Mosquito Bite Hypersensitivity

Exaggerated local or systemic reaction to mosquito saliva proteins (Aedes, Culex, Anopheles), well beyond the usual small itchy weal.

• Normal course of exposure: sensitisation, then an immediate weal at 15 to 30 minutes, a delayed papule at 12 to 24 hours, and finally tolerance after repeated exposure. Visitors and young children react more than long term residents.
• Forms:
  • Large local reactions (skeeter syndrome): swelling over 5 to 10 cm, redness, warmth, pain and sometimes low fever within hours of a bite, mimicking cellulitis. Common in infants, young children and visitors to endemic areas.
  • Bullous and necrotic reactions.
  • Anaphylaxis: rare, but reported with mosquito saliva IgE sensitisation.
  • Hypersensitivity to mosquito bites associated with Epstein-Barr virus: severe, necrotic, ulcerating bites, high fever, lymphadenopathy and hepatosplenomegaly, mainly in East Asian children and young adults, with chronic active Epstein-Barr virus infection and NK or T cell lymphoproliferative disease. It can progress to haemophagocytic lymphohistiocytosis and lymphoma.
• Higher risk: atopy, immunosuppression, haematological malignancy (chronic lymphocytic leukaemia) and HIV.

• Skeeter syndrome: warm, tender, red, swollen plaques at the bite site, which peak at 8 to 12 hours and settle in 3 to 10 days, with possible blistering.
• Persistent urticarial or papular lesions, prurigo nodules and post-inflammatory pigmentation in repeated exposure.
• The Epstein-Barr virus associated form shows bites that evolve into large blisters, then necrotic ulcers and scars, with fever, malaise, lymphadenopathy, hepatosplenomegaly and sometimes cytopenias.
• Anaphylaxis: urticaria, angioedema, wheeze, stridor, vomiting and hypotension within minutes.
• Differential diagnosis: cellulitis (spreading, painful, febrile, unwell), contact dermatitis, other insect bites, urticaria, scabies, bullous pemphigoid, vasculitis, pyoderma gangrenosum, and cutaneous lymphoma.
• Complications: secondary infection, scarring, haemophagocytic syndrome, lymphoma and anaphylaxis.

• Clinical, from timing and the clear relation to bites. Cellulitis is distinguished by the absence of fever and toxicity, rapid onset after the bite, and itch.
• Mild reactions need no investigation. For severe, necrotic or recurrent reactions with systemic features, check full blood count, liver enzymes, lactate dehydrogenase, ferritin, triglycerides and fibrinogen (for haemophagocytosis), and Epstein-Barr virus DNA load by PCR with serology.
• Flow cytometry for NK and T cell populations, and a skin or lymph node biopsy when lymphoproliferative disease is possible.
• Specific IgE to mosquito saliva allergens (where available) and skin prick testing with mosquito extract support the diagnosis in anaphylaxis.
• Check for HIV and immunoglobulins in recurrent severe disease.

• Avoidance and bite prevention:
  • Insect repellent on exposed skin: DEET 20 to 30% (children over 2 months, maximum 30%), picaridin 20%, or oil of lemon eucalyptus (not under 3 years).
  • Long sleeves and trousers, permethrin treated clothing, insecticide treated bed nets, screens, air conditioning or fans, and avoiding dusk and dawn outdoor activity.
  • Remove standing water near the home, and use mosquito coils or room insecticide devices where appropriate.
• Treatment of local reactions:
  • Cold compresses for 10 to 15 minutes, and elevation of the limb.
  • Mometasone furoate 0.1% or betamethasone valerate 0.1% cream once or twice daily for 3 to 7 days.
  • Cetirizine 10 mg orally once daily (child 2 to 5 years 2.5 mg, 6 to 11 years 5 mg), or loratadine 10 mg once daily. Doses up to twice the licensed dose are used when needed, under supervision.
  • Paracetamol 1 g orally 6 hourly (child 15 mg/kg 6 hourly) or ibuprofen 400 mg orally 8 hourly with food for pain.
  • Severe swelling or blistering: prednisolone 0.5 to 1 mg/kg per day (maximum 40 mg) for 3 to 5 days (evidence limited).
• Secondary infection: mupirocin 2% ointment 3 times daily for 5 to 7 days, or flucloxacillin 500 mg orally 6 hourly for 7 days (child 12.5 to 25 mg/kg 6 hourly).
• Prophylaxis before predictable exposure (travel, camping): a non-sedating antihistamine daily starting 1 to 2 days before, with repellent use.
• Anaphylaxis: adrenaline 1 mg/mL intramuscular into the anterolateral thigh, 0.5 mg for adults and children over 12 years, 0.3 mg for 6 to 12 years, 0.15 mg for under 6 years, repeated every 5 minutes if needed, with oxygen and IV fluids. Prescribe adrenaline auto injectors and refer for allergy assessment.
• Allergen immunotherapy with mosquito extracts has limited evidence and is not widely available.
• Epstein-Barr virus associated disease: urgent referral to haematology. Treatment is by specialists and includes systemic corticosteroids, etoposide based chemotherapy, and haematopoietic stem cell transplantation, which is the only curative therapy.
• Special groups:
  • Pregnancy: avoid DEET above 30% and use picaridin or DEET at recommended concentrations. Cetirizine and loratadine are acceptable, with calamine and mild topical steroids.
  • Infants: protective clothing and nets rather than repellent under 2 months. Treat large local reactions with cold compresses and mild steroid.
  • Immunosuppressed and haematological malignancy patients: expect exaggerated reactions and treat earlier.
• Follow up: review if reactions are severe, become necrotic, or recur with fever and systemic features. Refer to allergy, dermatology or haematology accordingly.