Report

CONTACT ALLERGY TO CORTICOSTEROIDS EVA TEGNER, M.D.

From the Department of Dermatology, University of Lund, Lund, Sweden

sensitized. Burckhardt supposed that in due time many cases of sensitization to corticosteroids would occur. Subsequently, several cases have been reported (Table 1).3-2o Bandmann and associates' in 1966 reABSTRACT: Contact dermatitis to topical corticosteroids does occur, although infreported 3 patients with contact allergy to quently. Patch testing to the available triamcinolone acetonide. The allergy was steroids is recommended lor patients with specific to triamcinolone acetonide to a long-standing dermatoses which have reconcentration of 1:100,000. Tests with sponded poorly to topical steroids. triamcinolone and hydrocortisone acetate gave no reactions. Gontact allergy to applied medicaFrom 1962 to 1969 the Finsen Institute, ments can commonly appear. Usually Gopenhagen, conducted a retrieval these result from sensitization to ointsearch for patients suspected of being ment bases, preservatives, antibiotics, sensitive to topical steroids. There folantimycotic preparations, antimicrobial lowed a prospective study (1963-1964) agents, balsams, local anesthetic preparaof 1,835 patients. All patients were patch tions and tars.' Moreover, during the tested with the routine patch test series last 16 years it has been noted that topiand with 2 mixtures of hydrocortisone cally applied corticosteroids can sensiand hydrocortisone acetate of 2 brands. tize. Such allergic reactions to corticosAll patients with positive test reactions teroids are most uncommon. to the corticosteroids were patch tested with previously used topical steroids and Literature Review related steroids and with all other conTopical steroids were introduced over stituents of the suspected steroid. 20 years ago; not for several years did Preliminary results of the investigation the first reports of contact allergy appear. were reported in 1965 by Tissot and In 1959, Burckhardt^ reported a patient Hjort^; a final report was published in with contact allergy to hydrocortisone 1972 by Alani and Alani." acetate. His patient had eczema of the Eighteen patients reacted to hydrocorears; he had been under treatment with tisone and 11 to hydrocortisone acetate, an ointment containing hydrocortisone 10 to purified hydrocortisone, 9 to purifor about 2 years before he became fied hydrocortisone acetate, 3 to triamcinolone and 2 to betamethasone. Address for reprints: Eva Tegner, M.D., DepartMost showed positive test reactions ment of Dermatology, University of Lund, S-22185 Lund, Sweden. both to the corticosteroid and to one or 520

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CORTICOSTEROID ALLERGY

more of the excipients. The same observation has been made in several of the previously reported cases of contact allergy to steroids. Thus, there was contact allergy to neomycin in the case described by Kooij' and in several described by Malten and associates.'^ Interestingly most of the patients in the Finsen study had leg ulcers. By using hydrocortisone supplied by 2 manufacturers, Alani and Alani presumed that contact allergy to impurities was excluded. Before that, Sonnichsen^ believed the allergic reaction in some cases to be due to impurities or byproducts. In 1960 Church^' reported 5 patients reacting adversely to hydrocortisone acetate ointment. Patch tests proved this reaction to be due to 21diol acetate, a precursor of hydrocortisone acetate, small quantities of which were present In the final product. Krook-" reported a patient with sensitivity to hydrocortisone in Ficortril, which he found when testing 213 patients who had different dermatoses. As many as 18.2% reacted positively to patch tests with Ficortril ointment. Patch tests with all 10 components of Ficortril on 12 of these patients gave positive reactions to sodium lauryl sulfate in 6 patients, to propylene glycol in 2 and to hydrocortisone in 1. Five were negative to all components. Krook assumed that practically none of these reactions were allergic and that they were produced by the sodium lauryl sulfate component, which constitutes 0.9% of the ointment. He also assumed that it was possible that the irritating effect of sodium lauryl sulfate had promoted the sensitization to hydrocortisone. Case Experience Recently, at the Department of Dermatology in Lund, a patient showed contact allergy to triamcinolone acetonide.



