Author Archives: gutsandgrowth

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About gutsandgrowth

I am a pediatric gastroenterologist at GI Care for Kids (previously called CCDHC) in Atlanta, Georgia. The goal of my blog is to share some of my reading in my field more broadly. In addition, I wanted to provide my voice to a wide range of topics that often have inaccurate or incomplete information. Before starting this blog in 2011, I would tear out articles from journals and/or keep notes in a palm pilot. This blog helps provide an updated source of information that is easy to access and search, along with links to useful multimedia sources. I was born and raised in Chattanooga. After graduating from the University of Virginia, I attended Baylor College of Medicine. I completed residency and fellowship training at the University of Cincinnati at the Children’s Hospital Medical Center. I received funding from the National Institutes of Health for molecular biology research of the gastrointestinal tract. During my fellowship, I had the opportunity to work with some of the most amazing pediatric gastroenterologists and mentors. Some of these individuals included Mitchell Cohen, William Balistreri, James Heubi, Jorge Bezerra, Colin Rudolph, John Bucuvalas, and Michael Farrell. I am grateful for their teaching and their friendship. During my training with their help, I received a nationwide award for the best research by a GI fellow. I have authored numerous publications/presentations including original research, case reports, review articles, and textbook chapters on various pediatric gastrointestinal problems. In addition, I have been recognized by Atlanta Magazine as a "Top Doctor" in my field multiple times. Currently, I am the vice chair of the section of nutrition for the Georgia Chapter of the American Academy of Pediatrics. In addition, I am an adjunct Associate Clinical Professor of Pediatrics at Emory University School of Medicine. Other society memberships have included the North American Society for Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN), American Academy of Pediatrics, the Food Allergy Network, the American Gastroenterology Association, the American Association for the Study of Liver Diseases, and the Crohn’s and Colitis Foundation. As part of a national pediatric GI organization called NASPGHAN (and its affiliated website GIKids), I have helped develop educational materials on a wide-range of gastrointestinal and liver diseases which are used across the country. Also, I have been an invited speaker for national campaigns to improve the evaluation and treatment of gastroesophageal reflux disease, celiac disease, eosinophilic esophagitis, hepatitis C, and inflammatory bowel disease (IBD). Some information on these topics has been posted at my work website, www.gicareforkids.com, which has links to multiple other useful resources. I am fortunate to work at GI Care For Kids. Our group has 17 terrific physicians with a wide range of subspecialization, including liver diseases, feeding disorders, eosinophilic diseases, inflammatory bowel disease, cystic fibrosis, DiGeorge/22q, celiac disease, and motility disorders. Many of our physicians are recognized nationally for their achievements. Our group of physicians have worked closely together for many years. None of the physicians in our group have ever left to join other groups. I have also worked with the same nurse (Bernadette) since I moved to Atlanta in 1997. For many families, more practical matters about our office include the following: – 14 office/satellite locations – physicians who speak Spanish – cutting edge research – on-site nutritionists – on-site psychology support for abdominal pain and feeding disorders – participation in ImproveCareNow to better the outcomes for children with inflammatory bowel disease – office endoscopy suite (lower costs and easier scheduling) – office infusion center (lower costs and easier for families) – easy access to nursing advice (each physician has at least one nurse) I am married and have two sons (both adults). I like to read, walk/hike, bike, swim, and play tennis with my free time. I do not have any financial relationships with pharmaceutical companies or other financial relationships to disclose. I have helped enroll patients in industry-sponsored research studies.

One year later

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It has been one year and 300 posts since I’ve started this blog.  I’ve enjoyed putting together my thoughts about recent articles.  In addition, I like being able to search for previous blogs for information that I find helpful.

Currently there are close to ~35 hits per day in addition to the email/wordpress followers (about 30).  This number has been increasing and it is fascinating to see that people from all over the world will sometimes stumble across this blog.

If you have suggestions for topics, articles or other ways to improve this pediatric GI blog, please send me an email at jjhochman@gmail.com.

