COVID-19-associated multisystem inflammatory syndrome: Difference between revisions

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== Classification of Disease Severity of MIS-C ==
== Classification of Disease Severity of MIS-C ==


*'''Mild Disease<ref name=":0"><https://www.chkd.org/uploadedFiles/Documents/COVID-19/CHKD%20MIS-C%20Guideline%20D2.pdf |title=www.chkd.org |format= |work= |accessdate=></ref>'''
*'''Mild Disease'''
*Children with MIS-C fall under this category who-
*Children with MIS-C fall under this category who-
**require minimal to no respiratory support.
**require minimal to no respiratory support.
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*Evidence of [[COVID-19|COVID]]-19 ([[Reverse transcription-polymerase chain reaction|RT-PCR]], antigen test or serology-positive), or likely contact with patients with [[COVID-19|COVID]]-19
*Evidence of [[COVID-19|COVID]]-19 ([[Reverse transcription-polymerase chain reaction|RT-PCR]], antigen test or serology-positive), or likely contact with patients with [[COVID-19|COVID]]-19


=====CDC Case Definition for MIS-C<ref><{{cite web |url=https://www.cdc.gov/mis-c/hcp/ |title=Information for Healthcare Providers about Multisystem Inflammatory Syndrome in Children (MIS-C) &#124; CDC |format= |work= |accessdate=}}></ref>=====
=====CDC Case Definition for MIS-C=====


*An individual aged <21 years presenting with fever, laboratory evidence of inflammation**, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological);
*An individual aged <21 years presenting with fever, laboratory evidence of inflammation**, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological);<ref><{{cite web |url=https://www.cdc.gov/mis-c/hcp/ |title=Information for Healthcare Providers about Multisystem Inflammatory Syndrome in Children (MIS-C) &#124; CDC |format= |work= |accessdate=}}></ref>


AND
AND
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=== Signs and Symptoms ===
=== Signs and Symptoms ===


*[[Fever]] lasting 24 hours or longer.<ref>{{cite web |url=https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf|title=Guidance: Paediatric multisystem inflammatory
*[[Fever]] lasting 24 hours or longer.
syndrome temporally associated with COVID-19 |format= |work= |accessdate=}}</ref>
*[[Vomiting]]<ref name=":1" />
*[[Vomiting]]
*[[Diarrhea]]<ref name=":1" />
*[[Diarrhea]]
*[[Abdominal pain]]<ref name=":1" />
*[[Abdominal pain]]
*[[Skin rash]]<ref name=":1" />
*[[Skin rash]]
*[[Conjuctivitis]]<ref name=":1" />
*[[Conjuctivitis]]
*[[Erythrocyte sedimentation rate|High ESR]]<ref name=":1" />
*[[Erythrocyte sedimentation rate|High ESR]]
*Redness or swelling of the lips and tongue<ref name=":1" />
*Redness or swelling of the lips and tongue
*[[Lethargy]]<ref name=":1" />
*[[Lethargy]]
*[[Redness]] or swelling of the hands or feet
*[[Redness]] or swelling of the hands or feet
*[[Confusion]]
*[[Confusion]]<ref name=":1" />
*[[Headache]]
*[[Headache]]<ref name=":1" />
*[[Sore throat]]
*[[Sore throat]]<ref name=":1" />
*[[Syncope]]
*[[Syncope]]<ref name=":1" />
*[[Lymphadenopathy]]
*[[Lymphadenopathy]]<ref name=":1" />


'''Emergency Warning Signs'''
'''Emergency Warning Signs'''


*[[Shortness of breath|Difficulty Breathing]]
*[[Shortness of breath|Difficulty Breathing]]<ref name=":1" />
*[[Chest pain]]
*[[Chest pain]]<ref name=":1" />
*[[Confusion|New onset confusion]]
*[[Confusion|New onset confusion]]<ref name=":1" />
*[[Lethargy]]
*[[Lethargy]]<ref name=":1" />
*[[Cyanosis]]
*[[Cyanosis]]<ref name=":1" />
*[[Abdominal pain]]
*[[Abdominal pain]]<ref name=":1" />


=== Physical Examination ===
=== Physical Examination ===
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'''Blood Investigations'''
'''Blood Investigations'''


*[[Lymphopenia]], [[Neutrophilia]], [[Anemia]], [[Thrombocytopenia]] have been seen in MIS-C pateints. [[Fibrinogen|Abnormal fibrinogen]], [[Hypoalbuminaemia]], elevated [[Creatine kinase|creatiine kinase]] (CK), [[Lactate dehydrogenase|LDH]], [[Triglyceride|triglycerides]] have been observed in MIS-C patients.
*[[Lymphopenia]], [[Neutrophilia]], [[Anemia]], [[Thrombocytopenia]] have been seen in MIS-C pateints. [[Fibrinogen|Abnormal fibrinogen]], [[Hypoalbuminaemia]], elevated [[Creatine kinase|creatiine kinase]] (CK), [[Lactate dehydrogenase|LDH]], [[Triglyceride|triglycerides]] have been observed in MIS-C patients.<ref name=":1" />


