Claudio Ughi

The coeliac iceberg in Italy. A multicentre antigliadin antibodies screening for coeliac disease in school-age subjects

Background: Recent studies suggest that coeliac disease (CD) is one of the commonest, life‐long disorders in Italy. The aims of this multicentre work were: (a) to establish the prevalence of CD on a nationwide basis; and (b) to characterize the CD clinical spectrum in Italy. Patients and methods: Fifteen centres screened 17201 students aged 6–15 years (68.6% of the eligible population) by the combined determination of serum IgG‐ and IgA‐antigliadin antibody (AGA) test; 1289 (7.5%) were IgG and/or IgA‐AGA positive and were recalled for the second‐level investigation; 111 of them met the criteria for the intestinal biopsy: IgA‐AGA positivity and/or AEA positivity or IgG‐AGA positivity plus serum IgA deficiency. Results: Intestinal biopsy was performed on 98 of the 111 subjects. CD was diagnosed in 82 subjects (75 biopsy proven, 7 not biopsied but with associated AGA and AEA positivity). Most of the screening‐detected coeliac patients showed low‐grade intensity illness often associated with decreased psychophysical well‐being. There were two AEA negative cases with associated CD and IgA deficiency. The prevalence of undiagnosed CD was 4.77 × 1000 (95% CI 3.79–5.91), 1 in 210 subjects. The overall prevalence of CD, including known CD cases, was 5.44 × 1000 (95% CI 4.57–6.44), 1 in 184 subjects. The ratio of known to undiagnosed CD cases was 1 in 7. Conclusions: These findings confirm that, in Italy, CD is one of the most common chronic disorders showing a wide and heterogeneous clinical spectrum. Most CD cases remain undiagnosed unless actively searched.

Introduction of Gluten, HLA Status, and the Risk of Celiac Disease in Children

BACKGROUND The relationship between the risk of celiac disease and both the age at which gluten is introduced to a childs diet and a childs early dietary pattern is unclear. METHODS We randomly assigned 832 newborns who had a first-degree relative with celiac disease to the introduction of dietary gluten at 6 months (group A) or 12 months (group B). The HLA genotype was determined at 15 months of age, and serologic screening for celiac disease was evaluated at 15, 24, and 36 months and at 5, 8, and 10 years. Patients with positive serologic findings underwent intestinal biopsies. The primary outcome was the prevalence of celiac disease autoimmunity and of overt celiac disease among the children at 5 years of age. RESULTS Of the 707 participants who remained in the trial at 36 months, 553 had a standard-risk or high-risk HLA genotype and completed the study. At 2 years of age, significantly higher proportions of children in group A than in group B had celiac disease autoimmunity (16% vs. 7%, P=0.002) and overt celiac disease (12% vs. 5%, P=0.01). At 5 years of age, the between-group differences were no longer significant for autoimmunity (21% in group A and 20% in group B, P=0.59) or overt disease (16% and 16%, P=0.78 by the log-rank test). At 10 years, the risk of celiac disease autoimmunity was far higher among children with high-risk HLA than among those with standard-risk HLA (38% vs. 19%, P=0.001), as was the risk of overt celiac disease (26% vs. 16%, P=0.05). Other variables, including breast-feeding, were not associated with the development of celiac disease. CONCLUSIONS Neither the delayed introduction of gluten nor breast-feeding modified the risk of celiac disease among at-risk infants, although the later introduction of gluten was associated with a delayed onset of disease. A high-risk HLA genotype was an important predictor of disease. (Funded by the Fondazione Celiachia of the Italian Society for Celiac Disease; CELIPREV ClinicalTrials.gov number, NCT00639444.).

Effect of celiac disease and gluten-free diet on growth hormone-binding protein, insulin-like growth factor-I, and insulin-like growth factor-binding proteins.

Failure to thrive is common in children with celiac disease. As alterations in the growth hormone-insulin-like growth factor I (GH-IGF-I) growth axis have been reported in these patients, we studied the behavior of growth hormone-binding proteins (GH-BPs I and II), IGF-I and its binding proteins in 14 children with celiac disease, either before or after a 6-month gluten-free diet. GH-BP II levels were significantly lower in patients during the active phase of the disease than after the diet or in comparison with control subjects, appropriate for age and sex. There was no difference in the GH-BP-I levels of patients and controls, nor did they change after the diet. Blood levels of IGF-I and IGFBP-3 were reduced before the diet in all patients while ligand blotting showed that IGFBP-2 and 1 were increased. All of these parameters normalized after the gluten-free diet. IGFBP-4 was not greatly influenced by the disease. Furthermore, we found a significant, positive correlation between GH-BP II and IGF-I or IGFBP-3 levels. The height standard deviation scores and body mass indices of the patients improved significantly after the diet. The body mass index significantly and positively correlated with GH-BP II, IGF-I or IGFBP-3 levels. In conclusion, our data show that celiac children had multiple alterations in the growth axis during the active phase of the disease which disappeared during the gluten-free diet.

Effectiveness and safety of ciclosporin as therapy for autoimmune diseases of the liver in children and adolescents

Background : Conventional treatment for autoimmune hepatitis results in a significant percentage of failures and several, poorly tolerated, side‐effects. Therapy for autoimmune cholangitis and giant cell hepatitis associated with autoimmune haemolysis is poorly documented. Ciclosporin is a promising treatment for all of these diseases.

