Clinical and Anthropometric Profile of Children with Celiac Disease in Punjab (North India) by Puneet Aulakh Pooni,a Rajoo Singh Chhina,b B. K. Jaina,a Daljit Singh,a and Anil Gautama Departments of aPediatrics and bGastroenterology, Dayanand Medical College & Hospital, Ludhiana, Punjab, India
Summary This prospective study was carried out to evaluate the clinical and anthropometric profile of 71 children confirmed to have celiac disease on the basis of clinical features, duodenal biopsy and unequivocal improvement on gluten-free diet. Serological tests were performed in 35 cases. The patients were divided into three age groups _5 years, 5–10 years, and `10 years as per the age of presentation to the hospital. Mean age was 8.7 years with a slight female preponderance. Diarrhea was the commonest presentation in group I and failure to thrive in group III. All patients in group III, had weight for age (w/a) _3rd percentile and majority (83 per cent) had short stature, with delayed puberty in all. All children had significant improvement in symptoms and growth on gluten restriction. None of the patients had been suspected to have celiac disease before, which signifies that in spite of increasing incidence of celiac disease, this disease is grossly under-diagnosed in North India where wheat is the staple diet. It is essential to make an early diagnosis of celiac disease in children to prevent growth delay.
Introduction Celiac disease (CD) also called non-tropical sprue; gluten sensitive enteropathy is characterized by villous atrophy due to chronic reaction to certain protein chains-glutens leading to malabsorption and other clinical features. In the last few years the prevalence of celiac disease seems to have increased.1 It is clear that subclinical and silent CD exists in a large subgroup of celiac population. Using antigliadin (AGA) or antiendomyseal (AEA) antibodies for initial screening, prevalence is found to be about 1:300 in Europe,2 which may be higher in countries similar to India, particularly in geographical regions where wheat is the staple diet. Celiac disease is frequently under-diagnosed because of its protean presentations. The age of onset ranges from infancy to old age. Complete resolution of symptoms occurs with a gluten-free diet. Celiac disease is documented in India in children and also in adults,3–5 but still it is not suspected routinely. None of the patients who were diagnosed to have celiac disease were referred with this diagnosis and all the patients had been to various doctors before presenting to our hospital. Although gastrointestinal symptoms predominate in the first year of life, confirmation is important to prevent significant growth problems. Symptoms vary
Correspondence: Dr Puneet Aulakh Pooni, 9/25 P.A.U. Campus, Ludhiana 141 004, Punjab, India. E-mail
[email protected].
with age group. Since no study was available from this state where wheat is a staple diet and this disease is grossly under-diagnosed, this study was carried out in confirmed cases of celiac disease to know the clinical features, signs, symptoms and growth including detailed anthropometry in patients according to various age groups. Materials and Methods This prospective study was jointly carried out by the departments of pediatrics and gastroenterology in a multispeciality, tertiary care, referral teaching hospital Dayanand Medical College & Hospital, Ludhiana over a period of 5 years. All patients under the age of 18 years diagnosed as celiac disease based on the basis of clinical features,6 demonstration of histological changes on intestinal biopsy while on gluten, and unequivocal clinical improvement on gluten-free diet were included. In 36 cases, tests for malabsorption including d-xylose etc were performed followed by biopsy but later on with the availability of initially anti-endomyseal antibodies (20 cases) and then antibodies against tissue transglutaminase (anti-tTG:15 cases), initial screening was done using antibody titer followed by biopsy. All patients were thoroughly examined for growth and degree of malnutrition and categorized as per guidelines of Indian Academy of Pediatrics into various grades of malnutrition, grades I, II, III, IV with weight 71–80 per cent, 61–70 per cent, 51–60 per cent, 550 per cent of 50th percentile of NCHS
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[email protected] doi:10.1093/tropej/fmi054 Advance Access Published on 9 June 2005
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Table 1 Clinical features of children with celiac disease Symptoms
Group I 55 years (n ¼ 16)
Group II 5–10 years (n ¼ 31)
Group III 410 years (n ¼ 24)
Total (per cent) n ¼ 71
Diarrhea Failure to thrive Abdominal distension Anorexia Foul stools Lethargy Vomiting Irritability Abdominal pain Increased appetite Pallor
15 8* 15 7 4 5 6 4 5 3 4
27 20 23 16 15 11 11 10 9 9 10
19 21* 14 17 11 12 7 10 10 4 11
61 49 52 40 30 28 24 24 24 16 25
Total
16
31
24
71 (100)
(86) (69)* (73.2) (56.4) (42.2) (39.4) (33.8) (33.8) (33.8) (22.5) (35.2)
*p50.05.
respectively. Three groups were made as per the age of the patients at the time of diagnosis, groups I, II, III including children less then 5 years, 5–10 years, more than 10 years respectively. Follow up evaluation was carried out at monthly intervals for 3 months and every 3 monthly thereafter maximum of 4 years. During each visit, clinical status and adherence to gluten-free diet was assessed. Clinical response to dietary restriction was documented in all the cases. Statistical analysis was carried out using -square to find the significance of factors.
