Kikuchi Disease

Updated: Aug 12, 2017
  • Author: John Boone, MD; Chief Editor: Koyamangalath Krishnan, MD, FRCP, FACP  more...
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Overview

Practice Essentials

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

The most common clinical manifestation of Kikuchi disease is cervical lymphadenopathy, with or without systemic signs and symptoms. [2, 3, 4, 5] Clinically and histologically, the disease can be mistaken for lymphoma or systemic lupus erythematosus (SLE). [1, 2, 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, 16]

In a retrospective study of 24 cases of Kikuchi disease in southern India over a 4-year period, the findings included the following [17] :

  • Sex - 17  females, 7 males
  • Most common presenting feature - Painless cervical lymphadenopathy
  • Most common laboratory abnormalities - Leukopenia, increased erythrocyte sedimentation rate (ESR), increased liver enzyme levels
  • Lymph node biopsy findings - Typical morphology of Kikuchi disease, with necrosis, karyorrhectic debris, and the presence of the typical cell types, namely crescentic histiocytes and plasmacytoid monocytes
  • Clinical resolution - Within 1 month

Treatment of Kikuchi disease is generally supportive. (See Treatment.) Pharmacologic therapy that has been recommended includes the following:

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) - To alleviate lymph node tenderness and fever
  • Corticosteroids  - For severe extranodal or generalized Kikuchi disease
  • Hydroxychloroquine - For steroid-resistant or recurrent cases
  • Intravenous immunoglobulin - For steroid-resistant or recurrent cases

See also Cutaneous Kikuchi Disease

For patient education resources, see Swollen Lymph Nodes and Lymphoma.

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Pathophysiology

The cause of Kikuchi disease is unknown, although infectious and autoimmune etiologies have been proposed. [18] 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, [19] 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. [6, 8, 9, 11, 12] 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.

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Epidemiology

Although uncommon, Kikuchi disease has been reported throughout the world and in all races. Most cases have been reported from East Asia and Japan, with fewer cases from Europe and North America. [1]

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. Four deaths have been reported, from hemophagocytic syndrome and severe infection, pulmonary hemorrhage, acute heart failure, and multiorgan failure and disseminated intravascular coagulation. [20]

Race-, Sex-, and Age-related Demographics

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. [6] In a study of 91 cases from France, Dumas et al reported increased risk for severe disease in patients of North African origin. [12]

Kikuchi disease is reported more often in women, with a female-to-male ratio as high as 4:1 in some studies. [1] However, other studies have shown a smaller female preponderance, with a ratio closer to 2:1. [36]

A study of Korean patients by Jung et al reported clinical differences between males and females with Kikuchi disease. Females were more likely to have autoimmune features, including antinuclear antibodies, while males were more likely to present with a profile of fever, headache, bilateral lymphadenopathy, thrombocytopenia, and elevated levels of liver enzymes, C-reactive protein, and lactate dehydrogenase (LDH). [21]

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). In a Korean study of children with severe Kikuchi disease, the mean age was 13.2 years, and the male-to-female ratio was 1:1.32. [22]

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