Unknown's avatar

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.

Is it possible to avoid allergic food reactions?

In subjects with known food reactions, avoiding food ingestions is quite difficult (Pediatrics 2012; 130: e26-e32).

This study enrolled 512 children at ages 3-15 months and followed them for a median of 35.5 months.  Patients had to have positive skin prick test to milk or egg in addition to either a history consistent with an IgE-mediated food reaction to milk or egg or a history of moderate-to-severe atopic dermatitis.

Key findings:

  • High rate of reactions: 1171 reactions reported in 367 (72%) of subjects.
  • Most reactions were attributed to lack of vigilance, like not checking ingredients
  • Parents most frequently were the providers at time of incident (36%); however, about half of all allergic reactions were attributed to other providers (eg. grandparents, teachers)
  • Of severe reactions (n=134, 11%), only 30% were treated with epinephrine. Almost all severe reactions were due to ingestions (95%) rather than skin or inhalation exposures.

Bottom line: More work is needed to prevent these reactions and to improve the treatment when they occur.

Save a life with free allergy education

www.cofargroup.org

A double whammy –obesity and GERD

“A double whammy is when something causes two problems at the same time, or when two setbacks occur at the same time.”  Double whammy – Idiom Definition – UsingEnglish.com

Obesity probably doesn’t fit this definition strictly because it causes a lot more than two setbacks.  However, obesity clearly causes its own set of problems and, even in childhood, contributes to the development of gastroesophageal reflux disease (GERD) (JPGN 2012; 55: 72-75).

This study consisted of 153 healthy children from a well-child clinic; among this group 31 were obese and 122 were nonobese.  All caregivers completed a reflux questionnaire.  The reflux symptomatic score was significantly higher in children with waist circumference (WC) >90th percentile compared with those <75th percentile.  Furthermore, the rise in GERD symptoms (heartburn, epigastric pain, and regurgitation) was shown to rise progressively with increasing BMI and WC.

One of the shortcomings of the study was the use of a questionnaire that has not been validated for assessment of reflux symptoms in children (according to the authors, none are available in children); though, this questionnaire has been used in a few prior publications.

More references on GERD and obesity:

  • -Gastroenterology 2010; 139: 1902, 1823.. Abdominal visceral adipose tissue increases risk for Erosive esophagitis.
  • -Ann Intern Med 2005; 143: 199-211. Pooled studies showed GERD symptoms with ORs of 1.43 c BMI 25-30 & 1.94 for > 30. OR for esophagitis was 1.76 for BMI>25 & increased risk of adenoca of 1.68-2.02
  • -Gastroenterology 2006; 130: 1925-6.  Obese youth have more reflux symptoms as with adults.

Previous post on GERD and asthma:

Treating reflux does not help asthma

Optimizing lipids to minimize cholestasis

As discussed in previous blog entries (PNAC, PNALD, and IFACMore on PNACFour advances for intestinal failure), the right amount of lipid and the type of lipid both can contribute to parenteral nutrition associated cholestasis (PNAC).  More information about SMOFlipid which is a complex mixed-type lipid emulsion derived from soybean, coconut, olive, and fish oils is available (JPGN 2012; 54: 797-802).  SMOF contains 30% soybean oil, 30% MCT, 25% monounsaturated fatty acids, and 15% fish oil.

This study had a retrospective cohort comparison design & examined serum bilirubin over 6 months in children with PN-associated cholestasis (PNAC).  In one cohort, 8 patients received the SMOFlipid and the other 9 patients continued on Intralipid (IL).

The SMOF cohort was receiving 81% of caloric needs as PN at entry whereas the IL cohort was receiving 92%.  Six months later, SMOF cohort was receiving 68% of caloric needs as PN compared with 50% for IL cohort.  Nevertheless, the SMOF group had improved cholestasis with a median bilirubin drop of 99 μmol/L compared with an increase of 79 μmol/L among IL patients.  Overall, 5 of 8 children in the SMOF group had resolution of jaundice compared with 2 of 9 in the IL group.

While the authors state that SMOF may have important properties to prevent PNALD, the study has limited ability to draw any firm conclusions.

The authors state that no other treatment innovations were introduced; however, the authors overlook the large discrepancy in lipid volume administered.  The IL group was receiving much more lipid both before and during study.  Prior to entry of study, the IL group was receiving about 3.1 g/kg/day whereas the SMOF group about 2 g/kg/day; the SMOF group continued initially at the same lipid dosing with the new formulation.  This is one of the problems with historical controls.  While the authors might believe that the cholestasis improved because of the lipid content, the key factor may in fact be the amount of lipid given.

