Penyakit Kawasaki

01Pathophysiology

Kawasaki disease is a self-limited, acute systemic vasculitis that predominantly targets medium-sized muscular arteries, with a striking predilection for the coronary arteries. Although the exact cause remains unknown, the prevailing theory is that an unidentified infectious agent (viral or bacterial superantigen) triggers an exaggerated innate and adaptive immune response in children who are genetically predisposed. This leads to a cascade of immune activation involving T lymphocytes, macrophages, and plasma cells that infiltrate the arterial wall.
The inflammatory infiltrate releases pro-inflammatory cytokines including TNF-alpha, IL-1, and IL-6, which cause direct endothelial cell injury and damage to the internal elastic lamina and the media of the vessel wall. The destruction of these structural layers weakens the arterial wall, and the persistent intraluminal pressure causes the weakened segment to balloon outward, forming aneurysms. The coronary arteries are disproportionately affected because of their hemodynamic exposure and anatomic branching pattern.
The disease follows a predictable triphasic clinical course that directly mirrors the underlying vascular pathology. During the acute febrile phase (weeks 1 to 2), the systemic inflammation manifests as high fever and widespread mucocutaneous findings; myocarditis and pericarditis may also develop. In the subacute phase (weeks 2 to 4), the fever resolves, but a marked thrombocytosis (often exceeding 700,000/mm³) emerges as a reactive phenomenon to prior inflammation. This combination of endothelial damage and platelet surge creates the highest risk window for coronary artery aneurysm formation and thrombosis. The convalescent phase (weeks 4 to 8) marks clinical resolution, but coronary artery changes may persist or progress, underscoring the need for long-term echocardiographic surveillance.
The reason Kawasaki disease is the leading cause of acquired heart disease in children in developed countries is precisely this: untreated, approximately 25% of children develop coronary artery aneurysms, a number that drops to below 5% with timely IVIG therapy.

02Classification and Clinical Manifestation

The five principal clinical features, each of which reflects the underlying mucocutaneous vasculitis, are detailed below:

A critical clinical nuance: in incomplete Kawasaki disease, the child may present with prolonged unexplained fever and only 2 or 3 features. When inflammatory markers are elevated (CRP ≥ 3.0 mg/dL or ESR ≥ 40 mm/hr) and supplemental lab criteria are met (albumin ≤ 3.0 g/dL, anemia, elevated ALT, platelets > 450,000 after day 7, WBC ≥ 15,000, urine WBC ≥ 10/hpf), treatment should not be delayed. An echocardiogram showing coronary abnormalities in this setting clinches the diagnosis.

03Diagnostic Workup

Kawasaki disease is a clinical diagnosis. There is no single laboratory test or imaging study that confirms it in isolation. The role of the workup is twofold: (1) to support the diagnosis when clinical criteria are not fully met (incomplete Kawasaki disease), and (2) to assess for cardiac involvement.
The best initial step when you suspect Kawasaki disease is to apply the clinical criteria. If the child meets the criteria for complete disease, you order baseline labs (CBC, CRP, ESR, CMP, urinalysis) and an echocardiogram, then begin treatment immediately. You do not wait for the echocardiogram to start IVIG.
For incomplete Kawasaki disease, the algorithm is more nuanced. A child with ≥ 5 days of fever and 2 to 3 principal features should have CRP and ESR checked. If CRP ≥ 3.0 mg/dL or ESR ≥ 40 mm/hr, you then look for supplemental laboratory criteria (≥ 3 of the following: albumin ≤ 3.0, anemia for age, elevated ALT, platelets > 450,000 after day 7, WBC ≥ 15,000, urine WBC ≥ 10/hpf). Meeting ≥ 3 supplemental criteria or having a positive echocardiogram triggers treatment.
The echocardiogram is the most important imaging study. It should be obtained at the time of diagnosis, repeated at 2 weeks, and again at 6 to 8 weeks. Coronary artery Z-scores are used to classify the degree of involvement: a Z-score of 2.0 to 2.5 indicates dilation, 2.5 to < 5 indicates a small aneurysm, 5 to < 10 a medium aneurysm, and ≥ 10 (or an absolute dimension ≥ 8 mm) a giant aneurysm, which carries the highest risk of thrombosis, stenosis, and myocardial infarction.
A classic exam trick involves sterile pyuria: the urinalysis shows white blood cells, but the urine culture is negative. This occurs because the inflammation originates from the urethral mucosa (urethritis), not the bladder or kidney. If you see a vignette with a febrile child who "failed antibiotics for a UTI" but the culture is negative, think Kawasaki disease.

