Weak Link in Celiac Screening Guidelines

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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?

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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 Autism: A Nationwide Cohort Study

Grapefruit Frequently Affects Medication Levels

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A recent NT Times article: Can Grapefruit Juice Affect My Thyroid Medicine?

Link: list of medications affected by grapefruit/grapefruit juice

An excerpt:

“You don’t have to drink liters and liters of the stuff to have an effect,” Dr. Bailey said. For example, he said, “if you take simvastatin and drink a single glass of grapefruit juice, it’s like taking three times the dose,” though the impact can be much more or much less, since individual susceptibilities vary widely….Other citrus fruits like Seville oranges, limes and pomelos can also produce a similar effect.

Genetically-Modified Gut Bacteria

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A recent NPR story (A Gulp Of Genetically Modified Bacteria Might Someday Treat A Range Of Illnesses) explored new research regarding ingestion of genetically modified gut bacteria for medical purposes.

Two of the examples that were highlighted included phenylketonuria (PKU) and cirrhosis.  For each disorder, the researchers are modifying E coli. For PKU, this may allow individuals to consume foods like milk and meat that usually would make them sick because individuals with PKU develop toxicity in response to phenylalanine in their diet.  For cirrhosis, the genetically modified E coli help eliminate the elevation of ammonia which is due in part to gut bacteria and in part due to liver dysfunction.  The report notes that the application of this science is likely to impact many other disorders including ulcerative colitis.

These efforts represent an exponential change to modifying the gut microbiome to enhance health.

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A Role for Thiopurine Therapy

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In high school, the usual advice on multiple choice questions was to avoid picking “always” and “never” on multiple choice questions.

A recent commentary (KH de Boer et al.”Thiopurine Therapy in Inflammatory Bowel Diseases: Making New Friends Should Not Mean Losing Old Ones”Gastroenterol 2019; 156: 11-4) makes the point that “never” is probably the wrong answer with regard to thiopurine usage.

Key points:

  • “Thiopurine therapy has proven its value in maintenance of remission, decreased need for surgery, lowered colorectal cancer risk, less phenotypic disease progression, and synergistic effects when used with infliximab therapy, including increased biologic drug levels and less antibody formation.”
  • “Notwithstanding the extensive experience by many physicians, the clinical use of conventional immunosuppressive therapies has been questioned in recent years.”
  • “In this issue of Gastroenterology, Hanauer et al share their expert opinion on the evolving use of thiopurines and methotrexate in daily practice. In their literature review, the importance of assessing the risks (infections and cancer risk) and benefits (maintenance of remission) of thiopurine therapy is highlighted”
  • Lymphoma risk: “The recent nationwide cohort study based on French National Health Insurance databases is illustrative. Including 189,289 patients, it was demonstrated that both thiopurine (adjusted hazard ratio of 2.6) and anti-TNF monotherapy (adjusted hazard ratio of 2.4) were associated with a similar small but statistically significant increased risk of lymphoma. Furthermore, combination therapy of thiopurine and anti-TNF was associated with a higher chance of developing a lymphoma (adjusted hazard ratio of 6.1).”
  • “The individual absolute risk remains low, especially in patients without additional risk factors such as a young age in male patients and negative Epstein-Barr virus serology.”

The author’s conclusion: “The thiopurines are not perfect regarding both efficacy and toxicity, but in recent years they may have been portrayed in a worse light than they deserved. No doubt, the thiopurines will be surpassed eventually by newer safe and economical (oral) therapies, but it is too early to discard these old friends.”

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  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.

Monticello

 

Mortality Risk from Childhood Inflammatory Bowel Disease

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A recent study (O Olen et al. Gastroenterol 2019; 156: 614-22) was summarized quite succinctly by NEJM journal watch:

Using the Swedish National Patient Registry data, investigators identified 9442 incident cases of IBD diagnosed in patients under age 18 years from 1964 through 2014. Based on 139,000 person-years of follow-up, results were as follows:

  • There were 259 deaths among people with IBD (133 were from cancer and 54 from digestive disease).
  • The all-cause mortality rate in these patients was 2.1/1000 person-years, compared with 0.7 in matched reference individuals from the general population.
  • The average age at death was 61.7 compared with 63.9 years in the reference group.
  • The hazard ratio for death was 3.2 and was higher in those with ulcerative colitis (HR, 4.0), especially if they had concomitant primary sclerosing cholangitis (HR, 12.2), a first-degree relative with ulcerative colitis (HR, 8.3), or a history of surgery (HR, 4.6).
  • Mortality risks were similar when limited to the period after the introduction of biologics (2002–2014).

My take: This study found that having IBD diagnosed in childhood increased the risk of mortality (~1 extra death for every 700 patients followed for 1 year) especially in patients with concomitant PSC and in patients with severe ulcerative colitis.  The study did not see an effect of the newest therapies but was underpowered to directly assess this effect.

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Chattahoochee River, near Azalea Drive

 

What Happens When Topical Steroids Are Stopped in Eosinophilic Esophagitis

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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

Promising Biologic for Eosinophilic Esophagitis

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A recent study (I Hirano et al. Gastroenterol 2019; 156: 592-603) showed that RPC4046, a monoclonal antibody against IL13 is a promising agent for eosinophilic esophagitis. This multicenter double-blind study with 99 adults compared RPC4046 at doses of either 180 mg or 360 mg to placebo for 16 weeks.  Endoscopy was performed at baseline and at 16 weeks.  The study population included a high number who were considered steroid-refractory and excluded patients who were responsive to proton pump inhibitors. The study drug was administered initially as an IV load followed by weekly subcutaneous injections.

Key findings:

  • Mean changes in esophageal eosinophil count dropped by 94.8 in patients receiving 180 mg dosing and 99.9 in patients receiving 360 mg dosing.  In contrast, placebo-treated patients had a meager reduction of 4.4.
  • In this phase II study, there were no serious safety issues identified
  • There were no significant changes relative to placebo in dysphagia symptoms using the DSD (dysphagia symptom diary) composite score. Though there was improvement in global PRO measures compared to placebo.

There is an associated editorial (pg 545) explains the need for better therapies.  While both dietary therapies and topical steroids are likely effective in >70%, dietary therapy is plagued by problems with long-term adherence and there may become less effective with longer-term administration.

My take: Particularly for patients with refractory EoE, newer therapies are needed.  Given the chronic nature of EoE, cost of new treatments could be another hurdle.

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NY Times:Supplements Don’t Help Dementia

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It is tiresome how many products are marketed with baseless claims of preventing dementia.  Some pushback:

NY Times: Supplements Won’t Prevent Dementia. But These Steps Might.

An excerpt:

The Food and Drug Administration estimates that 80 percent of older adults rely on dietary supplements, many purporting to prevent or treat Alzheimer’s and other forms of dementia…

Vitamins, various antioxidants, concoctions derived from animals and plants — “we see plenty of ads on TV, but we have no evidence that any of these things are preventive,” said Dr. Steven DeKosky, a neurologist and deputy director of the McKnight Brain Institute at the University of Florida.

Dr. DeKosky led a federally supported study of Ginkgo biloba extract, for instance, following more than 3,000 people for seven years to see if it reduced dementia. It didn’t.

Some of the steps that may help according to article:

  • Increased physical activity;

  • Blood pressure management for people with hypertension, particularly in midlife;

  • And cognitive training.