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Abstract：
Hymenoptera venom (HV) is injected into the skin during a sting by Hymenoptera such as bees or wasps. Some components of HV are potential allergens and can cause large local and/or systemic allergic reactions (SAR) in sensitized individuals. During their lifetime, ~ 3% of the general population will develop SAR following a Hymenoptera sting. This guideline presents the diagnostic and therapeutic approach to SAR following Hymenoptera stings. Symptomatic therapy is usually required after a severe local reaction, but specific diagnosis or allergen immunotherapy (AIT) with HV (VIT) is not necessary. When taking a patient\'s medical history after SAR, clinicians should discuss possible risk factors for more frequent stings and more severe anaphylactic reactions. The most important risk factors for more severe SAR are mast cell disease and, especially in children, uncontrolled asthma. Therefore, if the SAR extends beyond the skin (according to the Ring and Messmer classification: grade > I), the baseline serum tryptase concentration shall be measured and the skin shall be examined for possible mastocytosis. The medical history should also include questions specific to asthma symptoms. To demonstrate sensitization to HV, allergists shall determine concentrations of specific IgE antibodies (sIgE) to bee and/or vespid venoms, their constituents and other venoms as appropriate. If the results are negative less than 2 weeks after the sting, the tests shall be repeated (at least 4 - 6 weeks after the sting). If only sIgE to the total venom extracts have been determined, if there is double sensitization, or if the results are implausible, allergists shall determine sIgE to the different venom components. Skin testing may be omitted if in-vitro methods have provided a definitive diagnosis. If neither laboratory diagnosis nor skin testing has led to conclusive results, additional cellular testing can be performed. Therapy for HV allergy includes prophylaxis of reexposure, patient self treatment measures (including use of rescue medication) in the event of re-stings, and VIT. Following a grade I SAR and in the absence of other risk factors for repeated sting exposure or more severe anaphylaxis, it is not necessary to prescribe an adrenaline auto-injector (AAI) or to administer VIT. Under certain conditions, VIT can be administered even in the presence of previous grade I anaphylaxis, e.g., if there are additional risk factors or if quality of life would be reduced without VIT. Physicians should be aware of the contraindications to VIT, although they can be overridden in justified individual cases after weighing benefits and risks. The use of β-blockers and ACE inhibitors is not a contraindication to VIT. Patients should be informed about possible interactions. For VIT, the venom extract shall be used that, according to the patient\'s history and the results of the allergy diagnostics, was the trigger of the disease. If, in the case of double sensitization and an unclear history regarding the trigger, it is not possible to determine the culprit venom even with additional diagnostic procedures, VIT shall be performed with both venom extracts. The standard maintenance dose of VIT is 100 µg HV. In adult patients with bee venom allergy and an increased risk of sting exposure or particularly severe anaphylaxis, a maintenance dose of 200 µg can be considered from the start of VIT. Administration of a non-sedating H1-blocking antihistamine can be considered to reduce side effects. The maintenance dose should be given at 4-weekly intervals during the first year and, following the manufacturer\'s instructions, every 5 - 6 weeks from the second year, depending on the preparation used; if a depot preparation is used, the interval can be extended to 8 weeks from the third year onwards. If significant recurrent systemic reactions occur during VIT, clinicians shall identify and as possible eliminate co-factors that promote these reactions. If this is not possible or if there are no such co-factors, if prophylactic administration of an H1-blocking antihistamine is not effective, and if a higher dose of VIT has not led to tolerability of VIT, physicians should should consider additional treatment with an anti IgE antibody such as omalizumab as off lable use. For practical reasons, only a small number of patients are able to undergo sting challenge tests to check the success of the therapy, which requires in-hospital monitoring and emergency standby. To perform such a provocation test, patients must have tolerated VIT at the planned maintenance dose. In the event of treatment failure while on treatment with an ACE inhibitor, physicians should consider discontinuing the ACE inhibitor. In the absence of tolerance induction, physicians shall increase the maintenance dose (200 µg to a maximum of 400 µg in adults, maximum of 200 µg HV in children). If increasing the maintenance dose does not provide adequate protection and there are risk factors for a severe anaphylactic reaction, physicians should consider a co-medication based on an anti-IgE antibody (omalizumab; off-label use) during the insect flight season. In patients without specific risk factors, VIT can be discontinued after 3 - 5 years if maintenance therapy has been tolerated without recurrent anaphylactic events. Prolonged or permanent VIT can be considered in patients with mastocytosis, a history of cardiovascular or respiratory arrest due to Hymenoptera sting (severity grade IV), or other specific constellations associated with an increased individual risk of recurrent and/or severe SAR (e.g., hereditary α-tryptasemia). In cases of strongly increased, unavoidable insect exposure, adults may receive VIT until the end of intense contact. The prescription of an AAI can be omitted in patients with a history of SAR grade I and II when the maintenance dose of VIT has been reached and tolerated, provided that there are no additional risk factors. The same holds true once the VIT has been terminated after the regular treatment period. Patients with a history of SAR grade ≥ III reaction, or grade II reaction combined with additional factors that increase the risk of non response or repeated severe sting reactions, should carry an emergency kit, including an AAI, during VIT and after regular termination of the VIT.
