Materiały źródłowe

• #1 Clinical Treatment of Multisystem Inflammatory Syndrome in Children | MIS | CDC

  https://www.cdc.gov/mis/hcp/clinical-care-treatment/index.html

  Once a child has been diagnosed with multisystem inflammatory syndrome (MIS-C), they will be hospitalized and may receive care from a variety of specialists. […] Some children will need to be in the intensive care unit (ICU) to closely monitor symptoms. […] Depending on the child’s illness severity and manifestations, multiple specialists (e.g., cardiologists, critical care specialists, hematologists, infectious disease specialists, and rheumatologists) may participate in management. […] Laboratory testing for inflammatory markers (e.g., C-reactive protein) should be performed and may be repeated over the course of hospitalization to monitor response to treatment. Other laboratory markers may be followed depending on MIS-C organ involvement (e.g., cardiac enzymes, liver enzymes, platelets, absolute lymphocyte count).

• #2 Multisystem inflammatory syndrome in children (MIS-C) and COVID-19 | Altru Health System

  https://www.altru.org/health-library/conditions/multisystem-inflammatory-syndrome-in-children-mis-c-and-covid-19

  Children with MIS-C are treated in a hospital. Some need treatment in a pediatric intensive care unit. Treatment is supportive care and efforts to lower inflammation in any affected vital organs to protect them from permanent damage. Treatment depends on the type and severity of symptoms and which organs and other parts of the body are affected by inflammation. […] Supportive care may include: […] Treatment to limit swelling and inflammation may include: […] There is no proof that MIS-C is contagious. But there’s a chance that your child could have an active infection with the COVID-19 virus or another type of contagious infection. So the hospital will use infection control measures while caring for your child.

• #3 Multisystem Inflammatory Syndrome In Children (MIS-C) Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/24592-multisystem-inflammatory-syndrome-in-children

  Multisystem inflammatory syndrome in children (MIS-C) is a rare side effect of COVID-19. Treatment takes place in a hospital. Most children make a full recovery. […] Treatment for MIS-C may include: Receiving fluids from an IV (a needle placed into a vein in your childs arm). Taking medications (oral or IV) to reduce inflammation (corticosteroids, immune globulin IVIG and glucocorticoids). Antiviral therapy (remdesivir) to treat COVID-19 if your child has an active infection. Receiving oxygen from an assisted breathing device (ventilator). Treatment focuses on reducing inflammation and preventing possible life-threatening symptoms. If your child has MIS-C, theyll receive treatment in a hospital or a pediatric intensive care unit (PICU) depending on how severe their symptoms are. […] Most children diagnosed with MIS-C make a complete recovery. It can be life-threatening and severe in rare cases. Theyll need treatment in a healthcare facility, most likely a hospital. Your child may need to see their primary care provider after theyve completed treatment for MIS-C.

• #4 Combination regimen proves effective for multisystem inflammatory syndrome in children | MUSC | Charleston, SC

  https://web.musc.edu/about/news-center/2021/07/26/mack-misc-therapy

  A team of pediatricians at MUSC Childrens Health contributed to a nationwide study of effective treatments for multisystem inflammatory syndrome (MIS-C), a novel COVID-19-associated disease found in children and adolescents. The results of the study, published in the New England Journal of Medicine, show that a combination of steroids and intravenous immunoglobulin (IVIG) is effective against MIS-C. […] The study describes the outcomes associated with treating MIS-C with IVIG alone or in combination with steroids. The results show that the use of the combination therapy is effective against MIS-C. […] The kids treated upfront with both IVIG and steroids have better cardiovascular outcomes, said Mack. […] The MIS-C team at MUSC Childrens Health provided the depth of subspecialty expertise and clinical experience needed to make contributions to this study, which has identified a much-needed therapy for MIS-C. […] It really requires a high level of networking and attention to science as it comes out to be able to provide the best therapy, said Mack.

• #5 Multisystem Inflammatory Syndrome in Children (MIS-C) > Fact Sheets > Yale Medicine

  https://www.yalemedicine.org/conditions/multisystem-inflammatory-syndrome-in-children-mis-c

  Treatments include intravenous fluids and antibiotics. […] Many children with MIS-C will need to be cared for in the intensive care unit, where medical providers can treat and closely monitor their condition. […] Treatment typically includes supportive care, which means that the focus is on relieving symptoms and preventing complications while the patient recovers. This usually involves the delivery of intravenous fluids and medications including antibiotics, with the goal of reducing fever, keeping blood pressure up, and eliminating any underlying bacterial infections. […] Given that the symptoms of MIS-C are caused by the body’s own exaggerated immune response, doctors may also administer medications to temporarily suppress the body’s immune system. […] Drugs commonly used to suppress immune response in children with MIS-C include steroids and certain biologic drugs that are typically used in people with autoimmune disorders and rheumatoid arthritis.

• #6 Multisystem inflammatory syndrome in children (MIS-C) – Children’s Health Cardiology

  https://www.childrens.com/specialties-services/conditions/multisystem-inflammatory-syndrome-in-children

  There is no cure for MIS-C, but the experts at Children’s Health have developed a comprehensive approach to treating it. Multiple specialists collaborate to provide all the care your child needs. Your child will receive care that helps support the damaged organs. Usually, children need to be in the intensive care unit (ICU). Without this care, MIS-C can be life-threatening. […] Most children with MIS-C need supportive care to help their damaged organs function while their body heals. This might include: Extra fluids to support blood pressure, Medicines to raise low blood pressure and help the heart pump more strongly, Extra oxygen to ensure oxygen gets to all organs. […] Your child’s doctor might also use medicines that can calm an overactive immune system and reduce inflammation. These medicines have been used in other conditions with overactive immune system in children, like Kawasaki disease. They include: Steroids, IV immunoglobulin, Anakinra (Kineret®).

