Leonardo Antonicelli

Epidemiology of Hymenoptera allergy.

Purpose of reviewEpidemiology and especially the natural history of Hymenoptera allergy form the background that is essential to improving the clinical management of insect venom allergic patients. This review focuses on the emergence of recent data which could help provide further enlightenment in this field. Recent findingsThe latest data on the extent of the disease, the risk factors for sensitization and for local, systemic and fatal reactions after a hymenoptera sting are reviewed. The emerging problems concerning asymptomatic sensitization, the meaning of constitutively elevated tryptase serum levels and the persisting widespread poor awareness of available therapies in Hymenoptera allergic patients are particularly emphasized. SummaryThe assessment of the risk for systemic reaction in skin-positive subjects with a negative case history, and the suggestion of the baseline serum tryptase level as a risk factor for reaction severity after a sting, are the most important clinical implications of the latest studies. The genetic and environmental factors involved in the persistence of venom specific immunoglobulin E after a sting and the factors which orient towards a systemic or a large local reaction after apparently the same sting remain open questions.

Quantitative assessment of the compliance with once‐daily sublingual immunotherapy in children (EASY Project: Evaluation of A novel SLIT formulation during a Year)

Compliance is a major determinant for allergy treatment, especially in children. Sublingual immunotherapy (SLIT) is self‐managed at home, and no quantitative data on pediatric adherence are available. We studied the compliance in a large real‐life setting. A simplified schedule of SLIT was used, consisting of a 10‐day updosing phase followed by maintenance treatment in monodose containers to be taken daily (SLITOne®). Italian specialists throughout Italy assessed the compliance in children who were newly prescribed SLIT according to guidelines. Parents were contacted with unscheduled telephone interviews at the third and sixth month of therapy and asked to count at that moment the remaining vials. Data from 71 children (38 boys, age range 2–13 yr) were enclosed in the database. Thirty had rhinoconjunctivitis, four asthma and 37 rhinoconjunctivitis + asthma. SLIT was prescribed for: mites in 57 (81%) subjects, grasses in 11 (15%) and 3 (4%) grass + olive mixture. Compliance data were available for all children at 3 months, and for 56 at 6 months. At 3 months, 85% of subjects had a compliance rate >75% (69% of them adhered >90%). At 6 months, 84% had a compliance rate >75% (66% of them adhered >90%). In four cases SLIT was discontinued for economical reasons, and in one case (1.4%) for side effects probably related to therapy. These data obtained in a quite large sample of children and in real‐life confirm that the compliance with SLITOne® is good, despite the therapy managed at home.

Does Sensitization to Foods in Adults Occur Always in the Gut

It is widely accepted that, under normal conditions, the contact between allergens and the immune system via the gut results in immune tolerance. Thus, it is rather surprising that normal adults may become sensitized to foods that they have consumed a number of times without any consequence. However, the medical literature is crowded with reports suggesting that sensitization to food allergens may occur outside the intestinal tract in many instances. The present article reviews and discusses current data suggesting, either directly or indirectly, a possible initiation of food allergy in the respiratory tract or in the skin in the light of recent findings about mechanisms of tolerance and sensitization.

Honeybee venom immunotherapy: certainties and pitfalls

The honeybee is an interesting insect because of the fundamental agricultural role it plays, together with the composition of its venom, which presents new diagnostic and immunotherapeutic challenges. This article examines various aspects of honeybee venom allergy from epidemiology to diagnosis and treatment, with special emphasis on venom immunotherapy (VIT). Honeybee venom allergy represents a risk factor for severe systemic reaction in challenged allergic patients, for the diminished effectiveness of VIT, for more frequent side effects during VIT and relapse after cessation of treatment. Some strategies are available for reducing the risk of honeybee VIT-induced side effects; however, there is considerable room for further improvement in these all-important areas. At the same time, sensitized and allergic beekeepers represent unique populations for epidemiological, venom allergy immunopathogenesis and VIT mechanism studies.

Purified vs. nonpurified venom immunotherapy.

Purpose of reviewAlthough highly effective, venom immunotherapy (VIT) may be responsible for local and systemic allergic reactions. There is a good theoretical basis for believing that purified aqueous and purified aluminium hydroxide adsorbed (so-called depot) extracts, commercially available in Europe, have the potential to reduce the incidence of VITs side effects. The aim of this article is to review the literature on safety and effectiveness of purified preparations as well as compare them with nonpurified extracts. Recent findingsOld and new noncomparative studies reveal good tolerance of purified aqueous and purified depot extracts. In comparative trials purified extracts appear to be better tolerated than nonpurified extracts, whereas depot extracts seem to be safer than the corresponding purified aqueous preparation, especially in the prevention of severe large local reactions. The efficacy of purified aqueous and depot extracts is supported by studies using both sting challenge and in-field stings and is comparable to that of nonpurified preparations. SummaryThe theoretical basis of the safer profile of purified extracts is supported by a number of clinical studies, making the use of purified depot preparations preferable for conventional treatment also by specialists with less experience in managing VIT. In specialized centres purified aqueous extracts may be preferred for faster build-up protocols. However, further prospective controlled studies are needed in order to evaluate the ability of purified extracts to reduce the frequency of severe systemic reactions over the corresponding nonpurified preparation.

