Kikuchi-Fujimoto disease (ORPHA:50918)
A rare systemic disease characterized by subacute, necrotizing, regional lymphadenopathy with tenderness, usually accompanied with mild fever, night sweats, myalgia, leukopenia and anemia. Less frequent symptoms include weight loss, nausea, vomiting and sore throat. It is a self-limiting benign disease that usually recedes within six months, even without drug treatment.
Epidemiology
Kikuchi-Fujimoto disease is an extremely rare disease known to have a worldwide distribution, with higher prevalence among Japanese and other Asian populations. It is found in both sexes, with female predominance, albeit sex ratio has been found close to 1:1 in some reports and male predominance was observed in Asian pediatric populations.
Clinical description
Kikuchi-Fujimoto disease is self-limiting, with acute to subacute course evolving during several weeks. It usually affects young adults (< 40 years old), but can occur in any age group. Patients most commonly present with posterior cervical lymphadenopathy, frequently with concomitant involvement of axillary and/or supraclavicular lymph nodes. Affected lymph nodes are tender and painful. Lymphadenopathy is most commonly associated with fever; other infrequent symptoms include weight loss, nausea and vomiting, weakness, headache, arthralgia, night sweats, upper respiratory symptoms, and sore throat. Hepatomegaly and splenomegaly rarely occur.
Etiology
Two competing theories exist to explain the etiology of this disease: infectious or autoimmune origin. The prevailing explanation for Kikuchi-Fujimoto disease is that a viral, bacterial or other infectious agent triggers an inflammatory process in susceptible individuals. The co-occurrence of different autoimmune diseases, including systemic lupus erythematosus (most commonly), relapsing polychondritis, Sjögren-Larsson syndrome, systemic sclerosis or antiphospholipid syndrome, is suggestive of an alteration of the immune system in these patients. The chronology of co-occurrence was found to be variable; autoimmune disease may appear before, during, or after the course of Kikuchi-Fujimoto disease.
Diagnostic methods
Diagnosis is based on the histological analysis and immunohistochemistry of biopsies from affected lymph nodes, essential for the exclusion of other clinically similar entities (i.e. lymphoma, metastasis or tuberculous adenitis). Histological landmarks include follicular hyperplasia with paracortical infiltration of histiocytes and lymphocytes, absence of neutrophils and eosinophils (in the proliferative stage), and necrotic foci with a high degree of karyorrhexis (in the necrotizing stage).
Differential diagnosis
The differential diagnosis includes infectious lymphadenitis of different etiologies, autoimmune lymphadenopathy (primarily systemic lupus erythematosus) and non-Hodgkin lymphoma.
Management and treatment
Treatment is symptomatic and includes antipyretics, analgesics, nonsteroidal anti-inflammatory drugs and, rarely, corticosteroids. Patients with Kikuchi-Fujimoto disease should be followed up for several years to monitor the possible development of systemic lupus erythematosus and other autoimmune diseases.
Prognosis
Spontaneous recovery occurs in 1 to 6 months, but recurrences (3-4%) and fatal cases have been reported.

                            Last update: 
                            June 2023


                            - Expert reviewer(s): 
                            Dr Massimo FUSCONI  - Dr Fabiana ZACCARELLI