Most patients that I see with celiac disease (CD) do very well after diagnosis/implementation of dietary therapy. A recent study indicates a subset of patients have significant work disability as adults.

SR Bozorg et al. Clin Gastroenterol Hepatol 2022; 20: 1068-1076. Open Access: Work Loss in Patients With Celiac Disease: A Population-based Longitudinal Study

In this large-scale nationwide study (part of the ESPRESSO study) from Sweden, the authors used prospectively recorded register data to estimate work loss in patients with CD in comparison to the general population, including the temporal relationship of work loss before and after diagnosis. This study included more than 16,000 patients with CD.

Key findings:

• In 2015, patients with prevalent CD had a mean of 42.5 lost work days as compared with 28.6 in comparators
• More than one-half of the work loss (60.1%) in patients with CD was derived from a small subgroup (7%), whereas 75.4% had no work loss
• The annual mean difference between patients and comparators was 8.0 days of lost work 5 years before CD diagnosis, which grew to 13.7 days 5 years after diagnosis in the incident CD group (dx between 2008-2015)

In the discussion, the authors speculate about whether the work loss could be due to inadequate response to a gluten free diet; however, in this study, the authors found similar work loss between patients with CD with or without mucosal healing (only 25% underwent f/u biopsy).

My take: It would be interesting to see the pediatric corollary of work loss, namely school absenteeism and whether this is increased in a small subset as well. My suspicion is that the subset with increased work loss likely has a higher rate of functional disorders, in addition to CD, than the comparator group and probably accounts for a significant amount of the work disability.

Related blog posts:

• Functional Abdominal Pain in Children with Celiac Disease
• Persistent Villous Atrophy in Celiac Disease Despite a Gluten-Free Diet
• Is functional pain more common in children with Celiac disease?
• IBS Symptoms in Patients with Celiac Disease
• Is a Gluten-Free Diet Possible? DOGGIE BAG Study
• #NASPGHAN19 Postgraduate Course (part 2)
• Celiac Disease: “”80 percent of success is just showing up”
• Improving Care Process in Celiac Disease
• How Slow Do Objective Markers of Celiac Disease Improve
• How Accurate is Serology at Predicting Mucosal Healing in Pediatric Patients with Celiac Disease

R Yadiatpati et al. Clin Gastroenterol Hepatol 2022; 20: 984-994. AGA Clinical Practice Update on the Personalized Approach to the Evaluation and Management of GERD: Expert Review

The general approach, outlined in Figure 1, is to empirically treat patients with typical GERD symptoms for 4-8 weeks with single-dose PPI. In those with response, the goal is to use the lowest effective dose and consider reflux testing (“offer endoscopy with prolonged wireless reflux monitoring”) if needing prolonged treatment (>1 yr). In those without a response, adjusting treatment (possibly change medication or change to twice a day) should be considered and reflux testing (off treatment) is recommended as well in those lacking response to treatment.

Some of the recommendations/best practice advice:

• Clinicians should provide standardized educational material on GERD mechanisms, weight management, lifestyle and dietary behaviors, relaxation strategies, and awareness about the brain-gut axis relationship to patients with reflux symptoms.
• Clinicians should emphasize safety of proton pump inhibitors (PPIs) for the treatment of GERD.
• Clinicians should provide patients presenting with troublesome heartburn, regurgitation, and/or non-cardiac chest pain without alarm symptoms a 4- to 8-week trial of single-dose PPI therapy. With inadequate response, dosing can be increased to twice a day or switched to a more effective acid suppressive agent once a day. When there is adequate response, PPI should be tapered to the lowest effective dose.
• If troublesome heartburn, regurgitation, and/or non-cardiac chest pain do not respond adequately to a PPI trial or when alarm symptoms exist, clinicians should investigate with endoscopy and, in the absence of erosive reflux disease (Los Angeles B or greater) or long-segment (≥3 cm) Barrett’s esophagus, perform prolonged wireless pH monitoring off medication (96-hour preferred if available) to confirm and phenotype GERD or to rule out GERD.
• Clinicians should perform upfront objective reflux testing off medication (rather than an empiric PPI trial) in patients with isolated extra-esophageal symptoms and suspicion for reflux etiology.
• Clinicians should provide pharmacologic neuromodulation, and/or referral to a behavioral therapist for hypnotherapy, cognitive behavioral therapy, diaphragmatic breathing, and relaxation strategies in patients with functional heartburn or reflux disease associated with esophageal hypervigilance reflux hypersensitivity and/or behavioral disorders.
• In patients with proven GERD, laparoscopic fundoplication and magnetic sphincter augmentation are effective surgical options, and transoral incisionless fundoplication is an effective endoscopic option in carefully selected patients.

