What is Kawasaki Disease?
Kawasaki disease, also known as mucocutaneous lymph node syndrome, is a short-lived condition that causes inflammation of medium-sized blood vessels and often affects the heart’s coronary arteries. It’s the main source of heart disease acquired after birth in developed countries, and it is gradually overtaking rheumatic heart disease as a cause of heart issues in developing countries.
What Causes Kawasaki Disease?
Doctors aren’t exactly sure what causes Kawasaki disease. Some think it might be due to a type of germ that moves through the wind or water. However, recent studies have found that certain genetic markers can make someone more likely to get Kawasaki disease. Examples of these genetic markers include certain types of HLA-B genes, chemokine receptor genes, and FCGR3A gene which affects the behavior of a part of your immune system called the IgG receptor IIIa.
What’s interesting is that brothers and sisters of someone with Kawasaki disease are 10-20 times more likely to get it themselves compared to the rest of the people. But, there’s no proof that Kawasaki disease can spread directly from one person to another.
Multiple germs, both bacterial and viral, have been thought to possibly cause Kawasaki disease, yet we haven’t singled out one specific germ that is the main cause. Yet, it’s important to note that over 40% of children diagnosed with Kawasaki disease were found to have germs that cause respiratory illnesses.
Risk Factors and Frequency for Kawasaki Disease
Kawasaki disease mainly affects children under five years old, but it can also happen in adults. It is more common in boys, who also have a higher risk of complications and death from the disease. Very young babies under 4 months rarely get it, possibly because they are protected by their mother’s antibodies. Children of Asian descent, especially Japanese, are more likely to get Kawasaki disease than Caucasian children. There are also more cases in the colder spring and winter months.
- Kawasaki disease is most common in children under five but can occur in adults.
- Boys are more affected by the disease and also suffer more from complications and death.
- The disease is rare in babies less than 4 months old, suggesting that they may be protected by their mother’s antibodies.
- Children of Asian descent, particularly Japanese, are more likely to get Kawasaki disease than Caucasian children.
- The disease is more common in the colder winter and spring months.
- In the U.S. and Canada, it affects 10 to 20 out of every 100,000 children under five, compared to 50 to 250 out of 100,000 in Japan, Taiwan, or Korea.
Signs and Symptoms of Kawasaki Disease
Kawasaki disease in children often begins with multiple days of fever and a general feeling of illness. During a physical exam, doctors look for certain diagnostic criteria that may have appeared at any point during the illness, even if the symptoms aren’t present during the exam. It’s crucial to get a full medical history because all symptoms count towards the diagnosis of Kawasaki disease.
The disease generally goes through three stages:
- The acute phase: This starts suddenly with a high fever that lasts one to two weeks and can stretch to three to four weeks if not treated. Skin rashes, eye infection (conjunctivitis), and heart muscle inflammation (myocarditis) usually occur during this phase.
- The subacute phase: This starts when the fever eases and typically lasts up to the sixth week of the disease. Symptoms may include peeling skin on the hands, an excess of platelets in the blood (thrombocytosis), and swelling in the coronary arteries (aneurysms).
- The convalescent phase: This is when the noticeable signs of the disease stop, typically by three months after the disease starts. Although the signs of the disease have ceased, abnormalities in the heart can still be detected.
Less common symptoms of Kawasaki disease may include stomach pain, vomiting, diarrhea, liver inflammation (hepatitis), inflammation of the salivary glands (parotitis), telescoping of the intestines (intussusception), joint pain (especially in the larger, weight-bearing joints), seizures, inflammation of the tissues that surround the brain and spinal cord (aseptic meningitis), a runny nose and cough, and inflammation of the testes (orchitis) or inflammation of the urethra (urethritis).
In 2014, the American Heart Association published the criteria needed for a diagnosis:
- The patient must have fevers for five or more days, plus at least four of the following criteria (which can occur all at once or over a series of days)
- Bilateral painless bulbar conjunctival injection without exudate
- Erythematous mouth and pharynx, strawberry tongue or red, cracked lips
- Polymorphous exanthem (morbilliform, maculopapular, or scarlatiniform)
- Swelling of hands and feet with erythema of the palms and soles
- Cervical lymphadenopathy (over 1.5 cm in diameter)
Usually, patients will have a spotted general reddish rash over the trunk and extremities within 5 days of the fever, similar to a viral rash or drug reaction, but without itchiness. Another common sign is skin peeling near the fingernails, starting about 2 to 3 weeks after the fever begins. Changes in the nails, typically horizontal grooves (Beau’s lines), appear about five to eight days after the fever and can last for two to four weeks. These changes are seen in over 75% of patients with the disease.
