22.1 Kawasaki Disease, MIS-C & Staphylococcal/Streptococcal Toxic Shock Syndromes

A child with fever, rash and shock may have bacterial sepsis, toxin-mediated disease or a hyperinflammatory syndrome. Stabilize perfusion and investigate infection and cardiac dysfunction in parallel. The history, exam and serial results help distinguish Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C) and toxic shock syndrome (TSS).

Kawasaki disease

KD is a clinical diagnosis. The vasculitis can injure the coronary arteries, especially in young infants. The 2024 American Heart Association (AHA) statement allows complete KD at four days of fever with at least four of the five principal findings, even if they occurred on different days. Count the first day of fever as day 1. Consider other explanations, particularly with exudative conjunctivitis or pharyngitis, oral ulcers or a vesicular rash.

• Eyes. Bilateral nonexudative bulbar injection, often with limbic sparing.
• Rash. Polymorphous eruption, sometimes with early perineal changes.
• Cervical nodes. Usually unilateral adenopathy with a node or cluster measuring at least 1.5 cm.
• Oral changes. Erythema or cracking of the lips, strawberry tongue or diffuse oral and pharyngeal erythema.
• Extremities. Erythema or swelling of the hands and feet acutely. Periungual peeling can appear later.

Incomplete disease and echocardiography

Evaluate a child with prolonged unexplained fever and two or three principal findings. The detailed AHA algorithm uses at least five days of fever for that entry and prompts evaluation in infants six months or younger with at least seven days of unexplained fever even without the typical findings. Obtain CRP, ESR and a prompt echocardiogram when incomplete KD is suspected. In the algorithm, CRP ≥3.0 mg/dL or ESR ≥40 mm/h leads to assessment of supplemental findings and coronary imaging.

• Supplemental findings. Anemia for age, platelets ≥450,000/µL after day 7, albumin ≤3.0 g/dL, elevated ALT, WBC ≥15,000/µL, or urine ≥10 WBC per high-power field. Three or more support treatment in the compatible clinical and inflammatory setting.
• Positive echocardiogram. Proximal LAD or RCA Z-score ≥2.5, a coronary aneurysm, or at least three supporting echo findings. The four supporting findings are reduced LV function, mitral regurgitation, pericardial effusion and a proximal LAD or RCA Z-score of 2 to <2.5. Early normal imaging does not exclude KD. Reassess ongoing unexplained fever, new peeling, or rising concern even if the first evaluation is nondiagnostic.

Hypotension and poor perfusion can occur in KD shock syndrome, with or without myocardial dysfunction. Obtain urgent cardiac assessment, cultures and empiric antibiotics when bacterial shock remains possible. AHA 2024 statement · AHA detailed incomplete KD algorithm

Treatment and coronary follow-up

Give IVIG 2 g/kg with aspirin promptly after diagnosis, ideally within ten days. Beyond day 10, seek treatment when fever persists or coronary abnormalities accompany ongoing systemic inflammation. Use the product-specific IVIG infusion protocol and consider slower infusion when ventricular function is depressed. AHA describes moderate-dose aspirin at 30–50 mg/kg/day or high-dose aspirin at 80–100 mg/kg/day in the acute phase, followed by 3–5 mg/kg once daily after defervescence. High-dose aspirin has no established coronary advantage. Age under six months and baseline proximal LAD or RCA Z-score ≥2.5 are high-risk findings that should prompt early discussion of intensified primary therapy such as adjunctive corticosteroids or infliximab.

Persistent or recurrent fever ≥36 hours after completion of initial IVIG suggests IVIG resistance. Reassess for competing causes, then discuss a second IVIG infusion, infliximab or corticosteroids. The KIDCARE trial found faster fever resolution with infliximab than with second IVIG, with no demonstrated difference in coronary outcome.

Use the same Z-score equation for serial measurements. For an evolving aneurysm, cardiology may repeat echo every two to three days until dimensions stabilize. Follow-up incorporates both the maximum past and the current coronary dimensions. The corrected AHA table allows continued anticoagulation for selected patients whose giant aneurysm regressed to medium size, based on thrombosis risk. Apparent regression can reflect thrombosis, so review imaging and treatment with cardiology. A four-month-old with prolonged fever, conjunctival injection, hand changes and LAD Z-score 11.2 has an incomplete clinical presentation with a giant aneurysm. Defervescence after IVIG leaves the coronary thrombosis risk in place.

After 2 g/kg IVIG for KD, CDC's routine interval before measles- or live varicella-containing vaccine is 11 months. Continue other age-appropriate vaccines, including inactivated influenza vaccination when age-eligible, and discuss prompt contact for influenza or varicella exposure or illness during aspirin therapy. AHA 2024 statement · 2025 AHA correction to follow-up table · KIDCARE trial · CDC vaccine spacing

MIS-C

MIS-C usually follows SARS-CoV-2 infection by several weeks. Gastrointestinal symptoms, lymphopenia, thrombocytopenia, shock or myocardial injury in an older child are clues, but overlap with bacterial sepsis and KD. Obtain ECG and echocardiography, follow troponin and BNP or NT-proBNP when elevated, and assess coronary size and ventricular function. Collect cultures and evaluate alternate diagnoses, including a surgical abdomen when indicated. Treat possible bacterial shock promptly while investigating MIS-C.

