169 Artigo de Revisão Allergic cutaneous reactions to systemic corticosteroids* Reações cutâneas alérgicas a corticóides sistêmicos* Raymond Ramirez 1 Ronald R. Brancaccio 2 Abstract: Contact allergic reactions to topical corticosteroids are common. Cutaneous hypersensitivity reactions to systemically administered corticosteroids might occur though less frequently. The purpose of this literature review is to examine reported cases of cutaneous reactions to systemically administered corticosteroids. The data are presented considering route of administration, type of drug, type of reac- tion, and testing results. Corticosteroid classifications, cross-reactions, and allergy testing methods are also discussed. Keywords: Adrenal cortex hormones; Adrenal cortex hormones/adverse effects; Betamethasone; Hydrocortisone; Hypersensitivity; Intradermal tests; Prednisolone; Prednisone; Triamcinolone; Patch tests Reumo: São comuns as reações alérgicas de contato a corticóides tópicos. Podem ocorrer reações cutâneas de hipersensibilidade a corticóides sistêmicos, mas são menos frequentes. O objetivo desta revisão da literatura é examinar relatos de casos de reações cutâneas a corticóides sistêmicos. Os dados apresentados levam em consideração a via de administração, tipo de medicamento, tipo de reação e resultados dos testes. A revisão discute também sobre classificações de corticóides, reações cruzadas e testes alérgicos. Palavras-chave: Betametasona; Corticosteróides; Corticosteróides/efeitos adversos; Hidrocortisona; Hipersensibilidade; Prednisolona; Prednisona; Testes do emplastro; Testes intradérmicos; Triamcinolona ALLERGIC CUTANEOUS REACTIONS TO SYSTEMIC CORTICOSTEROIDS Corticosteroids are commonly used in dermatol- the presentation of corticosteroid haptens.5 ogy and other medical specialties for their anti-inflam- Immediate hypersensitivity (Type I) reactions matory and immunosuppressive effects. Cutaneous have also been reported, generally in the setting of hypersensitivity reactions to topical corticosteroids are intravenous administrations. The exact mechanism of a well established and relatively common phenome- these reactions is unclear, but an IgE-mediated mech- non, with a reported incidence of up to 5% in dermati- anism is presumed. 3 tis patients.1,2 Cutaneous hypersensitivity reactions have The intent of this article is to review the various also been reported with systemically administered cor- systemic administration routes for corticosteroids, ticosteroids, though much less frequently, especially in reported allergic cutaneous reactions, the most com- light of their widespread usage worldwide. mon offending agents, methods for testing for hyper- Cutaneous reactions to corticosteroids are usu- sensitivity, and cross reaction patterns. ally delayed hypersensitivity reactions (type IV). 3 These delayed hypersensitivity reactions occur more readily Reactions and methods of administration following topical exposure to corticosteroids than via Corticosteroid therapies are utilized in a multi- other routes of administration. 4 This appears to be due tude of formulations by nearly all fields of medicine. In to the role of epidermal Langerhans cells essential for dermatology, corticosteroids are most commonly used Approved by the Editorial Council and accepted for publication on 19.01.2007. 1 D.O. Dermatology Resident Lutheran Medical Center Dept. of Dermatology Brooklyn New York, (NY), United States of America. 2 M.D. Clinical Professor of Dermatology Ronald O. Perelman Department of Dermatology New York University, School of Medicine New York, (NY), United States of America. ©2007 by Anais Brasileiros de Dermatologia An Bras Dermatol. 2007;82(2):169-76. 170 Ramirez R , Brancaccio RR. topically. Other medical specialties, however, frequent- Intramuscular ly utilize systemic formulations via oral, inhaled, and Triamcinolone acetonide is the most common- injected routes. We reviewed the relevant literature for ly used intramuscular corticosteroid and reactions reports of cutaneous reactions to systemically adminis- including generalized rash and urticaria have been tered corticosteroids. No doubt there are other reports reported (Table 2).10-17 In one case, the diagnosis was not captured in this review. Our intent is that the infor- achieved with patch testing, while the other cases mation presented in this article will provide the reader required intradermal testing. Cases of reactions to with an overview of the types of allergic cutaneous reac- methylprednisolone and hydrocortisone have also tions to systemically administered corticosteroids. been reported. Patch testing was not, however, per- formed and the diagnosis was made by intradermal Oral testing.18-19 The most common reactions to orally adminis- tered