can we avert the impending epidemic in india?

8/2/2019 Can we avert the impending epidemic in India?

1/5

Indian J Med Res 133, January2011, pp 5-8

Editorial

Celiac disease: can we avert the impending epidemic in India?

Celiac disease, caused by allergy to gluten presentin wheat and related g rains, is a disorder of co nsiderableand increasing importance in Western countries'.Originally recognized primarily in children presentingwith diarrhoea and malabsorption, we now understandthat it often affects adu lts, that it may present primarilywith non-gastrointestinal manifestations includinganaemia, arthropathy, osteoporosis and growthretardation, and what we see clinically is the tip of aniceberg that threatens to grow bigger. The diagnosisof celiac disease is now made with serological testswhich may capture those at risk as well as those withactual disease. While small bowel mucosal biopsy isconsidered essential to the diagnosis of disease, thereis now increasing recognition that even a positiveserological test is associated with increased risks for

vascular disease.The estimated population prevalence of diagnosed

celiac disease in many Western countries approaches 1per cent^^ The highest prevalence rates ofthe diseaseare noted in the Saharawi people of Africa in whomceliac disease prevalence is believed to be around 5per cent^. There is little information on celiac diseaseprevalence in South Asia, and indeed celiac disease isbelieved to be rare in this part of the world'. There isa strong genetic tendency, 75 per cent of monozygotictwins are concordant for the disease, compared to 10per cent of dizygotic twins; 10 per cent of first degreefamily relatives of an index patient have celiac diseasedHLA aleles encoding the antigens DQ2 and DQ8 showthe strongest association with celiac disease; however,most individuals expressing DQ2 or DQ8 do notdevelop the diseased Multiple other genes contribute tothe disease each having a weak effect. Recent genomewide studies show that, in addition to HLA locus genes,the second strongest association is for an SNP closeto the IL2 and IL21 genes on chromosome 4q27. Six

of 7 additional loci are close to the immune responsegenes'. Geographic differences in disease prevalenceare explained to an extent by genetic differencesbetween populations. For instance, carriage of DQ2and DQ8 is up to 40 per cent in Caucasians and thereis a very high carriage of DQ8 among the Saharawi.On the other hand, DQ2 is absent in the population ofBurkina-Faso where celiac disease is also absent'".

Willem-Karel Dicke recognized the associationbetween consumption of wheat and manifestation ofclinical sym ptom s"; during the Second World War whenfood was in very short supply he observed that childrenwith celiac disease flourished on a diet that did notcontain wheat, providing a clue to the aetiology of thedisease. It has been realized that the prevalence of celiacdisease in a population broadly parallels the amount ofwheat co nsumed in the diet. Thus, celiac disease is lowor absent in Japan and southeast Asia where rice is themain cereal consumed and in sub-Saharan Africa w heremaize is the staple cereal in the diet. Even within Europe'the prevalence of celiac disease is lower in Denmark!,Estonia and Finland where lower amounts of glutenare consumed in infancy than in Sweden where glutenconsumption during infancy is higher.

The classical presentation of celiac disease, withsymptoms referable to the gastrointestinal tract, mayaccount for only a proportion of the cases. We nowrealize that celiac disease is actually a multi-systerndisorder which is highly variable in its clinicalexpression, may occur at any age, and may presentwith a variety of manifestations^ The diagnosis isoften delayed for these reasons. Gastrointestinalmanifestations may include diarrhoea, weight lossfailure to thrive, stunting, abdominal pain, bloatingand distension, anorexia, vomiting and constipationOn the other hand, celiac disease patients oftenpresent with extraintestinal manifestations with


2/5

INDIAN J MED RES, JANUARY 2011

minimal gastrointestinal symptom s. They may presentto the internist or relevant sub-specialist with oneor more manifestations including iron deficiencyanaemia, stunting, osteoporosis, vitamin deficiencies,or fatigue. They may present to the obstetrician/

gynae cologist with delayed pub erty,, infertility, orrecurrent foetal loss. They may present to the dentalsurgeon with recurrent aphthous ulcration or dentalenamel hypoplasia. Celiac disease may be associatedwith autoimmune endocrinologie disorders such asthyroiditis and type 1 diabetes mellitus. It is associatedwith neuropsychiatrie conditions such as depression,anxiety, peripheral neuropathy, ataxia and epilepsy.Asymptomatic elevation of transaminases may occurin these patients and an unusual association of celiacdisease is with chronic liver disease and non-cirrhoticportal fibrosis'^'^

