Anaphylaxis to 6-α-methylprednisolone in an eight-year-old child

Abstract

Corticosteroids are widely used in the treatment of several diseases, including allergic or pseudoallergic reactions. It is therefore somewhat ironic that they may be responsible for adverse events and provoke allergic or allergic-like reactions. Allergic reactions to hydrocortisone have been reported since the 1950s.1Peller JS Bardana EJ Anaphylactoid reaction to corticosteroids: case report and review of the literature.Ann Allergy. 1985; 54: 302-305PubMed Google Scholar, 2Preuss L Allergic reactions to systemic glucocorticoids: a review.Ann Allergy. 1985; 55: 772-775PubMed Google Scholar These reactions may be immunologic or nonimmunologic in nature, and they are very rare. Allergic contact dermatitis caused by corticosteroids, however, seems to be more common, and prevalences near 4% have been reported in recent studies of patients who have undergone patch testing.3Dooms-Goossens A Morren M Result of routine patch testing with corticosteroids: series in 2073 patients.Contact Dermatitis. 1992; 26: 182-191Crossref PubMed Scopus (184) Google Scholar Hydrocortisone and methylprednisolone are the most common drugs involved in systemic adverse reactions. Prednisone, betamethasone, and dexamethasone are reported less frequently as causative agents.1Peller JS Bardana EJ Anaphylactoid reaction to corticosteroids: case report and review of the literature.Ann Allergy. 1985; 54: 302-305PubMed Google Scholar, 2Preuss L Allergic reactions to systemic glucocorticoids: a review.Ann Allergy. 1985; 55: 772-775PubMed Google Scholar, 6Rasanen I Hasan T Allergy to systemic and intralesional corticosteroids.Br J Dermatol. 1993; 128: 407-411Crossref PubMed Scopus (54) Google Scholar Allergic or pseudoallergic reactions to systemic corticosteroid therapy include bronchospasm,1Peller JS Bardana EJ Anaphylactoid reaction to corticosteroids: case report and review of the literature.Ann Allergy. 1985; 54: 302-305PubMed Google Scholar, 2Preuss L Allergic reactions to systemic glucocorticoids: a review.Ann Allergy. 1985; 55: 772-775PubMed Google Scholar, 4Szczeklik A Nizankowska E Czerniawska-Mysik G Sek S Hydrocortisone and airflow impairment in aspirin-induced asthma.J ALLERGY CLIN IMMUNOL. 1985; 76: 530-536Abstract Full Text PDF PubMed Scopus (54) Google Scholar, 5Dajani 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: 201-204Abstract Full Text PDF PubMed Scopus (78) Google Scholar urticaria with or without angioedema,1Peller JS Bardana EJ Anaphylactoid reaction to corticosteroids: case report and review of the literature.Ann Allergy. 1985; 54: 302-305PubMed Google Scholar, 2Preuss L Allergic reactions to systemic glucocorticoids: a review.Ann Allergy. 1985; 55: 772-775PubMed Google Scholar, 6Rasanen I Hasan T Allergy to systemic and intralesional corticosteroids.Br J Dermatol. 1993; 128: 407-411Crossref PubMed Scopus (54) Google Scholar and anaphylaxis.1Peller JS Bardana EJ Anaphylactoid reaction to corticosteroids: case report and review of the literature.Ann Allergy. 1985; 54: 302-305PubMed Google Scholar, 2Preuss L Allergic reactions to systemic glucocorticoids: a review.Ann Allergy. 1985; 55: 772-775PubMed Google Scholar, 7Mendelson LM Meltzer EO Hamburger RN Anaphylaxis-like reactions to corticosteroid therapy.J ALLERGY CLIN IMMUNOL. 1974; 54: 125-131Abstract Full Text PDF PubMed Scopus (94) Google Scholar Previous contact dermatitis resulting from topical corticosteroid therapy may occasionally predispose the patient to a generalized reaction after systemic corticosteroid therapy.6Rasanen I Hasan T Allergy to systemic and intralesional corticosteroids.Br J Dermatol. 1993; 128: 407-411Crossref PubMed Scopus (54) Google Scholar We report a case of anaphylaxis resulting from an intramuscular injection of 6-α-methylprednisolone. Type 1 hypersensitivity was proved by a positive skin test response. Other corticosteroids were tolerated. An 8-year-old boy with mild cat dander–induced asthma consulted us because he had had an adverse reaction to Urbason (6-α-methylprednisolone hemisuccinate, monosodium phosphate, disodium phosphate, and distilled water). He had been treated with this drug before and had shown good tolerance. No other diseases were reported. After the boy spent the night at the house of a friend who kept several cats, cough and wheezing developed. He was seen at our hospital’s emergency department where he was treated with nebulized albuterol. When symptoms remitted and before he was sent home, 20 mg of Urbason was administered intramuscularly. Immediately after the injection, sneezing, severe generalized erythematous urticaria, and a marked increase of