SCIT: Preparation of allergen extracts for therapeutic use
- Harold Nelson, MD
Harold Nelson, MD
- Professor of Medicine
- National Jewish Health
- University of Colorado Denver School of Medicine
Subcutaneous immunotherapy (SCIT) is administered differently around the world and even within the United States. Over the past few decades, professional allergy societies in the United States have made attempts to reduce variations in practice and identify best practices. Practice parameters for SCIT have been published and the approach described in this topic review is consistent with the American guidelines .
Terminology — An allergen immunotherapy extract is a solution of one or more allergens that is used for immunotherapy. This topic review will use the term "allergen immunotherapy extract" or "allergen extract," although other terms in use include "allergy serum," "allergen vaccine," "allergen solution," and "allergen product" .
The preparation of allergen extracts for use in SCIT, including effective doses, types of extracts, mixing of different allergens, training of compounding personnel, storage and stability, and recording of vaccine "recipes" will be discussed in this topic review. Administration techniques, schedules, and choice of allergens, as well as an overview of the manufacture of allergen extracts are reviewed separately. (See "Subcutaneous aeroallergen immunotherapy: Accelerated schedules (cluster and rush)" and "Allergen extracts: Composition, manufacture, and labeling".)
TYPES OF ALLERGEN EXTRACTS
Several types of allergen stock solutions are available from commercial sources in the United States. The allergen may be in an aqueous solution, a solution containing 50 percent glycerin, in an alum-precipitated form, or lyophilized. The manufacture of allergen extracts is reviewed in detail elsewhere. (See "Allergen extracts: Composition, manufacture, and labeling" and 'Dilutions and diluents' below.)
A specific allergen may only be available in a limited number of forms. As examples:
- Cox L, Nelson H, Lockey R, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol 2011; 127:S1.
- Patterson ML, Slater JE. Characterization and comparison of commercially available German and American cockroach allergen extracts. Clin Exp Allergy 2002; 32:721.
- Meiser JB, Nelson HS. Comparing conventional and acetone-precipitated dog allergen extract skin testing. J Allergy Clin Immunol 2001; 107:744.
- Lent AM, Harbeck R, Strand M, et al. Immunologic response to administration of standardized dog allergen extract at differing doses. J Allergy Clin Immunol 2006; 118:1249.
- Nelson HS. Subcutaneous injection immunotherapy for optimal effectiveness. Immunol Allergy Clin North Am 2011; 31:211.
- Plunkett G, ALK-Abello, Round Rock, Texas, personal communication. Values are based on analysis of dozens of extracts from all manufacturers in the US, 2011.
- Kang B, Vellody D, Homburger H, Yunginger JW. Cockroach cause of allergic asthma. Its specificity and immunologic profile. J Allergy Clin Immunol 1979; 63:80.
- Nanda A, Wasan AN. Clinical assessment of allergen immunotherapy with differing doses of horse extract. Ann Allergy Asthma Immunol 2014; 112:76.
- Bousquet PJ, Castelli C, Daures JP, et al. Assessment of allergen sensitization in a general population-based survey (European Community Respiratory Health Survey I). Ann Epidemiol 2010; 20:797.
- Arbes SJ Jr, Gergen PJ, Elliott L, Zeldin DC. Prevalences of positive skin test responses to 10 common allergens in the US population: results from the third National Health and Nutrition Examination Survey. J Allergy Clin Immunol 2005; 116:377.
- de Jong AB, Dikkeschei LD, Brand PL. Sensitization patterns to food and inhalant allergens in childhood: a comparison of non-sensitized, monosensitized, and polysensitized children. Pediatr Allergy Immunol 2011; 22:166.
- Lowell FC, Franklin W. A double-blind study of the effectiveness and specificity of injecton therapy in ragweed hay fever. N Engl J Med 1965; 273:675.
- Franklin W, Lowell FC. Comparison of two dosages of ragweed extract in the treatment of pollenosis. JAMA 1967; 201:915.
- Johnstone DE, Dutton A. The value of hyposensitization therapy for bronchial asthma in children--a 14-year study. Pediatrics 1968; 42:793.
- Frew AJ, Powell RJ, Corrigan CJ, et al. Efficacy and safety of specific immunotherapy with SQ allergen extract in treatment-resistant seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006; 117:319.
- Cox L, Esch RE, Corbett M, et al. Allergen immunotherapy practice in the United States: guidelines, measures, and outcomes. Ann Allergy Asthma Immunol 2011; 107:289.
- Niemeijer NR, Kauffman HF, van Hove W, et al. Effect of dilution, temperature, and preservatives on the long-term stability of standardized inhalant allergen extracts. Ann Allergy Asthma Immunol 1996; 76:535.
- Plunkett G. Stability of allergen extracts used in skin testing and immunotherapy. Curr Opin Otolaryngol Head Neck Surg 2008; 16:285.
- Calabria CW, Coop CA, Tankersley MS. The GILL study: glycerin-induced local reactions in immunotherapy. J Allergy Clin Immunol 2008; 121:222.
- Van Metre TE Jr, Rosenberg GL, Vaswani SK, et al. Pain and dermal reaction caused by injected glycerin in immunotherapy solutions. J Allergy Clin Immunol 1996; 97:1033.
- Nelson HS, Iklé D, Buchmeier A. Studies of allergen extract stability: the effects of dilution and mixing. J Allergy Clin Immunol 1996; 98:382.
- Grier TJ, LeFevre DM, Duncan EA, Esch RE. Stability of standardized grass, dust mite, cat, and short ragweed allergens after mixing with mold or cockroach extracts. Ann Allergy Asthma Immunol 2007; 99:151.
- Grier TJ, Hall DM, Duncan EA, Coyne TC. Mixing compatibilities of Aspergillus and American cockroach allergens with other high-protease fungal and insect extracts. Ann Allergy Asthma Immunol 2015; 114:233.
- Grier TJ, LeFevre DM, Duncan EA, et al. Allergen stabilities and compatibilities in mixtures of high-protease fungal and insect extracts. Ann Allergy Asthma Immunol 2012; 108:439.
- Cox L, Jacobsen L. Comparison of allergen immunotherapy practice patterns in the United States and Europe. Ann Allergy Asthma Immunol 2009; 103:451.
- TYPES OF ALLERGEN EXTRACTS
- Standardized allergens
- Nonstandardized allergens
- CREATING A MAINTENANCE EXTRACT
- Multiple-allergen immunotherapy extracts
- Dilutions and diluents
- - Diluent options
- Human serum albumin
- OTHER CONSIDERATIONS
- Cross-allergenicity among allergens
- Compatibility of allergen extracts
- Individual versus shared allergen immunotherapy extracts
- Mixing extracts in a syringe before administration
- Transport of extracts
- TRAINING FOR QUALITY CONTROL IN PREPARATION OF ALLERGEN IMMUNOTHERAPY EXTRACTS
- Clinician responsibility
- Qualifications of extract preparation personnel
- RECORDING PRESCRIPTIONS FOR ALLERGEN IMMUNOTHERAPY
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS