Clinico-laboratory profile of Seropositive Celiac Diseases in Severe Acute Malnutrition

Introduction: Celiac Disease shares clinical features with malnutrition and may be responsible for malnutrition. The objective of this study was to study clinico-laboratory profile of seropositive Celiac Diseases in Severe Acute Malnutrition. Material & Methods: The present study was a prospective, hospital based, observational study conducted at Malnutrition Treatment Centre (MTC) of tertiary care Pediatric hospital associated with government medical college of southern Rajasthan. The study was conducted over the period of one year from Dec. 2017 to Nov. 2018. Total 110 children with Severe Acute Malnutrition enrolled and screened for Celiac Disease on the basis of celiac serology (tTgIgA/IgG). Clinico-laboratory findings of celiac seropositive and seronegative patients were recorded and analysed statistically. Results: Celiacsero-positivity was observed in 30 cases (27.28%). Out of these seropositive cases 14 cases (46.66%) were seropositive for both tTg-IgA and IgG, while 9 cases (30%) were positive for only tTg-IgA and rest 7 cases (23.33%) were positive for only tTg-IgG. Most of the seropositive patients (12, 40%) were in age group of 4-5 years of age group. In seropositive cases recurrent blood in stool (54.45%) and recurrent diarrhoea (52.94%) were common clinical features at the time of admission. S. Vit. B12 & Folic Acid were low in all the patients but more seropositive patients showed low levels of S. Folic acid (P value <0.05). Conclusions: Recurrent diarrhoea and blood in stool were common presenting feature on admission in celiac seropositive patients suffering from severe acute malnutrition. Vit. B12 and Folic acid deficiency were also observed as a common finding in seropositive patients.


Introduction
The word "Celiac" came from Greek word "Koilia", which means belly or abdomen. Celiac Disease is also known as celiac sprue, non-tropical sprue, gluten intolerance, gluten sensitive enteropathy [1].
Celiac Disease is a common cause of mal-absorption in the children and adults. It is characterized by an enteropathy and lifelong intolerance to gluten initiated by ingestion of gliadin related prolamines from cereals such as wheat, barley and rye in genetically susceptible individual [2]. The intolerance to gluten results in immune-mediated damage to the mucosa of the small intestine characteristically inducing villous atrophy and crypt hyperplasia that resolve with the removal of gluten from the diet [1].
Exact incidence of disease in India is not known. CD is estimated to constitute 26% of all cases of malabsorption syndrome or 4-5% of all chronic diarrheas, In PGI, Chandigarh, 20-40 new patients are seen every year and CD constitutes 7% of indoor admissions and about 5% of the patients attending Pediatric Gastroenterology clinic [10].
Nutrition in Celiac Disease is an important issue. When someone who has Celiac Disease consumes food containing gluten, it reacts by attacking the intestinal villi.
Eventually, those tiny tentacles can be completely flattened, leaving them unable to do their job of absorbing nutrients. It doesn't matter how well a person eat if villi are destroyed by untreated celiac disease he is almost certain to be malnourished [11][12][13].
The clinical features of Severe Acute Malnutrition (SAM) often overlap with the common manifestations of Celiac Disease such as recurrent diarrhea, failure to thrive, vomiting, abdominal distension, anemia and weight loss [14][15]. As per NFHS-4 (2015-16) Severe Acute Malnutrition afflicts nearly 7.5% of children below 60 months of age in India [16].
Celiac disease could be major contributor or co-morbid condition in children with Severe Acute Malnutrition. This study was designed to evaluate the clinicolaboratory profile of seropositive Celiac Disease in children suffering from Severe Acute Malnutrition in 1-5 years age group.

Materials & Methods
The present study was single centric hospital based observational prospective study, conducted at Malnutrition Treatment Center (MTC) attached with tertiary care pediatric hospital associated with Government Medical College of Southern Rajasthan. The study was conducted during Dec. 2017 to Nov. 2018.
Study subject: All the children of 1-5 years age group suffering from Severe Acute Malnutrition (SAM) admitted in Malnutrition Treatment Centre. 3. Patients with known celiac serology.
Intervention: Prior approval for ethical clearance was sought from Institutional Ethical Committee. After obtaining informed written consent from both the parents, patients were enrolled for the study.
Detailed clinical and dietary history followed by anthropometric measurements and examination was done.
Blood sample was collected for relevant investigations. Celiac serology was accessed by screening for tissue trans-glutaminase IgA/IgG by ELISA method (Aeskulisat tTg-IgA/ tTG-IgG new generation antigen based kit by Aesku. Diagnostics. Gmbh & Co. Kg). As per manufacturer manual of the kit cut off value for seropositivity for tTg-IgA/IgG was >18 U/ml (As per manufacturer manual of the kit -normal range for tTg-IgA & tTg-IgG: 12-18 unit/ml) [17].
All the collected data were managed and analyzed with standard software (SPSS Version 20). P-value of <0.05 was considered significant.

