Tag Archives: celiac disease

Shout out for Gluten-Free Camp

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One enjoyable aspect about my work with my colleagues has been their willingness to use their free time to participate and develop programs for children.  For many years, this has included several camps at Camp Twin Lakes, particularly Camp Oasis for children with inflammatory bowel disease. Most of the physicians in our group have given their time to support this camp.  In recent years, Larry Saripkin has spent a week there every summer  and Stan Cohen really established this camp in Atlanta.  In addition, our nurses have volunteered their time as well; they stay busy attending to the medical needs of these kids so they can enjoy a camp experience.

More recently, a camp for kids with celiac disease has been started, Camp WeeKanEatIt.   Under Jeff Lewis’ direction and fundraising, this camp has been started and allows kids  (8-17 yrs) who need to be maintained on a gluten-free diet to experience camp.  Siblings are allowed to attend as well.  Don’t forget this year’s camp dates: June 23-28!

Related links:

Duodenal IELs and the likelihood of celiac disease

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The diagnosis of celiac disease has definitely become more complex due to the interplay of serology, genetic markers, clinical response to gluten-free diets, and histology.  The Mayo clinic pediatric experience with duodenal intraepithelial lymphocytosis (IELs) with normal villous architecture highlights this issue (JPGN 2013; 56: 51-55).

Between 2000-2009, 56 children from the Mayo clinic pathology database of duodenal biopsies (n=1290) were identified.  Among this group, 48 had serological testing for celiac disease (CD).  Ultimately, 9 were labeled with CD, though only 5 met the ‘definite’ criteria.  Other conditions that were associated with increased IELs included the following:

  • Medication exposure
  • Inflammatory bowel disease
  • H pylori infection
  • Autoimmune conditions
  • IgA deficiency

So, which patients with duodenal IELs had CD?

  • “Definite” CD was used to define patients with elevations in two different serologic markers (TTG and EMA) or those with elevation in one serologic marker along with a documented clinical response to a gluten-free diet (GFD).
  • “Possible” CD described patients with normal serology, but serologic titer and clinical response was noted on a GFD.
  • “Unlikely” CD categorized patients with two negative serology markers who had compatible human leukocyte antigen haplotype and had clinical response to GFD.

In addition, if the IELs were predominantly on the villi tips, this increased the likelihood of CD.

Related blog posts:

False-positive serology for Celiac disease

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It is prudent to exercise caution in establishing a diagnosis of Celiac disease (CD) in young asymptomatic children who are identified with screening serology (J Pediatr 2012; 161: 980-14).

In this Italian study, a nationwide, multicenter, prospective intervention trial was established to assess the role of age at gluten introduction on development of CD.  Subjects were recruited at birth who were at increased risk for CD; they had at least one first-degree relative with CD.

In their cohort, 96 children were identified.  In addition to having an affected first-degree relative, all children had positive serology (21 with positive tissue transglutaminase IgA antibody [tTG] and 1 with IgA deficiency/positive gliadin IgG antibody) and results of a small intestinal antibody.

While 72 had definitive CD, 24 were considered potential CD (serology positive/Marsh 0-1 histology) and asymptomatic.  The fascinating part of this study was the followup of the potential CD cases –21/24 continued on a regular diet.  Only 1 developed overt CD. 18 (86%) developed normal serology and 2/21 had fluctuating antibody levels after two years.

Based on their findings as well as consensus guidelines, the authors propose that asymptomatic young patients with abnormal serology should be followed for at least 3-6 months as long as tTG < 11 times ULN.

Other findings:

  1. Breastfeeding may have a protective role; individuals with overt CD had a shorter mean duration of breastfeeding than the potential CD group (4.2 months compared with 5.1 months).
  2. Gluten introduction at age 6 months did not increase risk of overt CD (compared to potential CD) relative to introduction at 12 months.

