The importance of clinical history in the diagnosis of drug hypersensitivity in children.

BACKGROUND: In case of suspected hypersensitivity reactions (HRs) to drugs, a challenging area for pediatricians is detecting relevant elements in the parent-reported history, in order to reach a definite diagnosis. We analyzed the concordance between the description of the HR and the medical reports documented at the time of the event. Furthermore, we studied any correlation between clinical history variables and the prediction of true allergy. METHODS: We retrospectively collected 50 charts of children referred to our Allergy Unit, after a previous access to the Emergency Department. We compared the description of the HR at acute phase to the history told by parents. Type and timing of the HR and culprit drug were classified as "known" or "unknown." The diagnosis was confirmed or excluded at the end of the investigations. Logistic regression analysis was performed to find any significant association. RESULTS: The type of the HR was known in 74%, the timing in 28%, and the culprit drug in 98%. We showed that having had a severe HR had an increased odds of remembering the timing; being older >6 years and having had an immediate HR had an increased odds of remembering the type; time to diagnostic was lower in patients whose parents remembered the type of HR. CONCLUSION: Our paper underlines the importance of an accurate anamnesis at the time of the event. Providing the physicians with a standardized Case Report Form could be a useful tool to simplify the diagnostic work-up and minimize mistakes due to lack of memory.

How to manage drug-virus interplay underlying skin eruptions in children.

The majority of viral rashes occurring during an antibiotic therapy are considered as a drug hypersensitivity reaction (DHR). Differentiating a viral rash versus a DHR is difficult or even impossible. In delayed DHRs the interplay between viruses and drugs is summarized according to the recent literature. The question is if the same reaction will again occur in case of drug re-exposure in absence of the concomitant viral infection because of persistent immune reactivity. Epstein Barr Virus (EBV) and Human Herpes virus 6 (HHV-6) models are analyzed in case of maculopapular exanthemas (MPEs) and drug reaction with eosinophilia and systemic symptoms (DRESS) over a course of drug therapy. MPEs are the most common skin manifestation during a viral infection and a concomitant drug therapy. In type IVb reactions to drugs a hapten/pro-hapten mechanism and a pharmacological interaction (p-i mechanism) are described as the 2 major ways to make T cells response functional. Rarely the altered repertoire model is involved. The Human Leukocyte Antigen (HLA) predisposition is an additional essential factor that can facilitate DHR. In MPEs rarely a DHR is confirmed by allergy testing. Severity and duration of MPEs, the presence of eosinophilia and systemic symptoms make more reliable the persistent nature of the reaction. Research on this topic is needed in order to provide the clinicians with instruments to decide when to suspect future reactions upon drug re-exposure even in the absence of a viral infection, because those patients should be investigated by a complete drug allergy work up.

Glycemic Control, Basal/Bolus Distribution, BMI and Meal Management in Children and Adolescents with Type 1 Diabetes and Advanced Hybrid Closed Loop.

Evidence about the impact of advanced hybrid closed loop (AHCL) on body mass index (BMI) and eating habits in children with type 1 diabetes (T1D) is lacking. This real-world study aimed at evaluating glycemic control, BMI, meals and basal/bolus distribution in young subjects with T1D treated by AHCL. Glycemic metrics, HbA1c, basal/bolus distribution, meals/day, BMI, total daily dose (TDD), and carbohydrates/kg (CHO/kg) have been evaluated in 83 subjects, aged 13 ± 4.5 years, in manual mode, 3 and 6 months after auto-mode. Time in range (TIR) increased after 3 months, exceeding the target of 70% and was maintained at 6 months. While coefficient of variation (CV) did not change, the glucose management indicator (GMI) decreased in auto-mode (6.7 ± 0.3 vs. 7.1 ± 0.5%; p < 0.001), as well as HbA1c. Basal proportion decreased in favor of boluses (38.3 ± 7.3 vs. 43.6 ± 10.9%; p < 0.001). Meals increased at 3 and 6 months (4.4 ± 1.2 vs. 5.0 ± 1.5, p 0.002 and 5.1 ± 1.7, p < 0.001), as well as TDD/kg, without changes in BMI and CHO consumed. No differences in meal composition have arisen from food diaries. In conclusion, AHCL ensured the achievement and maintenance of target TIR in young T1D subjects. The number of meals, TDD, and insulin bolus proportion increased over time, but BMI remained stable.

Pearls and Pitfalls of Weaning an Infant with Severe Atopic Dermatitis and Sensitization/Allergy to Food.

