Controversies in the treatment of mild asthma. What novelties and practical implications?

Mild asthma is prevalent in childhood and causes as many as 30%-40% asthma exacerbations requiring emergency visits. The management of "intermittent" and "mild persistent" asthma phenotypes is still a matter of debate, even if the role of inhaled corticosteroids, both continuous and intermittent, is a cornerstone in this field. Recent updates of the guidelines on the strategies to manage these patients are coming, since the role of inflammation in these asthma phenotypes is crucial, as well as the potential side effect and risks of short-acting beta 2 agonists overuse, prescribed as the only "as-needed" treatments. In this paper, we overview the new (r)evolution regarding intermittent and mild persistent asthma management.

Intermittent and mild persistent asthma: how therapy has changed.

In the last few years much attention has been focused on research on severe asthma and the role of biologicals in its treatment, also in children. However, mild asthma is way more common in childhood and still causes as many as 30-40% of asthma exacerbations requiring emergency consultation. The management of "intermittent" and "mild persistent" asthma phenotypes is still a matter of debate, even if the role of inhaled corticosteroids, both continuous and intermittent, is a cornerstone in this field. Nevertheless, updates on the strategies to manage these patients are coming, since evidence emerged on the role of inflammation also in these asthma phenotypes as well as on the potential side effect and risks of short-acting beta 2 agonists overuse, which is common in patients for which they have been prescribed as the only as-needed treatment. Unsurprisingly, international guidelines, including GINA, are starting to recommend associating a corticosteroid when using a reliver. In this paper we overview the (r)evolution regarding the management of intermittent and mild persistent asthma. We also focus on the importance of knowing the chemical and physical characteristics of drugs and inhaler devices in order to optimize the treatment and reach the distal airways, as well as of trying to achieve a good compliance to treatments, especially in adolescents, for which it is currently possible to rely also on new digital health technologies.

Evolution of congenital hypothyroidism in a cohort of preterm born children.

BACKGROUND: Congenital hypothyroidism (CH) is reported to be more common in preterm infants than in term infants, especially in sick preterm infants. Though a frequent possibility of transitory thyroidal alterations in this category of neonates, the evolution of CH to transient or permanent forms is unpredictable. METHODS: We retrospectively analyzed medical records of 28 preterm infants (<37 weeks gestation) who had exhibited a positive screening for CH at birth during the period 2000-2015 followed in our Center. Children were divided into three groups: permanent CH (PCH) with thyroid dysgenesis, PCH with eutopic normal-sized thyroid gland, and transient CH (TCH) with eutopic normal-sized thyroid gland. In all groups we described clinical and biochemical characteristics. Secondly, we analyzed the differences between patients with thyroid dysgenesis and patients with eutopic normal-sized gland and we compared PCH and TCH groups with normal-sized thyroid gland in order to identify clinical or biochemical data for early detection of transient forms. RESULTS: Of all patients, 21.4% showed thyroid dysgenesis while 78.6% presented eutopic normal-sized gland. Infants with thyroid dysgenesis had higher median (IQR) baseline s-TSH and levothyroxine (L-T4) dose per weight at 12 months (12 m-dose) than patients with eutopic normal-sized gland. At re-evaluation of the patients with eutopic normal-sized gland, 36% showed PCH and 64% had TCH. The age of the patients at the beginning of L-T4 treatment, gestational age (GA), birth weight, blood thyroid stimulating hormone levels (b-TSH) at first newborn screening (NBS), baseline serum thyroid stimulating hormone (s-TSH), and L-T4 12 m-dose were statistically different between the two groups. CONCLUSIONS: Our results demonstrate that factors as GA, birth weight, b-TSH levels at first NBS, baseline s-TSH, L-T4 12 m-dose and age at the start of the treatment may be considered useful predictive elements for the evolution of CH.

Case Report: Acute hemorrhagic edema of infancy (Seidlmayer purpura) - a dramatic presentation for a benign disease.

