REACTIONS TO MOSQUITO

Introduction

This time of year (May) I start to receive referrals and calls from parents about children who have had huge reactions to mosquito bites. I usually re-assure the parents and indicate that the management is local in order to prevent the children from scratching and getting the bite infected. The bite usually itches and the parent often gives the child an antihistamine. But are there any data that anti-histamines actually give some relief? What do we know about reactions to mosquito bites?

One of the world's experts on mosquito sensitivity is here in Canada in Winnipeg. Dr. F. Estelle Simons and her laboratory have published extensively on the nature of the reactions to mosquito bites. Dr. Simons and her colleagues described a syndrome that they called the "Skeeter syndrome" which characterizes the nature of the local reactions to mosquito bites.

ABSTRACTS:

Simons FER, Peng Z. Skeeter syndrome. J Allergy Clin Immunol 1999;104:705-7.

Large local reactions to mosquito bites are underdiagnosed and are sometimes assumed to have an infectious etiology when in fact they are caused by allergenic polypeptides in the mosquito saliva. Young children, immune-deficient persons, and immigrants or visitors to an area with indigenous mosquitoes to which they have not been previously exposed are at increased risk for severe reactions to mosquito bites. Here we report how specific and sensitive ELISAs using mosquito salivary gland extract as the antigen enabled us to recognize and to describe skeeter syndrome for the first time. This syndrome is defined as mosquito bite-induced large local inflammatory reactions accompanied by fever. The reactions were initially misdiagnosed as cellulitis and investigated and treated as such, although by history they developed within hours of a mosquito bite, a time frame in which it would have been highly unlikely for an infection to develop.

Peng Z, Yang M, Simons FE. Immunologic mechanisms in mosquito allergy: correlation of skin reactions with specific IgE and IgG antibodies and lymphocyte proliferation response to mosquito antigens. Ann Allergy Asthma Immunol 1996;77:238-44.

BACKGROUND: Allergic reactions to mosquito bites are a common problem. Although IgE-mediated hypersensitivity has been reported, other immunologic mechanisms may be involved. OBJECTIVES: To study the relationship between skin bite reactions and immunologic parameters. METHODS: Forty-one subjects were experimentally exposed to mosquito (Aedes vexans) bites. Immediate and delayed skin reactions were traced at 20 minutes and 24 hours, respectively, after the bites. Sera were analyzed for mosquito salivary gland-specific IgE (mosquito-IgE) and IgG (mosquito-IgG) by ELISA. Lymphocyte proliferation assays with mosquito extract were also performed. RESULTS: One of 41 subjects had only a delayed skin reaction to the bite, 23 had both immediate and delayed reactions, 6 had only immediate reactions, and 11 had no reaction. The mean mosquito-IgE and -IgG concentrations were higher in the subjects with immediate reactions than in those without immediate reactions (P < .007). The mean lymphocyte proliferation stimulation index was higher in the subjects with delayed reactions than in those without delayed reactions (P < .015). Further, both mosquito-IgE and -IgG levels correlated with skin immediate and delayed reactions (P < .04), while lymphocyte proliferation indices only correlated with skin delayed reactions (P < .006). Inverse correlations were found between the size of skin reactions and the number of years lived in Canada (P < .04), but not with age. CONCLUSION: These results indicate that IgE-, lymphocyte- and, probably, local IgG immune-complex-mediated hypersensitivities are involved in mosquito allergy. Naturally acquired desensitization to mosquito bites occurs during long-term exposure.

Reunala T, Brummer-Korvenkontio H, Palosuo T. Are we really allergic to mosquito bites? Ann Med 1994;26:301-6.

Most, if not all, people are sensitized to mosquito bites in childhood. Cutaneous symptoms include immediate wheal-and-flare reactions and delayed bite papules, which tend to be more severe at the onset of the mosquito season. Systemic reactions to mosquito bites are, however, very rare. Recent immunoblot studies have demonstrated IgE antibodies to Aedes communis mosquito saliva 22 and 36 kD proteins. This confirms that specific sensitization occurs in man and indicates that mosquito-bite whealing is a classic type I allergic reaction. The delayed mosquito-bite papules seem to be cutaneous late-phase reactions mediated by eosinophils or they could also represent type IV lymphocyte-mediated immune reactions. People living in heavily infested areas such as Lapland frequently acquire tolerance to mosquito bites, and seem to have negligible levels of IgE but high amounts of IgG4 antisaliva antibodies. Desensitization treatment is a theoretical possibility but prophylactically given cetirizine, an H1-blocking antihistamine, has been shown to be helpful for people suffering from mosquito bites.

