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Background: Epicutaneous immunotherapy (EPIT) is a new way of allergen administration that has a high rate of adherence and safety. The aim of this manuscript is to review clinical trials on EPIT for respiratory and food allergies published in the last 10 years, taking into account how different variables (i.e., dose, patch application duration, skin preparation, and efficacy and safety evaluation) have influenced study results., Main Body: From a review of the literature, we identified eight placebo-controlled, double-blind trials conducted on children and adults, including four studies on grass pollen rhino-conjunctivitis, one on cow's milk allergy and three on peanut allergy. Different methods for skin pre-treatment, such as skin abrasion and tape stripping or stratum corneous hydration by an occlusive system, different endpoints and cumulative allergen doses, and different durations of patch application and tape stripping, were used in the rhino-conjunctivitis studies. A visual analogue system was used for the efficacy evaluation. Several local skin reactions (eczema) and some systemic adverse reactions were reported at higher rates in the active group compared to placebo in one study, but this was not shown by other authors. Local eczema reactions were correlated to the times for applying the tape stripping, while systemic side effects were correlated to the deepness of scraping. In the food allergy trials, differences in the food challenge thresholds, endpoints and allergen sites of the cutaneous patch application influenced the study results. A slight dose-dependent efficacy was found in the peanut allergy studies, which was confirmed by a more significant increase in the following progressive open study. Few adverse events and high adherence in all of the food allergen trials were reported., Conclusions: Overall, the EPIT study results, even if they were affected by great heterogeneity among the methodologies applied, have shown not only the high safety and adherence with this kind of immunotherapy but also suggested the possibility for obtaining definitive evidence of the efficacy of EPIT, especially for food allergies.

Introduction: The efficacy of venom immunotherapy (VIT) in patients with insect sting allergy is not questioned. However, its safety, especially when honeybee is used, is a matter of concern., Areas Covered: A systematic review of the literature on VIT was done, with both aqueous and depot extracts, to compare the frequency of systemic reactions to honeybee and vespid venoms. A Medline search was performed using the keywords 'venom immunotherapy', 'safety' and 'tolerability'. The articles obtained were analyzed regarding the total number of patients treated with either honeybee or vespid VIT, the number and severity of systemic reactions during therapy, the type of extract used (aqueous or depot) and the administration regimen., Expert Opinion: The incidence of systemic reactions to VIT was 25.1% for honeybee venom and 5.8% for vespid venom (p < 0.0001), while it was similar with aqueous and depot extracts in the whole population of patients. This confirms that during VIT systemic reactions are significantly more frequent with honeybee venom compared with vespid venom, while there are no significant overall differences in systemic reactions between aqueous and depot extracts.

Sublingual immunotherapy (SLIT) is an alternate route of administration of allergen-specific immunotherapy with an improved safety profile; to clarify the immune mechanisms elicited by this therapy, we analyzed the clinical and immunologic effects of SLIT in patients with a clinical history of ragweed sensitization. To analyze possible difference among immunotherapeutic protocols, we also compared patients receiving preseasonal, seasonal, or prolonged sublingual therapy (≥ 3 y); patients receiving symptomatic therapy alone were enrolled as well in the study. Clinical and immunological parameters were measured twice in and out of the pollination period. Clinical benefits, as measured by the visual analog scale for symptoms and for use of drugs, were evident in all three groups of individuals receiving immunotherapy, but were significantly better in patients undergoing prolonged SLIT. Immunologically, SLIT resulted in increased IL-10 production, programmed cell death ligand 1 expression, and concentration of allergen-specific IgG4, as well as in the reduction of CD80 and CD86 expression and IL-4 production. SLIT, thus, is associated with modulation of programmed cell death ligand 1 expression and IL-10 synthesis and favors the production of allergen-specific IgG4. These effects are evident from the first pollen season, independently from therapeutic regimen (preseasonal or seasonal) even if a prolonged treatment is necessary to obtain full clinical efficacy. A more detailed understanding of the interaction of allergen and APCs within the oral mucosa will allow improved targeting of allergy vaccine.

