Journal of Human Nutrition and Dietetics
LETTER TO THE EDITOR Monitoring gluten-free diet in coeliac patients with Down’s syndrome
Down’s syndrome (DS) is the most common chromosomal abnormality among live-born infants, affecting 1 : 800 newborns worldwide (Pueschel et al., 1995). The impairment of the immunological system has been associated with a higher incidence of autoimmune disease [e.g. thyroiditis and coeliac disease (CD)] (Kusters et al., 2009). The prevalence of CD among apparently healthy blood donors in Southern Brazil is approximately 1 : 417 (Pereira et al., 2006) and, in a previous study, we demonstrated a prevalence of CD of 5.6% in DS patients living in South Brazil (Nisihara et al., 2005). A wide spectrum of signs and symptoms, related to the gastrointestinal tract, as well as extra-intestinal manifestations, may be presented by patients without the classical clinical form (Mubarak et al., 2012). The majority of CD patients respond positively to lifelong gluten-free diet (GFD), which is the decisive therapy. Compliance with a permanent GFD is essential to prevent long-term complications and leads to the disappearance of symptoms (Hill et al., 2005). However, this is difficult for children to maintain, especially for those with DS. In this context, few data exist about the effects of GFD in DS patients; therefore, we evaluated the compliance of GFD in DS patients with CD, as well as the impact of this treatment on their life. The present study was approved by the Ethical Committee of the Federal University of Parana. Nine DS patients diagnosed with CD (six male, three female, median age 17 years, range 12–50 years), and seen by the Down Syndrome Clinic of the Clinical Hospital, Federal University of Parana (Curitiba, Brazil), were included in the study. A diagnosis of CD was based on the serological determination of immunoglobulin A antiendomysium antibodies (IgA-EmA) and confirmed on duodenal biopsies. At diagnosis, all patients showed typical and atypical symptoms for CD, such as anaemia (42.8%), diarrhoea (77.8%) and abdominal distension (55.5%), amongst others (Table 1). After diagnosis, the patients and their relatives were informed by a paediatrician and a nutritionist about CD and how to adhere to a GFD. Seven patients were previously diagnosed as having Hashimoto’s thyroiditis. Follow-up of the patients consisted of interviews, clinical examination and serological tests with respect to IgA-EmA. GFD compliance was evaluated by the use of ª 2013 The British Dietetic Association Ltd
validated questionnaires. All the evaluations were carried out by the same physician once a month, every 6 months and and once a year after diagnosis Seven patients (77.8%) with strict adherence to a GFD presented total or partial remission of symptoms such as anaemia, diarrhoea and abdominal pain and, once a year after diagnosis and treatment, had negative serological tests. The caregivers related improvement in their daily routine, with less irritability (66.6%), as well as improved behaviour. The two patients with non-adherence to GFD were older (18 and 50 years), were symptomatic when ingesting gluten, and remained with a positive IgA-EmA (titre 1 : 80 in both cases). Seven patients had a previous diagnosis of Hashimoto’s thyroiditis and were treated with levothyroxine. After GFD, five of them (71.4%) presented better control of the thyroid disease with a decrease in daily medication (Table 1). Coeliac Disease may occur with mild and/or atypical symptoms and, when patients with DS have CD, the clinical signs and symptoms can mistakenly be attributed to DS generating long delays between the onset of symptoms and correct diagnosis of the disease. Adherence to a strict GFD is indispensable but not simple. Recently, it has been reported that individuals with CD have a diminished quality of life, especially with respect to the social aspects of life (Lee et al., 2012). As a result of a cognitive deficit, the DS patient can have additional difficulties in adapting to GFD, as well as in understanding the disease and its restrictions. In this context, we attest to the value of a detailed explanation concerning CD to the parents, including how to perform GFD (benefits, charges, care), stressing that this will be for the rest of their lives. The DS patients who presented the best clinical improvement were those whose families understood the treatment and were committed to patient care. On the other hand, the two older DS patients showing noncompliance with a GFD had elderly parents who showed less understanding about CD and GFD. It is known that even foods and medications containing gluten in small quantities may be harmful. At the time of diagnosis, the majority of our patients presented weight loss, anaemia and evidence of overt vitamin/mineral deficiencies. In our study, a high concomitance of thyroid disease and 1
