Kawasaki Disease: Symptoms, Types, Causes and Treatment

Kawasaki disease (KD) is a mysterious yet critical illness that primarily strikes young children. While most children recover fully with timely intervention, KD can have serious, even life-threatening, complications if left untreated. Understanding the symptoms, types, causes, and treatment options is key for caregivers, healthcare providers, and anyone interested in pediatric health. This comprehensive guide synthesizes the latest scientific research to bring clarity to this complex syndrome.

Symptoms of Kawasaki Disease

Kawasaki disease often begins abruptly, leaving parents and clinicians puzzled by its rapid onset and unusual combination of symptoms. Early recognition is essential for preventing serious complications, especially those affecting the heart.

Symptom	Description	Frequency/Significance	Sources
Fever	High, persistent (>5 days), often unresponsive to meds	Cardinal feature; present in all	4 5 7
Rash	Polymorphous (varied), non-vesicular	Very common	4 5 7
Conjunctivitis	Red eyes, no pus	Characteristic sign	4 5 7
Oral Changes	Red, cracked lips; strawberry tongue	Distinctive and prominent	4 5 7
Extremity Changes	Swollen, red hands/feet; later, skin peeling	Appears early, then desquamation	4 7
Lymphadenopathy	Swollen neck lymph nodes (usually one side)	Less common, but a key sign	4 5 7
GI Symptoms	Vomiting, diarrhea, abdominal pain	Common, especially in outbreaks	1 3
Irritability	Marked fussiness/unusual behavior	Common, often overlooked	3

Table 1: Key Symptoms of Kawasaki Disease

Classic Clinical Features

Kawasaki disease is diagnosed primarily on clinical grounds. The hallmark is a high fever lasting at least five days, with at least four out of five principal features: rash, conjunctival injection (red eyes without pus), oral mucosal changes, extremity changes, and cervical lymphadenopathy. These features may not all appear simultaneously, which can delay diagnosis 4 5 7.

Gastrointestinal and Nonspecific Symptoms

A significant number of children also experience gastrointestinal symptoms such as abdominal pain, vomiting, and diarrhea. These are especially prominent in recent outbreaks, sometimes leading to misdiagnosis as other illnesses 1 3. Respiratory symptoms (cough, rhinorrhea) and neurological signs (irritability, weakness) may also be present, reflecting the widespread inflammatory impact of the disease 3.

Cardiac Manifestations

The most feared complications of KD are cardiac, particularly inflammation of the coronary arteries. Myocarditis (inflammation of the heart muscle) and Kawasaki disease shock syndrome—characterized by low blood pressure and poor perfusion—can occur in severe cases 1 2 6. Without prompt treatment, up to 25% of patients may develop coronary artery aneurysms 2 7.

Types of Kawasaki Disease

Although often referred to as a single disease, KD presents in several clinical forms. Recognizing these types helps guide diagnosis and treatment, especially in atypical or severe cases.

Type	Key Features/Criteria	Age/Population Affected	Sources
Classic KD	Meets full diagnostic criteria	Mostly <5 years	4 6 7
Incomplete KD	Fewer than 4 principal criteria, but with fever	Young infants, older kids	5 7
Atypical KD	Unusual presentations (e.g., shock, GI-only)	All ages	1 5 7
KD Shock Syndrome	Profound hypotension, multi-organ involvement	Severe cases	1
Kawasaki-like MIS-C	KD features + multisystem inflammation (COVID-19)	School-age children	1 11

Table 2: Types of Kawasaki Disease

Classic (Typical) Kawasaki Disease

Classic KD is defined by fever plus four of the five principal features. It is most common in children under five years old 4 6 7. Classic presentations are easier to diagnose, which is crucial for timely treatment.

Incomplete (Atypical) Kawasaki Disease

Incomplete KD describes cases that do not fulfill all diagnostic criteria but have persistent fever and laboratory or echocardiographic evidence of inflammation or coronary involvement. This type is more common in very young infants and older children, both of whom are at higher risk for cardiac complications due to delayed diagnosis 5 7.

KD Shock Syndrome and Severe Variants

Some children present with KD shock syndrome, marked by low blood pressure and signs of organ dysfunction. These cases require intensive care and are more often linked to viral triggers such as SARS-CoV-2 1. Other atypical forms might mimic diseases like retropharyngeal abscess or present primarily with gastrointestinal symptoms 1 5.

Kawasaki-like Multisystem Inflammatory Syndrome (MIS-C)

During the COVID-19 pandemic, a Kawasaki-like syndrome associated with SARS-CoV-2 infection emerged, known as MIS-C (Multisystem Inflammatory Syndrome in Children). These children exhibit many KD features, but with more severe and widespread inflammation, often affecting older children than classic KD 1 11.

Causes of Kawasaki Disease

The roots of Kawasaki disease remain enigmatic. However, advances in research have shed light on several contributing factors, from infectious triggers to genetic predisposition and immune system dysregulation.