Background: Grass pollen is a worldwide cause of respiratory allergy. Identifying the causative species is essential, for example for choosing the appropriate immunotherapy, because not all grass allergens are totally cross-reacting, and the pollen calendars provide only a gross estimate. Phenologic analyses allow identification of the pollen release for each individual grass., Objectives: To assess, using phenologic analyses, the true flowering periods of grasses and to compare the data with the standard pollen calendar., Methods: Phenologic analyses were performed of the following grasses: black grass, sweet vernal grass, common wild oat, barren brome, cocksfoot, tall fescue, Yorkshire fog, ryegrass, Timothy grass, bulbous meadow-grass, Kentucky bluegrass, and Bermuda grass. Sampling was performed every 10 days, starting in April 2009, at 50 stations distributed across Italy. The flowering phase was assessed using a stereomicroscopy-based method for the detection of spreading stamens. The official pollen calendar was used for comparison., Results: Relevant differences were found between grass pollen count and effective flowering of the grass species. Only some species contributed to the pollen peak, and a relevant pollen load for other species was also present out of the peak. Important Pooideae, such as Timothy grass, were not present during the pollen peak in northern and central Italy, and the same occurred with Bermuda grass., Conclusions: The various species of grasses release their pollen grains at different times during the pollen season, and this information is missing with pollen calendars. This may have a relevant effect on the choice of an appropriate immunotherapy., (Copyright © 2010 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Grass pollen is a very common cause of allergic rhinitis and asthma. The only treatment targeting the underlying causes of allergy is immunotherapy (IT). Sublingual immunotherapy (SLIT) has been introduced to solve the problem of systemic reactions to subcutaneous IT (SCIT). This article evaluates the characteristics of the allergen extract, Staloral, in terms of practical administration, effectiveness, safety, and mechanism of action. Efficacy data were obtained from double-blind, placebo-controlled studies using Staloral in patients sensitized to grass pollen, while practical administration, cost-effectiveness, and mechanism of action data were provided by well designed studies. The efficacy and safety of Staloral, as demonstrated by review of published studies which used doses up to 1125 times those administered with SCIT, shows that this allergen extract has optimal characteristics for treating patients with seasonal allergies due to grass pollens. The main mechanism of action is the interaction between dendritic cells of the oral mucosa and the subsequent tolerance induced in T-cells.

Background: There is ample evidence to support the efficacy of sublingual immunotherapy (SLIT) on allergic rhinitis, while there is less solid data regarding asthma. We evaluated the effects of a high dose birch SLIT on birch-induced rhinitis and asthma in a controlled study., Methods: This double-blind, placebo-controlled, randomised, single centre trial on SLIT with birch pollen allergen extract (Stallergenes, Antony, France) included 24 patients presenting severe rhinitis and slight to moderate asthma, 14 actively and 10 placebo treated. SLIT was performed by a pre-coseasonal protocol, and was repeated for 2 years. The study plan included a selection visit, a visit at the start of the first and the second treatment cycle, a follow-up visit after 1-3 months from the start of each cycle, and a final visit at the end of each yearly cycle., Results: A significant decrease (p < 0.05) in rhinorrhoea and nasal obstruction occurred in actively treated patients. The median number of days with asthma at visit 3 was 10 (0-27) in the active (SLIT) group and 13 (0-29) in the placebo group. The median number of days with asthma at visit 6 was 2 (0-6) in the SLIT group and 7 (0-15) in the placebo group (p < 0.05 between groups). A stepdown of asthma occurred in 77% of actively treated vs. none of placebo treated patients (p = 0.05). No severe adverse events were observed., Conclusions: This pilot study suggests that SLIT with high dose birch extract may be able to step down seasonal pollen-induced asthma after prolonged treatment.

