Hypersensitivity reactions to systemic glucocorticoids
- Rima Rachid, MD
Rima Rachid, MD
- Assistant Professor of Pediatrics
- Harvard Medical School
- Boston Children's Hospital
Glucocorticoids are prescribed for their immunosuppressive, antiproliferative, anti-inflammatory, and antiallergenic effects and are integral to the management of numerous conditions, including malignancies, transplantation, autoimmune and allergic diseases, and asthma. They are also administered to prevent late-phase anaphylactic reactions. However, injected, infused, or orally administered systemic glucocorticoids have been associated with immediate hypersensitivity (allergic) reactions, including life-threatening anaphylaxis.
This topic will review the epidemiology, clinical manifestations, diagnosis, and management of hypersensitivity reactions to systemic glucocorticoids. Topical corticosteroids, usually in the form of skin preparations or inhaled glucocorticoids, can cause contact hypersensitivity, which is discussed elsewhere. (See "General principles of dermatologic therapy and topical corticosteroid use", section on 'Side effects' and "Major side effects of inhaled glucocorticoids", section on 'Contact hypersensitivity'.)
Hypersensitivity reactions to systemic glucocorticoids are rare, although the exact incidence is unknown. These reactions appear to occur in ≥0.1 percent of parenteral administrations, as demonstrated in the following studies:
●An early report in the 1950s described 6700 glucocorticoid injections given to 2256 patients . There were 20 instances of urticaria (including reactions localized to the injection site) or bronchospasm (0.29 percent of injections and 0.89 percent of patients).
●In a prospective study involving 202 children with rheumatologic diseases, approximately 0.1 percent of 10,000 doses of glucocorticoids administered were thought to cause reactions that were possibly of an allergic nature . Symptoms included pruritus, hives, and anaphylactic-like reactions. There was no statistical difference with respect to the ethnicity or underlying rheumatologic condition.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- KENDALL PH. Untoward effects following local hydrocortisone injection. Ann Phys Med 1958; 4:170.
- Klein-Gitelman MS, Pachman LM. Intravenous corticosteroids: adverse reactions are more variable than expected in children. J Rheumatol 1998; 25:1995.
- Caduff C, Reinhart WH, Hartmann K, Kuhn M. [Immediate hypersensitivity reactions to parenteral glucocorticoids? Analysis of 14 cases]. Schweiz Med Wochenschr 2000; 130:977.
- Saito R, Moroi S, Okuno H, Ogawa O. Anaphylaxis following administration of intravenous methylprednisolone sodium succinate in a renal transplant recipient. Int J Urol 2004; 11:171.
- Laine-Cessac P, Moshinaly H, Gouello JP, et al. [Severe anaphylactoid reactions after intravenous corticosteroids. Report of a case and review of the literature]. Therapie 1990; 45:505.
- Dajani BM, Sliman NA, Shubair KS, Hamzeh YS. Bronchospasm caused by intravenous hydrocortisone sodium succinate (Solu-Cortef) in aspirin-sensitive asthmatics. J Allergy Clin Immunol 1981; 68:201.
- Partridge MR, Gibson GJ. Adverse bronchial reactions to intravenous hydrocortisone in two aspirin-sensitive asthmatic patients. Br Med J 1978; 1:1521.
- Vatti RR, Ali F, Teuber S, et al. Hypersensitivity reactions to corticosteroids. Clin Rev Allergy Immunol 2014; 47:26.
- Kamm GL, Hagmeyer KO. Allergic-type reactions to corticosteroids. Ann Pharmacother 1999; 33:451.
- Rachid R, Leslie D, Schneider L, Twarog F. Hypersensitivity to systemic corticosteroids: an infrequent but potentially life-threatening condition. J Allergy Clin Immunol 2011; 127:524.
- Butani L. Corticosteroid-induced hypersensitivity reactions. Ann Allergy Asthma Immunol 2002; 89:439.
- Karsh J, Yang WH. An anaphylactic reaction to intra-articular triamcinolone: a case report and review of the literature. Ann Allergy Asthma Immunol 2003; 90:254.
- Mace S, Vadas P, Pruzanski W. Anaphylactic shock induced by intraarticular injection of methylprednisolone acetate. J Rheumatol 1997; 24:1191.
- Pryse-Phillips WE, Chandra RK, Rose B. Anaphylactoid reaction to methylprednisolone pulsed therapy for multiple sclerosis. Neurology 1984; 34:1119.
- Johansson SG, Bieber T, Dahl R, et al. Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol 2004; 113:832.
- Burgdorff T, Venemalm L, Vogt T, et al. IgE-mediated anaphylactic reaction induced by succinate ester of methylprednisolone. Ann Allergy Asthma Immunol 2002; 89:425.
- Venturini M, Lobera T, del Pozo MD, et al. Immediate hypersensitivity to corticosteroids. J Investig Allergol Clin Immunol 2006; 16:51.
- Freedman MD, Schocket AL, Chapel N, Gerber JG. Anaphylaxis after intravenous methylprednisolone administration. JAMA 1981; 245:607.
- Fulcher DA, Katelaris CH. Anaphylactoid reaction to intravenous hydrocortisone sodium succinate: a case report and literature review. Med J Aust 1991; 154:210.
- Erdmann SM, Abuzahra F, Merk HF, et al. Anaphylaxis induced by glucocorticoids. J Am Board Fam Pract 2005; 18:143.
- Calogiuri GF, Muratore L, Nettis E, et al. Anaphylaxis to hydrocortisone hemisuccinate with cross-sensitivity to related compounds in a paediatric patient. Br J Dermatol 2004; 151:707.
- Mendelson LM, Meltzer EO, Hamburger RN. Anaphylaxis-like reactions to corticosteroid therapy. J Allergy Clin Immunol 1974; 54:125.
- Koutsostathis N, Vovolis V. Severe immunoglobulin E-mediated anaphylaxis to intravenous methylprednisolone succinate in a patient who tolerated oral methylprednisolone. J Investig Allergol Clin Immunol 2009; 19:330.
- Ben Said B, Leray V, Nicolas JF, et al. Methylprednisolone-induced anaphylaxis: diagnosis by skin test and basophil activation test. Allergy 2010; 65:531.
- Patterson DL, Yunginger JW, Dunn WF, et al. Anaphylaxis induced by the carboxymethylcellulose component of injectable triamcinolone acetonide suspension (Kenalog). Ann Allergy Asthma Immunol 1995; 74:163.
- Preuss L. Allergic reactions to systemic glucocorticoids: a review. Ann Allergy 1985; 55:772.
- Ventura MT, Calogiuri GF, Matino MG, et al. Alternative glucocorticoids for use in cases of adverse reaction to systemic glucocorticoids: a study on 10 patients. Br J Dermatol 2003; 148:139.
- Patel A, Bahna SL. Immediate hypersensitivity reactions to corticosteroids. Ann Allergy Asthma Immunol 2015; 115:178.
- Padial A, Antunez C, Blanca-Lopez N, et al. Non-immediate reactions to beta-lactams: diagnostic value of skin testing and drug provocation test. Clin Exp Allergy 2008; 38:822.
- López-Serrano MC, Moreno-Ancillo A, Contreras J, et al. Two cases of specific adverse reactions to systemic corticosteroids. J Investig Allergol Clin Immunol 1996; 6:324.
- Ventura MT, Sanapo F, Calogiuri GF, Satriano F. Anaphylaxis induced by intramuscular betamethasone disodium phosphate: reflections on a clinical case. Int J Immunopathol Pharmacol 2007; 20:387.
- Coopman S, Degreef H, Dooms-Goossens A. Identification of cross-reaction patterns in allergic contact dermatitis from topical corticosteroids. Br J Dermatol 1989; 121:27.
- Wilkinson SM. Corticosteroid cross-reactions: an alternative view. Contact Dermatitis 2000; 42:59.
