Photosensitization occurs when skin (especially areas exposed to light and lacking significant protective hair, wool, or pigmentation) becomes more susceptible to ultraviolet light because of the presence of photodynamic agents. Photosensitization differs from sunburn and photodermatitis, because both of these conditions result in pathologic skin changes without the presence of a photodynamic agent.
In photosensitization, unstable, high-energy molecules are formed when photons react with a photodynamic agent. These high-energy molecules initiate reactions with substrate molecules of the skin, causing the release of free radicals that in turn result in increased permeability of outer cell and lysosomal membranes. Damage to outer cell membranes allows for leakage of cellular potassium and cytoplasmic extrusion. Lysosomal membrane damage releases lytic enzymes into the cell. This can lead to skin ulceration, necrosis, and edema. The time interval between exposure to the photodynamic agent and the onset of clinical signs depends on the type of agent, its dose, and the exposure to sunlight.
Photosensitization is typically classified according to the source of the photodynamic agent. These categories include primary (type I) photosensitivity, aberrant endogenous pigment synthesis (type II) photosensitivity, and hepatogenous (secondary, type III) photosensitivity. A fourth category termed idiopathic (type IV) photosensitivity has been described.
A wide range of chemicals, including some that are fungal and bacterial in origin, may act as photosensitizing agents. However, most compounds that are important causes of photosensitivity in animals are plant-derived. Photosensitization occurs worldwide and can affect any species but is most commonly seen in cattle, sheep, goats, and horses.
Primary photosensitization occurs when the photodynamic agent is either ingested, injected, or absorbed through the skin. The agent enters the systemic circulation in its native form, where it results in skin cell membrane damage after the animal is exposed to ultraviolet light. Examples of primary photosensitizing agents include hypericin (from Hypericum perforatum [St. John’s wort]) and fagopyrin (from Fagopyrum esculentum [buckwheat]).
Plants in the families Umbelliferae and Rutaceae contain photoactive furocoumarins (psoralens), which cause photosensitization in livestock and poultry. Ammi majus (bishop’s weed) and Cymopterus watsonii (spring parsley) have produced photosensitization in cattle and sheep, respectively. Ingestion of A majus and A visnaga seeds has produced severe photosensitization in poultry. Species of Trifolium, Medicago (clovers and alfalfa), Erodium, Polygonum, and Brassica have been incriminated as primary photosensitizing agents. Many other plants have been suspected, but the toxins responsible have not been identified (eg, Cynodon dactylon [Bermudagrass]).
Additionally, coal tar derivatives such as polycyclic aromatic hydrocarbons, tetracyclines, and some sulfonamides have been reported to cause primary photosensitization. Phenothiazine anthelmintics have been reported to cause primary photosensitivity in cattle, sheep, goats, and swine.
Type II photosensitivity due to aberrant pigment metabolism is known to occur in both cattle and cats. In this syndrome, the photosensitizing porphyrin agents are endogenous pigments that arise from inherited or acquired defective functions of enzymes involved in heme synthesis. Bovine congenital erythropoietic porphyria (see Congenital Erythropoietic Porphyria) and bovine erythropoietic protoporphyria (see Cutaneous Manifestations of Multisystemic and Metabolic Defects in Animals) are the most commonly reported diseases in this category.
Secondary or type III photosensitization is by far the most frequent type of photosensitivity observed in livestock. The photosensitizing agent, phylloerythrin (a porphyrin), accumulates in plasma because of impaired hepatobiliary excretion. Phylloerythrin is derived from the breakdown of chlorophyll by microorganisms present in the GI tract. Phylloerythrin, but not chlorophyll, is normally absorbed into the circulation and is effectively excreted by the liver into the bile. Failure to excrete phylloerythrin due to hepatic dysfunction or bile duct lesions increases the amount in the circulation. Thus, when it reaches the skin, it can absorb and release light energy, initiating a phototoxic reaction.
Phylloerythrin has been incriminated as the phototoxic agent in the following conditions: common bile duct occlusion; facial eczema; lupinosis; congenital photosensitivity of Southdown and Corriedale sheep; and poisoning by numerous plants, including Tribulis terrestris (puncture vine), Lippia rehmanni, Lantana camara, several Panicum spp (kleingrass, broomcorn millet, witch grass), Cynodon dactylon, Myoporum laetum (ngaio), and Narthecium ossifragum (bog asphodel).