• #7 Multisystem Inflammatory Syndrome in Children (MIS-C) > Fact Sheets > Yale Medicine

  https://www.yalemedicine.org/conditions/multisystem-inflammatory-syndrome-in-children-mis-c

  In some cases, children with MIS-C require breathing or cardiac support via mechanical ventilation or extracorporeal membrane oxygenation (ECMO) treatment. […] Though MIS-C is a serious condition that usually requires hospitalization, with prompt medical attention, the vast majority of children with it recover.

• #8 Multisystem Inflammatory Syndrome in Children (MIS-C) and What You Should Know | Lovelace Health System in New Mexico

  https://lovelace.com/news/blog/multisystem-inflammatory-syndrome-children-mis-c-and-what-you-should-know

  Multisystem inflammatory syndrome in children (MIS-C) can cause different parts of the body, such as the heart, lungs, kidneys, brain, skin, eyes or gastrointestinal organs, to become inflamed. […] At this time, the exact cause of MIS-C is not known, said Kristina Gutierrez-Barela, MD, board-certified pediatrician with Lovelace Medical Group. […] To look for signs of MIS-C, your doctor may conduct a series of tests, including blood tests, a chest x-ray, heart ultrasound (echocardiogram) and abdominal ultrasound. If MIS-C is diagnosed, treatment may require a hospital stay and involve multimodal therapy with medications, such as steroids and immunoglobulin, to target the bodys immune system and inflammatory response. […] Early signs do indicate that most children are able to recover with treatment, said Gutierrez-Barela. Therefore, if your child has any of the above symptoms and has either tested positive for COVID-19 or been around someone with coronavirus, it is important to seek medical advice.

• #9 PTA: Multisystem Inflammatory Syndrome in Children (MIS-C)

  https://www.uspharmacist.com/article/pta-multisystem-inflammatory-syndrome-in-children-misc

  Most children with MIS-C will require treatment in the hospital, with a smaller percentage requiring treatment in pediatric intensive care. […] While in the hospital, the treatment focus is on reducing the symptoms while also managing the inflammation. Depending on the symptoms and the child’s condition, treatment may include anti-inflammatory medications such as corticosteroids, immunomodulators like IV immunoglobulin, and anticoagulants like aspirin to reduce the risk of blood clots. […] In some cases, medications used to increase blood pressure, called vasopressors, will be given to maintain adequate blood flow. Treatment with a ventilator or oxygen may be needed to ensure appropriate oxygen levels are maintained. With monitoring and treatment, most children will fully recover and return home. Rarely, children have died as a result of MIS-C.

• #10 Treatment of MIS-C in Children and Adolescents

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8741532/

  Different treatment approaches have been described for the management of COVID-19-related multisystem inflammatory syndrome in children (MIS-C), the pathogenesis of which has not yet been fully elucidated. […] MIS-C patients are treated with different regimens, mostly revolving around the use of immunomodulatory medications, including IVIG and glucocorticoids as first-tier therapy. Refractoriness to IVIG and glucocorticoids warrants a step-up of immunomodulatory therapy to biologic agents such as anakinra, tocilizumab, and infliximab. […] Current practices and published guidelines for the treatment of MIS-C support the use of intravenous immunoglobulin (IVIG) and/or high-dose corticosteroids as a first-line cornerstone of therapy. […] Intravenous immunoglobulin (IVIG), glucocorticoids, and biologic agents constitute the main therapeutic modalities, with different combinations depending on the treatment center.

• #11

  https://link.springer.com/article/10.1007/s40124-021-00259-4

  Different treatment approaches have been described for the management of COVID-19-related multisystem inflammatory syndrome in children (MIS-C), the pathogenesis of which has not yet been fully elucidated. Here, we comprehensively review and summarize the recommendations and management strategies that have been published to date. […] MIS-C patients are treated with different regimens, mostly revolving around the use of immunomodulatory medications, including IVIG and glucocorticoids as first-tier therapy. Refractoriness to IVIG and glucocorticoids warrants a step-up of immunomodulatory therapy to biologic agents such as anakinra, tocilizumab, and infliximab. […] Current practices and published guidelines for the treatment of MIS-C support the use of intravenous immunoglobulin (IVIG) and/or high-dose corticosteroids as a first-line cornerstone of therapy.

• #12 Treatment of MIS-C in Children and Adolescents

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8741532/

  Immunomodulation is a cornerstone of treatment, with consensus guidelines recommending a stepwise progression of immunomodulatory therapies starting with the first-tier therapy, IVIG, which can sometimes be used as needed before full diagnostic evaluation is completed. […] Consensus guidelines support the use of high-dose IVIG for all hospitalized patients, administered in a single dose at 2 gm/kg based on ideal body weight (max 100 gm). […] The rationale for using steroids are their anti-inflammatory properties and frequent use in Kawasaki disease and other inflammatory disorders. […] The American College of Rheumatology (ACR) consensus guidelines for MIS-C suggest that intravenous low-to-moderate dose corticosteroids (methylprednisolone 12 mg/kg/day, typically in two doses) should be used alongside IVIG in patients demonstrating shock or organ-threatening disease.

• #13

  https://link.springer.com/article/10.1007/s40124-021-00259-4

  Clinical decision-making and treatment plans should be modified as new evidence emerges, especially in patients with comorbid conditions. Treatment should be individualized, based on both multidisciplinary consensus approach and expert opinion. […] Intravenous immunoglobulin (IVIG), glucocorticoids, and biologic agents constitute the main therapeutic modalities, with different combinations depending on the treatment center. […] The ultimate aims of management are to decrease systemic inflammation and restore organ function, with the goal of preventing long-term sequelae such as persistent cardiac dysfunction. […] Consensus guidelines support the use of high-dose IVIG for all hospitalized patients, administered in a single dose at 2 gm/kg based on ideal body weight (max 100 gm). […] The American College of Rheumatology (ACR) consensus guidelines for MIS-C suggest that intravenous low-to-moderate dose corticosteroids (methylprednisolone 12 mg/kg/day, typically in two doses) should be used alongside IVIG in patients demonstrating shock or organ-threatening disease.

