Venom Immunotherapy and Aeroallergen Immunotherapy: How Do Their Outcomes Differ?

: 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

Patient's Adherence and Compliance and Quality of Life During/After VIT

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, <10% of whom stopped VIT. Instead, only 35% of the patients treated for allergy to imported fire ant remained adherent after 1 year of treatment. However, also concerning honeybees and vespids, although adherence is satisfactory, it is possible to further improve it by increasing information and support for patients. Health-related quality of life (HRQL) is an efficient measure to estimate the effectiveness and safety of medical treatment. Tools designed to make patients aware of its improvement through VIT and, in particular, of the complete prevention of the risk of fatal reactions have an important role in reinforcing adherence. However, aspects not yet evaluated, such as the possible relationship between the efficacy of VIT and HRQL or its particular features in patients with mastocytosis, deserve specific studies

Il profilo degli Anticorpi anti peptidi citrullinati nell'Artrite Reumatoide

Gli Anticorpi anti peptidi/proteine citrullinati (ACPA) sono un importante strumento per la diagnosi di Artrite Reumatoide. La presenza di ACPA di differenti specificità in soggetti sani è strettamente correlata allo sviluppo di Artrite Reumatoide; non è invece noto il valore predittivo dei singoli anticorpi per quanto riguarda le manifestazioni di malattia e la risposta alla terapia in pazienti con Artrite Reumatoide. Lo scopo del presente studio è quindi quello di valutare il valore diagnostico e prognostico dell’uso combinato dei peptidi VCP1 e VCP2 (derivati da proteine di virus di Epstein Barr) e di HCP1 e HCP2 (derivati dall’istone H4) per la ricerca di ACPA nel siero. In 413 pazienti con diagnosi di Artrite Reumatoide è stata valutata la presenza di anticorpi anti-VCP1, anti-VCP2, anti-HCP1 e anti-HCP2 attraverso test ELISA. I pazienti sono stati valutati sulla base delle manifestazioni articolari ed extrarticolari, sulla base della attività e gravità della malattia, sulla base delle terapie in corso e delle terapie assunte in passato. I dati sono stati valutati attraverso analisi dei gruppi (cluster analysis). Il 44% dei pazienti ha mostrato positività per anticorpi anti-VCP1, il 52% per anticorpi anti-VCP-2; il 46% dei pazienti ha mostrato positività per anticorpi anti-HCP1 e il 63% per anticorpi anti-HCP2. I pazienti sono stati quindi suddivisi in cinque gruppi sulla base del numero di anticorpi rilevati: è stato riscontrato che all’aumentare del numero di anticorpi rilevati corrispondeva un aumento del valore medio del titolo anticorpale, della positività per Fattore Reumatoide e della frequenza di coinvolgimento polmonare. Ad un più elevato numero di ACPA sierici corrisponde quindi un aumento del rischio di coinvolgimento polmonare. Pazienti con diverse tipologie di ACPA sono pazienti spesso trattati con farmaci biologici, probabilmente affetti da forme più gravi della malattia. Lo studio del profilo degli ACPA nei pazienti con Artrite Reumatoide potrebbe quindi essere importante per definire alcuni aspetti della malattia

Mabs for treating asthma: omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab

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

Prevalence and Clinical Significance of Symptoms at Ultra High Risk for Psychosis in Children and Adolescents with Obsessive⁻Compulsive Disorder: Is There an Association with Global, Role, and Social Functioning?

In literature nothing is known about the clinical significance of Ultra High Risk (UHR) symptoms in children and adolescents with diagnosis of obsessive⁻compulsive disorder (OCD). In this study, we examined the prevalence of UHR symptoms and their relationship with severity of obsessive⁻compulsive symptomatology, global, social, and role functioning, and level of associated depressive symptoms in a clinical sample (n = 51) of children and adolescents aged between 8 and 17 years with a diagnosis of OCD. The prevalence of UHR symptoms in this sample was 43.1%. We divided the whole sample into two groups: children and adolescents with OCD and UHR symptoms (n = 22) and children and adolescents with OCD without UHR symptoms (n = 29). Our findings suggest that the group with OCD and UHR symptoms shows worse global, social, and role functioning than the group with OCD without UHR symptoms. No differences were found on the severity of obsessive⁻compulsive symptomatology, the number of psychiatric diagnoses associated, and the level of depressive symptoms. The presence of UHR symptoms in children and adolescents with OCD could cause significant functional impairment and should be considered in order to plan specific and targeted therapeutic interventions

Lipid transfer protein syndrome: How to save a life through careful education

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

Diagnostic performance of nasal cytology

Purpose Nasal pathologies are characterized by a symptomatology that hardly allows to distinguish allergic rhinitis (AR), non-allergic rhinitis (NAR), and chronic rhinosinusitis (CRS). Nasal cytology (NC) has shown increasing importance in helping the clinician to differentiate the various phenotypes of rhinitis. NC allows us to evaluate nasal cellularity by distinguishing AR and various types of NAR. The objective of the study is to assess the diagnostic performance of the NC by evaluating its sensitivity, specificity, and predictive value. Methods We recruited 387 patients with persistent rhinitis symptoms, and nasal cytology was performed. The rhinocytogram was obtained by reading for fields and the cellular count was made using quantitative and semi-quantitative grading together. Results Two hundred and fifteen patients (55.5%; 38 had acute rhinitis, 24 acute sinusitis, 153 chronic rhinosinusitis) out of 387 referred nasal symptoms. Cytological specimen showed a mean of 94 +/- 4% ciliated cells, 29 +/- 0.2% mucinous cells, 16 +/- 0.1% neutrophils, 11 +/- 0.08% eosinophils, 4 +/- 0.03 lymphocytes, 4 +/- 0.03% mast cells, and 4 +/- 0.01% other cells. NC was positive in 271 cases (70%). After revision of medical history, 153 patients (39%) were considered positive for NAR. Test sensibility was 100% (95% CI 97-100), specificity was 49.6% (95% CI 43-56%). Positive predictive value (PPV) was 56% (95% CI 50-62%), and negative predictive value (NPV) was 100% (95% CI 96-100%). The positive likelihood ratio was 1.98 (95% CI 1.75-2.25). Accuracy of the test was 69.5% (95% CI 64.6-74.0%). Conclusion Our data showed ability to identify the true-positive patients with NAR but a low ability to identify the true-negative patients, with a global accuracy of 69.5%