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Abstract Lorentzian correlators of local operators exhibit surprising singularities in theories with gravity duals. These are associated with null geodesics in an emergent bulk geometry. We analyze singularities of the thermal response function dual to propagation of waves on the AdS Schwarzschild black hole background. We derive the analytic form of the leading singularity dual to a bulk geodesic that winds around the black hole. Remarkably, it exhibits a boundary group velocity larger than the speed of light, whose dual is the angular velocity of null geodesics at the photon sphere. The strength of the singularity is controlled by the classical Lyapunov exponent associated with the instability of nearly bound photon orbits. In this sense, the bulk-cone singularity can be identified as the universal feature that encodes the ubiquitous black hole photon sphere in a dual holographic CFT. To perform the computation analytically, we express the two-point correlator as an infinite sum over Regge poles, and then evaluate this sum using WKB methods. We also compute the smeared correlator numerically, which in particular allows us to check and support our analytic predictions. We comment on the resolution of black hole bulk-cone singularities by stringy and gravitational effects into black hole bulk-cone “bumps”. We conclude that these bumps are robust, and could serve as a target for simulations of black hole-like geometries in table-top experiments.

Abstract We show that holographic thermal two-sided two-point correlators take the form of a product over quasi-normal modes (QNMs). Due to this fact, the two-point function admits a natural dispersive representation with a positive discontinuity at the location of QNMs. We explore the general constraints on the structure of QNMs that follow from the operator product expansion, the presence of the singularity inside the black hole, and the hydrodynamic expansion of the correlator. We illustrate these constraints through concrete examples. We suggest that the product formula for thermal correlators may hold for more general large N chaotic systems, and we check this hypothesis in several models.

Abstract We study the analytic structure of the heavy-heavy-light-light holographic correlators in the supergravity approximation of the AdS3 × S 3/CFT2 duality. As an explicit example, we derive the correlator where the heavy operator is a classical microstate of the 5D supersymmetric black hole and its dual geometry interpolates as a function of a continuous parameter between global AdS3 and the extremal BTZ black hole. The simplest perturbation of this interpolating geometry by a light field is described by the Heun equation and we exploit the relation of its connection coefficients to the Liouville CFT to analytically compute the correlator in the two limits, focusing in particular on the black hole regime. In this limit we find that the real poles of the correlator become dense and can be approximated by a cut. We show that, when the charges of the heavy state are in the black hole regime, the discontinuity across the cut has complex poles corresponding to the quasi-normal modes of BTZ. This behaviour is qualitatively similar to what is expected for the large central charge limit of a typical black hole microstate.

Abstract Introduction Allergic rhinitis (AR) is very commonly caused by pollens. The symptoms of AR consist of sneezing, nasal congestion, rhinorrhea, nasal itching and airflow obstruction. The diagnosis has long been based on clinical history, skin prick tests and in vitro measurement of specific IgE, but the innovative approach of precision medicine has made diagnostic tools of much greater accuracy available. Areas covered This review covers the advances in the treatment of seasonal AR concerning the drugs to be used according to the grade of disease and the characteristics of the patients, and the role of allergen immunotherapy (AIT), which is the only treatment capable of acting, in addition to the symptoms, on the cause of AR and therefore to modify its natural history. Expert opinion Drug treatment of AR include a large number of agents, the choice of which depends on the severity of the disease. AIT has high evidence of efficacy demonstrated by meta-analyses, and further improvement is currently apparent, as for diagnosis, applying the means of precision medicine. However, when AIT is performed in current practice, without the strict rules of controlled trials, long-term low adherence is a major problem to be solved.

Abstract Background Biologics are currently one of the main treatment options for a number of diseases. The IgG4 monoclonal antibody dupilumab targets the Interleukin-4 receptor alpha chain, thus preventing the biological effects of the cytokines IL-4 and IL-13, that are essential for the Th2 response. Several controlled trials showed that dupilumab is effective and safe in patients with atopic dermatitis (AD), severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), thus resulting in approval by regulatory agencies. Aim of the study was to evaluate the efficacy and safety of dupilumab in adult patients with CRSwNP stratified by common overlapping comorbid conditions. Methods We performed a multicenter, observational, prospective study enrolling adult patients with severe CRSwNP who had started dupilumab treatment in the context of standard care from January 2021 to October 2021. Data were collected from twentynine Italian secondary care centers for allergy and clinical immunology, all of which were part of the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC). A number of efficacy parameters were used. Patient data were compared using the Wilcoxon test for paired data. All statistical analyses were performed with SPSS version 20 (IBM, Armonk, NY, USA). Results In total, 82 patients with nasal polyposis were identified. A significant improvement was detected for all the applied efficacy parameters, i.e. 22-item Sino-Nasal Outcome Test (SNOT-22) and bilateral endoscopic nasal polyp score (NPS) scores for CRSwNP, Rhinitis Control Scoring System (RCSS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores for allergic perennial rhinitis, Forced Expiratory Volume in the 1st second (FEV1) and Asthma Quality of Life Questionnaire (AQLQ) scores for asthma, Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI) scores for AD. A non-significant improvement was also obtained in the Urticaria Activity Score over 7 days (UAS7) for chronic spontaneous urticaria. Treatment with dupilumab was well tolerated. Conclusions These data suggest that dupilumab treatment in patients suffering from CRSwNP and associated comorbidities may be suitable. Such outcome, although confirmation by trials is warranted, suggests the possibility to treat different disorders with a single therapy, with favorable effects especially under the cost-effectiveness aspect.

Abstract The concept of personalized medicine as a diagnostic and therapeutic approach tailored to the medical needs of each patient is currently revolutionizing all fields of medicine and in particular allergology. Allergen immunotherapy (AIT) meets the three main needs for precision medicine: identification of molecular mechanism of disease, diagnostic tools for the mechanism and treatment blocking the mechanism itself. AIT adapts to the spectrum of specific IgE of each individual subject, changing the course and natural history of the disease, so is a clear model of precision and personalized medicine. This first step before the prescription of AIT is to define the sensitization profile of the patient; after that, the healthcare professional has numerous levers for adapting the treatment to the physio-pathological mechanisms involved. AIT allows to adapt treatments to the profile of the patients, but also to the its preferences, to ensure optimal treatment efficacy, resulting in an agile and personalized approach, with the aim to ensure adherence to the treatment, which is usually quite low. AIT also broadens the field of possibilities for healthcare professionals and patients, by allowing to choose the galenic formulation according to patient preferences and on the basis of their clinical history, adapting the product composition to the patient’s sensitization profiles and the underlying biological mechanisms identified at the diagnostic stage, while guaranteeing quality of the prescribed product as the production of allergens and allergoids is today more regulated than in the past years. In the management of AIT, it is also possible to involve patients in decisions throughout their care pathway thanks to multiple services, offering personalized follow-up and support, to ensure the highest treatment efficacy levels, and recalling medication intake, medical appointments and prescription renewals.

