Positive Venom Skin Tests Research Articles

Venom immunotherapy reduces large local reactions to insect stings

Large local reactions to insect stings cause significant morbidity and impair quality of life. Venom immunotherapy is not recommended because of a low risk for future systemic reaction and unproven efficacy in preventing large local reactions. To determine the feasibility of performing a controlled trial to examine the efficacy of venom immunotherapy in reducing the size and duration of large local reactions. Sting challenge in 41 patients with previous large local reactions and positive venom skin tests caused large local reactions 16 cm or larger in 34 patients, and 29 consented to treatment. Venom immunotherapy was initiated in 19, and 10 were untreated controls. Sting challenge was repeated after 7 to 11 weeks (control patients then began venom immunotherapy), and annually for as long as 4 years. After 7 to 11 weeks of treatment, the size and duration of large local reactions decreased 42% and 53%, respectively, in treated patients and 18% in controls (P < .01 for both). The response was similar after 1 year, and improved after 2 to 4 years to 60% and 70%, respectively. Venom immunotherapy significantly reduced the size and duration of the large local reactions, and the efficacy improved over a period of 2 to 4 years of treatment. Further studies are needed to establish the safety and efficacy of venom immunotherapy for large local reactions, the optimal duration of treatment, and the mechanism for the differences in degree and rate of clinical response compared with venom immunotherapy in systemic reactors.

Venom immunotherapy (VIT) for large local reactions (LLR) to insect stings: A pilot study

Rationale Patients with LLR to stings may have frequent reactions and fear systemic reactions(SR), but VIT is not recommended because their risk of SR is only 10%. We aim to investigate, in patients with previous LLR, the frequency of SR from sting challenge, and the efficacy of VIT in reducing LLR. Methods Consenting patients with a history of LLR and positive venom skin tests had an initial sting challenge while being monitored for SR (n=21). LLR >16 cm occurred in18 patients (86%), in whom VIT was started in 11 patients (3 HB, 6 YJ & 2 both) and 5 were untreated controls. All 16 patients had repeat sting challenge after 6-8 weeks. Results Skin tests did not cause LLR and were generally the same, or stronger than, those of patients with previous SRs. SR occurred in 1/21(5%) of patients stung. In treated patients the peak diameter of the LLR was reduced >30% in 78%, and >50% in 56%. The duration of the LLR was reduced >40% in 100% of the treated patients, and the time to reach the peak size was reduced >50% in 89% of patients. Controls had no change in LLR. Conclusions Patients with a history of LLR and positive venom skin tests have <10% risk of future systemic reaction, but often have recurrent LLR. VIT greatly reduced LLR and almost all patients requested to continue VIT. Further studies are required to determine the prevalence of LLR requiring VIT, and the efficacy of VIT.

Stinging insect allergy

Stinging insect allergy is a relatively common medical problem, responsible for an estimated 40 fatalities per year in the USA and considerable anxiety and lifestyle modification. There are no criteria to identify people at risk of initial venom anaphylaxis. Reactions may occur at any age and are unrelated to the time interval of prior venom exposure. There is an approximate 60% re-sting reaction rate in people who have had sting anaphylaxis and have positive venom skin tests. Re-sting reactions are more likely to occur in adults than in children and in people who have had more severe anaphylactic symptoms. Positive venom intradermal skin tests confirm the diagnosis of potential stinging insect allergy in people who have had sting reactions. Venom immunotherapy provides almost 100% protection from further sting reactions. It is recommended for all people who have had venom anaphylaxis and have positive skin tests, except for children who have dermal reactions only. Details of venom dosing are well established. The adequate duration of venom immunotherapy is still an unresolved issue. Conversion to a negative skin test appears to be an absolute criterion to discontinue treatment. In the presence of a persistent positive skin test, 3–5 years of immunotherapy is generally sufficient. People who have had severe reactions, such as loss of consciousenss, may require indefinite therapy.

HYMENOPTERA

Systemic reactions due to insect stings are relatively frequent, affecting up to 3.0% of the population. These reactions are due to IgE antibodies, which react with antigenic components contained in honeybee, yellow jacket, hornet, and wasp venoms. In addition, stings of the fire ant and harvester ant, nonwinged Hymenoptera, cause similar anaphylaxis. There are no reliable criteria that identify people at potential risk for sting anaphylaxis other than the occurrence of a prior reaction. Systemic reactions may occur at any age. Milder reactions, such as urticaria and angioedema, are more common in children. Severe reactions, such as shock, hypotension, and loss of consciousness, are relatively more common in adults. It is estimated that at least 40 deaths occur yearly in this country from insect sting anaphylaxis. People with prior systemic reactions have an approximately 60% rate of recurrent anaphylaxis. This incidence is higher in people who have had more severe symptoms and generally higher in adults than children. People who have had insect anaphylaxis and demonstrate positive venom skin tests should receive venom immunotherapy.

INSECT STING ANAPHYLAXIS

Insect sting anaphylaxis is a relatively common problem, estimated to affect at least 0.4% of the population. The allergic reactions are mediated by IgE antibodies directed against constituents in honeybee, yellow jacket, hornet, and wasp venoms. In addition, anaphylaxis occurs following stings by nonwinged Hymenoptera, the fire ant, and harvester ant. The anaphylactic symptoms are typical of those occurring from any cause. The majority of reactions in children are mild and frequently dermal (hives, edema) only. The more severe reactions such as hypotension and loss of consciousness can occur at any age but are relatively more frequent in adults. It is estimated that 40 to 50 deaths per year occur in this country from insect sting anaphylaxis, with the likelihood that others are undiagnosed. The majority of severe reactions and deaths have occurred in patients unaware of potential allergy. After sting anaphylaxis, about 50% of unselected patients will continue to react to re-stings in the absence of venom immunotherapy. Children with dermal reactions only have a benign course and are unlikely to have recurrent reactions. Patients with more severe reactions are likely to have repeat anaphylaxis of similar severity. Patients with a history of insect sting anaphylaxis and positive venom skin tests should have epinephrine available for self-administration, and are candidates for subsequent venom immunotherapy.

Stinging insect allergy

Insect sting anaphylaxis is a relatively common problem estimated to affect at least 0.4% of the population and is responsible for at least 40 deaths per year in the United States. The allergic reactions are mediated by IgE antibodies directed at constituents in honeybee, yellow jacket, hornet, and wasp venoms. In addition, increasing numbers of reactions occur from fire ant stings, non-winged Hymenoptera present in the Southeastern United States. The anaphylactic symptoms are typical of those occurring from any cause. Most reactions in children are mild, frequently involving dermal manifestations (hives, edema) only. The more severe reactions, such as shock and loss of consciousness, can occur at any age but are relatively more common in adults. Following sting anaphylaxis, approximately 50% of unselected patients will continue to have allergic reactions to subsequent stings. The natural history of the disease process is influenced by the severity of the anaphylactic symptoms. Children with dermal reactions only have a benign course and are unlikely to have recurrent reactions. Patients with more severe reactions are at risk for repeat anaphylaxis. Patients with a history of insect sting anaphylaxis and positive venom skin tests should have epinephrine available and are candidates for subsequent venom immunotherapy, which provides almost 100% protection against subsequent re-sting reactions. Recommendations for the duration of immunotherapy are evolving. Venom therapy can be stopped if skin test reactions become negative. For most patients, 3 years of therapy appears adequate, despite persistence of positive venom skin tests.

INSECT STING ALLERGY

Venom immunotherapy is highly effective prophylaxis for individuals at risk for insect sting anaphylaxis. Venom immunotherapy should be administered to all patients who have had a serious anaphylactic sting reaction (e.g., throat edema, dyspnea, hypotension, shock, loss of consciousness) and have positive venom skin tests. Children who have dermal (hives, edema) reactions only have a very benign course and do not require venom immunotherapy. Adults with similar mild sting reactions also appear to have a benign course, but data are still insufficient to recommend withholding venom immunotherapy. A positive venom skin test has been defined as a reaction to venom concentrations of 1.0 μg/mL or less. Reactions to only this top concentration of 1.0 μg/mL should be interpreted with caution, as nonspecific reactions may occur with this dose. Venom immunotherapy is usually administered with all venoms to which there is a positive skin test. Immunologic studies suggest that these multiple positive reactions are due to venom cross-reactivity. If the culprit insect can be identified, single venom therapy is effective. Recommended maintenance doses are 100 μg of single venoms and 300 μg of mixed vespid venoms. A lower dose, 50 μg of single venoms, appears to be adequate. After 1 year of therapy, the 4-week interval between maintenance doses can be extended to 6 and even 8 weeks, without loss of effectiveness or increased reactions. Recommendations for duration of therapy are evolving. Venom immunotherapy can be stopped if skin test reactions become negative. For most patients, 3 years of therapy appears adequate, despite persistence of positive venom skin tests.

