Marina Mauro

Incidence of anaphylaxis in the emergency department of a general hospital in Milan.

OBJECTIVE To evaluate incidence and causes of anaphylactic reactions in the emergency room (E.R.) of a general hospital in Milan during a 2-year period. METHODS We retrospectively studied the computerized records of patients discharged from an E.R. with a diagnosis of anaphylactic reaction. Anaphylaxis was established on the presence of at least two cutaneous, respiratory, gastrointestinal or cardiovascular system symptoms. RESULTS During 1997 and 1998, out of 38 685 patients referred to the E.R., 13 had severe anaphylaxis with loss of consciousness (LOC) and 127 had anaphylactic symptoms, without LOC. Of the 13 patients with LOC, a possible cause was identified in 12 (five foods, six drugs, one hair dye). In the other 127 patients anaphylaxis was related to foods in 49 cases (38.5%), drugs in 44 (34.6%), unknown causes in 29 (22.8%), hymenoptera stings in two (1.5%), and other causes in three (2.3%). CONCLUSION The incidence of anaphylactic reactions was 0.4% and mainly affected females and atopic subjects. Foods, particularly fruits and vegetables, appeared to be the most important cause; other important causes were non steroidal antiinflammatory drugs and beta-lactam antibiotics.

Birch-Apple Syndrome Treated with Birch Pollen Immunotherapy

Background: The most common pollen-fruit cross-reaction is the birch-apple syndrome. Allergen immunotherapy (IT) is clearly effective for birch allergy, but its efficacy on apple allergy is controversial. We performed a randomized study on patients with birch-apple syndrome to evaluate the outcome of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). Methods: Forty patients underwent IT with a birch extract (Staloral; Stallergenes, Antony, France), 20 by SCIT and 20 by SLIT. After 1 year of treatment, 15 patients (8 for SCIT and 7 for SLIT) accepted to undergo an oral apple challenge. Measurements of specific IgE to Bet v 1 and Mal d 1 and related allergens Api g 1 and Dau c 1 were obtained in 10 patients, at baseline and after IT. Results: Two of 8 SCIT-treated patients (25%) and 1 of 7 SLIT-treated patients (14.2%) developed complete tolerance to apple. In the remaining patients, an increase in the provocative dose was found in 3 of the SCIT-treated (37.5%) and 2 of the SLIT-treated patients (28.6%). Changes in the levels of specific IgE to Mal d 1 were unrelated to clinical results. Conclusions: These findings suggest that different doses of birch extract may be needed in different patients to improve the associated apple allergy and that a finer diagnostic work-up in selecting patients with birch-apple syndrome who are candidates to respond to birch pollen IT also concerning apple allergy is required.

Patient's compliance with allergen immunotherapy.

Background Allergen immunotherapy (IT) is an effective treatment of respiratory allergy, but requires strict rules of performance. This makes compliance particularly relevant, but thus far only a few studies have investigated this issue. Methods We reviewed all the available articles on compliance and adherence with IT in its different forms of administration, ie, subcutaneous (SCIT), sublingual (SLIT), and local nasal (LNIT). Results Early studies, when only SCIT was available, reported a low compliance, ranging from 45% to 60%, but the demanding schedules used, with very frequent injections, accounted for this outcome, as shown by patients’ recognition of inconvenience as the major cause of noncompliance. The most recent studies reported a good compliance, estimated in 75% to 90%, to both SCIT and SLIT, inconvenience remaining the major cause of noncompliance, followed by cost of the treatment. The only study addressing LNIT found a very poor compliance (27%), the major cause being the side effects, with repeated nasal reactions to the allergen extract. Conclusions Adequate education of patients and optimization of administration schedules, with fine balancing between dose effectiveness and cost, are the factors most likely to achieve further improvement of compliance with IT.

Hymenoptera stings in conscripts

T CLINICAL Weight of Hymenoptera venom allergy can be assessed by evaluating both its mortality rate and prevalence in the general population. Studies have suggested a mortality rate ranging from 0.09 to 0.45 cases per million of inhabitants per year (1). The prevalence of systemic reactions to Hymenoptera stings ranges between 0.3 and 3.3% (1-4). In Europe, a study in France (2) More than half of the reported prevalences Italian male population ^^ 0-9-3.3% m three difterent surveys; is slung before 20 years studies in Switzerland

Safety of hymenoptera venom immunotherapy: a systematic review

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.

Omalizumab, an anti-immunoglobulin E antibody: state of the art

A large number of trials show that the anti-immunoglobulin (Ig) E antibody omalizumab is very effective in patients with severe allergic asthma. This is acknowledged in consensus documents. The drug also has a good safety profile and a pharmacoeconomic advantage due to a reduction in the number of hospitalizations for asthma attacks. In recent years, some studies have shown that omalizumab is effective also in nonallergic asthma. Effects on the complex signaling mechanisms leading to activation of effector cells and to mediator release may account for this outcome. Indeed, omalizumab has been reported to be effective in a number of IgE-mediated and non-IgE-mediated disorders. Concerning the former, clinical efficacy has been observed in rhinitis, allergic bronchopulmonary aspergillosis, latex allergy, atopic dermatitis, allergic urticaria, and anaphylaxis. In addition, omalizumab has been demonstrated to be able to prevent systemic reactions to allergen immunotherapy, thus enabling completion of treatment in patients who otherwise would have to stop it. Concerning non-IgE-mediated disorders, omalizumab has been reported to be effective in nasal polyposis, autoimmune urticaria, chronic idiopathic urticaria, physical urticaria, idiopathic angioedema, and mastocytosis. Current indications for treatment with omalizumab are confined to severe allergic asthma. Consequently, any other prescription can only be off-label. However, it is reasonable to expect that the use of omalizumab will be approved for particularly important indications, such as anaphylaxis, in the near future.

Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy

BACKGROUND Venom immunotherapy is an effective method for the treatment of Hymenoptera venom allergy. Different extracts and treatment schedules are available. OBJECTIVE To compare the safety and efficacy of immunotherapy in 3 cohorts of patients sensitized to Vespula species. METHODS In this open study, 43 patients were treated with a subcutaneous aqueous extract for induction and maintenance (AA), 34 with a subcutaneous depot extract for induction and maintenance (DD), and 29 with subcutaneous aqueous and subcutaneous depot extracts for induction and maintenance, respectively (AD). Cluster schedules were followed to reach maintenance, and adverse effects during treatment and after naturally occurring stings were recorded. RESULTS Depot immunotherapy was better tolerated mainly owing to the lower frequency of local adverse effects in the induction phase (5.9% vs 42.5% and 1.3% vs 5.1% on a per patient and per dose basis, respectively; P < .001 for both) and for effects occurring within 60 minutes after vaccination (2.9% vs 19.2% and 0.2% vs 2.8% on a per patient and per dose basis; P = .03 and P < .001, respectively). Furthermore, 19 of 20 AA, 9 of 9 AD, and 10 of 10 DD patients who were restung experienced only minor local effects. CONCLUSIONS Venom immunotherapy is efficacious. Although there was no decrease in systemic reactions, depot immunotherapy to Vespula venom induced fewer early local adverse effects. Patients undergoing an induction phase with an aqueous extract can benefit from switching to a depot extract during maintenance. Increasing the flexibility of the immunization schedules may improve compliance with this potentially lifesaving treatment.

A Pitfall to Avoid When Using an Allergen Microarray: The Incidental Detection of IgE to Unexpected Allergens

The introduction of new laboratory techniques to detect specific IgE antibodies against single allergen molecules rather than whole extracts represents a significant advance in allergy diagnostics. The advantages of such component-resolved diagnosis can be summarized as follows: (1) the ability to identify the truly responsible allergens in polysensitized patients, whether they be genuine (causing specific sensitization to their corresponding allergen source) or primary (the original sensitizing molecule); (2) distinguishing these allergens from simply cross-reactive components; (3) improving the appropriateness of the prescribed specific immunotherapy; and (4) identifying a risk profile for food allergens. Component-resolved diagnosis is performed using either a singleplex (1 assay per sample) platform or a multiplex (multiple assays per sample) platform. Using an immuno solid-phase allergen chip microarray that falls into the latter category--it currently tests sensitivity to 112 allergens--may lead to a pitfall: detecting IgE to unexpected allergens, such as Hymenoptera venom. In fact, testing insect venom sensitivity in individuals with no history of reactions to stings is contrary to current guidelines and presents the physician with the dilemma of how to manage this information; moreover, this may become a legal issue. Based on what is currently known about venom allergy, it remains likely that a positive sensitization test result will have no clinical significance, but the possibility of reacting to a future sting cannot be completely ruled out. Because this problem has not been previously encountered using the more common allergy tests, no indications are currently available on how to effectively manage these cases.

Effects of Different Up-Dosing Regimens for Hymenoptera Venom Immunotherapy on Serum CTLA-4 and IL-10

Background Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) is involved in the activation pathways of T lymphocytes. It has been shown that the circulating form of CTLA-4 is elevated in patients with hymenoptera allergy and can be down regulated by immunotherapy. Objective to assess the effects on CTLA-4 of venom immunotherapy, given with different induction protocols: conventional (6 weeks), rush (3 days) or ultra rush (1 day). Methods Sera from patients with hymenoptera allergy were collected at baseline and at the end of the induction phase. CTLA-4 and IL-10 were assayed in the same samples. A subset of patients were assayed also after 12 months of VIT maintenance. Results Ninety-four patients were studied. Of them, 50 underwent the conventional induction, 20 the rush and 24 the ultra-rush. Soluble CTLA-4 was detectable in all patients at baseline, and significantly decreased at the end of the induction, irrespective of its duration. Of note, a significant decrease of sCTLA-4 could be seen already at 24 hours. In parallel, IL-10 significantly increased at the end of the induction. At 12 months, sCTLA-4 remained low, whereas IL-10 returned to the baseline values. Conclusions Serum CTLA4 is an early marker of the immunological effects of venom immunotherapy, and its changes persist after one year of maintenance treatment.

New Applications for Sublingual Immunotherapy in Allergy

Specific immunotherapy is the only treatment targeting the causes, and not only the symptoms, of allergic diseases. Sublingual immunotherapy (SLIT) was introduced and developed to solve the problem of the adverse reactions, uncommon but possibly severe and rarely fatal, to the traditional subcutaneous immunotherapy (SCIT). The evidence of SLIT efficacy concerns rhinitis and asthma caused by sensitization to pollens and to house dust mites, but there are increasing data suggesting that SLIT could be applied in forms of allergy hardly feasible for SCIT because of its poor safety (this is true for food allergy and latex allergy) or could be considered for new applications, such as atopic dermatitis or bakers asthma. In particular, there are placebo-controlled trials indicating good efficacy and safety of SLIT in patients allergic to latex and to foods and in children with atopic dermatitis, that indicate SLIT as a real treatment option in such clinical entities. This article also discusses some patent related to the field.