Photoactivated vasculitis in Horses (Equis) | Vetlexicon
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Photoactivated vasculitis

ISSN 2398-2977

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Synonym(s): Photodermatitis

Introduction

  • Cause:
    • Type 1: secondary to ingestion (less commonly skin penetration) of plants Poisonous plants: overview, drugs, fungi or other chemicals containing photo-dynamic agents.
    • Type 2: due to phylloerythrin accumulation within the skin usually seen with hepatic insufficiency Liver disease: overview or impaired bile secretion that lead to an inability to detoxify and excrete phylloerythrin.
    • Type 3: aberrant pigment synthesis (porphyria).
    • Type 4: idiopathic photosensitization.
    • In all cases, exposure to UV light causes vasculitis and cellular damage.
  • Signs:
    • Photophobia and discomfort due to pruritus and/or pain.
    • Erythema, edema, serous and/or suppurative exudate, vesicles, scab formation and subsequent skin necrosis, sloughing and ulceration. Conjunctivitis, keratitis and corneal edema may be associated.
    • Found most frequently on non-pigmented or lightly pigmented skin. In severe cases it can affect pigmented skin.
    • Can lead to secondary bacterial infections due to damaged epithelium.
    • Systemic signs of generalized disease associated to hepatic failure.
  • Diagnosis:
    • History (with botanical investigation).
    • Physical examination.
    • Skin biopsy Dermatology: biopsy.
    • Biochemistry and liver function tests to assess hepatic function.
    • Detection of pyrrolizidine alkaloids on erythrocytes (only during ingestion stages).
    • Liver biopsy Liver: biopsy.
  • Treatment:
    • Treatment can be difficult and time consuming.
    • Avoidance of any possible source of photodynamic agents.
    • Removal from UV sources throughout the day.
    • Steroids, both topical and systemic may help but with risk of exacerbation of hepatic failure.
    • Emollients, soothing and local anesthetic creams.
    • NSAIDs for pain relief; antibiotics in case of secondary infection.
  • Prognosis:
    • Control can generally be achieved in idiopathic cases, but lifelong prophylactic treatment is often required.
    • If hepatic failure is the cause, then the prognosis is guarded.

Presenting signs

  • Crusts/scales and edema of the non-pigmented skin (although can progress to pigmented skin).
  • Erythema of non-pigmented skin.
  • Vesicles, serous and/or purulent exudation.
  • Necrosis of the skin with subsequent ulceration.
  • Photophobia
  • Pruritus, pain and secondary self-trauma.
  • Conjunctivitis, keratitis and corneal edema.
  • Systemic signs of liver failure Liver disease: overview may be associated: weight loss, jaundice, inappetence, peripheral/ventral edema, anemia, hemorrhage, colic, laminitis, fever, central nervous system signs.

Acute presentation

  • Erythema with secondary exudation, crusting and edema.

Geographic incidence

  • Generally seen where there are high UV levels but worldwide.

Breed/Species predisposition

  • Horses with non-pigmented skin most frequently affected.

Public health considerations

  • None unless a contact dermatitis due to chemicals is suspected.

Cost considerations

  • Treatment can be prolonged.

Pathogenesis

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.

Diagnosis

Presenting problems

  • Erythema with secondary edema.
  • Progression to serous exudate, necrosis and sloughing in the skin.
  • Ulceration of the skin with scabs.
  • Pruritus, pain and secondary trauma due to this.
  • Systemic signs.

Client history

  • Often relatively long-standing problem.
  • History of exposure to photodynamic agent sources.
  • History of clinical signs of hepatic disease.

Clinical signs

  • Most frequently lesions are found on the distal legs although face and neck often affected too.
  • Generally non-pigmentated skin but in severe cases pigmented skin can be involved.
  • Crust/scales in most cases.
  • Vesicles.
  • Edema.
  • Alopecia.
  • Urticaria.
  • Erythema.
  • Nodules.
  • Photophobia and discomfort with pruritus and pain.
  • Clinical signs of liver failure may be associated: weight loss, jaundice, inappetence, peripheral/ventral edema, anemia, hemorrhage, colic, laminitis, fever, central nervous system signs Liver disease: overview.

Diagnostic investigation

All horses presenting with skin lesions consistent with photosensitization must be investigated for possible hepatic function.

Confirmation of diagnosis

Discriminatory diagnostic features

  • Culture: often a secondary infection can occur and if present should be treated.
  • Dermatophyte culture or PCR.
  • Sunburn generally is insidious with slow inflammation of the skin following extended exposure to light.