Background: The worldwide increased prevalence of allergic diseases, and especially of respiratory allergy, is paralleled by increased health costs. This requires consideration of the cost to efficacy ratio of the available treatment to identify the optimal choice., Objective: To compare the different economic relevance, over a long evaluation time, of symptomatic pharmacologic therapy and sublingual immunotherapy (SLIT) in patients with allergic asthma., Methods: Seventy patients with perennial allergic asthma, sensitized to dust mites, were enrolled; 50 of these patients were treated with SLIT against house dust mites and 20 were treated with symptomatic drugs. The patients were evaluated for 2 years after discontinuing immunotherapy, which was performed for 3 years, to obtain a more complete follow-up. Symptom scores, medication scores, and all other direct medical costs were evaluated with a specific questionnaire., Results: Patients treated with SLIT plus drugs had a higher mean annual cost in the first year of SLIT treatment compared with patients only receiving drug treatment, but the mean annual cost became significantly lower since the end of SLIT both in the whole population and in the subgroups defined by disease severity., Conclusion: The economic advantage measured alongside this prospective observational study was long lasting and still present at the fifth year of the follow-up (2 years after discontinuing SLIT) and could positively be related to the persistent good clinical control of patients.

Background: Specific immunotherapy (IT) is an effective treatment for rhinitis and asthma caused by aeroallergens sensitization. Sublingual IT (SLIT) was introduced to solve the problem of systemic reactions to subcutaneous IT (SCIT) and developed to represent an actual treatment option. It is now generally accepted that allergen doses much higher than those administered by SCIT must be used to achieve clinical efficacy on allergic symptoms., Objective: To evaluate the characteristics of Staloral, an allergen extract produced by Stallergenes (Antony, France) in terms of practical administration, efficacy, safety and mechanism of action., Methods: Data were obtained from 20 double-blind, placebo-controlled studies using Staloral in patients sensitized to pollens and house-dust mites, and also from open studies concerning practical administration and the mechanism of action., Results/conclusion: Efficacy and safety of Staloral, as demonstrated by the revision of the studies, which used doses up to 1125 times those administered with SCIT, are very satisfactory and confer to this allergen extract optimal characteristics for treating patients with seasonal allergies due to pollens or with perennial symptoms induced by dust mites. The main mechanism of action is the interaction with dendritic cells of the oral mucosa and the subsequent tolerance induced in T cells.

Purpose of Review: To analyse and discuss the growing body of evidence on the economic advantages offered by immunotherapy for allergic rhinitis and asthma, in the various perspectives (society, national healthcare system, patients, etc) and according to the various types of standardized economic evaluations., Recent Findings: This review shows that the economic studies of allergic rhinitis and asthma focus on three main research areas: studies aimed at determining the cost of illness and studies focused either on a simple cost comparison amongst available therapeutic alternatives, or directly comparing alternatives using full economic evaluations (cost-effectiveness, cost-utility measures, etc)., Summary: Studies exploring the full cost of allergic rhinitis and asthma are still lacking; on the contrary, studies on immunotherapy (in its many administration forms, subcutaneous, sublingual, tablet, etc) in comparison with standard pharmaceutical treatment, have shown that immunotherapy may be very beneficial to the healthcare systems, in that either it could bring more clinical outcome at a reduced cost, versus standard therapy alone, or it could bring extra benefit at a very acceptable extra cost. This is even more correct under the societal perspective, that is, when indirect costs of lost productivity are considered and included in the economic analysis.

