Can Epinephrine Coated Syringe for Subcutaneous Immunotherapy (SCIT) Reduce Large Local Reaction?
Condition: Injection Reactions Site; Systemic Reactions
MeSH terms: Injection Site Reaction
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Allergen immunotherapy is effective in the management of allergic asthma, allergic
      rhinitis/conjunctivitis, and stinging insect hypersensitivity. The most common side effect of
      subcutaneous allergen specific immunotherapy (SCIT) is local reactions (LR). Although some
      studies indicated that LR did not predict systemic reaction (SR), patients with higher
      frequency of large local reaction (LLR) were reported to have higher risk for SR. Epinephrine
      may decrease LLR due to its vasoconstrictive effect . The objective of this study was to
      compare the size of LLR in patients receiving SCIT with epinephrine or normal saline coated
      syringe. The patients who complained of frequent LLR despite pre-medication and local
      treatment were recruited.
    

Detailed description: 
      Allergen immunotherapy (AIT) is an immune mediated treatment which modifies T helper (Th)
      2-directed response through the interplay between regulatory T and B cells, blocking IgG4
      antibodies and tissue effector-mediated mechanisms. Aeroallergen immunotherapy is recommended
      for patients with allergic rhinitis, allergic conjunctivitis or allergic asthma whose
      symptoms were not adequately controlled by antigen avoidance and pharmacotherapy. AIT could
      reduce symptoms and medication usage in respiratory allergy. In children, AIT prevented the
      progression from allergic rhinitis to asthma and prevented new onset of allergen
      sensitization in monosensitized patients. The administration of allergen by subcutaneous
      injection (SCIT) is a common practice among allergists.

      The benefits of SCIT must be weighed against the risks of side effects which can be mild or
      life threatening. Adverse allergic reactions to SCIT were classified as either local (LR) or
      systemic reactions (SR).6 Large local reactions (LLR) are defined as erythema and/or swelling
      (> 25 mm) at the site of injection. The timing of adverse reactions were categorized into
      immediate (occurring within 30 min) and late reactions (occurring > 30 min after injection).
      LR associated with SCIT ranged from 26-72% of patients and 0.7-4% of injections. SR were
      reported to occurred in 3.7% of patients and 0.3% of injection. Recent prospective study in
      pediatric patients who received SCIT showed immediate LR in 54.6%, delayed LR in 56.1%,
      immediate SR in 2.2% and delayed SR in 7.4% of the patients. Severe SR were seen in 0.03% of
      all treatments which appeared within 30 minutes after the injections. The author concluded
      that children had similar rates of LR compared to adult patients but had lower rates of
      severe SR.

      Several studies indicated that individual LR did not predict subsequent SR. The rate of SR
      were not change despite the dose adjustment after a LR. However, patients with greater
      frequency of LLR might be at an increased risk for future SR. Recognizing the significance of
      frequent LLRs is important for designing safer protocols for successful SCIT.

      In the Division of Allergy and Clinical Immunology, Department of Pediatrics, Faculty of
      Medicine Siriraj Hospital, Mahidol University, we performed SCIT in approximately 100
      patients and 2000 injections per year. The LR associated SCIT were complained in 75% of the
      patients. Of the patients who experienced LR, 80% had LR more than 25 mm which was considered
      LLR.

      Many strategies to prevent or minimize LR were reported. Oral antihistamines, leukotriene
      receptor antagonist (LTRA) or anti-IgE could reduce LR during the built-up phase. Cold
      compression or topical steroid were used to reduce the LR without any strong evidence. To our
      knowledge, the benefit of epinephrine coated syringe prior to drawing the allergen extract
      for SCIT in patients with frequent LLR has never been explored in any controlled trial.

      The objective of this study is to compare the size of LR in patients with frequent LLR who
      receive SCIT by coating syringe with epinephrine or placebo prior to drawing allergen
      extract.
    

Intervention name(s): Epinephrine or normal saline
Intervention type(s): Drug
Intervention description(s): epinephreine or normal saline coated syringe before drawing allergen for injection.
Other intervention name(s): Adrenaline or normal saline
Intervention MeSH terms: Epinephrine
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: A randomized, double-blind, crossover trial with epinephrine coated syringe before injected and placebo was done in each visit in patients who developed large local reactions after subcutaneous immunotherapy.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Large local reaction; adrenaline, epinephrine