Kikuchi disease; Kikuchi Fujimoto lymphadenopathy; Histiocytic necrotizing lymphadenitis.

Subacute necrotizing regional lymphadenopathy associated with mild fever, more common in young Asian people.

Described independently in 1972 by Kikuchi (1) and Fujimoto et al. (2), this subacute necrotizing lymphadenitis has been commonly recognized in Asia and sporadically in Western countries (3,4,5,6,7,8,9). The patients are generally young adults, and a slight female prevalence has been reported (8,9,10,11).

The etiology of necrotizing lymphadenitis is unknown. A viral infection is suggested by the clinical and histologic features, and various viruses including Epstein-Barr (EBV) virus (12,13), cytomegalovirus, parvovirus B19 (14) human herpesvirus 6 (HHV-6) (15,16) and HHV-8 (17) have been investigated, so far with negative results (18,19).

A variety of mechanisms have been proposed, some of them discussed in a recent review of Kikuchi disease (20). The extensive cell death is attributed to early apoptosis, which is characterized by excessive nuclear fragmentation (21,22). The same authors have determined that the CD8+ T lymphocytes are the cells that predominantly undergo apoptosis in this lymphadenopathy. Ohshima et al. have also noted that the serum concentrations of interferon-γ, interleukin-6, FAS-L, and other cytokines are increased in the acute phase of Kikuchi disease (23).

The patients are young adults, predominantly women, most commonly in Japan and neighboring Asian countries (18). In a study of 376 cases in Japan, the average age was 27.4 years and the male-to-female ratio 1:1.6 (24); in a recent series of 61 cases from Taiwan, the average age was 22 years and the gender ratio 1:1 (11). More than 85% of the patients present with swollen cervical lymph nodes, unilateral in 88.5% of cases, usually involving the posterior cervical triangle (20). Less commonly axillary, inguinal lymph nodes are involved and cases of generalized lymphadenopathy have been also reported (8,9,10,11). The involvement of deep lymph nodes is very rare (24). The lymphadenopathy is painless and unaccompanied by other symptoms or associated with moderate fever, chills, myalgia, sore throat, and skin rashes resembling measles or drug eruptions in 20% to 30% of cases (24). The course is benign with spontaneous resolution of the adenopathy in a few weeks or months and rare recurrences (4,5,6,7,8,9). Involvement of extranodal sites, such as a moderate liver and spleen enlargement, is unusual but well documented, particularly in Asia, where Kikuchi disease is more common. In a report of five cases, the patients presented with cutaneous involvement in addition to the typical necrotizing lymphadenopathies. They had cutaneous eruptions on the upper body that, in some cases, resembled systemic lupus (25). A few fatal cases have been reported in which fever and systemic necrotizing lymphadenitis were associated with organ transplantation, necrotizing myocarditis, or fulminant hepatitis (24,26). Leukopenia below 4,000/mm³ in 56% of cases with mild lymphocytosis and occasional atypical lymphocytes may occur in 25% to 30% of cases (9,24). Bone marrow biopsy, when performed, revealed no abnormalities (4). Elevation of lactate dehydrogenase, interferon, and interleukin-6 may occur but returns to normal. Most patients recover within 1–2 months without any treatment. About 3% have a recurrence within several years (24).