Category Archives: Pediatric Gastroenterology Intestinal Disorder

How helpful are serologies in pediatric inflammatory bowel disease?

Posted on by

For quite some time, I have been unimpressed with the utility of serologies in distinguishing Crohn’s disease and Ulcerative Colitis.  While some of these tests claim some usefulness, when one excludes the obvious cases of Crohn’s disease (eg. perianal disease, fistulizing disease, small bowel disease), these claims seem quite dubious  Another study backs up my interpretation: L Birimberg-Schwartz et al. Inflamm Bowel Dis 2016; 22: 1908-14

This longitudinal report from the IBD Porto Group examined a multicenter retrospective cohort of 406 children with isolated colonic disease.  These children had a mean age of 10.5 years.  117 had Crohn’s colitis, 143 had ulcerative colitis, and 146 had IBD-unclassified (IBDU).

Key findings:

  • Among those with IBDU, the most prevalent serologic profile was pANCA neg/ASCA neg (41%).  34% had pANCA pos/ASCA neg, and 17% and pANCA neg/ASCA pos.
  • ANCA+: present in 43% of patients with IBDU, 64% of patients with UC, and 30% of patients with Crohn’s.
  • ASCA+ (IgA or IgG): present in 26% of  patients with IBDU, 6% of patients with UC, and 40% of patients with Crohn’s.
  • pANCA neg/ASCA pos did help differentiate Crohn’s colitis versus IBDU with 83% specificity, 96% positive predictive value; however the sensitivity was only 33% and the negative predictive value was only 13%.
  • pANCA neg/ASCA pos also differentiated Crohn’s colitis compared with ulcerative colitis with 97% specificity, and 90% positive predictive value however the sensitivity was only 33% and the negative predictive value was only 40%.
  • pANCA pos/ASCA neg did NOT differentiate well.  For IBDU versus UC, the specificity was 66%, the positive predictive value was 94%; the sensitivity was 65% and the negative predictive value was 38%.

In short, these tests generally have poor sensitivity.  If ASCA antibodies are present, which occurred in only 23%, the serology performs better but still usually not well-enough to help with big decisions. The presence of positive serology was associated with an increased likelihood of more severe disease.

Before you order IBD serology, you may want to consider whether you might use the money for this costly test in a better way.

My take (borrowed from authors): “Serology cannot routinely be recommended for differentiating between IBDU versus CC or UC as a sole diagnostic criterion given its low diagnostic utility.”

Related blog posts:

Trail to Iceberg Lake, Glacier Natl Park

Trail to Iceberg Lake, Glacier Natl Park

More advice on Proton Pump Inhibitors

Posted on by

L Laine, A Nagar. Am J Gastroenterol 2016; 111: 913-15.

This reference explains how these clinicians discuss the long-term use of proton-pump inhibitors with their adult patients.  Thanks to Ben Gold for this reference.  Here are a couple pointers:

  • “The recent studies about CKD (chronic kidney disease) and dementia, similar to many prior studies assessing PPI risk, are retrospective observational studies…This results in differences between PPI users and non-users in factors that may impact study outcomes and confound results.”
  • Gastroesophageal reflux disease: The authors suggest that PPIs for GERD can be stopped >2 weeks after symptoms resolve.  For infrequent symptoms, H2RAs, lifestyle modifications and intermittent PPIs often suffice.
  • Barrett’s esophagus: “observational sutdies suggest that PPIs may decrease progression to neoplastic Barrett’s esophagus”

WHAT WE TELL PATIENTS: “Because of inherent risk of bias and low effect sizes we cannot conclude that associations of PPIs and adverse outcomes such as dementia and CKD in recent observational studies are vailid…Nevertheless, we cannot conclude that risks do not exist…we need to ensure that benefits outweigh potential risk.  If PPIs are indicated, using the lowest effective dose and, if possible, intermittent rather than daily therapy..should decrease the risk of potential side effects.”

On the same topic, Paul Moayyedi (in Gastroenterology and Endoscopy News, August 2016): “Every study has shown that sicker patients tend to be prescribed PPIs…Sick patients tend to develop other illnesses so PPIs will be associated with about any disease you can imagine in a database.”  As such, he asserts that weak associations (OR <2) are usually due to cofounding factors.  “The only benefit [these studies]..have is that it is another opportunity to discuss with the patients about stopping their PPI therapy, as there are a significant proportion…on these drugs unnecessarily.”

purple flowers

Biologic Exposure Prenatally and Perinatally

Posted on by

The widespread use of anti-TNF therapy for inflammatory bowel disease has improved clinical outcomes including fewer surgeries, hospitalizations, and complications.  One consequence of this usage has been the exposure of infants to biologics due to their usage by their mothers during pregnancy.  A recent study (M Julsgaard et al. Gastroenterol 2016; 151: 110-19) explores this topic further.

