EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy.

Hymenoptera venom allergy is a potentially life-threatening allergic reaction following a honeybee, vespid, or ant sting. Systemic-allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate to severe with a risk of life-threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H1 -antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence-based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta-analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom-allergic children and adults to prevent further moderate-to-severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline autoinjector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence-based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence.

Allergen immunotherapy for insect venom allergy: a systematic review and meta-analysis.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines on Allergen Immunotherapy (AIT) for the management of insect venom allergy. To inform this process, we sought to assess the effectiveness, cost-effectiveness and safety of AIT in the management of insect venom allergy. METHODS: We undertook a systematic review, which involved searching 15 international biomedical databases for published and unpublished evidence. Studies were independently screened and critically appraised using established instruments. Data were descriptively summarized and, where possible, meta-analysed. RESULTS: Our searches identified a total of 16 950 potentially eligible studies; of which, 17 satisfied our inclusion criteria. The available evidence was limited both in volume and in quality, but suggested that venom immunotherapy (VIT) could substantially reduce the risk of subsequent severe systemic sting reactions (OR = 0.08, 95% CI 0.03-0.26); meta-analysis showed that it also improved disease-specific quality of life (risk difference = 1.41, 95% CI 1.04-1.79). Adverse effects were experienced in both the build-up and maintenance phases, but most were mild with no fatalities being reported. The very limited evidence found on modelling cost-effectiveness suggested that VIT was likely to be cost-effective in those at high risk of repeated systemic sting reactions and/or impaired quality of life. CONCLUSIONS: The limited available evidence suggested that VIT is effective in reducing severe subsequent systemic sting reactions and in improving disease-specific quality of life. VIT proved to be safe and no fatalities were recorded in the studies included in this review. The cost-effectiveness of VIT needs to be established.

Sjögren's syndrome: why autoimmune epithelitis?

The expression 'autoimmune epithelitis' has been proposed as an alternative for Sjögren's syndrome (SS) based on data pointing out the central role of the epithelial cell in the pathogenesis of the syndrome. Clinically, apart from exocrine glands that are the main target, the epithelial component of the other organs such as kidneys, liver, lungs or thyroid is commonly affected resulting in various extraglandular manifestations. On the other hand, at the molecular and cellular level, the epithelial cell plays a major role in the initiation and perpetuation of the autoimmune lesion. Mechanisms such as antigen presentation, apoptosis, chemokine production or germinal center formation lie in the center of SS pathogenesis and the epithelial cell has a very important role. Herein, we present both aspects, review the data that support the proposed terminology and finally, suggest a unifying theory for the pathogenesis of SS.

The role of epithelial cells in the initiation and perpetuation of autoimmune lesions: lessons from Sjogren's syndrome (autoimmune epithelitis).

Sjögren's syndrome (SS) is a chronic autoimmune disease affecting epithelial tissues. Exocrine glands are the primary target and their functional impairment comes as a result of immune attack of epithelial cells of the affected organs (autoimmune epithelitis). In this interplay, the role of the epithelial cell is pivotal. Extensive data point to an intrinsically activated status. Moreover, the epithelial cells possess all the features needed in order to act as non-professional antigen presenting cells. Through apoptosis and exosomes release endocellular antigens contributing to tolerance breakdown. In addition, produce cytokines and chemokines that recruit lymphocytes in the immunopathogenic lesion. Herein, we review all the aforementioned aspects of the epithelial activity that lead to the perpetuation of the lesion as well as the probable viral factors for the intrinsic activation. Finally, we propose a model for SS pathogenesis that integrates the knowledge accumulated during the last decade.

The Th1/Th2 cytokine balance changes with the progress of the immunopathological lesion of Sjogren's syndrome.

Expression of type-1 and type-2 cytokines at the mRNA level in labial salivary glands (LSG) of patients with Sjogren's syndrome (SS), as reported by several groups, have generated conflicting results. In the present study we have directly examined the production of IL-4, IL-13 and IFN-gamma by lymphocytes infiltrating the LSG of 44 consecutive patients referred for SS evaluation. Cytokines production was evaluated following in vitro culture of LSG in the presence of IL-2. IFN-gamma and IL-13 were detected in the majority of SN (24/44 and 26/44, respectively) while IL-4 was present in 5/44 SN. The presence of IFN-gamma was significantly higher in SS patients, as opposed to patients who did not fulfil the criteria for SS (P < 0.01). In addition, almost all cultured lymphocytes expressed mRNA for IFN-gamma (17/19 cultures) and IL-13 (18/19) while IL-4 mRNA was also expressed at high frequency (14/19 cultures). Interestingly, the IFN-gamma mRNA copies in cultured lymphocytes correlated significantly with the intensity of lymphocytic infiltration as evaluated by Chisholm's score (P < 0.01). Furthermore, RT-PCR of RNA extracted from whole LSG from 14 SS patients also demonstrated the presence of all cytokines in the majority of the cases and the prevalence of IFN-gamma in LSG with high-grade infiltration. Because IL-13 was produced by the majority of the cultured LSG, IgE production was also evaluated. Interestingly, IgE was detected in 21/44 LSG culture SN and mainly in those biopsies that had Chisholm's score less than 0.5 (P < 0.05). We conclude that lymphocytes infiltrating the LSG are capable of producing both Th1 and Th2 cytokines and that the balance between them shifts in favour of Th1 in LSG with high infiltration score and in patients with SS.