Testing for Kawasaki Disease
Kawasaki disease can be challenging to diagnose because its symptoms often appear one after the other, rather than all at once. However, doctors can use the criteria “Warm CREAM” or “FEBRILE” to help determine if a child has this disease.
The core sign is a persistent fever, often higher than 38.5 degrees Celsius, that doesn’t respond well to fever-reducing medications. Eye redness and sensitivity to light is also common, often connected with inflammation within the eye in about 65% of patients.
“Warm CREAM” stands for Fever (warm) lasting over 5 days, Conjunctivitis (redness of the eyes), Rash, Edema or redness of hands or feet, Adenopathy (swollen glands), and Mucosal redness, fissures, or crusting of the lips or a strawberry tongue.
“FEBRILE” stands for Fever lasting over 5 days, Enanthem (rash inside the mouth), Bulbar conjunctivitis (redness in the white part of the eye), Rash, Internal organ involvement, changes in the Extremity, and an unusually Low count of red blood cells in the body.
In some cases, children may have only two or three of the major symptoms associated with Kawasaki disease. This is known as incomplete Kawasaki disease, which is often seen in younger infants and older children. If an infant younger than six months has a continuous fever for more than a week, an echocardiogram (an ultrasound of the heart) can rule out the condition.
In the case of incomplete Kawasaki disease, doctors may conduct laboratory tests and an echocardiogram according to the guidelines created by the American Heart Association. This includes checking for a C-reactive protein (an indicator of inflammation) level less than 30mg/l and an erythrocyte sedimentation rate (ESR, which shows how quickly red blood cells settle in a tube of blood and may indicate inflammatory activity) less than 40 mm/hr.
Other useful tests may include a complete blood count, ESR, metabolic panel, urinalysis, and C-reactive protein. Anaemia (a low number of red blood cells) is a typical sign in the early stages of Kawasaki disease, while high platelet counts occur in the subacute phase. Low albumin levels, a type of protein in your blood, could also be a sign of a severe and long-lasting Kawasaki disease.
Your doctor may also opt to use other imaging techniques like an echocardiogram to check for coronary artery aneurysm in the heart, computed tomography angiography or magnetic resonance angiography depending on the severity of the case.
Finally, while not a part of the criteria used to diagnose Kawasaki disease, some children may also experience gastrointestinal symptoms, liver congestion leading to elevated liver enzymes, and gallbladder issues.
Remember, even if your child meets the criteria, they might not have Kawasaki disease. Similarly, children who don’t meet all the criteria might still have the disease. Therefore, it’s crucial to seek medical advice if your child has a fever that lasts more than five days or has any other symptoms associated with Kawasaki disease.
Treatment Options for Kawasaki Disease
The primary goal when treating Kawasaki disease is to reduce the chances of forming coronary artery aneurysms (CAA), which are abnormal bulges in the heart’s arteries. This risk peaks two to four weeks after the onset of the disease. It is achieved by reducing inflammation in the coronary arteries. Providing supportive care to the patient is also an essential part of the treatment.
One of the main treatments for Kawasaki disease is high-dose IVIG (a type of medication given via an IV). It is generally given in conjunction with high-dose aspirin until the patient doesn’t have a fever for over 48 hours. After that, the aspirin dosage is decreased and continues until there are no signs of heart-related changes, usually about six to eight weeks after the disease’s onset. The idea here is that aspirin helps regulate the activity of blood cells known as platelets and reduces inflammation, helping prevent blood clot formation. However, it’s important to note that there’s no concrete proof that aspirin actually prevents the CAA development.
While taking aspirin, patients should receive a flu vaccine and avoid the varicella (chickenpox) vaccine, as there’s an increased risk of developing a rare condition called Reye’s syndrome when developing the flu or varicella infections. If the patient is allergic to aspirin or has contracted influenza or varicella and needs to prevent Reye syndrome, alternative medicines like clopidogrel or dipyridamole can be used.
If the patient still has a fever 36 to 48 hours after the first IVIG dose, the dose can be repeated. Ideally, the IVIG treatment should start within the first week to ten days after the fever starts to avoid potential heart complications. This treatment can reduce the risk of forming a CAA from 25% to 3-5%. But keep in mind, this treatment may not work for everyone; about 15-20% of patients still have a persistent fever after getting the medication and need a second dose.
In addition to IVIG and aspirin, doctors may also consider using corticosteroids. Some studies suggest that corticosteroids may help reduce the chances of developing heart abnormalities, the duration of fever, hospital stay, and faster normalization of inflammation markers. In some cases, where the disease does not respond to initial IVIG therapy, corticosteroids could be beneficial.