Related blog entries:

Closer followup for Celiac disease & pediatric guidelines

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Data from the Mayo clinic indicate that Celiac patients are not followed up adequately (Clin Gastroenterol Hepatol 2012; 10: 893-99).

Data was extracted on 122 patients from Olmsted County.  Due to the Rochester Epidemiology Project, a comprehensive medical record is available for the entire county population (since 1966).

Results:

  • At 1 year following diagnosis, 41% of patients had followup visits; 89% within 5 years.
  • At followup visits, gluten-fee diet compliance was assessed in 33.6% and 79.8% respectively at 1 and 5 years.
  • The minority met with a dietician: 3.3% and 15.8% respectively at 1 and 5 years.
  • Serological followup was performed in 22.1% and 65.6% respectively at 1 and 5 years.

The related editorial (pages 900-901) makes the point that quality follow-up and outcomes would be aided by clear guidelines.  General guidelines in our practice are noted below.

When I review lists of patients with specific diagnoses, I am often surprised by the lack of follow-up for a number of conditions, not just celiac disease.  Developing a system to remind patients about follow-up for a wide range of conditions would be a worthwhile goal for pediatric practices.

Additional references/blog entries:

General Guidelines in our practice (developed by Dr. Jeff Lewis in 2009)
1. Who to test
There is a wide spectrum of clinical presentation from the classical malabsorption to a number of non-GI presentations.  Some studies suggest that the frequency of celiac in a peds GI clinic is as high as 1:40 (general population is 1:130).  Presentations that are common other than diarrhea, distention or FTT include constipation, anemia, abdominal pain, intussception, vomiting, short stature abnormal LFT’s, pancreatitis, and asymptomatic detection upon screening.  30% of newly diagnosed patients are overweight.  There is about a 5% risk in 1st and 2nd degree relatives, patients with type I DM, Down syndrome, and thyroiditis.  In 300 pediatric patients over 9 years, 10% presented with diarrhea, 20% abdominal pain, 23% as a result of screening, 5% with constipation, and 26% with growth issues.  Rates in family members include 1st degree relative 5 – 10%, MZ twins – 75% concordance rate, DZ twins – 10% concordance rate and HLA identical sibs – 30% concordance rate.

Recommend: Think about celiac disease with a variety of GI symptoms including those present in overweight patients.  Screen asymptomatic patients with Down’s, William’s syndrome, Type I DM, Thyroiditis, and in patients who are family members of celiac patients.

2. How to Test

Serology: Under age 3 years (some say 2 years) there is consensus that to consider including antigliadin IgA and AGA IgG along with anti-TTG and quantitative IgA.  Over age 3, anti-TTG and quantitative IgA should suffice but many are recommending also ordering EMA.  There is good evidence that anti-TTG assays vary from lab to lab.  There is also good evidence that anti-TTG in an individual may fluctuate over time.  Patients in the Teddy study (The Environmental Determinants of Diabetes in the Young (TEDDY …) have had abnormal anti-TTG followed by normal levels on the next blood draw.  17/82 had a positive anti-TTG convert to a negative on a regular diet and remain negative at all follow-ups.  For purposes of the Teddy study, two consecutive abnormal anti-TTG over 0.5 should be the threshold for EGD.  EGD after one abnormal TTG in the asymptomatic screened individual, may be too soon and lead to a false sense of security.  In a patient on a GF diet, testing serology may still be useful if the GF diet is less than 6 months.  HLA typing may help rule out celiac in patients on GF diet.

Gluten exposure prior to biopsy: There is no consensus on how long a patient needs to be back on gluten before testing but most experts suggest at least a month and some 2 or more months.

Biopsy is still considered essential in confirming the diagnosis.  Some studies suggest that some patients (2 to 3% of kids and perhaps adults) may show abnormalities in the bulb but not in the 2nd or 3rd portion of the duodenum.

