Category Archives: Pediatric Gastroenterology Intestinal Disorder

Characteristics of Skin Lesions Associated with Anti-Tumor Necrosis Factor Therapy

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As noted in previous blog posts (see below), anti-tumor necrosis factor (anti-TNF) therapy has been associated with skin problems.  The following study/abstract elaborate on this issue further and indicate that while ~30% of patients with IBD may develop skin reactions, only 28 of 917 (3%) patients required anti-TNF therapy to be discontinued due to skin reactions.

I Cleynen et al. Ann Intern Med. Published online 8 December 2015 doi:10.7326/M15-0729  Characteristics of Skin Lesions Associated With Anti–Tumor Necrosis Factor Therapy in Patients With Inflammatory Bowel Disease: A Cohort Study ONLINE FIRST

 Background: A subgroup of patients with inflammatory bowel disease (IBD) treated with anti–tumor necrosis factor (TNF) antibodies develop skin lesions, but the lesions and their clinical course are not well-characterized.

Objective: To describe patients treated with anti-TNF antibodies who did and did not develop skin lesions.

Design: Retrospective cohort.

Setting: Single IBD tertiary referral center.

Patients: 917 consecutive patients with IBD who initiated anti-TNF therapy.

Measurements: Skin lesions, patient demographic characteristics, treatments, clinical course, and serologic and genetic markers.

Results: During a median follow-up of 3.5 years (interquartile range [IQR], 0.5 to 7.4 years), skin lesions associated with the use of anti-TNF therapy developed in 264 of 917 (29%) patients (psoriasiform eczema, 30.6%; eczema, 23.5%; xerosis cutis, 10.6%; palmoplantar pustulosis, 5.3%; psoriasis, 3.8%; other, 26.1%). Lesions typically developed at flexural regions, genitalia, and the scalp, especially the psoriasiform lesions. Thirty-one percent of women and 26% of men developed lesions. Median cumulative doses (2864 mg/y [IQR, 2203 to 3819 mg/y] and 2927 mg/y [IQR, 2377 to 3667 mg/y]) and trough levels (4.2 µg/mL [IQR, 2.6 to 5.8 µg/mL] and 4.0 µg/mL [IQR, 1.6 to 5.9 µg/mL]) of infliximab were similar in patients with and without lesions. All but 28 patients (11%) were successfully managed without needing to stop therapy because of lesions.

Limitation: Retrospective nature and no matched control group of patients not receiving anti-TNF therapy.

Conclusion: Skin lesions occur frequently in association with anti-TNF therapy but rarely require discontinuation of therapy. Close surveillance and early referral to a dedicated dermatologist are recommended.

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Proton Pump Inhibitors Webinar

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For those who missed the live NASPGHAN webinar, it is also available on demand: Link: Proton Pump Inhibitors Webinar. CME credit is available too.

Overall, this is a terrific review and intended for a high level audience. Here are a couple of key points from the talk:

  • Dr. Jennifer Lightdale introduced the webinar.  She noted that there has been a tremendous rise in the use of proton pump inhibitors (PPIs) in children over the past 15 years, including in infants.
  • Preponderance of evidence does not support use of PPIs for reducing GER symptoms or crying in infants.
  • PPIs are extremely effective at acid suppression.
  • Excellent discussion by Dr. Rachel Rosen on Nonerosive Reflux Disease (NERD) and distinguishing this entity from erosive reflux disease, hypersensitive esophagus, and functional heartburn.
  • On a microscopic level, NERD is similar to erosive reflux with microscopic inflammation and dilated intracellular spaces.
  • With regard to testing, it is recommended that for impedance studies, that acid suppression be stopped prior due to improved sensitivity/accuracy.
  • For those at odds with their pulmonologists and ENT colleagues, Dr. Ben Gold reviewed the literature on asthma, cough, and laryngeal-pharyngeal pathology related to reflux. The sensitivity of laryngoscopic findings to identify reflux is poor.  “There is insufficient evidence to recommend for OR against the use of acid suppression therapy.”
  • Dr. Jose Garza reviewed the indications for PPI use which include eosinophilic esophagitis/PPI-REE, erosive esophagitis, NSAID prophylaxis, Upper GI bleeding, and H pylori therapy.
  • Dr. Carlo DiLorenzo provided an in-depth discussion of the potential risks of PPI therapy and explained some of the context as well as absolute risks.  He noted that besides the risk of infection, particularly C difficile, other risks demonstrated in adults have not yet been confirmed in children.
  • “Prolonged acid suppression should be used only when indicated.”  Thus, management should include strategies for treatment discontinuation in the majority of those receiving PPI therapy.

