Kikuchi-Fujimoto病

Kikuchi—Fujimoto病，或称组织细胞坏死性淋巴结炎，是一种自限性疾病。其特征是良性的淋巴结肿大，可伴有发热和系统性症状。该病最常累及亚裔人，常为小于40岁的年轻成人患者。受累淋巴结常显示副皮质区凋亡坏死，可见大量核碎片以及组织细胞、浆样树突细胞和CD8阳性的T细胞增生，但缺乏中性粒细胞浸润。Kikuchi—Fujimoto病的病变进程分3期：增生期、坏死期和黄色瘤期。

Kikuchi-Fujimoto病多模态超声特征探讨

目的:总结Kikuchi-Fujimoto病(Kikuchi-Fujimoto disease,KFD)多模态超声特征,探讨多模态超声对KFD的诊断价值。方法:回顾性分析2017年1月—2018年10月南京市中西医结合医院收治的36例KFD患者的临床资料。检查模式包括常规二维超声(ultrasound,US)、彩色多普勒血流成像(color Doppler flow imaging,CDFI)、超声造影(contrast enhanced ultrasound,CEUS)、超声弹性成像(elastography imaging,EI)、三维超声重建(three-dimensional ultrasound,3-DUS)等多模态超声检查形式。所有病例均经切除或穿刺活检病理证实。结果:①常规US:36例KFD中单侧颈部30例(其中单侧多枚多区域淋巴结肿大者27例),双侧多发6例;3例单发,33例多发;多广泛累及颈上、颈中、颈下或锁骨上淋巴结群(颈部Ⅱ、Ⅲ、Ⅳ、Ⅴ区),呈簇状分布或串珠状排列,未见明显融合,形态饱满,少数为类圆形,36个淋巴结平均最大横径(T)(10.5±4.1)mm;平均最大纵径(L)(19.8±7.1)mm;T/L平均0.70±0.36。其均有完整、清晰的边界回声,其中30例周围组织水肿、回声增强(83.3%),内部为不均匀低回声;31例可见淋巴门回声(86.1%),5例淋巴门结构显示不清或消失(13.9%)。②CDFI及CEUS:CDFI显示KFD内部多为淋巴门型血流,信号丰富。血流Adler分级Ⅱ~Ⅲ级,阻力指数(resistive index,RI)0.60±0.08,搏动指数(pulsatility index,PI)0.85±0.12。CEUS成像模式下,在增强动力学模式方面,20例为离心型增强,13例为弥漫型增强,3例不典型改变;在增强的均匀性方面,多为弥漫非均匀充盈型,内可见小片状坏死组织无充盈区域。③EI:36例KFD病灶质地中等偏硬,弹性应变率比值(elasticity strain ratio,ESR)2.05±0.78;④3-DUS:KFD内部可见粗细不等的网状条索样结构立体分布。结论:KFD超声表现具有一定特征性,多模态超声检查有助于全面把握KFD信息,综合评价其相关特点,具有较高临床应用价值。

Fatality in Kikuchi-Fujimoto disease: A rare phenomenon

Kikuchi-Fujimoto disease(KFD), also known as histiocytic necrotizing lymphadenitis, is an uncommon condition, typically characterized by lymphadenopathy and fevers. It usually has a benign course; however, it may progress to fatality in extremely rare occasions. The diagnosis is made via lymph node biopsy and histopathology. Our patient was a young female who presented with shortness of breath, fever, and malaise. Physical examination revealed significant cervical and axillary lymphadenopathy. Chest X-ray displayed multilobar pneumonia. She required intubation and mechanical ventilation for progressive respiratory distress. Histopathology of lymph nodes demonstrated variable involvement of patchy areas of necrosis within the paracortex composed of karyorrhectic debris with abundant histiocytes consistent with KFD. After initial stabilization, the patient's condition quickly deteriorated with acute anemia, thrombocytopenia and elevated prothrombin time, partial prothrombin time, and D-dimer levels. Disseminated intravascular coagulopathy(DIC) ensued resulting in the patient's fatality. DIC in KFD is not well understood, but it is an important cause of mortality in patients with aggressive disease.

