SPORIDESMIN TOXICITY: FIELD AND DIAGNOSTIC OBSERVATIONAL INTERPRETATIONS

Sporidesmin toxicity (i.e. facial eczema) is poorly understood and difficult to recognise clinically until significant liver damage has occurred, but subclinical liver damage may already have caused a drop in milk production and specifically in milk solids. This may be experienced in a small percentage of cattle on a farm and the production loss may not be too severe, but it nevertheless shows that this is a toxin that can be affecting a herd without there being any means at this stage of diagnosing the presence of the toxin on affected farms.

The implication of this is that making a diagnosis of sporidesmin toxicity must be herd-based and to make the diagnosis, the epidemiology and pathophysiology of the disease must be considered:                                                                                                                                                                                                                                                                                                                                    1. The fungal spores must be demonstrable in pasture.                                                                                                                                                                                                                                                        2. There must be evidence of a clinical effect, which could manifest as skin irritability, erythema, drop in milk production or other related clinical signs.                                                                              3. A laboratory test must confirm liver involvement, gamma-glutamyl transferase (GGT) being most useful.                                                                                                                                                            4. There must be histological evidence of sporidesmin toxicity.                                                                                                                                                                                                                                          Even though a drop in milk production could occur without any increase in GGT, in a population of cattle grazing infected pasture, there should be a range of manifestations within the herd ranging from significant liver and secondary skin involvement. However, veterinarians are hesitant to make a definitive diagnosis, especially in a system as varied as a pasture-based dairy farm where health issues are generally multifactorial, but even amidst all the potential confusion, it is essential to learn to recognise a herd that could be affected by the toxin.

On the other side of the coin, it is comparatively easy to recognise severe cases of sporidesmin toxicity because of the obvious ‘sunburn-like’’ lesions. As with any toxicity, there will be a range of symptoms based on the concentration of toxin to which the animal is exposed, so one would expect there to be different degrees of skin lesions too. In the study in the Eastern Cape, 210 cattle were assessed using a skin scoring system based on a photographic record and blood collected for clinical chemistry. It would be ideal if a clear relationship between GGT and skin scores exist, as this would introduce skin scores as a useful visual screening tool to determine whether sporidesmin toxicity is present in a herd or not.

Central to the pathogenesis of sporidesmin toxicity is bile duct destruction and blockage resulting in the accumulation of phylloerythrin in circulation, which then accumulates in epithelium and where this is exposed to sunlight (in non-pigmented skin), being a photodynamic agent, there is an immediate response and an inflammatory reaction ensues which results in the secondary skin lesions. As true as this may be in cases of chronic sporidesmin toxicity, this argument does not hold true in early cases where subtle skin lesions are seen despite any appreciable bile duct blockage or damage.

Sporidesmin has always been regarded as primarily a biliary toxin, but not all the experimental evidence from histological studies here and elsewhere support this argument. In histological study of sheep fed sporidesmin and slaughtered sequentially to examine the histological changes in these sheep, observations of parenchymal cell damage were clear in the early stages of toxicity. In the first three days of that study, it was observed that the biliary epithelium appears to be intact and unaffected, but the parenchymal cells were swollen and in some cases had burst, presumably due to an inactivation of the sodium/potassium pump, which resulted in cell swelling due to accumulation of fluid and the subsequent rupture of the cell membrane . These observations are very pertinent and demonstrate the possibility that the primary site for sporidesmin toxicity is in fact the liver parenchyma and not the biliary tract. That sporidesmin has a marked impact on the biliary epithelium is clearly demonstrable and irrefutable, but this is not necessarily where it all starts. Of the 210 blood samples collected from cattle in the Eastern Cape study, during the peak period of exposure to sporidesmin toxicity, none of the cattle demonstrated an increase in bilirubin concentration, but increases in aspartate aminotransferase (AST), bile acids and GGT were noted together with clinical evidence of skin changes. While examining liver biopsy samples collected from a cohort of these cattle, it was also clear on histopathology that very little or no material was evident in the bile ducts. It would seem then that phylloerythrin accumulates prior to biliary obstruction.

In an international study, it was postulated that a phytoporphyrin-excreting mechanism existed that transported structurally diverse toxic substances and phytoporphyrins from the liver parenchyma into the bile canaliculi. This transporter action was confirmed as being an ATP-binding cassette transporter termed ABCG2. If this transporter is compromised, this would lead to a decreased excretion of phytoporphyrins into the bile canaliculi resulting in their accumulation which would then induce photosensitivity when exposed through non-pigmented skin. Furthermore, it was hypothesized that hepatotoxic compounds consumed by livestock could result in decreased expression of ABCG2 in hepatocytes which, in turn, could lead to decreased (biliary) excretion of phytoporphyrin. It seems feasible then, based on the observation made in previous studies and in the Eastern Cape study, that the primary mechanism of action of sporidesmin or one of its metabolites is to disrupt ABCG2 transporters in the liver parenchyma, which would result in the initial increase of phytoporphyrins in circulation. The importance of this is that it mainly elucidates a mechanism of action which should be investigated further, and introduces the possibility of a novel approach to bind sporidesmin or its metabolites if the toxic mechanism can be identified. If both parenchymal and biliary tissues are affected, this places additional emphasis on the potentially destructive capacity of this toxin.