4 genes' activity could be key to faster appendicitis diagnosis

Father carries his daughter who buries her head into his shoulder in front of a doctor in the foreground
The genetic markers of severe appendicitis identified in this study may help doctors diagnose the condition more quickly and prescribe the correct treatment to children. (Image credit: izusek via Getty Images)

Doctors could use distinct patterns of gene activity in the blood to more quickly diagnose and treat children with life-threatening appendicitis, new research suggests. 

These genetic measures could help doctors differentiate between so-called simple and complicated appendicitis at early stages of the disease, researchers wrote in a paper published Monday (Feb. 19) in the journal JAMA Pediatrics. This method of diagnosis could flag which patients should be rushed into surgery and which might be able to be treated through nonsurgical methods, such as antibiotics, they noted.

The appendix is a finger-like tube that extends from the large intestine. If the appendix becomes blocked — for example, by food or feces — disease-causing pathogens can get trapped within it, triggering inflammation. The appendix can then swell and push against nearby blood vessels, reducing blood supply to the organ and causing sharp abdominal pain. 

There are several forms of appendicitis. One is chronic, with milder symptom flare-ups that come and go over weeks, months or years. Another is "acute," involving symptoms that suddenly emerge over 12 to 24 hours and can be life-threatening, requiring immediate surgical removal of the appendix. 

Related: What if humans didn't have an appendix?

One life-threatening complication of appendicitis is that the appendix can burst due to the pressure caused by swelling; this is known as "perforated" or "ruptured" appendicitis. In this scenario, infected fluid can leak into the abdomen and throughout the body, potentially causing blood poisoning or sepsis. If the appendix doesn't burst or develop other complications, patients are described as having "simple appendicitis," which usually requires shorter hospital stays and has a reduced risk of readmission. And in some cases, simple appendicitis can be successfully treated with antibiotics rather than with surgery.

Children are the most likely age group to get appendicitis — but when a child is brought into the hospital, doctors may struggle to distinguish between simple and complicated appendicitis, especially at early stages of the condition. This is because, apart from taking ultrasounds, clinicians have to rely on insensitive lab diagnostic tests and scoring systems that are based on physical symptoms, such as nausea or fever. These measures can result in misdiagnosis, leading to delayed treatment, the study authors wrote. 

In their new analysis, the researchers looked at the gene activity of more than 70 children ages 5 to 17 who were hospitalized with suspected appendicitis in Canada. They found that the kids could be retroactively diagnosed as having either simple or complicated appendicitis based on the level of activity of four genes. The researchers measured the gene activity by looking at the amount of RNA — a molecule used to convert DNA into proteins — in samples of the children's blood taken when they were admitted to the hospital. 

Appendicitis is caused by the inflammation of the appendix, a small, finger-like extension of the large intestine, illustrated in orange above.  (Image credit: decade3d via Getty Images)

The gene activity analysis delivered an accurate diagnosis 85% of the time. If the test can be used to help doctors reach accurate diagnoses faster, it could help them select the best drugs, namely antibiotics, to prescribe patients and prioritize who receives surgery first, the authors wrote. 

"It is well known that the earlier the physician applies appropriate therapy, the better the outcome," Bob Hancock, co-senior study author and director of the Centre for Microbial Diseases and Immunity Research at the University of British Columbia, in Canada, told Live Science in an email. 

In the case of perforated appendicitis, "a diagnosis would indicate the use of potent antibiotics and supportive therapy as well a triage of the patient into the Intensive Care Unit," he said. 

In a separate analysis, the authors also discovered that children with perforated appendicitis had a dysregulated immune response to infection, similar to that seen in sepsis. This was evidenced by the activity of immune-related genes in their blood. Recognizing that perforated appendicitis shares features with sepsis may help doctors recognize the deadly condition as soon as patients arrive at the hospital, pediatric surgeon Dr. Maurizio Pacilli and biomedical data researcher Rishikesan Kamaleswaran wrote in a commentary of the study. 

That said, while these findings are a "step forward" in our understanding of appendicitis, the newly identified gene markers will need to be tested in more people in large clinical trials before they can be used for diagnoses in hospitals, the commentary authors wrote. 

Future research should also assess whether these tests could feasibly be put into widespread use, taking into account how much they may cost and how long they would take to perform, the commentary authors added. 

This article is for informational purposes only and is not meant to offer medical advice. 

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Emily Cooke
Staff Writer

Emily is a health news writer based in London, United Kingdom. She holds a bachelor's degree in biology from Durham University and a master's degree in clinical and therapeutic neuroscience from Oxford University. She has worked in science communication, medical writing and as a local news reporter while undertaking journalism training. In 2018, she was named one of MHP Communications' 30 journalists to watch under 30. (emily.cooke@futurenet.com