ORIGINAL ARTICLE: GASTROENTEROLOGY
Is It Necessary to Assess for Fat-Soluble Vitamin Deficiencies in Pediatric Patients With Newly Diagnosed Celiac Disease?
Mohamad H. Imam, yYousef Ghazzawi, Joseph A. Murray, and Imad Absah
ABSTRACT Background: The purpose of this study was to identify the frequency of fatsoluble vitamin deficiencies in children with celiac disease (CD) and to determine the value of routine testing for these deficiencies. Methods: We conducted a retrospective medical record review of patients with a confirmed diagnosis of CD and fat-soluble vitamin levels measured at diagnosis between 1995 and 2012 at Mayo Clinic. Patients’ demographics, fat-soluble vitamin levels, and pertinent clinical factors at the time of diagnosis were collected. Results: Eighty-three patients were included in the final analysis: 51 girls and 32 boys, with an average age at diagnosis of 12.8 years in girls and 13.0 years in boys. The most commonly reported symptoms were abdominal pain in 49 patients and diarrhea in 30 patients. Family history of CD was reported in 32 patients. Average vitamin levels for vitamin E, 25-hydroxyvitamin D (25 (OH) D), and vitamin A were 7.5 mg/L, 32.8 ng/mL, and 334.5 mg/dL, respectively. No patients had vitamin A deficiency, 2 patients had vitamin E deficiency, and 9 patients had mild-to-moderate vitamin D deficiency (none had severe deficiency). Both patients with vitamin E deficiency were symptomatic and had complete villous atrophy. Thirty-one patients had insufficiency of 25 (OH) D, which was less than the reported frequency of vitamin D insufficiency in the general pediatric population in the United States in 2004. None of the patients were receiving vitamin supplements at the time of diagnosis. Conclusions: Fat-soluble vitamin deficiencies are uncommon in children with new diagnosis of CD. Routine measuring of fat-soluble vitamins levels may not be necessary. Key Words: celiac disease, deficiency, fat-soluble, vitamin
(JPGN 2014;59: 225–228)
C
eliac disease (CD) is a chronic immune-based disease affecting primarily the absorption surface of the proximal small intestine. It is known now that CD is the most common genetically predetermined condition in humans, with a childhood prevalence of 1% in the United States and many European countries (1). Many reports have suggested major changes in the presenting symptoms of CD in both adults and children, with severe malabsorptive gastrointestinal (GI) tract symptoms becoming less common (2–4). Received September 4, 2013; accepted March 3, 2014. From the Division of Gastroenterology and Hepatology, and the yDivision of Pediatric Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN. Address correspondence and reprint requests to Imad Absah, MD, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (e-mail: [email protected]). The authors report no conflicts of interest. Copyright # 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0000000000000368
JPGN
Volume 59, Number 2, August 2014
Historically, CD has been associated with many micronutrient deficiencies, particularly the fat-soluble vitamins (A, D, E, and K); however, in the past, CD was believed to be a rare childhood disease, which was usually diagnosed late following a period of prolonged diarrhea. With recent diagnostic advances and the ability to target asymptomatic children in high-risk groups (on the basis of family history and the presence of type 1 diabetes mellitus, immunoglobuline (Ig)A deficiency, and Down syndrome), children are being diagnosed early in the course of the disease. Hence, many present with mild non-GI symptoms or even no symptoms at all. The rate of diagnosis of pediatric CD has also risen dramatically in the last decade (5). This may be attributable to the increased application of sensitive serologic tests that can enable earlier diagnosis, or a true increase in CD incidence may have occurred. It is important to note that some manifestations of CD can occur in the absence of any substantial overt GI symptoms. For example, bone loss (manifest most commonly as osteoporosis or classically as osteomalacia) is a common feature in adult CD and can happen in patients who have no GI tract symptoms (6). These patients may have secondary hyperparathyroidism, which is caused by vitamin D deficiency (7). There are many reports about fat-soluble vitamins and trace element deficiencies in adult patients with CD. For all of the adult patients with a new CD diagnosis, the expert opinion recommends checking for vitamin D, vitamin A, zinc, copper, folic acid (serum), and ferritin (8–11). In pediatric patients with a new CD diagnosis, there are no clear guidelines about whether fat-soluble vitamin levels should be routinely checked, although some expert opinion suggests checking the vitamin D level. Moreover, data are limited concerning the prevalence of vitamin deficiencies in children with CD and whether routine assessment is required at diagnosis. Some data have suggested a correlation between low vitamin D level and low bone density, without a clear recommendation to check the vitamin level or bone density (12,13). Can routine testing for vitamin deficiency at initial CD diagnosis prevent long-term complications that may result from an undiagnosed vitamin deficiency, or is it needlessly subjecting patients to multiple blood tests and increased financial burden without clear benefit? We aim to identify the frequency of fatsoluble vitamin deficiency in children diagnosed as having CD to determine whether there is any clinical value in routine testing for these deficiencies.