Background: Few data are available on the pharmacoeconomic aspects of immunotherapy., Objective: To evaluate, from the health care system and societal perspectives, the costs and consequences of sublingual immunotherapy (SLIT) added to pharmacotherapy compared with drugs alone for respiratory allergy., Methods: This study compared costs, clinical outcomes, and cost-effectiveness ratios of 2 strategies in the management of allergic rhinitis and asthma, namely, SLIT associated with pharmacotherapy and pharmacotherapy alone (no SLIT). A decision tree was developed and populated with epidemiologic and resource utilization data concerning approximately 2,200 patients. Direct costs included visits, tests, pharmacotherapy, immunotherapy, and hospitalizations. Indirect costs and out-of-pocket drugs were also included. Outcome was calculated as the number of improved patients and asthma cases avoided at 6 years. Sensitivity analysis was performed by varying costs and epidemiologic data., Results: SLIT improved the symptoms of 399 of 1,000 patients and prevented asthma in 229 of 1,000 patients compared with drugs alone. For SLIT added to pharmacotherapy and pharmacotherapy alone, the direct cost per patient at more than 6 years was Euro2,400 and Euro3,026, whereas the indirect cost was Euro1,913 and Euro3,400., Conclusion: From both perspectives and for both effectiveness end points, SLIT is less expensive and more effective than pharmacotherapy alone.

A panel of Italian allergists gathered to discuss the issue concerning the management of polysensitized patients. The main conclusions were as follows: polysensitization is a relevant clinical characteristic as it affects about 70–80% of the global allergic population; the diagnostic pathway needs the use of an adequate and thorough methodology, based on the demonstration of consistency between history and documented sensitization; polysensitization and polyallergy are not synonymous: true allergy should always be demonstrated; polysensitization does not constitute a limitation to allergen immunotherapy prescription, as 1–2 allergen extracts could be effective in polysensitized patients; the allergen immunotherapy product characteristics should include the following: high efficacy and optimal safety profile, standardized production, and documented presence and titration of the major allergen. [ABSTRACT FROM AUTHOR]

The molecular allergy technique, currently defined as component-resolved diagnosis, significantly improved the diagnosis of allergy, allowing for differentiation between molecules actually responsible for clinical symptoms (genuine sensitizers) and those simply cross-reacting or shared by several sources (panallergens), thus influencing the appropriate management of a patient's allergy. This also concerns allergen immunotherapy (AIT), which may be prescribed more precisely based on the component-resolved diagnosis results. However, the advance in diagnosis needs to be mirrored in AIT. According to consensus documents and to expectations of specialists, therapy should be based on standardized extracts containing measured amounts of the clinically relevant molecules, ie, the major allergens. The new generation of extracts for sublingual immunotherapy fulfills these requirements and are thus defined as biomolecular (BM). BM refers to natural extracts with a defined content of major allergens in micrograms. All Staloral BM products are indicated for the treatment of allergic rhinitis with or without asthma. The effectiveness of AIT is related to its ability to modify the immunological response of allergic subjects. The 5-grass and house dust mite extracts were evaluated addressing the T helper 1, T helper 2, and T helper 3 cells by polymerase chain reaction array on mRNA extracted from Waldeyer's ring tissue (adenoids). Sublingual immunotherapy with a defined content of major allergens in micrograms induced a strong downregulation of genes involved in T helper 2 and T helper 1 activation and function, allowing the definition of the immunologic effect as "bio-homeostatic". This clinical and immunological model must be implemented with respect to other allergens, thus expanding the application of a treatment with a unique disease-modifying capacity. [ABSTRACT FROM AUTHOR]

The efficacy of allergen immunotherapy (AIT) is well supported by evidence from trials and meta-analyses. However, its actual performance in daily practice may be diminished by several pitfalls, including inappropriate patient selection, and, especially, the use of allergen extracts of insufficient quality. We performed a survey, the Allergen Immunotherapy Decision Analysis, to evaluate which criteria specialists use to choose products for sublingual immunotherapy (SLIT) in adult patients suffering from allergic respiratory disease. We surveyed a total of 169 Italian allergists randomly chosen from a database belonging to a market research company (Lexis Ricerche, Milan, Italy). The survey was performed between October and November 2012 under the aegis of the European Center for Allergy Research Foundation and consisted of a questionnaire-based electronic survey prepared by a scientific board of 12 AIT experts. The questionnaire comprised two parts, the first of which contained 14 items to be ranked by each participant according to the importance assigned to each when choosing SLIT products. The physicians' rankings assigned major importance to the level of evidence-based validation of efficacy and safety, standardization of the product, efficacy based on personal experience, and defined content(s) of the major allergen(s) in micrograms. The results of this survey show that Italian allergists rank the quality-related characteristics of allergen extracts as highly important when choosing products for AIT. The allergists' preference for high-quality products should be addressed by regulatory agencies and by producers. [ABSTRACT FROM AUTHOR]

