Kawasaki Disease

Kawasaki disease is a very serious disease that can mimic many infections.

Kawasaki disease (KD) is a pediatric inflammatory systemic illness, with previously healthy children ranging from 6 months to 5 years of age most likely to be diagnosed. The signs and symptoms of Kawasaki disease include

• fever (often > 102 F) for 5 days,
• characteristic skin changes of the hands and feet,
• redness without discharge of the eyes,
• abdominal organ involvement (for example, gallbladder, liver, and kidneys),
• generalized body rash, and
• non-tender enlargement of the lymph nodes of the neck.

The most concerning association of KD is the potential enlargement (aneurysms) of the blood vessels of the heart. While relatively rare, such changes may be associated with a myocardial infarction (heart attack). As such, Kawasaki disease is the most common cause of acquired pediatric heart disease in the developed world. (Rheumatic fever is the most common cause of acquired pediatric heart disease in the non-developed/underdeveloped world.)

Japanese pediatrician Tomisaku Kawasaki initially described Kawasaki disease (KD) in 1967 and initially gave it the descriptive name "mucocutaneous lymph node syndrome" (MCLNS). While it most commonly occurs in people of Asian descent, all ethnic and cultural populations have reported cases of KD.

The exact cause of Kawasaki disease remains a mystery. There exist a number of similarities between infectious viral agents (Epstein-Barr virus, adenovirus, herpesviruses, leptospirosis, etc.). Several bacteria (staph and strep) release toxins into the bloodstream, resulting in similar symptoms and physical findings as KD. Conditions such as toxic shock syndrome serve as an example. A number of investigators of Kawasaki disease believe that the above viruses and bacteria are not a direct cause for KD. Rather, in a genetically sensitive population, such viruses and bacteria stimulate the patient's immune system to become "supercharged" and trigger an immunological final common pathway that ultimately results in injury to the medium-sized arteries of certain organs.

Early in 2020, doctors noted that another at-risk population for a condition mimicking Kawasaki disease are children recovering from COVID-19 infection. Most patients seem to have an onset of these symptoms 2-3 weeks following the start of COVID-19 symptoms. At the time this article is being composed, there remains only an association (not a direct causation) between the COVID-19 virus (SARS-CoV-2) and a constellation of symptoms and physical changes noted in KD. Doctors call this condition "MIS-C" (multisystem inflammatory syndrome in children). There have been about 200 cases internationally with the largest number in the New York City area. This would be reasonable given that this same region has the largest COVID-19 patient population.

Kawasaki disease is the result of an acute inflammatory process of medium-size blood vessels (vasculitis) that affects multiple organs in otherwise healthy children. Most children will be diagnosed with the typical form of KD. A smaller percentage are termed atypical or incomplete and as such are often more challenging to diagnose correctly. The diagnosis of typical Kawasaki disease is based upon the criteria below.

The child must have a persisting fever (generally >102 F) for at least 5 days' duration (with exclusion of other causes of fever) and at least four of the following five clinical features:

1. Bilateral non-purulent conjunctival injection (red eyes without discharge)
2. Changes in the lips and oral cavity (red and cracked lips, strawberry tongue) generally without enlargement of the tonsils or a purulent discharge on the tonsils
3. Rash: non-petechial and non-blistering (Petechia represent the rupture of tiny skin capillaries and appear as 1 mm flat dots that are not affected when rubbed.)
4. Changes in the extremities (tenderness and swelling of the hands or feet, red hands or feet, and peeling of the skin of the palms or soles)
5. Cervical lymphadenopathy (large lymph nodes of the neck, often one-sided): Lymph node size is often >1.5 cm and non-tender to the touch.
6. Fewer of the above findings but with evidence of coronary aneurysms or coronary enlargement observed on echocardiogram

A child with typical Kawasaki disease will have the sudden onset of moderate fever (generally over 102 F) that has no apparent source. Without therapy (see below), the fever typically will last for 11-12 days and rarely last up to 3 weeks. The child becomes irritable and generally appears ill. In addition to the fever, the above symptoms and signs may develop in any order and duration. Doctors can make a diagnosis when a patient meets the above criteria and there is no other explanation for the symptoms and signs, such as strep throat or an acute drug reaction. Other physical findings may be present and support the diagnosis:

1. Sore muscles and joints
2. Abdominal pain with or without vomiting or diarrhea
3. Liver or gall bladder abnormalities
4. Abnormal lung function
5. Meningitis
6. Hearing loss
7. Kidney/bladder dysfunction
8. Testicular swelling and discomfort

The untreated presentation of a case of typical Kawasaki disease can be divided into three phases:

1. an acute early phase (fever and other major symptoms noted above) lasting from 5-10 days;
2. a subacute phase (development of coronary artery aneurysms) from day 11-30; and
3. a convalescent phase (resolution of acute symptoms) lasts from 4-6 weeks. For untreated patients, up to 25% develop coronary artery aneurysms that place a child at risk for a heart attack (acute myocardial infarction). This threat may occur from months to years after the diagnosis of Kawasaki disease.

It's possible to mistake the clinical features of Kawasaki disease for other illnesses such as streptococcal or staphylococcal infections (scarlet fever or toxic shock syndrome), parasitic or viral infections (leptospirosis, measles, or adenovirus), and drug reactions (Stevens-Johnson syndrome). Acute mercury poisoning (acrodynia) has many signs and symptoms of Kawasaki disease. Whether COVID-19 infection is merely mimicking KD or is a causative agent remains to be determined.

Some patients, especially toddlers or older patients, may develop atypical or incomplete Kawasaki disease. Such a child will experience the persisting and prolonged fever but will not have the minimum of four characteristic clinical features described above. Diagnosis in these situations is much more difficult. Patients with atypical Kawasaki disease are actually more likely to develop coronary artery disease.

While an office visit may not always be indicated, pediatricians and associated health care professionals prefer to be aware of any significant fever in your child. If he/she has a fever that lasts longer than a few days, it is extremely important to consult with your child's doctor. The fever associated with Kawasaki disease is generally 102 F or higher. Your doctor will probably want to evaluate your child to identify the source of the fever. If your child has fever and develops any of the common signs and symptoms of Kawasaki disease listed above, it is important to discuss this with your doctor immediately. Obviously, if your child appears dehydrated and is not passing urine normally, is having a difficult time breathing, or seems to be out of it, he/she needs to be evaluated right away.

There are no unique or specific tests for Kawasaki disease. There are, however, a number of blood, urine, and spinal fluid tests that support the clinical diagnosis and eliminate other conditions with similar physical symptoms. These tests include throat cultures, urine cultures, and blood counts. All children with possible Kawasaki disease should have an electrocardiogram (ECG) and echocardiogram (ECHO) to evaluate the child's coronary arteries.

Once the diagnosis or Kawasaki disease is confirmed, it is imperative to initiate treatment within the first 7 days of the onset of fever. This is due to the fact that the damage to the coronary arteries usually occurs after the 10th day of illness during the subacute phase of the disease. The current recommended therapy includes admission to the hospital and administration of intravenous immunoglobulin (IVIG or gamma globulin) and high-dose aspirin until the child's fever resolves. Approximately 15% of those with KD will have recurrent or persisting fever following the first dose of immunoglobulin. Most specialists will repeat a dose of immunoglobulin in such circumstances. Doctors administer high-dose oral aspirin therapy until the patient has not had a fever for 48 hours. However, some specialists prefer to continue high-dose aspirin for a total of 2 weeks. Following high-dose aspirin, a doctor will switch their patient to a low-dose regimen until the patient's 6-week follow-up visit with a cardiologist. If the echocardiogram demonstrates no aneurysms, the patient can stop taking the medication. Should aneurysms exist, then a patient would continue with low-dose aspirin.

Due to the association with Reye syndrome (a potentially fatal condition affecting the brain and liver) in children and adolescents taking aspirin while recovering from influenza and varicella (chickenpox), it is imperative that vaccinations to these conditions be up to date.

Kawasaki disease is the most common cause of acquired heart disease in children in the developed world. When diagnosed and treated early with gamma globulin, the incidence of coronary artery lesions decreases from 20% to 3%. It is very uncommon for patients who have no evidence of coronary abnormalities at 2-3 months after the acute illness to develop coronary abnormalities. Patients with larger coronary lesions have the greatest risk, and it has been shown that patients with giant aneurysms (>8mm) have a highest risk of developing future heart attacks (myocardial infarctions). The long-term risk of patients with small aneurysms is currently unknown. Establishment and adherence to a heart healthy diet, daily physical exercise, control of blood pressure, and avoiding obesity and smoking are goals for all but especially those with potential risk factors for cardiovascular disease.