In the same issue (JPGN 2012; 54: 803-11), specific plant sterols (PS) were elevated among neonates with intestinal failure-associated liver disease (IFALD).  This study looked at 28 neonates and 11 children from Finland who required PN for more than 28 days.  Specific markedly-elevated PS included stigmasterol, sitosterol, avenasterol and campesterol (Table 4 in study).  Some of these PS in the neonates were more than 20-fold higher than healthy controls.

What to do with delayed gastric emptying/gastroparesis

More information for pediatric patients with the perplexing problem of poor gastric emptying is available in three articles:

JPGN 2012; 55: 166-72, 185-90, & 194-199.

The first study by Waseem et al describes the “Spectrum of Gastroparesis:”

  • Retrospective chart review included 239 eligible children with mean age of 7.9 years.  Nearly equal numbers of males and females. .
  • Time to empty half of solid or liquid considered abnormal if more than 45-90 minutes for solid and more than 60 minutes for liquid (labelled pediasure)
  • Etiology: idiopathic 70%, drug-induced 18%, postsurgical 12%
  • Treatment in 74% diet and erythromycin (74%)
  • Over 24 months, 60% had significant improvement regardless of treatment

The second study by Rodriguez et al is titled “Clinical Presentation, Response to Therapy, and Outcome of Gastroparesis in Children.”

  • Restrospective study with 230 children, mean age 9 years.  In adolescents, female gender was more common (77%) whereas in infants (n=36), male gender was more common (61%).  Most common causes were postviral in 42%, mitochondrial in 18%, and diabetes in 5%.
  • Delayed gastric emptying was defined as having solids or liquids emptying <40% of the meal at one hour.
  • Resolution occurred in 22% at 6 months, 53% at 18 months, and 61% at 36 months.  Median time to resolution was 14 months; though among resolvers, 84% did so by 12 months.
  • Presence of longer duration of symptoms and mitochondrial disorder was associated with lower rates of resolution.
  • Younger age and response to promotility agents increased likelihood of resolution
  •  Treatment with proton pump inhibitors (PPIs) were used in 79% as first-line agents; only 3% reported resolution of symptoms with PPIs.
  • Prokinetics: Domperidone (0.1-0.2mg/kg/dose qid to max of 10mg) in 33 patients. Tegaserod in 20 patients.  Metoclopropramide in 142 patients. Erythromycin (EES) in 40 patients (3-10 mg/kg/dose qid).  Of these agents, metoclopropramide was inferior with an 80% failure rate.  In contrast, EES was associated with symptom resolution in 5% and symptom improvement in 46%.  Domperidone was associated with symptom resolution in 26% and symptom improvement in 48%.

The third study by Bhardwaj et al highlights “Impaired Gastric Emptying and Small Bowel Transit in Children with Mitochondrial Disorders.”

  • Prospective study enrolled 26 subjects from mitochondrial clinic.  58 patients were screened but the majority were not eligible; the most common reasons included the following: 14 were receiving enteral feedings, 1 was receiving parenteral nutrition, 6 had no GI symptoms.
  • Delayed gastric emptying was considered if >50% at 90 minutes of a solid meal was present, at 60 minutes for semisolid, and at 40 minutes for liquid meal. For small bowel transit, delayed transit was considered if radiotracer had not reached cecum within 4 hours.  Severely prolonged transit was diagnosed if transit time exceeded 6 hours.
  • In this cohort, 18 (69%) had delayed gastric emptying and 12 (46%) had prolonged small bowel transit.  Common symptoms included abdominal pain and vomiting.
  • In the small numbers of patients who received prokinetics,there was a poor response.  One of three patients with bethanecol and two of five patients with metoclopropramide had normalized GE time; one patient treated with azithromycin continued with abnormal GE time

Additional references:

