Multisystem Inflammatory Syndrome (MIS-C), COVID-19, and Autoinflammatory Diseases in Children

As news has grown about the hyperinflammation syndrome happening in some children possibly connected with COVID-19, we know many parents of kids with periodic fever syndromes are concerned.

Originally reports came out that this syndrome was similar to Kawasaki Disease, but as doctors and researchers have learned more, this new syndrome has some different symptoms and blood test results than Kawasaki’s. The CDC health advisory here refers to this hyperinflammation syndrome as Multisystem Inflammatory Syndrome in Children (MIS-C), previously named by some researchers as Pediatric Inflammatory Multisystem Syndrome (PIMS).

We’ve collected some good and updated information below on MIS-C/PIMS to help learn more about it, as many with an autoinflammatory disease have noticed that it looks like a very bad autoinflammatory disease flare. Hyperinflammation in both adults and children related to COVID-19 infections is thought to be a an overactive immune response to the virus. The hyperinflammation, either during an active COVID-19 infection, or in the case of MIS-C/PIMS, weeks after the COVID-19 infection may cause symptoms similar to the cytokine storms some adults get with COVID, but at this time, it has not been connected to any systemic autoinflammatory diseases (SAIDs).

“The family of conditions characterized by cytokine storm. Malig. = malignancy; Assoc. = associations; SJIA = systemic juvenile idiopathic arthritis; MAS = macrophage activation syndrome; CRS = cytokine release syndrome; ARDS = acute respiratory distress syndrome; EBV = Epstein‐Barr virus; HLH = hemophagocytic lymphohistiocytosis.” – Wiley Online Library: On the Alert for Cytokine Storm: Immunopathology in COVID-19

In fact, a number of reports state that the majority of children that develop MIS-C/PIMS were previous healthy with no pre-existing conditions or chronic illnesses. We are aware that many patients and caregivers are very concerned about the risk for MIS-C in patients with autoinflammatory, or other rheumatic diseases, but at this time, no connection or increased risk has been identified.

Timing of the development of MIS-C/PIMS seems to happen after a COVID-19 infection when antibodies to the virus are developing. According to Dr. Levin of Imperial College in London, “There is a concern that we are seeing a dysregulated immune response…The timing of this illness does seem to coincide with when acquired immunity would be developing.”

MIS-C/PIMS is currently considered very rare, but for those living with a rare autoinflammatory disease, saying something is “rare” may not give much comfort.  Knowledge is power, so it is helpful to learn about MIS-C/PIMS, and the symptoms of COVID-19 infections to try and recognize a autoinflammatory disease flare, vs something different. It may be difficult to determine what is a viral-triggered flare, or hyperinflammation associated with COVID-19, or MIS-C/PIMS, so if there are any concerns, it is essential to contact your doctor right away, or seek urgent care or emergency care if you cannot reach your doctors easily.

Here are some helpful guidelines to always remember–no matter what virus is going around, but especially with COVID-19, as we still know so little about it:

If your or your child’s periodic fever/autoinflammatory syndrome symptoms are:

  • New = CALL/SEE A DOCTOR (or NP or PA)
  • Different = CALL/SEE A DOCTOR (or NP or PA)
  • More severe than typical = CALL/SEE A DOCTOR (or NP or PA)
  • Not responding to treatment(s) as would be typical = CALL/SEE A DOCTOR (or NP or PA)
  • Concerning to you = CALL/SEE A DOCTOR (or NP or PA)

In one of the articles posted below, one doctor stated, “Because parents are afraid of coming to the hospital, they may delay bringing sick children in, which can lead to serious complications…” So, don’t be afraid to go to the ER when needed.

With COVID-19, and MIS-C/PIMS, patients can quickly become more sick, so consider calling for EMS (911 in the US) for an ambulance, if you or your child/loved one is having increased difficulty breathing, responding, or you are not confident you can drive yourself, or your loved one safely to the hospital for urgent care.