• #14 Childhood multisystem inflammatory syndrome associated with COVID-19 (MIS-C): a diagnostic and treatment guidance from the Rheumatology Study Group of the Italian Society of Pediatrics | Italian Journal of Pediatrics | Full Text

  https://ijponline.biomedcentral.com/articles/10.1186/s13052-021-00980-2

  To date, there is limited evidence to establish the optimal therapeutic approach to a child with MIS-C. Given the partial overlap of the clinical manifestations of MIS-C with those of Kawasaki disease, the majority of patients have been treated with the standard therapeutic protocols for the latter illness. It is important to consider that the spectrum of clinical manifestations and severity of MIS-C is wide. Thus, the best treatment approach should be defined on an individual basis, and the following proposals are to be interpreted only as suggestions. […] […] Intravenous immunoglobulin 2g/kg IV (up to 70-80g) to be administered over at least 12h. In patients with heart failure immunoglobulins should be administered over at least 16h or, alternatively, the total dose should be split in two infusions 12h apart. A second dose of immunoglobulins should be considered in case of inadequate response. […]

• #15

  https://link.springer.com/article/10.1007/s40124-021-00259-4

  In patients refractory to initial treatment with IVIG and low-to-moderate dose corticosteroids, corticosteroid treatment can be intensified to pulse doses of methylprednisolone (10-30 mg/kg/day). […] Anti-cytokine agents are often successfully used as an initial adjunct therapy to IVIG. However, data evaluating the efficacy of using targeted biologic agents is not yet available, and later recommendations emphasize the use of biologics primarily for cases refractory to treatment with IVIG and corticosteroids. […] Anakinra should primarily be considered in MIS-C patients with disease refractory to IVIG and/or corticosteroids, or in patients with contraindications to steroids, especially in cases of MIS-C with features of macrophage activation syndrome. […] Tocilizumab is not recommended for the majority of MIS-C patients; however, it can be considered for use in children with the life-threatening disease in whom prior therapy, including anakinra, has not been effective.

• #16 The Role of Glucocorticoids in the Treatment of Multisystem Inflammatory Syndrome (MIS-C)—Data from POLISH MIS-C Registry

  https://www.mdpi.com/2227-9067/9/2/178

  According to the American College of Rheumatology, high-dose, IV pulse GCS (10–30 mg/kg/day) may be considered in MIS-C patients who do not respond to IVIG and low-to-moderate-dose GCS, or if a patient requires high-dose inotropes and/or vasopressors. […] In our study, children were treated with different types and doses of GCS, usually longer than seven days. […] The inflammatory response in MIS-C is similar to the immune response to acute COVID-19. […] Most of the recent studies comparing treatment with IVIG and methylprednisolone vs. IVIG alone have given positive results. […] Combination therapy was associated with a lower risk of persistent or recurrent fevers, reduced need for adjunctive immunomodulatory therapy or hemodynamic support. […] Our study demonstrated GCS+IVIG is the treatment most widely used in Poland and may be beneficial for MIS-C patients.

• #17 Frontiers | Multisystem Inflammatory Syndrome in Children (MIS-C)—A Case Series in December 2020 in Vienna, Austria

  https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2021.656768/full

  Multisystem Inflammatory Syndrome in Children (MIS-C) is a novel clinical syndrome that first appeared in 2020. […] The treatment resulted in rapid clinical improvement. The patients’ fever returned to normal, while inflammatory signs and elevated heart enzymes were reduced. […] All patients were treated with intravenous immunoglobulins (usually for 2–3 days), high doses of cortisone, high doses of aspirin, antithrombotic therapy with low-molecular heparin, and antibiotics. […] Simultaneous administration of the medications listed in Table 4 was started in all eight patients with MIS-C. […] A single course of immunoglobulins (2 g/kg body weight) was divided into two doses of 1 g/kg body weight, administered on 2 consecutive days. […] Concomitantly, a high dose of methylprednisolone (20–30 mg/kg body weight) was administered for 3 days, reduced to 2 mg/kg body weight until day 7, and then tapered over 2–3 weeks.

• #18 Combination regimen proves effective for multisystem inflammatory syndrome in children | MUSC Health | Charleston SC

  https://muschealth.org/patients-visitors/news/2021/07/26/mack-misc-therapy?utm_source=hootsuite&utm_medium=facebook&utm_term=musc+health&utm_content=9e0212c6-fa3c-473d-8908-45379e6b7fd1

  A team of pediatricians at MUSC Childrens Health contributed to a nationwide study of effective treatments for multisystem inflammatory syndrome (MIS-C), a novel COVID-19-associated disease found in children and adolescents. The results of the study, published in the New England Journal of Medicine, show that a combination of steroids and intravenous immunoglobulin (IVIG) is effective against MIS-C. […] The study describes the outcomes associated with treating MIS-C with IVIG alone or in combination with steroids. The results show that the use of the combination therapy is effective against MIS-C. […] The kids treated upfront with both IVIG and steroids have better cardiovascular outcomes, said Mack. […] The MIS-C team at MUSC Childrens Health provided the depth of subspecialty expertise and clinical experience needed to make contributions to this study, which has identified a much-needed therapy for MIS-C.

