Introduction

In this presentation, we will cover two of the most common autoimmune skin diseases affecting dogs and cats: pemphigus foliaceus and discoid lupus erythematosus.

1. Pemphigus Foliaceus

Canine pemphigus encompasses four variants: pemphigus foliaceus, pemphigus vulgaris, pemphigus vegetans and paraneoplastic pemphigus. Pemphigus foliaceus is the most common variant and also the most common autoimmune skin disease affecting dogs and cats.

Pathomechanism

Anti-keratinocyte antibodies induce loss of cohesion (acantholysis) between keratinocytes resulting in formation of pustules that rapidly progress to erosions, crusts and alopecia. In the dog, the major autoantigen is desmocollin 1. Pemphigus foliaceus can occur spontaneously or secondary to triggers such as drugs, vaccine or ultraviolet light.

Signalment

• Chow chows and Akitas are predisposed
• Typically middle age
• No sex prediction for dogs; possibly more common in female cats

Clinical Signs

The characteristic lesion in both dogs and cats is a pustule, which evolves rapidly into erosions, crusts and alopecia. Lesions often develop in waves and may wax and wane. Depigmentation affecting nasal planum and footpads are common.

Distribution

Dogs

The face is the most common initial site of lesions. The disease progresses to affect the dorsal muzzle, nasal planum, periocular areas, ears, trunk and footpads. Lesions are typically bilateral and symmetrical but can be localised (e.g., face or claw folds). Affected dogs may show pruritus and systemic symptoms such as anorexia and lethargy. Weight loss may be present in severe cases.

Cats

Lesions most commonly affect the face, ears and feet and are typically bilateral and symmetrical. Claw folds may reveal suppurative exudation. Perimammary crusting is considered highly suspicious for pemphigus foliaceus.

Clinical differentiation between pemphigus foliaceus and bacterial pyoderma

Diagnostic Approach

Cytology

An easy test to increase suspicion for pemphigus foliaceus is to perform cytological evaluation of an intact pustule. The typical findings are “rafts” of acantholytic keratinocytes with non-degenerated neutrophils with or without eosinophils.

The presence of acantholytic keratinocytes does not confirm the dog/cat has pemphigus foliaceus. Acantholysis can also occur secondary to other diseases such as pustular dermatophytosis (especially due to Trichophyton mentagrophytes) and bacterial diseases (i.e., bullous impetigo and exfoliative superficial pyoderma).

Histopathology

Biopsies of intact pustules and/or crusts will reveal subcorneal pustules with acantholytic keratinocytes. Special stains (e.g., Gram stain for bacteria and PAS for fungi) can rule out infectious causes for the acantholysis. Tissue cultures should be performed to definitely rule out infections.

Immunopathology

Direct and indirect immunofluorescence can detect antikeratinocyte autoantibodies and circulating pemphigus autoantibodies, respectively.

Treatment Options

Immunosuppressive therapy is used to treat pemphigus foliaceus. In dogs, the treatment of choice is oral glucocorticoid with or without concurrent steroid-sparing therapies such as azathioprine, chlorambucil, ciclosporin and mycophenolate mofetil.

In cats, glucocorticoid (most commonly prednisolone or triamcinolone) monotherapy usually produces a good response. Steroid-sparing therapies include ciclosporin or chlorambucil.

Topical glucocorticoids (moderate to high potency [e.g., 0.1% mometasone]) are also very effective at treating focal lesions.

Veterinarians should also try to identify any potential triggers such as drugs, preventatives and ultraviolet light. If a dog/cat relapses, it is important to rule out development of bacterial pyoderma, dermatophytosis or demodicosis. These diseases can be managed without the need to increase the level of immunosuppression.

Monitoring

Regular blood and urine monitoring is recommended to identify potential side effects to immunosuppressive therapy.

Outcome

The outcomes for both canine and feline pemphigus foliaceus are generally good. The main reasons for euthanasia are lack of response to treatments and unacceptable side effects to treatments. These can be managed by client education, and regular blood and urine monitoring.

2. Cutaneous Lupus Erythematosus (CLE) in Dogs

Current recognised forms of cutaneous lupus erythematosus in dogs are discoid lupus erythematosus (localised and generalised), vesicular cutaneous lupus erythematosus, exfoliative cutaneous lupus erythematosus and mucocutaneous lupus erythematosus. Localised facial-predominant discoid lupus erythematosus is the most common form seen in dogs.

Localised (Facial-Predominant) Discoid Lupus Erythematosus (FDLE)

Signalment

• German shepherds and their crosses make up about 31% of cases.
• Median age of onset is 7 years (range from 1 to 12 years).
• Female to male ratio is 0.7.

Clinical Signs

The early signs include erythema, depigmentation and scaling, most commonly affecting the nasal planum. These progress to erosions and ulcerations, atrophy and loss of the normal cobblestone appearance on the nasal planum. Less commonly, lesions may also affect the skin around the dorsal muzzle, lips, eyes and pinnae. Pruritus is variable and more likely with secondary bacterial infections. The main differential diagnoses include mucocutaneous pyoderma (MCP), uveodermatologic syndrome and localised epitheliotropic lymphoma.

