“How to Approach a Patient with Difficult-to-Treat IBS”

L Chang. Gastroenterol 2021; 163: 1092-1098. How to Approach a Patient with Difficult-to-Treat IBS

For a short article, this review provides a lot of practical advice. Challenges with IBS include the lack of objective biomarkers and “patients are often dissatisfied with a positive diagnostic approach or even after multiple negative tests.” The author recommends the following:

  • Confidently communicate the diagnosis of IBS
  • Explain visceral hypersensitivity and its associated with pain, and bloating and why central neuromodulators and behavioral therapy are often used. Explain that IBS can be associated with high-amplitude propagating contractures which can cause pain/diarrhea
  • Treatment focused on ‘RESET’ =Relationship with patient-provider, Education/reassurance, Symptom assessment, Exacerbating/alleviating factors, and Targeting treatment (see Table 1)

Treatment may need to target gut, brain and/or both

  • Dietary treatments considered 1st line approach
  • Treatment pharmacology options for IBS-D include antidiarrheals, antispasmotics, rifaximin, eluxadoline, alosetron (rarely, can cause ischemic colitis), bile acid sequestrants
  • Treatment pharmacology options for IBS-C include polyethylene glycol, lubiprostone, linaclotide, plecanatide, and tegaserod (restricted to women <65 yrs w/o cardiovascular dz)
  • Treatment pharmacology options for all IBS include TCAs (start with low dose and can titrate upwards; amitriptyline for IBS-C, nortriptyline or desipramine for IBS-M or IBS-C), SNRI (eg. duloxetine (may be better than TCAs in patients with IBS-C and comorbidities like fibromyalgia and depression), mirtazapine (small studies demonstrated benefit for IBS-D and functional dyspepsia), SSRIs (“consider…in patients with predominant anxiety and/or depression…advise against its use as primary treatment for IBS w/o comorbid psychological disorder”), delta ligand agent (eg. pregabalin) (consider if refractory to other treatments), and brain-gut therapies (eg. CBT, GDH)

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Likelihood of Gastrostomy Tube in Infants with Congenital Diaphragmatic Hernia

M Schwab et al. JPGN 2021: 73: 555-559. Factors and Growth Trends Associated With the Need for Gastrostomy Tube in Neonates With Congenital Diaphragmatic Hernia

My take: The need for a gastrostomy for nutritional support is associated with more severe CDH (~1/3rd of patients). Over a third of patients who received a GT, no longer needed a GT at a median of 26 months.

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Gastric Polyposis in 16 Year-Old

AG Roberts et al. JPGN Reports; 2021. – Volume 2 – Issue 4 – p e123. Open Access: Gastric Adenocarcinoma and Proximal Polyposis of the Stomach in a Hispanic Pediatric Patient With APC Gene Variant c.-191T>G

“Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare gastric polyposis syndrome defined by numerous polyps (>100) in the fundus and body of the stomach with sparing of the lesser curvature and antrum.” Case report in a 16 yo who ultimately underwent a total gastrectomy. The geneticist identified the APC gene mutation with the OncoGeneDx Colorectal Panel by GeneDx. The rationale for the selection of this gene panel was its ability to examine 20 different genes involved in hereditary colorectal cancer and other gastrointestinal cancers. This panel checks APC, POLE, PTENSTK11BMPR1ASMAD4ATMAXIN2CDH1CHEK2EPCAMMLH1MSH2MSH6MUTYHNTHL1PMS2POLD1SCG5/GREM1, and TP53 genes

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Electrocardiograms -Will We Ever Know If They Are Useful Prior to Tricyclic Antidepressants?

LJ Klein et al. JPGN 2021; 73: 523-528. Electrocardiogram Before Tricyclic Antidepressant Use: Minimal Impact in Pediatric Functional Gastrointestinal Disorders

Key findings from this retrospective review (n=233):

  • TCAs were not started in only 1.7% (4/233) due to ECG results
  • Eight (3.4%) had a cardiology referral; one (0.4%) had a prolonged QTc interval
  • No deaths and no emergency department or hospital visits for arrhythmia or drug overdose occurred

The discussion lists a number of studies generally questioning the utility of pre-medication ECGs while at the same time acknowledging that guidelines in the GI and psychiatric literature support an ECG prior to TCA use. In a large study of sudden cardiac deaths in an adult population, there was no increased risk of death with TCA dosing less than 100 mg/day (Clin Pharmcol Ther 2004; 75: 234-41).

