes than patients without MAS (29.2% vs. 0.0%, p<0.001). Among patients with MAS in KFD, AOSD, and SLE, the number of patients requiring glucocorticoid treatment after 3 months was significantly lower among patients with MAS and KFD (KFD 33.3%, AOSD 88.9%, SLE 100%, p<0.001). CONCLUSIONS: The presence of MAS in KFD was associated with adverse clinical outcomes including higher steroid usage and worse hospitalisation outcomes. However, compared to those with AOSD and SLE, patients with MAS and KFD were less likely to require long-term glucocorticoid treatment.

Kikuchi-Fujimoto disease in children: two case reports and a review of the literature.

BACKGROUND: Kikuchi-Fujimoto disease is a rare, idiopathic and generally self-limiting cause of lymphadenitis of unknow etiology with a low recurrence rate. The typical clinical signs are cervical lymphadenopathy, fever, and symptoms of respiratory infection, and less frequently chills, night sweats, arthralgia, rash, and weight loss. CASE PRESENTATION: Here we describe two case reports of Kikuchi Fujimoto disease presenting in Milan within the space of a few months. The first involved the recurrence of KFD in a young boy from Sri Lanka; the second was a rare case of severe KFD complicated by HLH. CONCLUSIONS: Pediatricians must consider KFD in the differential diagnosis of fever of unknown origin in children, even in western countries. Although rare, recurrence and severe complications are possible. Where symptoms suggest KFD, a systematic diagnostic approach is key. Since no guidelines on the management of KFD are available, further studies should be conducted to investigate the therapeutic options and long term outcome in children.

Kikuchi-Fujimoto disease: an uncommon cause of neck swelling.

Kikuchi-Fujimoto's disease (KFD) is a rare, benign condition characterized by histiocytic necrotizing lymphadenitis predominantly in the cervical region and prolonged fever. It has a higher prevalence in the Japanese and Asian populations although it may be seen in a wide geographic distribution, but rare are the cases reported in Europe. While symptoms resolve spontaneously between 2 weeks and 2 months, complications are described in: CNS, eyes, respiratory tract, kidney and liver. KFD also described an association with systemic lupus erythematosus. This paper describes a rare case of Kikuchi-Fujimoto lymphadenitis and discusses the features of the disease. A 24-year-old man presented with fever and a swollen 3-cm lymph node in the left side of the neck. The definitive diagnosis was established, after excision of level VB nodes on the left, by histologic examination. It revealed structurally intact tissue with scalloping in the paracortical area presenting activated T cells, focal monocytoid B cells, sinus histiocytosis and normally polarized follicles. Other two samples presented focal alterations of the tissue structure due to broad areas of necrosis, conspicuous nuclear debris, large lymphoid cells as well as numerous histiocytes. Immunohistochemistry revealed CD3+ and CD8+ T lymphocytes and histiocytes expressing CD68/PGM-1 (specific for macrophage lineage) and myeloperoxidase (MPO, specific for myeloid lineage). Correct, prompt diagnosis should be established through the findings of imaging and pathologic studies to avoid unnecessary investigation and ineffective therapies.

Kikuchi-Fujimoto Disease in aYoung African American Male: Are we Seeing a Paradigm Shift in Disease Epidemiology? A Case Report.

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis (HNL), is a rare, self-limiting disease most commonly reported in young Asian women worldwide. We present the case of a 27-year-old African American male who had three weeks of high-grade fevers, night sweats, a 10-pound weight loss, and tender unilateral posterior cervical lymphadenopathy. A complete workup of infectious, rheumatologic, and neoplastic diseases was pursued. Lymph node biopsies revealed histiocyte proliferation with areas of necrosis. These findings were diagnostic of KFD. While KFD has been reported most commonly in young Asian women, in the US, this disease must be considered in both males and females and in diverse ethnicities.

Kikuchi-Fujimoto disease: a clinicopathologic update.

Kikuchi-Fujmoto disease (KFD), also known as "histiocytic necrotizing lymphadenitis", is a rare lymphadenitis of unknown origin, but with an excellent prognosis. It is more common in Asia, but isolated cases are also reported in America, Africa and Europe. The disease can have an acute or subacute course, usually develops in 1 to 3 weeks, with spontaneous resolution in 1-4 months. The main clinical sign is cervical lymphadenopathy, especially in the posterior cervical triangle with bulky and painful lymph nodes, usually affecting only one side; rare cases of generalized lymphadenopathy can be seen. This common clinical presentation can also be accompanied by nausea, vomiting, weight loss, weakness, headache and arthralgia. An extranodal extension of the disease, including involvement of skin, eye, and bone marrow localizations, has been rarely described. Most patients have leukopenia or neutropenia with a relative leukocytosis. At an ultrasound exploration of the affected lymph nodes, a hypoechoic aspect can be seen, with an external, thick and irregular hyperechoic ring. As there are no specific tests for KFD, the final diagnosis is histologically-based from lymph node excisional biopsy. Histological examination shows paracortical foci of coagulative necrosis containing karyorrhectic debris, which are surrounded by numerous CD68+/myeloperoxidase (MPO)+ histiocytes, CD68+/CD123+ plasmacytoid dendritic cells, and a minority of small- to large-sized CD8+lymphocytes and immunoblasts. Differential diagnosis mainly includes systemic lupus erithematous (SLE)-related lymphadenopathy and large cell lymphoma. The histological absence of neutrophils, plasmacells, as well as hematoxylin bodies, is a feature which argues against the diagnosis of SLE. In addition, the absence of auto-antibodies and anti-nuclear antibodies is useful in ruling out an autoimmune disorder. Early diagnosis of KFD is crucial to prevent the patients undergo extensive investigations related to suspected malignant lymphomas or other diseases.