Oka K, Ohtaki N. Clinical observations of mosquito bite reactions in man: a survey of the relationship between age and bite reaction. J Dermatol 1989;16:212-9.

To evaluate the mechanism of mosquito bite reaction in man, the reaction to Aedes albopictus was observed in 162 subjects ranging in age between 1 to 68 years old. Bite reactions were found to consist of both an immediate and a delayed reaction. The eruption and time course of the immediate reaction were consistent with type I hypersensitivity. The eruption and time course of the delayed reaction were consistent with cutaneous basophil hypersensitivity. Positive rates of immediate reaction increased from early childhood to adolescence and decreased with age from adulthood. The appearance and intensity of the delayed reaction decreased with age. Mosquito bite reactions in human beings exposed continuously and regularly are known to change from stage 1 to stage 5 (stage 1; no reaction, 2; delayed reaction only, 3; immediate and delayed reaction, 4; immediate reaction only, 5; no reaction). Analysis of the relationship between age and bite reaction in this study indicated that the principle held true even when the exposures were irregular or at random.

Reunala T, Brummer-Korvenkontio H, Karppinen A, Coulie P, Palosuo T. Treatment of mosquito bites with cetirizine. Clin Exp Allergy 1993;23:72-5.

Eighteen adult subjects sensitive to mosquito bites participated in a double-blind, placebo-controlled study with 10 mg cetirizine. The drug was given prophylactically and the subjects were then exposed to bites of Aedes communis mosquitoes in the field. Bite lesions were measured and pruritus was scored with a visual analogue scale at 15 min, 60 min, 12 hr and 24 hr. Cetirizine significantly decreased immediate wealing and pruritus and, interestingly, also had a clear effect on the delayed 12 hr and 24 hr bite papules and pruritus. The diameter of a 15 min mosquito-bite weal was 10.1 +/- 10.4 mm (mean +/- s.d.) with the placebo and 5.9 +/- 5.9 mm with cetirizine treatment (P < 0.05). The 15 min pruritus scores were 36.0 +/- 25.2 and 11.2 +/- 13.2 (P < 0.001), respectively. The diameter of the 24 hr mosquito-bite lesion was 12.6 +/- 21.9 mm with the placebo and 7.4 +/- 16.1 mm with cetirizine treatment (P < 0.01). The 24 hr pruritus scores were 18.9 +/- 25.5 and 6.6 +/- 14.8 (P < 0.01), respectively. These results indicate that, in mosquito-sensitive subjects, prophylactically administered cetirizine is an effective drug against both immediate and delayed mosquito-bite symptoms.

Karppinen A, Petman L, Jekunen A, Kautiainen H, Vaalasti A, Reunala T. Treatment of mosquito bites with ebastine: a field trial. Acta Derm Venereol 2000;80:114-6.

Wealing and pruritic, long-lasting papules are a common nuisance from mosquito bites. Antihistamines can be expected to decrease wealing, but their effect on the delayed bite symptoms needs to be elucidated. We studied the effect of ebastine in 28 mosquito-bite sensitive adult subjects exposed to Aedes communis bites in the field. Ebastine 20 mg and placebo were given for 4 days in a cross-over fashion, and the size of the bite lesion and the intensity of pruritus (visual analogue scale) were measured at 15 min and 2, 6 and 24 h after the bites. Ebastine decreased significantly (p <0.001) the size of the bite lesion and pruritus at 15 min. Ebastine also had a significant effect (p<0.01) on pruritus at 2 and 24 h, and this effect was highly significant when the measurements at all 4 time points were pooled. Five patients (18%) on ebastine, but none on placebo, experienced sedation (ns). The present field study shows that ebastine 20 mg given prophylactically is effective against immediate mosquito bite symptoms, and that it also significantly decreases pruritus associated with the delayed bite papules.

CONCLUSIONS:

Clearly there is clinically useful information in the literature on mosquito bite reactions. The reactions are immunologic in nature to polypeptide antigens in the mosquito saliva. There seems to be the full range of immune responses including immediate IgE-mediated whealing, intermediate immune complex arthus reactions and both late phase allergic and delayed cellular reactions. Fortunately anaphylaxis is extremely rare. The reactions usually decrease with age and there is some evidence that prophylactic antihistamine seems useful in reducing the reactions. However if taking prophylactic anti-histamine does not seem that appealing, not to worry Canada, winter is always around the corner!