Abstract
Corticosteroids are anti-inflammatory medications used widely to treat allergic inflammation. Although the endocrine and gastrointestinal side effects of corticosteroids have been described, the occurrence of immediate hypersensitivity reactions and delayed contact dermatitis due to corticosteroids remains under-recognized. Hypersensitivity reactions can occur to a corticosteroid itself, or to the additives and vehicles in corticosteroid preparations. Skin testing and oral graded challenge can help confirm the suspected culprit agent in immediate hypersensitivity reactions and help identify an alternative tolerated corticosteroid. Patch testing can help identify the culprit agents in delayed hypersensitivity contact dermatitis. Cross-reactivity patterns have not been observed for immediate hypersensitivity reactions as they have been for delayed contact dermatitis. Sensitization in contact dermatitis exhibits cross-reactivity patterns based on corticosteroid structure. We review the current understanding regarding the clinical presentation, evaluation, and management of immediate and delayed hypersensitivity reactions to corticosteroids.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
Zoorob RJ, Cender D. A different look at corticosteroids. Am Fam Physician. 1998;58:443–50.
Baeck M, Nicolas JF, Pilette C, Tennstedt D, Goossens A. Allergic hypersensitivity to topical and systemic corticosteroids: a review. Allergy. 2009;64:978–94.
Matura G. Contact allergy to corticosteroids. Allergy. 2000;55:698–704.
Patel A, Bahna S. Immediate hypersensitivity reactions to corticosteroids. Ann Allergy Asthma Immunol. 2015;115:178–182.e3. Comprehensive review of IgE-mediated reactions to corticosteroids from 2004–2014.
Kamm GL, Hagmeyer KO. Allergic-type reactions to corticosteroids. Ann Pharmacother. 1999;33:451–60.
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;45:669–76. Case series of 23 patients evaluated for IgE-mediated reactions with skin testing.
Nowak-Wegrzyn A, Shapiro G, Beyer K, Bardina L, Sampson H. Contamination of dry powder inhalers for asthma with milk proteins containing lactose. J Allergy Clin Immunol. 2004;113:558–60.
Stubbs SS, Morrell RM. Intravenous methylprednisolone sodium succinate: adverse reactions reported in association with immunosuppresive therapy. Transplant Proc. 1973;5:1145–6.
McDougal BA, Whittier FC, Cross DE. Sudden death after bolus steroid therapy for acute rejection. Transplant Proc. 1976;8:493–6.
Thompson JF, Chalmers DH, Wood RF, Kirkham SR, Morris PJ. Sudden death following high-dose intravenous methylprednisolone. Transplantation. 1983;36:594–6.
Al-Mahdy H, Hall M. Anaphylaxis and hydrocortisone. Ann Intern Med. 1988;108:487–8.
Bocanegra TS, Castañeda MO, Espinoza LR, Vasey FB, Germain BF. Sudden death after methylprednisolone pulse therapy. Ann Intern Med. 1981;95:122.
Pryse-Phillips WE, Chandra RK, Rose B. Anaphylactoid reaction to methylprednisolone pulsed therapy for multiple sclerosis. Neurology. 1984;34:1119–21.
Hayhurst M, Braude A, Benatar SR. Anaphylactic-like reaction to hydrocortisone. S Afr Med J. 1978;53:259–60.
Dajani B, Sliman N, Shubair K, Hamzeh Y. Bronchospasm caused by intravenous hydrocortisone sodium succinate (Solu-Cortef) in aspirin-sensitive asthmatics. J Allergy Clin Immunol. 1981;68:201–4.
Chan CS, Brown IG, Oliver WA, Zimmerman PV. Hydrocortisone-induced anaphylaxis. Med J Aust. 1984;141:444–6.
Mansfield LE, Ting S, Haverly RW. Anaphylaxis caused by the sodium succinate ester of hydrocortisone and methylprednisolone. J Asthma. 1986;23:81–3.
Doezema D. Anaphylaxis following administration of intravenous methylprednisolone sodium succinate. Am J Emer Med. 1987;5:42–4.
