Alimentary Pharmacology and Therapeutics Invited Editorials 2. Biagi F, Andrealli A, Bianchi PI, Marchese A, Klersy C, Corazza GR. A glutenfree diet score to evaluate dietary compliance in patients with coeliac disease. Br J Nutr 2009; 102: 1–6. 3. Leffler DA, Edwards-George J, Dennis M, et al. Factors that influence adherence to a gluten-free diet in adults with celiac disease. Dig Dis Sci 2008; 53: 1573–81. 4. Ludvigsson JF, Brandt L, Montgomery SM, Granath F, Ekbom A. Validation study of villous atrophy and small intestinal inflammation in Swedish biopsy registers. BMC Gastroenterol 2009; 9: 19. 5. Lebwohl B, Murray JA, Rubio-Tapia A, Green PH, Ludvigsson JF. Predictors of persistent villous atrophy in coeliac disease: a population-based study. Aliment Pharmacol Ther 2014; 39: 488–95. 6. Ludvigsson JF, Bai JC, Biagi F, et al. Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology. Gut 2014; 63: 1210–28.
Editorial: mucosal healing and adherence to the gluten-free diet in coeliac disease – authors’ reply G. Galli, G. Esposito, E. Lahner & B. Annibale Department of Digestive and Liver Disease, Ospedale Sant’Andrea, University Sapienza, Rome, Italy. E-mail: [email protected] doi:10.1111/apt.12975
We thank Drs Lebwohl and Ludvigsson for their interest and the comments about our work.1, 2 We are aware that our strict definition of complete histological recovery (Marsh 0 and ≤30/100 intraepithelial lymphocytes) makes difficult the comparison with other earlier studies on histological findings during gluten-free diet (GFD). However we believe that, according to Marsh classification,3 minimal histological lesions are truly to be considered coeliac disease because they represent intestinal damage, especially considering its immunological nature. We agree that the number of study participants (n = 65) could be a limitation of the study, decreasing statistical power. We support the idea that age is probably an important biological factor linked with mucosal healing.4 In fact our multivariate analysis (OR = 8.74) showing positive association between risks factors and mucosal healing has been adjusted for age over/under 45 years.2 Unfortunately, due to the relatively low sample size, no statistically significant results were found between mucosal healing and age at time of diagnosis. Considering our findings of hypocholesterolaemia and increased frequency of osteoporosis in patients without complete healing, we want to specify that these findings are related to the diagnosis time and not to 1 year of 1242
7. Hopper AD, Hadjivassiliou M, Hurlstone DP, et al. What is the role of serologic testing in celiac disease? A prospective, biopsyconfirmed study with economic analysis Clin Gastroenterol Hepatol 2008; 6: 314–20. 8. Lebwohl B, Michaelsson K, Green PH, Ludvigsson JF. Persistent mucosal damage and risk of fracture in celiac disease. J Clin Endocrinol Metab 2014; 99: 609–16. 9. Lebwohl B, Granath F, Ekbom A, et al. Mucosal healing and mortality in coeliac disease. Aliment Pharmacol Ther 2013; 37: 332–9. 10. Ludvigsson JF, James S, Askling J, Stenestrand U, Ingelsson E. Nationwide cohort study of risk of ischemic heart disease in patients with celiac disease. Circulation 2011; 123: 483–90. 11. Lebwohl B, Granath F, Ekbom A, et al. Mucosal healing and risk for lymphoproliferative malignancy in celiac disease: a population-based cohort study. Ann Intern Med 2013; 159: 169–75.
gluten-free diet (GFD) as discussed by Lebwohl et al. These results probably reflect that their presence is associated with more severe initial histological damage of intestinal mucosa as previously observed in patients with lack of complete healing.5 We are convinced that an optimal management of coeliac patients in the first year of GFD should include diet adherence assessment by means of validated tools linked to evaluation of an accurate histological recovery. This approach could be useful to reduce the future risk of both lymphoproliferative malignancy and fractures as pointed out by Lebwohol et al.5, 6
ACKNOWLEDGEMENT The authors’ declarations of personal and financial interests are unchanged from those in the original article.2 REFERENCES 1. Lebwohl B, Ludvigsson JF. Editorial: mucosal healing and adherence to the gluten-free diet in coeliac disease. Aliment Pharmacol Ther 2014; 40: 1241–2. 2. Galli G, Esposito G, Lahner E, et al. Histological recovery and gluten-free diet adherence: a prospective 1-year follow-up study of adult patients with coeliac disease. Aliment Pharmacol Ther 2014; 40: 639–47. 3. Marsh MN. Gluten major histocompatibility complex and the small intestine. A molecular approach to the spectrum of gluten sensitivity (celiac sprue). Gastroenterology 1992; 102: 330–54. 4. Lebwohl B, Murray JA, Rubio-Tapia A, Green PH, Ludvigsson JF. Predictors of persistent villous atrophy in coeliac disease: a population-based study. Aliment Pharmacol Ther 2014; 39: 488–95. 5. Lebwohol B, Michaelsson K, Green PH, et al. Persistent mucosal damage risk of fracture in celiac disease. J Clin Endocrinol Metab 2014; 99: 609–16. 6. Lebwohl B, Granath F, Ekbom A, et al. Mucosal healing and risk for lymphoproliferative malignancy in celiac disease: a population-based cohort study. Ann Intern Med 2013; 159: 169–75.
