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Multisystem Inflammatory Syndrome in Children
MIS-C

Presentation

[…] this diagnosis,” Andrea Maderal, MD, said during the presentation. [healio.com]

This type of presentation is rare in KD. [pediatrics.aappublications.org]

Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management. [mdpi.com]

Case Presentation A nine-year-old female presented to a primary care physician with a two-day history of fever and a one-day history of emesis with loss of appetite and fatigue. Her medical history was significant only for mild asthma. [cureus.com]

During the coronavirus disease 19 (COVID-19) pandemic, there has been an influx of children presenting with clinical characteristics of multisystem inflammatory syndrome in children (MIS-C) and incomplete Kawasaki Disease, according to a study published [infectiousdiseaseadvisor.com]

Immune System

  • Cervical Lymphadenopathy

    The diagnosis of classic KD is based on the presence of fever lasting five days or longer together with at least four of five additional clinical findings: bilateral conjunctivitis, oral mucosal changes, cervical lymphadenopathy, extremity changes, and [pediatricsresearchjournal.com]

    lymphadenopathy, and the consequences of vascular inflammation leading to damage to the coronary arteries and aneurysm formation).12 Some differences have been noted in pediatric inflammatory multisystem syndrome, including older age; higher prevalence [cmaj.ca]

    (%) 38 (100) 27 (75) 45 (40) 110 (59) Cervical lymphadenopathy >1.5 cm diameter — no. (%)§ 7 (18) 3 (8) 8 (7) 18 (10) Echocardiography performed — no. (%) 37 (97) 35 (97) 98 (88) 170 (91) LAD or RCA z score of ≥2.5¶ 3 (8) 8 (23) 4 (4) 15 (9) Treatment [nejm.org]

    There was no cervical lymphadenopathy or abnormal tongue manifestations. His lungs were clear and he had no murmurs or cardiac friction rub. His abdomen was soft without tenderness or hepatosplenomegaly. [academic.oup.com]

Entire Body System

  • Fever

    Persistent fever without a clear clinical source is the first clue. Any fever that is accompanied by symptoms concerning in their severity or coincident with recent exposure to a person with COVID-19 should raise suspicions. [services.aap.org]

    Because of persistent fever and cytopenias, we added anakinra, a recombinant interleukin (IL)-1 receptor antagonist, at 100 mg/d (about 2.75 mg/kg/d) on DAA 7. His fever resolved on the same day. [cmaj.ca]

    If your child has a persistent high fever, see a doctor. Does your child have persistent fever, skin rash, vomiting, or other symptoms related to MIS-C? If they're under 21, Dr. [parents.com]

    All presented with fever, 117 of 183 (63.9%) with gastrointestinal symptoms, and 79 of 183 (43.2%) with shock, which was associated with Black race, higher inflammation, and imaging abnormalities. [pubmed.ncbi.nlm.nih.gov]

    If at any time, while you are awaiting results, your child becomes ill or shows high fever over several days, please seek immediate medical attention at your nearest emergency room. [chla.org]

  • High Fever

    If at any time, while you are awaiting results, your child becomes ill or shows high fever over several days, please seek immediate medical attention at your nearest emergency room. [chla.org]

    Symptoms include a high fever, rash, swollen glands in the neck, swollen hands and feet, cracked lips, and red eyes. [prevention.com]

    The red eyes, high fever, and sometimes cracked lips, those are typical signs of Kawasaki. [healthmatters.nyp.org]

    If your child has a persistent high fever, see a doctor. Does your child have persistent fever, skin rash, vomiting, or other symptoms related to MIS-C? If they're under 21, Dr. [parents.com]

    “If you got a high fever for a kid for three days or more, then you might want to call in,” said Aspirus Regional Medical Director Dr. Larry Gordon. [wsaw.com]

  • Fatigue

    […] several symptoms with you, and will be particularly alert to children who have experienced a high fever combined with other symptoms that may include: Abdominal pain/diarrhea/vomiting without another explanation Red eyes Red, cracked lips Rash Severe fatigue [chla.org]

