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Pemphigus vulgaris

ISSN 2398-2977


Introduction

  • Description: pemphigus vulgaris (PV) is a rare autoimmune disease in the horse Immune-mediated disease: overview Skin: immune-mediated disease - overview.
  • Cause: in all pemphigus variants, autoantibodies target extracellular molecules important for keratinocyte cell-to-cell adhesion and epithelial integrity and function Pemphigus antibodies. In PV affecting humans and dogs, the cadherin Desmoglein-3 (Dsg3) is the major antigen, and Desmoglein-1 (Dsg1) may also be targeted. In the mucocutaneous phenotype of PV in people, Dsg1 and Dsg3 autoantibodies are both involved in the disease process. Dsg3 may be the major autoantigen in PV in horses, based on one case report.
  • Signs: vesicles, bullae, crusts, scales, erosions and ulcers on the skin, mucocutaneous junctions, mucous membranes (oral cavity), associated pain and pruritus. Dysphagia Gastrointestinal: dysphagia, anorexia, weight loss Weight loss: overview, depression, pyrexia Pyrexia: overview.
  • Diagnosis: history, clinical presentation, histopathology. Exclusion of differential diagnoses. 
  • Treatment: immunosuppressants (oral, injectable, topical glucocorticoids Therapeutics: glucocorticoids), “steroid-sparing” drugs like azathioprine, gold salts and pentoxifylline.
  • Prognosis: grave.

Presenting signs

  • Skin lesions (vesicles, bullae, scales, crusts, erosions, ulcers) affecting skin, mucocutaneous junctions and mucous membranes, especially oral cavity.
  • Lesion distribution:
    • Skin (head, neck, mane/tail, coronary bands, ergots and chestnuts).
    • Mucocutaneous junctions (muzzle, anus, perineum, vulva/sheath).
    • Oral cavity (mucous membranes/tongue).
    • Esophagus/stomach can be affected.
  • Pain, especially oral ulcers.
  • Pruritus can be present.
  • Dysphagia/anorexia if lesions affect the upper gastrointestinal tract (esophagus, stomach).
  • Systemic signs (anorexia, weight loss, depression, pyrexia, gross edema) can be present in severe cases.

Acute presentation

  • Progressive skin lesions (vesicles, bullae, scales, crusts, erosions, ulcers) with involvement of mucocutaneous junctions and oral mucosa.
  • Vesicles and bullae are fragile and transient; hence erosions-ulcerations might be more commonly seen.
  • Pain, especially oral ulcers.
  • Pruritus can be present.
  • Dysphagia/anorexia may occur if lesions affect the upper gastrointestinal tract.
  • Systemic signs (anorexia, weight loss, depression, pyrexia, edema) can be present in severe cases.

Geographic incidence

  • Only a few cases reported worldwide.

Age predisposition

  • Unknown/not enough cases reported.

Breed/Species predisposition

  • Unknown/not enough cases reported.
  • The single detailed published case report is a Welsh pony stallion.

Public health considerations

  • Non-infectious disease.

Cost considerations

  • The recommended diagnostic work-up (see below) implies some costs but is crucial to establish the diagnosis.
  • Glucocorticoid treatment is affordable compared to other treatments but bears a relatively high potential for adverse effects and associated complications.

Special risks

  • Immunosuppressive glucocorticoid treatment and associated potential adverse effects, including increased susceptibility to infections, polydipsia/polyuria Polydipsia/polyuria, poor wound healing, weight loss, behavioral changes, hepatopathy, laminitis Foot: laminitis (anecdotal but horses with a history of laminitis appear at greater risk).
  • Rapid disease progression and/or lack of treatment response can cause further complications such as dysphagia/anorexia.

