Psyllium laxative-induced anaphylaxis, asthma, and rhinitis.

A 69-year-old nurse was evaluated for a recent episode of anaphylaxis that had occurred after psyllium ingestion. She had experienced recurrent rhinitis and asthma related to psyllium exposure for the past 15 years. The diagnosis of psyllium hypersensitivity was established by a positive psyllium puncture skin test, an elevated psyllium-specific IgE level in serum, and a confirmatory soluble-antigen competitive inhibition test. The patient was symptomatic for several years, and this diagnosis was not considered until she suffered potentially life-threatening anaphylaxis. Psyllium hypersensitivity may be a more common phenomenon than is currently appreciated by physicians and other health-care providers.

Discontinuing venom immunotherapy: outcome after five years.

BACKGROUND: The clinical and immunologic consequences of discontinuing venom immunotherapy are not well-defined. To determine which patients can safely stop treatment, we accepted all volunteers who had completed at least 5 years of maintenance venom immunotherapy regardless of the severity of the historical sting reaction, the persistence of venom skin test sensitivity, or any other variable. METHODS: Sting challenge was performed every 1 to 2 years after therapy was stopped; and venom-specific skin tests were performed, and IgE antibody levels were measured. RESULTS: Systemic symptoms occurred after challenge in eight of 270 stings (3%), in seven of 74 patients (10%); only two reactions were clinically significant. Venom skin test results became negative in 28% after 5 years of venom immunotherapy (at the time of discontinuation) and were negative in 56% to 67% of patients after 2 to 4 years without venom immunotherapy. There was a parallel decrease in the venom-specific IgE antibody levels. Challenge stings did not prevent the progressive decline in sensitivity, nor did they increase the risk of sting reaction even after two sequential stings 1 month apart. CONCLUSIONS: Venom immunotherapy can be safely discontinued after 5 years of maintenance therapy in virtually all patients, with the possible exception of those in whom the level of venom sensitivity has not declined during therapy. Venom sensitivity decreases with time even after venom therapy is stopped. Insect stings do not cause re-sensitization, and there was no increased risk from sequential stings. There appears to be a late-onset, non-IgG-mediated mechanism for long-term suppression of allergic sensitivity by prolonged high-dose venom immunotherapy.

A clinical trial of ipratropium bromide nasal spray in patients with perennial nonallergic rhinitis.

Intranasal ipratropium bromide has been shown to significantly reduce rhinorrhea. Use of a freon-propelled intranasal preparation has resulted in side effects associated with the drying properties of the propellant. The purpose of the present trial was to study the safety and efficacy of a new isotonic aqueous ipratropium bromide nasal spray pump, specifically in patients with perennial nonallergic rhinitis. Two hundred thirty-three patients participated in an 8-week double-blind parallel comparison of ipratropium bromide nasal spray with its vehicle, a saline solution. Treatment with the ipratropium spray resulted in a 30% reduction in rhinorrhea; this reduction was significantly greater than that seen with the saline vehicle. There was a modest reduction in postnasal drip, sneezing, and congestion with both treatments, which may be attributable to the salutary effects of the saline solution. Patients also perceived a significant reduction in the degree to which rhinorrhea interfered with their daily activities and moods. Treatment was well tolerated, with no drug-related systemic adverse events and no evidence of nasal rebound on discontinuation of treatment. Minor, infrequent episodes of nasal dryness and epistaxis were the only significant adverse events reported; these did not limit treatment.

Selection of Hymenoptera venoms for immunotherapy on the basis of patient's IgE antibody cross-reactivity.

BACKGROUND: Positive skin test results to multiple venoms in patients with Hymenoptera venom allergy may result from IgE antibody cross-reactivity among venom proteins. To avoid treatment with unnecessary and costly venoms, we have developed a venom RAST inhibition test that identifies individuals in whom a positive venom IgE RAST result is due to cross-reactive venom-specific IgE antibody. METHODS: Serum samples (n = 412) were collected over 5 years from patients with clinically characterized Hymenoptera venom allergy who had positive skin test results to more than one venom. Venom allergosorbent was added to serum containing IgE antivenin and buffer or 100 micrograms of homologous or heterologous venom. Bound IgE was detected with radiolabeled anti-human IgE. Intraassay variation less than 10% coefficient of variation and homologous venom inhibition greater than 80% were required for acceptance of data. A "cross-reactivity index" (CRI) was computed as a ratio of percent inhibition produced by heterologous versus homologous venom. RESULTS: Of the 412 sera-venom combinations analyzed, 41 (10%) were excluded because of incomplete homologous venom inhibition. Of the 371 remaining sera, 82% (n = 305) were studied for IgE anti-Polistes wasp venom (PWV) cross-reactivity with yellow jacket venom (YJV) and the other 66 for other venom specificity cross-inhibitions. Of the serum samples tested, 36.4% (111 of 305) contained IgE anti-PWV venom of which the binding to solid-phase PWV was inhibited with soluble YJV to a level that produced CRIs greater than 95%. We believe that this constitutes complete inhibition and demonstrates exclusively YJV cross-reactive antibody in these samples. The remaining 63.6% had CRIs from 0% to 95%, indicating IgE specific for a spectrum of unique and cross-reactive PWV allergens. Only 4.3% (13 of 305) had CRIs less than 5%, which is consistent with IgE restricted to PWV unique allergens. The degree of the IgE anti-PWV inhibition to solid-phase PWV by YJV was independent of the IgE anti-PWV level. CONCLUSIONS: This study shows that one third of patients with Hymenoptera venom allergy evaluated with positive YJV- and PWV-reactive IgE in the skin and/or serum were identified as candidates for exclusion of PWV from their immunotherapy regimen because their IgE anti-PWV was more than 95% cross-inhibitable with YJV. Cost analysis of the venom RAST inhibition test and a conventional 5-year Hymenoptera venom immunotherapy program indicates that this serologic evaluation is cost-effective.