EoE: Drugs, Diets, Dilatation and PPI-REE

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PPI-REE or proton pump inhibitor-responsive esophageal eosinophilia remains a problematic issue for our eosinophilic esophagitis (EoE) patients.  PPI-REE and the 3 D’s (Drugs, diet, and dilatation) have been reviewed recently (Clin Gastroenterol Hepatol 2012; 10: 1066-78).

The issues with PPI-REE that are problematic:

  • If a patient with suspected EoE is pretreated with a PPI and they do not have eosinophils present at the time of endoscopy then a diagnosis of PPI-REE cannot be established.
  • If patients are not pretreated, then determining that they have PPI-REE compared with typical EoE, requires repeat endoscopy.  Furthermore, response to PPI may be transient and/or natural variation in EoE could make definitive diagnosis of PPI-REE quite difficult.
  • If a patient presents with classic-appearing EoE, choosing to treat with a PPI is difficult as the response rate is much lower than with either dietary therapy or drug therapy.  In addition, many symptomatic patients may have been treated to some extent with a PPI.  Do they warrant repeat treatment and repeat endoscopy prior to using more typical treatment for EoE?

Beyond this topic, this review covers the recent consensus guidelines and the typical treatments: diets, drugs, and dilatation.

With regard to dilatation, the author notes that it may be safer than previously believed.  Furthermore, in a recent trial, 81% were symptom free at 3 months and 46% were symptom free at 1 year.  Despite better safety results, 74% of patients in one study complained of retrosternal pain after in endoscopy (moderate in 21% and severe in 17%).

With regard to drug or dietary therapy, the author recommends checking on the effectiveness after 6-8 weeks with a repeat endoscopy.  Until better tools for assessing response to therapy become available, endoscopy remains the only accurate way to determine if treatment is working.

Related blog entries:

Predicting Necrotizing Enterocolitis with Fecal Biomarker

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A recent study has shown some promise in detecting necrotizing enterocolitis (NEC) with a fecal biomarker, S100A12 (J Pediatr 2012; 161: 1059-64).

In this prospective study of 145 preterm infants with a birth weight <1500 g, stool samples were collected on alternated days for 4 weeks.  Fecal S100A12 and calprotectin were measured.  Calprotectin in previous studies has been shown to be a poor marker for NEC.

Fecal S100A12, also called calgranulin C, belongs to a novel group of proinflammatory molecules. It is released by activated or damaged cells under conditions of cell stress and indicates phagocyte-specific damage.

18 (12.4%) developed NEC.  Fecal S100A12 levels were elevated in severe NEC and also at 4-10 days beforehand.  The sensitivity, specificity, positive predictive values, and negative predictive values were 70%, 68%. 37%, and 89% respectively.  Thus, there is limited utility of this stool test due to the limited sensitivity/specificity.  There is substantial overlap between control patients and patients who developed NEC.  Furthermore, fecal S100A12 levels are age-dependent.  Generally, they are higher early in life, likely due to increased mucosal permeability.

Calprotectin levels were elevated at the onset of NEC (median 349 mg/kg) and 48 hours before onset (median 83 mg/kg).  The difference at 48 hours prior to onset did not reach statistical significance.

Congenital Sucrase Isomaltase Deficiency

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Congenital Sucrase Isomaltase Deficiency (CSID) has an extensive review in a recent JPGN supplement (JPGN 2012; supplement 2: S1-47).

A concise update of the clinical aspects is provided by William Treem (S7-S13).   Specific points that he makes includes the following:

