Issue 1 • 2021

Paediatric immune and inflammatory disorders

There are exciting and innovative clinical updates in paediatrics, which were discussed during the final webinar of the RACP Online Congress 2020 series, Paediatric immune and inflammatory disorders. Chaired by Professor Jim Buttery, an infectious diseases physician at the Royal Children’s Hospital, we heard from Dr Dean Tey, Dr Sam Mehr and Professor David Burgner in a thought-provoking session covering food allergies, autoinflammatory disorders and paediatric multi-system inflammatory syndrome (PIMS-TS).
“Today’s sessions are linked as they all address clinical problems with immune dysfunctions that spreads as inflammation,” shared Professor Buttery.
Dr Dean Tey is a paediatric allergist and immunologist at the Royal Children’s Hospital in Melbourne. He enjoys an active role in teaching medical students, junior trainees and general practitioners. He also has a key research involvement with HealthNuts and the Probiotic and Peanut Oral Immunotherapy Trial (PPOIT).
Dr Tey instantly captured our attention, as he spoke about pivotal moments in history. “The equivalent pivotal moment in allergy is this study that was published in 2015, the Learning Early About Peanut Allergy (LEAP) Study, by Dr George Du Toit. This really changed the course of food allergy, in particular, how we approach early introduction of peanut in infants.”
Dr Tey explained that in this randomised controlled trial of 640 high-risk infants with severe eczema and/or egg allergy, infants who had peanut introduced before the age of one were 85 per cent less likely to have peanut allergy, in comparison to where peanut was introduced after the age of five.
An important question was then raised: “What has been the global response to peanut introduction post-LEAP?” Dr Tey discussed a US article published in 2018 in the World Allergy Organization Journal by Shaker. “In America, the recommendation was that if one does not have eczema or food allergy, or if they’ve got mild to moderate eczema, peanut can be introduced into the child’s diet. However, if the child has severe eczema, egg allergy, or both, it is strongly recommended that the child is screened for peanut allergy via either a specific IgE or a skin prick test. The infant would then introduce peanut only if the results were negative, but if the test was positive, they would have to undergo a medically-supervised food challenge test.”
Dr Tey contrasted what was recommended in the US with the Australian Feeding Guidelines, using examples from 1998 through to 2016. The key takeaway is that “the current infant feeding guidelines have been successfully implemented in Australia. The rate of early peanut introduction before age one jumped from 28 per cent in 2007-2011 to a staggering 89 per cent in 2017-2018.”
The session concluded with some interesting questions from the audience, including “why is peanut allergy more prevalent in the west compared with for example, South-East Asia?” Dr Tey said researchers don’t really know why, but “what is interesting is that epidemiological studies from HealthNuts revealed that Australian-born Asian children are amongst the highest risk group for developing food allergies.”
Dr Sam Mehr then took the virtual stage to explore autoimmune inflammatory disorders. Dr Mehr has been a paediatric allergist/immunologist for more than 10 years and his appointments include Consultant Staff Specialist at the Royal Children’s Hospital in Melbourne and Sub-Editor of the Journal of Paediatrics and Child Health.
Dr Mehr commenced the session with an interesting periodic fever syndromes (PFS) case study. “This is a real case that came to us in the clinic. It’s a 10-year-old girl who had recurrent fevers since the age of four. Her fever duration went for five days and the fevers were very predictable. Every four weeks, like clockwork, the child presented fevers.” He discussed the patient’s symptoms, family origin and family history, which showed the girl’s mother had recurrent fever and pharyngitis as a child. “The mother couldn’t remember why, but she had a tonsillectomy and all of a sudden these fevers stopped.” He explained the investigations, management tried and genetics. “Along the way, the child had a genetic test before she came to us. She was known to be a heterozygous carrier for the common MEFV mutation which is found in Familial Mediterranean Fever (FMF).”
