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peds.mis-c.v1

Multisystem inflammatory syndrome in children (MIS-C)

pediatricsacutesyndromepediatricacuteinpatient
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NEW dossier authored 2026-05-15 by shard-5-obped-id Phase C wave 2. Promoted PLANNED->INTEGRATED 2026-05-25 after manifest authoring + live PMID/RxCUI verification. Manifest authored 2026-05-25 at prisma/seed/manifests/peds.mis-c.v1.ts (batch-23 scaffold; terminology projected 1:1 from dossier). Co-located _briefs/peds.mis-c.v1.md and _research-bundles/peds.mis-c.v1.md authored in original pass. Safety verification 2026-05-25 (live PubMed E-utilities + RxNav): corrected 2 fabricated PMIDs — Belhadjer Circulation 2020 32320524->32418446 ("Acute Heart Failure in MIS-C"); Henderson ACR guidance 2020 32861530->32705809 ("ACR Clinical Guidance for MIS-C Version 1"). Corrected 2 wrong RxCUIs — tocilizumab 1442407(invalid)->612865; milrinone 41126(was fluticasone)->52769. Whittaker 32511692 + Feldstein 32598831 confirmed; remaining 12 RxCUIs confirmed. NEXT STEPS: (1) author manifest at prisma/seed/manifests/peds.mis-c.v1.ts; (2) write package _design-brief.md when package authored; (3) RxCUI validation via npm run research:rxnav for IVIG / methylprednisolone / prednisolone / anakinra / infliximab / tocilizumab / aspirin / enoxaparin / warfarin / clopidogrel / epinephrine / norepinephrine / milrinone / acetaminophen; (4) PMID verification for Belhadjer 32418446 / Whittaker 32511692 / Feldstein 32598831 / Henderson 32705809 + BATS + RECOVERY-C lookups; (5) calculator gaps — CDC MIS-C 2020 criteria-checker, LV-dysfunction-grade, MAS-overlap detector, biologic-escalation tier classifier; (6) Bayesian linkage ROS/DDx seed entries for MIS-C-specific LRs (GI prominence, reduced LVEF, D-dimer, troponin, BNP, ferritin, SARS-CoV-2 PCR / serology, CDC criteria meta-LR). Clinical content grounded in CDC MIS-C 2020 + 2023 update + AHA 2022 + AHA/ACC 2024 MIS-C management + Henderson AHA 2020 ACR/AHA tiered approach + Belhadjer Circulation 2020 cardiac involvement + Whittaker JAMA 2020 UK cohort + Feldstein NEJM 2020 US cohort + BATS observational + RECOVERY-C trial. Sibling differentiation: peds.kawasaki.core.v1 (KD-overlap MIS-C — ~ 33% UK cohort; coordinate both pathways; do not delay IVIG) + id.sepsis.peds.v1 (initial empirics until MIS-C confirmed). Cross-routing: id.covid19.core.v1 (parent illness + booster timing), peds.status_epilepticus.v1 (if seizing). Severity triggers (8 explicit): mis_c_with_cardiogenic_shock_or_severe_lv_dysfunction (life_threatening — PICU + inotropes + IVIG + pulse methylpred + early anakinra/tocilizumab + ECMO consideration; AHA 2022 + Belhadjer 32418446); mis_c_with_coronary_aneurysm_emergent (life_threatening — Z ≥ 10 → anticoagulation + cardiology; routes to peds.kawasaki.core.v1 aneurysm management; AHA 2017 + AHA 2022); ivig_refractory_mis_c_at_36_48h (severe — second IVIG OR pulse