In this study, the authors prospectively followed 80 pregnant women: 36 received adalimumab & 44 infliximab. In addition, 39 received concomitant thiopurine therapy.

Key findings:

  • The time from last exposure to anti-TNF agent correlated inversely with the concentration of these drugs in the umbilical cord and in mothers at the time of birth.
  • Median ratio for infant: mother drug concentration at birth was 1.21 for adalimumab and 1.97 for infliximab.
  • Mean time for drug clearance: 4.0 months for adalimumab and 7.3 months for infliximab. Drugs were not detected after 9 months of life for adalimumab and after 12 months of life for infliximab.
  • No increased risk of adverse pregnancy outcomes were identified; preterm birth was low (n=3 or 3.8%). 48% of women experienced a disease relapse during pregnancy.
  • In this small study, the relative risk for infection was 2.7 in infants exposed to combination therapy.  Benign courses of viral infections were noted in 16 (20%) of the entire cohort and of bacterial infections in 4 (5%).

The authors recommend avoidance of live virus vaccines in biologically-exposed infants for up to 1 year unless drug clearance has been documented. Currently, this would affect only rotavirus vaccination.

My take (borrowed from editorial pgs 25-26): “For now, the sum of evidence seems to support continued use of anti-TNF therapy in pregnancy when clinically indicated and, despite measureable levels in offspring, there does not seem to be a significant clinical consequence.”

Related study: “Adverse Pregnancy Outcomes among women with inflammatory bowel disease: a population-basd study from England” Inflamm Bowel Dis 2016; 22: 1621-30. The authors identified 1969 pregnancies from a total of 364,363 singleton pregnancies.  Women with Crohn’s had increased preterm births with an Odd ratio of 1.42, babies with low birth weight (OR 1.39); women with ulcerative colitis had only a small increase risk in preterm birth (absolute risk <2.7%).

Related blog posts:

Art at Big Creek Greenway, Alpharetta

Art at Big Creek Greenway, Alpharetta

Lower Fiber Intake May Increase Risk of Crohn’s Flare

Posted on by

According to a recent study, lower fiber intake was associated with an increased risk of a flare of Crohn’s disease over a 6-month period (CS Brotherton et al. Clin Gastroenterol Hepatol 2016; 1130-36).

This study examined dietary surveys from 1619 participants (Crohn’s disease in 1130, Ulcerative colitis in 489).  All participants were considered to be in remission at baseline. The key endpoint was disease flare at 6 months which was defined as a disease activity index score exceeding remission cutoff values.

Key finding: “Compared with those in the lowest quartile of fiber consumption, participants with Crohn’s disease in the highest quartile were less likely to have a flare” (adjusted odds ratio 0.58). There was no significant association with ulcerative colitis.

The associated editorial (1137-39) notes that “among 12 RCTs that enrolled patients with Crohn’s disease, fiber did not influence disease activity in studies of induction (flare to remission) or maintenance (remission to flare)…most RCTs had small sample size.”

My take (borrowed from editorial): “A high fiber diet is likely safe in patients with IBD [in the absence of a known stricture/obstructive symptoms] and may impart a weak benefit.”  Overall, dietary approaches are gaining traction and careful evaluation of competing claims will likely be of great benefit.

Related blog posts:

This is where I was completely soaked. Grinnell Trail

This is where (moments later) I was completely soaked. Grinnell Trail

More on Ustekinumab, plus Allopurinol Study

Posted on by

More data emerging that indicates that subcutaneous ustekinumab will be useful for refractory Crohn’s disease: S Khorrami et al. Inflamm Bowel Dis 2016; 22: 1662-69.

  • This open-label cohort of 116 patients identified a clinical response (Harvey-Bradshaw Index) in 97 (84%) after loading dose, and clinical benefit in 58% at 12 months of followup.
  • Perianal disease improved in 11 of 18 (61%).
  • This cohort had refractory disease with almost 90% had failed or were intolerant to 2 or more anti-TNFs.

