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In Conversation With… Professor Paul Brogan, MBBS MRCP

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"Kids aren't small adults. You have to score growth, puberty, and neurodevelopment, and weigh a symptom's impact differently in a two-year-old versus a fourteen-year-old."
 

When Professor Paul Brogan first walked the wards, he was struck by both the life-saving power of steroids and their profound, age-specific harms. Now Professor of Vasculitis at University College London (UCL) and Consultant Pediatric Rheumatologist at Great Ormond Street Hospital, Professor Brogan has spent two decades reshaping pediatric care through genomic insights and rigorous toxicity measurement.

 

It was during one of his first rotations in training that Professor Brogan encountered ANCA-associated vasculitis in its most devastating form.

 

"Watching someone slip through our fingers despite our best efforts showed me both the limits and the incredible potential of rheumatology."
 

Realizing that 1 in every 1000 young people in the UK has arthritis, Professor Brogan gravitated toward pediatrics, where the clues hidden in a child's genetic code often reveal diseases that would never surface in adults.

 

Long before national genomics initiatives picked up steam, Professor Brogan's team at UCL launched an in-house sequencing effort in 2008.

 

"We set up our own 'cottage industry,' diving headfirst into whole-genome sequencing before the large-scale programs in the UK were up and running. This has enabled us to uncover unexpected mutations, sometimes rewriting a patient's diagnosis entirely."
 

One of the most striking examples came when his group identified five children with an IRAK4 mutation, later nicknamed "NASA" for its dramatic presentation: Neuroinflammation, Autoinflammation, Splenomegaly, and Anemia.

 

"When we administered tocilizumab, the children's CRP (C-reactive protein) levels dropped overnight, and their anemia reversed. They were back to school in days."
 

Yet, the mutation's neurological component remained impervious to treatment; the blood-brain barrier blocked every therapeutic antibody.

 

"It taught me that diagnosis alone isn't enough; we need drugs that can reach every corner of the body, including the brain."
 

These bittersweet breakthroughs underscore Professor Brogan's conviction that accurate diagnosis is only half the battle: therapies must reach every affected tissue.

 

Navigating the steroid paradox

"The first confusion you've got to overcome is that many people equate steroids to anabolic steroids; these are catabolic steroids with muscle-wasting as one of many side effects."
 

Despite the rise of targeted biologics, glucocorticoids still offer unmatched speed, transforming a child from wheelchair-bound to walking within days. But their side effects can range from cosmetic distress and mood changes to growth disruption.

 

"Clinical trials often pit two fantastic treatments head-to-head, but what they don't focus on enough is the steroid going on in each limb of the trial, which profoundly influences the outcome."
 

Questioning long-held dosing norms led Professor Brogan to collaborate with John Stone, MD MPH, on the development of the Pediatric Glucocorticoid Toxicity Index (pGTI). This tool scores age-specific harms and prompts clinicians to ask about sleep, mood, and appearance.

 

"High doses up front will make the patient better, and make the doctor feel good, but you likely don't need that high a dose for as long as we once thought."
 

In parallel with measuring toxicity, Professor Brogan's group is also launching the first investigator-led trial in Kawasaki disease.

 

"We designed a pediatric-specific protocol testing a novel biologic to cut back high-dose steroids in the acute phase, tailoring taper schedules to children's physiology."
 

Early results will reveal whether fewer steroids can deliver the same life-saving benefits with less harm.

 

"The pGTI is designed for clinical trials, but the training to use it has changed my everyday clinic. Now I routinely ask about sleep, mood change, and cosmetic effects that used to be brushed under the carpet. If you can measure steroid-toxicity, you can move it."
 

As genomics and precise toxicity scoring become integrated into standard care, the future for children with autoimmune and autoinflammatory diseases looks brighter and gentler than ever before.

 

 

Professor Paul Brogan is Professor of Vasculitis at UCL and Honorary Consultant in Paediatric Rheumatology at Great Ormond Street Hospital.

 

He leads a clinical service in vasculitis and rare autoinflammatory disease at GOSH, and a clinical academic research programme in the same conditions at University College London's Institute of Child Health.

 

He is the chief investigator of a number of current UK and European clinical trials and has led successfully completed trials, including the MYPAN study funded by Versus Arthritis.

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