Category Archives: Pediatric Gastroenterology Intestinal Disorder

Something You Probably Have Not Seen with Celiac Disease and Headaches

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An “image of the month” in the NEJM shows the association between celiac disease and occipital calcifications in a 24 year-old with a 10 year history of headaches, here’s the link: 

The course and explanation: Treatment with a gluten-free diet, folic acid supplementation, and carbamazepine was initiated, and the patient’s condition improved, with remission of all symptoms. The combination of celiac disease, epilepsy, and cerebral calcification is a rare condition known as the CEC syndrome. Folate malabsorption is a suggested mechanism

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Also, there is a useful patient celiac education page from JAMA Pediatrics & University of Chicago: http://dlvr.it/55h6Rd 

Why is Celiac Disease Becoming More Prevalent?

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A recent editorial helps provide some answers and even explains the term “protopathic bias.”  Ostensibly, the editorial’s task is to explain the potential interaction of maternal serum iron ingestion and the risk of celiac disease (see previous blog post: Is There a Link Between Maternal Iron Supplementation and …).  However, the editorial provides an explanation for the Swedish epidemic and the ongoing slower, wider epidemic.

Here’s the link, http://ow.ly/vQGQ7, and here’s an excerpt:

The Swedish epidemic of CD of 1985–1994 has been extensively documented, and resulted in the development of hypotheses regarding environmental risk factors for this disorder.7 This epidemic was restricted to children younger than 2 years; in that age group, the incidence of diagnosed CD rose from 65 cases per 100,000 person-years to 198 cases per 100,000 person-years. In contrast, incidence data for older children were relatively flat during this period. The epidemic abruptly ended in 1995, although children born during the period of the epidemic have an ongoing increased risk of developing CD. Subsequent investigation led to the hypothesis that infant feeding practices affect the risk of CD in young children. The epidemic occurred during a period of relatively low rates of breastfeeding at the age of 6 months and during the same period of time, the quantity of gluten in infant formula greatly increased. Although it is difficult to separate the relative importance of each feeding practice, it seemed that high quantity of initial gluten intake without overlapping with breastfeeding was responsible for this epidemic. Although a systematic review of the issue has concluded that breastfeeding has not been definitively proved to be associated with risk of CD,8 subsequent research has indicated that the timing of gluten introduction is important in determining risk.9PreventCD, a prospective randomized trial of infants with a family history of CD, is testing specifically whether the introduction of small quantities of gluten beginning at age 4 months of age will induce tolerance to gluten in this high-risk group.

The second epidemic is more diffusely spread over time and space. Studies from the United States and elsewhere have shown that the seroprevalence of CD (as defined by positive tissue transglutaminase and endomysial antibodies) has increased markedly in recent decades. An analysis of stored serum from military recruits at the Warren Air Force Base in the years spanning 1948–1954 found a CD seroprevalence of 0.2%, whereas 2 recent cohorts from Olmsted County (spanning the years 2006–2008) matched by year of birth and age at sampling found a seroprevalence of 0.9% and 0.8%, respectively.11 An analysis of another cohort in this country found a doubling in seroprevalence during adulthood from 1974 (0.21%) to 1989 (0.45%).12 The mode of presentation of CD has changed in the past generation, with rising numbers of patients presenting without diarrhea.13 Patients presenting with anemia may have more severe disease expression (as measured by the degree of villous atrophy and the presence of metabolic bone disease) than patients presenting with diarrhea.14 Because most individuals in the United States with CD are undiagnosed,15 this is largely a hidden epidemic, but there is no reason to believe that the prevalence has peaked. In Finland, which had a higher prevalence of CD than the United States to begin with, the seroprevalence of CD doubled between the years 1978 (1.05%) and 2000 (1.99%).16 It is not known whether this epidemic will subside or if the prevalence of CD will continue to rise to a new set-point. But given the morbidity associated with CD17 and the cost and difficulty of the gluten-free diet18, 19 these data have sparked interest in identifying the cause of this less visible epidemic.

