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.