Letter to the Editor United European Gastroenterology Journal 2017, Vol. 5(1) 140–141 ! Author(s) 2017 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/2050640616659999 journals.sagepub.com/home/ueg
Potential celiac disease in Indian patients: Response Raghuram Kondala1, Amarender Singh Puri1, Ameet Kumar Banka1, Sanjeev Sachdeva1 and Puja Sakhuja2
We thank Repo et al. for their kind appreciation of our study on short-term prognosis of potential celiac disease (PCD) in Indian patients.1 We agree with their observation that the number of patients with PCD is constantly increasing due to active case-finding and screening. This would likely lead to interesting research in near future in this hitherto scarcely explored aspect of celiac disease (CD). Repo et al. have raised a genuinely pertinent issue of the need to identify a subgroup of patients with PCD who would merit prescription of a gluten-free diet (GFD). Since symptoms in patients with PCD may be due to co-existent common clinical conditions like irritable bowel syndrome (IBS) or other functional gastrointestinal disorders, the crucial decision of advising GFD to a patient with PCD must be based on a comprehensive review of clinical, laboratory and histopathology data. We thus suggest a careful and calibrated approach to each patient with PCD based on available parameters. Till more stronger scientific evidence emerges regarding optimal management of PCD, GFD may be considered in those patients who have either (a) iron deficiency anaemia (IDA) with any one or more features including failure to thrive (FTT), short stature (SS), metabolic bone disease (MBD), wasting, chronic small-bowel type of diarrhoea, or (b) Marsh-II histology with any one or more features including IDA, FTT, SS, MBD, wasting, chronic small-bowel type of diarrhoea with evidence of macro- or micronutrient deficiencies. None of our patients with IDA or Marsh-II histology fulfilled any of these criteria. Hence, regular, meticulous follow-up was an appropriate clinical decision rather than starting GFD, which is perceived as an unwelcome dietary restriction by most if not all patients. Worsening of clinical symptoms during follow-up may be another situation for which empirical GFD may be considered in patients with PCD, but none of our patients faced this scenario either. Histological progression to Marsh-III occurred in only 7% of our patients over one-year follow-up, which vindicates our management strategy. Tosco et al. proposed that the only marker which could help
in the early identification of patients at higher risk to develop intestinal damage seems to be the presence of anti-transglutaminase 2 (TG2) immunoglobulin (Ig)A intestinal deposits at the time of the initial biopsy.2 We could not perform tissue testing for TG2 antibodies as these are not available in India. Regarding the second comment by Repo et al. that more than half of our patients had either clinical symptoms or IDA in spite of absence of villous atrophy, we would like to respond that anaemia is a fairly common problem in rural as well as urban India. Prevalence rates of anaemia among children, young women of childbearing age, and pregnant women in India have been reported as high as 66%–75.3%,3,4 60.8%– 82%5,6 and 80%–93%,7,8 respectively. The commonest form of anaemia in all these population groups is IDA, which is mostly nutritional due to suboptimal oral iron intake or covert blood loss due to the high prevalence rate of intestinal parasitic infestations. Hookworm (Ankylostoma duodenale) infestation is one of the major causes of IDA, especially among school children.9,10 The major source of dietary iron is meat in the West; India on the other hand is a predominantly vegetarian country where nearly two-thirds of the nonMuslim population lack this important source of iron due to the prevalent social norms. Therefore unlike in the West the presence of IDA in Indian patients is mostly due to other reasons as specified earlier. The study by Javid et al. underscores this point as they showed that CD accounted for only 8% of adult patients with unexplained IDA.11 Thus in the Indian context it may be pertinent to evaluate for other causes of IDA before attributing it to CD in patients
1
Department of Gastroenterology, GB Pant Hospital, JL Nehru Marg, New Delhi, India 2 Department of Pathology, GB Pant Hospital, JL Nehru Marg, New Delhi, India Corresponding author: Amarender Singh Puri, Department of Gastroenterology, Room No. 201, Academic Block, GB Pant Hospital, New Delhi 110002, India. Email: [email protected]
Kondala et al. who have only minimal changes on duodenal biopsy specimens. We agree with the final comment by Repo et al. that more well-designed prospective studies are needed to conclude on the role of GFD in patients with PCD. Despite a recent vital study from Finland,12 current scientific evidence is not strong enough to advocate GFD ‘universally’ to all patients with PCD at the ‘outset.’ Newer diagnostic modalities like metabonomics13 or other future biomarkers may help to identify that crucial subset of patients with PCD who may benefit from the prescription of GFD. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Declaration of conflicting interests None declared.