Introduction: Lipid transfer proteins (nsLTPs) are ubiquitous allergens. Patients affected by nsLTP syndrome experience symptoms to various plant-derived foods, ranging from local manifestations to anaphylaxis, the critical treatment of which is represented by self-administration of adrenaline. The principle aim of this study is to assess how dietary recommendations influence the occurrence of new and severe cases and if poly-sensitization to different nsLTPs may play a role. We also investigated about the appropriate use of adrenaline auto-injector during the episodes of anaphylaxis. Moreover, we examinated how other features (ie, co-sensitization to profilin and PR-10 and the presence of risk co-factors) affect these events. Materials and methods: We evaluated 78 patients allergic to nsLTPs, investigating adherence to diet and ability to use the adrenaline auto-injector. Number of sensitization to nsLTPs, co-sensitization to other panallergens, and presence of risk factors for new reactions were also assessed. Diagnosis was based on clinical history and positivity to in vivo and in vitro tests. During the follow-up, compliance, diet modifications, and new reactions were noted, and re-training for the use of epinephrine auto-injector was performed. At the last visit we evaluated the patients’ ability to use the self-injector. Results: The whole of fruits belonging to the Rosaceae family emerged as the most frequent culprit foods (28%), followed by walnut (17%), peanut (17%), and hazelnut (10%). At the baseline visit 23% of the patients described the presence of a risk factor during the allergic reaction (mainly nonsteroidal anti-inflammatory drugs [NSAIDs] and exercise). Forty-five percent of the patients reported anaphylactic reactions; no association between the type of food and the severity of the reactions was found. The presence of sensitization to 4 or more nsLTPs was associated to more severe reactions (p < .05; OR 1.67). During the follow-up 38% of the patients experienced at least 1 new allergic reaction: in 79% of them the culprit food was previously tolerated, and in 69% the reaction was an anaphylaxis. Only 47% of the patients showed a proper use of adrenaline auto-injector during the final evaluation, but a significant correlation between periodic education and reduction of the probability of mistakes in the use was reported (p < .05; OR 0.34). Furthermore, an association between co-sensitization to PR-10 (in particular Bet v1) and profilin and less severe symptoms was found, but without a significant odds ratio. Conclusion: A careful education aimed to the prevention of new reactions, through dietary restrictions and avoidance of risk co-factors, and to the management of anaphylaxis, through the training for the correct use of adrenaline auto-injector, should be a routine practice in nsLTP syndrome.

The introduction of biologics for the treatment of patients with refractory asthma represented a marked therapeutic advance. For more than 10 y, the only biologic available has been the monoclonal anti-IgE antibody omalizumab, reserved for patients with asthma caused by perennial allergen. In recent years, other biologics have been licensed for the treatment of severe eosinophilic asthma. They include monoclonal antibodies that target the Th2-pathway cytokines, such as IL-5 (mepolizumab and reslizumab) or its receptor (benralizumab) and the IL-4 and IL-13 receptor (dupilumab). The effectiveness of these biologics was demonstrated in several placebo controlled trials, the main outcomes being the significant reduction of the rate of asthma exacerbation and the improvement of respiratory function in actively treated patients. Based on the further understanding of the pathogenesis of asthma, new cytokines network and new targets are emerging, such as thymic stromal lymphopoietin, which can activate Th2 cells, innate lymphoid cells, or both, or prostaglandin D2 (PGD2), to develop additional biologics.

Abstract Hypersensitivity reactions (HRs) to contrast media (CM) can be distinguished in immune-mediated (including allergic reactions) and non-immune-mediated reactions, even if clinical manifestations could be similar. Such manifestations range from mild skin eruptions to severe anaphylaxis, making it important for radiologists to know how to identify and manage them. A panel of experts from the Società Italiana di Radiologia Medica e Interventistica (SIRM) and the Società Italiana di Allergologia, Asma e Immunologia Clinica (SIAAIC) provided a consensus document on the management of patients who must undergo radiological investigations with CM. Consensus topics included: the risk stratification of patients, the identification of the culprit CM and of a safe alternative by an allergy workup, as well as the use of premedication and the correct procedure to safely perform an elective (i.e., scheduled) or urgent examination. The most important recommendations are: (1) in all patients, a thorough medical history must be taken by the prescribing physician and/or the radiologist to identify at-risk patients; (2) in patients with hypersensitivity reactions to CM, the radiologist must consider an alternative, non-contrast imaging study with a comparable diagnostic value, or prescribe a different investigation with another class of CM; (3) if such options are not feasible, the radiologist must address at-risk patients to a reference centre for an allergy evaluation; (4) if timely referral to an allergist is not viable, it is recommended to use a CM other than the responsible one, taking into account cross-reactivity patterns; in the case of patients with histories of severe reactions, the presence of an anesthesiologist is also recommended and a premedication is suggested.

Abstract Background Urticaria is a disorder affecting skin and mucosal tissues characterized by the occurrence of wheals, angioedema or both, the latter defining the urticaria-angioedema syndrome. It is estimated that 12–22% of the general population has suffered at least one subtype of urticaria during life, but only a small percentage (estimated at 7.6–16%) has acute urticaria, because it is usually self-limited and resolves spontaneously without requiring medical attention. This makes likely that its incidence is underestimated. The epidemiological data currently available on chronic urticaria in many cases are deeply discordant and not univocal, but a recent Italian study, based on the consultation of a national registry, reports a prevalence of chronic spontaneous urticaria of 0.02% to 0.4% and an incidence of 0.1–1.5 cases/1000 inhabitants/year. Methods We reviewed the recent international guidelines about urticaria and we described a methodologic approach based on classification, pathophysiology, impact on quality of life, diagnosis and prognosis, differential diagnosis and management of all the types of urticaria. Conclusions The aim of the present document from the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC) and the Italian Society of Allergological, Occupational and Environmental Dermatology (SIDAPA) is to provide updated information to all physicians involved in diagnosis and management of urticaria and angioedema.

