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Summary: Cannabis is the most widely used drug worldwide sought for recreational and medicinal purposes. Cannabis allergy was first described 50 years ago but has become more frequently reported over the past decade due to a larger industrial and domestic cultivation, and an evolving legal status. However, it remains an infrequent cause of allergy in the Mediterranean European countries. We describe three clinical cases with primary sensitization to cannabis characterized by anaphylactic reactions. We hypothesize that in all three case reports, sensitization to Can s 3 nsLTP played a crucial role in the development of anaphylaxis, either directly following ingestion of hemp-containing food, or even indirectly through primary sensitization via involuntary exposure or occupation exposure to cannabis sativa.

In Europe more than 50% of asthmatic treated patients have a not well-controlled asthma. The present survey aims at investigating how different specialists approach asthmatic patients. A web anonymous questionnaire was randomly administered to 604 General Practitioners (GPs), 241 Pneumologists and 131 Allergists. It concerned: epidemiology, diagnostic workup, follow-up and risk factors, treatment and future risk. A general agreement emerges about asthma diagnostic work-up. All categories are aware of the impact of comorbidities on asthma. LABA/inhaled steroids combination is considered the first choice treatment. Surprisingly, depot steroids and long-acting beta2 agonists (LABA) alone are still prescribed by GPs. Concerning monitoring tools, Allergists rely on inflammation biomarkers, whereas reduction of rescue medication is more relevant for GPs. Asthma Control Test (ACT) is considered time consuming by more than 50% of all physicians and is not known by most of GPs. Adherence is considered a crucial problem in asthma management. All categories seem to have a good knowledge about asthma. The cultural background may account for mild differences in asthma control tools and treatment options. GPs have a pivotal role in discriminating patients who need specific assessment by specialists. It is thus important that GPs and specialists share common tools for recognizing and managing those patients.

The Component Resolved Diagnostic (CRD) approach has been developed when highly purified or recombinant allergen molecules have become available. These molecules are the allergenic proteins toward which the specific and clinically relevant IgE immune response is directed. So, the identification of protein families and cross-reactivity patterns of importance in allergy have been possible. The Italian advisory BOARD for ISAC was born: to evaluate the advantages, disadvantages and placement in diagnosis of CRD studying its application in allergic patients; to facilitate the interpretation of molecular diagnostics for clinical allergists; to evaluate the effectiveness of CRD in improving diagnostic risk assessment and early preventive treatment of allergic diseases. In the last years, its fields of interest have been: the evaluation of the performance of CRD on multi-sensitized allergic patients with respiratory symptoms and on poly-sensitized athletes; the evolution of IgE repertoire directed to single allergenic components by evaluating allergic patients with different age at a molecular level; the relevance of results obtained using allergen microarray technique for describing the IgE repertoire in allergic patients by reviewing the main articles focused on CRD published in the last 2 years; the need for an educational program focused on this new diagnostic tool also through the creation of an exhaustive and interactive explanation of the laboratory report molecular allergy; the investigation of the performance and potential additional diagnostic values of the ISAC microarray in a real-life clinical setting, taking into account also the economic values.

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

We performed a survey, based on a questionnaire including 20 items, submitted anonymously to Italian trainees in Allergology and Clinical Immunology, in order to obtain information about their specific allergen immunotherapy (AIT) practices. The questionnaire was sent to 40 trainees, who had attended the last two years of the training course. Thirty-four subjects (mean age: 27 years, 65% females) adequately completed the survey. The answers to the questionnaire showed that only 60% of the training programs included lectures on AIT. Among the trainees using AIT, only 40% declared being able to prescribe it independently, while 60% were guided by a tutor. Of the trainees who were able to prescribe AIT autonomously, 60% were familiar with both routes of administration, i.e. subcutaneous (SCIT) and sublingual immunotherapy (SLIT), while 25% of these used only SLIT. In 80% of the training institutions involved, the trainees could attend a dedicated AIT outpatient ward for SCIT administration; only 40% administered AIT personally, and in half of these cases, they were guided by a tutor. Only 70% of trainees had experience in the follow-up of patients still under treatment and of patients who had completed treatment. Analysis of the answers obtained for questions on venom immunotherapy (VIT) showed that, in 90% of cases, the trainees attended a dedicated outpatients ward where VIT is administered, but with a role limited to observation/cooperation. Only 30% were involved in the follow-up of patients who were under treatment or who had completed VIT. Only 20% of the trainees felt confident enough about VIT to prescribe this treatment independently, 80% knew there were several administration protocols, and the majority prescribed products from three different manufacturers. These findings suggest that there is significant room for improving the instructions provided regarding allergology and clinical immunology to trainees in Italy with respect to AIT.

