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Three Part Question

In [patients with previous symptomatic reactions to insect bites] are [oral antihistamines] effective in [reducing symptoms]?

Clinical Scenario

You are going on a family holiday to Scandinavia during the summer. You wonder what evidence there is that oral antihistamines will reduce the symptoms of the inevitable insect bites.

Search Strategy

Medline 1966 - 30.09.2005
CINAHL (R) - 1982 to date 4th Oct 2005
Cochrane
Medline : [(exp Insect Bites/ and Stings.mp.) or insect bite$.mp. AND exp insects/ or insect$.mp. AND (exp Bites/ and Stings.mp.) or bite$.mp. or sting$.mp.]
AND
[exp Histamine H1 Antagonists OR antihistamine$.mp OR exp chlorpheniramine OR chlorpheniramine.mp OR exp pyrilamine OR mepyramine.mp]
CINAHL: "( INSECT-BITES-AND-STINGS#.DE. OR MOSQUITOES#.W..DE. OR BEES-AND-WASPS#.DE. OR BITES-AND-STINGS#.DE. OR INSECTS#.W..DE. OR TICKS#.W..DE. OR ARTHROPODS#.W..DE. OR TICK-BORNE-DISEASES#.DE. OR SPIDERS#.W..DE. ) AND ABSTRACT=YES NOT ( EXECUTIVE ADJ SUMMARY ) .AB. AND LG=EN":

Search Outcome

Medline search returned 214 citations, only seven of which were clinical trials addressing the question.
CINAHL search returned 780 citations. None were trials addressing the question.
Search of the Cochrane database did not find any relevant reviews.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Karppinen et al, 2002, Finland	29 adults, sensitive to mosquito bites, exposed to Aedes egypti in the laboratory.	Double-blind, cross-over study comparing cetirizine 10 mg, ebastine 10 mg, loratadine 10 mg and placebo.	Effect on pruritus and cutaneous reaction.	Cetirizine and ebastine reduced immediate cutaneous reaction and pruritus compared with placebo. Loratadine seemed ineffective.	27 subjects completed the study. Dose of loratadine probably too low, given dose used in paediatric study (above).
Karppinen et al, 2000, Finland	28 children (2-11 years), sensitive to mosquito bites. Exposure to Aedes egypti mosquitoes in the laboratory.	Double-blind, cross-over of 0.3 mg/kg loratadine v placebo	Effect on immediate and delayed cutaneous reaction, and immediate pruritus.	Loratadine reduced cutaneous reaction and pruritus.	25 completed the study. Only 12 evaluated pruritus on a visual analogue scale.
Karppinen et al, 2000, Finland	28 mosquito allergic adults exposed to Aedes communis in forests in Finland.	Double-blind, cross-over study of ebastine 20 mg OD v placebo.	Effect on pruritus and cutaneous reaction.	reduced immediate cutaneous reaction and both immediate and delayed pruritus.	Different forest sites.
Reunala et al, 1997, Finland	30 volunteers, all sensitive to mosquito bites. Exposure to Aedes egypti in the laboratory.	Double-blind, cross-over of ebastine (10 mg or 20 mg) v placebo.	Effect on prutitus and cutaneous reaction.	Ebastine reduced immediate pruritus and cutaneous reaction.	Only 25 subjects evaluable because of trial violations (2) and possible adverse events (2) ... numbers don't add up, I know.
Reunala et al, 1993, Finland	28 adults with previous significant reaction tomosquito bites. Exposed to Aedes communis in forests in Finland	Double-blind, cross-over trial of cetirizine 10 mg OD v placebo.	Effect on pruritus and cutaneous skin reaction.	Cetirizine reduced immediate pruritus and cutaneous reaction.	Subjects were patients and hospital employees. Field studies in 2 different forests. No washout period. All subjects allowed to use 1% hydrocortisone cream. Only 18 subjects completed the study.
Reunala et al, 1991, Finland	27 adult volunteers exposed to Aedes Communis mosquitoes in a forest in Southern Finland.	Double-blind, placebo-controlled trial of cetirizine 10 mg OD.	Effect on pruritus and cutaneous reaction.	Cetirizine reduced immediate but not delayed pruritus and cutaneous skin reaction.	4 subjects excluded because baseline reactions to bites were too mild.
Coulie et al, 1989, Belgium	10 healthy adult volunteers exposed to Anopheles stephensi mosquitoes in a laboratory.	Double-blind randomized cross-over trial of cetirizine 10 mg BD v placebo.	Effect on pruritus and cutaneous reaction	Reduced pruritus but not intensity or duration of cutaneous reaction	1 volunteer dropped out after a severe skin reaction to cetirizine.

Comment(s)

6 of the 7 trials were performed by a small group of researchers, addressing the problem of mosquito bites in Finland. Three mosquito species were studied. Inclusion criteria were not uniform: in some studies subjects were known to suffer significant reactions, in others they did not. Most studies used a cross-over design, however neither the treatment nor the the washout periods were not uniform.

Clinical Bottom Line

Anti-histamines, used before and after, appear to be effective in reducing the immediate/early symptoms of mosquito bites in both adults and children. It is not clear whether the same antihistamine will be effective for both adults and children.

References

1. Karppinen A, Kautiainen H, Petman L, Burri P, Reunala, T. Comparison of cetirizine, ebastine and loratadine in the treatment of immediate mosquito-bite allergy. Allergy 2002; 57: 534-537.
2. Karppinen A, Kautiainen H, Reunala T, Petman L, Brummer-Korvenkontio H. Loratadine in the treatment of mosquito-bite-sensitive children. Allergy 2000; 55: 668-671.
3. Karppinen A, Petman L, Jekunen A, Kautianen H, Vaalsti A, Reunala, T. Treatment of mosquito bites with ebastine: A field trial. Acta Derm. Venereol. 2000; 80: 114-116.
4. Reunala T, Brummer-Korvenkontio H, Petman L, Palosuo T, Sarna, S. Effect of ebastine on mosquito bites. Acta Derm. Venereol. 1997; 77: 315-316.
5. Reunala T, Brummer-Korvenkontio H, Karppinen A, Coulie P, Palosuo, T. Treatment of mosquito bites with cetirizine. Clinical and Experimental Allergy 1993; 23: 72-75.
6. Reunala T, Lappalainen P, Brummer-Korvenkontio H, Coulie P, Palosuo, T. Cutaneous reactivity to mosquito bites: effect of cetirizine and development of anti-mosquito antibodies. Clinical and Experimental Allergy 1991; 21: 617-622.
7. Coulie P, Wery M, Ghys L, Rihoux, J-P. Pharmacologic modulation by cetirizine-2 HCl of cutaneous reactions and pruritus in man after experimental mosquito bites. Skin Pharmacol 1989; 2: 38-40.