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INTRODUCTION Asthma symptoms can be relieved through a maintenance treatment combining long-acting β2-agonist and inhaled corticosteroids (LABA/ICS). However, for patients with inadequately controlled asthma, the LABA/ICS combination might not be sufficient. Under these conditions, clinical guidelines recommend the administration of inhaled long-acting muscarinic antagonists (LAMA) as an add-on therapy to LABA/ICS to better control asthma and improve lung function. For nearly two decades, the only LAMA to be approved on the market has been tiotropium. AREAS COVERED We reviewed recent clinical studies evaluating the safety and efficacy of LABA/LAMA/ICS fixed dose combinations by searching PubMed database. Molecular mechanisms and clinical data support the use of a once-daily, single-inhaler fixed dose combination of the LABA/LAMA/ICS indacaterol/glycopyrronium/mometasone (IND/GLY/MF), the first therapy combining three agents in a fixed dose approved in Europe for the treatment of uncontrolled asthma. EXPERT OPINION IND/GLY/MF was superior to both IND/MF and salmeterol/fluticasone (SAL/FLU), a well-established LABA/ICS combination improving lung function in uncontrolled asthma. Moreover, IND/GLY/MF, delivered through the Breezhaler inhaler in a single inhalation, is the first inhaled therapy prescribed alongside a digital companion, a sensor and the Propeller app, allowing for improved treatment adherence, reduced rescue inhaler usage and hospitalizations, increased patient satisfaction and asthma control.

BACKGROUND Alexithymia is among psychological factors reported to interfere with asthma management. Severe allergic asthma (SAA) is characterized by uncontrolled asthma despite maximal standard pharmacological treatment which can benefit from an add-on treatment with Omalizumab, an anti-IgE monoclonal antibody. OBJECTIVE To evaluate if alexithymia influences the efficacy of omalizumab in SAA. METHODS The total alexithymia score 20 (TAS 20) questionnaire allowed to detect alexithymia. SAA was monitored recording number of exacerbations, asthma control test (ACT) and asthma quality of life questionnaire (AQLQ) scores, as well as forced expiratory volumes in 1 second % (FEV1%) levels before starting omalizumab, 1 and 2 years after. RESULTS The study was conducted on 18 patients; Group 1, TAS 20 ≥ 61, was of 2 males and 4 females with SAA and alexithymia, while Group 2 , TAS 20 ≤ 51, was of 8 males and 4 females, without alexithymia. Group 1 had a statistically significant decrease in asthma exacerbations "p = 0.004", while ACT "p = 0.008" and AQLQ scores statistically increased. FEV1 values increased but not statistically significantly. Group 2 had a highly statistically significant decrease in the number of exacerbations and a highly statistically significant increase of ACT "p < 0.0001", FEV1 "p = 0.008" and AQLQ scores. CONCLUSIONS Regardless the presence or not of alexithymia, all patients with SAA obtained a marked improvement after starting treatment with omalizumab. Therefore alexithymia does not seem to influence the treatment outcome of omalizumab.

Background Processionary caterpillar (PC), also named Thaumatopea pityocampa, has been reported to cause hypersensitivity reactions after contact with a toxin contained in hair-like bristles which cover this insect. Occupational exposure to PC is underestimated in outdoor workers and especially in forestry workers (FW) and is globally diffusing because of rising temperatures. Cases presentation We present the first three cases of FW from Sicily, a Southern Italy (SI) region, which reported hypersensitivity reactions due to exposure to PC infested trees. These cases were identified by the occupational health physician during the annual screening of FW working in the Mountains of north-eastern Sicily. Interviewing a population of 630 FW, 1 male and 2 females reported direct contact skin reactions together with airborne contact reactions to PC hairs causing mild respiratory symptoms in two cases and ocular symptoms in one case, which needed treatment with systemic corticosteroids and antihistamines. Conclusions This is the first report of hypersensitivity reactions in SI FW due to occupational exposure to PC. Further screenings not only in FW but also in other populations of outdoor workers are needed in order to assess the real incidence of contact and airborne reactions due to occupational exposure to PC. Though so far no correlation has been found with atopy, it seems apparent that the reactions occur in susceptible subjects; further research is needed for a correct diagnosis and to identify possible desensitization procedures.