Certain infections (eg, rotavirus among infants20 and Campylobacter among adults21) have recently been shown to be associated with a increased risk of CD, but rates of these infections have not increased markedly, and so are not likely to be driving this epidemic. In contrast, a lack of exposure to certain microbes is a hallmark of modern times, and the increase in CD disease is congruent with the hygiene hypothesis, which states that decreased exposure to microbes may be driving the rise in autoimmune and atopic conditions. This hypothesis is particularly compelling in light of a recent study that found a dramatically different seroprevalence of CD in Finland (1.4%) and the Russian Karelia (0.6%), geographically proximate areas with a similar prevalence of HLA DQ2 and DQ8 but with major differences in economic development.22

Further evidence implicating the modern relationship with microbes is now accumulating. Children who were born by elective cesarean section are at increased risk of developing CD, whereas those born by emergent cesarean section (and may have had contact with the birth canal) are not.23 In addition, there seems to be an inverse relationship between Helicobacter pylori colonization and CD.24 Drugs are another modern innovation that may be affecting the CD epidemic. Population-based studies from Sweden have shown that prescription of antibiotics25 and proton pump inhibitors26 are each associated with an increased risk of the subsequent development of CD.

The associations identified in these studies are not necessarily causal. Studies of drug exposure in particular may be prone to protopathic bias, wherein early symptoms of the outcome of interest (CD) may lead to the prescription of the exposure (eg, antibiotics or proton pump inhibitors).

From the NY Times: Gluten-free, veggie snacks, vegan desserts, spring salads. They’re all in our new recipe finder.

Parenteral Omega-3 Lipid Emulsions and Risk of Bleeding

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A recent study indicates that patient’s placed on omega-3 lipid emulsions (eg. Omegaven) may be at risk for bleeding due to platelet dysfunction (J Pediatr 2014; 164: 652-4).

While omega-3 lipid emulsions have received a lot of attention due to improvements in intestinal failure associated liver disease (IFALD) (see previous links to prior posts below), the amount of data supporting their usage and potential advantages compared with standard lipids at similar dosing remains limited.

This case report describes a 9-month old who developed life-threatening hemorrhage following a standard central line placement.  Due to difficulty stopping the bleeding, the patient’s omegaven was discontinued.  Standard workup for bleeding disorders were negative.  Subsequently, the authors investigated clot formation and platelet function in a neonatal animal model.

Key Result: Piglets treated with omegaven had a doubling of time to clot formation and marked platelet agonist inhibition.

The discussion notes that “there is an acknowledged risk of high dose O3FA lipids [omegaven] increasing bleeding time because of competitive inhibition of AA [arachidonic acid] production, hence decreased TxA2 [thromboxane A2].  In addition, platelet-derived growth factor-like protein and endothelial platelet activation factor are decreased.”

Take home points (from the authors):

  • “the case report and piglet studies together demonstrate that there is potential for a significant antiplatelet effect and inhibition of the coagulation cascade with O3FA therapy…”
  • “We would suggest discontinuation of Omegaven therapy 72 hours preoperatively in high-risk cases where bleeding may be difficult to directly control.”
  • “Institutionally, we have abandoned the sole use of Omegaven therapy.”

Related blog posts:

Pulmonary Complications Associated with Chronic Liver Disease

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A useful review of “pulmonary complications in chronic liver disease” (Hepatology 2014; 59: 1627-37) has been published.

The main topics included hepatopulmonary syndrome (HPS) , portopulmonary hypertension (POPH), and hepatic hydrothorax (HH).

A few of the key points:

HPS is most common of these conditions and is identified in 5-30% of cirrhosis patients.  It is identified with abnormal oxygenation (screening with pulse ox <96%) due to intrapulmonary vascular dilatations. There is no established medical therapy.  It is reversible with liver transplantation.

The hallmark of POPH is the development of pulmonary arterial hypertension associated with portal hypertension.  It occurs in 5-10% of cirrhosis patients and often presents as dyspnea on exertion/fatigue.  There are numerous pharmacologic treatments that may be useful, include the following:

  • prostacyclin analogs like epoprostenol
  • endothelin receptor antagonists like boesentan
  • phosphodiesterase-5 inhibitors like sildenafil, vardenafil, and tadalafil

Severe POPH is a relative contraindication for liver transplantation.

HH is a transudative pleural effusion seen in 5-10% of cirrhosis patients. Initial management includes salt restriction and diuretics.  Transjugular intrahepatic portosystemic shunt and thoracentesis are second-line options.  Liver transplantation is curative.

Related blog entries:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

 

 

The Search for a Dietary Culprit in IBD

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Uniformly, patients diagnosed with inflammatory bowel disease (IBD), both ulcerative colitis and Crohn disease, are interested in whether there is a dietary culprit which triggered their IBD and what modifications in their diet can help improve their IBD.  A really good summary of what we know has been published (Inflamm Bowel Dis 2014; 20: 732-41).