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My take (borrowed in part from authors): While “the benefit of screening ECGs remains elusive,” it is still needed to try to avoid “extremely rare but catastrophic events.” The authors, however, recommend followup ECGs only on “patients on concomitant QT prolonging medications or increases to higher dosing ranges.”

Why Stool Hoarding Might Be A Good Idea

SK Hourigan et al. JPGN 2021; 73: 430-432. Updates and Challenges in Fecal Microbiota Transplantation for Clostridioides difficile Infection in Children

This good update provides a lot of useful information regarding fecal microbiota transplantation (FMT) and a word of caution regarding its future availability.

Key points regarding FMT:

  • Long-term safety remains unknown. FMT may lead to susceptibility to chronic inflammatory, allergic, and autoimmune diseases. “FMT has been associated with durable transmission of pro-carcinogenic bacteria from adult donors to pediatric recipients…although the long-term consequences…are unknown.”
  • Due to transfer of extended spectrum beta-lactamase (ESBL) E coli to 2 immunocompromised adult recipients, further screening of FMT was implemented.
  • Though there is no published evidence of SARS-CoV-2 fecal transmission, the FDA “advised additional precautions and testing in March 2020; “however, there are no molecular tests with stool…which have received emergency use authorization.” Hence, most FMT programs were on hold as of January 2021.
  • After 2021, OpenBiome, whose product was recently available again, is expected to stop distribution of FMT donor product due to increased costs of screening and the “promising biotherapeutics” that are in phase III trials.
  • Biotherapeutic is “loosely defined as drug therapy products where the active substance is extracted from a biological specimen.” The new products are likely to have “increased standardization, safety and practicality.”
  • The problem in pediatrics: none of these biotherapeutic products have started trials in children. This will lead to treatment problems. Even if one wanted to set up donor-directed FMT, it will be difficult to complete all of the screening recommended by the FDA. It could lead to self-administration by families with uncertain risks.

My take: My first reaction to this article: ‘Oh crap!’ It is sad and ironic that I will miss having available commercial stool for FMT.

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From The Onion
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Outcomes of Collagenous Gastritis

BC Beinvogl et al. JPGN 2021; 73: 513-519. Pediatric Collagenous Gastritis: Clinical and Histologic Outcomes in a Large Pediatric Cohort

In this retrospective single-center cohort study with 40 patients (1992-2020), the authors describe the outcomes and heterogeneity of treatments for pedicatric collagenous gastritis (CG). The mean age at diagnosis was 11 years with mean followup of 2.9 years.

Key points:

  • Presenting symptoms: abdominal pain, vomiting, symptomatic anemia, and nausea. 25 of 40 had a colonoscopy at time of index EGD
  • 75% had iron-deficiency anemia which responded well to iron supplementation
  • Comorbid conditions included autoimmune disorders in 12.5% and immunodeficiencies in 5%. 7 (17.5%) had excess collagen in duodenum, 3 (7.5%) had collagenous colitis, and 1 (2. 5%)had collagenous ileitis.
  • 85% of diagnosis were made on initial review of biopsy slides; other cases were identified subsequently either due to repeat endoscopy or further slide review. CG is “known to be patchy
  • No treatments were clearly effective in improving histology. Treatments included PPI/H2RAs in 40%, laxatives in 20%, cyproheptadine in 12.5%, antiemetics in 12.5%, cafafate in 7.5%, budesonide in 7.5% and others less frequently
  • 92% had persistent abnormal endoscopic findings and 73% had persistent thickened subepithelial collagen. In those without excess collagen deposition at last EGD, some of this could be related to patchy distribution as well as improvement
  • Though histology often did not improve, 87.5% had improvement or resolution of symptoms
  • Long-term outcomes remain unknown. While there is concern for possible malignant transformation, to date “no gastric epithelial or lymphoid malignancies have been…reported”

My take: Collagenous gastritis is poorly understood. Fortunately, most patients symptoms resolve/improve.

Related blog post: Collagenous gastritis (2020) -useful reference

Irritable Bowel After Campylobacter Enteritis

A Berumen et al. Clin Gastroenterol Hepatol 2021; 19: 1855-1863. Characteristics and Risk Factors of Post-Infection Irritable Bowel Syndrome (IBS) After Campylobacter Enteritis

The Minnesota Department of Health collects data on symptoms and exposures upon notification of Campylobacter cases. In this 6-9 month followup survey of 1667 (2011-2019) out of a total of 3586 patients, the authors identified 1418 without preexisting IBS.