Kikuchi disease.

Kikuchi-Fujimoto Disease or Necrotizing Lymphadenitis is a rare, benign, self-limiting disease. It usually effects young females in the third decade of life. The most common presentation is cervical lymphadenopathy, though the etiology of the disease is still controversial. Clinical findings, histological diagnosis and immunohistochemistry help in diagnosis. Once diagnosed, steroids have been found to alleviate symptoms in patients with systemic manifestations. Antibiotics should not be prescribed until infective element is identified. We report the case of a female patient who presented with tender cervical lymphadenopathy. She was diagnosed on excision biopsy of one of her lymph nodes. Anti-inflammatory drugs were started but the disease relapsed briefly after. Her symptoms have improved remarkably after initiation of steroid therapy, since her relapse.

[Kikuchi-Fujimoto's disease and adult-onset Still's disease. A rare co-occurence]. / Kikuchi-Fujimoto-Syndrom und adulter Morbus Still. Eine seltene Koinzidenz.

Kikuchi-Fujimoto's disease and adult-onset Still's disease are rare inflammatory conditions with overlapping clinical features. Adult-onset Still's disease causes high fevers, a typical salmon-colored rash, and joint pain. The principal symptom of Kikuchi's disease is cervical lymphadenopathy with typical histopathological features including extensive necrosis of the involved lymph nodes. Here, we report on a rare case of concurrent adult-onset Still's disease and Kikuchi-Fujimoto syndrome in a young Caucasian patient.

Kikuchi-Fujimoto Disease: part of the differential diagnosis of cervical lymphadenopathy in an HIV-positive patient.

A 38-year-old HIV-positive Nigerian woman presented with a three-week history of cervical lymphadenopathy, night sweats, weight loss and fever. Provisional diagnoses of tuberculosis and lymphoma were considered; however, a histological diagnosis of Kikuchi-Fujimoto Disease was reached. This rare benign disease has presenting features that mimic more serious conditions commonly occurring in HIV-positive patients. This case report emphasises the importance of Kikuchi-Fujimoto Disease in the differential diagnosis of cervical lymphadenopathy in HIV-positive patients.

An unusual presentation of Kikuchi-Fujimoto disease.

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare, self-limited disease of unknown etiology. This condition is most commonly encountered in Asian and Caucasian females of childbearing age who usually present with cervical lymphadenopathy and fever. Though rarely, KFD has been described in younger African-American females as well. It often mimics more serious conditions such as lymphoma, metastatic solid malignancy, HIV infection, tuberculosis, sarcoidosis, or systemic lupus erythematosus. Although its etiopathogenesis has not been fully elucidated, literature suggests viral or possibly autoimmune components to play a role. We describe a 34-year-old African-American female who presented with constitutional symptoms and polyadenopathy on clinical examination and imaging, of which the portacaval and portahepatis lymph nodes were most prominent. An extensive workup was otherwise unremarkable, and biopsy showed histiocytic necrotizing lymphadenitis. Initially, her clinical condition improved spontaneously, and she required only a short course of oral steroids. Three months later, she relapsed with bilateral cervical adenopathy and constitutional symptoms and was successfully managed again with steroids. Our case is unique with respect to (a) portahepatis and portacaval node enlargement as the dominant adenopathy and (b) her underlying conditions of fibromyalgia and chronic fatigue syndrome.

A case series of autoimmune diseases accompanied by incidentally diagnosed monoclonal gammopathy: is there a link between the two diseases?

AIM: Although the etiology of plasma cell dyscrasia is poorly understood, there is evidence for immune dysregulation or sustained immune stimulation playing a pivotal role in the pathogenesis of these diseases, including chronic infection and autoimmune disorders. In this study, we report four autoimmune disease cases where monoclonal gammopathy (MG) was incidentally found during follow-up. METHODS: We retrospectively reviewed the medical charts and laboratory test results in the following four cases: neuromyelitis optica, Kikuchi disease, Sjögren syndrome and ankylosing spondylosis. RESULTS: The four patients were older than 55 years and the male-to-female ratio was 2 : 2. The autoimmune disease in each case developed differently because two patients had coincidental detection of MG, whereas MG was detected 2 years and 10 years after diagnosis in the other two patients. The amount of M-components in the blood for two cases was ≤ 1 g/dL. For the other two subjects, M-components were ≥ 3 g/dL. CONCLUSION: A high prevalence of MG of undetermined significance (MGUS) has been noted in a series of patients with immune disorders, suggesting a possible association with MG. Further studies should focus on determining how MG relates to various clinical information and laboratory parameters, such as disease duration, disease activity and higher sedimentation rate. In the future, we also need to identify which stimuli, such as cytokine types and levels, can induce lymphocyte clonal transformation and the production of monoclonal antibodies.