Table 1. Year

Publications on Contact to Corticosteroids

Author

1959 1959

Burckhardt Kooij

1959 1962 1963

Dorn Sonnichsen Vermeulen, Huidarts, Mallen Coskey

1965

1965 1966

1967

Hjort, Tissot Bandmann, HuberRiffeser, Woyton Wulf

1967

Coskey, Bryan

1967

Wilkinson, McGarry, Solomon Zina, Bonu

1967

1970 1971

1972

1972 1973 1974 1974

521

Tegner

Allergy

Steroid hydrocortisone acetate hydrocortisone prednisolone hydrocortisone hydrocortisone

6-alfa-chIorprednisone hydrocortisone hydrocortisone alcohol prednisolone hydrocortisone

triamcinolone acetonide triamcinolone triamcinolono acetonide methyl prednisolone acetate

hydrocortisone acetate hydrocortisone succinate cortisone hydrocortisone prednisolone fluocinolone acetonide fluperolone acetonide methyl prednisolone Edwards, Rudner hydrocortisone alcohol Foussereau, LimamMestiri, fluocinolone acetonide Khochnevis hydrocortisone Alani, Alani hydrocortisone acetate triamcinolone betamethasone betamethasone 17 Bunney valerate Malten betamethasone 17 valerate van Ketel fluocortolone Krook hydrocortisone

For several years she had been treated with difi'erent topical steroids for eczema of the axillae. She noted exacerbation of her eczema when treated with

INTERNATIONAL JOURNAL OF DERMATOLOGY

522 Table 2.

Steroid Standard Test Series in Lund

Hydrocortisone, 10% petrolatum Hydrocortisone acetate, 10% petrolatum Hydrocortisone alcohol, 2% petrolatum Prednisolone, 2.5% petrolatum Fluocortolone, 2.5% petrolatum Flumethasone, 0.2% petrolatum Fluorometholone, 0.5% petrolatum Fluprednidene, 1 % petrolatum Methyl prednisolone-21-hem isuccinate, 2.5% petrolatum Triamcinolone, 1 % petrolatum Triamcinolone acetonide, 1 % petrolatum Betamethasone-17-valerate, 1 % petrolatum Fluocinolone acetonide, 0.25% petrolatum Fluclorolone acetonide, 0.25% petrolatum Fluocinonide, 0.5% petrolatum Betamethasone dipropionate, 0.5% petrolatum

Kenacutan cream. Patch tests gave positive reactions to neomycin, lanolin and to the steroid triamcinolone acetonide ( 1 % , 0 . 1 % and 0.001% in petrolatum and 1 % in propylene glycol). She had negative test reactions to the other corticosteroids, including triamcinolone, and to parabens, sterosan, Vioform and propylene glycol. Discussion Here in Lund a special steroid standard test series has been prepared (Table 2). Patients with a nonhealing eczema, particularly on the lower legs, have been tested. Up to now 1 more patient has shown contact allergy to corticosteroids (fluocinolone acetonide). Probably we have missed cases, as we have not tested with steroids as a matter of routine, as in the Finsen study. We have chosen a steroid concentration 10 times higher than in the commercial preparation. The vehicle has

September 1976

Vol. 15

been petrolatum. As to the concentration, many authors when testing have used the same concentration as in the commercial preparation. In the report from the Finsen Institute, testing with 25% hydrocortisone was recommended as the reactions to 10% hydrocortisone were weaker and fewer than those to 25% hydrocortisone. However, the optimal concentration and vehicle is still being developed. Probably it is not sufficient to patch test only with the commercial preparation since the anti-inflammatory effect of the steroid may depress the reaction and give false negative reactions. We assume that the concentration for patch testing should be higher than in the commercial preparation. Since the steroids probably are not cross-sensitizing, as many different steroids as possible should be included in the test battery. We do not know the role played by possible impurities; therefore, we do not know if there really is a contact allergy to a substance naturally occurring in the body. Conclusions Contact allergy to corticosteroids seems to be uncommon. Patch testing with steroids is indicated in patients with long-standing eczemas, as the result may be important for the prognosis of the individual case. Drug Names betamethasone dipropionate: Diprosone betamethasone valerate: Valisone flumethasone pivlate: Locorten fluocinoione acetonide: Fluonid, Synalar fluocinonide: Lidex, Topsyn methylprednisolone acetate: Medrol triamcinolone: Aristocort, Kenacort triamcinolone acetonide: Aristocort, Kenalog, Tramacin

