Dissertations

Clinical and Experimen- tal Studies in Cortico- steroid Contact Allergy

Marléne Isaksson Department of Occupational and Environmental Dermatology, Malmö University Hospital, S - 205 02 Malmö, Sweden. Tel: +46-40 337859. Fax: +46- 40 336213. marlene.isaksson@ derm.mas.lu.se.

Corticosteroids are anti-inflammatory and anti-proliferative substances that also can induce sensitization, mainly through skin contact. In a sensitized individual, it can be hard to disclose Marléne Isaksson (middle) defended her thesis on April 14th, 2000 at the University Hospital, the contact allergy at patch testing Malmö, Sweden. Faculty Opponent was Antti I Lauerma (right), Skin and Allergy Hospital, Helsinki, Finland and supervisor was Magnus Bruze (left), University Hospital, Malmö, Sweden. because the anti-inflammatory effect may mask the allergic contact reac- tion. This is primarily seen when patch testing to potent corti- mended concentration gave negative The edge reaction, consisting of a costeroids is performed and the reactions. If testing with a corti- blank centre representing the whole reading is done early, when the anti- costeroid at a high concentration area of the test unit and surrounded inflammatory effect still prevails. results in a negative patch-test by an eczematous infiltrate, is seen reaction, lowering the concentration in some corticosteroid allergic

A hypothetical model is presented, may result in a positive patch-test patients when potent corticosteroids which can explain the different reaction. are patch-tested. This phenomenon situations that emerge, when the anti- can also be explained by the same model. If an edge reaction appears, a inflammatory effect influences the Introducing another parameter into late reading or testing with a lower elicitation depending on the indivi- the model, the time factor, made it concentration should be done. dual degree of hypersensitivity in a possible also to explain why negative sensitized subject. patch test reactions are sometimes seen at early readings, while the tests The cross-reactivity pattern for the

Some patients allergic to the corti- may turn positive on late reading two diastereomers of budesonide, the costeroid budesonide only reacted to occasions. Therefore, not to miss R and S diastereomers, was also very low concentrations of the sensiti- contact allergy to corticosteroids, a investigated. Results concurred with zer at early readings. When patch reading after one week in addition to the theory that the R diastereomer testing the corticosteroid triamcino- an early reading is advocated. The cross-reacts with other substances lone acetonide, concentrations 1,000 multicentre study showed that 25% of from the group to which it belongs, to 10,000 times lower than interna- the allergic reactions to cortico- group B, while the S diastereomer tionally recommended resulted in steroids would have been missed if a cross-reacts not only with other group allergic reactions while the recom- late reading had not been done. B substances but also with some esters of group D.

Forum for Nord Derm Ven Vol. 6 February 2001 16 No inhibition of the patch test reac- stable for at least one year in room Key words: corticosteroids, allergic tions was observed when patch temperature, refrigerated and frozen. contact dermatitis, budesonide, testing the corticosteroid tixocortol Budesonide and tixocortol pivalate in tixocortol pivalate, hydrocortisone- pivalate and potentially cross-reacting ethanol showed the same stability. Hc- 17-butyrate, dose-response relation- substances at high concentrations. 17-B 1.0% in ethanol was only stable ship, mixes, stability, clinical relevan- frozen for one year and at room ce, ROAT, inhalation. temperature for three months. Aldehydes of corticosteroids are thought to be intermediates in the List of original publications sensitization process. The aldehyde of In the study on local clinical relevance, hydrocortisone was therefore tested the flare-up reactions in the budeso- I. Isaksson M, Bruze M, Goossens A, Lepoittevin J-P. Patch testing with in subjects allergic to hydrocortisone. nide-allergic individuals consisted not budesonide in serial dilutions: the Patients reacting to hydrocortisone only of a severe deterioration of the significance of dose, occlusion time also reacted to the aldehyde, speaking Preferid® treated eczema but also and reading time. Contact Dermatitis 1999; 40: 24–31. in favour of the aldehyde being an toxicoderma-like eruptions with a II. Isaksson M, Bruze M, Goossens A, intermediate in the sensitization. conspicuous distribution. A correla- Lepoittevin J-P. Patch-testing with tion was found between contact serial dilutions of tixocortol pivalate allergy to budesonide and deteriora- and potential cross-reactive substan- When trying to elucidate whether a ces. Acta Derm Venereol 2000; 80: 33– tion of the eczema treated with corticosteroid mix, consisting of the 38. Preferid® cream containing budesoni- three corticosteroids budesonide, III. Isaksson M, Andersen KE, Brandão FM, de. Bruynzeel DP, Bruze M, Camarasa JG, tixocortol pivalate and hydrocorti- Diepgen T, Ducombs G, Frosch PJ, sone-17-butyrate (Hc-17-B) in petrola- Goossens A, Lahti A, Menné T, Rycroft tum, could disclose corticosteroid To study flare-up reactions at earlier RJG, Seidenari S, Shaw S, Tosti A, Wahlberg JE, White IR, Wilkinson JD. allergy, it was found that 60% of the budesonide test sites a systemic Patch testing with corticosteroid mixes patients allergic to tixocortol pivalate provocation with Pulmicort® Turbu- in Europe. A Multicentre Study of the were missed. Thus, in a corticosteroid haler® (budesonide) via inhalation was EECDRG. Contact Dermatitis 2000; 42: mix containing budesonide and Hc- performed in subjects allergic to 27–35. IV. Isaksson M, Gruvberger B, Persson L, 17-B, tixocortol pivalate should not be budesonide but without asthma or Bruze M. Stability of corticosteroid a part. Of the separate markers that other lung dysfunction. The study patch test preparations. Contact were patch-tested simultaneously in clearly showed that flare-up reactions Dermatitis 2000; 42: 144–148. petrolatum, budesonide 0.10% detect- were found after normal doses of V. Isaksson M, Bruze M, Goossens A, Lepoittevin J-P. Patch testing with ed most allergic subjects, followed by budesonide. Therefore, a person serial dilutions of budesonide, its R budesonide 0.002% and tixocortol hypersensitive to budesonide should and S diastereomers, and potentially pivalate, both concentrations (1.0% not be given the drug as an inhalant. cross-reacting substances. Submitted. and 0.10%) detecting the same num- In the same study a new method in VI. Isaksson M, Bruze M. ROAT with budesonide on experimental allergic ber of patients. Hc-17-B at 1.0% humans to test for cross-sensitivity contact dermatitis from nickel in detected more than 0.10%. was used. When budesonide was individuals hypersensitive to budeso- inhaled, a flare-up was noted where nide. Submitted. VII. Isaksson M, Bruze M. Allergic contact triamcinolone acetonide had been Investigations on the stability of dermatitis to budesonide reactivated tested previously, indicating cross- budesonide, tixocortol pivalate and by inhalation of the allergen. Sub- reactivity between budesonide and mitted. Hc-17-B patch-test preparations in triamcinolone acetonide. petrolatum disclosed that these were

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