Background and Design: Most corticosteroidallergic patients react to several corticosteroids. Irrefutable proof for the existence of cross-reactions is provided by reactions to substances to which the patient has never been exposed. Four groups of cross-reactions have been proposed, and our own observations support this. However, we have found that budesonide, in particular, tends to be involved not only in cross-reactions with corticosteroids of its own group (group B) but also with those of the ester group (group D). To test clinical observations on patients sensitive to corticosteroids and to establish a molecular basis for cross-reactivity patterns, a statistical analysis of our cases and a conformational study of major corticosteroids were performed.
Results: Statistically highly significant positive or negative correlations were found for the combination of tixocortol pivalate plus hydrocortisone and hydrocortisone plus budesonide, respectively. This indicates that budesonide and hydrocortisone or tixocortol pivalate detect different groups of corticosteroid-sensitive patients. Moreover, significant positive correlations were found between budesonide and amcinonide, both molecules belonging to the acetonide group C, and also between budesonide and some esters of group D such as hydrocortisone-17 butyrate and alclometasone dipropionate. These clinical observations were fully supported by a conformational analysis of the electronic shape of corticosteroids involved in this study. Groups A, B, and D were found to be highly homogeneous within each group in terms of molecular structures, while significant differences were observed among the groups. The special behavior of budesonide can be fully explained on the base of its unique molecular structure. Finally, molecular characteristics have been defined for each group. This could be useful for the prediction of potential cross-reactions to new corticosteroid molecules.
Conclusions: The statistical analysis confirms that tixocortol pivalate and hydrocortisone contact allergies are definitely associated, while reactions to budesonide are strongly correlated with the reactions to both the acetonide group and the ester group. These clinical observations are fully supported by the conformational analysis of the molecules involved in this study. Tixocortol pivalate and budesonide should certainly be added to the standard series for the detection of patients sensitized to corticosteroids.