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Allergic reactions to COVID-19 vaccine components are rare but should be considered. Polyethylene glycol (PEG) is responsible for anaphylaxis in mRNA vaccines. Skin tests have been used in the allergological work-up programs for COVID-19 vaccine evaluation. However, the reproducibility of the skin prick test is time-dependent and the reactivity declines over time. Therefore, we combined the administration of the skin tests with the basophil activation test (BAT) using PEG2000, PEG4000 and DMG-PEG2000, where the BAT was considered positive when the percentage of activated basophils was higher than 6%, 5% and 6.5%, for PEG 4000, PEG2000 and DMG-PEG2000, respectively. To this end, among the subjects that underwent allergy counseling at the Allergy Unit of our Institution during the 2020/2021 vaccination campaign, 13 patients had a suggested medical history of PEG/drug hypersensitivity and were enrolled together with 10 healthy donors. Among the enrolled patients 2 out of 13 tested patients were positive to the skin test. The BAT was negative in terms of the percentages of activated basophils in all analyzed samples, but the stimulation index (SI) was higher than 2.5 in 4 out of 13 patients. These data evidenced that, when the SI is higher than 2.5, even in the absence of positivity to BAT, the BAT to PEG may be a useful tool to be coupled to skin tests to evidence even low-grade reactions.

Vernal keratoconjunctivitis (VKC) is a persistent, severe allergic eye disease, mainly occurring in children, that can lead to severe ocular complications including visual loss. The underlying etiology and pathophysiology of VKC remain unclear. Common therapies include topical antihistamines and mast cell stabilizers that are effective in mild-to-moderate forms of VKC but are often ineffective in severe forms that require topical or systemic corticosteroids. Dependence on steroids is common with potential adverse effects both local, as increased intraocular pressure, glaucoma, infection and cataract, as well as systemic ones, as reduction in child growth velocity. Alternative therapies are immunosuppressive drugs, like cyclosporine A and tacrolimus, that usually are effective but may also cause adverse effects. A promising therapeutic option is omalizumab, a recombinant anti-IgE humanized monoclonal antibody, currently used as add-on therapy for moderate to severe uncontrolled allergic asthma and chronic spontaneous urticaria. Here, we report the short-time duration of effective relief of symptoms after the prolonged use of omalizumab in a patient affected by refractory VKC. However, in our case any apparent beneficial effect was short lasting, and we propose that the duration of the disease and the concomitant long-term use of steroids leads to iatrogenic damage; thus, the disease becomes refractory to anti-IgE treatment., Competing Interests: The authors declare that they have no conflict of interest in relation to the content of this study., (Copyright © 2020 by S. Karger AG, Basel.)

Purpose of Review: Understanding prevalence of diseases within specific regions of a country is important for optimal allocation of healthcare resources/funds. We performed a systematic review to obtain a clearer picture of the epidemiology of psoriasis and psoriatic arthritis across and within specific regions of Italy., Recent Findings: Prevalence of psoriasis in specific regions showed more variability (0.8-4.5%) than that in the total population (1.8-3.1%). Prevalence of psoriatic arthritis in the general population was reported for only two regions, Chiavari (0.09%) and Marche (0.42%). All other studies reported prevalence of psoriatic arthritis in patients with psoriasis in single centres and Italy-wide (4.7-47.1%). Prevalence of psoriatic arthritis was highest in patients with nail and/or scalp psoriasis and/or intergluteal/perianal region involvement. Based on current available data, these conditions appear to affect a substantial number of people and will likely have an important impact on the Italian healthcare system.

Omalizumab has been recognized to be effective in the treatment of chronic spontaneous urticaria (CSU). The Italian Medicines Agency authorizes two omalizumab courses, only for patients with CSU unresponsive to antihistamines, and this schedule may limit omalizumab use. Unfortunately, in the majority of CSU, the schedule is unsatisfactory because symptoms usually recur shortly after discontinuation of treatment. A case of a patient needing more than two treatment courses with omalizumab is reported, in order to discuss the rationale for its long-term use. Patient had needed systemic steroids almost continuously for 4 years. Two severe glucocorticoid-associated adverse events (GAEs) occurred during long-term treatment. Omalizumab 300 mg monthly was started with immediate disappearance of the urticarial lesions. Beneficial effects waned shortly after discontinuation of treatment, and further steroid use was needed. A second omalizumab course showed the same clinical pattern, with prompt response and recurrence of symptoms after suspension. Therefore, we decided to repeat the 6 months omalizumab treatment as soon as symptoms recurred, to avoid further emergency steroid treatments and GAEs. This experience suggests that long-term use of omalizumab could be useful. Evidences show that omalizumab is effective and safe for re-treatment and long-term use of responding patients after recurrence.

Inhaled corticosteroids (ICS)/long-acting beta-agonists (LABA) association offers a better asthma control than a higher steroid dose with short-acting beta-agonists as needed. In this study, we evaluated the effect of the association on bronchial hyperreactivity (BHR) and peak expiratory flow (PEF) variability, as such parameters are positively correlated with increased asthma morbidity and exacerbations. Thirty-six adult patients with mild persistent asthma were enrolled. After a 7-day run-in, they were randomly assigned to three therapy regimens for 6 weeks: Group 1, fluticasone 125 μg + formoterol 5 μg in the same device; Group 2, fluticasone 125 μg + formoterol 12 μg as needed; Group 3, fluticasone 250 μg + formoterol 12 μg as needed. We evaluated changes induced in weekly PEF variability (measured during the entire study and 4 weeks of follow-up) and pre- and post-study PD20 methacholine (MCH). Weekly PEF variability decreased in all groups during treatment with the greatest reduction in Group 1, followed by Group 3, and finally Group 2. During the follow-up, no significant changes were detected in Group 1, whereas a trend towards an increased variability was found in Groups 2 and 3. Post-treatment PD20 MCH was significantly higher versus the pre-treatment. The increase observed in Group 1 was significantly higher compared to Groups 2 and 3 and that observed in Group 3 in respect to Group 2. The study proves that both BHR and PEF variability are influenced by ICS. This effect was greater with fluticasone/formoterol association compared to fluticasone alone with formoterol as needed even at higher steroid dose., (© The Author(s) 2016.)

Background: Dementia, including Alzheimer's disease (AD), is one of the most burdensome medical conditions. In order to better understand the epidemiology of dementia in Italy, we conducted a systematic search of studies published between 1980 and April 2014 investigating the prevalence of dementia and AD in Italy and then evaluated the quality of the selected studies., Methods: A systematic search was performed using PubMed/Medline and Embase to identify Italian population-based studies on the prevalence of dementia among people aged ≥60 years. The quality of the studies was scored according to Alzheimer's Disease International (ADI) criteria., Results: Sixteen articles on the prevalence of dementia and AD in Italy were eligible and 75 % of them were published before the year 2000. Only one study was a national survey, whereas most of the studies were locally based (Northern Italy and Tuscany). Overall, the 16 studies were attributed a mean ADI quality score of 7.6 (median 7.75)., Conclusions: Available studies on the prevalence of dementia and AD in Italy are generally old, of weak quality, and do not include all regions of Italy. The important limitations of the few eligible studies included in our analysis, mostly related to their heterogeneous design, make our systematic review difficult to interpret from an epidemiologic point of view. Full implementation of a Dementia National Plan is highly needed to better understand the epidemiology of the disease and monitor dementia patients.

Background: Hymenoptera venom immunotherapy (VIT) is a safe and effective approach to insect sting allergy. However, after discontinuation, relapses can occur in some patients, especially those with a high occupational risk, and they may need to prolong VIT indefinitely. In order to improve adherence, we propose extending the interval between injections of maintenance VIT (MVIT)., Objective: To evaluate the safety, efficacy, and patient acceptance of a 3-month interval between MVIT injections in a group of Hymenoptera-allergic patients who are occupationally exposed to insect stings., Patients and Methods: We included 72 patients with severe systemic reactions to Hymenoptera stings. MVIT was administered for 4 years at intervals increasing up to 3 months and then continued for a further 2 years. Patients were informed of the risk of relapse after discontinuation and of the need for indefinite treatment at 3-month intervals., Results: During the 3-month interval maintenance phase, only 235 local reactions (17.8%) were observed in 17 patients. Sixty patients experienced 125 field re-stings and only 1 experienced a systemic reaction with generalized urticaria., Conclusions: The study confirms that the conventional MVIT interval of 4 to 6 weeks can be extended to 3 months in most patients with no adverse events, while maintaining safety and efficacy, improving adherence, and guaranteeing safe continuation of professional activity.

This study evaluates the effectiveness and safety of cyclosporine (CsA) in the treatment of patients with chronic idiopathic urticaria with a positive autologous serum skin test (ASST), who fail to respond to conventional therapy, and requiring long-term oral steroid treatment. In a double-blind study, 40 adults were assigned randomly to receive CsA (5 mg/kg per day for 8 weeks and then 4 mg/kg per day for 8 weeks) or cetirizine (10 mg/day) and then they were followed up for 9 months. After 2 weeks, the study was opened because 16 patients (40%) had daily severe relapses requiring systemic steroids treatment. All of these patients had been receiving antihistamines and, therefore, all patients also were assigned to the CsA treatment regimen (5 mg/kg per day for 8 weeks and then 4 mg/kg per day for 8 weeks). The ASST and clinical severity score were evaluated before and after treatment. All of the 40 patients completed the 16-week CsA course without dropping out because of relevant side effects. In three patients, CsA was reduced by 0.5 mg/kg per day after the 1st month of treatment for a mild and reversible increase in serum creatinine. During CsA treatment, 20 patients had relapses resolving spontaneously (8 patients) or with antihistamines (12 patients). During the 9-month follow-up period, 22 patients had relapses resolving spontaneously (10 patients) or with antihistamines (12 patients). Only two patients failed to complete the study because of severe symptoms occurring after 4 and 7 days of follow-up and requiring long-term steroid treatment. After 9 months of follow-up, 16 patients were still in full remission. The clinical severity score of chronic idiopathic urticaria dropped significantly by the end of the 4th month of treatment (p = 0.002) as well as by the completion of follow-up (p = 0.007). The ASST was negative in 13 patients and positive in 3 of 16 patients, with total remission of symptoms. Significant score reduction also was observed in patients experiencing relapses that resolved spontaneously (p = 0.005) or with antihistamines (p = 0.03). These results show the long-term efficacy and tolerability of CsA in patients with severe chronic idiopathic urticaria, unresponsive to conventional treatments.

The association of eosinophilic fasciitis and immunological defects is rare, especially hypogammaglobulinemia. We report a case of eosinophilic fasciitis occurring in a female, 53 years old, with common variable immunodeficiency. The diagnosis of common variable immunodeficiency was established by chance observation of persistently low levels of all immunoglobulin classes unrelated to protein loss or immunosuppressive treatment, one year after the appearance of eosinophilic fasciitis, which is usually characterized by hypergammaglobulinemia. Our description may prompt the investigation of an increased rate of simultaneous occurrence of eosinophilic fasciitis and common variable immunodeficiency.

The aim of the study was to assess the seasonal variability of non-specific bronchial responsiveness to methacholine in allergic asthma. One hundred sixty-five patients (83 male and 82 female) entered the study: 86 subjects (group A) with allergy exclusively to mites and 79 (group B) with concomitant allergy to pollens, e.g., "Graminae" and "Parietaria." Inclusion criteria were the absence of sensitization to other allergens, no smoking habit, withdrawal from steroids, bronchodilators, sodium cromoglycate, and antihistamines for at least four weeks before enrollment, FEV1 > 70% of the predicted value, and absence of other respiratory diseases and of upper and lower respiratory tract infections for at least one month before the methacholine challenge. None of the patients had been previously treated with specific immunotherapy. Subjects of each group (A and B) underwent methacholine challenge at first visit and were divided into four subgroups according to the period when the challenge was performed. Subgroups A1 and B1 performed the challenge in December, January, and February; subgroups A2 and B2 in March, April, and May; subgroups A3 and B3 in June, July, and August; subgroups A4 and B4 in September, October, and November. PD20 values were expressed as the natural logs of the cumulative dose of methacholine causing at least a 20% fall in FEV1. Statistical analysis was carried out using multiple group analysis and Student's t-test. Results showed that the highest non-specific bronchial responsiveness was observed in autumn (ln PC20 = 4.54 +/- 1.51) in patients allergic to mites only (group A), and in summer (ln PC20 = 4.72 +/- 2.11) in those of group B. Multiple group analysis showed statistical significant differences between subgroups within each group (group A, p = 0.039; group B, p < 0.001). In patients allergic exclusively to house dust mites (group A), multiple comparisons and Student's t-test showed statistically significant differences between non-specific bronchial responsiveness (NSBR) assessed in autumn and those of other seasons (winter, p = 0.002; spring, p < 0.001; summer, p = 0.082). These results confirm that the level of allergen exposure may influence NSBR. Mite-allergic patients showed an increase of NSBR in autumn, possibly as a consequence of higher indoor mite concentration. However, mite- and grass-allergic patients had wider variations of NSBR, possibly reflecting changes in seasonal pollen concentration.