Adherence and compliance, respectively considered as a more positive, proactive behavior, resulting in a patient's lifestyle change to follow a daily regimen, and, as a more enforced response to an external command, are a critical aspect of any medical therapy, since it is estimated that less than half of the patients who are prescribed a therapy perform it, respecting the doses and duration. As far as aeroallergen immunotherapy is concerned, current data show that adherence is respected in about 50% of subcutaneous immunotherapy and in percentages even lower than 20% in sublingual immunotherapy treatments. This review analyzes the adherence to venom immunotherapy (VIT), in which, given its purpose of preventing potentially fatal anaphylactic reactions to insect stings, this aspect plays a critical role. In fact, protection from stings already takes place when the maintenance dose is reached, but VIT interruption before the recommended duration of 5 years exposes patients to new sting reactions. The data on adherence to VIT are far less abundant than that for aeroallergen immunotherapy. One of the first studies reported poor adherence in Austria, but the model used, consisting in the estimate of the percentage of patients with systemic reactions who accepted or rejected VIT, does not meet the criteria that define adherence to treatment. As for appropriate adherence studies, rates higher than 70% were reported in the United States and European countries. Studies from Italy found that good adherence were observed also in patients receiving, after 4 years of VIT, 3 months extended maintenance dose, as well as in patients treated during the COVID-19 pandemic,

Allergen immunotherapy (AIT) and venom immunotherapy (VIT) are meant to work on the causes of allergies, respectively, to respiratory allergens and Hymenoptera venom, inducing tolerance to the allergens and modifying the natural history of allergy. Both types of immunotherapies have evidence of efficacy, but actually they present wide differences in both effectiveness and safety. Indeed, as far as the effectiveness of VIT is concerned, if the protection against fatal reactions to stings is considered as the primary objective, more than 40 years of clinical practice demonstrate complete success. The clinical success of AIT is measurable on the basis of reduction or disappearance of allergic symptoms. The difference between the two treatments is even higher as regards safety: AIT has been concerned in the past by a series of fatal reactions caused, which underwent a progressive decrease when it was understood that they were related to the presence of uncontrolled asthma. However, fatal reactions related to failure to recognize the presence of risk factors or administration errors are still reported. Similarly to what has been observed for efficacy, VIT has never been affected by fatal reactions to the administration of venom, and the most important risk of anaphylaxis, which is the concomitance of mastocytosis, is now identified by measuring its marker serum tryptase. To date, mechanisms of hypersensitivity reactions that differentiate respiratory allergy from Hymenoptera venom allergy have not been successfully demonstrated. We have examined the past and present literature in order to propose reasonable hypotheses about the mechanisms actually involved.

Abstract The new observation of eosinophilic lingual tonsillitis as a possible adverse reaction to sublingual immunotherapy is likely to stimulate new investigations aimed at improving the understanding of the mechanisms of biodistribution of extracts placed at the sublingual level.

Patients with severe aortic stenosis are increasingly treated with transcatheter aortic valve implantation (TAVI) as a safer option to surgical aortic valve replacement (sAVR). Similar to many other heart diseases, after the specific therapeutic intervention patients are eligible for cardiac rehabilitation (CR) for the purpose of functional recovery. Thus far, CR after both sAVR and TAVI has been used to a limited extent, as shown by the availability of only two meta-analyses including 5 studies and 6 studies, respectively. Recent observational studies reported a significant improvement in functional indexes such as the Barthel scale and the 6-minute walk test (6MWT). We evaluated the outcome of CR in patients after TAVI treatment by measuring changes in the commonly used Barthel scale and 6MWT and adding the short physical performance battery (SPPB) scale as an index to assess lower extremity function. All indexes demonstrated a significant improvement, namely p

Abstract Background Chronic rhinosinusitis with nasal polyps (CRSwNP) frequently presents with dysfunction or loss of the sense of smell, resulting in a significant impairment in quality of life. The medical treatments currently available may improve the olfactory function in patients with CRSwNP, but such an outcome is generally only transitory. We report the case of a patient with CRSwNP who completely recovered from smell sense loss by treatment with mepolizumab. Case presentation The patient was a 62-year-old female who has severe asthma induced by allergy to Dermatophagoides and concomitant CRSwNP. Any treatment for the latter, including oral and injective corticosteroids, was unsuccessful in the loss of smell. Due to the satisfaction of admission criteria to mepolizumab treatment for severe asthma, treatment was initiated on March 2018, resulting in good clinical control of both asthma and CRSwNP, and particularly in complete recovery of the smell loss after 4 months of treatment and still persisting. Conclusion In this case report, the treatment with mepolizumab in a patient allergic to Dermatophagoides and affected by CRSwNP was associated with an improvement of anosmia. That finding may be explained by a reduction of the nasal obstruction by nasal polyps.

Abstract Background The pigeon tick Argas reflexus is a temporary parasite of pigeons. It bites during night hours and lies briefly on its prey, as long as it takes the blood meal. When pigeons are not accessible, ticks look for other hosts, invading nearby flats and biting humans. Case presentation We present the case of a woman aged 46 years who experienced severe anaphylaxis during the night which required emergency medical treatment, tracheal intubation and hospitalization in intensive care unit. Kounis syndrome was documented by transient ST depression and elevation of troponin. The allergological work up ruled out hypersensitivity to drugs, latex and foods containing alpha-gal, which is a cause of anaphylaxis. Basal serum tryptase was in normal range (8.63 ng/ml). When questioned about the presence of ticks, the patient brought into view various specimens of ticks that were recognized by an entomologist as Argas reflexus. Conclusions An in vitro diagnosis of allergy to Argas reflexus is currently not feasible because, though the major allergen Arg r 1 has been isolated, allergen extracts are not commercially available. Therefore, the diagnosis of anaphylaxis from Argas reflexus, when other causes of anaphylaxis are excluded, must rely only on history and clinical findings, as well as on the presence of pigeons and/or pigeon ticks in the immediate domestic environment.

Abstract Background Based on meta-analyses results, it is currently acknowledged that there is an increased risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD) undergoing inhaled corticosteroids (ICS) treatment. However, this is not found to be true in those with asthma. No data on this risk are available for COPD patients involved in pulmonary rehabilitation program (PR). Methods For 1 year, we prospectively studied 2 cohorts of COPD patients—undergoing PR and not undergoing PR. The first group included 438 patients undergoing PR of which 353 were treated with ICS, and 85 were treated with bronchodilators only. The second group was comprised of 76 COPD patients who were treated with ICS, but not PR. The control group consisted of 49 ICS-treated patients with asthma. The diagnosis of pneumonia, when suspected, had to be confirmed with a chest x-ray. Results Overall, 6 cases of pneumonia were diagnosed in the first study group: 5 ICS-treated patients and 1 patient treated only with bronchodilators. This corresponded to a rate of 1.41 and 1.17%, respectively, compared to a rate of 6.6% in COPD patients not treated with PR, which was significantly higher (p = 0.029) than that in the first study group. No case of pneumonia was registered among patients with asthma. Conclusions These findings suggest that a significantly lower incidence of pneumonia is found in COPD patients treated with ICS and PR than in patients treated with ICS but not with PR. This observation deserves to be investigated in large populations of PR-treated COPD patients, possibly in multi-centric cohort studies.