The diagnosis of celiac disease is based on thepresence of srologie tests (ELISA) confirming thepresence of antibody to tissue transglutaminase (anti-tTG)^ The IgA anti-tTG provides the best specificityand is widely used. However, about 6 per cent ofhealthy individuals are partially IgA deficient'" andin these individuals the diagnosis may be missedif only the IgA antibody test is done. Currentlyavailable diagnostic kits often provide both IgA andIgG antibody levels, enhancing the ability to make

the diagnosis. The presence of positive serology isnot in itself sufficient to make a diagnosis of celiacdisease. Deep duodenal biopsies, obtained at uppergastrointestinal endoscopy, are often used to confirmthe diagnosis by demonstrating infiltration of theepithelium by lymphocytes and the presence of villousatrophy. It also requires the demonstration that glutenwithdrawal fi-om he diet will reverse or ameliorate theclinical sym ptoms. Based on the clinical p resentation,serology, and biopsy findings, celiac disease has beenclassified as classical celiac disease (dominated bygastrointestinal malabsorption), atypical celiac disease(with prominent extraintestinal symptoms and a fewor no gastrointestinal symptoms), silent celiac disease(asymptomatic individuals with positive serology andvillous atrophy on biopsy) and latent celiac disease(asymptomatic individuals with positive serology butnorm ar biops y)'. Clinical celiac disease is associatedwith a doubling of all-cause m ortality'. However, thereis now intriguing evidence from serological studies ofarchived blood that latent celiac disease may also beassociated with excess m ortality when compared to thenormal population. A recent study examined archived

blood specimens from a cohort of US Air Force

personnel followed for over 45 years and two recohorts. Prevalence of anti-tTG antibody and endomysial antibody {i.e. undiagnosed or latent Cincreased 4.5- fold fi-om 0.2 per cent in the Air Fcohort to 0.9 per cent in the recent cohorts. At the stime, mortality in individuals with undiagnosed CD4 times greater than in those who were serone gativ

Celiac disease was recognized in northern Inprimarily in children, since the 1960s'^"". Ac om mubased study in Lu dhiana. that involved a step-approach to case detection and diagnosis estimthat celiac disease prevalence in this city was at leain 310 individuals^". Hospital-based studies examia general paediatric patient population suggepreva lence of 1 per cent^'. Celiac disease affecadults is also now well recognized in northern Indiand in many of these individuals the presentatioatypical, i.e. without diarrhoea or overt m alabsorptThe prevalence of celiac disease in southern Indinot known. Anecdotal experience of physicians gastroenterologists in southern India suggests that very infrequent in southern

Differences in celiac disease prevalence betwnorth and south India could be ascribe d to differein dietary patterns (rice being the staple cerealsouth India) or due to differences in genetic ma ke

Celiac disease occurrence is determined by the HDQ antigen expression pattern of the individualparticular, almost all patients with celiac diseexpress either HLA-DQ2 or HLA-DQ8, ' and thHLA types are also present in about 30 per centhe normal population. The absence of expressof either HLA-DQ2 or DQ8 in a population is acorrelated with the absence of celiac disease in population. The genes that determine expressof HLA-DQ2 or DQ8 have been studied in mpopulations. Fourteen of the 15 children with cedisease in Lucknow were HLA-DQ2 positive serotyping and 29 of30 children in the sam e institutwere positive in anotherstudy^*-^'.In anotherstudy, 3435 north Indian children with celiac disease were HDQ2 positive^". H LA-D Q2 is carried onDR3 haplotypdue to linkage disequilibrium, and the DR3 haplotyin these 34 n orth Indian children w ere different fromDR3 haplotypes described in Caucasian children wceliac disease^". The H LA-D Q p henotype of the genpopulation in north and south India is not adequaknown. Studies suggest that the prevalence of HDQ 2 in a north Indian popu lation is around 32 per ce

There are significant differences in prevalence of HL


3/5

RAMAKRISHNA: CELIAC DISEASE: CAN WE AVERT THE IMPENDING EPIDEMIC IN INDIA?

DQ2 in different Indian communities but these studieshave all been on limited num bers of individuals, thus notproviding confidence in the estimated prevalence^^"^*.The other variable is that cereal consumption patternsare very different between north and south India,

although there has been a recent change in these patternsparticularly in urban areas. In south India, rice is theprimary cereal consumed in the diet. In the Indian sub-continent, wheat consump tion is high in Pakistan and inthe States of north India, w hich also constitute the celiacbelt of India.

