Reference:  St Peter, et al. Appendicectomy versus antibiotics for acute uncomplicated appendicitis in children: an open-label, international, multicentre, randomized noni-inferiority trial. The Lancet. Jan 2025

Date: March 19, 2025

Dr. Camille Wu

Guest Skeptic: Dr. Camille Wu is a paediatric surgeon based at Sydney Children’s Hospital where she is the Head of Department. She is also on the Training Committee of Paediatric Surgery for Australia and New Zealand.

Case: A 10-year-old boy presents to the emergency department (ED) with his parents. He started having abdominal pain yesterday and did not want to eat. Today, his abdominal pain worsened, and he developed a fever. On examination, he looks uncomfortable and is tender to palpation in the right lower quadrant. You tell the parents that his examination is concerning for appendicitis. You order an ultrasound that demonstrates a dilated and non-compressible appendix. You consult the surgery team and both of you come to speak with the family. His parents tell you, “His sister was diagnosed with appendicitis during the Covid pandemic. At that time, she was admitted to the hospital but just treated with antibiotics. She was able to go home and has done well since that time. Do you think he needs surgery, or can he be treated with antibiotics as well?”

Background: Acute appendicitis is one of the most common pediatric surgical complaints that we encounter in the ED. Traditionally, appendicectomy has been the gold standard for treatment, based on its effectiveness in preventing complications such as perforation, abscess formation, and peritonitis​. This is typically done laparoscopically through a few small incisions.

The concept of non-operative treatment of appendicitis (NOTA) with antibiotics has gained interest over the past decade. This has been supported by growing evidence suggesting that some cases of uncomplicated appendicitis may resolve without surgery​.

We have covered NOTA before on the SGEM that included some meta-analyses, randomized controlled trials, and observational studies.

The results have been mixed. Some of these studies have suggested that antibiotic therapy is non-inferior to surgical management while other studies have suggested antibiotic therapy did not meet criteria for non-inferiority compared to appendectomy. Most of these studies were conducted in the adult population with fewer studies conducted in children. The question remains:

To cut or not to cut?

Reference:  St Peter, et al. Appendicectomy versus antibiotics for acute uncomplicated appendicitis in children: an open-label, international, multicentre, randomized noni-inferiority trial. The Lancet. Jan 2025

Authors’ Conclusions: Based on cumulative failure rates and a 20% non-inferiority margin, antibiotic management of non-perforated appendicitis was inferior to appendicectomy.

Quality Checklist for Randomized Clinical Trials:

Results: They recruited 936 patients from 11 children’s hospitals in Canada, the US, Finland, Sweden, and Singapore. 459 were assigned to the appendicectomy group and 477 were assigned to the antibiotic group.

Primary Outcome:

34% of the patients in the antibiotic group had treatment failure compared to 7% of the appendicectomy group. That was a difference of 26.7% (90%CI 22.4-30.9). Most treatment failure in the appendicectomy group was due to negative pathology.

In the antibiotic group, 72 (47%) met definition of treatment failure during the first admission.

Secondary Outcomes: 

Neither of the groups had deaths or serious adverse events.

The relative risk of having an adverse event related to the antibiotic treatment compared to the appendicectomy was 4.3 (95% CI 2.1-8.7). Most of these adverse events were classified as Gastrointestinal Distress.

Median length of stay was 1.0 day (IQR 0.76-1.68) for the appendicectomy group compared to 1.25 days (IQR 0.92-2.09) for the antibiotic group. The patients from the antibiotic group spent more time in the hospital during the 12 month follow up period 1.6 days (IQR 1.0-2.6) compared to 1.0 days (IQR 0.75-1.7).

The antibiotic group was able to return to normal activity and school faster than the appendicectomy group. They also did not require pain medications compared to the appendectomy Approximately three-quarters (73%) of the families surveyed from both groups reported being satisfied with their treatment.

Diagnosis of Appendicitis

In previous studies, the way a diagnosis of appendicitis is made has varied. Some studies have included imaging findings on CT scan or ultrasound. Some studies have included lab tests.