Do Children with Autoinflammatory Diseases Have an Increased Risk for MIS-C/PIMS?

We don’t know at this time. The answer is the same as for adults with autoinflammatory diseases, and the risk of a COVID cytokine storm; There’s no research to help answer this question at this time. The virus is just too new, and with autoinflammatory disease being rare, there’s very little known. If you have concerns, contact your doctor regarding your concerns and risks.

The Expert/Autoinflammatory/Rheumatology organization statements here have more guidance on managing your autoinflammatory disease and possible risks in regards to COVID-19. We are adding and updating the list regularly, as the care and treatment for COVID-19 is emerging.

Also, if you or your child with an autoinflammatory disease does get diagnosed with COVID-19, please encourage your doctor to register them with Rheum-COVID.org. This is how we can all best learn about autoinflammatory diseases and COVID-19. You can also complete the Patient Experience Survey on the rheum-covid.org page at this link, to report yours or your child/loved one’s experience with COVID (diagnosed with testing, or clinically based on symptoms.)

Pediatric Inflammatory Multisystem Syndrome (PIMS): What Parents Should Know – Children’s Hospital of Los Angeles

“PIMS stands for pediatric inflammatory multisystem syndrome [now referred to as MIS-C]. It describes a new health condition seen in children who have been infected with novel coronavirus, recovered from it and later have an immune response that results in significant levels of inflammation in organ systems and symptoms. PIMS is similar to other inflammatory conditions like Kawasaki disease and toxic shock syndrome.

Children who have PIMS generally did not have obvious symptoms when they were infected with novel coronavirus, like cough, and generally were healthy prior to developing PIMS.”

Kids with suspected COVID-related syndrome need immediate attention, doctors say

“The syndrome appears to develop two to six weeks after infection with Covid-19 and affects mostly children who were perfectly healthy beforehand.”

“”Any child at home who has fever, abdominal pain or symptoms such as rash and conjunctivitis should be seen by a pediatrician right away,” he advised. “I think we need to have a low threshold for evaluation.”

“And most of the children had no underlying conditions that might make parents wary. “No definitive underlying conditions predispose children to this,” he said.”

Mystery Inflammatory Syndrome in Kids And Teens Likely Linked To COVID-19

“The inflammatory syndrome can appear days to weeks after COVID-19 illness, doctors say, suggesting the syndrome arises out of the immune system’s response to the virus.

“One theory is that as one begins to make antibodies to SARS-COV-2, the antibody itself may be provoking an immune response,” says Newburger.”

“”They all present in varying ways,” says Parikh, who is also a spokesperson for Physicians for Patient Protection. “But the common theme was fever and rash. One had very, very swollen lymph nodes and lymph glands. And then, aside from that, they had markers of inflammation elevated in their blood.””

15 states now investigating child illness possibly linked to coronavirus, Cuomo says

“COVID-19 symptoms are predominantly respiratory; but the Kawasaki-like syndrome [now referred to as MIS-C] seen in children appears to be caused by an inflammation of blood vessels, presenting cardiac symptoms. Predominant symptoms include prolonged fever, abdominal pain and a skin rash. Afflicted children, however, have also shown had changes in skin color (becoming, pale, patchy, or blue), difficulty feeding (for infants), difficulty breathing, a racing heart, as well as lethargy, irritability or confusion. “

Severe COVID-19 in Children and Young Adults in the Washington, DC Metropolitan Region – Published in The Journal of Pediatrics

This is a detailed overview of 177 children and young adults with PIMS. It includes details of symptoms, ages, underlying medical conditions and more.

The authors noted in the results:

With regard to symptoms, shortness of breath was more common in hospitalized compared with non-hospitalized children/young adults, but other features did not clearly distinguish them from less ill children, including presence of fever. Minor symptoms such as congestion/rhinorrhea, sore throat, cough and headache were also present more commonly in the non-hospitalized cohort. As has been the case in adult reports, fewer than half of the patients had both fever and respiratory symptoms present at the time of their diagnosis, but the majorities have one or the other. Our critically ill cohort includes a previously well child with the newly emerged hyper-inflammatory phenotype of SARS-CoV-2- associated KD-like shock syndrome [now referred to as MIS-C] that has been identified concurrently within the same time frame at other centers internationally.

