CAD has been reported in Europe, Asia, and North America, with largest numbers observed in Northwestern Europe. Although AR, the most severe type, almost exclusively affects elderly men with history of chronic sun exposure through work or hobby, CAD as a whole showed only a moderate preference of men over women in the ratio of 2.6:1 in a study conducted in the United States and Japan.^1,2 CAD has been reported human immunodeficiency virus (HIV)-infected as the first sign of advanced asymptomatic HIV infection.^3,4,5 These HIV+ patients are younger than the general CAD population. There also have been sporadic reports of CAD in young patients with history of atopic dermatitis.^6,7,8 Susceptibility for CAD has been found in all Fitzpatrick skin types. In the United States, predominantly affected types are V and VI.^1,2,9

Etiology of CAD remains unknown despite conjecture and debate over the last several decades. The most important diagnostic feature in CAD is decreased minimal erythema dose to broad spectrum of light. In many European patients, but not in those in the United States or Asia, history of photoallergic contact dermatitis predates development of CAD. Sesquinterpene lactone mix from Compositae plant oleoresin was found to be an allergen in 25% to 36% of patients with CAD.^10,11 Patch testing with oleoresin extracts from daisy, dandelion, and thistle also produced similar results.¹² Photoallergy to sunscreens and fragrance was another common finding.⁹

It has been suggested that CAD is a delayed hypersensitivity reaction to a known or yet unidentified photoallergen. Predominance of CD8⁺ T cells and increased Langerhans cells in the inflammatory infiltrate of the CAD skin^13,14 are histologic features that are similar to allergic contact dermatitis. Expression of adhesion molecules, such as E-selectin, VCAM-1, and ICAM-1, on dermal blood vessels for recruitment of inflammatory cells in CAD also supports this notion.¹⁵ It has been postulated that allergic photocontact dermatitis became persistent light reaction, when an endogenous protein was modified into an autoantigen in the presence of the initial photoallergen. In support of this theory, photooxidation of the histidine moiety of human serum albumin was observed in the presence of tetrachlorosalicylanilide, an antimicrobial agent and preservative.¹⁶ In another study, persistent light reaction was induced in guinea pigs after intradermal injection with Freud’s adjuvant and UVA radiation, suggesting that concurrent dermatitis and UV radiation may be sufficient to create an endogenous photoallergen.¹⁷ Elevated levels of kynurenic acid, which is involved in the tryptophan metabolic pathway, was suggested as a possible pathogenic mechanism,¹⁸ but this hypothesis was later disputed by a tryptophan metabolism study.¹⁹ Defective ability to respond to UV-induced oxidative stress in fibroblasts in CAD has also been suggested as the cause.²⁰ In summary, although causality is difficult to establish with these associated findings, AR may be best considered a delayed hypersensitivity reaction to an exogenous or endogenous photoallergen.