A summary of the key points:

Traditional dietary recommendations:  These diets may help decrease symptoms but are not thought to improve disease control.

  • Low-residue: <10-15 g/d of fiver. Potential deficiencies: folate, vitamin A, vitamin C, and potassium.  Overall, this diet is poorly studied.  “One small randomized controlled trial showed that low-residue diet made no difference in symptoms, need for hospitalization, need for surgery…when compared with an unrestricted diet.”
  • Lactose-free: potential deficiencies: calcium, vitamin D

Carbohydrate-restrictive:  Potential deficiencies with all carbohydrate restriction: folate, thiamine, vitamin B6

  • Specific carbodydrate diet: allows only monosaccharides.  Restricts complex sugars, starches, grains and legumes.  This diet was popularized by Elaine Gottschall in 1994 (Breaking the Vicious Cycle) but was developed by Dr. Sidney Haas in 1924.  The premise of SCD is that “complex carbohydrates and legumes are poorly absorbed in gastrointestinal disease…they promote bacterial overgrowth and fermentation.  By-products from bacterial dysbiossis are postulated to contribute to gut inflammation.”  Nevertheless, it “has been poorly studied.”
  • Low FODMAPs (see numerous previous posts).  “A small restrospective study…showed that the low FODMAPs diet resulted in improvement in functional symptoms present in patients with IBD who were in remission.”  This diet is difficult for long-term adherence.
  • Gluten-free: not truly a carbohydrate-restrictive diet, but breads/cereals contain large amounts of carbs. “No evidence that a gluten-free diet has any effect on disease activity in IBD.”

Fat-modified diets

  • Fat-restrictive diets: “On a cellular level, multiple animal studies have shown that prolonged feeding of a high-fat diet seems to promote colitis/ileitis and to perturb barrier function…shifts in microbiome composition…Despite some biologic plausibility, there is a paucity of data evaluating efficacy of fat-restrictive diet for IBD management.”
  • Vegetarian/semi-vegetarian: Potential deficiencies: iron, vitamin B12 (vegans), calcium, vitamin D, ω-3 fatty acids.   A small study of 22 patients with Crohn’s disease who adhered to a semi-vegetarian diet, had lower rate of relapse.  “There does not seem to be sufficient evidence at this time to recommend eliminating meat to patients with IBD as a means to control their disease.”
  • Modified ratio of ω-3/ω-6 polyunsaturated fat: “The efficacy of dietary interventions with ω-3 PUFA has been disappointing..recently, 2 large multicenter clinical trials demonstrated that ω-3 PUFA (fish oil) at a dose of 4 g/day was not significantly better than placebo at maintaining remission in CD.”

Restriction of Multiple food groups

  • Paleolithic: based on the “premise that human genetics have scarcely changed over the past 3000 years, and thus modern humans are genetically adapted to the diet of their Paleolithic ancestors (i.e. Stone Age)…daily calories should come from plant sources (50-65%) and from animal sources (35-45%) with fish preferred over meat.  Most of the restricted foods are carbohydrates..refined salt, and refined oils as well as any “processed foods.”  However, there are “no data that this diet has any effect in IBD.”  Previous reports of improvement in IBD are mainly testimonials (anecdotal evidence).
  • Exclusive enteral nutrition (EEN)/Elemental/Semielemental: In pediatric CD, “EEN has been shown to be as effective as corticosteroids in inducing remission (70-90%)..EEN does not seem to be effective in UC.”  High rate of relapse when diet is stopped.  Formula type does not seem to be very important.

Take-home message: “Clinical trials in all dietary strategies (with possible exception of EEN in pediatric patients) are lacking and further study is needed.” “From the current evidence available, a low FODMAPS or gluten-free diet may be the most helpful in controlling diarrheal and bloating symptoms…However, …symptom improvement does not equate to remission or objective evidence of disease regression.”

Related Blog Posts:

ImproveCareNow has published information on IBD and Nutrition as well.  Here’s an excerpt from their Circle eNewsletter:(initially published April 2013, Stacie Townsend, MS, RD, LDN, CSP)

Diet is an important part of your IBD treatment plan and should be used in conjunction with medications. Proper nutrition plays a critical role in managing IBD. Eating healthfully and in appropriate amounts will improve IBD symptoms, contribute to age-appropriate growth, and decrease risk of anemia, poor bone density, and vitamin/mineral deficiencies. It can also increase effectiveness of IBD medications.

