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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: 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.

Sublingual immunotherapy with monomeric carbamylated allergoid (LAIS) is an effective and well tolerated treatment of respiratory allergy. The aim of the present study was to correlate the efficacy of two maintenance doses (1000 AU vs 3000 AU) of LAIS with the immunological modulation of allergen-driven Th1, Th2 and T regulatory cytokines produced in vitro by PBMCs, in patients suffering from mite allergic rhinitis. Forty-eight consecutive patients with mite allergic rhinitis were recruited. Patients were randomly assigned to group A (n=24) or group B (n=24), respectively receiving 1000 AU or 3000 AU weekly during one-year maintenance phase. Each patient was evaluated for rhinitis severity (ARIA protocol), and for drug consumption at the time of the inclusion and after 6 and 12 months of treatment. Patients were also asked to report the perceived severity of the disease and the tolerability of the treatment in a visual analogical scale (VAS). Before and at the end of the treatment allergen-driven release of cytokines by PBMCs in vitro was measured. After 1-year treatment, a statistically significant reduction of all clinical parameters was observed in all patients, associated with reduction of IL-4 and increase of INF-γ secreted in vitro by mite-challenged PBMCs. Notably, the group treated with the higher dose showed significantly better clinical and immunological results. The efficacy of LAIS is correlated to the immune modulation in a clear dose-dependent effect.

The central role of T regulatory cells in the responses against harmless environmental antigens has been confirmed by many studies. Impaired T regulatory cell function is implicated in many pathological conditions, particularly allergic diseases. The "hygiene hypothesis" suggests that infections and infestations may play a protective role for allergy, whereas environmental pollutants favor the development of allergic diseases. Developing countries suffer from a variety of infections and are also facing an increasing diffusion of environmental pollutants. In these countries allergies increase in relation to the spreading use of xenobiotics (pesticides, herbicides, pollution, etc.) with a rate similar to those of developed countries, overcoming the protective effects of infections. We review here the main mechanisms of non-self tolerance, with particular regard to relations between T regulatory cell activity, infections and infestations such as helminthiasis, and exposure to environmental xenobiotics with relevant diffusion in developing countries., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: In asthmatics, a rapid decline in pulmonary function is observed, likely as a consequence of airways remodeling. Persistence of allergen exposure in patients with occupational asthma (OA) maintains chronic bronchial inflammation, resulting in a more severe lung function decline. Few studies were performed on the effects of allergen exposure cessation., Objective: This study aims at evaluating the influence of allergen exposure cessation on respiratory decline in allergic asthmatic workers., Methods: Two groups of workers with allergic OA were selected. The first group (30 workers) changed job after the diagnosis and was no more exposed to sensitizing allergens, and the second group (28 subjects) did not and, as a consequence of preventive measures in the work place, was exposed to a lower level of allergens. All were treated with conventional therapy, according to GINA protocols. FEV1 changes during a 12-year period were evaluated., Results: Despite pharmacological therapy, the pulmonary function decay slope was steeper in workers continuously exposed to the sensitizing agent (even at reduced level) than in those with a complete cessation of exposure: final FEV1 loss was 512.5 ± 180 ml versus 332.5 ± 108 ml, respectively. The difference became significant after 4 years from the cessation of the exposure., Conclusions: The study shows that the cessation of the exposure to allergen in the work place appears the most effective measure in limiting pulmonary function decline in asthmatic workers and underlines the importance of allergic risk assessment and control in the management of occupational asthma.

Clinical evidences and epidemiological studies show that allergic pathologies of the respiratory tract are increasing in the world areas with high pollution impact, demonstrating how many polluting substances favor both allergic sensitization and the bronchial inflammatory changes characteristic of asthma. It has been shown that asthma, as many other diseases, is a complex interaction between genetic predisposition and environmental stimuli that results in clinical expression of various phenotypes of asthma: allergic, intrinsic etc. Many pollutants have such a potential. Diesel exhaust particles (DEP) can favor allergic sensitization, induce acute asthma attacks and increase bronchial reactivity, acting both on allergen, on bronchial mucosa and on immune cells. In fact, DEP can favor B lymphocytes to shift to a production of IgE and T cells to produce Th2 cytokines. Asthma can be also induced by high exposure to many other substances as NO2 and first of all ozone (O3): strong oxidizing substance that is synthesized, in absence of ventilation, by photochemical reaction due to the combination of ultraviolet sun radiation on exhaust gases as NO2 and hydrocarbons. Ozone is abundant in cities with minimal concentration in the morning gradually increasing during the day until maximal levels in the afternoon and then decreasing during the night. Epidemiological studies show that the number of access to hospital for acute asthma and even the use of bronchodilator by asthmatics increase during the high level periods when Ozone constitute almost 90 percent of the total oxidants in the environment. Particulate matter of very small diameter have a crucial role in favoring asthma attacks, and smaller the substance deeper the penetration in the bronchial tree, with an inflammatory reaction in the peripheral bronchial mucosa characterized by increased vessel permeability, mucosal edema, inflammatory mediator production by damaged epithelium and inflammatory cells that determines acutely a high narrowing of the bronchial lumen and in a long period favor airways remodeling and a rapid decline of respiratory function.

