• Disease Overview
  • Synonyms
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • References
  • Programs & Resources
  • Complete Report

Kikuchi-Fujimoto Disease


Last updated: 9/28/2023
Years published: 1992, 2000, 2004, 2006, 2023


NORD gratefully acknowledges Behnaz Akbari, PhD student, Department of Chemistry, Division of Analytical Chemistry, Purdue University, and Janet Hope Sherman, MD, MA, MRI Fellowship Trained Diagnostic Radiologist, Boston University, for assistance in the preparation of this report.

Disease Overview

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenopathy, is a rare, benign (noncancerous, nonmalignant) disorder of the lymph nodes, predominantly of young adults and school aged children. While slightly more common in females, it is also seen in males. This disorder presents with similar signs and symptoms as lymphoma, including enlarged lymph nodes (lymphadenopathy) The exact cause is not known. KFD shows up as painful swelling of lymph nodes, often in the neck, along with general symptoms like fever and fatigue.

KFD is similar to a type of inflammatory response called granulomatous response. When the lymph nodes are examined under a microscope, specific changes may be seen such as tissue necrosis (cell death) and an absence of a particular type of immune cell called neutrophils. Instead, the necrotic areas mainly contain remnants of cells undergoing apoptosis, where the cell nucleus breaks down. In simpler terms, KFD is a unique condition where the affected tissue shows signs of cell death, but the immune cells generally associated with that kind of reaction are missing. This unusual pattern makes it distinct from other diseases with similar symptoms.

Usually, this disease does not cause severe problems and gets better on its own. However, in some people, it can be associated with autoimmune disorders, conditions where the immune system mistakenly attacks the body’s cells and tissues.

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  • histiocytic necrotizing lymphadenitis (HNL)
  • KFD
  • Kikuchi Disease
  • Kikuchi’s histiocytic necrotizing lymphadenitis (KHNL)
  • necrotizing lymphadenitis (NL)
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Signs & Symptoms

KFD is a rare nonmalignant disorder that affects the lymph nodes. Lymph nodes are present throughout the body as small oval or kidney bean shaped structures that filter lymph fluid, fight infection and form white blood cells and blood plasma cells. Enlarged and painful lymph nodes are commonly in the neck region, but supraclavicular, axillary, thoracic, intraparotid, abdominal and pelvic lymph nodes may also be involved.

Affected individuals may develop a mild fever, night sweats, muscle pain (myalgia) and a rash. Less common symptoms include headaches, fatigue, joint pain (arthralgia), nausea and vomiting. Some affected individuals may experience liver or spleen enlargement (hepatosplenomegaly). The symptoms of KFD may develop slowly over two to three weeks.

In summary, the clinical features of KFD are the presence of enlarged lymph nodes associated with signs and symptoms such as:

• Fever
• Fatigue
• Night sweats
• Body aches
• Weight loss (in some people)
• Loss of appetite
• Hepatosplenomegaly

The abnormal tissue growth and inflammation in KFD usually clears up spontaneously within a few weeks or months without further therapy (self-limited disease).

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The exact cause of KFD is not known (idiopathic). It is thought that an abnormal immune response, possibly influenced by viral infection or genetic factors, may play a role. It is thought to be related to viral infections like HIV, HSV, VZV and EBV, as well as autoimmune conditions such as lupus, sarcoidosis, lymphoma and Sjogren’s syndrome. Another theory is that KFD is a self-limited autoimmune condition. Autoimmune disorders are caused when the body’s natural defenses against “foreign” or invading organisms begin to attack healthy tissue for unknown reasons.

Our bodies have a normal protective response to infection from viruses. Small proteins called Interferon create signals to help protect the body against infections, including infection from viruses. KFD has been shown to be associated with an increase in interferon response (aberrant type I interferon response).

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Affected populations

KFD, first identified in Japan in 1972, is extremely rare.

In 2014, after conducting a PubMed search, 590 articles were found that described KFD. Among them, 22 cases have been thoroughly documented in the United States. Of the 22 patients, 10 (45%) were male and 12 (55%) were female. The ethnic distribution of the cases was as follows: 20% Caucasian, 20% Asian American, and the remaining 60% represented various other ethnic backgrounds. It appears to affect young adults particularly but can occur at any age. From the literature, a total of 335 cases of KFD were reviewed with a distribution of cases among different age groups. Among these cases, in 2020, it was reported that 14 (4.2%) occurred in children under six years of age, while the majority, 321 (95.8%) of cases were reported in school-age children (6-20 years). School-age children were more commonly affected by KFD and the characteristic presentation in this group included pyrexia, leukopenia and cervical lymphadenopathy with tenderness. In contrast, children under six years of age with KFD had different significant symptoms. Three cases were associated with lung lesions, six had leukocytosis and eight presented with generalized lymphadenopathy, which differed from the symptom profile observed in school-age children. It is noteworthy that leukocytosis, generalized lymphadenopathy in locations other than cervical lymph nodes and lung lesions are characteristic symptoms of severe KFD in patients under six years old, an age group in which KFD occurs infrequently. For instance, in 2022, a 7-year-old African American girl who was previously healthy presented to an academic-affiliated community hospital pediatric emergency department (ED) for a rapid, enlarged postauricular lymph node along with fever. However, it primarily affects young adults (Age<40), which is more commonly seen in females than males. In 2022, a rare case of KFD was documented in a patient with coexisting Crohn’s disease. The patient, a 23-year-old African American female with a significant past medical history of Crohn’s disease, presented to the clinic due to a painless lump on the right side of her neck, which had been present for the past 3 weeks. KFD may be more prevalent than previously recognized since swollen glands are common and frequently ignored. This, combined with the self-limiting nature of the disorder, has led some clinicians to speculate that KFD is more common than initially thought. Since diagnosis of this disorder can only be confirmed by biopsy of the tissue in the affected lymph nodes, many affected people may be undiagnosed.

