Journal of Global Infectious DiseasesOfficial Publishing of INDUSEM and OPUS 12 Foundation, Inc. Users online:786  
Print this pageEmail this pageSmall font sizeDefault font sizeIncrease font size     
Home About us Editors Ahead of Print Current Issue Archives Search Instructions Subscribe Advertise Login 
 


 
   Table of Contents     
ORIGINAL ARTICLE  
Year : 2014  |  Volume : 6  |  Issue : 4  |  Page : 147-150
Kikuchi-Fujimoto disease: Clinical and laboratory characteristics and outcome


1 Department of Community Health, Christian Medical College, Vellore, Tamil Nadu, India
2 Department of Internal Medicine, Christian Medical College, Vellore, Tamil Nadu, India
3 Department of Pathology, Christian Medical College, Vellore, Tamil Nadu, India

Click here for correspondence address and email

Date of Web Publication21-Nov-2014
 

   Abstract 

Introduction: Kikuchi-Fujimoto disease is an uncommon disorder with worldwide distribution, characterized by fever and benign enlargement of the lymph nodes, primarily affecting young adults. Awareness about this disorder may help prevent misdiagnosis and inappropriate investigations and treatment. The objective of the study was to evaluate the clinical and laboratory characteristics of histopathologically confirmed cases of Kikuchi's disease from a tertiary care center in southern India. Materials and Methods: Retrospective analysis of all adult patients with histopathologically confirmed Kikuchi's disease from January 2007 to December 2011 in a 2700-bed teaching hospital in South India was done. The clinical and laboratory characteristics and outcome were analyzed. Results: There were 22 histopathologically confirmed cases of Kikuchi's disease over the 5-year period of this study. The mean age of the subjects' was 29.7 years (SD 8.11) and majority were women (Male: female- 1:3.4). Apart from enlarged cervical lymph nodes, prolonged fever was the most common presenting complaint (77.3%). The major laboratory features included anemia (54.5%), increased erythrocyte sedimentation rate (31.8%), elevated alanine aminotransferase (27.2%) and elevated lactate dehydrogenase (LDH) (31.8%). Conclusion: Even though rare, Kikuchi's disease should be considered in the differential diagnosis of young individuals, especially women, presenting with lymphadenopathy and prolonged fever. Establishing the diagnosis histopathologically is essential to avoid inappropriate investigations and therapy.

Keywords: Histiocytic necrotizing lymphadenitis, Kikuchi, Lymphadenopathy, Prolonged fever

How to cite this article:
Rakesh P S, Alex RG, Varghese GM, Mathew P, David T, Manipadam MT, Nair S, Abraham OC. Kikuchi-Fujimoto disease: Clinical and laboratory characteristics and outcome . J Global Infect Dis 2014;6:147-50

How to cite this URL:
Rakesh P S, Alex RG, Varghese GM, Mathew P, David T, Manipadam MT, Nair S, Abraham OC. Kikuchi-Fujimoto disease: Clinical and laboratory characteristics and outcome . J Global Infect Dis [serial online] 2014 [cited 2019 Aug 22];6:147-50. Available from: http://www.jgid.org/text.asp?2014/6/4/147/145234



   Introduction Top


Kikuchi's disease, also known as Kikuchi-Fujimoto disease (KFD) or histiocytic necrotizing lymphadenitis, is a rare disorder with a worldwide distribution, with a higher prevalence among Asians. Although the cause is unknown, infectious and autoimmune etiologies have been proposed for this disease. [1] The disease is characterized by benign enlargement of lymph nodes, frequently cervical, and is often associated with fever. [2] Other symptoms and signs include upper respiratory symptoms, sore throat, night sweats, weight loss, nausea, vomiting, splenomegaly, erythematous papules, plaques, acneiform or morbilliform lesions and facial erythema. [1] Common laboratory findings include anemia, leucopenia and a high erythrocytic sedimentation rate. [3] The disease is frequently mistaken for lymphoma, tuberculous lymphadenitis, systemic lupus erythematosis (SLE), sarcoidosis, infectious mononucleosis, cat-scratch disease, Sweet's syndrome, Still's disease and drug eruptions. [2],[4]

The diagnosis may be missed or delayed as it is often not considered in the differential diagnosis due to similarity to other more common conditions, lack of awareness and its rarity. Although the disease is often self limiting, early diagnosis by a biopsy of the lymph nodes is essential to avoid misdiagnosis, unnecessary investigations and inappropriate therapy. [4] The objective of the current study was to describe the clinical and laboratory characteristics of histopathologically confirmed cases of Kikuchi's disease over a period of 5 years from a tertiary care center in southern India.


   Materials and methods Top


Retrospective analysis of records of all adult patients with histopathologically confirmed Kikuchi's disease from January 2007 to December 2011 at a 2700-bed teaching hospital in Southern India was done. A case of Kikuchi's disease was defined as individuals with localized or generalized lymphadenopathy that showed confirmatory findings (necrotizing lymphadenitis with karyorrhexis and a paucity of granulocytes) on histology in the absence of an alternative diagnosis such as tuberculosis, lymphoma, or connective tissue diseases. Relevant data were recorded using a predesigned data collection proforma and analyzed. The data included demographic characteristics, accompanying symptoms, physical findings, co-morbidities, laboratory results, histological findings, treatment offered and therapeutic outcome in terms of relief of symptoms.


   Results Top


There were a total of 22 histopathologically confirmed cases of Kikuchi's diseases over the five year period. Among them, 17 (77.3%) were females. The mean age of the patients was 29.7 years (SD 8.11), ranging from 16 to 45 years old. Lymphadenopathy was present in all the cases, with 21(95.5%) involving the cervical lymph nodes. These cervical lymph nodes were unilaterally involved in 12 (54.5%). Both cervical and axillary lymph nodes were palpable in six (27.2%) patients. The lymph nodes were less than 3 cm in diameter in all the cases.

The majority (77.3%) of patients reported prolonged fever, with a mean duration of 39.7 days (SD 22.7, range 7-90 days) at presentation. The main signs, symptoms and laboratory characteristics of the cases are summarized in [Table 1]. Anti-nuclear antibody was positive in three cases (13.3%) cases, but additional investigation including anti-dsDNA did not suggest any connective tissue disorder.
Table 1: Signs, symptoms and laboratory characteristics of the cases of Kikuchi's disease (N = 22)

Click here to view


All patients were treated with antipyretics and non-steroidal anti-inflammatory drugs. Two individuals initially received an antibiotic which was discontinued once the diagnosis was confirmed. None of them received steroids. The fever settled in all patients without any additional treatment and none had recurrence on 3 month follow-up.


   Discussion Top


The study describes the clinical and laboratory characteristics and outcome of 22 pathologically confirmed cases of Kikuchi's disease from a tertiary care center in south India. As reported from other Asian countries, a majority of our subjects with a diagnosis of KFD were young (<30 years) females. A female preponderance has been reported in the literature. However, a few recent studies reported a male to female ratio closer to 1:1. [1],[2]

Our finding of cervical lymphadenopathy in majority was consistent with many previous reports. A comprehensive review has reported that the proportion of cases with cervical lymphadenopathy ranged from 56% to 98%, more commonly involving unilateral posterior cervical triangle (88.5%). [1] In our series, a majority of patients (77.3%) had prolonged fever as the presenting complaint. The proportion of cases with fever, as reported by various studies ranges from 35% to 50%. [1] We noticed anemia (54.5%) and high ESR (31.8%) as the common laboratory finding, which is consistent with many previous reports. [3] An increase in lactate dehydrogenase, C-reactive protein and aminotransferase was also noticed in few subjects, which is a similar finding from many other studies. [1] All these findings were consistent with other case series reported from India. [5],[6],[7],[8]

KFD is usually diagnosed on the basis of an excision biopsy of affected lymph nodes. Histology of the lymph nodes in KFD shows paracortical expansion with foci of incipient necrosis laden with karyorrhectic debris both within and outside macrophages. The macrophages with ingested debris are classically described as crescentic because the nucleus is pushed to the periphery [9] [Figure 1]. Neutrophils are absent. Later stages may show sheets of foamy histiocytes replacing the necrotic foci (xanthomatous phase). The necrotic foci can be surrounded by transformed lymphoid cells. [10]

In India, tuberculosis is widely prevalent and is the most commonly considered diagnosis in any one presenting with prolonged fever and lymphadenopathy; and often is started on empiric therapy. Although necrosis is seen in both conditions, epithelioid granulomas are not seen in KFD, a helpful feature in differentiating from tuberculosis. [9]
Figure 1: X 200, medium power view of paracortex showing paracortical expansion with foci of incipient necrosis laden with karyorrhectic debris and macrophages with ingested nuclear debris

Click here to view


Collagen vascular diseases will be an important differential diagnosis among young females presenting with fever and lymphadenopathy. The differentiation of Kikuchi's disease from systemic lupus erythematosis may be challenging because both can have same clinical and histological features. [11] Kikuchi's disease has been reported in association with SLE also. [12] Similar histological picture can be seen in both disease conditions, and hence work up for connective tissue disorders are indicated in each case of necrotizing lymphadenitis. The histological features which favor lupus lymphadenitis over Kikuchi's disease are the presence of vasculitis, presence of neutrophils, plasma cells and the presence of hematoxyphil bodies. [9]

Several immunohistochemical studies have shown that the predominant proliferating cells in KFD lymph nodes are CD8+ T lymphocyte. [2] Plasmacytoid dendritic cells (plasmacytoid monocytes) which are positive for CD123 have been reported as a striking feature of Kikuchi's disease. [9]

