Giselda Colombo

Causes of food-induced anaphylaxis in Italian adults: a multi-centre study.

Background: Data about food-induced anaphylaxis in Italy are missing. Objective: It was the aim of this study to detect the main foods/food allergens causing anaphylaxis in Italy. Methods: The frequency of anaphylaxis and the relative importance of many offending foods were assessed in 1,110 adult patients with food allergy diagnosed by common criteria at 19 allergy centres scattered throughout Italy from 1 January to 31 December 2007. Results: Fifty-eight of 1,110 (5%) food-allergic patients experienced at least 1 episode of anaphylaxis. On average, they were older than other food-allergic patients (34 vs. 31 years; p < 0.05). The majority of anaphylactic episodes occurred in patients sensitized to lipid transfer protein (LTP; n = 19), followed by shrimp (n = 10), tree nuts (n = 9), legumes other than peanut (n = 4), and seeds (n = 2); peanut, spinach, celery, buckwheat, wheat, avocado, tomato, fish, meat, and Anisakis caused an anaphylactic reaction in single patients. Among LTP-hypersensitive patients, peach caused 13/19 anaphylactic episodes. Shrimp-allergic patients were significantly older than other patients with food-induced anaphylaxis (p < 0.05), whereas patients allergic to LTP experienced their anaphylactic episodes at a younger age (p < 0.001). The frequency of anaphylaxis among patients sensitized to LTP, shrimp or tree nuts did not differ between northern and central/southern Italy. Conclusion: LTP is the most important allergen causing food-induced anaphylaxis in Italy, peach being the most frequently offending food. Peanut-induced anaphylaxis seems very uncommon. Geographic and environmental differences both between Italy and other countries and within Italy seem to play a relevant role in the pattern of sensitization to foods.

Shrimp Allergy in Italian Adults: A Multicenter Study Showing a High Prevalence of Sensitivity to Novel High Molecular Weight Allergens

Background: Shrimp is a frequent cause of food allergy worldwide. Besides tropomyosin, several allergens have been described recently. Objective: We investigated which allergens are involved in Italian shrimp-allergic adults. Methods: Sera from 116 shrimp-allergic patients selected in 14 Italian allergy centers were studied. Skin prick tests with house dust mite (HDM) as well as measurements of IgE to Pen a 1 (shrimp tropomyosin) and whole shrimp extract were performed. All sera underwent shrimp immunoblot analysis, and inhibition experiments using HDM extract as inhibitor were carried out on some Pen a 1-negative sera. Results: Immunoblots showed much variability. IgE reactivity at about 30 kDa (tropomyosin) was found in <50% of cases, and reactivity at about 67 kDa and >90 kDa was frequent. Further reactivities at 14–18, 25, 43–50, about 60 and about 80 kDa were detected. Most subjects had a history of shrimp-induced systemic symptoms irrespective of the relevant allergen protein. IgE to Pen a 1 were detected in sera from 46 (41%) patients. Skin reactivity to HDM was found in 43/61 (70%) Pen 1-negative subjects and inhibition studies showed that pre-adsorption of sera with HDM extract induced a marked weakening of the signal at >67 kDa. Conclusions: Several allergens other than tropomyosin are involved in shrimp allergy in adult Italian patients. Some hitherto not described high molecular weight allergens seem particularly relevant in this population and their cross-reactivity with HDM allergens makes them novel potential panallergens of invertebrates.

Illness perception, mood and coping strategies in allergic rhinitis: Are there differences among ARIA classes of severity?