The prevalence of asthma in Italy is estimated to be around 4%; it affects approximately 2,000,000 citizens, and up to 80-90% of patients have mild-to-moderate asthma. Despite the clinical relevance of mild-to-moderate asthma, longitudinal observational data are very limited, including data on disease progression (worsening vs. improvement), the response to treatment, and prognosis. Studies are needed to develop long-term, observational, real-life research in large cohorts. The primary outcomes of this study will be based on prospective observation and the epidemiological evolution of mild and moderate asthma. Secondary outcomes will include patient-reported outcomes, treatments over time, disease-related functional and inflammatory patterns, and environmental and life-style influences.This study, called the Mild/Moderate Asthma Network of Italy (MANI), is a research initiative launched by the Italian Respiratory Society and the Italian Society of Allergology, Asthma and Clinical Immunology. MANI is a cluster-based, real world, cross-sectional, prospective, observational cohort study that includes 20,000 patients with mild-to-moderate asthma. (ClinicalTrials.gov Identifier: NCT04796844).Despite advances in asthma care, several research gaps remain to be addressed through clinical research. This study will add important new knowledge about long-term disease history, the transferability of clinical research results to daily practice, the efficacy of currently recommended strategies, and their impact on the burden and evolution of the disease.MANI:Mild/Moderate Asthma Network of ItalySANI:Severe Asthma Network ItalyGINA:Global Initiative for AsthmaSABA:short acting β2-agonistsICS:inhaled corticosteroidsCRF:Case Report Form.

Background Clinicians are increasingly recognizing severe asthma patients in whom biologics and other add-on therapies lead to dramatic improvement. Currently, there is no agreed-upon super-responder (SR) definition. Objective To survey severe asthma experts using a modified Delphi process, to develop an international consensus-based definition of a severe asthma SR. Methods The Delphi panel was composed of 81 participants (94% specialist pulmonologists or allergists) from 24 countries and consisted of three iterative online voting rounds. Consensus on individual items, whether acceptance or rejection, required at least 70% agreement by panel members. Results Consensus was achieved that the SR definition should be based on improvement across three or more domains assessed over 12 months. Major SR criteria included exacerbation elimination, a large improvement in asthma control (two or more times the minimal clinically important difference), and cessation of maintenance of oral steroids (or weaning to adrenal insufficiency). Minor SR criteria were composed of a 75% exacerbation reduction, having well-controlled asthma, and 500 mL or greater improvement in FEV1. The SR definition requires improvement in at least two major criteria. In the future, the SR definition should be expanded to incorporate quality of life measures, although current tools can be difficult to implement in a clinical setting and further research is needed. Conclusions This international consensus-based definition of severe asthma SRs is an important prerequisite for better understanding SR prevalence, predictive factors, and the mechanisms involved. Further research is needed to understand the patient's perspective and to measure quality of life more precisely in SRs.

Background: Cross-reactivity between pollens and plant food has been widely described. Pollen extract subcutaneous immunotherapy in patients with pollens and plant food allergy has been shown to improve tolerance not only to inhalant allergens but also to reduce symptoms in patients with various food allergies. Methods: We retrospectively report our experience with 15 female patients with a positive history for moderate, persistent allergic rhinitis due to grass pollen and oropharyngeal symptoms after ingestion of different plant food. These patients followed a five-grass pollen sublingual tablet immunotherapy for three years in a discontinuous pre-co-seasonal scheme. Results: All 15 patients treated with the 5-grass pollen sublingual tablet immunotherapy, taken once daily for 3 years on a 7-month course, showed improved ocular/nasal symptoms, with a reduction in the use of symptomatic drugs (e.g., nasal corticosteroids and H1 antihistamines). After the first seven-month course of immunotherapy, all patients declared a good tolerance to the intake of fruits and vegetables, and in particular, good tolerance to the offending foods. Conclusions: In conclusion, we have observed improvement of both respiratory and plant food allergies after sublingual immunotherapy (SLIT) with a five-grass pollen tablet.