Abstract Background The use of drugs in the elderly is very extensive because of the frequent occurrence of chronic diseases. Adverse drug reactions (ADRs) commonly occur in geriatric patients receiving multiple therapeutic regimens. In the literature, little attention has been given to ADRs in the elderly, and particularly to allergic reactions. Objective The aim of the present study is to provide data on possible inappropriate prescriptions in the elderly in relation to allergic reactions and to identify a list of drugs which are likely inducers of allergic reactions. Methods We retrospectively evaluated ADRs in patients referring to Immunoallergy Unit of Hospital Policlinico in Bari on the basis of Beers criteria. Among adverse reactions, hypersensitivity reactions were extracted and a comparison between different age groups was assessed. Results Out of 823 patients with ADRs, in 30.6% hypersensitivity drug reactions (HDR) were diagnosed. Data about drug intake, comorbidities and clinical presentation were collected, aiming to identify possible risk factors. An evaluation of drugs most commonly involved was assessed. Conclusions HDR are reported to represent 5–10% of all ADRs, while in our study population the prevalence was about 30%. This suggests the need to develop strategies to minimize the incidence of drug allergy in the elderly, as well to reduce the phenomenon of inappropriate prescriptions.

Abstract The discovery of an exclusive local production of IgE antibodies dates back to the 1970s, but only recently the pathophysiology of such phenomenon was deeply investigated, leading to the concept of local allergic rhinitis (LAR). Currently, LAR is defined by the occurrence, in patients with symptoms clearly suggesting allergic rhinitis but with negative results to common allergy testing, of allergen specific IgE in the nasal mucosa. Most studies investigating LAR were based on the development of rhinitis symptoms following nasal provocation test (NPT) with the suspected allergens, but such test may be performed by a number of options, none of them being as yet acknowledged and recommended in consensus document. On the other hand, also the mere detection of IgE in the nasal mucosa indicates, as for IgE measurement in blood or other tissues, allergic sensitization but cannot give the certainty of clinical allergy. Therefore, the combination of IgE detection in nasal mucosa and a positive result of NPT should be used to diagnose LAR. Recent data on the use for in vitro testing of molecular allergy diagnostics in place of whole allergen extracts suggest that this method could improve the sensitivity and specificity of laboratory tests, and an appraisal of the basophil activation test as a third level technique, to be implemented when the results of local IgE testing and NPT are uncertain, is currently ongoing.

Abstract Asthma, allergic rhinitis (AR) and atopic dermatitis are very common in young people, but in the latest decades it was increasingly recognized that also individuals of higher ages, including the population over 65 years, are concerned. Actually, it is now acknowledged the aging does not considerably alter the immune response to allergens. Allergen immunotherapy (AIT) is the only treatment that works on the causes of allergy, but elderly people are commonly excluded from AIT, except the cases of insect sting allergy. A number of recent studies showed that aged individuals also successfully respond to AIT for respiratory allergy. Therefore, there is no reason to exclude elder patients from AIT. Anyhow, clinical conditions that are considered absolute or relative contraindications are quite frequent in this aged population, thus the risk/benefit ratio must be carefully evaluated for each patient, taking into account that the more frequent occurrence of co-morbidities and the consequent need of daily-based multidrug regimen can favor adverse effects. An important issue concern the ability of AIT, and particularly of sublingual immunotherapy, to significantly improve the quality of life, that often is particularly impaired in the elderly, reducing symptoms and drugs consumption.

Abstract Background Sublingual immunotherapy (SLIT) is a feasible option to classical subcutaneous immunotherapy to treat respiratory allergy and is increasingly prescribed in Europe. However, the lack of reimbursement may limit its prescription. In 2015, the 5-grass pollen tablets was authorized by the European Medicine Agency to treat grass-pollen induced rhinitis and was approved in Italy for full reimbursement. We evaluated the opinions of allergy specialists after the availability of the reimbursed 5-grass pollen tablets. Methods A multiple choice questionnaire composed by six questions was used to assess the specialists opinion. The questionnaire was uploaded on the free access online platform SurveyMonkey. The link to access the platform was sent to all members of the Società Italiana di Asma, Allergologia e Immunologia Clinica (SIAAIC). The access to the questionnaire was anonymous. At survey ending, the access was closed and data were downloaded directly from SurveyMonkey website. Results The questionnaire was filled by 70 allergists. The majority of allergists felt as most important the concept of SLIT as a drug, the content of allergen extract mirroring the natural exposure, the pre-coseasonal schedule as the most patient’s oriented, the very good profile of tolerability and safety, the importance of the build-up phase, and the importance of checking the patient after starting immunotherapy. Conclusions The opinions of the Italian allergy specialists about the reimbursed 5-grass-pollen tablets are very positive and make likely an appropriate prescription of SLIT for grass-pollen induced rhinitis in the next years.

Abstract Allergen immunotherapy (AIT) is the only treatment that works on the causes of allergy. Available AIT nowadays are subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) for allergic rhinitis and asthma, while for allergy to Hymenoptera venom only subcutaneous route is recommended. A bulk of trials and meta-analyses demonstrated that efficacy and safety of AIT in decreasing allergic clinical symptoms and use of rescue medications, while its preventive capacity is yet under investigation. The most important of these effects is the prevention of potentially fatal anaphylactic reactions to Hymenoptera stings by venom immunotherapy (VIT). A certain number of studies thus far available showed that AIT, in both forms, is able to prevent the progress of allergic rhinitis into asthma and the development of new sensitizations. These effects should be related to the mechanisms of action of AIT. In fact, it has been demonstrated that both SCIT and SLIT are able to modify the allergen presentation by dendritic cells, with result in modification of the phenotype of allergen-specific T cells, switching from the typical of allergic inflammation Th2-type response to a Th1-type one. Also allergen-specific T regulatory (Treg) cells play a pivotal role by producing suppressive cytokines, such as IL-10 and TGF-beta. However, the only plain evidence of a preventive effect concerns VIT, while the other outcomes need to be furtherly investigated.