John GT, Thomas PP, Kirubakaran MG, Thomas M, Jacob CK, Shastry JC. Methylprednisolone sodium succinate-induced anaphylaxis in a nonatopic renal transplant recipient. Transplantation. 1989;48:543.
Sieck JO, al-Ohaly Y, Saour J, Khan M, Henriquez H. An allergic reaction to intravenous methylprednisolone administration. Br J Clin Pract. 1990;44:723–5.
Fulcher DA, Katelaris CH. Anaphylactoid reaction to intravenous hydrocortisone sodium succinate: a case report and literature review. Med J Aust. 1991;154:210–4.
Peces R, Gorostidi M, Azofra J, Sánchez L, Alvarez J. Anaphylaxis following intravenous methylprednisolone sodium succinate in a renal transplant recipient. Nephron. 1991;59:497–8.
Husum B, Palm T, Andersen K, Vejlsted H. Immediate hemodynamic effect of pharmacological doses of methylprednisolone in dogs, and the influence of speed of injection. Acta Anaesthesiol Scand. 1980;24:61–4.
Coopman S, Degreef H, Dooms-Goossens A. Identification of cross-reaction patterns in allergic contact dermatitis from topical corticosteroids. Br J Dermatol. 1989;121:27–34.
Baeck M, Chemelle J-AA, Terreux R, Drieghe J, Goossens A. Delayed hypersensitivity to corticosteroids in a series of 315 patients: clinical data and patch test results. Contact Dermatitis. 2009;61:163–75.
Venturini M, Lobera T, del Pozo MD, González I, Blasco A. Immediate hypersensitivity to corticosteroids. J Investig Allergol Clin Immunol. 2006;16:51–6.
Rodrigues-Alves R, Spínola-Santos A, Pedro E, Branco-Ferreira M, Pereira-Barbosa M. Immediate hypersensitivity to corticosteroids: finding an alternative. J Investig Allergol Clin Immunol. 2007;17:284–5.
Rachid R, Leslie D, Schneider L, Twarog F. Hypersensitivity to systemic corticosteroids: an infrequent but potentially life-threatening condition. J Allergy Clin Immunol. 2011;127:524–8.
Ehret GB, Deluze C, Dayer P, Desmeules JA. Systemic allergic reaction and diffuse bone pain after exposure to a preparation of betamethasone. Eur J Intern Med. 2005;16:612–4.
Escobosa M, Granados C, Quesada M, López A. Anaphylaxis due to methylprednisolone. J Investig Allergol Clin Immunol. 2008;18:407–8.
Aranda A, Mayorga C, Ariza A, Doña I, Blanca Lopez N, Canto G, et al. IgE mediated hypersensitivity reactions to methylprednisolone. Allergy. 2010;65:1376–80.
Calogiuri GF, Muratore GF, Nettis L, Ventura MT, Ferrannini A, Tursi A. Anaphylaxis to hydrocortisone hemisuccinate with cross sensitivity to related compounds in a paediatric patient. Br J Dermatol. 2004;151:707–8.
Angel-Pereira D, Berges-Gimeno M, Madrigal-Burgaleta R, Ureña-Tavera M, Zamora-Verduga M, Alvarez-Cuesta E. Successful rapid desensitization to methylprednisolone sodium hemisuccinate: a case report. J Allergy Clin Immunol: In Pract. 2014;2:346–8.
Kim S, Kim H. Anaphylaxis induced by oral methylprednisolone in a 10 year old boy. Pediatr Int. 2014;56:783–4.
Deruaz, Spertini, Lima S, Pasquier D, Schluep. Anaphylactic reaction to methylprednisolone in multiple sclerosis: a practical approach to alternative corticosteroids. Mult Scler. 2007
de Sousa NG, Santa-Marta C, Morais-Almeida M. Systemic corticosteroid hypersensitivity in children. J Investig Allergol Clin Immunol. 2010;20:529–32.
