What is Kikuchi-Fujimoto Disease?
Kikuchi-Fujimoto disease, also known as histiocytic necrotizing lymphadenitis, is a rare inflammatory condition that typically improves on its own over time. This disease was first identified by two Japanese pathologists, Kikuchi and Fujimoto, in 1972. It primarily affects young people and children from Asian backgrounds, but cases have been observed in people of varying ages and ethnicities. The usual symptoms begin quickly or moderately and include painful, swollen neck glands along with features like fever, tiredness, weight loss, joint pain, and different skin problems.
To make sure of the diagnosis, a surgeon needs to remove and test a lymph node – a small, bean-shaped structure that filters lymph fluid. This test will show a deficit of two types of white blood cells, neutrophils and eosinophils. Other tests can be performed to find the presence of certain proteins and cells that suggest Kikuchi-Fujimoto disease. A needle biopsy is often not enough to confirm the disease because it doesn’t provide enough tissue for thorough examination.
It’s essential to tell Kikuchi-Fujimoto disease apart from lymphomas (cancer of the lymph nodes) and infectious diseases. Doctors can use cultures and blood tests for this purpose. Although the tissue changes in Kikuchi-Fujimoto disease can look similar to those seen in lymph node inflammation associated with lupus (an autoimmune disease), certain structures called hematoxylin bodies help differentiate the two.
Interestingly, lupus is the most common associated condition with Kikuchi-Fujimoto disease. However, Kikuchi-Fujimoto disease generally resolves on its own within a few months and rarely reoccurs, which is different from lupus.
Managing Kikuchi-Fujimoto disease involves comfort care for patients. In severe or recurring cases, corticosteroids and immune-system-suppressing drugs may be considered. The patient’s outlook is generally excellent, with rare complications such as a severe immune reaction called hemophagocytic lymphohistiocytosis (HLH). Because this disease is so rare, it may not be immediately recognized, leading to treatment for a different disease. So, making more healthcare professionals aware of this disease can considerably improve patient outcomes.
What Causes Kikuchi-Fujimoto Disease?
The exact cause of Kikuchi-Fujimoto disease is still a mystery. However, there are two main theories that doctors believe might explain it. The first is an infectious cause, meaning the disease might be triggered by various types of infections. The second theory is that it might be an autoimmune disease, a type of condition where your body’s immune system mistakenly attacks your own body.
Various types of infections, including those caused by both bacterial and viral agents, have been suggested as possible triggers of this disease. Some of the viruses that have been investigated include Epstein-Barr virus, herpes simplex virus types 1 and 2, varicella-zoster virus, cytomegalovirus, and human herpesvirus, among others. However, so far, there’s no definitive proof that any of these viruses directly cause the disease.
On the bacterial side, a few culprits have been suggested, including Brucella, Bartonella henselae, Toxoplasma gondii, Yersinia enterocolitica, Entamoeba histolytica, and Mycobacterium species. But again, most tests for infection in patients with Kikuchi-Fujimoto disease come back negative.
In the autoimmune theory, there’s some evidence that specific human leukocyte antigens (HLAs), a type of protein on our cells, could make some people more likely to get Kikuchi-Fujimoto disease. Asian populations, which are more likely to have these types of HLAs, also have higher rates of the disease. In addition, Kikuchi-Fujimoto disease has shown associations with various autoimmune conditions such as lupus, Sjögren syndrome, granulomatosis with polyangiitis, rheumatoid arthritis, and Still’s disease.
Interestingly, those with Kikuchi-Fujimoto disease usually don’t test positive for markers typically found in autoimmune diseases. This makes the diagnosis a bit challenging, especially in individuals who already have pre-existing autoimmune conditions.
Some reports have also linked Kikuchi-Fujimoto disease to other conditions or occurrences such as cancer, infections in the brain, kidney failure, lung disease, foreign body implants, and even certain types of surgery. However, so far, the overall agreed-upon explanation for Kikuchi-Fujimoto disease is that a viral or unknown infectious agent might start an inflammatory process in people who are susceptible.
