A recent image (available online only N Engl J Med 2014; 370:e33) shows a clearcut case of gastric emphysema and the narrative explains the differential diagnosis:
“The differential diagnosis included infection, ischemia, and gastric-outlet obstruction due to volvulus, annular pancreas, intestinal malrotation, and duodenal hematoma or stenosis. Laparotomy revealed diffuse gastric and omental emphysema resulting from duodenal stenosis.”
Recently ESPGHAN assembled an international group of European experts in pediatric inflammatory bowel disease (PIBD) to establish practice recommendations (JPGN 2014; 58: 795-806). Their aim was “to revise the original Porto criteria using an evidence-based approach and consensus process to yield specific practice recommendations for the diagnosis of PIBD.”
Before detailing some of their recommendations, I want to state my main criticism: these recommendations do not consider cost or cost-effectiveness. This is important since we do not live in a world where costs are irrelevant.
Some specific recommendations/observations:
1. “We recommend performing small bowel imaging in all suspected cases of IBD at diagnosis; this may be deferred in typical UC.” In addition, all suspected cases of IBD should undergo esophagogastroduodenoscopy (EGD) and ileocolonoscopy. “The diagnostic yield of an EGD to diagnose Crohn’s disease (CD) in patients with an otherwise normal workup [ileocolonoscopy/small bowel imaging] is ~7.5%. ”
2. The authors clarify the use of IBD-unclassified (IBD-U). “IBD-U should be …for patients with colitis and highly atypical findings.” Atypical findings for ulcerative colitis: include rectal sparing, and cecal patch (present in 2% of pediatric patients with left-sided colitis). Table 3 suggests that if at least one “class 2” (rare feature) exists or at least 2 “class 3” (uncommon) feature exists, then labeling IBD-U is appropriate.
Rare (Class 2):
Uncommon (Class 3):
3. Crohn’s disease, according to Table 3, should be diagnosed with any of the following:
4. “Normal blood tests do not exclude the diagnosis of IBD”… Fecal markers (eg. calprotectin) are “extremely sensitive in the detection of mucosal inflammation but are not specific for IBD.”
5.”Although small bowel imaging is encouraged in all of the patients with suspected IBD, it is essential in pediatric patients with CD, IBD-U, or atypical UC.” Magnetic resonance enterography (MRE) is currently the imaging modality of choice in PIBD. Wireless capsule endoscopy (WCE) is a “useful alternative.” The authors advocate for imaging because it may “detect small intestinal involvement…and identify disease complications.”
6. Evaluation for primary immune deficiency should be performed in all cases of PIBD diagnosed <2 years of age.
While the authors acknowledge that “clinical considerations may require taking a course of action that varies from these criteria,” nevertheless, they are likely to influence clinical practice. My personal belief is that there are many situations in which small bowel imaging will not result in changes in clinical care. Furthermore, many patients, especially younger patients, would require anesthesia in order to complete a MRE which is an added burden. In addition, with the added emphasis on assessing response to therapy, one could envision that some patients would be better served with imaging after implementing treatment.
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Here’s the link (Enteral Nutrition Study) from a summary of the study in Healio Gastroenterology (from their twitter feed) and an excerpt:
Frivolt K. Aliment Pharmacol Ther. 2014;39:1398-1407.
A retrospective study of all pediatric Crohn’s disease (CD) patients treated with exclusive enteral nutrition (EEN) at a children’s hospital in Munich between January 2004 and June 2011. Fifty-two included patients (mean age, 13.2 years; 59.6% male) had newly diagnosed CD (n=40) or had relapsed (n=12) while maintaining treatment for at least 3 months….The first course of EEN showed a higher median starting wPCDAI score compared with the second (59 vs. 40; P<.0001), as well as higher remission rates after 3 months (92% vs. 77%). Relapse rates after 1 year were comparable (67% vs. 70%), but fewer relapses occurred in the first 120 days after the first EEN course compared with the second (25% vs. 45%).
Of 48 patients with NOD2 genotype, 44 went into remission with EEN; 11 of 12 patients carrying R702W or G908R genotype relapsed within 1 year; and there were significantly lower rates of relapse in patients with wild-type (60%) or 1007fs (50%) mutations.
