Plants Producing Photosensitization/Photosensitivity
Plants Producing
Photosensitization/Photosensitivity
Photosensitization
is a condition in which lightly pigmented skin becomes hyper-reactive to
sunlight due to the presence of photodynamic agent(s) in the peripheral circulation and skin. 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.
Photosensitization occurs in
many countries of the world and at one
time or another in all species of farm animals, and human beings. Photosensitization
occurs worldwide and can affect any species but is most commonly seen in
cattle, sheep, goats, and horses.
Among farm animals, it is most common in cattle and sheep.
Types of photosensitization
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 veterinary medicine are plant-derived.
Photosensitization
produced by plants and some other
exogenous substances is of two types:
Primary
Photosensitization
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, acridine dyes 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 and bovine
erythropoietic protoporphyria are the most commonly reported diseases in this
category.
Congenital erythropoietic porphyria
(CEP) is a rare hereditary disease of cattle, pigs, cats, and people that
results from a significant yet variable decrease in uroporphyrinogen III
synthase (URO-synthase) activity. URO-synthetase is the fourth enzyme in the
heme biosynthesis pathway, and it normally converts hydroxymethylbilane to
uroporphyrinogen III. With decreased URO-synthase activity, hydroxymethylbilane
accumulates primarily in erythrons and is nonenzymatically converted to
uroporphyrinogen I. Further decarboxylation of uroporphyrinogen I leads to the
formation of various porphyrinogen I isomers, with coproporphyrinogen I
occurring as the final product. Coproporphyrinogen I cannot be further
metabolized to heme and is thus nonphysiologic. Porphyrinogen I isomers are
pathogenic when they accumulate in large amounts and are oxidized to their
corresponding porphyrins. Accumulation of porphyrinogen isomers in bone marrow
erythroid precursors results in cell damage and hemolysis. Porphyrin I isomers
are also released into circulation and deposited in skin, bone, and other
tissues. Cutaneous photosensitivity occurs, because porphyrins deposited in
skin are photocatalytic and cytotoxic. Presumably, exposure of skin to sunlight
(and other sources of long-wave ultraviolet light) leads to phototoxic
excitation of isomers, formation of oxygen radicals, and subsequent tissue and
vessel damage. Urinary porphyrin excretion is greatly increased (100–1,000
times normal) and primarily consists of uroporphyrin I and coproporphyrin I
with lesser amounts of other isomers. Although isomer l porphyrins predominate,
isomer lll porphyrins are also increased.
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 alkaloid (eg, Senecio spp, Cynoglossum spp, Heliotropium
spp, Echium spp, cyanobacteria (Microcystis spp, Oscillatoria
spp), Nolina spp (bunch grass), Agave lechuguilla (lechuguilla), Holocalyx
glaziovii, Kochia scoparia, Tetradymia spp (horse brush or
rabbit brush), Brachiaria brizantha, Brassica napus, Trifolium
pratense and T hybridum (red and alsike clover), Medicago sativa,
Ranunculus spp, phosphorus, drugs like carbon tetrachloride, phenanthridium, etc. Phylloerythrin
is likely the phototoxic agent in many of these poisonings.
1.
Pyrrolizidine alkaloids The
pyrrolizidine alkaloids are a group of substances of related structure produced
by a variety of plants, e.g. Senecio spp., Crotolaria
spp., Heliotropium spp., that are
consumed by animals. Over 100 pyrrolizidine alkaloids have been isolated from various plants and their levels range from
traces to 5% of the dry weight of the plant. Some pyrrolizidine
alkaloids in addition to being hepatotoxic, are potent carcinogen and mutagen.
2.
Lantana camara It is an ornamental plant which is widely distributed
all over India and several other countries. Among various varieties of this
plant, the red flowered variety is considerably toxic. The plant contains two toxic constituents, the polycyclic
triterpenes, i.e. Lantadene A and Lantadene B which cause damage to liver
and bile ducts. Animals generally eat this plant in drought conditions. Sheep
is most susceptible species; however, cattle, goats and camels are also
susceptible to its toxicity.
Photosensitivity where 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.
Mechanism of action 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.
Clinical
signs 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.
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.
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.
Post-mortem findings Fatal cases
usually result from the icterogenic form of the disease. Necropsy lesions
include superficial necrosis on the unpigmented skin and on the tender parts of
the pigmented surfaces. Extensive necrosis may be found around the eyes,
muzzle, ears and other areas. The carcass may be emaciated and dehydrated and
visible mucous membranes are usually icteric. The body tissues may show the
yellow colour of icterus. Liver may be enlarged with abnormally thin margins,
gall bladder is usually distended, and there may be proliferation of bile
ducts. The kidneys may show degenerative changes and hyaline casts.
Diagnosis 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. 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.
Photosensitization
should also be differentiated from mycotic dermatitis on the basis that photodynamic substance removal in photosensitization causes
quick recovery. Serum analysis and liver biopsy for hepatic disease, and
examination of blood, faeces and urine for porphyrin should be considered.
Treatment and management
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. In hepatogenous photosensitization, appropriate
supportive therapy may be started, e.g. fluid and electrolyte therapy.
Prognosis The prognosis for animals with
hepatogenous photosensitization and porphyria is poor; however, the prognosis
for animals with primary photosensitization is generally good. The prognosis and eventual productivity of an animal
is related to the site and severity of the primary lesion and to the degree of
resolution. The skin lesions heal remarkably well, even after extensive
necrosis.
Comments
Post a Comment