Background and aims Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS) which worsen patients’ health and increase healthcare spending. Aim of this study was to assess the clinical and economic effect of adding mepolizumab (MEP) for the treatment of these patients. Methods Patients >18 years old, referred to 8 asthma clinics, starting MEP between May 2017 and December 2018, were enrolled and followed-up for 12 months. Information in the 12 months before mepolizumab were collected retrospectively. The evaluation parameters included: OCS use, number of exacerbations/hospitalizations, concomitant therapies, comorbidity, and annual number of working days lost due to the disease. The primary objective was to compare the annual total cost per patient pre- and post-MEP. Secondary outcomes included rates of exacerbations and number of OCS-dependent patients. Results 106 patients were enrolled in the study: 46 male, median age 58 years. Mean annual cost pre- and post-MEP (cost of biologic excluded) was €3996 and €1,527, respectively. Total savings due to MEP resulted in €2469 (95%CI 1945–2993), 62% due to exacerbations reduction and 33% due to productivity increase. Such savings could fund about 22% of the total cost of MEP for one year. The introduction of MEP induced a clinical benefit by reducing both OCS-dependent patients (OR = 0.12, 95%CI 0.06–0.23) and exacerbation rate (RR = 0.19, 95%CI 0.15–0.24). Conclusions Patients with severe eosinophilic asthma experienced a clinical benefit in asthma control adding MEP to standard therapy. Biologic therapy can be, partially, funded by the savings produced by patients’ improvement.

Background: Adherence to medications is crucial in patients with severe asthma in light of the negative clinical impact and costs of non-adherence. Adherence to omalizumab has not been well studied in real-world settings. The aim of this study was to assess adherence to omalizumab and evaluate treatment effectiveness in relation to adherence. Methods: This was a retrospective, observational, and multicenter real-world study. Omalizumab dose, timing of administration, and duration of treatment ( 4 years) were analyzed. Adherence was evaluated by examining rates of expected and missing doses. Good adherence (10% doses missed) were determined. For effectiveness in relation to adherence of omalizumab we considered asthma exacerbations, hospitalizations, asthma control test (ACT), and Forced Expiratory Volume in 1 s (FEV1). Results: A total of 196 patients were evaluated, and 161 were suitable for data analyses. Good adherence was shown in 90.7% of patients and poor adherence in 9.3%. Considering adherence in relation to treatment duration: 4 years, 100% were adherent (expected doses, 6120; missed doses, none). Indices of efficacy between pre- and post-treatment showed significant improvement (p

Common variable immunodeficiency (CVID) is a primary immunodeficiency due to a disorder of the adaptive immune system which causes hypogammaglobulinemia and therefore an increased susceptibility to infection; noninfectious, inflammatory conditions including systemic autoimmunity and lymphoproliferative complications are also commonly associated with CVID. Castleman disease (CD) is a systemic disease clinically characterized by diffuse lymphadenopathy, splenomegaly, anemia, and systemic inflammatory symptoms. This makes CD a great mimicker of more common benign and malignant masses in the neck, chest, abdomen, and pelvis. A novel case of primary immunodeficiency (CVID) in a middle-aged woman, who developed multicentric CD (MDC) with splenomegaly, is described. The authors suggest that the onset of MCD and of the correlated splenomegaly was due to incorrect management of the hypogammaglobulinemia as immunoglobulin G (IgG) levels were not kept within normal ranges. Correct management of the hypogammaglobulinemia allowed splenectomy to be performed without any infectious surgical complications. MCD is reported for the first time in association with an adult case of CVID. The above reported case highlights the need for a timely correct diagnosis and treatment of CVID to avoid complications, which could cause recourse to splenectomy, such as in our case or development of malignancies.

Background Kounis syndrome (KS) has been described as the coincidental occurrence of acute coronary syndromes during an allergic reaction with cardiac anaphylaxis. It is caused by inflammatory mediators released after exposure to drugs, food, environmental and other triggers. Oxidative stress occurring in various inflammatory disorders causes molecular damage with the production of advanced oxidation products (AOPPs) and advanced glycation end products (AGEs). Case presentation Markers of oxidative stress were evaluated in a patient who had experienced KS after antibiotic administration in order to investigate the possible role of these molecules in KS. No data, up to now, are available on biomarkers of oxidative stress in patients with drug-induced KS. Conclusions AOPPs, but not AGEs, were significantly increased in the KS affected patient compared to controls as already reported in mastocytosis affected patients.

