Self-limited medium-vessel vasculitis of young children; principal threat is coronary artery aneurysms; treated with IVIG and aspirin within 10 days of fever onset.
Also known as: mucocutaneous lymph node syndrome, MCLS, Kawasaki syndrome, infantile polyarteritis
Overview
An acute, self-limited febrile vasculitis of medium-sized arteries that predominantly affects children under 5. Cardinal feature is fever ≥5 days with at least four of: bilateral non-exudative conjunctivitis, oral mucosal changes, extremity changes, polymorphous rash, and unilateral cervical lymphadenopathy. Untreated, 20-25% develop coronary artery aneurysms.
Epidemiology
Highest incidence in children of Asian (especially Japanese) descent; ~6,000 US cases/year. 80% of cases in children <5 years. Slight male predominance. Peak in late winter and spring. Etiology unknown, presumed infectious trigger in a genetically predisposed host.
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Question 1CardiovascularMedium
A 3-year-old girl has had 6 days of fever, bilateral non-exudative conjunctivitis, a strawberry tongue with cracked lips, a polymorphous truncal rash, and a swollen erythematous right hand. She meets clinical criteria for Kawasaki disease and receives intravenous immunoglobulin within 7 days of fever onset to lower her risk of coronary artery aneurysm. Through which mechanism does intravenous immunoglobulin act in this disease?
AInhibition of platelet aggregation at injured endothelium
BSelective blockade of tumor necrosis factor-alpha
CNeutralization of a single identified bacterial toxin
DDirect relaxation of coronary arterial smooth muscle
EGeneralized dampening of the systemic inflammatory response
Reveal answer & full explanation
Correct answer: E — Generalized dampening of the systemic inflammatory response
AInhibition of platelet aggregation at injured endothelium
BSelective blockade of tumor necrosis factor-alpha
CNeutralization of a single identified bacterial toxin
DDirect relaxation of coronary arterial smooth muscle
EGeneralized dampening of the systemic inflammatory response✓
Why Generalized dampening of the systemic inflammatory response is correct
This is Kawasaki disease, an acute medium-vessel vasculitis of childhood whose feared complication is coronary artery aneurysm.
Intravenous immunoglobulin (IVIG) given within the first 10 days — ideally within 7 — markedly reduces aneurysm risk.
IVIG is pooled polyclonal IgG and works through broad, nonspecific immunomodulation: it saturates Fc receptors on macrophages, neutralizes circulating cytokines and putative superantigens, modulates T-cell and complement activity, and globally quiets the systemic inflammatory cascade driving the vasculitis.
Why the others are wrong
Neutralization of a single identified bacterial toxin — no single causative organism or toxin has been confirmed in Kawasaki disease, and IVIG does not target one defined pathogen.
Inhibition of platelet aggregation at injured endothelium — inhibition of platelet aggregation describes the role of aspirin, which is co-administered for its antiplatelet and anti-inflammatory effects, not the mechanism of IVIG.
Direct relaxation of coronary arterial smooth muscle — IVIG is not a vasodilator and does not act directly on coronary vascular tone; its benefit comes from suppressing the inflammatory injury to the vessel wall.
Selective blockade of tumor necrosis factor-alpha — tempting because infliximab, a monoclonal antibody against tumor necrosis factor-alpha, is an option for IVIG-resistant Kawasaki disease, but IVIG is pooled polyclonal IgG whose benefit comes from broad immunomodulation rather than selective blockade of one cytokine.
Question 2Infectious DiseaseMedium
A 7-year-old has fever for 6 days, bilateral conjunctival injection, cracked lips, cervical lymphadenopathy, rash, and swollen hands. Which of the following diagnostic studies assesses the major feared complication?
ASlit-lamp examination for anterior uveitis
BMicroscopic urinalysis for sterile pyuria
CLumbar puncture for aseptic meningitis
DEchocardiography for coronary aneurysms
EAbdominal ultrasound for gallbladder hydrops
Reveal answer & full explanation
Correct answer: D — Echocardiography for coronary aneurysms
ASlit-lamp examination for anterior uveitis
BMicroscopic urinalysis for sterile pyuria
CLumbar puncture for aseptic meningitis
DEchocardiography for coronary aneurysms✓
EAbdominal ultrasound for gallbladder hydrops
Why Echocardiography for coronary aneurysms is correct
The constellation of prolonged fever with conjunctival injection, mucosal changes, cervical lymphadenopathy, rash, and extremity swelling fits Kawasaki disease, a medium-vessel vasculitis.
Coronary artery aneurysms are the major feared complication, so baseline echocardiography is required.
Timely IVIG reduces the aneurysm risk, making cardiac imaging central to management.
Why the others are wrong
Lumbar puncture for aseptic meningitis — Aseptic meningitis with a mononuclear CSF pleocytosis occurs in some children with Kawasaki disease, but it is self-limited, and an LP does not evaluate the coronary arteries that are the real threat.
Slit-lamp examination for anterior uveitis — Anterior uveitis is common in the first weeks of Kawasaki disease and supports the diagnosis, but it resolves without visual sequelae and is not the complication that drives morbidity.
Abdominal ultrasound for gallbladder hydrops — Gallbladder hydrops is a recognized, self-resolving feature of Kawasaki disease that rarely needs intervention; it is not the coronary injury that determines long-term risk.
Microscopic urinalysis for sterile pyuria — sterile pyuria is one of the supplemental laboratory findings that support Kawasaki disease, particularly incomplete cases, but it is benign and transient and does not evaluate the coronary arteries that determine long-term risk.
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MIS-C following SARS-CoV-2 has overlapping features but is a distinct entity
Pathophysiology
Postulated infectious trigger initiates an immune cascade in genetically susceptible children, leading to medium-vessel vasculitis with prominent coronary artery involvement. Activated T cells, macrophages, and cytokine surge produce endothelial dysfunction and arterial wall edema, weakening and dilating affected vessels.
Clinical presentation
Symptoms
Fever ≥5 days, often 39-40 °C, unresponsive to antipyretics
Bilateral non-exudative conjunctival injection with limbic sparing
Extremity changes: erythema and edema of palms and soles in week 1; periungual desquamation in week 2-3
Polymorphous rash: morbilliform, scarlatiniform, or erythema multiforme-like; perineal accentuation in infants
Unilateral cervical lymphadenopathy ≥1.5 cm
Irritability disproportionate to exam, especially infants
Signs / physical exam
Tachycardia disproportionate to fever
BCG site reactivation (red, indurated) where BCG given
Hydrops of gallbladder, sterile pyuria, arthritis, aseptic meningitis can occur
Classic findings
Cracked red lips, strawberry tongue, red palms and soles, bilateral conjunctivitis, and a polymorphous rash in a febrile irritable toddler.
Differential diagnosis
Scarlet fever — Strep pharyngitis with sandpaper rash; lacks extremity changes and conjunctivitis
Measles — Three Cs and Koplik spots; cephalocaudal rash
Stevens-Johnson syndrome — Mucosal involvement with sloughing and target lesions, drug exposure
Staphylococcal or streptococcal toxic shock — Hypotension and end-organ failure; toxin-mediated
Multisystem inflammatory syndrome in children (MIS-C) — Recent SARS-CoV-2 exposure, older children, more cardiac dysfunction and shock; overlaps significantly with Kawasaki
Classic Kawasaki: fever ≥5 days plus ≥4 of 5 principal features (conjunctivitis, lip/oral changes, extremity changes, rash, cervical adenopathy). Suspected incomplete Kawasaki (fever ≥5 days with 2-3 features, or an infant ≤6 months with ≥7 days of unexplained fever): check CRP and ESR; if CRP ≥3.0 mg/dL and/or ESR ≥40 mm/h, treat when ≥3 supplemental labs are present (anemia for age, platelets ≥450,000 after day 7, albumin ≤3.0 g/dL, elevated ALT, WBC ≥15,000, urine ≥10 WBC/hpf) or the echocardiogram is positive.