• #19 Initial Treatment of Multisystem Inflammatory Disease in Childrenlogo-32logo-40logo-60NEJM Journal WatchnejmJW_1L_RGB-b

  https://www.jwatch.org/na53772/2021/07/12/initial-treatment-multisystem-inflammatory-disease

  Two observational studies leave unanswered questions about the optimal initial treatment for MIS-C. […] Given the clinical similarities to Kawasaki disease, MIS-C was treated with immunomodulatory agents, including intravenous immunoglobulin (IVIG) and corticosteroids. […] Those initially treated with both IVIG and glucocorticoids had a lower risk for subsequent overall cardiovascular dysfunction (left ventricular dysfunction and shock requiring vasopressor use) than those who initially received IVIG alone (17% vs. 31%). […] Other than a lower frequency of escalation of immunomodulatory therapy in the group receiving IVIG plus glucocorticoids, outcomes did not differ for children receiving various initial therapies for MIS-C. […] These studies are a start to guiding clinicians toward the most effective initial therapy, but because neither is a randomized, controlled trial, treatment outcome is difficult to interpret. […] Until then, aggressive initial therapy with an immunomodulatory agent or a combination of agents is certainly indicated.

• #20 Treatment of MIS-C in Children and Adolescents

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8741532/

  Anti-cytokine agents are often successfully used as an initial adjunct therapy to IVIG. […] Anakinra should primarily be considered in MIS-C patients with disease refractory to IVIG and/or corticosteroids, or in patients with contraindications to steroids, especially in cases of MIS-C with features of macrophage activation syndrome. […] Tocilizumab is not recommended for the majority of MIS-C patients; however, it can be considered for use in children with the life-threatening disease in whom prior therapy, including anakinra, has not been effective. […] Infliximab is not recommended for use in a majority of patients and can be considered on a case-by-case basis in patients who have failed to respond to prior treatments or in patients who present with comorbid conditions such as Crohns disease.

• #21 Immunomodulators in MIS-C: Evidence-based guidance – Boston Children’s Answers

  https://answers.childrenshospital.org/immunomodulators-mis-c-covid-19/

  A working group at Boston Children’s Hospital has developed a treatment framework based on clinical observations, a handful of published reports and ongoing studies, and clinical trial data for other inflammatory conditions. […] A rheumatologist should be involved whenever MIS-C is suspected. […] Children with hyperinflammation (persistent fever and elevated inflammatory markers) may benefit from immunomodulators, especially if they have organ involvement. […] Based on the evidence, Boston Children’s is primarily using IV immunoglobulin, glucocorticoids, and anakinra. […] The goal of using immunomodulators in MIS-C is to prevent progression to shock, reduce the need for ICU admission or organ support, and prevent coronary artery dilation and aneurysms. […] IV immunoglobulin (IVIG) is a standard first-line treatment for Kawasaki disease to protect the coronary arteries from inflammation, and has been used for decades in immune deficiencies, autoimmune problems, and persistent infections. IVIG is now also used in MIS-C even when there are no clear Kawasaki-like features, although it’s still not clear how much benefit it provides.

• #22 The Effect of Biologics in the Treatment of Multisystem Inflammatory Syndrome in Children (Mis-C): A Single-Center Propensity-Score-Matched Study

  https://www.mdpi.com/2227-9067/10/6/1045

  The Effect of Biologics in the Treatment of Multisystem Inflammatory Syndrome in Children (Mis-C): A Single-Center Propensity-Score-Matched Study […] Multisystem inflammatory syndrome in children (MIS-C) is a serious condition characterized by excessive inflammation that can arise as a complication of SARS-CoV-2 infection in children. While our understanding of COVID-19 and MIS-C has been advancing, there is still uncertainty regarding the optimal treatment for MIS-C. […] The primary outcome was observed in none of the patients in the IVIG and CS group, while it occurred in eight patients in the IVIG plus CS and biologic group (p = 0.04). […] MIS-C is a severe condition that might need treatment in the intensive care unit (ICU). Since it is a critical multisystem disorder, rapid and intense treatment options should be considered. Suppressing systemic inflammation and improving cardiac functions are the main objectives of the therapy. […] However, the distinct characteristics of MIS-C, such as its resemblance to KD shock syndrome and MAS, differentiate it from classical KD. Consequently, IVIG alone may not be sufficient for all patients, leading to the utilization of various immunosuppressive and immunomodulatory agents, including corticosteroids and biologics like interleukin (IL)-1 inhibitors (such as anakinra) and IL-6 blockers (such as tocilizumab). […] Despite these treatment options, the optimal management of MIS-C remains unknown. […] In this retrospective propensity-score-matched cohort study, our aim was to compare the clinical and laboratory outcomes of MIS-C patients who were given a combination of IVIG plus corticosteroids (CS) versus those who received IVIG plus CS along with an additional biologic drug. […] The primary outcome was cardiovascular dysfunction and/or the requirement for an inotrope at least 48 h after starting initial therapy. […] IVIG was given in a single 12 h infusion at a dose of 2 g/kg. We gave either high-dosage methylprednisolone 10–30 mg/kg/d intravenously for 3 days or 1–2 mg/kg/day oral prednisolone for at least five days or longer. As an anti-IL-1 agent, anakinra was used subcutaneously at a dosage of 2–6 mg/kg/day divided in two doses. As an anti-IL-6 agent, tocilizumab was used as a single IV dose (<30 kg: 12 mg/kg IV; ≥30 kg: 8 mg/kg IV; max.: 800 mg). [...] The current study analyzes the effect of treatment options on the outcome of patients with MIS-C. [...] The American College of Rheumatology (ACR) has published their comprehensive set of guidelines for MIS-C patients as version 1 in June 2020 and versions 2 and 3 later. [...] Even though there are a comprehensive set of recommendations and protocols, the present therapeutic approaches are purely empirical and not based on evidence. [...] The aforementioned guidelines stress the use of biologics mainly for conditions that are resistant to therapy with IVIG and CS. [...] However, there is currently a lack of evidence evaluating the specific indication, dosing, and timing of anti-cytokine treatments in MIS-C. [...] In the present study, both before and after PS matching, patients who received additional biologic therapy exhibited more severe clinical and laboratory features. After the PS matching, patients having combination therapy had a significantly higher primary outcome. [...] These results imply that individuals with more serious illnesses may have required further biologic treatments earlier. [...] Patients diagnosed with MIS-C exhibit prominent signs of high inflammation, potentially accompanied by shock and cardiac dysfunction. This condition necessitates a thorough differential diagnosis to distinguish it from other disorders like TSS, KD, KD shock syndrome, or MAS. [...] With all these results, considering the elevated levels of inflammatory markers and intense inflammatory profile observed in MIS-C patients, the utilization of biologic agents appears to be a reasonable approach. [...] Despite being an area of contention in the literature, the use of biologic agents like anakinra and tocilizumab as the first-line treatment, along with other immunosuppressive drugs, for patients with MIS-C remains controversial. [...] Although we could not show any significant differences in clinical features, our results showed that lower platelet and lymphocyte counts and albumin levels and higher d-dimer, ferritin, and CRP levels might justify the use of aggressive treatments in the early phase of the disease.

