tixocortol-pivalate and Drug-Hypersensitivity

Topics: Anti-Inflammatory Agents; Budesonide; Dermatitis, Allergic Contact; Drug Hypersensitivity; Humans; Hydrocortisone; Patch Tests; Skin

The anti-inflammatory properties of topical corticosteroids are well documented; additionally, their sensitization potential is also known. We aimed to assess the relative sensitization potential of hydrocortisone and tixocortol pivalate in an animal assay as it relates to potential for sensitization in humans. Using the guinea pig maximization test (GPMT), animals were sensitized intradermally on d0, and again topically on d7. On d21 the animals were challenged topically with a closed patch for 24 h and readings were taken 24 h and 48 h post-challenge. A sham control group received the same induction and challenge applications excluding the test agent. Animals were subsequently rechallenged with open application; the tixocortol pivalate group was further retested at different test agent concentrations to determine threshold concentration that elicited response. Tixocortol pivalate resulted in sensitization rates of 42% (24 h) and 80% (48 h); hydrocortisone exhibited 0% (24 h) and 5% (48 h). Scores ranged from 0% (sham group) to 2.4 (48 h tixocortol pivalate). Open rechallenge also resulted in greater tixocortol pivalate sensitization rates compared to hydrocortisone, 82% verse 16% at 48 h, respectively. All tested concentrations of tixocortol pivalate induced sensitization, albeit at differing rates dependant on concentration and timepoint. We conclude that the GPMT remains largely for hazard identification, as it was originally designed, and requires further data sets regarding quantitative induction and elicitation for risk assessment of various compounds in clinical implications.

Topics: Allergens; Animals; Anti-Inflammatory Agents; Dermatitis, Allergic Contact; Dose-Response Relationship, Drug; Drug Hypersensitivity; Guinea Pigs; Hydrocortisone; Skin; Skin Tests

Topics: Anti-Allergic Agents; Drug Hypersensitivity; Humans; Hydrocortisone

In spite of their intrinsic anti-inflammatory properties, corticosteroids can induce contact allergy. When studying the allergenic properties of corticosteroids it has to be considered that both the allergenic and anti-inflammatory effect may influence the induction phase as well as the elicitation phase and that such effects may be dose-dependent. A multiple dose guinea pig maximization test (GPMT) was therefore used to study the dose-response relationship of tixocortol pivalate. The GPMT was conducted according to OECD guideline #406, using a multiple-dose design and test results were analysed with logistic regression analysis. There was a significant tixocortol pivalate sensitization of the test animals compared to the control group (p<0.05), after both challenge and re-challenge. The challenge with 1% tixocortol pivalate gave more positive reactions than the challenge with 3%. The highest frequency of positive animals was observed when the animals were treated with low to intermediate induction concentrations and intermediate to high challenge concentrations with tixocortol pivalate in the TRUE Test. Cross-reactivity was found between tixocortol pivalate and hydrocortisone, which was expected from their close molecular resemblance, whereas no cross-reactivity was seen between tixocortol pivalate and the 3 other corticosteroids: amcinonide, budesonide, and hydrocortisone-17-butyrate.

Topics: Allergens; Animals; Anti-Inflammatory Agents; Cross Reactions; Dermatitis, Allergic Contact; Dose-Response Relationship, Drug; Drug Hypersensitivity; Female; Guinea Pigs; Hydrocortisone; Molecular Structure; Skin; Skin Tests

This study investigated whether a corticosteroid mix containing tixocortol pivalate, budesonide, and hydrocortisone-17-butyrate could detect contact allergy to corticosteroids. 2 corticosteroid mixes, 1 with a high (mix I) and 1 with a low (mix II) concentration and the 3 individual constituents, each at 2 concentrations, were inserted into the standard series of 16 participating clinics. Tests were read on day (D) 3 or 4. 5432 patients were tested, and 110 (2.0%) had positive reactions to at least 1 of the 8 test preparations. Of the 8 preparations, mix I identified most allergic patients, followed by mix II, budesonide 0.10%, budesonide 0.002%, and tixocortol pivalate, both concentrations (1.0 and 0.10%) tracing the same number. With the mixes, 53.2-59.6% of tixocortol pivalate allergy was missed. 47 patients were allergic to either concentration of tixocortol pivalate, 25% of these only to 1.0% and another 25% only to 0.10%. Testing with mix I and tixocortol pivalate 0.10% picked up 98/110, testing with tixocortol pivalate 1.0% and 0.10% and budesonide 0.10% picked up 105/110. 3379 patients were read on both D3 or D4 as well as on D7. Without a late reading (D7), up to 30% of contact allergy to corticosteroid markers was missed.

Topics: Administration, Topical; Anti-Inflammatory Agents; Budesonide; Dermatitis, Allergic Contact; Drug Combinations; Drug Hypersensitivity; Female; Humans; Hydrocortisone; Male; Patch Tests