wheezing with dyspnea developed. Further administration of nebulized albuterol, intravenous aminophiline, and epinephrine was necessary to reverse this reaction. Complete resolution of symptoms was observed in 4 days. Skin prick tests with Urbason, 10 mg/ml, and pure 6-α-methylprednisolone dissolved in water at a concentration of 10 mg/ml were performed. Skin prick tests with additives at 10 mg/ml and several other corticosteroids (hydrocortisone at 10 mg/ml and 50 mg/ml; prednisone, prednisolone, betamethasone, dexamethasone, and deflazacort at 10 mg/ml and 20 mg/ml; and budesonide at 0.5 mg/ml) were performed. Epicutaneous patch tests with hydrocortisone, methylprednisolone, budesonide, tixocortol, and prednisolone 10% in petrolatum and 10 mg/ml in dimethylsulfoxide–ethanol (1:1) were performed to obtain more information regarding the mechanism of the reaction. The patient tolerated the additives in other pharmacologic preparations, so challenges were not deemed necessary. Challenges with corticosteroids, theophylline, sulfites, and aspirin were carried out. The total amount of IgE (IMX System; Abbott Laboratories, Diagnositic Div., Chicago, Ill.) was estimated, but RAST system (Pharmacia, Uppsala, Sweden) failed to measure serum-specific IgE. Results of skin prick tests with both Urbason (wheal, 6 × 6 mm; flare, 10 × 13 mm) and pure 6-α-methylprednisolone (wheal, 6 × 7 mm; flare, 12 × 13 mm) were positive. Tests were repeated twice with same result (histamine control wheal, 5 × 5 mm; flare, 11 × 10 mm; saline solution, 0 mm). Skin prick tests were also performed on 10 atopic patients and on 10 nonatopic control subjects, and in both cases results were negative. Results of skin prick tests performed on our patient with the other corticosteroids and additives were negative. All patch test results were negative at 24, 48, and 72 hours. Total IgE was 346 IU/ml. Haematologic and biochemical findings were within the normal range. Our patient was challenged with the most commonly prescribed corticosteroids (except methylprednisolone), beginning with the most structurally different drugs. Therapeutic doses of deflazacort, budesonide, hydrocortisone, prednisone, and prednisolone were tolerated. All drugs were given on different days. Aspirin, sulfites, and aminophylline were also tolerated. Cases of allergic and pseudoallergic reactions resulting from systemic corticosteroid therapy have been reported in the literature.1Peller JS Bardana EJ Anaphylactoid reaction to corticosteroids: case report and review of the literature.Ann Allergy. 1985; 54: 302-305PubMed Google Scholar, 2Preuss L Allergic reactions to systemic glucocorticoids: a review.Ann Allergy. 1985; 55: 772-775PubMed Google Scholar, 4Szczeklik A Nizankowska E Czerniawska-Mysik G Sek S Hydrocortisone and airflow impairment in aspirin-induced asthma.J ALLERGY CLIN IMMUNOL. 1985; 76: 530-536Abstract Full Text PDF PubMed Scopus (54) Google Scholar, 5Dajani 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: 201-204Abstract Full Text PDF PubMed Scopus (78) Google Scholar, 6Rasanen I Hasan T Allergy to systemic and intralesional corticosteroids.Br J Dermatol. 1993; 128: 407-411Crossref PubMed Scopus (54) Google Scholar, 7Mendelson LM Meltzer EO Hamburger RN Anaphylaxis-like reactions to corticosteroid therapy.J ALLERGY CLIN IMMUNOL. 1974; 54: 125-131Abstract Full Text PDF PubMed Scopus (94) Google Scholar Severe allergic reactions caused by corticosteroids, however, have not been described in childhood. We report on an 8-year-old boy who had an anaphylactic reaction to 6-α-methylprednisolone, which he had used and tolerated to treat his asthma before. We did not perform a challenge test with 6-α-methylprednisolone because of the risk of a new anaphylactic episode. A positive skin test response to the pure 6-α-methylprednisolone shows a type 1 immunologic hypersensitivity mechanism. We made an attempt to link the drug to different solid phases in order to quantify serum-specific IgE by RAST, but results were negative. It was very important to determine which corticosteroid could be tolerated by this patient, because he would need corticosteroid therapy for his asthma; thus, it was necessary to perform challenges with other corticosteroids. The structure of methylprednisolone differs from that of the other corticosteroids in its six-carbon methyl group. This structure is quickly broken down in the body, and most corticosteroids share a common metabolic pathway; thus, a true allergic reaction to one specific corticosteroid should probably be based on the allergenic properties of the original, unmetabolized compound. Because of this, it is really difficult to define patterns of cross-reactivity in adverse reactions to systemic corticosteroids. Thus the recent classification of topical corticosteroids on the basis of patterns of cross-reactivity in patients who have undergone patch testing8Coopmans S Degreef H Dooms-Goossens A Identification of cross-reaction patterns in allergic contact dermatitis from topical corticosteroids.Br J Dermatol. 