Efficacy and safety of rush immunotherapy in patients with Hymenoptera allergy in Japan

In Japan, approximately 40 persons die annually from anaphylaxis caused by Hymenoptera stings. Venom immunotherapy is considered safe and effective for the treatment of allergic systemic reactions caused by Hymenoptera stings in patients with Hymenoptera allergy. We studied the efficacy and safety of rush immunotherapy in patients who had a history of systemic reactions to Hymenoptera stings in Japan. Between 1988 and 2002, 95 patients with a history of systemic reactions to Hymenoptera stings were investigated. The stings originated from honeybees in 5 patients, yellow jackets in 28, wasps in 48, both yellow jackets and wasps in 9, and both yellow jackets and honeybees in 5. All patients had venom-specific IgE antibodies in sera (RAST score > or = 2) and received rush immunotherapy with venom extracts at our hospital. Forty-three patients had 63 field re-stings during immunotherapy. Of these patients, 41 (95.3%) with 59 field re-stings (93.7%) had no systemic reactions. Two patients (4.7%) with four field restings (6.3%) had anaphylactic shock. Although anaphylactic reactions developed in two patients (2.1%) during rush immunotherapy with honeybee venom and one patient (1.1%) during maintenance therapy wasp venom, systemic adverse reactions were mitigated by treatment with antihistamines before venom injection. Our results show that immunotherapy is safe and effective for the prevention of systemic reactions to Hymenoptera re-stings in patients with Hymenoptera allergy. We therefore recommend that patients who are allergic to Hymenoptera venom prophylactically receive immunotherapy.     

Studies of the natural history of stinging-insect allergy: long-term follow-up of patients without immunotherapy

This study reports the clinical and immunologic responses of 29 patients who were observed during a prolonged period after insect-sting anaphylaxis without venom immunotherapy. At the time of their initial evaluation, all patients had venom-specific IgE, detected by skin test or RAST. Their mean age was 21 years; 16 patients were 16 years of age or less. There were 18 male and 11 female patients. Eleven patients had urticaria and angioedema as their only symptoms of anaphylaxis, and 18 patients had respiratory and/or cardiovascular symptoms. Reassessment was done 5 or more years after the initial evaluation. The average time at reevaluation was 10.1 years after the initial sting reaction. There had been 25 re-stings in 17 patients, with three systemic reactions occurring in two patients, an overall reaction rate of 12%. The time interval between the initial sting reaction and the follow-up sting was 2 to 14 years, mean 7.3 years. In patients with initial urticaria/angioedema symptoms only, there were 11 re-stings with no reactions. In patients with initial cardiovascular/respiratory symptoms, there were 14 re-stings with three reactions. At the time of follow-up evaluation, venom-specific IgE had generally decreased. In six of 25 patients, venom skin tests became negative, and in eight of 24 patients, the RAST became negative. These observations suggest that in many patients, stinging insect allergy is a self-limited process, with loss of clinical sensitivity and immunologic reactivity.     

Clinical and immunologic studies of patients with large local reactions following insect stings

During the summer of 1978, 22 patients who had large local reactions following insect stings were evaluated for the development of potential systemic sensitivity. Approximately half the patients had venom IgE antibodies, detected by either the immediate skin test or radioallergosorbent test (RAST). A control group of 26 patients experiencing normal sting reactions had only a 15% incidence of venom-specific IgE. No correlations could be found between the presence of venom-specific IgE and age, sex, sting location, atopic history, or prior stings. IgE antibodies were found in 13 of 17 patients who had experienced local reactions lasting more than 48 hr. Serum venom-specific IgG was detected in only three of 19 patients. These results suggest that following large local reactions from insect stings patients must be individually assessed for the presence of venom-specific IgE and consideration for specific immunotherapy.     

Insect venom allergy: a prospective case study showing lack of correlation between immunologic reactivity and clinical sensitivity

This case report demonstrates the lack of correlation between clinical sensitivity to insect venoms and immunologic reactivity as indicated by the presence of venom-specific IgE. A 20-yr-old venom collector was monitored over a 3-yr period with measurements of venom-specific IgE (skin test and RAST) and venom-specific IgG. In the first year of venom collection, multiple stings were tolerated with no reaction. In the second season, she had an anaphylactic reaction after a yellow jacket sting. Subsequently, there was a rising titer of serum yellow jacket and bee venom-specific IgE and positive skin-test reactions. In the third season, yellow jacket, hornet, and bee venom skin tests remained positive and serum IgE antibody titers remained elevated. Stings from all three insects were tolerated with no reaction. Throughout the 3-yr course, serum venom-specific IgG remained low and unchanged. The factors other than IgE-modulating clinical anaphylaxis, perhaps responsible for this clinical and immunologic dichotomy, are unknown. These observations add a further complication to the choice of patients for venom immunotherapy.     

