Likelihood of Opioid Dependency If Opioid Given During an IBD Flare

According to a recent study (Full Link: MR Noureldn, PDR Higgins et al. Aliment Pharmacol Ther. 2019;49:74–83. Incidence and predictors of new persistent opioid use following inflammatory bowel disease flares treated with oral corticosteroids), and with the limitation of using an insurance database –Key Findings:

  • 5411 (35.8%) were opioid‐naïve patients (mean age 43.9 yrs) of which 35.0% developed persistent opioid use after the flare
  • Factors associated with new persistent opioid use include a history of depression (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.13‐1.47), substance abuse (HR 1.36, 95% CI 1.2‐1.54), chronic obstructive pulmonary disease (COPD) (HR 1.17, 95% CI 1.04‐1.3), as well as, Crohn’s disease (HR 1.26, 95% CI 1.14‐1.4) or indeterminate colitis (HR 1.6, 95% CI 1.36‐1.88)

My take: As noted in previous blog (Increased Narcotic Usage in Pediatric Patients with IBD), opioid usage is an issue with pediatric IBD patients as well, particularly in those with associated depression and/or anxiety.

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Childhood Obesity: It is NOT Getting Better

A recent study (AC Skinner et al. Pediatrics 2018; 141: e20173459) examined obesity prevalence data in children 2-19 years of age from a nationally representative sample (n=3340).  Specifically, the authors used NHANES data from 1999-2016. Thanks to John Pohl’s twitter feed for pointing out this reference.

PDF Link: Prevalence of Obesity and Severe Obesity in US Children, 1999-2016

This article is packed with data and breaks down obesity in categories: overweight, class I obesity, class II obesity & class III obesity.  It provides data based on gender, age, and ethnicity.

The trend in obesity prevalence is best captured in Figure 1.

Among girls:

  • In 1999-2000: class I obesity noted in 14.6% –>17.8% in 2015-16
  • In 1999-2000: class II obesity noted in 4.0% –>5.2% in 2015-16
  • In 1999-2000: class III obesity noted in 0.9% –>1.8% in 2015-16

Among boys:

  • In 1999-2000: class I obesity noted in 14.7% –>19.1% in 2015-16
  • In 1999-2000: class II obesity noted in 4.1% –>6.7% in 2015-16
  • In 1999-2000: class II obesity noted in 1.0% –>2.0% in 2015-16

My take: This article indicates that the prevalence of childhood obesity in the U.S. is not improving and does not appear to have leveled off as has been suggested by some studies.

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Latiglutenase Not Effective for Celiac Disease, Plus One

A recent study (JA Murray et al. Gastroenterol 2017; 152: 787-98) examined the effectiveness of  latiglutenase for celiac disease.  Latiglutenase (aka ALV003) is an oral medicine which is a mixture of two recombinant gluten-targeting proteases.

The concept of latigluenase is that a medicine that degrades the gluten protein could obviate the need for a gluten free diet.  Unfortunately, in this study with 494 patients with celiac disease for at least 1 year, the medicine at various doses for 12 to 24 weeks was ineffective. There was no difference between the medicine and placebo with regard to villous height:crypt depth ratio, number of intraepithelial lymphocytes or serologic markers of celiac disease.  Symptom scores increased in both the active treatment group and the placebo group.  While this was a negative study, the authors did note some effect on symptom domains on higher dosing regimens. “This observation suggests that treatment with latiglutenase may affect symptoms before showing clinically meaningful effects on serologic and histologic end points.

A second study (RS Choung et al. Gastroenterol 2017; 152: 830-9) examined prevalence and morbidity of undiagnosed celiac disease in Olmstead County. After excluding patients with celiac disease, sera from 30,425 adults and 830 children were tested for tissue transglutaminase IgA antibody (tTG)  and endomysial antibody (EMA).  Case definition: patients were considered to have celiac serologically if tTG titer was 2.0 U/mL or greater with a positive EMA. The prevalence of celiac disease was 1.1% in adults and 1.0% in children. The majority of patients with celiac disease (>80%) have not received the diagnosis.  By comparing those with positive celiac serology to matched controls (2 controls for each positive), the authors determined that undiagnosed celiac disease was associated with increased rates of hypothyroidism (OR 2.2) but no other significant morbidities.  Median followup period was 6.3 years.

My take: A promising new therapy for celiac disease, latiglutenase, looks like it will not be effective and there are a lot of individuals with celiac disease who are unaware of their diagnosis.

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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.

