Prophylaxis by vaccination, as well as preventive measures like protective clothing, tick control, and mosquito control are advised. The vaccine for KFDV consists of formalin-inactivated KFDV. The vaccine has a 62.4% effectiveness rate for individuals who receive two doses. For individuals who receive an additional dose, the effectiveness increases to 82.9%. Specific treatments are not available.

There are a variety of animals thought to be reservoir hosts for the disease, including porcupines, rats, squirrels, mice and shrews. The vector for disease transmission is "Haemaphysalis spinigera", a forest tick. Humans contract infection from the bite of nymphs of the tick.

Some studies have suggested a genetic predisposition to the proposed autoimmune response. Several infectious candidates have been associated with Kikuchi disease.

Many theories exist about the cause of KFD. Microbial/viral or autoimmune causes have been suggested. "Mycobacterium szulgai" and "Yersinia" and "Toxoplasma" species have been implicated. More recently, growing evidence suggests a role for Epstein-Barr virus, as well as other viruses (HHV6, HHV8, parvovirus B19, HIV and HTLV-1) in the pathogenesis of KFD. However, many independent studies have failed to identify the presence of these infectious agents in cases of Kikuchi lymphadenopathy. In addition, serologic tests including antibodies to a host of viruses have consistently proven noncontributory and no viral particles have been identified ultrastructurally.

KFD is now proposed to be a nonspecific hyperimmune reaction to a variety of infectious, chemical, physical, and neoplastic agents. Other autoimmune conditions and manifestations such as antiphospholipid syndrome, polymyositis, systemic juvenile idiopathic arthritis, bilateral uveitis, arthritis and cutaneous necrotizing vasculitis have been linked to KFD. KFD may represent an exuberant T-cell-mediated immune response in a genetically susceptible individual to a variety of nonspecific stimuli.

Human leukocyte antigen class II genes are more frequent in patients with Kikuchi disease, suggesting a genetic predisposition to the proposed autoimmune response.

Kikuchi-Fujimoto disease (KFD) is a rare, self-limiting disorder that typically affects the cervical lymph nodes. Recognition of this condition is crucial, especially because it can easily be mistaken for tuberculosis, lymphoma, or even adenocarcinoma. Awareness of this disorder helps prevent misdiagnosis and inappropriate treatment.

Kikuchi's disease is a very rare disease mainly seen in Japan. Isolated cases are reported in North America, Europe, and Asia. It is mainly a disease of young adults (20–30 years), with a slight bias towards females. The cause of this disease is not known, although infectious and autoimmune causes have been proposed. The course of the disease is generally benign and self-limiting. Lymph node enlargmeent usually resolves over several weeks to six months. Recurrence rate is about 3%. Death from Kikuchi disease is extremely rare and usually occurs due to liver, respiratory, or heart failure.