Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at NSU
A 31-year-old Caucasian male has been on subcutaneous immunotherapy for allergic rhinitis for 3 months. The subcutaneous immunotherapy (SCIT) consists of 3 injections with extracts of grasses, trees, weeds (vial A), dust mite, molds (vial B), cat and ragweed (vial C). His maintenance dose goal is 0.5 ml.
The SCIT dose was gradually increased with weekly injections and the dose he received last week was 0.3 ml. The patient reports large local reactions which started at the level of 0.1 ml and increased progressively as the dose increased to 0.2 ml.
During the last visit, the size of the local reaction was 30 x 30 mm in terms of swelling. He has no history of prior systemic reactions to SCIT.
Past medical history (PMH)
Allergic rhinitis. He has a remote history of mild asthma, which has been asymptomatic for years and he used only occasionally a prn albuterol inhaler in the remote past.
Benadryl PRN, Flonase (fluticasone) nasal spray daily
The patient received three injections of immunotherapy today at 10:50 and within two to three minutes of the injection, he started to complain of feeling that his throat was closing, dry cough and itchy eyes. He was evaluated immediately by the nurses and his allergist.
What is the most likely diagnosis?
He was found to have an anaphylactic reaction to the subcutaneous immunotherapy.
What treatment would you suggest?
He was given a dose of epineprine 0.3 mg IM at 10:51 and Alavert 10 mg po dissolvable tablet at 10:52. At that time, his blood pressure was 140/55, heart rate was 112, and his pulse-oximetry was 93% on room air.
At 11:00, he was given 40 mg of prednisone po x 1.
What happened next?
The patient reported that his throat sensation was better; however, his pulse-oximetry was noted to be in the range of 90% and on physical examination, he developed diffuse bilateral expiratory wheezing. The physical examination was also remarkable for conjunctival injection and development of swelling around the injection site on both arms with large, local reaction in the range of 8 to 9 cm on the left arm with wheals and satellite wheals around the injection sites.
What treatment would you suggest next?
He was treated with albuterol four puffs at 11:15. At 11:20, he reported improvement in his throat sensation and shortness of breath. His pulse-oximetry was 96%; blood pressure was 130/80.
At 11:30, the patient reportedly returned to baseline in terms of his symptoms. On physical examination, he had no more wheezing.
He was given a prescription for prednisone 40 mg po daily for three days and loratadine 10 mg po daily for seven days.
How would you change the immunotherapy prescription?
His dose of immunotherapy was returned to the dose two steps before the current one, which was 0.1 ml and he is to stay on this dose for two months.
The patient was discharged from the clinic at 12:50, two hours after the event. He is on prednisone, which should prevent any symptoms of late reaction.
Anaphylactic reaction to subcutaneous immunotherapy
Anaphylaxis mind map diagram.
Allergen immunotherapy was introduced by Leonard Noon 100 years ago and is the only disease-modifying treatment for allergic individuals (Allergy, 2012).
During a retrospective chart review of 388 patients, the rate of systemic reactions during subcutaneous immunotherapy was 0.28% per injection and 7.4% per patient. It was concerning that 48% of the systemic reactions occurred more than 30 minutes after the injection and many of these reactions required epinephrine.
This study was unable to identify risk factors that predict the reactions. Gender, phase (build-up versus maintenance), asthma, angiotensin-converting enzyme inhibitors, beta-blockers, initial skin-prick test size, or allergen type did not increase the odds of a systemic reaction.
Skin prick testing (SPT) on beta-blockers was safe in 199 patients in a 2012 study (http://goo.gl/3vGSl). However, incidence of systemic reactions is 1:250 with SPT.
Mnemonics for anaphylaxis
Clinical features of anaphylaxis: S ECG
Expiratory wheezing and other respiratory symptoms, 70%
GI and oral, 24%
Risk factors for anaphylaxis due to immunotherapy include: OH BEA
Observation - insufficient, following injection
High allergen dose
Errors in administration
Asthma, poorly controlled
Drugs for acute management of anaphylaxis: EASI
Antihistamines PO, IM
Steroids PO, IM, IV
Inhaled b2-agonists, if wheezing. IV fluids if hypotension
Epinephrine (adrenaline) is the first-line the treatment of anaphylaxis. Adult intramuscular dose is 0.3 to 0.5 ml of 1:1,000 concentration. This should be given in the lateral aspect of the thigh by intramuscular injection. The dose can be repeated every 5 to 15 minutes, depending upon the response, for 3-4 doses. The same is true for children except the dose is 0.01 mg per kg (AAAAI Ask the Expert, 2012).
What are the 4 standardized allergen extracts?
(E) Dust Mite
The 4 standardized extracts are Cat, Dust Mite, Grass and Ragweed.
Allergen immunotherapy safety: Characterizing systemic reactions and identifying risk factors. Rank, Mathew A.; Oslie, Corrine L.; Krogman, Jennifer L.; Park, Miguel A.; Li, James T. Allergy and Asthma Proceedings, Volume 29, Number 4, 7/8 2008 , pp. 400-405(6).
Evaluation of near-fatal reactions to allergen immunotherapy injections. Amin HS, Liss GM, Bernstein DI. J Allergy Clin Immunol. 2006 Jan;117(1):169-75.
Anaphylactic reactions during immunotherapy. Rezvani M, Bernstein DI. Immunol Allergy Clin North Am. 2007 May;27(2):295-307, viii.
Allergen immunotherapy: A practice parameter second update. JACI, 2007 (PDF).
Anaphylaxis: A Short Review
Rate of systemic reactions during subcutaneous immunotherapy: 0.28% per injection
Mind Maps: Anaphylaxis
Anaphylaxis guidelines by World Allergy Organization. JACI, 2011.