Is Allergy Immunotherapy Safe? What the Evidence Shows for SCIT and SLIT

Fatal reactions from SCIT (allergy shots) are extremely rare and have become rarer over time. The Bernstein 2004 fatality survey (covering 1990-2001) recorded approximately 1 fatal reaction per 2.5 million injection visits — roughly 3.4 deaths per year in the United States. The most recent surveillance period (2008-2017, Epstein 2019) found approximately 1 fatal reaction per 9 million injection visits — fewer than 1 death per year nationally. For SLIT (sublingual drops and tablets), no confirmed fatality has ever been published in the clinical literature across over three decades of use and approximately 1 billion administered doses. The absence of confirmed SLIT fatalities holds across both FDA-approved tablet use and European drops programs. The primary risk factor for SCIT fatality is uncontrolled asthma, present in 88% of detailed fatalities in the Bernstein 2004 survey.

Both SCIT and SLIT are used in children with established safety records. SLIT demonstrates substantially fewer treatment-related adverse events in pediatric populations compared to SCIT: a meta-analysis by Yang et al. (2023, Front Immunol) found a relative risk of 0.17 for treatment-related adverse events with SLIT versus SCIT in children — meaning SLIT patients experienced roughly one-sixth the rate of adverse events seen with shots. Several FDA-approved SLIT tablets (Oralair, Grastek, Ragwitek) are indicated from age 5. The PAT Study (Jacobsen 2007, Allergy) and its 10-year follow-up demonstrated that early childhood SCIT not only is safe but reduces new allergen sensitization rates and cuts asthma development by approximately half (25% versus 45% of controls). Both modalities have a favorable long-term safety profile in appropriately selected pediatric patients.

Allergy immunotherapy does not worsen the underlying allergic disease. Temporary symptom flares that some patients experience during the build-up phase — sneezing, nasal congestion, or mild wheezing after a dose — are immune responses to treatment, not disease progression. These flares indicate that the immune system is being challenged with increasing allergen doses, which is the intended mechanism of desensitization. Long-term data consistently show the opposite of worsening: the PAT Study found SCIT-treated children developed new allergen sensitizations at lower rates than controls; multiple studies show reduced asthma development in immunotherapy-treated children. Temporary flares during the first 3-6 months of build-up are expected and manageable — if they are uncomfortable or interfere with daily function, dose adjustment rather than discontinuation is usually the appropriate response.

Allergy immunotherapy can be continued during pregnancy but is generally not initiated in a pregnant patient — this is the clear guidance of the 2011 AAAAI/ACAAI Practice Parameter (Summary Statement 20). The rationale is that systemic reactions during pregnancy carry fetal risks — potential for hypoxia, uterine contractions, and premature labor. Patients already at a stable maintenance dose when pregnancy occurs may safely continue at that dose without escalation. Evidence supporting continuation is reassuring: Metzger 1978 found no excess complications in 121 pregnancies of SCIT-treated mothers; a Swedish nationwide registry (Larsson 2022) of 743 AIT-exposed pregnancies found no association with congenital malformations, preterm birth, or stillbirth. For venom immunotherapy in a patient with life-threatening sting allergy, the risk-benefit calculation reverses and treatment is recommended even during pregnancy.

SCIT fatality rates (approximately 1 per 9 million injections) are lower than the penicillin anaphylaxis fatality rate (approximately 1 per 100,000 courses). SLIT has zero confirmed fatalities worldwide. By comparison, depot corticosteroid injections (Kenalog/triamcinolone) — often used as 'allergy shots' in a different sense — cause HPA-axis suppression lasting 30-40 days per injection and carry long-term risks of bone density loss, hyperglycemia, cataracts, and immune suppression, which is why the AAAAI/ACAAI 2020 Rhinitis Practice Parameter states that depot parenteral corticosteroids 'are not recommended for treatment of allergic rhinitis.' Immunotherapy's adverse events occur during a defined treatment course and produce lasting immune modification; steroid injections suppress symptoms without disease modification and carry ongoing metabolic risks.

Traditionally, SCIT has been administered in a healthcare setting with immediate access to epinephrine, resuscitation equipment, and personnel trained in anaphylaxis management — the standard described in the 2011 AAAAI/ACAAI Practice Parameter, which also calls for a 30-minute observation period after each injection. At-home SCIT programs are built to reproduce each of those safeguards: a sterile-compounded serum, a prescribed epinephrine auto-injector confirmed on hand, a first dose and every dose change supervised live over Zoom by the prescribing allergist, gradual week-by-week dose escalation, and a 30-minute self-monitoring window after each dose. Pre-injection screening for asthma control and peak flow assessment is recommended for asthmatic patients. For SLIT, FDA-approved tablets require the first dose to be administered under medical supervision with 30-minute observation, followed by home administration with a mandatory prescribed epinephrine auto-injector. SLIT drops prescribed off-label follow similar protocols from prescribing allergists. Both modalities require regular follow-up to assess therapeutic response, adjust dosing, and screen for emerging contraindications. Patients on beta-blockers require additional risk-benefit discussion before starting SCIT.