DISCUSSION
The results of our cross-sectional study, which conducted in a group of children with mosquito allergy, revealed the high frequency of aeroallergen sensitization along with atopic diseases in the study population. The diagnostic role of the mosquito commercial extract was very limited in children. Our results also found out several associations between the duration of symptoms and the features of skin reactions after mosquito bites in children with mosquito allergy.
One third of the children had at least one allergic disease such as allergic rhinitis, asthma or atopic dermatitis. When we tried to compare our findings with previous studies, we have noticed a lack of studies that were performed by children with mosquito allergy. The study of Manuyakorn et al.(10) is the only previous childhood study that presents the demographic and clinical features of children with mosquito allergy. They have reported data from 50 Thai children and although they did not perform skin prick tests with aeroallergens, the frequency of accompanying atopic diseases was 76% in children with mosquito allergy. However, the details and the definitions of the atopic diseases were not described. In the study of Kulthanan et al.(11) which reported the clinical features of 70 adults with mosquito allergy, 58.6% of the patients had a personal history of atopy. Similar to our results, nearly half of the patients had allergic rhinitis. Due to the design of our study, we have included only healthy children without any physician-diagnosed allergic disease in the control group. Therefore, a clear statement regarding the increased prevalence of allergic rhinitis in children with mosquito allergy cannot be extracted from our results. Nevertheless, the prevalence of physician-diagnosed allergic rhinitis in children varies between 8.1%-13.4% according to the results of previous childhood studies in Turkey (12, 13). In consequence with the previous studies, it can be speculated that large local reactions and/or unusual reactions after mosquito bites are more encountered in patients with allergic diseases. Further studies including children with allergic diseases and without reactions after mosquito bites are needed to support this hypothesis.
The prevalence of atopy and particularly grass pollen allergy were significantly more frequent in our cohort of children with mosquito allergy when compared to healthy children without any unusual reaction after mosquito bites. We have found a positive relationship between grass pollen allergy and mosquito reactivity in skin prick tests.
In the study of Kulthanan et al. house dust mite was the most common allergen in skin prick tests in patients with mosquito allergy (11). Scala et al. (14) have performed a multicenter study in 205 individuals reporting large local reactions after mosquito bites and found significant relationships in SPT reactivity between mosquito (Aedes communis) and house dust mite (D.pteronyssinus ), cockroach (B. germanica ), bee (Apis mellifera ) allergens. They have concluded that in individuals with severe local reactions following mosquito bites, the immune response to mosquito allergens is associated with both species-specific and cross-reactive bee venom components, suggesting the a “bee-mosquito syndrome.” In our cohort, there was no child with bee or wasp allergy. Nevertheless, only 32 children (34%) had a history of bee and/or wasp sting.
Bemanian et al. have investigated the prevalence of insect aeroallergens in their cohort of 86 patients (31 children and 55 adults) with allergic rhinitis (15). Approximately one third of the patients were sensitized to mosquito allergen in skin prick test. However, there are no data about the reactions after mosquito bites. Cantillo et al.(16) have evaluated the cross-reactivity between mosquito allergens (Aedes aegypti ) and other arthropods in serum samples of 34 patients with asthma and/or allergic rhinitis and reported a cross-reactivity between Aedes aegypti and mites, shrimp and cockroach.
Arias-Cruz et al. (17) have aimed to identify the prevalence of mosquito allergy and performed skin prick tests with a common mosquito species in Mexico (Aedes aeigypti) in 482 patients ranged in age from 2 to 58 years. Mosquito prick test was positive in 3 of 12 patients (25%) with large local reactions and no significant difference were found between patients with or without mosquito allergy. In the childhood study of Manuyakorn et al., 34% of the children were positive to skin prick test with Culex pipenes, whereas 32% of the children had positive specific IgE against Aedes communis . In adults with mosquito allergy the reported prevalences of positive skin prick tests and positive IgE antibodies to various mosquito species are higher compared to children and vary between 46.8-80 % and 45.8-73.8%, respectively (11, 14). The prevalence of skin prick test positivity to mosquito allergen was 6.4% in our cohort and there was no difference when compared to control group. The sensitivity and specificity of currently available tests in patients with a history of exaggerated or unusual responses to mosquito bites are reported to be limited (2).
Various researchers have investigated the natural course of reactions after mosquito bites and classified the patients in 5 stages (18, 19). Delayed reactions are frequent in children whereas the prevalence of immediate reactions reported to increase with age during adolescence (20, 21). In parallel with the previous findings, the majority of the children in our cohort were in stage 2 and 3 (10, 11). Moreover, we found out that the children who develop wheals in a short time after mosquito bites had longer history of symptoms. Erythematous papules were the most frequent lesions in our group. Another interesting finding of our study is the significantly higher prevalence of bullous reactions in children with asthma (41.7% vs.15.9, p=0.034). Bullous reactions to mosquito bites have been previously reported (22, 23), however there is no observed association with an atopic background so far. The exact pathogenesis of the reactions are unknown, however a hypersensitivity reaction against salivary antigens emerges as a plausible explanation (24). Severe skin reactions with various systemic symptoms are encountered in patients with certain conditions such as Epstein-Barr virus (EBV) associated lymphoproliferative diseases and natural killer (NK) cell lymphoproliferative disorders. We have consulted the children in our cohort with our pediatric hematology department and none of the children in the study group had an underlying hematologic disease during our follow-up period. Mosquito bites must be kept in mind in the differential diagnosis of children with bullous reactions and particularly with asthma.
We did not perform specific IgE testing in our patients, nevertheless performing these in vivo or in vitro tests especially in young children may have little benefit. On the other hand, it was performed in a center which was specialized for children with allergic diseases. The diagnostic procedures and the longitudinal follow-up of the patients were made by pediatric allergy specialists. Our study is one of the few childhood studies that provide unique data about children with unusual or exaggerated reactions after mosquito bites. Its prospective and controlled design along with a fairly large number of participants are other superiorities.
In conclusion, our results indicate that the role of commercially available tests in the diagnosis of children with mosquito allergy is limited. There is an association between unusual, large local or exaggerated reactions after mosquito bites and allergic diseases in children. The severity of reactions increases with age and particularly in children with atopic background.