The role of skin tests with polyethylene glycol and polysorbate 80 in the vaccination campaign for COVID-19: results from an Italian multicenter survey.

Summary: Background. International guidelines suggested skin tests with Polyethylene-glycol (PEG) and polysorbate 80 (PS-80), to investigate a possible hypersensitivity to these excipients either to identify subjects at risk of developing allergic reactions to Covid-19 vaccines, or in patients with suspected IgE mediated hypersensitivity reactions (HR) to the Covid-19 vaccine. The main purpose of this study was to investigate the prevalence of PEG and PS sensitization in patients with a clinical history of HR to drugs containing PEG/PS and in patients with a suspected Covid-19 vaccine immediate HR. Methods. This was a multicenter retrospective study conducted by allergists belonging to 20 Italian medical centers. Skin testing was performed in 531 patients with either a clinical history of suspected hypersensitivity reaction (HR) to drugs containing PEG and/or PS-80 (group 1:362 patient) or a suspected HR to Covid-19 vaccines (group 2: 169 patient), as suggested by the AAIITO/SIAAIC guidelines for the "management of patients at risk of allergic reactions to Covid-19 vaccines" [1]. Results. 10/362 (0.02%) had positive skin test to one or both excipients in group 1, 12/169 (7.1%) in group 2 (p less than 0.01). In group 2 HRs to Covid-19 vaccines were immediate in 10/12 of cases and anaphylaxis occurred in 4/12 of patients. Conclusions. The positivity of skin test with PEG and or PS before vaccination is extremely rare and mostly replaceable by an accurate clinical history. Sensitization to PEG and PS has to be investigated in patients with a previous immediate HR to a Covid-19 vaccine, in particular in patients with anaphylaxis.

Systemic nickel allergy syndrome: epidemiological data from four Italian allergy units.

The prevalence of nickel hyper-sensitivity varies widely in different countries, nevertheless it is the leading cause of contact dermatitis. The presence of nickel in the diet (mainly plant foods) in some nickel-sensitive subjects can provoke/aggravate eczema and systemic contact dermatitis as well as cause extra-cutaneous symptoms (respiratory, gastrointestinal, neurological). These symptoms, correlated to the ingestion of nickel-containing foods and beverages, in nickel patch test positive individuals, defines the so called Systemic Nickel Allergy Syndrome (SNAS), a condition successfully treated by oral desensitization. Although numerous studies have investigated the prevalence of contact nickel allergy or addressed the relationship between nickel intake and onset of systemic symptoms, to our knowledge no epidemiological studies have attempted to estimate the prevalence of SNAS. Therefore, we decided to evaluate consecutive patients (1,696), afferent to four allergy units in Sicily, a region of southern Italy, from October 2010 to March 2011. SNAS was confirmed in 98 patients (5.78 percent) of the 1,696 studied, suggesting that this clinical entity may be an emergent allergological condition rather than an occasional finding. The most common symptoms complained of in our population were cutaneous (51 patients), gastrointestinal (87 patients) and other systemic clinical manifestations (37 patients). Furthermore, 16 out of the 98 SNAS patients (16.3 percent) presented IgE-mediated food allergy with a statistically significant association (X2=16.950; P<0.0001), therefore suggesting underlying cross-facilitating pathways. These findings need confirmation on wider populations but may help allergists to suspect, during common clinical practice, that cutaneous and extra-cutaneous symptoms may be referred to nickel intake and deserve specific in-depth investigation.

Factors influencing the prescription of allergen immunotherapy: the allergen immunotherapy decision analysis (AIDA) study.