The U.S. CSTE/CDC surveillance definition applies to patients under 21 years and uses subjective or documented fever ≥38°C, hospitalization or death, CRP ≥3.0 mg/dL, new manifestations in at least two of five categories, and absence of a more likely diagnosis. The categories are cardiac, mucocutaneous, shock, gastrointestinal and hematologic. The hematologic category uses platelets <150,000/µL or absolute lymphocytes <1,000/µL. For reporting, a positive RNA or antigen test up to 60 days before or during hospitalization, or serology tied to the current illness, can support confirmed classification. Qualifying close contact in the 60 days before hospitalization can support a probable case. Anti-nucleocapsid antibodies indicate prior infection, whereas anti-spike antibodies may also follow vaccination. A final KD diagnosis is an alternative for surveillance. Clinical decisions depend on the full presentation and can precede complete reporting data. CDC surveillance criteria · CDC clinical overview

• Initial immunomodulation. ACR guidance supports IVIG 2 g/kg based on ideal body weight, maximum 100 g, plus glucocorticoids 1–2 mg/kg/day for most hospitalized patients. Assess fluid status and ventricular function before IVIG. With dysfunction, slower or divided administration over two days may be needed. After specialist evaluation, some mild cases may be monitored without immunomodulation. IVIG alone can be considered when glucocorticoids are contraindicated. ACR guidance is informed partly by observational comparisons. Later randomized trials tested specific regimens, including steroid or IVIG monotherapy, and do not establish that every presentation needs both agents.
• Refractory illness and monitoring. With persistent fever or significant ongoing organ involvement despite initial treatment, reassess for infection and discuss escalation with rheumatology and cardiology. Options include pulse glucocorticoids, anakinra or, in selected patients without macrophage activation syndrome, infliximab. Clinical, cardiac and laboratory response guides taper and repeat echocardiography, commonly at 7–14 days and 4–6 weeks.
• Thrombosis and bleeding. Use low-dose aspirin 3–5 mg/kg/day, maximum 81 mg/day, when bleeding risk allows. ACR advises avoiding it with active bleeding, significant bleeding risk or platelets ≤80,000/µL. ACR recommends therapeutic anticoagulation for LV ejection fraction <35%, a coronary Z-score ≥10 or documented thrombosis, with specialist review of bleeding risk. For other patients, individualize prophylaxis by thrombosis and bleeding risk.

ACR MIS-C guidance, version 3 · Swissped randomized trial · RECOVERY platform trial

Staphylococcal and streptococcal toxic shock

Staphylococcal and GAS toxins can act as superantigens, producing systemic inflammation, capillary leak and shock. A retained tampon, packing, postoperative wound or burn suggests a possible staphylococcal source. Diffuse erythroderma with vomiting and hypotension can precede later desquamation. A local source can produce systemic illness without bacteremia. Invasive GAS should be considered with severe focal pain, rapidly progressing soft-tissue findings or varicella-associated skin infection. The CDC streptococcal surveillance definition combines GAS isolation with hypotension and multiorgan involvement. A normally sterile isolate supports confirmed classification, while a nonsterile isolate can support probable classification. Treat on clinical suspicion while cultures and surveillance criteria evolve.

1. Resuscitate and obtain source control in parallel. Give titrated isotonic crystalloid with reassessment after each bolus, and start vasoactive support promptly when needed. Obtain blood and source cultures when feasible without delaying treatment. Remove implicated packing or a retained tampon and drain or debride an infected focus. Call surgery urgently for possible necrotizing infection.
2. Choose antimicrobials for the source and local resistance. When the organism is uncertain, cover likely pathogens, including MRSA when indicated, and use a protein-synthesis inhibitor for suspected toxin-mediated disease. One pediatric pathway adds clindamycin to ceftriaxone plus vancomycin for undifferentiated toxic shock. When MSSA is identified, use a susceptible antistaphylococcal beta-lactam and reassess the duration of adjunctive toxin suppression. For confirmed GAS toxic shock, CDC recommends penicillin plus clindamycin. Linezolid is a specialist-directed alternative for toxin suppression when clindamycin resistance or intolerance limits use.
3. Discuss IVIG selectively. CDC allows consideration early in severe streptococcal toxic shock. A small adult randomized trial was stopped early, and a pediatric observational study did not demonstrate a mortality benefit. Continue source control and antibiotics regardless of that decision.

2026 pediatric sepsis guideline · CDC streptococcal toxic shock guidance · CDC nonstreptococcal TSS definition · Children’s Healthcare of Atlanta pathway · Pediatric IVIG cohort · Adult IVIG trial