1989; 121: 27-34Crossref PubMed Scopus (281) Google Scholar is not completely useful in adverse reactions resulting from systemic treatments. Three main adverse reactions have been reported in the literature: anaphylaxis, urticaria/angioedema, and bronchospasm. Anaphylactic reactions often occur after intravenous therapy with hydrocortisone or methylprednisolone.1Peller JS Bardana EJ Anaphylactoid reaction to corticosteroids: case report and review of the literature.Ann Allergy. 1985; 54: 302-305PubMed Google Scholar, 2Preuss L Allergic reactions to systemic glucocorticoids: a review.Ann Allergy. 1985; 55: 772-775PubMed Google Scholar There are few cases with positive skin test results showing allergic reactions.1Peller JS Bardana EJ Anaphylactoid reaction to corticosteroids: case report and review of the literature.Ann Allergy. 1985; 54: 302-305PubMed Google Scholar, 2Preuss L Allergic reactions to systemic glucocorticoids: a review.Ann Allergy. 1985; 55: 772-775PubMed Google Scholar, 6Rasanen I Hasan T Allergy to systemic and intralesional corticosteroids.Br J Dermatol. 1993; 128: 407-411Crossref PubMed Scopus (54) Google Scholar, 7Mendelson LM Meltzer EO Hamburger RN Anaphylaxis-like reactions to corticosteroid therapy.J ALLERGY CLIN IMMUNOL. 1974; 54: 125-131Abstract Full Text PDF PubMed Scopus (94) Google Scholar Urticaria (with or without angioedema) is often reported as a late adverse reaction to oral or parenteral corticosteroids.1Peller JS Bardana EJ Anaphylactoid reaction to corticosteroids: case report and review of the literature.Ann Allergy. 1985; 54: 302-305PubMed Google Scholar, 2Preuss L Allergic reactions to systemic glucocorticoids: a review.Ann Allergy. 1985; 55: 772-775PubMed Google Scholar, 6Rasanen I Hasan T Allergy to systemic and intralesional corticosteroids.Br J Dermatol. 1993; 128: 407-411Crossref PubMed Scopus (54) Google Scholar Some cases show late positive intradermal skin test results (range, 4 to 12 hours), and positive patch test results. This shows that cutaneous delayed sensitization might predispose the patient to generalized cutaneous reactions after systemic corticosteroid therapy in certain cases.6Rasanen I Hasan T Allergy to systemic and intralesional corticosteroids.Br J Dermatol. 1993; 128: 407-411Crossref PubMed Scopus (54) Google Scholar In our opinion, in cases of urticaria or angioedema reactions with negative skin test results, challenges are necessary to establish a diagnosis, because corticosteroids are commonly prescribed and very useful drugs. Bronchospasm caused by systemic corticosteroid therapy usually occurs immediately after intravenous administration of hydrocortisone.4Szczeklik A Nizankowska E Czerniawska-Mysik G Sek S Hydrocortisone and airflow impairment in aspirin-induced asthma.J ALLERGY CLIN IMMUNOL. 1985; 76: 530-536Abstract Full Text PDF PubMed Scopus (54) Google Scholar, 5Dajani 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: 201-204Abstract Full Text PDF PubMed Scopus (78) Google Scholar Most of these reactions appear in nonatopic patients with aspirin-sensitive intrinsic asthma. This shows an idiosyncratic mechanism.1Peller JS Bardana EJ Anaphylactoid reaction to corticosteroids: case report and review of the literature.Ann Allergy. 1985; 54: 302-305PubMed Google Scholar, 2Preuss L Allergic reactions to systemic glucocorticoids: a review.Ann Allergy. 1985; 55: 772-775PubMed Google Scholar Tolerance to other corticosteroids must be determined by challenge. True allergic reactions resulting from systemic corticosteroid therapy are not frequent; nevertheless, they should be kept in mind, because this kind of therapy is a potential cause of allergic or pseudoallergic reactions. We report a new case of anaphylaxis caused by 6-α-methylprednisolone. A positive skin prick test response shows a type 1 immunologic hypersensitivity mechanism. We do not know which part of the molecule caused our patient’s reaction, but in this particular case, no cross-reactive mechanism with other corticosteroids seems to be involved. Further studies are needed to establish the allergenicity and cross-reactivity of systemic corticosteroids. We thank Drs. Elena de Terán Bleiberg and Javier Gómez Aguirre for their assistance in writing the manuscript. We also thank Dr. Ana Carmen Gil-Adrados for her useful comments.