Factor	Description/Mechanism	Key Evidence	Sources
Infectious	Suspected viral/bacterial triggers (esp. RNA viruses)	Epidemiology, outbreaks	11 13 20
Genetic	Ethnic risk, family clustering, specific gene variants	Higher rates in Asians	12 13 14 17
Immune	Abnormal immune activation, autoimmunity, cytokines	Hyperinflammation, AECAs	8 10 14 15
Environmental	Seasonality, unclear exposures	Winter-spring peaks	13

Table 3: Causes and Risk Factors for Kawasaki Disease

Infectious Triggers

Epidemiological evidence strongly suggests that infectious agents—especially viruses—are involved in KD onset. Outbreaks often coincide with peaks in respiratory infections. The dramatic rise in KD and MIS-C cases during the COVID-19 pandemic further supports a viral trigger, though no single causative pathogen has been confirmed 11 13 20.

Genetic Susceptibility

Genetics play a clear role in KD risk. The disease is far more common in children of Asian descent, especially Japanese, Korean, and Taiwanese populations. Certain gene variants, such as those affecting immune regulation, have been linked to increased susceptibility and severity 12 13 14 17. Family clustering of cases has also been documented.

Immune and Autoimmune Mechanisms

KD is characterized by intense, uncontrolled inflammation. Research points to abnormal activation of both the innate and adaptive immune systems, leading to widespread vasculitis. Autoimmune responses—such as the production of anti-endothelial cell autoantibodies (AECAs)—may target blood vessels, especially the coronary arteries 8 10 14 15. Hypercytokinemia (elevated inflammatory cytokines) further amplifies the disease process.

Environmental Factors

Seasonal trends, with peaks in winter and spring, suggest that environmental or infectious factors modulate disease incidence 13. However, no specific environmental exposures have been conclusively linked to KD.

Treatment of Kawasaki Disease

Prompt, effective treatment is essential to reduce the risk of serious complications in KD, especially coronary artery aneurysms. Over the years, therapy has evolved, with new options emerging for resistant or severe cases.

Treatment	Purpose/Mechanism	Notes/Indications	Sources
IVIG	Reduces inflammation; lowers risk of coronary aneurysms	First-line; 2g/kg dose	7 17 19 20
Aspirin	Anti-inflammatory, anti-platelet	Used with IVIG; high then low dose	7 17 19 20
Corticosteroids	Suppress severe inflammation	For high-risk or IVIG-resistant cases	1 16 17 19
Infliximab	Anti-TNF biologic agent	For IVIG-resistant KD	18 20
Other Immunomodulators	Cyclosporine, anti-IL-1 agents	Investigational, for refractory cases	15 17 20

Table 4: Main Treatments for Kawasaki Disease

First-Line Therapy: IVIG and Aspirin

The standard of care for KD is a single high-dose infusion of intravenous immunoglobulin (IVIG), combined with aspirin. IVIG dramatically reduces the risk of coronary artery aneurysms if given within the first 10 days of illness 7 17 19 20. Aspirin is initially used in high doses to curb inflammation, then continued at lower doses for its anti-platelet effect.

Adjunctive and Second-Line Therapies

Corticosteroids

Recent studies support the use of corticosteroids in addition to IVIG for children at high risk of IVIG resistance or with severe disease. Steroids can reduce the incidence of coronary artery abnormalities, shorten fever duration, and decrease hospital stays, with no significant increase in adverse events 1 16 17 19. The optimal regimen and identification of high-risk patients remain areas of active research.

Infliximab and Other Biologics

For the 10–20% of children who do not respond to initial IVIG, options include a second dose of IVIG or biologic agents like infliximab (anti-TNFα). Infliximab has been shown to resolve fever more rapidly, reduce hospital stay, and result in fewer side effects (notably less severe anemia) compared to a second IVIG infusion 18 20. Other targeted therapies, such as cyclosporine and anti-IL-1 agents, are under investigation, particularly for refractory cases 15 17 20.

Cardiac Monitoring and Long-Term Care

All children with KD require cardiac monitoring with echocardiography during the acute illness and follow-up to detect coronary artery changes. Those with persistent aneurysms may need long-term anticoagulation and specialized cardiac care 2 7 17 19.

Conclusion

Kawasaki disease is a complex, multisystem illness with potentially life-altering consequences if not recognized and treated early. While its precise cause remains elusive, a combination of genetic, infectious, and immune factors is at play. Rapid diagnosis and evidence-based treatment can prevent most of the serious complications, especially those involving the heart.

Key Takeaways:

• Symptoms: High fever, rash, red eyes, oral changes, extremity swelling, and lymphadenopathy are hallmark features; gastrointestinal and cardiac symptoms are common, especially in severe or atypical cases.
• Types: KD can present as classic, incomplete, or atypical forms; severe variants like KD shock syndrome and Kawasaki-like MIS-C (especially during COVID-19) require special attention.
• Causes: The interplay of infectious triggers, genetic susceptibility, and immune dysregulation drives KD; no single cause has been identified.
• Treatment: Timely IVIG and aspirin are the foundation of therapy; corticosteroids and biologics like infliximab are essential for severe or resistant cases; careful cardiac monitoring is crucial for all patients.

By staying informed and vigilant, caregivers and clinicians can ensure the best outcomes for children affected by Kawasaki disease.