This study included patients with a diagnosis of simple, non-perforated appendicitis. They excluded those with suspicion of perforated appendicitis. How was this diagnosis made? We went back to the trial protocol on ClinicalTrials.gov to find some more details. It appears that all children with suspected acute non-perforated appendicitis were assessed by the on-call surgeon. The diagnosis could be made based on clinical suspicion with or without ultrasound imaging.

What is the gold standard for diagnosing appendicitis? We would imagine that surgical pathology consistent with the diagnosis is best but also recognize that is does not make any sense to remove the appendix of every child in the study.

Camille does not rely on imaging. However, often by the time she’s called to see the patient in ED, they’ve already had an ultrasound. Sometimes it’s helpful, sometimes it’s unnecessary, and sometimes it’s distracting. One of the common annoying scenarios is the finding of a mildly thickened 7mm appendix in a child who does have right inferior quadrant tenderness with no other signs of appendicitis, and parents are expecting an operation as the ultrasound says “appendicitis’ and the referring hospital has told them that’s why they were getting transferred. Many of these kids have a viral illness, causing lymphoid tissue in the wall of the appendix to hypertrophy, thereby enlarging the appendix.

Treat the patient, not the test or image finding.

Tests are an adjunct to clinical evaluation. They help us to confirm our diagnosis. How sure does a surgeon need to be to take a patient to theatre? How sure does an ED doctor need to be to call their surgeon to review? Seems like the threshold is different for different specialties, different hospitals, different practitioners, and different countries!

Selection Bias

Of the patients screened for eligibility in the study, 90% were excluded. Of those excluded, ~40% were excluded due to perforated appendicitis or suspected perforation, and the other 60% were excluded because they either declined to participate or “other reasons.”

Suspected perforation seems fairly subjective. I asked Camille to comment on how she clinically distinguishes between perforated or non-perforated appendicitis and the accuracy of making that determination based solely on physical exam.

The other group that was excluded were those who declined to participate or had other reasons. It would have been nice to know what those reasons were. A previous study found that a common reason parents declined to participate was they wanted to choose their treatment arm. Authors acknowledge this in the discussion section that they weren’t able to track the reasons for refusal or declined consents due to lack of funding.

Finally, another group that was excluded was pregnant patients, but pregnant people can get appendicitis too.

Appendicectomy Group vs. Antibiotic Group

There were two groups in this study, one group had surgery while the other received antibiotics. The patients in the antibiotic group received a minimum of 12 hours of IV antibiotics and were discharged if they were tolerating regular diet, pain was controlled, and vital signs were stable. If the patients in this group were not getting better, they could opt for another day of antibiotics or go for appendicectomy.  The surgical group was scheduled for appendicectomy in the next available slot. While these patients were waiting for the operating room, they also received IV antibiotics. The paper does not go into detail as to how long these patients who were in the surgery group waited. Previous research has demonstrated that it is fairly safe to delay surgery for appendicitis for 12 to 24 hours after presentation.

It is possible that these two group received similar treatment.  An antibiotic group  patient might have been on antibiotics for 1-2 days before changed over to getting an operation. An appendicectomy arm patient might be waiting 24-36 hours before getting their operation. Their study protocol specifies that the antibiotic group would have appendectomy by 48 hours if there was no clinical improvement. The surgery group would receive an appendectomy within 18 hours of randomization. We read both the paper and supplementary appendix to see if this actually occurred but couldn’t find any more information. And yes, a paper about appendicitis also has an appendix.

Additionally, the antibiotics given to patients may have varied. The authors write that the choice of antibiotic was dependent on the local centre. The variation in antibiotic regimen may also add some confounding but does help with generalizability. There is no consensus about the best antibiotic regimen for non-operative treatment of appendicitis.

Loss to Follow Up

The proportion of loss to follow up differed between the two groups. There was more data missing from the appendicectomy group compared to the antibiotic group (14% vs 5%). This may lead to attrition bias and over-estimate the treatment effect.

It is unclear why there was a higher proportion that were lost to follow up in the appendicectomy group. Is this because the patients who underwent appendicectomy did great and did not feel the need to follow up? Alternatively, did they not do as well? We don’t know.

Having more patients lost to follow up in the appendicectomy group may also lead to overestimating the difference in treatment failure between the two groups. The authors did perform a sensitivity analysis assuming event rates were the same in the missing data as the complete data without a change in their conclusions.

