Technologies for Type 1 Diabetes and Contact Dermatitis: Therapeutic Tools and Clinical Outcomes in a Cohort of Pediatric Patients.

The increasing use of technological devices for the management of diabetes is related to the prolonged exposure of patients' skin to chemical and mechanical agents and, consequently, to the increased risk of developing dermatological complications. Among these, contact dermatitis is the most insidious skin disorder. Despite the magnitude of the issue, no universally accepted recommendations on the management of this common complication are currently available. Our observational study aimed to describe all the solutions adopted by patients and their caregivers to treat and prevent the appearance of contact dermatitis and to describe the clinical impact of this cutaneous complication. Twenty-one pediatric patients (mean age 12.1 ± 3.7 years) with type 1 diabetes were recruited in the study. The most common treatment used to treat acute skin lesions was the application of topical corticosteroids, sometimes associated with topical antibiotics (9.5%). In order to prevent the further appearance of dermatitis, the most frequently adopted measure was the use of hydrocolloid and/or silicone-based adhesives, followed by the application of protective barrier films. One patient reported benefit from the off-label use of fluticasone propionate nasal spray. However, only 52.4% of the study participants achieved a definitive resolution of the skin issue, and 38.1% of patients were forced to discontinue insulin pump therapy and/or continuous glucose monitoring. No differences were observed in glycated hemoglobin values between the period before and after the onset of contact dermatitis. Our study confirms the severity of this dermatological complication that may hinder the spread of new technologies for the management of diabetes. Finally, our findings highlight the importance of establishing close collaboration both with pediatric allergy specialists to prescribe the most suitable treatment and with manufacturing companies to ensure that adhesives of technological devices are free of harmful well-known sensitizers.

Long term treatment with omalizumab in adolescent with refractory solar urticaria.

BACKGROUND: Solar urticaria represents an uncomfortable form of chronic inducible urticaria. First and second-line treatments are ineffective in some patients, leading to an impairment in their quality of life. Omalizumab represents a safe therapeutic option in case of refractory solar urticaria. CASE PRESENTATION: We update a case of a 21-year-old Caucasian girl affected by solar urticaria from the age of 14. Poor disease control was achieved with standard or high-dose of H1-antihistamines. Several omalizumab courses, including a 1-year-long course, were practiced resulting in clinical remission and significant improvement in patient's quality of life. CONCLUSION: Our experience confirms the effectiveness and safety of omalizumab for the management of refractory solar urticaria. Future studies are awaited in order to monitor long term effects and chronic doses of this treatment, particularly in patients who need concomitant therapy with antihistamines.

Novel diagnostic techniques and therapeutic strategies for IgE-mediated food allergy.

Background: Immunoglobulin E (IgE) mediated food allergy is a potentially life-threatening condition and represents a heavy burden for patients and their families. Identification of the most suitable way for management of each patient has currently become the primary goal for physicians. Methods: This study reviewed the current literature related to IgE-mediated food allergy. Results: The use of innovative diagnostic tools, such as allergen-specific IgG4 determination, basophil activation test, and component-resolved diagnostics, is currently available to facilitate a proper diagnosis of food allergy. After several decades of "passive clinical management" of the disease, which was based only on avoidance of the allergenic food and the use of epinephrine in the event of anaphylaxis, there has been a switch to active treatment. The most recent evidence-practice guidelines strongly recommend the use of immunotherapy as an effective therapeutic option, particularly in cases of allergy to cow's milk, egg, or peanut. The use of omalizumab, in association with immunotherapy or alone, has been tested in several studies, and results on its effectiveness seemed to be encouraging. Other biologics, such as dupilumab, reslizumab, mepolizumab, and other anticytokines therapies, are being investigated. Another interesting future treatment strategy could be the use of DNA vaccines. Conclusion: In recent years, the management of IgE-mediated food allergy has greatly improved. Knowledge of pathogenetic mechanisms, understanding of the disease course, and the introduction of novel biomarkers led to more accurate diagnoses along with the active treatment of patients.

Biologics in food allergy: up-to-date.

Introduction: In recent years, the advent of immunotherapy has remarkably improved the management of IgE-mediated food allergy. However, some barriers still exist. Therefore, the effort of researchers aims to investigate new perspectives in the field of non-allergen specific therapy, also based on the current knowledge of the pathogenesis of this disease.Areas covered: This review aims to focus on the role of biologics as a treatment option in patients with IgE-mediated food allergy. These agents are characterized by their ability to inactivate the Th2 pro-inflammatory pathways. Biologics can be used both alone and in association with immunotherapy. Monoclonal antibodies targeting IgE, the IL-4/IL-13 axis, IL-5, and alarmins have been proposed and investigated for treating food allergy.Expert opinion: The clinical efficacy and safety of biologics have been demonstrated in several preclinical studies and randomized controlled trials. Future studies are still required to address current unmet needs, including the identification of the optimal dose to be used by ensuring the effectiveness of therapy.

Pubertal induction in girls with Turner Syndrome.

