eMedicine Specialties > Hematology > Stem Cells and Disorders

Kikuchi Disease

Author: John Boone, MD, Consulting Staff, Department of Otolaryngology, Naval Hospital Oak Harbor
Coauthor(s): Charles S Kuzma, MD, Consulting Staff, Cancer Care Associates
Contributor Information and Disclosures

Updated: Dec 28, 2009

Introduction

Background

Kikuchi disease, also called histiocytic necrotizing lymphadenitis or Kikuchi-Fujimoto disease, is an uncommon, idiopathic, generally self-limited cause of lymphadenitis.1,2 Kikuchi first described the disease in 1972 in Japan. Fujimoto and colleagues independently described Kikuchi disease in the same year.

The most common clinical manifestation of Kikuchi disease is cervical lymphadenopathy, with or without systemic signs and symptoms.3,4,5,6 Clinically and histologically, the disease can be mistaken for lymphoma or systemic lupus erythematosus (SLE).1,3,4,5,6,7,8,9,10,11,12,13,14,15 Kikuchi disease almost always runs a benign course and resolves in several weeks to months. Disease recurrence is unusual, and fatalities are rare, although they have been reported.1

For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center. Also, see eMedicine's patient education articles Swollen Lymph Glands and Lymphoma.

Pathophysiology

The cause of Kikuchi disease is unknown, although infectious and autoimmune etiologies have been proposed. The most favored theory proposes that Kikuchi disease results when one or more unidentified agents trigger a self-limited autoimmune process. Lymphadenitis results from apoptotic cell death induced by cytotoxic T lymphocytes. Some human leukocyte antigen (HLA) class II genes are more frequent in patients with Kikuchi disease, suggesting a genetic predisposition to the proposed autoimmune response.

Features that support a role for an infectious agent include the generally self-limited course of the disease and its frequent association with symptoms similar to those of upper respiratory tract infections (URTIs). Several viral candidates have been proposed, including cytomegalovirus, Epstein-Barr virus,16 human herpesvirus, varicella-zoster virus, parainfluenza virus, parvovirus B19, and paramyxovirus. However, serologic and molecular studies have failed to link Kikuchi disease to a specific pathogen, and more than one pathogen may be capable of triggering the characteristic hyperimmune reaction leading to Kikuchi disease.

Several authors have reported an association between Kikuchi disease and SLE. Kikuchi disease has been diagnosed before, during, and after a diagnosis of SLE was made in the same patient. Additionally, the histologic appearance of lymph nodes in patients with Kikuchi disease is similar to that of lymph nodes in patients with SLE lymphadenitis. Some authors have suggested that Kikuchi disease may represent a forme fruste SLE, but this theory has not been substantiated, and the association of Kikuchi disease with SLE, if any, remains unclear.

Frequency

United States

Kikuchi disease is uncommon. Only isolated cases are reported in North America.

International

Although uncommon, Kikuchi disease has been reported throughout the world and in all races. Most cases have been reported from East Asia, with fewer cases from Europe and North America.

Mortality/Morbidity

The course of Kikuchi disease is generally benign and self-limited. Lymphadenopathy most often resolves over several weeks to 6 months, although the disease occasionally persists longer. The disease recurs in about 3% of cases. Three deaths have been reported that occurred during the acute phase of generalized Kikuchi disease. One patient died from cardiac failure; the second, from the effects of hepatic and pulmonary involvement; and the last, from an acute lupuslike syndrome. Another fatality has been reported in which Kikuchi disease appeared concurrently with SLE and was complicated with hemophagocytic syndrome and severe infection.1

Race

Kikuchi disease was first diagnosed and described in Japan. To date, most cases have been reported from East Asia. More recently, the disease has been reported throughout the world and in all races. Outside of Asia, it is possible that Kikuchi disease has been underdiagnosed and therefore underreported. Dorfman and Berry reported 108 cases, including 68 in the United States; 63% of the 108 patients were white.

