IgA anti-tTG antibodies in children with severe short stature without gastrointestinal...

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LETTER IgA anti-tTG antibodies in children with severe short stature without gastrointestinal manifestations Faraz Ahmad & Seema Alam & Indu Shukla & Rana Sherwani & Syed Manazir Ali Received: 24 October 2010 / Accepted: 18 December 2011 / Published online: 4 February 2012 # Indian Society of Gastroenterology 2012 Atypical celiac disease (CD) in children, with stunted growth and anemia, is increasingly recognized in India [14]. In a recent study published from northern India, six of 25 (24%) short stature cases were diagnosed as celiac disease [2]. We report here the prevalence of immunoglobulin A tissue trans- glutaminase (IgA anti-tTG) antibody positivity among short stature (<-3 SD) children and adolescents without gastrointes- tinal symptoms in the age group of 118 years. A prospective hospital based study was done in the Pediatric Gastroenterology Section of Department of Pediatrics, between February 2006 and October 2007. All children in the age group of 118 years, having height less than -3 SD for their age and sex (as per CDC charts), were included if they had no gastrointestinal symptoms suggestive of celiac disease. An age and sex-matched control (children with upper respiratory infection, or those brought for vaccination with height more than -2 SD and no symptoms suggestive of celiac disease) was taken from the Pediatric outpatient services for every case within a week of enrolling the case. Previously diagnosed cases of celiac disease, cases with gastrointestinal symptoms and those with height not less than -3 SD for their age and sex were excluded. All children were northern Indian by ethnicity. All subjects (study and control groups) underwent testing for IgA anti-tTG assay (Bindazyme TM Human Anti Tissue Transglutaminase IgA EIA kit, The Binding Site Limited, Birmingham, United Kingdom). Total IgA was not done. Results were interpreted as per manufacturers instructions (negative was <4 U/mL, weak positive was 410 U/mL and positive was >10 U/mL). The sample size of 44 cases and controls was calculated to be adequate if the anticipated prevalence was 1.7% [5], keeping estimate to be within 5 percentage points with 99% confidence interval and 90% power of the study. Fisher s exact test was used to compare proportions. One hundred and twelve patients with short stature with height <-3 SD presented at the center; 61 of them had gastro- intestinal symptoms suggestive of celiac disease and were excluded. Fifty-one cases of short stature with height <-3 SD without gastrointestinal symptoms were included. Majority of cases were in the age group of 16 years (47.1%); 33 of 51 cases had weight z score less than -3 SD and 25 (49%) had height z score less than -4 SD. The median weight and height z scores of the cases were -3.13 and -3.99, respectively. The corresponding values in control subjects were -0.80 and -0.65, respectively. Six cases (11.8%) were IgA anti-tTG positive, and all controls were seronegative. One of these patients had Marsh score IIIB on duodenal biopsy, 2 patients refused biopsy and 3 did not come back for further follow up. F. Ahmad : S. M. Ali Department of Pediatrics, J N Medical College, Aligarh Muslim University, Aligarh 202 002, India S. Alam (*) Pediatric Gastroenterology Section, Department of Pediatrics, J N Medical College, Aligarh Muslim University, Aligarh 202 002, India e-mail: [email protected] I. Shukla Department of Microbiology, J N Medical College, Aligarh Muslim University, Aligarh 202 002, India R. Sherwani Department of Pathology, J N Medical College, Aligarh Muslim University, Aligarh 202 002, India Present Address: S. Alam Pediatric Hepatology, Institute of Liver and Biliary Sciences, DI Vasant Kunj, New Delhi 110070, India Indian J Gastroenterol (JanuaryFebruary 2012) 31(1):3233 DOI 10.1007/s12664-011-0160-2

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Page 1: IgA anti-tTG antibodies in children with severe short stature without gastrointestinal manifestations

LETTER

IgA anti-tTG antibodies in children with severe short staturewithout gastrointestinal manifestations

Faraz Ahmad & Seema Alam & Indu Shukla &

Rana Sherwani & Syed Manazir Ali

Received: 24 October 2010 /Accepted: 18 December 2011 /Published online: 4 February 2012# Indian Society of Gastroenterology 2012

Atypical celiac disease (CD) in children, with stunted growthand anemia, is increasingly recognized in India [1–4]. In arecent study published from northern India, six of 25 (24%)short stature cases were diagnosed as celiac disease [2]. Wereport here the prevalence of immunoglobulin A tissue trans-glutaminase (IgA anti-tTG) antibody positivity among shortstature (<-3 SD) children and adolescents without gastrointes-tinal symptoms in the age group of 1–18 years.

A prospective hospital based study was done in the PediatricGastroenterology Section of Department of Pediatrics, betweenFebruary 2006 and October 2007. All children in the age groupof 1–18 years, having height less than -3 SD for their age andsex (as per CDC charts), were included if they had no

gastrointestinal symptoms suggestive of celiac disease. Anage and sex-matched control (children with upper respiratoryinfection, or those brought for vaccination with height morethan −2 SD and no symptoms suggestive of celiac disease) wastaken from the Pediatric outpatient services for every casewithin a week of enrolling the case. Previously diagnosed casesof celiac disease, cases with gastrointestinal symptoms andthose with height not less than −3 SD for their age and sexwere excluded. All children were northern Indian by ethnicity.