  • -Gastroenterol 2011; 140: 101.  Clinical features -mostly females, often incr BMI.  Defined as severe gastroparesis if >35% at 4hrs, moderate if 20-35%, and mild if <20%.
  • -Clincal Gastro & Hep 2011; 9: 5.  Review of diabetic gastroparesis & mgt.
  • -Clin Gastro & Hep 2009; 7: 823. Radiation from gastric emptying is ~10mrad, CXR is 12mrad, yearly background is 300mrad.
    Norms:
    1 hr 37-90%
    2 hr 30-60%
    4 hr 0-10%
  • -Gastroenterol 2009; 136: 1526.  Tests of gastric emptying -review.
  • -Clin Gastro & Hep 2008; 6: 1309. algorithm for nausea & delayed GE.  REC;
    1. small meals, low fiber/fat
    2. prokinetic: reglan, EES, ?domperidone
    3. Antiemetics: zofran, prochloroperazine
    4. TCA
    5. ?Botox injection
    6. jejunal feeds
  • -Gastroenterol 2009; 136: 1526.  Tests of gastric emptying -review.  Consider domperidone, reglan, ?gastric stimulation, ?surgery, discusses novel Rxs.
  • -Gastroenterol 2009; 136: 1225.  Review of prevalence and outcomes in Olmsted County.
  • -Am J Gastro 2008; 103: 416-23.  Botox is NOT effective for gastroparesis/delayed GE.
  • Need to distinguish delayed gastric emptying from rumination. Treatment for rumination and belching

Keep it cool

Now, what cooler than being cool?
Ice cold!
I can’t hear ya! I say what’s, what’s cooler than being cool?
Ice cold!
Alright alright alright alright alright alright alright alright alright alright alright alright alright alright alright alright!

Lyrics for “Hey Ya!” by Outkast

Keeping it cold is also the advice if you want to keep the bactericidal activity of breastmilk intake (JPGN 2012; 55: 146-49).  This study examined the effects of freezing from 48 healthy donors who provided samples of fresh breastmilk.  Bactericidal activity was determined by thawing breastmilk (in duplicate) and innoculating with bacterial strains and then comparing growth in breastmilk compared with control samples.

Freezing at -20 degrees celsius (C) for 1 month did not effect the bactericidal activity of breastmilk against either E coli or P aeruginosa.  In contrast, when samples were stored for three months, freezing at -80 degrees C was protective of this activity whereas -20 degrees C was not.

So if you are storing breastmilk for longer than 1 month, keep it cold if you can.

Related blog entry:

Long-chain polyunsaturated fatty acids, breastmilk, and infant cognition

More on IBD medicine risks

As noted in a recent post (Assessing and discussing risk of lymphoma in IBD), diagrams can be useful to convey the absolute risks for IBD medicines; this risk is often poorly understood by patients and their families. Two articles add additional insight that may help with counseling. (Thanks to Ben Gold for forwarding these articles.)

  • Am J Gastroenterol 2012; 107: 964-70.
  • Am J Gastroenterol 2012; 107: 1051-63.

The first article reviews the risk of lymphoma with regard to inflammatory bowel disease treatment decisions.  Important points in this article include the following:

1. Relative risks may appear large while absolute risk may be quite low.  The estimate for absolute risk for lymphoma:

  • For azathioprine or 6-mercaptopurine: 1 additional case for every 4357 persons treated
  • For anti-TNF (infliximab, adalimumab, certolizumab): 1 additional case for every 2380 persons treated between ages 20-29.

2. Framing the discussion with regards to risk of continued active disease, continued exposure to steroids, and potential need for surgery can be helpful:

  • “It would take only three patients discontinuing their azathioprine to cause one additional relapse of IBD per year”
  • Seven patients stopping anti-TNF therapy would result in an additional hospitalization each year and 14 patients stopping anti-TNF therapy would result in an additional abdominal surgery each year
  • While the ‘relative risks of lymphoma associated with these medications may sound inappropriately large…A more appropriate comparison is the absolute risk of lymphoma versus the absolute risk of active/untreated disease or corticosteroid therapy.’  An example: if 2000 patients with IBD took one of these medications (eg. anti-TNF agent), probably one patient will develop a lymphoma; however, if none of those patients took an anti-TNF agent, it would result in more than 100 hospitalizations and nearly 60 surgeries.

3. “Patients can also be very sensitive to numerators and pay relatively insufficient attention to denominators.” This has been called “anchoring and adjustment” or “base-rate neglect.”  This issue has to do with “numeracy;” this is defined as the basic math skill needed for health-related activities. To help families, consider the following:

  • avoid labels such as “very low” when describing risk
  • use absolute risk data
  • use similar denominators when comparing risks
  • use visual aids

The second study cited is a pooled analysis of infections, malignancy, and mortality risks associated with infliximab and immunomodulator treatment in adult IBD patients.  This study collected safety data from 10 previous trials.  Five of these trials were randomized, controlled studies.  Table 3 and Table 4 detail extensive safety data for immunomodulators (eg. azathioprine) and for infliximab respectively.

