Kikuchi’s Disease

Definition

Kikuchi’s disease, or Kikuchi-Fujimoto disease (KFD) is an enigmatic, benign and self-limited syndrome characterized by regional lymphadenopathy with tenderness, predominantly in the cervical region, usually accompanied by mild fever and night sweats.

Initially described in Japan, KFD was first reported in 1972 almost simultaneously by Kikuchi [1] and by Fujimoto et al. [2] as a lymphadenitis with focal proliferation of reticular cells accompanied by numerous histiocytes and extensive nuclear debris [3].

Etiology and pathogenesis

There is much speculation about the etiology of KFD. A viral or autoimmune cause has been suggested. The role of Epstein-Barr virus, as well as other viruses (HHV6, HHV8, parvovirus B19) in the pathogenesis of KFD remains controversial and not convincingly demonstrated [4]. A viral infection is, nonetheless, possible by virtue of clinical manifestations, as described by Unger et al. [6] that include upper respiratory prodrome, atypical lymphocytosis and lack of response to antibiotic therapy, and certain histopathologic features (i.e., T-cells as revealed by immunological marker studies). KFD has also been recorded in HIV- and HTLV-1-positive patients [7].

Some authors hypothesized that KFD may reflect a self-limited autoimmune condition induced by virus-infected transformed lymphocytes [8]. It is possible that KFD may represent an exuberant T-cell mediated immune response in a genetically susceptible individual to a variety of non-specific stimuli [4].

Clinical manifestations

The onset of KFD is acute or subacute, evolving over a period of two to three weeks. Cervical lymphadenopathy is almost always present consisting of tender lymph nodes that involve mainly the posterior cervical triangle. Lymph node size has been found to range from 0.5 to 4 cm, but it may reach 5 to 6 cm and rarely larger than 6 cm. Generalized lymphadenopathy can occur [5,10] but is very rare. In addition to lymphadenopathy, 30 to 50% of patients with KFD may have fever, usually of low-grade, associated with upper respiratory symptoms. Less frequent symptoms include weight loss, nausea, vomiting, sore throat and night sweats [11,12]. Leukopenia can be found in up to 50% of the cases. Atypical lymphocytes in the peripheral blood have also been observed. Involvement of extranodal sites in KFD is uncommon but skin, eye and bone marrow affection, and liver dysfunction have been reported [4]. KFD has also been reported as a cause of prolonged fever of unknown origin [13]. There are occasional reports describing cases of extranodal skin involvement or, even more rarely, of fatal multicentric disease.

Diagnosis

Kikuchi-Fujimoto disease is generally diagnosed on the basis of an excisional biopsy of affected lymph nodes. No specific diagnostic laboratory tests are available. The results of a wide range of laboratory studies are usually normal. Nevertheless, some patients have anemia, slight elevation of the erythrocyte sedimentation rate and even leukopenia. Of note, one third of patients present atypical peripheral blood lymphocytes [5]. Characteristic histopathologic findings of KFD include irregular paracortical areas of coagulative necrosis with abundant karyorrhectic debris, which can distort the nodal architecture, and large number of different types of histiocytes at the margin of the necrotic areas.

Differential diagnosis

The histological differential diagnosis of KFD mainly includes reactive lesions as lymphadenitis associated with SLE or herpes simplex, non-Hodgkin’s lymphoma, plasmacytoid T-cell leukemia, Kawasaki’s disease, myeloid tumor and even metastasic adenocarcinoma [4].

Clinical course and management

Kikuchi-Fujimoto disease is typically self-limited within one to four months. A low but possible recurrence rate of 3 to 4% has been reported [3]. In some few patients, SLE may occur some years later. No risk to other family members is felt to be associated with KFD [7]. Symptomatic measures aimed to relief the distressing local and systemic complains should be employed.

Analgesics-antipyretics and nonsteroidal anti-inflammatory drugs may be used to alleviate lymph node tenderness and fever. The use of corticosteroids has been recommended in severe extranodal or generalized KFD but is of uncertain efficacy. Surgical consultation may be indicated for a diagnostic excisional lymph node biopsy. Patients with KFD require a systematic survey and regular follow-up for several years to rule out the development of SLE. The cervical lymphadenopathy runs a benign course and appears to resolve spontaneously 1 to 6 months after definite diagnosis.

 

Adapted from Orphanet Journal of Rare Diseases 2006, 1:18  doi:10.1186/1750-1172-1-18