Sex

The initial studies of Kikuchi disease reported women were affected more often than men by a ratio of approximately 3:1. However, more recent studies have shown a smaller female preponderance, with a ratio closer to 1.25:1.

Age

Kikuchi disease occurs in a wide age range of patients (ie, 2-75 y), but it typically affects young adults (mean age, 20-30 y).

Clinical

History

Kikuchi disease most frequently manifests as a relatively acute onset of cervical adenopathy associated with fever and a flulike prodrome.

  • Lymphadenopathy
    • Cervical nodes are affected in about 80% of cases.
    • Posterior cervical nodes are frequently involved (65-70% of cases).
    • Lymphadenopathy is isolated to a single location in 83% of cases, but multiple chains may be involved.
    • Cases of generalized adenopathy involving axillary, inguinal, and mesenteric nodes are unusual.
  • A flulike prodrome with fever is present in 50% of cases. The following are less common symptoms:
    • Headache
    • Nausea, vomiting
    • Malaise, fatigue
    • Weight loss
    • Arthralgias, myalgias
    • Night sweats
    • Rash (up to 30%)
    • Thoracic/abdominal pain

Physical

  • Lymphadenopathy
    • Lymphadenopathy is isolated to 1 location in 83% of patients, although multiple nodal chains may be involved.
    • Cervical nodes are affected in 80% of patients; of these, 65-70% involve posterior triangle cervical nodes.
    • Less commonly affected nodes include those in axillary, mediastinal, celiac, abdominal, and inguinal locations.
    • The nodes are usually described as painless or mildly tender.
    • The nodes tend to be 2-3 cm in diameter, although masses of multiple nodes may reach 6 cm.
    • The nodes are usually firm and mobile, but they are not fluctuant or draining.
  • Extranodal findings
    • Skin17,18
      • The incidence of skin involvement varies from 5-30%.
      • Findings are varied and nonspecific and include maculopapular lesions, morbilliform rash, nodules, urticaria, and malar rash, which may resemble that of SLE.
      • Skin lesions resolve in a few weeks to months.
    • Hepatosplenomegaly
      • This finding is not uncommon.
      • Monitor lactase dehydrogenase (LDH) levels.
    • Neurologic involvement
      • Neurologic involvement is rare but has included conditions such as aseptic meningitis, acute cerebellar ataxia, and encephalitis.19
      • Patients with aseptic meningitis may report headache, but they do not exhibit nuchal rigidity or positive Kernig or Brudzinski signs. Cerebrospinal fluid (CSF) findings are similar to those noted in patients with aseptic meningitis of viral etiology.
    • Rarely involved extranodal sites include the bone marrow, myocardium, uvea, and thyroid and parotid glands.
    • Arthritic involvement was reported in the case of a 14-year-old body.2
    • Widespread involvement of multiple organ systems in Kikuchi disease has been described in solid-organ transplant patients.

More on Kikuchi Disease

Overview: Kikuchi Disease
Differential Diagnoses & Workup: Kikuchi Disease
Treatment & Medication: Kikuchi Disease
Follow-up: Kikuchi Disease
References
Further Reading
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References

  1. Kampitak T. Fatal Kikuchi-Fujimoto disease associated with SLE and hemophagocytic syndrome: a case report. Clin Rheumatol. Aug 2008;27(8):1073-5. [Medline].

  2. Singh YP, Agarwal V, Krishnani N, Misra R. Enthesitis-related arthritis in Kikuchi-Fujimoto disease. Mod Rheumatol. May 10 2008;epub ahead of print. [Medline].

  3. Bosch X, Guilabert A, Miquel R, Campo E. Enigmatic Kikuchi-Fujimoto disease: a comprehensive review. Am J Clin Pathol. Jul 2004;122(1):141-52. [Medline]. [Full Text].

