Robert E. Reisman

Natural history of insect sting allergy: Relationship of severity of symptoms of initial sting anaphylaxis to re-sting reactions

To examine the postulate that the nature of the symptoms of initial insect sting anaphylaxis is related to the risk and severity of subsequent sting reactions, the results of field re-stings were analyzed in 220 patients who had had venom anaphylaxis and did not receive venom immunotherapy. The incidence of a reaction after the first re-sting was 56% in the total group, was more frequent in adults (74%) than in children (40%), and was unrelated to the time interval since the initial sting reaction. When re-sting reactions did occur, the nature of the symptoms was similar to the symptoms of the initial sting reaction. Reactions to repeated re-stings tended to be similar. Overall, more severe reactions to re-stings occurred eventually in 24 patients. These observations confirm the frequent self-limiting course of insect sting allergy, especially in children, and the repetitive nature of specific anaphylactic symptoms, and the observations thus suggest that patients with mild to moderate anaphylactic symptoms probably do not require venom immunotherapy.

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 testings 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 testings 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.

Asthma induced by adrenergic aerosols

Abstract Thirty significantly symptomatic asthmatic patients were divided into 2 groups on the basis of the FEV 1 determined 60 minutes following isoproterenol inhalation. One group consisted of 18 patients who had a 10 per cent or greater increase in the 60 minute postisoproterenol FEV 1 as compared to base-line levels. Eight patients in this group overused isoproterenol aerosols. Discontinuation of isoproterenol by 6 of these 8 patients and 4 other normal users failed to influence asthmatic symptoms. Of the other 12 patients, 9 had a 60 minute FEV 1 near base-line levels, and 3 patients had a precipitous fall in the FEV 1 well below base-line levels after 60 minutes. Nine of these 12 patients greatly overused isoproterenol aerosols. Eight patients discontinued the isoproterenol, with dramatic clinical improvement noted immediately in 7. Pulmonary function studies were repeated in 6 of these patients following cessation of aerosol therapy and confirmed the marked improvement. The clinical data confirmed the induction and persistence of asthma as a result of adrenergic aerosol overuse. The pulmonary function data indicated the 60 minute postisoproterenol FEV 1 is a reliable method of detecting such patients.

Stinging insect allergy: Natural history and modification with venom immunotherapy☆

The natural history of stinging insect allergy and its modification by venom immunotherapy was investigated by follow-up observations of patients with histories of venom anaphylaxis and detectable venom-specific IgE. The patients were divided into three categories: (1) receiving venom immunotherapy, (2) declined venom immunotherapy, and (3) terminated venom immunotherapy. One hundred twenty-seven patients were evaluated after 6 mo to 9 yr of venom immunotherapy. Most received top venom doses of 50 micrograms of yellow jacket and/or honeybee venoms every 4 wk. There were 87 restings in 48 patients resulting in two systemic reactions, only one of which could be considered a treatment failure (1%). Fifty-six patients never received venom immunotherapy. In this group there were 40 restings in 28 patients with 14 systemic reactions (35%). In 88 patients who stopped venom immunotherapy, 61 restings in 41 patients led to 11 systemic reactions (17%). Patients with cardiovascular/or respiratory symptoms with initial sting anaphylaxis were at risk for subsequent reactions. With one exception, patients with hives and edema only as the initial reaction either had a similar or no reaction when they were restung. These results confirm the efficacy of venom immunotherapy but also suggest that there are factors other than the presence of venom-specific IgE modulating the occurrence of clinical anaphylaxis.

Venom skin tests in insect-allergic and insect-nonallergic populations

Intradermal skin tests with varying concentrations of honeybee, yellow jacket, white-faced hornet, yellow hornet, and Polistes venoms were done on 85 patients with histories of insect-sting anaphylaxis and on 56 insect-nonallergic subjects. Positive skin tests (wheal greater than or equal to 5 to 10 mm and flare greater than or equal to 11 to 20 mm) were present in 67 insect-allergic patients at venom concentrations ranging from 0.001 microgram/ml to 0.1 microgram/ml. Seven additional allergic patients had positive skin tests with the 1.0 microgram/ml venom concentration. Twenty-six nonallergic subjects had positive skin tests at the venom concentration of 1.0 microgram/ml, and two patients had positive skin tests at the lower venom concentrations (0.001 to 0.1 microgram/ml). These results confirm venom skin tests as a highly sensitive method of detecting venom-specific IgE in the evaluation of patients with stinging-insect hypersensitivity. Since a large percentage of insect-nonallergic subjects reacted to the 1.0 microgram/ml concentration, clinical judgment and further in vitro testing should be considered in the evaluation of patients who react only at this venom concentration.