Nucera E, Lombardo C, Aruanno A, Colagiovanni A, Buonomo A, de Pasquale T, et al. “Empty sella syndrome”: a case of a patient with sodium succinate hydrocortisone allergy. Eur J Endocrinol. 2011;164:139–40.
Calogiuri GF, Nettis E, Di Leo E, Muratore L, Ferrannini A, Vacca A. Long-term selective IgE-mediated hypersensitivity to hydrocortisone sodium succinate. Allergol Immunopathol (Madr). 2013;41:206–8.
Compalati E, Guerra L, Rogkakou A, Zanella C, Scordamaglia A, Passalacqua G. Angioedema after administration of methylprednisolone to treat drug allergy. Allergy. 2007;62:1346–8.
Currie G, Paterson E, Keenan F, Nath S, Watt S. An unexpected response to intravenous hydrocortisone succinate in an asthmatic patient. Br J Clin Pharmacol. 2005;60:342.
Caimmi S, Caimmi D, Bousquet PJ, Demoly P. Succinate as opposed to glucocorticoid itself allergy. Allergy. 2008;63:1641–3.
Gelincik A, Yazici H, Emre T, Yakar F, Buyukozturk S. An alternative approach to a renal transplant patient who experienced an immediate type systemic reaction due to methylprednisolone sodium succinate. J Investig Allergol Clin Immunol. 2009;19:162–3.
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;19:330–2.
Walker AI, Räwer H-C, Sieber W, Przybilla B. Immediate-type hypersensitivity to succinylated corticosteroids. Int Arch Allergy Immunol. 2010;155:86–92.
Eda A, Sugai K, Shioya H, Fujitsuka A, Ito S, Iwata T, et al. Acute allergic reaction due to milk proteins contaminating lactose added to corticosteroid for injection. Allergol Int. 2009;58:137–9.
Savvatianos S, Giavi S, Stefanaki E, Siragakis G, Manousakis E, Papadopoulos NG. Cow’s milk allergy as a cause of anaphylaxis to systemic corticosteroids. Allergy. 2011;66:983–5.
Levy Y, Segal N, Nahum A, Marcus N, Garty B-Z. Hypersensitivity to methylprednisolone sodium succinate in children with milk allergy. J Allergy Clin Immunol In Pract. 2014;2:471–4.
Laing ME, Fallis B, Murphy GM. Anaphylactic reaction to intralesional corticosteroid injection. Contact Dermatitis. 2007;57:132–3.
Field S, Falvey E, Barry J, Bourke J. Type 1 hypersensitivity reaction to carboxymethylcellulose following intra articular triamcinolone injection. Contact Dermatitis. 2009;61:302–3.
Steiner U, Gentinetta T, Hausmann O, Pichler W. IgE-mediated anaphylaxis to intraarticular glucocorticoid preparations. AJR Am J Roentgenol. 2009;193:W156–7.
Hadithy A, van Maaren M, Vermes A. Anaphylactic reactions following Kenacort A® injection: carboxymethylcellulose is involved once again. Contact Dermatitis. 2011;64:179–80.
Patterson DL, Yunginger JW, Dunn WF, Jones RT, Hunt LW. Anaphylaxis induced by the carboxymethylcellulose component of injectable triamcinolone acetonide suspension (Kenalog). Ann Allergy Asthma Immunol. 1995;74:163–6.
Dewachter P, Mouton-Faivre C. Anaphylaxis to macrogol 4000 after a parenteral corticoid injection. Allergy. 2005;60:705–6.
Sohy C, Vandenplas O, Sibille Y. Usefulness of oral macrogol challenge in anaphylaxis after intra articular injection of corticosteroid preparation. Allergy. 2008;63:478–9.
Moran D, Moynagh M, Alzanki M, Chan V, Eustace S. Anaphylaxis at image-guided epidural pain block secondary to corticosteroid compound. Skelet Radiol. 2012;41:1317–8.
Borderé A, Stockman A, Boone B, Franki A, Coppens M, Lapeere H, et al. A case of anaphylaxis caused by macrogol 3350 after injection of a corticosteroid. Contact Dermatitis. 2012;67:376–8.
