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.
- Skin17,18
More on Kikuchi Disease |
Overview: Kikuchi Disease |
| Differential Diagnoses & Workup: Kikuchi Disease |
| Treatment & Medication: Kikuchi Disease |
| Follow-up: Kikuchi Disease |
| References |
| Further Reading |
| Next Page » |
References
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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].
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].
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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].
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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].
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Further Reading
Related eMedicine Topics
- Corticosteroid-Induced Myopathy [in the Physical Medicine and Rehabilitation section]
- Cutaneous Kikuchi Disease [in the Dermatology section]
- Fever of Unknown Origin [in the Infectious Disease section]
- Histiocytosis [in the Pediatrics: General Medicine section]
- Immunosuppression [in the Transplantation section]
- Lymph Node Disorders [in the Pediatrics: Surgery section]
- Lymphadenopathy [in the Pediatrics: General Medicine section]
- Toxicity, Nonsteroidal Anti-inflammatory Agents [in the Emergency Medicine section]
Clinical Trial
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
Overview: Kikuchi Disease