Duration of venom immunotherapy: Relationship to the severity of symptoms of initial insect sting anaphylaxis

BACKGROUND This study assessed the postulate that the adequate duration of venom immunotherapy (VIT) is related to the severity of the initial sting anaphylactic symptoms. METHODS Data were collected from patients with venom allergy who had sting anaphylaxis and subsequent positive venom skin test results, received maintenance VIT, and had field re-stings after cessation of VIT. There were 217 re-stings in 113 patients with 15 systemic reactions in 10 patients (a re-sting reaction rate of 9% per sting and 7% per patient). RESULTS Re-sting reactions occurred in 1 of 25 patients with initial mild anaphylaxis (4%), 2 of 41 patients with moderate reactions (5%), and 7 of 47 patients with initial severe symptoms (15%). The results were not influenced by the duration of VIT or the interval between cessation of VIT and the re-sting. Eighteen patients who converted to negative skin test reactions had no reactions when re-stung. CONCLUSIONS These results suggest a relationship between the severity of anaphylaxis and subsequent duration of VIT. Two to three years is sufficient for patients who had mild to moderate anaphylaxis. Longer duration of therapy is advisable for patients who had severe symptoms and continue to have positive venom skin test results.

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.

Studies of coexisting honeybee and vespid-venom sensitivity

Honeybee and vespid venom-specific IgE were measured by RAST in randomly selected sera of 87 patients who had had anaphylactic reactions after insect stings. Overall there was a poor correlation between the titers of honeybee venom and yellow jacket or hornet venom-specific IgE. Sera from nine patients with high titers of both honeybee venom and yellow jacket venom-specific IgE were selected for RAST-inhibition studies, with these two venoms as coupling and inhibiting antigens. Three patterns of IgE-antibody specificity were detected. Four patients had unique antibody activity with no cross-reactivity between the yellow jacket and honeybee venom-specific IgE. This is probably the most common pattern in patients with dual sensitivity. Three patients reacted to a major allergen in yellow jacket venom cross-reacting with a minor allergen in honeybee venom. Their RAST-inhibition patterns demonstrated that the yellow jacket-venom RAST was inhibited by yellow jacket venom only and the honeybee-venom RAST was inhibited by both yellow jacket venom and honeybee venom. Two patients had the opposite pattern with honeybee-venom RAST inhibited by honeybee venom only and the yellow jacket RAST inhibited by both honeybee venom and yellow jacket venom. These latter patients reacted to a major allergen in honeybee venom that was cross-reacting with a minor allergen in yellow jacket venom. Studies with rabbit antisera raised to vespid and honeybee venoms demonstrated major antigens that were unique to each family that did not cross-react and several minor cross-reacting antigens.

Unusual reactions following insect stings: Clinical features and immunologic analysis

Fifteen patients were studied who had unusual reactions following insect stings. These included serum sickness, neurologic disease, renal disease, and delayed hypersensitivity-type reactions. The clinical features are briefly outlined. Measurements were made of serum venom-specific IgE and IgG antibodies. These antibodies were present in some patients and in these instances suggested an immunologic pathogenesis for the reactions. Alternative etiologies for the unusual reactions are also discussed.

Clinical and immunologic features and subsequent course of patients with severe insect-sting anaphylaxis

One hundred fifty-eight patients were evaluated because of symptoms of potentially fatal venom anaphylaxis, as defined by hypotension, including loss of consciousness (LOC), throat/laryngeal edema, or marked respiratory distress. The demographic characteristics were 118 male and 40 female patients; age range, 3 to 80 years; mean, 29.7 years; 33 patients less than 10 years; and incidence of atopy, 20%. One hundred twenty-seven patients had had prior stings; 27 had prior systemic reactions (SR), including one with LOC. Almost all patients had venom-specific IgE; RAST titers covered a wide range. As compared to the total group, the subset of 45 patients with LOC were older, had an increased incidence of cardiac disease and beta-blocker use, stings in the head area, and re-sting reactions in patients who did not receive venom immunotherapy (VIT). One hundred six re-stings occurred in 37 patients receiving VIT with no SR. There were 38 re-stings in 18 patients who refused VIT, with 14 SRs in 11 patients. These studies suggest no distinguishing characteristics, including age, that would identify patients susceptible to severe venom anaphylaxis and confirm the prophylactic effectiveness of VIT.