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Isla Verde, San Juan

Isla Verde, San Juan

 

 

 

 

 

 

 

 

 

Nummular Eczema due to Infliximab

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An image report (YM Dawkins et al. Clin Gastroenterol Hepatolo 2016; 14: xxxv-xxxvi) describes a 30-year-old with ulcerative colitis who developed nummular eczema two years after the start of infliximab.  He was treated with topical agents and a course of systemic corticosteroids.  The authors note that in a few patients, withdrawal of anti-TNF therapy is needed, but this was not needed in their patient.

SkinRxnNumEczemaIFX

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Increasing Rates of Abdominal Wall Birth Defect (Gastroschisis)

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From NY Times summary of recent study, “Rate of Birth Defect of Abdominal Wall Increasing, CDC Says“:

The prevalence of gastroschisis has increased by about 30 percent, to 4.9 births out of 10,000 during the period from 2006 to 2012, from 3.6 per 10,000 live births from 1995 to 2005, according to the Centers for Disease Control and Prevention.

My take: This epidemiology is definitely concerning.  Though most children with gastroschisis do well over time, some have serious problems and many require prolonged hospitalizations after birth.

 

Living Liver Donors: 97% Would Do It Again

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A recent study (VR Humphreville et al. Liver Transpl 2016; 22: 53-62) indicates that living liver donors report a high satisfaction following donation.

The authors examined a cohort of 127 living liver donors from the University of Minnesota; donation had occurred between 2 years and 16 years previously.  In addition to a donor-specific survey (DSS) completed by 107, the participants completed the short-form 36 health survey to assess health-related quality of life.

Key findings:

  • Almost all donors reported that they would donate again (97.2%)
  • Satisfaction rate correlated with the outcome of the liver transplant recipient along with pain after donation and vitality after donation. 91.6% rated their satisfaction with the donation process as >8 on a 10 -point scale, with 10 being “extremely satisfied”
  • Health-related quality of life was higher among donors than the general population (though they likely had higher scores than the general population at baseline)

The study elaborates on the potential complications with the most frequent  being incisional discomfort in 34%.

My Take: this information on high satisfaction will be useful for transplant programs and those considering living liver donation.

 

Good Press for PPIs

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A lot of medical publications focus on infrequent complications of medications.  This is problematic for many who have trouble understanding absolute risks and relative risks.  If a medication increases the relative risk of a rare problem, the absolute risk to the individual remains quite low.

For proton pump inhibitors, there has been a fair amount of focus on potential complications.  In my view, some of this is due to the fact that there are many taking these medications who may not be receiving much benefit.   Many of the adverse effects for most patients would result in a low absolute risk. In fact, stopping PPIs in those who have indications for their usage could result in significantly greater harm.

For those who’ve been thinking that proton pump inhibitors (PPIs) have been getting a ‘bum rap,’ here are a few publications have highlighted their success in problems other than ulcers and gastroesophageal reflux disease.

  • AJ Lucendo et al. Clin Gastroenterol Hepatol 2016; 14: 13-22.
  • RMM van Aerts et al.  Clin Gastroenterol Hepatol 2016; 14: 147-52.

The first study, a systemic review and meta-analysis of PPIs in inducing remission for eosinophilic esophagitis (EoE).  In all 33 studies (11 prospective) of adults and children were included with 619 patients. Key findings:

  • Clinical response was noted in 60.8%
  • Histologic remission (<15 Eos/hpf in this study) in 50.5%
  • In prospective studies, once-daily therapy had similar effectiveness to twice daily (55.9% vs. 49.7%)
  • pH monitoring did not predict response to PPI therapy

My take: While the conclusion from this study (by the authors) is that PPIs should be considered a first-line therapy for EoE, they also indicate that the findings need to interpreted cautiously due to poor-quality evidence, heterogeneity of the studies, and publication bias.  Despite these limitations, most experts agree that PPI therapy should be undertaken prior to use of other treatments like diets or topical steroids for EoE.

The second study showed that patients with hereditary hemochromatosis needed less phlebotomy if they were taking PPIs.  The study was a retrospective study which divided patients into 3 groups, including a paired group of 12 patients who had ferritin levels and number of phlebotomies compared for 3 years prior and 3 years after the start of PPI therapy.  In this group, phlebotomies were needed 3.16 times per year prior to PPI and only 0.5 per year subsequently (to keep ferritin less than 100 mcg/L).  The authors note that studies have shown that PPIs reduced postprandial iron absorption.  PPIs effect on iron metabolism “acts at cellular level in the endosomes and in the stomach, and it seems to have no influence on the hepcidin regulation.”  For PPI fans, the editorial (pgs 153-55) comments that “an attractive aspect of this strategy is the safety of PPIs, which has been shown even with long-term use.’ [Aliment Phamacol Ther 2015; 41: 1162-74]

My take: While this study is not recommending that patients with hereditary hemochromatosis start PPI therapy, those who are taking PPI therapy may need less frequent phlebotomy.