Background Hymenoptera sting reactions are among life-threatening causes of allergy. Several epidemiology studies have assessed the risk of these kind of reactions, among the general population, around 3% of adults. This incidence increases among highly at risk populations such as outdoor workers. Hymenoptera stings among forestry workers (FW) are occupational triggers but it has not yet been well defined which is the real incidence of anaphylaxis in these workers, not even in Italy. Two Italian studies reported on the risk of hymenoptera stings (HS) in northern Italy (NI) and central Italy (CI) FW while no data is available on the prevalence in southern Italy (SI) ones. Methods A population of 341 SI FW (301 males and 40 females, mean age 51 years, range 43–63 years), who worked in Sicily, was investigated submitting a standardized questionnaire dealing with reactions to Hymenoptera stings, such as large local reactions (LLR) and systemic reactions (SR). Results HS occurred in 203 FW (59%) and caused reactions in 77 (22%); LLR occurred in 46 (13%) and SR in 31 (9%); SR were life threatening in 9/341 (3%) FW and were treated with epinephrine at the emergency unit as workers did not carry an epinephrine auto-injector. A SR at a subsequent HS followed a LLR in 21/46 FW (46%). Conclusions FW in SI have a generic risk of HS anaphylaxis as in the general population but a higher risk of SR and LLR respect to forestry populations from different Italian geographical areas.SR among SI FW occurred in 9% of them, while published data report the incidence of SR around 2 and 4%, respectively, in the Centre and North Italy FW. The incidence of LLR in SI FW was also higher (13%) than in CI (2%) and NI (10%) ones. Previous LLR in our SI population represented a high risk factor for developing a SR and therefore a red flag for future anaphylaxis and prescription of an epinephrine auto-injector.

In the last decade, the ingestion of gluten, a heterogeneous complex of proteins present in wheat, rice, barley and probably in oats, has been associated with clinical disorders, such as celiac disease, wheat allergy and recently to non-celiac gluten sensitivity or wheat intolerance syndrome. Gluten-related disorders, which are becoming epidemiologically relevant with an estimated global prevalence of about 5%, require the exclusion of gluten from the diet. For the past 5 years, an important shift in the availability of gluten-free products, together with increased consumption in the general population, has been recorded and is estimated to be about 12-25%. Many people follow a self-prescribed gluten-free diet, despite the fact that the majority have not first been previously excluded, or confirmed, as having gluten disorders. They rely on claims that a gluten-free diet improves general health. In this review, we provide an overview of the clinical disorders related to gluten or wheat ingestion, pointing out the current certainties, open questions, possible answers and several doubts in the management of these conditions. KEY MESSAGE Incidence of gluten-related disorders is increased in the last decade and self-diagnosis is frequent with inappropriate starting of a gluten-free diet. Gluten and wheat are considered as the most important triggers to coeliac disease, wheat allergy and non-celiac gluten sensitivity. Pediatricians, allergologist and gastroenterologist are involved in the management of these conditions and appropriate diagnostic protocols are required.

Introduction: Sublingual immunotherapy (SLIT) was introduced as a safer option to subcutaneous immunotherapy (SCIT) which was associated with the possible occurrence of systemic reactions including anaphylaxis and, though very rarely, fatalities. Some anaphylactic reactions to SLIT are reported, mainly in adults but also in children. It is therefore important to investigate the risk factors related to such reactions.Areas covered: Data from the literature on the safety of SLIT in children were reviewed. The data reviewed concerned the application of this treatment to patients with respiratory allergy and also possible new indications such as food allergy, atopic dermatitis and latex allergy. Reports of anaphylactic reactions were analyzed to identify the potential risk factors.Expert opinion: SLIT is a well tolerated treatment, the common side effect being local reactions in the mouth. Systemic reactions, concerning the skin and the airway, are rare and anaphylactic reactions are extremely rare.