  • CSID was first described in 1960 by Weijers and colleagues
  • Sucrase-isomaltase gene (3q25-26) identified in 1992; now more than 55 mutations have been described.  At least one of the four most common mutations are identified in about 80% of affected individuals.
  • Prevalence: estimates range from 1 in 500 to 1 in 2000 in caucasians; the prevalence is lower in other populations.  Some patients suspected of having CSID may be heterozygotes with low enzyme activity (but not truly deficient).
  • Clinical features determined by degree of enzyme deficiency and amount of sugar and starch consumed.  In the U.S. typically 60% of calories consumed are derived from carbohydrates and 30% from sucrose.  A typical U.S. adult consumes 150 lb of sugar per year.
  • Classical presentation: severe watery diarrhea and poor weight gain in a 9- to 18-month old after exposure to juices, baby foods/fruits, and other starches.
  • Other symptoms: gas/bloating, abdominal pain, irritable bowel syndrome
  • Diagnosis: intestinal biopsy analysis.  A potential pitfall includes mishandling of biopsy specimens. An alternative means of diagnosis is the 13-C sucrose breath test.
  • Treatment: 1. dietary avoidance results in improvement in many, though only 10% respond fully to diet. 2. enzymatic treatment. Baker’s yeast (Saccharomyces cerevisiae) contains a sucrase.  Development of sacrosidase (Sucraid) from Baker’s yeast has allowed 81% of patients to consume an unrestricted diet.  Dosing: 1 mL with meals/snacks if <15 kg and 2 mL if >15 kg.
  • Despite sacrosidase treatment, 27% of patients required strict sucrose restriction with either mild or strict starch restriction to maintain acceptable suppression of symptoms.
  • What is not noted in this summary–cost information: sucraid may cost as much as $3700 per month.  A similar product in Europe costs about $400 per month

Multiple other articles in this supplement address related subjects.

On page S31, information is given from parent support group.  This parent support group (CSIDinfo.com) offers dietary advice specific for each phenotype (A,B,C,D and F) which is based on their disaccharidase levels, ability to outgrow symptoms, and tolerance of starch and maltodextrins.

On page S34, the major genetic mutations are discussed.  Use of genetic testing will detect the majority with CSID which could become an alternative means of diagnosing CSID in this population.

Additional Information

Norovirus -now more important than rotavirus

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Norovirus has become more important than rotavirus.  This is evident based on a recent review (NEJM 2012; 367: 2126-32).

Key points:

  • Noroviruses are the most common cause of acute gastroenteritis requiring hospital ER evaluation in U.S. adults.  It is predicted to become the most common cause of diarrhea in all age groups worldwide once rotavirus infection is controlled through vaccination.
  • Noroviruses are small nonenveloped single-stranded RNA viruses from the Calciviridae family.  There are six major genogroups.
  • Exposure can occur from other individuals, contaminated food/water, and environment sources, including nosocomial.
  • Chronic infection is common in immunocompromised hosts, perhaps 15-20% of some immunocompromised populations.  Evolution of the norovirus genome in patients infected for extended periods is relatively rapid (3.3% amino acid substitutions per year).
  • In normal hosts, viral shedding lasts 20-40 days; in the immunocompromised, shedding can occur for years.
  • Can be detected readily with RT-PCR assays.
  • There are no vaccines or specific viral agents available that have proven efficacy.  Passive antibody therapies have been given in individual cases.
  • Hand-washing is crucial, especially in the hospital.  In one study, 80% of hospital surfaces were contaminated with multiple norovirus strains—this study was done in a unit for children with immunodeficiencies.

Additional References:

Related blog entry:

Immunoglobulin deficiencies with DiGeorge Syndrome

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I participate in a Children’s Healthcare of Atlanta multidisciplinary clinic to help provide care for children with DiGeorge syndrome/22q deletion.  As such, I am interested in a range of issues in these patients.  A recent discovery has been that humoral immunity and not just T-lymphocyte immunodeficiency occurs in a significant number of patients with DiGeorge syndrome (J Pediatr 2012; 161: 950-3).

A cohort of 1023 patients were identified from a number of registries that spanned 21 countries and 40 different contributors. Among this group, 3% were receiving immunoglobulin therapy and 6% over the age of 3 years had hypogammaglobulinemia (IgG <500 mg/dL).

