Tommaso Aversa

Comparison between two maintenance feeding regimens after successful cow's milk oral desensitization

Cows milk allergy is common in infancy, and total avoidance of this food is the only effective approach. In alternative, oral immunotherapy has been proposed to achieve tolerance. Once desensitization is achieved, daily intake of milk is recommended to maintain it, but this may be impractical for children/parents. We assessed whether a twice weekly maintenance regimen is effective.

Comparative Evaluation of Therapy with L -Thyroxine versus No Treatment in Children with Idiopathic and Mild Subclinical Hypothyroidism

Background: The question of whether children with subclinical hypothyroidism (SH) should be treated or not is controversial due to the lack of studies on outcomes of SH children treated with L-thyroxine (L-T4) versus those receiving no therapy. Objectives: (a) To evaluate thyroid tests under L-T4 and after therapy withdrawal in 69 SH children (group A) and (b) to compare our results with those recorded in 92 untreated children (group B). Design: Group A children were treated for 24 months and TSH and FT4 levels 3 months after therapy withdrawal were compared with those measured in group B at the end of follow-up in order to investigate treatment effects. Results: The prevalence of children who had normalized TSH at the end of follow-up was higher in group A, but the prevalence of those who had normalized or maintained unchanged TSH was similar in the two groups, as was the prevalence of children who exhibited a TSH increase >10 mU/l. In group A, TSH values at 27 months were associated with baseline values. Conclusions: (a) Two-year treatment in SH children is unable to modify posttherapy outcome of hyperthyrotropinemia; (b) therapy is unable to prevent the risk of further TSH increase after treatment withdrawal, and (c) posttherapy TSH outcome is conditioned by baseline TSH.

Thyroid Function Patterns at Hashimoto’s Thyroiditis Presentation in Childhood and Adolescence Are Mainly Conditioned by Patients’ Age

Background: There are few studies investigating the factors which may affect different biochemical presentations of Hashimoto’s thyroiditis (HT) and these are frequently based on limited pediatric populations. Aims: (1) To assess the frequency of thyroid function patterns at HT diagnosis in 608 children and adolescents, and (2) to analyze the factors that affect thyroid status at diagnosis. Results: At presentation, test results showed euthyroidism in 52.1% of patients (subgroup A), overt or subclinical hypothyroidism in 41.4%, and overt or subclinical hyperthyroidism in 6.5%. The mean age of patients with thyroid dysfunctions (subgroup B) was significantly lower than that of subgroup A, and the rate of children below 10 years of age was significantly greater in subgroup B. Other variables related to thyroid function patterns were prepubertal status; association with either Down or Turner syndromes, which correlated with increased risk of thyroid dysfunctions, and association with other autoimmune diseases, which correlated with decreased risk of thyroid dysfunctions. None of the remaining factors analyzed were associated with increased risk of thyroid dysfunctions. Conclusions: Biochemical thyroid function patterns at HT presentation in childhood and adolescence are mainly conditioned by patients’ age.

Adherence to sublingual immunotherapy in preschool children.

