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.