The evidence of efficacy of allergen immunotherapy (AIT) for respiratory allergy has been demonstrated by a number of meta-analyses. However, the daily practice of AIT is quite different from controlled trials, facing challenges in terms of selection of patients, practical performance, and, of particular importance, use of allergen extracts of inadequate quality. We here performed a survey, named the Allergen Immunotherapy Decision Analysis (AIDA), to evaluate which criteria are used by specialists to choose a product for sublingual immunotherapy (SLIT) in patients with respiratory allergy. A questionnaire composed of 14 items to be ranked by each participant according to the importance attributed when choosing SLIT products was submitted to 444 Italian specialists. The responses of the 169 (38.1%) physicians, who answered all questions, were analysed. Most of the respondents were allergists (79%), followed by pulmonologists (10.8%), both allergists and pulmonologists (4.8%), and otorhinolaryngologists (3%); 59.8% of the respondents were males and 40.2% were females. The age distribution showed that 89.9% of the respondents were aged between 35 and 64 years. All respondents usually prescribed AIT products in their clinical practice: 31.4% used only SLIT, whereas 69.2% used both subcutaneous and sublingual administration. The rankings, expressed as means, attributed by physicians for each of the 14 items were as follows: level of evidence-based medicine (EBM ) validation of efficacy (3.44), level of EBM validation of safety (4.30), standardization of the product (5.37), efficacy based on personal experience (5.82), defined content(s) of the major allergen(s) in micrograms (5.96), scientific evidence for each single allergen (6.17), safety based on personal experience (6.32), ease of administration protocol (8.08), cost and terms of payment (e.g. instalments) (9.17), dose personalization (9.24), patient preference (9.25), ease of product storage (9.93), reimbursement (10.12), and availability of a helpline or on-line assistance from the manufacturer (11.89). These attitudes need to be taken into consideration by regulatory agencies as well as by producers.

Characteristics of patients with allergic polysensitization: the POLISMAIL study.

BACKGROUND: The natural history of respiratory allergy is commonly characterized by a worsening of symptom severity, frequent comorbidity of rhinitis and asthma, and polysensitization to aeroallergens. The polysensitization phenomenon starts since childhood and is rare to find monosensitized adult patients. However, there are few studies investigating the characteristics of polysensitized patients. METHODS: This study was performed on a large cohort of patients with allergic rhinitis (assessed by ARIA criteria) and/or mild to moderate asthma (assessed by GINA). The kind and the number of sensitizations, their patterns, and the relation with quality of life (QoL) measured by the Juniper's RQLQ guestionnaire, were evaluated. RESULTS: Globally 418 patients (50.2% males, 49.8% females, mean age 26.4 years, range 3.5-65 years, 64 smokers, 371 non-smokers) were enrolled: 220 had allergic rhinitis alone, and 198 allergic rhinitis and asthma. The mean number ofsensitizations was 2.6. Three hundred-five patients (73%) had persistent rhinitis (PER), 220 of them with moderate-severe form. There was no significant derence in rate of rhinitis and asthma in monosensitized or polysensitized patients. Most patients were sensitized to pollens, whereas only 24.2% of them were sensitized to perennial allergens. Polysensitization was significantly associated with some issues of QoL, confirming previous findings, but not with number ofsensitizations. CONCLUSIONS: This study provides data confirming for poly-sensitized patients the relevance of ARIA classification of AR. PER is the most common form of AR in this cohort, symptoms are frequently moderate-severe, and asthma is present in about the half of patients with AR.

Pharmacoeconomics of subcutaneous allergen immunotherapy.