References 1. Kondala R, Puri AS, Banka AK, et al. Short-term prognosis of potential celiac disease in Indian patients. United European Gastroenterol J 2016; 4: 275–280. 2. Tosco A, Salvati VM, Auricchio R, et al. Natural history of potential celiac disease in children. Clin Gastroenterol Hepatol 2011; 9: 320–325. 3. Hanumante NM, Kanvinde S, Sanwalka NJ, et al. Iron deficiency anemia in an urban slum. Indian J Pediatr 2008; 75: 355–357.
141 4. Pasricha SR, Black J, Muthayya S, et al. Determinants of anemia among young children in rural India. Pediatrics 2010; 126: e140–e149. 5. Panigrahi A and Sahoo PB. Nutritional anemia and its epidemiological correlates among women of reproductive age in an urban slum of Bhubaneswar, Orissa. Indian J Public Health 2011; 55: 317–320. 6. Rao S, Joshi S, Bhide P, et al. Dietary diversification for prevention of anaemia among women of childbearing age from rural India. Public Health Nutr 2014; 17: 939–947. 7. Agarwal AK, Sen AK, Kalra NK, et al. Prevalence of anaemia during pregnancy in district Burdwan, West Bengal. Indian J Public Health 1999; 43: 26–31. 8. Kapil U, Saxena N and Ramachandran S. Iron deficiency anemia in pregnancy. Indian Pediatr 1996; 33: 606. 9. Chakma T, Rao PV and Tiwary RS. Prevalence of anemia and worm infestation in tribal areas of Madhya Pradesh. J Indian Med Assoc 2000; 98: 567, 570–571. 10. Sampathkumar V and Rajaratnam A. Prevalence of anaemia and hookworm infestation among adolescent girls in one rural block of Tamil Nadu. Indian J Matern Child Health 1997; 8: 73–75. 11. Javid G, Lone SN, Shoukat A, et al. Prevalence of celiac disease in adult patients with iron-deficiency anemia of obscure origin in Kashmir (India). Indian J Gastroenterol 2015; 34: 314–319. 12. Repo M, Lindfors K, Ma¨ki M, et al. Anemia and iron deficiency in children with potential celiac disease. J Pediatr Gastroenterol Nutr. Epub ahead of print 11 April 2016. DOI: 10.1097/MPG.0000000000001234. 13. Bernini P, Bertini I, Calabro` A, et al. Are patients with potential celiac disease really potential? The answer of metabonomics. J Proteome Res 2011; 10: 714–721.
Potential celiac disease in Indian patients: Response Raghuram Kondala1, Amarender Singh Puri1, Ameet Kumar Banka1, Sanjeev Sachdeva1 and Puja Sakhuja2
We thank Repo et al. for their kind appreciation of our study on short-term prognosis of potential celiac disease (PCD) in Indian patients.1 We agree with their observation that the number of patients with PCD is constantly increasing due to active case-finding and screening. This would likely lead to interesting research in near future in this hitherto scarcely explored aspect of celiac disease (CD). Repo et al. have raised a genuinely pertinent issue of the need to identify a subgroup of patients with PCD who would merit prescription of a gluten-free diet (GFD). Since symptoms in patients with PCD may be due to co-existent common clinical conditions like irritable bowel syndrome (IBS) or other functional gastrointestinal disorders, the crucial decision of advising GFD to a patient with PCD must be based on a comprehensive review of clinical, laboratory and histopathology data. We thus suggest a careful and calibrated approach to each patient with PCD based on available parameters. Till more stronger scientific evidence emerges regarding optimal management of PCD, GFD may be considered in those patients who have either (a) iron deficiency anaemia (IDA) with any one or more features including failure to thrive (FTT), short stature (SS), metabolic bone disease (MBD), wasting, chronic small-bowel type of diarrhoea, or (b) Marsh-II histology with any one or more features including IDA, FTT, SS, MBD, wasting, chronic small-bowel type of diarrhoea with evidence of macro- or micronutrient deficiencies. None of our patients with IDA or Marsh-II histology fulfilled any of these criteria. Hence, regular, meticulous follow-up was an appropriate clinical decision rather than starting GFD, which is perceived as an unwelcome dietary restriction by most if not all patients. Worsening of clinical symptoms during follow-up may be another situation for which empirical GFD may be considered in patients with PCD, but none of our patients faced this scenario either. Histological progression to Marsh-III occurred in only 7% of our patients over one-year follow-up, which vindicates our management strategy. Tosco et al. proposed that the only marker which could help