So, in addition to patients with gastroesophageal reflux disease and peptic ulcer disease, patients with eosinophilic esophagitis and those with hereditary hemochromatosis often benefit from PPI therapy.

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Half Dome, Yosemite

Half Dome, Yosemite

Expect More on Microbiome Modulation with Enteral Nutrition

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Similar to a study reviewed on this blog (Why Does Enteral Nutrition Work for Crohn’s Disease? Is it due to the Microbiome?), another publication has shown decreased microbiome diversity associated with exclusive enteral nutrition (C Quince et al. Am J Gastroenterol 2-15; 110: 1718-29 -thanks to Ben Gold for this reference). The overall findings suggest that enteral nutrition makes the gut microbiome more ‘dysbiotic’ (more dissimilar to healthy controls) than prior to enteral nutrition.  This study examined 23 children with Crohn’s disease and 21 healthy children.

My take: Due to the increased ease and fascination of studying our stools, a lot more of this research is going to be published.  At some point, hopefully, these observational studies will transition to hypothesis-driven studies regarding which microbial species need to be modulated to improve inflammatory bowel disease.

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Salvage Therapy and Standard Therapy for H pylori

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A recent review (thanks to KT Park for reference) provides helpful resource for treating H pylori infection; this is becoming more important in this era of frequent antibiotic resistance. While this blog has reviewed expert recommendations for treatment, this article provides more insight into salvage treatments.  Table 1 reviews standard quadruple and triple regimens. Table 2 (below) provides dosing in adults for salvage therapy.

Thung, I., et al. (2015), Review article: the global emergence of Helicobacter pylori antibiotic resistance. Alimentary Pharmacology & Therapeutics. doi: 10.1111/apt.13497

Full link: Review article: the global emergence of Helicobacter pylori antibiotic resistance

 

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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.

Do You Know the Best Way to Use Antegrade Enemas?

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Currently, there is no best way to use antegrade enemas.  This is the obvious conclusion after reading a study by S Kuizenga-Wessel et al (JPGN 2016; 62: 71-9).  In this study, the authors reviewed 21 articles and also surveyed 23 physicians involved in the care of children who receive antegrade continence enemas (ACE). While the study provides a lot of details, the bottom-line is that there is wide variation in outcomes, definition of success, workup prior to institution of ACE, and irrigation solutions (16 out of 23 used saline).  The only areas of agreement seem to be the following:

  • use of ACE daily: 22 of 23
  • use of antibiotics with placement: 23/23 (though wide variation in specific regimen)
  • indications for ACE were largely in agreement, including constipation with fecal incontinence (21 of 23), anorectal malformations (22 of 23) and spinal abnormalities (23 of 23); however, only 8 of 23 considered due to functional non-retentive fecal incontinence as an acceptable indication

With regard to the type of enema, the vast majority of physicians (19 of 23) only add a stimulant to the solution after initial failure.  Though, one study (J Pediatr 2012; 161: 700-4) has reported “that subjects who use stimulants from the very beginning had significantly better outcomes.”

My take: Like of a lot areas in medicine and throughout pediatric gastroenterology, there is wide variation in clinical treatment approaches.  Variation in treatment is obvious in the use of ACE.  Collaborative work and consensus building in management would improve success; that is, after we define what success looks like.

In the same issue a link to “History of Pediatric Endoscopy” is provided.  This is a ~15 minute video with interviews with many pioneers/leaders in pediatric gastroenterology.

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Golden Gate Bridge

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Fecal Transplantation: “Frozen is as Good as Fresh”

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Besides pointing out that someone could make $13,000 per year selling their stool, a recent Washington Post story summarized a JAMA study (JAMA. 2016;315(2):142-149. doi:10.1001/jama.2015.18098) which indicated that frozen stool works as well as fresh stool in treating Clostridium difficile infection.

In this study:

Design: Randomized, double-blind, noninferiority trial enrolling 232 adults with recurrent or refractory CDI, conducted between July 2012 and September 2014 at 6 academic medical centers in Canada.

Key finding: In the per-protocol population, the proportion of patients with clinical resolution was 83.5% for the frozen FMT group and 85.1% for the fresh FMT group

Washington Post Summary In fecal matter transplants, frozen is as good as fresh

Here’s an excerpt:

The new study, led by McMaster University’s Christine H. Lee and published Tuesday in JAMA, found that patients given donations that had been frozen for up to 30 days fared just as well as those given fresh samples…

Lee and her colleagues administered one or two FMT enemas to 178 patients, splitting them into two groups to compare freshly-harvested samples and ones that had been frozen and defrosted. Thirteen weeks later, 85 percent of the fresh patients were diarrhea-free. In the frozen group, the success rate reached 83.5 percent – a margin that allows Lee and her team to dub the treatment “noninferior.”

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Bryce Canyon

Bryce Canyon.  This is where I was told to beware of ‘poison rock’ —  one drop can kill you