Canis ISSN: 2398-2942

Skin: immunological disease - overview

Contributor(s): David Scarff, Richard Squires, David Godfrey

Introduction

  • Immunological skin diseases are uncommon, accounting for 1.4% of the dermatology caseload in one study.
  • Cause: the exact mechanisms causing disease are unknown.
  • May be:
    • Primary autoimmune diseases, where antibodies or activated lymphocytes are directed against self antigens. A failure in immune tolerance.
    • Secondary immune-mediated, where tissue damage results from immunological processes that do not involve self antigen but from an immune response against a foreign antigen (pathogen or chemical).
  • Signs: all are characterized by an inappropriate immune response causing skin disease.
  • Diagnosis: usually by histopathology of skin biopsy. This may be considered a tentative diagnosis in the absence of specific identification of the offending antibodies or targeted antigens (but these tests have low availability in our species compared with human medicine).
  • Treatment: immunosuppression (varies considerably in individual conditions) and, sometimes, avoidance of trigger factors.
  • Prognosis: very variable and dependant on the individual conditions. Some are localized or benign conditions that may be left untreated; severe, life-threatening and clinically unresponsive immunological conditions are also seen.

Pathogenesis

Etiology

  • Defective T cell activity.
  • Drugs.
  • Bacteria.
  • Viruses.
  • Idiopathic.
  • Genetic factors have been identified in some autoimmune diseases, There are strong breed predispositions for some conditions, eg systemic lupus erythematosus (German Shepherd dog), vesicular cutaneous lupus erythematosus (Shetland sheepdog and Rough Collie); exfoliative cutaneous lupus erythematosus; canine uveodermatologic syndrome (Akita and others).
  • Hormonal influences may be present. This is seen in women.
  • Other trigger factors can include UV light.

Pathophysiology

  • Primary autoimmune disease: a failure to eliminate self-reactive, high-affinity lymphocytes in primary lymphoid organs; or a failure to regulate (suppress) the activity of low-affinity self-reactive lymphocytes present within the body.
  • Secondary disease: foreign antigens provoke and immune response.
    • Drugs.
    • Neoplasia.
    • Vaccines.
    • Infectious agents.
  • Autoantigens in close proximity, or with similar epitopes, become targets of the immune response.
  • The anatomic site that is targeted will affect the disease produced and the clinical signs and consequences.

Epidermal intercellular desmosomal connections

Proteins of the basement membrane

  • A group of poorly defined diseases feature an autoimmune attack on the basement membrane or adjacent sites. These are all very rare and are grouped as autoimmune subepidermal blistering disease (AISBD) with possible individual conditions called: acquired junctional epidermolysis, bullous pemphigoid Skin: bullous pemphigoid, bullous systemic lupus erythematosus, epidermolysis bullosa acquisita Skin: epidermolysis bullosa, linear IgA disease Skin: linear IgA disease, mixed AISBD and mucus membrane pemphigoid. These all show with primary lesions of vesicles and ulceration.

DNA

  • The hall mark of human systemic lupus erythematosus (SLE) Systemic lupus erythematosus is antibodies to DNA but other immune dysfunction is seen in humans and dogs. SLE is thus, by definition, multisystemic. Skin lesions are seen in about 50% of canine SLE cases but the lesions are highly variable depending on the sites being targeted in the individual - alopecia, scarring, ulceration, seborrhea, depigmentation.

Hair follicle proteins

  • Various proteins in the hair follicle bulbs including melanin have been shown to be targets in human and canine alopecia areata Skin: alopecia - overview
  • In pseudopelade the target may be stem cells in the mid isthmus of the hair follicle.

Erythrocytes

  • In cold agglutinin disease Skin: cold agglutinin disease and similar pathologies, cryoglobins and cryofibrinogens attack erythrocytes only in the body's extremities, leading to intracapillary obstruction and cyanosis and necrosis of the skin of extremities.

Pigment proteins

  • Melanin is the likely target in canine uveodermatologic syndrome Uveodermatological syndrome.
  • Some forms of vitiligo are autoimmune and some immune-mediated with genetics being important.

Sebaceous gland components

Keratinocyte proteins

  • The details of erythema multiforme Skin: erythema multiforme and toxic epidermal necrolysis Skin: toxic epidermal necrolysis are unclear but interactions of the immune system with antigens on keratinocytes, drugs and pathogens are important. Visible lesions are very variable - target lesions, macules, vesicles and ulcers and can be limited or widespread over the body and with or without systemic disease - depending on the extent of epidermal cell damage.

Blood vessel wall proteins

  • Vasculitis Cutaneous vasculitis is not always immune mediated but usually it is a secondary immune-mediated disease triggered by infection or a drug via a type III hypersensitivity. With cutaneous vasculitis, vessels are dermal or subcutaneous. Lesions tend to be worse on extremities, where collateral supply is less and vary according to the degree of disruption of blood supply and associated inflammation - purpura, urticaria, angioedema, plaques, pustules.
  • Syndromes of vasculitis with distinct presentations include: proliferative thrombovascular necrosis of the pinnae; proliferative arteritis of the nasal philtrum; focal cutaneous vasculitis and alopecia at the site of rabies vaccination; vasculopathy of greyhounds; cutaneous and renal glomerular vasculopathy (Alabama rot) Skin: idiopathic cutaneous and renal glomerular vasculopathy; familial cutaneous vasculopathy of German shepherd dogs; ischemic dermatopathy.

Collagen

  • Auricular chondritis has been reported in one dog. Multiple papules on the pinnae were seen

There are autoimmune diseases with unknown or more generalized targets

  • Linear immunoglobulin A pustular dermatosis in dachshunds Skin: linear IG A syndrome.
  • Drug reactions immune-mediate pathology is probably usually present in cutaneous drug reactions but this is likely variable and complicated. This shows in that cutaneous drug reactions can mimic any dermatosis Skin: adverse drug reactions.
  • Amyloidosis is a systemic immune-mediated disease which sometimes causes skin lesions due to accumulation of the amyloid protein in skin tissue Amyloidosis.

Diagnosis

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Treatment

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Outcomes

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Further Reading

Publications

Referred papers

  • Recent references from PubMed and VetMedResource.
  • Day M J, Hanlon L & Powell L M (1993) Immune-mediated skin disease in the dog and cat.  J Comp Pathol 109 (4), 395-407 PubMed.

Other sources of information

  • Miller W H, Griffin C E & Campbell K L (2013) Autoimmune and immune-mediated dermatoses. In:  Muller & Kirk’s Small Animal Dermatology. 7th edn, Elsevier, St Louis. pp 432.
  • Scott D W  et al (1987) Immune-mediated dermatoses in domestic animals: ten years after, part I.  Compendium of Continuing Education in Small Animal Practice 9, 423.

 


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