Results There were total 71 patients diagnosed to be having celiac disease. The female to male ratio was 1.03:1 (a slight female preponderance). There were 16, 31 and 24 children in groups I, II and III respectively. Age ranged from 2 to 18 years with a mean age of 8.92 years. Detailed clinical symptoms and signs are shown in Table 1. Follow-up till 3 months could be done in all cases but long follow-up up to 4 years was done in 34 cases only. In group III failure to thrive was the commonest presenting feature, whereas in group I, diarrhea was the commonest symptom. On examination majority 65 (95.5 per cent) were having weight for age 580 per cent of 50th percentile of NCHS standards (protein energy malnutrition grade I). Forty-five patients (63.4 per cent) had weight for height 590 per cent. Malnutrition was more common in group III, where all patients had w/a 53rd percentile and 2/3rd of patients were having severe malnutrition i.e. w/a 550 per cent of the expected, whereas in groups I and II malnutrition was seen in 81 per cent and 90.3 per cent respectively. In group I, 75 per cent children had normal height Journal of Tropical Pediatrics
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whereas stunting was noted in 68 per cent in group II and 87.5 per cent in group III respectively (Table 2). Other clinical findings were pallor seen in nearly two-thirds of cases, followed by abdominal distention, wasted muscles, mouth ulcers, clubbing, edema, vitamin deficiencies of mainly A and K. Abdominal distention was more frequent in group II and group III. Pallor was commonest in group III. In all adolescents no sign of puberty was seen in any of the child. All patients had received multiple courses of antihelminthics and anti-giardiasis, and 18 patients (25.3 per cent) also had received anti-tubercular therapy empirically for suspecting abdominal tuberculosis without definite improvement. Anti-tTG levels were abnormal in all the cases tested (range from 16–150, normal 55iU/l). All patients showed total villous atrophy except for one patient in group I who showed partial villous atrophy. Age of clinical manifestations as noted by the parents was 51 years, 1–2 years, 2–4 years, 44 years in 6, 12, 21 and 11 patients respectively. Age of weaning varied from 4 months to 1 year. Hemoglobin levels were done in 43 cases with 20 cases having mild to moderate anemia, 11 patients had severe anemia. Average gain in weight was 2.17 kg in the first month of gluten-free diet. All patients were given a dietary chart form the dietary department mentioning the foods to be avoided (BROW-barley, rye, oat, wheat). Symptomatic improvement was noticed in all patients within 1 month of treatment, with increased activity and decreased irritability. At the end of 1st year mean gain in weight over the pretreatment weight was 6.22, 9.18 and 11.55 kg in groups I, II and III respectively. Group I reached their expected weight at the end of 6 months glutenfree diet, group II in 1 year and none of the patients in group III reached the expected weight and height 31
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Table 2 Clinical signs in children of celiac disease Signs
Group I 55 years (n ¼ 16)
Group II 5–10 years (n ¼ 31)
Group III 410 years (n ¼ 24)
Total (per cent) n ¼ 71
Weight:# 480 per cent 71–80 per cent 61–70 per cent 51–60 per cent 550 per cent Height:# 490 per cent 80–90 per cent 580 per cent* Pallor Abdominal distension Wasted muscles Mouth ulcers Clubbing Edema Vitamin deficiency
3 7 3 2* 1*
3 3 11 11* 3*
0 2 5 6* 11*
6 12 19 19 15
(8.4) (16.9) (26.7) (26.7)* (22.5)*
12 4* 0* 9 6 5 0 3 2 3
10 16* 5* 20 18 14 8 8 3 4
4 7* 13* 19 7 11 9 5 2 4
26 27 18 48 31 30 17 16 7 11
(36.6) (38.0)* (25.3)* (67.6) (43.6) (42.2) (23.9) (22.5) (9.8) (15.5)
Total
16
31
24
71 (100)
#
50th percentile of NCHS. *p 5 0.01.