Background: Extra-European immigrants are increasingly seen in allergy clinics. In view of their different genetic background they represent an opportunity to investigate the dynamics of sensitization to airborne allergens., Objective: We investigated the pattern of airborne sensitization among allergic extra-European immigrants living in two areas of northern Italy., Methods: Extra-European immigrants living in Milan and Verona were compared with age- and sex-matched or allergen-matched allergic Italians. Based on number of sensitizations to airborne allergens, patients and controls were divided into mono-/oligo-sensitized or multi-sensitized (1-3 or > 3, respectively)., Results: In Milan grass pollen allergy was more frequent among immigrants than in controls (75% vs 49%; p < 0.01), whereas ragweed allergy prevailed among Italians (56% vs 20%; p < 0.001). In Verona, immigrants were rarely multi-sensitized (21% vs 43%; p < 0.01), more frequently sensitized to grass and birch. In both areas immigrants became allergic at a significantly older age than Italian controls (p < 0.0001), particularly to grass and mites. Allergy to HDM and ragweed was rare in Central & South Americans, whereas Africans showed the lowest proportion of multi-sensitizations. On average, immigrants became allergic after 2-4 years of stay in Italy., Conclusion: Subjects genetically prone to become allergic to a particular allergen get eventually sensitized irrespective of their age when they are exposed to the "right" allergen for a sufficiently long time. The higher proportion of mono-/oligo-sensitized immigrants might reflect a shorter exposure to airborne allergen load in this group.

Allergen immunotherapy (AIT) is the only treatment able to act on the causes and not merely on the symptoms of allergy. AIT was introduced 100 years ago but remained an empirical treatment for more than 40 years, when the first controlled trial in 1954 opened the era of scientific evidence. A major advance was the introduction of venom immunotherapy to prevent anaphylaxis from insect stings in 1978. Concerning inhalant allergens, currently AIT may be administered in two forms, subcutaneous (SCIT), and sublingual immunotherapy (SLIT). A large number of trials, globally analyzed in a number of meta-analyses, gave sound evidence to the efficacy and safety of SCIT and SLIT in allergic rhinitis and asthma. Adverse systemic reactions are still a drawback for SCIT while safety and tolerability of SLIT are very good, provided recommended doses and schedules of administration are used A significant advance for SLIT development was the registration in Europe of the standardized quality tablets. New applications, such as food allergy and atopic dermatitis, as well as new routes of administration, are currently under evaluation. After 100 years of use, AIT has a central role in the management of allergy and the ongoing improvement seems able to warrant to AIT an even brighter future.

Allergen subcutaneous immunotherapy is a long lasting treatment which can modify the natural history of allergic respiratory diseases. Recommended administration is required for a minimum of three years. During this long term therapy the daily management is based on two crucial points, discussed in this review, such as the prevention and the treatment of side effects and the improvement and follow-up of patient adherence. This review specifically focuses on subcutaneous immunotherapy.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are a frequent cause of hypersensitivity reactions, therefore, in clinical practice, it's important to find safe and effective substances., Objective: To evaluate the tolerability of etoricoxib and its subsequent actual use and safety at home., Methods: Etoricoxib tolerance was assessed by single-blind-placebo-controlled oral challenges and its subsequent use was checked by a standardized telephone call. The test was performed in 139 subjects (83 single NSAID reactors and 56 multiple NSAID reactors)., Results: The drug was not tolerated in 4 cases (2.8%) causing wheals on the face area in 3 single reactors and a severe generalised reaction occurring three hours after the intake of a therapeutic dose in a multiple reactor. The phone calls showed that 64 (52.8%) patients did not take etoricoxib, mostly due to the fear of adverse effects; in 5 cases (4.2%), the practitioner prescribed a different NSAIDs. Only 52 (43%) subjects took etoricoxib after oral challenges; all tolerated the drug but 2 single reactors, who reported a very mild labial oedema., Conclusion: Our study confirmed the good long-term tolerability of etoricoxib in patients with a history of hypersensitivity to other NSAIDs without differences between single and multiple reactors. Nonetheless, in NSAID-intolerant subjects this drug should be first challenged in specialised centres due to the risk ofsevere reactions.