With regard to immunomodulators, the combined studies enrolled 947 on immunomodulators in comparison to 1170 without immunomodulators.  With ulcerative colitis (UC) patients but not with Crohn’s disease (CD), immunomodulator use increased the risk of infections (120/100 patient years versus 92.5 among placebo-treated patients).  CD patients, but not UC patients, had an increased risk of malignancy with immunomodulator use (1.84/100 patient years compared with 0/100 patient years in the control group).  With the exception of the SONIC study, use of immunomodulator was not randomly assigned.  So, some of the increased risk in these patients could be due to having more severe IBD rather than due to the medication.

With regard to infliximab, and in contradiction to the previous article’s estimated risks, infliximab treatment did not appear to affect the incidence of infection, mortality, or malignancy.  This study and several others have not demonstrated an increased risk of malignancy with infliximab. This could be that even with this pooled data it is difficult to detect a rare adverse outcome.  More prospective studies and more long-term followup will be needed to truly determine the risk.

While it is known that these agents may increase the risk of some infections, the limited increase in infections which was detected only with immunomodulator use in UC is likely due to a lowered risk of infection when active inflammatory bowel disease is controlled.  A much bigger risk factor for infection is the use of corticosteroids.  When effective IBD medications are administered, this helps control inflammation and allows tapering of corticosteroids.

Related posts:

TNF-α antagonists and infections

Disease modifying treatment in IBD

Only one chance to make first impression

Choosing topical therapy for EoE

A brief report adds useful information for topical therapy for eosinophilic esophagitis (EoE) (Gastroenterol 2012; 143: 321-24).  This study involved 25 subjects in a prospective randomized open label design that compared budesonide delivered via either as a metered nebulized form (NEB) or as oral viscous solution (1 mg BID).  The mean age of the subjects was 35 years, 60% were male, 88% were caucasian, and all had dysphagia.

Findings:

  • Orally administered viscous budesonide (OVB) was more effective at lowering esophageal eosinophilia.  After treatment, eosinophil count per high power field was 11 for OVB compared with 89 for NEB formulation.
  • Nuclear scintigraphy showed that OVB had a significantly higher level of esophageal exposure to the therapeutic agent than NEB and did not result in lung exposure (which occurred in NEB group)
  • Both groups had improvement in dysphagia.  Poor correlation of symptoms and histology has frequently been reported.

These findings along with the fact that budesonide has less systemic corticosteroid effects, due to a high first-pass metabolism, makes OVB a logical choice for patients treated with topical steroids.

Previous related blog entries:

Guidelines for Eosinophilic Esophagitis

Looking better or feeling better in EoE?

Look of improvement on an EoE diet

Eosinophilic Esophagitis -Six Food Group Diet

MicroRNA signature for eosinophilic esophagitis

The undiscovered country

Cholesterol controversy

Recent guidelines (Pediatrics 2012; 130: 353-56) have recommended universal screening for hypercholesterolemia between ages 9-11 along with additional targeted screening.  These recommendations have been met with a number of criticisms (Pediatrics 2012; 130: 349-52).

In the first referenced commentary, the experts who issued the guidelines commissioned by the National Heart Lung and Blood Institute (NHBLI) claim that the criticism “misrepresent the evidence regarding screening and the specificity and rigor of the guideline development.”  In the second commentary, the guidelines are considered overly aggressive and not adequately founded on evidence-based medicine.  In addition, they cite two JAMA commentaries that also question the wisdom of the guidelines (JAMA 2012; 307: 257-58, & 259-60).

NHBLI recommendations:

▪  Universal screening of all 9-11 year-olds with a nonfasting lipid panel.

▪  Targeted screening of 2-8 year-olds and 12-16 year-olds with 2 fasting lipid profiles.  The targeted group are for those with diabetes, hypertension, BMI >95%, smoke cigarettes, have a parent with cholesterol >240 (or known dyslipidemia), 1st or 2nd degree relative (includes parents, aunts, uncles, and grandparents) with stroke or coronary artery disease <55 years for men or <65 for women.  According to the critical commentary, 30-40% of children will meet family history criteria and many more will meet other criteria.

▪  If LDL ≥130 mg/dL, then a “CHILD-1” diet is recommended.

▪  Individuals with abnormal screening are to have fasting lipid panels every 6-12 months indefinitely even if their values become acceptable.