04Management and Treatment

The cornerstone of acute management is IVIG 2 g/kg given as a single infusion. This is one of the highest-yield treatment facts tested: IVIG reduces the incidence of coronary aneurysms from approximately 25% to below 5% when given within the first 10 days of illness. The mechanism is immunomodulatory, involving Fc receptor blockade, downregulation of inflammatory cytokines, and neutralization of potential superantigens. Timing matters: treatment before day 5 has not been shown to be more effective and may increase the rate of IVIG resistance, while treatment after day 10 is less effective at preventing coronary damage.
High-dose aspirin (80 to 100 mg/kg/day) is used concurrently for its anti-inflammatory properties during the acute febrile phase. This is a frequently tested exception to the general rule of avoiding aspirin in children due to the risk of Reye syndrome. Once the child has been afebrile for 48 to 72 hours, aspirin is reduced to a low antiplatelet dose (3 to 5 mg/kg/day). If the echocardiogram at 6 to 8 weeks shows no coronary abnormalities, aspirin is discontinued. If coronary aneurysms are present, low-dose aspirin continues indefinitely.
For children with giant coronary aneurysms (Z-score ≥ 10 or absolute internal diameter ≥ 8 mm), the risk of thrombotic occlusion is substantial. These patients require dual antiplatelet therapy (aspirin + clopidogrel) or aspirin combined with systemic anticoagulation (warfarin, targeting an INR of 2.0 to 3.0), along with lifelong cardiology follow-up.
Approximately 10 to 20% of patients are IVIG-resistant, defined as persistent or recurrent fever at least 36 hours after the initial IVIG infusion. The next best step is to administer a second dose of IVIG (2 g/kg) or IV methylprednisolone (30 mg/kg/day for 1 to 3 days). Infliximab (anti-TNF-alpha, 5 mg/kg IV) is an emerging option for refractory cases.
An important contraindication to remember: live vaccines (MMR, varicella) must be deferred for at least 11 months after IVIG administration, because the passive antibodies in IVIG can neutralize the live vaccine virus and render vaccination ineffective.

05Differential Diagnosis and Distractors

06Traps and High-Yield Pearls

The single most common trap with Kawasaki disease is failing to diagnose incomplete (atypical) Kawasaki disease. The exam will present a child, often an infant younger than 12 months, with prolonged fever and only 2 or 3 of the classic features. Students fixate on "needing 4 of 5 criteria" and dismiss the diagnosis, choosing an infectious etiology instead. The vignette will often include the phrases "fever unresponsive to antibiotics" and "irritability out of proportion to exam findings" as deliberate clues. When you see a febrile child who does not meet full criteria but has elevated inflammatory markers and no other explanation, order an echocardiogram.

A second common error is selecting the wrong dose or phase of aspirin. High-dose aspirin is for the acute febrile phase only (anti-inflammatory intent); low-dose aspirin is for the post-fever period (antiplatelet intent). A question asking for the "next step" after the fever resolves is testing whether you know to reduce, not stop, the aspirin.

Students also stumble on vaccine timing. A question about a child who received IVIG for Kawasaki disease and is now due for MMR or varicella vaccination tests whether you know to defer live vaccines for 11 months after IVIG.

Finally, be alert for the "early presentation" trap: a child with only 3 days of fever and classic features. Students may hesitate to diagnose Kawasaki disease because the formal criterion requires ≥ 5 days. Current guidelines, however, allow diagnosis before day 5 if the clinical picture is classic and the child has already developed coronary changes on echocardiogram. Do not let the "5-day rule" prevent you from making the diagnosis when the presentation is otherwise textbook.

The core competency being tested across all Kawasaki disease questions is pattern recognition in a febrile child with mucocutaneous findings, the decision to treat despite diagnostic uncertainty (especially in incomplete cases), and knowledge of the time-sensitive IVIG window to prevent coronary artery complications.