Is immunotherapy (immunologic therapy) life-threatening for patients with a history of severe allergic reactions?

Is Immunotherapy Life-Threatening?

Yes, allergen immunotherapy carries a real risk of life-threatening anaphylaxis and death, though the absolute risk is low when properly administered—approximately 1 fatal reaction per 2.5 million injections and 1 life-threatening anaphylactic event per 160,000 injection visits. 1, 2, 3

Understanding the Risk Profile

The risk exists but is quantifiable and manageable:

• Fatal reactions occur at a rate of approximately 1 per 2.5 million injections (roughly 3.4 deaths per year in the United States). 1
• Life-threatening grade 4 anaphylactic reactions occur in approximately 0.005% of patients receiving subcutaneous immunotherapy, or 1 in 160,000 injection visits. 2, 3
• Overall systemic reactions occur in approximately 0.1-0.15% of injection visits (1 per 1000 injections), though most are mild and non-life-threatening. 2, 3
• Most severe reactions (nearly all) occur within 30 minutes of injection, which is why mandatory observation periods exist. 1, 2

High-Risk Patient Populations

Patients with a history of severe allergic reactions or anaphylaxis represent a relative contraindication to immunotherapy due to increased risk of severe, difficult-to-manage reactions. 1

Specific High-Risk Factors:

• Uncontrolled or symptomatic asthma is the single most important risk factor for fatal and near-fatal reactions—immunotherapy should be withheld until asthma is stable. 1
• FEV1 less than 80% of predicted dramatically increases systemic reaction risk (73.3% vs 12.6% in patients with FEV1 >80%). 1
• Concurrent beta-blocker use makes reactions more difficult to treat and can cause unopposed alpha-vasoconstriction with epinephrine administration, though this is a relative rather than absolute contraindication. 1
• Severe cardiovascular disease reduces ability to survive systemic reactions and their treatment. 1
• Systemic immunosuppression (chemotherapy, immunosuppressive medications, HIV) represents a relative contraindication due to weakened immune response. 1

Critical Risk Factors for Severe Reactions

Beyond patient characteristics, specific circumstances increase danger:

• Injections during peak pollen season or symptom exacerbation accounted for 46% of near-fatal reactions in one survey. 1
• Dosing errors were responsible for 25% of near-fatal reactions. 1
• Rush or accelerated immunotherapy protocols carry higher systemic reaction rates (up to 36% in some studies) compared to conventional schedules (<1%). 1
• Injections from newly prepared extracts have been associated with fatal reactions. 1
• High degree of allergen hypersensitivity increases risk. 1

Mandatory Safety Requirements to Mitigate Risk

All immunotherapy must be administered in a physician's office or medical facility equipped for immediate anaphylaxis recognition and treatment. 1, 4

Pre-Injection Assessment:

• Evaluate current asthma control before every injection—withhold if symptomatic or during exacerbations. 1
• Consider objective airway measurement (peak flow) in asthmatic patients before each injection. 1
• Screen for recent health changes, current medications (especially beta-blockers), and symptom status. 1

Post-Injection Protocol:

• Patients must remain in the medical facility for at least 30 minutes after injection, as 70-96% of severe reactions occur within this timeframe. 1, 4
• Epinephrine must be immediately available as first-line treatment for anaphylaxis. 4
• Note that 15% of systemic reactions may begin after 30 minutes, though nearly all severe (grade 4) reactions begin within 30 minutes. 1, 2

Clinical Decision-Making for High-Risk Patients

For patients with history of anaphylaxis: Shared decision-making is essential, weighing the severity of allergic disease against the real risk of severe immunotherapy reactions. 1

Exception to relative contraindications: Immunotherapy is indicated even in patients requiring beta-blockers when treating life-threatening stinging insect hypersensitivity, because the risk of insect sting anaphylaxis exceeds the risk of immunotherapy-related reactions. 1

Absolute contraindications include:

• Severe uncontrolled asthma despite pharmacotherapy 1
• Significant cardiovascular disease that reduces ability to survive systemic reactions 1
• Active systemic illness at time of injection 1

Common Pitfalls to Avoid

• Never administer immunotherapy in medically unsupervised settings—93% of near-fatal reactions occurred in allergist-staffed clinics where immediate treatment was available; none occurred in unsupervised settings. 1
• Do not allow patients to leave before 30 minutes—several fatal reactions occurred when patients left early or did not wait. 1
• Avoid dose escalation during peak allergy season in high-risk patients. 2, 5
• Do not initiate or continue immunotherapy when asthma is symptomatic or uncontrolled—this is the most preventable risk factor for fatal reactions. 1