Abstract Hypersensitivity to para-phenylenediamine (PPD) and related compounds induced by temporary black henna tattoos has become a serious health problem worldwide. Different patterns of sensitization with various clinical aspects are described in literature due to PPD associated to henna tattoo and these manifestations are likely correlated with the immunological and dermatological pathomechanisms involved. Henna is the Persian name of the plant Lawsonia inermis, Fam. Lythraceae. It is a woody shrub that grow in regions of North Africa, South Asia, India and Sri Lanka. Nowadays it is rather frequent to see temporary “tattoos” performed with henna. To make tattoos darker and long-lasting PPD has been associated to henna in tattoo drawings mixtures, so obtaining “black henna”. In these years there has been a rise of contact sensitization to PPD and in medical literature an increased number of cases have been reported on temporary henna tattoo application. Here we review the various clinical patterns related to PPD and henna tattoo, to investigate the possible link between clinic-morphological pictures and the immunological response to PPD and henna. The literature underlines that different clinical manifestations are related to black henna containing PPD, and its derivative products may cause delayed-type as well as immediate-type reactions. Further studies are needed to investigate the relationship between clinical and morphological aspects of PPD contact dermatitis and the T cell subsets predominance.

Abstract Background Early recognition of inflammatory markers and their relation to asthma, adverse drug reactions, allergic rhinitis, atopic dermatitis and other allergic diseases is an important goal in allergy. The vast majority of studies in the literature are based on classic statistical methods; however, developments in computational techniques such as soft computing-based approaches hold new promise in this field. Objective The aim of this manuscript is to systematically review the main soft computing-based techniques such as artificial neural networks, support vector machines, bayesian networks and fuzzy logic to investigate their performances in the field of allergic diseases. Methods The review was conducted following PRISMA guidelines and the protocol was registered within PROSPERO database (CRD42016038894). The research was performed on PubMed and ScienceDirect, covering the period starting from September 1, 1990 through April 19, 2016. Results The review included 27 studies related to allergic diseases and soft computing performances. We observed promising results with an overall accuracy of 86.5%, mainly focused on asthmatic disease. The review reveals that soft computing-based approaches are suitable for big data analysis and can be very powerful, especially when dealing with uncertainty and poorly characterized parameters. Furthermore, they can provide valuable support in case of lack of data and entangled cause–effect relationships, which make it difficult to assess the evolution of disease. Conclusions Although most works deal with asthma, we believe the soft computing approach could be a real breakthrough and foster new insights into other allergic diseases as well.

Introduction: The diagnostic work-up of allergic rhinitis (AR) is first and foremost based on the combination of clinical history data and results of skin prick tests (SPT). Other tests, including specific IgE measurement, nasal challenge, and, as a third option, component resolved diagnosis or basophil activation test, may be useful when the diagnosis is difficult because of polysensitization or when negative results of SPT are observed despite a suggestive history for allergy. The atopy patch test (APT) that assesses the type 4 delayed hypersensitivity allergy is currently not sufficiently used. The data obtained in recent studies on the diagnostic utility of the APT in patients with AR was reviewed. Data Sources: Review of the literature. Conclusion: The data from available studies show that the APT is frequently positive in patients with AR, especially when there is a positive history for atopic dermatitis. Very often, APT is the only positive test and therefore performing only SPT or in vitro IgE measurement may lead to an erroneous diagnosis of nonallergic rhinitis. Recent data suggest a role for APT not only for diagnosis but also in epidemiological investigation on respiratory allergy.

Background. Up to one-third of the patients suffering from eosinophilic esophagitis (EoE) present a refractory form, as defined by nonresponsiveness in clinical, endoscopic, or histological assessment after first-line therapy. Several studies recently investigated which factors can influence the development of this disease, but very few analyzed the factors underlying refractory EoE. Methods. Medical charts of patients affected by EoE were retrospectively evaluated. Phenotyping of patients was conducted according to demographic, clinical, histological, and treatment variables. Then, patients were divided into responder and nonresponder to therapy and distinguished among children and adults. Results. Forty-five children and 35 adult EoE patients were included. In the pediatric population, female sex (p

Abstract The natural history of large local reactions to Hymenoptera stings allowed to estimate the risk to develop a systemic reaction after an initial large local reaction in about 4% of patients. A recently published study claimed that such risk concerns instead around one‐fourth of patients. However, such study is flawed by serious imprecision, particularly the unreliable identification by patients of the culprit insect, as well as the dubious identification of the causative venom in multisensitized patients. Also, the authors criticized previous studied because of the limited number of patients, while they included in the study 662 patients. Indeed, when only patients clearly restung by the same insect according to their history data were considered, the number of patients fell to 35. These data are unable to change the current shared concept on the low risk of systemic reactions in patients with initial large local reaction.

The recent introduction of direct oral anticoagulants, including rivaroxaban, dabigatran, apixaban, and edoxaban, for the acute treatment and secondary prevention of venous thromboembolism and in atrial fibrillation has been shown to provide greater clinical benefit than oral vitamin K antagonists. However, direct oral anticoagulants are associated with adverse events, the most common being major bleeding; such events require the reversal of the anticoagulant effects by specific agents. In this case report, we describe an 87-year-old female with atrial fibrillation treated with dabigatran who had massive rectal bleeding. Idarucizumab 5 g (2 × 2.5 g/50 mL) was successfully used to reverse dabigatran effect; subsequent to this, treatment with dabigatran was resumed, and there were no further bleeding events. This suggests that dabigatran can be safely restarted after major bleeding, but this outcome needs to be confirmed in studies involving larger groups of patients.

Venom immunotherapy (VIT) is highly effective in preventing allergic reactions to insect stings, but the appropriate venom must be used to achieve clinical protection. In patients with multiple positive results to venoms, molecular allergy diagnostics or CAP-inhibition may identify the causative venom. Concerning allergy to venom from Polistes spp. it has been proposed that only the European species P. dominulus should be used for VIT. However, this recommendation is not present in any international guideline. Using both laboratory and clinical data, we aimed to evaluate the reliability of this proposal.We performed an in vitro study using CAP-inhibition to determine sensitization of 19 patients allergic to Polistes venom. The clinical study included 191 patients with positive tests to Polistes treated with VIT, 102 were treated with P. dominulus and 89 were treated with a mix of American Polistes (mAP).The difference in % of inhibition was significant concerning inhibition of P. dominulus sIgE by P. dominulus venom (79.8%) compared with inhibition by mAP venom (64.2%) and not significant concerning the inhibition of mAP sIgE by P. dominulus venom (80.1%) and by mAP venom (73.6%). Instead, the clinical protection from stings was not statistically different between the two kinds of venom.The data from CAP inhibition would suggest that the choice of either P. dominulus venom or mAP venom for VIT is appropriate in patients with CAP inhibition higher than 70%, but the clinical data show the same odds of protection from stings using for VIT P. dominulus or mAP venom.