• #23 Dual Therapy Effective for MIS-C | Children’s Hospital Colorado

  https://www.childrenscolorado.org/advances-answers/recent-articles/mis-c-dual-therapy/

  Starting in December of 2020, the team also added, for the sickest patients, another intravenous therapy to the IVIG regimen: infliximab, a lab-grown antibody that blocks the production of tumor necrosis factor alpha, or TNF. […] We had four initial criteria: If they were in shock, they needed pressure support, they had dilated coronary arteries and they had ventricular dysfunction, we’d give them infliximab, says Dr. Jone. But when we looked back in February 2021 at the 72 patients we’d treated since December 2020, we realized only 20 had received IVIG alone. The rest had gotten dual therapy. […] What’s more, the 52 patients who’d received both therapies had better outcomes. They recovered faster. They required less additional therapy. In fact, a retrospective study the team published in Pediatrics showed patients who received dual therapy did better by every measure. The data was so strong the team has since implemented dual therapy into the protocol for every patient diagnosed with MIS-C. […] Dr. Jone believes TNF blockers are a more intuitive treatment either way: the course of steroid treatment lasts six weeks. Infliximab requires just one intravenous dose.

• #24 Multisystem Inflammatory Syndrome in Children – The Western Journal of Emergency Medicine

  https://westjem.com/articles/multisystem-inflammatory-syndrome-in-children.html

  A multidisciplinary team approach involving cardiology, infectious disease, immunology, rheumatology, hematology, and intensive care can be helpful in optimizing patient outcomes in an inpatient setting. […] Anakinra and tocilizumab may be alternative options in children with severe MIS-C and in patients with markedly elevated pro-inflammatory cytokines, who do not respond to IVIG and corticosteroid treatment. […] Anticoagulation therapy has been recommended for patients with elevated D-dimer levels or evidence of thrombosis. […] Currently, there are no definitive guidelines for anticoagulation therapy in children with MIS-C. […] Consultation with pediatric infectious disease and critical care experts on the use of remdesivir is recommended if suspected or confirmed MIS-C patients are not responding to other treatment options. […] Close follow-up is recommended for all patients with KD features, cardiac dysfunction, or evidence of coronary artery abnormalities.

• #25 Clinical Treatment of Multisystem Inflammatory Syndrome in Children | MIS | CDC

  https://www.cdc.gov/mis/hcp/clinical-care-treatment/index.html

  Treatment generally involves the use of anti-inflammatory drugs. Anti-inflammatory measures have included the frequent use of intravenous immunoglobulin (IVIG) and steroid therapy. […] Prolonged duration of outpatient steroids should be avoided. The use of other anti-inflammatory medications (e.g., anakinra) and the use of anti-coagulation treatments have been variable and data are limited regarding their benefit. […] Aspirin has commonly been used because of concerns for coronary artery involvement, and antibiotics are routinely used to treat potential sepsis while awaiting bacterial cultures. Thrombotic prophylaxis is often used given the hypercoagulable state typically associated with MIS-C. […] Evaluation and testing after hospitalization are based on the presentation and clinical course of each patient with MIS.

• #26

  https://link.springer.com/article/10.1007/s40124-021-00259-4

  Some studies utilizing infliximab, the monoclonal anti-TNF antibody, have reported efficacy in the treatment of MIS-C. However, currently, infliximab is not recommended for use in a majority of patients and can be considered on a case-by-case basis in patients who have failed to respond to prior treatments or in patients who present with comorbid conditions such as Crohn’s disease. […] Consensus guidelines support the use of LMWH as the anticoagulant of choice for prophylactic dosing, which is commonly administered subcutaneously twice daily. […] For MIS-C, recommendations for low-dose (prophylactic) anticoagulation include mild to moderate ventricular dysfunction, coronary dilation/aneurysm with z-score 2.5-10, D-dimer 5-10 ULN, TEG MA >80 mm, or any new significant rhythm abnormalities such as heart block, premature atrial and ventricular contractions, conduction abnormalities, and ST-segment changes. […] The timely and swift administration of immunomodulatory therapy improves outcomes and decreases the need for escalation of life-supportive care.

• #27 Multisystem Inflammatory Syndrome in Children (MIS-C) | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/mis-c

  Children diagnosed with MIS-C need close observation. All need to be admitted to the hospital, and some may need intensive care. Pediatric specialists in rheumatology, critical care, and cardiology can anticipate and address different aspects of the illness. […] Treatments include IV immunoglobulin (used to treat Kawasaki disease), and anti-inflammatory drugs (corticosteroids, and drugs blocking IL-1 or IL-6). Other treatments may be used depending on the results of laboratory tests. Children are also treated with low-dose aspirin to decrease the risk of blood clots. […] Children need to be followed after discharge from the hospital, with repeat echocardiograms to monitor their heart and coronary arteries, even if they didn’t have serious problems in the hospital. Children who are fully recovered at six months no longer need close follow-up.