Non-inferiority Margin

The non-inferiority trial format is particularly relevant in this context, as it assesses whether antibiotic therapy is “not significantly worse” than surgery in terms of efficacy and safety.

This study had a proposed non-inferiority margin of 20%. This was decided as a compromise between patients and families and surgeons. Nonetheless, it is quite generous. Despite this margin that was set, this study still demonstrated that for appendicitis was inferior.

Different families and patients and surgeons probably have differing thresholds for how much risk of complications they are willing to tolerate.

The other question that we need to ask is what aspect of treatment is non-inferior? The primary outcome was treatment failure, but there were other aspects in the secondary outcomes that were also patient-oriented outcomes such as a faster return to school and activity, and less pain medication requirement in the antibiotic group. Those aspects may be more important to the family and patient. We saw very similar satisfaction rates between the two groups.

Although “appendicitis” is the one entity, it affects individuals in different ways, so that in patient-centered care, one size does not fit all.

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ conclusion but think there is more research to be done to investigate if there is a subset of low-risk patients who may do well with non-operative treatment.

Case Resolution: You and the surgical team engage in shared decision-making with the family and patient. You discuss the potential harms and benefits of operative versus non-operative management. The family expresses their desire to try and avoid surgery and the patient is admitted to the hospital for observation on IV antibiotics.

Clinical Application: 

Tune in to the podcast to hear how this paper changed or didn’t change Dr. Wu’s practice and her personal experience with non-operative treatment for appendicitis.

What do I tell my patient/family?

Thank you for your question. There have been many people studying whether we need to do surgery for appendicitis or if we can treat it with antibiotics. The results have been mixed. Let’s talk about the potential harms and benefits of each choice. If you decide that you want to try to avoid surgery, we can have your child stay in the hospital on IV antibiotics and observe him. If he gets better, we can send him home with oral antibiotics. If he gets worse or does not improve, we can revisit the discussion about performing surgery.

References

The post PODCAST: Cuts like a Knife or Antibiotics for Pediatric Appendicitis first appeared on האיגוד הישראלי לרפואה דחופה.

In this episode, we tackle the clinical mischief of Parvovirus B19, a common viral infection with a surprisingly wide range of manifestations—from the classic “slapped cheek” rash of erythema infectiosum to aplastic crises in children with hemolytic anemias and fetal hydrops in pregnant contacts. We’ll break down the virology, epidemiology, clinical presentation, and complications of Parvovirus B19. You’ll also learn how to manage exposures in the emergency department, especially when the child has a pregnant caregiver, and why isolation isn’t always necessary once the rash shows up.

Jordan, Jeanne A. “Treatment and Prevention of Parvovirus B19 Infection.” UpToDate, Jun. 14, 2024. https://www.uptodate.com/contents/treatment-and-prevention-of-parvovirus-b19-infection

Edwards, Morven S. “Clinical Manifestations and Diagnosis of Parvovirus B19 Infection.” UpToDate, Jun. 14, 2024. https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-parvovirus-b19-infection

Macri, Angela, and Crane, Jonathan S. “Parvoviruses.” StatPearls, NCBI Bookshelf, Jun. 28, 2023. https://www.ncbi.nlm.nih.gov/books/NBK482245/

Kostolansky, Sean, and Waymack, James R. “Erythema Infectiosum.” StatPearls, NCBI Bookshelf, Jul. 31, 2023. https://www.ncbi.nlm.nih.gov/books/NBK513309/

“Parvovirus B19 Infection and Pregnancy.” Centers for Disease Control and Prevention. https://www.cdc.gov/parvovirusb19/pregnancy.html

Note: This transcript was partially completed with the use of the Descript AI and the Chat GPT 4o AI

Welcome to PEMCurrents, the Pediatric Emergency Medicine Podcast. As always, I’m your host, Brad Sobolewski, and today we are covering Parvovirus B19—a common but clinically diverse viral infection that you will definitely encounter in pediatrics, and not just in the form of a rash. Parvovirus B19 is best known for causing fifth disease, but in certain patients it can lead to some serious complications like aplastic crises, fetal hydrops, or chronic anemia.