The time of first exposure to wheat influencesthe development of celiac disease. In countries suchas Finland, Estonia, and Denmark, characterized bylow gluten consumption in infancy, celiac diseaseprevalence is much lower than in Sweden wheregluten consumption is high in infancy. A naturalexperiment occurred in Sweden about two decadesago when national recommendations were made tointroduce wheat into the diet after cessation of breastfeeding at six mon ths" . This change was coupled w ithincreased wheat gluten consumption through infantfeeds. Together these measures resulted in a two-foldincrease in incidence of celiac disease in Sweden,which was attributed to introduction of wheat intothe diet after cessation of breast feeding. In 1996 thisrecommendation was changed to introduce gluten in

gradually increasing amounts while the infant was stillbeing breast fed. This led to a dramatic decrease inceliac disease incidence. The other dimension to thisproblem is that not all wheat is alike when it comes toinducing celiac disease. The ancient or diploid wheats(e.g. Triticum monococcum)are poorly antigenic, whilethe modem hexaploid wheats{e.g. Triticum aestivum)have highly antigenic glutens, more capable of inducingceliac disease-'l India, for centuries, grew diploid andlater tetraploid wheat which is less antigenic, whilehexaploid wheat used in making bread is recentlyintroduced. Thus a change back to older varieties ofwheat may have public health consequences. Publichealth authorities may well want to examine both theseavenues,i,e. infant feeding recomm endations and wheatvarieties cultivated in the country, for opportunities toavert the epidem ic of celiac disease which is impe ndingin our country..

B.S. Ramakrishna

Department of Gastrointestinal SciencesGhristian Medical Gollege

Vellore 632 004, [email protected]

References

1. Green PHR, Cellier C. Celiac disease . A'Engl J Med 2007;357: 1731-43.

2. Fasano A, Berti I, Gerarduzzi T, Not T, Colletti RB, DragoS, et al. Prevalence of celiac disease in at-risk and not-at-risk

groups in the United States: a large multicenter study.Ar;hIntern Med 2003; 163 : 286-92.

3. Mki M, Mustalahti K, Kokkonen J, KulnialaP, Haapalahti M ,Karttunen T,et al Prevalence of celiac disease among childrenin Finland. Af Engl J Med 2003; 34 8 : 2517-24.

4. West J, Logan RF, Hill PG, Lloyd A, Lewis S, Hubbard R,et hi,Seropr evalence , correlates, and characteristics of undete ct ;coeliac disease in England.Gut 2003; 52 : 960-5.

5. NIH consensus development conference on celiac diseaieNIH Consens State Sei Statements2004; 2 / : 1 -23.

6. Catassi C, Ratsch IM, Gandolfi L, Pratesi R, Fabiani E, EAsmar R, et al. Why is coeliac disease endemic in the peof leof the Sahara? Z,aceM999; 55-^ : 647 -8.

7. Cummins AG, Roberts-Thomson IC. Prevalence of celiadisease in the Asia-Pacific region.J Gastroenterol Hepatol2009; 2-^: 1347-51.

8. Sollid LM . Hunting for celiac disease genes.Gastroenterology2 0 0 8 ; / J 4 : 869-81.

9. van Heel DA, Franke L, Hunt KA, Gwilliam R, Zhema kova AInouye M, et al, A genome-wide association study for celiacdisease identifies risk variants in the region harboringL 2 andIL21. Nat Genet2001; 39: 827-9,

10. Cataldo F, Lio D, Simpore J, Musumeci S. Consumption owheat foodstuffs not a risk for celiac disease occurrence iBurkina Faso.J Pediatr Gastroenterol Nutr 2002; 35 : 233-4.

11. van Berge-Henegouwen GP, Mulder C J. Pioneer in the glutefree diet: Willem-Karel Dicke 1905-1962, over 50 years ogluten free diet.Gut 1993; 34 : 1473-5.

12. Di Biase AR, Colecchia A, Scaioli E, Berri R, Viola L, VestitA, et al. Autoimmune liver diseases in a paediatric populatiowith celiac disease - a 10-year single-centre experiencAliment Pharmacol Ther2010; 31 : 253-60.

13. Eapen CE, Nightingale P, Hubscher SG, Lane PJ, PlanT, Velissaris D, et al, Non-cip-hotic intrahepatic portahypertension: associated gut diseases and prognostic factorDig Dis Sei 2010 May 25. [Epub ahead of print] PubMePMID: 20499175.

14. Chandran S, Khetn D, Chaudhary R, Misra R, Aggarwal A

Low prevalence of IgA deficiency in north Indian populatioIndian J Med Res 2006; 12 3 : 653-6.

15. Rubio-Tapia A, Kyle RA, Kaplan EL, Johnson DR, PagW, Erdtmann F, et al. Increased prevalence and mortality|inundiagnosed celiac disease.Gastroenterology 2009; 13 7 : ' '93 .

16. Walia BN, Sidhu JK, Tandon BN, Ghai OP, Bhargava SCoeliac disease in North Indian children.Br Med J 1966; 2: 1233-4 .