Kikuchi's disease is a self-limiting disorder and the treatment is generally supportive. Spontaneous resolution occurs in most cases within 6 months. Non-steroidal anti-inflammatory drugs (NSAIDs) may be used to alleviate the symptoms and controlling the fever. Treatment with systemic corticosteroids hastens resolution. [13] Immediate resolution has been reported with minocyclin and ciprofloxacin. [14] Excellent response to hydroxychloroquine or immunoglobulins has been reported. The disease has a recurrence rate of 3% to 4%. [1],[15]

Even though rare, Kikuchi's disease should be considered in the differential diagnosis of young individuals, especially women, presenting with lymphadenopathy and prolonged fever. Histopathological evaluation should be considered in such cases, as it can mimic common disorders like tuberculous lymphadenitis and lymphoma, which can avoid unnecessary investigations and inappropriate treatment.

 
   References Top

1.
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. 1
    
2.
Tsang WY, Chan JK, Ng CS. Kikuchi's lymphadenitis. A morphologic analysis of 75 cases with special reference to unusual features. Am J Surg Pathol 1994;18:219-31.  Back to cited text no. 2
    
3.
Kucukardali Y, Solmazgul E, Kunter E, Oncul O, Yildirim S, Kaplan M. Kikuchi-Fujimoto disease: Analysis of 244 cases. Clin Rheumatol 2007;26:50-4.   Back to cited text no. 3
    
4.
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. 4
    
5.
Rammohan A, Cherukuri SD, Manimaran AB, Manohar RR, Naidu RM. Kikuchi-Fujimotodisease: A sheep in wolf's clothing. J Otolaryngol Head Neck Surg2012;41:222-6.  Back to cited text no. 5
    
6.
Singhania P, Paul R, Maitra S, Banerjee A, Hashmi M. Kikuchi-fujimoto disease from eastern India. J Glob Infect Dis 2010;2:305-6.   Back to cited text no. 6
    
7.
Basu D, Mutha SM. Histiocytic necrotizing lymphadenitis (Kikuchi Fujimoto Disease) - a report of four cases. Indian J Pathol Microbiol 2002;45:89-91.   Back to cited text no. 7
[PUBMED]  Medknow Journal  
8.
Mohan A, Reddy MK, Phaneendra BV, Chandra A. Aetiology of peripheral lymphadenopathy in adults: Analysis of 1724 cases seen at a tertiary care teaching hospital in southern India. Natl Med J India 2007;20:78-80.   Back to cited text no. 8
    
9.
Ioachim HL, Medeiros LJ. Kikuchi lymphadenopathy. In: Ioachim's Lymph Node Pathology. 4 th ed. Philadelphia: Lippincott Williams &Wilkins; 2009. p. 200-2.  Back to cited text no. 9
    
10.
Specific clinical entities. Kikuchi-Fujimoto disease (Histiocytic necrotizing lymphadenitis). In :O'Malley DP, George TI, Orazi A, Abbondanzo SL, editors. Benign and Reactive Conditions of Lymph Node and Spleen (Atlas of Nontumor Pathology). Washington DC: ARP Press; 2009. p. 150-4.  Back to cited text no. 10
    
11.
Bosch X, Guilabert A. Kikuchi-Fujimoto disease. Orphanet J Rare Dis 2006;1:18.   Back to cited text no. 11
    
12.
Martínez-Vázquez C, Hughes G, Bordon J, Alonso-Alonso J, Anibarro-Garcia A, Redondo-Martínez E, et al. Histiocytic necrotizing lymphadenitis, Kikuchi-Fujimoto's disease, associated with systemic lupus erythemotosus. QJM 1997;90:531-3.  Back to cited text no. 12
    
13.
Jang YJ, Park KH, Seok HJ. Management of Kikuchi's disease using glucocorticoid. J Laryngol Otol 2000;114:709-11.  Back to cited text no. 13
    
14.
Mahajan VK, Sharma NL. Kikuchi-Fujimoto disease: Immediate remission with ciprofloxacin. Int J Dermatol 2004;43:370-2.  Back to cited text no. 14
    
15.
Blewitt RW, Kumar SN, Abraham JS. Recurrence of Kikuchi's lymphadenitis after 12 years. J Clin Pathol 2000;53:157-8.  Back to cited text no. 15
    

Top
Correspondence Address:
P S Rakesh
Department of Community Health, Christian Medical College, Vellore, Tamil Nadu
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0974-777X.145234

Rights and Permissions


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1]



 

Top
  
 
  Search
 
  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
   Introduction
    Materials and me...
   Results
   Discussion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed2138    
    Printed60    
    Emailed1    
    PDF Downloaded16    
    Comments [Add]    

Recommend this journal

Sitemap | What's New | Feedback | Copyright and Disclaimer | Contact Us
2008 Journal of Global Infectious Diseases | Published by Wolters Kluwer - Medknow
Online since 10th December, 2008