methylpred OR anakinra OR infliximab/tocilizumab; AHA/ACC 2024 + Henderson AHA 2020 Tier 3); mis_c_with_neuro_involvement (severe — MRI + LP + steroids + IVIG; routes to peds.status_epilepticus.v1 if seizing; AHA/ACC 2024); mis_c_in_immunocompromised (severe — ID + immunology consult + broader workup; AHA/ACC 2024); mis_c_late_presentation_beyond_4_weeks (severe — reconsider differential incl. atypical KD, autoimmune, immunodeficiency; Henderson AHA 2020); mis_c_vs_kawasaki_overlap_features (moderate — sibling pathway coordination; do NOT delay IVIG; AHA 2017 + AHA 2022); mis_c_with_macrophage_activation_syndrome (life_threatening — ferritin > 10,000 + cytopenia + LFT + hypofibrinogenemia → anakinra primary + pulse methylprednisolone; Henderson AHA 2020 Tier 3 + HLH-94/2004 + MAS literature). Phenotype matrix (age-band × severity × cardiac × KD-overlap × COVID-evidence × prior-immunity × treatment-response — 5 × 4 × 4 × 3 × 4 × 2 × 2 collapsed cross-product) encoded indirectly via setting_playbooks (ed / inpatient / icu / outpatient) + severity_triggers (8 explicit) + regimen_axes.mis_c_acute_4stage.steps (Stage 1 IVIG + methylpred; Stage 2 biologic escalation; Stage 3 aspirin + anticoagulation; Stage 4 outpatient taper + cardiac surveillance). First-class TS field for phenotype matrix is schema-blocked. Bayesian linkage (CDC MIS-C 2020 criteria met LR+ ~ 15-25 for MIS-C diagnosis; GI prominence LR+ ~ 3-5 for MIS-C vs KD; reduced LVEF < 55 LR+ ~ 5-10; D-dimer > 1000 LR+ ~ 5-10; troponin elevation LR+ ~ 4-8; BNP elevation LR+ ~ 3-5; ferritin > 500 LR+ ~ 3-5; > 10,000 LR+ for MAS overlap; SARS-CoV-2 PCR-current LR+ ~ 10-15; serology-prior LR+ ~ 8-12; older age 5-12 y vs KD 6mo-5y LR+ ~ 2-3; T_treat IVIG + steroids at CDC criteria met OR strongly suspected with shock; T_treat anakinra at refractory 36-48 h OR severe at presentation; T_treat anticoagulation at EF < 35 OR aneurysm Z ≥ 2.5 OR thrombus; T_test echo every confirmed/suspected MIS-C; cross-routing peds.kawasaki.core.v1 for KD-overlap, id.sepsis.peds.v1 for initial empirics, id.covid19.core.v1 for parent illness, peds.status_epilepticus.v1 for seizing) documented in _research-bundles/peds.mis-c.v1.md. ROS/DDx LR seed data audited by npm run audit:ros-ddx-coverage (cross-cutting; not touched by this shard). Prehospital state-of-play (parental concern: persistent fever + GI + COVID exposure → urgent ED referral) currently encoded implicitly via flow.entry_points; a first-class "prehospital" DossierSetting value is schema-blocked. AAP MIS-C parent education materials referenced for return-precaution guidance. Manifest authoring deferred to next deepening pass (preferred precedent: peds.kawasaki.core.v1 manifest structure with phenotypes for full / KD-overlap / refractory / cardiogenic-shock; medications for IVIG / methylpred / anakinra / infliximab / tocilizumab / aspirin / enoxaparin / warfarin; calculators for CDC MIS-C 2020 criteria-checker + LV-grade + MAS-overlap).

