Episode 75 - Multisystem Inflammatory Syndrome - a podcast by Rio Bravo Family Medicine Residency Program

Episode 75: Multisystem Inflammatory Syndrome in Children (MIS-C).  

Dr Schlaerth explains the signs, symptoms, and basic management of MIS-C. Lam explain the role of anti-obesity medications in weight management. 

Introduction: The Role of Drugs in Weight Loss Management    
By Lam Chau, MS3, Ross University School of Medicine   

  

Today about 70% of adult Americans are overweight or obese. Obesity is associated with increased risk of heart disease, stroke, and diabetes, among many other diseases. Studies have shown losing 5-10% of your body weight can substantially reduce your risk of cardiovascular disease. 

 

Traditional belief is that weight loss can only be attributed to diet and exercise. While there are certainly elements of truth to that statement, medication is a safe and proven method for weight management that is often overlooked. The fact of the matter is that weight loss is an ongoing field of study with constant new research and innovations. 

 

In June of this year, a medication named Wegovy was approved for weight loss management by the 

FDA. This drug is indicated for chronic weight management in patients with a BMI of 27 or greater with an accompanying weight-related ailment or in a patient with a BMI of 30 or greater. 

Rachel Batterham, PhD, of the Centre for Obesity Research at University College London, shared: "The findings of this study represent a major breakthrough for improving the health of people with obesity. No other drug has come close to producing this level of weight loss — this really is a game changer.”

 

Despite breakthroughs like these, the use of medication for weight loss is still relatively low. Dr. Erin Bohula, a cardiologist and assistant professor at Harvard Medical School, believes “there are probably a few reasons for this, including cost, if not covered by insurance, and a perception these agents are not safe in light of the history with weight loss agents.”

 

A study from 2019 examined the medical records from eight geographically dispersed healthcare organizations. They found that out of 2.2 million patients who were eligible for weight loss medication, only 1.3% filled at least 1 prescription.

 

Weight loss is a dynamic process with many different variables. While it may not necessarily be for everyone, medication can help tremendously and is an option you should consider if you are interested in weight loss[1,2].

 

This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it’s sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. 

 

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Multisystem Inflammatory Syndrome in Children (MIS-C).   
By Katherine Schlaerth, MD, and Hector Arreaza, MD.

 

History and epidemiology

Most children who get COVID-19 have either no symptoms or very mild symptoms. However, about 18 months ago, a new pediatric complication of COVID-19, possibly postinfectious, was described. 

 

The eight children who were initially described had a clinical presentation which was similar to either Kawasaki Disease or perhaps toxic shock syndrome, and since these children had signs of a hyperinflammatory state coupled with shock, the new syndrome was named Multisystem Inflammatory Syndrome in Children, or MIS-C for short. By midsummer of 2021, the United States had about two thousand cases and 30 deaths in children under 21. 

 

Other name for this condition is Pediatric Hyperinflammatory Shock.

 

Diagnosis

What are the criteria for a diagnosis of Multisystem Inflammatory Syndrome? 

They include:

Age below 21

Fever above 100.4 degrees Fahrenheit or 38 degrees centigrade for 24 hours (a subjective fever for more than 24 hours counts too). 

Laboratory evidence of inflammation which should include at least two of the following tests: elevated CRP, elevated ESR, elevated fibrinogen level, procalcitonin, D-dimer, ferritin, lactic acid dehydrogenase (LDH), interleukin-6, and neutrophil counts, low lymphocyte count and low albumin.

Severe disease necessitating hospitalization with multisystem organs affected. The systems affected include cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic, and neurologic (at least three systems need to be involved). 

No creditable other diagnosis.

 

Other symptoms include:

GI complaints (diarrhea, vomiting, abdominal pain)

Skin rash

Conjunctivitis

Headache

Lethargy

Confusion

Respiratory distress

Sore throat

Myalgias

Swollen hands/feet

Lymphadenopathy

Cardiac signs and symptoms include troponin/BNP elevation and arrhythmia. Findings on ECHO may include depressed LVEF, coronary artery abnormalities, including dilation or aneurysm, mitral regurgitation, and pericardial effusion.