BACKGROUND According to the Federal Institution of Health Insurance, ENT doctors perform more skin prick tests for the diagnosis of allergic rhinitis (AR) than other medical specialties in Belgium. However, immunotherapy (IT) is not practiced by all. This study aims to obtain insight into IT practice by ENT doctors, the type of IT performed and the reasons not to perform IT. METHODOLOGY A questionnaire was sent to all registered ENT doctors of Belgium (n=648), involving questions on type and duration of ENT practice, geography and gender. In addition, the questionnaire informed about diagnosis of AR, indication for IT, type of IT performed, and reasons not to perform IT and referral pattern. RESULTS The response rate among ENT doctors was 54%, with 7% of responders being excluded as they do not diagnose AR. 81% of Belgian ENT doctors make the indication for IT in AR patients, with 19% neglecting the indication for IT in AR patients. The two main reasons for not indicating IT are lack of expertise and the perception of high costs associated with IT. 70% of ENT specialists are practicing IT themselves, with sublingual IT being mostly performed. Interestingly, IT is mostly frequently performed by those ENT doctors with long-standing ENT practice, in private practice and in Wallonia. CONCLUSION Despite the high prevalence of AR in ENT practice, IT is most frequently performed by ENT doctors with longstanding practice, working in private practice and/or in the French speaking part of Belgium. Among the different types of IT, sublingual IT is the most frequently performed means of IT by ENT doctors.OBJECTIVE To investigate the role of inflammation in non-allergic rhinitis (NAR) patients in a large series to establish the prevalence of different NAR-subtypes, clinical features and the role of nasal cytology in the diagnostic algorithm. METHODOLOGY Patients were selected out of 3650 individuals who spontaneously presented at our institution. We consecutively enrolled 519 NAR-patients in an analytical cross-sectional study between November 2007 and June 2013 (level of evidence: 3b). All patients underwent rhinological evaluation including symptoms questionnaire, endoscopy, CT scan, allergy tests and nasal cytology. RESULTS The inflammatory cell infiltrate affects the severity of symptoms differently, allowing for identification of different phenotypes of NAR. We distinguished two groups: “NAR without inflammation”(NAR-) and “NAR with inflammation”(NAR+), in addition to different NAR-subtypes with inflammation. A significant difference was observed in terms of clinical symptoms and association with comorbidities (previously diagnosed asthma and aspirin intolerance) between NAR–, NAR+ and between different NAR+ subtypes. CONCLUSION Our data suggest that NAR- and NAR with neutrophils behave similarly, showing lower symptom score values and a lower risk of association with comorbidities compared to NAR with eosinophils and mast cells (singularly or mixed). In our belief it is very important to establish the presence and type of inflammation in non-allergic rhinitis patients and nasal cytology is a very useful test in correct differential diagnosis.OBJECTIVE To assess the applicability of the Peak Nasal Inspiratory Flow (PNIF) curves in follow-up of children in the treatment of allergic rhinitis. METHODS Prospective study of 40 patients with AR, grouped in corticosteroid spray versus physiological saline solution use. Follow up for 10 weeks through clinical score and PNIF percentages in relation to the reference curves, with was-out at week 8. Statistical assessment of the effect of treatment on variation of PNIF and clinical score was calculated by ANOVA model and Multiple Comparison of Means Test - Least Significant Difference. RESULTS There was a statistically significant influence of the group, time and interaction between time and group on PNIF percentages. Throughout follow up, patients from the treatment group had mean PNIF percentages significantly higher than the placebo group. Clinical score results also demonstrated a statistically significant influence between the groups, time and interaction between time and group. CONCLUSION Increase in PNIF percentage values observed in children treated with intranasal corticosteroids revealed the applicability of PNIF curves in their follow up.OBJECTIVE This study aims to examine humans ́ abilities to localize odorants within the open field. METHODOLOGY Young participants were tested on a localization task using a relatively selective olfactory stimulus (2-phenylethyl-alcohol, PEA) and cineol, an odorant with a strong trigeminal component. Participants were blindfolded and had to localize an odorant source at 2 m distance (far-field condition) and a 0.4 m distance (near-field condition) with either two nostrils open or only one open nostril. RESULTS For the odorant with trigeminal properties, the number of correct trials did not differ when one or both nostrils were used, while more PEA localization trials were correctly completed with both rather than one nostril. In the near-field condition, correct localization was possible in 72-80% of the trials, irrespective of the odorant and the number of nostrils used. Localization accuracy, measured as spatial deviation from the olfactory source, was significantly higher in the near-field compared to the far-field condition, but independent of the odorant being localized. CONCLUSION Odorant localization within the open field is difficult, but possible. In contrast to the general view, humans seem to be able to exploit the two-nostril advantage with increasing task difficulty.BACKGROUND This study was designed to assess if illness perception, mood state and coping strategies differ according to allergic rhinitis (AR) persistence and severity. METHODS Illness perception, mood profiles, coping behaviors and rhinitis symptoms were assessed by means of validated tools inpatients classified according to the Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines. RESULTS Two hundred and thirty-one patients underwent data analysis. No difference in age, sex, socio-economic status, smoking habits was detected comparing patients according to AR severity, duration or 4 ARIA classes. Patients with intermittent AR reported higher scores than those with persistent AR in confusion-bewilderment of Profile of Mood States (POMS); patients with moderate/severe rhinitis had significantly higher scores than those with mild rhinitis in TSSS, Identity and Consequences. No differences were detected in all assessed outcomes in the 4 ARIA classes. CONCLUSIONS The patients perspective about AR is independent of persistence and severity of symptoms. This may explain why AR remains under-diagnosed and under-treated, even in its most severe forms. Self-management plans should consider the patients perspective.The assessment of Chronic Rhinosinusitis, like any other disease, may involve multiple possible disease manifestations, including subjective patient-reported outcomes, objective disease (e.g. endoscopy or radiographic), and physician-driven (e.g. need for systemic medications). Disease control is often used as a global metric of disease burden and represents the extent to which disease manifestations are within an acceptable range. Achieving control is an important treatment goal.The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012(1-3). The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings.BACKGROUND Endoscopic dacryocystorhinostomy (EN-DCR) is a commonly used procedure in the treatment of nasolacrimal duct obstruction (NLDO). However, there is no generally accepted disease-specific questionnaire for assessing outcomes. METHODOLOGY We conducted a prospective study to initially validate a Nasolacrimal Duct Obstruction Symptom Score questionnaire(NLDO-SS) and to evaluate the long-term success of EN-DCR procedures. Seventy-six patients (86 eyes) were evaluated in follow-up visits at 1-8 years after EN-DCR. The patients completed the NLDO-SS questionnaire twice, first, at home and, second,after receiving information from the otorhinolaryngologist, during the visit. The surgical outcome was considered successful if the irrigation succeeded and if the patient symptoms were relieved as assessed with the NLDO-SS. RESULTS The diagnostic accuracy of the NLDO-SS was 84%, sensitivity 82%, specificity 85%, positive predictive value 58%, negative predictive value 95%, odds ratio 26, risk ratio 11 and usefulness index 0.55. Cronbachs alpha was 0.85, and the test-retest reliability coefficient was 0.87. The long-term success rate after EN-DCR was 79%. CONCLUSION The NLDO-SS iss a feasible clinical tool in assessing the success of EN-DCR. The success rate was found to decrease EN-DCR at long-term follow-up.