Background: Allergen immunotherapy (AIT) is aimed at modifying the immune response to a causative allergen, thereby reducing clinical symptoms and symptomatic medication intake and improving quality of life. Long-term AIT research has led to the development of 5-grass pollen tablets, currently indicated for the treatment of grass pollen-induced allergic rhinitis (AR). Methods: A post-hoc analysis was conducted using the Average Adjusted Symptom Score (AAdSS) to compare the effect of treatment of AR with 5-grass pollen tablets versus placebo treatment. Using the results of the VO34.04 and VO53.06 trials and economic data, cost-effectiveness analysis of 5-grass pollen tablet treatment was performed from the Italian third-party payer perspective with cost data derived from a study of 2008 updated to 2011. Also a societal perspective was considered by using the costs related to the losses of productivity by following the human capital approach. Using the results of the analysis, the estimated receiver-operating characteristic curve was plotted to evaluate medication effectiveness in terms of quality-adjusted life years (QALYs) and a decision tree constructed to model the possible outcomes and costs for adults and paediatric patients with a low, medium, and high AAdSS. Finally, probabilistic sensitivity analysis was conducted to test the robustness of the results as well as their consistency at an assumed cost-effectiveness threshold of € 30,000/QALY. Results: The results indicate that compared to the placebo, the 5-grass pollen tablet treatment provides a benefit of 0.127 QALYs in medium AAdSS patients and of 0.143 QALYs in high AAdSS patients. The 5-grass pollen tablet treatment was found to cost € 1,024/QALY for patients with a medium AAdSS and € 1,035/QALY for patients with a high AAdSS. Of all the simulations performed in the probabilistic sensitivity analysis, 99 % indicated that the incremental cost-effectiveness ratio of the 5-grass pollen tablet treatment was below the threshold of € 30,000/QALY in patients with medium and high AAdSS, whereas it was found to be dominated in 67 % of simulations related to patients with low AAdSS. Conclusion: The 5-grass pollen tablet is a cost-effective treatment for adult AR patients with a medium or high AAdSS. This finding should be carefully considered when deciding the management strategy for these patients. [ABSTRACT FROM AUTHOR]

Background: The introduction of component-resolved diagnosis was a great advance in diagnosis of allergy. In particular, molecular allergy techniques allowed investigation of the association between given molecular profiles and clinical expression of allergy. We evaluated the possible correlation between the level of specific IgE (sIgE) to single components of Phleum pratense and clinical issues such as the severity of allergic rhinitis (AR) and the presence or absence of asthma. Methods: The study included 140 patients with rhinitis and/or asthma caused by sensitization to grass pollen. sIgE to Phl p 1, Phl p 5, Phl p 7, and Phl p 12 from Phleum pratense were measured, and the correlation between the stage of AR according to Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines and the presence of asthma was studied by multivariate logistic regression in terms of sIgE and ARIA stage, while univariate logistic regression was used for IgE and a dichotomic classification of asthma as present or absent. Results: Ten patients had intermittent AR, 48 had mild persistent AR, and 82 had severe persistent AR. Asthma was present in 86 patients and absent in 54. A significant correlation was found between severe persistent AR and presence of asthma (p < 0.01). The only significant correlation between clinical data and sIgE values was that of low values of sIgE to Phl p 5 and absence of asthma (p < 0.01). Conclusions: This preliminary finding suggests that low values of sIgE to Phl p 5 are correlated with the absence of asthma in patients with grass-pollen induced allergy. The data, provided they are confirmed by further studies, could be useful when selecting patients who are candidates for allergen immunotherapy, since a higher risk of asthma could be used as a selection criterion for using this approach. [ABSTRACT FROM AUTHOR]