Risk Factors and Frequency for Kikuchi-Fujimoto Disease
Kikuchi-Fujimoto disease is a very rare condition. Its exact number of cases is unknown. While this disease can affect people of all ages, including children, it’s more commonly seen in people under 30. Though initially more common in females, recent studies in Asian populations show a near-equal number of male and female cases.
- Kikuchi-Fujimoto disease is most frequently seen in Asian populations, but can appear in any racial or ethnic group.
- There are only a few case studies of this disease in the United States and Europe.
- People with certain HLA genotypes in Asian populations, specifically HLA-DPB1 and HLA-DPA1, are associated with the disease.
- However, routine tests for these genotypes are not done in a clinical setting.
- Though there have been cases reported within families, it’s not certain if these are due to shared genetic factors or environmental circumstances.
Signs and Symptoms of Kikuchi-Fujimoto Disease
Kikuchi-Fujimoto disease is a condition that gradually develops over several weeks. The most common symptom is swelling of the lymph nodes at the back of the neck, which is tender and painful to touch. This is observed in 60% to 90% of cases, but the lymph nodes above the collarbones and armpits can also get affected. Typically, the swollen lymph nodes are approximately 1 to 2 cm in diameter, although sizes of up to 7 cm have been reported.
In some cases, the lymph nodes may enlarge on both sides of the body or all over the body. Other related symptoms often resemble the B-symptoms associated with some diseases like fever, weight loss, night sweats, fatigue, headaches, joint pain, sore throat, upper respiratory symptoms, nausea, and vomiting. Additionally, in about 5% of people with this disease, it may also affect the spleen, liver, bone marrow, and nervous system.
- Swelling of lymph nodes at the back of the neck
- Swelling can also occur above the collarbones and in the armpits
- Swollen lymph nodes can be tender and painful
- Fever, weight loss, night sweats, fatigue
- Headaches, joint pain, sore throat
- Upper respiratory symptoms, nausea, vomiting
- Enlargement of spleen and liver
Around 40% of people with Kikuchi-Fujimoto disease can see changes in their skin, such as a rash, hair loss, skin reddening, ulcers, or symptoms similar to lupus. In more severe cases, the rash can turn into spots or patches caused by bleeding under the skin, hinting at inflammation of the blood vessels when biopsied.
Interestingly, children and adults may show different symptoms. Children tend to have prolonged and severe periods of fever and are more likely to experience lymph node necrosis (the death of tissue) than adults.
Testing for Kikuchi-Fujimoto Disease
Kikuchi-Fujimoto disease is a rare condition that’s hard to diagnose because it doesn’t have one specific set of symptoms. Doctors need to rule out other possible causes of enlarged lymph nodes, such as infections, cancer, and autoimmune diseases, before they can diagnose Kikuchi-Fujimoto disease.
If you are being tested for this disease, the doctors will look at different markers in your blood. These markers might be slightly higher than normal, including proteins indicating inflammation, liver enzymes, and iron-containing proteins. You might also have fewer or more white blood cells than usual or abnormal types of lymphocytes, a type of white blood cell, in your blood. However, none of these tests can specifically pinpoint Kikuchi-Fujimoto disease.
In determining whether you have Kikuchi-Fujimoto disease, your doctor will take into account recent illnesses, travel, exposure to certain animals, tuberculosis, or antibiotic use. Your doctor will test your blood to see if viruses or other infections might be causing your symptoms. If tuberculosis is suspected, further tests will be done.
You might have already received treatment for some common bacterial infections before being tested for Kikichi-Fujimoto disease, which your doctor will take into account as well.
Testing for other autoimmune diseases is crucial. One such disease is lupus, and for this, the tests include looking for different types of antibodies in your blood. This is vital because the tissue of the lymph nodes in both diseases can look very similar. An enzyme related to lung diseases might also be checked. It’s also important to consider any family history of autoimmune diseases.