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A recent commentary explains why “functional” pain is such a lousy term (JAMA Pediatr. Published online June 02, 2014. doi:10.1001/jamapediatrics.2014.530 –thanks to Ben Gold for this reference). In pediatric GI practice, functional gastrointestinal disorders (FGIDs) constitute a large part of clinical work.
The author, Neil Schechter from the Chronic Pain Program in Boston, makes several important observations:
Take-home message: I wish I had written this commentary. Explaining “functional” pain and “irritable bowel syndrome” are Sisyphean tasks. Better nomenclature could ease the burden. Join me in abandoning the use of the word “functional.”
In the same issue, an editorial on the “Role of Celiac Disease Screening for Children with Functional Gastrointestinal Disorders” (JAMA Pediatr. 2014;168(6):514-515. doi:10.1001/jamapediatrics.2013.5418) comments on a study (JAMA Pediatr. 2014; 168(6):555-60) in the same issue which reports a 4-fold higher prevalence of celiac disease among children who meet clinical criteria for irritable bowel syndrome. The study reports the results from a cohort of 992 children identified with recurrent abdominal pain in a primary care setting. In the editorial, the authors note: “When grouped together, the prevalence rate of celiac disease among all children with FGIDs (IBS included) approaches 2%. Celiac disease screening in this population would result in a positive tTG-IgA test result in 4%…However, 53% of all positive test results would be falsely elevated.” As such the editorial advocates in favor of screening for celiac disease in children with IBS but not all FGIDs.
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As alluded to in a previous post (CCFA Conference Notes 2014 (part 2) | gutsandgrowth), there has been increasing discussion and efforts aimed at mucosal healing (MH) because it is associated with improved clinical outcomes in patient’s with Crohn’s disease (CD). Even before its print publication, this study (Clin Gastroenterol Hepatol 2014; 12: 978-85) by William Sandborn’s group has influenced the discussion.
This retrospective study analyzed 67 patients with CD (2011-2012). These 67 were selected from a population of 510 patients seen at UCSD who had at least several endoscopies and ulcers seen at the initial procedure. In this cohort of 67 patients, the median disease duration was 9.8 years. Only 26 (38.8%) were naive to both immunosuppressives and biologics at referral.
Key findings:
The authors conclude that “serial endoscopic procedures to guide treatment to the goal of MH is feasible in clinical practice.” Ultimately the goal is to influence the natural history of Crohn’s disease.
Study limitations:
From Dr. Sandborn: (from Healio Gastro summary):
“Evidence has accumulated that the complications of Crohn’s disease [CD] … are due to chronic inflammation that has not been fully treated,” William J. Sandborn, MD, chief of the gastroenterology division and director at the University of California, San Diego, IBD Center, told Healio.com. “This in turn has led to the concept of ‘treat to target’ in which patients are assessed with endoscopy for active inflammation prior to making important changes in therapy, and then reassessed with endoscopy within 4 to 6 months to ensure that the therapy change healed the bowel and resolved the inflammation.
“If active disease persists at endoscopy, even in the absence of clinical symptoms, then therapy is intensified and this cycle is repeated until mucosal healing (MH) is achieved.”
Take-home message: This study is one of many that are likely to influence the practice of clinicians to prove that the treatment is exerting a biologic effect and not solely improvement in clinical scoring indices. With the emergence of multiple modalities to assess improvement, including biomarkers and imaging, it is not clear that repeated endoscopy will be the best assessment tool.
Related blog post: EXTEND & MUSIC: Optimizing Crohn Disease Care …
Also noted:
Clin Gastroenterol Hepatol 2014; 12: 986-94. “Association Between Telephone Activity and Features of Patients with Inflammatory Bowel Disease.” The authors found that 15% of patients were responsible for half of all telephone calls. These patients were more likely to be seen in ED and hospitalized.
Clin Gastroenterol Hepatol 2014; 12: 929-34. “Histologic Remission: The Ultimate Therapeutic Goal in Ulcerative Colitis?” This article reviews definitions for histologic remission and highlights questions that need to be addressed before histologic remission is used more widely as a clinical endpoint in trials and in practice.