Editor, Specific immunotherapy is the only effective causal treatment that can modify the natural history of respiratory allergy (1). This effect is important in children, where a secondary prevention is desirable. Sublingual administration (SLIT) is accepted as a valid therapeutic option (2), and children represent an ideal population for SLIT, because of the good safety profile (2). Nonetheless, as per all chronic treatments, adherence is essential, but no data are available in preschool children. We assessed the adherence to SLIT in children aged <6 yrs and analyzed the factors possibly affecting adherence itself. Children (age, 3–6 yrs) referred for respiratory diseases (bronchial asthma and/or rhinitis) and eligible for SLIT were enrolled. None had food allergy (possible confounding factor), and respiratory symptoms had to be present at least in the previous 6 months. The diagnosis of allergic asthma/ rhinitis was made according to guidelines (3, 4). Patients receiving SLIT were stratified according to age: group A (3£ yrs <4.0), group B (4.0£ yrs <5.0), group C (5.0£ yrs <6.0). All the procedures involved standard clinical approaches; thus, the study was simply notified to the Ethical Committee of the University of Messina, and all parents provided written informed consent. Children were followed up during the 2-yr observation period with 3-month regular visits. SLIT extracts were from Stallergénes, Lofarma, ALK– Abellò, Allergopharma. Parents were allowed to choose drops or tablets, and SLIT was given according to manufacturers’ recommendations. The administration technique was checked by pediatricians, using a placebo. Specific diary cards to assess the adherence (pre-compiled list), side effects, and reasons for discontinuation/temporary interruption of SLIT (free answers) were given to parents and collected at each visit. The time and reasons for interruption/discontinuation were carefully recorded. The remaining vials/tablets were checked at control visits. If >80% of the scheduled doses were taken, the patient was considered adherent. One hundred and fifty children (3–5.9 yrs, 86 boys) received SLIT for respiratory allergy (76% drops and 24% tablets). All suffered from allergic asthma and/or rhinitis from at least 6 months, and all received standard medications (antihistamines, intranasal corticosteroids, inhaled corticosteroids, bronchodilators). Mite SLIT accounted for 89.4% of prescriptions. Overall, 46% of 150 children discontinued SLIT. The percentage of discontinuations during the first year was significantly higher in group A than in groups B (52% vs. 18%, v = 12.7, p = 0.035) and C (52% vs. 13%, v 2 = 17.33, p = 0.032), whereas during the second year, there was no difference between groups (v 2 > 0.5). The reasons for discontinuation, as determined by parents’ interviews, are summarized in Table 1. The most common cause for withdrawal in group A was the subjective discomfort in keeping under the tongue drops/tablets, or children’s refusal, without apparent side effects. The refusal was generally attributed to unpleasant taste. For groups B and C, withdrawals were attributed to ineffectiveness, or to family problems, not better defined. All withdrawals occurred during the first 3 months of treatment in group A, and within the first 6 months in the other groups. In those patients who did not discontinue SLIT, short interruptions (all <5 days), as a

Outcomes of Children with Hashitoxicosis

Aim: To investigate hashitoxicosis outcome in 14 children with persistent absence of thyrotropin receptor autoantibodies who were followed for 1.3-8.8 years (mean 3.5 ± 2.5). Due to a more severe presentation, 4 patients required methimazole (subgroup A1), whilst in the remaining 10 cas es (subgroup A2) no treatment was given. Results: A definitive resolution of hyperthyroidism was recorded 8.3 ± 6.3 months after diagnosis, even though there was a wide variability between subjects (3-23 months). In subgroup A2, hyperthyroidism resolution occurred spontaneously and earlier with respect to subgroup A1 (4.8 ± 2.0 months after diagnosis vs. 17.0 ± 4.5, p = 0.00001). After hyperthyroidism resolution, no relapses were recorded in any patients. Hyperthyroidism duration positively correlated with thyroid peroxidase autoantibody (TPOAb) levels at presentation (r = 0.729, p = 0.002). Conclusions: In all the 14 hashitoxicosis children with persistently absent thyrotropin receptor autoantibodies, the hyperthyroid phase was widely variable and always followed by definitive resolution with no relapses and persistent euthyroidism or hypothyroidism. In the few patients with a more severe presentation, methimazole treatment was required, and definitive hyperthyroidism resolution was delayed. In this subgroup, TPOAb levels at diagnosis were higher than in the subgroup with less severe presentation and earlier hyperthyroidism resolution, suggesting a relationship between TPOAb levels and severity of the disease.

Hashimoto's thyroiditis in childhood: presentation modes and evolution over time

Aim of this survey is to report the most recent views about Hashimoto’s thyroiditis (HT) natural history according to the different presentations. In children presenting with either euthyroidism or subclinical hypothyroidism HT spontaneous course is frequently characterized by a trend towards deterioration of thyroid function, whereas in those presenting with overt hyperthyroidism a definitive resolution of hyperthyroid phase is to be expected. Another possible even though unusual outcome of HT is the conversion to Graves’ disease.

Treatment with omalizumab in a 16‐year‐old Caucasian girl with refractory solar urticaria

Based on recent evidence, including our results, we believe that the usefulness of the sIgE/total IgE ratio to predict tolerance to food allergens needs to be revisited in larger studies which can control for factors potentially influencing the results. In conclusion, in this cohort, the diagnostic performance of the OVA-sIgE/total IgE ratio was superior to sIgE or SPT to EW, OVA or OVM alone in predicting raw egg tolerance development in school-aged children and teenagers with IgE-mediated egg allergy. Acknowledgments The authors would like to thank Dr Paul Turner, MRC Clinician Scientist at Imperial College London, for his valuable comments on this letter.