Labs
CBC: leukocytosis with left shift in week 1, thrombocytosis (>450,000) classically appears in week 2
ESR and CRP elevated; persistent elevation supports diagnosis
LFTs: mild transaminitis, hypoalbuminemia
Urinalysis: sterile pyuria
BNP/NT-proBNP often elevated
Echocardiogram at diagnosis, 1-2 weeks, and 4-6 weeks — assess coronary artery dimensions (z-scores)
Consider SARS-CoV-2 testing (PCR and antibody) to distinguish from MIS-C in current era
Imaging
Transthoracic echocardiogram is mandatory and serial
ECG to detect arrhythmias and ischemia
Cardiac MRI or coronary CT for follow-up of aneurysms
Diagnostic algorithm
flowchart TD
A[Fever ≥5 days<br/>young child] --> B{≥4 of 5 features?<br/>conj / lips / extremities<br/>rash / cervical node}
B -->|Yes| C[Classic Kawasaki]
B -->|2-3 features| D[Incomplete Kawasaki<br/>check CRP/ESR + echo]
D -->|Supportive| C
C --> E[IVIG 2 g/kg + high-dose ASA<br/>within 10 days]
E --> F{Fever resolves<br/>≤36 h?}
F -->|Yes| G[Low-dose ASA<br/>+ serial echo]
F -->|No| H[IVIG-resistant:<br/>repeat IVIG ± steroids<br/>± infliximab]
G --> I{Coronary aneurysm?}
I -->|Small| J[Continue low-dose ASA]
I -->|Large/giant| K[ASA + anticoagulation<br/>lifelong cardiology follow-up]
Kawasaki disease diagnostic and treatment algorithm.
Treatment
First-line
IVIG + ASA for Kawasaki — IVIG 2 g/kg as a single infusion over 10-12 hours within 10 days of fever onset (and ideally before day 7)
Moderate-dose (30-50 mg/kg/day) or high-dose (80-100 mg/kg/day) aspirin in 4 divided doses until afebrile for 48-72 hours, then low-dose aspirin 3-5 mg/kg/day until inflammatory markers and coronary imaging normalize
Continue low-dose aspirin if coronary aneurysms develop; add anticoagulation (warfarin, LMWH) for large or giant aneurysms
IVIG-resistant Kawasaki
Persistent or recurrent fever ≥36 hours after IVIG
Re-treat with second IVIG 2 g/kg
Corticosteroids (methylprednisolone pulse or prednisolone taper) as an alternative or add-on to the second IVIG
Infliximab or cyclosporine as third-line
Late presentation (>10 days)
Treat with IVIG if persistent fever, ongoing inflammation, or coronary changes
Aspirin and serial echocardiography
High-risk at diagnosis
High-risk features (e.g., LAD or RCA z-score ≥2.5 at diagnosis, age <6 months): consider adding corticosteroids or infliximab to the initial IVIG (AHA 2024); Japanese risk scores such as Kobayashi perform poorly in North American children
Second-line / adjunct
Live vaccines (MMR, varicella) should be delayed 11 months after IVIG (passive antibody interferes with the live-vaccine immune response); inactivated influenza vaccine is unaffected and need not be deferred
Avoid live MMR/varicella for 11 months after IVIG
Complications
Coronary artery aneurysms (giant aneurysm = z-score >10 or >8 mm) with risk of thrombosis, stenosis, MI, and sudden death
Myocarditis, pericarditis, valvular regurgitation
Arrhythmias
Long-term: risk of late coronary stenosis and ischemia scales with maximal aneurysm size; whether KD without coronary involvement causes premature atherosclerosis is uncertain
Fever ≥5 days with at least four principal features — start IVIG within 10 days to reduce aneurysm rate from 20-25% to ~3-5%.
Periungual desquamation in week 2-3 is a retrospective clue but cannot wait — diagnose and treat early on fever and other features.
Aspirin is one of the few pediatric indications that overrides Reye-syndrome avoidance; benefits outweigh risks here.
Defer live vaccines (MMR, varicella) for 11 months after IVIG.
Incomplete Kawasaki is more common in infants and requires supportive labs plus echo to support diagnosis.
References
AHA 2017 — AHA Scientific Statement: Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease (McCrindle et al., Circulation 2017;135:e927-e999)
AAP Red Book — American Academy of Pediatrics Red Book — Kawasaki Disease
AHA 2024 — Update on Diagnosis and Management of Kawasaki Disease: A Scientific Statement From the American Heart Association (Jone et al., Circulation 2024;150(23):e481-e500)
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