Some have suggested using statins due to their immunomodulating properties. However, more research is needed in this area before it becomes a standard treatment. Similarly, angiotensin receptor blockers (ARBs) have also been found to prevent artery narrowing once a CAA is detected.
Patients who end up with severe blood flow problems because of an aneurysm may need bypass surgery. This operation is especially important to consider for children who have reversible ischemia (restricted blood flow that could lead to damage) or in cases of recurrent heart attacks.
After the acute phase of the disease (usually five to six weeks after fever onset), the focus shifts to long-term management. During this period, doctors will monitor the patient closely, and treatment plans will vary based on individual disease severity. It’s worth noting that more than half of the patients have seen a complete resolution of their coronary artery issues one to two years from the onset of the disease, especially when the initial lesions were not very large.
What else can Kawasaki Disease be?
Kawasaki Disease can sometimes present symptoms similar to a variety of other infections, making it tricky to diagnose without a test. Some conditions that might be mistaken for Kawasaki Disease include:
- Cellulitis (skin infection)
- Tonsil abscess
- Retropharyngeal Abscess (throat abscess)
- Cervical lymphadenitis (lymph node inflammation)
- Strep throat
- Various viral infections (adenovirus, enterovirus, parvovirus B19)
- Measles
- Mononucleosis (caused by Epstein-Barr virus)
- Scarlet Fever
- Rheumatic fever
- Toxic Shock Syndrome
- Meningitis
- Rocky Mountain Spotted Fever
- Staphylococcal scalded skin syndrome (SSSS)
- Toxic epidermal necrolysis (TEN, a serious skin disorder)
- Lyme disease
- Leptospirosis (a bacterial infection)
Common symptoms like redness and swelling in the eyes can occur in both Kawasaki Disease and adenovirus infection, but only adenovirus leads to eye discharge. Likewise, while both disorders can lead to swollen lymph nodes, this symptom typically appears on just one side in Kawasaki Disease cases.
Kawasaki Disease can also look a lot like illnesses that cause immune reactions, such as juvenile arthritis, multiple drug sensitivity, and lupus. However, these can typically be ruled out by checking for the specific symptoms of Kawasaki Disease and considering the length of the illness and the number of joints affected.
What to expect with Kawasaki Disease
The outlook for Kawasaki Disease largely depends on how severe the heart problems are. Children who are diagnosed between the ages of 6 months and 9 years generally have a better prognosis, possibly because the disease is caught earlier due to typical symptoms. Recurrence of the disease is rare but if it does happen, it’s more likely in younger children who had heart complications during their first bout of the disease.
All deaths related to Kawasaki Disease are basically due to heart complications, and they usually happen between 15 to 45 days from when the fever started.
Possible Complications When Diagnosed with Kawasaki Disease
The disease can lead to serious heart problems like aneurysms, heart failure, heart attacks, heart muscle inflammation, valve inflammation, fluid in the covering of the heart, and the rupture of the heart’s major arteries. This could even result in sudden death. Around 9% of patients may experience heart-related complications during the acute stage of the disease, while about 3% may experience heart-related effects later on.
Patients often suffer heart attacks during sleep or at rest, hinting at a cause related to spasms in the heart’s arteries. Inflammatory effects on the heart muscle are observed in 50 to 70% of patients during the disease’s acute phase, raising concerns about the long-term effects that the disease has on heart function. Conditions like heart valve leakages have been recorded in a small number of children affected.
About 15-25% of untreated children may develop Coronary Artery Aneurysms (CAAs). Factors that increase the risk of these heart aneurysms include:
- Fever for more than 8 days (most significant risk factor)
- A setback of fever after a period of 48 hours without it
- Boys (3 times more likely to develop large aneurysms)
- Enlarged heart in less than 1-year-old patients
- Asian or Pacific Islander descent, or Hispanic ethnicity
- Lower levels of a type of antibody (IgG) in the blood
- Increased levels of certain types of proteins in the blood
- Low platelet count at initial presentation
- An incomplete diagnosis of the disease
In the case of children, aneurysms are classified as blood vessels having a diameter of more than 3mm for children under five years, and more than 4mm for children older than five years. Heart complications in adults are more familiar in patients who had a CAA of more than 6.0mm in diameter. Giant aneurysms, larger than 8.0mm, are likely to get clogged by blood clots within the first year of development, thus causing a heart attack.
Even when aneurysms are resolved, there may still be significant thickening of the blood vessel, which increases the risk of early onset of heart disease due to cholesterol deposits (atherosclerosis). A study conducted on adults who had suffered a heart attack later in life, after having had a heart aneurysm in childhood due to the disease, showed no evidence of a remaining aneurysm. Yet, the resolution of an aneurysm does not necessarily mean that the risk of heart complications later in life also disappears.