Peculiarities of autoimmune thyroid diseases in children with Turner or Down syndrome: an overview

Aim of this commentary is to summarize the salient literature news on the relationships between autoimmune thyroid diseases (ATDs) and either Down syndrome (DS) or Turner syndrome (TS).According to literature reports both Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) are more frequent in children with DS or TS than in those without these chromosomopathies.An up-regulation of proinflammatory cytokines might be responsible for the enhanced susceptibility of TS children to ATDs, whereas a dysregulation of immune system may favor the development of ATDs in DS.In TS children biochemical presentation of HT is less severe than in peer controls. In both DS and TS GD picture at the time of diagnosis is not significantly different than in the pediatric general population.The evolution over time of GD in DS and TS does not differ from that observed in the pediatric general population, whereas the evolution of HT in both TS and DS is more severe than in girls without these chromosomopathies.Conclusions: The association with TS or DS is able to affect both epidemiology and course of ATDs by conditioning: a) an increased susceptibility to these disorders; b) a less severe biochemical presentation and a more severe evolutive pattern of HT in TS girls; c) a more severe biochemical presentation and evolution of HT in DS patients.

Underlying Hashimoto's thyroiditis negatively affects the evolution of subclinical hypothyroidism in children irrespective of other concomitant risk factors

BACKGROUND The pediatric literature does not contain any studies comparing the evolution of Hashimotos thyroiditis (HT)-related subclinical hypothyroidism (SH) with idiopathic SH longitudinally. AIM AND DESIGN In the present study, the two-year evolution of HT-related SH in 32 children with no concomitant risk factors (group A) was compared to that observed in 90 age-matched children with idiopathic SH (group B). The aim was to ascertain whether the association with HT could, per se, affect the evolution of thyroid status over time in SH children irrespective of other coexisting factors, such as thyromegaly, association with other autoimmune diseases, and/or concomitant therapies. RESULTS During the two-year follow-up, the percentage of children whose thyrotropin (TSH) values increased >10 mIU/L was significantly higher in group A (p<0.0005), whereas the percentages of those who either maintained a stable TSH (5-10 mIU/L) or normalized the TSH (<5 mIU/L) were significantly higher in group B (p<0.025). Moreover, the percentage of children who developed a pathological thyroid enlargement during follow-up was significantly higher in group A (p<0.0005). CONCLUSIONS The association with HT exerts a negative influence on the evolution over time of mild SH, irrespective of other concomitant risk factors. In children with mild and HT-related SH, the risk of a deterioration in thyroid status over time is high (53.1%), while the probability of spontaneous TSH normalization is relatively low (21.9%). In contrast, in children with mild and idiopathic SH, the risk of a deterioration in thyroid status over time is very low (11.1%), whereas the probability of spontaneous TSH normalization is high (41.1%).

Five-year prospective evaluation of thyroid function in girls with subclinical mild hypothyroidism of different etiology

AIM To follow-up for 5 years thyroid status evolution in 127 girls with mild (TSH 5-10 mU/l) subclinical hypothyroidism (SH) of different etiologies. PATIENTS The population was divided into two age-matched groups of 42 and 85 girls with either idiopathic (group A) or Hashimotos thyroiditis (HT)-related SH (group B). Group B was in turn divided into three subgroups, according to whether SH was either isolated or associated with Turner syndrome (TS) or Down syndrome (DS). RESULTS At the end of follow-up the rate of girls who became euthyroid was higher in group A (61.9% vs 10.6%), whereas the rates of patients who remained SH (55.3% vs 26.2%), became overtly hypothyroid (30.6% vs 11.9%) or required levothyroxine (l-T4) therapy (63.5% vs 23.8%) were higher in group B. Among the girls of group B, the risk of remaining SH or developing overt hypothyroidism was higher in the subgroups with TS or DS than in those with isolated HT. CONCLUSIONS Long-term prognosis of mild and idiopathic SH is frequently benign, even though a l-T4 treatment may be needed throughout follow-up in almost a quarter of cases; long-term prognosis is different in the girls with either idiopathic or HT-related SH; and the association with either TS or DS impairs the outcome of HT-related SH.