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Cardiac Implication in Pediatric Multisystemic Inflammatory Syndrome – Three Case Reports and Review of the Literature

Eliza Cinteza
Eliza Cinteza
, 
Cristiana Voicu
Cristiana Voicu
, 
Cosmin Grigore
Cosmin Grigore
, 
Dan Stefan
Dan Stefan
, 
Malina Anghel
Malina Anghel
, 
Felicia Galos
Felicia Galos
, 
Marcela Ionescu
Marcela Ionescu
, 
Mihaela Balgradean
Mihaela Balgradean
 und 
Alin Nicolescu
Alin Nicolescu
   | 05. Mai 2022
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Article Category: Case Presentation
Online veröffentlicht: 05. Mai 2022
Seitenbereich: 885 - 892
DOI: https://doi.org/10.47803/rjc.2020.31.4.885
Schlüsselwörter
© 2021 Eliza Cinteza et al., published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.

Figure 1

Best practices for the management of MIS-C, based on literature review and IKDR survey responses3. IKDR, International Kawasaki Disease Registry; IVIG, intravenous immunoglobulin; KD, Kawasaki disease; MIS-C, multisystem inflammatory syndrome in children.
Best practices for the management of MIS-C, based on literature review and IKDR survey responses3. IKDR, International Kawasaki Disease Registry; IVIG, intravenous immunoglobulin; KD, Kawasaki disease; MIS-C, multisystem inflammatory syndrome in children.

Figure 2

Treatment algorithm for children with multisystem inflammatory syndrome associated with COVID-19. †Prophylactic anticoagulation was considered if D-dimer was >1,000 ng/dL or progressively increasing: treatment was 1 mg/kg/d of low molecular weight heparin (Enoxaparin). When thrombosis was suspected or confirmed, the dose was increased to 1 mg/kg every 12 hours and adjusted with anti-Xa factor activity. ‡Favorable response was considered absence of fever for 48 hours, hemodynamic stability, and improvement of inflammatory parameters. AAS, acetylsalicylic acid; APTT, activated partial thromboplastin time; COVID-19, coronavirus disease; CRP, C-reactive protein; IVIG, intravenous immunoglobulin; KD, Kawasaki disease; MIS-C, pediatric inflammatory multisystem syndrome temporally associated with coronavirus disease; PCT, procalcitonin; pro-BNP, pro–brain natriuretic peptide; PT, prothrombin time; SARS-CoV-2, severe acute respiratory syndrome coronavirus 23.
Treatment algorithm for children with multisystem inflammatory syndrome associated with COVID-19. †Prophylactic anticoagulation was considered if D-dimer was >1,000 ng/dL or progressively increasing: treatment was 1 mg/kg/d of low molecular weight heparin (Enoxaparin). When thrombosis was suspected or confirmed, the dose was increased to 1 mg/kg every 12 hours and adjusted with anti-Xa factor activity. ‡Favorable response was considered absence of fever for 48 hours, hemodynamic stability, and improvement of inflammatory parameters. AAS, acetylsalicylic acid; APTT, activated partial thromboplastin time; COVID-19, coronavirus disease; CRP, C-reactive protein; IVIG, intravenous immunoglobulin; KD, Kawasaki disease; MIS-C, pediatric inflammatory multisystem syndrome temporally associated with coronavirus disease; PCT, procalcitonin; pro-BNP, pro–brain natriuretic peptide; PT, prothrombin time; SARS-CoV-2, severe acute respiratory syndrome coronavirus 23.

Figure 3

Echocardiography showing cardiac dysfunction – ejection fraction measurement by Simpson's method.
Echocardiography showing cardiac dysfunction – ejection fraction measurement by Simpson's method.

Figure 4

Coronary artery dilation and increased perivascular echogenicity in a child diagnosed with multisystem inflammatory syndrome.
Coronary artery dilation and increased perivascular echogenicity in a child diagnosed with multisystem inflammatory syndrome.

Figure 5

Tissue Doppler Imaging at septal wall showing reduced velocity of the S’ septal wave of 7 cm/s in Case 2.
Tissue Doppler Imaging at septal wall showing reduced velocity of the S’ septal wave of 7 cm/s in Case 2.

