Contributors: Richard Squires, David Scarff, David Godfrey

 Species: Feline   |   Classification: Diseases

Introduction Pathogenesis Diagnosis Treatment Outcomes Further Reading

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:
    • Primary autoimmune diseases, where antibodies or activated lymphocytes are directed against self-antigens. A failure in immune tolerance.
    • Secondary immune-mediated diseases, 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 appropriate 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 (these tests have low availability in cats compared to human medicine).
  • Treatment: immunosuppression (varies considerably in individual conditions) and, sometimes, avoidance of trigger factors.
  • Prognosis: very variable and dependent on the individual condition. 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 are possible but are poorly investigated in cats.
  • Hormonal influences may be seen. (This is seen in women.)
  • UV light is a common trigger in other species.

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 an immune response:
    • Drugs.
    • Neoplasia.
    • Vaccines.
    • Infectious agents.
  • Autoantigens in close proximity, or with similar epitopes, then 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

  • This site is a common target for autoimmune skin diseases causing the pemphigus complex of pemphigus foliceus  Skin: pemphigus foliaceus  (more superficial lesion showing as pustules and erosion) is quite common in cats but pemphigus vulgaris  Skin: pemphigus vulgaris  (rarer with slightly deeper lesions - pustules and ulcers and usually oral lesions) and pemphigus erythematosus  Skin: pemphigus erythematosus  are very rare.

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) but have not been reported in cats.

DNA

  • The hallmark of human systemic lupus erythematosis (SLE)   Systemic lupus erythematosus  is autibodies to DNA but other immune dysfunction is seen in humans and dogs. SLE is thus, by definition, multisystemic. SLE is rare in cats and skin lesions are seen in about 50% of feline SLE cases but the lesions are highly variable depending on the sites being targeted in the individual - alopecia, scarring, ulceration, seborrhea, depigmentation. Neurological signs are common in cats with SLE.
  • A localized form of lupus erythematosus exists with cutaneous lupus erythematosus (previously called discoid lupus erythematosus) occurring but only rarely in cats.

Hair follicle proteins

  • Various proteins in the hair follicle bulbs including melanin have been shown to be targets in human and canine alopecia areata. The situation is probably the same in cats which rarely suffer from alopecia areata.
  • In pseudopelade the target may be stem cells in the mid isthmus of the hair follicle.

Erythrocytes

  • In cold agglutinin disease  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 extremities.

Pigment proteins

  • Some forms of vitiligo are autoimmune and some are immune-mediated with genetics being important.

Sebaceous gland components

  • The cause of granulomatous sebaceous adenitis is unclear and may vary but autoimmunity to a component of the sebaceous gland may well be important. This is a rare disease in cats.

Keratinocyte proteins

  • The details of erythema multiforme and toxic epidermal necrolysis  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 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 vascultitis, 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 assocated inflammation - purpura, urticaria, angioedema, plaques, pustules.

Collagen

  • Auricular chondritis has been reported rarely in cats with swollen, erythematous pinnae.

There are autoimmune diseases with unknown or more generalized targets

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

Diagnosis

Presenting Problems

  • These vary greatly.
  • Some diseases have typical presentations - sites and lesions:
    • Vesicles and bullae in cutaneous and mucocutaneous sites.
    • Mucous membrance ulceration.
    • eg Cutaneous lupus erythematosis, vitiligo, auricular chondritis.
  • Some are highly variable:
    • Drug reactions.
    • Erythema multiforme.
    • Vasculitis.

Diagnostic Investigation

Histopathology

  • Skin biopsy is indicated whenever immunological disease is suspected.
  • Diagnosis is confirmed by typical histopathological appearance of lesions.
  • Biopsy only early representative lesions. The best lesions will vary according to the disease suspected:
    • In SLE and CLE depigmenting areas are best.
    • In pemphigus intact vesicles, pustules or bullae are best. Fresh ulcers are useful.
    • It can often be worthwhile delaying biopsy of suspected vesicular diseases in order to obtain a primary lesion.
    • However, antibiotic treatment to remove any secondary bacterial infection may be helpful.
  • Ideally do not biopsy if the patient is receiving immunosuppressive treatment or have the owner understand that repeat biopsy after stopping immunosuppressives might be required in case of inconclusive results. Take multiple biopsies - minimum of three. Wedge biopsies are more likely to include diagnostic lesions and less likely to rupture vesicles during the process than punch biopsies.
  • Send samples to a specialist veterinary dermatohistopathologist.
  • Direct fluorescent antibody testing positive or immunohistochemistry Immunohistochemistry (IHC) is not necessary for routine diagnosis of immune-mediated skin disease and results cannot be interpreted without histological findings. It is essential for a definitive case. Discuss these immunological tests with your lab before sampling as special sampling requirements often apply.
  • Cytology of intact pustules/vesicles can be very helpful especially for pemphigus cases where it can sometimes be more easily diagnostic than histopathology.

Other

  • May be vital for many immunological diseases:
    • Systemic disease may be part of the suspected condition and detection of this esssential for making the diagnosis, eg SLE - hematology, biochemistry, urinalysis and ANA testing Anti-nuclear antibody.
    • Underlying disease may be present.
    • Baseline assessment of internal organs is important before commencing therapy that may consist of drugs with significant side effects.

Treatment

Initial Symptomatic Treatment

Principles of treatment

  • Make a specific diagnosis - prognosis varies greatly.
  • Minimize trigger factors - avoid UV light, stop any possible drugs that might have initiated the disease.
  • Control secondary infections.
  • Consider treating localized disease topically.
  • Bear in mind that the quality of evidence for treating feline immunological disease is low and that side effects of treatments are likely.
  • Tailor treatment trials to the individual animal and their owners.
  • Combinations of drugs may have additive immunosuppression with fewer side effects.
  • Treatment is considered in 4 phases:
    • Induction:
      • High dose.
      • For a limited perioid if it is not working then try a different induction regime.
      • The period depends on the drug being used, eg steroids should work within 10 days.
    • Transition:
      • Taper the dose of all the drugs to the minimum that control the problem (total control of all lesions may not be essential).
      • Reduce the most dangerous first (or the most expensive if necessary). Also consider the requirements for monitoring and the problems this incurs.
    • Maintenance:
      • If tapering causes recurrence then the doses are increased to find the suitable long-term maintenance doses for the individual.
      • Consider tapering again in the future if signs are totally controlled.
    • Cure:
      • Stopping medication may be considered after the patient has been totally controlled on maintenance for 8-12 months.
      • Recurrence may occur and the level of problem will guide whether removing medication should be attempted in the future.

Outcomes

Prognosis

  • There is the full spectrum of possibilities from death to full recovery or living with a benign condition, so diagnostic precision is important.
  • With some immunological conditions the side effects of treatment can outweigh the effects of the disease.

Expected Response to Treatment

Reasons for Treatment Failure

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Day M J, Hanlon L & Powell LM (1993) Immune-mediated skin disease in the dog and cat. J Comp Pathol 109 (4), 395-407 PubMed.
  • Scott D W (1990) Feline dermatology 1986-1988 - looking to the 1990s through the eyes of many counselors. JAAHA 26, 515-537.
  • Scott D W, Walton D K, Slater M R et al (1987) Immune-mediated dermatoses in domestic animals: ten years after, I II. Compend Contin Educ Small Anim Pract (4), 424-53 VetMedResource.
  • Scott D W (1986) Feline Dermatology 1983-1985: "the Secret sits". JAAHA 23 (3), 255-274 VetMedResource.

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.

Other Sources of Information