Pasquale Comberiati

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.

Endotypes of pollen-food syndrome in children with seasonal allergic rhinoconjunctivitis: a molecular classification.

Pollen‐food syndrome (PFS) is heterogeneous with regard to triggers, severity, natural history, comorbidities, and response to treatment. Our study aimed to classify different endotypes of PFS based on IgE sensitization to panallergens.

Consensus Conference on Clinical Management of pediatric Atopic Dermatitis

The Italian Consensus Conference on clinical management of atopic dermatitis in children reflects the best and most recent scientific evidence, with the aim to provide specialists with a useful tool for managing this common, but complex clinical condition. Thanks to the contribution of experts in the field and members of the Italian Society of Pediatric Allergology and Immunology (SIAIP) and the Italian Society of Pediatric Dermatology (SIDerP), this Consensus statement integrates the basic principles of the most recent guidelines for the management of atopic dermatitis to facilitate a practical approach to the disease. The therapeutical approach should be adapted to the clinical severity and requires a tailored strategy to ensure good compliance by children and their parents. In this Consensus, levels and models of intervention are also enriched by the Italian experience to facilitate a practical approach to the disease.

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.

Clinical practice recommendations for allergen-specific immunotherapy in children: the Italian consensus report

Allergen-specific immunotherapy (AIT) is currently recognized as a clinically effective treatment for allergic diseases, with a unique disease-modifying effect. AIT was introduced in clinical practice one century ago, and performed in the early years with allergenic extracts of poor quality and definition. After the mechanism of allergic reaction were recognized, the practice of AIT was refined, leading to remarkable improvement in the efficacy and safety profile of the treatment. Currently AIT is accepted and routinely prescribed worldwide for respiratory allergies and hymenoptera venom allergy. Both the subcutaneous (SCIT) and sublingual (SLIT) routes of administration are used in the pediatric population.AIT is recommended in allergic rhinitis/conjunctivitis with/without allergic asthma, with an evidence of specific IgE-sensitization towards clinically relevant inhalant allergens. Long-term studies provided evidence that AIT can also prevent the onset of asthma and of new sensitizations. The favorable response to AIT is strictly linked to adherence to treatment, that lasts 3–5 years. Therefore, several factors should be carefully evaluated before starting this intervention, including the severity of symptoms, pharmacotherapy requirements and children and caregivers’ preference and compliance.In recent years, there have been increasing interest in the role of AIT for the treatment of IgE-associated food allergy and extrinsic atopic dermatitis. A growing body of evidence shows that oral immunotherapy represents a promising treatment option for IgE-associated food allergy. On the contrary, there are still controversies on the effectiveness of AIT for patients with atopic dermatitis.This consensus document was promoted by the Italian Society of Pediatric Allergy and Immunology (SIAIP) to provide evidence-based recommendations on AIT in order to implement and optimize current prescription practices of this treatment for allergic children.

Breast-Milk Characteristics Protecting Against Allergy

Breast milk and colostrum are the first feeding sources for a child, providing nutrients, growth factors and immunological components, which are crucial for the newborns correct development and health. Length of exclusive breastfeeding and time of solid foods introduction is a key factor that may influence allergy development. There is an emerging evidence of a relationship between breastfeeding, milk composition and lower risk of chronic diseases, such as diabetes, obesity, hypertension and allergies. This review examines current evidence regarding humoral and cellular characteristics of breast-milk, and potential role of environment, maternal diet and breastfeeding on the allergy development in children.

Flavor, relative palatability and components of cow's milk hydrolysed formulas and amino acid-based formula.

BackgroundBoth extensively hydrolysed formulas (eHF) and amino acid-based formula (AAFs) have been demonstrated effective for the treatment of CMA. However, in clinical practice, parents complain that hydrolysates are rejected by children due to their bad taste. Flavor of hydrolysed formulas has been poorly investigated although it affects the acceptance of milk over all the other attributes. The aim of the present study was to understand the factors underlying the unpleasant flavor of hydrolysed 25 formulas and amino acid-based formula.Subjects and methodsOne hundred and fifty trained panelists performed a randomized-double-blind test with different milks. The smell, texture, taste and aftertaste of each formula were evaluated on a scale ranging from −2 (worst) to 2 (best).ResultsFormulas showed significant difference, as compared to cow’s milk, in smell, texture, taste and aftertaste. Overall, whey eHFs were judged of better palatability than casein eHF and the AAFs (p < 0.05). Whey eHF showed significant differences among them for sensory attributes, especially for taste and aftertaste.ConclusionsThese results suggest that a broad range of flavor exists among the hydrolysed formulas. Further studies, adequately designed to investigate the relationship between milks’ flavor and nutrient profile of hydrolysed formulas are warranted.