• #28 Childhood multisystem inflammatory syndrome associated with COVID-19 (MIS-C): a diagnostic and treatment guidance from the Rheumatology Study Group of the Italian Society of Pediatrics | Italian Journal of Pediatrics | Full Text

  https://ijponline.biomedcentral.com/articles/10.1186/s13052-021-00980-2

  Glucocorticoids to be administered with IVIg upfront in case of heart involvement, severe disease, impending sHLH or toxic shock syndrome. i or ii should be chosen depending on disease severity, based on clinical/laboratory features. Methylprednisolone pulses are recommended in case of sHLH diagnosis/suspicion. […] […] Consider Dexamethasone 10mg/m2 q1d in case of sHLH or CNS involvement. […] […] Biologic medications to be used SQ as second line treatment, in case of persistent disease activity 48h after first-line treatment or in case of sHLH. […] […] Ancillary treatments: Large-spectrum antibiotics while waiting for microbiology tests. Acetylsalicylic acid: 5mg/kg for at least 68 wks. In case coronary abnormalities are found, refer to AHA recommendations for Kawasaki Disease. Proton Pump Inhibitor as needed. Thromboprophylaxis with LMWH: since adults with COVID-19 are at high risk of thromboembolism, and given the high inflammatory state of children with MIS-C, it appears reasonable to start prophylaxis with LMWH. […]

• #29 Ten Things to Know About MIS-C

  https://www.acc.org/Latest-in-Cardiology/Articles/2021/11/02/14/41/Ten-Things-to-Know-About-MIS-C

  First identified in April 2020, Multisystem Inflammatory Syndrome in Children (MIS-C) is a systemic inflammatory syndrome associated with exposure to SARS-CoV-2. […] Current accepted therapy is based on experience with Kawasaki disease. Intravenous immunoglobulin (IVIG) is most often used, and glucocorticoids have been shown to aid cardiac recovery. Some report treating mild cases with glucocorticoids alone. In severe cases, immune modulators such as anakinra and tocilizumab have been helpful. Due to the risk of thrombosis with MIS-C, prophylactic anticoagulation while hospitalized is common and aspirin may be prescribed for 6 weeks. Those with documented coronary dilation are treated according to Kawasaki disease therapeutic guidelines. […] About 65% of patients require critical care, with almost half requiring inotropic support.

• #30 Multisystem inflammatory syndrome in children (MIS-C) – Children’s Health Cardiology

  https://www.childrens.com/specialties-services/conditions/multisystem-inflammatory-syndrome-in-children

  Some children with MIS-C will need blood thinners because COVID-19 and related-illnesses like MIS-C can cause blood clots. Blood thinners help prevent blood clots, which can cause strokes or blockages in the lungs. […] Most children with MIS-C spend 7-10 days in the hospital, including 3-4 days in the ICU, but some severe cases need more time to improve. Fortunately, most children bounce back quickly after treatment. However, they may need to limit physical activity until a heart doctor clears them.

• #31 Multisystem-Inflammatory Syndrome Treatment

  https://www.nationaljewish.org/conditions/mis-c/treatment

  Treatment may be different for each child, but common treatments for Multisystem-Inflammatory Syndrome in Children (MIS-C) can include: […] Steroids […] Intravenous immunoglobulin […] High-dose aspirin […] Antibiotics […] Oxygen support.

• #32 Multisystem inflammatory syndrome in children (MIS-C) and neonates (MIS-N) associated with COVID-19: optimizing definition and management | Pediatric Research

  https://www.nature.com/articles/s41390-022-02263-w

  Serial laboratory monitoring every 2448h is recommended to assess response to treatment, including C-reactive protein, complete blood count, D-dimer, ferritin, troponin T, and BNP. Tapering of immunomodulatory therapy is recommended, typically over a 23-week period, and should be guided by clinical, laboratory, and echocardiographic response. Low-dose aspirin is recommended for all patients, although patients with moderate-severe disease or other risk factors for thrombosis should receive prophylactic anticoagulation (Table 5). […] For patients with ongoing refractory shock, fever, or inflammation despite treatment with IVIG and steroids, the addition of anakinra or higher doses of glucocorticoids is recommended. Depending on clinical status, electrocardiogram (EKG) and/or echocardiography may be repeated while the patient is still hospitalized. Discharge is recommended once a patient has been afebrile for 48h with improving inflammatory markers and resolving multisystem organ involvement.

• #33 Clinical Treatment of Multisystem Inflammatory Syndrome in Children | MIS | CDC

  https://www.cdc.gov/mis/hcp/clinical-care-treatment/index.html

  Cardiology follow-up with repeat echocardiogram is generally recommended for patients with MIS cardiac manifestations. […] Exercise, sports, and strenuous activity are generally limited for children with MIS cardiac manifestations until cleared by a cardiologist. […] Follow-up with the patient’s primary care provider is important. A conversation between the patient, their guardian(s), and the clinical team or a specialist should occur to assist with decisions about COVID-19 vaccination after MIS.

• #34 MIS-C and COVID-19 in Children | Children’s Hospital Colorado

  https://www.childrenscolorado.org/conditions-and-advice/conditions-and-symptoms/conditions/mis-c-covid-19-in-children/

  Children who have recovered from MIS-C should receive checkups at 2 weeks and 6 weeks after they leave the hospital. At Childrens Colorado, our experts in Kawasaki disease and MIS-C will follow up with these patients. […] During the visit, doctors will take samples for laboratory testing and will perform an echocardiogram to check on the patients heart. This is to ensure that the child has healed and is returning to normal health. If any test results are abnormal, the doctor will determine whether additional follow-up care is needed. Because this is still a relatively new disease, we also see children one year after they leave the hospital to make sure everything is going well.