in the early identification of patients at higher risk to develop intestinal damage seems to be the presence of anti-transglutaminase 2 (TG2) immunoglobulin (Ig)A intestinal deposits at the time of the initial biopsy.2 We could not perform tissue testing for TG2 antibodies as these are not available in India. Regarding the second comment by Repo et al. that more than half of our patients had either clinical symptoms or IDA in spite of absence of villous atrophy, we would like to respond that anaemia is a fairly common problem in rural as well as urban India. Prevalence rates of anaemia among children, young women of childbearing age, and pregnant women in India have been reported as high as 66%–75.3%,3,4 60.8%– 82%5,6 and 80%–93%,7,8 respectively. The commonest form of anaemia in all these population groups is IDA, which is mostly nutritional due to suboptimal oral iron intake or covert blood loss due to the high prevalence rate of intestinal parasitic infestations. Hookworm (Ankylostoma duodenale) infestation is one of the major causes of IDA, especially among school children.9,10 The major source of dietary iron is meat in the West; India on the other hand is a predominantly vegetarian country where nearly two-thirds of the nonMuslim population lack this important source of iron due to the prevalent social norms. Therefore unlike in the West the presence of IDA in Indian patients is mostly due to other reasons as specified earlier. The study by Javid et al. underscores this point as they showed that CD accounted for only 8% of adult patients with unexplained IDA.11 Thus in the Indian context it may be pertinent to evaluate for other causes of IDA before attributing it to CD in patients
1
Department of Gastroenterology, GB Pant Hospital, JL Nehru Marg, New Delhi, India 2 Department of Pathology, GB Pant Hospital, JL Nehru Marg, New Delhi, India Corresponding author: Amarender Singh Puri, Department of Gastroenterology, Room No. 201, Academic Block, GB Pant Hospital, New Delhi 110002, India. Email: [email protected]
Kondala et al. who have only minimal changes on duodenal biopsy specimens. We agree with the final comment by Repo et al. that more well-designed prospective studies are needed to conclude on the role of GFD in patients with PCD. Despite a recent vital study from Finland,12 current scientific evidence is not strong enough to advocate GFD ‘universally’ to all patients with PCD at the ‘outset.’ Newer diagnostic modalities like metabonomics13 or other future biomarkers may help to identify that crucial subset of patients with PCD who may benefit from the prescription of GFD. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Declaration of conflicting interests None declared.
References 1. Kondala R, Puri AS, Banka AK, et al. Short-term prognosis of potential celiac disease in Indian patients. United European Gastroenterol J 2016; 4: 275–280. 2. Tosco A, Salvati VM, Auricchio R, et al. Natural history of potential celiac disease in children. Clin Gastroenterol Hepatol 2011; 9: 320–325. 3. Hanumante NM, Kanvinde S, Sanwalka NJ, et al. Iron deficiency anemia in an urban slum. Indian J Pediatr 2008; 75: 355–357.
141 4. Pasricha SR, Black J, Muthayya S, et al. Determinants of anemia among young children in rural India. Pediatrics 2010; 126: e140–e149. 5. Panigrahi A and Sahoo PB. Nutritional anemia and its epidemiological correlates among women of reproductive age in an urban slum of Bhubaneswar, Orissa. Indian J Public Health 2011; 55: 317–320. 6. Rao S, Joshi S, Bhide P, et al. Dietary diversification for prevention of anaemia among women of childbearing age from rural India. Public Health Nutr 2014; 17: 939–947. 7. Agarwal AK, Sen AK, Kalra NK, et al. Prevalence of anaemia during pregnancy in district Burdwan, West Bengal. Indian J Public Health 1999; 43: 26–31. 8. Kapil U, Saxena N and Ramachandran S. Iron deficiency anemia in pregnancy. Indian Pediatr 1996; 33: 606. 9. Chakma T, Rao PV and Tiwary RS. Prevalence of anemia and worm infestation in tribal areas of Madhya Pradesh. J Indian Med Assoc 2000; 98: 567, 570–571. 10. Sampathkumar V and Rajaratnam A. Prevalence of anaemia and hookworm infestation among adolescent girls in one rural block of Tamil Nadu. Indian J Matern Child Health 1997; 8: 73–75. 11. Javid G, Lone SN, Shoukat A, et al. Prevalence of celiac disease in adult patients with iron-deficiency anemia of obscure origin in Kashmir (India). Indian J Gastroenterol 2015; 34: 314–319. 12. Repo M, Lindfors K, Ma¨ki M, et al. Anemia and iron deficiency in children with potential celiac disease. J Pediatr Gastroenterol Nutr. Epub ahead of print 11 April 2016. DOI: 10.1097/MPG.0000000000001234. 13. Bernini P, Bertini I, Calabro` A, et al. Are patients with potential celiac disease really potential? The answer of metabonomics. J Proteome Res 2011; 10: 714–721.