Effects of Sublingual Immunotherapy on Allergic Inflammation: An Update

The most common allergic diseases, and especially the respiratory disorders such as rhinitis and asthma, are closely related to the allergic inflammation elicited by the causative allergen. This makes inflammation the main target of anti-allergic therapies. Among the available treatments, allergen specific immunotherapy (AIT) has a patent effect on allergic inflammation, which persists also after its discontinuation, and is the only therapy able to modify the natural history of allergy. The traditional, subcutaneous route of administration was demonstrated to modify the allergen presentation by dendritic cells (DCs) that in turn correct the phenotype of allergen-specific T cells, switching from the Th2-type response, typical of allergic inflammation and characterized by the production of IL-4, IL-5, IL-13, IL-17, and IL-32 cytokines to a Th1-type response. This immune deviation is related to an increased IFN-gamma and IL-2 production as well as to the anergy of Th2 or to tolerance, the latter being related to the generation of allergen-specific T regulatory (Treg) cells, which produce cytokines such as IL-10 and TGF-beta. Anti-inflammatory mechanisms observed during sublingual AIT with high allergen doses proved to be similar to subcutaneous immunotherapy. Data obtained from biopsies clearly indicate that the pathophysiology of the oral mucosa, with particular importance for mucosal DCs, plays a crucial role in inducing tolerance to the administered allergen.

Drug induced exfoliative dermatitis: state of the art

Drug induced exfoliative dermatitis (ED) are a group of rare and severe drug hypersensitivity reactions (DHR) involving skin and usually occurring from days to several weeks after drug exposure. Erythema multiforme (EM), Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the main clinical presentations of drug induced ED. Overall, T cells are the central player of these immune-mediated drug reactions. Here we provide a systematic review on frequency, risk factors, pathogenesis, clinical features and management of patients with drug induced ED.

Optimal management of DRESS syndrome in course of infectious endocarditis

[3] Bernstein JA, Herd ZA, Bernstein DI, Korbee L, Bernstein IL. Evaluation and treatment of localized vaginal immunoglobulin E-mediated hypersensitivity to human seminal plasma. Obstet Gynecol. 1993;82:667e673. [4] Lee-Wong M, Collins JS, Nozad C, Resnick DJ. Diagnosis and treatment of human seminal plasma hypersensitivity. Obstet Gynecol. 2008;111:538e539. [5] Freeman S. Woman allergic to husband’s sweat and semen. Contact Dermatitis. 1986;14:110e112. [6] Valyasevi MA, Maddox DE, Li JT. Systemic reactions to allergy skin tests. Ann Allergy Asthma Immunol. 1999;83:132e136.