    For children with MIS-C, symptoms can vary from one child to another and can involve any combination of fever lasting more than 24 hours; stomach pain; vomiting; diarrhea; rash; red and bloodshot eyes; extreme fatigue; confusion; trouble breathing; or [uspharmacist.com]

    People are getting COVID-19 fatigue, and much of the recent rise in case numbers is due to community spread of the infection. Taking precautions to prevent the spread of COVID-19 is critical, particularly as the virus continues to evolve. [newsnetwork.mayoclinic.org]

    The main thing to watch for is a persistent fever (lasting more than 24 hours and usually present for several days), your child appearing fatigued and ill, or loss of appetite or not drinking enough fluids. [childrenshospital.org]

    Other common MIS-C symptoms include fever, vomiting, diarrhea, abdominal pain, extreme fatigue, bloodshot eyes, rash, and neck pain. [parents.com]

  • Edema of the Hands and Feet

    […] of the hands and feet, cervical adenopathy, and rash (11). [jci.org]

    Mucocutaneous involvement was defined as presence of any of the following: rash, inflammation of the oral mucosa, conjunctivitis, and extremity findings, including erythema or edema of the hands or feet, or periungual peeling. [jamanetwork.com]

    Notably, fever, adenomegaly, rash, involvement of the mucous membranes, edema of the hands and feet, and involvement of the coronary arteries are clinical criteria for the diagnosis of Kawasaki disease. [jped.elsevier.es]

Respiratoric

  • Cough

    Practice cough and sneeze etiquette by covering your nose and mouth with a tissue when sneezing or coughing, throwing the tissue in the closest garbage can, and washing your hands after you throw it away. [cdc.gov]

    Children who have MIS-C generally did not have obvious symptoms when they were infected with novel coronavirus, like cough, and generally were healthy prior to developing MIS-C. Do you need to have another health condition to get MIS-C? No. [chla.org]

    […] general, these seem to be the main signs of pediatric multi-system inflammatory syndrome: Fever Skin rash Unusual abdominal pain Vomiting or diarrhea Pink or red eyes Swollen hands or feet Enlarged lymph nodes on the neck Respiratory symptoms like a cough [prevention.com]

    Most kids report mild respiratory symptoms, namely fever, dry cough and fatigue. However, some children can become seriously ill. [cnbc.com]

  • Dyspnea

    Case 1 Case 2 Characteristics       Gender Male   Female Age (years) 15   14   1stadmission 2ndadmission   Weight (kg) 60 67 50 BMI (kg/m2) 19.59 21.88 34.72 Signs and symptoms       Fever Yes No Yes Cough, dyspnea Yes Yes Yes Sore throat No No Yes Decreased [hindawi.com]

    Imaging tests are indicated for patients who have respiratory symptoms (tachypnea, dyspnea, and/or hypoxemia). [jped.elsevier.es]

    He had dry lips and appeared tired, but reported no history of photophobia, nasal congestion, rhinorrhea, sore throat, chest pain, dyspnea, abdominal pain, swelling or redness of hands or feet, rash, irritability, neck pain, or neurological changes. [academic.oup.com]

    […] months to 21 years, (median 13.1 years) 1 months to 21 years, (median 15 years) Comorbidities None 40 (83%) None CHD (2) Obesity, asthma Obesity, respiratory, heart disease, hematologic system, diabetes, neurologic, 74.3% Presentation Fever, cough Fever, dyspnea [liebertpub.com]

Gastrointestinal

  • Vomiting

    [citation needed] Special bags are often supplied on boats for sick passengers to vomit into. Most people try to contain their vomit by vomiting into a sink, toilet, or trash can, as vomit is difficult and unpleasant to clean. [en.wikipedia.org]

    Vomiting. Diarrhea. Stomach pain. Skin rash. Red eyes. Redness or swelling of the lips and tongue. Feeling unusually tired. Redness or swelling of the hands or feet. [newsnetwork.mayoclinic.org]

    Children and adolescents 0-19 years of age requiring hospitalization with fever ≥ 3 days AND two of the following: a) Acute gastrointestinal symptoms (abdominal pain, vomiting, diarrhoea) b) Rash or bilateral non-purulent conjunctivitis or muco-cutaneous [bccdc.ca]