OBJECTIVE: Allergic rhinitis (AR) is a disease with high and increasing prevalence. The management of AR includes allergen avoidance, anti-allergic drugs, and allergen specific immunotherapy (AIT), but only the latter works on the causes of allergy and, due to its mechanisms of action, modifies the natural history of the disease. Sublingual immunotherapy (SLIT) was proposed in the 1990s as an option to traditional, subcutaneous immunotherapy. MATERIAL AND METHODS: We reviewed all the available controlled trials on the efficacy and safety of SLIT. RESULTS AND CONCLUSION: Thus far, more than 60 trials, globally evaluated in 6 meta-analyses, showed that SLIT is an effective and safe treatment for AR. However, it must be noted that to expect clinical efficacy in the current practice SLIT has to be performed following the indications from controlled trials, that is, sufficiently high doses to be regularly administered for at least 3 consecutive years.

Atopic dermatitis (AD) is a common, chronic or chronically relapsing, multifactorial skin disease that mainly occurs in children but affects also adults. AD usually begins early in life and often concerns people with a personal or family history of asthma and allergic rhinitis. AD is characterized by eczematous changes in the epidermis and originates from a late, T-cell mediated reaction associated to the formation and production of memory T-cell of TH2 type, occurrence of homing receptor at skin level and cutaneous lymphocyte-associated (CLA) antigens. Extrinsic or allergic AD, but not intrinsic AD, shows high total serum IgE levels and the presence of specific IgE for environmental and food allergens. A pivotal role in the pathogenesis of AD is played by filaggrin, a protein contained in the granular layer of the epidermis regulating the aggregation of keratin filaments. Mutation in the filaggrin gene causes decreased barrier function of the corny layers of the epidermis. This favours the enter through the skin of environmental allergens, especially the house dust mite, that further facilitates such entering by the proteolytic activity of its major allergen Der p 1. In fact, recent advances suggest that the dust mite, more than foods, is the major cause of allergic AD. As far as the causal diagnosis of AD is concerned, there is notable evidence supporting the capacity of the atopy patch test (APT) to reproduce the pathophysiologic events of AD. This makes APT a valuable diagnostic tool for AD.

Cristoforo Incorvaia1, Simonetta Masieri2, Silvia Scurati3, Silvia Soffia3, Paola Puccinelli3, Franco Frati31Allergy/Pulmonary rehabilitation, Istituti Clinici di Perfezionamento, Milan, Italy; 2ENT Clinic, University La Sapienza, Rome, Italy; 3Medical and Scientific Department, Stallergenes, Milan, ItalyAbstract: Allergic rhinitis is a very common disease affecting about 20% of people. It may be treated by allergen avoidance when possible, by antiallergic drugs such as antihistamines and topical corticosteroids, and by allergen-specific immunotherapy. The latter is the only treatment able to act on the causes and not only on the symptoms of respiratory allergy and is able to maintain its efficacy even after stopping, provided an adequate duration of treatment of 3–5 years is ensured. Sublingual immunotherapy (SLIT) was introduced in the 1990s as a possible solution to the problem of adverse systemic reactions to subcutaneous immunotherapy and has been demonstrated by more than 50 trials and globally evaluated thus far by five meta-analyses as an effective and safe treatment for allergic rhinitis. Life-threatening reactions are extremely rare. However, it is important to note that clinical efficacy occurs only if SLIT meets its needs, ie, sufficiently high doses are regularly administered for at least 3 consecutive years. This is often overlooked in the current practice and may prevent the same success reported by trials from being achieved.Keywords: allergic rhinitis, sublingual immunotherapy, efficacy, safety, compliance, meta-analysis

Parietaria pollen is the most important cause of pollen allergies in the Mediterranean area, as Parietaria is widespread in this region. Many issues are associated with Parietaria allergy, including the duration of the pollen season (many doctors in fact believe that it lasts throughout the year), pollen load (which seems to be increasing over time), the impact of age (on IgE production and symptom severity), inflammatory changes (after pollen exposure), and the choice of allergen immunotherapy (AIT). In addition, molecular diagnostics allows for the defining of a correct diagnosis, differentiating between mere sensitization and true allergy. This review considers these topics and will hopefully help the allergist in clinical practice. Parietaria allergy is an intriguing challenge for the allergist in clinical practice, but it may be adequately managed by knowing the peculiarities of respective territories and the clinical characteristics of each patient.

Gian Galeazzo Riario-Sforza1, Cristoforo Incorvaia1, Fulvia Paterniti1, Laura Pessina1, Roberta Caligiuri1, Chiara Pravettoni1, Fabiano Di Marco2, Stefano Centanni21Pulmonary Rehabilitation, Istituti Clinici di Perfezionamento, Milan, Italy; 2Unit of Respiratory Medicine, University of Milan, San Paolo Hospital, Milan, ItalyBackground: Pulmonary rehabilitation (PR) is recognized as an evidence-based treatment in improving dyspnea and quality of life in patients with COPD. We evaluated the number needed to treat (NNT) to achieve an increase in physical capacity, as defined by a significant improvement in the six-minute walk test (6MWT) in patients with COPD undergoing PR.Methods: The study enrolled 284 patients aged 41 to 86 years (mean age 69.4 years) divided into two groups: a study group (222 patients) undergoing a PR program, and a control group (62 patients) treated only with drugs. The study group included patients with COPD divided in four subgroups according to GOLD stages.Results: In the study group, 142 out of 222 patients (64%) had an increase of at least 54 m in the 6MWT following PR versus 8 out of 62 patients (13%) in the control group after the same time interval. The NNT in the overall study group was 2; the same NNT was obtained in GOLD stages 2, 3, and 4, but was 8 in stage 1.Conclusions: PR is highly effective in improving the exercise capacity of patients with COPD, as demonstrated by a valuable NNT, with better results in patients with a more severe disease.Keywords: chronic obstructive lung disease, exercise capacity, number needed to treat, pulmonary rehabilitation, six-minute walk test