Background: Grass pollen is a major cause of respiratory allergy worldwide and contain a number of allergens, some of theme (Phl p 1, Phl p 2, Phl p 5, and Phl 6 from Phleum pratense, and their homologous in other grasses) are known as major allergens. The administration of grass pollen extracts by immunotherapy generally induces an initial rise in specific immunoglobulin E (sIgE) production followed by a progressive decline during the treatment. Some studies reported that immunotherapy is able to induce a de novo sensitisation to allergen component previously unrecognized. Methods: We investigated in 30 children (19 males and 11 females, mean age 11.3 years), 19 treated with sublingual immunotherapy (SLIT) by a 5-grass extract and 11 untreated, the sIgE and sIgG4 response to the different allergen components. Results: Significant increases (p<0.001) were detected for Phl p 1, Phl p 2, Phl p 5, and Phl p 6, while sIgE levels induced in response to Phl p 7 and Phl p 12 were low or absent at baseline and unchanged following SLIT treatment; no new sensitisation was detected. As to IgG4, significant increases were found for Phl p2 and Phl p 5, while the increase for Phl p 12 was not significant. In the control group, no significant increase in sIgE for any single allergen component was found. Conclusions: These findings confirm that the initial phase of SLIT with a grass pollen extract enhances the sIgE synthesis and show that the sIgE response concerns the same allergen components which induce IgE reactivity during natural exposure. [ABSTRACT FROM AUTHOR]

Allergen-specific immunotherapy is aimed at modifying the natural history of allergy by inducing tolerance to the causative allergen. In its traditional, subcutaneous form, immunotherapy has complete evidence of efficacy in allergic asthma. However, subcutaneous immunotherapy (SCIT) has a major flaw in side effects, and especially in possible anaphylactic reactions, and this prompted the search for safer ways of administration of allergen extracts. Sublingual immunotherapy (SLIT) has met such need while maintaining a clinical efficacy comparable to SCIT. In fact, the safety profile, as outlined by a systematic revision of the available literature, was substantially free from serious systemic reactions. A number of meta-analyses clearly showed that SLIT is effective in allergic rhinitis by significantly reducing the clinical symptoms and the use of anti-allergic drugs, while the efficacy in allergic asthma is still debated, with some meta-analyses showing clear effectiveness but other giving contrasting results. Besides the efficacy on symptoms, the preventive activity and the cost-effectiveness are important outcomes of SLIT in asthma. The needs to meet include more data on efficacy in house dust mite asthma, optimal techniques of administration and, as previously done with SCIT, introduction of adjuvants able to enhance the immunologic response and use of recombinant allergens. [ABSTRACT FROM AUTHOR]

Polysensitization is quite frequent in allergic children and may cause difficulties for the allergist in prescribing allergen-specific immunotherapy. This study aimed at evaluating the clinical effectiveness of 1 year of sublingual immunotherapy (SLIT) in a cohort of Italian allergic children with polysensitization. This open study was performed on 51 polysensitized children (34 boys; mean age, 11.8 years; range, 5.2-17.7 years) with allergic rhinitis and/or mild to moderate asthma. All of them were treated with SLIT for 1 year. The kind and the number of prescribed allergen extracts, the type of diagnosis, the severity of symptoms, and the use of drugs were evaluated at baseline and after 1 year. The adverse events to SLIT were also evaluated. Forty-two children were treated with a single extract, four with two different extracts and three with a mix of allergens. SLIT treatment induced a significant reduction in the number of sensitizations (p = 0.018); significant improvement of allergic rhinitis classification and severity; significant reduction of ocular, nasal, and bronchial symptoms (p < 0.01 for all); and drugs use (p < 0.01 for all drugs). No systemic reactions to SLIT were observed. This open study provides evidence that polysensitization is not an obstacle for prescribing SLIT in polysensitized children. Indeed, SLIT efficacy on clinical parameters is significant after 1 year and the therapy is safe. [ABSTRACT FROM AUTHOR]