Additional references/resources:

  • –Growth charts for 22q: http://www.22q.org/index.php/growth-charts
  • -J Pediatr 2011; 159: 332. 22q guidelines.
  • -J Pediatr 2009; 155: 560. n=64. 22q11.2 deletion found in <60% of DiGeorge Anomaly pts. DiGeorge Anomaly =(at least 2): congenital heart dz, immune deficiency, hypocalcemia. Also, 86/121 with deletion do not fulfill requirement of anomaly (“syndrome”).
  • -Mol Syndromol. 2011 January; 1(4): 192–209. “Introduction: The 22q11.2 deletion syndrome is increasingly recognized in pediatric patients with an incidence of approximately 1 in 3,000. GI manifestations are common and can impact significantly on feeding and growth. To date, there have been few papers on feeding disorders and isolated case reports of various GI anomalies. Methods: A retrospective chart review was conducted on 766 patients with confirmed 22q11.2 deletions followed in the 22q and You Center at CHOP. Data abstracted included GI symptoms, evaluation and management. Results: Average age was 15 years (0.2–62 years). Male:female ratio was 1:1. Ethnic distribution was predominantly Caucasian (67%), Hispanic (33%) and African-American (10%). 32% of patients had no GI symptoms. In patients with GI symptoms, nasopharyngeal reflux, feeding problems, gastroesophageal reflux and constipation were common. Diagnoses included dysmotility (27), intestinal malrotation (7), esophageal diverticula (5), gastroparesis (5), rectal prolapse (2), esophageal atresia (2), gallstones (2), imperforate anus (1), tracheo-esophageal fistula (1), pyloric stenosis (1), choledochal cyst (1), Hirschsprung’s disease (1), and celiac disease (1). About 27% of patients underwent GI testing. Upper GI series and modified barium swallowing study were frequently performed. 5% of patients underwent fundoplication. Feeding tubes were common (27%). Conclusions: Significant GI manifestations are frequent in patients with the 22q11.2 deletion syndrome. Clinicians need to be aware of these conditions to avoid delays in diagnosis. Moreover, all patients with GI symptomatology will benefit from evaluation with a gastroenterologist.”
  • -Pediatrics 2003; 112: 101.n=43; 1 in 5950 births. phenotype in 43 pts
  • -JPGN 2002; 35: 423 (56 Abstract) DiGeorge syndrome GI manifestations; 6 of 46 c malrotation, dysmotility in 7
  • -J Pediatr 2001; 139: 715. DiGeorge immunologic features.

22q Deletions Resources for Families

SUPPORT GROUPS & WEB RESOURCES

  1. 22Q Foundation

  2. DiGeorge syndrome – Wikipedia, the free encyclopedia

  3. Welcome to the Velo-Cardio-Facial Syndrome (VCFS) Educationa

  4. DiGeorge Syndrome – American Heart Association

  5. Living with 22Q – Dempster Family Foundation

  6. Friends of Quinn | Blog | Quinn Bradlee

EDUCATIONAL RESOURCES:

Stopping criminality in ADHD

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While not much related to pediatric gastroenterology, I nevertheless found an article on the relationship between medication adherence for attention deficit-hyperactivity disorder (ADHD) and criminality to be provocative (NEJM 2012; 2006-14).

In this Swedish study with 25,656 patients, there was a significant reduction in the crime rate during periods of receiving the medication compared with nonmedication periods: 32% reduction for men and 41% for women.

Approximately 50% of the patients were between ages 15-24, 30% between 25-39, and the remainder >40 years.  Overall, 37% of the men had been convicted of any crime and 15% of the women.

To avoid possible bias from reverse causation, the investigators looked at whether the order of the change in medication status was important.  The criminality associations were significant regardless of the order, suggesting that this type of bias was unlikely.  The authors state that “it is possible that pharmacologic ADHD treatment helps patients to better organize their lives,” thereby decreasing their likelihood of crime.

There are many other concerns raised regarding ADHD medications, including adverse effects (eg. cardiovascular), overprescription, and side effects.  However, this inverse association with criminality should be added to other potential benefits.

Confronting Neglect

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A brief perspective article makes some useful points about involvement of child protective services (NEJM 2012; 367: 1976-77).

“A recent study of 595 high-risk children whose families were reported for CPS intervention showed no significant improvements in family functioning, social support, maternal education, or child behavior problems among children who received CPS intervention as compared with those who did not.”

The article concludes with an interesting quote:

“Theodore Roosevelt once said, ‘The welfare of each of us is dependent fundamentally upon the welfare of all of us.'”

