"Geographical distribution of risk genotypes in pediatric patients with celiac disease in Spain".

Celiac disease is strongly associated with HLA DQ, specifically with haplotypes. DRB1*03-DQA1*05:01/DQB1*02:01 (DQ2.5),DRB1*07-DQA1*02:01/DQB1*02:02 (DQ2.2), DRB1*11-DQA1*05:05/DQB1*03:01 (DQ7.5), and DRB1*04-DQA1*03:01/DQB1*03:02 (DQ8). The distribution of these risk haplotypes in patients with celiac disease is different in the geographical areas investigated. A high frequency of DRB1*07- DQA1*02:01/DQB1*02:02 (DQ2.2) and DRB1*11-DQA1*05:05/DQB1*03:01 (DQ7.5), has been described in Southern Europe. We analyzed 2102 confirmed CD cases with information on both DQB1* alelles and their distribution by geographical area in Spain. According to the presence of this haplotype in one or two chromosomes, the genotype is classified in: DQ2 homozygous, DQ2 heterozygous (cis or trans), DQ8 homozygous, DQ8/DQ2.5, DQ 2.2 homozygous and genotype known as "half DQ2". Two different patterns of risks related to CD were identified. In the Basque Country and Navarre, the Mediterranean Area (Aragon, Catalonia, Valencia, Balearic Islands, and Murcia), the South of Spain (Andalucía and Extremadura), and the Canary Islands, higher frequency of DQ2.5 trans, and more than 80% of DQ2.5/DQ2.2 homozygosis were described. The Cantabrian Coast (Cantabria, Asturias, and Galicia) and Central Areas (Castilla-León and Castilla-La Mancha) showed a higher percentage of DQ2.5/DQ2.5 homozygosis and a lower DQ2.5 in trans frequency, as in Northern Europe. Madrid has an intermediate model between the two described above. 17 cases (0.8%) did not carry any CD risk haplotypes.

Correlation of Anti-Tissue Transglutaminase Antibodies With the Mucosal Changes and IgA Status of Children With Celiac Disease.

OBJECTIVES: The objective of this study was to assess the association between serological markers and changes of the intestinal mucosa in children with celiac disease (CD). METHODS: Clinical data from CD patients under 15 years old were collected from the participating centers in an on-line multicenter nationwide observational Spanish registry called REPAC-2 (2011-2017). Correlation between anti-tissue transglutaminase antibodies (t-TGA) levels and other variables, including mucosal damage and clinical findings (symptoms, age, and gender), was assessed. RESULTS: A total of 2955 of 4838 patients had t-TGA and a small bowel biopsy (SBB) performed for CD diagnosis. A total of 1931 (66.2%) patients with normal IgA values had a Marsh 3b-c lesion and 1892 (64.9%) had t-TGA Immunoglobulin A (IgA) ≥ 10 times upper limit of normal (ULN). There is a statistically significant association between t-TGA IgA levels and the degree of mucosal damage ( P < 0.001), the higher the t-TGA IgA levels the more severe the mucosal damage. Those patients who reported symptoms had more severe mucosal damage ( P = 0.001). On the contrary, there was a negative association between age and changes of the intestinal mucosa ( P < 0.001). No association was found with gender. Regarding the IgA-deficient patients, 47.4% (18 cases) had t-TGA Immunoglobulin A (IgA) ≥ 10 times ULN and a Marsh 3b-c lesion was observed in 68.4% (26 patients). No statistical relation was found between t-TGA IgG levels and the changes of the intestinal mucosa, neither a relation with age, gender, or symptoms. CONCLUSIONS: There is a positive correlation between t-TGA IgA levels and the severity of changes of the intestinal mucosa. Such correlation was not found in IgA-deficient patients who had positive t-TGA IgG serology. The results in this group of patients support the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition recommendations about the need of performing a SBB in IgA-deficient individuals despite high t-TGA IgG levels.

Predictors of Response to Exclusive Enteral Nutrition in Newly Diagnosed Crohn´s Disease in Children: PRESENCE Study from SEGHNP.

