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Appendicitis Research at the Alberta Children's Hospital

Experts at the Alberta Children's Hospital and Research Institute have discovered a biological "fingerprint" for appendicitis and are close to developing a simple blood test that could diagnose children in the Emergency Department within an hour.

Abdominal pain is among the top reasons parents bring their child to the Emergency Department and emergency doctors will tell you that one of parents’ biggest worry is appendicitis. In fact, each day at the Alberta Children’s Hospital, at least one child is admitted for appendicitis surgery.

Pediatric emergency physician and clinician-scientist at the Alberta Children's Hospital, Dr. Graham Thompson, has treated hundreds of children with the illness over the last decade and agrees parents have the right to be concerned. Appendicitis is a serious medical condition, especially for children, where the appendix becomes inflamed and painful. If left untreated, an inflamed appendix will eventually burst, spilling infectious fluid into the child’s body. This can lead to a long hospital stay, a prolonged course of strong IV antibiotics, and in severe cases, it can even be fatal.

Nada Vulic remembers that day in March when her eight-year-old son, Pavel, had his emergency appendectomy. She says it’s frightening watching your healthy and active child suddenly ashen and doubled over in pain in the Emergency Department.

“The worst part was the ultrasound. They had to press quite hard to get the best picture of his appendix and Pavel almost hit the roof from the pain. He looked like he was about to go into shock,” says Nada. “And this is a child who didn’t even cry when he broke his arm. He has a very high pain tolerance, but that day he was in agony.”

Nada brought her son to the Alberta Children’s Hospital after he became ill on a ski trip with his dad in BC. When he preferred to sleep rather than ski, his parents could tell something wasn’t right. Thinking he was coming down with the flu, they kept a close eye on him. The severity of Pavel’s condition became more apparent as he began vomiting and doubled over in pain.

August eupdate 2018_Pavel_appendicitis_hospital“We arrived at Emergency and he was taken right in. They began tests immediately. I have a medical background and I was amazed at how much of it has rubbed off on Pavel. He was so sweet explaining to the doctor exactly how the pain started and how it had progressed. ‘The pain started up high, then radiated across my body, and then travelled down the other side.’ I was so proud of how he spoke to his doctors, but it did make me worried for younger children or babies who can’t articulate where it hurts.”

Diagnosing appendicitis can be challenging, even for the most experienced specialist. Many children present with non-specific signs and symptoms that mimic other common illnesses such as viral gastroenteritis, urinary tract infection and constipation. As well, today’s diagnosis methods – current blood tests and ultrasound – hold a wide margin for error. In up to half of all cases, the appendix can’t fully be seen with ultrasound and doctors are unable to confirm inflammation. And while biomarkers targeted in current blood tests simply demonstrate the presence of general inflammation and infection, they are not specific to appendicitis itself. 

“The clinical challenge is to diagnose appendicitis early enough to prevent progression to a perforation and to identify patients who require surgery,” says Dr. Thompson. “That isn’t easy. Picking out a child with appendicitis amongst all those with abdominal pain is sometimes like finding a needle in a haystack. We need to do better for these kids and families.”

Within five hours of arriving at the Alberta Children’s Hospital, Pavel’s doctors determined he must have appendicitis. While it was caught before his appendix could rupture and spill infectious fluid into his body, he needed a life-saving operation straight away. Within days of his surgery, Pavel was back to his energetic, boisterous self and it’s hard to imagine he was ever sick. However, Nada remembers being truly frightened in the Emergency Department that day, knowing that time was of the essence to help her son.

“It must be incredibly stressful for Emergency doctors because appendicitis is incredibly difficult to diagnose. And no one wants to operate on a healthy child just in case, but by the same token, sending a child with appendicitis home would be terrible. In the early stages especially, it’s almost a guessing game. A very educated guessing game.”

Dr. Thompson, who is a member of the University of Calgary Department of Pediatrics and the Alberta Children's Hospital Research Institute (ACHRI), led a multi-disciplinary team of researchers to test hundreds of proteins and by-products of metabolism, narrowing their scope to a bio-profile of 16 significant compounds that were found to be highly specific for pediatric appendicitis. The team then analyzed the blood and urine samples of 121 children with abdominal pain, some with appendicitis and some without, to re-examine these biomarkers. The study showed a clear distinction between those children with the illness and those without. Importantly, this testing also demonstrated the potential to identify which child had a perforated appendix and which child did not, which would be significant when determining the best treatment strategy for each child.

Nada was very excited to hear about this work.

August eupdate 2018_Pavel_appendicitis_after“A simple blood test would be a game changer for families! We are so grateful to the amazing team at the Alberta Children’s Hospital who saved Pavel. We were very lucky that his appendicitis was caught before his could rupture, but the ability to diagnose faster would have saved him so much pain.”

“These findings are very exciting. We are using precision medicine to soon diagnose a common and serious illness faster and more accurately than ever before,” says Dr. Thompson. “This research is world-class and we can’t do it alone. The support of this community has empowered our team to improve the care of acutely ill and injured children who rely on our Emergency Department. We are truly grateful for their continued investment and belief in our work.”

This research, thus far, has been supported by community donations through the Alberta Children’s Hospital Foundation and is published in Scientific ReportsDr. Graham and the research team have also just received funding from the Canadian Institutes of Health Research (CIHR) for a large, national multi-site trial in pediatric emergency departments through the Pediatric Emergency Research Canada (PERC) network. Dr. Graham says a simple finger prick test for appendicitis - like that for diabetes - could be available in Emergency Departments in as early as five (to ten) years.

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