Recommend:  anti-TTG and IgA will catch most patients with celiac.  Under age 3, consider obtaining AGA IgG and AGA IgA.  Addition of EMA may increase sensitivity of the anti-TTG.  Biopsy is still considered by celiac experts to be essential for the diagnosis.  At least 6 duodenal biopsies are recommended.  Some recommend 4 additional biopsies from the duodenal bulb. HLA testing has a role (mostly in excluding the possibility of celiac) though there are rare patients (about 1 in 100 celiac patients though some report much less) that are DQ2 and DQ8 negative.  Not all labs test for the beta chain and this can lead to a false negative HLA DQ2.

3. When might scoping not be necessary?

There is no expert consensus on this. If serology and symptoms are highly suggestive of celiac in a patient with a first degree relative with celiac disease, it is reasonable to make a diagnosis without endoscopic exam.  To confirm diagnosis, it is helpful to see the antibody levels fall on a GF diet (usually retest after 6 months).  Some studies have shown lower compliance rates in patients without biopsy proven celiac.

Recommend:  It is a personal MD:patient:parent decision as to diagnosing celiac without a scope.  If you do diagnose without biopsy, make sure that serology improves on a GF diet.  Celiac centers standard of care still includes biopsy all newly diagnosed patients.
4.Treatment once the diagnosis is made

NIH consensus conference on celiac recommends:1) treatment include referral to a trained dietician (Atlantametroceliacs.com lists nutritionists for adults)  2) availability of a community support group – georgiarock.org or email to celiacgroup@ccdhc.org 3) follow-up with an MD experienced with celiac. 3) lifelong adherence to gluten-free diet 4) identification and treatment of nutritional deficiencies 4) follow-up with an MD familiar with celiac ideally as part of a multidisciplinary team (primarily in partnership with nutritionist).

Recommend:  All newly diagnosed patients or those struggling with compliance should see a specially trained dietician.  You can also refer to the ROCK group – georgiarock.org or celiacgroup@ccdhc.org  You should see the patient in follow-up after diagnosis.
5. Follow-up

Follow up frequency varies widely from every 3 months after initial diagnosis with a nutritionist and an MD to lesser intervals.  Once well controlled, many experts recommend annual visits, some every 2 years.  At diagnosis it is often recommended to look for deficiencies in iron, folate, vitamin D and B12.  Patients are also at risk for other fat soluble vitamin deficiencies and zinc deficiency.  Bone mineral density is often performed one year after diagnosis with abnormalities referred to endocrinology – recommendations in pediatrics are still in debate.  As patients with celiac are at substantial risk for other autoimmune disorders, it is worth considering thryoid problems (eg. check TSH and free T4) early on after diagnosis and once every 1 to 2 years though this practice is of debatable cost effectiveness.  It can take up to a year for the anti-TTG to normalize but it should be coming down significantly in 6 months.

Recommend:  At time of diagnosis, usually a CBC should be obtained to allow you to look for clues about iron, folate, and B12.  It is not unreasonable to check 25 OH Vitamin D levels as well.  At least yearly follow-up labs should include an anti-TTG but may also include TSH, free T4, Vitamin D and a CBC.  Screening for folate, B12, and iron deficiency may also be considered.  Follow up closely after diagnosis can be helpful in dealing with the stress of a major life change and to ensure compliance and understanding of the disease.

6. Testing family members

It is clear that 1st and 2nd degree family members – with and without symptoms are at high risk.  Offering to screen siblings and parents once a diagnosis is made is reasonable due to risks associated with celiac disease.  If an at risk patient screens negative with serology, it does not mean that they can not get celiac disease in the future.  Some experts recommend retesting every few years or sooner if there are symptoms.  It is important to document that you recommended screening to 1st degree relatives.