Letter to the editor Table 1 Demographical and clinical findings in coeliac patients with Down’s syndrome before and after the gluten-free diet treatment Clinical findings before GFD
Case
Sex
Age at CD diagnosis
Anaemia
Diarrhoea
HD
Abdominal pain
Irritability
Clinical findings after GFD (1 year)
1
M
17
Yes
Yes
Yes
No
Yes
2
F
18
Yes
No
Yes
Yes
No
3
F
18
No
Yes
Yes
Yes
Yes
4 5
M M
12 15
No No
Yes Yes
No Yes
Yes Yes
No Yes
6
M
18
No
No
No
Yes
Yes
7
M
15
Yes
Yes
Yes
No
Yes
8
M
16
No
Yes
Yes
No
Yes
9
F
50
Yes
Yes
Yes
Yes
No
Improvement of anaemia, no diarrhoea and less irritability HD control was better Noncompliance with GFD Improvement of anaemia and other symptoms, when adherent to GFD No diarrhoea and less irritability HD control was better No diarrhoea and abdominal pain Improvement of all gastrointestinal symptoms and less irritability HD control was better Improvement of all gastrointestinal symptoms and less irritability No diarrhoea and less irritability HD control was better Improvement of anaemia, no diarrhea and less irritability Noncompliance with GFD Improvement of anaemia and other symptoms, when adherent to GFD
M, male; F, female; CD, coeliac disease; GFD, gluten-free diet; HD, Hashimoto’s disease.
CD in DS patients was observed; furthermore, the absorption of drugs used to treat hypothyroidism was affected by CD. When the patients were compliant with a GFD, the daily doses of this medication decreased and control of thyroid disease was better. Among patients malnourished at the time of diagnosis (n = 4), an increased body mass composition was recovered after 1 year of treatment. At the time of diagnosis, DS patients with CD expressed anger, anxiety and sadness. Anger can negatively affect the patient–clinician relationship and has been correlated with dietary compliance (Addolarato et al., 2004). DS patients adherent to GFD presented less irritability and psychomotor agitation, as described by their parents. In our experience, clinicians taking care of DS patients need to know about the emotional impact of CD diagnosis for these people because GFD treatment changes alimentary habits in patients with a cognitive deficit. Furthermore, GFD has financial implications worldwide (Singh & Whelan, 2011). Accordingly, these must be considered with respect to dietary counselling for maintaining economic balance in low income family households, which are common place in South America, as was observed for all families included in the present study.
2
In conclusion, in this series of cases with DS and CD, we observed that patients need to be followed and monitored. An improvement of CD symptoms, mainly in those with thyroiditis, is associated with those patients showing compliance with GFD. Conflict of interests, source of funding and authorship The authors declare that there are no conflicts of interest. The study was conducted without any outside financial support, grants or donations.All authors critically reviewed the manuscript and approved the final version submitted for publication.
R. M. NISIHARA*†; M. BONACIN†; L. M. DA SILVA KOTZE‡; N. P. DE OLIVEIRA† & S. UTIYAMA† *Department of Medicine, University Positivo, Curitiba, Parana, Brazil; †Laboratory of Immunopathology and Clinic of Down Syndrome, Clinical Hospital, Federal University of Parana, Curitiba, Parana, Brazil; ‡Gastroenterology Service, Cajuru Hospital, Pontifical Catholic University of Parana, Curitiba, Parana, Brazil E-mail: [email protected] ª 2013 The British Dietetic Association Ltd
Letter to the editor
References Addolarato, G., de Lorenzi, G., Abenavoli, L., Leggio, L., Capristo, E. & Gasbarrini, G. (2004) Psychological support counseling improves gluten-free diet compliance in coeliac patients with affective disorders. Aliment. Pharmacol. Ther. 20, 777–782. Hill, I.D., Dirks, M.H., Liptak, G.S., Colletti, R.B., Fasano, A., Guandalini, S., Hoffenberg, E.J., Horvath, K., Murray, J.A., Pivor, M. & Seidman, E.G. (2005) North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J. Pediatr. Gastroenterol. Nutr. 40, 1–19. Kusters, M.A., Verstegen, R.H., Gemen, E.F. & de Vries, E. (2009) Intrinsic defect of the immune system in children with Down syndrome: a review. Clin. Exp. Immunol. 156, 189–193. Lee, A.R., Ng, D.L., Diamond, B., Ciaccio, E.J. & Green, P.H. (2012) Living with coeliac disease: survey results from the USA. J. Hum. Nutr. Diet. 25, 233–238.
