IgE to cyclophilins in pollen-allergic children: Epidemiologic, clinical, and diagnostic relevance of a neglected panallergen.

BACKGROUND: Cyclophilins are ubiquitous panallergens whose epidemiologic, diagnostic, and clinical relevance is largely unknown and whose sensitization is rarely examined in routine allergy practice. OBJECTIVE: We investigated the epidemiologic, diagnostic, and clinical relevance of cyclophilins in seasonal allergic rhinitis and its comorbidities. METHODS: We examined a random sample of 253 (25%) of 1263 Italian children with seasonal allergic rhinitis from the Panallergens in Pediatrics (PAN-PED) cohort with characterized disease phenotypes. Nested studies of sensitization prevalence, correlation, and allergen extract inhibition were performed in patients sensitized to birch pollen extract but lacking IgE to Bet v 1/2/4 (74/1263) or with highest serum level of IgE to Bet v 1 (26/1263); and in patients with sensitization to various extracts (ragweed, mugwort, pellitory, Plantago, and plane tree), but not to their respective major allergenic molecule, profilins, and polcalcins. IgE to cyclophilin was detected with recombinant Bet v 7, and extract inhibition tests were performed with the same rBet v 7. RESULTS: IgE to rBet v 7 was detected in 43 (17%) of 253 patients. It was associated with asthma (P < .028) and oral allergy syndrome (P < .017) in univariate but not multivariate analysis adjusted for IgE to profilins (Phl p 12), PR-10s (Bet v 1), and lipid transfer proteins (Pru p 3). IgE to rBet v 7 was also highly prevalent (47/74, 63%) among patients with unexplained sensitization to birch pollen extract. In patients with unexplained sensitization to ragweed, mugwort, pellitory, Plantago and plane tree pollen, the levels of IgE to those extracts correlated with the levels of IgE to rBet v 7, and they were also significantly inhibited by rBet v 7 (inhibition range 45%-74%). CONCLUSIONS: IgE sensitization to cyclophilin is frequent in pollen-allergic patients living in temperate areas and can produce "false" positive outcomes in skin prick and IgE tests to pollen extracts. Molecular diagnostic guidelines should include this panallergen family.

IgE to cross-reactive carbohydrate determinants (CCD) in childhood: Prevalence, risk factors, putative origins.

BACKGROUND: IgE antibodies to cross-reactive carbohydrate determinants (CCD) are usually clinically irrelevant but they can be a cause of false positive outcomes of allergen-specific IgE tests in vitro. Their prevalence and levels have been so far cross-sectionally examined among adult allergic patients and much less is known about their origins and relevance in childhood. METHODS: We examined CCD with a cross-sectional approach in 1263 Italian pollen allergic children (Panallergen in Paediatrics, PAN-PED), as well as with a longitudinal approach in 612 German children (Multicenter Allergy Study, MAS), whose cutaneous and IgE sensitization profile to a broad panel of allergen extracts and molecules was already known. The presence and levels of IgE to CCD were examined in the sera of both cohorts using bromelain (MUXF3) as reagent and a novel chemiluminescence detection system, operating in a solid phase of fluorescently labelled and streptavidin-coated paramagnetic microparticles (NOVEOS, HYCOR, USA). RESULTS: IgE to CCD was found in 22% of the Italian pollen allergic children, mainly in association with an IgE response to grass pollen. Children with IgE to CCD had higher total IgE levels and were sensitized to more allergenic molecules of Phleum pratense than those with no IgE to CCD. Among participants of the German MAS birth cohort study, IgE to CCD emerged early in life (even at pre-school age), with IgE sensitization to group 1 and 4 allergen molecules of grasses, and almost invariably persisted over the full observation period. CONCLUSIONS: Our results contribute to dissect the immunological origins, onset, evolution and risk factors of CCD-sIgE response in childhood, and raise the hypothesis that group 1 and/or 4 allergen molecules of grass pollen are major inducers of these antibodies through an antigen-specific, T-B cell cognate interaction.

Radiocontrast Media Hypersensitivity Reactions in Children.

Hypersensitivity reactions to radiocontrast media seem to be rare in children. Furthermore, the use of radiocontrast media in children remains quite safe in terms of the severity of reactions. Since pediatric guidelines are lacking, the diagnostic workup employed in adults could be adapted to children, taking into account that results have not yet been validated in this age group. Specific protocols for risk stratification and management of severe reactions have been proposed so far.