Recommend:  Strongly recommend that symptomatic first degree relatives be screened for celiac disease.  It is reasonable and helpful to offer to do the screening of parents and siblings yourself.  There is good data that it is important to screen asymptomatic people at risk as there are increased risks in adults of developing cancers, auto-immune conditions, anemia, and osteoporosis in untreated celiac disease.  There are no good recommendations for retesting at risk individuals who initially test negative. HLA typing, if negative, can be useful in eliminating the need for routine rescreening.

7. Feeding infant siblings

A multicenter trial is underway to try to determine the best time to introduce gluten to genetically at risk individuals.  There is good evidence that breast-feeding can be protective.  There is good evidence that introducing small amounts of gluten while still breast-feeding may be protective.  There is good evidence that introduction of gluten before four months of age may increase the risk of developing celiac.  Some evidence exists that the best practice is to give a teaspoon of a gluten containing cereal a few time a week between 4 and 6 months of age (Scandinavian data and prospective data out of the Denver diabetes trial).  Fassano suggests that there may be benefit in keeping the infant gluten-free for the 1st year of life and introduce while still brest feeding after a year of age.  Final answer is still pending.  Gluten can be found intact in human breast milk but not cow’s milk.  No recommendations regarding mother’s diet while breastfeeding a patient with or at risk of getting celiac are available.

Recommend: Do not introduce gluten to at risk infants before 4 moths of age.  Support breast-feeding as something that may delay or even prevent the development of celiac disease.  There is some data to suggest that tolerance may be more likely of small amounts (1 tsp a day) of gluten containing food are introduced between 4 and 6 months of age.  During breast-feeding, a mother who does not have celiac may eat gluten during the pregnancy and throughout infancy.

Reasons for refeeding syndrome

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Refeeding syndrome (RFS) is defined as the potentially fatal shifts in fluid and electrolytes that may occur in malnourished patients who are abruptly refed either enterally or parenterally.  The biochemical hallmark is hypophosphatemia.  Other changes can include hypokalemia, hypomagnesemia, and thiamin deficiency.  RFS can worsen the prognosis of children with celiac crisis as well (JPGN 2012; 54: 522-5).

A chart review from Lucknow, India from Jan-Dec 2010, identified 5 cases of RFS among 35 celiac patients.  All were severely malnourished.  All had anemia, hypoalbuminemia, hypophosphatemia, hypokalemia, and hypomagnesemia.  All improved with initial caloric restriction followed by gradual escalation of caloric intake along with electrolyte supplementation.

This article shows that a variety of causes of malnutrition can lead to refeeding syndrome. Considering refeeding syndrome in any severely malnourished child may help improve the prognosis by altering the nutritional management.

Additional references:

  • Nutr Clin Pract 2012; 27: 34-40. Reviewed refeeding syndrome publications since 2000.  Hypophosphatemia occurred in 96% of cases (26 of 27).
  • Crit Care Med 2010; 14: R172-R178.  Refeeding syndrome with anorexia.
  • Nutrition 2010; 26: 156-67. Review of refeeding syndrome treatment.
  • Nutr Clin Pract 2008; 23: 166-71.  Death due to refeeding syndrome.
  • JPEN 1990: 14.1; 90-97. Refeeding syndrome review.
  • Crit Care Med 1990; 18: 1030-1033. Review.

Food choices, FODMAPs, and gluten haters

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Given the frequency of functional gastrointestinal diseases (FGID), including irritable bowel syndrome (IBS), dietary treatments that may improve symptoms receive a lot of attention.  A recent review of the role of food choices in the development and management of FGIDs is a useful reference (Am J Gastroenterol 2012; 107: 657-66 -thanks to Ben Gold for forwarding this article).

This review details specific dietary advice as well as the following specific physiologic effects of FODMAPs:

  • Osmotic effects
  • Bacterial fermentation
  • Motility effects
  • Prebiotic effects
  • Systemic effects –mild depression, tiredness
In addition, the review looks at other potential foods which could serve as a trigger for IBS symptoms, like gluten & summarizes why some IBS patients are gluten haters.  The authors acknowledge that gluten sensitivity, in the absence of celiac disease, does not have a known mechanism.  Until a reliable marker becomes available, the importance of gluten sensitivity for FGIDs is unknown.
Related posts:

What to make of FODMAPs

Gluten sensitivity without celiac disease

Is a biopsy necessary in Celiac disease?