corticosteroids occurred with prednisolone Intralesional (Table 1).6-11 Allergic reactions were also noted with Intralesional injection of corticosteroids is a prednisone, betamethasone, and triamcinolone, commonly used tool in dermatologic practices for though in lesser numbers.12-16 The majority of these the treatment of keloid scars, psoriasis, acne, and cutaneous reactions were widespread in their pre- other inflammatory dermatoses. sentations, including generalized dermatitis and Triamcinolone is the most commonly used urticarial reactions. intralesional corticosteroid agent. Two of the report- Patch testing appears to have been successful ed reactions to intralesional corticosteroids were as the primary tool for diagnosing allergy to orally localized cutaneous reactions, although one report of administered corticosteroids. Further investigations, a generalized reaction, a case of anaphylaxis to triam- such as intradermal testing, may be required and cinolone, occurred (Table 3).20-24 were positive in four of the above cases. TABLE 1: Allergic reactions to oral corticosteroids Drug Reactions Testing Results Prednisolone Worsening of dermatitis + Patch Test: tixocortol pivalate, hydrocortisone Prednisolone Angioedema, dermatitis + Patch Test: group A,C,D (prednisolone, betamethasone) + Intradermal Test: hydrocortisone, prednisolone, methylprednisolone Prednisolone Generalized maculopapular + Patch Test: betamethasone, pivalone, hydrocortisone, rash prednisolone, aclomethasone Prednisolone Generalized erythema + Patch Test: prednisolone, methylprednisolone Prednisolone Worsening of dermatitis + Patch Test: tixocortol pivalate, betamethasone, clobetasol, beclomethasone, fluocinolone, triamcinolone, methylprednisolone, prednisolone, dexamethasone Prednisolone Urticarial eruption of face + Intradermal Test: hydrocortisone, prednisolone, dexamethasone Prednisone Generalized urticaria and facial edema + Intradermal Test: hydrocortisone acetate, methylprednisolone Prednisone Generalized dermatitis + Patch Test: prednisone +Oral Challenge: prednisone Betamethasone Maculopapular rash + Patch Test: betamethasone, dexamethasone, fluocortisone Triamcinolone Papulovesicular eruption + Patch Test: triamcinolone, dexamethasone, desoxymethasone + Intradermal Test: triamcinolone, desoxymethasone Triamcinolone Generalized erythema- + Patch Test: budesonide, triamcinolone acetonide multiforme-like eruption + = positive An Bras Dermatol. 2007;82(2):63-70. Allergic cutaneous reactions to systemic corticosteroids 171 TABLE 2: Allergic reactions to intramuscular corticosteroids Drug Reactions Testing Results Triamcinolone Generalized rash + Patch Test: multiple corticosteroids Triamcinolone Urticaria Patch Test: Negative + Intradermal Test: prednisone acetonide, triamcinolone acetonide, dexamethasone acetate, hydrocortisone acetate Methylprednisolone Anaphylaxis + Intradermal Test: methylprednisolone Hydrocortisone Anaphylaxis + Intradermal Test: hydrocortisone sodium succinate + = positive Intravenous There are numerous reports of reactions to adverse reactions reported with the use of these med- intravenous corticosteroids. 25-36 Of 12 cases reviewed ications are localized. These reactions include ery- for reactions to intravenously administered corticos- thema, dryness, and irritation of the nasal and oral teroids, 10 cases noted anaphylactic or urticarial reac- mucosa. Such reactions may also extend to the peri- tions.25-34 The majority of these reactions are reported oral or perinasal skin and thus present to dermatol- to occur with methylprednisolone and are immediate ogy. hypersensitivity reactions reported as anaphylaxis or The three reports we reviewed noted two cases acute worsening of preexisting asthma. Examples of of dermatitis and one case of angioedema. Patch test- these cases are listed (Table 4). Other reported cuta- ing successfully diagnosed contact allergy in all three neous reactions were a pruritic rash and purpura to cases (Table 5).37-38 methylprednisolone and hydrocortisone. In some of Isaksson et al reviewed 34 patients with a his- the reported cases of reactions to intravenous corti- tory of side-effects following inhaled corticosteroid costeroids, allergy testing was not performed. use.39 These reactions included facial rash, epistaxis, urticaria, and pruritus. Of these 34 patients, however, Inhalation (oral inhalers and nasal inhalers) only one patient was found to be positive on patch Orally inhaled and intranasal steroids, such as testing to tixocortol pivalate. This raises the possibili- budesonide, fluticosone, betamethasone, and mome- ty of other possible allergens in inhaled corticos- tasone, have become common treatment modalities teroids which induce cutaneous hypersensitivity reac- for asthma