Entry points (6)

  • symptom
    Persistent fever ≥ 24 h in child < 21 y with SARS-CoV-2 exposure / infection in prior 4-6 weeks (CDC MIS-C 2020)
    persistent_fever_post_covid
  • symptom
    Abdominal pain / vomiting / diarrhea in child with recent COVID exposure — prominent in MIS-C (Whittaker JAMA 2020 PMID 32511692)
    gi_symptoms_with_recent_covid
  • vital_abnormality
    Age-based hypotension / poor perfusion / AMS in child with recent COVID — MIS-C cardiogenic shock phenotype (Belhadjer Circulation 2020 PMID 32418446)
    pediatric_shock_with_recent_covid
  • lab_abnormality
    CRP > 30 + ferritin > 500 + d-dimer > 1000 + lymphopenia + BNP/troponin elevation in child with recent COVID (CDC MIS-C 2020)
    hyperinflammation_pattern_peds
  • imaging
    Reduced LVEF on echo in child with recent COVID — MIS-C myocarditis (AHA 2022 MIS-C update)
    reduced_lvef_with_recent_covid
  • symptom
    Conjunctivitis + rash + lip/oral changes in child with recent COVID — KD-overlap MIS-C phenotype (Henderson Arthritis Rheumatol 2020 PMID 32705809)
    mucocutaneous_findings_post_covid

Required inputs (29)

  • agerequired
    demographic • used at CONTEXT
    CDC MIS-C 2020 requires age < 21 y; peak incidence 5-12 y vs KD 6 mo-5 y (Feldstein NEJM 2020 PMID 32598831)
  • weightrequired
    demographic • used at TREATMENT
    IVIG 2 g/kg + methylprednisolone 1-2 mg/kg/d + biologic dosing all weight-based (AHA 2022)
  • temperaturerequired
    vital • used at CONTEXT
    Fever ≥ 24 h required for CDC MIS-C 2020 criteria
  • sbprequired
    vital • used at CONTEXT
    Age-based hypotension threshold → cardiogenic shock / severe-MIS-C trigger (Belhadjer Circulation 2020)
  • hrrequired
    vital • used at CONTEXT
    Age-based tachycardia → severity indicator (Phoenix sepsis-style framing)
  • spo2required
    vital • used at CONTEXT
    Hypoxaemia indicates respiratory / cardiac compromise; intubation decision (AHA 2022)
  • gi_symptomsrequired
    symptom • used at INITIAL_WORKUP
    Abdominal pain / vomiting / diarrhea — prominent in MIS-C ~ 60-90% (Whittaker JAMA 2020)
  • mucocutaneous_findingsrequired
    symptom • used at INITIAL_WORKUP
    Conjunctivitis / rash / lip-oral changes — KD-overlap evaluation (Henderson AHA 2020)
  • mental_status_childrequired
    symptom • used at RED_FLAGS
    Neuro-involvement (encephalopathy / seizure / focal deficit) = severity marker (CDC MIS-C 2020 + AHA/ACC 2024)
  • sars_cov_2_evidencerequired
    history • used at CONTEXT
    CDC MIS-C 2020 requires PCR / serology / antigen / exposure within 4 weeks
  • covid_vaccination_historyrequired
    history • used at CONTEXT
    Vaccination status modifies likelihood + informs post-recovery COVID booster timing (CDC + AAP 2024)
  • immunocompromise_pedsrequired
    history • used at CONTEXT
    Transplant / oncology / biologics → broader workup + tiered escalation (AHA/ACC 2024)
  • crprequired
    lab • used at INITIAL_WORKUP
    CRP > 30 mg/dL supports hyperinflammation (CDC MIS-C 2020 inflammation criterion)
  • ferritinrequired
    lab • used at INITIAL_WORKUP
    Ferritin > 500 supports MIS-C; > 10,000 → consider MAS overlap (Henderson AHA 2020)
  • d_dimerrequired
    lab • used at INITIAL_WORKUP
    D-dimer > 1000 ng/mL supports hyperinflammatory + coagulopathy in MIS-C
  • troponinrequired
    lab • used at INITIAL_WORKUP
    Troponin elevation supports myocarditis in MIS-C (Belhadjer Circulation 2020)