Advising that he would come back to the case study after he had discussed PFS in more detail, Dr Mehr then shared the key points: “PFS is in the realms of paediatricians as it will usually present in infancy or early childhood. Taking family history and asking the parents that question of consanguinity is important given the genetic basis of many of these fever syndromes.” He continued with his discussion of the basics of periodic fever: “how I work it out in the clinic is, is this patient having stereotypical inflammatory attacks and is there evidence of biochemical inflammation at the time of the attack?” He also discussed how to keep a fever diary and showed some of the inflammatory clues present in some PFS.
Going back to his case study, Dr Mehr said: “here is this girl with a fever duration of five days, like clockwork, with pharyngitis and mouth ulcers, but the parents are from an area where FMF is common. The mother somehow had a tonsillectomy that made itself better, prednisolone shortens these attacks, and yet the child is heterozygous for MEFV mutation.
“So, what has she got? Has she got FMF? Has she got Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA)? In the end, your clinical acumen always wins, and we felt she had PFAPA because you don’t have cyclical attacks with FMF. With FMF, you’re not getting mouth ulcers and pharyngitis and don’t respond to steroids.”
Our last speaker, Professor David Burgner, then gave an exciting update on paediatric multisystem inflammatory syndrome (PIMS-TS). Professor Burgner is a clinician scientist, group leader and principal researcher at the Murdoch Children's Research Institute, and a paediatric infectious disease clinician at the Royal Children’s Hospital in Melbourne.
“We’re in the middle of a pandemic of information and data. In amongst that pandemic, it’s really hard to see the wood from the trees. We’ve had a huge explosion in non-peer reviewed pre-prints, which makes seeing what’s a true phenomena quite difficult. In amongst all this, in April of 2020, in the UK there was an alert from the Paediatric Critical Care Society (PICS UK) about this new condition, PIMS-TS,” explained Professor Burgner. He displays the alert from PICSUK, which National Health Service England retweeted on 27 April, asking people to share it widely.
“It generated quite a lot of anxiety and there was some scepticism at the start as to whether this was indeed a true phenomenon.” He confirms it is a true phenomenon and advises he will walk us through some of its features. News headlines such as ‘Kawasaki disease – The latest weird illness from Coronavirus’ from Forbes, 'Three children have died in New York of illness linked to virus' from The New York Times and ‘At least 12 UK children have needed intensive care due to illness linked to COVID-19’ from The Guardian are displayed. Professor Burgner dives into PIMS-TS, exploring what this condition is, the epidemiology, what it looks like immunologically, where it fits with Kawasaki disease, the clinical features and treatment. He keeps us engaged by using a range of modern references and memes.
“Why we get so worried about Kawasaki disease is the coronary artery damage that can occur in a quarter of untreated patients, and even with optimal therapy, up to five per cent of those treated in a timely manner.
“This isn’t the first time that coronavirus has been mentioned as the context of the cause of Kawasaki disease,” Professor Burgner shared, while drawing our attention to a list of suggested but then discarded aetiologies, with ‘human coronavirus New Haven’ highlighted. “The fake news of a novel coronavirus from about 15 years ago was suggested to be a cause of Kawasaki disease generated a lot of excitement but was swiftly dispatched.” He drew our attention to a range of news headlines, with ‘fake news’ displayed in red overlaying the screen.
The session concluded with some questions from the viewers, with one person asking “Do you think our understanding of Covid-related illnesses will see us find a potential cause for Kawasaki disease?” Professor Burgner responded that there have been some great studies resulting from COVID-19. “I don’t think there is a single cause for Kawasaki disease, personally. I think there are a number of potential triggers, probably two acting at once, but from COVID-19, we’ll understand a lot more about how infection triggers inflammation and how that might affect the vasculature. This will be relevant to Kawasaki disease and more broadly.”
Thank you to Professor Jim Buttery, Dr Dean Tey, Dr Sam Mehr and Professor David Burgner for forming a fascinating session, which truly ended RACP Congress 2020 on a great note.
If you would like to find out more, you can watch the recording of this engaging session on RACP Medflix.
© 2021 The Royal Australasian College of Physicians