Kikuchi-Fujimoto病

Kikuchi-Fujimoto病(KFD)临床上主要表现为淋巴结肿大及发热,其中40%的患者可有皮肤受累。淋巴结活检组织病理学检查可见含核碎屑的凝固性坏死灶。临床上常被误诊为结核、系统性红斑狼疮及血液系统肿瘤等疾病。KFD症状和体征常在1～4个月内消失且较少复发,一般只需对症支持治疗,及时明确诊断以避免过度治疗十分重要。本文对KFD的发病机制、临床表现、诊断及治疗进行综述。

EB病毒VCA-IgM抗体阳性的Kikuchi-Fujimoto病

目的：分析并探讨KDD的发病机制、临床特点、诊断及治疗方法。方法：对5例于1992～1996年收治的EBV－VCA-IgM抗体阳性的KFD患者进行回顾性研究。结果：5例病人均通过肿大淋巴结活检确诊。临床都表现为颈淋巴结肿大、发热、白细胞减少、血沉增快及LDH增高。对强的松治疗较敏感。结论：尚不能确定EBV即为KFD的发病原因。淋巴结活检是唯一确诊手段。该病报告日渐增多，应引起临床医师足够重视。

An atypical presentation of Kikuchi-Fujimoto disease mimicking systemic lupus erythematosus: case report and literature review

Purpose: To report a case of atypical Kikuchi-Fujimoto disease (KFD) that illustrates several overlapping features with systemic lupus erythematosus (SLE). Methods: A case is reported followed by a review of the current literature. Case report: A 16-year-old boy with an unusual manifestation of Kikuchi-Fujimoto disease (KFD) is described. The patient presented with fever, weight loss and severe abdominal pain, due to extensive necrotizing retroperitoneal and mesenteric lymphadenopathy. During the course of his illness, he developed several symptoms suggestive of systemic lupus erythematosus (SLE): a pericardial effusion, cotton wool spots on the retina and antibodies against nuclear antigens (ANA), Smith (Sm) and ribonucleoprotein (RNP) antigens. However, no additional features of SLE were found. The patient subsequently fully recovered within two months, without initiation of immunosuppressive therapy. His autoantibodies became negative five months after initial presentation and he remains well at his 23 month follow up visit. Discussion: We hypothesize that the autoantibodies developed by our patient were secondary to self-antigen induced autoimmunity related to his extensive tissue necrosis. Despite initially having clinical features suggestive of SLE, our patient’s full and spontaneous recovery strongly supports the diagnosis of KFD. This illustrates the need for careful diagnosis, in order to avoid unnecessary and potentially toxic treatment with immunosuppressive agents.

Kikuchi-Fujimoto Disease Mimicking Tuberculosis

A 32-year-old woman presented with a fever and cervical lymphadenopathies. The research for Mycobacterium tuberculosis was negative. Tuberculin skin test was positive. Laboratory investigations showed an elevated erythrocyte sedimentation rate and a normal white blood cell count. Bacteriological and viral investigations were negative. Quantiferon-Tb Gold test was indeterminate. Thraco-abdominal and pelvic computed tomography, FDG-PET and gallium scintigraphy revealed no abnormalities. Histological study of cervical lymph node biopsy found signs in favor of histiocytic necrotizing lymphadenitis. There were no epithelioid cell granulomas. A test tuberculosis treatment was refused by the patient. The evolution was marked by spontaneous clinical and biological resolution in fifty days. The negative Lowenstein-Jensen culture eliminated formally the tuberculosis. KFD was thus the most likely diagnosis.

Kikuchi-Fujimoto Disease Associated to the Epstein-Barr Virus. A Type of Rare Necrotizing Lymphadenitis and Its Differential Diagnosis

Introduction: Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a specific and self-limited disease;its etiology is unknown. Some causal microorganisms have been proposed. The objective of the present article is to emphasize the clinicopathological characteristics of this disease that has been associated to the Epstein-Barr virus and to compare the histological changes with other types of necrotizing lymphadenopathies. Material and Methods: We studied 32 patients of the Surgical Pathology Service with necrotizing lymphadenitis, diagnosed in the years from 2004 to 2012 to found more cases of this rare disease in our Institution. Patients were 18 women and 14 men with an average age of 37 years. Results: The lymph nodes were cervical and axillary ones, some were associated to autoimmune diseases and no cause was identified in others. One of the cases, was diagnosed as KFD, presented morphological changes characteristic of this disease, such as subcapsular lymphoid follicles, zones with cell debris, epithelioid macrophages, clear-cytoplasm histiocytes, and immunoblast-reactive lymphocytes. Immunohistochemical markers were determined, such as CD20, CD2, CD4, CD8, CD68, lysozyme, CD56, granzyme B and EBER, which demonstrated the presence of B, T lymphocytes, histiocytes and cells positive to EBER. Histological changes in KFD occurred in three stages: proliferative stage, necrotizing, and xanthomatous. It is important to identify the histological stages of the disease because a differential diagnosis must be performed in regard to lymphadenopathies with necrosis and diverse types of lymphomas. Conclusion: We present a case of necrotizing lymphadenitis (KFD) associated to the Epstein-Barr virus and in some cases it is not possible to render a specific diagnosis based on morphologic findings, alone, and a diagnosis of necrotizing lymphadenitis may be used.

