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Adherence and compliance, respectively considered as a more positive, proactive behavior, resulting in a patient's lifestyle change to follow a daily regimen, and, as a more enforced response to an external command, are a critical aspect of any medical therapy, since it is estimated that less than half of the patients who are prescribed a therapy perform it, respecting the doses and duration. As far as aeroallergen immunotherapy is concerned, current data show that adherence is respected in about 50% of subcutaneous immunotherapy and in percentages even lower than 20% in sublingual immunotherapy treatments. This review analyzes the adherence to venom immunotherapy (VIT), in which, given its purpose of preventing potentially fatal anaphylactic reactions to insect stings, this aspect plays a critical role. In fact, protection from stings already takes place when the maintenance dose is reached, but VIT interruption before the recommended duration of 5 years exposes patients to new sting reactions. The data on adherence to VIT are far less abundant than that for aeroallergen immunotherapy. One of the first studies reported poor adherence in Austria, but the model used, consisting in the estimate of the percentage of patients with systemic reactions who accepted or rejected VIT, does not meet the criteria that define adherence to treatment. As for appropriate adherence studies, rates higher than 70% were reported in the United States and European countries. Studies from Italy found that good adherence were observed also in patients receiving, after 4 years of VIT, 3 months extended maintenance dose, as well as in patients treated during the COVID-19 pandemic,

Allergen immunotherapy (AIT) and venom immunotherapy (VIT) are meant to work on the causes of allergies, respectively, to respiratory allergens and Hymenoptera venom, inducing tolerance to the allergens and modifying the natural history of allergy. Both types of immunotherapies have evidence of efficacy, but actually they present wide differences in both effectiveness and safety. Indeed, as far as the effectiveness of VIT is concerned, if the protection against fatal reactions to stings is considered as the primary objective, more than 40 years of clinical practice demonstrate complete success. The clinical success of AIT is measurable on the basis of reduction or disappearance of allergic symptoms. The difference between the two treatments is even higher as regards safety: AIT has been concerned in the past by a series of fatal reactions caused, which underwent a progressive decrease when it was understood that they were related to the presence of uncontrolled asthma. However, fatal reactions related to failure to recognize the presence of risk factors or administration errors are still reported. Similarly to what has been observed for efficacy, VIT has never been affected by fatal reactions to the administration of venom, and the most important risk of anaphylaxis, which is the concomitance of mastocytosis, is now identified by measuring its marker serum tryptase. To date, mechanisms of hypersensitivity reactions that differentiate respiratory allergy from Hymenoptera venom allergy have not been successfully demonstrated. We have examined the past and present literature in order to propose reasonable hypotheses about the mechanisms actually involved.