Cardiovascular issues in obstructive sleep apnoea in children: A brief review.

Obstructive sleep apnoea (OSA) is a very common disease with a prevalence that ranges from 1% to 6% in children. It is characterized by intermittent partial or complete occlusion of the upper airway during sleep, leading to recurrent arousals and disturbed sleep architecture, to neurocognitive disorders and alterations in homeostatic gas exchange. Cardiovascular complications may develop in children with OSA through various mechanisms including activation and dysregulation of the sympathetic nervous system, induction of pro-inflammatory and pro-oxidant status and increased risk of systemic hypertension. As the deleterious effects of OSA on the cardio-vascular system may start early in life, in this brief review we focused our attention both on early and late cardiological changes induced by apnoeic events in the paediatric population, by reviewing recent findings in the literature.

The Predictive Role of Biomarkers and Genetics in Childhood Asthma Exacerbations.

Asthma exacerbations are associated with significant childhood morbidity and mortality. Recurrent asthma attacks contribute to progressive loss of lung function and can sometimes be fatal or near-fatal, even in mild asthma. Exacerbation prevention becomes a primary target in the management of all asthmatic patients. Our work reviews current advances on exacerbation predictive factors, focusing on the role of non-invasive biomarkers and genetics in order to identify subjects at higher risk of asthma attacks. Easy-to-perform tests are necessary in children; therefore, interest has increased on samples like exhaled breath condensate, urine and saliva. The variability of biomarker levels suggests the use of seriate measurements and composite markers. Genetic predisposition to childhood asthma onset has been largely investigated. Recent studies highlighted the influence of single nucleotide polymorphisms even on exacerbation susceptibility, through involvement of both intrinsic mechanisms and gene-environment interaction. The role of molecular and genetic aspects in exacerbation prediction supports an individual-shaped approach, in which follow-up planning and therapy optimization take into account not only the severity degree, but also the risk of recurrent exacerbations. Further efforts should be made to improve and validate the application of biomarkers and genomics in clinical settings.

Mast Cell Activation Disorders.

Background and Objectives: Mast cell disorders comprise a wide spectrum of syndromes caused by mast cells' degranulation with acute or chronic clinical manifestations. Materials and Methods: In this review article we reviewed the latest findings in scientific papers about mast cell disorders with a particular focus on mast cell activation syndrome and mastocytosis in pediatric age. Results: Patients with mast cell activation syndrome have a normal number of mast cells that are hyperreactive upon stimulation of various triggers. We tried to emphasize the diagnostic criteria, differential diagnosis, and therapeutic strategies. Another primary mast cell disorder is mastocytosis, a condition with a long-known disease, in which patients have an increased number of mast cells that accumulate in different regions of the body with different clinical evolution in pediatric age. Conclusions: Mast cell activation syndrome overlaps with different clinical entities. No consensus was found on biomarkers and no clearly resolutive treatment is available. Therefore, a more detailed knowledge of this syndrome is of fundamental importance for a correct diagnosis and effective therapy.

Cutaneous manifestation during COVID-19 pandemic.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, causing COVID-19, is rapidly spread across the world, by posing novel challenges for all physicians. Cutaneous manifestations of COVID-19 may be present in 20% of patients, but they are still now poorly characterized. METHODS: We search literature to describe all the various cutaneous manifestation observed during COVID-19 pandemic. RESULTS: Different cutaneous clinical patterns were described, showing a wide polymorphism. CONCLUSION: We provided an overview of all the various cutaneous manifestations of COVID-19 described in the literature today, to improve our knowledge and lead a more prompt and accurate diagnosis, especially in asymptomatic or paucisymptomatic cases.

Hypersensitivity Reactions to Monoclonal Antibodies in Children.

Biologic drugs are widely used in pediatric medicine. Monoclonal antibodies (mAbs) in particular are a therapeutic option for rheumatic, autoinflammatory and oncologic diseases. Adverse drug reactions and hypersensitivity reactions (HSR) to mAbs may occur in children. Clinical presentation of HSRs to mAbs can be classified according to phenotypes in infusion-related reactions, cytokine release syndrome, both alpha type reactions and type I (IgE/non-IgE), type III, and type IV reactions, all beta-type reactions. The aim of this review is to focus on HSRs associated with the most frequent mAbs in childhood, with particular attention to beta-type reactions. When a reaction to mAbs is suspected a diagnostic work-up including in-vivo and in-vitro testing should be performed. A drug provocation test is recommended only when no alternative drugs are available. In selected patients with immediate IgE-mediated drug allergy a desensitization protocol is indicated. Despite the heavy use of mAbs in childhood, studies evaluating the reliability of diagnostic test are lacking. Although desensitization may be effective in reducing the risk of reactions in children, standardized pediatric protocols are still not available.