All subjects (study and control groups) underwent testingfor IgA anti-tTG assay (BindazymeTM Human Anti TissueTransglutaminase IgA EIA kit, The Binding Site Limited,Birmingham, United Kingdom). Total IgA was not done.Results were interpreted as per manufacturer’s instructions(negative was <4 U/mL, weak positive was 4–10 U/mL andpositive was >10 U/mL).

The sample size of 44 cases and controls was calculatedto be adequate if the anticipated prevalence was 1.7% [5],keeping estimate to be within 5 percentage points with 99%confidence interval and 90% power of the study. Fisher’sexact test was used to compare proportions.

One hundred and twelve patients with short stature withheight <−3 SD presented at the center; 61 of them had gastro-intestinal symptoms suggestive of celiac disease and wereexcluded. Fifty-one cases of short stature with height <−3 SDwithout gastrointestinal symptoms were included. Majority ofcases were in the age group of 1–6 years (47.1%); 33 of 51cases had weight z score less than −3 SD and 25 (49%) hadheight z score less than−4 SD. Themedian weight and height zscores of the cases were −3.13 and −3.99, respectively. Thecorresponding values in control subjects were −0.80 and−0.65, respectively. Six cases (11.8%) were IgA anti-tTGpositive, and all controls were seronegative. One of thesepatients had Marsh score IIIB on duodenal biopsy, 2 patientsrefused biopsy and 3 did not come back for further follow up.

F. Ahmad : S. M. AliDepartment of Pediatrics, J N Medical College,Aligarh Muslim University,Aligarh 202 002, India

S. Alam (*)Pediatric Gastroenterology Section, Department of Pediatrics,J N Medical College, Aligarh Muslim University,Aligarh 202 002, Indiae-mail: [email protected]

I. ShuklaDepartment of Microbiology, J N Medical College,Aligarh Muslim University,Aligarh 202 002, India

R. SherwaniDepartment of Pathology, J N Medical College,Aligarh Muslim University,Aligarh 202 002, India

Present Address:S. AlamPediatric Hepatology,Institute of Liver and Biliary Sciences, DI Vasant Kunj,New Delhi 110070, India

Indian J Gastroenterol (January–February 2012) 31(1):32–33DOI 10.1007/s12664-011-0160-2

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Gluten withdrawal was done in the confirmed case and un-equivocal response in the form of increase in height was seenat 6 months follow up. On univariate analysis, hemoglobin<7 gm% (OR 10.25, 95% CI 1.53–68.62) in short staturechildren was associated with tTG positivity.

We found that 11.8% of 51 cases with short stature and withno gastrointestinal symptoms had IgA anti-tTG seropositivity.The estimated prevalence was higher than the prevalenceof CD reported (1.7% to 8.3%) in children with height<−2 SD, where the endocrine diseases were not excluded[5]. In this study we have studied only anti-tTG positiv-ity, and not the prevalence of celiac disease. The anti-tTG antibody is as good as anti-endomyseal antibody indetecting celiac seropositivity [6, 7], and this could be areason for a high prevalence in our cases.

Sharma et al. [2] found a prevalence of 24% CD amongshort stature children, however they did not mention whetherendocrine workup was done in their children. In studies wherethe endocrine causes had been ruled out, the prevalence of CD(4.7% to 59%) was higher [8, 9]. On univariate analysis wefound that only the presence of hemoglobin <7 gm% was therisk factor for celiac autoimmunity. We can conclude that 12%of the short stature with height <−3 SD who are severelyanemic and have no gastrointestinal symptoms could be sero-positive for IgA anti-tTG.

References

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2. Sharma A, Poddar U, Yaccha SK. Time to recognise atypicalceliac disease in Indian children. Indian J Gastroenterol.2007;26:269–73.

3. Poddar U, Thapa BR, Singh K. Clinical features of celiac disease inindian children: are they different from the west? J Pediatr Gastro-enterol Nutr. 2006;43:313–7.

4. Ahmad F, Alam S, Shukla I, Sherwani R, Ali SM. Screeningchildren with severe short stature for celiac disease using tissuetransglutaminase. Indian J Pediatr. 2010;77:387–90.

5. Rossi TM, Albini CH, Kumar V. Incidence of celiac disease iden-tified by the presence of serum endomysial antibodies in childrenwith chronic diarrhea, short stature, or insulin-dependent diabetesmellitus. J Pediatr. 1993;123:262–4.

6. Bhadada SK, Bhansali A, Kochhar R, et al. Does every short staturechild need screening for celiac disease? J Gastroenterol Hepatol.2008;23 8 pt 2:e353–6.

7. Rostom A, Dube C, Cranney A, et al. The diagnostic accuracy ofserologic tests for celiac disease: a systematic review. Gastroenter-ology. 2005;128 Suppl 1:S38–46.

8. Bonamico M, Sciré G, Mariani P, et al. Short stature as the primarymanifestation of monosymptomatic celiac disease. J Pediatr Gastro-enterol Nutr. 1992;14:12–6.

9. Queiroz MS, Nery M, Cançado EL, Gianella-Neto D, Liberman B.Prevalence of celiac disease in Brazilian children of short stature.Braz J Med Biol Res. 2004;37:55–60.

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