Eosinophils from Physiology to Disease: A Comprehensive Review

Despite being the second least represented granulocyte subpopulation in the circulating blood, eosinophils are receiving a growing interest from the scientific community, due to their complex pathophysiological role in a broad range of local and systemic inflammatory diseases as well as in cancer and thrombosis. Eosinophils are crucial for the control of parasitic infections, but increasing evidence suggests that they are also involved in vital defensive tasks against bacterial and viral pathogens including HIV. On the other side of the coin, eosinophil potential to provide a strong defensive response against invading microbes through the release of a large array of compounds can prove toxic to the host tissues and dysregulate haemostasis. Increasing knowledge of eosinophil biological behaviour is leading to major changes in established paradigms for the classification and diagnosis of several allergic and autoimmune diseases and has paved the way to a “golden age” of eosinophil-targeted agents. In this review, we provide a comprehensive update on the pathophysiological role of eosinophils in host defence, inflammation, and cancer and discuss potential clinical implications in light of recent therapeutic advances.

Evaluation of basophil activation test in suspected food hypersensitivity

Food hypersensitivity is characterized by a wide range of symptoms. The relationship between symptoms and food is more frequently suspected than objectively proven. Basophil activation test (BAT) is based on the evaluation of activation markers on blood basophils in vitro stimulated with drugs or allergens.

Omalizumab in elderly patients with chronic spontaneous urticaria: An Italian real-life experience

BACKGROUND Omalizumab therapy is effective and safe in patients with chronic spontaneous urticaria (CSU) resistant to nonsedating histamine1 (H1) antihistamines (nsAHs). OBJECTIVE To evaluate the efficacy and safety of omalizumab in elderly (aged ≥65 years) patients with nonsedating H1-antihistamine-refractory CSU in a real-life setting. METHODS Patients with nonsedating H1-antihistamine-refractory CSU (n = 322) treated with omalizumab administered every 4 weeks in doses of 300 mg for 24 weeks were divided into 2 groups according to age at omalizumab treatment onset: 15 to 64 years and 65 years or older. Treatment response was assessed using a 7-day urticaria activity score (UAS7). Adverse effects of omalizumab therapy were recorded. RESULTS Among patients, 32 (9.9%) were 65 years or older. At baseline, CSU characteristics were generally similar among the groups, although the presence of angioedema was statistically significantly lower in patients younger than 65 years. Any differences in weekly itch severity score, hive score, and UAS7 between the 2 age groups were not significant at weeks 4, 12, and 24, with the exception of the hive score at 24 weeks and the UAS7 at week 24. No significant between-group differences were seen in the proportion of patients with a UAS7 of 6 or lower and with a UAS7 score of 0 at weeks 4, 12, 24, and 40. The proportion of patients with at least one adverse event reported as suspected to be caused by study drug was 10% in the younger group vs 6.3% in the older group (P = .53). CONCLUSION Our study found that omalizumab is a well-tolerated and effective therapy for elderly patients with nonsedating H1-antihistamine-refractory CSU.

Immune Mechanisms of Allergen-Specific Immunotherapy

Allergen immunotherapy (AIT) has the exclusive ability to modify the natural history of allergy and to maintain its clinical efficacy also after stopping the treatment. This occurs because of the AIT mechanism of action, mainly consist- ing in a specific induction of tolerance to the causative allergen. Such tolerance takes place as a result of a complex inter- action of innate and adaptive immunity processes, that involve inflammatory cells, cytokines and chemokines. The first response to allergens is provided by the antigen-presenting cells, and particularly by dendritic cells (Dcs) that, following activation, acquire chemokine receptors (CCRs), useful for migration to lymphoid organs, where adaptive immune re- sponse is induced. DCs act by presenting the antigen(s) to effectors T cells (T helper CD4 + and T suppressor CD8 +) de- rived from naive T cells. The development of different cell subtypes from naive T cells (Th0) may follow various path- ways and depends on both individual genetic background (atopic/non atopic) and environmental factors. The T cell re- sponse in atopic subjects is influenced by the Th2 polarization promoting the production of cytokines such as IL-4 and IL- 5. On the contrary, the expression of CD80 may determine a Th1 cytokines production, and ICOS-L supports the T- regulatory cells activation that significantly reduce allergic inflammation. The suppressive effect of Treg is due to the ex- pression of high level of the transcription factor Foxp3 on their surface, to the production of IL-10 and TGF-s and to the expression of membrane molecules as CTL-4 PD-1 and BTLA. Recent advances highlighted a role also for Th9 and Th17 lymphocytes. Such immunologic modification leads to the long noted events in studies on mechanisms of action, such as the decrease of specific IgE and the increase of specific IgG1 and IgG4, and ultimately on the inhibition of inflammatory cells such as mast cells, basophils and eosinophils and on the control of clinical symptoms.