Background: This is the first randomized, double-blind, placebo-controlled trial (EUDRACT No. 2009-013923-43) evaluating nickel oral hyposensitizing treatment (NiOHT) in patients with “systemic nickel allergy syndrome” (SNAS), characterized by Ni-allergic contact dermatitis and systemic reactions after eating Ni-rich food. Methods: Adults with positive Ni-patch test, who reported symptoms suggesting SNAS, which improved after Ni-poor diet, and were positive to Ni-oral challenge were eligible. Patients were randomly assigned to three treatments (1.5 μg, 0.3 μg, or 30 ng Ni/week) or placebo for a year, with progressive reintroduction of Ni-rich foods form the 5th month. Out of 141 patients randomized, 113 completed the trial. Endpoints were efficacy and tolerability of treatment. Results: During Ni-rich food re-introduction, the 1.5 μg Ni/week group had a mean VAS score significantly higher than placebo (p = 0.044), with significant improvement of gastrointestinal symptoms (p = 0.016;) and significantly fewer rescue medications. Cutaneous manifestations also improved but without reaching statistical significance. After the treatment, oral challenge with higher Ni doses than at baseline were needed to cause symptoms to flare-up in significantly more patients given 1.5 μg Ni/week than placebo (p = 0.05). Patients reported no side-effects. Conclusions: NiOHT is effective in SNAS, in particular on gastrointestinal manifestations, with trend toward improvement of cutaneous symptoms.

Chronic heart failure (CHF) is a complex and heterogeneous clinical syndrome and because of its rising incidence and prevalence, it can be considered a global epidemic. Interleukin (IL)-22 is a pro-inflammatory cytokine, belonging to the IL-10 family. Forty-seven consecutive older patients, hospitalized with an admitting diagnosis of CHF at the Geriatric Medicine Unit (University of Messina, Italy), from 01/01/06 to 30/06/06, were enrolled in the study. Serum concentrations of IL-22 were measured by a quantitative enzyme immunoassay technique. IL-22 levels in all CHF patients were significantly higher than those in controls, in particular, only the II and III NYHA class had IL-22 values significantly higher than the controls, whereas there was no difference between the IL-22 levels of NYHA class IV and the controls. The reason may be the declining immune function in CHF older patients, in fact we can hypothesize that the fall in IL-22 levels, with the progression of NYHA class, is due to the reduced ability in CHF patients to respond to infections, as IL-22 has anti-microbial properties. We detected different outcomes correlated to different IL-22 levels, and the Kaplan-Meier curves suggest a trend.

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

Background Specific immunotherapy is the only currently available allergen-orientated treatment able to modify the natural history of respiratory allergic diseases. Safety and clinical efficacy of this treatment are well documented, but evidence about the ability to reduce new sensitizations is still poor. Objective We report a retrospective study conducted in order to assess the prevention of new sensitizations in monosensitized subjects treated with specific immunotherapy vs. monosensitized patients treated with anti-allergic drugs. Methods 8396 monosensitized patients with respiratory symptoms were selected according to an open, retrospective design. Group A included 7182 patients submitted to specific immunotherapy (and anti-allergic drugs when needed) for 4 years and then treated with drugs for at least 3 years. Group B included 1214 patients treated only with drugs for at least 7 years. All patients underwent prick test with a standard panel of allergens and total and specific IgE determination before and after 4 years of treatment and again 3 years later. Results Groups were well balanced. Polysensitized subjects were 23.75% in Group A and 68.03% in Group B after 4 years (P

Background Nonallergic rhinitis with eosinophilia (NARES), accounting for some 15% of perennial rhinitis, is a nasal disorder whose main features are eosinophil counts in nasal smear higher than 10% and negative IgE tests. The mainstay of treatment is topical corticosteroids. Objective To evaluate the adjunctive effect of loratadine, a non-sedating antihistamine with anti-allergic activity, on nasal symptoms and eosinophil counts in nasal secretions in patients with NARES. Methods Thirty patients with NARES were divided in two groups, half receiving flunisolide two 25 μg puffs per nostril morning and night plus loratadine 10 mg u.i.d. and half the same doses of flunisolide plus placebo, according to a double-blind fashion, for 3 weeks. The effectiveness of the treatment in the two groups was evaluated by comparing symptom scores and eosinophil counts, and safety was assessed by comparing the adverse effects. Results The loratadine treated group had better results both in nasal symptoms, with a decrease in sneezing (P