Criticisms and responses by guideline authors in italics

▪  While the critics concede that cumulative exposure to high LDL and hypertension increase the risk of cardiovascular disease (CVD), they indicate that with the exception of a small number of individuals (rare homozygous familial hypercholesterolemia) that there is not proof that intervention in childhood is necessary.  The chain of evidence cited by the panel has “notably the absence of even observational evidence or modeling to estimate the clinical event benefits of screening for and intervening on these risk factors in children.”  Atherosclerosis is a lifelong process…Heterozygous familial hypercholesterolemia affects 1:500 and 51% of untreated men develop CV disease events by age 50 years… Accidental death studies (ages 15-30 years) have shown that a 30 mg/dL increase in non-HDL was equivalent to 2 years of vascular aging.  Bogalusa Heart Study showed that number of risk factors correlated with increased atherosclerosis at autopsy after accidental death.  Carotid intima media thickness in adulthood correlates with LDL levels obtained between 12-18 years of age.

▪  No quantification of potential harms such as neuroses, family conflict, CVD anxiety or from medication.  Among children with familial cardiovascular disease, interview studies have shown positive future health perceptions and effective coping.  ‘A study of universal CV risk screening in schools, accompanied by environmental change, showed improvements in healthy lifestyle behaviors and CV risk profiles.’  Risk of statin therapy, (only 0.8% of adolescents would be eligible per authors) has shown no adverse effects in children and adolescents.

The majority of the panel members…disclosed an extensive assortment of financial relationships with companies making lipid-lowering drugs and lipid-testing instruments.  Evidence regarding the efficacy and safety of these medications would not be available without academic partnership with industry.  Potential conflicts of interest were declared and vetted.

▪  Cost/cost-effectiveness. The present policy proposes an intervention applied to a healthy and asymptomatic population, with an enormous impact on costs and the potential to transform well children into patients with a chronic disease label. “Any intervention with nonzero benefit may be recommended, regardless of how much it costs and how much better health might be achieved by investing those resources elsewhere.”  There have been several studies exploring the cost-effectiveness of screening and management strategies for familial hypercholesterolemia (FH). In the Netherlands, a genetic screening program showed that new cases of FH gained 3.3 years of life at an average lifetime cost of US$8700 per year gained.  More complex cost-effectiveness modeling of treatment of children and adolescents has not yet been performed.

So who is right in this debate?

Previous related blog entry:

Cardiovascular disease for the entire family

Delays in diagnosing Crohn’s disease

Delayed diagnosis remains a problem in Crohn’s disease (Inflamm Bowel Dis 2012; 18: 496-505).  This study included a total of 1591 IBD patients (932 CD, 625 UC, 34 indeterminate colitis) from the Swiss IBD cohort study (SIBDCS).

  • Diagnostic delay in CD patients was significantly longer compared to UC patients (median 9 versus 4 months, P < 0.001).
  • 75% of CD patients were diagnosed within 24 months compared to 12 months for UC and 6 months for IC patients.
  •  Independent risk factors for long diagnostic delay in CD (>24 months)  included age <40 years at diagnosis (odds ratio [OR] 2.15, P = 0.010) and ileal disease (OR 1.69, P = 0.025)
  • In UC patients, nonsteroidal antiinflammatory drug (NSAID intake (OR 1.75, P = 0.093) and male gender (OR 0.59, P = 0.079) were associated with long diagnostic delay (>12 months)

Diagnostic delay has been a problem for quite a long time; in children, delays can worsen growth failure.  In 1988, Kanof et al reported that decreased height velocity preceded the diagnosis of CD in 88% of their patients (pediatric cohort). In addition, 42% of their population had a reduction in height velocity before intestinal symptoms were noted.

Especially when there is not a lot of colonic disease, a high degree of suspicion needs to be maintained.  This is not difficult for pediatric gastroenterologists.  For pediatricians and family physicians, the increased availability of biomarkers (Biomarkers identify patients who benefit and how) should be helpful in reducing diagnostic delays.

Additional blog entries and references:

  • Kanof ME, Lake AM, Bayless TM. Decreased height velocity in children and adolescents before the diagnosis of Crohn’s disease. Gastroenterology.1988; 95 :1523– 1527.
  • Differentiating ulcerative colitis from Crohn disease in children and young adults: report of a working group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn’s and Colitis Foundation of America.  North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, Colitis Foundation of America, Bousvaros A, Antonioli DA, Colletti RB, Dubinsky MC, Glickman JN, Gold BD, Griffiths AM, Jevon GP, et al.J Pediatr Gastroenterol Nutr. 2007 May; 44(5):653-74.