In this report we describe un unusual case of exclusive allergic sensitization to furry animals, as a possible study model to speculate about different modalities ofsensitization to allergens of common and less common mammalian species. A 27-year-old woman referred in our Allergological Centre for the occurrence of conjunctival and severe respiratory symptoms after contact with several animals such as cats, dogs, rabbits, horses, cows etc. Patient underwent clinical and anamnestic evaluation including a detailed information on the modality of exposure to different furry animals. Skin-prick-test (SPT) was performed with our routine panel of commercial standardized extracts (Lofarma Laboratories, Milan, Italy). Some animal allergenic extracts (rabbit, horse, rat, mouse, cavia, cow and hamster) have been tested by SPT one week after the routine SPT A blood sample was taken for measurement of total IgE and specific IgE (CAP System, Phadia, Uppsala, Sweden) as well as Immunoblotting procedures. The results of in vivo and in vitro procedures revealed allergic sensitization only to animal-derived allergens. Total IgE were 59.3 kU/L. Immunoblotting showed a specific IgE-mediated sensitization of the patient to cow's, rabbit's and horse's serum albumins (SA). In conclusion, our case report confirms the role of SA as cross-reacting agent in allergic sensitization to furry animals. This finding suggests to perform SPTs to several furry animal allergens in all individuals with high level of allergic sensitization to common pets (cats and/or dogs) in order to identify allergy to other animals and consequently to avoid future exposures at risk.

Background: Epinephrine is the treatment of choice for acute food-allergic reactions but existing guidelines state that it should be prescribed uniquely to patients who already experienced at least one food-induced anaphylactic episode., Objective: We investigated whether in Italy epinephrine auto-injector is prescribed uniquely following the existing guidelines only, or is allergen-informed as well (i.e., based on the potential risk associated with sensitization to certain food allergens), and hence preventive., Methods: 1110 adult patients (mean age 31 years; M/F 391/719) with food allergy seen at 19 allergy outpatient clinics were studied. Patients with a history of probable anaphylaxis were identified. Subjects were classified as having primary (type 1) and/or secondary (type 2) food allergy and were divided into several subgroups based on the offending allergen/food. Epinephrine prescriptions were recorded and analyzed both as a whole and by sensitizing allergen., Results: Epinephrine was prescribed to 138/1100 (13%) patients with a significant difference between subjects with type-1 and type-2 food allergy (132/522 [25%] vs. 6/629 [1%]; p < 0.001). The epinephrine group included most patients with a history of anaphylaxis (55/62 [89%]) or emergency department visits 106/138 (77%). In some specific subsets, namely fish-, tree nuts-, and lipid trasfer protein (LTP)-allergic patients, epinephrine was prescribed to patients without a history of systemic allergic reactions., Conclusions: Italian allergy specialists prescribe epinephrine auto-injectors both on the basis of clinical history of severe reactions and on a critical analysis of the hazard associated with the relevant protein allergens, which suggests a good knowledge of allergens as well as acquaintance with the guidelines for prescription of emergency medication.

Although the increase in the rate of hamster ownership, no report of allergic sensitization to common hamster (Cricetus cricetus)-derived allergens as a consequence of domestic exposure has been published in Italy. A 64-year-old woman was referred to our Allergy Centre for the recent onset of conjunctival and severe respiratory symptoms (rhinitis, cough, wheezing and dyspnea). About three months ago she had purchased a common hamster as home pet. Another hamster had lived at patient's home for about four months nine years ago. The results of SPT revealed allergic sensitization to Cricetus cricetus dander only (wheal 6x7 mm, positive control 7x7 mm). Total IgE were 59.3 kU/L. Specific IgE only to Cricetus cricetus epithelia (2.10 kUA/L), were also detected. Spirometry revealed a moderate degree of bronchial obstruction. Some important considerations can be drawn from our report: a) few months of hamster ownership are probably sufficient to induce an allergic sensitization and clinical symptoms, b) older age of sensitization in comparison to other studies, c) rapid remission of clinical symptoms after the removal of hamster d) skin prick tests and/or evaluation of specific IgE for hamster allergens should be performed in all potentially susceptible individuals.