  • bnp_or_ntprobnprequired
    lab • used at INITIAL_WORKUP
    BNP / NT-proBNP elevation supports MIS-C cardiac involvement (AHA 2022)
  • esr
    lab • used at INITIAL_WORKUP
    ESR elevated supports inflammation (CDC MIS-C 2020)
  • wbcrequired
    lab • used at INITIAL_WORKUP
    Lymphopenia + neutrophilia pattern supports MIS-C (Whittaker JAMA 2020)
  • plateletsrequired
    lab • used at INITIAL_WORKUP
    Thrombocytopenia early; recovery thrombocytosis subacute (Whittaker JAMA 2020)
  • albumin
    lab • used at INITIAL_WORKUP
    Hypoalbuminemia ≤ 3 g/dL = severity marker (Henderson AHA 2020)
  • alt
    lab • used at INITIAL_WORKUP
    Hepatitis pattern common in MIS-C (Whittaker JAMA 2020)
  • creatininerequired
    lab • used at INITIAL_WORKUP
    AKI complicates MIS-C (CDC organ-system criterion)
  • fibrinogen
    lab • used at INITIAL_WORKUP
    Hypofibrinogenemia → MAS overlap (Henderson AHA 2020)
  • sars_cov_2_pcrrequired
    lab • used at INITIAL_WORKUP
    CDC criterion — current infection (AAP Red Book 2024)
  • sars_cov_2_serologyrequired
    lab • used at INITIAL_WORKUP
    CDC criterion — prior infection within 4 weeks (most common evidence in MIS-C)
  • blood_culturerequired
    lab • used at INITIAL_WORKUP
    Exclude bacterial sepsis (CDC MIS-C exclusion criterion)
  • echocardiogramrequired
    imaging • used at INITIAL_WORKUP
    LVEF + coronary z-score + pericardial effusion at baseline + 1-2 wk + 6 wk + 1 y (AHA 2022 + AHA/ACC 2024 MIS-C surveillance)
  • ecgrequired
    imaging • used at INITIAL_WORKUP
    Arrhythmia / conduction / myocarditis screen at presentation (AHA 2022)

12-phase flow (12)

  1. 1FRAME
    MIS-C per CDC 2020 + 2023 — age < 21 y + fever ≥ 24 h + ≥ 2 organ systems + lab inflammation + SARS-CoV-2 evidence + no alt dx. Distinguish from Kawasaki (older age, GI prominence, myocarditis with reduced LVEF vs coronary aneurysm).
    inputs: age
    advance: MIS-C pattern identified per CDC 2020
  2. 2ENTRY
    Persistent fever ≥ 24 h in child < 21 y with SARS-CoV-2 exposure / infection in prior 4-6 wk; or shock with recent COVID; or hyperinflammation pattern with recent COVID
    inputs: age, weight, temperature, sars_cov_2_evidence
    advance: Trigger captured + demographic complete
  3. 3CONTEXT
    COVID exposure timing (PCR-current / serology-prior / antigen / exposure-only); vaccination history; immune status; KD criteria check; MAS overlap risk factors; comorbidities
    inputs: hr, spo2, covid_vaccination_history, immunocompromise_peds
    advance: Context complete
  4. 4RED_FLAGS
    Cardiogenic shock / severe LV dysfunction (LVEF < 35), coronary aneurysm Z ≥ 10 emergent, MAS overlap (ferritin > 10,000 + cytopenia + LFT + hypofibrinogenemia), neuro-involvement (encephalopathy / seizure / focal deficit), refractory disease at 36-48 h, immunocompromised host
    inputs: sbp, mental_status_child
    advance: Red flags screened + ICU/biologic-escalation triggers actioned
  5. 5INITIAL_WORKUP
    CDC MIS-C 2020 lab panel — CBC + CMP + LFT + coag + CRP + ESR + ferritin + d-dimer + procalcitonin + troponin + BNP/NT-proBNP + LDH + IL-6 (if available) + SARS-CoV-2 PCR + serology + blood culture + UA + imaging (CXR / echo / ECG); MRI brain + LP if neuro symptoms; imaging for abdominal source if GI dominant (rule out appendicitis)
    inputs: crp, ferritin, d_dimer, troponin, bnp_or_ntprobnp, wbc, platelets, creatinine, sars_cov_2_pcr, sars_cov_2_serology, blood_culture, echocardiogram, ecg, gi_symptoms, mucocutaneous_findings
