Mosquito bite allergies, also termed hypersensitivity to mosquito bites, are excessive reactions of varying severity to mosquito bites. They are allergic hypersensitivity reactions caused by the non-toxic allergenic proteins contained in the saliva injected by a female mosquito (male mosquitos do not take blood-meals) at the time it takes its blood meal, and are not caused by any toxin or pathogen. By general agreement, mosquito bite allergies do not include the ordinary wheal and flare responses to these bites although these reactions are also allergic in nature. Ordinary mosquito bite allergies are nonetheless detailed here because they are the best understood reactions to mosquito bites and provide a basis for describing what is understood about them.
Mosquito bite allergies are informally classified as 1) the skeeter syndrome, i.e., severe local skin reactions sometimes associated with low-grade fever; 2) systemic reactions that range from high-grade fever, lymphadenopathy, abdominal pain, and/or diarrhea to, very rarely, life-threatening symptoms of anaphylaxis; and 3) severe and often systemic reactions occurring in individuals that have an Epstein-Barr virus-associated lymphoproliferative disease, Epstein-Barr virus-negative lymphoid malignancy, or another predisposing condition such as eosinophilic cellulitis or chronic lymphocytic leukemia. The term papular urticaria is commonly used for a reaction to mosquito bites that is dominated by widely spread hives. Here, papular urticaria is regarded as a symptom of mosquito bite allergy manifested in individuals with one of the other mosquito bite allergies, but particularly in those associated with eosinophilic cellulitis.
Mosquitos belong to the biological order of Diptera (which includes all two-winged insects), suborder Nematocera, family Culicidea. There are >3,500 different mosquito species with the Aedes and Culex genera being common in North America. It is assumed that any species of mosquito that causes an ordinary mosquito bite reaction in humans is capable of causing mosquito bite allergies. In addition to mosquitoes, the Diptera order includes numerous other types of biting insects such as midges (e.g. sand flies) and gnats. Bites by the latter insects or possibly some other insects may cause reactions that are mechanistically and clinically similar to those seen with mosquito bites.
Mosquito bite allergies occur more often where insect bites are frequent. Consequently, cases (as well as various other allergic disorders) are more prevalent in tropical climates, underdeveloped areas, and areas dominated by poverty. That is, not only climate but also cultural and socioeconomic conditions play roles in facilitating the development and prevalence of diverse allergic diseases, including mosquito bite allergies.
Ordinary reactions
Presentations The typical reaction to mosquito bites involves the development of an itchy wheal that may contain a central red dot and is surrounded by splotchy redness. This "immediate reaction" occurs at some time during the first 20 minutes following the bite. Within hours of the bite, a "delayed reaction", in which the wheal evolves into a papule develops and then dissipates over the next few days or weeks. However, there is a wide variability in the type of reaction that individuals mount in response to these bites. The initial mosquito bites in previously unexposed individuals do not cause a skin reaction but do initiate the development of antibodies and/or lymphocytes that are directed against the allergens in mosquitoes' saliva. These individuals thereby become sensitized and reactive to subsequent mosquito bites. After repetitive mosquito bites, individuals may become less sensitive or completely insensitive to the bites in the natural process of allergen desensitization. Individuals therefore progress through five stages in which the type of reaction to a mosquito bite depends on the number of their previous bite exposures and levels of acquired sensitization and desensitization to these bites. The 5 stages an individual may undergo in reacting to repetitive mosquito bites are: Stage I: Previously unexposed individuals have no immediate or delayed reaction. Stage II: Shortly after their initial exposure, individuals become partly sensitized and therefore develop a delayed but no immediate reaction. Stage III: Following further exposures, individuals become fully sensitized and therefore have an immediate reaction followed by a delayed reaction. Stage IV: After >2–20 years of repetitive exposures, individuals may become partially desensitized and therefore have an immediate but no delayed reaction. Stage V: After many further exposures during the 2–20 years of repetitive exposures, individuals may become fully desensitized and therefore show no reaction.
In a study of 41 Canadian adults experimentally exposed to mosquito bites, 11 individuals exhibited no reaction, 23 individuals exhibited immediate followed by delayed reactions, 6 individuals exhibited only immediate reactions, and 1 individual exhibited only a delayed reaction. Overall, 70-90% of individuals experience an immediate reaction, and 55-65% experience a delayed reaction to mosquito bites.
Individuals also vary in the severity of their reactions to mosquito bites. Most individuals show a "small reaction" in which a 2–10 mm (0.1-0.4 inches) diameter wheal evolves into a similarly sized papule that dissipates over several days. About 2.5% of individuals (based on self reports) show a "large reaction" in which the wheal is much larger than 10 mm (it may exceed 3 cm, i.e. 1.2 inches) in diameter and evolves into an extensive lesion that has black and blue discolorations due to subcutaneous bleeding, blistering, and/or necrosis. The latter reactions, which appear to be caused by the development of an inflammatory Arthus reaction at the site, may be very painful.