Kikuchi-Fujimoto Disease with Hemophagocytic Syndrome and Pleural Effusion in an Elder Man: A Case Report and Literature Review

Background: Kikuchi-Fujimoto disease (KFD), also named Histiocytic necrotizing lymphadenitis (HNL), is a rare and self-limited necrotizing lymphadenitis, most commonly affects young Asian female. KFD is characterized by lymphadenopathy, cytopenia, fever, rashes, and weight loss, however, hemophagocytic syndrome and pleural effusion are rarely reported. Case Presentation: We present the case of a 61-year-old man with clinical features including fever, lymphadenopathy, purpura, arthralgia, pleural effusion and pulmonary infection. He had cervical lymphnodebiopsy and the pathology is consistent with KFD, laboratory tests and clinical manifestations were consistent with hemophagocytic syndrome (HLH). After initial treatment including corticosteroid and anti-infection drugs, the patient showed improvement but soon deteriorated. Conclusion: KFD is a self-limited disease with spontaneous resolution. However, the cases of KFD with HLH may have a fatal course. Early appropriate intensive immunosuppressive therapy and strong anti-infection therapy could be beneficial for the treatment outcome.

与Epstein Barr病毒感染相关的抗生素不良反应所致皮疹,组织学表现类似Kikuchi-Fujimoto病

The antibiotic-induced eruption of infectious mononucleosis is a well-known clinical phenomenon. Latent viral infection with herpesviridae (eg, human herpes virus 6 (HHV-6) and Epstein-Barr virus (EBV)) is suspected to play a role in the drug hypersensitivity syndrome. The cutaneous pathologic findings have not been reported in the former, and are infrequently reported in the latter entity. Herein, we describe the biopsy findings of a cefprozil-induced rash in infectious mononucleosis and a minocycline-associated drug hypersensitivity syndrome. Biopsy of these exanthematous eruptions revealed an acute vacuolar interface superficial and deep perivascular and interstitial lymphocytic dermatitis. CD8+lymphocytes predominated and were associated with non-neutrophilic nuclear (karyorrhectic) debris and numerous small CD68+and CD123+monocytes. These aforementioned features have been described in cutaneous lesions of Kikuchi-Fujimoto disease, an entity whose clinicopathologic findings overlap with both infectious mononucleosis and lupus erythematosus. Serologic evidence of active and chronic active EBV infection was found in both patients, respectively. No evidence of EBV or HHV6 was found in the cutaneous lesions. Plasmacytoid monocytes (CD68+/CD123+cells), which produce type I interferon, are believed to play a role in viral immunity by protecting other cells from viral infections and promoting survival of antigenactivated T cells. Their presence in these two putative examples of viral-drug immune dysregulation could be a clue to pathogenesis and represent a common cellular component of some adverse cutaneous drug eruptions.

Kikuchi-Fujimoto Disease in Patients with Sjogren’s Syndrome

Sjogren’s syndrome is a chronic autoimmune exocrinopathy associated with dry eyes and dry mouth as major clinical manifestations. It is characterized by lymphocytic infiltration of lacrimal and salivary glands and autoantibody production, especially anti-Ro (or SSA) and anti-La (or SSB). Lymphoproliferative disorders are a feature of Sjogren’s syndrome, and can be considered an extraglandular manifestation of the disease. Kikuchi-Fujimoto disease or histiocytic necrotizing lymphadenitis is a rare form of lymphadenitis. It is reported more often in young adult women with localized lymphadenopathy (usually cervical), fever, rashes, and leukopenia. It is a self-limiting disease with resolution within 1 - 4 months in almost all patients. Sjogren’s syndrome has been reported in patients with other systemic diseases including SLE and lymphomas. Here we present a patient with Kikuchi-Fujimoto disease who developed Sjogren’s Syndrome 8 years after her diagnosis of Kikuchi-Fujimoto disease.