Is a biopsy necessary in Celiac disease?

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Yes, at least for now.  That is the conclusion of a recent editorial (JPGN 2012; 54: 310-11) regarding Kurpa et al (JPGN 2012; 54: 387-91).  The article by Kurpa et al discusses the utility of the ESPGHAN criteria for diagnosis of celiac disease.  Among the patients with strongly positive TTG (> 100 units), 94% had a diagnosis of Celiac disease confirmed with biopsy; in addition, this result correlated well with positive endomysial antibody and with positive DQ2/8. In those with TTG (30-99 units), Celiac disease was diagnosed in 69% of children and 86% of adults.

Additional references:

  • -JPGN 2011;52: 554. May not need to biopsy if TTG >100 & responds to GFD
  • -Clin Gastro & Hep 2011; 9: 320. Nat’l hx in children with +serology. n=106. 33% developed villous atrophy c/in 2 yrs.
  • -Gastroenterology 2010; 139: 763. Mortality NOT worsened in undiagnosed celiac dz in Olmstead County, though bone density decreased. n=129 of 16,847. (?milder cases undiagnosed)
  • -J Pediatr 2010; 157: 373, 353. Even pts w/o villous atrophy & +serology, benefited from GFD with regard to GI symptoms and serological markers.
  • -JPGN 2010; 50: 397. n=250. +association
  • -Mohamed BM, et al. The Absence of a Mucosal Lesion on Standard Histological Examination Does Not Exclude Diagnosis of Celiac Disease.  Dig Dis Sci. 2007 May 9;
  • -JPGN 2009; 49: 52. deamidated gliadin -new, accurate biomarker for celiac. n=302.
  • -Gastroenterology 2009; 137: 88. Increased mortality in undiagnosed celiac –4-fold increase. Also, increasing prevalence ~4 fold in last 50 yrs.
  • -Gastroenterology 1967; 52: 893-897. Seminal article ‘gluten as culprit in celiac’
  • -Gastroenterology 2009; 136: 816. Mild enteropathy w Celiac –still needs GFD
  • -JPGN 2008; 47: 618. duodenal bulb always abnl, n=665
  • -Clin Gastro & Hep 2008; 6: 753. Incidence of autoimmune diseases less in those compliant with diet. n=178.
  • -Clinical Gastro & Hep 2008; 6: 426. Usefulness of deamidated gliadin antibodies (about as useful as TTG). In this study with n=216 celiac pts and 124 controls, TTG had sensitivity of 78% and 98% specificity.
  • -JPGN 2007; 45: 497. ~1% of UK kids c celiac; 90% missed. Avon study (ALSPAC). n=5470 screened from cohort of 13,971
  • -NEJM 2007; 357: 1731. Nice review which suggests the introduction of gluten 4-7 months in healthy infants. HLA DQ2 present in 90-95%; HLA DQ8 in remainder. Both also present in gen population, 30-40%. Scalloping of mucosal folds often seen. Can stain bx for CD3, CD8 receptors. More refractory cases stain only for CD3 (neg for CD8).

Common to be “D-ficient”

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Many of the children that a pediatric gastroenterologist sees are at risk for Vitamin D deficiency, including children with inflammatory bowel disease, cystic fibrosis, celiac disease, and liver diseases.  In addition, vitamin D deficiency is widespread: in U.S. 50% of children aged 1-5 years and 70% 6-11 years are vitamin D deficient or insufficient. A thorough review on this “D-lightful” vitamin was in a recent JPEN (JPEN J Parenter Enteral Nutr 2012; 9S-19S).

