Oral immunotherapy for food allergy

Current management of food allergy involves strict avoidance, education on recognizing and managing allergic reactions, and carrying an adrenaline autoinjector. This approach is burdensome and associated with reduced quality of life. Patients with food allergy would benefit greatly from a treatment that could achieve desensitization or long-term tolerance. Recent studies have shown that oral immunotherapy (OIT) can induce desensitization and modulate allergen-specific immune responses; however, it remains uncertain whether OIT can induce long-term tolerance. Nevertheless, successful desensitization provides a major advance in management by reducing the risk of reaction to low amounts of allergen. Allergic reactions during OIT are common, although severe reactions are less common. Therefore, OIT should be performed in specialist centers under close medical supervision and would ideally be conducted as part of ongoing research studies. OIT holds promise as a novel approach to managing food allergy.     

Oral immunotherapy for food allergy

Food allergy is an increasingly prevalent disorder with potentially life-threatening complications that requires life-altering changes in dietary habits and psychosocial interactions. The standard of care presently includes strict dietary elimination of the implicated allergen and ready access to injectable epinephrine; however, no active, definitive therapeutic options exist for food-allergic patients. Although the detailed immunologic mechanisms underlying the development of food allergy are still being fully defined, food allergy appears to be the direct result of a breakdown in oral tolerance. Thus, current therapeutic approaches to food allergy are focused on modulating the immunologic response to food proteins to promote induction of oral tolerance. In this review, we examine gastrointestinal mucosal immunity and the mechanisms of oral tolerance, as well as the breakdown in oral tolerance that promotes food allergy, and we also explore novel therapeutic interventions for treatment of food allergy.     

Treatment perspectives: immunotherapy with latex

Latex allergy currently constitutes a serious problem because of the severity of its symptoms and the at-risk groups it affects. Since complete avoidance of this substance is practically impossible, in the last few years intense efforts have been made to standardize a latex extract with the aim not only of improving clinical diagnosis but also of being able to offer other therapeutic alternatives, such as specific immunotherapy.Since 1998, reports of immunotherapy with oral (three patients) subcutaneous (one patient) and sublingual latex desensitization (one patient) have been published. In all cases, clinical improvement was evident. In 2000, Laynadier published the first pilot study, a phase IIB multicenter, randomized, double-blind, placebo-controlled trial that evaluated the efficacy and safety of specific immunotherapy with latex in patients with occupational allergy. Twenty health care workers without obvious latex exposure and with latex allergy-induced symptoms of rhinitis and/or asthma were included. Treatment started with a 2-day course of rush immunotherapy in hospital and maintenance therapy was continued for 1 year. Efficacy was assessed by symptom and medication scores and by variation in the conjunctival reactivity threshold. The safety of the extract was also evaluated. In the overall analysis of symptom score, the treated group showed a marked improvement and the medication score was significantly lower in patients in the active treatment group than in the placebo group. Concerning safety, almost half the patients receiving active treatment showed local reactions starting with the first injection and four of the nine patients in this group suffered moderate-to-severe systemic reactions. In view of this first clinical trial, it can be concluded that this treatment is effective but that its tolerance is low.A second clinical trial with the same characteristics and extract is currently underway. Its aim is to validate the previous protocol, confirm the efficacy of specific immunotherapy with latex, improve its safety and, if possible, determine the optimal dose.J. Sastre et al. have recently (Formigal 2002) presented the results of the first double-blind study with latex immunotherapy using an extract standardized by the ALK-Abelló-Espa?a group. The authors included 24 patients with latex sensitization and symptoms of occupational allergy. To diagnose respiratory allergy, an inhalation challenge was performed in a closed 7-m2 chamber and, in case of contact urticaria, glove-wearing and rubbing tests were performed, using a vinyl glove as negative control. Treatment consisted of a first phase of incremental doses for 14 weeks, with 18 injections, followed by maintenance doses for 6 months. Sixteen patients received active treatment and 8 received placebo. Of the 578 doses administered, adverse effects were observed in 41 (7.1 %). There were 21 immediate systemic reactions (5.7 % of the doses) and 10 delayed systemic reactions (2.6 % of the doses). Adverse effects were more frequent in patients with underlying respiratory disease (p < 0.05). After 6 months' treatment, a clear improvement in the cutaneous response index was found in the active treatment group and in the rubbing and glove-wearing tests. The authors conclude that the immunotherapy tested was a high-risk treatment and that the greatest clinical improvement was found in cutaneous symptoms.In conclusion, although effective, latex immunotherapy is currently a high-risk treatment.     

Spermicide condoms linked to latex allergy

The use of the spermicide nonoxynol-9 (N-9) with latex condoms may increase the risk of hypersensitivity to latex. Researchers formally thought that the genital reaction was to the spermicide, not to the latex, but N-9 appears to increase the release of natural rubber latex proteins. Studies are underway to determine whether N-9 is effective against HIV.     

Natural rubber latex allergy and asthma

Allergic responses to natural rubber latex (NRL) continue to be reported. In adults, the major exposure is in the occupational setting, especially in relation to NRL glove use by health care workers. Issues addressed over the past year include improving diagnostic methods for NRL allergy and characterization of NRL allergens relevant to various exposure groups and evaluating strategies for prevention and early detection of NRL allergy. Assessment of in vitro tests show good intertest correlation but lower sensitivity compared with skin test responses. NRL allergens have been further characterized as reported in the past year. Development of recombinant Hev b 3, a major NRL allergen relevant to children with spina bifida, enhances the likelihood for improved diagnostic reagents. Preliminary reports of primary preventive strategies suggest that avoidance of high-protein, powdered gloves in health care facilities can be cost-effective and is associated with a decline in sensitized workers.     