Turner Syndrome (TS) is the most common female sex chromosome aneuploidy in females, and patients may present with hypergonadotropic hypogonadism due to gonadal dysgenesis. Timing and modalities of pubertal induction in these patients is still a matter of debate. Aim of this review was to focus on the latest update on pubertal induction in TS. Based on literature data, the following practical approach to this issue is recommended. Pubertal induction should begin between 11 and 12 years of age, starting with low doses of estradiol to preserve height potential. Transdermal 17ß-Estradiol (17ß-E2) could represent the first-choice induction regimen as it is more physiologic compared to an oral regimen and avoids the first-pass mechanism in the liver. In the case of poor compliance, administration of oral 17ß-E2 or ethinyl estradiol could be offered. Incremental dose increases, approximately every 6 months, can contribute to mimic normal pubertal progression until adult dosing is reached over a 2- to 3-year period. Progestin should be added once breakthrough bleeding occurs or after 2 to 3 years of estrogen therapy or if ultrasound shows a mature uterus with thick endometrium. Treatment needs to be individualized and monitored by clinical assessment in relation to patient compliance and satisfaction. Well-designed prospective randomized clinical trials aimed to identify the best estrogen regimen for pubertal induction in TS girls are needed.

Direct drug provocation test for the diagnosis of self-reported, mild and immediate drug hypersensitivity reaction in children and adolescents: our real-life experience.

BACKGROUND: Approximately 10% of the parents report suspected drug hypersensitivity reactions to at least one drug in their children, but most of these reactions are not confirmed after an adequate diagnostic work-up. The diagnosis of drugs hypersensitivity is frequently laborious and based on anamnesis, skin tests, serum specific IgE research and drug provocation test. Nevertheless, drug provocation test is necessary to confirm or definitively exclude the diagnosis of allergy. Aims of our study were to evaluate the real incidence of drug hypersensitivity in a large pediatric population and the validity of a short diagnostic algorithm. METHODS: One hundred nine patients with a history of self-reported, immediate and mild drug hypersensitivity reactions to ß-lactam antibiotics, macrolides and non-steroidal anti-inflammatory drugs underwent drug provocation test without prior skin or blood tests. After one-year, a telephone questionnaire was conducted in order to evaluate patient's use of the tested drug and any reactions. RESULTS: Only 7 of the 109 patients (6.4%) resulted positive to drug provocation test. No severe reactions were reported. After the challenge, 64 patients took the culprit drug again within one year and only two reported a drug reaction. CONCLUSIONS: Drug hypersensitivity is highly overestimated. Our results prompt the opportunity to directly perform the challenge for those children with self-reported, mild and immediate drug hypersensitivity reaction.

Allergen Immunotherapy in children with respiratory allergic diseases.

Allergen immunotherapy (AIT) is a well-established treatment for allergic respiratory diseases. It represents a cornerstone in the clinical management of allergic children since it is the only curative option to date able to modify the natural history of Ig-E mediated allergic diseases. Through a well-defined immunologic mechanism, AIT promotes regulatory T cells and cuts down the immune response induced by allergens. According to current guidelines based on up-to-date evidence, AIT should be offered to children with moderate-severe allergic rhinitis and/or controlled asthma starting from 5 years of age, further to an adequate risk-benefit assessment which includes patient's adherence to the treatment and a proper selection of the right product. Younger age and mild disease could be considered based on an individual evaluation. Both subcutaneous (SCIT) and sublingual (SLIT) routes of administration have a good efficacy and safety profile with safer outcomes for SLIT compared to SCIT. Only standardized products with documented evidence of clinical efficacy should be used. Although AIT is used worldwide, there are still gaps and limitations, including the lack of reliable biomarkers predictive of the clinical outcome. Novel adjuvants are currently under investigations to boost the strength and efficiency of the immune response, as well as new formulations with better efficacy and better patient's adherence to the treatment. Herein, we aim to provide an overview of current key evidence with major regard to clinical practice as well as knowledge gaps and future research needs in the context of AIT in children with respiratory allergic diseases.

Omalizumab in children and adolescents with chronic spontaneous urticaria: Case series and review of the literature.

The recent EAACI/GA2 LEN/EDF/WAO guidelines recommend omalizumab (anti-IgE) for the management of patients aged ≥12 years with chronic urticaria unresponsive to high-doses second-generation H1 -antihistamines (antiH1 ). However, there is little published information on the success of omalizumab for such a treatment in children. We reported our experience of six patients with chronic spontaneous urticaria (CSU) treated with omalizumab. Mean age of our case series was 14.7 years (range 11-16 years) with a prevalence of male gender (66.7%). All six patients were treated with at least one 6-months course of omalizumab. The average follow-up period was 13 ± 6 months. Only one patient was no responder to omalizumab therapy. Thus far, two patients have experienced a complete CSU regression over 12 months after the final omalizumab administration. The remaining three patients needed a second course of treatment. Our experience demonstrates that omalizumab is effective and safe as treatment option for CSU unresponsive to antiH1 , even in adolescent age.

Omalizumab for treatment of refractory severe atopic dermatitis. A pediatric perspective.