History: In 1822 Sniadecki recognized children in urban but not rural Poland developed rickets. He postulated the effects of the sun as the reason for rickets; his idea was dismissed.  In 1920s, the concept of irradiating milk to prevent rickets emerged. In 1950s, outbreak of hypercalcemia in infants in Great Britain was thought to be related to vitamin D fortification and curtailed this practice in Europe.  However, these cases were likely due to Williams syndrome.

Sources of vitamin D: oily fish (salmon), cod liver oil, some mushrooms, egg yolk, & sunlight. Exposure of an adult in a bathing suit to one minimal erythemal dose (MED) is equivalent to ingesting 20,000 IUs of Vitamin D. (The minimal dose that induces any visible reddening at that point is defined as one MED.)

Effect of sunscreen: A sun protection factor (SPF) of 30 absorbs approximately 98% of solar ultaviolet radiation & thus lowers vitamin D production by 98%.

Ethnicity: Melanin is an effective SPF.  A person of african-american descent, on average, has an SPF of 15, which reduces vitamin D production by 90%.

Age: Aging decreases 7-dehydrocholesterol in human skin.  Due to this, the elderly produce much less vitamin D.  For example, a 70 year old has a 75% reduction compared to a 20 year old.

Forms of vitamin D:  25-hydroxyvitamin D (25OH-D) is the major circulating form of vitamin D & physicians measure 25OH-D. 25OH-D is metabolized in kidney to 1,25-dihydroxyvitamin D (1,25OH-D), also called calcitriol.  This is the most biologically-active and is responsible for increasing intestinal calcium absorption and mobilizing calcium from bone.  However, 1,25OH-D provides no information vitamin D deficiency; it can be elevated or normal in deficiency states.

  • Cholecalciferol (vitamin D-3) is formed in the skin from 5-dihydrotachysterol.
  • Ergocalciferol (Vitamin D-2) is the form in Drisdol (8000 IU/mL) & Ergocalciferol Capsules (1.25 mg =50,000 USP Units)

Vitamin D deficiency:  The exact numbers are debated.  The institute of medicine (IOM) has considered individuals deficient if 25OH-D is <20 ng/mL.  The Endocrine Society and the author suggest vitamin D deficiency as <20 ng/mL & insufficiency as <30 ng/mL.  The author recommends ideal levels between 40-60 ng/mL.

Consequences of deficiency:

Osteoporosis, Osteopenia, Rickets (see references below): Bone weakening occurs due to loss of phosphorus from the kidneys.  Vitamin D deficiency lowers accrual of calcium in skeleton and leads to osteoporosis, osteopenia, and rickets. Imaging for rickets: the best single radiographic view for infants and children younger than 3 years is an anterior view of the knee that reveals the metaphyseal end and epiphysis of the femur and tibia. This site is best because growth is most rapid in this location, thus the changes are accentuated.

Nonskeletal consequences: vitamin D deficiency is associated with increased risk for preeclampsia, URIs, asthma, diabetes (type 1), multiple sclerosis, hypertension, and schizophrenia.

Treatment:

  • Infants who are breastfed should be receiving supplemental vitamin D, 400 IU/day.
  • Adults/children (>1 year) RDA 600 IU/day –mostly from diet per IOM. Yet author states, “it is unrealistic to believe that diet alone can ….provide this requirement.”
  • In vitamin D deficient patients: (initial treatment) 2000 IU/day or 50,000 IU/week for 6 weeks.
Toxicity from vitamin D (from NEJM 2010; 364: 248-254.): “Toxicity from vitamin D supplementation is rare and consists principally of acute hypercalcemia, which usually results from doses that exceed 10,000 IU per day; associated serum levels of 25-hydroxyvitamin D are well above 150 ng per milliliter (375 nmol per liter). The tolerable upper level of daily vitamin D intake recently set by the Institute of Medicine (IOM) is 4000 IU.”