  4. Lin HC, Su CY, Huang CC, Hwang CF, Chien CY. Kikuchi's disease: a review and analysis of 61 cases. Otolaryngol Head Neck Surg. May 2003;128(5):650-3. [Medline].

  5. Baumgartner BJ, Helling ER. Kikuchi's disease: a case report and review of the literature. Ear Nose Throat J. May 2002;81(5):331-5. [Medline].

  6. Kuo TT. Kikuchi's disease (histiocytic necrotizing lymphadenitis). A clinicopathologic study of 79 cases with an analysis of histologic subtypes, immunohistology, and DNA ploidy. Am J Surg Pathol. Jul 1995;19(7):798-809. [Medline].

  7. Dorfman RF, Berry GJ. Kikuchi's histiocytic necrotizing lymphadenitis: an analysis of 108 cases with emphasis on differential diagnosis. Semin Diagn Pathol. Nov 1988;5(4):329-45. [Medline].

  8. Gallien S, Lagrange-Xelot M, Crabol Y, et al. [Systemic lupus erythematosus and Kikuchi-Fujimoto disease mimicking tuberculosis] [French]. Med Mal Infect. Jun 17 2008;epub ahead of print. [Medline].

  9. Yilmaz M, Camci C, Sari I, et al. Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto's disease) mimicking systemic lupus erythematosus: a review of two cases. Lupus. 2006;15(6):384-7. [Medline].

  10. Poulose V, Chiam P, Poh WT. Kikuchi's disease: a Singapore case series. Singapore Med J. May 2005;46(5):229-32. [Medline]. [Full Text].

  11. Scagni P, Peisino MG, Bianchi M, et al. Kikuchi-Fujimoto disease is a rare cause of lymphadenopathy and fever of unknown origin in children: report of two cases and review of the literature. J Pediatr Hematol Oncol. Jun 2005;27(6):337-40. [Medline].

  12. Hedia G, Jamel A, Maher A, et al. Kikuchi-Fujimoto disease associated with systemic lupus erythematosus. J Clin Rheumatol. Dec 2005;11(6):341-2. [Medline].

  13. Onciu M, Medeiros LJ. Kikuchi-Fujimoto lymphadenitis. Adv Anat Pathol. Jul 2003;10(4):204-11. [Medline].

  14. Spies J, Foucar K, Thompson CT, LeBoit PE. The histopathology of cutaneous lesions of Kikuchi's disease (necrotizing lymphadenitis): a report of five cases. Am J Surg Pathol. Sep 1999;23(9):1040-7. [Medline].

  15. Sierra ML, Vegas E, Blanco-González JE, et al. Kikuchi's disease with multisystemic involvement and adverse reaction to drugs. Pediatrics. Aug 1999;104(2):e24. [Medline]. [Full Text].

  16. Hudnall SD. Kikuchi-Fujimoto disease. Is Epstein-Barr virus the culprit?. Am J Clin Pathol. Jun 2000;113(6):761-4. [Medline]. [Full Text].

  17. Atwater AR, Longley BJ, Aughenbaugh WD. Kikuchi's disease: case report and systematic review of cutaneous and histopathologic presentations. J Am Acad Dermatol. Jul 2008;59(1):130-6. [Medline].

  18. Yasukawa K, Matsumura T, Sato-Matsumura KC, et al. Kikuchi's disease and the skin: case report and review of the literature. Br J Dermatol. Apr 2001;144(4):885-9. [Medline].

  19. Sato Y, Kuno H, Oizumi K. Histiocytic necrotizing lymphadenitis (Kikuchi's disease) with aseptic meningitis. J Neurol Sci. Mar 1 1999;163(2):187-91. [Medline].

  20. Tong TR, Chan OW, Lee KC. Diagnosing Kikuchi disease on fine needle aspiration biopsy: a retrospective study of 44 cases diagnosed by cytology and 8 by histopathology. Acta Cytol. Nov-Dec 2001;45(6):953-7. [Medline].