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder in childhood. Skin barrier impairment exposes infants to food allergens, potentially causing sensitization followed by IgE-mediated food allergy. We describe the case of an infant with severe AD in whom several sensitizations to foods are detected, with consequently difficult weaning, and a history of anaphylaxis to cashew nut. Foods for which skin tests were negative were introduced into the infant's diet. Then, when AD control was managed, oral food challenges (OFCs) for foods to which the patient was sensitized, with the exception of cashew nut, were performed. The simultaneous presence of sensitization toward multiple foods made it difficult to introduce them using classic OFC. Therefore, it was decided to perform the low-dose, gradual controlled OFC. This led to an introduction of sensitized foods into the infant's diet, with the exception of cashew nut, avoiding allergic reactions. Absolute recommendations on how, when, and where to perform OFCs with allergenic food to which the child with AD is sensitized are lacking so far. In our opinion, OFCs and the subsequent ntroduction of allergenic foods should be individualized, evaluating some factors such as their social and nutritional importance, the patient's age and clinical phenotype (including the history of anaphylaxis), and the sensitization profile. There is agreement on the fact that the dietary approach in children with moderate-severe AD should no longer include a strict elimination diet. We believe that an early, gradual controlled introduction of all allergenics to identify the amount of food tolerated in the absence of reactions, even if low dose, may improve patients' and families' quality of life. However, even if discussing a vast relevant literature, the limitation of our work is that we describe the management of a single patient. Extensive and high-quality research is needed in this field to improve the available evidence in the area.

Eruption of Permanent Teeth As Risk Factor for Allergic Reactions During Oral Immunotherapy.

Background: Oral immunotherapy (OIT) increases the threshold of reaction in children older than 4 years with food allergy. The risk for severe allergic reactions (ARs) during OIT has been reported in several studies, often in the presence of concomitant cofactors such as physical exercise, empty stomach, medications, poorly controlled asthma, menses, and alcohol consumption. Cases Presentation: We describe a case series of 5 scholar age patients undergoing OIT who showed ARs to a known, previously tolerated dose of allergen during permanent tooth eruption, in which other known cofactors were excluded. Conclusions: Patients may be exposed to cofactors due to behavioral habits not only in the second and third decades of life, but also in the first decade of life, due to the timing of mixed dentition. More studies are needed to estimate the frequency and entity of tooth eruption as cofactor, as well as to know the correct management of children undergoing dentition during OIT.

Hidden and Rare Food Allergens in Pediatric Age.

In food allergy management, the avoidance of the allergen that caused the reaction plays a fundamental role. Nevertheless, that can be thwarted in case of accidental exposure to a rare or hidden allergen, causing the adoption of a monotonous diet and a consequent reduction in the quality of life of the patient and their family. The identification of a rare and hidden allergen is an important diagnostic challenge, taking into account that a significant proportion of all food reactions is in reality due to them. The aim of the present review is to provide the pediatric allergist an overview of the possible sources of rare and hidden food allergens, taking into consideration the routes of exposure to these potential allergens with the main examples published in the scientific literature and the distinction between types of direct or cross-contamination. The identification of the allergen responsible for the reaction and the provision of a dietary advice customized for the specific individual's dietary habits is essential to improve quality of life of the familiar nucleus and to reduce the risk of further allergic reactions.

Long-term effectiveness of advanced hybrid closed loop in children and adolescents with type 1 diabetes.

BACKGROUND: Advanced hybrid closed loop (AHCL) systems are the newest tool to improve metabolic control in type 1 diabetes (T1D). Long-term glycemic control of children and adolescents with T1D switching to MiniMed™ 780G in a real clinical setting was evaluated. METHODS: Time in range (TIR) and in different glucose ranges, glycemic variability indexes, HbA1c and basal-bolus insulin distribution were evaluated in 44 subjects (mean age 14.2 ± 4.0 years, 22 males) during manual mode period, first 14 days (A14d) and first month after auto-mode activation (A1M), first 14 days after 3 months (A3M) and 6 months (A6M) in auto-mode. RESULTS: Mean TIR at A14d was 76.3 ± 9.6% versus 69.3 ± 12.6% in manual mode (p < 0.001), and this improvement was maintained over 6 months. Subjects with TIR >70% and >80% in manual mode were 45% and 23%, respectively, and increased to 80% (p = 0.041) and 41% (p = 0.007) at A14d. Basal-bolus distribution changed in favor of bolus, and auto-correction boluses inversely correlated with TIR. HbA1c was 7.2 ± 0.7% (55 mmol/mol) at baseline and significantly improved after 3 months (6.7 ± 0.5%, 50 mmol/mol, p < 0.001) and 6 months (6.6 ± 0.5%, 49 mmol/mol, p < 0.001). TIR was higher in individuals >13 years at all time periods (p < 0.001). Glycemic target <120 mg/dl was associated with better TIR. CONCLUSIONS: AHCL MiniMed™ 780G allowed rapid and sustained improvement of glycemic control in young T1D patients, reaching recommended TIR. Teenagers showed good technology adherence with optimal TIR, maintained better over time compared to younger children. Stricter settings were associated with better metabolic control, without increase in severe hypoglycemia occurrence.