Early molecular biomarkers predicting the evolution of allergic rhinitis and its comorbidities: A longitudinal multicenter study of a patient cohort.

BACKGROUND: Pollen-related seasonal allergic rhinoconjunctivitis (SAR) is a very frequent pediatric disease in Westernized countries. Risk factors and disease phenotypes have been thoroughly examined in several cross-sectional studies. By contrast, only a few studies have examined disease evolution in patient cohorts. We investigated predictive biomarkers of disease evolution in a large cohort of children with SAR. METHODS: During 2015-2017 (follow-up), we re-examined 401 patients from those enrolled in 2009-2011 (baseline) by the "Panallergens in Pediatrics" study, a large multicenter survey of Italian children with SAR. Information on clinical history (standard questionnaire, AllergyCARD®; TPS, Italy) and skin prick tests for inhalant and foods extracts (ALK-Abelló, Hørsholm, Denmark) was acquired as at baseline visit. Evolution in clinical and sensitization data of patients was analyzed over time, as well as their association with the main baseline characteristics and atopy risk factors. RESULTS: The average age of participants was 10.4 ± 3.4 years at baseline and 16.2 ± 3.6 years at follow-up. SAR persisted in 93.3% of patients at follow-up and became more frequently associated with asthma (from 36.7% at baseline to 48.6% at follow-up) and oral allergy syndrome (OAS, from 23.4% to 37.7%). Compared to baseline, the prevalence of skin sensitization to some pollens (Phleum pratense, Corylus avellana, Platanus acerifolia, Artemisia vulgaris) and vegetables (hazelnut, wheat, and apple) significantly decreased at follow-up. Earlier onset of SAR and polysensitization at baseline were associated with incident asthma at follow-up. The presence at baseline of serum IgE to the following allergen molecules was identified as biomarkers of clinical evolution: (a) Phl p 1, for persistence of SAR; (b) Phl p 5, for persistence of both rhinitis and asthma; (c) Pru p 3, for new onset of asthma; (d) Bet v 1, for persistence of OAS. CONCLUSIONS: Seasonal allergic rhinoconjunctivitis is clinically heterogeneous in its evolution from childhood to adolescence. The detection of serum IgE to specific molecules (Phl p 1, Phl p 5, Bet v 1, Pru p 3) may be useful as biomarkers to predict SAR persistence and future onset of comorbidities, such as asthma and/or OAS.

Asthma and Food Allergy: Which Risks?

Over the past few decades, an increase in the prevalence of asthma and food allergy has been observed in the pediatric population. In infants, food sensitization, particularly to egg, has increased the risk of developing allergic asthma. This is even more likely if sensitization to food allergens occurs early within the first few years of life. It is indeed known that both diseases may be present simultaneously in the pediatric population, but coexistence may negatively influence the severity of both conditions by increasing the risk of life-threatening asthmatic episodes as well as food-related anaphylaxis. Therefore, an accurate clinical and phenotype characterization of this high-risk group of children with both asthma and food allergy and a more aggressive management might lead to reducing related morbidity and mortality. The aim of this review is to provide an updated overview on the close link between food allergy and asthma and their negative mutual influence.

Hazardous Medications in Children with Egg, Red Meat, Gelatin, Fish, and Cow's Milk Allergy.

Childhood food allergies are a growing public health problem. Once the offending food allergens have been identified, a strict elimination diet is necessary in treatment or prevention of most of the allergic reactions. Accidental food ingestion can lead to severe anaphylaxis. Food- derived substances can be used in medications at various stages of the manufacturing process. In this review, the possible roles of medications which may contain egg, red meat, gelatin, and fish allergens on allergic reactions in children with food allergy were evaluated.

Influence of Atopic Dermatitis on Cow's Milk Allergy in Children.

