Photocontact Allergy to Ketoprofen and Simultaneous Contact Allergies

Sammanfattning: Ketoprofen is a non-steroidal anti-inflammatory drug with analgesic, antipyretic, and anti-inflammatory properties. It is available in both oral and topical formulations. Photocontact allergy to topically applied ketoprofen has been the most frequent side effect of the formulation, and is fairly well studied. The risk of development of photocontact allergy and of persistent photosensitivity as the result of photosensitization has led to warnings and restricted distribution of ketoprofen-containing gels. Apart from the risk of developing a photoallergic contact dermatitis upon repeated exposure to ketoprofen, the sensitized individuals show higher rates of photocontact and contact allergy to some other sensitizers. Simultaneous photocontact allergic reactions to benzophenones, fentichlor, chlorpromazine, bithionol, tetrachlorosalicylanilide and promethazine were described in patients with photocontact allergy to ketoprofen in the middle of 2000s. Similarly, an overrepresentation of contact allergy to fragrance mix I and Myroxylon pereirae in the same group has been known for decades. There is no known common mechanism of simultaneous photocontact and contact allergy, but several research groups have suggested the possibility of cross-reactivity between ketoprofen, which is a substituted benzophenone, and other chemicals with a benzophenone moiety.This thesis forms a part of the search for an explanation of the phenomenon of simultaneous contact allergies in individuals with photocontact allergy to ketoprofen. A broad perspective is essential in order to understand any phenomenon, which in this case means that we need to obtain better knowledge of which sensitizers individuals with photocontact allergy to ketoprofen may react to more often compared to controls.Study I examined the possibility of simplifying the procedure of photopatch testing with ketoprofen, and found that reliable results can be obtained by shortening the occlusion time from 24 hours to 1 hour, with no need to change other parameters such as concentration or UVA dose. Studies II, III, and IV were concerned with the epidemiology of simultaneous contact allergy in patients with photocontact allergy to ketoprofen. Study II revealed that patch testing with some of the individual components of fragrance mix I (cinnamal, cinnamyl alcohol, eugenol, and isoeugenol) produced significantly higher numbers of positive patch test reactions in those with photocontact allergy to ketoprofen compared to controls. Similarly, Study IV found that a number of sensitizers tested within the baseline series led to significantly higher rates of contact allergy in those with photocontact allergy to ketoprofen than in dermatitis patients and in the general population. Study III confirmed a clinical suspicion that contact allergy to oxidized linalool and oxidized limonene was indeed overrepresented in the ketoprofen group.The clinical relevance of these findings is yet to be investigated, but this thesis discusses some of the hypotheses proposed by various researchers in order to explain the phenomenon of simultaneous contact allergies that arise in connection with photosensitization to ketoprofen. Although no definite explanation can be given to date, the main goal of this research is to gain a better understanding of the epidemiology of simultaneous contact allergy, which can act as a building block in future research.

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