Given seasonal fluctuation in the activity of eosinophilic esophagitis (EoE), aeroallergens have been considered a trigger in some patients.
Briefly noted: A recent study (A Ravi et al. Gastroenterol 2019; 157: 255-6, editorial 17) showed that dust mite antigen was present in esophageal biopsy specimens at a greater level in adult patients with EoE compared to controls. With active EoE, patients had dust mite staining in 1.6% of the field which was significantly greater than patients with inactive EoE (0.7). The control group had a complete absence of epithelial dust mite staining.
The editorial (Seena Aceves) notes that these investigators have also shown gluten accumulation in the EoE esophagus. Whether dust mite antigens or other specific postulated aeroallergens plays a causative role is unclear. This study shows the presence of these antigens in the esophagus but does not show whether this is an epiphenomenon due to increased permeability or whether these antigens activate the local immune system.
A second study (T Patton et al. JPGN 2019; 69: e43-e48) describes the outcome of coexisting celiac disease and eosinophilic esophagitis in 22 children (from a cohort of 350 children with celiac disease. 17 had repeat biopsies. Four of 17 (23.5%) had resolution of EoE with a gluten-free diet. Related blog post: Is there a Link Between Eosinophilic Esophagitis and Celiac Disease?
Sagrada Familia, Barcelona
In a recent study (A Fritscher-Ravens et al. Gastroenterol 2019; 157: 109-18) uses confocal laser endomicroscopy (CLE) for “real-time detection and quantification of changes in intestinal tissues” related to food challenges. The authors previously had used this technique in a feasibility study (Gastroenterol 2014; 147: 1012-20). In this study, two-thirds of patients with CLE+ IBS showed improvement of IBS symptoms after a 12-month exclusion diet.
In the current study, the authors prospectively examined patients (n=108 completed study) who had irritable bowel syndrome and were convinced that this was triggered by foods (with negative IgE food allergy testing). The CLE testing evaluated four food components
- 76 of 108 (70%) had abnormal CLE; 46 of these reactions were to wheat
- In those with CLE+ reactions, intraepithelial lymphocytes were significantly higher compared to those with CLE-negative (normal evaluations).
- Other biomarkers associated with CLE+ included increased claudin-2 expression from crypt to villous tip, lower levels of occludin, and higher eosinophilic cationic protein.
Abnormal CLE indicated abnormal mucosal appearance including formation of epithelial leaks/gaps and widening of the intervillous spaces after food challenge.
My take: This study shows that in individuals with a strong suspicion of food-triggered IBS, immediate reactions in the mucosa can be detected with CLE in more than 50%. Whether this type of approach could/should be developed for wider use in targeting a specific diet is unclear. More studies are needed.
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Sagrada Familia, Barcelona
A recent double-blind, double-dummy study (ES Dellon et al. Gastroenterol 2019; 157: 65-73) found similar efficacy between budesonide and fluticasone for newly-diagnosed eosinophilic esophagitis. They had hypothesized that an oral viscous budesonide would be more effective due to increased esophageal contact time.
Methods: The authors compared an oral viscous budesonide OVB) at 1 mg BID (n=56) to fluticasone (swallowed) MDI dosed at 880 mcg BID (n=55). Patients aged 16-80 years, with mean of 37 years.
- ~95% in both groups with dysphagia
- ~75% with any atopic condition
- ~50% with dilatation required at baseline
- Similar drop in eosinophil count: 73 (OVB) and 77 (MDI) eos/hpf at baseline to 15 and 21 respectively
- Histologic response (<15 eos/hpf) rates of 71% (OVB) and 64% (MDI).
- Response to <5 eos/hpf occurred in 61% OVB and 49% MDI; response to <1 eos/hpf was noted in 41% and 35% respectively
- Symptom scores (DSQ) responded similarly as well
- Similar degree of candidiasis 12% for OVB and 16% for MDI
In the associated editorial, the authors speculate that one reason for similar efficacy was the detailed instructions given for patients taking the MDI.
My take: This study supports both topical steroid therapies; practical issues like cost and insurance coverage could be influential in selecting the specific treatment for an individual patient.