Definitive diagnostic features

  • Histopathology Dermatology: biopsy: shows a cell-poor lymphocytic/histiocytic change: small vessels generally the most affected.
  • Liver biopsy in hepatic insufficiency cases with histopathology Liver: biopsy.

Gross autopsy findings

  • As per histopathological changes on biopsies.

Histopathology findings

  • Skin: cell poor, lymphocytic or histiocytic changes with fibrin deposits and thrombi within small vessels.
  • Liver: dependent on the inciting cause hepatitis or fibrinous changes .

Differential diagnosis

Treatment

Initial symptomatic treatment

  • Removal of any inciting cause is essential.
  • Non-steroidal anti-inflammatories Therapeutics: anti-inflammatory drugs can be used as an adjunctive therapy to reduce pain: flunixin meglumine Flunixin meglumine 1.1 mg/kg q12-24 h IV or PO, phenylbutazone Phenylbutazone 2.2-4.4 mg/kg q12h IV or PO.
  • Anti-histamines have a limited efficacy in horses and a very limited effect in photo-activated dermatitis.
  • If liver disease is suspected, then supportive care should be instigated.
It is essential to remove all access to UV light. This is best achieved by reducing turn out and wearing stable wraps (if distal limbs) always except night. Any exposure, even minutes, can negatively affect the healing.

Standard treatment

  • Antibiotics might be warranted systemically but should be used following confirmation of an infection with a bacterial culture.
  • Topical washes are beneficial to remove crusts as well as treat an underlying infection. Ethyl-lactate shampoos have excellent penetration into hair follicles.
  • Systemic corticosteroids: prednisolone Prednisolone 1 mg/kg q24h PO, dexamethasone Dexamethasone 0.1 mg/kg q24h IV, IM or PO.
  • Topical steroids are useful once the crusts have been removed.
  • Topical emollients/soothing and local anesthetic creams may be helpful.
  • Rheologic agents may help increase blood flow to the area and decrease the neutrophil reaction: pentoxifylline 6-10 mg/kg q12h PO.

Monitoring

  • If hepatic insufficiency is involved, then regular (2-4 weekly) blood samples should be taken.
  • During the first week of treatment close monitoring should be undertaken to ensure compliance.

Subsequent management

Treatment

  • Depending on inciting cause further management may not be required (if intake of photoactivating agents is stopped).
  • Idiopathic cases may well require contact removal from UV light.

Monitoring

  • As required.

Prevention

Control

  • Ensure that pastures do not contain toxic plants, if they do offer adequate other food.
  • Monitor bailed hay/haylage for evidence of toxic plants.

Outcomes

Prognosis

  • Type I: good once inciting cause has been removed.
  • Type II: dependent on the severity of the hepatitis.

Expected response to treatment

  • Type I: complete resolution.
  • Type II: if hepatitis is mild complete resolution, if hepatic failure then a grave prognosis.
  • Idiopathic: good response but likely reoccurrence.

Reasons for treatment failure

  • Poor owner compliance.
  • Re-exposure to toxin and UV light.
  • Non-resolution of inciting cause.

Further Reading

Publications

Refereed Papers

  • Recent references from PubMed and VetMedResource.
  • Puschner B, Chen X, Read D & Affolter V K (2016) Alfalfa hay induced primary photosensitization in horses. Vet J 211 (1), 32-38 PubMed.
  • White S D, Affolter V K, Dewey J, Kass P H et al (2009) Cutaneous vasculitis in equines: a retrospective study of 72 cases. Vet Derm 20 (5‐6), 600-606 PubMed.
  • Pilswoth R C & Knottenbelt D C (2007) Photosensitisation and sunburn. Eq Vet Edication 19 (1), 32-33 VetMedResource.
  • Petersen A D & Schott A C II (2005) Cutaneous Markers of Disorders Affecting Adult Horses. Clin Tech in Eq Pract 4 (4), 324-338 VetMedResource.

Other sources of information

  • Reed S M, Bayly W M & Sellon D C (2017) Equine Internal Medicine E-Book. Elsevier, UK.
  • Gupta R C (2012) Veterinary Toxicology. 2nd edn. Academic Press, UK.
  • Scott D W & Miller W H (2011) Equine Dermatology. 2nd edn. Elsevier Saunders, USA.
  • Knottenbelt D C (2009) Pascoe’s Principles and Practice of Equine Dermatology. 2nd edn. Elsevier Saunders, USA.
  • Stegelmeier B L (2002) Equine photosensitization. Clin Tech in Eq Pract 1 (2), pp 81-88.
  • Pascoe R R & Knottenbelt  D C (1999) Manual of equine dermatology. W B Saunders, USA.