Background and Objectives: Cow's milk protein allergy (CMA) is the most common allergy in children. The natural history of CMA is generally favorable and the majority of children reach tolerance during childhood, even if studies show variable results. Atopic dermatitis (AD) is a complex disease from an immunological point of view. It is characterized by an impaired skin barrier function and is often the first clinical manifestation of the so-called "atopic march". The aim of our study is to evaluate, in a cohort of children with CMA, if the presence of AD in the first months of life can influence the atopic status of patients, the tolerance acquisition to cow's milk, the level of specific IgE (sIgE), and the sensitization towards food and/or inhalant allergens. Materials and Methods: We enrolled 100 children with a diagnosis of CMA referred to our Pediatric Allergology Unit, aged 1-24 months at the time of the first visit. Results: 71 children had AD and 29 did not. The mean follow-up was 5.28 years. The CMA manifestations were mainly cutaneous, especially in children with AD (91.6% vs. 51.7%; P < 0.001). Patients with AD showed higher rates of polysensitization to foods and higher levels of both total IgE and sIgE for milk, casein, wheat, peanuts, and cat dander at different ages when compared to patients without AD. We analyzed the presence of IgE sensitization for the main foods and inhalants at various ages in the two groups of patients: a statistically significant difference emerged in the two groups of patients for milk, yolk and egg white, hazelnut, peanuts, soybean, grass pollen and cat dander. Meanwhile, we did not find significant differences in terms of tolerance acquisition toward cow's milk, which was nonetheless reached around 5 years of age in 61% of patients. The level of cow's milk sIgE at the age of 5 years was significantly higher in the group of patients who did not acquire tolerance (38.38 vs. 5.22 kU/L; P < 0.0001). Conclusions: An early barrier deficiency appears to promote the development of allergic sensitization, but does not seem to influence the acquisition of tolerance.

Wheat Allergy in Children: A Comprehensive Update.

Gluten-related disorders are very common in pediatric patients. Wheat allergy is triggered by an immunoglobulin E (IgE)-dependent mechanism; its prevalence varies according to the age and region, and in Europe has been estimated to be lower than 1%. Many studies investigated the potential role of several external factors that can influence the risk to developing wheat allergy, but results are still inconclusive. It can be responsible for several clinical manifestations depending on the route of allergen exposure: food-dependent exercise-induced anaphylaxis (FDEIA), occupational rhinitis or asthma (also known as baker's asthma), and contact urticaria. The prognosis of IgE-mediated wheat allergy in children is generally favorable, with the majority of children becoming tolerant by school age. Patients who experienced an anaphylactic reaction prior to 3 years of age and patients with higher level of wheat- or ω-5 gliadin-specific IgE antibodies seem to be at higher risk of persistent wheat allergy. The current management of patients is dietary avoidance. Nowadays, oral immunotherapy has been proposed for wheat allergy with promising results, even if further studies are necessary to establish the best protocol in order to promote tolerance in wheat-allergic children.

Safety profile of H1-antihistamines in pediatrics: an analysis based on data from VigiBase.

PURPOSE: H1-antihistamines are commonly used in infants and children for the relief of histamine-mediated symptoms in a variety of conditions. Little is known about their safety profile in these patients. We performed a comparative analysis of the safety profiles of H1-antihistamines using data from the WHO database (VigiBase). METHODS: We selected adverse drug reaction (ADR) reports on H1-antihistamines in children (0-16 years) up to June 2014 from VigiBase. ADRs were codified according to MedDRA terminology. The reporting odds ratios (RORs) with 95% confidence for drug-reaction pairs were calculated. RESULTS: The analysis was performed on 8918 reports related to antihistamines, corresponding to 19503 drug reaction pairs for 68 different drugs. Most of reports involved children aged 2 to 6 years (32%) and 6 to 12 years (34%). Most reported drugs were cetirizine (1608 reports, corresponding to 18%), loratadine (16%), and diphenhydramine (10%). ADRs were classified as serious in 23% of cases, and 400 cases had a fatal outcome. We found a significant associations for several drug-reaction pairs such as levocetirizine and epilepsy (ROR, 6.57; 95% confidence interval [CI], 1.51-28.53) and chlorphenamine and toxic epidermal necrolysis (ROR, 7.29; 95% CI, 2.39-22.2). CONCLUSIONS: H1-antihistamines are among the most used drugs in pediatrics, also in an off-label manner. Our data highlights associations with serious and unexpected ADRs. Educative intervention to clinicians and parents are needed to help doctors to make proper choices on the drug treatment and for the early detection of ADRs to maximize the benefits and reduce the risk of ADRs in these patients.

