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Just as there is no one optimal treatment (Rx) for allergies, there isn’t one overarching risk for anaphylaxis. This is because allergies are of different types affecting different tissues and organs. As such, AIT (allergy immunotherapy) is relatively safe when used for treating allergic rhinitis and allergic asthma. OTOH, it’s more controversial for atopic dermatitis and food allergy. This means AIT risk of anaphylaxis is higher with atopic dermatitis and food allergy. As well anaphylaxis risk depends on the kind of therapy, being higher with SCIT (subcutaneous immunotherapy) than with SLIT (sublingual immunotherapy). This is the main reason SCIT is administered in a medically supervised setting with appropriate staff and equipment to monitor and immediately treat anaphylaxis (1, 2).

AIT (allergy immunotherapy): Risk of overall adverse reactions

Initially, most AIT was by means of a subcutaneous injection of the allergen (SCIT) but since ~1990, SLIT (under the tongue) has increased substantially. Safety of SCIT was the main impetus for this change. Specifically, fatal adverse reactions from SCIT were reported in the 1980s (3). As a result, some European countries restricted the use of SCIT, which resulted in research for alternative routes. SLIT is also easier and more practical since it doesn’t require specific time commitment for an injection regimen, and doesn’t require medical supervision.

Adverse reactions following AIT can be either local or systemic.

  • Local reactions are quite common and include redness (erythema), itching (pruritis) and injection site swelling with SCIT and oropharyngeal itch or swelling or both with SLIT.
  • ~82% of SCIT (4) and ~75% of SLIT patients can have such reactions (5).
  • SLIT-related local reaction starts shortly after Rx starts and is usually self-limiting, ending by itself within a few days to a few weeks.

It was only in 2010 that a consensus 5-grade classification system based on reaction severity and organ systems involved was developed for SCIT and SLIT (6).

SCIT Anaphylactic Reactions

Overall, post-SCIT severe reactions including anaphylaxis range from 0.1 to 0.2% of injections and from 2 to 5% of patients (6, 7).

In a 4-year survey of 23.3 million injection visits, systemic reaction rate was ~0.1% with 97% classified as mild or moderate in severity (7, 8).

In another survey, incidence of severe systemic reactions was 1 per 1 million injections (9). This survey included one confirmed case of SCIT-related fatality.

Other surveys had a fatality rate of 1 in 2 to 2.5 million SCIT injections or 3 to 4 SCIT-related fatalities per year (10).

  • Risk factors for SCIT-related systemic reactions include asthma, prior SCIT-related systemic reactions and a strong skin test response to the allergen (4).
  • Features of asthma that increase risk of fatal or near-fatal SCIT-related systemic reactions are symptomatic or poorly controlled (7).

Thus, scientists speculate that SCIT-related systemic reactions have reduced simply due to better pre-injection safety measures and more precise asthma assessments (11).

SLIT Anaphylactic Reactions

Systematic reactions to SLIT are significantly lower.

A thorough review of 104 SLIT studies published until 2005 found a SLIT-related systemic reaction rate to be 0.054% (169 of 314959 doses administered) or 1.4 serious adverse events per 100000 administered SLIT doses (5). An update in 2013 reported local oral or GI tract side effects were more common (12).

Til date, there are no confirmed reports of SLIT-related fatalities though systemic reactions severe enough to be classified as anaphylaxis have been reported (13, 14, 15, 16, 17 ,18, 19, 20, 21; see below a table with pertinent details from 12).

If you look at the data carefully, this table shows one case of SLIT-induced anaphylaxis for house dust mite Rx (Blazowski; reference 13 in this answer), which was treated with intramuscular (IM) epinephrine. That patient, a 16 year old girl with a history of perennial allergic rhinitis, also had intermittent asthma. The anaphylactic episode occurred in her 3rd year of Rx when, after a 3-week break in her maintenance dose (10 drops), for reasons unknown, she self-administered 60 drops of allergen extract. This serves to emphasize AIT safety critically depends on strictly adhering to physician-mandated regimen of dosing, up-dosing and maintenance dosing.

In a few anaphylaxis cases post-SLIT, patients had previously experienced a systemic reaction to a SCIT Rx (15, 19).

Thus, a review estimated risk of systemic anaphylactic reactions as ~1 in >30000 injections with SCIT but as low as 1 in 100 million administrations with SLIT (22). See table below from 23 that lists results from some large-scale clinical trials and systematic reviews.

As for carrying an epi-pen, though the risk is low in light of this data, discuss that with your consulting physician.


1. Alvarez‐Cuesta, Emilio, et al. “Standards for practical allergen‐specific immunotherapy.” Allergy 61.s82 (2006): 1-3. Standards for practical allergen-specific immunotherapy

2. Erekosima, Nkiruka, et al. “Effectiveness of subcutaneous immunotherapy for allergic rhinoconjunctivitis and asthma: a systematic review.” The Laryngoscope 124.3 (2014): 616-627.

