Immunotherapy

Aka: Immunotherapy, Allergen Immunotherapy, Allergen Vaccine, Allergy Vaccination, Desensitization

1. See Also
   1. Cancer Immunotherapy
   2. Palforzia (Peanut Allergen Powder)
2. Indications
   1. Allergic Rhinitis
   2. Allergic Conjunctivitis
   3. Allergic Asthma
   4. Hymenoptera Sting systemic reaction
   5. Inadequate response to medical therapy of allergy
3. Contraindications
   1. Uncontrolled Asthma
      1. Recent Asthma Exacerbation (last 7 days)
      2. Current Wheezing
      3. Peak Expiratory Flow below 75% of personal best
   2. Current Beta-Blocker or ACE Inhibitor use
      1. Impairs Epinephrine effect in Anaphylaxis
   3. Concurrent significant illness, fever or Fatigue
   4. Recent Insect sting or food reaction
4. Mechanism
   1. Immunotherapy is based on active Immunity, similar to Vaccination against microbes
   2. Immunotherapy builds Immunity to specific Antigens and decreases symptom response on exposure
   3. Process
      1. Small subcutaneous dose given initially (see test vial technique below)
      2. Weekly injections are titrated with increasing dose until 6 months when maintenance dosing is performed
      3. Maintenance dosing (continuous dose) is administered every 2-4 weeks for 3-5 years
   4. Results
      1. Allergan specific IgG Antibody (blocking Antibody) forms and competes with allergan-specific IgE
      2. Mast Cells and Basophils release fewer reaction mediators
      3. Th2 CD4+ T Cells shift towards Th1 CD4+ T Cells
   5. References
      1. Mahmoudi (2014) Immunology Made Ridiculously Simple, MedMaster, Miami, FL
5. Types: Immunotherapy Vaccines
   1. Factors affecting potency
      1. Shelf time (do not use expired Vaccines)
      2. Storage Temperature
         1. Refrigerate at 4 C or 39.2 F
         2. Vaccines lose potency in weeks at room Temperature
         3. Vaccines lose potency in days at higher Temperature
      3. Concentration (high concentrations are most stable)
      4. Vial surface area (related via volume effect)
         1. Increased vial surface area adheres more allergens
         2. Glycerol or albumin decrease volume effect
      5. Additives
         1. Preservative
         2. Diluent
         3. Mix of allergens
            1. Dilutes each individual allergen
            2. Interacts with other allergens
               1. Insect venom
               2. Fungi, Dust mites, Insect venoms, cockroaches
   2. Vaccine types
      1. Standardized Vaccines
         1. Potency graded by Bioequivalent Allergy Unit (BAU)
         2. BAUs assigned by FDA based on skin tests
         3. Examples of standardized Vaccines
            1. Cat dander
            2. Grass pollen
            3. Dust mites
            4. Ragweed pollen
      2. Unstandardized Vaccines
         1. Potency varies by manufacturer and lot
         2. Labeling reflects only content, and not potency
            1. Protein Nitrogen Units (PNU)
            2. Weight by volume (wt/V)
6. Technique: Vial Test
   1. Technique
      1. Place 5 skin wheals
         1. High Class Antigen
         2. Low Class Antigen
         3. Saline
         4. Negative Control (phenylated Glycerin)
         5. Positive Control (histamine)
      2. Place 4 mm wheal (0.5cc weakest dilution) intradermal
      3. Read in 10 minutes
   2. Interpretation
      1. Wheal size 15 mm or less is acceptable
      2. Wheel size 16 mm or over requires dilution
         1. Dilute 0.5 cc Antigen in 2 cc of phenylated saline
         2. Repeat intradermal wheals as above
7. Preparation
   1. Anaphylaxis preparation
      1. Albuterol MDI
      2. Epinephrine 0.1 to 0.3 cc 1:1000 SQ
      3. Oxygen Delivery
   2. Patient history
      1. Patient identifies Antigen vial
         1. Vial identified by patient name and date of birth
      2. Ask about history of delayed reactions