Paolo Scarpazza1, Cristoforo Incorvaia2, Giuseppe di Franco1, Stefania Raschi1, Pierfranco Usai1, Monica Bernareggi1, Cristiano Bonacina1, Chiara Melacini1, Silvia Vanni1, Serena Bencini1, Chiara Pravettoni2, Giuseppe Di Cara3, Mona-Rita Yacoub4, Gian Galeazzo Riario-Sforza2, Enrico Guffanti5, Walter Casali11Divisione di Broncopneumotisiologia, Ospedale Civile, Vimercate, Italy; 2Pulmonary rehabilitation, Istituti Clinici di Perfezionamento, Milan, Italy; 3University Department of Medical and Surgical Specialties and Public Health, Perugia, Italy; 4Allergy and Immunology Unit, IRCCS San Raffaele Hospital, Milan, Italy; 5Pulmonary rehabilitation, INRCA, Casatenovo, ItalyAbstract: Noninvasive mechanical ventilation (NIMV) is effective in the treatment of patients with acute respiratory failure (ARF). It proved to reduce the need of endotracheal intubation (ETI), the incidence of ETI-associated pneumonia, and mortality compared to nonventilated patients. A particular aspect concerns the outcome of NIMV in patients referring to an emergency room (ER) for ARF, and with a do-not-intubate (DNI) status due to advanced age or critical conditions. The aim of our study is to assess the outcome of NIMV in a group of elderly patients with acute hypercapnic ARF who had a DNI status. An overall number of 62 subjects (30 males, 32 females, mean age 81 ± 4.8 years, range 79–91 years) referred to our semi-intensive respiratory department were enrolled in the study. The underlying diseases were severe chronic obstructive pulmonary disease (COPD) in 50/62 subjects, restrictive thoracic disorders in 7/62 subjects, and multiorgan failure in 5/62 subjects. Fifty-four/62 patients were successfully treated with NIMV while 2/62 did not respond to NIMV and were therefore submitted to ETI (one survived). Among NIMV-treated patients, death occurred in 6 patients after a mean of 9.9 days; the overall rate of NIMV failure was 12.9%. Negative prognostic factors for NIMV response proved to be: an older age, a low Glasgow Coma Score, a high APACHE score at admission, a high PaCO2 after 12 hours and a low pH both after 1 and 12 hours of NIMV. We conclude that elderly patients with acute hypercapnic ARF with a DNI status can be successfully treated by NIMV.Keywords: acute respiratory failure, noninvasive mechanical ventilation, endotracheal intubation, do-not-intubate, COPD, oxygen therapy

Cristoforo Incorvaia1, Marina Mauro2, Gian Galeazzo Riario-Sforza1,Franco Frati3, Francesco Tarantini4, Maurizio Caserini41Allergy/Pulmonary rehabilitation, ICP Hospital, Milan, Italy; 2Allergy Unit, Sant’Anna Hospital, Como, Italy; 3University Department of Obstetric, Gynaecologic and Pediatric Sciences, Perugia, Italy; 4Respiratory Clinical Research, Novartis Farma S.p.A., Origgio, ItalyAbstract: IgE antibodies are a pivotal factor in pathophysiology of allergic diseases, and the possibility of reducing their level by anti-IgE has long been envisioned. Following several attempts, an effective biologic agent was obtained with the recombinant humanized monoclonal antibody (rhuMAb)-E25, known as omalizumab. A number of controlled clinical trials demonstrated its efficacy and safety in the treatment of severe allergic asthma uncontrolled by standard drug treatment with maximal recommended doses, and treatment with omalizumab is currently included in international guidelines on asthma management. Other studies reported a clear effectiveness also in allergic rhinitis, but the cost of the anti-IgE treatment suggests its use in patients with rhinitis concomitant with asthma. Other indications to be further investigated are skin disorders such as atopic dermatitis and IgE-mediated urticaria, as well as adverse reactions to foods, with a particularly important role in preventing food-induced anaphylaxis. Finally, there are data indicating the usefulness of omalizumab when used in combination with allergen specific immunotherapy, in terms of reducing the adverse reactions to treatment and increasing the clinical efficacy.Keywords: IgE, anti-IgE, omalizumab, allergic asthma, allergic rhinitis, atopic dermatitis, food allergy, allergen immunotherapy

Cristoforo Incorvaia1, Gian Galeazzo Riario-Sforza1, Chiara Pravettoni1, Mona-Rita Yacoub2, Franco Frati31Pulmonary Rehabilitation Unit, ICP Hospital, Milan, Italy; 2Allergy and Rheumatology Unit, IRCCS San Raffaele Hospital, Milan, Italy; 3Institute of Pediatrics, Department of Medical and Surgical specialty and Public Health, University of Perugia, Policlinico Monteluce, Perugia, ItalyAbstract: Disease exacerbations are an important aspect of COPD, because they affect its course and are associated with higher lung function decline. On the other hand, data obtained by biopsies have demonstrated that the progression of COPD is related to an increasing impairment of small airways. We sought to evaluate the small airway impairment (FEF25–75) in two groups of COPD patients (each group had 37 subjects) in relation to the frequency of exacerbations and the effectiveness of treatment with tiotropium bromide on the small airway impairment. The mean number of exacerbations was 3.6/year and 1.38/year in frequent and in infrequent exacerbators, respectively (p < 0.001). The mean value of FEF25–75 at baseline was 624 mL and 865 mL in frequent and in infrequent exacerbators respectively (p = 0.002). The changes in respiratory parameters versus baseline showed increases in mean FEV1, FVC, and FEF25–75 in both groups but only the increase in FEF25–75 in frequent exacerbators was statistically significantly (p = 0.013). During the 3-month period of the study the mean number of exacerbations was 0.66 in frequent and 0.12 in infrequent exacerbators. These findings indicate that COPD patients with frequent exacerbations have a higher impairment of small airways. Treatment with tiotropium in COPD subjects with frequent exacerbations proved to be effective in improving small airway impairment.Keywords: COPD, exacerbations, small airways, FEF25–75, tiotropium

The international guidelines on chronic obstructive pulmonary disease (COPD) recommend inhaled bronchodilators for maintenance treatment of the disease. These drugs include β2-agonists and muscarinic antagonists, which are both available as short-acting agents (to be used as needed for dyspnea) and long-acting agents. To the latter belong salmeterol and formoterol (long-acting β2-agonists) and indacaterol, vilanterol and olodaterol (very long-acting β2-agonist) as β2-agonists, and tiotropium, aclidinium and glycopyrronium bromide as long-acting muscarinic antagonists. The efficacy and safety of indacaterol and glycopyrronium as monotherapies has been demonstrated in several controlled trials. However, in some patients with moderate-to-severe COPD, symptoms are poorly controlled by bronchodilator monotherapy; in these cases the addition of a second bronchodilator from a different pharmacological class may be beneficial. Here we review the evidence from published randomized trials concerning the efficacy and safety of the once-daily fixed-dose dual bronchodilator combining indacaterol and glycopyrronium.