The progressive understanding of the nature and mechanisms of T regulatory (Treg) cells in the last decade has changed the concept of immune tolerance, that is no longer considered as a mere lack of immune reactivity but as a finely regulated process that requires specific activity of cells, adhesion and secreted molecules. Tregs play a key role in maintenance of self-tolerance and induction of tolerance against ubiquitous innocuous non-self antigens, so preventing the onset of autoimmune diseases and allergies. This review will focus on the Treg response in allergy that is characterized by a down-regulation of allergen specific T cell proliferation and inhibition of both Th1 and Th2 cytokines production. Hence, Treg cells suppress allergen-specific Th1 and Th2 cell responses playing an important role in the physiological immune response to allergens. Further, Treg cells are able to suppress IgE production by B lymphocytes and directly or indirectly inhibit the activity of allergic inflammation effector cells, namely eosinophils, basophils and mastcells. Finally, increasing evidence suggests that Treg cells are also implicated in chronicity development of inflammatory diseases. This appears to happen through a fine interaction they entertain with resident tissue cells and has been particularly highlighted in the study of airways remodeling in asthma. The understanding of the mechanisms underlying allergen tolerance has brought new interest in the development of new allergy treatment, able to target Treg cells, both in allergy prevention and in the therapy of established allergy.

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.

The influence of different treatment schedules of sublingual immunotherapy (SLIT) in activating IL-10-producing T-cells, crucial in inducing allergen-specific tolerance, is not completely understood. The present work was designed to evaluate allergen driven interleukin release by mononuclear cells in the early phase of SLIT, after application of different induction schemes. Twenty mite-allergic patients were enrolled, 10 (group A) treated with a traditional 98 day induction scheme and 10 (group B) with a 16 day scheme with monomeric allergoid vaccine. At the end of the induction phase, the cumulative doses taken by group A and group B patients were equivalent to 50.5 and 50.3 microg of mite group 1 allergens, respectively. The release of Th1-, Th2- and Treg-related interleukins was assessed in culture supernatants of 5 microg/ml Der-p1-stimulated mononuclear cells, isolated before and after the induction phases. No relevant treatment-related side effects were observed. Interleukin release was similar in the two groups at the enrolment. Non-stimulated and Der p 1 stimulated release of studied cytokines was similar in the two groups at enrolment. Der p 1 stimulation significantly increased IL-10 release (p<0.0002) after treatment in group B patients, and this effect was higher (p=0.05) compared to group A patients. Furthermore, at the end of SLIT induction TNF-alpha, IL-4 and IFN-gamma production were reduced in group B patients (p<0.05, p=0.062 and p=0.060, respectively). The rapid induction scheme of sublingual immunotherapy induces an early immune suppression more effectively than the slower one. The rapid induction scheme should be the preferential way to start sublingual immunotherapy, particularly when monomeric allergoids are utilized.

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.

