AGA Practice Guidelines for Celiac Disease

AGA Clinical Practice Update on Diagnosis and Monitoring of Celiac Disease—Changing Utility of Serology and Histologic Measures: Expert Review (S Husby et al. Gastroenterol 2019; 156: 885-89)

Best Practice Advice 1: Serology is a crucial component of the detection and diagnosis of CD, particularly tissue transglutaminase–immunoglobulin A (TG2-IgA), IgA testing, and less frequently, endomysial IgA testing.

Best Practice Advice 2: Thorough histological analysis of duodenal biopsies with Marsh classification, counting of lymphocytes per high-power field, and morphometry is important for diagnosis as well as for differential diagnosis.

Best Practice Advice 2a: TG2-IgA, at high levels (> ×10 upper normal limit) is a reliable and accurate test for diagnosing active CD. When such a strongly positive TG2-IgA is combined with a positive endomysial antibody in a second blood sample, the positive predictive value for CD is virtually 100%. In adults, esophagogastroduodenoscopy (EGD) and duodenal biopsies may then be performed for purposes of differential diagnosis.

Best Practice Advice 3: IgA deficiency is an infrequent but important explanation for why patients with CD may be negative on IgA isotype testing despite strong suspicion. Measuring total IgA levels, IgG deamidated gliadin antibody tests, and TG2-IgG testing in that circumstance is recommended.

Best Practice Advice 4: IgG isotype testing for TG2 antibody is not specific in the absence of IgA deficiency.

Best Practice Advice 5: In patients found to have CD first by intestinal biopsies, celiac-specific serology should be undertaken as a confirmatory test before initiation of a gluten-free diet (GFD).

Best Practice Advice 6: In patients in whom CD is strongly suspected in the face of negative biopsies, TG2-IgA should still be performed and, if positive, repeat biopsies might be considered either at that time or sometime in the future.

Best Practice Advice 7: Reduction or avoidance of gluten before diagnostic testing is discouraged, as it may reduce the sensitivity of both serology and biopsy testing.

Best Practice Advice 8: When patients have already started on a GFD before diagnosis, we suggest that the patient go back on a normal diet with 3 slices of wheat bread daily preferably for 1 to 3 months before repeat determination of TG2-IgA.

Best Practice Advice 9: Determination of HLA-DQ2/DQ8 has a limited role in the diagnosis of CD. Its value is largely related to its negative predictive value to rule out CD in patients who are seronegative in the face of histologic changes, in patients who did not have serologic confirmation at the time of diagnosis, and in those patients with a historic diagnosis of CD; especially as very young children before the introduction of celiac-specific serology.

Management

Best Practice Advice 10: Celiac serology has a guarded role in the detection of continued intestinal injury, in particular as to sensitivity, as negative serology in a treated patient does not guarantee that the intestinal mucosa has healed. Persistently positive serology usually indicates ongoing intestinal damage and gluten exposure. Follow-up serology should be performed 6 and 12 months after diagnosis, and yearly thereafter.

Helicobacter Pylori 2019 Review

A recent review (SE Crowe. NEJM 2019; 1158-65) provides a succinct summary of current H pylori management.

A couple of key points:

  • It is essential to test for cure after treatment 1 month afterwards
  • If retreatment is needed, use an alternative regimen
  • In the discussion of treatment, Dr. Crowe does NOT emphasize quadruple therapy except in individuals with a clarithromycin resistance probability of >25% (based on geographic incidence rates) or prior macrolide use.  She notes that in some populations that clarithromycin-based triple therapy had similar effectiveness as bismuth-based quadruple-based therapy.  Table 2 lists the 7 ACG approved treatment regimens.
  • It is noted that U.S. clarithromycin-resistance is between 21-30%.

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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.

AGA Recommendations for Management of Functional Symptoms in Patients with Inflammatory Bowel Disease

Full text: AGA Clinical Practice Update on Functional Gastrointestinal Symptoms in Patients With Inflammatory Bowel Disease: Expert Review (JF Columbel et al. Clin Gastroenterol Hepatol 2019; 17: 380-90).

My take: Overall, this article presents a concise review of a tricky problem and appropiriate management.  The algorithm, tables and figures are useful.

Best practice advice 1: A stepwise approach to rule-out ongoing inflammatory activity should be followed in IBD patients with persistent GI symptoms (measurement of fecal calprotectin, endoscopy with biopsy, cross-sectional imaging).

In the report, the authors note that endoscopy and cross-sectional imaging are not needed in all patients; mainly in patients with a suspected flare based on presentation, calprotectin, and blood work.

Best practice advice 2: In those patients with indeterminate fecal calprotectin levels and mild symptoms, clinicians may consider serial calprotectin monitoring to facilitate anticipatory management.

Best practice advice 3: Anatomic abnormalities or structural complications should be considered in patients with obstructive symptoms including abdominal distention, pain, nausea and vomiting, obstipation or constipation.

Best practice advice 4: Alternative pathophysiologic mechanisms should be considered and evaluated (small intestinal bacterial overgrowth, bile acid diarrhea, carbohydrate intolerance, chronic pancreatitis) based on predominant symptom patterns.

Best practice advice 5: A low FODMAP diet may be offered for management of functional GI symptoms in IBD with careful attention to nutritional adequacy.

Best practice advice 6: Psychological therapies (cognitive behavioural therapy, hypnotherapy, mindfulness therapy) should be considered in IBD patients with functional symptoms.