Rethinking COVID-19 in Children

“Dr. Newburger said that the Covid-19-related cases are a multisystem severe inflammatory syndrome modulated by the immune system, which many people think may appear a few weeks after the initial encounter with the coronavirus. The children come in with high fevers, with dysfunction in one or more body organs, and with lab tests suggesting inflammation.”

“Because parents are afraid of coming to the hospital, they may delay bringing sick children in, which can lead to serious complications, he said.”

Kawasaki’s Disease and PIMS/MIS-C

Since some children with an autoinflammatory disease have a history of a Kawasaki Disease (KD) or an incomplete KD diagnosis, it’s reassuring that various KD organizations, such as Societi Foundation The UK Kawasaki Disease Foundation and Kawasaki Disease Foundation, have stated the following:

“There is no information to suggest that children who have had KD are at increased risk for complications of COVID-19 infection compared to the general population.  Our team at Rady Children’s Hospital San Diego and UCSD are at the forefront of research to understand this new, complicated form of COVID-19/KD and are collaborating with colleagues around the country and around the world to better understand this condition and how to treat it.” – Dr. Jane Burns

“There is no current evidence of any increased incidence or greater susceptibility to Covid-19 infection for children who had Kawasaki Disease in the past.” – Societi Foundation

Autoinflammatory COVID-19 Resources for Information

COVID-19 (coronavirus) is on the minds of many around the world, and in some regions, it has hit very hard. We know our autoinflammatory/periodic fever syndrome patient community is very concerned.

Below is a list of trusted resources, but know that right now there is
not a lot of specific information geared to these very rare autoinflammatory
diseases.

*If you have complex, chronic medical issues, or have any medical
concerns, consult with your doctors and medical professionals that care for
you or your loved ones on the proper disease management and infection
prevention for your family.*

*Please follow the WHO and CDC recommendations, and follow your local
and state guidelines for your part of the world.*

International Society of Systemic Auto-Inflammatory Diseases (ISSAID) Recommendations for COVID-19 

Key recommendations for the care of autoinflammatory patients:

“3. At the moment for all patients with autoinflammatory diseases on medication, we recommend to continue all therapies as usual.

4. Don’t stop your medications including colchicine and biologics, without consulting your doctor. This may cause a flare of your autoinflammatory disease.

5. If you are on corticosteroid therapy – consult your doctor regarding possible dose adjustment.

6. Patients in isolation or quarantine (without symptoms) should continue therapy as usual.

7. In case of fever and suspicion of infectious diseases follow your national advice for access to health care and to test for Covid-19. In the meantime, continue colchicine and, if taking biologics, get in touch with your treating physician for guidance.”

(adapted from the EULAR recommendations) 

COVID-19 Global Rheumatology Registry

“In response to the evolving global COVID-19 coronavirus pandemic, we are
creating a secure, de-identified, international case reporting registry. It is
our hope that the information collected will help guide rheumatology clinicians in assessing and treating patients with rheumatologic disease and in evaluating the risk of infection in patients on immunosuppression.”

Please share this registry with your rheumatologist or immunologist so the
doctor can submit a case report. http://rheum-covid.org/

Paediatric Rheumatology European Association (PReS) Recommendations for Coronavirus Outbreak

“3. At the moment for children with rheumatic diseases on medication, we recommend to continue all therapies as usual.

  1. Don’t stop your medications including methotrexate (MTX) and biologics, without consulting your rheumatologist. This may cause a flare of your rheumatic disease.
  2. If you are on corticosteroid therapy – consult your rheumatologist regarding possible dose adjustment.
  3. In case of fever and suspicion of infectious diseases follow your national advice for access to health care and to test for Covid-19. In the meantime, withhold MTX and, if taking biologics, get in touch with your treating rheumatologist for guidance.”

