Background: In our 1976 controlled venom immunotherapy trial, 33% of 182 pa
tients with a history of systemic reactions to insect stings were excluded
because of negative venom skin test responses, There have been reports of p
atients with negative skin test responses who have had severe reactions to
subsequent stings,
Objective: Our aim is to increase awareness about the patient with a negati
ve skin test response and insect sting allergy and to determine the frequen
cy and significance of negative skin test responses in patients with a hist
ory of systemic reactions to insect stings.
Methods: We prospectively examined the prevalence of negative venom skin te
st responses in patients with 3 history of systemic reactions to stings, In
patients who gave informed consent, we analyzed the outcome of retesting a
nd sting challenge.
Results: Of 307 patients with positive histories screened for our sting cha
llenge study, 208 (68%) had positive venom skin test responses (up to 1 mug
/mL concentration), and 99 (32%) had negative venom skin test responses. In
36 (36%) of the 99 patients with negative skin test responses, the venom R
AST result was a low positive (1-3 ng/mL), or repeat venom skin test respon
ses were positive; another 7 (7%) patients had high venom-specific IgE anti
body levels (4-243 ng/mL), Notably, 56 (57%) of 99 patients with positive h
istories and negative skin test responses had negative RAST results, In pat
ients with positive skin test responses, sting challenges were performed in
141 of 196 patients, with 30 systemic reactions. Sting challenges were per
formed on 37 of 43 patients with negative skin test responses and positive
venom-specific IgE and in 14 of 56 patients with negative skin test respons
es and negative RAST results. There were 11 patients with negative skin tes
t responses who had systemic reactions to the challenge sting: 2 had negati
ve RAST results, and 9 had positive RAST results at 1 ng/mL, The frequency
of systemic reaction was 21% in patients with positive skin test responses
and 22% in patients with negative skin test responses (24% in those with po
sitive RAST results and 14% in those with negative RAST results);
Conclusions: Venom skin test responses can be negative in patients who will
subsequently experience another systemic sting reaction. Venom skin test r
esponses are negative in many patients with a history of systemic allergic
reactions to insect stings and may be associated with positive serologic te
st responses for venom-specific IgE antibodies (sometimes strongly positive
results). Venom skin test responses should be repeated when negative, alon
g with a serologic IgE antivenom test. Better diagnostic skin test reagents
are urgently needed.