Photosensitization also has been reported in animals that have liver damage associated with various poisonings:
pyrrolizidine alkaloids (eg, Senecio spp, Cynoglossum spp, Heliotropium spp, Echium spp)
cyanobacteria (Microcystis spp, Oscillatoria spp)
Nolina spp (bunch grass)
Agave lechuguilla (lechuguilla)
Tetradymia spp (horse brush or rabbit brush)
Trifolium pratense and T hybridum (red and alsike clover)
Phylloerythrin is likely the phototoxic agent in many of these poisonings.
Photosensitivity in which the pathogenesis is unknown or the photodynamic agent is not identified is classified as type IV. One such example involved a case of primary photosensitivity in cattle presumed to be caused by Thlaspi arvense (field pennycress), even though field pennycress has not been reported to cause photosensitization. Outbreaks of photosensitization have been reported in cattle exposed to water-damaged alfalfa hay, moldy straw, and foxtail-orchardgrass hay. These cases were suspected to be hepatogenous in origin. Ranunculus bulbosus (buttercup) has also been presumed to be a cause of hepatogenous photosensitization. Other plants associated with photosensitization include winter wheat (cattle), Medicago spp (alfalfa), Brassica spp (mustards), and Kochia scoparia (fireweed). Many of these plants are believed to be type I photosensitizers. Forages such as oats, wheat, and red clover have been suspected in cases of photosensitization and may be associated with specific environmental conditions such as heavy rainfall.
Dermatologic signs associated with photosensitivity are similar regardless of the cause. Photosensitive animals are photophobic immediately when exposed to sunlight and appear agitated and uncomfortable. They may scratch or rub lightly pigmented, exposed areas of skin (eg, ears, eyelids, muzzle).
Lesions initially appear in white-haired, nonpigmented, or hairless areas such as the nose and udder. However, severe phylloerythrinemia and bright sunlight can induce typical skin lesions, even in black-coated animals. Erythema develops rapidly and is soon followed by edema. If exposure to light stops at this stage, the lesions soon resolve. When exposure is prolonged, lesions may progress to include vesicle and bulla formation, serum exudation, ulceration, scab formation, and skin necrosis.
The final stage involves skin sloughing. In cattle, and especially in deer, exposure of the tongue while licking may result in glossitis, characterized by ulceration and deep necrosis. Irrespective of coat color, cattle may develop epiphora, corneal edema, and blindness.
Depending on the initial cause of the accumulation of the photosensitizing agent, other clinical signs may be seen. For example, if the photosensitivity is hepatogenous, icterus may be present. In bovine congenital erythropoietic porphyria, discoloration of dentin, bone (and other tissues), and urine often accompanies the skin lesions. Photodermatitis is the sole manifestation seen in bovine erythropoietic protoporphyria.
Diagnosis of photosensitization is based on clinical signs, evidence or history of exposure to photosensitizing agents or hepatotoxins, and characteristic lesions. Photophobia in combination with erythema and edema of hairless, nonpigmented areas of skin is strongly suggestive of the disease. The period from exposure to photodynamic or hepatotoxic agents to the onset of clinical signs can vary from several hours up to 10 days. Clinical signs; increased serum biochemical measurements, including sorbitol dehydrogenase, gamma glutamyltransferase, alkaline phosphatase, and direct bilirubin; and gross or histologic signs of liver disease help support a diagnosis of hepatogenous photosensitization. A presumptive diagnosis of porphyria is based on signalment (sex, breed, age) combined with clinical signs, and a definitive diagnosis can be made by measuring porphyrin levels in blood, feces, and urine.
The prognosis for animals with hepatogenous photosensitization and porphyria is poor; however, the prognosis for animals with primary photosensitization is generally good. Treatment involves mostly palliative measures. While photosensitivity continues, animals should be shaded fully or, preferably, housed and allowed to graze only during darkness. The severe stress of photosensitization and extensive skin necrosis can be highly debilitating and increase mortality. Corticosteroids, given parenterally in the early stages, may be helpful. Secondary skin infections and suppurations should be treated with basic wound management techniques, and fly strike prevented. The skin lesions heal remarkably well, even after extensive necrosis.
Photosensitization is caused by production or ingestion of photodynamic agents, which lead to increased susceptibility to skin damage following exposure to sunlight.
Secondary (type III) photosensitization caused by abnormal hepatic metabolism of phylloerythrin is the most common type seen in livestock.