RANTES plays a crucial role in cell recruitment in allergic inflammation. We investigated the pharmacological modulation of RANTES release in cultured peripheral blood mononuclear cells obtained from allergic patients with active asthma. Chemokine production was assessed before and after 15 day treatment with histamine-1 receptor antagonists (antihistamines) (Loratadine or Cetirizine) and a steroid (Deflazacort), both in unstimulated and PHA-stimulated cell cultures. Results were compared with those obtained from placebo-treated patients. During the treatment period, patients recorded morning and evening peak expiratory flow (PEF) by the mini-Wright procedure. PEF absolute values and diurnal variability significantly improved respect to the pre-treatment in steroid-treated patients, in comparison to the placebo and antihistamine-treated groups (p&#x003C;0.001 and 0.01, respectively). PEF diurnal variability in the antihistamine-treated group were lower than placebo-treated group without statistical significance (p=0.06). No differences could be found in RANTES levels in supernatants of all cultures between the two antihistamines. RANTES release significantly decreased in supernatants of all cell cultures from steroid (p&#x003C;0.01) and antihistamine (p=0.03 and 0.04) groups after treatments, compared to the basal values; whereas it increased slightly in controls. Co-variance analysis on RANTES levels, adjusting for pre-treatment values, showed a significant reduction of RANTES release by PHA-stimulated PBMCs from steroid (p=0.003) and anti-histamine (p=0.03) groups, with respect to the placebo group. The same statistical tool applied between the steroid and the antihistamine groups showed, after therapy, the lowest levels of RANTES to be associated with steroid treatment (p=0.005). The study shows that the steroid is the most effective drug in modulating RANTES release from PBMCs. However, antihistamines, which are able to reduce cell recruitment due to chemokine release, avoiding important side effects, may be useful in long term therapy in controlling and preventing allergic inflammation.

The definition of probiotics is always evolving, since it includes natural live micro-organisms, cellular subfractions, as well as genetically engineered derivatives or proteins. The scope of probiotic administration is beneficial change of the intestinal microflora, and improvement of non immune or immune resistance in the intestinal tract. Very few controlled human studies have been reported, but many in vitro and experimental animal studies point to their safety and potentially useful applications. We shall review the published reports and discuss mainly the prospective uses in the field of allergic diseases, with reference to the implication of the natural (innate) immune system as regulator of the development of abnormal responses to ingested food antigens.

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 reactivity (NSBR) evaluated with methacholine in asthmatic farmers allergic to pollens. Twenty farmers (16 male and four female) with allergy to pollens, e.g. 'Graminae' and 'Parietaria', entered the study. None of the patients had been previously treated with specific immunotherapy. Patients underwent a methacholine challenge at the first visit and then in the subsequent seasons. Four groups of tests were obtained according to the period when the challenge was performed. Group 1: challenges performed in December, January and February; group 2 in March, April and May; group 3 in June, July and August; group 4 in September, October and November. PD20 values were expressed as the natural logarithm of the cumulative dose of methacholine causing at least a 20% fall in FEV1. Bronchial hyperreactivity was highest in summer, followed by spring and autumn; in winter it was much lower. Multiple group analysis (ANOVA) showed statistically significant differences between the groups (P < 0.01). When the groups were compared individually, statistically significant differences existed only between group 1 (winter) and each of the other groups, respectively 2 (spring) (P = 0.02), 3 (summer) (P = 0.004) and 4 (autumn) (P = 0.02). The results underlined the importance of allergic inflammation in determining changes in NSBR. In the region where the study was carried out (central Italy), the grass and Paretaria pollination lasts from March to November. Therefore, farmers had a progressive increase in NSBR from spring to summer and a decrease in fall as a consequence of the varying pollen concentration in different seasons. The level of allergen exposure is, in fact, the main factor that determines the severity of bronchial inflammation, thus affecting NSBR.

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.

Background: This study correlates biomarkers of atopy (serum total and specific IgE) and inflammation (serum eosinophil cationic protein) with bronchial hyperreactivity assessed after the complete end of pollination, in a group of farmers suffering from grass-allergic asthma., Methods: A total of 28 asthmatic farmers, with allergy to grass pollen, reporting persistent asthma symptoms after grass pollination, were enrolled. An accurate allergologic screening excluded other sensitizations. Analysis of total and grass-specific IgE and eosinophil cationic protein was carried out before (March) and during (May) the following spring. After the complete end of pollination, bronchial hyperreactivity was assessed., Results: Symptoms (cough, wheezing) persisted during the autumn for a mean period of 41 days (range 13-69). Total IgE was moderately high and grass-specific IgE ranged from 9.25 to 41.12 kU/l without significant differences before and during spring. On the contrary, serum ECP levels significantly increased during the pollination period. PD20 methacholine evaluated after the end of grass pollination was negatively significantly correlated with levels of total IgE (r=-0.73; P<0.01) and the increase (from March to May) of serum ECP (r=-0.75; P<0.01). However, PD20 methacholine did not correlate with grass-specific IgE and serum ECP absolute values of both March and May. A positive correlation was found between number of postseasonal days with symptoms and both spring increase of serum ECP (r=0.75; P=0.04) and levels of total IgE (r=0.76; P<0.01). The number of postseasonal days with symptoms inversely correlated with postseason PD20 methacholine (r=-0.76; P<0.01)., Conclusions: The study demonstrates that in grass-sensitized farmers with asthmatic symptoms persisting for several weeks after grass pollination has ceased, the degree of airways hyperreactivity and the duration of postseasonal symptoms are directly related to the spring increase of ECP levels, as well as to the level of total IgE in serum. This allows us to identify two candidate biomarkers for the risk of developing prolonged asthma symptoms, and for the effective monitoring of anti-inflammatory treatment and allergen-specific immunotherapy.