ª 2013 The British Dietetic Association Ltd
Mubarak, A., Houwen, R.H. & Wolters, V.M. (2012) Celiac disease: an overview from pathophysiology to treatment. Minerva Pediatr. 64, 271–287. Nisihara, R.M., Kotze, L.M.S., Utiyama, S.R.R., Oliveira, N.P., Fiedler, P.T. & Messias-Reason, I.T. (2005) Celiac disease in children and adolescents with Down syndrome. Jornal de Pediatria 81, 373–376. Pereira, M.A.G., Ortiz-Agostinho, C.L., Nishitokukado, I., Sato, M.N., Dami~ao, A.O., Alencar, M.L., Abrantes-Lemos, C.P., Cancßado, E.L., de Brito, T., Ioshii, S.O., Valarini, S.B. & Sipahi, A.M. (2006) Prevalence of celiac disease in an urban area of Brazil with predominantly European ancestry. World J. Gastroenterol. 12, 6546–6550. Pueschel, S.M, Anneren, G., Durlach, R., Flores, J., Sustrova, M. & Verma, I.C. (1995) Guidelines for optimal care of persons with Down syndrome. Acta Paediatr. 84, 823–827. Singh, J. & Whelan, K. (2011) Limited availability and higher cost of gluten-free foods. J. Hum. Nutr. Diet. 24, 479–486.
3
LETTER TO THE EDITOR Monitoring gluten-free diet in coeliac patients with Down’s syndrome
Down’s syndrome (DS) is the most common chromosomal abnormality among live-born infants, affecting 1 : 800 newborns worldwide (Pueschel et al., 1995). The impairment of the immunological system has been associated with a higher incidence of autoimmune disease [e.g. thyroiditis and coeliac disease (CD)] (Kusters et al., 2009). The prevalence of CD among apparently healthy blood donors in Southern Brazil is approximately 1 : 417 (Pereira et al., 2006) and, in a previous study, we demonstrated a prevalence of CD of 5.6% in DS patients living in South Brazil (Nisihara et al., 2005). A wide spectrum of signs and symptoms, related to the gastrointestinal tract, as well as extra-intestinal manifestations, may be presented by patients without the classical clinical form (Mubarak et al., 2012). The majority of CD patients respond positively to lifelong gluten-free diet (GFD), which is the decisive therapy. Compliance with a permanent GFD is essential to prevent long-term complications and leads to the disappearance of symptoms (Hill et al., 2005). However, this is difficult for children to maintain, especially for those with DS. In this context, few data exist about the effects of GFD in DS patients; therefore, we evaluated the compliance of GFD in DS patients with CD, as well as the impact of this treatment on their life. The present study was approved by the Ethical Committee of the Federal University of Parana. Nine DS patients diagnosed with CD (six male, three female, median age 17 years, range 12–50 years), and seen by the Down Syndrome Clinic of the Clinical Hospital, Federal University of Parana (Curitiba, Brazil), were included in the study. A diagnosis of CD was based on the serological determination of immunoglobulin A antiendomysium antibodies (IgA-EmA) and confirmed on duodenal biopsies. At diagnosis, all patients showed typical and atypical symptoms for CD, such as anaemia (42.8%), diarrhoea (77.8%) and abdominal distension (55.5%), amongst others (Table 1). After diagnosis, the patients and their relatives were informed by a paediatrician and a nutritionist about CD and how to adhere to a GFD. Seven patients were previously diagnosed as having Hashimoto’s thyroiditis. Follow-up of the patients consisted of interviews, clinical examination and serological tests with respect to IgA-EmA. GFD compliance was evaluated by the use of ª 2013 The British Dietetic Association Ltd