Background Identifying allergic rhinitis requires allergy testing, but the first-line referral for rhinitis are usually primary care physicians (PCP), who are not familiar with such tests. The availability of easy and simple tests to be used by PCP to suggest allergy should be very useful.Methods The Respiratory Allergy Prediction (RAP) test, based on 9 questions and previously validated by a panel of experts, was evaluated in this study.Results An overall number of 401 patients (48.6% males, age range 14–62 years) with respiratory symptoms was included. Of them, 89 (22.2%) showed negative results to SPT, while 312 (77.8%) had at least one positive result to SPT. Cohen’s kappa coefficient showed that all questions had an almost perfect excellent agreement between pre and post-test. The algorithm of decision-tree growth Chi-squared Automatic Interaction Detector showed that answering yes to the question 4 (Your nasal/ocular complains do usually start or worsen during the spring?), 6 (Did you ever had cough or shortness of breath, even during exercise?) and 8 (Do you use nasal sprays frequently?) gave a probability to have a positive SPT of 85%.Conclusions These findings show that RAP test can be proposed as an useful tool to be used by physician other than allergists when evaluating patients with rhinitis, suggesting the need of allergy testing. Keywords: Allergy, Allergic rhinitis, Allergy testing, Primary care physicians, Pharmacists

Infection from Toxocara species may give rise to a large array of clinical symptoms, including apparent manifestations of allergy such as asthma, urticaria/angioedema, and dermatitis. We report a case, thus far not described, of contact dermatitis attributed to nickel allergy but caused by Toxocara infection. The patient was a 53-year-old woman presenting from 10 years a dermatitis affecting head, neck, and thorax. Patch tests initially performed gave a positive result to nickel, but avoidance of contact with nickel did not result in recovery. The patient referred to our Allergy Service in 2010 because of dermatitis to feet. Patch testing confirmed the positive result for nickel, but expanding the investigation a positive result for IgG antibodies to Toxocara was detected by Western blotting and ELISA. Treatment with mebendazole achieved immediate efficacy on feet dermatitis. Then, two courses of treatment with albendazole resulted in complete regression of dermatitis accompanied by development of negative ELISA and Western blotting for Toxocara antibodies. This report adds another misleading presentation of Toxocara infection as apparent contact dermatitis caused by nickel and suggests bearing in mind, in cases of contact dermatitis not responding to avoidance of the responsible hapten and to medical treatment, the possible causative role of Toxocara.

Allergic rhinitis (AR) may be cured by allergen immunotherapy (AIT). However, patient characteristics for prescribing AIT are not well defined. This study aimed at evaluating the patient's profile to be a candidate for AIT in a cohort of patients suffering from AR, evaluated in 20 Italian Allergy or Ear, Nose, and Throat Centers. The study has been performed on 198 patients (98 men; mean age, 26.8 years) with AR (assessed by Allergic Rhinitis and Its Impact on Asthma [ARIA] criteria). The kind and the number of prescribed allergen extracts, type of diagnosis, severity of symptoms, and patient's perception of symptoms and drug use were evaluated. Patients were subdivided in AIT-treated and without AIT (as controls) subgroups. Most of the patients (69.7%) had persistent AR with moderate–severe symptoms. The mean number of sensitization was 3.4. ARIA classification and sensitization number did not affect AIT choice, but the type of allergen was relevant. AIT-treated patients had milder symptoms than controls if assessed by doctors, but AIT patients perceived more severe symptoms and larger drug use than controls. This study shows that the choice of AIT is based on patient's perception and type of allergen, but number of sensitizations, symptom severity assessed by doctors, and ARIA classification are not relevant factors. The key message might be that it is always relevant to pay attention to the complaints referred by the patient.

In the common practice of respiratory allergy, the confirmation by IgE tests of the relationship between the occurrence and duration of symptoms and the exposure to specific inhalant allergens allows an aetiological diagnosis. However, to see patients with suggestive history but negative IgE tests is not rare, and this generally leads to a diagnosis of nonallergic rhinitis or asthma. In many cases, such diagnosis is wrong, because the patient may be revealed as allergic by using additional testing. This is true for local allergic rhinitis, characterized by an exclusive IgE production in the nasal mucosa, that may be correctly diagnosed by performing a nasal IgE measurement or a nasal provocation test with the suspected allergen (s). Another misleading issue is the role of T cell-mediated, delayed hypersensitivity in the pathophysiology of rhinitis and asthma. Recent studies showed that in patients with rhinitis or asthma and negative IgE tests, especially when there is a positive history for current or past atopic dermatitis, the clinical symptoms are actually driven by such mechanism, that may be detected by performing an atopy patch test (APT). The allergen source most frequently responsible for this kind of allergy is the house dust mite, but other allergens may also be involved. Thus, before delivering a diagnosis of nonallergic rhinitis or asthma in patients with negative result to common allergy testing, further tests are needed. To miss the diagnosis of allergy has obvious consequences in terms of management, including allergen avoidance, patient’s education, and specific immunotherapy. Keywords: Rhinitis, Asthma, LgE tests, Nonallergic, Local allergic rhinitis, T-cell mediated hypersensitivity, Atopy patch test

Toxocara canis is an intestinal nematode affecting dogs and cats that causes human infestations by ingestion of embryonated eggs excreted in dogs' faeces. Humans are transport hosts, in whom the larvae do not develop to adult worms, but may migrate to various tissues and organs, and survive for several years, giving rise to several clinical symptoms, which include allergy-like presentations. We report three cases presenting as dermatitis, rhinitis, asthma, and conjunctivitis which were diagnosed and unsuccessfully treated as allergy. The correct diagnosis was established after detecting anti-Toxocara antibodies by Western blotting. All clinical symptoms showed improvement after starting treatment with mebendazole and subsequent courses of the antiparasitic drug resulted in full recovery. This suggests the possible role of Toxocara canis in inducing chronic symptoms of allergic type. This is particularly important for asthma, where it has been demonstrated that Toxocara canis infection causes allergic inflammation in the lungs associated with bronchial hyperreactivity. On the other hand, in our patients with asthma and with dermatitis the positive results from allergy tests were a confounding factor in delaying the correct diagnosis, which was finally obtained by the detection of antibodies to Toxocara canis.

Abstract Nasal cytology is a very useful diagnostic tool in nasal disorders, being able to detect both the cellular modifications of the nasal epithelium caused by either allergen exposure or irritative stimuli (that may be physical or chemical, acute or chronic), or inflammation. Over these past few years, nasal cytology has allowed to identify new disorders, such as the non-allergic rhinitis with eosinophils (NARES), the non-allergic rhinitis with mast cells (NARMA), the non-allergic rhinitis with neutrophils (NARNE), and the non-allergic rhinitis with eosinophils and mast cells (NARESMA). The rhinocytogram is actually able to distinguish the different forms of allergic rhinitis and to suggest the appropriate treatment, such as antinflammatory drugs or allergen immunotherapy. The technique is easy to perform and nasal cytology is therefore particularly suitable even for children. Such a consideration suggests the utility of a systematic use of nasal cytology in the diagnostic work-up of nasal disorders in children, in order to reach a proper defined diagnosis and to set a rational therapeutic approach: in facts, these two elements are fundamental in order to prevent from complications and to improve the patient’s quality of life.