No one diet has been proven to prevent IBD or to prevent flare ups, although several diet books and plans have claimed to “cure IBD”. Unfortunately, there is little scientific evidence to prove that these diet plans, such as the Specific Carbohydrate Diet (still being studied) and the Guts and Glory Program, are effective, and most of these plans avoid entire food groups, which can then lead to vitamin and mineral deficiencies and poor weight gain.

Nutritionists frequently get asked what foods are safe for people with IBD, and creating a diet plan for you is often trial and error… The best diet plan is one that includes all food groups (proteins, grains, fruits, vegetables, dairy, and oils) and in appropriate portions for your age, weight, and physical activity level… If gas, bloating, and diarrhea are among your symptoms, lactose free dairy products may be better tolerated.

So what IS the most appropriate diet for IBD? The United States Department of Agriculture’s food guidance system, MyPlate, is the appropriate diet plan for you… and the SuperTracker within the MyPlate website can help you track what you eat each day, and how your diet measures up to the recommended diet plan for you.

General nutrition guidelines for individuals with IBD include:

  • choose foods from all food groups
  • limit fried/fatty foods, caffeine and spicy foods, especially if these foods worsen symptoms of IBD
  • drink fluids at each meal to maintain hydration
  • consume a multivitamin daily to aid nutrient absorption
  • consume small frequent meals (eat every 2-3 hours while awake) if volume of foods at a meal is an issue

…If you want additional help with your diet, make an appointment to see our nutritionist.

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.

 

Shwachman-Diamond Syndrome

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A recent study provides an update on the variable clinical presentation of Shwachman-Diamond syndrome (SDS) (J Pediatr 2014; 163: 866-70).

SDS, an autosomal recessive disorder, is characterized by exocrine pancreatic dysfunction, bone marrow dysfunction, and predisposition to myelodysplasia/leukemia.  It is due to a mutation in the SBDS gene located on chromosome 7q11 (found in ~90% of classically presenting cases of SDS.

Using a North American Registry, the authors reviewed the records of 37 patients (all who have had mutations in SBDS gene). Key findings:

  • Neutropenia was evident at presentation in 30/37 (81%)
  • Only 51% had both neutropenia and steatorrhea at presentation
  • 24/37 (65%) had congenital anomalies: 3 with ventricular septal defects, 1 malrotation, 1 imperforate anus, 9 thoracic dystrophy (rib abnormalities), 2 with short arms/legs, 4 with metaphyseal dysplasia, 1 with Chiari malformation (type 1), 2 with testicular atrophy.
  • Medical comorbidities included elevated LFTs in 15, adrenal insufficiency in 1, hypopituitarism in 1, type 1 diabetes in 1, hypothyroid in 1, and eczema in 11.

Take-home message: Normal pancreatic imaging studies and normal fecal elastase do not rule out SDS. In addition, frequently there are associated anomalies and comorbidities.

Will Lubiprostone Help Children with Functional Constipation?

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A recent open-label study of lubiprostone examined its use in children younger than 18 years (2007-2008) at 22 U.S. centers (JPGN 2014; 58: 283-91).

Lubiprostone (Amitiza) activates chloride-channel protein-2 in the gastrointestinal epithelium and promotes secretion of chloride ions and fluid.  This results in more frequent bowel movements (BMs) and improved motility.  To determine its safety and effectiveness in the pediatric population, the investigators enrolled 127 patients (124 were treated and analyzed and 109 completed the 4-week study).  After a 2-week observation period, several doses of lubiprostone were compared: 12 μg QD, 12 μg BID, 24 μg BID.  There was no placebo group.  The mean age of the participants was 10.2 years.

Results:

  • Mean spontaneous BM frequency increased from baseline: 3.1/week versus 1.5/week.  Overall, at each week in treatment ≥ 43% achieved ≥ 3 spontaneous BMs/week.
  • 62% experienced a spontaneous BM within 48 hours of starting treatment.
  • Common adverse reactions: Nausea (18.5%), vomiting (12.1%), diarrhea (8.1%), abdominal pain (7.3%) and headache (5.6%). Overall, 65% of patients experienced ≥ 1 adverse effect and this was highest (78%) in the subset of patients receiving the highest dosage

Bottomline: Current guidelines recommend osmotic agents like polyethylene glycol (PEG) (Miralax) as first-line treatment.  This short-term study shows lubiprostone may be an alternative in nonresponders, though more data on long-term outcomes are needed.

