Discussion
VIT has been defined as a disease modifying treatment, since it can target the pathogenic pathways of allergic response altering its natural history and inducing tolerance to allergens.24
In the case of hymenoptera venom allergy, in which risk of anaphylaxis is elevated, VIT is responsible for a strong reduction of risk and a significant improvement in QoL.24
The lack of an immunotherapy for mosquito allergy, or other therapeutic options capable of reducing the risk of analphylaxis for at-risk patients living in mosquito endemic area, could result in a failure of management of risk and QoL, as seen in other allergic conditions.25
Looking for other drugs targeting the underlying pathophysiology, anti-IgE monoclonal antibody was judged the most suitable choice.
Omalizumab is a recombinant humanized monoclonal anti-IgE antibody approved in Europe for the treatment of severe allergic asthma and chronic spontaneous urticaria refractory to standard therapies.26,27
Its efficacy is explained with the established omalizumab mechanism of action of binding free IgE and subsequent downregulation of FcϵRI on mastcells, basophils, eosinophils and antigen presenting-cells.27,28 Moreover, some Authors postulated an apoptotic effect of omalizumab on mastcells.29–31
Even if omalizumab use is off-label for this indication, it resulted capable of reducing incidence of anaphylaxis triggered by different allergens in clinical trials and real-life settings,32and evidence is increasing in this regard.
In the context of food allergy, previous studies demonstrated that peanut allergic adults receiving omalizumab showed a 56-fold increase in the threshold challenge dose, in most cases this change emerged early after the beginning of the treatment.33
When using omalizumab before and during peanut desensitization protocols, tolerance was achieved faster and to higher amounts of food compared to those receiving placebo.34
Its capacity in increasing the tolerability towards offending allergens has been demonstrated even in the context of Hymenoptera venom allergy. Those experiencing severe reactions during the build-up phase of Hymenoptera VIT did not relapse if premedicated with omalizumab,35–37 and this effect was confirmed also in patients with mast cell disorders.31,38
Moreover, omalizumab showed a favourable effect in reducing the risk of idiopathic anaphylaxis, even in the context of IgE-independent reaction and in patients with mast-cell disorders.32,39–44
These subjects sometimes do not exhibit specific IgE against Hymenoptera venom nor positive skin tests despite life threatening anaphylactic reactions. Since VIT is not indicated when venom hypersensitivity is not demonstrable, Omalizumab was successfully used to mitigate relapsing episodes in two cases.39,40
In these studies, a quick achievement of protection was observed42 and the dosage of 300 mg/monthly was considered effective41, while 150 mg every second week was associated with lower degree of protection.42
To date, there is no established protocol for the use of omalizumab in the prevention of anaphylaxis, especially regarding dosage. However, based on the aforementioned publications, in our patient we chose a dosage of 300 mg every 4 weeks, which proved effective in guaranteeing a protective effect against anaphylaxis episodes after mosquito bite.
Although a therapy with omalizumab in preventing severe allergic reactions after mosquito bite in a mastocytosis patient was already proposed by Reiter N et al.,16 to our knowledge this is the first reported case in which omalizumab was used and proved to be effective in relapsing anaphylaxis after mosquito bite.