Exclusive enteral nutrition (EEN) has been shown to be more effective than corticosteroids in achieving mucosal healing in children with Crohn´s disease (CD) without the adverse effects of these drugs. The aims of this study were to determine the efficacy of EEN in terms of inducing clinical remission in children newly diagnosed with CD, to describe the predictive factors of response to EEN and the need for treatment with biological agents during the first 12 months of the disease. We conducted an observational retrospective multicentre study that included paediatric patients newly diagnosed with CD between 2014-2016 who underwent EEN. Two hundred and twenty-two patients (140 males) from 35 paediatric centres were included, with a mean age at diagnosis of 11.6 ± 2.5 years. The median EEN duration was 8 weeks (IQR 6.6-8.5), and 184 of the patients (83%) achieved clinical remission (weighted paediatric Crohn's Disease activity index [wPCDAI] < 12.5). Faecal calprotectin (FC) levels (µg/g) decreased significantly after EEN (830 [IQR 500-1800] to 256 [IQR 120-585] p < 0.0001). Patients with wPCDAI ≤ 57.5, FC < 500 µg/g, CRP >15 mg/L and ileal involvement tended to respond better to EEN. EEN administered for 6-8 weeks is effective for inducing clinical remission. Due to the high response rate in our series, EEN should be used as the first-line therapy in luminal paediatric Crohn's disease regardless of the location of disease and disease activity.

Spanish national registry of celiac disease: incidence and clinical presentation.

OBJECTIVES: The aim of this study was to assess the incidence and clinical pattern of celiac disease (CD) presently diagnosed in Spanish children. METHODS: A prospective, multicenter, nationwide registry of new cases of CD in children <15 years was conducted from June 1, 2006 to May 31, 2007. The parameters studied were age at diagnosis, sex, clinical symptoms, associated diseases, nutritional status, CD serology, histological lesions, and HLA-DQ2/-DQ8. The crude incidence rate of CD was calculated as new cases per 1000 live births and as new cases per 100,000 person-years <15 years of age. RESULTS: A total of 974 new cases of CD were included. The median age at diagnosis was 2.3 years; 39.5% of CD diagnoses occurred in the first 2 years, 42% between 2 and 6, and 18.4% from 6 to 15. Total number of cases in each age group was 385, 409, and 180, respectively. Regarding clinical presentation 70.9% showed classical symptoms, 21.9% were nonclassical, and 7% were asymptomatic. A total of 95.7% of 931, 94.7% of 611, and 86.7% of 651 children tested positive, respectively, for immunoglobulin A (IgA) anti-transglutaminase type 2 antibodies, IgA endomysial antibodies, and IgA anti-gliadin antibodies. Villous atrophy was observed in 92.4% and increased intraepithelial lymphocytes with crypt hyperplasia in 3.3%. Of the children, 55% had normal growth, and 3.4% were overweight. The HLA phenotype was DQ2: 88.3%, DQ2/DQ8: 8.4%, and DQ8: 2.3%. The incidence rate was 7.9 cases of CD per 1000 live births and 54 cases per 100,000 person-years. CONCLUSIONS: In Spain, the most frequent clinical presentation of CD is the classical form, mainly diagnosed during the first 2 years of life. The observed incidence of CD in Spanish children is much higher than the present CD incidence rates observed in other European countries.

Factors influencing pregnancy outcome in women with type 2 versus type 1 diabetes mellitus.

AIM: To compare pregnancy outcome and factors related to adverse perinatal outcome in women with type 1 versus type 2 diabetes mellitus (DM). MATERIAL AND METHODS: Multicentre retrospective study. Some 404 women were studied, 257 with type 1 DM and 147 with type 2 DM. Main outcome measures were rates of prematurity, macrosomia, instrumental deliveries, congenital malformations, need for neonatal intensive care unit (NICU), and perinatal mortality. RESULTS: There were no significant differences in pregnancy outcome between women with type 1 and type 2 DM, except for an increased rate of instrumental deliveries in women with type 1 DM. In these women, duration of diabetes was a significant predictor of caesarean delivery (OR =1.06 (1.01-1.12); p=0.02). Chronic hypertension was positively related to prematurity (p=0.02), and proved to be a significant predictor of birth weight lower than 2,500 g (OR =3.54 (1.4-12.49); p=0.043) and perinatal mortality (OR =10.6 (1.15-117.6); p=0.04). In women with type 2 DM, third trimester higher glycosylated haemoglobin was related to both prematurity (OR 4.9 (1.7-14.4; p=0.004) and low birth weight. Macrosomia was a significant risk factor for caesarean section. First trimester glycosylated haemoglobin was related to congenital malformations and proved to be a significant predictor of perinatal mortality (OR =2.4 (1.02-5.74); p=0.04). CONCLUSIONS: Duration of DM and chronic hypertension were the most influential factors related to adverse perinatal outcomes in women with type 1 DM, and poor metabolic control and macrosomia in women with type 2 DM.