 

There also must be a positive test for SARS-CoV-2 and this test can be either a reverse transcriptase polymerase chain reaction (RT-PCR), serologic, or antigen testing. Exposure to someone who has had or is suspected of having had COVID-19 within the last 4 weeks also counts. 

 

Patients with MIS-C may have predominately gastrointestinal symptoms, mucocutaneous findings, and may be hypotensive or “shocky” on presentation. Up to 80% require ICU admission. Thrombocytopenia and /or elevated transaminase levels can also be seen. 

 

MIS-C vs Kawasaki Disease

The big issue in diagnosing MIS-C is the overlap with Kawasaki’s disease and with toxic shock syndrome. Patients with Kawasaki Disease in their second week of illness often will have thrombosis, not thrombocytopenia. Whereas MIS-C usually affects school age children or adolescents, Kawasaki Disease is more commonly a problem in younger children, who have an average age of 2 years. 

 

Kawasaki Disease is also more common in Asian children and MIS-C disproportionately seems to affect Black and Hispanic children. 

 

Obesity seems to be another risk factor for MIS-C. 

 

Kawasaki’s Disease also has different cardiac manifestations from MIS-C. Coronary artery dilatation is common in Kawasaki’s disease and left ventricular dysfunction in MIS-C, although sometimes coronary artery dilatation and rarely aneurisms can be noted on echocardiogram in putative MIS-C, which is why differentiation from Kawasaki’s Disease is an issue. 

 

Pathophysiology

The cause of MIS-C is probably postinfectious immune dysregulation. Only a minority of MIS-C patients are identified as having COVID-19 by RT-PCR, but most have positive tests for immunoglobulin G. 

 

Statistically, there is a lag of 4-6 weeks between peak community cases of COVID-19 and the time at which children present with MIS-C.  

 

Although research is being done on MIS-C, and theories abound about etiology, there is no clear-cut answer to why some children get MIS-C and the vast majority do not.

 

In a review of the literature on MIS-C using literature from December 2019 through May 2020, gastrointestinal symptoms such as diarrhea, and abdominal pain were 4-5 times more common than cough and respiratory distress. 

 

There was a slight preponderance of male patients and mean age was 8 ½ years. ICU admission was common and 2/3 required inotropic support, over ¼ needed respiratory help with extracorporeal membrane oxygenation warranted in 31 children. The death rate was 1.5 % of these very sick children treated in hospital. 

 

In another smaller study, 80% had mild, but 44% had moderate to severe EKG abnormalities including coronary involvement. The good news was that coronary arteries were normal in all children after a month, and at 4-9 months, only 2-4% had mild heart abnormalities.

 

Unfortunately, mechanisms of MIS-C as well as universal treatment is still being worked out. Published articles may be delayed due to time constraints in publishing. Other immunologic interventions do not have sufficient data.

 

Treatment

What about the treatment of children diagnosed with MIS-C?

Usually, a variety of specialists become involved initially. These can include pediatric rheumatology, infectious disease, cardiology, and hematology. If children with MIS-C meet criteria for complete or incomplete Kawasaki disease as well, regardless of COVID-19 testing results, IVIG and aspirin are reasonable. 

 

Corticosteroid use must be individualized, and if used it may require a taper. 

 

An echocardiogram can be done initially looking for coronary aneurisms and repeated in a week. 

 

In severe cases, shock may be a presenting factor needing urgent attention. Generally, the treatments used are decided by the aforementioned consults and may consist of immunomodulating therapy, including possibly IVIG (2g/kg), and/or corticosteroids methylprednisolone (30mg/kg). 

 

Antivirals

The role of antiviral therapy is unclear and remdesivir should be reserved for children with acute COVID-19. 

 

COVID-19 vaccination-associated myocarditis

Another entity which needs further evaluation is COVID-19 vaccination-associated myocarditis in adolescents. This problem is more common in young males and may occur after the administration of mRNA based COVID-19 vaccines. The presentation occurs within 2 weeks of COVID-19 vaccination, and clinical presentation can include chest pressure, abnormal biomarkers (elevated troponins), and cardiac imaging findings. It is unknown if subclinical cases occur. 