Results
Total 110 children with Severe Acute Malnutrition in age group 1-5 years, admitted in MTC were enrolled and screened for celiac serology. Out of these 110 cases celiac serology was positive in 30 cases with sero-positivity of 27.28%. Total Seropositive *Cut-off values: tTg-IgA/tTg-IgG = >18 U/ml (As per manufacturer manual for the kit) [17].

12-18
Mean Age (Months) of starting Gluten containing diet The mean age of starting gluten containing diet in seronegative and seropositive gro respectively. This difference was statistically insignificant (P

Figure-2: Mean tTg sero
The mean sero-titre of tTg-IgA and IgG i Irritability (80%) and anorexia (76.47%) were common clinical features in seronegative cases while in seropositive cases recurrent blood in stool (54.45%) and recurrent diarrhoea admission (P value <0.05). In only tTgwhile in tTg-IgG seropositive cases recurrent blood in stool (21.43%) was common (P In seropositive cases chelosis of tongue was common sign (50%) followed by nail changes (30.76%) and pallor (27.05%) but there was no statistically significant difference (P value >0.05) among the clinical signs between seropositiv seronegative groups ( The mean age of starting gluten containing diet in seronegative and seropositive group was 8.47( respectively. This difference was statistically insignificant (P-value>0.05) ( Table-5).

sero-titre according to duration of gluten containing diet ingestion
IgA and IgG increases with the duration of gluten containing diet consumption Irritability (80%) and anorexia (76.47%) were common clinical features in seronegative cases while in seropositive cases recurrent blood in stool (54.45%) and recurrent diarrhoea (52.94%) were common clinical features at the time of -IgA seropositive cases common clinical feature was recurrent diarrhea (17.65%) IgG seropositive cases recurrent blood in stool (21.43%) was common (P value <0.05) ( Table   In seropositive cases chelosis of tongue was common sign (50%) followed by nail changes (30.76%) and pallor (27.05%) but there was no statistically significant difference (P value >0.05) among the clinical signs between seropositiv titre according to duration of gluten containing diet ingestion ncreases with the duration of gluten containing diet consumption (Figure-2). Irritability (80%) and anorexia (76.47%) were common clinical features in seronegative cases while in seropositive cases (52.94%) were common clinical features at the time of IgA seropositive cases common clinical feature was recurrent diarrhea (17.65%) value <0.05) ( Table-6).
In seropositive cases chelosis of tongue was common sign (50%) followed by nail changes (30.76%) and pallor (27.05%) but there was no statistically significant difference (P value >0.05) among the clinical signs between seropositive and

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April 2019/ Vol 6/ Issue 04  In seropositive cases folic acid deficiency was present in 30% (9 out of 30) children while in seronegative cases it was present in 6.25% (5out of 80) children. The difference observed in folic acid deficiency between seropositive and seronegative cases was statistically significant (P value<0.05) (Figure-3).

