Kawasaki disease is a rare disease that mainly affects children under five years of age. It is also known as mucocutaneous-lymph node syndrome because it involves the glands in the neck (lymph nodes), the skin and mucous membranes inside the mouth, nose and throat.
In addition to causing an increase in body temperature (fever) that lasts more than five days, the disorders (symptoms) that can distinguish it are:
- spots and bumps on the skin (rash)
- swelling of the glands in the neck (lymph nodes)
- dry and chapped lips
- redness of the toes and hands
- Red eyes
The symptoms (symptoms) tend to subside within a few weeks: in this phase, the sick child may have a characteristic peeling of the skin of the hands and feet.
If the disease is ascertained and treated as soon as it appears (promptly), it will heal completely within six to eight weeks in most cases. It is believed to be caused by an infection, although the exact cause is not yet fully understood.
If a child develops disorders that make one suspect the presence of the disease, it is advisable to consult the treating pediatrician as soon as possible. Kawasaki disease, in fact, requires hospitalization as it can cause serious complications: the sooner the patient begins treatment (possibly within 10 days of the onset of the first ailments), the faster the recovery and the lower the risk of complications.
The two main drugs used to treat Kawasaki disease are immunoglobulins (a solution of antibodies) to be administered intravenously (IVIG) and acetylsalicylic acid (aspirin).
Kawasaki disease causes inflammation and a build-up of fluid which, in turn, causes blood vessels to dilate (edema) with possible changes in the coronary arteries (blood vessels that carry blood to the heart). In 5% of children, this causes heart problems. Complications can be fatal in about 1% of cases.
Kawasaki disease is more common in Asian populations, particularly in Japan. The number of new cases per year (annual incidence) per 100,000 children under the age of five is 8.1 in Great Britain, 17.1 in the United States and 112 in Japan.
In addition, it has also been shown that the onset of the disease is 1.5 times more common in males than in females.
The disorders (symptoms) caused by Kawasaki disease develop in three stages over a period of six weeks.
Phase 1. Acute (1-2 weeks). Disorders (symptoms) appear suddenly and can be severe. They include:
- high temperature (38 ° C or higher), which is the first and most common symptom of Kawasaki disease and, at times, can manifest itself with some characteristics:
- not responding to antibiotics or drugs such as ibuprofen or acetaminophen, generally used to reduce fever
- be present for at least five days and, without adequate treatment, last up to 11 days. In some rare cases, it can last up to three to four weeks
- have a fluctuating trend, with moments in which it is present and others in which it is absent. It can reach a maximum of 40 ° C
- rash (red spots on the skin), usually starts in the genital area and then spreads to the chest, arms, legs and face.The red spots appear protruding and hard (in the absence of blisters).
The skin on the fingers or toes can become red and hard, and the hands and feet can swell (edema). The persistence of redness in the extremities and, above all, edema can cause pain to the touch that makes children reluctant to walk or crawl
- bilateral conjunctivitis without purulent discharge, both eyes turn red and swell in the absence of pain. Unlike normal conjunctivitis which causes inflammation of the thin layer of cells that covers the white part of the eye (conjunctiva), there is no leakage of fluid (purulent discharge)
- silky dyslipidemia, due to an increase in good cholesterol (HDL) levels. It acts as a cardiovascular risk factor and appears to positively correlate with the presence of coronary artery aneurysm
- other symptoms, the lips may become red, dry or chapped, swollen and bleeding. The inside of the mouth and throat may be inflamed. The tongue may appear red, swollen and covered with small lumps, also known as strawberry tongue. The lymph glands (lymph nodes) on either side of the neck can swell. Lymph nodes are part of the body's defense system against infection (immune system) and, in Kawasaki disease, can reach more than 1.5 centimeters in width causing pain
Phase 2. Sub-acute (2-4 weeks). The fever subsides, but the child is irritable and in pain. Disorders (symptoms) become less severe but longer lasting and include:
- peeling of the skin on the fingers and toes which, at times, can also manifest itself on the palms of the hands or on the soles of the feet
- abdominal pain
- He retched
- urine containing pus (a more or less dense material characterized by the presence of numerous cells, leukocytes, fragments of dead tissues and bacteria)
- feeling sleepy and lack of energy (lethargic state)
- joint pain and swelling
- yellowing of the skin and the whites of the eyes (jaundice)
- thrombocytosis (increase in the number of platelets due to a defect in the death of these cells)
Some complications are more likely to occur during the second stage of Kawasaki disease.
