Rapid Responses to:

EDITORIALS: R G Peter Watson Diagnosis of coeliac disease BMJ 2005; 330: 739-740 [Full text]

Rapid Responses: Submit a response to this article

Rapid Responses published:

Diagnosis of coeliac disease: what else can be done

Federico Marchetti, Tarcisio Not, Jenny Bua, Alessandro Ventura   (14 April 2005)

Recurrent adverse pregnancy outcomes - think of coeliac disease

Adam P Morton   (18 April 2005)

Diagnosis of coeliac disease: what else can be done 14 April 2005
Federico Marchetti, Clinical Paediatrician Clinica Pediatrica, IRCCS Burlo Garofolo, Università di Trieste, via dell'Istria 65/1, 34100 Trieste, Tarcisio Not, Jenny Bua, Alessandro Ventura Send response to journal: Re: Diagnosis of coeliac disease: what else can be done	EDITOR- We read with interest the editorial by Peter Watson on the diagnosis of coeliac disease in a recent issue of the journal (1). Peter Watson describes how to proceed when the diagnosis of coeliac disease is in doubt; that is, in the case of negative antibody testing with suggestive histological findings for coeliac disease, or in the case of positive antibody testing with normal histological findings. Notably, however, no consideration is given to genetic examinations, such as class II HLA determination. Coeliac disease is strongly associated with specific class II HLA loci. Overall, more than 95% of patients with coeliac disease have either HLA DQ2 or HLA DQ8 (2). Although one third of the general population is a healthy carrier of one of these HLA loci, we believe that their determination is very useful when the diagnosis is in doubt. When the histology is suggestive for coeliac disease but anti-endomysial, anti- gliadin and anti-transglutaminase antibodies are negative, the absence of HLA-DQ2/DQ8 indicates an alternative diagnosis. On the other hand, when a patient tests positive for anti-endomysial, anti-gliadin and anti- transglutaminase antibodies but has apparently normal histological findings, class II HLA determination can be useful in selecting those patients who need to be followed up. Finally, in high risk patients, such as 1st and 2nd degree relatives of patients with coeliac disease, patients with type I diabetes, or Down syndrome etc, the presence of HLA DQ2 or DQ8 suggests, at least in the first years of life, to follow them up with periodic antibodies testing, since it is in these patients that coeliac disease may develop when the high risk HLA loci are present (3,4). Finally, since the spectrum of histological alterations suggestive for coeliac disease varies from inflammatory infiltrate to villous atrophy, in the patients with highly suggestive clinical symptoms but normal histological findings, immunohystochemical analyses on the bioptical specimen should be always performed in order to determine the expected increased concentration of CD3 and gamma delta positives lymphocytes (5). References 1. Peter Watson RG Diagnosis of coeliac disease BMJ 2005;330:739-740 2. Kaukinen K, Partanen J, Maki M, Collin P. HLA-DQ typing in the diagnosis of celiac disease Am J Gastroenterol 2002;97(3):695-9 3. Hoffenberg EJ, Bao F, Eisenbarth GS, Uhlhorn C, Haas JE, Sokol RJ, Rewers M. Transglutaminase antibodies in children with a genetic risk for celiac disease. J Pediatr. 2000;137(3):356-60. 4. Csizmadia CG, Mearin ML, Oren A, Kromhout A, Crusius JB, von Blomberg BM, Pena AS, Wiggers MN, Vandenbroucke JP. Accuracy and cost- effectiveness of a new strategy to screen for celiac disease in children with Down syndrome. J Pediatr.2000;137(6):756-61. 5. Jarvinen TT, Collin P, Rasmussen M, Kyronpalo S, Maki M, Partanen J, Reunala T, Kaukinen K Villous tip intraepithelial lymphocytes as markers of early-stage coeliac disease. Scand J Gastroenterol 2004;39(5):428-33. Federico Marchetti, clinical paediatrician marchetti@burlo.trieste.it Tarcisio Not, clinical paediatrician Jenny Bua, resident in paediatrics Alessandro Ventura, Director Clinica Pediatrica, IRCCS Burlo Garofolo, Università di Trieste, via dell’Istria 65/1, 34100 Trieste Competing interests: None declared