IL-10 and early onset IBD

Among physicians who take care of patients with inflammatory bowel disease (IBD), there is an understanding that the labels “Crohn’s disease” (CD) and “ulcerative colitis” (UC) are imprecise labels.  There may be many subtypes of IBD that are classified as CD or UC.  This is becoming even more clear with advances in genetics which have shown specific genetic defects that predispose to an IBD phenotype.  In fact, more than 100 genetic loci have been uncovered that contribute to IBD, more than any other complex disease (according to editorial in same issue as reference below, pgs 285-87).

Immunodeficiency disorders, like chronic granulomatous disease, are well-recognized as potential mimics for IBD. More recently, IL-10 and IL-10 recpetor genetic mutations have been associated with early-onset IBD phenotypes (Gastroenterol 2012; 143: 347-55.)

In this study, 66 patients whose IBD started before age 5 were investigated for mutatons in the genes encoding IL-10, IL10R1, and IL-10R2.  IL-10R deficiency was confirmed with functional assays of patients’ mononuclear cells.  “Using a candidate gene sequencing approach, we identified 16 patients with IL-10 or IL-10R deficiency.”  In all 16 patients, the phenotype included refractory colitis with perianal disease; symptoms developed in the first three months of life in these 16 patients.  Five of these patients improved after hematopoietic stem cell transplantation with a median followup of 2 years.

Take-home message:

Test patients with infantile IBD for IL-10 and IL-10 receptor deficiency

Contact for IL-10 testing (free):

Karoline Fiedler, Clinical Research Coordinator, IBD Program, Toronto

karoline.fiedler@sickkids.ca

http://www.neopics.com

Crohn’s disease Differential Diagnosis:

  • Tuberculosis
  • Histoplasma
  • Sarcoidosis
  • Amebiasis
  • CMV
  • C. diff
  • Klebsiella oxytoca
  • Actinomycosis
  • Vasculitis (dermatomyositis, Wegener’s, SLE)
  • FMF
  • Allergic colitis
  • Hirschsprung’s
  • Autoimmune enteropathy
  • HIV
  • Chronic granulomatous disease
  • Glycogen storage dz, 1B
  • Hermansky-Pudlak syndrome
  • Wiskott Aldrich syndrome
  • NEMO (NF-kB essential modifier) deficiency
  • Leukocyte adhesion deficiency
  • SCID
  • Behcet’s
  • FELS/hemophagocytic lymphohistiocytosis
  • Typhlitis
  • HSP
  • Solitary rectal ulcer syndrome
  • Early-onset: IL10/IL10R deficiency, XIAP, ADAM17, NCF2 gene variant

Additional references:

  • -Gastroenterol 2012; 143: 347-55.  IL-10 signaling defects and IBD.
  • -Gut 2012; 61: 1028-35.  NCF2 gene variant and IBD.
  • -NEJM 2011; 365: 1502-408.  ADAM17 deletion and IBD.
  • -NEJM 2009; 361: 2033-45.  IL-10 receptor and IBD.
  • -JPGN 2010; 51: 690.  Discusses sarcoid (check angiotensin converting enzyme, CGD, Hermansky Pudlak)
  • -JPGN 2010; 50: 99.  Perianal dz in young children may be due to autoimmune neutropenia. -IBD 2008; 14: 1443.  phagocyte dysfunction.  Also, discusses Hermansky-Pudlak, GSD 1B, chronic granulomatous disease, Chediak-Higashi, leukocyte adhesion deficiency, cylic neutropenia, congenital neutropenia
  • -Clin Gastro & Hep 2009; 7: 1037.  MRI best study for perianal fistulas.
  • -JPGN 2006; 42: 405.  Vasculitis mimicking IBD.
  • -Pediatr 2008; 121:  447.  Consider chronic granulomatous disease -particularly if recurrent.  15-18% of CGD pts with perianal abscess.  Immunocompromised hosts at increased risk along with Crohn’s patients.  However, “vast majority” do not have underlying disease.  Can treat perianal abscess medicaly in otherwise healthy infants. (Peds 2007; 120: e548).  www.pediatrics.org/cgi/content/full/120/3/e548
  • -NEJM 2005; 352: 489-94.
  • -Gold B et al. NEJM 2003; 349 (26): 2541, Table 2

Previous related posts:

Add it to the list

Upper endoscopy useful for identifying Crohn’s disease

Serology in IBD