So as you can see, this virus does a lot of stuff. But what is it? Well, let’s get nerdy. It is a non-enveloped, single-stranded DNA virus in the Parvoviridae family. There are some forms of parvo that infect other mammals, but Parvovirus B19 is only for humans, and it loves erythroid progenitor cells. It was discovered by accident back in 1975, so a little bit before I was born, and it was labeled B19 because of the sample number in a Hepatitis B screening panel. Since then it has been identified as the cause of several syndromes. I’ll go over those as we move along here.

Parvovirus B19 is spread via respiratory droplets, much less commonly by blood products or vertical transmission. The incubation period is typically four to fourteen days. Viremia peaks at days five through ten after exposure, and that’s when the patient is most contagious. The classic rash and joint symptoms appear later, and at that point, the patient is actually no longer infectious. So that detail’s key—because when a kid shows up with a slapped cheeks rash, you no longer need to isolate them.

So the classic presentation that’s on every board exam ever is called erythema infectiosum, or fifth disease. This is the most well-known manifestation, seen primarily in school-aged children, especially in the spring and early summer. Again, it’s also known as fifth disease—this is one of the six classic childhood exanthems. These are a group of viral rash-causing illnesses that were originally numbered in the late 19th and early 20th centuries based on their order of description.

So: first disease was measles or rubeola, which obviously we don’t see as much anymore. Second disease was scarlet fever from group A Streptococcus. Third disease was rubella, or German measles. Fourth disease was Dukes’ disease, now believed to be a misclassified form of scarlet fever or staphylococcal scalded skin syndrome. Fifth disease is erythema infectiosum caused by Parvovirus B19. Sixth disease is roseola infantum, caused by HHV-6, and sometimes HHV-7.

Honestly, fifth disease is a historical happenstance—and I just think it’s fun to know that. Sometimes I share it with patients and families.

Here’s how it typically plays out. Phase one is the viral prodrome. This occurs during peak viremia. About 50% of symptomatic patients experience nonspecific flu-like symptoms: low-grade fever, malaise, myalgias, headache, coryza, nausea, and sometimes even diarrhea. This lasts about two to three days.

Phase two is the classic rash. This appears two to five days after the prodrome. You get an erythematous malar rash with circumoral pallor—the classic slapped cheeks appearance. You can also see a lacy, reticular rash on the trunk and extremities, which follows the slapped cheek rash about one to three days later. This rash can fade within a week or two, or it can wax and wane for weeks, especially worsening with sun, exercise, or stress. By the time the rash appears, viremia has resolved and the patient usually feels well.

Only about 25% of infected individuals will have this classic rash syndrome. Another 50% will only have mild flu-like illness, and 25% remain completely asymptomatic.

Let’s talk about the joint symptoms. These are seen in about one out of ten children. More commonly, adults—especially women—have joint symptoms, affecting up to 60% of them. Typically, joint symptoms are symmetric and affect the small joints of the hands, wrists, knees, and feet. The joint pains can last about one to three weeks. Chronic arthropathy occurs in a very small subset of patients and can last for months or more. Importantly, there’s no joint destruction—it hurts, but the joints are fine afterwards.

A serious manifestation of Parvovirus B19 infection that you do not want to miss is called transient aplastic crisis. This occurs when Parvovirus B19 halts erythropoiesis in patients with underlying hemolytic disorders like sickle cell disease, thalassemia, or hereditary spherocytosis. In one study of just over 300 patients with homozygous sickle cell disease, Parvovirus B19 infection caused transient aplastic crisis about 80% of the time.

Presenting symptoms are those of anemia: pallor, fatigue, tachycardia, weakness. You’ll often see a hemoglobin drop of greater than 30% from baseline, an undetectable reticulocyte count, and possibly leukopenia and thrombocytopenia. This often requires hospitalization and transfusion—in one series, 87% of children with transient aplastic crisis required packed red blood cell transfusions.