系统性红斑狼疮合并Kikuchi-Fujimoto病一例

患者女，58岁。2014年1月13日因口唇红斑1个月/发热8d至浙江大学阪学院附属邵逸夫医院就诊。患者1个月前出现下唇红斑，后增大并破溃。8d前出现发热，呈间歇热型，尤畏寒/寒颤，伴全身肌肉酸痛，尤关节肿痛/口腔溃疡及光敏感等。当地医院查抗核抗体（ANA）1：l000，抗双链DNA（dsl）NA）抗体阳性（＋），红细胞沉降率（ESR）56mm／1h，补体C3 390mg/L；胸部CT示两肺慢性感染惟病变，伴两侧少堵胸腔积液，心包少量积液；予抗感染补液等治疗效果不佳。既往史和个人史无特殊。人院体格检查：神智清，精神软；下唇可处“径约2cm溃疡面，上覆血痂。左侧胸锁乳突肌前可及一豌豆大小淋巴结，表面光滑，无触痛，活动欠佳。两下肺呼吸音粗，未闻及干湿啰音。心脏、腹部无特殊。旧肢轻度非凹陷性水肿。实验室检查：白细胞2．6×109／L，，淋巴细胞0．42．6×109／L，血红蛋由94g／L；ESR 44mm／1h，C反应蛋白（CRP）8mg／L；丙氨酸转氨酶49U／L，天冬氨酸转氨酶76U／L，谷氯酰转肽牌55U／L，肾功能正常；ANA 1：320均质型，抗dsDNA抗体（＋）；IgG26100 mg／L，C3 450mg／L，C4 50Mg／L；尿常规、前降钙素原、抗溶血链球菌素O、类风湿因子及肿瘤标志物均无异常。心脏彩超：少量心包积液。骨髓常规无异常。骨髓活检：骨髓组织增生活跃。综合临床及实验室检查结果：（1）白细胞和淋巴细胞减少；（2）ANA及抗dsDNA抗体阳性；（3）补体明显降低；（4）双侧少量胸水，少许心包积液等，本例患者符合系统性红斑狼疮（SLE）的诊断标准。予甲泼尼尼40mg／d及护肝补钾补钙护胃治疗，治疗第3天复查CRP 5．7mg／L，ESR3 6mm／1h，血常规未见明显异常。下唇痂皮脱落，全身肌肉酸痛明显好转，患者主诉左颈部淋巴结肿大，B超显爪双颈、腋下多发浅表淋巴结肿大，部分皮髓质不清。遂行颈部肿大淋巴结切除术，术后病理：副皮质区扩大，内见成片分布细胞：细胞核大空泡状，核仁清晰，核分裂象易见，部分细胞核偏位，胞质红染，内见坏死及大量核碎片（图lA）。免疫组化：CD5、CD20阴性，CD3、CD8阳性（图1B），CD4散在阳性，CD68（图1C）、髓过氧化物酶（MPO）、CD7部分阳性，CD56、EB病毒编码小RNA（EBER）个别阳性，Ki-67高增殖活性（图lD）。根据淋巴结病理结果诊断为组织细胞坏死性淋巴结炎（即Kikuchi-Fujimoto病，KFD）：继续甲泼尼龙40mg/d静滴治疗1周后，患者体温恢复正常，口唇皮疹完全消退，未及浅表肿大淋巴结。糖皮质激素逐渐减星，病情无反复。

检测153例儿童Kikuchi-Fujimoto病患者淋巴结组织中的分枝杆菌及疱疹病毒

Kikuchi-Fujimoto病(KFD),又称为组织坏死性淋巴结炎,是儿童的一种自限性疾病.一些研究表明其病因与微生物有关.既往研究显示,特定病原体的存在与临床、病理以及实验室检查结果之间没有明确关联.采用基于PCR的分子检测在KFD淋巴结组织中检测并鉴定分枝杆菌、疱疹病毒和细小病毒B19的DNA.收集2001~2010年间福尔马林固定后石蜡包埋的KFD淋巴结活检标本153例.在19例(12.4%)组织中检测到分支杆菌DNA,包括Mycobacterium intracellulare, M. avium, M. smegmatis, M. abscessus, M. conceptionense, M. riyadhense, M.vanbaalenii和M. monacense各1例; M. fortuitum, M. kansasii和M. mucogenicum各2例以及未明确的其他分枝杆菌5例. PCR方法也检测到10例(6.5%)细小病毒B19, 3例(2%) EBV, 1例(0.6%) CMV, 1例(0.6%) HHV-6, 1例(0.6%)HHV-7和5例(3.3%) HHV-8.本研究结果确定了KFD淋巴结组织中分枝杆菌以及病毒特异DNA的存在,但其临床以及病理学相关性未明.本研究是目前最大的采用覆盖分枝杆菌以及病毒病原体的分子技术的KFD研究.