Background: The major cat allergen, Fel d 1, is ubiquitous, and clothes of cat owners are important vehicles for its distribution and dispersal in cat-free environments., Objective: We assessed the efficiency of a standard vacuum-cleaning in removing the cat allergen from cotton fabrics, experimentally contaminated by a prolonged contact with cats., Methods: Fifteen rectangles (80 x 100 cm) of a widely used cotton material were kept in baskets of male cats for 1 week. Afterwards, the squares were cut in half. One half was immediately sampled for cat allergen, and the other half was vacuum-cleaned for 15 minutes by a commercially available device before sampling. Five identical cotton rectangles not exposed to cats served as controls. Samples were collected with a high-volume vacuum air-sampler. Particulate material was harvested onto filters with 25-mm diameter and 2 microm pore size, extracted in phosphate buffer with BSA and then assayed for the Fel d 1 allergen with an ELISA method. The results were expressed as micrograms of allergen per filter., Results: After vacuum-cleaning the amounts of Fel d 1 extracted from cat-exposed fabrics were not significantly reduced ( t = 3.118; P > 0.005), with respect to the non vacuum-cleaned tissues. No Fel d 1 was found in control fabrics., Conclusions: Our study suggest that vacuum-cleaning by using a commercially available device is not able to remove significant amounts of cat allergen from cotton fabrics exposed to cats.

Background: At present test tube allergy diagnosis is becoming increasingly more comparable to skin prick tests and is therefore increasingly more reliable, not only from an analytical point of view but also from a clinical one. The cost of test tube allergens has decreased over the years and the specific IgE dosage can quickly give a good diagnostic indication., Objective: To study the percentage of positive subjects for each individual allergen in cases of suspected allergy, the laboratory can easily identify, also by age bracket, the positivity for those well known allergens that are more commonly responsible for allergic pathologies by using the skin prick test. Our laboratory has studied the test tube diagnostic activity of 2002 and 2003. The inhaled allergens used to identify the positivity percentage were selected from those in our Allergy Unit and which literature identifies as those more commonly positive at skin prick tests., Methods: The positivity rate of specific IgEs (UniCAP100- Phamarcia) were analyses for two age brackets before and after the age of 12. The younger than 12 group was then subdivided further into pre-school age (3-5 years) and school age (6-12)., Results: It can be stated that in the grass group, the seasonal allergens, the most commonly positive were cereals and pellitory, the latter increasing in adult age (above 12 years). In the tree group of seasonal allergens, positivity was found to increase in adult age for olive and cypress trees. The more commonly positive perennial allergens in the adult age (above 12) are dermathophagoides and cat. Below 12, there is a strong positivity to alternaria., Conclusions: Such test tube studies on IgE positivity are not only useful for better defining diagnostic patterns to give an initial idea of suspected allergy, but also to highlight any changes in the IgE antibody count within different age brackets, with the possibility of documenting the progress of the pathology which is characteristic of the allergy in question.

Accelerated schedules of administration of immunotherapy (rush or clustered) allow to reach the maintenance dosage in shorter times with respect to traditional schedules. Nowadays formal assessments of the safety and economic aspects of those schedule lack for inhalant allergens. We compared in a prospective randomized open study a cluster and a traditional immunotherapy with standardized mite extracts. Thirty eight adult patients with persistent allergic rhinitis due to mites were randomized to receive either a traditional (N= 19) or a cluster (N=19) up-dosing scheme, lasting 13 and 3 weeks respectively. Side effects were carefully evaluated and recorded by physician and costs were calculated as well. In the cluster and traditional updosing 148 and 241 injections were given respectively. With the cluster up-dosing there were 8 local reactions (15.9% of patients and 5.4% of injections). With the traditional schedule 6 local reactions (31.5 % of patients and 2.4% of injections) occurred. There was no difference between the two treatments in occurrence of side effects per patient and per injection (chi-square 1.31 and 2.23, p= NS). No systemic reaction was recorded. Considering the cost of the extract, the cost of injections and the time spent, the cluster regimen resulted in a global spare of 244.95 euros per patient in the build-up phase. The cluster up-dosing is as safe as the traditional one and allows a significant economical save.