Lysinuric protein intolerance can be misdiagnosed as food protein–induced enterocolitis syndrome

To the Editor, Food protein–induced enterocolitis syndrome (FPIES) is a rising non-IgE-mediated food allergy triggered by specific food proteins (cow’s milk, soy, and grains are the common offending foods). FPIES requires total elimination of the offending food from the diet and typically resolves by 3 yr of age (1). Metabolic disorders, such as lysinuric protein intolerance (LPI), are often underestimated in the differential diagnosis of FPIES. Although rare, these inherited conditions require different and life-long nutrition and dietary intervention to prevent impaired developments in infants. We present the case of an infant with LPI misdiagnosed as FPIES and discuss the similarities and differences between these two conditions. A 12-month-old male infant, exclusively breastfed for the first 6 months of life, was admitted due to repetitive vomiting and diarrhea, commenced at 6 months after weaning began. These reactions typically occurred within 1–3 h after the consumption of the same foods–meat, chicken, fish, or eggs. None of these reactions were associated with bloody diarrhea, skin rash, angioedema, or dyspnea. Prior to our examination, the parents gradually eliminated these foods from his diet and reported an improvement in symptoms. The infant clinical and neurologic examinations were normal. A mild hepatosplenomegaly was revealed by an abdominal ultrasonography. Thyroid-stimulating hormone, free thyroxine, celiac serology, blood gases, ammonia, renal and liver functions, and urinalysis were all in the normal range. Only ferritin and LDH serum levels were very high (244 ng/ml and 1017 IU/l, respectively). A complete allergological work-up was performed, which came out negative for skin prick tests, patch tests, and serum-specific IgE antibodies to the suspected foods (total IgE < 2 kU/l). A FPIES to solid food was diagnosed. Due to the history of aversion to protein-rich foods associated with mild hepatosplenomegaly and very high ferritin and LDH serum levels, plasma and urinary amino acid analysis were carried out. The results showed in Table 1 led to a definitive diagnosis of LPI, which was confirmed by the molecular analysis of SLC7A7 gene (the patient was a homozygote with a missense mutation c. 1001T > G in SLC7A7 gene; his parents resulted heterozygous carriers of this mutation). The child started a low-protein diet (1.5 g/Kg/day) and oral supplementation with citrulline (100 mg/kg/day), reporting no further gastrointestinal or neurologic symptoms after 6 months of good compliance with this therapy. Lysinuric protein intolerance is a rare autosomal recessive defect of cationic amino acid (i.e. lysine, arginine, and ornithine) transport at the basolateral membrane of epithelial cells in intestine and kidney, which results in low activity of the urea cycle and possible episodes of hyperammonemia, particularly after ingesting protein-rich foods. The condition is caused by mutations in SLC7A7 gene (2, 3). Patients with LPI are usually asymptomatic while breast-feeding, but typically develop recurrent emesis and diarrhea during weaning, a few hours after being fed protein-rich foods. However, LPI can have a wide variability in its clinical manifestations, which range from aversion to protein-rich foods, failure to thrive and hepatosplenomegaly, to renal insufficiency, pulmonary alveolar proteinosis, and hematologic and immunologic abnormalities (4).

Diagnosis and treatment of pediatric food allergy: an update

The prevalence of pediatric food allergy and anaphylaxis has increased in the last decades, especially in westernized countries where this emerging phenomenon was marked as a “second wave” of the allergic epidemic. Over recent years great advances have been achieved in the field of in vitro allergy testing and component-resolved diagnosis has increasingly entered clinical practice. Testing for allergen components can contribute to a more precise diagnosis by discriminating primary from cross-reactive sensitizations and assessing the risk of severe allergic reactions.The basic concept of the management of food allergy in children is also changing. Avoidance of the offending food is still the mainstay for disease management, especially in primary health care settings, but it severely affects the patients’ quality of life without reducing the risk of accidental allergic reactions. There is a growing body of evidence to show that specific oral tolerance induction can represent a promising treatment option for food allergic patients. In parallel, education of food allergic patients and their caregivers as well as physicians about anaphylaxis and its treatment is becoming recognized a fundamental need. International guidelines have recently integrated these new evidences and their broad application all over Europe represents the new challenge for food allergy specialists.