validated questionnaires. All the evaluations were carried out by the same physician once a month, every 6 months and and once a year after diagnosis Seven patients (77.8%) with strict adherence to a GFD presented total or partial remission of symptoms such as anaemia, diarrhoea and abdominal pain and, once a year after diagnosis and treatment, had negative serological tests. The caregivers related improvement in their daily routine, with less irritability (66.6%), as well as improved behaviour. The two patients with non-adherence to GFD were older (18 and 50 years), were symptomatic when ingesting gluten, and remained with a positive IgA-EmA (titre 1 : 80 in both cases). Seven patients had a previous diagnosis of Hashimoto’s thyroiditis and were treated with levothyroxine. After GFD, five of them (71.4%) presented better control of the thyroid disease with a decrease in daily medication (Table 1). Coeliac Disease may occur with mild and/or atypical symptoms and, when patients with DS have CD, the clinical signs and symptoms can mistakenly be attributed to DS generating long delays between the onset of symptoms and correct diagnosis of the disease. Adherence to a strict GFD is indispensable but not simple. Recently, it has been reported that individuals with CD have a diminished quality of life, especially with respect to the social aspects of life (Lee et al., 2012). As a result of a cognitive deficit, the DS patient can have additional difficulties in adapting to GFD, as well as in understanding the disease and its restrictions. In this context, we attest to the value of a detailed explanation concerning CD to the parents, including how to perform GFD (benefits, charges, care), stressing that this will be for the rest of their lives. The DS patients who presented the best clinical improvement were those whose families understood the treatment and were committed to patient care. On the other hand, the two older DS patients showing noncompliance with a GFD had elderly parents who showed less understanding about CD and GFD. It is known that even foods and medications containing gluten in small quantities may be harmful. At the time of diagnosis, the majority of our patients presented weight loss, anaemia and evidence of overt vitamin/mineral deficiencies. In our study, a high concomitance of thyroid disease and 1
Letter to the editor Table 1 Demographical and clinical findings in coeliac patients with Down’s syndrome before and after the gluten-free diet treatment Clinical findings before GFD
Case
Sex
Age at CD diagnosis
Anaemia
Diarrhoea
HD
Abdominal pain
Irritability
Clinical findings after GFD (1 year)
1
M
17
Yes
Yes
Yes
No
Yes
2
F
18
Yes
No
Yes
Yes
No
3
F
18
No
Yes
Yes
Yes
Yes
4 5
M M
12 15
No No
Yes Yes
No Yes
Yes Yes
No Yes
6
M
18
No
No
No
Yes
Yes
7
M
15
Yes
Yes
Yes
No
Yes
8
M
16
No
Yes
Yes
No
Yes
9
F
50
Yes
Yes
Yes
Yes
No
Improvement of anaemia, no diarrhoea and less irritability HD control was better Noncompliance with GFD Improvement of anaemia and other symptoms, when adherent to GFD No diarrhoea and less irritability HD control was better No diarrhoea and abdominal pain Improvement of all gastrointestinal symptoms and less irritability HD control was better Improvement of all gastrointestinal symptoms and less irritability No diarrhoea and less irritability HD control was better Improvement of anaemia, no diarrhea and less irritability Noncompliance with GFD Improvement of anaemia and other symptoms, when adherent to GFD
M, male; F, female; CD, coeliac disease; GFD, gluten-free diet; HD, Hashimoto’s disease.