Pathophysiology Mosquito saliva contains >30 potentially allergenic proteins. More than 11 of these have been identified in the saliva of the Aedes egypti mosquito. Four such proteins, termed Aed a 1 (an apyrase), Aed 2 (Female-specific protein, D7), Aed 3 (an as yet undefined protein), and Aed a 4 (an α-glucosidase) have been purified as recombinant proteins. Each of these recombinants causes immediate and delayed skin reactions when injected into volunteers with a history of mosquito bite reactivity. As exemplified by the Aed proteins, the proteins in the saliva of any biting mosquito are thought to cause individuals who have not been previously bitten to: a) make IgE and IgG antibodies that bind the proteins inducing their formation and b) develop T cells (a type of lymphocyte) that react against parts of the inducing proteins that are displayed on the surface of cells at the bite site (see Antigen presentation). In subsequent mosquito bites, IgE and IgG appear involved in the development of both immediate and delayed skin reactions. T cells appear to be involved in the development of the delayed skin reactions. The acquired IgE binds mosquito saliva proteins and then triggers skin tissue cells such as mast cells to release at least two mediators of allergic reactions, histamine and leukotriene C4. These mediators contribute to the development of the wheal, itch, and other components of the immediate reaction. This part of the immediate reaction is a classical type I hypersensitivity reaction. The acquired IgG binds mosquito saliva proteins to form an immune complex-triggered type III hypersensitivity reaction that recruits blood leukocytes, including T cells, into the bite area; this response it thought to be required for developing the early stage of the delayed reaction. T cells present in or recruited to the mosquito bite area appear responsible for mediating the full delayed reaction. The full delayed reaction is a type IV hypersensitivity reaction.
Diagnosis The diagnosis of ordinary mosquito reactions is made based on the history and clinical features of mosquito bites.
Prevention Reducing mosquito breeding areas (e.g. eliminating standing water pools, stocking ponds with fish that consume mosquito larva) and the use of other mosquito control methods such as insecticides, mosquito traps, protective clothing, bed nets, and repellants (e.g., DEET or permethrin) are effective, highly recommended means for reducing mosquito bites. Daily doses of a non-sedating second-generation anti-histamines (e.g. cetirizine or levocetirizine) can effectively reduce the immediate and delayed reactions to mosquito bites. The use of recombinant mosquito saliva proteins to desensitize individuals against developing reactions to mosquito bites has yielded variable results and requires further study.
Treatment Treatment of ordinary small or large mosquito bite reactions is limited to the use of non-sedative H1 antihistamines, e.g. cetirizine or a drug with combined activity in inhibiting histamine and platelet-activating factor, e.g. rupatadine. Randomized, double-blinded, placebo-controlled studies are needed to determine if antileukotriene drugs or topical steroids have beneficial effects in reducing the symptoms of these bites.
Skeeter syndrome reactions
Presentation The Skeeter syndrome is by definition a mosquito bite allergy that consists of a large mosquito bite reaction that may be accompanied by a brief or longer-term (i.e., days to weeks) low-grade fever. and, on rare occasions, vomiting. The bite site shows an intense, large reaction often resembling a cellulitis infection that persists for days to weeks. The syndrome usually afflicts healthy children, immune-deficient persons, and individuals who are new to an area inhabited by mosquito species to which they have not been exposed.
Pathophysiology Mechanistically, the Skeeter syndrome appears to be a particularly intense variant of the ordinary mosquito bite reaction. It involves sequential Type I, III, and IV hypersensitivity reactions that are mediated by IgE, IgG, and T cells that are directed against mosquito salivary proteins.
Prognosis Children afflicted with the syndrome remain healthy, although subject to recurrent severe reactions to mosquito bites. The development of desensitization that follows repetitive mosquito bites and reduces the intensity or completely blocks reactions to mosquito bites may take longer to develop and/or be less effective in those with Skeeter syndrome compared to those with ordinary mosquito bite reactions.
Diagnosis The diagnosis of Skeeter syndrome is based mainly on the appropriate history of severe skin responses to mosquito bites that may be associated with fever. The diagnosis can be supported by the detection, using for example an ELISA assay), IgE directed against mosquito saliva proteins in the afflicted individual's serum. Direct mosquito bite testing is perhaps the best method for diagnosing mosquito bite allergy but difficulty in determining which mosquito species to use for the test, the possibility of transmitting a mosquito-borne disease, and the risk of triggering a very severe response make this test impractical for routine use.
Prevention and treatment The preventive measures listed for ordinary mosquito bite reactions are important for avoiding Skeeter syndrome reactions. In addition to second-generation, non-sedative H1 antihistamines, antipyretics and nonsteroidal anti-inflammatory drugs are typically used to treat patients with acute attacks of the syndrome.
Systemic allergic reactions Presentation