Photocontact dermatitis from ketoprofen and tiaprofenic acid: cross‐reactivity study in 12 consecutive patients

Abstract

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.

Study of Compounds Suppressing Free Radical Generation from UV-Exposed Ketoprofen

“…Although the free radical species were speculated to be benzophenone, [9][10][11][12] benzoyl radical, 13) carbonyl radical 14) and superoxide anion, 15) their true identities remain unknown to this day. We elucidated the pathways for the photo-degradation of ketoprofen and the generation of free radicals in our previous study.…”

Prolonged Photosensitivity following Contact Photoallergy to Ketoprofen

“…This explains the cross-reactivity to fenofibrate, tiaprofenic acid and sunscreens with a benzophenone structure but not to the other arylpropionic acid derivatives without the benzophenone structure [17, 18]. Cross-photoreactions between ketoprofen and sunscreens with a benzophenone structure have rarely been described [11, 12].…”

“…According to Le Coz et al [17], photoallergy to ketoprofen is due to the benzophenone structure or to the very similar thiophene phenylketone of tiaprofenic acid, but not to the arylpropionic function. This explains the cross-reactivity to fenofibrate, tiaprofenic acid and sunscreens with a benzophenone structure but not to the other arylpropionic acid derivatives without the benzophenone structure [17, 18].…”

Phototoxic and Photoallergic Reactions

“…As that radical is common to the benzophenone UV filters, cross-reactions are common with sunscreens containing mainly oxybenzone [96]. A similar structure is present in the systemic hypolipemic agent, fenofibrate, that also induces systemic photosensitivity with cross-reactions with ketoprofen [62] and, in patients taking this drug, it was a risk factor for more severe photoallergic contact dermatitis from ketoprofen [91,96].…”

“…Although such a high frequency might suggest phototoxicity, the clinical pattern with erythema multiform, positive lymphocyte stimulation tests with ketoprofen photomodified cells, animal studies with the absence of phototoxic potential [93], the capacity to photosensitize and transfer photoallergy by T-cells, both CD4 and CD8 exhibiting chemokine receptors for Th1 and Th2, in vitro activation and maturation of antigen-presenting cells by ketoprofen and UVA, [35,94,95], and characterization of a stable photoproduct -3-ethyl-benzophenone [34,96] -highly support a photoallergic reaction.…”