Antonella Esposito

Natural History of Potential Celiac Disease in Children

BACKGROUND & AIMS The presence of celiac disease-associated autoantibodies (antiendomysium and antitissue transglutaminase [anti-TG2]) with normal jejunal mucosa indicate potential celiac disease. We performed a prospective, 3-year cohort study to determine the natural history of potential celiac disease in children. METHODS The study included 106 children with potential celiac disease, based on serology analysis and normal duodenal architecture. All but 2 carried the HLA-DQ2 and/or DQ8 haplotype. In all children, every 6 months, growth, nutritional parameters, celiac disease serology, and autoimmunity were investigated. In biopsies, γδ intraepithelial-, CD3-, and lamina propria CD25-positive cells were counted; duodenal deposits of anti-TG2 immunoglobulin A were detected. Biopsy analysis was repeated after 2 years on patients with persistent positive serology and/or symptoms. RESULTS Celiac disease was detected primarily in first-degree relatives and patients with autoimmune disorders (40.6%). A gluten-free diet was prescribed to 20/106 patients because of symptoms, which were relieved in only 11. Eighty-nine of the 106 patients entered the follow-up study, with normal daily consumption of gluten. During the follow-up antibodies disappeared in 14.6% and fluctuated in 32.6%. Villous atrophy was observed in 12/39 patients (30.8%) who underwent a repeat biopsy. CONCLUSIONS Most children with potential celiac disease remain healthy. After 3 years, approximately 33% of patients develop villous atrophy. Intestinal deposits of anti-TG2 IgA identify children at risk for villous atrophy.

Osteoporosis and Psoriatic Arthritis

Osteoporosis (OP) is a skeletal disorder characterized by compromised bone strength that predisposes to an increased risk of fracture. The prevalence of OP in the general population is very high as established in several studies, and OP represents one of the possible aspects of bone involvement in arthritis. In psoriatic arthritis this involvement is particularly complex because it affects not only mechanisms of bone loss but also of bone formation. We will discuss these aspects and the available epidemiological data.

The influence of gluten free diet on quantitative ultrasound of proximal phalanxes in children and adolescents with type 1 diabetes mellitus and celiac disease

A reduced bone mineral density has been reported in patients with untreated celiac disease (CD) as well as in patients with poorly controlled type 1 diabetes mellitus (T1DM). The aim of this study was to evaluate the bone mineral status by phalangeal quantitative ultrasound in 52 children and adolescents with both diseases (mean age 13.3+/-4.9 years). As a control group 50 patients with T1DM and no CD (age 12.2+/-4.0 years) were studied. The following bone parameters, amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) were considered and expressed as z score. Compliance to gluten free diet and long term glycemic control (mean of four determinations of HbA1c in the last year) were also assessed. The lowest mean AD-SoS z score values were found in patients with T1DM and CD, who reported transgressions to gluten free diet and exhibited positivity for serum anti-tissue transglutaminase antibodies (tTG) and/or endomysial antibodies (EmA), compared with patients with occasional transgressions but negative for anti-tTG and/or -EmA, patients strictly adherent to the diet, and patients who suffered only from diabetes (ANOVA p=0.021). No difference was found between patients with diabetes alone and patients with both diseases strictly adherent to gluten free diet. Prevalence of osteopenia (z AD-SoS values <-2 SD) was higher in patients with T1DM and CD and poor compliance to the diet (45.5%) compared with patients with T1DM (8%) or patients with both diseases strictly compliant to diet (12.9%) (p=0.015). A negative correlation between Ad-SoS z score and HbA1c (r -0.236, p=0.036) was found when patients with T1DM and patients with T1DM and CD, who strictly adhere to the diet, were pooled. In conclusion the quality of bone as assessed by phalangeal ultrasound in patients with T1DM and CD, who strictly adhere to gluten free diet, is similar to that found in T1DM patients. A higher prevalence of osteopenia is present in patients with both diseases who reported habitual transgressions to gluten free diet. The gluten free diet, as well as the optimization of glycemic control, plays an important role in preventing the osteopenic status caused by the clustering of these two chronic diseases.