It has been well established that occupational exposure to horses increases the risk of allergic sensitization to horse hair, on the contrary very few data have been published in individuals without direct contact with horses. We describe two cases of severe respiratory symptoms triggered by a single direct exposure in two patients with only 4-5 previous short contacts with horses during the entire their life, since they live in urban area of Naples. Cutaneous and serological diagnostic tests showed significant sensitization to horse dander other than some common inhalant allergens. Our report suggests that, in already (but unaware) horse-sensitized patients, the last direct contact with a horse has triggered severe respiratory symptoms. Passive carriage of horse allergen by the clothes of individuals in contact with horses/horse environments or a cross-reactivity between horse allergen (a lipocalin) and the major allergens (also lipocalins) of several furred animals are likely to explain our findings. Some other considerations can be derived by the clinical observation. First, it is likely that allergic sensitization to horse allergens could be more frequent than expected also in subjects without direct exposure to horse because of living in urban areas. Secondly, individuals suspected to be highly atopic or those already sensitized to some pet dander should be tested by SPTs/radio-allergo-sorbent test before the introduction of a pet indoors or, in the case of a big animal as the horse, a direct horse contact/entering into environments containing a horse.

Background: It has been known for some time now that reactions to allergens, not only those inhaled but also those in food, varies with age in atopical patients., Objective: To evaluate the specific IgE positivity percentage in order to improve laboratory diagnosis in subjects with suspected food allergy., Methods: The positivity percentages of specific IgE were analysed (UniCAP100-Pharmacia) taking into consideration the two age brackets of below and above 12 years. The below 12 years age bracket was then further divided into pre-school age (3-5 years) and school age (6-12 years)., Results: By measuring the simple positivity percentage for specific IgE to food allergens, there is a clear decrease as the child matures in reactions to milk and eggs and an increase towards food IgEs that cross-react with grass and tree pollens or other inhaled allergens like moulds and mites., Conclusion: It will be necessary in the future to have the diagnostic means to identify this cross-reaction problem by using recombinant allergens that can demonstrate the combined reaction between inhaled and food allergens.

Background: The relationship between exposure to cat/dog in domestic environments and development of allergic sensitization to pet allergens is still controversial., Objective: To test the role of indirect exposure to cat, we aimed to evaluate the amounts of cat specific IgE in sensitized subjects with or without cat at home., Methods: Three hundred six adult patients with a previous diagnosis of allergic sensitization to cat allergens (by skin prick test) were enrolled for this study. Among 306 men and women sensitized to cat (and other allergens), 150 owned a cat for at least 10 years ( direct exposure) and 156 had never owned this animal (indirect exposure). An internal questionnaire specifically designed for the study was completed by the same allergists during the screening consultation: the results of skin prick tests, personal and clinical data, periods of symptoms and characteristics of cat ownership were carefully recorded. Specific IgE to cat extract was determined by the Pharmacia CAP System FEIA (Pharmacia Diagnostics, Uppsala, Sweden) and Immulite 2000 (Diagnostic Products Corporation, Los Angeles, USA) RESULTS: Although specific IgE to cat allergen were significantly higher in patients with cat at home (F = 42.77; p < 0.001), high amounts of these antibodies were found also in sera of subjects indirectly exposed to cats., Discussion: The results of our study demonstrate that the degree of serological sensitization to cat allergens may be relevant also in subjects without any direct contact with cats (indirect exposure).