Best practice advice 7: Osmotic and stimulant laxative should be offered to IBD patients with chronic constipation.

Best practice advice 8: Hypomotility agents or bile-acid sequestrants may be used for chronic diarrhea in quiescent IBD.

Best practice advice 9: Antispasmodics, neuropathic-directed agents, and anti-depressants should be used for functional pain in IBD while use of opiates should be avoided.

Best practice advice 10: Probiotics may be considered for treatment of functional symptoms in IBD.

Best practice advice 11: Pelvic floor therapy should be offered to IBD patients with evidence of an underlying defecatory disorder.

Best practice advice 12: Until further evidence is available, fecal microbiota transplant should not be offered for treatment of functional GI symptoms in IBD.

Best practice advice 13: Physical exercise should be encourage in IBD patients with functional GI symptoms.

Best practice advice 14: Until further evidence is available, complementary and alternative therapies should not be routinely offered for functional symptoms in IBD.

Monticello

Weak Link in Celiac Screening Guidelines

A recent study (AS Faye et al. Clin Gastroenterol Hepatol 2019; 17: 463-8) finds a weak link in the screening guidelines for celiac disease. Generally, guidelines recommend screening all symptomatic first degree relatives and consider screening of asymptomatic first-degree relatives.  Yet, little is known about adherence to these guidelines.

The authors utilized emergency contact information from the electronic records of 2081 patients with biospy-diagnosed celiac disease to assess how commonly celiac disease testing occurs in patients who are first-degree relatives.

Key findings:

  • Of the 539 relatives identified, 212 (39.3%) were tested for celiac disease including 193 of 383 (50.4%) of first-degree relatives and 118 of 165 (71.5%) of symptomatic first-degree relatives.
  • Of the 383 first-degree relatives, only 116 (30.3%) had a documented family history of celiac disease.

Thus, this study shows that ~30% of symptomatic first degree relatives have not received celiac testing and that ~70% of all first-degree relatives do not have a documented family history.

My take: If a family history of celiac disease is not conveyed to health care providers, this greatly reduces the likelihood that symptomatic first degree relatives will undergo recommended screening. This weakness in screening could be overcome by either:

  1. changing to a policy which encourages screening all first degree relatives, whether symptomatic or asymptomatic
  2. leveraging technology (when feasible) to assure that family history is documented in all at risk patients

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Shenandoah National Park

 

New Serology for Celiac Disease?

A recent study (RS Choung et al. Gastroenterol 156: 582-91) showed that synthetic neoepitopes of the transglutaminase-deamidated gliadin complex are better noninvasive biomarkers for detecting celiac disease and for monitoring mucosal healing.

Link to Graphical Abstract and Abstract: Synthetic Neoepitopes of the Transglutaminase–Deamidated Gliadin Complex as Biomarkers for Diagnosing and Monitoring Celiac Disease

The authors studied the serum samples from 90 patients with Celiac disease (CD) and from 79 healthy controls and developed a fluorescent peptide microarray platform  Then, the authors validated their findings in 82 patients with newly diagnosed CD and 217 controls.

Key findings:

  • 7% of patients with treated (with gluten free diet [GFD]) and healed CD had positive TTG-IgA and 27% of patients treated but unhealed CD mucosa had positive TTG IgA
  • With the synthetic neoepitopes, CD was identified with 99% sensitivity and 100% specificity.  The assay identified patients with CD with healed mucosa with an 84% sensitivity and 95% specificity.

My take: More precise noninvasive markers like these should help identify individuals with celiac disease and those who have responded (or not) to the recommended gluten free diet.

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Unrelated but important —NPR reports on another large study showing that MMR does not cause autism -Link: A Large Study Provides More Evidence That MMR Vaccines Don’t Cause Autism 

Related blog post: “Too many vaccines and autism” debunked

Link to full text of study from Annals of Internal Medicine: Measles, Mumps, Rubella Vaccination and AutismA Nationwide Cohort Study

What Happens When Topical Steroids Are Stopped in Eosinophilic Esophagitis

A recent retrospective study (T Greuter et al. Clin Gastroenterol Hepatol 2019; 17: 419-28) shows that patients with eosinophilic esophagitis who continued to take swallowed topical corticosteroids (STC) did much better than patients who did not.

Using the Swiss EoE database, the authors analyzed 229 patients with a mean age of 39 years at diagnosis.  Median followup was 5 years.  The authors initiated STC, almost all received fluticasone, at 1 mg BID for 2-4 weeks followed by maintenance treatment indefinitely.

Key findings:

  • There was frequent discontinuation of STC by patients, such that patients were actually taking STC at only 41% of visits.
  • Higher proportions of patients taking STCs were doing well compared to those not taking STCs:
    • clinical remission was 31% compared to 4.5% respectively (P<.001),
    • endoscopic remission was 49% compared to 18% respectively (P<.001)
    • histologic remission was 45% vs 10% respectively (P<.001)
    • complete remission was 16% vs 1% respectively (P<.001)
  • No dysplasia or mucosal atrophy was detected.  Esophageal candidiasis was observed in 2.7% of visits in patients taking STC

My take: This study shows that patients who maintained STC therapy had better esophageal outcomes than patients who stopped their treatment.  What is not known is the optimal long-term dose.

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Pictures from “Old Rag” Hike, Shenandoah National Park