Which advises for primary food allergy prevention in normal or high-risk infant?

In the last decades, international guidelines proposed different strategies of complementary foods introduction during weaning to prevent allergy. Avoidance measures, such as late introduction of allergenic foods, failed to show a significant preventive effect towards allergy. Recently, prospective randomized controlled studies suggested that the early introduction of solid foods - rather than the late introduction - could be a strategy to prevent allergic sensitization and food allergy. However, at today clear evidence of effectiveness and safety of early introduction are not yet available to recommend a radical change in the current clinical practice. A realistic advice for the general population could be to begin the weaning at 4-5 months with the progressive introduction of different foods. The advices for introduction of solid foods during weaning should also take in consideration the global development of child to chose the better timing of introduction of foods.

Atypical Forms of Hand, Foot, and Mouth Disease: A Prospective Study of 47 Italian Children.

BACKGROUND: Atypical forms of hand, foot, and mouth disease (HFMD) caused by coxsackievirus A6 have been reported in recent years. High fever and severe cutaneous lesions are common, whereas neurologic complications are rare. Eczematous areas of patients with atopic dermatitis show more lesions. The goal of the current study was to describe the clinical characteristics of children with atypical HFMD and to investigate the involvement of the different enterovirus serotypes associated. METHODS: All patients referred to our service for atypical HFMD from January 2012 to February 2014 were enrolled and classified as having the diffuse form (lesions extended to the trunk), the acral form (lesions with a mainly acral distribution), or eczema coxsackium (lesions on preexisting eczematous areas). RESULTS: Data from 47 patients were analyzed (median age 22 months [range 4-84 mos]); viral genotyping was performed in 11 cases. Sixty-two percent of the subjects developed the acral form, 23% eczema coxsackium, and 15% the diffuse form. Most patients had a nonclassical vesicular eruption and moderate to severe extent of cutaneous involvement. Approximately 80% of patients had palmoplantar purpuric macules. Most children younger than 2 years old had the acral form, most patients with eczema coxsackium were age 2 years and older, and the diffuse form was similarly distributed between the two age groups. Coxsackievirus A6 was detected in 9 of 11 genotyped cases. CONCLUSION: Our prospective study allowed the identification of three HFMD phenotypes differing from the classical form. Clinical care of these patients should include symptomatic treatment of extracutaneous features and, if necessary, hospitalization for complications.

Prevalence and Clinical Relevance of IgE Sensitization to Profilin in Childhood: A Multicenter Study.

BACKGROUND: Little is known about the prevalence and clinical relevance of hypersensitivity to the plant panallergen profilin in children. OBJECTIVES: The present study aimed to investigate prevalence, risk factors and clinical relevance of profilin sensitization in a large cohort of Italian children of different ages living in different geographic areas. METHODS: Children with pollen allergy enrolled by 16 pediatric outpatient clinics sited in three main geographic areas of Italy were studied. SPT were carried out with commercial pollen extracts and a commercial purified date palm pollen profilin. IgE specific for allergenic pollen molecules, Phl p 12 (grass profilin) and Pru p 3 (peach lipid transfer protein) were tested by ImmunoCAP FEIA. RESULTS: IgE to Phl p 12 (≥0.35 kU/l) was observed in 296 of the 1,271 participants (23%), including 17 of the 108 (16%) preschool children. Profilin SPT was positive (≥3 mm) in 320/1,271 (25%) participants. The two diagnostic methods were concordant in 1,151 (91%, p < 0.0001) cases. Phl p 12 IgE prevalence declined from northern to southern Italy and was directly associated with IgE to Phl p 1 and/or Phl p 5 and Ole e 1. Among children with IgE to Phl p 12, OAS was provoked by kiwi, melon, watermelon, banana, apricot and cucumber. CONCLUSIONS: Profilin sensitization is very frequent among pollen-allergic children, occurs at a very young age and contributes to the development of childhood OAS with a typical pattern of offending foods. Pediatricians should always consider IgE sensitization to profilin while examining pollen-allergic children, even if they are at preschool age.

Food Allergy in childhood: phenotypes, prevention and treatment.