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Eosinophilic Esophagitis Review -NEJM

Good review:  Glenn T. Furuta, M.D., and David A. Katzka, M.D. N Engl J Med 2015; 373:1640-1648

A couple pointers from this review:

  • Estimated prevalence of eosinophilic esophagitis (EoE) 0.4% in Western countries.  Symptoms are often underestimated due to patient ‘accommodation’ which includes eating slowly/carefully, drinking a lot of liquids and avoiding items more prone to become lodged (meats, pills, breads)
  • Pathogenesis: “Birth by cesarean section, premature delivery, antibiotic exposure during infancy, food allergy, lack of breast-feeding, and living in an area of lower population density have all been associated with eosinophilic esophagitis.”
  • Impaired barrier function and enhanced the activity play a role in pathogenesis
  • Food allergy is a non-IgE-mediated process.  Omalizumab, an anti-IgE biologic, is ineffective in EoE and EoE can develop in IgE-null mice
  • Male predominance (3:1) suggests that there is a genetic component.
Esophagus with ringed appearance, furrowing, and loss of vascular markings

Esophagus with ringed appearance, furrowing, and loss of vascular markings

Another useful reference on Eosinophilic Gastritis in Children: Am J Gastroenterol 2014; 109; 1277-85.  This article provides data on clinical and histologic remission with eosinophilic gastritis (>70 eos/hpf), n=30 children.  “Response to dietary restriction was high” (82% clinical, 78% histologic response) Thanks to Seth Marcus for this reference.

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Milder Celiac Disease Being Diagnosed Now

A study (Kivela L et al. J Pediatr 2015; 167: 1109-15) over a period of 48 years from Finland provides some hard data regarding the changing presentation of celiac disease.

Here are the key points;

  • Age at diagnosis has increased from a median of 4.3 years before 1980 to 7.6 years and 9.0 years in later periods.
  • Poor growth has decreased.  Among the 46 children diagnosed prior to 1980, poor growth occurred in 66% whereas 2010-2013: 23% had poor growth (had 14% were overweight or obese)
  • Severity of small-bowel mucosal damage was milder (Figure 1 D).  Among those with gastrointestinal presentation, total villous atrophy also declined from “61-62% to 18-22% (P=.001).”

Why is the presentation changing? There are increased “proportions of screen-detected and asymptomatic children…[this has] increased over 6-fold and simultaneously gastrointestinal symptoms …decreased.”  While there are improved diagnostic methods and increased knowledge, there has also been a “well-defined increase in the true prevalence of celiac disease.”

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IBD in Ontario: 1 in 200

A recent study notes an increasing incidence of and high prevalence of inflammatory bowel disease (IBD) in Ontario, Canada (Inflamm Bowel Dis 2014; 20: 1761-69).

This article notes that between 1999-2008, there was an increased incidence of IBD from 21.3 to 26.2 per 100,000.  This affected most age groups less than 65 years, but increased most rapidly in children younger than 10 years (increased 9.7% per year).  The highest incidence remained in adults aged 20 to 29 years. The overall prevalence in Ontario was estimated to be 1 in 200 overall, which is among the highest in the world.  This study relied on a validated health administrative data consisting of all Ontario residents.

The potential for misclassification bias is discussed and the potential difficulties with administrative health data is detailed in three related editorials (pages 1777-79, 1780-81, 182-83).  The editorials are helpful, in part, because a separate study in the same journal (Inflamm Bowel Dis 2014; 20: 1770-76) indicates that the incidence of Crohn’s disease and Ulcerative Colitis declined in Quebec between 2001-08. However, the authors of this study used less-rigorous methods and had a much shorter “washout” period (two years versus eight years).

At the end of the day, with conflicting studies, there remains some uncertainty with regard to IBD epidemiology.  That being said, the first study notes that “75% of CD studies and 60% of UC studies had reported increased incidence in the adult populations.”

This leads back to the question of what environmental exposures are leading to these changes in incidence.

Bottomline: This article and the associated editorials helps highlight the difficulties of using administrative health data and why many data points are needed to assess the epidemiology of IBD.  In all likelihood, the incidence of IBD is increasing.

Related blog postGlobal increases in IBD incidence | gutsandgrowth

 

How Common is Eosinophilic Esophagitis?

There have been numerous epidemiologic studies regarding eosinophilic esophagitis.  A recent summary of a recent study (Clin Gastroenterol Hepatol 2014; 12: 589-96) has been posted on the AGA Journals Blog.  Here’s the link to the full summary:  EoE Prevalence AGA Journal Blog

Here’s an excerpt:

Eosinophilic esophagitis (EoE), which was barely recognized 20 years ago, affects at least 150,000 people in the United States, with three-quarters being adults, report Evan Dellon et al. in the April issue of Clinical Gastroenterology and Hepatology.

EoE, also known as allergic esophagitis, is an allergic inflammatory disease characterized by increased numbers eosinophils in the esophagus. Symptoms include difficulty swallowing, food impaction, and heartburn…

They found that despite its relatively recent description, EoE is frequently diagnosed in the US, with an estimated prevalence of 56.7/100,000 persons. The mean age of patients, surprisingly, was 33.5 years; 65% were male, 55.8% had dysphagia, and 52.8% had at least 1 other allergic condition. Prevalence peaked in men 35–39 years old (see figure).

EoE Prevalence by Age

Dellon et al. identified patients based on the International Classification of Diseases (ICD), 9th revision code for EoE (530.13). They state that this prevalence could be an underestimate, because knowledge of the code and recognition of EoE are increasing…

Take home point: This study shows that EoE in adults and in children is much more common in males than females, especially in those with other allergic diseases.  Given the frequency of those with mild symptoms, the prevalence data are likely to be huge underestimates.

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