What’s Eating You? Mosquitoes (Culicidae)

Incidence and Characteristics

Mosquitoes are insects categorized into the order of Diptera and family of Culicidae, and more than 3500 different species have been identified.¹ In the United States, the most common genus of mosquitoes is Aedes, with other common genera including Culex, Anopheles, Culiseta, and Coquillettidia. Most bites are performed by female rather than male mosquitoes, as it serves to complete their life cycle (Figure 1).¹

FIGURE 1. Female mosquito.

There are a variety of possible reactions to mosquito bites. Severe local reactions that are large (papules >30 mm in diameter) or are accompanied by systemic manifestations are referred to as hypersensitivity to mosquito bites (HMB).² These hypersensitivity reactions vary according to multiple factors, including comorbid conditions, genetic predisposition, and geographic location. The majority of the world’s population will exhibit local reactions to mosquito bites at some point during life, with the median age of onset of the first bite at 2 years of age.³ In a study by Arias-Cruz et al,⁴ the incidence of patient-reported large local reactions was 2.5%. Hypersensitivity to mosquito bites, perhaps the most rare reaction, is more common among Asian and Central American children.⁵ The median age of diagnosis for HMB is 7 years, and most reactions occur during the first 2 decades of life.^6,7

Clinical Presentation

Mosquitoes bite vertebrates in an attempt to feed and thus must locate the host’s blood vessels through a process known as probing, which often necessitates changing the bite site several times. Once the vessel is located and lacerated, the mosquito feeds either from the vessel directly or the hematoma around it. Not only does the bite cause trauma to the skin, but a cutaneous reaction also may occur in response to salivary gland secretions that concurrently are deposited in the host tissue.⁸ Mosquitoes’ salivary gland components are the primary cause of cutaneous reactions, as one study showed that bites from mosquitoes lacking salivary gland ducts were not associated with these reactions.⁹ Mosquito saliva contains a large number of compounds with biologic activities, including lysozymes, antibacterial glucosidases, anticoagulants, antiplatelet aggregating factors, and vasodilators, as well as a potentially large number of unknown allergenic proteins. As of 2016, 70 mosquito-derived allergens have been identified, but this number continues to grow.² After a bite from a mosquito, these compounds may result in host sensitization over time, though interestingly, sensitization to mosquito bites from a species different from the original offender does not occur due to lack of cross-reactivity between species.¹

Because mosquitoes reproduce by laying their eggs directly on or near water, people who live near bodies of water or wetlands are at the highest risk for mosquito bites. Patient factors that have been found to lead to increased rates of mosquito bites include lower microbial diversity on the skin, the presence of sweat or body odor, pregnancy, increased body temperature, type O blood, dark clothing, and perfumes.² Exaggerated bite reactions are associated with Epstein-Barr virus (EBV) infection and hematologic malignancies.¹⁰

Immediate hypersensitivity is mediated by a specific IgE antibody and is characterized by erythema and a wheal at the bite site that peaks within minutes of the bite. In contrast, delayed hypersensitivity is lymphocyte mediated; occurs 24 hours after the bite; and causes an indurated, pruritic, and erythematous 2- to 10-mm papule that may blister.¹¹ Although the evidence of immediate hypersensitivity disappears within hours, symptoms of delayed hypersensitivity may last days to weeks. Accompanying symptoms may include local swelling, pain, and warmth. The itch that often is experienced in conjunction with erythema and papule formation is elicited in 3 main ways: direct induction utilizing classic pruritic pathways, IgE-mediated hypersensitivity reaction to salivary components, and IgE-independent host immune response to salivary antigens. Papular urticaria is a common additional finding in children with mosquito bites.¹ As an individual is repeatedly bitten, they may undergo 5 stages of sensitization: stage I (neither immediate nor delayed reaction), stage II (delayed reaction), stage III (immediate and delayed reaction), stage IV (immediate reaction), and stage V (neither immediate or delayed reaction).¹¹

Although most mosquito bites cause common local reactions, patients rarely demonstrate systemic reactions that can be much more severe. Skeeter syndrome is a milder systemic response characterized by large local reactions (papules >30 mm in diameter) developing hours after a bite with accompanying fever.¹² The reaction typically peaks over days to weeks.² Although the reaction may resemble cellulitis clinically, a history of a preceding mosquito bite can help make the distinction.¹³

A more severe systemic reaction is HMB, which is characterized by intense local skin findings as well as generalized systemic symptoms. Initially, indurated, clear, or hemorrhagic bullae appear at the bite site (Figure 2). Later, there is progression to swelling, necrosis, and ulceration.¹⁰ Biopsies from the skin lesions associated with HMB reveal necrosis, interstitial and perivascular eosinophilic and lymphocytic infiltrates, and small vessels with fibrinoid necrosis.⁷ Systemically, high fever, general malaise, liver dysfunction, proteinuria, hematuria, hepatosplenomegaly, and lymph node enlargement may occur. Patients typically experience these severe symptoms each time they are bitten.¹⁰

FIGURE 2. A and B, Hypersensitivity reaction to mosquito bites characterized by bullous lesions at the bite sites.