    actions: panel.cbc, panel.inflammation, panel.lft, panel.coag, panel.renal, panel.cardiac
    advance: CDC criteria evaluable + organ-system involvement quantified
  6. 6BRANCHING_WORKUP
    KD-overlap pathway if mucocutaneous criteria met (peds.kawasaki.core.v1 parallel) → echo for coronary z-score; sepsis pathway if shock without confirmed COVID evidence (id.sepsis.peds.v1 initial empirics until MIS-C confirmed); appendicitis / acute abdomen workup if GI prominent + no confirmed MIS-C; MRI + LP if neuro; MAS workup (NK function, sIL-2R, hemophagocytosis on BM if indicated) if MAS overlap suspected
    advance: Differential resolved or co-managed
  7. 7DIFFERENTIAL
    Phenotype: full MIS-C / KD-overlap MIS-C / MIS-C with shock-dominant / MIS-C with neuro / MIS-C with MAS overlap; rule out: bacterial sepsis with positive culture, TSS, appendicitis, leptospirosis, atypical viral, autoimmune flare, primary cardiomyopathy
    advance: Phenotype assigned + alt diagnoses excluded
  8. 8RISK_STRATIFICATION
    Henderson AHA 2020 tiered approach — Tier 1 (mild / no shock / no LV dysfunction) → IVIG ± methylpred; Tier 2 (moderate / shock or LV dysfunction managed without high-dose vasoactives) → IVIG + methylpred; Tier 3 (severe / cardiogenic shock / severe LV dysfunction / refractory) → IVIG + pulse methylpred + biologic. MAS overlap = Tier 3 + anakinra primary.
    advance: Tier + biologic-escalation plan set
  9. 9TREATMENT
    Stage 1 — IVIG 2 g/kg + methylprednisolone 1-2 mg/kg/d × 5 d → PO taper (mild-moderate); pulse methylpred 30 mg/kg × 1-3 d for severe/shock/MAS. Stage 2 — refractory at 36-48 h OR severe at presentation → anakinra 4-10 mg/kg/d OR infliximab 5-10 mg/kg OR tocilizumab 8-12 mg/kg. Stage 3 — aspirin 3-5 mg/kg/d × 4-6 wk; anticoagulation (enoxaparin or warfarin INR 2-3) if EF < 35 OR aneurysm Z ≥ 2.5 OR thrombus. Inotropes (epi for cold shock; norepi for warm) + ECMO consideration if refractory.
    inputs: weight, echocardiogram
    advance: IVIG + steroid initiated; biologic plan ready; cardiac surveillance started
  10. 10DISPOSITION
    Ward for mild/moderate (no shock, no severe LV dysfunction); PICU for cardiogenic shock / severe LV dysfunction / vasoactive support / refractory / mechanical ventilation / ECMO consideration; transfer to tertiary peds-cardiology center if local capability inadequate
    inputs: sbp, spo2
    advance: Level of care + consults secured
  11. 11MONITORING
    Daily fever curve + CRP/ferritin/d-dimer/troponin/BNP trend; serial echo at baseline + 1-2 wk + 6 wk + 1 y (AHA 2022 + AHA/ACC 2024); ECG; IVIG infusion reactions; steroid AEs (glucose, BP, GI bleed); biologic AEs (infection, infusion reaction)
    inputs: crp, ferritin, d_dimer, troponin, bnp_or_ntprobnp, echocardiogram
    actions: panel.inflammation, panel.cardiac
    advance: Fever resolved + inflammation trending down + LV function recovering
  12. 12FOLLOWUP
    Outpatient peds-cardiology + peds-rheum + peds-ID f/u at 1-2 wk + 6 wk + 1 y per AHA 2022; aspirin 3-5 mg/kg/d × 4-6 wk (longer if coronary aneurysm); steroid taper PO over 2-3 wk; live vaccine deferral × 11 mo after IVIG (AAP 2024); COVID booster timing per peds-ID (defer 90 d after IVIG or per recovery); neurodev screening if neuro-involvement; transition to adult cardiology if persistent aneurysm
    advance: Long-term cardiac plan + immunization plan + transition plan documented