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Pediatric Crohn's Disease and COVID-19 Treated with Infliximab

Pediatric Crohn's Disease and Multisystem Inflammatory Syndrome in Children (MIS-C) and COVID-19 Treated with Infliximab

2020 May

Michael T. Dolinger, MD, MBA; Hannibal Person, MD; Rachel Smith, MD; Lauren Jarchin, MD; Nanci Pittman, MD; Marla C. Dubinsky, MD; andJoanne Lai, MD.

Department of Pediatric Gastroenterology, New York

Abstract

Coronavirus disease 2019 (COVID-19) may lead to a severe inflammatory response referred to as a cytokine storm. We describe a case of severe COVID-19 infection in a recently diagnosed pediatric Crohn’s disease patient successfully treated with Tumor Necrosis Factor-alpha (TNF-α) blockade. The patient presented with five days of fever, an erythematous maculopapular facial rash, and abdominal pain without respiratory symptoms. SARS-CoV-2 PCR was positive. Despite inpatient treatment for COVID-19 and a perianal abscess, the patient acutely decompensated, with worsening fever, tachycardia, fluid-refractory hypotension, elevation of liver enzymes, and transformation of the rash into purpura extending from the face to the trunk, upper and lower extremities, including the palmar and plantar surfaces of the hands and feet. Cytokine profile revealed rising levels of interleukin (IL)-6, IL-8, and TNF-α, higher than those described in either inflammatory bowel disease (IBD) or severe COVID-19 alone. The patient was treated with infliximab for TNF-α blockade to address both moderately to severely active Crohn’s disease and multisystem inflammatory syndrome in children (MIS-C) temporally related to COVID-19. Within hours of infliximab treatment, fever, tachycardia and hypotension resolved. Cytokine profile improved with normalization of TNF-α, a decrease in IL-6, and IL-8 concentrations. This case supports a role for blockade of TNF-α in the treatment of COVID-19 inflammatory cascade. The role of anti-TNF agents in patients with MIS-C temporally related to COVID-19 requires further investig

What is known?

Coronavirus disease 2019 (COVID-19) may lead to severe inflammatory response and cytokine storm.

Morethan 200 patients with multisystem inflammatory syndrome in children and adolescents (MIS-C) temporally related to COVID-19 infection have been reported.

Anti-Tumor necrosis factor-α therapy with infliximab is effective for the induction and maintenance of remission in pediatric Crohn’s disease patients.

What is new?

Higher levels of pro-inflammatory cytokines can be seen in patients with inflammatory bowel disease and cytokine storm associated with COVID-19 infection than are reported in either inflammatory bowel disease or with COVID-19 alone.

Infliximab therapy can effectively treat both pediatric Crohn’s disease and MIS-C temporally associated with COVID-19 infection.


Figure 1.Purpuric rash on the dorsum of the hand and antecubital-fossa before and after treatment with infliximab on hospitalization day 8. Figure 1A and 1B represent the rash on the dorsum of the hand and antecubital fossa prior to infliximab treatment onhospitalization day 8. Figure 1C and 1D demonstrate the improvement in his rash on day 13 prior to discharge

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Many anti-inflammatories were never designed to treat crohn's disease of course, they were designed to treat infections.

This might seem like a paradox at first, how can suppression of the immune system help during an infection.

Many of the severe side effects of an infection are tissue and nerve tissue damage. Controlling the tissue damage from the inflammatory cascade, is often more important that treating the infection. The body is in a constant balancing act, trying to control the infection, but doing so in a way that doesn't result in damage to the body. This is likely what is happening in crohn's disease too, unresolved intestinal infections that lead to chronic inflammation, inflammation that can damage intestinal tissue, whereby anti-inflammatories help mitigate that damage by controlling the inflammatory cascade.

This inflammatory cascade, or "cytokine storm", whereby the body keeps releasing signaling molecules, is seen during chronic and unresolved infections. The body does not have right innate immunity or antibodies, and the adaptive response responds to cytokine signaling . This then leads to chronic inflammation, and possibly tissue damage, because the body is unable to resolve the infection in a timely manner. Unlike the innate response that is instant the moment a macrophage comes into contact with a pathogen, the adaptive response is a response that takes several days, and can cause a lot of tissue damage during the inflammatory cascade, especially if the infection become chronic and unresolved. The role of a vaccine is to make that adaptive response more competent, so the infection is resolved in a timely manner without a chronic inflammatory cascade.
 
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I have seen several doctors ask the question why hospitals aren't using infliximab to treat coronavirus for other patients, in response to study like this. Corticosteroids are used to treat COVID infections, but steroids are slow and harder to dose, infliximab is fast and can be dosed very precisely.

Stopping the inflammatory cascade during an infection was what infliximab was designed to do.

But I think everyone here knows the answer, the amount of money it would take, would be a cost unable to be carried by any hospital.
 
kiny, read these:



 
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