Phase 3. Convalescence (weeks 4-6). Disorders (symptoms) begin to improve and all signs of the disease tend to disappear. However, the child may still experience a lack of energy and fatigue (asthenia).
Cardiac complications rarely occur at this stage.
The disorders (symptoms) of Kawasaki disease are similar to those of an "infection but, so far, neither bacteria nor viruses have been identified that could be responsible for it. Furthermore, since the disease is not contagious it is unlikely that it can be caused by an agent. infectious.
Kawasaki disease usually does not affect infants under six months of age, possibly because they are protected by antibodies (proteins that destroy microorganisms that cause infections) passed on to them by their mother both before birth and during breastfeeding.
Children who develop Kawasaki disease may be genetically predisposed. This means that the genes inherited from their parents can put them at risk of getting sick. It has been hypothesized that Kawasaki disease may be the result of the action of many genes and not just one. It is common in children from Northeast Asia, especially Japan and Korea (this aspect supports the hypothesis of the genetic cause).
Another theory assumes that Kawasaki's disease may be of the autoimmune type, that is, caused by the body's defense system which, mistakenly, attacks healthy tissues.
Other theories suggest that it may result from the reaction to some drugs or environmental pollutants.
In conclusion, the cause of Kawasaki disease still remains unknown, even if several factors have been hypothesized that could determine its occurrence: infectious agents, alterations in the function of the immune system, genetic alterations and toxic agents. It has also been assumed that some of them may intervene simultaneously (multifactorial disease).
There is no specific test to ascertain (diagnose) Kawasaki disease. The attending physician confirms the presence of the disease based on the complaints he observes and a thorough medical examination.
A child can be said to have Kawasaki disease if their body temperature is 38 ° C or higher for more than five days (fever) and at least four "key" disorders (symptoms) are present:
- conjunctivitis in both eyes (bilateral) without purulent discharge: red and swollen eyes
- changes in the mouth or throat: dry and chapped lips or red and swollen tongue
- alterations in correspondence of hands / feet (extremities): swollen and painful hands / feet or red skin or peeling of the palms or soles of the feet
- spots and bumps on the skin (rash)
- swelling of the lymph nodes in the neck
The attending physician, to confirm that the observed disorders are caused by Kawasaki disease, will have to perform some tests to exclude the presence of other diseases characterized by similar disorders such as, for example:
- scarlet fever: a "bacterial infection that causes typical pink or red spots on the skin (skin rash)
- toxic shock syndrome: a rare life-threatening bacterial infection
- measles: a highly contagious viral disease that causes fever and red-brown patches on the skin
- mononucleosis: a viral infection that can cause fever and swelling of the lymph nodes
- Stevens-Johnson syndrome: a very serious allergic reaction to drugs
- viral meningitis: an "infection of the protective membranes surrounding the brain (meninges) and spinal cord
- lupus erythematosus: an autoimmune disease that can cause a variety of disorders (symptoms) including tiredness, joint pain and a rash
Several tests, carried out during the first 7-10 days after the onset of the disorders, contribute to the assessment (diagnosis) of Kawasaki disease:
- urine analysis (to evaluate for the presence of white blood cells)
- blood analysis (to check the number of white blood cells or platelets)
- lumbar puncture (taking a CSF sample through a needle inserted between the vertebrae of the lower spine)
While not conclusive when assessed individually, combined with some of the major ailments caused by the disease, these tests can help confirm the diagnosis.
Since Kawasaki disease can cause heart complications, the affected child will need to undergo some investigations:
- electrocardiogram (ECG), test that measures the electrical activity of the heart using electrodes applied to the arms, legs and chest
- echocardiogram, an analysis that uses high-frequency sound waves to produce images of the heart that the doctor can see on a screen
- computed tomography or magnetic resonance cardiovascular angiography, advanced "cardiovascular imaging" techniques that allow you to "identify central or peripheral aneurysmal dilations in the vascular system
During the acute phase of Kawasaki disease (weeks 1-2), several cardiac abnormalities can be identified such as:
- rapid heart rate (tachycardia)
- spillage of fluid into the membrane that lines the heart (pericardial effusion)
- inflammation of the heart muscle (myocarditis)
Most cases resolve six to eight weeks after the initial onset, although further complications may arise in some children.