We present a case of an 11-month-old girl who was referred to our unit for an erythematous rash that appeared on the face and extremities. Personal and family history was not relevant. Laboratory tests were normal. During recovery, diameter and colour intensity of the cutaneous lesions increased, but after some weeks, lesions had a self-limited resolution without any treatment. Based on clinical and laboratory findings, a diagnosis of acute hemorrhagic edema of infancy (AHEI) was made.  AHEI is a rare cutaneous leukocytoclastic vasculitis that usually affects children aged between 4 and 24 months. Etiology is unknown but almost of 75% of cases are preceded by infectious episodes, vaccinations or use of medications. In contrast to the dramatic cutaneous eruption, clinical conditions are usually optimal. Classically, AHEI is characterized by a triad of symptoms: fever, edema and purpura. Skin lesions are erythematous, annular, medallion-like, purpuric plaques that have a rapid onset and appear on the face and extremities, sparing trunk and mucosal membranes. Initially interpreted as a variant of Henoch-Schönlein purpura, now it is considered a distinct disease. In the majority of cases the disease is benign and self-limited without a visceral involvement, so a conservative approach is most often chosen.

A case of Kallmann syndrome associated to a novel missense mutation of the FGFR1 gene.

BACKGROUND: Loss-of-function mutations of fibroblast growth factor receptor 1 gene (FGFR1) have been reported so far. These mutations have been described in the extracellular domain, consisting of three Ig-like domains in the single transmembrane helix and in the intracellular region, containing a tyrosine kinase domain and cause about 10% of all cases of Kallmann syndrome. FRGR1 mutations could be associated with non reproductive phenotype such as cleft palate and dental agenesis and a wide spectrum of reproductive phenotype. CASE REPORT: The patient, 17 years and 11 months old, was a Bulgarian male referred to our Pediatric Endocrinology Unit for pubertal failure and hyposmia. Clinical evaluation revealed a highpitched voice, gynecomastia and obesity. Hormonal study revealed hypogonadotropic hypogonadism. Molecular analysis, performed by Next Generation Sequencing and confirmed by Sanger sequencing, led to the identification of a novel and previously undescribed mutation c.1058 C>G (p. S353C) in heterozygous state on exon 8 of the FGFR1 gene. CONCLUSION: The novel mutation, that we found in a boy with Kallman syndrome, could destabilize the D3 immunoglobulin like receptor domain that is crucial for the FGF-FGFR interaction. (www.actabiomedica.it).

Acute abdominal pain in an adolescent girl with an ovarian yolk sac tumor.

Yolk sac tumor (YST) is a rare tumor that usually occurs in the first two decades of life. It is considered the second most common malignant germ cell tumor of the ovary, characterized by a rapid growth and a bad prognosis due to the frequent metastasis. We report the case of a 12-year-old girl who came to our observation for an acute abdominal pain. Clinical examination evidenced a vague mass in the suprapubic region and a lower abdomen tenderness, the US imaging revealed a complex lesion of the left ovary (19 x 13 cm) and the alpha-fetoprotein (AFP) resulted high (5858 ng/mL). Computed tomography (CT) revealed a large pelvic mass. The treatment consisted of debulking surgery of yolk sac tumor followed by 4 cycles of BEP protocol (Bleomycin, Etoposide, Cisplatin). After 3 years of follow-up there was no evidence of disease recurrence. (www.actabiomedica.it).

Prediction of Transient or Permanent Congenital Hypothyroidism from Initial Thyroid Stimulating Hormone Levels.

OBJECTIVE: To identify factors that discriminate between transient and permanent congenital hypothyroidism. METHODS: Retrospective evaluation of 58 children with congenital hypothyroidism and eutopic thyroid gland. Gender, gestational age, birth weight, TSH and serum thyroxine levels at diagnosis and L-thyroxine dose at 12 and 24 months of age were analyzed. RESULTS: Median (IQR) initial TSH levels were 73.3 (276.5) µIU/mL in permanent hypothyroidism and 24.24 (52.7) µU/mL in transient hypothyroidism (P =0.0132). The optimum cut-off value of initial TSH to predict transient hypothyroidism was 90 µIU/mL. Mean (SD) L-thyroxine doses at 24 months of age were 2.64 (0.98) µg/kg/day in permanent hypothyroidism and 1.91 (0.65) µg/kg/day in transient hypothyroidism. Requirement of L-thyroxine dose at 24 months of ≤0.94 µg/kg/day had the highest sensitivity (100%) to predict transient hypothyroidism. CONCLUSIONS: L-thyroxine doses at 24 months can predict transient hypothyroidism in patients with eutopic thyroid gland earlier than at 36 months.