Imaging, like ultrasounds and X-rays, might be used to check for enlarged lymph nodes and other related symptoms in your body. A CT scan, which is a type of X-ray that gives detailed images, is not necessary but can be helpful. It might show certain characteristics of the lymph nodes that could support a diagnosis of Kikuchi-Fujimoto disease.
But the definite way to diagnose Kikuchi-Fujimoto disease is through a biopsy, a procedure where a small piece of the affected lymph node is removed for closer examination under a microscope. Sometimes this procedure may have to be done again if the initial results are unclear. In some cases, when there’s a suspicion of accompanying blood vessel inflammation or skin involvement, a skin biopsy might offer valuable insights for the diagnosis.
Treatment Options for Kikuchi-Fujimoto Disease
Kikuchi-Fujimoto disease usually resolves on its own without specific treatment in about 1 to 6 months. Even though there isn’t a direct cure, symptoms can be managed and made more bearable.
People with the illness typically receive support treatments to ease the discomfort. Medicines are given to lower fever and manage pain. However, in severe cases, doctors consider prescribing corticosteroids, a type of anti-inflammatory medication, but only once they’ve ruled out the possibility of an infection. Other treatments that have worked before include medications like hydroxychloroquine or minocycline, and an intervention called intravenous immunoglobulin.
Kikuchi-Fujimoto disease usually only occurs once in adults, with a return of the disease seen in just about 3 to 4% of cases. But in children, the disease may reappear more frequently, with some studies noting a 31 to 39% rate of recurrence.
People with Kikuchi-Fujimoto disease need ongoing monitoring to check for improvement in symptoms and to screen for the potential development of autoimmune diseases, especially systemic lupus erythematosus (SLE, a chronic autoimmune disease that causes the body’s immune system to attack its own cells), once the symptoms of Kikuchi-Fujimoto disease have subsided.
For folks who have both Kikuchi-Fujimoto disease and other autoimmune diseases, such as SLE, it’s important to ensure the other autoimmune disease is also treated. This might involve using medications like corticosteroids and hydroxychloroquine.
Regular check-ups with the primary care doctor and a specialist in autoimmune diseases, called a rheumatologist, are crucial. They monitor for any potential return of Kikuchi-Fujimoto disease and manage any existing autoimmune conditions properly.
What else can Kikuchi-Fujimoto Disease be?
When diagnosing Kikuchi-Fujimoto disease, medical professionals will consider ruling out several other conditions that might produce similar symptoms. These can include:
- Infectious lymphadenitis (infection of the lymph nodes)
- Autoimmune diseases such as lupus (SLE)
- Cancers, especially lymphoma
- Other benign causes of swollen lymph nodes in children, such as ear and throat infections
- Infections like tuberculosis, leprosy, histoplasmosis, cat-scratch disease, and syphilis
- Common bacterial infections caused by things like Staphylococcus aureus or Streptococcus pyogenes
To distinguish Kikuchi-Fujimoto disease from these other causes, a doctor might send samples for culture and staining, as well as examine the patient’s medical history and physical symptoms. Importantly, Kikuchi-Fujimoto disease often results in negative cultures and a lack of certain cells in samples, suggesting a non-infectious cause. If the doctor suspects an autoimmune cause, they will consider diseases like lupus, sarcoidosis, or Kawasaki disease, all of which can present similar symptoms but have unique distinguishing factors.
Lupus and Kikuchi-Fujimoto disease can look quite similar, but lupus often has specific markers in blood tests that aren’t seen in patients with Kikuchi-Fujimoto disease. Sarcoidosis usually causes a specific type of lumps in tissue and can be identified by changes in certain blood tests and X-rays. Kawasaki disease is another consideration in children and is distinguished by specific symptoms such as red eyes,rash, and inflammation in the mouth.
In rare cases, Kikuchi-Fujimoto disease might occur alongside other autoimmune conditions. It has been observed in combination with conditions like Sjögren syndrome, relapsing polychondritis, Still’s disease, and mixed connective tissue disease. Therefore, if symptoms do not align with the typical presentation of Kikuchi-Fujimoto disease, testing for other autoimmune conditions might be recommended.