Another strategy for managing inflammatory bowel disease is using allopurinol which can help low-dose azathioprine achieve therapeutic levels.  In the largest cohort to date, Pavlidis et al (Inflamm Bowel Dis 2016; 22: 1639-46) showed that at the end of followup (median 19 months after treatment initiation) 113/164 (69%) of patients with Crohn’s disease and 83/136 (61%) with ulcerative/unclassified colitis had a clinical response; 52% and 54% respectively were in remission. The azathioprine dose was 25% of weight-based monotherapy dose adjusted based on TPMT status; thus, for normal/high TPMT activity, azathioprine was dosed at 0.5 mg/kg whereas for heterozygous/intermediate activity, azathioprine was dosed at 0.25 mg/kg.

Related blog posts:

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.

Vickery Creek, Sandy Springs

Vickery Creek, Sandy Springs

FMT in the “Real World”

Posted on by

At DDW 2016, OpenBiome presented data (abstract Su1737) from 2,050 patients who received fecal microbiata transplants (FMT) in “the real world.”

Key findings:

  • Overall, 84% clinical cure rate with a single treatment
  • 85% of patients were treated with FMT via colonoscopy (250 mL) and 15% via nasal tube (50 mL). Nasal tube administration had a lower clinical cure rate of 77.9%, compared with 85.1% who had FMT via colonoscopy.

More information on this study: “Closet Thing to Miracle Cure”: Study Confirms Benefit of FMT in C difficile  Gastroenterology & Endoscopy News July 2016  This link also presents data on use of FMT in ulcerative colitis and the use of capsule FMT.

Related blog posts:

Lymphonodular Hyperplasia2

Psychological Therapies for Irritable Bowel Syndrome

Posted on by

A recent meta-analysis (KT Laird et al. Clin Gastroenterol Hepatol 2016; 14: 937-47) of 41 randomized, controlled trials shows that psychological therapies improved symptoms of irritable bowel in adults.

Key finding:

  • “On average, individuals who received psychotherapy had a greater reduction in GI symptoms after treatment than 75% of individuals assigned to a control condition…This effect remained significant” for at least 6-12 months.

A summary of this study from GIHepNews.com:  Psychological Therapies for Irritable Bowel Syndrome

Excerpt of commentary by Dr. Christopher Almario:

While these findings are impressive and continue to support the use of psychotherapy in IBS, important issues remain. First, these results are based on data gathered in the highly controlled environment of randomized controlled trials (RCTs), and it is unclear whether they will translate to the “real world.” RCT participants may be more willing to complete psychotherapy because they know they are being observed by research staff (referred to as the Hawthorne, or observer, effect). However, in real clinical practice, patients with IBS not subject to the Hawthorne effect may be less compliant with such therapies.

Other issues relate to the current limited adoption of psychotherapy in clinical practice. Factors contributing to the low uptake include variable third-party reimbursement and poor patient and provider acceptance (JAMA. 2015 Mar;313:949-58). Another factor is limited access to qualified psychotherapists.

My take: I often refer patients to a “pain psychologist” who works in our office.  With the right psychologist, this can be very helpful.  In addition, I feel that families are more willing to see a psychologist than in the past.

Related blog posts:

JulyClinGastroCover

 

Gold Medal Winner: Infliximab (anti-TNF competition)

Posted on by

According to a recent retrospective study, (S Singh et al. Clin Gastroenterol Hepatol 2016; 14: 1120-29), infliximab outperformed its rivals.  In the spirit of the recent olympics, we’ll give infliximab a gold medal in the anti-TNF category.

Here’s the play-by-play:

This study used an administrative claims database with more than 100 million US enrollees.  In total, there were 3205 biologic-naive patients with Crohn’s disease (CD) with a mean age of 41 years.  All of the participants had not received a biologic agent for at least 12 months prior to their first study dose (between 2006-2014). In addition, the authors excluded patients who had a concomitant diagnosis which could necessitate a biologic, including rheumatoid arthritis, ankylosing spondylitis, and psoriasis.

Race details:

  • Compared to adalimumab-treated patients, inlfiximab-treated patients had a lower risk of CD-related hospitalization (aHR [adjusted Hazard Ratio] 0.80), abdominal surgery (aHR 0.76), and corticosteroid use (aHR 0.85)
  • Compared to certolizumab pegol-treated patients, infliximab-treated patients had a lower risk of hospitalization (all-cause) (aHR 0.70), and CD-related hospitalization (aHR 0.59).
  • All agents had comparable risk of serious infections

Post-race analysis:

Was this a fair race (ie study)? Definitely.  If anything, this study may have underestimated the benefit of infliximab.  Due to trouble with confounders across retrospective studies, it may be that infliximab was chosen preferentially among sicker patients.