Dietary calcium intake and serum vitamin D are major determinants of bone mass variations in women. A longitudinal study.

Background and aims: Bone mineral density (BMD) is one of the main determinants in the pathogenesis of fractures. However, data on factors predicting longitudinal variations in BMD are still limited and incomplete. Such data would be of great importance in order to better focus prevention strategies in both the clinical setting and at the population level. The aim of the study was to investigate the predictive value of both serological and questionnaire variables for bone mass variations in healthy women participating in a population-based longitudinal study carried out in Napoli, Italy. Methods: High completion rate (85.2%) and adequate sample size were obtained: 139 women (45 to 79 years of age) were examined at study entry and then again after two years (24±2 months) following the same protocol. They underwent medical examination, questionnaire, anthropometric measurements, blood sampling and urine collection. BMD was measured by dual energy X-ray absorptiometry (DEXA) at the lumbar spine (L1-L4) and femoral neck. Data analysis included calculation of the percent variation in BMD in the 2-year period. Longitudinal data underwent stepwise analysis for a global evaluation of mutual interactions between independent variables. Results and conclusions: Our findings indicate that dietary and serum calcium, and serum 25(OH)vitamin D are the only independent determinants of BMD variations at the lumbar and femoral level, respectively. While the pharmacological significance of calcium and vitamin D in the therapy of established osteoporosis is still controversial, the present longitudinal data evidence their role as essential nutrients in determining the natural history of BMD variations.

Bone involvement in clusters of autoimmune diseases: just a complication?

Bone loss, described in individual groups of patients with Type 1 diabetes (T1D), autoimmune thyroid disease (ATD) or celiac disease (CD) is usually viewed as a complication of these diseases. There is increasing evidence that alterations in the immune system may directly affect bone mass. Clustering of autoimmune diseases in the same individual might predispose to higher risk of osteopenia due to imbalance in immune regulation. The aim of this study was to evaluate bone involvement in clusters of the most common autoimmune diseases (T1D, ATD and CD) in children. The study was performed at a tertiary care center for the care of pediatric diabetes. One-hundred-two patients with T1D alone or associated with ATD and/or CD were studied; 13 patients had cluster of three autoimmune diseases. Amplitude-dependent speed of sound (AD-SoS) was measured by phalangeal quantitative ultrasound and expressed as standard deviation score (SDS). AD-SoS SDS < -2 was considered indicative of osteopenia. Osteopenia was equally distributed among children with T1D alone (8.1%), T1D associated with ATD (7.7%) or CD (10.3%), while it was 53.8% in patients presenting with three autoimmune diseases. Poor compliance to gluten-free diet increased osteopenia to 18.8% in patients with T1D and CD and 80% in patients with three autoimmune disorders. No difference among groups was found with regard to gluco-metabolic control, calcium metabolism, thyroid function. In conclusion bone impairment in multiple autoimmune diseases might be considered not only a complication due to endocrine or nutritional mechanisms, but also a consequence of an immunoregulatory imbalance. Alterations of homeostatic mechanisms might explain an imbalance of osteoclast activity leading to osteopenia.

