Photosensitisation diseases of animals: Classification and a weight of evidence approach to primary causes

Clare’s (1952) classification system for photosensitisation diseases (types I, II, III and Uncertain) has endured many years of use despite some confusion regarding his secondary, or type III, category, as well as the more recent discovery of two mechanisms (types I and II) of phototoxicity. Therefore, to reduce confusion in terminology, I propose that Clare’s four groups be known as primary (or direct), secondary (indirect or hepatogenous), endogenous (aberrant porphyrin synthesis), and idiopathic. The use of the word type can then be reserved for the mechanisms of phototoxicity. Clare’s (1952, 1955) papers listed three plants as primary photosensitisers and three as idiopathic. In the literature, several other plants have been associated with photosensitisation in farm animals. Most of these are likely to have a primary pathogenesis; however, the weight of evidence for all but a few is sparse. With respect to plants (and certain mycotoxins and insects) implicated in primary photosensitisation outbreaks, McKenzie’s “toxicity confidence rankings” (Australia’s Poisonous Plants, Fungi and Cyanobacteria, 2012) has been adapted to “phototoxic agent confidence rankings”. Thus, plants, mycotoxins or insects can be categorised regarding phototoxicity, i.e. definite (A); some evidence (B); suspected (C); or phototoxin isolated but no field cases known (D), and weight of evidence, i.e. field cases (1); experimental feeding produces photosensitisation (2); phototoxin isolated (3); phototoxin produces photosensitisation experimentally (4); and/or correlation of the action spectrum/chromatogram in blood or skin with the absorption spectrum/chromatogram of the phototoxin (5). As a result, confidence rankings ranging from A5 to D1 can be allocated. From the available literature, at least seventeen plant species can be ranked as A5 (definite phototoxicity with a maximum weight of evidence). The relatively recent breakthrough regarding the discovery of phototoxic anthraquinones in Heterophyllaea spp. has led to the serendipitous association of the same and similar anthraquinones as the most likely phototoxins in alligator weed (Alternanthera philoxeroides).