 

COVID-19 infection in children, while usually benign, has the potential to become serious, and the association between some mRNA vaccines and the occurrence of myocarditis has yet to be thoroughly studied. We look forward to more and better data to guide the care of children and young adults in these spheres.

 

The risk of having myocarditis is still higher with the actual COVID-19 than the COVID-19 vaccine. The incidence of myocarditis after BioNtech/Pfizer vaccine was 2.13 cases per 100,000 persons in a large study done in a large health care organization in Israel where more than 2 million people were vaccinated (that represents 0.00213%). Another US study showed that there were 77 cases per million doses of vaccines in young male, in contrast, there were 450 cases of myocarditis per million COVID-19 cases in the same age group.

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Conclusion: Now we conclude our episode number 74 “Multisystem Inflammatory Syndrome in Children.” Dr. Schlaerth explained that MIS-C is a work in progress in terms of pathophysiology, diagnosis, treatment, and prognosis. MIS-C and Kawasaki Disease are very similar, but, for example, GI symptoms, cardiac dysfunction, shock and multisystem dysfunction are more prominent in MIS-C than Kawasaki Disease. Whereas coronary artery aneurysms are more common in Kawasaki disease than MIS-C. Even without trying, every night you go to bed being a little wiser.

Thanks for listening to Rio Bravo qWeek. If you have any feedback about this podcast, contact us by email RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. This podcast was created with educational purposes only. Visit your primary care physician for additional medical advice. This week we thank Hector Arreaza, Katherine Schlaerth, and Lam Chau. Audio edition: Suraj Amrutia. See you next week! 

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References:

FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014, June 04, 2021, U.S. Food and Drug Administration (FDA), https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014.

 

Saxon DR, Iwamoto SJ, Mettenbrink CJ, et al. Antiobesity Medication Use in 2.2 Million Adults Across Eight Large Health Care Organizations: 2009-2015. Obesity (Silver Spring). 2019;27(12):1975-1981. doi:10.1002/oby.22581. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868321/. 

 

Carroll, Linda, Weight-loss pills can help. So why don't more people use them? NBC News Health Care, September 2, 2018.  https://www.nbcnews.com/health/health-care/weight-loss-pills-can-help-so-why-don-t-more-n905211

 

World Health Organization, WHO recommends groundbreaking malaria vaccine for children at risk, October 6, 2021. https://www.who.int/news/item/06-10-2021-who-recommends-groundbreaking-malaria-vaccine-for-children-at-risk

 

Lee, Min-Sheng et. al, Similarities and Differences Between COVID-19-Related Multisystem Inflammatory Syndrome in Children and Kawasaki Disease, Front. Pediatr., 18 June 2021, https://doi.org/10.3389/fped.2021.640118. 

 

Gail F. Shust, Vijaya L. Soma, Philip Kahn and Adam J. Ratner, Pediatrics in Review July 2021, 42 (7) 399-401; DOI: https://doi.org/10.1542/pir.2020-004770.

 

Jain SS, Steele JM, Fonseca B, et al. COVID-19 vaccination-associated myocarditis in adolescents. Pediatrics. 2021; doi:10.1542/peds.2021-053427.  https://pediatrics.aappublications.org/content/pediatrics/early/2021/08/12/peds.2021-053427.full.pdf. 

 

Wilson, Clare, Myocarditis is more common after covid-19 infection than vaccination,  New Scientist, 4 August 2021, https://www.newscientist.com/article/mg25133462-800-myocarditis-is-more-common-after-covid-19-infection-than-vaccination/#ixzz79JPn2E47.

 

Son, Mary Beth F, MD, and Kevin Friedman, MD, COVID-19: Multisystem inflammatory syndrome in children (MIS-C) clinical features, evaluation, and diagnosis, Up to Date, September 2021, https://www.uptodate.com/contents/covid-19-multisystem-inflammatory-syndrome-in-children-mis-c-clinical-features-evaluation-and-diagnosis?search=kawasaki%20vs%20misc&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

 

 

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