- Baker A, Empson M, The R, Fitzharris P. Skin testing for immediate hypersensitivity to corticosteroids: a case series and literature review. Clin Exp Allergy 2015; 45:669.
- Nucera E, Lombardo C, Aruanno A, et al. 'Empty sella syndrome': a case of a patient with sodium succinate hydrocortisone allergy. Eur J Endocrinol 2011; 164:139.
- Levy Y, Segal N, Nahum A, et al. Hypersensitivity to methylprednisolone sodium succinate in children with milk allergy. J Allergy Clin Immunol Pract 2014; 2:471.
- Savvatianos S, Giavi S, Stefanaki E, et al. Cow's milk allergy as a cause of anaphylaxis to systemic corticosteroids. Allergy 2011; 66:983.
- Montoro J, Valero A, Elices A, et al. Anaphylactic shock after intra-articular injection of carboxymethylcellulose. Allergol Immunopathol (Madr) 2000; 28:332.
- Murrieta-Aguttes M, Michelen V, Leynadier F, et al. Systemic allergic reactions to corticosteroids. J Asthma 1991; 28:329.
- Laing ME, Fallis B, Murphy GM. Anaphylactic reaction to intralesional corticosteroid injection. Contact Dermatitis 2007; 57:132.
- Dewachter P, Mouton-Faivre C. Anaphylaxis to macrogol 4000 after a parenteral corticoid injection. Allergy 2005; 60:705.
- Borderé A, Stockman A, Boone B, et al. A case of anaphylaxis caused by macrogol 3350 after injection of a corticosteroid. Contact Dermatitis 2012; 67:376.
- Sohy C, Vandenplas O, Sibille Y. Usefulness of oral macrogol challenge in anaphylaxis after intra-articular injection of corticosteroid preparation. Allergy 2008; 63:478.
- Shah S, Prematta T, Adkinson NF, Ishmael FT. Hypersensitivity to polyethylene glycols. J Clin Pharmacol 2013; 53:352.
- Spoerl D, Scherer K, Bircher AJ. Contact urticaria with systemic symptoms due to hexylene glycol in a topical corticosteroid: case report and review of hypersensitivity to glycols. Dermatology 2010; 220:238.
- Walker AI, Räwer HC, Sieber W, Przybilla B. Immediate-type hypersensitivity to succinylated corticosteroids. Int Arch Allergy Immunol 2011; 155:86.
- Bousquet PJ, Gaeta F, Bousquet-Rouanet L, et al. Provocation tests in diagnosing drug hypersensitivity. Curr Pharm Des 2008; 14:2792.
- Solensky R. Drug desensitization. Immunol Allergy Clin North Am 2004; 24:425.
- Angel-Pereira D, Berges-Gimeno MP, Madrigal-Burgaleta R, et al. Successful rapid desensitization to methylprednisolone sodium hemisuccinate: a case report. J Allergy Clin Immunol Pract 2014; 2:346.
- Aouam K, Bouida W, Ben Fredj N, et al. Severe ranitidine-induced anaphylaxis: a case report and literature review. J Clin Pharm Ther 2012; 37:494.
- Barranco P, López-Serrano MC, Moreno-Ancillo A. Anaphylactic reaction due to diphenhydramine. Allergy 1998; 53:814.
- Shakouri AA, Bahna SL. Hypersensitivity to antihistamines. Allergy Asthma Proc 2013; 34:488.
- Rutkowski K, Wagner A. Cetirizine anaphylaxis. Ann Allergy Asthma Immunol 2014; 113:247.
- Risk factors
- CLINICAL MANIFESTATIONS
- Immediate reactions
- - Delayed recognition
- - Causative drugs
- Delayed reactions
- Skin testing
- - Suggested drug concentrations
- - Interpretation
- Other possible allergens in glucocorticoid preparations
- - Succinate esters
- - Preservatives and excipients
- In vitro testing
- Graded drug challenge
- - Indications
- - Safety issues
- DIFFERENTIAL DIAGNOSIS
- Allergy to antihistamines
- OTHER MANAGEMENT ISSUES
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS