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Year : 2014  |  Volume : 6  |  Issue : 4  |  Page : 139-140
State of the globe: Time to revisit kikuchi Fujimoto disease

1 Department of Emergency Medicine, Baylor College of Medicine, Houston, Texas, USA
2 Department of Trauma Surgery, St. Luke's University Hospital, Bethlehem, Pennsylvania, USA

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Date of Web Publication21-Nov-2014

How to cite this article:
Bezek S, Tucci V, Kalra S, Fisher A. State of the globe: Time to revisit kikuchi Fujimoto disease . J Global Infect Dis 2014;6:139-40

How to cite this URL:
Bezek S, Tucci V, Kalra S, Fisher A. State of the globe: Time to revisit kikuchi Fujimoto disease . J Global Infect Dis [serial online] 2014 [cited 2021 Oct 17];6:139-40. Available from:

Kikuchi-Fujimoto disease (KFD) is a rare and unusual condition, presenting in patients younger than 40 years of age, as a benign, self-limiting condition, characterized by cervical lymphadenopathy, fever, and joint pain. [1] A small percentage of patients may develop flu-like symptoms, skin rash, hepatitis, arthritis, and oral ulcers. [2],[3]

The cause of KFD is not completely known, however, certain infectious agents (Epstein-Barr virus (EBV), Yesinia, herpes virus 6 and 8, Toxoplasma, parvovirus B19, Brucella, human immunodeficiency virus) and the genetic deficiency of the human leukocyte antigen (HLA) class II are frequently associated with its incidence. [4],[5] Some studies have linked the higher prevalence of KFD in the Asian population with the deficiency of human leukocyte antigen (HLA) Class II genes such as the DPA1*01 allele and DPB10202 allele, which are commonly seen in the Asian population. [3],[6] A recent study of 88 patients with KFD, in the US, showed that nearly 75% of the patients were Caucasians, which showed that the disease might not be predominantly seen in the Asian population. [7]

Kikuchi-Fujimoto disease was initially reported to be more common in females, but recent studies have shown that the distribution is almost equal in both the sexes. [3],[6] Clinically, KFD is often misdiagnosed with systemic lupus erythematosus (SLE), malignant lymphoma or early stage tuberculosis. [3],[5],[8] The commonly affected site for lymphadenopathy in the neck is usually in the cervical area and is associated with tenderness. [7] The size of the lymph nodes varies from 0.5 cm to 8 cm. On rare occasions, lymphadenopathy can be generalized and involves the mediastinal, peritoneal, and retroperitoneal regions. [2],[4],[9] Neurological involvement can be seen in KFD, presenting as aseptic meningitis, brachial neuritis, mononeuritis multiplex or hemiparesis. In rare instances, rapid progressive cerebellar ataxia, disseminated encephalomyelitis, and peripheral neuropathy may create a diagnostic challenge. [10],[11],[12]

The characteristic histopathological features from lymph node biopsy help in distinguishing it from other conditions. The histopathological findings on biopsy show patchy necrosis in the cortical and paracortical areas of the lymph node, together with nuclear debris or extensive karyorrhexis. Cellular infiltration consists of CD68-positive plasmacytoid histiocytes and transformed lymphocytes, which largely originate from T-cells. In a majority of the cases, there is an absence of neutrophils, eosinophils, and plasma cells. [2],[4],[6],[13],[14] CD8-positive T cell-mediated apoptotic cell death has been postulated as the principal mechanism of cellular destruction. [14] In a study of four men with biopsy-confirmed KFD, interferon gamma and interleukin-6 were seen to be elevated in the acute phase of the illness. [15] Although specific diagnostic tests are not available for diagnosing KFD, an analysis of the serology titers for the commonly associated infectious agents is always helpful, for narrowing the diagnosis. [5] KFD also shares the histological features with SLE, with both the conditions presenting, with tubuloreticular structures in the lymphocytes and endothelial cells. [16]

The laboratory tests are consistent with non-specific signs of underlying inflammation. Leukopenia, atypical lymphocytosis, and thrombocytopenia are more frequently associated with other derangements. The erythrocyte sedimentation rate elevation to more than 60 mm/hour has been associated with nearly a third of the patients. Bone marrow studies can reveal an increase in macrophages without atypical cells. [7],[17] Computed tomography (CT) imaging of the involved lymph nodes shows peripheral infiltration and homogenous contrast enhancement. These are often mistaken as signs consistent with a malignancy. [18],[19]

As the signs and symptoms of KFD are consistent with an underlying inflammatory response, trials with high-dose glucocorticoids with intravenous immunoglobulins have shown improvement in a majority of patients with severe and persistent symptoms. [20],[21] Symptomatic management of other systemic symptoms provides temporary relief, without affecting the duration of the illness. Although KFD is a self-limiting condition, recurrences have been reported in some studies. In a series of 102 patients from Korea, it has been shown that three patients developed SLE, eight patients had an early relapse, and 13 patients had a late recurrence of the disease. [22]

As there are no confirmatory laboratory tests for diagnosing KFD, comprehensive evaluation, histopathological examination, and careful correlation with laboratory findings makes it imperative to think of KFD as a differential diagnosis in patients presenting with cervical lymphadenopathy and fever. The study conducted by Rakesh et al. has presented an exhaustive review, with results that are consistent with the previously published literature on the presentation and management of KFD. Future studies on KFD should be targeted toward generating a correlation between various clinical features and outcomes. This could provide a significant change in medical practice by augmenting the ability to assess disease severity and prepare the healthcare providers for managing rare complications associated with the disease. Studies evaluating treatment responses and tailoring them to early relapse and late recurrence will also provide further insight toward the outcome of patients with KFD.

   References Top

Lin HC, Su CY, Huang SC. Kikuchi's disease in Asian children. Pediatrics 2005;115:e92-6.  Back to cited text no. 1
Ifeacho S, Aung T, Akinsola M. Kikuchi-Fujimoto Disease: A case report and review of the literature. Cases J 2008;1:187.  Back to cited text no. 2
Mrowka-Kata K, Kata D, Kyrcz-Krzemień S, Sowa P. Kikuchi-Fujimoto disease as a rare cause of lymphadenopathy--two cases report and review of current literature. Otolaryngol Pol 2013;67:1-5.  Back to cited text no. 3
Bosch X, Guilabert A, Miquel R, Campo E. Enigmatic Kikuchi-Fujimoto disease: A comprehensive review. Am J Clin Pathol 2004;122:141-52.  Back to cited text no. 4
Seo JH, Kang JM, Lee H, Lee W, Hwang SH, Joo YH. Histiocytic necrotizing lymphadenitis in children: A clinical and immunohistochemical comparative study with adult patients. Int J Pediatr Otorhinolaryngol 2013;77:429-33.  Back to cited text no. 5
Mrowka-Kata K, Kata D, Kyrcz-Krzemień S, Helbig G. Kikuchi-Fujimoto and Kimura diseases: The selected, rare causes of neck lymphadenopathy. Eur Arch Otorhinolaryngol 2010;267:5-11.  Back to cited text no. 6
Dorfman RF, Berry GJ. Kikuchi's histiocytic necrotizing lymphadenitis: An analysis of 108 cases with emphasis on differential diagnosis. Semin Diagn Pathol 1988;5:329-45.  Back to cited text no. 7
Lin HC, Su CY, Huang CC, Hwang CF, Chien CY. Kikuchi's disease: A review and analysis of 61 cases. Otolaryngol Head Neck Surg 2003;128:650-3.  Back to cited text no. 8
Qadri F, Atkin GK, Thomas D, Das SK. Kikuchi's disease: An important cause of cervical lymphadenopathy. Clin Med 2007;7:82-4.  Back to cited text no. 9
Longaretti P, Savasta S, Caimmi D, Possenti I, Marseglia GL. Kikuchi-Fujimoto disease complicated by peripheral neuropathy. Pediatr Neurol 2012;46:319-21.  Back to cited text no. 10
Moon JS, Il Kim G, Koo YH, Kim HS, Kim WC, Kim OJ, et al. Kinetic tremor and cerebellar ataxia as initial manifestations of Kikuchi-Fujimoto's disease. J Neurol Sci 2009;277:181-3.  Back to cited text no. 11
Avkan-Oguz V, Yapar N, Ozakbas S, Demir-Onder K, Aktas E, Alp-Cavus S, et al. A case of fever of unknown origin: Co-existence of Kikuchi-Fujimoto disease and acute disseminated encephalomyelitis (ADEM). Intern Med 2010;49:1823-6.  Back to cited text no. 12
Vijayaraghavan R, Chandrashekar R, A S, Belagavi CS. Kikuchi-Fujimoto's disease involving mesenteric nodes: A report and review of literature. BMJ Case Rep 2011;2011.pii:bcr1020114945.  Back to cited text no. 13
Ura H, Yamada N, Torii H, Imakado S, Iozumi K, Shimada S. Histiocytic necrotizing lymphadenitis (Kikuchi's disease): The necrotic appearance of the lymph node cells is caused by apoptosis. J Dermatol 1999;26:385-9.  Back to cited text no. 14
Kubota M, Tsukamoto R, Kurokawa K, Imai T, Furusho K. Elevated serum interferon gamma and interleukin-6 in patients with necrotizing lymphadenitis (Kikuchi's disease). Br J Haematol 1996;95:613-5.  Back to cited text no. 15
Imamura M, Ueno H, Matsuura A, Kamiya H, Suzuki T, Kikuchi K, et al. An ultrastructural study of subacute necrotizing lymphadenitis. Am J Pathol 1982;107:292-9.  Back to cited text no. 16
Norris AH, Krasinskas AM, Salhany KE, Gluckman SJ. Kikuchi-Fujimoto disease: A benign cause of fever and lymphadenopathy. Am J Med 1996;101: 401-5.  Back to cited text no. 17
Kwon SY, Kim TK, Kim YS, Lee KY, Lee NJ, Seol HY. CT findings in Kikuchi disease: Analysis of 96 cases. AJNR Am J Neuroradiol 2004;25:1099-102.  Back to cited text no. 18
Youk JH, Kim EK, Ko KH, Kim MJ. Sonographic features of axillary lymphadenopathy caused by Kikuchi disease. J Ultrasound Med 2008;27:847-53.  Back to cited text no. 19
Deaver D, Horna P, Cualing H, Sokol L. Pathogenesis, diagnosis, and management of kikuchi-fujimoto disease. Cancer Control 2014;21:313-21.  Back to cited text no. 20
Lin DY, Villegas MS, Tan PL, Wang S, Shek LP. Severe Kikuchi's disease responsive to immune modulation. Singapore Med J 2010;51:e18-21.  Back to cited text no. 21
Song JY, Lee J, Park DW, Sohn JW, Suh SI, Kim IS, et al. Clinical outcome and predictive factors of recurrence among patients with Kikuchi's disease. Int J Infect Dis 2009;13:322-6.  Back to cited text no. 22

Correspondence Address:
Angela Fisher
Department of Emergency Medicine, Baylor College of Medicine, Houston, Texas
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0974-777X.145228

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