Further observations of stopping venom immunotherapy: Comparison of patients stopped because of a fall in serum venom-specific IgE to insignificant levels with patients stopped prematurely by self-choice

This study extends our experience applying the criterion of a fall in serum venom-specific IgE (RAST) to insignificant levels as an indication to stop venom immunotherapy (VIT) and compares the follow-up results with the results of re-stings in patients who stopped VIT "prematurely" by self-choice. All patients in both groups had a history of venom anaphylaxis, most with cardiovascular and/or respiratory symptoms and initial elevated serum venom-specific IgE; all patients received VIT. The groups were closely matched for age, sex, nature of initial sting reaction, and insect identification. In the group with low-level RAST titers, the duration of VIT was 6 months to 5 years (mean 2 1/2 years). Re-stings occurred from 1 month to 7 years (mean 2.2 years) after cessation of therapy. There were 75 re-stings in 41 patients with four systemic reactions (10% per patient and 5% per sting). All four reacting patients had tolerated several stings during cessation of VIT before the re-sting systemic reaction; two patients had subsequent stings with no reaction. In the group of patients who stopped VIT for other reasons, the duration of VIT was 5 months to 4 years (mean 1.8 years). Re-stings occurred from 4 months to 6 years (mean 2.1 years) after stopping therapy. There were 74 re-stings in 38 patients with seven systemic reactions in four patients (9.5% per patient and 10.5% per sting). Two of the reacting patients had tolerated stings before the re-sting reaction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Late-onset allergic reactions, including serum sickness, after insect stings

Allergic reactions after insect stings may have a delayed onset, differing from the usual immediate anaphylactic pattern. Ten patients, aged 6 to 78 years, had allergic reactions 1 to 2 weeks after an insect sting. Six patients had had multiple stings preceding the reaction. In two instances, immediate anaphylaxis also occurred. Four of the 10 patients had serum sickness-type reactions; two other patients had more severe anaphylactic symptoms, including throat edema. All patients in this group had venom-specific IgE; four of the 10 patients had serum venom-specific IgG. Eight patients subsequently received venom immunotherapy (VIT). There have been no reactions from seven re-stings. Five patients had generalized hives starting 6 to 24 hours after an insect sting. All patients in this group had venom-specific IgE; three patients have received VIT. Two other patients developed hives, one with throat edema 3 days after an insect sting. Both patients had high titers of serum venom-specific IgE; neither patient has received VIT, one patient because of extreme sensitivity. These observations suggest that after an insect sting, patients may develop delayed-onset allergic symptoms that range from typical anaphylaxis to serum sickness and are mediated by venom-specific IgE. VIT is recommended for patients with these reactions.     

Evaluation of decline in serum venom-specific IgE as a criterion for stopping venom immunotherapy

During a 7-year period, venom immunotherapy has been stopped in 57 patients because of a fall in IgE antibody titers to insignificant levels (RAST less than 10% STD). All patients had a history of venom anaphylaxis and elevated venom-specific IgE before therapy. Maintenance doses of 50 micrograms were administered every 4 to 6 weeks; 30 patients received yellow jacket venom, and 16 patients received honeybee venom only. Therapy was stopped after treatment from 1 to 8 years (mean 2.8 years). Repeat skin tests demonstrated an average two-log decrease in sensitivity; 35 of 55 tests remained positive at venom concentrations of less than or equal to 0.1 micrograms/ml. There were 55 re-stings in 24 patients, occurring from 3 months to 5 years after cessation of therapy, resulting in three systemic reactions. One patient, previously treated with bee venom, reacted to a yellow jacket sting. These re-sting reactors also had tolerated several other stings after therapy was stopped. Thus, the two actual reactions represent a "failure" rate of 8% per patient and 4% per sting, compared to reaction rates of 27% and 17% in patients who stopped therapy without physician advice. These data suggest that this criterion may be reliable for stopping therapy. However, subsequent tolerated re-stings may require continued patient evaluation.     