Pathogenesis

Etiology

  • PV belongs to the pemphigus complex of autoimmune diseases.
  • Diseases of the Pemphigus complex are characterized by autoantibodies in the skin and serum targeting specific molecules crucial for functional intercellular keratinocyte adhesion.
  • In PV of humans and dogs, the cadherin Dsg3 is the major antigen, and Dsg1 may be involved.
  • Dsg3 is characteristically expressed in the deeper epithelial layers, hence autoantibodies recognizing Dsg3 and interfering with intercellular adhesion cause the deep, vesicular or bullous lesions of (mucosal) PV. In pemphigus foliaceus (PF), on the contrary, molecules expressed in the more superficial epithelial layers are targeted (mainly Dsg1 in people, Desmocollin-1 in dogs), resulting in shallower lesions. In the mucocutaneous phenotype of PV in people, Dsg1 and Dsg3 autoantibodies are involved in the disease process. There are no larger studies regarding the causative autoantibody and targeted antigen in the horse, but Dsg3 may be the major autoantigen in horses, based on one case report.

Predisposing factors

General

  • Unknown/ not enough cases reported.
  • In PF, the presence of insects, seasonal antigens, UV light, and drugs and internal neoplasia might contribute to disease development.
  • In humans and dogs, genetic factors may play a role.
  • There are anecdotal reports of disease remission in equine PV. These cases may represent a subgroup of PV with an underlying (unidentified) trigger, and disease remission occurs once it is no longer present.

Specific

  • The exact mechanism/trigger of initial autoantibody formation is unknown.

Pathophysiology

  • Diseases of the pemphigus complex are characterized by autoantibodies in the skin and serum that target specific molecules which are crucial for functional intercellular keratinocyte adhesion.
  • Once intraepithelial adhesion is disrupted by the presence of autoantibodies, the keratinocytes are often separated and take a round shape (acantholytic cells). These cells can be seen in histopathology and sometimes in cytology samples, eg impression smear Staining techniques: Diffquick stain, however, cytology is more useful in superficial PF than in deeper PV.
  • Acantholysis of keratinocytes can be clinically seen as pustule, vesicle and bulla formation.

Timecourse

  • Progressive deterioration over a few months.
  • Not enough cases reported to establish an exact time course.
  • In one case report, the time period from first onset of clinical signs to euthanasia was 7 months.

Epidemiology

  • Unknown; not enough cases reported.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Knottenbelt D (2016) Integumentary disorders including cutaneous neoplasia in older horses. Vet Clin Equine 32 (2), 263-281 PubMed.
  • Rosenkrantz W (2013) Immune-mediated dermatoses. Vet Clin Equine 29 (3), 607-613 PubMed.
  • Winfield L D, White S D, Affolter V K et al (2013) Pemphigus vulgaris in a Welsh pony stallion: case report and demonstration of antidesmoglein autoantibodies. Vet Dermatol 24 (2), 269-273 PubMed.
  • Olivry T & Linder K E (2009) Dermatoses affecting desmosomes in animals: a mechanistic review of acantholytic blistering skin diseases. Vet Dermatol 20 (5-6), 313-326 PubMed.

Other sources of information

  • Knottenbelt D C (2014) Selected Equine Skin Diseases. In: Proc DGVD Annual Congress. Hamburg, Germany. pp 31-37.
  • Olivry T (2014) Keratinocyte Desmosomes: Comparative Animal Pathology. In: Proc ESVD Workshop From Skin Structure To Mechanism Of Animal Skin Disease. Spa, Belgium. pp 69-70.
  • Miller W H, Griffin C E & Campbell K L (2013) Muller and Kirk’s Small Animal Dermatology. 7th edn. Elsevier Mosby, USA. pp 445-446.
  • Bergvall K (2012) Immune Mediated Causes of Scaling – Pemphigus and Sarcoidosis. In: Proc ESVD Workshop Equine Dermatology. Amersfoort, The Netherlands. pp 66-69.
  • Whitbread T (2012) Histopathology of Pemphigus and Sarcoidosis. In: Proc ESVD Workshop Equine Dermatology. Amersfoort, The Netherlands. pp 73-75.
  • Scott D W & Miller W H (2011) Equine Dermatology. 2nd edn. Elsevier Saunders, USA. pp 315-324.
  • Knottenbelt D C (2009) Pascoe’s Principles and Practice of Equine Dermatology. 2nd edn. Elsevier Saunders, USA. pp 269-270.