While this is certainly true, it is difficult to figure out how to accomplish this sentiment.

Related post:

Is obesity neglect? | gutsandgrowth

Less stress after gastrostomy tube placement

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It has been said that it is easier to feed a child with a gastrostomy tube (GT) than by mouth.  Now a study reports improved maternal stress after GT placement (JPGN 2012; 55: 562-66), perhaps because it is easier to provide nutrition.

34 mothers from Norway took part in questionnaires (before, 6 months after, and 18 months after) as part of a study (2003-2005) to see how gastrostomy placement in a child affects maternal stress levels.  Median maternal age was 32 years.  The study was limited by a suboptimal response rate of 59% (34 of 59) and only 19 mothers answered questionnaires at all 3 timepoints.

While all of the children had some peristomal complications, 85% of the mothers reported that their preoperative expectations were met and that their child had improved quality of life.  Mothers had reduced psychological  distress at 6 and 18 months following placement, including less anxiety.

Related blog entries:

Monitoring TNF antagonists in inflammatory bowel disease

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Previously, this blog has discussed the use of drug monitoring in inflammatory bowel disease (Drug levels for inflammatory bowel disease | gutsandgrowth).  A good review of this topic has been published recently (Clin Gastroenterol Hepatol 2012; 10: 1079-87).

Some of the useful pointers:

  • Factors that influence clearance of TNF antagonists are reviewed:
  1. Antidrug antibodies (ADA) increase clearance and worsen outcomes
  2. Use of concomitant immunosuppressives reduces the likelihood of ADA formation and increase drug concentration.   In the SONIC trial, use of azathioprine was associated with trough infliximab (IFX) levels of 3.5 μg/mL compared with 1.6 μg/mL with monotherapy.  Also, ADA was reduce: 0.9% compared with 14.6% in the monotherapy group. [Other studies though have found variable effects of cotherapy.]
  3. Low serum albumin and high CRP are associated with increased drug clearance
  4. Individuals with high body size and males are more likely to have increased drug clearance.
  • Better assays for measurement of IFX and adalimumab (ADL) are now available.
  • Currently a trial evaluating trough levels is underway: Trough Level Adapted Infliximab Treatment (TAXIT).  With this study, the accepted target range for trough levels is 3-7 μg/mL.  Levels >7 μg/mL are considered supratherapeutic and allows for a prolongation of dosing interval.  Preliminary data confirm that trough levels inversely correlate with CRP.
  • Proposed algorithm in individuals with loss of response & positive ADA.  If ADAs present at high titer, then switch to different TNF antagonist.  If low  titer, could either switch or attempt drug escalation.
  • With IFX, when antibodies to infliximab (ATIs) are present, the likelihood of responding to increased dose is less than 20% whereas changing to different TNF antagonist has about an 90% response (in patients who were previous responders).
  • Proposed algorithm in individuals with loss of response & negative ADA.  If subtherapeutic trough levels (IFX ❤ μg/mL, ADL <8 μg/mL, or certolizumab <27.5 μg/mL), then dose escalation is worthwhile.  If drug levels are therapeutic, then dose escalation will not be effective.
  • With IFX, more than 85% of patients will respond to drug escalation when the trough level is subtherapeutic. This is much more favorable than switching agents.
  • One other issue with ADAs is that they may be transient is some patients.  Perhaps one-fourth of ATIs may be transient which may explain why some individuals with ATIs may still respond to dose escalation.

These points give several reasons why drug monitoring is useful in individuals with loss of response and may help determine whether patients responding to therapy may be able to prolong dose intervals.  At the same time, when an individual is not responding to therapy, it is also important to determine if in fact active inflammation is present with objective markers and to consider alternative explanations for GI symptoms (eg. Clostridium difficile infection, irritable bowel, bacterial overgrowth, etc.).

Related blog entries:

Only one chance to make first impression | gutsandgrowth

When nothing else is working | gutsandgrowth

Infliximab for children with Ulcerative Colitis | gutsandgrowth

Adalimumab for children with Crohn’s disease | gutsandgrowth

CHOOSE TNF TRIAL | gutsandgrowth