Lymphoma, a cancer of the lymph nodes, is a significant consideration when diagnosing Kikuchi-Fujimoto disease. Thorough testing and examination of patient samples can help rule out this malignant cause. Unlike lymphoma, Kikuchi-Fujimoto disease does not typically show certain cells and markers in test results.
What to expect with Kikuchi-Fujimoto Disease
Kikuchi-Fujimoto disease is usually a harmless and temporary inflammation that gets better on its own within a few months, without needing any particular treatment. There is a small chance of the disease coming back – this happens in roughly 3% to 4% of adults.
If the disease does return, doctors may use treatments like corticosteroids, which are medications that reduce inflammation; intravenous immunoglobulins, a treatment that helps strengthen the immune system; or hydroxychloroquine, a medication often used to treat conditions involving the immune system.
Unfortunately, it’s hard to predict if someone will experience a relapse. Some research suggests that relapses may be linked to a high count of a type of white blood cell known as lymphocytes, even if the total number of white blood cells is low. For children, the chance of having a relapse seems to be higher, potentially as much as 38.5%.
Another study found that removing a lymph node (a small structure, part of the immune system) for testing can have benefits for both diagnosis and treatment, with a lot of patients getting better very quickly after the procedure.
Despite some initial difficulties with diagnosis, the outlook for Kikuchi-Fujimoto disease is generally good. In rare cases, some scientists have observed the development of Systemic Lupus Erythematosus (SLE – an autoimmune disease where the immune system attacks healthy tissues) months or years after a diagnosis. They believe that this might be due to the immune system’s response to cleaning up cell debris after the inflammatory response to Kikuchi-Fujimoto disease. However, this happens very rarely and was reported in only a few cases; nevertheless, doctors suggest regular follow-ups with a primary care provider and a rheumatologist to watch out for this disease coming back, and to ensure the best possible health outcomes.
Possible Complications When Diagnosed with Kikuchi-Fujimoto Disease
In very rare circumstances, the immune system stress caused by a disease known as Kikuchi-Fujimoto can potentially activate a severe immune response called HLH. This reaction is characterized by the rapid increase of certain immune cells, systemic inflammation, and abnormal clotting throughout the body. HLH is a serious condition and can be life-threatening, with fatality rates ranging between 20% and 42%. HLH is typically managed by using treatments such as intravenous immunoglobulin and methylprednisolone to restrain the immune response. Children diagnosed with HLH usually have better results compared to adults.
Key Points to Remember:
- HLH is a severe immune reaction that can potentially be triggered by Kikuchi-Fujimoto disease.
- HLH is marked by the rapid increase of specific immune cells, body-wide inflammation, and abnormal clotting.
- The condition is life-threatening with fatality rates between 20% to 42%.
- Treatment often involves using intravenous immunoglobulin and methylprednisolone to control the immune response.
- Kids diagnosed with HLH usually have better outcomes compared to adults.
Preventing Kikuchi-Fujimoto Disease
It’s vital for patients and their families to understand Kikuchi-Fujimoto disease, especially as it’s quite rare. One comforting fact is that Kikuchi-Fujimoto disease is typically a condition that gets better on its own. This reassurance can be particularly useful in the early stages of diagnosis, when more serious conditions like cancer and infections may be ruled out.
However, it’s important to be aware that this disease can potentially lead to complications and be linked to autoimmune diseases, which are conditions where the body’s immune system mistakenly attacks normal cells.
Patients and their caregivers should be taught about the treatment strategy, which mainly focuses on easing symptoms using pain relievers and fever reducers. It’s also very important to highlight that antibiotics, which are used to treat infections, are not appropriate for treating this disease. Regular check-ups for monitoring symptoms and checking if the condition has resolved are extremely crucial. Patients need to know the importance of regular communication with their general doctor or rheumatologist – a specialist in arthritis and other diseases affecting joints – for long-term health monitoring.