Anisakis Allergy Component-Resolved Diagnosis: Clinical and Immunologic Differences between Patients from Italy and Spain

Background:Anisakissimplex is the main organism responsible for the zoonotic disease anisakiasis which follows the ingestion of live larvae present in raw or undercooked marine fish. Clinical features include severe epigastric pain, frequently accompanied by severe allergic reactions. We investigated the prevalence of immunoglobulin E (IgE) specific for 5 Anisakis allergens in Italian patients sensitized or allergic to the parasite. The results were compared with those obtained previously in a similar Spanish population. Patients and Methods: We conducted a descriptive, cross-sectional validation study. Asymptomatic Anisakis-sensitized subjects (15 Italian and 17 Spanish) and Anisakis allergic-patients (42 Italian and 35 Spanish) were studied by ImmunoCAP, Western-blotting with nAni s 4 and dot-blotting with rAni s 1, rAni s 5, rAni s 9 and rAni s 10. Results:Anisakis IgE CAP classes 1 or 2 were associated with a high probability of asymptomatic sensitization (66.7%) while CAP classes 4 or above, were associated with a very high probability of allergy to Anisakis (95.2%). The most frequently detected allergen among Italian and Spanish allergic patients was Ani s 1. All of the Spanish patients versus 76.2% of the Italian patients recognized at least one of the allergens tested. Patients suffering from gastrointestinal symptoms only were significantly more frequent among the Italians whereas the Spanish presented more frequently with urticaria, angioedema or anaphylaxis. Conclusions:Anisakis hypersensitivity shows different immunological patterns in different European countries. Allergen component diagnosis might help us to better understand this complex entity. Anisakis-specific IgE levels may have moderate prognostic significance.

The complex link between severity of asthma and rhinitis in mite allergic patients

AIM The aim of the study was to evaluate the link between the severity of upper and lower airways diseases in mite allergic patients with respiratory allergy. PATIENTS AND METHOD A multicentre, observational, cross-sectional study was carried out in 556 consecutively enrolled mite allergic patients with rhinitis and asthma comorbidity attending a specialist unit. Severity assessment of rhinitis and asthma was evaluated in accordance with ARIA and GINA guidelines. RESULTS Reliable data were available for 518 patients. The distribution of rhinitis severity was: 15.6% mild intermittent rhinitis, 4.4% moderate-severe intermittent rhinitis, 30.3% mild persistent rhinitis and 49.6% moderate persistent rhinitis. The distribution of asthma severity was: 41.3% mild intermittent asthma, 14.3% mild persistent asthma, 19.1% moderate persistent asthma and 25.3% severe persistent asthma. In patients with moderate-severe persistent rhinitis (49.5%) a significant trend (p = 0.005) was found pointing to an increased link with asthma severity. CONCLUSION A link between respective severities of rhinitis and asthma was found in only half of mite allergic patients with rhinitis and asthma.

Honeybee Venom Immunotherapy: A Comparative Study Using Purified and Nonpurified Aqueous Extracts in Patients with Normal Basal Serum Tryptase Concentrations

In this study, we compared a purified aqueous extract and the corresponding nonpurified aqueous preparation under the same build-up protocol in bee venom allergic patients with a normal baseline mast cell tryptase concentration. Eighty patients with a history of a systemic reaction were enrolled for immunotherapy using a 5-day rush protocol. Patients treated with the purified extract and those treated with the non purified aqueous extract who developed a systemic reaction underwent maintenance therapy with the purified aluminium hydroxide adsorbed preparations. Patients treated with the nonpurified aqueous extract who did not experience a systemic reaction during the rush phase underwent the maintenance phase with that extract. Systemic reactions during the build-up phase occurred significantly more often in patients treated with nonpurified aqueous extract than in those treated with the corresponding purified aqueous preparations. During the one-year maintenance phase, no systemic reactions occurred in either of the groups. Neither age nor baseline mast cell tryptase concentration presented a significant correlation with the occurrence of a systemic reaction during the treatment, while the type of extract did. In conclusion, nonpurified aqueous extracts induced more frequent systemic reactions than the purified aqueous preparations, during the same rush protocol. The efficacy seemed to be comparable.

Mast cell diseases and the severity and course of intraoperative anaphylaxis.

a higher probability of developing serum specific IgG to MDI, which could lead to a greater risk of MDI-OA. This study is the first, to our knowledge, to examine genetic susceptibility in MDI-OA using HLA analysis. We suggest that the HLA allele DRB1*0901-DQB1*0303-DPB1*0501 may increase specific IgG sensitization, which could contribute to the development of the MDI-OA phenotype in exposed workers.

Congruence between international guidelines and mite specific immunotherapy prescribing practices

Both rhinitis (ARIA) and asthma (GINA) guidelines recommend allergen-specific immunotherapy (SIT) tailored to the specific levels of severity of each disease. Real world studies evaluating congruence between these recommendations and prescribing practice in the single patient with comorbidity are lacking. An observational polycentric study was carried out in 518 patients recruited from 34 allergy centers throughout Italy. A questionnaire was administered to each consecutive patient over a span of four months. Taking into account guideline recommendations for both diseases, concomitant in the same patient, three subsets resulted: patients not eligible for SIT (11%); patients eligible for SIT for one disease only (60%); patients eligible for SIT for both diseases (29%). SIT was prescribed in 257 (49.6%) subjects. The level of SIT prescription was about 50% in all three groups. Consistent with the ARIA guidelines, a correlation between the prescription of SIT and the severity of rhinitis was documented (r=0.87; p=0.001). An association with asthma severity was found (p=0.02), but the trend was inconsistent with the GINA recommendations. Young age was the most important factor for SIT prescription both in the eligible for one disease and in the eligible for both diseases subset. The tendency towards worsening of symptoms was a factor for SIT in the eligible for one disease subset. In mite allergic patients with rhinitis and asthma comorbidity, the severity of rhinitis and the young age are the most important factors driving the SIT prescription. The congruence of SIT prescription was better for the ARIA than GINA guidelines.