Click here for the full statement.

Click here for translations in multiple languages.

From Rheumatologist Dr. Jack Cush at RheumNow

“First, it is important to counsel patients to NOT stop their anti-rheumatic, analgesic, anti-inflammatory, DMARD or biologic therapies. These are given to manage symptoms and/or to reverse inflammation or immune dysregulation. The message should be that uncontrolled disease is a much greater risk (because it would promote inflammation and immunosuppression) than the therapies we prescribe.”

Click here for more info and a summary of medications used by rheumatology patients in the treatment of COVID-19

AMRI: Associazione per le Malattie Reumatiche Infantili

COVID information for pediatric rheumatology patients (In Italian, but there is helpful info for anyone):

“….based on information currently available on the new coronavirus, children with rheumatic diseases are not at greater risk of infection…There is also no indication to discontinue immunomodulatory or immunosuppressive therapies except in special cases”

Click here for the complete letter in Italian.

Click here for the Google Translate link to English

FAI2R Flyer for COVID19

Click here for flyer in French

Click here for Google Translation in English

Arthritis Foundation Corona and Arthritis: What You Need to Know

“The CDC website goes on to say: “If you are at increased risk for
COVID-19 complications due to age or because you have a severe underlying medical condition, it is especially important for you to take actions to reduce your risk of exposure.” It recommends, if COVID-19 is spreading in your community, taking extra measures to put distance between yourself and other people, including staying home as much as possible and avoiding crowds, especially in poorly ventilated spaces.

We asked Michael George, MD, a rheumatologist and epidemiologist who studies infections in patients with autoimmune disease, who should follow this new guidance. He says. “The more at risk you are, the more you should consider this recommendation.”

He says this new guidance particularly applies to those with more severe
disease or who have been hospitalized in the past with a respiratory infection or have interstitial lung disease, COPD or asthma, for example. Those with more mild disease may want to ask their doctor for guidance.”

Click here for more from the Arthritis Foundation

Multisystem Inflammatory Syndrome (MIS-C), COVID-19, and Autoinflammatory Diseases in Children

Information on MIS-C, the hyperinflammation syndrome that is affecting children possibly post COVID-19 infection, and autoinflammatory diseases.

CDC Coronavirus Disease 2019 (COVID-19) Page for High Risk Patients

https://www.cdc.gov/coronavirus/2019-ncov/specific-groups/high-risk-complications.html

World Health Organization (WHO) Q&A on coronaviruses (COVID-19)
here

https://www.who.int/news-room/q-a-detail/q-a-coronaviruses

IPOPI Primary Immunodeficiency Statement

There is currently no data pointing to whether PID patients are actually at
higher risk of more severe diseasefrom COVID-19(as per the WHO, CDCs and PID expert healthcare professionals and NMO representatives along with patients themselves).

However, it is believed that PID patients might be at higher risk for this
infection or a more severe course of the disease. Thus, patients with PID need to take extra care to prevent from getting this infection”

Click here for the full statement.

Primary Immune Foundation

Regularly updated page with current information. Click here.

TRAPS Life Without Proper Medication – My Story

Written by Claire

I’m not too sure where to begin regarding my thoughts on no treatment or non-medical treatment for TRAPS (TNF-receptor associated periodic fever syndrome) and other autoinflammatory diseases. All I know is I have so much to tell you of the consequences of a lifetime without treatment. 

Hi, I’m a woman in my mid-50s with TRAPS. I was diagnosed approximately eight years ago .

As a child, I was sickly and spent a lot of time in Sick Kids Hospital in Toronto. Back in the sixties, no one knew what I had or what was going on except I always had blood in my urine and had issues with my digestive system. Then it seemed to have disappeared except for the rare flare at Christmas, Easter, or birthdays.  My mom always thought I was a delicate flower so too much excitement, too much of anything was very controlled.