The current burden of allergic diseases, estimated by both direct and indirect costs, is very relevant. In fact the cost estimation for rhinitis amount globally to 4-10 billion dollars/year in the U.S. and to an average annual cost of 1089 euros per child/adolescent and 1543 euros per adult in Europe. The estimated annual costs in Northern America for asthma amounted to 14 billion dollars. Consequently, preventive strategies aimed at reducing the clinical severity of allergy are potentially able to reduce its costs. Among them, specific immunotherapy (SIT) joins to the preventive capacity the carryover effect once treatment is discontinued. A number of studies, mainly conducted in the US and Germany demonstrated a favourable cost-benefit balance. In the nineties, most surveys on patients with allergic rhinitis and asthma reported significant reductions of the direct and indirect costs in subjects treated with SIT compared to those treated with symptomatic drugs. This is fully confirmed in recent studies conducted in European countries: in Denmark the direct cost per patient/year of the standard care was more than halved following SIT; in Italy a study on Parietaria allergic patients demonstrated a significant difference in favor of SIT plus drug treatment for three years versus drug treatment alone, with a cost reduction starting from the 2nd year and increasing to 48% at the 3rd year, with a highly statistical significance which was maintained up to the 6th year, i.e. 3 years after stopping immunotherapy, corresponding to a net saving for each patient at the final evaluation of 623 euros per year; in France a cost/efficacy analysis comparing SIT and current symptomatic treatment in adults and children with dust mite and pollen allergy showed remarkable savings with SIT for both allergies in adults and children.

Economic evaluation of sublingual immunotherapy: an analysis of literature.

Allergic rhinitis and asthma constitute a global health problem because of their very high prevalence and the consequent burden of disease, concerning medical and economical issues. Among the treatments of allergy, specific immunotherapy has the capacity to favourably alter the natural history of the disease both during and after its performance and thus to reduce the direct and indirect costs of allergic rhinitis and asthma. A number of studies reported such cost reduction for traditional, subcutaneous immunotherapy and recent data demonstrate that also sublingual immunotherapy (SLIT) is associated to economic advantages and/or monetary savings, specifically in terms of reduction of disease economic burden. Only few formal economic assessments of SLIT have been carried out so far, this article will present and discuss the published studies addressed to this issue. The data obtained, although the number of studies is still limited, provide preliminary evidence supporting a SLIT effect on sparing costs for respiratory allergy.

Differential up-regulation of circulating soluble selectins and endothelial adhesion molecules in Sicilian patients with Boutonneuse fever.

In 150 patients with Boutonneuse fever (BF), caused by Rickettsia conorii, we studied the plasma levels of soluble L-selectin (sL-selectin), vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1) and E-selectin (sE-selectin) in various phases of disease to clarify their role in disease evolution. Results indicate that during the acute phase of BF there is a significant increase in the serum levels of sL-selectin, sE-selectin, sVCAM-1 and sICAM-1. sL-selectin and sVCAM-1 returned to normal levels in the third week of disease, whereas sE-selectin and sICAM-1 persisted at significantly high levels even after the third week. The secretion of these soluble CAMs in BF is mainly the result of leucocyte expression and endothelial cell activation, but secretion also appears to mediate anti-inflammatory activities, moderating leucocyte adhesion and reducing in particular lymphocyte and monocyte infiltration. Only sL-selectin serum levels were found to correlate with the acute phase of infection characterized by fever.

Asthma after consumption of snails in house-dust-mite-allergic patients: a case of IgE cross-reactivity.

A group of 28 patients from Italy was studied who had asthma after consumption of snail. All patients also had asthma and/or rhinitis caused by house-dust mite. RAST analyses confirmed the combined sensitization to snail and mite. In a few sera, IgE antibodies reactive with other foods of invertebrate origin (mussel and shrimp) were detected. RAST inhibition showed that most IgE antibodies against snail were cross-reactive with house-dust mite. In contrast, the mite RAST was not significantly inhibited by snail. This indicates that house-dust mite was the sensitizing agent. Immunoblot analyses revealed multiple bands in snail extract recognized by IgE. In contrast to what has been described for cross-reactivity between shrimp and mite, tropomyosin played only a minor role as a cross-reactive allergen in these patients. The observations in this study indicate that snail consumption can cause severe asthmatic symptoms in house-dust-mite-allergic patients. It might, therefore, be advisable to screen mite-allergic asthma patients for allergy to snail and other invertebrate animal foods.

Exodonture. Technique and art.

An extraction technique and art form are described for extraction of fully erupted, normally placed teeth in the dento-alveolar arch. The use of few instruments, handled with experience and comfort, is strongly advised. The technique described is based on tooth morphology and root placement.