Related blog posts:

Is There a Link Between Maternal Iron Supplementation and Celiac Disease?

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According to a recent study, maternal iron supplementation may increase the risk of celiac disease in children (Clin Gastroenterol Hepatol 2014; 12: 624-31).

Using the Norwegian Mother and Child cohort study (1999-2008) which included data for 78,846 children, the authors analyzed the risk of developing celiac disease by examining prospectively collected questionnaires regarding iron supplements, diet, and anemia.  Questionnaires were obtained 3 times during pregnancy, then at age 18 months, 6 years, 7 years and 8 years.

Key Results:

  • 4.65 of 1000 children whose mothers took iron supplements while pregnant developed celiac disease compared to 3.15 of 1000 whose mothers did not.
  • After adjustment for multiple variables, the OR was 1.33 for children developing celiac disease if their mother took iron supplementation during pregnancy.
  • The authors note that maternal anemia was not associated with celiac disease in offspring nor was iron supplementation in childhood.

While these findings are intriguing, the associated editorial (pg 632-35) notes that unmeasured confounding variables could explain the findings.  For example, undiagnosed maternal celiac disease which could increase the likelihood of iron exposure could increase the risk of celiac disease in the offspring and account for the increased association with iron supplementation.

Take-home message (from the editorial): “it is premature to argue that iron supplementation during pregnancy should be avoided in individuals with celiac disease…the observed effect (an absolute risk increase of 0.15%) is modest in magnitude. This exposure is not driving the slow, ongoing epidemic of celiac disease.”

Related blog links:

Head-to-Head: Capsule Endoscopy versus Colonoscopy

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A recent study shows how useful capsule endoscopy (CE) can be in diagnosing Crohn disease (Clin Gastroenterol Hepatol 2014; 12: 609-15).  Congratulations to one of my partners, Dr. Stan Cohen, who is one of the authors.

This prospective study examined 80 patients with signs and/or symptoms of small-bowel Crohn disease (age, 10-65 years) who underwent CE, small-bowel follow-through (SBFT), and colonoscopy.

Presenting suggestive features included the following:

  • Diarrhea >6 weeks but less than 3 years
  • Abdominal pain >6 weeks but less than 3 years
  • Extraintestinal IBD manifestations: pyoderma gangrenosum, erythema nodosum, perianal disease, arthritis, aphthous stomatitis, and uveitis
  • Along with abnormal laboratory/clinical finding:
  1. positive inflammatory marker: sedimentation rate, C-reactive protein, calprotectin/lactoferrin
  2. unexplained iron deficiency
  3. hypoalbuminemia
  4. positive IBD serology (eg. anti-Saccharomyces cerevisiae antibodies)
  5. or other clinical findings: recurrent fevers, GI bleeding, growth failure, abnormal radiologic study

Results:

  • CE/colonoscopy in combination detected 107 of 110 inflammatory lesions (97.3%)
  • SBFT/colonoscopy detected 63 lesions (57.3%)
  • “The diagnostic yield of CE compared with colonoscopy was not different.”
  • Of the 80 patients with suspected Crohn disease, 25 (31.3%) had the diagnosis confirmed. 9 patients had diagnostic findings on at least 2 of the 3 modalities.  11 were diagnosed with CE alone and 5 by colonoscopy alone.

The authors conclude that colonoscopy remains the initial diagnostic test of choice.  However, “CE is safe and can establish the diagnosis of Crohn’s disease in patients when ileocolonoscopy results are negative or the terminal ileum cannot be evaluated.”

Take-home message: in patients with symptoms suggestive of Crohn disease, a negative colonoscopy is not sufficient to exclude the disease.  Other modalities like CE or MRE may be needed.

Related post:

Pediatric Capsule Endoscopy Experience

Macrolide Antibiotics and Pyloric Stenosis

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It is well-recognized that infants who receive macrolide antibiotics are at increased risk of pyloric stenosis. A recent study (BMJ 2014;348:g1908) indicates that maternal macrolide intake can also increase the risk of pyloric stenosis in their infants.

Link to article from NASPGHAN twitter feed: http://t.co/CnkbdZoRVf

Conclusions Treatment of young infants with macrolide antibiotics was strongly associated with IHPS and should therefore only be administered if potential treatment benefits outweigh the risk. Maternal use of macrolides during the first two weeks after birth was also associated with an increased risk of IHPS. A possible association was also found with use during late pregnancy.