Feline Immune-Mediated Skin Disease Study Guide

Overview and Clinical Importance

Immune-mediated skin diseases in cats represent a spectrum of disorders characterized by dysregulation of the normal immune response, resulting in cutaneous inflammation and tissue damage. These conditions, while relatively rare (accounting for less than 1% of feline dermatological cases), present significant diagnostic and therapeutic challenges for veterinary practitioners.

The pathogenesis of these conditions involves either autoantibody-mediated damage (as seen in the pemphigus complex) or autoreactive T-lymphocyte infiltration (as observed in cutaneous lupus erythematosus). Understanding the underlying mechanisms is essential for appropriate diagnosis and management.

Pemphigus Foliaceus (PF)

Pemphigus foliaceus is an autoimmune, vesicobullous to pustular skin disease characterized by autoantibody attack on desmosomal proteins, leading to acantholysis (loss of keratinocyte adhesion) in the superficial epidermis.

Pathogenesis

In PF, pathogenic IgG autoantibodies target desmosomal adhesion proteins between keratinocytes. The binding of autoantibodies to desmosomes results in:

• Acantholysis: Separation of keratinocytes due to loss of cell-to-cell adhesion
• Pustule formation: Subcorneal or intragranular vesicles filled with neutrophils and acantholytic cells
• Inflammatory recruitment: Neutrophil and eosinophil infiltration into epidermis

Signalment and Predisposing Factors

Clinical Signs

The primary lesion is a pustule; however, pustules are fragile and transient, so secondary lesions are more commonly observed:

Diagnosis

Diagnostic Criteria

• History and characteristic lesion distribution (face, pinnae, claw folds, periareolar)
• Exclusion of other acantholytic pustular diseases (superficial pyoderma, dermatophytosis)
• Supportive cytology AND/OR histopathology confirming acantholytic keratinocytes

Cytology (Tzanck Preparation)

Sample collection: Puncture intact pustule OR lift fresh crust and sample underlying material. Stain with Diff-Quik.

Key cytological findings:

• Acantholytic keratinocytes: Round cells with dark blue cytoplasm, "fried egg" appearance, seen individually or in rafts/clusters
• Nondegenerate neutrophils: Well-preserved neutrophils WITHOUT bacteria (sterile pustule)
• Variable eosinophils: May be present; more common with systemic signs

Histopathology

Biopsy site selection: Intact pustule (ideal) or fresh crusted lesion. Do NOT clip or scrub - preserve crusts!

Characteristic findings:

• Subcorneal or intragranular pustules containing acantholytic keratinocytes
• Pustules span multiple hair follicles
• Neutrophilic or mixed neutrophilic-eosinophilic infiltrate
• Negative Gram and PAS stains (ruling out bacterial/fungal infection)
• Epidermal hyperplasia with orthokeratotic hyperkeratosis

Differential Diagnosis

Treatment

First-Line Therapy: Glucocorticoids

Steroid-Sparing Agents

Prognosis

• Good overall: 90% achieve complete remission within 1 month
• Drug-free remission rare: Only 4-15% maintain remission without ongoing therapy
• Relapses common: Disease frequently waxes and wanes; flares with dose reduction
• Better than dogs: Feline PF has better prognosis than canine PF

Pemphigus Vulgaris (PV)

Pemphigus vulgaris is a rare, deep pemphigus variant characterized by suprabasilar acantholysis (separation occurs deeper in the epidermis, above the basal cell layer). The target autoantigen is suspected to be desmoglein-3, similar to humans and dogs.

Clinical Presentation

• MUCOSAL involvement: Oral cavity (erosive stomatitis, glossitis), lips, tongue - KEY differentiating feature from PF
• Deep erosions/ulcerations: Rather than superficial pustules and crusts
• Mucocutaneous junctions: Lips, eyelids, nares, vulva, prepuce commonly affected
• Positive Nikolsky sign: Epidermal separation with lateral pressure on normal-appearing skin
• Systemic signs: Often more severe than PF; painful lesions may cause anorexia

Diagnosis and Treatment

Histopathology: Suprabasilar acantholysis with "tombstoning" of basal cells (basal keratinocytes remain attached to basement membrane like tombstones while upper layers separate)

Treatment: Higher doses of glucocorticoids often required (prednisolone 4-6 mg/kg/day); combination therapy with steroid-sparing agents often necessary. Prognosis is more guarded than PF.

Lupus Erythematosus

Lupus erythematosus in cats is extremely rare, with only sporadic case reports in the literature. Two forms are recognized: Systemic Lupus Erythematosus (SLE) and Cutaneous/Discoid Lupus Erythematosus (CLE/DLE).