Figure 6

Dilatation of the left coronary artery with both anterior descending artery and circumflex artery aneurisms.
Dilatation of the left coronary artery with both anterior descending artery and circumflex artery aneurisms.

World Health Organization and Centers for Disease Control and Prevention definitions of the multisystem inflammatory syndrome in children. AEPC position paper2

MIS-C definition of WHO (required: all six criteria) MIS-C definition of CDC (required: all 4 criteria)
1. Children's age 0 – 19 years 1. Age <21 years
2. Fever for ≥3 days 2. Fever: documented ≥38.0°C ≥24 hours or reported subjective fever lasting ≥24 hours
3. Clinical signs of multisystem involvement (at least two of the following):

Rash or bilateral non-purulent conjunctivitis, or mucocutaneous inflammation signs (oral, hands, or feet)

Hypotension or shock

Features of myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities (including ECHO findings or elevated troponin/NT-proBNP).

Evidence of coagulopathy (prolonged prothrombin time or partial thromboplastin time, elevated D-dimer).

Acute gastrointestinal symptoms (diarrhoea, vomiting, or abdominal pain)

 3. Clinical presentation consistent with MIS-C, including all of the following:

Evidence of clinically severe illness requiring hospitalization, with multisystem (≥2) organ involvement.

Cardiovascular, renal, neurologic, haematologic, gastrointestinal, or dermatologic system.
4. Elevated markers of inflammation such as C-reactive protein, erythrocyte sedimentation rate, or procalcitonin. 4. Laboratory incidence of inflammation including, but no limited to any of the following:

Elevated C-reactive protein, erythrocyte sedimentation rate, fibrinogen, procalcitonin, D-dimer, ferritin, lactic acid dehydrogenase, interleukin 6, neutrophils.

Reduced lymphocytes, low albumin.
5. No other obvious microbial cause of inflammation, including bacterial sepsis and staphylococcal/streptococcal toxic shock syndromes. 5. No alternative plausible diagnoses.
6. Evidence of COVID-19 (RT-PCR, antigen test, or serolog positive), or likely contact with patients with COVID-19. 6. Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or exposure to a suspected or confirmed COVID-19 case within the 4 weeks prior to the onset of symptoms.

Comparative view of the treatment received by all three cases presented above

Medication Case 1 Case 2 Case 3
Corticotherapy (Methylprednisolone) ✓ ✓ ✓
Imunoglobulin ✓ ✓ ✓
Immunomodulator Anakinra ✓ – –
Inotropic support: + + –
• Dobutamine × ✓ ×
× Dopamine ✓ ✓ ×
× Adrenaline ✓ × ×
Anticoagulation (Enoxaparin) ✓ ✓ ✓
Antiplatelet therapy (Aspirin) ✓ ✓ ✓
Antibiotherapy ✓ ✓ ✓
ACE-inhibitor (Lisinopril) ✓ ✓ –
Diuretic
× Furosemide ✓ – –
× Spironolactone ✓ – –
Beta-blocant ✓ – –

Comparative view of the laboratory findings for all three patients

Parameters Case 1 Case 2 Case 3 Reference values
Leukocytes (/uL) 25.310 13.890 7.600 5.000–14.500
Neutrophils (%) 88,2% 92,4% 82,9% 30–75%
Thrombocytes (/uL) 178.000 141.000 186.000 150.000–450.000
C-reactive protein (mg/L) 137,92 231,68 161,25 0–5
Procalcitonin (ng/mL) 1,92 5,06 3,51 <0,05
Ferritin (mcg/L) 605 1518 670,32 14–124
IL-6 (pg/mL) 40,36 350,6 42,42 <7
NT-proBNP (pg/mL) 48,793 15.802 2.752 <125
D-dimers (ug/mL) 1,32 1,55 0,96 0–0,5
SARS-CoV2 Ig G antibodies Positive Positive Positive –
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Medizin, Klinische Medizin, Allgemeinmedizin, Innere Medizin, Kardiologie, Kinder- und Jugendmedizin, Kinderkardiologie, Chirurgie, Herzchirurgie
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