Spoerl D, Scherer K, Bircher A. Contact urticaria with systemic symptoms due to hexylene glycol in a topical corticosteroid: case report and review of hypersensitivity to glycols. Dermatology. 2010;220:238–42.
Drug allergy: an updated practice parameter. Ann. Allergy Asthma Immunol. 2010;105:259–273.
Muroi N, Nishibori M, Fujii T, Yamagata M, Hosoi S, Nakaya N, et al. Anaphylaxis from the carboxymethylcellulose component of barium sulfate suspension. N Engl J Med. 1997;337:1275–7.
Bigliardi PL, Izakovic J, Weber JM, Bircher A. Anaphylaxis to the carbohydrate carboxymethylcellulose in parenteral corticosteroid preparations. Dermatology. 2003;207:100–3.
Asakawa H, Araki T, Imai I, Tsutsumi Y, Kawakami F. Skin tests of steroid allergy. Allergy. 1999;54:645–6.
Figueredo E, Cuesta-Herranz JI, De Las Heras M, Lluch-Bernal M, Umpierrez A, Sastre J. Anaphylaxis to dexamethasone. Allergy. 1997;52:877.
Mace S, Vadas P, Pruzanski W. Anaphylactic shock induced by intraarticular injection of methylprednisolone acetate. J Rheumatol. 1997;24:1191–4.
Montoro J, Valero A, Serra Baldrich E, Amat P, Lluch M, Malet A. Anaphylaxis to paramethasone with tolerance to other corticosteroids. Allergy. 2000;55:197–8.
Vatti R, Ali F, Teuber S, Chang C, Gershwin E. Hypersensitivity reactions to corticosteroids. Clin Rev Allergy Immunol. 2013;47:26–37. Comprehensive review of immediate and delayed corticosteroid-induced reactions.
Skoet R, Zachariae R, Agner T. Contact dermatitis and quality of life: a structured review of the literature. Br J Dermatol. 2003;149:452–6.
Rodríguez-Serna M, Silvestre JF, Quecedo E, Martínez A, Miguel FJ, Gauchía R. Corticosteroid allergy: report of 3 unusually acute cases. Contact Dermatitis. 1996;35:361–2.
Miranda Romero A, Sánchez Sambucety P, Bajo C, Martinez M, Garcia Munoz M. Genital oedema from contact allergy to prednicarbate. Contact Dermatitis. 1998;38:228.
Valsecchi R, Reseghetti A, Leghissa P, Cologni L, Cortinovis R. Erythema-multiforme-like lesions from triamcinolone acetonide. Contact Dermatitis. 1998;38:362–3.
Stingeni L, Caraffini S, Assalve D, Lapomarda V, Lisi P. Erythema-multiforme-like contact dermatitis from budesonide. Contact Dermatitis. 1996;34:154–5.
Calista D, Schianchi S. Erythema multiforme-like eruption induced by contact dermatitis caused by topical corticosteroids. G Ital Dermatol Venereol. 2008;143:227–8.
Lepoittevin JP, Drieghe J, Dooms-Goossens A. Studies in patients with corticosteroid contact allergy. Understanding cross-reactivity among different steroids. Arch Dermatol. 1995;131:31–7.
Wilkinson SM, English JS. Hydrocortisone sensitivity: a prospective study of the value of tixocortol pivalate and hydrocortisone acetate as patch test markers. Contact Dermatitis. 1991;25:132–3.
Lauerma AI, Tarvainen K, Forström L, Reitamo S. Contact hypersensitivity to hydrocortisone-free-alcohol in patients with allergic patch test reactions to tixocortol pivalate. Contact Dermatitis. 1993;28:10–4.
Wilkinson SM, Jones MF. Corticosteroid usage and binding to arginine: determinants of corticosteroid hypersensitivity. Br J Dermatol. 1996;135:225–30.