Modified rapid venom desensitization

The clinical and immunologic response to a modified rapid (r) regimen of venom immunotherapy was evaluated and compared to a traditional (t) therapeutic regimen. Nineteen patients in the r group received a starting dose of 0.01 μg and reached a maintenance dose of 50 μg in 7 weeks. Twelve patients in the t group received an average of twenty-one injections on a weekly basis, reaching the same maintenance dose. The age and sex distribution and pre-treatment venom-specific IgE titres (RAST) of both groups were comparable. There were thirteen local reactions to venom therapy in both groups and no systemic reactions. Following therapy, most patients developed a rising titre of serum venom-specific IgG (V-IgG). Serum venom-specific IgE (V-IgE) changes were similar in the two groups; over half of the patients had a falling titre when on maintenance dose. Twelve patients were re-stung after reaching maintenance dose. Only one developed a mild systemic reaction, an individual who failed lo show a V-IgG response with rapid therapy. Five of nine patients did not have an anamnestic V-IgE response. This rapid method of venom immunotherapy appears to be safe, clinically effective, and comparable to traditional dosing without additional adverse reaction.     

Insect allergy. Predictive value of diagnostic tests: a three-year follow-up study

One hundred and six adults with various reactions to yellow jacket (YJ), honey bee (HB) or unidentified insects (UI) were tested for allergy to insect venoms. For various reasons none received immunotherapy. Individuals completed questionnaires annually for three consecutive years and described sting reactions within the previous season. Ninety subjects completed all the questionnaires and 77 of these were re-tested at the end of the period. Nine out of 25 patients reacted with a systemic reaction when re-stung. High IgE and low IgG venom-specific antibody levels indicated an unfavourable prognosis, since eight of 11 individuals who initially presented venom-specific IgE > RAST class 2 and venom-specific IgG below detection limit had systemic reactions at re-sting. No such reactions occurred in subjects with no specific IgE and only one out of six with specific IgE as well as IgG reacted systematically. Skin prick tests (SPT) of <3mm with YJ venom 1,000 μg/ml excluded later systemic symptoms to stings, whereas larger skin reactions gave an equal chance of systemic or local reactions at re-sting. In individuals not stung by UI, YJ and/or HB the decline in venom-specific IgG and IgE was significant, median values ranging from 41% to 75% over the 3-year period. The decline was unaffected by the type of sting reaction prior to the initial test. SPT results did not change significantly. The findings are relevant when testing patients several years after their last insect sting and the results might indicate that the antibody decline is accompanied by a decrease in clinical sensitivity.     

The value of immunotherapy with venom in children with allergy to insect stings

BACKGROUND. The treatment of patients allergic to insect stings with insect-venom injections has been shown to be 97 percent effective in reducing the risk of sting-induced anaphylaxis. However, the frequency of systemic reactions to subsequent stings in unimmunized adults with previous reactions is approximately 60 percent. To determine which factors, in addition to a history of reaction and evidence of venom-specific IgE antibody, predispose patients to future insect-sting reactions, we studied a venom-sensitive group of children who were deemed to be at relatively low risk for severe reactions; 28 percent of them received venom therapy. METHODS. We studied 242 children, 2 through 16 years of age, each of whom had had a systemic allergic reaction, affecting only the skin, to an insect sting. Each child had a positive skin-test reaction to one or more of five hymenopteran venoms. Sixty-eight children received immunotherapy with insect venom and 174 did not; about half were randomly assigned to treatment groups, and the rest were assigned on the basis of the patient's (or the parents') choice. The results of accidental stings during four years of observation were evaluated. RESULTS. In the treated group, 84 stings in 36 patients resulted in one systemic reaction (1.2 percent of stings). In contrast, 196 stings in 86 untreated children resulted in 18 systemic reactions (9.2 percent of stings, P less than 0.001). Sixteen of these 18 reactions were judged to be milder than the patient's reaction to the first sting, 2 were similar in severity, and none were more severe. CONCLUSIONS. These data confirm that immunotherapy with insect venom prevents recurrences of systemic reactions after subsequent insect stings. Because of the surprisingly low rate of reactions among untreated children, we could not identify any characteristics that were predictive of repeat reactions. Since only 9.2 percent of stings in the untreated children led to a systemic reaction and since there was no progression to a more severe reaction, we conclude that venom immunotherapy is unnecessary for most children who are allergic to insect stings.     