Specific immunotherapy is the only treatment able to act on the causes and not only on the symptoms of respiratory allergy. Sublingual immunotherapy (SLIT) was introduced as an option to subcutaneous immunotherapy (SCIT), the clinical effectiveness of which is partly counterbalanced by the issue of adverse systemic reactions, which occur at a frequency of about 0.2% of injections and 2-5% of the patients and may also be life-threatening. A large number of trials, globally evaluated by several meta-analyses, demonstrated that SLIT is an effective and safe treatment for allergic rhinitis and allergic asthma, severe reactions being extremely rare. The application of SLIT is favored by a good compliance, higher than that reported for SCIT, in which the injections are a major factor for noncompliance because of inconvenience, and by its cost-effectiveness. In fact, a number of studies showed that SLIT may be very beneficial to the healthcare system, especially when its effectiveness persists after treatment withdrawal because of the induced immunologic changes. [ABSTRACT FROM AUTHOR]

Background: Some studies reported the possible induction of food allergy, caused by neo-sensitization to cross-reacting allergens, during immunotherapy with aeroallergens, while other studies ruled out such possibility. Objectives: The aim of this study was to evaluate the development of neo-sensitization to Pen a 1 (tropomyosin) as well as the appearance of reactions after ingestion of foods containing tropomyosin as a consequence of sublingual mite immunization. Materials and methods: Specific IgE to Tropomyosin (rPen a 1) before and after mite sublingual immunotherapy in 134 subjects were measured. IgE-specific antibodies for mite extract and recombinant allergen Pen a 1 were evaluated using the immunoenzymatic CAP system (Phadia Diagnostics, Milan, Italy). Results: All patients had rPen a 1 IgE negative results before and after mite SLIT and did not show positive shrimp extract skin reactivity and serological rPen a 1 IgE conversion after treatment. More important, no patient showed systemic reactions to crustacean ingestion. Conclusions: Patients did not show neo-sensitization to tropomyosin, a component of the extract (namely mite group 10) administered. An assessment of a patient's possible pre-existing sensitisation to tropomyosin by skin test and/or specific IgE prior to start mite extract immunotherapy is recommended. [ABSTRACT FROM AUTHOR]

Patients throughout Europe are concomitantly exposed to multiple pollens from distinct Pooideae species. Given the overlap in pollination calendars and similar grain morphology, it is not possible to identify which grass species are present in the environment from pollen counts. Furthermore, neither serum IgE reactivity nor skin prick testing allow the identification of which grass species are involved in patient sensitisation. Due to their high level of amino acid sequence homology (e.g., >90% for group 1, 55–80% for group 5), significant cross-immunogenicity is observed between allergens from Pooideae pollens. Nevertheless, pollen allergens also contain species-specific T or B cell epitopes, and substantial quantitative differences exist in allergen (e.g., groups 1 and 5) composition between pollens from distinct grass species. In this context, a mixture of pollens from common and well-characterised Pooideae such as Anthoxanthum odoratum, Dactylis glomerata, Lolium perenne, Phleum pratense and Poa pratensis is suitable for immunotherapy purposes because (1) it has been validated, both in terms of safety and efficacy, by established clinical practice; (2) it reflects natural exposure and sensitisation conditions; (3) it ensures a consistent and well-balanced composition of critical allergens, thus extending the repertoire of T and B cell epitopes present in the vaccine. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Sublingual immunotherapy (SLIT) is an effective and safe treatment for respiratory allergy, and its mechanism of action currently is investigated with increasing attention. Studies of pharmacokinetics showed that allergen extracts administered via the sublingual route are not directly absorbed by the oral mucosa but are long retained at mucosal level, where the allergen molecules are captured by dendritic cells and, following their migration in the draining lymph nodes, presented to T cells. This seems to be the pivotal factor underlying the mechanisms of action of SLIT, at least for the long-term effects, and for the short-term efficacy, observed with ultrarush or coseasonal treatment, a down-regulation of mast cells resulting in hyporeactivity at the peak of the pollen season may be suggested. Regarding the clinically established long-lasting effects, the core mechanism is likely to consist of T regulatory (Treg) cell activation. In particular, Treg cells differentiate from naive T cells after application of soluble antigens to the mucosae, a crucial factor being the tolerogenic function of dendritic cells, and exert a suppressive effect on both Th1 and Th2 responses. Moreover, at least for the type 1 cells (Treg1), a production of IL-10 with consequent down-modulation of the immune response has been reported. Another characteristic of sublingual immunization is the absence of effectors cells, viz., mast cells, basophils, and eosinophils, in the oral mucosa of allergic subjects, which account for the excellent tolerability of SLIT. [ABSTRACT FROM AUTHOR]