==== Inflammatory biomarkers ====
==== Inflammatory biomarkers ====
Elevation of inflammatory markers including ESR, C reactive protein and procalcitonin are  usually seen in MIS-C. Increased level of  [[Interleukin-6]] (IL-6), Interleukin-10(IL-10) [[d-dimer]], serum [[ferritin]], [[prothrombin time]] have also been seen in MIS-C.
Elevation of inflammatory markers including ESR, C reactive protein and procalcitonin are  usually seen in MIS-C. Increased level of  [[Interleukin-6]] (IL-6), Interleukin-10(IL-10) [[d-dimer]], serum [[ferritin]], [[prothrombin time]] have also been seen in MIS-C.<ref name=":1" />


==== Cardiac biomarkers ====
==== Cardiac biomarkers ====
Elevation of cardic enzymes including  [[Cardiac troponin|cardiac troponins]] ([[Cardiac troponin I (cTnI) and T (cTnT)|cardiac troponin I(cTnI) and cardiac troponin T (cTnT)]]) and [[Brain natriuretic peptide]] ([[BNP]])) has been observed in MIS-C patients.
Elevation of cardic enzymes including  [[Cardiac troponin|cardiac troponins]] ([[Cardiac troponin I (cTnI) and T (cTnT)|cardiac troponin I(cTnI) and cardiac troponin T (cTnT)]]) and [[Brain natriuretic peptide]] ([[BNP]])) has been observed in MIS-C patients.<ref name=":1" />


=== Radiological Findings ===
=== Radiological Findings ===


* Following Radiological Findings are observed in MIS-C patients.
* Following Radiological Findings are observed in MIS-C patients.<ref name=":1" />


{| border="1" cellpadding="2"
{| border="1" cellpadding="2"
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*Supplemental [[oxygen]] is required in children with low oxygen saturation.
*Supplemental [[oxygen]] is required in children with low oxygen saturation.
*[[Fluid replacement|Fluid resuscitation]] in 10 ml/kg aliquots with reevaluation after each bolus. Maintain euvolemia. Avoid hypervolemia.
*[[Fluid replacement|Fluid resuscitation]] in 10 ml/kg aliquots with reevaluation after each bolus. Maintain euvolemia. Avoid hypervolemia.
*Anti-inflammatory treatments with [[Intravenous immunoglobulin|Intravenous immunoglobulin(IVIG]]) with or without [[Corticosteroid|corticosteroids]] have shown a good response rate.<ref name="RajapakseDixit20202">{{cite journal|last1=Rajapakse|first1=Nipunie|last2=Dixit|first2=Devika|title=Human and novel coronavirus infections in children: a review|journal=Paediatrics and International Child Health|year=2020|pages=1–20|issn=2046-9047|doi=10.1080/20469047.2020.1781356}}</ref>
*Anti-inflammatory treatments with [[Intravenous immunoglobulin|Intravenous immunoglobulin(IVIG]]) with or without [[Corticosteroid|corticosteroids]] have shown a good response rate.
*[[Aspirin]] has been used primarily for its antiplatelet effect. It is recommended in all patients with [[MIS-C]].<ref name="RajapakseDixit2020" />
*[[Aspirin]] has been used primarily for its antiplatelet effect. It is recommended in all patients with [[MIS-C]].<ref name="RajapakseDixit2020" />
*[[Anakinra]] is considered if fevers last more than 24 hours post [[Steroid|steroids]]/[[Intravenous immunoglobulin|IVIG]] or in the moderate or severe presentation.
*[[Anakinra]] is considered if fevers last more than 24 hours post [[Steroid|steroids]]/[[Intravenous immunoglobulin|IVIG]] or in the moderate or severe presentation.

Revision as of 22:56, 11 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Harmeet Kharoud M.D.[2]

Synonyms and keywords: Multisystem Inflammatory Syndrome in Children (MIS-C)

Overview

Multisystem Inflammatory Syndrome in Children (MIS-C) is a condition that causes inflammation of some parts of the body like heart, blood vessels, kidneys, digestive system, brain, skin, or eyes. According to recent evidence, it is suggested that children with MIS-C had antibodies against COVID-19 suggesting children had COVID-19 infection in the past. This syndrome appears to be similar in presentation to Kawasaki disease, hence also called Kawasaki -like a disease. It also shares features with staphylococcal and streptococcal toxic shock syndromes, bacterial sepsis, and macrophage activation syndromes.