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From AGA twitter feed
A recent study (V Jairath et al. AP&T 2019; https://doi.org/10.1111/apt.15408) provides evidence that 5-aminosalicylic acid therapy for IBD does NOT increase the risk of nephrotoxicity. This paper’s findings run counter to more than thirty years of teaching on this medication.
Full Free Link: No increased risk of nephrotoxicity associated with 5‐aminosalicylic acid in IBD: a population‐based cohort and nested case‐control study
Abstract (bold highlighted by blog author):
There is conflicting evidence about nephrotoxicity risk associated with 5‐aminosalicylates for treatment of IBD.
Retrospective cohort and nested case‐control study, using the Health Improvement Network primary care database linked to hospital discharge coding for patients in England, 1996‐2017. Nephrotoxicity risk analysis was a first recorded renal impairment diagnosis adjusted for key variables and was assessed between 2008 and 2017.
A total of 35 601 patients with prevalent UC or CD were included. The proportion of patients prescribed 5‐aminosalicylates fell from 83% in 1996‐1999 to 71% in 2012‐2015 for UC patients and 64% to 45% for CD patients. Thirty per cent of patients had prolonged 5‐aminosalicylate use. Between 2008 and 2017, the incident rate of nephrotoxicity was similar and stable for UC (12.6/1000 person‐years) and CD (10.9/1000 person‐years) patients. Multivariate analysis showed no evidence for association between current prescription of 5‐aminosalicylate and nephrotoxicity in UC or CD patients, comparing ≤ 30 days prescription prior to index vs 31‐≤180 days. However, active disease, disease duration, concomitant cardiovascular disease or diabetes and nephrotoxic drug use were independently associated with development of nephrotoxicity in UC and CD.
Despite the paucity of evidence for their benefit, 5‐aminosalicylates were prescribed to approximately half of CD patients (30% prolonged therapy). Nephrotoxicity was rare in this patient cohort, and was not associated with 5‐aminosalicylate use, but rather with disease status, comorbidity and use of nephrotoxic drugs.
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Park Guell, Barcelona
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
When someone gets bitten by a shark, it often makes the news. Yet, the frequency of shark attacks is rare and it is probably much more dangerous driving to the beach than getting into the water.
For proton pump inhibitors, it seems that they get similar press coverage as shark bites. Many times potential adverse effects are covered heavily by the media even though many of these effects are unproven or very infrequent.
A recent study (“Safety of Proton Pump Inhibitors Based on a Large, Multi-year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin” Moayyedi, Paul et al. Gastroenterology DOI: https://doi.org/10.1053/j.gastro.2019.05.056) shows that 3 years of pantoprazole had an excellent safety profile.
Here is the abstract:
Background & Aims
Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial.
We performed a 3×2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n=8791) or placebo (n=8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient years of follow up.
There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% CI, 1.01–1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant.
In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. Clinicaltrials.gov identifier: NCT01776424 (https://clinicaltrials.gov/ct2/show/NCT01776424)
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Madrid view from Círculo de Bellas Artes
Gastroendonews: Tea Leaves No More: Biologics Head-to-Head Produces a Winner
In the first head-to-head trial of biologic treatments for inflammatory bowel disease, vedolizumab (Entyvio, Takeda) was nearly 50% more effective than adalimumab (Humira, AbbVie) in inducing clinical and mucosal remission in patients with moderate to severe ulcerative colitis…
They enrolled 771 patients with moderate to severe ulcerative colitis in the VARSITY study and randomly assigned them to receive 52 weeks of treatment with either vedolizumab or adalimumab…
They had failed other conventional therapies, including 25% in each group that had received an anti–tumor necrosis factor (TNF) agent…
- 31.3% of vedolizumab recipients and 22.5% of those taking adalimumab were in clinical remission after 52 weeks (P=0.0061). Clinical remission was defined as a complete Mayo score of 2 or lower and no subscore greater than 1
- Nearly 40% of patients who received vedolizumab achieved mucosal healing at 52 weeks, compared with 27.7% of adalimumab recipients (P=0.0005).
My take: This study provides a rationale for vedolizumab to be used as a first-line biologic agent for ulcerative colitis.