Sublingual immunotherapy (SLIT) with monomeric carbamylated allergoid administered in accordance with the standard regimen has proven to be effective and safe. Achieving clinical benefit, however, requires a lengthy period of time so it is not very suitable for short-lasting allergies. We thus performed this study to compare an administration protocol starting in the coseasonal period (with a 4-day build-up phase) with a precoseasonal scheme to verify if the former regimen provides the same benefit in a shorter period of time. The prospective, randomized, drug therapy-controlled study was conducted in 33 rhinitic patients monosensitized to Olea with or without asthma. Ten patients were assigned to the coseasonal therapy with 5000 allergic units (AU)/week for 6 weeks, 11 to the precoseasonal therapy with 3000 AU/week for 10 weeks, and 12 to drug therapy. They were treated from April or May to June 2008. A visual analog scale (VAS) was performed at baseline and after treatment to assess the well being of the patients. Drug consumption was evaluated by means of a monthly diary. There was greater VAS improvement in both the SLIT groups versus the controls, but it was statistically significant only in the coseasonal group (p < 0.01). Furthermore, there was a reduction in the rescue medication only in the coseasonal SLIT (p < 0.05 versus drug therapy). One mild adverse event was observed. The allergoid SLIT was shown to be effective and safe in Olea allergy in particular when a coseasonal regimen was used.

Nickel sensitization can not only induce allergic contact dermatitis (ACD), but also can induce an overlapping disease referred to as "systemic nickel allergy syndrome" (SNAS), characterized by urticaria/angioedema and gastrointestinal symptoms correlated to the ingestion of nickel-containing foods. This study was designed to determine if oxidative stress occurs in patients with nickel allergy. Thirty-one female patients (mean age 31.26 + 13.04 years, range 16-64 years) with confirmed nickel CD underwent oral nickel challenge because of clinically suspected SNAS; serum concentrations of protein carbonyl groups (PCGs) and nitrosylated proteins (NPs; biomarkers of oxidative stress) were measured before and after oral nickel challenge as well as in healthy female controls. Twenty-three of these 31 patients were diagnosed with SNAS because they had a positive reaction to the oral nickel challenge, and 8 patients had no reaction and therefore were classified as patients with contact nickel allergy only. Although both nickel-allergic patients and controls presented similar serum levels of PCGs, NP values in nickel-allergic patients appeared higher than in controls and tended to decrease after the challenge; furthermore, serum levels of NPs in patients affected by SNAS were higher (although not significantly) than in patients with nickel ACD only. The involvement of specific biomarkers of oxidative stress such as NPs and the lack of involvement of other biomarkers such as PCGs may help to better understand the alteration of the redox homeostasis occurring in nickel ACD and particularly in SNAS.

A 34-year-old woman referred episodes of gastrointestinal disorders and sometimes angioedema of the lips which appeared within 2 hours from the ingestion of packed food like biscuits, cereals or fruit juice. A patch test with the standard European series and with food preservatives was positive for fragrances mix. The avoidance of packed food labelled as containing flavours among the ingredients caused the disappearance of the above reported symptoms.

Summary We present the case of bronchospastic reaction to clarithromycin had during a drug challenge test Personal allergic history was negative for respiratory allergies and positive for adverse drug reactions to general and regional anesthesia and to ceftriaxone After the administration of 1/4 of therapeutic dose of clarithromycin the patient showed dyspnea, cough and bronchospasm in all the lung fields The positivity of the test was confirmed by the negativity to the administration of placebo The quickness and the clinical characteristic of the adverse reaction suggest a pathogenic mechanism of immediate-type hypersensitivity On reviewing the literature we have found no reports of bronchospastic reaction to clarithromycin Macrolides are a class of antibiotics mainly used in the last years in place of b-lactams because of a broad spectrum of action and a low allergic power. In fact, there are few reports on allergic reactions to these molecules Clarithromycin is one of the latest macrolides, characterised by the presence of a 14-carbon-atom lactone ring as erythromycin, active on a wide spectrum of pathogens