Diagnostic Approach

Depigmentation of the nasal planum without loss of the cobblestone surface architecture may be normal in certain breeds (e.g., nasal hypopigmentation in golden and Labrador retrievers). Conversely, a thorough and immediate examination of the eyes for uveitis should be performed in breeds predisposed to uveodermatologic syndrome (e.g., Akitas and Alaskan Malamutes).

Cytology

MCP and DLE can be difficult to differentiate clinically and on histopathology. Furthermore, most cases of DLE are secondarily infected. It is important to perform cytology and treat any secondary infections before proceeding to further diagnostics.

Histopathology

DLE is characterised by a lichenoid cell rich, lymphocytic interface dermatitis with basal keratinocyte vacuolar degeneration apoptosis, loss of basal cells and basement membrane thickening. The interface reaction may be mild in FDLE but is usually well developed in generalised DLE.

Treatment Options

Systemic and/or topical immunosuppressive or immunomodulatory therapies can be used depending on the severity of disease.

For severe cases, oral prednisolone is recommended to achieve remission. The prednisolone doses can then be reduced or potentially withdrawn as less potent immunomodulatory therapies are added. These include combination of tetracycline/doxycycline and niacinamide, fish oils, vitamin E.

Topical therapies include topical cortisone (starting with higher potency [e.g., 0.1% mometasone], then changing to less potent [e.g., 1% hydrocortisone]) or 0.1% tacrolimus.

Distraction techniques should be employed to avoid dog rubbing/licking off topical therapies.

Avoidance of ultraviolet light is important, especially during initial treatment phase. Sunscreen should be applied to non-pigmented areas and the dog should preferably be kept away from sun exposure.

Tattooing of the nasal planum is not recommended. Apart from potential topical chemical reaction to the ink, this method does not protect against actinic damage because the tattoo ink is injected into the dermis but actinic damage occurs mostly on the epidermis.

Generalised Discoid Lupus Erythematosus

Signalment

In the ten dogs reported, the breeds include two Chinese crested dogs, two Labrador retrievers, and one each of miniature pinscher, Leonberger, Shih Tzu and toy poodle.

The median age of onset is 9 years (range from 5 to 12 years). Both female and male are equally affected.

Clinical Signs

The skin lesions include generalised or multifocal plaques, scaling, follicular plugging and alopecia affecting mainly the neck, dorsum and lateral thorax. The plaques can progress to ulcers with subsequent healing resulting in central atrophic or hypertrophic scars. Both depigmentation and hyperpigmentation may be observed. Four of the ten dogs had plaques around mucocutaneous regions (mainly genitalia). A pattern of reticulated hyperpigmentation affecting the ventral abdomen and lateral thorax was seen in two of these dogs. No systemic signs were reported. Pruritus was reported in four dogs and pain in three. The main differential diagnoses are ischemic dermatopathies and hyperkeratotic erythema multiforme (“Old dog” EM).

Treatment Options

A wide range of treatments has been reported to be successful in the few cases including ciclosporin (with initial short course of glucocorticoids), hydroxychloroquine, topical tacrolimus and tetracycline/niacinamide. However, relapses are common after medications were tapered.

Outcome

The prognosis for DLE is good. Progression of FDLE and GDLE to systemic lupus erythematosus (SLE) has not been reported. There was a single case of a DLE variant to “clinical” SLE reported in one dog.

References

Pemphigus Foliaceus

1.  Bizikova P, Dean GA, Hashimoto T, Olivry T. Cloning and establishment of canine desmocollin-1 as a major autoantigen in canine pemphigus foliaceus. Veterinary Immunology and Immunopathology. 2012;149:197–207.

2.  Olivry T. A review of autoimmune skin diseases in domestic animals: superficial pemphigus. Veterinary Dermatology. 2006;17:291–305.

3.  Gomez S, Morris DO, Rosenbaum MR, Goldschmidt MH. Outcome and complications associated with treatment of pemphigus foliaceus in dogs: 43 cases (1994–2000). Journal of the American Veterinary Medical Association. 2004;224(8):1312–1316.

Cutaneous Lupus Erythematosus

1.  Banovic F, Linder KE, Uri M, Rossi MA, Olivry T. Clinical and microscopic features of generalized discoid lupus erythematosus in dogs (10 cases). Veterinary Dermatology. 2016;26(6):488-e131.

2.  Wiemelt SP, Goldschmidt MH, Greek JS, Jeffers JG, Wiemelt AP, Mauldin EA. A retrospective study comparing the histopathological features and response to treatment in two canine nasal dermatoses, DLE and MCP. Veterinary Dermatology. 2014;15(6):341–348.

3.  Olivry T, Linder KE, Banovic F. Cutaneous lupus erythematosus in dogs: a comprehensive review. BMC Veterinary Research. 2018.