Kawasaki Disease
- 1. Department of Paediatrics, St. Joseph’s Health Centre, Canada
- 2. Department of Paediatrics, The Hospital for Sick Children, Canada
- 3. Department of Paediatrics, University of Toronto, Canada
- 4. Department of Emergency Medicine, King Saud University, Kingdom of Saudi Arabia
- 5. Department of Newborn and Developmental Paediatrics, Sunnybrook Health Sciences Centre, Canada
Abstract
Kawasaki disease is one of the most common vasculitides in childhood, predominantly affecting children less than 5 years of age. The disease often presents with a unique collection of signs and symptoms that include prolonged fever, bilateral nonexudative conjunctivitis, mucosal changes, and cervical lymphadenopathy, rash and extremity changes. Although changes in laboratory investigations are often present, none have been found to be specific for the disease. The diagnosis is based on the clinical criteria established by the American Heart Association, which requires the presence of fever for at least 5 days in addition to at least 4 principal clinical features. Although the acute phase of the disease is self-limited, coronary artery aneurysms and other serious cardiovascular sequelae may develop later, including a considerable proportion of those not appropriately treated. Intravenous immunoglobulin, usually given with acetylsalicylic acid, is the treatment of choice and has been proven to be highly effective in reducing the prevalence of coronary artery aneurysms in this population.
Citation
Etoom Y, Alnutayfi A, Banihani R, Soon GS (2017) Kawasaki Disease. JSM Arthritis 2(2): 1027.
Keywords
• Kawasaki disease
• Vasculitis
• Pediatrics
• Fever
ABBREVIATIONS
KD: Kawasaki Disease; CRP: C-Reactive Protein; ESR: Erythrocyte Sedimentation Rate; WBC: White Blood Cell; IVIG: Intravenous Immunoglobulin; ASA: Acetylsalicylic Acid
INTRODUCTION
Kawasaki disease (KD) is an acute vasculitis of unclear etiology that predominantly affects children [1]. KD often presents as an acute self-limited febrile illness; however, without appropriate treatment up to 25% of affected children develop coronary artery aneurysms [2]. First described in 1967 by Tomisaku Kawasaki, the disease is now one of the major leading causes of acquired heart disease in children and has recently surpassed rheumatic fever as the leading cause in developed countries [3,4]. KD is characterized by fever, bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rash, and cervical lymphadenopathy. The cause of KD remains unknown, although an infectious etiology is frequently cited due to the increased incidence of the disease observed in winter and early spring [4]. KD has been reported in children of all ages yet most commonly affects children less than 5 years of age [5]. The annual incidence of KD varies considerably between countries, with a reported annual incidenceper 100,000 children under 5 years of age ranging from 3.4 in Thailand to 218.6 in Japan [6]. The vasculitis in KD has a strong predilection for the coronary arteries. The pathological process is thought to begin with sub endothelial accumulation of mononuclear cells such as T cells and monocytes, which then leads to transmural inflammation and aneurysm formation [7]. Knowledge about this disease is crucial to physicians, especially pediatricians, because early recognition and prompt initiation of therapy results in considerable improvement in patient outcomes.