      3. Ask about present illnesses and recent exposures
         1. Fever or acute illness
         2. Asthma Exacerbation or other respiratory illness
         3. Current allergy exacerbation
         4. New medications (Beta Blockers or ACE Inhibitors)
   3. Vaccine Vial check
      1. Confirm match of patient name, birth, and MR number
      2. Check Immunotherapy mix components in vial
      3. Make certain the vial has not expired
      4. Check vial number
         1. Maintenance is number 1
         2. Dilutions are numbered starting from maintenance
      5. Check color coding (reflects concentration)
         1. Red: Maintenance concentration
         2. Yellow
         3. Blue
         4. Green
         5. Silver: Most dilute concentration
8. Dosing
   1. Build-up dosing schedule (directed by allergist)
      1. Anticipate 6 month course to get to maintenance
      2. Increase from most dilute toward maintenance dose
         1. Serial dose increments weekly (18-27 doses)
   2. Maintenance dosing schedule
      1. Administer every 3-4 weeks for 4-5 years
      2. Reduce dose when starting new vial from manufacturer
         1. Decrease maintenance dose to 50%
         2. Increase dose every 7-14 days until at maintenance
   3. Missed Dosages
      1. Build-Up interrupted
         1. 10 days or less: Continue build up
         2. 11-14 days: Repeat last dose
         3. 15-29 days: Half last dose
         4. 30 days or longer: 1/5 last dose
      2. Maintenance doses interrupted
         1. Less than 7 weeks: Continue same dose
         2. 7 weeks: Go back 2 incremental dilutions
         3. 8 weeks: Go back 3 incremental dilutions
         4. 9 weeks: See allergist
9. Technique
   1. See Preparation above
   2. Check and recheck today's dose (see above)
   3. Injection site: Upper arm lateral aspect
      1. Midpoint between Shoulder and elbow
      2. Inject at groove between deltoid and triceps
   4. Inject subcutaneously with 27 gauge needle
      1. Aspirate first (do not inject if blood aspirated)
      2. Slowly inject (do not raise wheal or cause pain)
   5. Hold pressure at injection site for one minute after
   6. Do not rub injection site due to increased absorption
   7. Observe for at least 20 minutes after injection
10. Adverse Effects: Systemic Reaction Symptoms (onset often within minutes)
    1. Itchy palms or hands
    2. Rapid nasal congestion
    3. Sneezing or coughing
    4. Urticaria (Hives) or Angioedema
    5. Vomiting or Diarrhea
    6. Headache or Nausea
    7. Shortness of Breath
11. Management: Allergy Vaccine reaction
    1. Local reaction (wheal/flare with Pruritus at <30 min)
       1. Local Cold Therapy
       2. Oral Antihistamine (e.g. Diphenhydramine)
       3. Topical Corticosteroid
       4. Consider allergy premedication (e.g. Diphenhydramine)
    2. Large local induration (Arthus with pain and swelling)
       1. Oral Corticosteroids
       2. NSAIDS
       3. Oral Antihistamine (e.g. Diphenhydramine)
    3. Systemic reaction (see symptoms above)
       1. Tourniquet above injection site
       2. See Anaphylaxis for specific management
    4. Delayed reaction
       1. Oral Antihistamine (e.g. Diphenhydramine)
       2. Oral Prednisone 5 to 20 mg PO q12 hours for 1 day
12. Efficacy: Grass Pollen Immunotherapy
    1. Sustained response 3 years after injections stopped
    2. Effects long-term clinical course
       1. Decreased immediate sensitivity
       2. Eliminated late phase response
       3. Decreased immune markers
          1. Decreased CD3+ T-Cells
          2. Decreased cells containing Interleukin-4 RNA
    3. References
       1. Durham (1999) N Engl J Med 341:468-75 [PubMed]
13. References
    1. Huggins (2004) Am Fam Physician 70:689-704 [PubMed]
    2. (2003) Ann Allergy Asthma Immunol 90:1-40 [PubMed]