Abstract
Mosquito allergy can rarely give raise to severe clinical
manifestations. Here we describe the case of a patient suffering from
relapsing anaphylaxis after mosquito bites, who completely responded to
off label therapy with anti-IgE monoclonal antibody. This is the first
demonstration of the efficacy of omalizumab in such unusual
life-threatening allergy.
Introduction and Background
Several immune mediated disorders are triggered by mosquito bites (Table
1).1,2 All of these are quite uncommon, including
mosquito allergy. In this latter case, sensitized individuals usually
develop immediate or delayed large local reactions, but in exceptional
circumstances anaphylactic episodes have been
described.3
Mosquitoes belong to the order Diptera, family Culicidae, which consists
of three subfamilies, namely Toxorhynchitinae, Anophelinae and
Culicinae. In Italy, three main mosquito species have been detected:
common mosquito (Culex pipiens), tiger mosquito (Aedes albopictus) and
the newly emerged korean mosquito (Aedes koreicus); Anopheles mosquitoes
is also present but it rarely bites humans.4
To date, studies conducted primarily on Aedes aegypti (the yellow fever
mosquito), which is present in tropical, subtropical and temperate
regions throughout the world, identified a total of 22 salivary
allergens and only four body allergens, including a tropomyosin (Aed a
7); among them, Aed a 1, Aed a 2 and Aed a 4 are potentially genuine
allergens5
Moreover, the mosquito hyaluronidase has been identified as cross
reactive with that of wasp’s venom, giving rise to the so-called
wasp/mosquito syndrome,6 and a recent study correlates
mosquito (Aedes communis) and bee allergy.7
In most cases, mosquito allergy is due to the presence of
saliva-specific IgE, and mosquitoes’ saliva has been confirmed as the
main allergen source.8 Even more uncommonly,
hypersensitivity reactions can take place in sensitized individuals
after inhalation of suspended allergens derived from mosquitoes’ bodies
and emanations.3
The prolonged exposure to mosquitoes’ bites seems to be protective
against the risk of developing hypersensitivity, due to a natural
desensitization: in these cases, mosquitoes’ specific-IgE levels could
increase but together with specific IgG1 and IgG4.9Hence, mosquito allergy is more frequent in children than in adults.
The few existing studies regarding mosquito venom immunotherapy (VIT)
are limited to little groups and have used whole-body
extracts.10–13
Their results were promising, but it has to be noted that their primary
endpoint was reduction of local reactions and eventually even
respiratory symptoms, that could depend, as previously mentioned, on
mosquito body allergens.10,11. Two subjects who
developed anaphylaxis after mosquito bite were given mosquito VIT using
mosquito body extracts: complete resolution was achieved in just one of
them.14
Of interest, vaccines against mosquito salivary proteins have been
tested to protect against mosquito-borne disease rather than allergies.
The interaction of the host with saliva of vectors (in this case,
mosquitoes) seems to favor the transmission of pathogens; the efficacy
of such vaccines could deeply change the approach of preventing severe
infectious diseases.15
On the other hand, interest toward mosquito allergy gradually faded over
time, both from a scientific and pharmaceutical point of view, so that
today VIT products for mosquito allergy are not commercially available
anymore.
Even if less than thirty cases of anaphylaxis to mosquito bites have
been reported to date worldwide,8,14,16–19 management
of risk and quality of life (QoL) is exceedingly challenging in these
patients.