Cholestasis as a presenting feature of acute Epstein- Barr virus infection

Biochemical evidence of hepatic involvement in Epstein-Barr virus disease is common but clinical features of cholestasis are rare in children. We present three children with cholestasis as a presenting feature of Epstein-Barr virus disease.

Changing Pattern of Coeliac Disease in Western Toscana

During the last few years various authors have reported significant variations in the coeliac disease (CD) incidence and presentation forms. In several British regions a decreased incidence of CD in the paediatric age was observed since 1974-1975 (1-5). Similar reports came from Finland, where a decline in CD rate had been observed together and also with a later presentation, often characterised by minimal or absent gastrointestinal symptoms, short stature, retarded puberty and anaemia (6). In 1987-1989, in the Paediatric Clinic of Pisa, an AGA assay was used for the CD screening; many CD cases were diagnosed in school children and teenagers with no gastroenteric manifestations, in contrast to our previous experience, when atypical forms of CD were rarely observed. During that period we also experienced a marked increment in the observed number of cases. To ascertain this fact we reviewed the CD cases diagnosed at the Department of Gastroenterology of the Paediatric Clinic in Pisa.

Platelet serotonin transporter in coeliac disease

Abstract We investigated a peripheral serotonergic marker, i.e. platelet tritiated imipramine (3H‐IMI) binding sites, which are part of the 5‐HT transporter complex similar to that present in the brain, in 20 patients affected by coeliac disease (CD), as compared with 20 healthy controls. Platelet membranes and 3H‐IMI binding were carried out according to a standardized protocol. The results showed that coeliac patients had significantly lower H‐IMI binding sites than controls. This finding would suggest the presence of a dysfunction at the level of the 5‐HT transporter that might underline the psychic disturbances frequently observed in coeliac patients.

Is childhood coeliac disease underdiagnosed

Sir: In the period 1978-1989 124 cases of coeliac disease (CD) aged f rom 7 months to 19 years (65 were younger than 2 years) were diagnosed in the Gastro-enterology Depar tment of the Paediatric Clinic of Pisa. In all cases the diagnosis of CD was based on a small bowel biopsy: 95 patients conformed to the criteria suggested by E S P G A N and 29 (all teenagers) to the recent suggestion of the Italian Society of Paediatrics Gastro-enterology Group [2]. Out of 124 coeliac children 95 were born in Pisa, Lucca and Livorno provinces, these areas being served by the Paediatric Clinic of Pisa to which all children with suspected CD are referred. Table i shows the number of live births, of coeliac children per year and the incidence of CD in the period 1978-1989. The incidences were 1 : 1611 and 1 : 535 for the 19781986 and 1987-1989 periods, respectively; the last 3 years coincided with the wide introduction of antigliadin antibodies ( A G A ) assay (both for IgA and IgG classes) for CD screening. In our experience (912 A G A assays) IgA class A G A has shown a 98.9% specificity and 88.6% sensitivity, while IgG A G A a 90.1% specificity and 100% sensitivity. Analysis of the above data suggests that A G A assay introduction caused a significant increase in the total number of CD diagnoses when compared to the previous years. In particular, we observed a more marked increase in late onset forms (from 3.4 to 9.7 new diagnoses/year) when compared to those of early onset (from 4.5 to 7.9 new diagnoses/year. We believe that the incidence of CD in Italy up to now assessed at around 1:2000 is probably underesti-

CO08 POTENTIAL CELIAC DISEASE IN A LARGE COHORT OF AT-RISK INFANTS: “THE ITALIAN BABY-STUDY ON WEANING AND CD RISK”

clinical psychological interview, which is then accompanied by standardized tests to complete the diagnosis. Results: The QoL of the patients who underwent the transplant improves in comparison to the pre-transplant stage. However, the anguish related both to the disease and the transplant, leaves a wound that needs to be healed. In this type of patients and in their relatives, the risk of developing a psychopathology, especially mood and anxiety disorders, is extremely high. Nevertheless, there is always a significant impact on both the short and long term development and psychological maturation, for two main reasons. The first: the arising of the chronic disease and the transplant per se are potentially traumatic. Confusion and dismay are the most typical feelings, both for patients and their relatives. This is an indication of a psychological wound that, if not treated, can disrupt the process of elaboration of the experiences connected to the transplant. In addition to that, this wound can cause a distortion in the relationship with the health staff, but also non-adherence to post-transplant treatments and the development of psychopathology. Moreover, the disease, the prolonged treatments, the recurrent checks and the drugs assumed daily after the transplant, can affect the building of the Self-Image. The latter is a particularly critical process in adolescence and therefore, teenagers are hampered in the development of friendships, in the building of affective relationships or in the planning of their future. Conclusion: In the most important international centres of reference, treatments are no longer just aimed at the tissue, organ or apparatus hit by the disease. There is an increasingly widespread trend to offer the person an overall treatment, where “to treat” becomes “to take care of”. In this perspective, the multidisciplinary approach to the patient and the relatives represents the best treatment method, aimed at reaching and keeping a good QoL.