In immunocompromised children, B19 can also cause chronic infection, with persistent viremia and pure red cell aplasia. You’ll see this in transplant patients, patients with leukemia, or advanced HIV. These patients don’t get rash or joint symptoms—those are immune-mediated—and these kids have compromised immune systems. Diagnosis is confirmed with PCR, often as part of a viral panel, or via characteristic bone marrow findings. Treatment is with IVIG and, if possible, reduction of immunosuppression, though this can be tricky. These patients often need admission and careful care.

Let’s talk about fetal infection. Parvovirus B19 is not routinely screened for in pregnancy, but vertical transmission can cause hydrops fetalis, stillbirth, and severe fetal anemia. The risk is highest in the second trimester. The overall rate of fetal loss after maternal infection is around 2 to 6%, but it may be higher depending on timing and fetal response.

Now, let’s talk about a wonderfully named manifestation: papular purpuric gloves and socks syndrome. This is why pediatrics is great—we have the best names for things. This is a rare manifestation of Parvovirus B19, often seen in adolescents or young adults. You get painful, pruritic petechiae and purpura of the hands and feet, with a sharp demarcation at the wrists and ankles. You may also see mucosal erosions. You’re probably thinking, this sounds like mycoplasma or other viral illnesses—and it does. But unlike fifth disease, patients are contagious when this rash appears.

Finally, let’s talk about some rare neurologic complications. These include encephalitis, Guillain-Barré syndrome, and brachial plexopathy. One review identified about 129 cases of parvovirus-related neurologic complications between 1970 and 2012, with encephalitis making up about two-thirds of those cases. These are rare, but something to keep in mind—especially if you’re in a large academic children’s hospital.

So how do we diagnose Parvovirus B19? It’s usually a clinical diagnosis—especially in cases of typical erythema infectiosum. In more complicated cases or in immunocompromised children, you can check IgM antibodies (which appear about 7 to 10 days after exposure and peak at 2 to 3 weeks). IgG indicates past infection. PCR is most useful in immunocompromised patients or when evaluating possible fetal infection.

Management of erythema infectiosum is supportive care only—antipyretics, hydration, and reassurance. The rash can be itchy; use moisturizers or antihistamines like cetirizine. Explain to families that the rash may last for days to weeks and can worsen with sunlight. I’ve seen a lot of visits in urgent care where this is the main concern during outbreaks.

For joint symptoms, use NSAIDs. A patient with transient aplastic crisis will likely need hospitalization and red blood cell transfusion, especially if unstable. In immunosuppressed patients with chronic infection, treat with IVIG and carefully consider immunosuppressive management.

What if the child has a pregnant caregiver? The child is most contagious **before** the rash appears—during the viral prodrome—so it’s easy to mistake for another virus. Once the rash appears, the child is no longer infectious. If a pregnant household contact was exposed during the contagious period—especially in the first or second trimester—they should contact their OB provider for serologic testing (IgG and IgM). If seronegative, serial ultrasound may be recommended to monitor for fetal hydrops.

Isolation of the child is not necessary after the rash appears. If they are in the viremic phase, then hand hygiene and respiratory precautions are important to limit household spread.

Take-home points:

Thank you for listening to this episode. If you found it helpful, let me know. Leave a review, shoot me a message on social media or email, and share it with your colleagues and learners. And as my 13-year-old would like to remind me: like and subscribe.

For PEM Currents, this has been Brad Sobolewski. See you next time.

Brad Sobolewski, MD, MEd is a Professor of Pediatric Emergency Medicine and an Associate Director for the Pediatric Residency Training Program at Cincinnati Children’s Hospital Medical Center. He is on Twitter @PEMTweets and authors the Pediatric Emergency Medicine site PEMBlog and produces and hosts the PEM Currents: The Pediatric Emergency Medicine Podcast.

The post PODCAST: Parvovirus B19 (Fifth Disease) first appeared on האיגוד הישראלי לרפואה דחופה.

0:00 – Introduction

0:41 – Overview

1:10 – Types of Necrotizing Fasciitis

2:21 – Pathophysiology & Risk Factors

3:16 – Clinical Presentation

4:06 – Diagnosis

5:37 – Treatment

7:09 – Prognosis and Recovery

7:37 – Take Home points

Early Signs & Symptoms

Late-Stage Signs

The post PODCAST: Necrotizing Fasciitis first appeared on האיגוד הישראלי לרפואה דחופה.