The Hymenoptera venom study II: Skin test results and safety of venom skin testing

Data are summarized in this Hymenoptera venom study (HVS) article on the safety of skin testing with venom extracts. Of the 3236 subjects studied, 89% had experienced an historical sting systemic reaction (SSR). Seventy-four percent of all subjects and 76% of subjects who had experienced an historical SSR had a positive skin test to at least one venom. More subjects tested positive to yellow jacket venom (51.8%) than to any other venom. There were no significant differences of the wheal and erythema sizes associated with different venoms or different historical sting reactions. Forty-five percent of subjects with positive venom skin tests (VST) were positive to wasp, and 89% of these subjects were also positive to at least one of the following venoms: yellow jacket, yellow hornet, or white-faced hornet. Sixty-four of the 3236 subjects studied (2%) had a systemic reaction (SR) during VST; 13 of the SRs (0.4%) were severe. Thirteen of 64 adverse reactions (20%) were possibly vasovagal, and six other subjects (9%) demonstrated no symptoms of immediate-type hypersensitivity. Thus, 45 (1.4%) of the 3236 subjects tested had an SR that was considered to be a reaction of hypersensitivity, of which eight reactions (0.25%) were severe. Allergic SRs are associated with VST but are unusual and are rarely severe.

Epidemiology of Insect Venom Sensitivity

The prevalence of insect sting reaction and of venom sensitization in adults is unknown. We report the results of intake evaluation of a stratified random sample of a large adult population previously studied for the determinants of atopic disease. In 269 subjects, the prevalence of systemic allergic sting reactions was 3.3% and 26.5% had IgE antibodies to venom demonstrated by skin test or radioallergosorbent test. Asymptomatic sensitization (positive venom skin test) was observed in 15% of subjects with no history of an allergic sting reaction. Positive venom skin tests were more frequent in men, in those with positive skin tests to inhalant allergens, and in subjects aged 20 through 29 years. A positive venom skin test or radioallergosorbent test was more frequent in subjects who had been stung within the previous 3 years (35%) than in those stung more than 3 years before (20%). We conclude that both systemic allergic reactions to insect stings and asymptomatic sensitivity to venom are common and that most affected persons never seek medical advice. The significance of asymptomatic venom sensitization is unknown.

A study of the prevalence and clinical significance of venom-specific IgE

The prevalence of unrecognized Hymenoptera-venom sensitization, assessed by venom skin tests (VSTs) in adults with no history of adverse reactions to sting, has been as high as 12% in previous epidemiologic studies. To assess further the clinical importance of positive VSTs in such individuals, we skin tested 33 subjects stung in the field during the preceding 12 months without reaction, and 33 persons who denied being stung in the preceding 3 years. Among the recently stung gruop, 12 33 had at least one positive VST (⩾2 +) at 1.0 μg/ml, whereas 5 33 had positive VST at 0.1 μg/ml. In contrast, only 2 33 nonstung subjects had positive VST at 1.0 μg/ml, and none were positive at 0.1 μg/ml. To estimate, prospectively, the sensitization rate after insect stings, we studied a third group of 11 nonsensitive patients with negative skin tests to Hymenoptera. After a deliberate in-hospital honeybee sting, only 1 11 developed a persistently positive honeybee VST. From among the three groups, we then performed nine sting challenges in eight patients with positive VSTs, and all stings were tolerated without significant reaction. We also measured IgE antibodies to Hymenoptera venoms in random blood bank donors. During April to May, 2 216 sera contained elevated venom-specific IgE antibodies, whereas 14 201 sera collected from October to November contained elevated venom-specific IgE antibodies. We conclude that a small but appreciable portion of the population has venom-specific IgE antibodies and that the prevalence is seasonably variable. Our data indicate that persons recently stung without significant reaction contribute to this group but that only a small portion of this group is at risk for a systemic reaction with a future sting.

Clinical and immunologic observations in patients who stop venom immunotherapy

It is currently recommended that venom immunotherapy (VIT) be continued as long as the sensitivity persists (indicated by positive venom skin tests or RAST). In this pilot study, we performed a retrospective survey of the clinical and immunologic effects of stopping VIT. The 82 patients studied had received maintenance VIT for a mean of 14 months and had stopped VIT a mean of 43 months before evaluation. Subsequent “field” stings in 28 patients caused systemic reactions in six cases (22%), which is significantly higher than the 1% to 3% systemic reaction rate in patients who remain on maintenance VIT. The 22% reaction rate is a minimal estimate caused by loss of venom sensitivity in some patients and residual venom-specific IgG antibody levels in others. Reevaluation of venom skin tests and IgG levels was possible in 43 patients. A tenfold decline from before VIT skin test results was observed in 27 patients (63%). Skin tests remained clearly positive in 32/43 (74%), became weakly positive in 9/43 (21%), and 2/43 (5%) became negative. The IgG level declined from typical maintenance levels before stopping VIT (mean 7.2 ± 1.2 μg/ml) to levels typical of untreated patients at the time of retesting (mean 1.95 ± 0.3 μg/ml). Despite the marked fall of IgG antibody, one third of the patients still had levels in the average range observed in patients receiving maintenance VIT. We conclude that there is a substantial risk of anaphylactic sting reaction if VIT is stopped while venom sensitivity persists.

