Kawasaki Disease, MIS-C & Juvenile Idiopathic Arthritis
Fever-plus patterns that threaten coronaries, joints, and eyes
Kawasaki disease: recognition
Overview. Kawasaki disease (KD) is an acute, self-limited medium-vessel vasculitis of unknown cause with a predilection for the coronary arteries. Most patients are younger than 5 years; boys and children of Asian, especially Japanese, ancestry are at highest risk. It is the leading cause of acquired heart disease in US children. About 25% of untreated children develop coronary artery aneurysms, compared with about 4% of those given IVIG promptly.
Complete KD. Fever for at least 5 days plus at least 4 of 5 principal features (mnemonic "CRASH and burn"):
- Conjunctivitis — bilateral bulbar injection without exudate, sparing the limbus
- Rash — polymorphous (maculopapular, diffuse erythroderma, or erythema multiforme-like), never vesicular or bullous; perineal accentuation with early perineal peeling
- Adenopathy — cervical node ≥1.5 cm, usually unilateral; the least frequent feature
- Strawberry tongue and oral changes — red, cracked lips and diffuse oropharyngeal erythema without exudate
- Hands and feet — erythema and edema of palms and soles acutely, periungual desquamation in weeks 2–3
Mimics. Exudates or vesicles argue against KD. Consider adenovirus (exudative conjunctivitis and pharyngitis), measles (cough, coryza, Koplik spots), scarlet fever (positive strep test, responds to antibiotics), toxic shock syndrome, drug reactions such as Stevens-Johnson syndrome, and systemic JIA. In BCG-vaccinated children, redness or crusting at the BCG scar is an early clue to KD.
Supporting labs. Elevated CRP and ESR, neutrophilic leukocytosis, normocytic anemia, hypoalbuminemia, elevated ALT, hyponatremia, and sterile pyuria; the platelet count rises after the first week.
Incomplete KD. Children with fewer criteria, especially infants younger than 6 months, still develop aneurysms; young infants are often incomplete and carry the highest aneurysm risk.
- Whofever ≥5 days with 2–3 principal features, or an infant ≤6 months with ≥7 days of otherwise unexplained fever
- InflammationCRP ≥3.0 mg/dL and/or ESR ≥40 mm/h; if lower, reassess serially and echo if peeling appears
- Supplemental labsalbumin ≤3.0 g/dL, anemia for age, elevated ALT, platelets ≥450,000 after day 7, WBC ≥15,000, urine ≥10 WBC/hpf
- Treatif ≥3 supplemental labs are positive or the echocardiogram is abnormal
Kawasaki disease: treatment and follow-up
IVIG and aspirin. Give IVIG 2 g/kg as a single infusion, ideally within the first 10 days of illness; treat after day 10 if fever or inflammation persists or aneurysms are present. Add aspirin at a moderate to high dose (30–100 mg/kg/day) until the child has been afebrile for 48–72 hours, then a low antiplatelet dose (3–5 mg/kg/day) until the 4–6-week echocardiogram is normal.
IVIG resistance. Persistent or recrudescent fever at least 36 hours after the IVIG infusion ends affects about 10–20% of patients and raises aneurysm risk. Options include a second dose of IVIG 2 g/kg, high-dose corticosteroids, or infliximab. Patients recognized as high risk at diagnosis, such as those with aneurysms already present, may receive corticosteroids with the first IVIG.
Echocardiography. Obtain echoes at diagnosis, 1–2 weeks, and 4–6 weeks after treatment, grading coronary size by z-score. If the 4–6-week study is normal, aspirin stops. Giant aneurysms (z-score ≥10 or ≥8 mm) can thrombose or become stenotic and cause myocardial infarction; they require low-dose aspirin plus anticoagulation with warfarin or low-molecular-weight heparin and lifelong cardiology follow-up.
Vaccines and aspirin. Passive antibodies in IVIG neutralize live vaccine viruses, so MMR and varicella are deferred for 11 months; inactivated vaccines stay on schedule. Children on prolonged aspirin receive yearly inactivated influenza vaccine, because influenza or varicella during salicylate therapy can cause Reye syndrome, and the live attenuated influenza vaccine is contraindicated.
Avoid ibuprofen in children taking antiplatelet aspirin: it blocks aspirin's irreversible acetylation of platelet COX-1.
Multisystem inflammatory syndrome in children
Presentation. MIS-C is a post-infectious hyperinflammatory syndrome that begins 2–6 weeks after SARS-CoV-2 infection, which was often mild or asymptomatic. Typical patients are school-age children with persistent fever and prominent gastrointestinal symptoms (abdominal pain, vomiting, diarrhea), often with rash or conjunctivitis, and many develop shock with myocardial dysfunction: reduced ejection fraction and elevated troponin and BNP. Laboratory findings include markedly elevated CRP, ferritin, and D-dimer, with lymphopenia, thrombocytopenia, and hyponatremia; SARS-CoV-2 serology is usually positive. Coronary aneurysms can occur.