Clinical correlation of the venom-specific IgG antibody level during maintenance venom immunotherapy.

Allergen immunotherapy is associated with a significant increase of specific IgG antibodies that have been suggested as a mechanism of action and as a marker of efficacy for immunotherapy. The value of venom-specific IgG antibody determinations as a measure of clinical protection against sting anaphylaxis has been difficult to prove in individual patients. We performed 211 insect sting challenges in 109 patients over a 4-year period to determine the significance of venom IgG levels 3 micrograms/ml or lower. Systemic symptoms occurred in only 1.6% of those with venom IgG more than 3 micrograms/ml, but in 16% of those with less than 3 micrograms/ml IgG, and notably in 26% of patients with low venom IgG who had received less than 4 years of treatment. The venom IgG level had no predictive value in patients who had received more than 4 years of therapy. Honeybee sting data were inconclusive because of the small number of subjects. We conclude that low venom-specific IgG levels are associated with an elevated risk of treatment failure during the first 4 years of immunotherapy with yellow jacket or mixed vespid venoms.

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.

Effects of a single-dose pretreatment with captopril on the immediate response to nasal challenge with allergen.

We performed a double-blind, placebo-controlled, crossover study using 12 subjects to determine the effects of a single 50-mg dose of captopril on the response to nasal challenge with increasing doses of allergen. Levels of kinins, histamine and N-alpha-p-tosyl-L-arginine methyl ester (TAME)-esterase activity were measured in nasal lavages, and symptom scores and the number of sneezes were recorded. Captopril had no significant effects on histamine, TAME-esterase, sneezing or symptom scores. Peak postchallenge kinin levels, however, were significantly elevated (p less than 0.05) compared to placebo, while an increase in the magnitude of the dose-response curve was of marginal significance (p = 0.058). Thus, captopril causes increases in the kinin levels in nasal secretions during the allergic response. If increased kinin levels persist or worsen with chronic therapy, it is possible that they could exacerbate allergic symptoms during repeated seasonal exposure.

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.

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.

Assessment of prolonged venom immunotherapy in children.

Venom immunotherapy was initiated in 94 children from April 1977 to October 1979. As of February 1983, 66 children had continued receiving treatment and had recent immunologic evaluation. Assessment of prolonged venom treatment included analysis of immunologic parameters, efficacy of treatment, and long-term safety. Venom skin tests, venom-specific IgE antibody levels, and venom-specific IgG antibody levels comprised the immunologic parameters evaluated. A decrease in allergic sensitivity was demonstrated over time in the skin and serum. Forty-three of 57 (75%) children had less positive vespid venom skin tests, and the mean venom-specific IgE antibody level declined to less than the pretreatment value with 3 or more years of yellow jacket venom therapy. Venom-specific IgG antibody measurements rose rapidly after the initiation of venom injections and were maintained for the duration of this evaluation. During a 3- to 6-year period, 200 stings in 49 treated children resulted in only four mild systemic reactions (98% efficacy). The benign nature of interval histories, physical examinations, and laboratory analyses in these children argues optimistically for the safety of prolonged venom immunotherapy.

Allergens of hymenopteran venoms.

Venoms of the Hymenoptera are mixtures of several antigens with nonimmunogenic small peptides and vasoactive amines. Limited local toxicity occurs with stings; systemic reactions to venoms are mediated by IgE antibodies and can be prevented by immunization with the appropriate venom. Skin testing with venoms detects the sensitized state, and a positive test predicts a 50 to 60% risk of an allergic response to a future sting. Because considerable crossreactivity exists between vespid venom allergens, choice of correct venom(s) for immunotherapy will not always be indicated by skin-testing with whole, unfractionated venom. Further efforts at skin testing with individual venom antigens may help to resolve problems regarding choice of venoms for immunotherapy.

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 micrograms/ml) to levels typical of untreated patients at the time of retesting (mean 1.95 +/- 0.3 micrograms/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.

Insect sting allergy in children: what is the real cost of the disease?

The impact of insect sting allergies on the quality of life of 118 children and their parents is assessed using attitudinal and psychometric questionnaires. Children, ranging in age from 7-15 years, manifested more anxiety in the clinical setting (state anxiety) than usual (trait anxiety), whereas for parents the trend was reversed. Most children believed that they could control being stung, and restrictions imposed by two-thirds of the parents assisted in preventing stinging episodes. Parents perceived their child's academic achievement, social abilities and extracurricular involvement as superior to that of their peers and closest aged siblings.