Nickel can elicit both Th1-type andTh2-type responses in vitro (1) inpatients with nickel allergic contactdermatitis,butthiscomplexcytokinecascade has still to be clarified. Therecently discovered Th17 subset,which has crucial functions in hostdefence against infections and hasbeen implicated in the developmentofautoimmunediseases(2),hasbeensupposed to play an important rolein some inflammatory and autoim-mune skin disorders, such as contacthypersensitivity(3)andpsoriasis(4),respectively. Th17 cells are charac-terized by expression of interleukin(IL)-6, tumour necrosis factor-a,granulocyte–macrophage colony-stimulating factor, IL-17A, IL-17F,IL-21, IL-22, and IL-26 (5).Among these cytokines, IL-22,a member of the IL-10 cytokine fam-ily, described as having proinflam-matory activities on liver, pancreas,intestine, and skin (reviewed in 6),has been demonstrated to have a cru-cial function in the development ofdermal inflammation and epidermalacanthosis induced by IL-23 in mice(4). Moreover, IL-22 seems to beinvolved in the pathogenesis of psori-asis in humans, as demonstrated bythehighserumlevelsshowedbypsori-atic patients and the high levels pro-duced by T cells isolated by psoriaticskin (6), where the IL-22 receptor isexpressed on a variety of epithelialtissues(4).However,nodataareavail-ableon thepossibleroleplayed byIL-22in nickel contacthypersensitivityinhumans, thus we measured the circu-latinglevelsofthiscytokineinpatientswith allergic nickel contact dermatitis.We enrolled 31 female patientsaffected by allergic contact dermatitisto nickel (mean age 31.9 years; range17–64 years) diagnosed followingpatch testing in accordance withthe International Contact DermatitisResearch Group guidelines. Bloodsamples were collected after patchtesting during a period of clinicalremission 1 month after nickel con-tact avoidance.15 sex- and age-matched blooddonors, with no contact dermatitisand negative patch tests, were re-cruited as controls. Each subject gavepreviously used written, informedconsent to the study.Serum IL-22 was measured usingan enzyme-linked immunosorbentassay kit (R&D System Europe,Abingdon, UK). All samples wereanalysed in duplicate.Differences in IL-22 blood levelswere assessed by the Student’s t-testfor unpaired comparison, assumingunequal variances. Data were ex-pressed as mean standard devia-tion. A P value

Background: New routes of administering immunotherapy in respiratory allergy are being studied as an alternative to conventional injective immunotherapy. We carried out a study to evaluate the clinical efficacy and effects of sublingual immunotherapy in patients with Parietaria judaica-induced respiratory allergy. Methods: A double-blind, placebo-controlled design was followed. Thirty patients with P. judaica rhinoconjunctivitis, mild asthma, or both were randomly chosen for sublingual immuno-therapy (14 patients) or placebo treatment (16 patients). The patients underwent preseasonal rush induction treatment followed by coseasonal maintenance treatment during the Parietaria pollen season. Symptom and drug scores, as well as specific IgE and specific IgG4, were recorded. Results: Significantly lower symptom and drug scores were found (P=0.04), especially during the Parietaria pollination period, in the immunotherapy group. No significant difference in specific IgE and specific IgG4 was detected between the active and placebo groups; a statistically significant increase of specific IgE was detected in both groups (P=0.05). No patient undergoing active sublingual immunotherapy reported local or systemic side-effects. Conclusions: Our data suggest that sublingual immunotherapy is both clinically effective and safe in treating patients with Parietaria-induced rhinoconjunctivitis and mild asthma.

Design of study Two groups of patients undergoing long-term dialysis were studied in order to evaluate the importance of ethylene oxide (EtO) in causing allergic reactions during dialysis. The first group of 50 subjects had never shown any hypersensitivity reactions related to dialysis, whereas the second group of 20 subjects had previously complained of reactions. All the patients underwent a prick test with a standard kit of aeroallergens in order to assess the presence of atopy (in doubtful cases a RAST test was carried out with the same aeroallergens). A blood sample for the investigation of EtO specific IgE antibodies was taken from all the patients; the immunoenzymatic method was used. Results Sensitivity to EtO is significantly higher in the group of patients with previous allergic reactions during dialysis (55 vs 6% in the control group).