Only a few studies analyzed the pharmacoeconomics of allergen immunotherapy compared with drug treatment in subjects with allergic rhinitis and asthma. This study was aimed at evaluating whether allergen immunotherapy has an economic advantage on standard antiallergic drugs in patients with pollen-induced rhinitis and asthma. Thirty patients with rhinitis and asthma caused by Parietaria pollen were included in the study, 20 (11 men and 9 women; mean age, 35.45 ± 10.45 years) were treated with subcutaneous immunotherapy by a Parietaria judaica extract (Alustal, Stallergénes, Antony, France) by a conventional build-up schedule in 12 weeks and a maintenance treatment every 4 weeks for 3 years, and 10 (6 men and 4 women; mean age, 31.90 ± 10.97 years) were treated with antiallergic drugs. Each patient was evaluated before starting the treatment and annually for 6 years in the pollen period of Parietaria by means of nose, eyes, and lung symptom scores, along with drug consumption registered in diary cards. In other specifically designated cards general practitioner's or specialist's visits, the number of desensitizing injections and the number of boxes of antiallergic drugs were registered. A significant difference in favor of immunotherapy plus drug treatment versus drug treatment alone was observed, reaching a cost reduction of ~15% the second year and 48% the third year, with a highly statistical significance that was maintained up to the sixth year, i.e., 3 years after stopping immunotherapy, when an 80% reduction was found. The net saving for each patient at the final evaluation corresponded to €623 ($830)/year. These findings confirm some previous observations in studies from Germany and the United States that subcutaneous immunotherapy has significant economic advantages over antiallergic drug treatment in the long term. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis (AR) is characterized by typical symptoms that are dependent on inflammation. Poly-allergy is a frequent phenomenon. Phenotyping AR represents an up-to-date issue. Objective: The aim of this study was to evaluate whether the number of allergies is able to define different phenotypes in patients with AR. Methods: 83 patients (43 males, mean age 34.7 years) suffering from AR were evaluated. Sensitization, VAS for nasal symptoms perception, and nasal cytology were evaluated. Results: Poly-allergic patients perceived more severe nasal obstruction than mono-allergic ones ( p = 0.0006) as well as they had more frequent sneezing ( p < 0.0001). Moreover, poly-allergic patients had a more intense inflammatory infiltrate, concerning both eosinophils ( p = 0.0005) and mast cells ( p = 0.0001), than mono-allergic patients. Conclusions: The present study demonstrates that the presence of poly-allergy could define a distinct AR phenotype in comparison with mono-allergy. It could be clinically relevant as poly-allergic patients have more intense inflammation and more severe symptoms than mono-allergic ones. [ABSTRACT FROM AUTHOR]

Two letters to the editor are presented in response to the article "Sublingual immunotherapy for the treatment of allergic rhinoconjunctivitis and asthma: a systematic review," published in the 2013 issue and also includes a response by the author regarding the same.

The authors reflect on the selection of the best allergen immunotherapy for patients with mite allergy. Topics discussed include the characterization of the allergic rhinitis and asthma by an Immunoglobulin E (IgE)-dependent reaction, the response of IgE to house dust mites (HDM), and the dependence of the symptoms of HDM allergy on allergic inflammation.