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CORTICOSTEROID ALLERGY • Tegner

References 1. Fregert, S., Manual of Contact Dermatitis, Copenhagen, Munksgaard, 1974, pp. 24-26. 2. Burckhardt, Von W., Kontaketekzem durch Hydrocortison. Hautarzt 10:42, 1959. 3. Kooij, R., Hypersensitivity to hydrocortisone. Br. J. Dermatol. 71:392, 1959. 4. Dorn, Von H., Kontaktallergie gegenuber Salben-Konservlerungsmittein und Hydrocortison. Z. Haut. Geschlechtskr. 27:305, 1959. 5. Sonnichsen, Von N., Beitrag zur Hydrocortison tJberempfindlichkeit. Hautarzt 13:226, 1962. 6. Vermeulen, C. W., Huidarts, T. V., and Malten, K. E., Contacteczeem door 6-alphachloorprednlson en neomycin. Ned. Tijdschr. Geneeskd. 12:548, 1963. 7. Coskey, R. J., Contact dermatitis due to topical hydrocortisone and prednisone. Mich. Med. 64:669, 1965. 8. Hjorth, N., and Tissot, )., Unpublished observation. 9. Bandmann, H. J., Huber-Riffeser, G., and Woyton, A. Kontaklallergie gegen Triamcinolonacetonid. Hautarzt 17:183, 1966. 10. Wulf, K., Beitrag zur Triamcinolon-Kontaktallergie. Z. Haut. Geschlechtskr. 42:765, 1967. 11. Coskey, R. J., and Bryan, H. G., Contact dermatitis due to methylprednisolone. JAMA 199:136, 1967.

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12. Wilkinson, H. D., McGarry, E. M., and Solomon, S., Allergic contact dermatitis to hydrocortisone. J. Invest. Dermatol. 43:295, 1967. K!. Zina, G., and Bonu, G., Contact sensitivity to corticosteroid. Contact Dermatitis Newsletter 2:26, 1967. 14. Edwards, M., and Rudner, E. J., Dermatitis venenata due to hydrocortisone alcohol. Cutis 6:757, 1970. 15. Foussereau, J., Limam-Mestiri, S., and Khochnevis, A., Contact allergy to nystatin. Contact Dermatitis Newsletter 10:221, 1971. 16. Alani, M. D., and Alani, S. D., Allergic contact dermatitis to corticosteroids. Ann. Allergy 30:181, 1972. 17. Bunney, M. H., Contact dermatitis due to betamethasone 17 valerate (Betnovat). Contact Dermatitis Newsletter 12:318, 1972. 18. Malten, K. E., Betnelan V lotion contact sensitivity. Contact Dermatitis Newsletter 13: 360, 1973. 19. Van Ketel, VV. G., Allergy to Ultralan preparations. Contact Dermatitis Newsletter 15:427, 1974. 20. Krook, G., Contact dermatitis due to Ficortril (hydrocortisone 1 % ointment, Pfizer). Contact Dermatitis Newsletter 15:460, 1974. 21. Church, R., Sensitivity to hydrocortisone acetate ointment. Br. J. Dermatol. 72:341, 1960.

Scabies Treatment, 1762 "Now what is of greatest moment in this theory is (of scabies), that the knowledge of the true cause of the disease naturally points out the acne. For neither catharticks, nor sweeteners of the blood, are of any service here; the whole management consists in external application, in order to destroy these corroding worms; and this is easily effected. Wherefore, first, let the patient go into a warm bath, and then let the parts affected be anointed every day, either with the ointment of sulphur or the ointment with the precipitate of mercury, which is less offensive to the olfactory organs; instead of which a liniment may be made of orange flowers, or red roses, the mercurial red corrosive and hog's lard pounded together; which is of a very pleasant smell, and of equal efficacy.—Mead, R.: The Medical Works of Richard Mead, M.D., London, Hitch, 1762. Chapter 14, page 547.

Contact allergy to corticosteroids.

Report CONTACT ALLERGY TO CORTICOSTEROIDS EVA TEGNER, M.D. From the Department of Dermatology, University of Lund, Lund, Sweden sensitized. Burckha...
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