Although copper sulfate can cause systemic contact dermatitis, few such cases have been recorded among copper-releasing IUD users. Reported in this paper is a case of endometritis and urticaria-angioedema syndrome in a 32-year-old user of a copper IUD. Widespread urticaria, as well as angioedema of the eyelids and the labia majora and minora, persisted for about 6 months and were not responsive to corticosteroids and H1-antagonists. Copper sulfate positivity was demonstrated in 72-hour patch test, 48-hour application of the copper spiral to forearm, and in vitro lymphocyte-stimulating test. Histologic examination of the endometrial biopsy revealed vulvovaginitis with hyperplasia of the cervical canal and T-cell and eosinophilic granulocyte infiltration. Removal of the IUD caused complete symptom remission. In experimental animals with a radioactively labeled copper IUD, small amounts of copper sulfate are absorbed through the mucus membrane and carried to the cutis through the blood or lymph. In the cutis, the allergen is intercepted from antigen-presenting cells and recognized by T cells that migrate to the lymph nodes with blastic transformation, proliferation of cytotoxic lymphocytes, and cytokine production.

The natural history of allergic rhinitis (AR) is commonly characterized by worsening of symptom severity, frequent comorbidity with asthma, and polysensitization to aeroallergens. The polysensitization phenomenon starts in early childhood. AR classification has been recently revised, and some studies investigated the new types: intermittent (IAR) and persistent (PER) AR. However, no study has been carried out on children regarding this issue. This preliminary study was performed on a large cohort of children with allergic rhinitis to evaluate the type and severity of rhinitis and its possible association with asthma, including severity grade. One hundred and thirty-nine children (86 males, 53 females, mean age 11.8 years, range 3.5–17.7 years) with allergic rhinitis were prospectively and consecutively evaluated. Seventy-one children had rhinitis alone and 68 had rhinitis associated with asthma. Forty children had IAR, 30 of whom with moderate-severe grade. Ninety-nine children had PER, 65 of whom had moderate-severe grade. The severity of AR was not associated with asthma presence (Fisher χ2 = 0.5765; Prob.=0.9018). Regarding asthma severity, 30 children had the intermittent form, whereas 38 had the persistent form: 15 mild, 22 moderate, and 1 severe. This study provides the first evidence concerning the ARIA classification in children, partially confirming findings obtained in adulthood.

School and Division of Allergy and ClinicalImmunology, University of Messina, Messina, ItalyKey words: nickel; endogenous dermatitis; IL-12;IL-10.Dr Luisa RicciardiScuola di Specializzazione in Allergologia eImmunologia Clinica PoliclinicoPadiglione H98100 MessinaItalyTel: +39 090 2212080Fax: +39 090 694773

Background Anisakis simplex , a fish and cephalopodes parasite, can cause either gastrointestinal symptoms or allergic reactions in humans on eating/handling contaminated fish. Objective The aim of our study was to determine the capacity of Anisakis simplex to induce specific IgE production and allergic reactions following eating and handling fish in a population at risk. Methods We determined the levels of total IgE, specific IgE, and eosinophil count in 28 fishermen/fishmongers (group A) and 15 healthy donors (group B). A skin prick test (SPT) with extracts from Anisakis and the most common species of fish in our country, were also carried out. Results Specific IgE to Anisakis were found in 14 subjects of group A (13 of them had a positive SPT to the same extract) and none of group B (only one subject had a positive SPT). The SPT with fish extracts was positive in 4 patients of group A but in none of group B. Subjects in group A with specific IgE to Anisakis showed higher total IgE levels and eosinophil counts compared with either other individuals of the same group or to those of group B. Conclusions These results indicate that fishermen/fishmongers are a population at risk for Anisakis simplex sensitization and suggest that this kind of sensitization should also be investigated not only in subjects like fishermen/fishmongers who live in countries where fish is likely to be contaminated with Anisakis simplex parasites, but also in those who handle fish for other reasons.