Treatment. First-line therapy is IVIG 2 g/kg plus methylprednisolone, escalating to high-dose steroids, anakinra, or infliximab if the child does not respond; antiviral therapy does not treat this post-infectious syndrome. Add low-dose aspirin unless the platelet count is very low, and enoxaparin for large coronary aneurysms, documented thrombosis, or an ejection fraction below 35%. Shock is managed in the ICU with cautious fluids and inotropes, and echocardiograms are repeated during follow-up.
| Feature | Kawasaki disease | MIS-C |
|---|---|---|
| Age | Usually younger than 5 years | School-age; 2–6 weeks after SARS-CoV-2 |
| Dominant features | Mucocutaneous criteria | GI symptoms, shock, myocardial dysfunction |
| Platelets and lymphocytes | Thrombocytosis after day 7 | Thrombocytopenia and lymphopenia |
| Other labs | ↑CRP/ESR, low albumin, sterile pyuria | Very high CRP, ferritin, D-dimer, troponin, BNP |
| First-line treatment | IVIG + aspirin | IVIG + glucocorticoids, low-dose aspirin |
Juvenile idiopathic arthritis: definition and subtypes
Definition. JIA is arthritis — joint swelling, or painful limitation of motion — lasting at least 6 weeks, beginning before age 16, with other causes excluded. Morning stiffness, gelling after rest, and a limp with surprisingly little complaint of pain are typical. It is a diagnosis of exclusion: infection, leukemia, reactive arthritis, and Lyme arthritis must be considered first. A chronically inflamed knee can overgrow, producing a leg-length discrepancy with the affected leg longer.
| Subtype | Pattern | Key features |
|---|---|---|
| Oligoarticular (most common) | ≤4 joints in the first 6 months; large joints such as the knee | Girls aged 1–5; ANA often positive; highest risk of silent chronic anterior uveitis |
| Polyarticular, RF-negative | ≥5 joints | More common polyarticular form; any age |
| Polyarticular, RF-positive | ≥5 joints, symmetric small joints of hands and feet | Adolescent girls; anti-CCP, nodules, early erosions — like adult RA |
| Systemic (Still disease) | Arthritis may lag behind systemic signs | Quotidian fever, salmon rash, serositis, hepatosplenomegaly, lymphadenopathy; ANA and RF negative |
Uveitis screening. The chronic anterior uveitis of oligoarticular JIA is painless, and the eye looks white and quiet, yet it can cause cataracts, glaucoma, band keratopathy, and blindness. Only slit-lamp examination detects it, so high-risk children (ANA-positive, young at onset) are screened about every 3 months.
Systemic JIA. Fever spikes of at least 39 °C occur once or twice daily and return to normal (quotidian) for at least 2 weeks, accompanied by an evanescent salmon-pink macular rash that appears with the fevers. Labs show leukocytosis, thrombocytosis, anemia, and very high ESR, CRP, and ferritin. Treatment centers on IL-1 blockade (anakinra, canakinumab) or IL-6 blockade (tocilizumab), with steroids as needed.
JIA: complications, treatment, and mimics
Macrophage activation syndrome. A form of secondary hemophagocytic lymphohistiocytosis that occurs mainly in systemic JIA. Signs are persistent fever, hepatosplenomegaly, encephalopathy, and bleeding. Platelets, white cells, and ESR fall — the ESR drops because fibrinogen is consumed — while ferritin, triglycerides, transaminases, and D-dimer rise. It is an emergency treated with high-dose IV methylprednisolone, anakinra, and cyclosporine.
Treatment. Therapy steps up with disease activity: NSAIDs relieve symptoms; intra-articular triamcinolone treats a few inflamed joints; weekly methotrexate with folic acid is used for persistent or polyarticular disease; biologics include TNF inhibitors (etanercept, adalimumab), abatacept, and IL-1 or IL-6 blockers for systemic disease. Systemic steroids serve only as a bridge because of growth and bone toxicity. Screen for latent tuberculosis before TNF inhibitors, and monitor methotrexate with CBC and liver tests.
Leukemia mimicking arthritis. Acute lymphoblastic leukemia often presents with bone or joint pain and a limp before blasts appear in the blood. Red flags against JIA: pain that wakes the child at night or is out of proportion to the exam, bone rather than joint tenderness, even mild cytopenias, high LDH or uric acid, and a normal or low platelet count despite a high ESR.
Obtain a peripheral smear and bone marrow examination before giving steroids to a child with possible leukemia; steroids can mask the diagnosis and compromise treatment.