Additional references:

  • -Pediatrics 2008; 122: 398. Should give 400 IU/day to breastfed babies. Consequences of Vit D deficiency: increased risk for DM, multiple sclerosis, cancer (breast, prostate,colon), rickets, and schizophrenia. Article lists vit D content of foods (high in cod liver oil, shrimp, fortified milk, many fish). Severe deficiency when < 5ng/mL, deficient if < 15 ng/mL; probably should be >32 ng/mL. Causes of vit D deficiency: decreased synthesis (due to lack of sun -skin pigmentation, sunscreen/clothing, geography, clouds), decreased intake, decreased maternal stores & breastfeeding, malabsorption (eg celiac, CF, EHBA, cholestasis), increased degradation; treatment of rickets: double-dose of vitamin d (~1000 IU/day for babies & 5000 for older kids) x 3-4 months along with calcium (30-75/mg/kg/day). Follow Ca/phos/alk phos monthly. Alternatively, give ~100,000 units over 1-5 days.
  • -JPEN J Parenter Enteral Nutr. 2011;35:308-316-Results: The study included 504 IBD patients (403 Crohn’s disease [CD] and 101 ulcerative colitis [UC]) who had a mean disease duration of 15.5 years in CD patients and 10.9 years in UC patients; 49.8% were vitamin D deficient, with 10.9% having severe deficiency. Vitamin D deficiency was associated with lower HRQOL (regression coefficient –2.21, 95% confidence interval [CI], –4.10 to –0.33) in CD but not UC (regression coefficient 0.41, 95% CI, –2.91 to 3.73). Vitamin D deficiency was also associated with increased disease activity in CD (regression coefficient 1.07, 95% CI, 0.43 to 1.71). Conclusions: Vitamin D deficiency is common in IBD and is independently associated with lower HRQOL and greater disease activity in CD. There is a need for prospective studies to assess this correlation and examine the impact of vitamin D supplementation on disease course.
  • -JPGN 2011;53: 361. similar prevalence of low Vitamin D as general population –58% with less than 32.
  • -JPGN 2011; 53: 11. Guidelines for bone disease with inflammatory bowel disease.
  • -Pediatrics 2010; 125: 633. Increasing Vit D deficiency noted in minority children. n=290. 22% w levels <20, 74% <30.
  • -Hepatology 2011; 53: 1118. Good vitamin D levels are another favorable predictive factor in antiviral response to Hep C along with IL28B.
  • -NEJM 2010; 364: 248-254. Vitamin D insufficiency. Levels between 20-30 may be OK -not enough evidence to determine conclusively whether this level is detrimental
  • -J Pediatr 2010; 156: 948. High rate among african americans with asthma, 86%. n=63.
  • -Pediatrics 2009; 124:e362. n=6275. 9% of pediatric patients vit D deficient & 61% were insufficient.
  • -Pediatrics 2009; 124:e371. n=3577. low 25OH-D levels inversely assoc with SBP/metabolic syndrome.
  • -NEJM 2009; 360: 398. case report of rickets
  • -J Pediatr 2003; 143: 422 & 434
  • -Pediatrics 2003; 111: 908. 200 IU Vit D recommended for all breastfed infants.
  • -J Pediatr 2000;137: 153 & 143.. Nutritional rickets–primarily in blacks; rec vitamin D 400 IU per day.

Why are we seeing so many more cases

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In this month’s Gastroenterology, two articles offer some insight into this question for two separate problems.

With regard to inflammatory bowel disease, (IBD) –both Crohn’s disease and UC –there is an increasing prevalence and incidence worldwide (Gastroenterology 2012; 142: 46-54). This article identified 8444 previous citations and then identified 262 studies with relevant data.  Overall, the highest incidence and prevalence of these disorders occurs in Europe and North America.  In North America, Canada has the highest prevalence with 0.6% of the population having IBD.

