Kawasaki disease

In few words…

Kawasaki disease is a febrile systemic vasculitis that, if left untreated, becomes complicatedcoronary aneurysms in 25 to 30% of cases. It is the most common cause of acquired heart diseasein children in industrialized countries, and may pose a risk of ischemic heart disease in adults.It has been reported worldwide, but it is much more common in Asian populations,and especially in Japan. The incidence of the disease in children under the age of 5 is estimated at 8.1 / 100,000in the United Kingdom, 17.1 / 100,000 in the United States, and 112/100,000 in Japan. 

The table associates with a constant fevermucocutaneous signs (conjunctivitis, pharyngitis, raspberry tongue, cheilitis, polymorphic rash,scaling of the extremities) and cervical lymphadenopathy. Its pathogenesis is still unknown, and severaltheories have been proposed, including the possibility of infection by toxin-secreting microorganism and aprocess related to superantigens. 

Despite a lot of research, there is still no diagnostic testavailable, and its diagnosis is based on clinical criteria after exclusion of other diseases withhigh and persistent fever. Prompt diagnosis is essential because early administration of immunoglobulinsintravenously combined with acetylsalicylic acid decreases the frequency of coronary artery abnormalitiesless than 5%.


Kawasaki disease is an acute systemic febrile vasculitis in young children and infantswhich affects medium and small caliber vessels  . Its seriousness is linked to the fact that a percentage notnegligible untreated patients (25 to 30%) have cardiovascular sequelae, especiallycoronary aneurysms which can be fatal.


Kawasaki disease is the leading cause of acquired heart disease in childhood inindustrialized countries (in developing countries, the first cause remains rheumatismacute articular). It is the most frequent vasculitis in pediatrics, after rheumatoid purpura.

Although this disease has been reported worldwide, it is much more commonin Asian populations, especially in Japan. So, since its description by Tomisaku Kawasaki in 1967, more than 170,000 cases were diagnosed in Japan. The incidence of the diseasein children under 5 is estimated to be 8.1 / 100,000 in the UK 4 , 17.1 / 100,000 in the UK United States , and 112/100000 in Japan  . The majority (80%) of patients are less than 5 years old, with a peakincidence around 12 months of age. 

The disease is rare before the age of 3 months, probably due tothe existence of maternal antibodies during the first months, and it is also very rarein adolescents and adults. It is more common in boys, with a boy / boy ratio1.5 daughter. There is a seasonal frequency, and epidemics have been reported.

Clinical description

Kawasaki disease begins acutely with a prolonged unexplained fever greater than38 ° C, which persists for at least 5 days and does not respond to antipyretics or antibiotics. 

It lasts1 to 2 weeks in untreated patients, but usually resolves quickly, with administration oral acetylsalicylic acid and intravenous immunoglobulins.In addition to fever, there are 5 other criteria, the diagnosis of Kawa-saki which can be retained if the fever is associated with at least 4 of these 5 criteria.In most cases, the rash is polymorphic, non-specific, diffuse and maculopapu-laire . The headquarters is a characteristic location.

Conjunctivitis appears with fever; the involvement of the bulbar conjunctiva is more important therethan palpebral involvement, and there is no exudate. Slit lamp examination sometimes shows aanterior uveitis. Oropharyngeal involvement includes erythema of the lips, dryness, cracks andsometimes bleeding. 

The tongue is raspberry, with protruding taste buds and an enanthemum.Cervical lymphadenopathy is often anterior, with a diameter greater than 1.5 cm, withor without erythema.Attacks on the feet and hands involve erythema of the palms or soles as wellthan edema. In the subacute phase, periungual scaling and trans-versals of Beau.

It is characteristic, even if it is not part of the cri-diagnostic mothers, that children with the disease Kawasaki are extremely irritable and in poor conditiongeneral; this may be related to aseptic meningitis.Other clinical manifestations can be attributed toKawasaki disease, but are not included in the cri-classic mothers: arthritis and arthralgia, abdominal pain,alithiasic cholecystitis, abacterial urethritis.Cardiac complications occur in 25 to 30%untreated patients. 

The most important complication isrepresented by coronary aneurysms, which arise ha-usually between 10 and 30 days after the onset of the disease.There are ultrasound criteria that allow the diag-gnostic and surveillance. Patients who have had a disease ofKawasaki in pediatric age can be affected by arterialand / or early atherosclerosis and calcifications of the arteries coronaries in adulthood. 

It is also possible that some infar-of myocardium are linked to an ancient history of diseasefrom Kawasaki.We can distinguish 3 clinical phases of the disease:- the acute, feverish phase, lasting 1 to 2 weeks,characterized by fever and standard criteria ;

  1. the subacute phase, where fever, rash andcervical lymphadenopathy disappears while irritability andconjunctivitis may persist;
  2. the late phase, after disappearance of clinical signs, whichlasts until the normalization of the biological parameters of theflammation (sometimes up to more than 6 to 8 weeks after onsetdisease).


The diagnosis of Kawasaki disease is clinical because there is nono specific biological marker. Laboratory dataroof show non-specific inflammation. 