CD in DS patients was observed; furthermore, the absorption of drugs used to treat hypothyroidism was affected by CD. When the patients were compliant with a GFD, the daily doses of this medication decreased and control of thyroid disease was better. Among patients malnourished at the time of diagnosis (n = 4), an increased body mass composition was recovered after 1 year of treatment. At the time of diagnosis, DS patients with CD expressed anger, anxiety and sadness. Anger can negatively affect the patient–clinician relationship and has been correlated with dietary compliance (Addolarato et al., 2004). DS patients adherent to GFD presented less irritability and psychomotor agitation, as described by their parents. In our experience, clinicians taking care of DS patients need to know about the emotional impact of CD diagnosis for these people because GFD treatment changes alimentary habits in patients with a cognitive deficit. Furthermore, GFD has financial implications worldwide (Singh & Whelan, 2011). Accordingly, these must be considered with respect to dietary counselling for maintaining economic balance in low income family households, which are common place in South America, as was observed for all families included in the present study.
2
In conclusion, in this series of cases with DS and CD, we observed that patients need to be followed and monitored. An improvement of CD symptoms, mainly in those with thyroiditis, is associated with those patients showing compliance with GFD. Conflict of interests, source of funding and authorship The authors declare that there are no conflicts of interest. The study was conducted without any outside financial support, grants or donations.All authors critically reviewed the manuscript and approved the final version submitted for publication.
R. M. NISIHARA*†; M. BONACIN†; L. M. DA SILVA KOTZE‡; N. P. DE OLIVEIRA† & S. UTIYAMA† *Department of Medicine, University Positivo, Curitiba, Parana, Brazil; †Laboratory of Immunopathology and Clinic of Down Syndrome, Clinical Hospital, Federal University of Parana, Curitiba, Parana, Brazil; ‡Gastroenterology Service, Cajuru Hospital, Pontifical Catholic University of Parana, Curitiba, Parana, Brazil E-mail: [email protected] ª 2013 The British Dietetic Association Ltd
Letter to the editor
References Addolarato, G., de Lorenzi, G., Abenavoli, L., Leggio, L., Capristo, E. & Gasbarrini, G. (2004) Psychological support counseling improves gluten-free diet compliance in coeliac patients with affective disorders. Aliment. Pharmacol. Ther. 20, 777–782. Hill, I.D., Dirks, M.H., Liptak, G.S., Colletti, R.B., Fasano, A., Guandalini, S., Hoffenberg, E.J., Horvath, K., Murray, J.A., Pivor, M. & Seidman, E.G. (2005) North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J. Pediatr. Gastroenterol. Nutr. 40, 1–19. Kusters, M.A., Verstegen, R.H., Gemen, E.F. & de Vries, E. (2009) Intrinsic defect of the immune system in children with Down syndrome: a review. Clin. Exp. Immunol. 156, 189–193. Lee, A.R., Ng, D.L., Diamond, B., Ciaccio, E.J. & Green, P.H. (2012) Living with coeliac disease: survey results from the USA. J. Hum. Nutr. Diet. 25, 233–238.
ª 2013 The British Dietetic Association Ltd
Mubarak, A., Houwen, R.H. & Wolters, V.M. (2012) Celiac disease: an overview from pathophysiology to treatment. Minerva Pediatr. 64, 271–287. Nisihara, R.M., Kotze, L.M.S., Utiyama, S.R.R., Oliveira, N.P., Fiedler, P.T. & Messias-Reason, I.T. (2005) Celiac disease in children and adolescents with Down syndrome. Jornal de Pediatria 81, 373–376. Pereira, M.A.G., Ortiz-Agostinho, C.L., Nishitokukado, I., Sato, M.N., Dami~ao, A.O., Alencar, M.L., Abrantes-Lemos, C.P., Cancßado, E.L., de Brito, T., Ioshii, S.O., Valarini, S.B. & Sipahi, A.M. (2006) Prevalence of celiac disease in an urban area of Brazil with predominantly European ancestry. World J. Gastroenterol. 12, 6546–6550. Pueschel, S.M, Anneren, G., Durlach, R., Flores, J., Sustrova, M. & Verma, I.C. (1995) Guidelines for optimal care of persons with Down syndrome. Acta Paediatr. 84, 823–827. Singh, J. & Whelan, K. (2011) Limited availability and higher cost of gluten-free foods. J. Hum. Nutr. Diet. 24, 479–486.
3