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.

Blood lymphocyte subset evaluation was performed before after oral challenge with 10 mg of Ni, in 9 healthy women and in 15 allergic to Ni. Following challenge, 7 allergic showed a flare up of eczema and/or urticaria. In the controls, CD4+ lymphocytes were modified 24 hours after Ni challenge: CD4+/CD44RO- "virgin" cells were reduced while CD4+/CD45RO+ "memory" cells increased. The allergic women, not sensitive to oral Ni, showed an increase of B lymphocytes after the test. On the contrary, the oral Ni reacting patients presented a reduction of monocytes 4 hours after Ni ingestion and marked reduction (ranging from 20 to 50%) of T and B lymphocytes after 24 hours. These significant T and B lymphocytes changes suggest a migration of the cells in peripheral tissues, likely skin and GUT mucosa.

In non-smoking policemen from a town of Central Italy, blood CD4+ lymphocytes were reduced and CD8+ were increased as compared with a control group. This immunological alteration was not evident in the smoking policemen. Urine lead (marker of exposure to toxic agents produced by traffic) and blood natural killer (NK) CD16+ lymphocytes as well as serum copper and HLA-DR+ cells (B, T, NK activated lymphocytes and monocytes) were significantly correlated in the whole group of 42 examined subjects. Another study was performed on 15 healthy men, occupationally not exposed to toxic agents and living in a suburban area. Their urine lead, was positively correlated with the serum IgA immunoglobulins and negatively correlated with blood CD5(+)-CD19+ (a B subset bearing the T CD5 antigen) lymphocytes. On the contrary, urine chromium was negatively correlated with serum IgA and positively correlated with CD16(+)-56+ NK and CD5(+)-CD19+ B lymphocytes as well as with HLA-DR+cells. Serum zinc was also correlated with total HLA-DR+and CD3-HLA+DR+ (activated B and NK lymphocytes and monocytes) cells. These later data suggest that only zinc and copper but also trivalent chromium (to which normal population is mainly exposed in ordinary environmental conditions) may play a role in the mechanisms regulating the immune response.

The study concerns the histological and immunohistochemical findings of the gastrointestinal mucosa of 20 patients (group A) suffering from contact allergic dermatitis (CAD) to Ni, with symptom recrudescence due to food ingested Ni. Results were compared with those observed in 20 patients suffering from CAD to Ni (group B), without sensitivity to food ingested Ni, and in 20 normal subjects (controls). The sensitivity to food ingested Ni, as suggested by history, was demonstrated by placebo-controlled oral-Ni challenge. The biopsies for histological and immunohistochemical study were performed during endoscopy and obtained from the antrum and from the duodenal mucosa. In the biopsies obtained from 16 of group A patients there was evidence of inflammatory infiltrate of lymphocytes and plasma cells with oedema and vasodilation in the lamina propria. Slight flattening of the villi and enlongation of the crypts were concomitant. These findings were light in the 4 patients of group A and in 11 of group B and instead were absent in the remaining group B patients and in the controls. Immunohistochemically, lymphocytes in the lamina propria were prevalently CD20 + (B cells) and CD4 + (Th cells), some were CD45RO + (memory) and finally few CD8 + (Tc/s cells). CD45RO + cells was found in cluster in patients of group A and in 4 of group B, whereas in the others were isolated. Since some studies have shown that immunological pattern of skin reaction to Ni is characterized by increased CD45RO + cells, it may be hypothesized that in patients suffering from CAD to Ni, the sensitivity to food-ingested Ni may be induced by a type IV immunological reaction in the gut.