A web-based tool for improving adherence to sublingual immunotherapy

To the Editor, Allergic rhinitis and asthma can be controlled by pharmacotherapy, but allergen-specific immunotherapy (AIT) is the only disease-modifying intervention (1). Sublingual immunotherapy (SLIT) is gaining attention due to lower risks of side effects compared with subcutaneous AIT, but requires regular administration for at least 3–4 yr to achieve a high immunologically active dose. However, poor compliance particularly with SLIT is an emerging problem in the treatment of allergic respiratory diseases (2). Recent real-life studies have shown that only about 50% of the allergic patients receiving SLIT continue the treatment in the 2nd year and even fewer in the 3rd year (3, 4). Therefore, improving adherence to SLIT is a priority to improve its efficiency. In the information era, parents and their children are making increasing use of the Internet, computers, and smart phones. Thanks to these technologies it is easier today to conceive programs which allow online communications between doctors and their patients (5). To this purpose, a new online platform, Allergymonitor© (AM) (Technology Projects & Software Productions, Rome, Italy), was developed. AM consists of two main graphic interfaces: one accessed by the patient or the ‘front end’, and one accessed by the doctor or the ‘back office’, both allowed after personalized login. The front end includes several features such as a personalized treatment plan, including SLIT dosage, an online diary for daily or weekly registration of symptoms and eventually therapy-related adverse events, real-time graphic visualization of symptoms trend, and access to a chat messaging system which allows a direct, even if not in real time, interaction with the physician. All patients’ data are encrypted in accordance with current Italian privacy and information laws. The back office permits doctors to assess all their patients’ data, monitor allergic symptoms, adherence and side effects to medications and AIT, adjust patients’ treatment plan, and remind patients of these adjustments in real time through the chat messaging system. Moreover, the back office provides validated graphic symptoms scores which can be matched to pollen count curves online and in real time (6). Doctors are then able to easily download every patient’s recorded data in an Excel© format for any statistical analysis. Finally, AM permits the activation of automatic email and/or SMS alerts to patients when data registration is interrupted for more than two consecutive days, improving patients’ management and adherence to the prescribed therapy. Between April and December 2011, we conducted an observational pilot study on adherence to SLIT in 27 patients (age range, 6–20 yr) affected by allergic rhinitis, with or without intermittent or mild-persistent asthma, who were recruited at the Pediatric Allergy Unit of the ‘S. Pertini Hospital’ in Rome and monitored with AM. The primary aim of the study was to determine whether the use of AM could improve patients’ adherence to the prescribed SLIT. Due to the observational design of the study, the starting month of the SLIT was different among the 27 patients. Nevertheless, all participants were asked to register their symptoms with AM on a daily basis for the first 2 months of SLIT and thereafter once a week. Data on SLIT dropouts in the AM group at the end of the studied period were also compared with dropouts of a control retrospective group treated with the same SLIT brand in the previous year by the same allergist (S.T.). The retrospective group was extracted in a blinded manner by an informatics engineer from electronic clinical records and was age-, sex-, skin prick tests(SPT), and allergic status-matched with the studied group but not monitored with AM. The number of dropouts in both groups was calculated on the basis of SLIT reorders to the producer at the beginning of the 2nd year of treatment, and these figures were kindly provided by the manufacturer as SLIT is patient named in Italy. Patients underwent a full allergologic workup and were recruited after parents’ informed consent. The SLIT (Staloral; Stallergenes, Antony, France) was prescribed according to current guidelines and with a scheme of three times per week (7). Exclusion criteria were a history of severe chronic disease, previous courses of immunotherapy, and lack of an Internetconnected computer at home. Instructions on the use of AM were given to each patient and his/her parents at the recruitment and were also made available online and through a help desk. The study was embedded in a larger epidemiological study on pollen allergy approved by the ethic committee of the ‘S. Pertini Hospital’, Rome (8). According to the ARIA classification, the 27 participants (17 males, 66.6%; mean age of all patients 11.1 3.5 yr) were affected by a moderate-to-severe persistent allergic rhinitis (9). A total of 12 children (44%) had also intermittent or mild-persistent asthma. A total of 19 of the 27 children (70.4%) had clinically relevant positive SPT (weal reaction ≥3 mm) to pollens and 8/27 (29.6%) had positive SPT to Dermatophagoides pteronyssinus and farinae. Pollens’ sensitization was as follows: 11/27 (40.8%) only to Grass pollens, 3/ 27 (11.1%) to Grass pollens and Parietaria judaica, 3/27 (11.1%) to Grass pollens and Olea europea, 1/27 (3.7%) only to P. judaica, 1/27 (3.7%) to P. Judaica and O. Europea. All these children were prescribed SLIT as follows: 11 for grasses, three for grasses and Parietaria, three for grasses and Olea, one for Parietaria, one for Parietaria and Olea, and eight for mites. The control retrospective group included 18 subjects (11 males, 61%; mean age of all patients 12.0 2.8 yr; p = NS). During the 9-month observation period, only one of 27 patients in the AM group (corresponding to 3.7% of the Abbreviations: AIT, allergen specific immunotherapy; AM, Allergymonitor©; SLIT, sublingual immunotherapy; SPT, skin prick tests.