Immunosuppressive Medications for Children with Autoimmune Hair Loss: Considerations during the COVID 19 pandemic

How does Immunosuppression Affect the Decisions We Make ?

Many children with autoimmune related hair loss receive oral immunosuppressive medications. This mostly commonly includes children with alopecia areata but can include other less common immune based hair disorders we see in children. For example, some paediatric patients use prednisone or dexamethasone, some use methotrexate, and some receive tofacitinib. Other immunosuppressive and immmunomodulatory medications are also used (such as the group of medications known as the TNF inhibitors).

Although we know that children in general have a much more mild course than adults, it’s important to consider whether this is also true of children who use immunosuppressive medications. Key questions that I am asked from parents whose children using immunosupressive medications are: how does my child being on an immunosuppressive medication affect the decisions we make during that pandemic? Is my child more likely to get COVID 19? Will my child get sicker if he or she gets COVID 19? Should he or she stay home from school?

COVID 19 and Immunosuppression in Children: What do we know?

It is now well known that children in general (ie non immunosuppressed children or what has also been termed “immunocompetent” children) are more likely to be asymptomatic when the infected with the Sars-COV-2 virus and more likely to have a milder disease course when they get COVID 19 than adults. in fact, a recent meta-analysis by Assaker et al suggested that about 16 % of children with COVID 19 are asymptomatic although this may in fact be as high as 45 % based on a recent study by Poline and colleagues.

In most COVID 19 patient databases around the world, children make up a very small proportion of patients (1-7 %). However, serious consequences can still occur in some children with COVID 19. Fortunately, this is very rare. One more recently studied consequence is the serious pediatric multisystem inflammation syndrome (PMIS) that can uncommonly occur in children.

The ideal recommendations for children using immunosuppressive medications is still not clear. Several medical groups have recommended that children with certain autoimmune diseases stay on their immunosuppressive drugs during this pandemic time period. Studies have suggested that the chances of children getting COVID disease is low and they do get COVID 19, most have a benign course. In general, if children do experience COVID 19, decisions on reducing or stopping treatment are made on a case by case basis. Traditionally, when immunosuppressed children experience viral infections, doctors generally reduce their immunosuppressive medications if possible. We don’t really know if that’s appropriate or not for immunosuppressed children with COVID 19 - but it does seem to be the case for some types of immunosupressive medications. We’ll get to that in a moment.

Therefore, the majority of the data to date would suggest that children on immunosuppressive medications tend to have a mild course if they get COVID 19. A recent report by the UK National Institute for Health and Care Excellence (NICE) states that immunosuppression in children does not increase risk for what is termed “severe” COVID 19. However, children on immunosuppression may have a variety of atypical presentations. In some, this may mean a lack of a fever. In others this may mean a prolonged duration of testing positive for the virus even if they remain asymptomatic.

Perez-Martinez described 8 children with COVID 19 who were using immunosuppressants. They had a mild to moderate disease course although immunosuppressant doses were reduced or stopped in most of these children. In a study by Melgosa and colleagues, children with kidney disease, even those on immunosuppressive medications showed the same evolution as healthy children when affected by COVID 19. The clinical course was typically mild.

Whether there are differences in ability of immunosuppressed children to spread the virus asymptomatically is not clear. A study by Canrutto and colleagues described a young 5 year old girl on immunosuppressive therapy (methylprednisolone and methotrexate) who was positive for the virus for 31 days before finally testing negative.

In general, several groups recommends delaying the immunosuppressive start of treatment in situations where this is at all possible. If children need immunosuppressive medications for treating their disease, it often will be started. All children who do use immunosuppressive medications should practice social distancing and good hand hygiene.

There are no pediatric hair loss specific societies that have offered guidelines on therapy in pediatric patients receiving immunosupresssion. However, data from other pediatric societies and professionals suggest the following information:

PREDNISONE AND ORAL STEROIDS IN CHILDREN

The precise role of steroids is not clear but some studies have suggested that being on systemic steroids (more than 10 mg per day) prior to COVID 19 infection increase the risk of a moderate to severe disease

Fragosa et al propose the following for children:

1) Prednisone (≥20 mg/d) increases the risk of infection with SARS-CoV-2 and COVID-19.

2) Patients being treated with prednisone (≥20 mg/d) should reduce the dose of the therapy, “if possible” to prevent infection by SARS-CoV-2.

3) Patients on prednisone therapy (≥20 mg/d) should discontinue therapy (staggered reduction) if they are positive for SARS-CoV-2 or develop COVID-19.

METHOTREXATE IN CHILDREN

Fragosa et al propose the following for children:

1) It is uncertain whether methotrexate increases the risk of infection with SARS-CoV-2 or COVID-19.

2) Patients using methotrexate for serious autoimmune disease should NOT reduce the dose or discontinue therapy to prevent SARS-CoV-2 infection.

3) Patients using methotrexate should discontinue treatment if they are positive for SARS-CoV-2 or develop COVID-19.

TNF INHIBITORS IN CHILDREN

Studies of TNF inhibitors may be associated with a reduced risk of severe infection in adults although the exact effects in children are not clear.

Fragosa et al propose the following for children:

1) It is uncertain whether anti-TNF therapy increases the risk of infection with SARS-CoV-2 or COVID-19.

2) Patients on anti-TNF therapy should NOT reduce the dose or discontinue therapy to prevent SARS-CoV-2 infection.

3) It is unknown whether patients on anti-TNF therapy should discontinue therapy if they only show positive laboratory results for SARS-CoV-2 but have no clinical manifestation of the disease.

4) Patients on anti-TNF therapy should stop the immunobiological if they develop COVID-19.

JAK INHIBITORS IN CHILDREN

We do not know fully about the role of JAK inhibitors in children with COVID 19. More studies are needed. Some researchers have have wondered whether JAK inhibitors might have a different role at different stages of the COVID 19 infection. For example, some have wondered whether patients who are using JAK inhibitors might have an increased risk of mild disease but yet prevent more severe complications later on. These questions are unanswered.

Some studies in adults have suggested that JAK inhibitors given to patients with COVID 19 may reduce the ‘cytokine storm” that occurs during infection and damages the lungs. We don’t know if this is partially or completely applicable to children.

Reference

Assaker, Rita, et al. Presenting symptoms of COVID-19 in children: a meta-analysis of published studies. BJA: British Journal of Anaesthesia.

Canarutto D et al. Prolonged asymptomatic SARS‐CoV‐2 infection in a child receiving immunosuppressive therapy. Pediatr Pulmonol. 2020 Jul 31

Covid-19 is no worse in immunocompromised children, says NICE. BMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m1802 (Published 01 May 2020). Cite this as: BMJ 2020;369:m1802.

Fragoso et al. COVID-19 and pediatric inflammatory bowel disease: How to manage it? Clinics (Sao Paulo). 2020; 75: e1962.

Marlais et al. The severity of COVID-19 in children on immunosuppressive medication. Lancet Child Adolesc Health. 2020 Jul; 4(7): e17–e18.

Martinez AP. Clinical outcome of SARS-CoV-2 infection in immunosuppressed children in Spain. Eur J Pediatr. 2020 Aug 29 : 1–5.

Melgosa M et al. SARS-CoV-2 infection in Spanish children with chronic kidney pathologies.Pediatr Nephrol. 2020 May 20 : 1–4.

She et al. COVID‐19 epidemic: Disease characteristics in children. J Med Virol. 2020 Apr 15 : 10.1002/jmv.25807.

Poline et al. Systematic SARS-CoV-2 screening at hospital admission in children: A French prospective multicenter study. Clinical Infectious Disease.