The prevalence of food allergy in childhood increased in the last decades, especially in Westernized countries where this phenomenon has been indicated as a second wave of the allergic epidemic. In parallel, scientific interest also increased with the effort to explain the reasons of this sudden rise and to identify potential protective and risk factors. A great attention has been focused on early exposures to allergenic foods, as well as on other nutritional factors or supplements that may influence the immune system in a positive direction. Both interventions on maternal diet before birth or during breastfeeding and then directly on infant nutrition have been investigated. Furthermore, the natural history of food allergy also seems to be changing over time; IgE-mediated cow's milk allergy and egg allergy seem to be more frequently a persistent rather than a transient disease in childhood, as described in the last years. Food avoidance and the emergency drugs in case of an adverse event, such as epinephrine self-injector, are currently the first-line treatment in patients with food allergies, with a resulting impairment in the quality of life and social behaviour. During the last decade, oral immunotherapy emerged as an optional treatment with remarkable results, offering a novel perspective in the treatment for and management of food allergy.

Patterns of aeroallergen sensitization predicting risk for asthma in preschool children with atopic dermatitis.

OBJECTIVE: Atopic dermatitis (AD) is a chronic inflammatory skin disorder mostly affecting young children. Although several studies aimed to identify the risk factors for asthma in AD children, many aspects still need to be clarified. The aim of this study was to investigate the possible risk factors for asthma at school age in 99 children with early-onset and IgE-mediated AD. METHODS: All children performed clinical evaluation and total and specific IgE assay for a panel of inhalant and food allergens at two different times (t1 and t2) during preschool, and asthma diagnosis was assessed at one follow-up visit (t3) at school age. RESULTS: At t3, 39% of children had developed asthma. Of the variables compared, the sensitization to more than one class of inhalant allergens at t2 (mean age = 30 months) was associated with asthma, with grass (OR = 3.24, p = 0.020) and cat sensitization (OR = 2.74, p = 0.043) as independent risk factors. CONCLUSIONS: The sensitization pattern of a child with early-onset AD, also within the first 2-3 years of life, can reflect his risk to develop asthma. Therefore, testing these children for the more common allergens during this time frame should be recommended to predict the evolution of atopic diseases.

The effect of component-resolved diagnosis on specific immunotherapy prescription in children with hay fever.

BACKGROUND: Sensitization to profilins and other cross-reacting molecules might hinder proper specific immunotherapy (SIT) prescription in polysensitized patients with pollen-related allergic rhinitis (AR). In these patients, component-resolved diagnosis (CRD) might modify SIT prescription by improving the identification of the disease-eliciting pollen sources. OBJECTIVES: We sought to measure the effect of CRD on SIT prescription in children with pollen-related AR. METHODS: Children (n = 651) with moderate-to-severe pollen-related AR were recruited between May 2009 and June 2011 in 16 Italian outpatient clinics. Skin prick test (SPT) reactivity to grass, cypress, olive, mugwort, pellitory, and/or Betulaceae pollen was considered clinically relevant if symptoms occurred during the corresponding peak pollen season. IgE sensitization to Phl p 1, Phl p 5, Bet v 1, Cup a 1, Art v 1, Ole e 1, Par j 2, and Phl p 12 (profilin) was measured by using ImmunoCAP. SIT prescription was modeled on SPT responses first and then remodeled considering also CRD according to GA(2)LEN-European Academy of Allergology and Clinical Immunology guidelines and the opinions of 14 pediatric allergists. RESULTS: No IgE to the respective major allergens was detected in significant proportions of patients with supposed clinically relevant sensitization to mugwort (45/65 [69%]), Betulaceae (146/252 [60%]), pellitory (78/257 [30%]), olive (111/390 [28%]), cypress (28/184 [15%]), and grass (56/568 [10%]). IgE to profilins, polcalcins, or both could justify 173 (37%) of 464 of these SPT reactions. After CRD, the SPT-based decision on SIT prescription or composition was changed in 277 (42%) of 651 or 315 (48%) of 651 children according to the European or American approach, respectively, and in 305 (47%) of 651 children according to the opinion of the 14 local pediatric allergists. CONCLUSIONS: In children with pollen-related AR, applying CRD leads to changes in a large proportion of SIT prescriptions as opposed to relying on clinical history and SPT alone. The hypothesis that CRD-guided prescription improves SIT efficacy deserves to be tested.