基于伏气温病理论探讨组织细胞坏死性淋巴结炎的诊疗思路

[目的]基于伏气温病理论,探讨组织细胞坏死性淋巴结炎(histiocytic necrotizing lymphadenitis,HNL)的病因病机和诊治思路。[方法]基于古代医籍对伏气温病理论的阐述和HNL的现代研究,分析该病的病因病机、症状特点及传变规律,总结其治疗原则,并报道医案一则予以佐证。[结果]HNL的病机以正虚邪伏为主,表现为在正虚基础上,外感邪气伏于膜原,阳郁化热,外发少阳三焦,内生痰瘀浊毒为病。治疗以扶正祛邪为法,重在祛邪,针对伏邪、郁热和病理产物内生三个病机环节,制定疏利透达、祛邪清热和清理夹邪、解毒散结的治疗原则;扶正重在顾护气阴和愈后调养,预防余邪复遗。所举医案为应用伏气温病理论治疗HNL一例,证属湿热毒蕴、痰瘀互结,先后方选升降散合三仁汤、甘露消毒丹治疗,随证加减,效果显著。[结论]从伏气温病理论探讨HNL的诊治思路具有临床实用意义,可为诊治HNL提供新思路和方法。

儿童组织细胞坏死性淋巴结炎临床及病理分析

组织细胞坏死性淋巴结炎（histiocytic necrotizing lymphadenitis，HNL）是一种少见的炎性免疫反应性非肿瘤性淋巴结肿大性疾病，1972年由日本病理学家Kikuchi及Fujimoto首次报道，又称为Kikuchi-Fujimoto病。儿童病例较少见，漏诊、误诊率较高。为进一步提高对本病的认识，现将我院收治的13例组织细胞坏死性淋巴结炎报告如下。

组织细胞坏死性淋巴结炎合并系统性红斑狼疮1例分析并文献复习

目的：提高临床医生对组织细胞坏死性淋巴结炎（HNL）合并系统性红斑狼疮（SLE）的认识.方法：报告1例组织细胞坏死性淋巴结炎合并系统性红斑狼疮并复习相关文献.结果：患者为35岁女性,以发热、淋巴结肿大、关节炎、白细胞减少、贫血、脾大为主要临床表现,血沉、C反应蛋白升高,自身抗体检测：抗核抗体、抗SSA抗体及抗心磷脂抗体阳性,补体C3、C4下降,淋巴结活检示组织细胞坏死性淋巴结炎.最后诊断为组织细胞坏死性淋巴结炎合并系统性红斑狼疮.给予糖皮质激素及对症治疗,随访病情稳定.结论：HNL临床突出表现是发热、淋巴结肿大、疼痛,合并SLE临床少见,与SLE本身引起的淋巴结病变难以鉴别,病理检测有利于疾病的诊断,临床医师应引起注意并长期随访.

49例坏死性淋巴结炎临床病理及免疫组化研究

作者报道49例坏死性淋巴结炎,其男女性别比为0.96:1,发病年龄9～62岁,平均26岁。临床表现为表浅淋巴结肿大,以颈部受累最多见,22例伴发热。应用免疫组化等方法对其病变组织观察发现:淋巴结皮质区及副皮质区T淋巴细胞灶性或(和)片状坏死,坏死区见核碎屑和核溶解,坏死周由吞噬坏死成分的巨噬细胞、组织细胞、免疫母细胞和T淋巴细胞构成,一般无中性粒细胞和浆细胞浸润,偶见B淋巴细胞,被膜外以小T淋巴细胞浸润为主,Gram、Giemsa、PAS、Ziehl-Neelsen、Warthin-Starry染色未见病原体。作者对该病的诊断、鉴别诊断及病因进行了讨论,并建议将其称为“Kikuchi-Fujimoto's病”。

38例Kikuchi淋巴结炎临床病理分析

为减少误诊率，提高诊断准确性，对３８例Ｋｉｋｕｃｈｉ病的临床、病理形态及免疫学观察分析。结果显示：组织学上可分为三型：增生型、坏死型、黄色瘤样型。病变内增生的细胞主要有：组织细胞（Ｋｐ１＋，Ｌｙｓｏｚｙｍｅ＋），转化Ｔ淋巴细胞（ＵＣＨＬ１＋）。根据该病的临床、病理形态及免疫酶标记特点能作出准确的诊断。