After going through the statistics, the authors offer some discussion on why IBD is increasing.  In the developing parts of the world, some of the increase is due to the ability to detect and differentiate these disorders due to improving access to medical care/colonoscopy.  In the areas of the world with the highest incidence/prevalence, environmental risk factors are playing an important role.  Potential factors include microbial exposures, sanitation, lifestyle behaviors, medications, and pollution.  These factors are supported by other epidemiological studies which show that individuals who move from low prevalence areas to higher ones are at increased risk for IBD, especially among first generation children (Gut 2008; 57: 1185-91).  Furthermore, in low prevalence regions, IBD is increasing with more industrialization (Chin J Dig Dis 2005; 6: 175-81, Indian J Gastroenterol 2005; 24: 23-24.)  Exact mechanisms are poorly understood; however, even in the U.S. it is recognized that rural/farm exposure at a young age reduces the likelihood of developing IBD at a later age (Pediatrics 2007; 120: 354).

Celiac disease, likewise, has seen an increase in prevalence.  With celiac disease, the proliferation of widely available and more accurate serology has been crucial in the identification of more patients.  However, like IBD, there is likely a role for changing microbial environment contributing to an increasing case burden.  Recently, reports have shown that the risk of celiac disease can be influenced at birth (Gastroenterology 2012; 142: 39-45).  Although the absolute risk was modest, there was an increased risk demonstrated with elective but not emergent cesarean delivery among a large nationwide case-control study from Sweden.  Among the cohort of 11,749 offspring with biopsy-proven celiac (with matched control group of 53,887), elective cesarean delivery resulted in an odds ratio of 1.15 (confidence intervals 1.04-1.26).  This study confirmed other studies which have shown an increased risk with cesarean delivery (Pediatrics 2010; 125: e1433-e1440).  Some of the strengths of this Swedish study, included the fact that the deliveries were separated based on elective or emergency cesarean delivery and were controlled for whether the mother had celiac disease.  (Pregnant women with celiac disease have an increased risk of cesarean delivery.)  The authors speculate that the reason why elective cesarean deliveries increase the risk of celiac disease is that microbial exposures at birth likely influences perinatal colonization –>affects intestinal immune response and mucosal barrier function. Offspring of women with emergency cesarean delivery would be more likely to be exposed to bacteria from the birth canal and no significant increase risk of celiac disease could be identified in this group.

Thus how we are born and where we live make a big impact on the likelihood of developing these GI disorders.

Additional References:

  • -Gut 2011; 60: 49-54. n=577,627 Danish children. Use of antibiotics associated with increase risk of Crohn’s disease (but not UC), especially at younger ages (3-11month of age, & 2-3yrs of age). Each course increased risk by 18%. In children with >7 courses, relative risk was 7.3. especially penicillins.
  • -NEJM 2011; 364: 701, 769. Living on a farm decreases risk of childhood asthma.
  • -Nature 2011; 476: 393. ‘Stop killing beneficial bacteria.’  For example, killing H pylori likely increases risk of esophageal adenocarcinoma
  • -Gastroenterology 2011; 141: 28, 208. GM-CSF receptor (CD116) defective expression & function in 85% of IBD pts. n=52.
  • -Gastroenterology 2010; 139: 1816, 1844. Microbiome & affect on IBD vs mucosal homeostasis
  • -J Pediatr 2010; 157: 240. Microbiota in pediatric IBD -increased E coli and decreased F praunsitzil in IBD pts.
  • -J Pediatr 2009; 155: 781. early child care exposures lessens risk for asthma.
  • -IBD 2008; 14: 575.  Role of E coli in Crohn’s
  • -Lab Invest 2007; 87: 1042-1054. Role of E coli in Crohn’s
  • -Pediatrics 2007; 120: 354. Crohn’s less common after repeated exposure to farm animals in 1st year of life.

More practical information and links to other websites can be found at http://www.gicareforkids.com.