Prolonged interval maintenance venom immunotherapy

Current guidelines recommend indefinite administration of venom immunotherapy at 4-week intervals. To simplify this therapy, we examined the clinical and immunologic response after extending the interval between maintenance venom injections to 6, 8, and 12 weeks. Twenty-six patients who had had sting anaphylaxis and positive skin tests received maintenance bee or yellow jacket venom immunotherapy at greater or equal to 6-week intervals. This extended interval was started after a prior average 4-week maintenance interval of 2.3 years. Injections were given at 6-week intervals to all 26 patients and extended to 8-week intervals in 10, and 12-week intervals in 3 patients. Following venom injections, there were 14 mild local reactions and no systemic reactions. No adjustment in dosing was necessary. While on prolonged interval maintenance venom immunotherapy, there were 17 re-stings in 12 patients with no systemic reactions. During prolonged interval maintenance venom immunotherapy, either the serum venom-specific IgG increased or the already elevated titers remained the same in 18 patients and decreased in 2. In the others, preexisting titers were low and unchanged. Serum venom-specific IgE tended to slowly decrease. These clinical and immunologic data suggest that a 4-week maintenance interval may be safely extended.     

Discontinuation of yellow jacket venom immunotherapy: Follow-up of 75 patients by means of deliberate sting challenge

Background: Venom immunotherapy is effective in preventing systemic reactions in patients with a history of an anaphylactic reaction to Hymenoptera stings. It is uncertain how long venom immunotherapy should be continued. Objective: We evaluated whether the duration of venom immunotherapy given to yellow jacket–sensitive patients related to the risk of an anaphylactic reaction to a later sting. Methods: Seventy-five yellow jacket–sensitive patients (29 male and 46 female) received a median number of three in-hospital sting challenges from a live insect in 3 subsequent years after discontinuation of venom immunotherapy. An anaphylactic reaction to one or more of the sting challenges was considered a relapse. We analyzed whether patients with and patients without a relapse differed in terms of gender, age, preimmunotherapy skin test data, preimmunotherapy level of venom-specific IgE, severity of the field-sting reaction that preceded immunotherapy, severity of the reaction to the sting challenge that preceded immunotherapy, adverse reactions to immunotherapy, changes in IgE and IgG₄ levels during immunotherapy, duration of immunotherapy, and presence of venom-specific IgE after cessation of therapy. Results: Venom immunotherapy was given for a median duration of 40 months (range, 7 to 120 months). Relapses were observed in six patients. In two of them, a rather severe anaphylactic reaction was observed after the second sting challenge. No relation was found between duration of venom immunotherapy and relapse risk. The relapse rate was higher among patients with high levels of specific IgE before and after immunotherapy. During therapy, the mean level of specific IgE decreased. This decline persisted in the 3 following years. No relapses of sting reactions were observed among patients without detectable specific IgE. Conclusion: Discontinuation of venom immunotherapy appears safe for patients with pretreatment IgE antibodies if these antibodies can no longer be detected during immunotherapy. For the remaining patients, a treatment period of 3 years may suffice. After discontinuation of immunotherapy, a clinical sting challenge can be considered to estimate the patient's current grade of hypersensitivity. (J Allergy Clin Immunol 1997;100:767-70.)     

Late onset reactions following venom immunotherapy and venom skin tests

This report describes patients who had late onset reactions following venom immunotherapy and venom skin tests. Six adult patients had symptoms of fatigue, malaise, fever, headache, and joint ache, starting four to six hours after venom immunotherapy and lasting up to four days. Two of the patients had prolonged reactions at or adjacent to the skin test sites. All of these patients had a history of venom anaphylaxis; four had severe cardiovascular symptoms. All received yellow jacket venom immunotherapy and four honeybee venom immunotherapy. In four patients, the reactions occurred following small venom doses, 0.1 to 2 micrograms. Two patients reacted after maintenance doses of 50 micrograms. There was no relationship to the serum IgE or IgG antibody titers. All but one patient had serum venom-specific IgE but the titers covered a wide range. Serum venom-specific IgG was present in four patients. There was no response in lymphocyte culture to bee venom stimulation in two patients. Two of these patients stopped venom immunotherapy; one had reached the maintenance dose. In three patients, prophylactic parenteral steroids have ameliorated the reactions. After a temporary dose reduction, the sixth patient is now asymptomatic. A seventh patient developed asthma, 12 hours following a maintenance dose of 50 micrograms of yellow jacket venom. Concomitant steroid administration has effectively prevented the reaction. Another patient, a 6-year-old boy, developed fever, edema of the face and lips, erythema of the leg, and a large, tender right inguinal node eight hours following venom skin tests.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prospective observations on stopping prolonged venom immunotherapy