METHODS Patients Pediatric patients with CD who had fat-soluble vitamin levels measured at diagnosis between 1995 and 2012 at Mayo Clinic were identified using the Mayo Clinic life science system (Rochester,
225
Copyright 2014 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
Imam et al MN) that allows for systematic searching of the entire electronic medical record system at Mayo Clinic. Inclusion criteria included children (0–18 years of age) at the time of diagnosis; presence of clinical or histologic evidence of CD; and determination of vitamin A, E, and D levels at the time of diagnosis. Patients without measured vitamin levels or a confirmed diagnosis of CD and adult patients were excluded from the final analysis. The study protocol was approved by the Mayo Clinic institutional review board.
CD Diagnosis of CD was established at Mayo Clinic using the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis and treatment of CD in children (14). All of the patients had positive celiac serologic testing (endomysial IgA antibodies or anti–tissue transglutaminase [anti-TTG] antibodies). All included patients except for 1 had a confirmatory duodenal biopsy at the time of diagnosis.
Clinical Factors Pertinent clinical factors were collected: family history of CD, autoimmune disorders (diabetes, rheumatoid arthritis, psoriasis, thyroid disease, and systemic lupus erythematosus), and clinical symptoms (abdominal pain, diarrhea, constipation, failure to thrive [FTT], and poor weight gain). Body mass index (BMI) was also collected to help assess the nutritional status of patients and its correlation with vitamin deficiency.
Laboratory Results Celiac serologic testing included serum IgA and anti-TTG IgA or IgG. Other collected variables included vitamin A (free retinol), D (25-hydroxy vitamin D), and E (a- tocopherol) levels, hemoglobin, hematocrit, and ferritin at the time of diagnosis of CD. Vitamin A was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with specific quantitation of retinol. Normal range for vitamin A was 0 to 6 years, 11.3 to 64.7 mg/dL; 7 to 12 years, 12.8 to 81.2 mg/dL; and 13 to 17 years, 14.4 to 97.7 mg/dL. Vitamin D was obtained using LC-MS/MS. Reference range for vitamin D was defined as
Is It Necessary to Assess for Fat-Soluble Vitamin Deficiencies in Pediatric Patients With Newly Diagnosed Celiac Disease?
Mohamad H. Imam, yYousef Ghazzawi, Joseph A. Murray, and Imad Absah
ABSTRACT Background: The purpose of this study was to identify the frequency of fatsoluble vitamin deficiencies in children with celiac disease (CD) and to determine the value of routine testing for these deficiencies. Methods: We conducted a retrospective medical record review of patients with a confirmed diagnosis of CD and fat-soluble vitamin levels measured at diagnosis between 1995 and 2012 at Mayo Clinic. Patients’ demographics, fat-soluble vitamin levels, and pertinent clinical factors at the time of diagnosis were collected. Results: Eighty-three patients were included in the final analysis: 51 girls and 32 boys, with an average age at diagnosis of 12.8 years in girls and 13.0 years in boys. The most commonly reported symptoms were abdominal pain in 49 patients and diarrhea in 30 patients. Family history of CD was reported in 32 patients. Average vitamin levels for vitamin E, 25-hydroxyvitamin D (25 (OH) D), and vitamin A were 7.5 mg/L, 32.8 ng/mL, and 334.5 mg/dL, respectively. No patients had vitamin A deficiency, 2 patients had vitamin E deficiency, and 9 patients had mild-to-moderate vitamin D deficiency (none had severe deficiency). Both patients with vitamin E deficiency were symptomatic and had complete villous atrophy. Thirty-one patients had insufficiency of 25 (OH) D, which was less than the reported frequency of vitamin D insufficiency in the general pediatric population in the United States in 2004. None of the patients were receiving vitamin supplements at the time of diagnosis. Conclusions: Fat-soluble vitamin deficiencies are uncommon in children with new diagnosis of CD. Routine measuring of fat-soluble vitamins levels may not be necessary. Key Words: celiac disease, deficiency, fat-soluble, vitamin
(JPGN 2014;59: 225–228)
C
eliac disease (CD) is a chronic immune-based disease affecting primarily the absorption surface of the proximal small intestine. It is known now that CD is the most common genetically predetermined condition in humans, with a childhood prevalence of 1% in the United States and many European countries (1). Many reports have suggested major changes in the presenting symptoms of CD in both adults and children, with severe malabsorptive gastrointestinal (GI) tract symptoms becoming less common (2–4). Received September 4, 2013; accepted March 3, 2014. From the Division of Gastroenterology and Hepatology, and the yDivision of Pediatric Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN. Address correspondence and reprint requests to Imad Absah, MD, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (e-mail: [email protected]). The authors report no conflicts of interest. Copyright # 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0000000000000368