    Symptoms of TSS include confusion, diarrhea, headaches, high fever, low blood pressure, muscle aches, nausea, vomiting, red eyes, seizures, and organ failure. [prevention.com]

    Symptoms that have been seen in kids include: a fever belly pain vomiting or diarrhea a rash neck pain red, cracked lips red eyes being extra tired swollen hands or feet swollen lymph nodes If your child has any of these symptoms, call your doctor. [kidshealth.org]

  • Diarrhea

    […] effects in chronic functional diarrhea, radiation-induced diarrhea, and chemotherapy-induced diarrhea.[46] Another absorbent agent used for the treatment of mild diarrhea is kaopectate. [en.wikipedia.org]

    Diarrhea. Stomach pain. Skin rash. Red eyes. Redness or swelling of the lips and tongue. Feeling unusually tired. Redness or swelling of the hands or feet. [newsnetwork.mayoclinic.org]

    Gastrointestinal symptoms such as abdominal pain, diarrhea, nausea/vomiting (patients have presented with colitis, hepatitis, and questionable appendicitis). [services.aap.org]

    Symptoms of TSS include confusion, diarrhea, headaches, high fever, low blood pressure, muscle aches, nausea, vomiting, red eyes, seizures, and organ failure. [prevention.com]

    Symptoms that have been seen in kids include: a fever belly pain vomiting or diarrhea a rash neck pain red, cracked lips red eyes being extra tired swollen hands or feet swollen lymph nodes If your child has any of these symptoms, call your doctor. [kidshealth.org]

  • Abdominal Pain

    […] edit] The location of abdominal pain can provide information about what may be causing the pain. [en.wikipedia.org]

    Some children may have one or more of the following symptoms: Unexplained or persistent fever Abdominal pain, which may lead to vomiting or diarrhea Neck pain Rash Red eyes Swelling around the eyes, hands or feet Most children with MIS-C appear to be [choa.org]

    Gastrointestinal symptoms such as abdominal pain, diarrhea, nausea/vomiting (patients have presented with colitis, hepatitis, and questionable appendicitis). [services.aap.org]

    Children and adolescents 0-19 years of age requiring hospitalization with fever ≥ 3 days AND two of the following: a) Acute gastrointestinal symptoms (abdominal pain, vomiting, diarrhoea) b) Rash or bilateral non-purulent conjunctivitis or muco-cutaneous [bccdc.ca]

    Again, the symptoms of pediatric multi-system inflammatory syndrome are varied right now, but if your child develops a rash, red eyes, a high fever, or abdominal pain, Dr. Schaffner says you should see your child’s pediatrician immediately. [prevention.com]

  • Loss of Appetite

    A week later, the headaches turned into sleepiness, a loss of appetite, and a fever. Sharp, who grew more concerned, checked her daughter into the High-Smith Rainey Specialty Hospital Services. [abc11.com]

    The main thing to watch for is a persistent fever (lasting more than 24 hours and usually present for several days), your child appearing fatigued and ill, or loss of appetite or not drinking enough fluids. [childrenshospital.org]

    Case Presentation A nine-year-old female presented to a primary care physician with a two-day history of fever and a one-day history of emesis with loss of appetite and fatigue. Her medical history was significant only for mild asthma. [cureus.com]

    He complained of fatigue, headaches, and loss of appetite. Characteristics and laboratory findings at admission and imaging results are noted in Table 3. A positive PCR for SARS-CoV-2 confirmed COVID-19 the day of admission. [hindawi.com]

  • Abdominal Distension

    […] pain (sudden onset of localized pain), abdominal distension, rigid abdomen Clinical (history & physical exam) Imaging (abdominal X-ray or CT showing free air) Labs (complete blood count) Aggressive IV fluid resuscitation General surgery consultation [en.wikipedia.org]

Cardiovascular

  • Hypotension

    […] requiring hospitalization with fever ≥ 3 days AND two of the following: a) Acute gastrointestinal symptoms (abdominal pain, vomiting, diarrhoea) b) Rash or bilateral non-purulent conjunctivitis or muco-cutaneous inflammation signs (oral, hands or feet) c) Hypotension [bccdc.ca]

    In addition to acute myocardial systolic dysfunction, all children were hypotensive and 15 showed clinical signs of vasoplegia (warm extremity and immediate capillary refill time). [annalsofintensivecare.springeropen.com]

    In 2009, Kanegaye et al. (18) noted an increasing number of patients at their center presenting with acute KD accompanied by shock and hypotension, and defined this severe presentation as Kawasaki disease shock syndrome (KDSS). [jci.org]

    Patients presented with a persistent fever and a constellation of symptoms including hypotension, multiorgan (e.g., cardiac, gastrointestinal, renal, hematologic, dermatologic and neurologic) involvement, and elevated inflammatory markers.2 Respiratory [emergency.cdc.gov]

    The following interventions have been used: If patients appear hypotensive and septic during evaluation for MIS-C, treatment with antibiotics, fluid resuscitation, and if necessary, inotropes is appropriate until bacterial infection has been ruled out [services.aap.org]

  • Tachycardia

    An electrocardiogram demonstrated sinus tachycardia with prolongation of his corrected QT interval (QTc) to 500 ms with biphasic and inverted T-waves in the precordial leads. [academic.oup.com]

    Shock was defined as tachycardia and one of the following signs: arterial systemic hypotension, cold extremity, decrease peripheral pulse, capillary refill time > 3 s, oliguria or arterial blood lactate > 2 mmol/L [9]. [annalsofintensivecare.springeropen.com]

    […] tumors, severe constipation, hemorrhoids Vascular: embolism, thrombosis, hemorrhage, sickle cell disease, abdominal angina, blood vessel compression (such as celiac artery compression syndrome), superior mesenteric artery syndrome, postural orthostatic tachycardia [en.wikipedia.org]

    This would result in clinical findings such as tachycardia, hypotension, erythema, edema, arrhythmias, urticaria, and diarrhea. [pediatricsresearchjournal.com]

Jaw & Teeth

  • Cracked Lips

    Symptoms that have been seen in kids include: a fever belly pain vomiting or diarrhea a rash neck pain red, cracked lips red eyes being extra tired swollen hands or feet swollen lymph nodes If your child has any of these symptoms, call your doctor. [kidshealth.org]

    Most children with MIS-C have fever lasting several days and may show symptoms of: Irritability or decreased activity Abdominal pain without another explanation Diarrhea Vomiting Rash Conjunctivitis Lack of appetite Red or cracked lips Red or bumpy tongue [nbc12.com]

    In younger children - it starts with a fever, symptoms like a rash, red palms, red and cracked lips, irritated eyes and an exceptionally red, strawberry tongue. [fox2detroit.com]

    Specific features of MIS-C may include: Kawasaki-like symptoms: Rash, bloodshot eyes, swollen hands and feet, cracked lips, a swollen tongue that looks like a strawberry, and an enlarged lymph node in the neck. [childrenshospital.org]

  • Strawberry Tongue

    Lip involvement is common, while eye and tongue involvement — including the strawberry tongue frequently reported in Kawasaki disease — is less common. [healio.com]

    The symptoms were varied and included rash (80%), conjunctivitis (60%), changes in oral mucosa (57%), erythema (51%), edema (40%), lip hyperemia (49%) or cracking (37%) and strawberry tongue (23%). [consultqd.clevelandclinic.org]

    In younger children - it starts with a fever, symptoms like a rash, red palms, red and cracked lips, irritated eyes and an exceptionally red, strawberry tongue. [fox2detroit.com]

    tongue) Fevera + cervical lymphadenopathy exanthematous polymorphous rash extremity changes (desquamation of hands and feet) bilateral nonsuppurative conjunctivitis oral mucosal changes (strawberry tongue) neurologic alterations abdominal pain diarrhea [pediatricsresearchjournal.com]

    Shared features include fever (38.5 °C) 5 days or longer plus the classic diagnostic features of Kawasaki disease (i.e., rash, nonexudative conjunctival injection, oromucosal changes [strawberry tongue, red and/or cracked lips], peripheral changes [swelling [cmaj.ca]

  • Tonsillar Exudate

    His exam was notable for bilateral non-exudative bulbar conjunctivitis, dry lips, and oropharyngeal hyperemia with a right tonsillar exudate. He did not display irritability or meningeal signs. [academic.oup.com]

Eyes

  • Photophobia

    He had dry lips and appeared tired, but reported no history of photophobia, nasal congestion, rhinorrhea, sore throat, chest pain, dyspnea, abdominal pain, swelling or redness of hands or feet, rash, irritability, neck pain, or neurological changes. [academic.oup.com]

Musculoskeletal

  • Ankle Pain

    He was immediately treated with intravenous immunoglobulin (IVIG) (2 g/kg) and aspirin (ASA) (80 mg/kg/day high dose), after which he defervesced and his diarrhea and ankle pain resolved. [academic.oup.com]

Skin

  • Skin Rash

    Skin rash and swelling of extremities. Faintness and low blood pressure that is new. If you or a loved one experiences any of the emergency warning signs, seek care immediately. [newsnetwork.mayoclinic.org]

    The symptoms vary depending on which organ system is affected, according to the New York Department of Public Health but, in general, these seem to be the main signs of pediatric multi-system inflammatory syndrome: Fever Skin rash Unusual abdominal pain [prevention.com]

    Does your child have persistent fever, skin rash, vomiting, or other symptoms related to MIS-C? If they're under 21, Dr. Daskalakis says to report it to the health department immediately, even if they have received a negative coronavirus test. [parents.com]

    At least one feature of Kawasaki disease was found in all children (fever, n = 20, skin rash, n = 10; conjunctivitis, n = 6; cheilitis, n = 5; adenitis, n = 2), but none had the typical form. [annalsofintensivecare.springeropen.com]

    Some signs suggestive of Kawasaki disease, such as skin rash, cervical adenopathy, cheilitis, and meningism, were also observed, without meeting all classic clinical criteria of the disease. [jped.elsevier.es]

Neurologic

  • Intracranial Hemorrhage

    […] vasopressor or vasoactive support Receipt of cardiopulmonary resuscitation or ECMO support Kidney Receipt of dialysis (for patients without chronic kidney failure) Acute kidney injuryc (in patients without prior kidney disease) Neurologic Stroke or acute intracranial [jamanetwork.com]

Workup

Although decisions about additional testing will be made by the multidisciplinary team managing the patient, pediatricians can prepare families for an expanded laboratory and cardiac workup that may include: Chest radiograph, EKG, and troponin. [services.aap.org]

[…] complete blood count, urine pregnancy test followed with quantitative blood beta-hCG Imaging: transvaginal ultrasound If patient is unstable: IV fluid resuscitation, urgent obstetrics and gynecology consultation If patient is stable: continue diagnostic workup [en.wikipedia.org]

Cases with clinical manifestations that completely fulfill the definition of MIS-C should be hospitalized for more extensive workup [64,65,66]. [link.springer.com]

Treatment

Treatment Most children with MIS-C need to be treated in a hospital. Some need treatment in a pediatric intensive care unit. [mayoclinic.org]

Hospitalization Is Common, Necessary Most children with MIS-C will require treatment in the hospital, with a smaller percentage requiring treatment in pediatric intensive care. [uspharmacist.com]

treatment has succeeded in keeping the morality rate to a relatively low 1.9%. [contagionlive.com]

IVIG treatment was used in 77% of these patients; 21% received a second dose. [jped.elsevier.es]

Prognosis

Prompt recognition is pivotal to insure a good individual prognosis." [contagionlive.com]

In this case, alterations indicated severity and worse prognosis. [jped.elsevier.es]

Whether a genetic susceptibility to MIS-C exists is unknown, and the long-term prognosis of MIS-C is not completely defined. [link.springer.com]

Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults. Acta Paediatr, 109 (2020), pp. 1088-1095 [2] S. Riphagen, X. Gomez, C. Gonzalez-Martinez, N. Wilkinson, P. Theocharis. [bjid.org.br]

Outcome: Evaluation of age, clinical presentation, diagnosis, therapeutic management, associated cardiac morbidity, and prognosis of children with MIS with COVID-19. Exclusion criteria  1. [journals.lww.com]

Etiology

Etiologies include both typical and atypical mycobacteria as well as fungal organisms. These lesions contain prominent granulomas; however, a finding is not seen in our case [11]. [cureus.com]

Any child with suspected MIS-C should also be evaluated for infectious and noninfectious etiologies. Persistent fever without a clear clinical source is the first clue. [services.aap.org]

Kawasaki disease: an unexpected etiology of shock and multiple organ dysfunction syndrome. Intensive Care Med. 2012;38:872–8. [annalsofintensivecare.springeropen.com]

The seasonality and temporal clustering of KD32,40 further support an infectious etiology. A mild cold may precede the onset of KD and up to one-third of patients have concurrent, confirmed infections at the time of KD diagnosis41. [pediatricsresearchjournal.com]

Such tests include:[11] Computed tomography of the abdomen/pelvis Abdominal or pelvic ultrasound Endoscopy and/or colonoscopy Management[edit] The management of abdominal pain depends on many factors, including the etiology of the pain. [en.wikipedia.org]

Epidemiology

Discussion Epidemiology Global epidemiologic studies in the current coronavirus disease 2019 (COVID-19) pandemic indicate that children are less affected than adults. [cmaj.ca]

What The Study Did: National COVID-19 registry data are used in this study to describe the epidemiology, clinical characteristics, complications, and hospital and postdischarge outcomes of pediatric patients with multisystem inflammatory syndrome in children [eurekalert.org]

[…] features.1 The cases occurred in children testing positive for current or recent infection by SARS-CoV-2, the novel coronavirus that causes COVID-19, based on reverse-transcriptase polymerase chain reaction (RT-PCR) or serologic assay, or who had an epidemiologic [emergency.cdc.gov]

The clinical presentation of MIS-C includes fever, severe illness, and the involvement of two or more organ systems, in combination with laboratory evidence of inflammation and laboratory or epidemiologic evidence of SARS-CoV-2 infection. [mdpi.com]

Among the patients with an epidemiologic link to a person with Covid-19, additional viral infections included human metapneumovirus (1 patient). 10.1056/NEJMoa2021680-t2 Table 2. [nejm.org]

Pathophysiology

Pathophysiology Blood vessels are thought to be the primary target of endothelial inflammation and injury triggered by SARS-CoV-2,11 mirroring the immunobiology identified in Kawasaki disease. [cmaj.ca]

Immunologic studies were done by both the Lee and Day-Lewis et al. and Diorio et al. groups to gain insight into the pathophysiology of the disease as well as to explore immunological biomarkers that could serve to differentiate MIS-C from KD, MAS, and [jci.org]

It thus is critical to have a deeper understanding of the pathophysiology and mechanisms associated with those that develop MIS‐C in order to effectively study vaccines in the pediatric population. [onlinelibrary.wiley.com]

[citation needed] Pathophysiology Receptors on the floor of the fourth ventricle of the brain represent a chemoreceptor trigger zone, known as the area postrema, stimulation of which can lead to vomiting. [en.wikipedia.org]

The pathophysiology and clinical course of this new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children are still unknown. [academic.oup.com]

Prevention

Clinical Topics: Prevention Keywords: ACC COVID-19 Podcast, African Americans, Coronavirus, COVID-19, Ethnic Groups, Hispanic Americans, Inflammation, Myocardial Ischemia, Pediatrics, Primary Prevention, Public Health Surveillance, Racism, Receptor, Insulin [acc.org]

Distributed via the CDC Health Alert Network May 14, 2020, 4:45 PM ET CDCHAN-00432 Summary The Centers for Disease Control and Prevention (CDC) is providing 1) background information on several cases of a recently reported multisystem inflammatory syndrome [emergency.cdc.gov]

Everyone has a part in preventing more children from developing MIS-C by preventing COVID-19 infections in the first place. [theconversation.com]

Recently, the Centers for Disease Control and Prevention published a report describing a multisystem inflammatory syndrome in adults (MIS-A). [newsnetwork.mayoclinic.org]

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