After a decade spent establishing the safety, efficacy, and optimal techniques for venom immunotherapy, we have begun a series of studies to determine how long venom immunotherapy must be continued. In retrospective surveys, patients who had stopped venom immunotherapy after 1 to 2 years had a substantial risk (25%) of systemic sting reactions, but this was less than 50% of the risk in untreated patients. In this first prospective study, 30 patients elected to stop venom immunotherapy after at least 5 years of therapy. Skin test sensitivity had decreased significantly during therapy in 18/30 patients but remained clearly positive in 23/30 (seven patients became equivocal or negative). Serum venom-specific IgE antibodies were at the lower limit of detection (1 ng/ml) in 11/30 patients. After stopping treatment, the mean serum venom-specific IgG antibody level declined from 5.5 +/- 0.6 micrograms/ml to 2.4 +/- 0.3 micrograms/ml by 9 months, which is the same as the mean venom IgG in untreated patients. After 12 months without therapy, live sting challenge caused no systemic reaction in 29 patients. The mean venom IgG level 1 month after the sting had risen significantly to 4.1 +/- 0.5 micrograms/ml, but there was no significant increase of venom IgE. These results suggest that prolonged venom immunotherapy leads to isotype-specific suppression of the venom IgE antibody response and may provide persistent clinical protection by mechanisms other than IgG blocking antibodies. The observations are to be interpreted very cautiously. Further investigations are needed to extend these observations in additional patients and for longer periods of time, and to examine possible mechanisms for this apparent loss of clinical reactivity.     

Venom-specific IgG antibodies in bee and wasp allergy: lack of correlation with protection from stings

This paper investigates the relationship between venom IgG levels and protection from stings. Venom-specific IgG antibody levels have been measured by radioimmunoassay in untreated wasp- (n= 38) and bee-allergic (n=16) patients presenting with systemic reactions to stings and in a sub-group of these (wasp= 15; bee = 9), before and after the initial course of venom immunotherapy (VIT). A history was taken of all reactions, the last systemic reaction being graded on a scale of 1–8 and of the number and timing of stings. In untreated patients venom IgG levels were much higher in bee-allergic patients (mean ± s.e. = 68.2 ± 7.1 % positive pool) than in the wasp group (27.1 ± 4.2%) (P< 0.05 Mann-Whitney U-test). There was a marked rise in venom IgG after the initial course of VIT in the wasp group (geometric mean and 95% confidence intervals = 40.5%, 28.8?54.3) but a much smaller rise in the bee group (15.3%, 6.6–24.1), with no overlap in the 95% confidence intervals. Bee patients, who were mainly beekeepers or their relatives, had been more heavily immunized with venom than wasp patients. They had received: (i) more stings (mean number of stings: bee, 26; wasp, 4; P< 0.001) and (ii) more stings per year. Wasp patients received their smaller number of stings over a much longer period, up to 40 yr. There was no correlation between the severity of the last systemic reaction and the venom IgG levels alone or venom IgG and IgE levels in combined analysis in either bee or wasp patients. This study shows that the pattern of IgG response differs in bee and wasp-allergic subjects, and that most bee-allergic subjects with systemic reactions have high levels of venom IgG. The degree of immunization with venom seems to be an important determinant of the venom IgG level. Our findings suggest thai venom-specific IgG levels do not predict systemic reactions to stings and are not useful for monitoring VIT. If protection from stings is IgG-mediated, our observations suggest that the relevant immune response is more complex, possibly involving IgG sub-classes, IgG antibodies to individual venom antigens or antibody affinity, and not adequately reflected by measurement of the concentration of venom-specific IgG.     

Systemic reactions during maintenance immunotherapy with honey bee venom

Immunotherapy with hymenoptera venoms is safe and effective in most patients but treatment failures have been reported. Five patients experienced systemic symptoms of anaphylaxis when they were in maintenance immunotherapy with honey bee venom. In one case, the patient presented a severe life-threatening reaction when stung by a honey bee. Three others had the development of new clinical sensitivity suggesting a re-sensitization. This occurred in the fifth patient after a severe viral infection. By means of a rush protocol and monthly doses of 200 to 400 micrograms of honey bee venom, the patients were subsequently protected efficiently. In most cases these reactions might have been predicted since patients experienced large local reactions prior to the systemic reactions when allergens were injected. Further, in four cases there was an increased skin test reactivity or raised serum honey bee venom IgE levels or both. In all patients, the levels of serum honey bee venom IgG was under 200 U/mL (IgG Pharmacia RAST).     

