ORIGINAL ARTICLE: GASTROENTEROLOGY
Spanish National Registry of Celiac Disease: Incidence and Clinical Presentation y
M Luz Cilleruelo, yEnriqueta Roman-Riechmann, zFelix Sanchez-Valverde, §Ester Donat, jj Jose Manuel-Ramos, ôEmilio Martı´n-Orte, #Maria-Jose Lo´pez, Dolores Garcı´a-Novo, yy Salvador Garcı´a, zzPilar Pavo´n, §§Manuel Martı´n, jjjjLuis Ortigosa, ôôJosefa Barrio, ## Carolina Gutierrez, Beatriz Espı`n, yyyGemma Castillejo, zzzLuis Pen˜a-Quintana, §§§ Idoia Hualde, jjjjjjjjjjMercedes Sebastia´n, ôôôCarmen Calvo, Sonia Ferna´ndez, ### Julio De Manueles, Honorio Armas, yyyyPedro Urruzuno-Tellerias, zzzz Mercedes Juste, §§§§Carlos Bouson˜o, and §Carmen Ribes-Koninckx
ABSTRACT 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 2–6
>6–15
years
FIGURE 1. Celiac disease patients: clinical presentation by age groups.
523
Copyright 2014 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
Cilleruelo et al
JPGN
Volume 59, Number 4, October 2014
TABLE 1. Clinical symptoms and signs by age groups Symptoms Diminished appetite Diarrhea Weight loss Abdominal distension Iron deficiency Elevated liver enzymes Aphthous ulcers Dental enamel defects
0–2 y n (%) 271/379 270/378 319/376 300/379 132/373 66/374 7/372 4/376
(71.5) (71.4) (85) (79) (35.3) (17.6) (1.9) (1)
nonclassical CD was the most frequent presentation form. There was a family history of CD (first-degree, second-degree, or both) in 19.4% of the cases. The symptoms and signs of CD were analyzed by sex and age groups. The only sex-related difference was weight loss (55.5% of boys vs 63% of girls, P ¼ 0.012). These results are presented by age groups categories in Table 1. All signs and symptoms were significantly more frequent in children diagnosed in the first 2 years of life except for dental enamel defects and recurrent oral aphthous ulcers. There was no difference between the age group categories in the frequency of iron deficiency. The most frequent symptom in children up to 6 years of age was abdominal distension, whereas diminished appetite and iron deficiency predominated in older children. Other nonclassical forms not included in Table 1 were extremely rare: dermatitis herpetiforme (0.6%), delayed puberty (0.4%), and arthritis (0.7%). Overall, 95.7% of 931, 94.7% of 611, and 86.7% of 651 children tested positive for immunoglobulin A (IgA) anti-transglutaminase type 2 antibodies (anti-TG2), IgA endomysial antibodies (EMAs) and IgA anti-gliadin antibodies (AGA), respectively. The figures for IgG-positive antibodies were 89.5% of 144, 72% of 65, and 87.5% of 120 for anti-TG2, EMA, and AGA, respectively. Thirty-one patients of 611, that is, 5.1%, tested negative for EMA; among these patients IgA deficiency was reported in 9 cases. If we do not consider the IgA-deficient patients, only 22 of 581 are EMA negative, which represents 3.7%. Thus, sensitivity would amount to 96.3%, which is in keeping with overall accepted sensitivity results for EMA. Histological examination showed villous atrophy in 92.4% of patients with CD: 19.3% had Marsh 3a, 46.4% Marsh 3b, and 28.4% Marsh 3c. Increased intraepithelial lymphocytes with crypt hyperplasia (Marsh 2) were found in 3.3% of patients with CD. Intestinal biopsy was not performed in 2% of the cases included in this study. The frequency of cases detected using the screening of relatives was 8%. Associated diseases were found in 8.6% of patients: IgA deficiency (3%), type 1 diabetes mellitus (2.2%), autoimmune thyroid disease (1.9%), Down syndrome (1.2%), and 1 case of Turner syndrome and Williams syndrome (Table 2). Except for IgA deficiency, the prevalence of associated diseases increased
>2–6 y n (%) 236/399 215/398 213/398 270/401 169/395 50/389 24/393 11/396
(59.1) (54) (53.5) (67.3) (42.7) (12.8) (6.1) (2.7)
>6–15 y n (%) 51/177 37/175 40/175 39/176 54/172 11/173 15/173 14/173
(28.8) (21.1) (22.8) (22.1) (29.6) (6.3) (8.6) (8)
P
Spanish National Registry of Celiac Disease: Incidence and Clinical Presentation y
M Luz Cilleruelo, yEnriqueta Roman-Riechmann, zFelix Sanchez-Valverde, §Ester Donat, jj Jose Manuel-Ramos, ôEmilio Martı´n-Orte, #Maria-Jose Lo´pez, Dolores Garcı´a-Novo, yy Salvador Garcı´a, zzPilar Pavo´n, §§Manuel Martı´n, jjjjLuis Ortigosa, ôôJosefa Barrio, ## Carolina Gutierrez, Beatriz Espı`n, yyyGemma Castillejo, zzzLuis Pen˜a-Quintana, §§§ Idoia Hualde, jjjjjjjjjjMercedes Sebastia´n, ôôôCarmen Calvo, Sonia Ferna´ndez, ### Julio De Manueles, Honorio Armas, yyyyPedro Urruzuno-Tellerias, zzzz Mercedes Juste, §§§§Carlos Bouson˜o, and §Carmen Ribes-Koninckx
ABSTRACT 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 2–6
>6–15
years
FIGURE 1. Celiac disease patients: clinical presentation by age groups.