Figure-4: PBF-type of anemia in cases
Celiac Disease is a common disorder in children with variable presentation. Clinical manifestation of Celiac Disease and Severe Acute Malnutrition (SAM) in overlap each other. Celiac Disease may be underlying cause responsible for Malnutrition in these children. Purpose of this study was to evaluate the laboratory profile of seropositive Celiac Disease in children of 1 to 5 years age suffering from Severe prevalence of Celiac Disease in our study among the children suffering from severe acute malnutrition was 27.28% (30 out of 110). Out of these seropositive cases 7 patients (23.33%) showed only gy and these patients may have underlying IgA deficiency and may be missed if Prevalence reported by Kumar P et al was 13.1% (sero positive and biopsy confirmed) among the SAM children [14]. Sero-prevalence for Celiac Disease reported by Beniwal N et al was 15.38% while prevalence of biopsy confirmed Celiac disease was 14.42% among the SAM children [15]. We compared various parameters in Celiac Disease seronegative and seropositive cases. Sero-positivity was more in males as compared to females. Similarly male preponderance in sero-positivity was reported by Kumar Pet al [14] and Sharma M et al [18]. This suggests gender biasness in society as more male children brought for admission as compared to females.
Celiac Disease sero-positivity was maximum in 4 years age groups, suggesting cumulative effect of gluten in ingested diet with the age. Microcytic hypochromic anemia was more common finding in seronegative cases (66.25%) than seropositive cases (50%), while normocytic normochromic more common in seropositive cases but the difference between two groups was Prevalence reported by Kumar P et al was 13.1% (seropositive and biopsy confirmed) among the SAM prevalence for Celiac Disease eported by Beniwal N et al was 15.38% while prevalence of biopsy confirmed Celiac disease was 14.42% among the SAM children [15]. We compared various parameters in Celiac Disease seronegative and positivity was more in males as pared to females. Similarly male preponderance in positivity was reported by Kumar Pet al [14] and This suggests gender biasness in society as more male children brought for admission as ositivity was maximum in 4-5 years age groups, suggesting cumulative effect of gluten in ingested diet with the age. Anthropometric measurements were comparable in sero-nergative and sero-positive cases without statistical significant difference. Anthropometric measurements were consistent with Severe Acute Malnutrition. There was no significant difference in mean age of starting gluten containing diet in sero-negative and sero-positive cases. The mean age of starting gluten containing diet in seropositive cases was 8.35±2.15 months. Beniwal N et al [15] reported mean age of starting gluten containing diet in Celiac Disease children of 10.33±5.20 months.
In our study mean age of starting gluten containing diet in sero-positive cases was less because most of the enrolled cases were between 1-2 years of age. We also observed that mean titre of tTg-IgA and IgG increased with duration of gluten containing diet consumption which is suggestive of cumulative effect of gluten with duration of gluten ingestion.
We observed that recurrent diarrhea was more common clinical features at the time of admission in seropositive cases in comparison to seronegative cases (Pvalue <0.001). In only tTg -IgA sero-positive cases common clinical feature was recurrent diarrhea while in tTg-IgG sero-positive cases recurrent blood in stool was common clinical feature. Only tTg-IgG seropositive cases may have underlying IgA deficiency leading to recurrent invasive GI infection causing recurrent blood in stool.
In these patients serum IgA estimation needed to rule out IgA deficiency. Kumar P et al [14] and Beniwal N et al [15] reported chronic diarrhea as a common clinical feature of Celiac Disease in children suffering from Severe Acute Malnutrition.
We observed that in sero-positive cases chelosis of tongue was common (50%) clinical sign followed by nail changes (30.76%), pallor (27.05%), hair hypopigmentation(26.15%) and skin change (21.72%), but there was no statistical significant difference (P-value >0.05) among the clinical signs between sero-positive and sero-negative cases. All the clinical signs were consistent with signs of Severe Acute Malnutrition.
We analyzed hematological parameters (Hb, Hct, MCV, MCH, MCHC) and observed that the microcytic hypochromic anemia was common in all the malnourished children.
In this study we assessed for Vit.-B12 and Folic Acid deficiency status by estimation of S.Vit.-B12 and Folic acid levels. Both seropositive and seronegative cases were Vit-B12 and Folic acid deficient (S. Vit.-B12 levels <200 pg/dl and Folic Acid <3ng/dl) but difference of Vit.
B-12 in between two groups was statistically insignificant but difference of Folic Acid deficiency was statistically significant (P-value <0.05) between two groups. Macrocytic anemia in PBF was found in 10% of seropositive cases and only in 3.75% of seronegative cases. This is suggestive that S.Vit.-B12 and Folic Acid deficiency was more in seropositive cases. Subclinical hypothyroidism was reported in both seronegative (5%) and seropositive (13.33%). Although subclinical hypothyroidism was reported more in seropositive cases than seronegative but this difference was statistically insignificant (P value >0.05). So in our study we observed that Celiac Diseases should be suspected and may be diagnosed in children suffering with Severe Acute Malnutrition on the basis of clinical features and Celiac Disease serology (tTg-IgA/IgG). By early screening and sero-diagnosis of Celiac Disease in malnourished children we can prevent further growth and development related morbidity.
Limitation of the Study-Our study was solely based on clinical features and serology for diagnosis of Celiac Disease. We were not able to do upper GI endoscopy for duodenal biopsy or HLA-DQ2/DQ8 typing for confirmation because of non-availability/feasibility at our centre.

Conclusion
Sero-positivity of Celiac Disease observed in children of 1-5 years age, suffering from Severe Acute Malnutrition was 27.28% in our study. Recurrent diarrhea was found to be common clinical features at the time of admission in sero-positive patients. In tTg -IgA sero-positive cases recurrent diarrhea was common clinical feature while in tTg-IgG sero-positive cases recurrent blood in stool was common. Macrocytic anemia in peripheral blood film associated with S. Vit. B12 & Folic acid deficiency was more common in celiac seropositive children with severe acute malnutrition. This study enforces the existing knowledge that we should have high index of suspicion for celiac disease in children suffering from severe acute malnutrition who