DIAGNOSIS
Pathognomonic features and specific laboratory tests cannot confirm the presence of KD. Rather, a set of specific clinical criteria are used to diagnose KD. The classic clinical criteria is based on the presence of high fever for ≥5 days and ≥4 of the following 5 principal clinical features: (1) bilateral bulbar conjunctival injection, generally nonexudative; (2) changes in mucosa of the oropharynx, including injected pharynx, injected and/or dry fissured lips, and strawberry tongue; (3) changes of the peripheral extremities such as edema and/or erythema of the hands or feet in the acute phase or periungual desquamation in the subacute phase; (4) rash, primarily truncal, polymorphous but non-vesicular; and (5) cervical lymphadenopathy, ≥1.5 cm and usually unilateral [1]. The term “incomplete” Kawasaki disease describes cases where the diagnosis of KD is strongly suspected but the clinical criteria are not fully met. The prevalence of this type of presentation ranges from 16.1% to 40.5% [8,9]. The diagnosis of incomplete (sometimes also referred to as atypical) KD is supported by laboratory features as well as echocardiography to detect coronary artery abnormalities. Although non-specific, laboratory investigations that may be abnormal in KD include elevated acute-phase reactants such as C-reactive protein [CRP] and/or erythrocyte sedimentation rate [ESR], anemia for age, elevated platelet count, elevated white blood cell (WBC) count, elevated serum alanine aminotransferase, low serum albumin and sterile pyuria [1].Given the risk of coronary artery aneurysms and other serious cardiovascular sequelae in untreated KD, a high index of suspicion is required for all infants and children with prolonged fever. While the differential diagnosis includes many conditions with features that overlap with those of KD (such as group A streptococcal, measles, adenovirus, and Epstein-Barr virus infections; drug reactions such as Stevens-Johnson syndrome or serum sickness; and systemic juvenile idiopathic arthritis), the possibility of KD must be especially considered in certain clinical situations. For example, in infants <6 months with irritability, in patients with pyuria or cervical adenitis unresponsive to antibiotic therapy, and in older children and adolescents with prolonged fever, supportive laboratory investigations and even echocardiography should be used to appropriately diagnose and treat potential cases of incomplete (atypical) KD.
MANAGEMENT
The most important intervention once the diagnosis of KD has been established is the administration of intravenous immunoglobulin (IVIG). Early IVIG therapy, ideally within the first 10 days of illness, has been shown to reduce the prevalence of coronary artery abnormalities [10]. Although the exact mechanism of action of IVIG in KD is unknown, it is thought to have an anti-inflammatory effect as demonstrated by the resolution of fever and decrease in acute phase reactant levels. IVIG is administered 2 g/kg as a single infusion, usually over 10 to 12 hours [11]. Acetylsalicylic acid (ASA) is usually given together with IVIG because of its anti-inflammatory activity at high doses. Although dosing practices vary worldwide, ASA is typically administered every 6 hours during the acute phase of illness (30-50 mg/kg/day in Japan and Western Europe; 80- 100 mg/kg/day in the United States) until the child has been a febrile for 2-3 days. Low-dose ASA (3-5 mg/kg/day) is generally then started for ongoing anti platelet activity and continued until documentation of the absence of coronary abnormalities at 6-8 weeks after the onset of illness [12,13]. The term IVIG resistant KD has been used to describe cases where fever persists for more than 36 hours despite treatment with IVIG. The management of such cases is less clear and often involves retreatment with IVIG. Other treatments that may be employed include corticosteroids, infliximab, and cyclosporine and plasma exchange [13]. A number of risk scores have been developed to predict IVIG non-responders, but their use in non-Japanese patients and in those with incomplete (atypical) presentations remain a challenge [14].
COMPLICATIONS
Cardiovascular manifestations of the disease are the leading cause of long-term morbidity and mortality, with coronary artery aneurysms being the most frequently observed serious complication [13,15]. Other cardiac sequelae include decreased myocardial function, valvular regurgitation and pericardial effusion [16]. Although the disease has a predilection for coronary arteries, the vasculitis can affect any blood vessel [17]. Other reported complications include macrophage activation syndrome, acute interstitial nephritis, hydrops of the gallbladder, and transient sensorineural hearing loss [18-21]. Late cardiovascular complications of KD are generally limited to those who were affected by coronary artery abnormalities in the acute phase and include progressive coronary artery stenosis or occlusion, myocardial infarction, and arrhythmias [16]. While there is ongoing debate whether the vasculopathy of KD is associated with accelerated atherosclerosis, the threshold for treatment of atherosclerotic heart disease in adults with a history of KD is lower than in the general population [22]. For children who never had coronary artery abnormalities, however, the risk of long-term cardiovascular disease is likely not increased compared with the general pediatric population [23], and only routine preventative counseling is recommended [13]. Further studies with longer follow-up into adulthood are needed.
CONCLUSION
KD causes considerable morbidity and mortality in the pediatric population when not identified early and managed appropriately. Coronary artery changes represent the most common serious sequelae in KD. There is no specific test that can identify the disease, so clinicians must be aware of the well-defined clinical criteria used in its diagnosis and have a high index of suspicion to allow early identification of cases and thus early initiation of the highly effective but time sensitive therapy with IVIG.
