Chronic abdominal pain and diarrhea are common symptoms in children. In any given 6-month period, up to half of the children in the United States report persistent abdominal pain, which often leads to a medical evaluation.15  When evaluating children with chronic abdominal pain and diarrhea, clinicians have the challenge of determining how much of an evaluation is necessary because a functional gastrointestinal disorder (FGID) is most likely. Rome IV criteria (international guidelines used to define FGIDs) state that the diagnosis of an FGID can be supported when “after appropriate medical evaluation the symptoms cannot be attributed to another medical condition.”5  The central question is as follows: what is appropriate medical evaluation? Certainly the presence of “alarm” signs and symptoms (eg, weight loss, poor weight gain, poor linear growth, significant vomiting, chronic severe diarrhea, hematochezia, persistent right upper or lower quadrant pain, fever, unexplained anemia, family history of inflammatory bowel disease [IBD]) should prompt a full diagnostic evaluation.3  When should an extensive evaluation, including upper gastrointestinal endoscopy or ileocolonoscopy be done? These procedures carry a 1% risk for complications including gastrointestinal bleeding, hypoxia, perforation, and drug reactions caused by anesthesia.6  In addition, other factors, including cost and absenteeism from school or work, may be considered.7  In this issue of Pediatrics, Van de Vijver et al8  help resolve this dilemma, finding that it may be reasonable to rely on history, examination, and specific noninvasive testing to determine if endoscopic evaluation is warranted in children with these symptoms.

The authors studied children with persistent or recurrent abdominal pain and nonbloody diarrhea to determine if a noninvasive test strategy (using symptoms, C-reactive protein [CRP], hemoglobin, and fecal calprotectin) could accurately predict who does not have IBD, without missing any cases over a 6-month period.8  When this test strategy was negative or normal, IBD did not manifest or endoscopic evaluation was normal. Whereas hemoglobin and serum inflammatory markers (CRP, erythrocyte sedimentation rate) are familiar to primary care providers, noninvasive fecal markers of inflammation (fecal calprotectin) are less commonly used. This study suggests these tests may be helpful tools to assist in predicting pathologic gastrointestinal disorders versus FGIDs.9  Fecal calprotectin, a measure of leukocyte trafficking to the gut, is increased in patients with IBD and is recommended by the American Gastroenterological Association for adults with chronic diarrhea to screen for IBD.10  There is variability in fecal calprotectin cutoff values used in various studies; a lower cutoff (<50 µg/g) is highly sensitive and is recommended by the American Gastroenterological Association.10,11  Fecal calprotectin levels may also be elevated by infections (particularly bacterial gastrointestinal infections), colorectal carcinoma, polyps, pepticulcer disease, obesity, and nonsteroidal antiinflammatory drug use.11,12 

Van de Vijver et al8  describe a noninvasive strategy based on identifying symptoms and measuring CRP, hemoglobin, and fecal calprotectin that can help avoid invasive testing for IBD. Although this is an important finding, clinicians should also consider a broader differential diagnosis, including infection, lactose malabsorption, small bowel bacterial overgrowth, allergic enteropathy, celiac disease, and FGIDs.13  Infants with early-onset diarrhea and immunocompromised children can have a far broader differential diagnosis. It is important to tailor testing to patient-specific risks on the basis of a full understanding of the differential diagnosis. Endoscopy may be an important part of this diagnostic evaluation. Previously published guidelines recommend that upper gastrointestinal endoscopy should be used to diagnose causes of gastrointestinal bleeding, dysphagia, odynophagia, feeding refusal, chest pain, upper abdominal pain, weight loss, persistent vomiting, unexplained anemia, chronic gastroesophageal reflux disease, caustic ingestion, and unexplained diarrhea.14,15  Diagnostic indications for ileocolonoscopy include unexplained anemia, gastrointestinal bleeding, perianal disease, failure to thrive, suspicion for ileocolonic stricture, polyposis syndromes, and chronic diarrhea.14,15  Thus, previously published guidelines have recommended upper gastrointestinal endoscopy and ileocolonoscopy for chronic diarrhea. When considering the aforementioned differential diagnosis for chronic nonbloody diarrhea and abdominal pain, noninvasive testing can screen for celiac disease (tissue transglutaminase, immunoglobulin A, and total immunoglobulin A levels), infection (stool pathogen studies), and lactose malabsorption (lactose breath hydrogen testing), but upper gastrointestinal endoscopy may still be warranted to evaluate for allergic enteropathy, IBD, or tissue transglutaminase–negative celiac disease. When taking into account the results of this study, however, we note ileocolonoscopy may not be necessary in children with abdominal pain and nonbloody diarrhea with certain negative result findings. Avoiding an unnecessary ileocolonoscopy is important because of cost, absenteeism from school or work, longer anesthesia time, and risk of complications such as intestinal perforation.

In conclusion, this study suggests the addition of fecal calprotectin to symptoms and CRP provides added useful guidance when screening children for IBD, resulting in fewer ileocolonoscopies without likely missing IBD. When deciding against endoscopic evaluation, it is important to closely monitor the patients, particularly if alarm signs or symptoms develop.

Opinions expressed in these commentaries are those of the authors and not necessarily those of the American Academy of Pediatrics or its Committees.

FUNDING: No external funding.

COMPANION PAPER: A companion to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2019-2235.

CRP

C-reactive protein

FGID

functional gastrointestinal disorder

IBD

inflammatory bowel disease

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Competing Interests

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.