Position statement

Beta-adrenergic blockers, immunotherapy, and skin testing

These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma and Immunology; the American College of Allergy, Asthma and Immunology; and the Joint Council of Allergy, Asthma and Immunology.

The American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) have jointly accepted responsibility for establishing “The diagnosis and management of anaphylaxis: an updated practice parameter.” This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion.

This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients.

B-Blockers may aggravate anaphylactic reactions and interfere with treatment. There is therefore concern about their use in patients who have a history of anaphylaxis or are on allergen immunotherapy. Immunotherapy is the best available treatment for prevention of life-threatening anaphylaxis to Hymenoptera stings, which is often observed in elderly patients who have cardiovascular disease and therefore are on β-blocker treatment.

To analyze the risk of β-blocker treatment during venom immunotherapy.

We screened all 1682 patients with Hymenoptera venom allergy seen during a period of 34 months for immunotherapy, cardiovascular disease, and treatment with β-blockers.

Of the 1389 patients in whom immunotherapy was recommended, 11.2% had cardiovascular disease, and 44 of these were on β-blockers before immunotherapy. In 31 of those, the drug was replaced before starting treatment. In 3 with coronary heart disease and 1 with severe ventricular arrhythmia, the drug was continued throughout immunotherapy. In 9, it was reintroduced after reaching the maintenance dose. In an additional 12 patients, β-blockers were newly started during immunotherapy. Of 25 patients on β-blockers during immunotherapy, 3 (12%) developed allergic side effects, compared with 23 (16.7%) of 117 with cardiovascular disease but without β-blockers. Systemic allergic symptoms after re-exposure by sting challenge or field sting were observed in 1 of 7 (14.3%) with and 4 of 29 (13.8%) without β-blockade. No severe reactions to treatment or sting reexposure were observed in patients with β-blockade.

Combination of β-blockers with venom immunotherapy may be indicated in heavily exposed patients with severe cardiovascular disease.

Stings and bites from various insects are responsible for many anaphylactic events.

To document the clinical features of specific forms of anaphylaxis and investigate clinical concerns regarding stinging and biting insect allergy.

All patients presenting for evaluation of adverse reactions to insect stings or bites between December 1980 and December 1997 had the clinical details of their reactions recorded and their reactions classified.

The spectrum of clinical symptoms and signs is similar to that seen in anaphylaxis from other sources; stings on the head or neck are not more likely to cause life-threatening reactions than stings elsewhere on the body; a lesser reaction will not necessarily lead to a more serious reaction from a future sting; asthmatic patients do appear to have an increased risk of asthma as a feature of their anaphylactic response; anaphylaxis is usually confined to a particular insect species for the individual patient; patients who have had multiple stings at one time may have experienced true anaphylaxis and not a “toxic” response; and patients who have had anaphylaxis from other sources are at no greater risk than that of the general population of reacting similarly to insect stings or bites.

Anaphylactic events from insect stings show the same clinical features as those from other sources. Systemic reactions seem confined to a specific insect species. Patients who experience RXN3 reactions from multiple stings at one time should undergo specific venom testing, because many have experienced true anaphylaxis and not a toxic response. Future consideration should be given to the role of β-adrenergic antagonists and ACE inhibitors in patients with systemic reactions.

β-Blocker therapy postmyocardial infarction is generally recommended because it reduces mortality. However, β-blockers may increase anaphylaxis mortality in the growing population of patients with peanut-induced anaphylaxis.

We sought to assess the risks and benefits of β-blocker therapy among patients with peanut allergy and heart disease.

We created a Markov model for patients with heart disease at risk for peanut-induced anaphylaxis to compare life expectancy with the following strategies: (1) β-blocker and (2) no β-blocker. Meta-analysis and a literature review were used to estimate model parameters. We performed sensitivity analysis to explore parameter uncertainty.

For peanut-allergic patients who are postmyocardial infarction or who have congestive heart failure, the heart disease benefit of β-blockers outweighs the increased likelihood of dying from anaphylaxis, increasing life expectancy by 9.4 and 17.4 months, respectively. β-Blocker was preferred unless (1) the annual rate of moderate to severe anaphylaxis exceeded 6.0% for postmyocardial infarction and 15% for congestive heart failure patients; (2) β-blocker therapy increased the incidence of moderate to severe anaphylaxis >2.5-fold for postmyocardial infarction and >5.8-fold for congestive heart failure patients; (3) anaphylaxis case fatality exceeded 6.5% postmyocardial infarction; or (4) β-blocker therapy increased anaphylaxis case fatality >25-fold postmyocardial infarction.

Our results suggest that for patients postmyocardial infarction or with congestive heart failure who are at risk for peanut-induced anaphylaxis, β-blocker use should still improve survival. However, the epidemiology of anaphylaxis and effects of β-blocker therapy on anaphylaxis incidence and mortality require further study.

Because many antihypertensive drugs can affect airway function, the treatment of hypertension in patients with airway dysfunction is complex. For example, the worsening or precipitation of asthma by β-adrenoceptor antagonists is well-recognized, butβ ₁-adrenoceptor blockers that exert mildβ ₂-agonist effects, and those that modulate the endogenous production of nitric oxide, affect airway function to a lesser extent. Therapy with selective α₁-blockers is not contraindicated in cases of chronic airway obstruction. Conversely,α ₂-agonists must not be given to asthmatic subjects because they can adversely affect the bronchi. Calcium channel blockers do not exert severe side effects on the airways. Angiotensin-converting enzyme inhibitors may cause cough and exacerbate or even induce asthma; however, angiotensin II type I (AT₁) antagonists do not cause cough. 5-Hydroxytryptamine modifiers such as urapidil are a treatment option for patients with chronic airway obstruction. In patients with airway dysfunction, we suggest treatment with thiazide diuretics as the initial drug choice, and calcium channel blockers if the response is poor. In the case of no response, calcium channel blockers alone must be used. However, there is no strict rule because individual patients may respond differently to individual drugs and drug combinations. Consequently, it is important to adopt a flexible approach. For patients who are unresponsive to the aforementioned drugs, AT₁ receptor antagonists, newerβ ₁-adrenoceptor-blocking agents with ancillary properties (eg, celiprolol or nebivolol), and/or vasodilators can be considered.