  21. Viguer JM, Jiménez-Heffernan JA, Pérez P, et al. Fine-needle aspiration cytology of Kikuchi's lymphadenitis: a report of ten cases. Diagn Cytopathol. Oct 2001;25(4):220-4. [Medline].

  22. Kwon SY, Kim TK, Kim YS, et al. CT findings in Kikuchi disease: analysis of 96 cases. AJNR Am J Neuroradiol. Jun-Jul 2004;25(6):1099-102. [Medline]. [Full Text].

  23. Han HJ, Lim GY, Yeo DM, Chung NG. Kikuchi's disease in children: clinical manifestations and imaging features. J Korean Med Sci. Dec 2009;24(6):1105-9. [Medline]. [Full Text].

  24. Youk JH, Kim EK, Ko KH, Kim MJ. Sonographic features of axillary lymphadenopathy caused by Kikuchi disease. J Ultrasound Med. Jun 2008;27(6):847-53. [Medline].

  25. Jang YJ, Park KH, Seok HJ. Management of Kikuchi's disease using glucocorticoid. J Laryngol Otol. Sep 2000;114(9):709-11. [Medline].

  26. Hamdan AL, Jaber M, Tarazi A, Tawil A, Fuleihan N. Kikuchi Fujimoto disease: case report and review of the literature. Scand J Infect Dis. 2002;34(1):69-71. [Medline].

  27. Kishimoto K, Tate G, Kitamura T, Kojima M, Mitsuya T. Cytologic features and frequency of plasmacytoid dendritic cells in the lymph nodes of patients with histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease). Diagn Cytopathol. Nov 25 2009;epub ahead of print. [Medline].

  28. Lim GY, Cho B, Chung NG. Hemophagocytic lymphohistiocytosis preceded by Kikuchi disease in children. Pediatr Radiol. Jul 2008;38(7):756-61. [Medline].

  29. Ramirez AL, Johnson J, Murr AH. Kikuchi-Fujimoto's disease: an easily misdiagnosed clinical entity. Otolaryngol Head Neck Surg. Dec 2001;125(6):651-3. [Medline].

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Further Reading

Related eMedicine Topics

Clinical Trial

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Keywords

Kikuchi disease, KD, histiocytic necrotizing lymphadenitis, cervical lymphadenopathy, Kikuchi-Fujimoto disease, Kikuchi's disease, Kikuchi lymphadenitis, lymph node enlargement, lymphoma, systemic lupus erythematosus, SLE, upper respiratory tract infections, URTIs, cytomegalovirus, Epstein-Barr virus, human herpesvirus, varicella-zoster virus, parainfluenza virus, parvovirus B19, paramyxovirus, lymphadenitis, fever of unknown origin, FUO

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Contributor Information and Disclosures

Author

John Boone, MD, Consulting Staff, Department of Otolaryngology, Naval Hospital Oak Harbor
John Boone, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery
Disclosure: Nothing to disclose.

Coauthor(s)

Charles S Kuzma, MD, Consulting Staff, Cancer Care Associates
Charles S Kuzma, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology, and California Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Karen Seiter, MD, Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College
Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, and American Society of Hematology
Disclosure: Novartis Honoraria Speaking and teaching; Schering Honoraria Speaking and teaching; Cephalon Honoraria Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Lawrence H Brent, MD, Associate Professor of Medicine, Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center
Lawrence H Brent, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, and American College of Rheumatology
Disclosure: Genentech Honoraria Speaking and teaching; Genentech Grant/research funds Other; Amgen Honoraria Speaking and teaching; Wyeth Honoraria Speaking and teaching; Abbott Immunology Honoraria Speaking and teaching; Takeda Honoraria Speaking and teaching; UCB  Speaking and teaching; Omnicare Consulting fee Consulting; Centocor Consulting fee Consulting; Roche Grant/research funds Other

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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