17. Walia BN, Mehta S, GupteSP. Coeliac disease.Indian PedU1972; 9 : 16-9.

18. Nelson R, McNeish AS, Anderson CM. Coeliac diseasechildren of Asian immigrants.Lancet 1973; / . 348-50.

ttr

in


4/5

INDIAN J MED RES, JANUARY 2011

19. Khoshoo V, Bhan MK. Celiac disease in Indian children.Indian Pediatr 1989; 26 : 627-9.

20 . Sood A, Midha V, Sood N , Avasthi G, Sehgal A. Prevalence ofceliac disease among school children in Punjab, north India.J Gastroenterol Hepatol 2006; 21: 1622-5.

21 . Bhattacharya M, DubeyAP, Mathur NB. Prevalence of celiacdisease in north Indian children.Indian Pediatr 2009; 46 415-7 .

22 . Sachdev A, Srinivasan V, Maheswary S, Mohan H, AshishB, Singh LS. Adult onset celiac disease in north India.TropGastroenterol 2002; 23 : 117-9.

23 . Sood A, Midha V, Sood N , Malhotra V. Adult celiac disease innorthern India.Indian J Gastroenterol 2003; 22 : 124-6.

24 . Makharia GK, Baba CS, Khadgawat R, Lai S, Tevatia MS,Madan K, et al. Celiac disease: variations of presentations inadults. Indian J Gastroenterol 2007; 26 : 162-6.

25 . Agarwal N, PuriAS, Grover R. Non-diarrheal celiac disease: areport of 31 cases from northern India.Indian J G astroenterol2007; 26 : 122-6.

26 . Yachha SK, Poddar U. Celiac disease in India.Indian JGastroenterol 2007; 26 : 230-7.

27 . Ganesh R, Suresh N, Sathiyasekaran M. Celiac disease, stillan uncommon problem in Tamilians?Indian J Gastroenterol2009; 28: 189.

28 . Agrawal S, Gupta A, Yachha SK, M Uer-MyhsokB, MehrotraP, Agarwal SS. Association of human leucocyte-DR and DQ

' antigens in coeliac disease: a family study.J GastroenterolHepatol 2000; 15:771-4.

29 . Srivastava A, Yachha SK, Mathias A, Parveen F, Poddar U,Agrawal S. Prevalence, human leukocyte antigen typing andstrategy for screening among Asian first-degree relatives ofchildren with celiac disease.J Gastroenterol Hepatol 2010-25 :319 -24 .

30. Kaur G, Sarkar N, Bhatnagar S, Kumar S, Rapthap CC, BMK, et al. Pdiatrie celiac disease in India is associated wmultiple DR3-DQ2 haplotypes.Hum Immunol2002; 63 682 .

31. Rani R, Fernandez-Vina MA , Stastny R. Association betwHLA class II aleles in a north Indian population.TissAntigens \99S; 52: 37-43.

32. Shanmugalakshmi S, Balakrishnan K, Manoharan Pitchappan RM. HLA-DRBl, DQBl in Piramalai Kaand Yadhavas, two D ravidian-speaking castes of Tamil Nsouth India. Tissue Antigens 2003; 61 : 451-64.

33 . Kaur G, K umar N, Szilagyi A, Blasko B, Fust G, Rajczy Kal. Autoimmune-associated H LA-B 8-DR3 haplotypes in AIndians are unique in C4 complement gene copy numbers HSP-2 1267A/G.Hum Immunol 2008; 69 : 580-7.

34. Sanjeevi CB, Kanungo A, Shtauvere A, Samal KC, TripBB. Association of HLA class II aleles with diffesubgroups of diabetes mellitus in Eastern India idendifferent associations with IDDM and malnutrition-reldiabetes. Tissue Antigens 1999; 54 : 83-7.

35. Balakrishnan K, Pitchappan RM, Suzuki K, Kumar Santhakumari R, Tokunaga K. HLA affinities of IyersBrahmin population of Tamil Nadu, South India.Hum Bi1996; 68 : 523-37.

36. Subramanian VS, Selvaraj P, Narayanan PR, PrabhakarDamodaran C. Distribution of HLA (class I and classantigens in the native D ravidian Hindus of T amil Nadu, soIndia. Gene Geogr 1995; P : 15-24.

37. Olsson C, Hemell O, Hmell A, Lnnberg G, IvarssonDifference in celiac disease risk between Swedish birth cohsuggests an opportunity for primary prevention.Pediatric2008; 122 :528-34.

38. Molberg O, Uhlen AK, Jensen T, Flaete NS, FleckensteinArentz-Hansen H, et al. Mapping of gluten T-cell epitopin the bread w heat ance stors: implication s for. celiac diseGastroenterology 2005; 12 8 : 393-401.


5/5

Copyright of Indian Journal of Medical Research is the property of Indian Council of Medical Research and its

content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's

express written permission. However, users may print, download, or email articles for individual use.

can we avert the impending epidemic in india?

Documents