Matura M, Lepoittevin JP, Arbez Gindre C, Goossens A. Testing with corticosteroid aldehydes in corticosteroid sensitive patients (preliminary results). Contact Dermatitis. 1998;38:106–8.
Fonacier L, Sher J. Allergic contact dermatitis. Ann Allergy Asthma Immunol. 2014;113:9–12.
Saripalli Y, Achen F, Belsito D. The detection of clinically relevant contact allergens using a standard screening tray of twenty-three allergens. J Am Acad Dermatol. 2003;49:65–9.
Boffa MJ, Wilkinson SM, Beck MH. Screening for corticosteroid contact hypersensitivity. Contact Dermatitis. 1995;33:149–51.
Camacho-Halili M, Axelrod S, Michelis M, Lighvani S, Khan F, Leon S, et al. A multi-center, retrospective review of patch testing for contact dermatitis in allergy practices. Ann Allergy Asthma Immunol. 2011;107:487–92.
Warshaw EM, Belsito DV, Taylor JS, Sasseville D, DeKoven JG, Zirwas MJ, et al. North American Contact Dermatitis Group patch test results: 2009 to 2010. Dermatitis. 2013;24:50–9.
Schalock P, Dunnick C, Nedorost S, Brod B, Warshaw E, Mowad C. American Contact Dermatitis Society Core Allergen Series. Dermatitis. 2013;24:7.
Ljubojevic S, Lipozencic J, Basta-Juzbasic A. Contact allergy to corticosteroids and Malassezia furfur in seborrhoeic dermatitis patients. J Europ Acad Dermatol Venereol Jeadv. 2010;25:647–51.
Wilkinson SM, Beck MH. Corticosteroid contact hypersensitivity: what vehicle and concentration? Contact Dermatitis. 1996;34:305–8.
Förström L, Lassus A, Salde L, Niemi KM. Allergic contact eczema from topical corticosteroids. Contact Dermatitis. 1982;8:128–33.
Isaksson M, Gruvberger B, Persson L, Bruze M. Stability of corticosteroid patch test preparations. Contact Dermatitis. 2000;42:144–8.
Yim E, Baquerizo Nole KL, Tosti A. Contact dermatitis caused by preservatives. Dermatitis. 2014;25:215–31.
Wolf R, Orion E, Ruocco E, Baroni A, Ruocco V. Contact dermatitis: facts and controversies. Clin Dermatol. 2013;31:467–78.
Hogan DJ. Allergic contact dermatitis to ethylenediamine. A continuing problem. Dermatol Clin. 1990;8:133–6.
Asarch A, Scheinman PL. Sorbitan sesquioleate, a common emulsifier in topical corticosteroids, is an important contact allergen. Dermatitis. 2008;19:323–7.
Funk JO, Maibach HI. Propylene glycol dermatitis: re-evaluation of an old problem. Contact Dermatitis. 1994;31:236–41.
Warshaw EM, Botto NC, Maibach HI, Fowler JF, Rietschel RL, Zug KA, et al. Positive patch-test reactions to propylene glycol: a retrospective cross-sectional analysis from the North American Contact Dermatitis Group, 1996 to 2006. Dermatitis. 2009;20:14–20.
Coloe J, Zirwas MJ. Allergens in corticosteroid vehicles. Dermatitis. 2008;19:38–42.
Nelson J, Mowad C. Allergic Contact Dermatitis: patch testing beyond the TRUE Test. J Clin Aesthet Dermatol. 2010;3:36–41.
Pereira F, Cunha H, Dias M. Contact dermatitis due to emulsifiers. Contact Dermatitis. 1997;36:114.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare that they have no competing interests.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Additional information
This article is part of the Topical Collection on Anaphylaxis and Drug Allergy
Rights and permissions
About this article
Cite this article
Otani, I.M., Banerji, A. Immediate and Delayed Hypersensitivity Reactions to Corticosteroids: Evaluation and Management. Curr Allergy Asthma Rep 16, 18 (2016). https://doi.org/10.1007/s11882-016-0596-7
Published:
DOI: https://doi.org/10.1007/s11882-016-0596-7