• #35 COVID-19 and Multisystem Inflammatory Syndrome in Children (MIS-C) (for Parents) | Nemours KidsHealth

  https://kidshealth.org/en/parents/pmis.html

  How Is MIS-C Treated? […] How doctors treat MIS-C depends on a child’s symptoms and test results. They can give oxygen, medicines, and intravenous (IV) fluids to reduce inflammation, prevent excessive blood clotting, or protect the affected organs from more problems. Some children might need treatment in the ICU (intensive care unit). […] […] […] Most kids with MIS-C get better after being treated in the hospital. But some can have lasting problems and need care from specialists after they go home. […] […] […] For example, kids who develop heart problems due to MIS-C will need regular visits with a cardiologist. They may have to avoid exercise or sports for a while, until the cardiologist says it’s OK. Kids who get some kinds medicines (like steroids for easing inflammation) will see a specialist, such as a rheumatologist or endocrinologist, who can help them adjust their medicines as needed.

• #36 COVID-19 and Rheumatology

  https://www.healio.com/news/rheumatology/20210325/misc-mystery-persists-even-as-rheumatologists-arsenal-proves-key-to-treatment

  These similarities both in presentation and treatment have led to pediatric rheumatologists becoming highly involved in diagnosing and managing MIS-C. […] Although ICU physicians often represent the true first line for patients first presenting with MIS-C, Grom said rheumatologists are almost always brought in to manage immunosuppressant therapy for each case. […] And, I think, with the proper treatment at least in our experience in Cincinnati the vast majority of patients do recover very nicely. […] The only concern, and what distinguishes this condition, is the very high risk for myocarditis inflammation in the heart muscle, Grom added. […] According to Grom, these potential long-term impacts are just some of the major unknown aspects of this disease. […] According to the CDC, some patients with the disease develop myocarditis and cardiac dysfunction, a common driver of patients with MIS-C requiring ICU treatment.

• #37 MIS-C and COVID-19 in Children | Children’s Hospital Colorado

  https://www.childrenscolorado.org/conditions-and-advice/conditions-and-symptoms/conditions/mis-c-covid-19-in-children/

  How is MIS-C treated? Doctors may provide supportive care for symptoms (medicine and/or fluids to make your child feel better) and may use immune globulin (IVIG), infliximab, steroids or other medications that strengthen the immune system that are used for Kawasaki disease and toxic shock syndrome. Fortunately, most children have responded well to those treatments. […] Most children who become ill with MIS-C will need to be treated in the hospital. Some will need to be treated in the Pediatric Intensive Care Unit (PICU). […] Yes. Doctors in our Infectious Disease Program are experts in treating infectious conditions in children, including COVID-19 and MIS-C. Multiple pediatric specialists are likely to help care for patients with MIS-C; these include infectious disease, cardiology, hematology, rheumatology and critical care doctors.

• #38 COVID-19 and Rheumatology

  https://www.healio.com/news/rheumatology/20210325/misc-mystery-persists-even-as-rheumatologists-arsenal-proves-key-to-treatment

  MIS-C shares many features with Kawasaki disease such as conjunctivitis, red eyes, red or swollen hands and feet, rash, red cracked lips and swollen neck lymph nodes as well as with macrophage activation syndrome. […] Fortunately, its recommended treatments are also similar. […] The American College of Rheumatology recommends a stepwise progression of immunomodulatory therapies to treat patients with MIS-C, starting with high-dose intravenous immunoglobulin (IVIG). Glucocorticoids should be used as adjunctive therapy in patients with severe disease, or as intensification therapy in those with refractory disease. […] IVIG as a first-tier therapy will be familiar exercise for any rheumatologist who has treated Kawasaki disease. […] In some cases, its close to impossible to distinguish MIS-C from Kawasaki disease, he said.

• #39

  https://www.who.int/news/item/23-11-2021-who-issues-guidelines-on-the-treatment-of-children-with-multisystem-inflammatory-syndrome-associated-with-covid-19

  WHO today issued updated guidelines on the management of multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C). […] WHOs updated guidelines recommend the use of corticosteroids in hospitalized children (aged 0-18 years) with this condition, in addition to supportive treatment and care. […] Although MIS-C is a serious condition, with the right medical care, children with this condition recover.

• #40 Multi-system Inflammatory Syndrome in Children (MIS-C) | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/multi-system-inflammatory-syndrome-children

  Children diagnosed with MIS-C are treated with medications often used to treat Kawasaki disease, including steroids and intravenous immunoglobin (IVIG). These medications reduce the bodys excessive immune response, lowering fever and inflammation and allowing heart function to return to normal. […] Most patients diagnosed with MIS-C recover quickly with treatment. Because this is a newly discovered syndrome, however, the long-term outlook of this condition is still unknown.

• #41 MIS-C Review Finds Severe Symptoms, Low Fatality Rate

  https://www.contagionlive.com/view/mis-c-review-finds-severe-symptoms-low-fatality-rate

  A review of approximately 1000 children with multisystem inflammatory syndrome (MIS-C) from SARS-Cov-2 finds low fatality with aggressive treatment. […] A systematic review of reports comprising almost 1,000 children affected with multisystem inflammatory syndrome (MIS-C) subsequent to SARS-CoV-2 infection details its presentations and finds that aggressive treatment has kept the fatality rate low. […] Prompt, intensive treatment has succeeded in keeping the morality rate to a relatively low 1.9%. […] Therapeutic interventions included intravenous immunogloblins (IVIG) in 75.9%; and multiple doses were administered to 73 of the 662 patients (11%). […] Acetylsalicyic acid was received by 52.3%; with high, anti-inflammatory dosages of 80-100mg/kg/day received in 39/171 (22.8%). […] Heparin was administered in 46% of cases. […] Biopharmaceuticals included IL-1R antagonist (anakinra) 7.6%; IL-6 inhibitors (tocilizumab/siltuximab) 6.7%, and TNF-inhibitor (infliximab) 2.3%. […] Inotropics were required by 55.3%. […] Mechanical and non-invasive ventilation was initiated in 23.6% and 25.8%, respectively.