Briefly noted:
“Physician Knowledge Regarding Concomitant Antibiotic and Oral Contraceptive Use in Patients with IBD.” Gastroenterology & Hepatology 2014; 10: 302-06.
Key finding:
Previous studies suggested that antibiotics reduced OCP efficacy. The authors note that “more recent, prospective, pharmacokinetic studies in women demonstrate no evidence of an interaction between OCPs and most antibiotics, with the exception of rifampin.” (J Am Acad Dermatol 2002; 46: 917-23)
Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.
In my training, one of my mentors would be critical of the mentality “scope first, think second.” He was concerned that too many gastroenterologists/pediatric gastroenterologists used endoscopy as a tool simply “because if all you have is a hammer, the world looks like a nail.”
A recent publication (Clin Gastroenterol Hepatol 2014; 12: 963-69) on first glance, however, provides ammunition to the “scope first” gastroenterologists and undermines the concept that “functional” GI disorders vastly outnumber “organic” GI disorders. The key finding was that esophagogastroduodenoscopy (EGD) provided an “accurate” diagnosis in 38%. This included reflux esophagitis in 21%, eosinophilic esophagitis (EoE) in 5%, eosinophilic gastroenteritis (EGE) in 4%, H pylori in 2%, celiac disease 0.6%, and Crohn’s disease 0.4%. This finding is dramatically higher than previous studies. In fact, in a recent published study (Understanding Idiopathic Nausea | gutsandgrowth) on idiopathic nausea, a control group of patients with chronic abdominal pain had a normal endoscopy in 100%!
In this prospective study of 290 children (ages 4-18 years with a mean age of 11.9 years), the primary indication for upper endoscopy was chronic abdominal pain. Of this 290, 216 had at least 1 alarm feature and 125 had at least 2 alarm features. Alarm features were considered to be the following:
There is little debate that abdominal pain in combination with true alarm symptoms (True red flags in recurrent abdominal pain | gutsandgrowth) merits further evaluation. The aspect of this report that is worthy of close inspection is the diagnostic yield in the 74 patients without alarm symptoms. The authors note that 25 (33.7%) had a diagnosis established with EGD including 16 with reflux esophagitis, 4 with EGE, 2 with EoE, 1 with erosive esophagitis, 1 with celiac and 1 with H pylori. The diagnostic criteria for EGE included ≥10 eosinophils per hpf in the stomach and ≥20 eosinophils per hpf in the duodenum.
The authors note that the diagnostic yield was based on gross endoscopic findings in procedure notes or histologic changes in biopsy reports; “final pathology report on biopsies provided the data source for histologic diagnosis.”
In my opinion there are multiple flaws of this prospective study.
1. There is a very high rate of reflux esophagitis in both the alarm group and the non-alarm group patients with chronic abdominal pain. Of the entire cohort (n=290), the authors identified reflux esophagitis in 21% and this was “primarily histologic esophagitis.” Furthermore, the authors state that “the presence or response to PPI therapy was not predictive of esophagitis or GERD.” So, the obvious problems:
2. In the entire cohort, the authors try to validate their findings by indicating that identification of a diagnosis led to medical therapy that was “effective in approximately 67%” of children with short-term followup. (Only 81% had short-term followup outcomes available). Yet, there is no control group. How many children with chronic abdominal pain will improve for a short period without an EGD-based diagnosis? The answer: a lot of them.
3. Limitations include selection bias toward those with more severe symptoms or alarm symptoms. In addition, this study included only a small number who were considered to have no alarm symptoms. Finally, the short-term followup makes conclusions about the response to therapy questionable.
This study will be a useful reference for any pediatric gastroenterologist who wants to justify the need for an endoscopy. The authors note “the majority of children in our study (93%) met criteria for functional gastrointestinal disorders, and a significant proportion (38%) still had significant histologic findings. Therefore, we conclude the Rome III criteria alone are not sufficient to identify children who require upper endoscopy, and screening for alarm symptoms has limited utility.”