One century of allergen-specific immunotherapy for respiratory allergy

Among the treatments available for respiratory allergy, which include allergen avoidance and pharmacotherapy, specific immunotherapy (SIT) is the only treatment able to not only act on the symptoms of allergy but also act on the causes. SIT is the practice of administering gradually increasing doses of the specific causative allergen to reduce the clinical reactivity of allergic subjects and was introduced one century ago. SIT remained an empirical treatment for more than 40 years, but the first controlled trial in 1954 paved the way for the scientific era. At present, SIT may be administered in two forms: subcutaneous (SCIT) and sublingual immunotherapy (SLIT). A large number of trials, globally analyzed in several meta-analyses, evaluated the efficacy and safety of SCIT and SLIT in allergic rhinitis and asthma. Current available data give solid evidence to the clinical efficacy of both SCIT and SLIT in allergic rhinitis and asthma. Providing the recommended doses and administration schedules are adhered to, the safety and tolerability are very good; however, adverse systemic reactions remain a drawback for SCIT. After one century of use, accumulating evidence surrounds SIT and the central role in the management of respiratory allergy.     

Immediate allergy to latex. 12 cases

Immediate hypersensitivity to latex is now well known. Contact urticaria is the most common manifestation, sometimes associated with rhinitis, asthma or a generalized rash. Atopy and frequent contact with latex favor sensitization. Anaphylactic shock is to be feared in sensitized patients during contact with latex, especially in peroperative situations (latex surgical gloves), as in the 12 cases reported. The shock is unusual in its delayed appearance and its progressive course. Positive skin tests to latex, the presence of specific IgE antibodies and negative skin tests to anesthetics confirm the diagnosis. However, the latex allergen has not yet been identified. Due to the increasing use of protective rubber (gloves, condoms, etc), the frequency of latex sensitization should increase. Systematic screening during history taking will be important before treatment.     

Efficiency of diagnosis of latex allergy by the combined use of three latex materials for prick-tests

The diagnosis of latex allergy is mainly based on prick-tests. In order to improve the efficiency of the diagnosis, a comparative study of three latex materials is carried out in 64 controls and 29 patients allergic to latex = Stallergènes and Allerbio extracts, prepared from crude natural latex, and an ammoniated emulsion of rubber latex (AEL). No adverse reactions are recorded. The specificity is 100% for both extracts, 85% for AEL. Sensitivity is respectively 68%, 63%, 72%. The range of values of the wheal is significantly narrower for Stallergènes extract. 46% of allergic patients are reactive to the three materials. The combined use of three materials reaches an 80% efficiency similar to that of Rast Cap System and the addition of three prick-tests and Rast obtains an efficiency of 93.1%. Using several latex materials could increase the efficiency of the diagnosis, inasmuch as the extracts are generated from natural latex, whereas patients are sensitized to manufactured products originating from ammoniated latex.     

支气管哮喘的特异性免疫治疗

支气管哮喘（简称哮喘）的特异性免疫治疗已在世界卫生组织和世界变态反应学会出版的指导性文件中详细阐述。但从目前国内外的临床研究和应用的情况来看，特异性免疫治疗的作用机制尚不完全清楚，临床应用因受到安全性的限制而未能广泛普及，临床的实际操作流程尚待规范，所以如何能在最大程度上发挥特异性免疫治疗的作用，真正改变患者的过敏状态并保持长期疗效是关键问题。     

Specific immunotherapy in allergic asthma

Asthma is a chronic inflammatory disease of the airways considered as the result of a deregulated immune response, with a pivotal role played the TH2 cytokine phenotype. The treatment of allergic asthma is based on allergen avoidance, pharmacotherapy, allergen-specific immunotherapy, and patient education. Specific immunotherapy is able to normalize the upraised TH2 cytokine phenotype and indicated for patients who have demonstrable evidence of IgE-mediated clinically relevant sensitisation to pollens, house-dust mites and cat or dog allergens. The exposure to the allergens must be related to the appearance of symptoms. Randomised controlled trials in asthma have found that immunotherapy was effective (evidence 1a, strength of recommendation A) in reducing specific and non-specific bronchial hyperreactivity, asthmatic symptoms, and medication requirements. Patient selection is important and efficacy must be balanced against the risk of side effects. Immunotherapy should be used by pneumologists with a training in allergology in patients with mild asthma.     

Sublingual rush immunotherapy with latex extract in children

Latex allergy prevalence has increased notably in the last two decades. Latex ubiquity and its cross-reactivity with fruits make complete avoidance difficult to attain and studies have questioned long-term avoidance efficacy. Subcutaneous and sublingual routes of specific immunotherapy (SIT) to latex have been tested in double blind placebo controlled studies, with significant improvement in patients' tolerance to latex. We present our experience with a sublingual desensitization protocol in three latex allergic children. The build-up phase consisted of rush, with daily admission for 4 consecutive days, followed by a maintenance period at home. Only local reactions, with good response to antihistamines were observed during rush and no reactions have been reported with maintenance dose during 6, 5 and 2 months, respectively. The first patient has accomplished 6 months maintenance treatment. Allergological re-evaluation has shown a decrease in skin reactivity and serum specific IgEs to latex and cross-reactive fruits. Comparison of the results of specific IgEs measurement to a panel of latex recombinant allergens before rush and 6 months later clearly showed a decrease in Hev b 5 and Hev b 6.01, with no other detectable new sensitizations. Immunoblot was also performed before rush and 6 months later and shows a decrease in sensitization without appearance of new bands. Future enlargement of our series and prospective follow-up will help to clarify the real clinical efficacy of sublingual SIT. As this is a safe and easy to use protocol, it seems to be specially appropriate for children.