Key findings:

  • 301 (21%) subsequently developed IBS. Most of these individuals had IBS-mixed (54%), followed by IBS-diarrhea (38%), and IBS-constipation (6%)
  • Additionally, the authors note that 121 patients (8.5%) had new GI problems after infection that did not meet thresholds set by Rome criteria
  • Among patients with IBS-mixed or IBS-diarrhea before infection, 78% retained their subtypes after infection. In contrast, only 50% of patients with IBS-constipation retained that subtype after infection;40% transitioned to IBS-mixed
  • Of patients with pre-existing IBS, 38% had increased frequency of abdominal pain after Campylobacter infection
  • One limitation of the study is ‘responder bias.’ There may be a lower rate of IBS/GI symptoms in the subset of patients who did not respond to survey.

My take: A lot of people develop IBS and other GI symptoms after Campylobacter infection; those with IBS often have intensification of their symptoms.

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Related study: Am J Gastroenterol  2012 Jun;107(6):891-9. “Norovirus GE leads to the development of PI-IBS in a substantial proportion of patients (13%), similar to that reported after bacterial GE.”

Nutritional Management of Intestinal Failure in Pediatrics

A recent terrific update from Kipp Ellsworth: Nutritional Management of Intestinal Failure Patients. Slides:

Some selected slides:

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It Hurts Here and Here and Here

A recent study (below) reminded me of a joke. First the joke (better with the visual effect):

A guy goes to his doctor. The patient says, “Doctor when I touch here on my shoulder (with index finger) it hurts, when I touch here on my leg (with index finger) it hurts, and when I touch here on my stomach (with index finger) it hurts.”

The doctor says: “Your finger is broken.”

BP Chumpitazi et al. J Pediatr 2021; 236; 131-136. Multisite Pain Is Highly Prevalent in Children with Functional Abdominal Pain Disorders and Is Associated with Increased Morbidity

In this cross-sectional study of 7-17 year olds (n=406) with Rome III functional abdominal pain disorder (FAPD), the authors examined the frequency of pain outside GI tract over a 2 week study period. Patients were recruited from both a large academic pediatric GI practice and general pediatric offices in same hospital system.

Key findings:

  • In total, 295 (73%) children endorsed at least 1 co-occurring nonabdominal pain, thus, were categorized as having multisite pain with the following symptoms: 172 (42%) headaches, 143 (35%) chest pain, 134 (33%) muscle soreness, 110 (27%) back pain, 94 (23%) joint pain, and 87 (21%) extremity (arms and legs) pain
  • In addition, 200 children (49%) endorsed 2 or more nonabdominal pain symptoms
  • Participants with (vs without) multisite pain had significantly higher abdominal pain frequency (P < .001) and severity (P = .03), anxiety (P < .001), and depression (P < .001). Similarly, children with multisite pain (vs without) had significantly worse functional disability (P < .001) and health-related quality of life scores (P < .001).

The authors note that due to the design of their study, they cannot establish a causal association between pain symptoms and psychosocial functioning.

My take: A lot of kids with stomach pain have multisite pain as well as anxiety and depression. This study reminds us to ask about them.

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Latest on VTE in Pediatric IBD

MA Aardoom et al. JCC 2021; https://doi.org/10.1093/ecco-jcc/jjab171 The incidence and characteristics of venous thromboembolisms in paediatric-onset inflammatory bowel disease; a prospective international cohort study based on the PIBD-SETQuality Safety Registry

Design: 2016-2020: paediatric gastroenterologists prospectively replied to the international Safety Registry, monthly indicating whether they had observed a VTE case in a patient <19 years with IBD. n=24,802 PIBD patients

Key findings:

  • Twenty cases of VTE were identified (30% Crohn’s disease)
  • The VTE incidence was 3.72 [95%CI 2.27 – 5.74] per 10,000 person-years, 14-fold higher than in the general pediatric population (0.27 [95%CI 0.18-0.38], p<0.001)
  • All but one patient had active IBD, 45% were using steroids and 45% hospitalized.
  • Cerebral sinus venous thrombosis was most frequently reported (50%) VTE

My take: The absolute risk of VTE is low in the pediatric population. In those with active disease, the presence of CVC and use of steroids are known risk factors and require consideration of, at minimum, nonpharmacologic interventions.

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