During the phaseacute, the number of platelets is normal and one can even sometimes note a thrombocytopenia; thisnumber increases significantly at the end of the second week. Urine can showpresence of leukocytes and red cells without bacteria. The cerebrospinal fluid may contain aincreased number of cellular elements. 

Interrogation and physical examination are essential forthe exclusion of other diseases that are included in the differential diagnosis, such as viral infectionsand bacterial or drug reactions . The absence of inflammatory syndrome(C-reactive protein, sedimentation rate), long-term fever or no fever,Presence of clinical atypia must call into question the diagnosis of Kawasaki disease.All patients with typical or suspected Kawasaki disease should beregular monitoring by electrocardiogram (ECG) and echocardiography. 

ECGmay reveal rhythm disturbances, signs of ventricular dysfunction and is-myocardial chemistries. In the acute phase, myocarditis and pericarditis can also be observed.Two-dimensional ultrasound is useful for detecting dilations and coronary aneurysms.

Aneurysms can also be visualized inperipheral arteries. In children with an-giant coronary vessels (of diameter greater than 8mm), a stress test can assess themyocardial function. Corona tomo-densitometryand magnetic resonance imaging aretechniques for the future from a diagnostic point of view, andbably also prognostic. In some cases, the an-Selective coronary geography may also be helpful.

Etiology and pathophysiology

The cause of Kawasaki disease is unknown. There ishas reason to believe, however, that infection andKawasaki disease are closely related. The argu-on the one hand, are based on epidemiology, accountheld seasonal peaks and epidemic forms ofthe disease, and, on the other hand, the fact that very often the resolution of the disease is spontaneous. 

Ageof appearance also pleads for an infectious cause, because there are few cases after infancy,which suggests that the infectious agent is immunizing.An immune mechanism is surely involved in the pathogenesis, in particular in the attackof the vascular endothelium. We thus note an activation of T lymphocytes and monocytes,high levels of cytokines such as interleukin 6 , as well as antibodies against endothelial cells. 

TheKawasaki disease, through its clinical and immunological manifestations, evokes pathologiesmediated by toxins; thus, the role of superantigens has been mentioned in its pathogenesis 11 . The su-perantigens bind directly to T cell receptors without HLA restriction. They interactin a limited way with the Vβ of the T cell receptor, leading to a possible bias in the repertoiresVβ2 and Vβ8. Finally, the superantigens cause a large T lymphocyte activation. 

However, itto date, there is no absolute proof of the responsibility of superantigens, and data frompublications on this point are contradictory. Recent studies have shown an oligoclo-immunoglobulin A in the vascular walls during the acute phase of the disease, suggestingalso a possible response mediated by conventional antigen. 12Among the offending infectious factors are also included Yersinia enterocolitica , coronaviruses, 13 theadenovirus, Epstein-Barr virus, and Herpes virus.


The evolution of Kawasaki disease is most often favorable in the absence of coro-nostril. Relapses are possible but rare. The dimensions of the coronary aneurysm seembe an important prognostic factor 14 , since a dilation greater than 4 mm makes it possible to predicta high probability of late thickening of the intima and the media . Regression of aneurysmsoccurs in 60% of cases within 2 years. 

The high-risk group for coronary artery disease is re-presented by infants less than 6 months of age and by patients whose fever lasts more than 2weeks. Among the long-term sequelae, recent data suggest a risk of arteriosclerosis.coronary pink in adulthood, as well as morphological abnormalities (thickening of the intima ) andfunctional (reduced contractility) of the coronary arteries.


Treatment should be as early as possible. It is based on the prescription of acetylsalicylic acid(50-80 mg / kg / day during the acute phase, then 3-5 mg / kg / day) and on the administration of immunoglobulins by intravenously (2 g / kg in a single dose) 16 . The response to this treatment is usually verygood, apyrexia being obtained in a few hours. 

The prevalence of abnormalities has been shown tocoronary depends on the dose of immunoglobulins and not on the dose of aspirin, the treatmentby intravenous immunoglobulin to reduce the frequency of co- aneurysmsless than 5%. The administration of immunoglobulins should be early, as far as possible.possible during the first week of illness; however, in the presence of signs of inflammationpersistence, treatment can be carried out even after the first week. 

The mechanismspossible actions of immunoglobulins include the effect of specific antibodies against toxins orinfectious agents, the presence of anti-idiotype antibodies, or non-specific effects such as blockingcage of Fc receptors or an acceleration of the clearance of complement fractions.In the event of failure after an immunoglobulin infusion, defined as the persistence or recurrence offever 36 hours after the end of the infusion, you can proceed to a second and even a thirdtherapeutic cycle 1 .

Corticosteroids have long been contraindicated in Kawasaki disease, but there is evidencerecent studies show that corticosteroid therapy can be advised today in the event of initial failure ofimmunoglobulins 17 . Acetylsalicylic acid is administered in an anti-inflammatory dose during the acute phase and inantiplatelet in subacute phase. 

In the absence of cardiac complications, a low dose ismaintained until normalization of sedimentation rate and platelet count.In children with coronary artery abnormalities, treatment is continued untilcomplete regression of aneurysms, and for life if these aneurysms persist. 

In the event of an-giant vrisme, there is sometimes a need for anticoagulation by an antivitamin K or by heparin and,in selected cases, surgical intervention (bypass, transplant)