Calcium and vitamin D intakes in children: a randomized controlled trial

BackgroundCalcium (Ca2+) and vitamin D (VitD) play an important role in child health. We evaluated the daily intake of Ca2+ and VitD in healthy children. Moreover, we demonstrate the efficacy of Ca2+ and VitD supplementation.MethodsDaily Ca2 + and VitD intake was evaluated in consecutive healthy children through a validated questionnaire. Subjects with <70% of dietary reference intakes (DRIs) of Ca2+ and VitD were invited to participate in a prospective randomized trial with 2 groups of nutritional intervention: Group 1, dietary counseling aiming to optimize daily Ca2+ and VitD intake plus administration of a commercially available Ca2 + and VitD supplementation product; Group 2, dietary counseling alone. At the enrollment (T0) and after 4 months (T1) serum 25(OH) Vitamin D levels were assessed.ResultsWe evaluated 150 healthy children (male 50%, mean age 10 years); at baseline a low VitD intake was observed in all subjects (median 0.79 μg/die, IQR 1.78; range 0.01-5.02); this condition was associated with Ca2+ intake <70% of the DRIs in 82 subjects (55%). At baseline serum 25(OH)D levels were low (<30 ng/ml) in all study subjects and after 4 months of nutritional intervention, a normalization of serum 25(OH)D levels (≥30 ng/ml) was observed in all children in Group 1 and in only one subject in Group 2 [Group 1: T1 33.8 ng/ml (IQR 2.5) vs Group 2: T1 24.5 ng/ml (IQR 5.2), p <0.001].ConclusionsAdequate Ca2+ and VitD intakes are difficult to obtain through dietary counseling alone in pediatric subjects. Oral supplementation with of Ca2+ and VitD is a reliable strategy to prevent this condition.Trial registrationThe study was registered in Clinical Trials Protocol Registration System (ID number: NCT01638494).

Fragility Fractures in Patients with Psoriatic Arthritis

Psoriatic arthritis (PsA) can have peculiar effects on bone, including mechanisms of bone loss such as erosions, but also of bone formation, such as ankylosis or periostitis. The aim of the present study was to describe the prevalence of fractures in patients with PsA as compared to healthy controls and to investigate determinants of fractures among cases. For both cases and controls, radiographs were read to identify vertebral fractures (VF), and the presence of femoral neck or other nonvertebral fractures was obtained from patients’ medical history. The prevalence of fragility fractures on radiographic readings did not differ between cases and controls. The number of subjects showing a VF was 33 (36%) among PsA patients and 36 (36%) among controls, with a prevalence of severe VF of 8% among cases and 4% among controls. Controlling for covariates in a logistic model, the only variables showing a significant correlation with the presence of nonvertebral fractures (NVF) were disease duration (p = 0.02), age (p = 0.03), and bone mineral density at femoral neck (inverse correlation, p = 0.04). Fractures should be carefully considered when evaluating the global picture of the patient with PsA for their contribution to the “fragility” profile.

[The complex interplay between health services administration, health professionals and patients. A challenge to take up].

The risk of loss of essential elements of our professionalism, such as sense of duty, altruism and collegiality, contributes to the difficulties in the interplay between health services administration, health professionals and patients. It is not enough to increase salaries or change organization models. It is also insufficient a generic reference to the values of our profession, but it is mandatory to overcome the self-referencing attitude of health professions.

Scores versus clinical profiles in therapeutic decisions: a positive example from the Italian Medicines Agency (AIFA) decisions in the field of osteoporosis

The attempt to mathematicise the cognitive approach to reality can be traced back to ancient Greek culture. Mathematics is a most powerful cognitive tool, whose potential is evoked by the name itself, asmathesismeans Blearning reality .̂ Actually, and surprisingly enough, reality reveals a peculiar correspondence between this approach and its intrinsic constitutive mechanisms, and the development of a favorable cultural context has disclosed the operative potential of this approach. The link between science and praxis has changed completely our relationship with reality. Mathematization has been a driving element also in the field of medical care, generating levels of progress that have recently involved also the strict clinical milieu. An example of this is the contribution to the definition of risk profile for a given patient to develop a given outcome. In Rheumatology, for instance, the use of diagnostic scores is employed to assess the activity profile of the disease in patients with Rheumatoid Arthritis (RA) using the 28-joint Disease Activity Score (DAS28) [1], or to calculate the risk of fragility fractures, using the fracture risk assessment tool (FRAX) [2]. The importance of these tools, however, has generated a tendency deserving careful analysis, as it goes beyond a specific medical field, and that, in our opinion, requires a more general evaluation for the possible problems that may ensue. Indeed, this issue evolves in a totally different way and with very specific implications when the approach is automatically extrapolated to the domain of therapeutic decision-making.