Related blog posts:

• ACG Adult GERD Guidelines 2022 (to read the recommendations, you have to click on the figures)
• 2018 Pediatric Gastroesophageal Reflux Guidelines
• How Many Kids with Reflux have Reflux?
• pH Probe Testing: Rumors of My Death are Premature
• Better to do a coin toss than an ENT exam to determine reflux

Yesterday, this blog discussed what is needed to achieve high cure rates for H pylori. One of my microbiology colleagues informed me that until recently there have only been susceptibility standards for clarithromycin from the Clinical Laboratory Standards.  Now, the European Committee on Antimicrobial Susceptibility Testing has criteria for clarithromycin, tetracycline, amoxicillin, levofloxacin, metronidazole, and rifampin. Given the difficulty culturing H pylori, his view is that stool testing is the most promising avenue for susceptibility testing because we now have the genes that determine resistance delineated for all of these drugs.

A related issue is antimicrobial stewardship: DY Graham. J-M Liou. Clin Gastroenterol Hepatol 2022; 20: 973-983. Open Access: Primer for Development of Guidelines for Helicobacter pylori Therapy Using Antimicrobial Stewardship

Key points:

• “Therapies that fail to achieve at least a 90% cure rate should be abandoned as unacceptable”
• “Antibiotics in the access group have lower resistance potential … They should be widely available and affordable. Amoxicillin, tetracycline, and metronidazole are classified as the access group. In contrast, clarithromycin and levofloxacin have higher resistance potential and are classified as the watch group. They should be prioritized as key targets of stewardship program and monitoring”
• “Therapies that contain antibiotics which do not contribute to outcome should be eliminated”
• The “full antisecretory activity of PPIs requires 3–4 days. This makes the actual duration of effective therapy shorter than the days it is administered…However, pharmaceutical companies often have chosen to shorten the recommended duration of therapy to obtain a marketing advantage at the expense of reduced effectiveness”
• “Currently most H pylori infections receive empiric therapy, and the clinician does not know or even have access to treatment guidance based on local or regional antimicrobial susceptibility patterns…few hospitals or clinics offer susceptibility testing”
• Even without susceptibility testing, clinicians could achieve much better results if test of cure data were carefully collected and analyzed
• “Metronidazole-containing bismuth quadruple therapy is unique in that it appears that metronidazole resistance can be partially or completely overcome by increasing the dose and duration of therapy…metronidazole resistance as assessed in vitro does not correlate well with its effectiveness in vivo, especially when used as a component of a triple or quadruple therapy”

H pylori is difficult to eradicate:

• Location: “the organisms reside within the highly acid stomach, which is physically outside of the body and thus poorly accessible to blood-borne antibiotics and the immune system”
• Inoculum effect: “H pylori is also typically present in vast numbers, resulting in an inoculum effect … the inoculum effect is largely responsible for the failure of dual therapy with PPIs clarithromycin, metronidazole, or levofloxacin, as their effectiveness is undermined by emergence of resistance during therapy”
• Biofilm and intracellular: “A proportion of H pylori attach to the surface of gastric cells, leading to a biofilm phenomenon, and some are present intracellular by requiring the use of antibiotics capable of penetrating into cells”
• Dormant state: “H pylori can become dormant in part because they can replicate only when the pH is approximately 6…this results in a persister effect”

My take: The lack of action on H pylori susceptibility despite the current tools is a bad look for the GI community. Would this still be the case if the treatment were relegated to our infectious disease colleagues? Antibiotic stewardship is coming for H pylori -children and adults with this infection should have higher cure rates and easier treatment regimens.

Related blog posts:

• Next-Generation Treatment for H pylori
• Why Is There Low Adherence to H pylori Guidelines
• Quadruple Therapy for Helicobacter Pylori Favored in Toronto Guidelines -Adult Guidelines
• ACG Guideline for Helicobacter Pylori | gutsandgrowth -Adult Guidelines
• AGA: Best Practice Advice for Refractory H pylori
• Lots of Room to Improve with H pylori Treatment | gutsandgrowth
• Rifabutin-based Triple Therapy for H pylori | gutsandgrowth
• It is Getting Harder to Treat H pylori -Here’s Why
• Updated Pediatric H pylori Guidelines