523
Copyright 2014 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
Cilleruelo et al
JPGN
Volume 59, Number 4, October 2014
TABLE 1. Clinical symptoms and signs by age groups Symptoms Diminished appetite Diarrhea Weight loss Abdominal distension Iron deficiency Elevated liver enzymes Aphthous ulcers Dental enamel defects
0–2 y n (%) 271/379 270/378 319/376 300/379 132/373 66/374 7/372 4/376
(71.5) (71.4) (85) (79) (35.3) (17.6) (1.9) (1)
nonclassical CD was the most frequent presentation form. There was a family history of CD (first-degree, second-degree, or both) in 19.4% of the cases. The symptoms and signs of CD were analyzed by sex and age groups. The only sex-related difference was weight loss (55.5% of boys vs 63% of girls, P ¼ 0.012). These results are presented by age groups categories in Table 1. All signs and symptoms were significantly more frequent in children diagnosed in the first 2 years of life except for dental enamel defects and recurrent oral aphthous ulcers. There was no difference between the age group categories in the frequency of iron deficiency. The most frequent symptom in children up to 6 years of age was abdominal distension, whereas diminished appetite and iron deficiency predominated in older children. Other nonclassical forms not included in Table 1 were extremely rare: dermatitis herpetiforme (0.6%), delayed puberty (0.4%), and arthritis (0.7%). Overall, 95.7% of 931, 94.7% of 611, and 86.7% of 651 children tested positive for immunoglobulin A (IgA) anti-transglutaminase type 2 antibodies (anti-TG2), IgA endomysial antibodies (EMAs) and IgA anti-gliadin antibodies (AGA), respectively. The figures for IgG-positive antibodies were 89.5% of 144, 72% of 65, and 87.5% of 120 for anti-TG2, EMA, and AGA, respectively. Thirty-one patients of 611, that is, 5.1%, tested negative for EMA; among these patients IgA deficiency was reported in 9 cases. If we do not consider the IgA-deficient patients, only 22 of 581 are EMA negative, which represents 3.7%. Thus, sensitivity would amount to 96.3%, which is in keeping with overall accepted sensitivity results for EMA. Histological examination showed villous atrophy in 92.4% of patients with CD: 19.3% had Marsh 3a, 46.4% Marsh 3b, and 28.4% Marsh 3c. Increased intraepithelial lymphocytes with crypt hyperplasia (Marsh 2) were found in 3.3% of patients with CD. Intestinal biopsy was not performed in 2% of the cases included in this study. The frequency of cases detected using the screening of relatives was 8%. Associated diseases were found in 8.6% of patients: IgA deficiency (3%), type 1 diabetes mellitus (2.2%), autoimmune thyroid disease (1.9%), Down syndrome (1.2%), and 1 case of Turner syndrome and Williams syndrome (Table 2). Except for IgA deficiency, the prevalence of associated diseases increased
>2–6 y n (%) 236/399 215/398 213/398 270/401 169/395 50/389 24/393 11/396
(59.1) (54) (53.5) (67.3) (42.7) (12.8) (6.1) (2.7)
>6–15 y n (%) 51/177 37/175 40/175 39/176 54/172 11/173 15/173 14/173
(28.8) (21.1) (22.8) (22.1) (29.6) (6.3) (8.6) (8)
P