The evaluation of the common diagnostic methods of hypersensitivity for bee and yellow jacket venom by means of an in-hospital insect sting

Between 1979 and 1983 230 patients visited our clinic in connection with allergic reactions after insect stings. One hundred six patients were subjected to a diagnostic provocation test with a live insect; 86 of these patients had a history of systemic reactions and a positive skin test and RAST with insect venom. Thirty-one of these patients, including one patient with a negative RAST and another with a negative skin test, demonstrated a generalized reaction and were subjected to immunotherapy with pure insect venom. Comparison of the diagnostic data from 31 patients with reactions with those of the 57 nonreacting patients from the 86 patients aforementioned reveals that at this time only a provocation test with a live insect can provide the evidence of an allergy to insect venom leading to such a severe generalized reaction that admission to probably lifelong immunotherapy is justified. The measurement of the venom-specific IgG, the ratio of IgG/IgE, and (for bee patients) the serum antibody titer against the bee venom components phospholipase A and hyaluronidase did not improve the diagnosis of a current hypersensitivity against insect venom.     

Allergic reactions following first insect sting exposure

Over a 10-year period, 750 patients were evaluated because of anaphylaxis following insect stings. Sixty-five patients were identified who had reactions after their first sting exposure. Their clinical features and symptoms of anaphylaxis were the same as the much larger group of patients who had allergic reactions following prior exposure to insect stings. When evaluated following the sting reaction, the majority of these patients had venom-specific IgE detected by skin test or in the serum by the RAST. Fifty-three re-stings occurred in 31 patients. In untreated or whole body extract-treated patients, there were 43 re-stings resulting in 13 reactions. There were no reactions following 10 re-stings in venom-treated patients. In a subgroup of 15 patients with undetectable venom-specific IgE, there were 16 re-stings in eight patients, leading to three systemic reactions. The occurrence of allergic reactions following first sting exposure adds further support to the thesis that some sting reactions are non-IgE-mediated.     

Insect sting allergy with negative venom skin test responses

BACKGROUND: In our 1976 controlled venom immuno rapy trial, 33% of 182 patients with a history of systemic reactions to insect stings were excluded because of negative venom skin test responses. There have been reports of patients 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 negative skin test response and insect sting allergy and to determine the frequency and significance of negative skin test responses in patients with a history of systemic reactions to insect stings. METHODS: We prospectively examined the prevalence of negative venom skin test responses in patients with a history of systemic reactions to stings. In patients who gave informed consent, we analyzed the outcome of retesting and sting challenge. RESULTS: Of 307 patients with positive histories screened for our sting challenge study, 208 (68%) had positive venom skin test responses (up to 1 microg/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 RAST result was a low positive (1-3 ng/mL), or repeat venom skin test responses were positive; another 7 (7%) patients had high venom-specific IgE antibody levels (4-243 ng/mL). Notably, 56 (57%) of 99 patients with positive histories and negative skin test responses had negative RAST results. In patients with positive skin test responses, sting challenges were performed in 141 of 196 patients, with 30 systemic reactions. Sting challenges were performed 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 responses and negative RAST results. There were 11 patients with negative skin test responses who had systemic reactions to the challenge sting: 2 had negative 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 positive 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 responses are negative in many patients with a history of systemic allergic reactions to insect stings and may be associated with positive serologic test responses for venom-specific IgE antibodies (sometimes strongly positive results). Venom skin test responses should be repeated when negative, along with a serologic IgE antivenom test. Better diagnostic skin test reagents are urgently needed.     

Insect sting anaphylaxis in patients without detectable serum venom-specific IgE

Following insect sting anaphylaxis, twenty-five patients of over 500 evaluated, did not have detectable serum venom-specific IgE. Twenty-two were evaluated within 1 year of the reaction, fifteen within 6 months. Anaphylaxis occurred in six patients after their first sting exposure. The clinical features of the sting reaction were typical of the reaction occurring in insect-allergic patients with serum venom-specific IgE. Eleven of the twenty-five patients had negative venom skin tests. These observations suggest that a non-IgE mechanism may be responsible for a minority of insect sting reactions.