till the follow up though all the patients gained weight significantly. Discussion This study was undertaken to determine the clinical and anthropometrical findings of celiac disease in patients attending DMC and hospital. No study is available of incidence and prevalence of celiac disease in India, but according to western data and studies of celiacs in India the incidence is on the rise. Our study suggests that celiac disease may be greatly under-diagnosed (as none of the patient was diagnosed from outside) and is relatively common. Mean age in the present study was 8.92 years which correlates with some other studies.3,7,8 Although classically the symptoms appear in 9–18 months.9 In developed countries the diagnosis is usually made 6 months from the onset of symptoms,7–10 but in the majority of studies there is a delay varying from 2–6 years from the appearance of symptoms.7 In other studies where diagnosis is made earlier the mean age was less, varying from 1.5 years to 4 years. 8,10,11 In this study no child was less than 2 years of age whereas in some studies 32.6 per cent patients were 51 year, 77 per cent less than 2 years.11,12 This is probably because in developing countries there are other causes of chronic diarrhea in children and infections are more common in infancy so celiac is missed. Overall there has been a trend for the diagnosis to be made at a later stage 32
from 52 years to 44 years, and mean age is showing increasing trend, because of diagnosis of less typical cases at an older age and also due to a steady rate of diagnosis of cases with a classic clinical picture. There is a marked increase in late beginning forms and atypical forms.11,13–15 The classical triad of growth failure, chronic diarrhea and abdominal distension is more frequently seen but atypical monosymptomatic cases are increasingly seen particularly constipation and anemia. However, to prevent significant growth problems in infants, confirmation of celiac disease is important.12 With age, presentation becomes more subtle. On examination only 8.4 per cent children had normal expected weight, this was even more marked in older children (410 years), in which group no child has normal weight and two-thirds falling in moderate to severe malnutrition group. The majority of the children (83 per cent) in group III (410 years) had stunting, which was less common in other groups. These figures are higher than reported previously;12 this may be because patients were diagnosed late. In the older children main clinical finding was stunting, aphthous ulcers and pallor. All children in the third group had delayed puberty, which is reported before also.10 Symptom less celiac disease is a more common cause of short stature then is hypopitutarism.10 It has been observed that though growth failure and chronic diarrheas are important features there is a diminishing trend for chronic diarrhea when symptoms were distributed Journal of Tropical Pediatrics
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by year of diagnosis.13,16 Twenty-five per cent patients may present with severe symptoms. In this study in the higher age group, 8 children presented in emergency with extreme weakness and inability to walk. Typical clinical symptoms are seen in younger children, but in older children they may be completely asymptomatic except for severe growth retardation, and celiac disease should always be considered in differential diagnosis of retarded growth and bone age. In developing countries several conditions give rise to total villous atrophy and using it as diagnostic criteria may lead to over diagnosis of celiac disease. Immunological tests are very useful under these conditions to prove the diagnosis.17 Antigliadin antibodies (AGA) have high sensitivity (98 per cent) and specificity (90 per cent) and are an ideal adjunct to modified ESPGAN criteria.18 With the introduction of AGA assay, number of children diagnosed with celiac disease each year has increased by 3 times.16 Diagnosis and screening for celiac disease has been dramatically facilitated by serological tests like tTG, although biopsy and demonstration of characteristic histological lesions remains definitive diagnostic investigation. Treatment with gluten-free diet is effective but requires good patient compliance and monitoring to succeed. The use of screening tests is cost-effective. It is obvious from this study that celiac disease is still grossly under-diagnosed and that it is essential to make the diagnosis at the earliest opportunity to prevent stunting and long term complications. tTG should be a part of routine investigation of any child presenting with failure to thrive, biopsy is needed for positive cases for confirmation of celiac disease. References 1. Rostami K, Mulder CJ, Werre JM, van Beukelen FR, Kerchhaert J, Crusius JB, Pena AS, Willekens FL, Meijer JW. High prevalence of celiac disease in apparently healthy blood donors suggests a high prevalence of undiagnosed celiac disease in the Dutch population. Scand J Gastroenterol 1999; 34: 276–79. 2. Not T, Horvath K, Hill ID, Partanen J, Hammed A, Magazzu G, Fasano A. Celiac disease risk in the USA: high prevalence of antiendomysium antibodies in healthy blood donors. Scand J Gastroenterol 1998; 33: 494–98. 3. Mohindra S, Yachha SK, Srivastava A, Krishnani N, Aggarwal R, Ghoshal UC, Prasad KK, Naik SR. Coeliac disease in Indian children: assessment of
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