Historical Perspective

Classification of Disease Severity of MIS-C

  • Mild Disease
  • Children with MIS-C fall under this category who-
    • require minimal to no respiratory support.
    • minimal to no organ injury
    • normotensive
    • Do not meet the criteria for ICU admission.
  • Severe Disease[1]
  • Children with MIS-C fall under this category who-
    • have significant oxygen requirements (HFNC, BiPAP, mechanical ventilation).
    • have a mild-severe organ injury and ventricular dysfunction.
    • have a vasoactive requirement.
    • meet the criteria for ICU admissions

Pathophysiology

Differentiating Any Disease from other disease

Epidemiology and Demographics

  • According to a recent study among the 186 children with MIS-C, the rate of hospitalization was 12% between March 16 and April 15 and 88% between April 16 and May 20.
  • 80% of the children were admitted to the intensive care unit and 20% of the children required mechanical ventilation.
  • 4% of the children required extracorporeal membrane oxygenation.
  • The mortality rate among 186 children with MIS-C was 2%.

Age

  • Among the 186 children with MIS-C distribution of age group was
    • <1yr-7%
    • 1-4yr-28%
    • 5-9yr-25%
    • 10-14yr-24%
    • 15-20yr-16%.

Gender

  • Among the 186 children with MIS-C

Comorbidities

  • Children with MIS-C had following underlying comorbidities.
    • Clinically diagnosed Obesity-8%
    • BMI-Based Obesity-29%
    • Cardiovascular diasease-3%
    • Respiratory disease-18%
    • Autoimmune disease or immunocompromising condition-5%

Organ System Involved

  • 71% of children had involvement of at least four organ systems.

The most common organ system involved in MIS-C children among a total of 183 children were.

  • Gastrointestinal(92%)
  • Cardiovascular(80%)
  • Hematologic(76%)
  • Mucocutaneous(74%)
  • Pulmonary(70%)
  • Historical perspective

Risk Factors

Natural History, Complications and Prognosis

Natural history

Complications

Prognosis

Diagnosis

Diagnostic Criteria

Preliminary WHO case definition: Children and adolescents
  • 0–19 years of age with fever >3 days

AND

  • Two of the following:
  1. Rash or bilateral non-purulent conjunctivitis or mucocutaneous inflammation signs (oral, hands or feet)
  2. Hypotension or shock
  3. Features of myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities (including ECHO findings or elevated Troponin/NT-proBNP)
  4. Evidence of coagulopathy (by PT, PTT, elevated D-Dimers)
  5. Acute gastrointestinal problems (diarrhea, vomiting, or abdominal pain)

AND

AND

AND

  • Evidence of COVID-19 (RT-PCR, antigen test or serology-positive), or likely contact with patients with COVID-19
CDC Case Definition for MIS-C
  • An individual aged <21 years presenting with fever, laboratory evidence of inflammation**, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological);[2]

AND

No alternative plausible diagnoses;

AND

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.

Signs and Symptoms

Emergency Warning Signs

Physical Examination

Laboratory Findings

Blood Investigations

Inflammatory biomarkers

Elevation of inflammatory markers including ESR, C reactive protein and procalcitonin are usually seen in MIS-C. Increased level of Interleukin-6 (IL-6), Interleukin-10(IL-10) d-dimer, serum ferritin, prothrombin time have also been seen in MIS-C.[3]

Cardiac biomarkers

Elevation of cardic enzymes including cardiac troponins (cardiac troponin I(cTnI) and cardiac troponin T (cTnT)) and Brain natriuretic peptide (BNP)) has been observed in MIS-C patients.[3]

Radiological Findings

  • Following Radiological Findings are observed in MIS-C patients.[3]
Test Findings
Chest Xray patchy symmetrical infiltrates, pleural effusion
Echocardiogram and EKG myocarditis, valvulitis, pericardial effusion, coronary artery dilatation
Abdominal USG colitis, ileitis, lymphadenopathy, ascites, hepatosplenomegaly

Blood Culture, Viral PCR

  • Absence of other potential causative organisms. IgGlevels and IgM levels of SARS-CoV-2 are detected.

Treatment

Medical Therapy

  • All the children with MIS-C are treated as suspected COVID-19.
  • Mild to Moderate cases of MIS-C are managed supportively.
  • Supplemental oxygen is required in children with low oxygen saturation.
  • Fluid resuscitation in 10 ml/kg aliquots with reevaluation after each bolus. Maintain euvolemia. Avoid hypervolemia.
  • Anti-inflammatory treatments with Intravenous immunoglobulin(IVIG) with or without corticosteroids have shown a good response rate.
  • Aspirin has been used primarily for its antiplatelet effect. It is recommended in all patients with MIS-C.[4]
  • Anakinra is considered if fevers last more than 24 hours post steroids/IVIG or in the moderate or severe presentation.
  • Tocilizumab is also considered if fevers last more than 24 hours post steroids/IVIG or in the moderate or severe presentation.
  • Empiric antibiotics like vancomycin, ceftriaxone, and clindamycin are given for community-acquired shock presentation until cultures are negative for 48 hours.
Presentation Treatment
Mild Disease
  • Symptomatic Treatment
Severe Disease


Prevention of MIS-C

  • MIS-C can be prevented by reducing the risk of child exposure to COVID-19 infection.

References

  1. <"Information for Healthcare Providers about Multisystem Inflammatory Syndrome in Children (MIS-C) | CDC".>
  2. 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 3.17 3.18 3.19 3.20 3.21 3.22