Etiology

• Type I: ingestion of plants, drugs, fungi or chemicals containing photo-active products with accumulation in the skin. Less commonly skin penetration is reported.
• Type II: accumulation of phylloerythrin following hepatic insufficiency and/or hepatic cholestasis.
• Both reasons lead to increased cell damage secondary to release of reactive oxygen molecules, hydrolytic enzymes and inflammatory mediators.
• Resultant vasculitis with thrombi and necrosis.

Predisposing factors

General

• Exposure to light.

Specific

• Plants involved in primary photosensitization Poisonous plants: overview:
  • Hypericum perforatum, H. pseudomaculatum and H. punctatum – contain hypericin.
  • Medicago sativa, alfalfa hay exposure although no specific toxin has been associated with the disease.
  • Other plants: Fagopyrum spp (toxin: fagopyrin), Lolium perenne (toxin: peroline), Medicago denticulata (aphids), Trifolium hybridum, Medicago spp, Trifolium spp, Cooperia pedunculata, Avena sativa, Brassica napus, Vicia spp, Brassica rapa, Froelichia humboldtiana.
  • Mycotoxins: Microcystis – blue-green algae.
  • Furocoumarins produced by Cymopterus watsonii, Ammi majus, Thamnosma texana, Heracleum mantegazzianum, Pastinaca sativa, Apium graveolensis and by the fungus Pithomyces chartarum.
• Drugs and chemicals: thiazides, acriflavins, sulfonamides, tetracyclines, furosemide, quinidine, methylene blue, promazine, chlorpromazine, coal-tar derivatives, retinoids, therapeutic photoagents, some antimicrobial soaps, carbon tetrachloride, copper, phosphorus, iron and phenanthridium.
• Secondary or hepatogenous photosensitization Poisonous plants: overview:
  • Plants with pyrrolizidine alkaloid toxins Toxicity: pyrrolizidine alkaloid: Senecio jacobaea, Seneco riddellii, Senecio douglas var longilobus, Senecio vulgaris, Crotalaria spp, Amsinckia spp, 
Echium plantgineum, Heliotropium europeaum, Cynoglossum officinale.
  • Plants with other hepatotoxins: Lantana camara, Trifolium hybridum, Tribulus terrestris, Narthecium ossifragum, Nolina texana, Myoporum laetum, Kochia scoparia, Tetradymia spp, Holocalyx glazlovli, Medicago spp.
  • Plants associated to crystalline hepatopathy: Panicum spp, Agave lecheguilla, Nolina texana, Brachiaria brizantha, Brassica rapa.
  • Plants associated with mycotoxins: Lupinus spp, Polygonum fagopyrum, Thamnosma texana, Lolium perenne, Sphenociadium capitellatum.
  • Diseases: bile duct occlusion (inflammation, cholelithiasis, parasites) Liver: cholangiohepatitis, Theiler’s disease Liver: hepatitis – acute (Theiler’s disease) , chronic active hepatitis Liver: hepatitis – chronic active, bacterial infection, immunologic or neoplastic disease.

Pathophysiology

• Type I: due to exposure to photosensitizing agents. Two steps are needed:
  • Ingestion of or contact with a photosensitizing agent that accumulates in the skin.
  • Concurrent normal exposure to UV light Dermatitis: solar.
• Type II: due to hepatic insufficiency Liver disease: overview Liver: hepatotoxicosis leading to increased concentrations of circulating phylloerythrin. Phylloerythrin, normally absorbed from the intestine and detoxified by the liver, leads to increased sensitization to light Dermatitis: solar. Three steps are required for hepatic photosensitization:
  • liver damage with impairment of biliary secretion to reduce phylloerythrin secretion
  • the horse must eat chlorophyll-rich food
  • the horse must be normally exposed to sun.
• Sunburn: due to excessive exposure to UV rather than a disproportionate response to a normal amount of UV light Dermatitis: solar.
• All lead to an increased sensitivity and reactivity to light, often due to the presence of photodynamic agents in the circulation and skin.
• Dermatological changes are secondary to inflammation of the blood vessels where there can be hyalinization or fibrinoid necrosis of the vascular walls.
• Most damage is caused by the energy from the light exciting the photosensitizing agent or phylloerythrin leading to the production of reactive molecules which cause direct damage to the cells lysosomes and other organelles with the release of hydrolytic enzymes and inflammatory mediators.
• Endothelial damage and thrombi block blood vessels leading to decreased blood supply and contributing to the necrotic process.
• Secondary trauma can occur due to self-excoriation and subsequent necrosis and sloughing.
• Pigment is protective as it absorbs the energy from light hence why non-pigmented skin is the most likely to be affected.

Timecourse

• Can occur within hours of exposure to strong sunlight or can be cumulative over days.
• In chronic hepatic failure, it may take months after hepatic damage (winter feeding and subsequent exposure to UV light).

Epidemiology

• Can occur if there is poor grazing leading to horses eating toxic plants.
• If toxic plants are baled, then horses will not be able to selectively eat, and outbreaks can occur.