• #42 COVID-19 and Rheumatology

  https://www.healio.com/news/rheumatology/20210325/misc-mystery-persists-even-as-rheumatologists-arsenal-proves-key-to-treatment

  Certainly MIS-C is a new entity that we had not seen before, and many of these kids end up in the intensive care unit, mainly because of significant cardiac complications, he said. […] I think some of them probably may have long-term sequela. […] According to Grom, some patients who recover from MIS-C may develop arrythmia and require long-term care. […] According to a prospective study conducted by Grom and colleagues from the Cincinnati Childrens Hospital Medical Center and the University of Cincinnati, MIS-C may be distinguished from Kawasaki disease by elevated levels of the biomarker CXCL9. […] The resulting paper, which is currently being reviewed for publication by The Lancet Rheumatology, additionally states that the stratification of CXCL9 levels in patients with MIS-C provides support for macrophage activation syndrome pathophysiology in some of those with severe MIS-C. […] At the moment, we are trying to understand a little bit better the nature of the biology of this heterogeneity, he said.

• #43 Management of Multisystem Inflammatory Syndrome in Children: Decision-Making Regarding a New Condition in the Absence of Clinical Trial Data

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9705008/

  The larger US-based Overcoming COVID-19 surveillance registry performed a propensity score-matched comparison of 103 patients who received IVIG and glucocorticoids vs 103 who received IVIG alone. […] An analysis by the Best Available Treatment Study (BATS) Consortium, published simultaneously with the Overcoming COVID-19 study, provided what seemed to be conflicting results. […] In a more recent single-centre retrospective study the potential for steroids as monotherapy, including standard therapy (2 mg/kg/d methylprednisolone) or pulse dosing was reviewed. […] Patients with MIS-C might decompensate quickly, and there should be a low threshold to escalate therapy. […] However, current recommendations for additional thromboprophylaxis in addition to low-dose aspirin are on the basis of expert consensus, and include consideration of pre-COVID-19 risk factors, presence of cardiovascular abnormalities (severe ventricular dysfunction, large coronary aneurysms, etc), markedly elevated D-dimer ( 5 times the upper limit of normal), and risk factors for hospital-associated venous thrombosis and thromboembolism. […] Although results have been encouraging, the optimal treatment of children with MIS-C remains to be determined. Current therapies are on the basis of expert opinion, similarities to other pediatric conditions like KD, and multiple observational studies.

• #44 Methylprednisolone Pulses as an Effective Treatment in Multisystem Inflammatory Syndrome in Children Associated with SARS-CoV-2 (MIS-C), and the Best Alternative for IVIG

  https://brieflands.com/articles/ijp-147357

  Methylprednisolone pulses (MPP) as initial treatment in MIS-C have not been clearly prescribed, similar to secondary HLH or KDSS. […] At Tehran Children Medical Center, a pediatric center of excellence in Iran, based on the pathophysiology of KDSS (with coronary and myocardial involvement) and macrophage activation syndrome (MAS) as secondary HLH, MPP was initiated as the first-line treatment according to an algorithm. […] Based on this experience, outcomes of patients treated with MPP therapy were reported in December 2022. […] Recently, in a randomized, controlled, open-label platform trial published by the RECOVERY Collaborative Group in January 2024, authors reported that MPP reduced the duration of hospital stay in children with MIS-C. […] Methylprednisolone pulses appears to be the most effective treatment currently available.

• #45 Immunomodulators in MIS-C: Evidence-based guidance – Boston Children’s Answers

  https://answers.childrenshospital.org/immunomodulators-mis-c-covid-19/

  Glucocorticoids (methylprednisolone, prednisone, prednisolone, dexamethasone) offer general immune suppression. […] Anakinra is among several biologic drugs that target specific inflammatory cytokines, based on laboratory findings. […] There are studies indicating that anakinra is relatively safe in severe infections, including sepsis. […] So far, patients with MIS-C at Boston Children’s have done well with these treatments. […] Canakinumab, a monoclonal antibody also targets IL-1, but has a longer half-life. […] Tocilizumab, mainly studied in adults to date, targets the cytokine IL-6. […] JAK inhibitors, developed for rheumatoid arthritis, block a pathway that turns on multiple cytokine genes. […] Some immunologic treatments, such as IVIG, may be in short supply, while others are very expensive. […] Most patients identified to date with MIS-C have been more severe, many of them in the ICU, but there are probably children who are much more mildly affected, with just a fever and rash, and may only need observation. […] We need clinical trials.

• #46

  https://link.springer.com/article/10.1007/s10787-023-01272-3

  In conclusion, although MIS-C can be managed with available treatments, more scientific research is still required to fully understand the condition (Gruber et al. 2020). […] Fortunately, treatments for MIS-C are available and have been shown to be effective. The prognosis for patients with MIS-C is excellent and only a few patients have experienced long-term sequelae. […] Studies carried out in various countries have found that the prevalence of MIS-C is significantly decreasing but remains a serious complication of SARS-CoV-2 infection (Cohen et al. 2022; Levy et al. 2022; Miller et al. 2022; Sorg et al. 2022b; Whittaker et al. 2022). […] In the USA, a recent case-control study showed that the Pfizer BioNTech vaccine is 91% effective in preventing MIS-C among vaccinated individuals aged 12-18 years.

• #47 Multisystem inflammatory syndrome in children in Singapore – Annals Singapore

  https://annals.edu.sg/multisystem-inflammatory-syndrome-in-children-in-singapore/

  Antiplatelet and antithrombotic prophylaxis are also part of our management as MIS-C causes a prothrombotic state. […] The management of MIS-C in our institution involves multidisciplinary care according to guidelines jointly formulated by the paediatric intensive care units of KKH and National University Hospital, Singapore. […] Prompt treatment of MIS-C with both IVIg and steroids are our first-line therapy, with high-dose steroids given to those with shock or end-organ disease. […] Early diagnosis and administration of treatment likely contributed to the positive outcomes of our patients.

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