In my opinion, the reliance on histology as well as selection bias weaken the findings of this study. If a patient with a histologic diagnosis of reflux (or several other entities) and a presentation of chronic abdominal pain does not improve, the pediatric gastroenterologist should remember that only “a poor carpenter blames his tools.”
Bottomline: EGD remains an important tool in evaluating abdominal pain. However, I think this study substantially overestimates its utility.
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Here is a link, bit.ly/1xb1kk8, (from JPGN) and the abstract to an article on the Specific Carbohydrate Diet in Children. This study shows clinical improvement and mucosal healing, confirmed by capsule endoscopy, in response to the specific carbohydrate diet (SCN). Congratulations to my colleagues/partners from GI Care for Kids who published this study in JPGN:
Objective: To prospectively evaluate clinical and mucosal responses to the specific carbohydrate diet (SCD) in children with Crohn’s disease (CD).
Methods: Eligible patients with active CD (Pediatric Crohn’s Disease Activity Index, PCDAI >= 15) underwent a patency capsule and if passed intact, capsule endoscopy (CE) was performed. Patients were monitored on SCD for 52 weeks while maintaining all prescribed medications. Demographic, dietary and clinical information, PCDAI, Harvey Bradshaw (HB) and Lewis score (LS) were collected at 0, 12 and 52 weeks. CE’s were evaluated by an experienced reader blinded to patient clinical information and timing.
Results: Sixteen patients were screened; 10 enrolled; and 9 completed the initial 12 week trial; receiving 85 % of estimated caloric needs prior to, and 101%, on the SCD. HB significantly decreased from 3.3 + 2.0 to 0.6 + 1.3 (p = 0.007) as did PCDAI (21.1 + 5.9 to 7.8 + 7.1; p = 0.011). LS declined significantly from 2153 + 732 to 960 + 433 (p = 0.012). Seven patients continued the SCD to 52 weeks with HB (0.1 + 0.4) and PCDAI (5.4 + 5.5) remaining improved (p = 0.016 and 0.027 compared to baseline) with mean LS at 1046 + 372 and 2 patients showing sustained mucosal healing.
Impressions: Clinical and mucosal improvements were seen in children with CD using the SCD over 12 and 52 weeks. Additionally, CE can monitor mucosal improvement in treatment trials for pediatric CD. Further studies are critically needed to understand the mechanisms underlying SCD’s effectiveness in children with CD.
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Here’s a link to the abstract: gastrojournal.org/article/S0016-5085(14)00609-X/abstract …
Methods: “We performed a prospective trial of 3031 individuals at risk for celiac disease based on screens for EmA. Of 148 seropositive individuals, 40 fulfilled inclusion criteria and were randomly assigned to groups placed on a GFD or gluten-containing diets.”
Results: “The GFD group also had reduced indigestion (P=.006), reflux (P=.05), and anxiety (P=.025), and better health, based on the visual analog scale (P=.017), than the gluten-containing diet group.”
Take-home message: A gluten free diet improves symptoms (even in “asymptomatic” patients) with celiac disease
A recent study has reviewed biologic therapies for ulcerative colitis (Ann Intern Med. 2014;160(10):704-711). Here’s the abstract link: bit.ly/1o5PpRX .
Data Synthesis: ..There were 7 double-blind, placebo-controlled trials that were rated as low risk of bias and showed that all biological agents (adalimumab, golimumab, infliximab, and vedolizumab) resulted in more clinical responses, clinical remissions, and mucosal healings than placebo for induction therapy. The results of network meta-analysis suggested that infliximab is more effective to induce clinical response (odds ratio, 2.36 [95% credible interval, 1.22 to 4.63]) and mucosal healing (odds ratio, 2.02 [95% credible interval, 1.13 to 3.59]) than adalimumab. No other indirect comparison reached statistical significance. For maintenance, 6 double-blind, placebo-controlled trials that were rated high risk of bias showed that all biological agents have greater clinical efficacy than placebo. The occurrence of adverse events was not different between biological agents and placebo.
Limitation: Few trials, no head-to-head comparisons, and inadequate follow-up in maintenance trials.
Conclusion: Biological agents are effective treatments for UC, but head-to-head trials are warranted to establish the best therapeutic option.
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