Recurrent adverse pregnancy outcomes - think of coeliac disease 18 April 2005
Adam P Morton, Physician Mater Hospital South Brisbane 4101 Send response to journal: Re: Recurrent adverse pregnancy outcomes - think of coeliac disease	Two lessons of the week in this issue of the BMJ emphasised atypical presentations of coeliac disease in the overweight and antibody negative coeliac disease presenting in the elderly. Coeliac disease has a number of well known associations with other disease states (table 1). In the setting of diagnosed coeliac disease a gluten-free diet has been shown to improve cardiac function in idiopathic dilated cardiomyopathy1 , renal function in IgA nephropathy2, normalise thyroid function with subclinical hypothyroidism3, improve bone density in individuals with osteopenia4 and improve glycaemic control and possibly reduce hypoglycaemia in type 1 diabetes mellitus.5 6 Another less well known but important association is between coeliac disease and adverse pregnancy outcomes. Coeliac disease has been shown to affect 4-8 % of women with otherwise unexplained infertility7. Women with untreated coeliac disease had a later menarche, higher rate of secondary amenorrhoea and a higher rate of spontaneous abortions than control women with irritable bowel syndrome8. In one study women with undiagnosed coeliac disease had an 8.9 fold increased risk of multiple abortions and low birthweight babies compared with individuals with coeliac disease on a gluten-free diet9. Introduction of a gluten- free diet resulted in a 9.2 fold reduction in abortion rate and reduction in the prevalence of low birthweight babies from 29.4 % to 0 %. Thus screening for coeliac disease is important in any woman of potential child -bearing age who has one of the known associated conditions, and in any woman with infertility or a history of recurrent miscarriage or low birthweight babies. Table 1. - Prevalence coeliac disease in other conditions Primary condition / Prevalence coeliac disease Type 1 Diabetes Mellitus 2.8 – 7.8 % Hashimotos thyroiditis 3-8 % Idiopathic dilated cardiomyopathy 5 % Primary biliary cirrhosis 6-11 % IgA nephropathy Up to 44 % antibody positive Osteoporosis 3.4 % References 1. Curione M, Barbato M, Viola F, Francia P, De Biase L, Cucchiara S. Idiopathic dilated cardiomyopathy associated with coeliac disease: the effect of a gluten-free diet on cardiac performance. Dig Liver Dis 2002;34(12):866-9. 2. Woodrow G, Innes A, Boyd SM, Burden RP. A case of IgA nephropathy with coeliac disease responding to a gluten-free diet. Nephrol Dial Transplant 1993;8(12):1382-3. 3. Sategna-Guidetti C, Volta U, Ciacci C, Usai P, Carlino A, De Franceschi L, et al. Prevalence of thyroid disorders in untreated adult celiac disease patients and effect of gluten withdrawal: an Italian multicenter study. Am J Gastroenterol 2001;96(3):751-7. 4. Bai JC, Gonzalez D, Mautalen C, Mazure R, Pedreira S, Vazquez H, et al. Long-term effect of gluten restriction on bone mineral density of patients with coeliac disease. Aliment Pharmacol Ther 1997;11(1):157-64. 5. Amin R, Murphy N, Edge J, Ahmed ML, Acerini CL, Dunger DB. A longitudinal study of the effects of a gluten-free diet on glycemic control and weight gain in subjects with type 1 diabetes and celiac disease. Diabetes Care 2002;25(7):1117-22. 6. Mohn A, Cerruto M, Lafusco D, Prisco F, Tumini S, Stoppoloni O, et al. Celiac disease in children and adolescents with type I diabetes: importance of hypoglycemia. J Pediatr Gastroenterol Nutr 2001;32(1):37-40. 7. Bradley RJ, Rosen MP. Subfertility and gastrointestinal disease: 'unexplained' is often undiagnosed. Obstet Gynecol Surv 2004;59(2):108-17. 8. Kotze LM. Gynecologic and obstetric findings related to nutritional status and adherence to a gluten-free diet in Brazilian patients with celiac disease. J Clin Gastroenterol 2004;38(7):567-74. 9. Ciacci C, Cirillo M, Auriemma G, Di Dato G, Sabbatini F, Mazzacca G. Celiac disease and pregnancy outcome. Am J Gastroenterol 1996;91(4):718 -22. Competing interests: None declared