Aliment Pharmacol Ther 2014; 40: 1241-1249 ª 2014 John Wiley & Sons Ltd
Editorial: mucosal healing and adherence to the gluten-free diet in coeliac disease – authors’ reply G. Galli, G. Esposito, E. Lahner & B. Annibale Department of Digestive and Liver Disease, Ospedale Sant’Andrea, University Sapienza, Rome, Italy. E-mail: [email protected] doi:10.1111/apt.12975
We thank Drs Lebwohl and Ludvigsson for their interest and the comments about our work.1, 2 We are aware that our strict definition of complete histological recovery (Marsh 0 and ≤30/100 intraepithelial lymphocytes) makes difficult the comparison with other earlier studies on histological findings during gluten-free diet (GFD). However we believe that, according to Marsh classification,3 minimal histological lesions are truly to be considered coeliac disease because they represent intestinal damage, especially considering its immunological nature. We agree that the number of study participants (n = 65) could be a limitation of the study, decreasing statistical power. We support the idea that age is probably an important biological factor linked with mucosal healing.4 In fact our multivariate analysis (OR = 8.74) showing positive association between risks factors and mucosal healing has been adjusted for age over/under 45 years.2 Unfortunately, due to the relatively low sample size, no statistically significant results were found between mucosal healing and age at time of diagnosis. Considering our findings of hypocholesterolaemia and increased frequency of osteoporosis in patients without complete healing, we want to specify that these findings are related to the diagnosis time and not to 1 year of 1242
7. Hopper AD, Hadjivassiliou M, Hurlstone DP, et al. What is the role of serologic testing in celiac disease? A prospective, biopsyconfirmed study with economic analysis Clin Gastroenterol Hepatol 2008; 6: 314–20. 8. Lebwohl B, Michaelsson K, Green PH, Ludvigsson JF. Persistent mucosal damage and risk of fracture in celiac disease. J Clin Endocrinol Metab 2014; 99: 609–16. 9. Lebwohl B, Granath F, Ekbom A, et al. Mucosal healing and mortality in coeliac disease. Aliment Pharmacol Ther 2013; 37: 332–9. 10. Ludvigsson JF, James S, Askling J, Stenestrand U, Ingelsson E. Nationwide cohort study of risk of ischemic heart disease in patients with celiac disease. Circulation 2011; 123: 483–90. 11. Lebwohl B, Granath F, Ekbom A, et al. Mucosal healing and risk for lymphoproliferative malignancy in celiac disease: a population-based cohort study. Ann Intern Med 2013; 159: 169–75.
gluten-free diet (GFD) as discussed by Lebwohl et al. These results probably reflect that their presence is associated with more severe initial histological damage of intestinal mucosa as previously observed in patients with lack of complete healing.5 We are convinced that an optimal management of coeliac patients in the first year of GFD should include diet adherence assessment by means of validated tools linked to evaluation of an accurate histological recovery. This approach could be useful to reduce the future risk of both lymphoproliferative malignancy and fractures as pointed out by Lebwohol et al.5, 6
ACKNOWLEDGEMENT The authors’ declarations of personal and financial interests are unchanged from those in the original article.2 REFERENCES 1. Lebwohl B, Ludvigsson JF. Editorial: mucosal healing and adherence to the gluten-free diet in coeliac disease. Aliment Pharmacol Ther 2014; 40: 1241–2. 2. Galli G, Esposito G, Lahner E, et al. Histological recovery and gluten-free diet adherence: a prospective 1-year follow-up study of adult patients with coeliac disease. Aliment Pharmacol Ther 2014; 40: 639–47. 3. Marsh MN. Gluten major histocompatibility complex and the small intestine. A molecular approach to the spectrum of gluten sensitivity (celiac sprue). Gastroenterology 1992; 102: 330–54. 4. Lebwohl B, Murray JA, Rubio-Tapia A, Green PH, Ludvigsson JF. Predictors of persistent villous atrophy in coeliac disease: a population-based study. Aliment Pharmacol Ther 2014; 39: 488–95. 5. Lebwohol B, Michaelsson K, Green PH, et al. Persistent mucosal damage risk of fracture in celiac disease. J Clin Endocrinol Metab 2014; 99: 609–16. 6. Lebwohl B, Granath F, Ekbom A, et al. Mucosal healing and risk for lymphoproliferative malignancy in celiac disease: a population-based cohort study. Ann Intern Med 2013; 159: 169–75.
Aliment Pharmacol Ther 2014; 40: 1241-1249 ª 2014 John Wiley & Sons Ltd