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Diagnosis requires proper evaluation by a healthcare professional and pathologist, including a thorough medical history, physical examination and sometimes a biopsy of the affected lymph node.

In some people, the histological and immunohistochemical characteristics of the lymph nodes in SLE and KFD can be similar. However, there are differences, and careful analysis is needed to distinguish between the two. Practically, KFD affects the lymph nodes, causing them to become swollen and possibly enlarged. A part or all of an enlarged lymph node is removed and examined under a microscope to diagnose the condition. The characteristic features include tissue necrosis and the presence of certain types of cells. Immunohistochemistry is used to identify specific markers that help confirm the diagnosis.

The following conditions have been associated with Kikuchi disease in some patients. They are not necessary for a diagnosis:

Pancytopenia – a reduction in the number of red and white blood cells and platelets in the circulating blood.

Splenomegaly – an abnormal enlargement of the spleen.

Still’s disease – also called juvenile rheumatoid arthritis or rheumatic arthritis, is a form of arthritis that usually, but not exclusively, affects the larger joints of children. In addition to occasional high fever and rash, patients have inflammation of several thin layers of tissue that line certain body areas (serous membranes) and enlarged lymph nodes.

Post Vaccination

Post-vaccinal lymphadenitis, a reactive response to vaccination, can occur following the administration of various vaccines, including those against smallpox, influenza, varicella zoster, BCG and pneumococcal infections. Rarely, KFD has been reported after human papillomavirus and influenza vaccinations. Temporary lymphadenopathy on the same side as vaccination, including after COVID-19 vaccine may be seen, and may involve the armpit or neck nodes. There have been very rare, reported cases of KFD following COVID-19 vaccinations. The mechanism by which a vaccine may lead to the development of KFD remains unknown, but it is hypothesized that viral or other antigens in the vaccine could trigger an abnormal immune response in some people, resulting in the development of KFD. Sometimes, reactions in lymph nodes after vaccination can last for a while. If a patient has a high fever that persists for a long time, even up to three to four months after vaccination, a doctor might consider the possibility of KFD, especially if signs and symptoms like swollen lymph nodes, abnormal lymphocyte counts and liver issues are also present.

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Standard Therapies

Treatment of KFD is symptomatic and supportive. Usually, the disorder resolves spontaneously within a few weeks or months. Analgesics-antipyretics and nonsteroidal anti-inflammatory (NSAIDs) may be used to treat pain, tenderness and lymphadenopathy-related fever. In extremely rare cases, KFD may recur.

There is no specific treatment for KFD as it is a self-limited disorder which can be resolved in less than 4 months. Management focuses on relieving symptoms (e.g., pain and fever) with nonsteroidal anti-inflammatory drugs (NSAIDs) or other symptomatic treatments. Fever tends to subside after removal of the affected lymph node, indicating the potential therapeutic benefit of excisional biopsy as both a diagnostic and treatment measure. Patients with prolonged fever, severe symptoms lasting over two weeks, or recurrent disease may require treatment with immunomodulators and systemic corticosteroids (prednisolone 1-2 mg/kg body weight), either alone or in combination. Corticosteroids and intravenous immune globulin (IVIg) are commonly used in the treatment of KFD, particularly in patients with the severe or generalized disease, extra nodal involvement or hemophagocytic syndrome, and have shown positive therapeutic outcomes. Hydroxychloroquine alone or combined with systemic corticosteroids has been reported as a successful treatment option for recurrent or steroid-resistant KFD. One study achieved a rapid response in a KFD patient with systemic symptoms by administering chloroquine, leading to significant improvement within four days. In one case, anakinra, an IL-1 inhibitor, demonstrated effectiveness in a patient unresponsive to steroid therapy. The potential benefit of ciprofloxacin, minocycline and ofloxacin in managing KFD requires further evaluation, despite some anecdotal evidence suggesting their effective doses of glucocorticoids are often required to control the disease. In some people, hydroxychloroquine is used, which may have a critical role in avoiding disease recurrence in flared patients, although the current research study has not thoroughly investigated this condition. It is worth noting that antibiotics do not impact the progression of KFD in the studied patients.

Currently, there is a lack of literature outlining the optimal approach for long-term follow-up of KFD patients, particularly regarding potential complications and associations with diseases such as SLE. It appears reasonable to conduct an SLE screening upon the initial diagnosis of KFD, followed by annual screenings for several years. Additionally, monitoring erythrocyte sedimentation rate (ESR) can help identify any autoimmune, infectious or malignant developments. KFD generally has an excellent prognosis, with most cases resolving within six months.

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Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov All studies receiving US government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Some current clinical trials also are posted on the following page on the NORD website:

For information about clinical trials sponsored by private sources, contact:

For information about clinical trials conducted in Europe, contact:

For information about clinical trials sponsored by private sources, contact:www.centerwatch.com

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