Introduction

Kawasaki disease (KD) is an acute, self-limiting vasculitic illness predominantly affecting infants and young children. It is now a leading cause of acquired heart disease in children in Western countries. The diagnosis is made clinically, and effective treatment is available to reduce the likelihood of potentially fatal coronary vasculitis. KD was first described in 1967 as ‘mucocutaneous lymph node syndrome’ in a series of 50 Japanese children.¹ Although it is most common in Japanese and Korean children (annual incidence 90–150/100 000 children younger than five years), it occurs in all ethnic groups, with an annual incidence in the United States of approximately 10/100 000 children younger than 5 years old. The majority of cases (85%) occur in children aged less than 5 years of age. It is 1.5 times more common in boys than girls.²

Many features of KD suggest an infectious aetiology. These include: seasonal variation (peak in winter/spring); occasional outbreaks; 10-fold higher risk in siblings than in the general population; rarity in young infants (suggesting protection from maternally acquired antibody); low recurrence rate (4%, which suggests acquired immunity); as well as the resemblance of the clinical presentation to other self-limiting infectious diseases, such as measles, adenovirus infection and staphylococcal toxic shock syndrome. However, despite much investigation of a variety of viral and bacterial pathogens, there is as yet no good evidence to implicate any known organism in KD. The ethnic variation suggests a genetic predisposition.

There is debate as to whether the inflammatory response in KD is initiated by a conventional antigen or a superantigen, and there are some immunological features to support both hypotheses. Unreplicated reports of increased expression of specific T-cell receptor V β-regions suggests toxin activation, whereas infiltration of paratracheal and vascular tissue with reactive clonal IgA plasma cells suggests entry of a conventional antigen via the respiratory route.³

Pathophysiology

The pathophysiology of KD involves vasculitis of medium-sized vessels including coronary, renal, hepatic and splanchnic arteries, beginning in both adventitial and intimal surfaces and proceeding toward the media. Coronary changes occur in approximately 20% of untreated patients.⁴ Immune activation involving cytokines and growth factors leads to inflammation and aneurysm formation, with the risk of thrombosis. The process evolves for a long period after the acute illness. In the majority of patients with echocardiographically demonstrable coronary artery lesions, the vessels remodel and have a normal appearance within a year or so. However, there is evidence of subtle long-term changes in coronary artery function, the clinical significance of which remain unclear.⁵ The risk of early adult coronary artery disease in these patients is unknown.

A diffuse inflammatory process of a variety of tissues has been found in autopsy specimens including lymph nodes, liver and gall-bladder.² Endothelial changes are prominent, with hyperplasia, necrosis and thrombosis. Myocardial abnormalities include hypertrophy of myocytes and fibrosis.

Clinical features

KD should be considered in the differential diagnosis of all infants and young children with a fever, rash and red eyes, as well as those with a prolonged fever without an alternative explanation. The diagnostic criteria are outlined in Table 5.8.1.

The diagnosis can be made earlier than day 5 if other features are present. This is important, as there is evidence that earlier administration of intravenous immunoglobulin (IVIG) is associated with a shorter illness and reduced risk of coronary disease.⁶

The fever is often associated with irritability, which responds poorly to paracetamol. Over 90% of patients develop a rash, which can take any of a number of forms – scarlatiniform, morbilliform or maculopapular. It often has the appearance of a viral eruption or allergic reaction, but can appear urticarial. Petechiae are sometimes seen, as are micropustules. The red eyes demonstrate characteristic sparing of the avascular perilimbic region, giving the appearance of a halo around the cornea. There is not usually an exudate. The changes may resolve rapidly, such that this important feature may be present only on history rather than being present when the child is examined. The cervical nodes are commonly unilateral and in the anterior chain. Generalised lymphadenopathy and splenomegaly are absent. The subacute phase occurs from 2–4 weeks, with resolution of fever. Desquamation (periungual) of fingers and toes may occur during this time.

KD is a multisystem disease with many and varied clinical manifestations. In addition to those in the diagnostic criteria, common features include marked irritability, diarrhoea, cough, arthralgia/arthritis, urethritis with sterile pyuria, otitis media, mild hepatic dysfunction, hydrops of the gallbladder and aseptic meningitis. Diagnosis is more likely to be delayed in older children, in whom less classical manifestations such as gastrointestinal and joint symptoms often predominate.⁷

Incomplete KD

Cases of incomplete or ‘atypical KD’ are being increasingly recognised, in which full criteria are not met, but the patient has coronary artery abnormalities. This is more common in young infants.⁸ The incidence of coronary artery aneurysms is at least as high in incomplete KD as in classical cases. Given that infants under 6 months appear to be at increased risk of developing coronary abnormalities;⁸ a lower threshold for treatment is probably indicated in this group. KD should be considered in all children with unexplained fever for 5 days and at least two major features of KD, and any infant with unexplained fever for over a week.⁴