JPGN
Volume 59, Number 2, August 2014
Historically, CD has been associated with many micronutrient deficiencies, particularly the fat-soluble vitamins (A, D, E, and K); however, in the past, CD was believed to be a rare childhood disease, which was usually diagnosed late following a period of prolonged diarrhea. With recent diagnostic advances and the ability to target asymptomatic children in high-risk groups (on the basis of family history and the presence of type 1 diabetes mellitus, immunoglobuline (Ig)A deficiency, and Down syndrome), children are being diagnosed early in the course of the disease. Hence, many present with mild non-GI symptoms or even no symptoms at all. The rate of diagnosis of pediatric CD has also risen dramatically in the last decade (5). This may be attributable to the increased application of sensitive serologic tests that can enable earlier diagnosis, or a true increase in CD incidence may have occurred. It is important to note that some manifestations of CD can occur in the absence of any substantial overt GI symptoms. For example, bone loss (manifest most commonly as osteoporosis or classically as osteomalacia) is a common feature in adult CD and can happen in patients who have no GI tract symptoms (6). These patients may have secondary hyperparathyroidism, which is caused by vitamin D deficiency (7). There are many reports about fat-soluble vitamins and trace element deficiencies in adult patients with CD. For all of the adult patients with a new CD diagnosis, the expert opinion recommends checking for vitamin D, vitamin A, zinc, copper, folic acid (serum), and ferritin (8–11). In pediatric patients with a new CD diagnosis, there are no clear guidelines about whether fat-soluble vitamin levels should be routinely checked, although some expert opinion suggests checking the vitamin D level. Moreover, data are limited concerning the prevalence of vitamin deficiencies in children with CD and whether routine assessment is required at diagnosis. Some data have suggested a correlation between low vitamin D level and low bone density, without a clear recommendation to check the vitamin level or bone density (12,13). Can routine testing for vitamin deficiency at initial CD diagnosis prevent long-term complications that may result from an undiagnosed vitamin deficiency, or is it needlessly subjecting patients to multiple blood tests and increased financial burden without clear benefit? We aim to identify the frequency of fatsoluble vitamin deficiency in children diagnosed as having CD to determine whether there is any clinical value in routine testing for these deficiencies.
METHODS Patients Pediatric patients with CD who had fat-soluble vitamin levels measured at diagnosis between 1995 and 2012 at Mayo Clinic were identified using the Mayo Clinic life science system (Rochester,
225
Copyright 2014 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
Imam et al MN) that allows for systematic searching of the entire electronic medical record system at Mayo Clinic. Inclusion criteria included children (0–18 years of age) at the time of diagnosis; presence of clinical or histologic evidence of CD; and determination of vitamin A, E, and D levels at the time of diagnosis. Patients without measured vitamin levels or a confirmed diagnosis of CD and adult patients were excluded from the final analysis. The study protocol was approved by the Mayo Clinic institutional review board.
CD Diagnosis of CD was established at Mayo Clinic using the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis and treatment of CD in children (14). All of the patients had positive celiac serologic testing (endomysial IgA antibodies or anti–tissue transglutaminase [anti-TTG] antibodies). All included patients except for 1 had a confirmatory duodenal biopsy at the time of diagnosis.
Clinical Factors Pertinent clinical factors were collected: family history of CD, autoimmune disorders (diabetes, rheumatoid arthritis, psoriasis, thyroid disease, and systemic lupus erythematosus), and clinical symptoms (abdominal pain, diarrhea, constipation, failure to thrive [FTT], and poor weight gain). Body mass index (BMI) was also collected to help assess the nutritional status of patients and its correlation with vitamin deficiency.
Laboratory Results Celiac serologic testing included serum IgA and anti-TTG IgA or IgG. Other collected variables included vitamin A (free retinol), D (25-hydroxy vitamin D), and E (a- tocopherol) levels, hemoglobin, hematocrit, and ferritin at the time of diagnosis of CD. Vitamin A was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with specific quantitation of retinol. Normal range for vitamin A was 0 to 6 years, 11.3 to 64.7 mg/dL; 7 to 12 years, 12.8 to 81.2 mg/dL; and 13 to 17 years, 14.4 to 97.7 mg/dL. Vitamin D was obtained using LC-MS/MS. Reference range for vitamin D was defined as