摘要：
膜翅目毒液（HV）在蜜蜂或黄蜂等膜翅目的叮咬过程中注入皮肤。HV的一些组分是潜在的过敏原,并且可在致敏个体中引起大的局部和/或全身性过敏反应(SAR)。在他们的一生中,约3％的普通人群在膜翅目叮咬后会发展成SAR。本指南介绍了膜翅目叮咬后SAR的诊断和治疗方法。严重的局部反应后通常需要对症治疗，但没有必要进行特异性诊断或使用HV（VIT）进行过敏原免疫疗法（AIT）。在SAR后服用患者的病史时，临床医师应讨论更频繁的叮咬和更严重的过敏反应的可能危险因素.更严重的SAR最重要的危险因素是肥大细胞病和,尤其是在儿童中，不受控制的哮喘。因此,如果SAR超出皮肤（根据RingandMessmer分类：等级>I），应测量基线血清类胰蛋白酶浓度，并检查皮肤是否有肥大细胞增多症。病史还应包括特定于哮喘症状的问题。为了证明对HV的敏感性，变态反应学家应确定特定IgE抗体（sIgE）对蜜蜂和/或蜂毒的浓度，他们的成分和其他适当的毒液。如果在刺痛后不到2周结果为阴性，试验应重复(至少4-6周后)。如果仅测定了总毒液提取物的sIgE，如果有双重敏感，或者如果结果令人难以置信，变态反应学家应测定不同毒液成分的sIgE。如果体外方法提供了明确的诊断，则可以省略皮肤测试。如果实验室诊断和皮肤测试都没有得出决定性的结果，可以进行额外的细胞测试。HV过敏的治疗包括预防再暴露，患者自我治疗措施（包括使用抢救药物），以防再次刺痛，和VIT。在I级SAR之后，在没有其他反复刺痛暴露或更严重过敏反应的危险因素的情况下，没有必要开肾上腺素自动注射器（AAI）或管理VIT。在一定条件下,甚至在存在先前的I级过敏反应的情况下也可以进行VIT，例如，如果有其他风险因素，或者如果没有VIT会降低生活质量。医生应该意识到VIT的禁忌症，尽管在权衡收益和风险后，在合理的个别情况下可以推翻它们。使用β受体阻滞剂和ACE抑制剂不是VIT的禁忌症。应告知患者可能的相互作用。对于VIT，应使用毒液提取物，根据患者的病史和过敏诊断结果，是疾病的导火索.如果,在双重敏感和关于触发的历史不清楚的情况下，即使有额外的诊断程序，也不可能确定罪魁祸首毒液，应使用两种毒液提取物进行VIT。VIT的标准维持剂量为100µgHV。在有蜂毒过敏的成年患者中，刺痛暴露或特别严重的过敏反应的风险增加，从VIT开始就可以考虑200µg的维持剂量。给予非镇静H1阻断性抗组胺药可被认为减少副作用。维持剂量应在第一年以4周的间隔给予，按照制造商的说明，从第二年开始每5-6周，取决于所使用的制剂；如果使用仓库制剂，从第三年开始，间隔可以延长到8周。如果在VIT期间发生明显的复发性全身反应，临床医生应确定并尽可能消除促进这些反应的共因素。如果这是不可能的，或者如果没有这样的共同因素，如果预防性给予H1阻断性抗组胺药无效，如果更高剂量的VIT没有导致VIT的耐受性，医师应考虑使用抗IgE抗体如奥马珠单抗进行额外治疗,作为停用药物.出于实际原因,只有少数患者能够进行刺激挑战测试，以检查治疗的成功，这需要院内监控和紧急待命。为了进行这样的挑衅测试，患者必须在计划的维持剂量下耐受VIT.如果在使用ACE抑制剂治疗时治疗失败，医师应考虑停用ACE抑制剂.在没有耐受性诱导的情况下，医生应增加维持剂量(成人200µg至最大400µg，儿童最高200µgHV)。如果增加维持剂量不能提供足够的保护，并且存在严重过敏反应的风险因素，在昆虫飞行季节,医师应考虑基于抗IgE抗体(奥马珠单抗;标签外使用)的联合用药.在没有特定危险因素的患者中，如果维持治疗耐受且无复发性过敏性事件，则可在3-5年后停用VIT。肥大细胞增多症患者可以考虑延长或永久的VIT，因膜翅目叮咬引起的心血管或呼吸骤停病史（严重程度为IV级），或与复发和/或严重SAR的个体风险增加相关的其他特定星座(例如，遗传性α-色胺血症)。在强烈增加的情况下，不可避免的昆虫暴露，成年人可以接受VIT，直到激烈接触结束。在具有SARI级和II级病史的患者中，当达到VIT的维持剂量并耐受时，可以省略AAI的处方，前提是没有其他风险因素。一旦在常规治疗期后终止VIT，情况也是如此。有SAR等级≥III反应史的患者，或II级反应与增加无应答或反复严重刺痛反应风险的其他因素相结合，应该携带应急工具包，包括AAI,在VIT期间和定期终止VIT之后。