Spondylodiscitis in Pediatric Age: A Retrospective Cohort Study.

BACKGROUND: Pediatric spondylodiscitis is rare, hardly diagnosed and treated due to the nonspecificity of clinical presentation and laboratory investigations, difficulty of etiologic identification and lack of management guidelines. METHODS: A retrospective study was conducted on 29 children with spondylodiscitis. Clinical, hematic and radiologic data were collected and compared between 2 age-subgroups (below and from 4 years old on) to investigate age-related differences. Epidemiologic, management and follow-up data were also described. RESULTS: Slight male predominance and a peak of incidence <2 years were observed. Symptoms were significantly differently distributed in the 2 age-subgroups: children <4 years showed mainly refusal/inability to sit or bear weight, irritability, limping and poor general conditions; children ≥4 years most frequently had back pain and fever, and pain upon palpation of the spine. The lumbar spine and more than 1 vertebra were most frequently involved. Median diagnostic delay of 12 days was observed, without significant difference between age-subgroups, and delay >2 months was always associated with multivertebral involvement and complications. All children were treated with broad-spectrum antibiotics for a median of 12 weeks. Only in 1 complicated case, surgical treatment was also required. CONCLUSIONS: The clinical presentation of spondylodiscitis may be age-specific, with younger children often exhibiting subtle signs and symptoms. Broad-spectrum antibiotics covering for Staphylococcus aureus should be initiated as soon as possible and performed many weeks, being effective in treating the infection without clinical sequelae, even in patients with comorbidities. Surgical treatment should be reserved for complicated cases with neurologic involvement.

COVID-19 vaccination in adolescents and young adults with type 1 diabetes: Glycemic control and side effects.

BACKGROUND: Two vaccines against SARS-CoV-2 are approved by the World Health Organization (WHO) for minors aged 12 years and over. Currently, people with both type 1 diabetes (T1D) and type 2 diabetes (T2D) are prioritized for vaccination. OBJECTIVE: To evaluate possible glycemic control modification, insulin dose adjustment and adverse effects after COVID-19 vaccination in young T1D individuals, users of different technology levels. METHODS: Thirty-nine T1D individuals, who received a whole vaccination cycle of either Moderna or Pfizer- BioNTech vaccines, were enrolled, 24 of whom using advanced hybrid closed loop systems (AHCLs) and 15 using intermittently scanned continuous glucose monitoring (isCGM). Symptoms after each dose and the following variables were considered: time in range 70-180 mg/dl (TIR), time in different glucose ranges, mean glucose levels, coefficient of variation (CV), total daily dose (TDD) and bolus proportion RESULTS: No significant differences in TIR, time in different glucose ranges, mean glucose levels, TDD, bolus proportion, were observed before and after any dose nor before and after the whole vaccination cycle. CV was significantly lower after the whole vaccination cycle (CV pre-vaccination 35.1 ± 6.9% vs. CV post-vaccination 33.5 ± 6.3%; p 0.031) in subjects treated by AHCLs. Side effects after the vaccination were mild and more frequent after the second dose. No severe adverse reactions were reported. CONCLUSIONS: COVID-19 vaccination was safe and not associated with significant perturbation of glycemic control in adolescents and young adults with T1D. This information could be of clinical use when counseling families about SARS-CoV-2 vaccination in young people with T1D.

CD4+CD25+CD127hi cell frequency predicts disease progression in type 1 diabetes.

Transient partial remission, a period of low insulin requirement experienced by most patients soon after diagnosis, has been associated with mechanisms of immune regulation. A better understanding of such natural mechanisms of immune regulation might identify new targets for immunotherapies that reverse type 1 diabetes (T1D). In this study, using Cox model multivariate analysis, we validated our previous findings that patients with the highest frequency of CD4+CD25+CD127hi (127-hi) cells at diagnosis experience the longest partial remission, and we showed that the 127-hi cell population is a mix of Th1- and Th2-type cells, with a significant bias toward antiinflammatory Th2-type cells. In addition, we extended these findings to show that patients with the highest frequency of 127-hi cells at diagnosis were significantly more likely to maintain ß cell function. Moreover, in patients treated with alefacept in the T1DAL clinical trial, the probability of responding favorably to the antiinflammatory drug was significantly higher in those with a higher frequency of 127-hi cells at diagnosis than those with a lower 127-hi cell frequency. These data are consistent with the hypothesis that 127-hi cells maintain an antiinflammatory environment that is permissive for partial remission, ß cell survival, and response to antiinflammatory immunotherapy.