Systemic Lupus Erythematosus (SLE)

SLE is a multisystemic autoimmune disease often called the "great imitator" due to its variable presentation. It involves multiple organ systems beyond the skin.

Clinical Signs

• Cutaneous (60% of cases): Symmetric erythema, scaling, crusting on face ("butterfly rash"), ears, extremities
• Polyarthritis: Shifting leg lameness (most common non-cutaneous sign)
• Hematologic: Anemia, thrombocytopenia, leukopenia (immune-mediated cytopenias)
• Renal: Glomerulonephritis, proteinuria
• Oral ulcerations
• Fever, lethargy, anorexia

Diagnosis

Based on adapted American Rheumatism Association criteria (3 of 11 criteria in cats):

• Positive ANA (antinuclear antibody) test
• Immune-mediated cytopenias
• Skin biopsy showing interface dermatitis
• Oral ulceration, polyarthritis, glomerulonephritis

Discoid Lupus Erythematosus (DLE)

DLE is a cutaneous-only form of lupus that is considered relatively benign compared to SLE.

Clinical Signs

• Nasal planum: Depigmentation, erythema, scaling, erosion/ulceration; loss of "cobblestone" texture
• Periocular: Alopecia, scaling, depigmentation
• Pinnae: Highly predictable involvement in feline DLE
• Sun exposure: May trigger or exacerbate lesions

Histopathology

Interface dermatitis: Lymphocyte-rich inflammation at dermal-epidermal junction with basal cell vacuolar (hydropic) degeneration and apoptotic keratinocytes. Lymphocytic mural folliculitis may also be present.

Treatment

• Sun avoidance
• Topical glucocorticoids or tacrolimus for localized lesions
• Prednisolone 1-2 mg/kg q24h with taper for generalized disease
• Ciclosporin 5 mg/kg q24h if steroid-sparing needed

Thymoma-Associated Exfoliative Dermatitis

This is a rare paraneoplastic syndrome where cutaneous signs often appear BEFORE the tumor is detected. Thymoma is the second most common cranial mediastinal tumor in cats (after lymphoma).

Pathogenesis

Suspected to be a CD3+ T-cell-mediated process similar to graft-vs-host disease. Abnormal antigen presentation by neoplastic thymic epithelial cells leads to autoreactive T cells that cross-react with epidermal keratinocytes, causing cytotoxic damage.

Clinical Signs

• Age: Middle-aged to older cats (can occur as young as 4 years)
• Cutaneous: Severe generalized EXFOLIATION (large, dry, adherent scales); alopecia; mild hyperpigmentation
• Distribution: Head, face, preauricular areas, trunk; footpads may show scaling
• Systemic signs: Lethargy, weight loss; may develop myasthenia gravis

Diagnosis

• Thoracic imaging: Radiographs, ultrasound, or CT reveal cranial mediastinal mass
• FNA of mass: Thymic epithelial cells mixed with small mature lymphocytes
• Skin biopsy: Interface dermatitis with CD3+ lymphocytes; marked hyperkeratosis; absent/atrophic sebaceous glands; transepidermal apoptotic keratinocytes
• Cytology: NO acantholytic keratinocytes (differentiates from PF)

Treatment and Prognosis

• Surgical excision: Treatment of choice; skin lesions resolve after tumor removal
• Prognosis: Good for non-invasive, resectable tumors (74% 3-year survival); guarded for invasive thymomas (11-22% postoperative mortality)
• Staging: Masaoka-Koga system determines prognosis based on tumor invasion

Non-Thymoma-Associated Exfoliative Dermatitis

Identical clinical and histopathological features to thymoma-associated disease but WITHOUT an underlying tumor. Etiology unknown but suspected immune-mediated.

• Treatment: Ciclosporin (6.75-7.5 mg/kg q24h) alone or combined with prednisolone (2-4 mg/kg q24h)
• Prognosis: Responds to immunosuppression but requires long-term therapy; relapses common with discontinuation

"PF = Face-Feet-Nipples"

Pemphigus Foliaceus distribution: Face (nose, ears, periocular), Feet (claw folds with paronychia, footpads), Nipples (periareolar crusting)

"Fried Eggs = Acantholytic Cells"

Acantholytic keratinocytes on cytology look like fried eggs - round cells with dark blue cytoplasm and central nucleus

"PrednisoLONE, not predniSONE"

Cats cannot efficiently convert prednisone to active prednisolone - always use prednisoLONE

"AZA = A-voiZ-A-thioprine in cats"

Azathioprine causes fatal myelosuppression in cats due to low thiopurine methyltransferase

"Scales = Search for Thymoma"

Exfoliative (scaling) dermatitis in a cat warrants thoracic radiographs to rule out thymoma