My take: There is limited data on comparative effectiveness of anti-TNF agents.  This retrospective study  indicates that infliximab is likely superior to its competitors.  Definitive proof would necessitate a head-to-head live-action (prospective) competition.

Related blog posts:

Screen Shot 2016-08-14 at 11.46.48 AM

Quirky HIDA Study Shows That HIDA Scans Not Too Helpful

Posted on by

As noted in a previous post, Biliary Dyskinesia –“Only in America” | gutsandgrowth, gallbladder dykinesia is a quite dubious diagnosis.  A recent pediatric study (PM Jones et al. JPGN 2016; 63: 71-75) adds to the uncertainty.

This study utilized a large database for a retrospective review of HIDA scans in patients <22 years.  In a group of 2558 patients, 310 patients had a full-text gallbladder pathology report paired with HIDA scan. The majority of these HIDA scans (64.5%) were performed in teenage Caucasian girls.  Key finding:

  • Gallbladder ejection fraction (GBEF) did not correlate with the presence of gallbladder pathology.  The Odd Ratio (OR) for cholecystitis with EF of 16-34 was 0.98.
  • The majority had at least microscopic pathology: 71.6% had microscopic cholecystitis

The authors indicate that other studies have shown that the diagnosis of gallbladder dyskinesia is controversial “because some point to the strong placebo effect of a surgical intervention, as well as the finding that patients who were observed for a year or more had similar symptom improvement  compared with those who had an operation.” [J Pediatric Surg 2006; 41: 1894-8]

Ultimately, the utility of HIDA scans can only be addressed with randomized prospective studies. Perhaps, these studies will show that HIDA scans are not predictive of who needs a cholecystectomy.

My take: It is interesting that pathology did not correlate with HIDA results.  However, the bigger question is whether abnormal gallbladder function, as assessed by HIDA, triggers symptoms that merit cholecystectomy. This is not addressed by this study.

Beach Art

Beach Art

4 Points for C diff in Inflammatory Bowel Disease

Posted on by

A nice review: K Rao, PDR Higgins. Inflamm Bowel Dis 2016; 22: 1744-54.

Many aspects of Clostridium difficile with and without coexisting inflammatory bowel disease has been reviewed on this blog.  This review adds a few additional points:

  1. C difficile testing in patients with IBD, “start with enzyme immunoassay-based tests with a reflex to PCR test for discordant enzyme immunoassay results.”  Rationale: “PCR is quite sensitive for the presence of toxigenic C difficile, it may increase the detection of asymptomatic colonization and shedding.”
  2. Don’t test for C difficile in patients in clinical remission. “Clayton et al evaluated outpatients with IBD who were in clinical remission and had no recent exposure to antimicrobials, corticosteroids, immunomodulatory agents, or hospitalizations.  These patients had toxigenic C difficile carriage rates of 8.2%.”
  3. What to do when IBD patients test positive for C difficile infection (CDI) -treat which one or both? The authors recommend, that “if there is no response to the treatment for CDI after 48 hours, then concurrent immunologic therapy can be started/escalated.”
  4. Safety of FMT with IBD. “There may be additional risk incurred in the IBD population…[in a recent study] 14% of the subgroup of patients with IBD experienced adverse events including IBD flare, requiring hospitalization in some instances.” Overall, there is not enough data to “risk stratify patients in terms of these adverse outcomes.”

In addition to these pointers, advice on treatment based on severity and whether CDI is recurrent is listed on Table 1.

  • For primary CDI (nonsevere): metronidazole, vancomycin or fidaxomicin.
  • For primary CDI (severe): vancomycin or fidaxomicin.
  • For primary CDI (severe & complicated*): vancomycin at highest dose and IV metronidazole and (if ileus present) vancomycin rectally
  • Recurrent CDI: 1st recurrence — same as initial Rx, 2nd recurrence -same as initial Rx, then use either vancomycin pulsed and/or tapered regimen of 6 or more weeks

Related blog posts:

View from Grinnell Glacier Trail, Glacier Nat'l Park

View from Grinnell Glacier Trail, Glacier Nat’l Park

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.