It is generally recommended in consensus documents on allergen immunotherapy to avoid any kind of physical exercise in the 24 hours following the administration of the allergen extract but such recommendation is not supported by scientific evidence. We evaluated the risk of developing adverse reactions in a group of patients submitted to sublingual immunotherapy by performing a controlled exercise test. Eleven patients were included in the study, 8 treated with grass pollen and 3 with Parietaria pollen extract by Staloral300 (Stallergénes, Antony, France), with the build-up phase in 11 days suggested by the manufacturer and a top dose of 300 IR. At the first maintenance dose, in all patients were measured heart rate, blood pressure, FEV1, and tryptase in blood. Then the maintenance dose was assumed and the physical exercise performed by cycloergometer maintaining a heart rate around 100 b/min and measuring again tryptase, blood pressure and FEV1. The results showed that no patient had adverse reaction following physical exercise, neither showed significant changes in FEV1, blood pressure, or tryptase level, which was 5.57 +/- 4.54 mcg/l before and 5.81 +/- 4.34 mcg/l after exercise. This suggests that there is no reason to advise against physical exercise, and particularly sporting activity, in patients treated with sublingual immunotherapy thus avoiding to interfere with the subject's lifestyle and consequently with his quality of life.

Background: Acetaminophen (paracetamol--P) and Nimesulide (N) are widely used analgesic-antipyretic/anti-inflammatory drugs. The rate of adverse hypersensitivity reactions to these agents is generally low. On the contrary non-steroidal anti-inflammatory drugs (NSAIDs) are commonly involved in such reactions. Celecoxib (CE) is a novel drug, with high selectivity and affinity for COX-2 enzyme., Objective: We evaluated the tolerability of CE in a group of patients with documented history of adverse cutaneous reactions to P and N associated or not to classic NSAIDs., Methods: We studied 9 patients with hypersensitivity to P and N with or without associated reactions to classic NSAIDs. The diagnosis of P and N-induced skin reactions was based in vivo challenge. The placebo was blindly administered at the beginning of each challenge. After three days, a cumulative dosage of 200 mg of CE in refracted doses were given. After 2-3 days, a single dose of 200 mg was administered. All patients were observed for 6 hours after each challenge, and controlled again after 24 hours to exclude delayed reactions. The challenge was considered positive if one or more of the following appeared: erythema, rush or urticaria-angioedema., Results: No reaction was observed with placebo and eight patients (88.8%) tolerated CE. Only one patient developed a moderate angioedema of the lips., Conclusion: Only one hypersensitivity reaction to CE was documented among 9 P and N-highly NSAIDs intolerant patients. Thus, we conclude that CE is a reasonably safe alternative to be used in subjects who do not tolerate P and N.

The epidemiology of Hymenoptera venom allergy in Europe showed prevalence of systemic reactions of about 3%, but is scantly investigated in Italy. We studied two samples of the general and an at risk population, i.e. the foresters, in northern Italy. A standardized questionnaire dealing with allergic reactions to Hymenoptera stings was submitted to the subjects included in the study, who were factory workers in Milan and Verona and foresters in Lombardy. An overall number of 574 subjects participated to the study, 462 (299 males and 163 females, mean age 40.1 yrs, range 20-63 yrs) were factory workers and 112 (all males, mean age 38.8 yrs, range 24-59 yrs) were foresters. Among factory workers, 302 (65.4%) were stung by Hymenoptera, 49 (10.6%) had had large local reactions, and 13 (2.8%) systemic reactions. Among foresters, 76 (67.8%) were stung, 11 (9.8%) had had large local reactions, and 5 (4.5%) systemic reactions. The systemic reactions were life-threatening in 3 (0.6%) industrial workers and 2 (1.8%) foresters. The prevalence of systemic reaction of 2.8% in the general population agrees with the data reported from a number of countries with temperate climate. The prevalence of 4.5% in foresters attributed to this population a risk only slightly increased.

Background: Patients with aspirin-sensitive respiratory and cutaneous diseases experience cross reactions to all nonsteroidal anti-inflammatory drugs (NSAIDs) which inhibit cyclo-oxigenase (COX) enzymes. As are now available drugs which selectively inhibit COX-2, questions are raised whether cross-reactivity occurs between aspirin and these COX 2 inhibitors., Objective: The aim of this study was to evaluate the tolerability of three COX-2 inhibitors (meloxicam, celecoxib and rofecoxib) in subjects with previous pseudoallergic respiratory and cutaneous reactions to NSAIDs., Methods: 76 subjects with documented previous cutaneous and respiratory pseudoallergic reactions to aspirin and/or other NSAIDs underwent a single blind challenge with celecoxib, meloxicam and rofecoxib., Results: All subjects with previous respiratory reactions tolerated all drugs. Three subjects with multiple-drug induced urticaria complained of a generalized reaction after challenge (Two due to celecoxib and one due to meloxicam). Among the group of patients with NSAIDs-induced urticaria five complained of a relapse of the disease due to rofecoxib (one subject), celecoxib (two subjects and meloxicam (two subjects)., Conclusions: According to these results the cross-reactivity between aspirin and these COX-2 inhibitors does not occur in subjects with previous respiratory pseudoallergic reactions. A good safety profile was also demonstrated in patients with cutaneous reactions, being few reactions observed. However for this reason a controlled oral challenge with these drugs is useful for the proper management of patients sensitive to classic NSAIDs.