Natural history of large local reactions from stinging insects

In ongoing studies of the natural history of stinging-insect allergy, 133 patients with large local reactions have been evaluated over 8 yr; 79 patients returned for reevaluation. Based on RAST analysis with honeybee and vespid venoms, patients were divided into RAST-positive and RAST-negative groups. Sixty-six patients were RAST-negative with positive venom skin tests in 58%. Seventy-five restings in this group led to no systemic reactions and 74 large local reactions. At follow-up RASTs remained negative, and the incidence of positive skin tests was unchanged. Sixty-seven patients had detectable serum venom-specific IgE covering a wide range in antibody titers, indistinguishable from patients with systemic reactions. Twenty-four of 67 patients received venom immunotherapy (VIT). RAST titers decreased similarly in the VIT and untreated groups. There were 55 restings resulting in 40 recurrent large local reactions occurring in equal incidence in treated and untreated patients. One systemic reaction occurred in an untreated patient. In reviewing 118 patients with sting anaphylaxis, a previous large local reaction occurred in five. These results suggest that after repeat stings, patients with large local reactions tend to have subsequent large local reactions, regardless of the presence of venom-specific IgE or immunotherapy. There is small risk of anaphylaxis. Determination of serum venom-specific IgE by RAST or skin tests does not aid in treatment or in predicting prognosis. Thus skin tests are not necessary in patients who have had large local reactions, and venom immunotherapy is not indicated.

The development of negative skin tests in children treated with venom immunotherapy

Twenty-eight of 62 children (45%) with a history of sting-induced anaphylaxis and initially positive skin tests to venom(s) developed negative venom skin tests to one or more of the venoms used in their treatment after 3 yr or more of immunotherapy. Children who developed negative venom skin tests were less sensitive prior to treatment, as judged by venom skin tests and venom specific IgE antibody determinations, than children who maintained positive venom skin tests. Levels of venom-specific IgE antibodies declined with time in most children, but to lower levels in those with negative skin tests. Venom specific IgG antibody levels were similar in both patients with negative skin tests and those with persistently positive skin tests. The development of negative skin tests may reflect a loss of allergic sensitivity, which is sufficient to allow the physician to consider the discontinuation of venom injections.

Epidemiologic study of insect allergy in children. II. Effect of accidental stings in allergic children

One hundred eighty-one children with non-life-threatening reactions to insect stings and positive venom skin tests were randomized to treatment (53) or no-treatment (128) groups and followed up clinically and immunologically for at least two years to assess the results of accidental stings. Twenty-eight stings in 17 treated patients and 74 stings in 47 untreated children occurred, leading to one mild reaction in a treated patient, and eight in the no-treatment group (P = NS). No reaction was more serious than the original. Based on IgE antibody changes and skin test results, 87% of the untreated children were stung by an insect to which they had clinical sensitivity by skin test. Vespid skin test sensitivity decreased 10-fold or more in both treated (72%) and untreated (44%) children. Of those with increased sensitivity, congruent to 70% had been stung. These data indicate that the incidence of severe reactions on resting is low in insect-allergic children, and that the majority show decreased skin test sensitivity over time.

An epidemiologic study of insect allergy in children. I. Characteristics of the disease

Of 235 children with a history of allergic reactions to insect stings studied, 59 had severe life-threatening systemic reactions, 123 had mild, non-life-threatening systemic reactions, and 53 had large local reactions. The overall male-female ratio was 2:1. Venom skin tests were positive in approximately 89% of each group. Prior whole body extract therapy increased the likelihood of venom skin test reactivity to multiple insect venoms from 51 to 78%. Venom skin test results did not correlate with the severity of previous allergic reactions. One hundred and nine children with NLTR and positive venom skin tests were entered into one of two groups--venom immunotherapy or observation only. During the first six months the treatment group had the expected fourfold rise in venom-specific IgE antibody titers, whereas the observation group had a decline of the mean IgE titer. Patients in the observation group who were accidentally stung had a transient rise in IgE antibody titers. The small number of accidental stings which occurred in both groups resulted in reactions milder than the original reactions. Although based on preliminary data, venom immunotherapy may not be necessary for some children with previously mild systemic symptoms.