Le Coz C J, Bottlaender A, Scrivener J N, Santinelli F, Cribier B J, Heid E, Grosshans E M
Department of Dermatology, University Hospital, Strasbourg, France.
Contact Dermatitis. 1998 May;38(5):245-52. doi: 10.1111/j.1600-0536.1998.tb05737.x.
The arylpropionic acid derivatives (APADs) ketoprofen and tiaprofenic acid can provoke photoallergic dermatitis. Possible cross-reactivity between APADs is of importance in patients using nonsteroidal anti-inflammatory drugs. Because of the similarities in chemical structures, we investigated patients with photoallergy to ketoprofen or tiaprofenic acid, in order to study cross-reactivity between APADs and a possible pattern of cross-reactivity between benzophenone-containing molecules, so as to determine the molecular basis of photoallergy to ketoprofen or tiaprofenic acid. 10 patients with photoallergy to topical ketoprofen, 2 with photoallergy to oral tiaprofenic acid, and 15 control subjects with no history of contact dermatitis from APADs, nor from benzophenone-containing molecules, were photopatch tested in triplicate with ketoprofen, tiaprofenic acid, other APADs (alminoprofen, fenoprofen, flurbiprofen, ibuprofen and naproxen), benzophenone-containing molecules (fenofibrate, oxybenzone, sulisobenzone), and unsubstituted benzophenone. 1 set was irradiated with UVA light, 1 with solar-simulated irradiation and 1 dark control. Tests were read at 2, 3 and 4 days. Patients reacted to both ketoprofen and tiaprofenic acid (12/12), fenofibrate (8/12), oxybenzone (3/12) and unsubstituted benzophenone (11/12), but not to other APADs, nor to sulisobenzone. Tests remained negative in control patients. Photoallergy is due to the benzophenone moiety of ketoprofen, or to the very similar thiophene-phenylketone of tiaprofenic acid, but not to their arylpropionic function. This induces cross-reactivity to fenofibrate and oxybenzone but not to APADs without a benzophenone moiety, which may therefore probably be used in such patients. Unsubstituted benzophenone should be added to standard phototesting series.
芳基丙酸衍生物(APADs)酮洛芬和噻洛芬酸可引发光变应性接触性皮炎。对于使用非甾体抗炎药的患者而言,APADs之间可能存在的交叉反应至关重要。鉴于化学结构的相似性,我们对酮洛芬或噻洛芬酸光过敏的患者进行了研究,以探讨APADs之间的交叉反应以及含二苯甲酮分子之间可能的交叉反应模式,从而确定对酮洛芬或噻洛芬酸光过敏的分子基础。10例对局部用酮洛芬光过敏的患者、2例对口服噻洛芬酸光过敏的患者以及15例既无APADs接触性皮炎病史也无含二苯甲酮分子接触性皮炎病史的对照受试者,分别用酮洛芬、噻洛芬酸、其他APADs(阿明洛芬、非诺洛芬、氟比洛芬、布洛芬和萘普生)、含二苯甲酮分子(非诺贝特、氧苯酮、舒利苯酮)以及未取代的二苯甲酮进行了一式三份的光斑贴试验。一组用UVA光照射,一组用模拟阳光照射,一组为黑暗对照。分别在第2、3和4天读取试验结果。患者对酮洛芬和噻洛芬酸(12/12)、非诺贝特(8/12)、氧苯酮(3/12)和未取代的二苯甲酮(11/12)均有反应,但对其他APADs以及舒利苯酮无反应。对照患者的试验结果均为阴性。光过敏是由于酮洛芬的二苯甲酮部分,或者是由于噻洛芬酸非常相似的噻吩 - 苯基酮部分,而非其芳基丙酸官能团。这导致了对非诺贝特和氧苯酮的交叉反应,但对没有二苯甲酮部分的APADs无交叉反应,因此这类患者可能可以使用后者。应将未取代的二苯甲酮添加到标准光斑贴试验系列中。