About 30% of women suffer from nasal symptoms during pregnancy. The hormonal changes occurring during pregnancy favour per se mucosal oedema and relaxation of smooth muscles, thus contributing to nasal congestion. The most common forms of rhinitis are allergic, drug-induced, infectious and vasomotor rhinitis. In addition to the detrimental effects that rhinitis can have on quality of life, it is important to correctly treat rhinitis itself since it can influence concomitant asthma, as underlined in ARIA document. In pregnancy, the safety profile of drugs is the primary item to be considered. The American FDA pointed out that foetal damage could not be totally excluded with the majority of antirhinitis drugs. It is recommended to use "older drugs" because more data about their safety are available. Cromones are the safest drugs but, although they need multiple daily administrations. Antihistamines should be considered as second choice drugs, and their use is not recommended during the first three months of pregnancy. Topical steroids are useful in moderate-severe rhinitis, being beclometasone the most documented molecule. Topical vasoconstrictors should not be used continuously because they can induce pharmacological rhinitis. It is not recommended to start specific immunotherapy in pregnancy but it can be continued in patients who benefit from its use. Infective rhinitis should be treated with beta-lactams, cephalosporins or macrolides. Finally it is important to evaluate the cost/usefulness ratio before any drug prescription.

Unlabelled: High dose sublingual immunotherapy (SLIT) is generally well tolerated, since most side effects are local reactions involving the oral or gastrointestinal mucosa. However, such reactions, if not adequately managed, may lead the patient to stop SLIT., Objective: We introduce a method to manage side effects of SLIT, which was successfully applied on a group of children undergoing SLIT., Methods: SLIT was performed with Staloral 300 (Stallergénes, Antony, France) by the schedule in 11 days indicated by the manufacturer with a tap dose of 8 pressures of the 300 IR concentration. The treatment was managed by flow charts suggesting adjustment of dose, regimen, or kind of assumption depending on the kind of reactions (oral, gastrointestinal, respiratory)., Results: An overall number of 200 children (120 males, 80 females, mean age 9 yrs, range 3-14 yrs) were treated. Of them, 155 (77.5%) had no reaction, while 45 (22.5%) had side effects, consisting of 20 oral itching or burning, 15 gastrointestinal symptoms and 10 rhinitis. No systemic reaction was observed. All side effects were successfully managed by the proposed method, thus reaching the maintenance dose in all patients but one, reporting repeated intense oral itching, who stopped SLIT., Conclusions: High dose SLIT is well tolerated in treated patients. In most patients with side effects, which are mainly oral itching or gastrointestinal disturbances due to contact with the allergen extract, a proper management allows to reach the maintenance dose with no further reactions.

In the recent years, the importance of sports in everyday life has rapidly increased. Asthma and respiratory allergy are among the most common problems to be afforded in those individuals practising sports and therefore, the diagnostic and therapeutic aspects of allergy in athletes have received in recent times a great interest. The experimental studies performed on allergy and sport have lead to take in consideration a more general aspect, that is the effects of exercise on the immune system. In fact, it has been observed that exercise can induce significant and measurable immunological changes, involving a transient immune suppression (changes in number and activity of neutrophils, lymphocytes, macrophages, and secretion of cytokines). This is probably the reason why athletes seem to be more prone to upper respiratory viral infections. These infections usually appear after exercise discontinuation (within 3 days) particularly in those athletes practising sports which require a long term effort and resistance. The problem is further complicated by the effect of nutrition, since nutrition regimen itself and dietary supplementation were demonstrated able to interfere with the immune response. In the present article we will review the present knowledge and experimental data concerning the effects of sport on immune system and some of the most important clinical implications.