Omalizumab is a monoclonal antibody, targeting Fc receptor of IgE, approved for the treatment of allergic asthma and chronic spontaneous urticaria. Its utility in atopic dermatitis appears controversial from data in literature since the molecule is well tolerated but it seems less effective than other medications used in adult patients (eg, Dupilumab). At present, the use of Dupilumab is not approved in pediatric patients therefore there are no second level treatments available in this age group. Here we report two clinical cases of patients (15 and 16 years old) suffering from both atopic dermatitis and asthma, treated with Omalizumab. Our experience suggests that atopic eczema of young patients with allergic comorbidities can benefit from asthma treatment with Omalizumab observing improvement on both conditions.

Oral immunotherapy in pediatrics.

IgE-mediated food allergy (FA) has been emerging as a public health priority, mainly in children. It represents a heavy burden for the entire society and not only for the patients and their families. There is evidence that in children with persistent FA, at least to cow's milk, hen's egg, and peanut, oral immunotherapy (OIT) may increase the reaction threshold to food allergen(s), while receiving active therapy (the so-called "desensitization"). Furthermore, OIT protects patients from the occurrence of severe reactions in the event of accidental ingestion of the culprit food during treatment. However, many gaps are still unsolved, including safety issues, identification of predictive biomarkers, and post-desensitization efficacy. This article briefly summarizes the current evidence and the main needs in OIT to stimulate the development of longitudinal, prospective, well-designed studies able to fill the current gaps soon.

Maturity Onset Diabetes of the Young is Not Necessarily Associated with Autosomal Inheritance: Case Description of a De Novo HFN1A Mutation.

Maturity onset diabetes of the young (MODY) accounts for up to 4% of all cases of diabetes in pediatric patients. MODY is usually characterized by autosomal dominant inheritance, impaired insulin secretion, and an average age at diagnosis of 18-26 years. Mutations in the hepatocyte nuclear factor 1-alpha (HNF1A), glucokinase, hepatocyte nuclear factor 4-alpha, and hepatocyte nuclear factor 1-beta genes are the mutations most frequently observed in cases of MODY. We herein report a case of HNF1A-MODY characterized by an early onset of diabetes. Genetic investigations revealed a de novo heterozygous substitution, N237D (HNF1A c.709A>G), in exon 3 of the HNF1A gene. Our case supports the hypothesis that de novo mutations are more frequent than expected. This recent evidence may suggest that conventional clinical diagnostic criteria for MODY should be revised and personalized according to the individual patient.

EAACI guidelines on allergen immunotherapy: Prevention of allergy.

Allergic diseases are common and frequently coexist. Allergen immunotherapy (AIT) is a disease-modifying treatment for IgE-mediated allergic disease with effects beyond cessation of AIT that may include important preventive effects. The European Academy of Allergy and Clinical Immunology (EAACI) has developed a clinical practice guideline to provide evidence-based recommendations for AIT for the prevention of (i) development of allergic comorbidities in those with established allergic diseases, (ii) development of first allergic condition, and (iii) allergic sensitization. This guideline has been developed using the Appraisal of Guidelines for Research & Evaluation (AGREE II) framework, which involved a multidisciplinary expert working group, a systematic review of the underpinning evidence, and external peer-review of draft recommendations. Our key recommendation is that a 3-year course of subcutaneous or sublingual AIT can be recommended for children and adolescents with moderate-to-severe allergic rhinitis (AR) triggered by grass/birch pollen allergy to prevent asthma for up to 2 years post-AIT in addition to its sustained effect on AR symptoms and medication. Some trial data even suggest a preventive effect on asthma symptoms and medication more than 2 years post-AIT. We need more evidence concerning AIT for prevention in individuals with AR triggered by house dust mites or other allergens and for the prevention of allergic sensitization, the first allergic disease, or for the prevention of allergic comorbidities in those with other allergic conditions. Evidence for the preventive potential of AIT as disease-modifying treatment exists but there is an urgent need for more high-quality clinical trials.

Safety profile of oral immunotherapy with cow's milk and hen egg: A 10-year experience in controlled trials.

BACKGROUND: Oral immunotherapy (OIT) for food allergy is gaining interest due to the favorable clinical results reported with cow's milk, hen egg and peanut. The safety of the procedure remains a critical aspect that can limit the introduction of OIT in clinical practice. OBJECTIVE: We described herein, in detail, the occurrence and characteristics of adverse events (AE) with OIT in children who participated in controlled trials at our unit. METHODS: The clinical records of 68 children who received active treatment (40 for cow's milk and 28 for hen egg) were carefully reviewed. The inclusion and exclusion criteria, and the grading of AEs were the same across the trials. Of the 68 children involved, 6 (9%) had to discontinue the OIT procedure due to severe AEs. Fifty percent of the children underwent the buildup and maintenance phases without AEs. Mild-to-moderate AEs were documented in 28 patients, who could complete the desensitization. The majority of reactions were mild or moderate, occurred during an acute intercurrent illness and required only symptomatic treatment. CONCLUSION: A careful review of the patients who received food OIT in controlled trials confirmed that AEs were not rare but that ∼90% of children could achieve an effective desensitization. The procedure remains investigational and should be performed only by trained physicians, especially in the pediatric setting.