This study investigates lymphocyte subsets in both the gastrointestinal mucosa and blood, in patients with nickel allergic contact dermatitis, after 10 mg oral nickel challenge (double-blind, placebo-controlled). 6 such patients with cutaneous symptoms induced only by skin contact with nickel (group A), 6 with a flare-up of cutaneous symptoms after food nickel ingestion (group B) and 6 healthy controls (group C) were enrolled. Blood lymphocyte subsets (CD4, CD45RO, CD8) were analyzed before and after 4 and 24 h from the challenge (test 1, 2, and 3), and intestinal biopsies were performed 2 days later. Challenges were positive in group B and negative in group A and controls. Serum and urine nickel levels significantly increased after nickel ingestion, with no differences between the 3 groups. At test 3, a significant decrease of the all CDs studied was found in group B. Biopsies of this group showed higher levels of CD45RO+ cells in the lamina propria and in the epithelium and lower levels of epithelial CD8+ lymphocytes. This study confirms that ingested nickel may induce flare-up of cutaneous reactions in some nickel-allergic patients, independently of the degree of sensitization and the intake of metal. In these patients, oral nickel stimulates the immune system, inducing maturation of T lymphocytes from virgin into memory cells; these latter cells seem to accumulate in the intestinal mucosa. The immunoreaction also involves CD8+ cells, whose role is not yet clear.

The aims of this study were to determine the incidence of toxoplasmosis in children ofthe northern Greece region through the evaluation of serologic examination. Sera of 486 children, aged between 6 months and 15 years, suffering from different clinical entities, were tested for anti-Toxoplasma gondii specific IgG antibodies, using an ELISA (enzyme linked immunosorbent assay) technique. In this survey, a high percentage (11.1 percent) of the hospitalized children reacted positively to this method. Males and females had equal prevalence, 11 percent and 11.2 percent, respectively. Seropositivity rate was higher in children aged between 6 and 10 years old. In conclusion, our results indicate toxoplasma infection is an important public health problem affecting children and adolescents in northern Greece. We believe that the study described here could be considered for inclusion in existing national screening programs for hospitalized children.

We assessed the infiltration of CD45RO+ cells in conjunctival biopsies of fifteen subjects affected by seasonal allergic conjunctivitis by means of immunohistochemistry. Correlations between infiltration of CD45RO+ cells and serum and mucosal indices of eosinophilic activation were investigated. The study was performed in autumn and all selected patients showed <> also in absence of sensitising pollens. Fifteen healthy subjects were used as controls. The semi-quantitative count of CD45RO+ cells in biopsy specimens demonstrated that positive cells were higher in allergic patients than in controls (p < 0.001) and EG2+ eosinophils were present only in biopsies of allergic patients. Furthermore, a statistically significant positive correlation (r = 0.73; p < 0.001) between CD45RO+ lymphocytes and EG2 positive eosinophils, was observed in the biopsies of allergic patients. Total serum IgE significantly correlated with CD45RO+ cells (r = 0.61; p < 0.02) and EG2+ eosinophils (r = 0.67; p < 0.01) in the conjunctiva. On the other hand serum ECP did not correlate with any histological and immunohistochemical parameters in the conjunctival biopsies. The present study shows that mild symptoms in SCA patients out of pollen season are associated with inflammation of the conjunctiva as shown by an increased number of CD45RO and EG2 positive cells.

Allergen-specific immunotherapy (IT) consists in administering gradually increasing doses of an allergen extract to sensitive patients. This practice results in ameliorating symptoms associated with the subsequent exposure to the causative allergen. Presently, the lack of therapies which affect the pathogenesis of the disease make IT the only treatment that may improve the natural course of allergic diseases.