Kawasaki disease should be treated in the hospital as soon as possible to avoid serious complications.
The main treatments (therapies) are: acetylsalicylic acid and / or intravenous immunoglobulins.
It is a drug that, exceptionally, can be administered to children with Kawasaki syndrome. In fact, acetylsalicylic acid is not normally used in children because it can cause side effects. It is a non-steroidal anti-inflammatory drug (NSAID). It is used to treat Kawasaki disease because:
- it can relieve pain and discomfort
- can help reduce fever
- in high doses, acetylsalicylic acid is an anti-inflammatory, i.e. it reduces swelling
- in low doses, acetylsalicylic acid is an antiplatelet agent and prevents the formation of blood clots
The dose of acetylsalicylic acid that your doctor prescribes depends on the symptoms (symptoms) present.
It is used because it helps prevent the development of heart complications by working as both an anti-inflammatory and an antiplatelet agent.
Intravenous immunoglobulin (IVIG)
The treatment consists in "injecting directly into the vein (intravenously) a solution of antibodies (immunoglobulins) taken from healthy donors. Antibodies are proteins produced by the body's defense system (immune system) to fight disease-carrying microorganisms.
Research has shown that IVIGs can reduce fever and the risk of heart disease. The immunoglobulins used to treat Kawasaki disease are gamma globulins.
In the child undergoing IVIG, the complaints (symptoms) improve within 36 hours; if the fever does not decrease after this period, a second dose of IVIG may be used.
They are steroidal anti-inflammatory drugs, made up of molecules similar to cortisol (a hormone produced by the adrenal glands).
They can be used when a second dose of IVIG is not effective, or they can be used as a first treatment when the sick child is at risk for heart complications.
They are monoclonal antibodies with an anti-inflammatory function. They can be used in patients who are unresponsive to standard therapy.
They are used in patients with bacterial infections.
Immediate treatment with appropriate medications allows for full recovery for most sufferers. However, complications affecting the heart can sometimes develop due to inflammation of the blood vessels.
The inflammation of the blood vessels that supply blood to the heart (coronary arteries) can cause the weakening of their wall. As a consequence, the pressure of the blood flowing inside them causes them to swell outwards: the aneurysm.
Some aneurysms heal on their own over time but sometimes a blood clot (thrombosis) can form in the weak artery wall which can cause:
- heart attack
- acute myocarditis with heart failure
In rare cases, rupture of the aneurysm can occur causing severe internal bleeding.
It is also possible that other important arteries such as the brachial artery (main blood vessel in the arm), or the femoral artery (main blood vessel in the thigh) are compromised.
Heart complications caused by Kawasaki disease are serious and can be fatal in 1% of cases. The risk of them occurring is reduced in children receiving intravenous immunoglobulin (IVIG).
Possible cures for complications include:
- anticoagulant and antiplatelet drugs (medicines that stop blood clotting, preventing a heart attack)
- coronary artery bypass grafting (surgery which consists of creating new channels for blood circulation from the aortic vein to the coronary arteries, to get around the obstructions)
- coronary angioplasty (procedure that serves to dilate the blocked or narrowed tract of the coronary arteries to improve blood flow to the heart; in some cases, a hollow metal tube called a "stent" is inserted into the blocked artery to maintain the dilation obtained)
Babies with severe complications may have permanent damage to their heart or heart valves (flaps that control blood flow). In the latter cases, patients will be subjected to regular checks with the cardiologist to carefully monitor their condition over time.
NHS. Kawasaki disease (English)
Marchesi A et al. Kawasaki disease: Guidelines of the Italian Society of Pediatrics, Part I - Definition, Epidemiology, Etiopathogenesis, Clinical Expression and Management of the Acute Phase. Italian Journal of Pediatrics, 2018; 44: 102
Marchesi et al. Kawasaki disease: Guidelines of the Italian Society of Pediatrics, Part II - Treatment of Resistant Forms and Cardiovascular Complications, Follow-up, Lifestyle and Prevention of Cardiovascular Risks. Italian Journal of Pediatrics, 2018; 44: 103