The limited scope and depth of existing literature on childhood eosinophilic gastrointestinal disorders (EGIDs) beyond eosinophilic esophagitis (EoE) spurred an international group of researchers and clinicians to develop the first clinical practice guidelines for diagnosing and treating these rare conditions.
The consensus-based guidelines also aim to facilitate high-quality randomized controlled trials of various treatment modalities using a standardized nomenclature.
They were developed jointly by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.
Non-EoE EGIDs are rare chronic inflammatory disorders of the gastrointestinal (GI) tract, estimated at less than 200,000 cases annually in the United States, with unknown long-term consequences, Glenn Furuta, MD, professor of pediatrics at University of Colorado School of Medicine and section head of gastroenterology at the Children's Hospital, Aurora, Colorado, told Medscape Medical News.
"There are many unmet needs. Research has been limited and has not progressed at the pace we want it to," added Furuta, who is corresponding author of the guidelines.
The guidelines were published online in the Journal of Pediatric Gastroenterology & Nutrition, by lead author Alexandra Papadopoulou, MD, Division of Gastroenterology and Hepatology, First Department of Pediatrics, University of Athens, Children's Hospital Agia Sofia, Athens, Greece, and colleagues.
With these, we provide guidance for clinicians to better understand the conditions and also how to diagnose and initiate care for patients with these rare diseases, said Furuta.
Guideline development involved a working group of 26 pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists from 16 countries across five continents. The consensus document includes 34 statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices. In cases where the supporting evidence was weak but agreement was strong, the authors issued conditional recommendations.
The guidelines subdivide the non-EoE EGIDs according to inflammation location: eosinophilic gastritis, eosinophilic duodenitis (EoD), eosinophilic colitis, and eosinophilic enteritis. The latter can be further subdivided into EoD, eosinophilic jejunitis, and eosinophilic ileitis.
Non-EoE EGIDs are hard to diagnose because symptoms are relatively nonspecific and may include abdominal pain, vomiting, diarrhea, and bloody stools, all of which could have any number of underlying causes, Furuta said.
If you are treating a patient who is not getting better with such symptoms as persisting infections, acid-related problems, significant bleeding leading to anemia, intestinal perforation or obstruction, or low serum protein leading to swelling, then you should think that something else is going on that requires more of an evaluation, Furuta noted.
Patients with personal or family histories of eosinophilic or allergic disease should raise greater suspicion, Furuta said. "The next step requires an endoscopy and biopsy."
Awareness of non-EOE EGIDs has been higher among pediatric gastroenterologists than among those treating adult disease because pediatric gastroenterologists have always obtained biopsies of the intestinal tract, Furuta noted.
The guidelines recommend that diagnosis of non-EoE EGIDs in children and adolescents must include signs or symptoms of gastrointestinal dysfunction, dense eosinophilic infiltrates found in mucosal or full-thickness biopsies above organ-specific threshold values included in the document, and absence of other diseases associated with GI mucosal eosinophilic inflammation.
The authors note that the strength of recommendations varies with the often-modest availability of randomized controlled trial data on treatment efficacy.
For example, they recommend that systemic steroids be considered to induce remission but only conditionally recommend topical steroids. They conditionally recommend consideration of empiric elimination diets and conditionally recommend against using food allergy testing to guide diet.
The choice of treatment should be individualized on the basis of the affected GI segment, severity of the disease, patient characteristics, and family resources and capabilities, the authors add.
"We've provided guidance on how to care for patients based on the consensus of experts who have the necessary experience and knowledge base," Furuta said. "Our ability to say, 'Here are the established treatments,' is lacking, though. We need research studies to verify that our recommended approaches are indeed correct."
The authors conditionally recommend that treatment goals include achieving symptom resolution, improving gross endoscopic and histologic abnormalities, promoting normal childhood growth and development, and preventing disease complications.
No pediatric study has determined the natural history of non-EoE EGIDs, and no study of maintenance therapy has been conducted, the authors note.
For this reason, they conditionally recommend that the clinical decision to continue therapy should be discussed with patients and their parents/caregivers, and those discussions include the benefits and risk of long-term treatment, its cost, and its impact on health-related quality of life.
A Starting Point for Patient Management
When asked to comment, Vincent Mukkada, MD, professor of pediatrics at the University of Cincinnati College of Medicine and an attending physician in gastroenterology, hepatology, and nutrition at Cincinnati Children's Hospital and Medical Center, observed that though improved awareness among pediatric gastroenterologists may account for some of the increase in GI eosinophil disease, the incidence is also likely growing.
"We're looking for them much more," said Mukkada in an interview with Medscape Medical News.
"But I also think they're increasing, just like all other atopic diseases. We're not sure why," he added.
"The hope is that these guidelines will allow non-subspecialized gastroenterologists and allergists feel comfortable to at least start on the journey of managing these patients. And, for pediatricians who learn that their patient has received a non-EoE EGID diagnosis, they can go to the summary figures in this one document and very quickly get an overview of the disease and its course," Mukkada said.
Guideline development was funded by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology and Nutrition. The authors and Mukkada report no relevant financial relationships.
J Pediatr Gastroenterol Nutr. Published online July 4, 2023. Abstract