3. Update, C. S. M. “Desensitising vaccines.” Br Med J (Clin Res Ed) 293 (1986): 948.

4. Cox, Linda, et al. “Allergen immunotherapy: a practice parameter third update.” Journal of Allergy and Clinical Immunology 127.1 (2011): S1-S55. http://www.alabmed.com/uploadfil…

5. Cox, Linda S., et al. “Sublingual immunotherapy: a comprehensive review.” Journal of allergy and clinical immunology 117.5 (2006): 1021-1035. http://allergyspecific.com/sites…

6. Cox, L., et al. “Speaking a common language in immunotherapy. WAO grading of systemic reactions.” J Allergy Clin Immunol 125 (2010): 569-574.

7. Epstein, Tolly G., et al. “AAAAI/ACAAI surveillance study of subcutaneous immunotherapy, years 2008-2012: an update on fatal and nonfatal systemic allergic reactions.” The Journal of Allergy and Clinical Immunology: In Practice 2.2 (2014): 161-167. http://www.jacionline.org/articl…

8. Bernstein, David I., et al. “Surveillance of systemic reactions to subcutaneous immunotherapy injections: year 1 outcomes of the ACAAI and AAAAI collaborative study.” Annals of Allergy, Asthma & Immunology 104.6 (2010): 530-535.

9. Amin, Hetal S., Gary M. Liss, and David I. Bernstein. “Evaluation of near-fatal reactions to allergen immunotherapy injections.” Journal of allergy and clinical immunology 117.1 (2006): 169-175.

10. Roy, Sitesh R., et al. “Increased frequency of large local reactions among systemic reactors during subcutaneous allergen immunotherapy.” Annals of Allergy, Asthma & Immunology 99.1 (2007): 82-86.

11. Cox, Linda, et al. “Allergy immunotherapy safety: location matters!.” The Journal of Allergy and Clinical Immunology: In Practice 1.5 (2013): 455-457.

12. Canonica, Giorgio Walter, et al. “Sublingual immunotherapy: World Allergy Organization position paper 2013 update.” World Allergy Organ J 7.1 (2014): 6. World Allergy Organization Journal

13. Blazowski, L. “ALLERGY Net: Anaphylactic shock because of sublingual immunotherapy overdose during third year of maintenance dose.” Allergy 63.3 (2008): 374-374. ALLERGY Net: Anaphylactic shock because of sublingual immunotherapy overdose during third year of maintenance dose

14. Dunsky, E. H., et al. “Anaphylaxis to sublingual immunotherapy.” Allergy 61.10 (2006): 1235-1235. Anaphylaxis to sublingual immunotherapy

15. Antico, A., M. Pagani, and A. Crema. “Anaphylaxis by latex sublingual immunotherapy.” Allergy 61.10 (2006): 1236-1237. Anaphylaxis by latex sublingual immunotherapy

16. Eifan, A. O., et al. “Anaphylaxis to multiple pollen allergen sublingual immunotherapy.” Allergy 62.5 (2007): 567-568. http://onlinelibrary.wiley.com/d…

17. Rodríguez-Pérez, Noel, et al. “Frequency of acute systemic reactions in patients with allergic rhinitis and asthma treated with sublingual immunotherapy.” Annals of Allergy, Asthma & Immunology 101.3 (2008): 304-310.

18. Cochard, Marie M., and Philippe A. Eigenmann. “Sublingual immunotherapy is not always a safe alternative to subcutaneous immunotherapy.” Journal of Allergy and Clinical Immunology 124.2 (2009): 378-379.

19. De Groot, Hans, and Annemarie Bijl. “Anaphylactic reaction after the first dose of sublingual immunotherapy with grass pollen tablet.” Allergy 64.6 (2009): 963-964. Anaphylactic reaction after the first dose of sublingual immunotherapy with grass pollen tablet

20. Buyukozturk, Suna, et al. “Latex sublingual immunotherapy: can its safety be predicted?.” Annals of Allergy, Asthma & Immunology 104.4 (2010): 339-342.

21. Dretzke, Janine, et al. “Subcutaneous and sublingual immunotherapy for seasonal allergic rhinitis: a systematic review and indirect comparison.” Journal of Allergy and Clinical Immunology 131.5 (2013): 1361-1366.

22. Calderon, M. A., et al. “Sublingual allergen immunotherapy: mode of action and its relationship with the safety profile.” Allergy 67.3 (2012): 302-311. http://onlinelibrary.wiley.com/d…

23. Soyka, Michael B., et al. “Scientific foundations of allergen-specific immunotherapy for allergic disease.” CHEST Journal 146.5 (2014): 1347-1357. Scientific Foundations of Allergen-Specific Immunotherapy for Allergic Disease