I grew into my twenties and like most of us in my time, I got married and started a family. It was the healthiest time of my life! I had the energy of three people. I was on top of the world. Nothing could stop me or bring me down. Great family, awesome children, best career ever…I was unstoppable! 

Then I turned 35. 

I woke up one morning unable to move. My youngest son stayed home from school that day–his first time ever missing school. I was so weak I could not even sip or hold a juice box. My husband was out of town working so all I had was my young son. He ran to a neighbor’s house. They came over and could not believe how swollen and distorted I looked. Immediately, they called 911. The ambulance  arrived and they took one look at me and said,  “I hope she makes it to the hospital.” I was in total organ failure!  This was the beginning of my nightmare. I was in the hospital for weeks. That year I had three major flares. I had a hysterectomy and was  diagnosed with everything from lupus to a rare form of lymphoma. Needless to say, my life changed tremendously. 

The next decade and a half brought countless doctors appointments, most telling me, “we know something is not right” and others saying, “it’s all in your head.”  It cost me my marriage, my security, and life as I knew it. 

One day I was in the emergency room with a swollen rash everywhere and my c-reactive protein (an inflammatory marker in my blood) at 465. I honestly thought, “Today I’m gonna die not knowing why…perhaps during my autopsy they will figure it out.” Sadly, that gave me comfort. A young doctor, his first week on the job, walked by me, stopped, pointed, and said, “I know what you have. I’ll be right back.” I thought, “Buddy, you’re just another *bleep* who will get my hopes up and then call my crazy.” He came back with a rheumatologist  (who is still my doctor), and for the first time explained to me what they believed was going on and what we needed to do to prove it. So we did genetics, countless hours of documentation, and countless hours of submitting applications for biological medicine only to be denied.

TRAPS periodic fever syndrome
With genetic testing, small mistakes in DNA that can cause systemic autoinflammatory diseases can be found, which can lead to a diagnosis and better treatment for patients with periodic fever syndromes. Learn more about genetic testing here.

Eight years have passed since my confirmed diagnosis of TRAPS and my only effective medicine has been prednisone. I have tried Humira, Enbrel, and a few more that never helped me.  I was too far gone for those medicines. I have not been able to get access to the treatments that are more effective for TRAPS. The inflammation  with no proper treatment over decades put me in a very terrible position. I could no longer work and enjoy my lifestyle.

Amyloidosis, high blood pressure, kidney issues, eye issues, and liver issues were the first to crop up. During this time, I was still flaring and being treated with prednisone. Almost four years ago I had a flare, a  real bad one, and was on Enbrel at that time. I ended up blowing my L3, L5, and S1 in my spine. It was classified as catastrophic. I am still in therapy after learning to walk again and my bladder stopped working. I now have a pacemaker in my right bum cheek attached to my spine so I can urinate and use my bowels, plus I have a multitude of issues that come with a spinal cord injury. For a long time Enbrel was blamed, but with evidence from many  x-rays, we now realize that constant, prolonged, untreated inflammation was to blame.

Needless to say, I wish I could turn back time.

I’m telling you my story so you are aware that this is what happens when you are not properly treated or are not any treatment plan for autoinflammatory syndromes. It angers me to see parents go through years of doctors and tests and stress with their children, only to resort to tart cherry or diet*, or nothing at all.  If you have the option of a biological treatment that could stop unseen inflammation from destroying your children’s body in the future, why would you not try it? Treatment plans are not always convenient, easy, fashionable, or 9 to 5. They are designed to treat your child now, so that in the future they can live a happy, productive, and healthy life.

I share my experience to show what happens when treatment is never given or comes too late. 

*Research has shown the most effective treatments for TRAPS are biologic medications that target the cytokine Il-1. Tart cherry supplements and diet are not proven treatments for any periodic fever syndrome. Read more here to learn about TRAPS.