{"id":25994,"date":"2021-10-08T18:53:53","date_gmt":"2021-10-08T18:53:53","guid":{"rendered":"https:\/\/todaysveterinarypractice.com\/?p=24573"},"modified":"2025-09-24T19:07:26","modified_gmt":"2025-09-24T19:07:26","slug":"review-of-pemphigus-foliaceus-in-dogs-and-cats","status":"publish","type":"post","link":"https:\/\/navc.sitepreview.app\/todaysveterinarypractice.com\/dermatology\/review-of-pemphigus-foliaceus-in-dogs-and-cats\/","title":{"rendered":"Review of Pemphigus Foliaceus in Dogs and Cats"},"content":{"rendered":"

Pemphigus foliaceus (PF) is the most common autoimmune skin disease in dogs and cats. It is also the most common variant of pemphigus diseases,1,2<\/sup> which are characterized by autoantibodies that target keratinocyte desmosomal proteins, leading to loss of cell-to-cell adhesion (acantholysis). Acantholysis of keratinocytes causes separation and loss of integrity of the epidermal cell layers, resulting in transient pustules and\/or blisters that rapidly develop into erosions, crusts, scales, and alopecia on the skin and\/or mucous membranes.1-5<\/sup> In dogs and cats, PF may occur spontaneously or, more rarely, may be associated with drugs,6-12<\/sup> environmental factors,13<\/sup> or concurrent thymoma1<\/sup> or autoimmune diseases.3,14<\/sup><\/span><\/p>\n

The stratified epithelia are made up of different layers that each contain keratinocytes and nonkeratinocyte cells (e.g., melanocytes, Langerhans cells, Merkel cells). Keratinocytes and the surrounding cells are held together predominantly by desmosomes, forming a type of cell adhesion with a complex network of many types of proteins. These desmosomal proteins are expressed with varying intensities among different epithelial layers and tissues (i.e., mucosa versus footpads).15<\/sup> The anatomic distribution and depth of lesions therefore depend on the targeted desmosomal protein. For instance, desmocollin-1 (DSC-1) is a desmosomal protein that is distributed primarily in the superficial layers of the follicular and interfollicular epidermis (stratum granulosum and stratum spinosum) but not in mucosae. DSC-1 is the major autoantigen in dogs with PF.15<\/sup> As such, disruption of DSC-1 by different mechanisms by pathogenic immunoglobulin G (IgG) autoantibodies results in superficial blister formation in the skin but not the mucosae. Conversely, when desmoglein-3 (DSG-3), another type of desmosomal protein expressed at higher intensity in the deeper layers of the epidermis and mucosae, is targeted by these autoantibodies, a deep erosive form of pemphigus develops (pemphigus vulgaris).16<\/sup> A recent study confirmed the presence of anti-keratinocyte IgG in cats with PF and different substrate immunoreactivity compared with that in the dog, suggesting the role of a different autoantigen target in cats with PF.17<\/sup> These studies seem to demonstrate variation in IgG autoantibody targets between dogs and cats and different forms of pemphigus within each species.\u00a0<\/span><\/span><\/p>\n

Signalment\u00a0<\/span><\/h2>\n

For dogs and cats, predisposition to PF does not seem to be associated with the animal\u2019s sex; although PF can occur at any age, median age of onset is around 6\u00a0years (middle-aged).2,18<\/sup> Canine PF can affect dogs of any breed or crossbreed; however, certain breeds (e.g., Akitas and chow chows) are overrepresented,19<\/sup> suggesting a genetic predisposition.3<\/sup> Other dog breeds in which PF incidence may be higher include Labrador retrievers, cocker spaniels, German shepherds, and English bulldogs.5<\/sup> No strong cat breed predisposition to PF has been reported; however, the most represented breeds are domestic shorthair, medium-hair, and longhair cats.18<\/sup><\/span><\/p>\n

Associated Diseases and Risk Factors<\/h2>\n

Data purporting possible associations between PF and drugs, environmental factors, or concurrent disease remain scant; most cases of PF are presumed to be idiopathic. However, a possible association between allergic skin diseases (e.g., atopic dermatitis and flea allergy dermatitis) and development of PF has been reported.3<\/sup> The high prevalence of allergic dermatitis and long-term drug use for chronically affected animals with allergies, and thus possible drug-related PF, complicates the etiology of PF. Reported drugs associated with PF include antibiotics (e.g., sulfonamides, penicillins, cephalosporins),6,8<\/sup> cimetidine in cats,1<\/sup> and 3\u00a0topical ectoparasitic preparations containing metaflumizone, fipronil, amitraz, S-methoprene, dinotefuran, pyriproxyfen, or permethrin.9-11<\/sup> In studies of dogs, clinical lesions resolved spontaneously after withdrawal of the suspected drug for some, but others required immunosuppressive therapy to achieve clinical remission.8,11<\/sup> Of note, after the adverse drug reaction probability scale was applied, the scores obtained indicated that drug-related cases of canine PF were possible.19<\/sup> Other potential associations include concurrent systemic disease (e.g., cutaneous polyautoimmunity reported for 2 dogs with concurrent PF and generalized discoid lupus erythematous),14<\/sup> sunlight exposure,13<\/sup> and exposure to drugs in other groups (isolated cases).12<\/sup><\/span><\/p>\n

Clinical Presentation<\/h2>\n

The primary lesion in patients with PF is the pustule (<\/span>FIGURE 1<\/span><\/strong>). However, because most PF pustules are superficial, small, and therefore transient, identification of pustules can be a rare and challenging opportunity. Most pustules will instead rapidly evolve into erosions and crusts. Indeed, crusts are the most common clinical presentation of PF in dogs and cats and will often appear thick (multilayered) with a yellowish coloration due to the cyclic nature of PF (<\/span>FIGURE 2<\/span><\/strong>).1-3,5,18<\/sup> Other lesions include pustules of variable size, erosions, and alopecia. The lesions can coalesce or cluster and organize into different patterns. Pruritus is variable but commonly reported and can be severe in patients of both species.1-3,5,18<\/sup> A relatively high number of dogs and cats also exhibit systemic signs of lethargy, pyrexia, hyporexia or anorexia, weight loss, and pain.1-3,5,18<\/sup><\/span><\/p>\n

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Figure 1. Pustules and margin crusting on digital pad of a cat.<\/p><\/div>\n

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Figure 2. Coalescing, thick, yellowish crusts forming a large alopecic lesion with peripheral erythema and erosions on the dorsum of a cat.<\/p><\/div>\n

Lesions typically first appear on the face and for most patients progress to other body sites such as the trunk and feet\/footpads (<\/span>FIGURE 3<\/span><\/strong>). Lesions may also become generalized or appear commonly in other parts of the body as well (<\/span>TABLE 1<\/span><\/strong>). However, in dogs some PF variants can affect only a few localized areas of the body without appearing anywhere else (e.g., lesions may be restricted to the face or footpads only or to the trunk only).18,20<\/sup> A notable distinction between PF in dogs and in cats is the presence of lesions in the ungual folds (47%) and periareolar region (27%) of cats;18<\/sup> however, it is uncommon (11%) for cats to display skin lesions affecting only the ungual folds or footpads (<\/span>FIGURE 4<\/span><\/strong>).1<\/sup> Periareolar lesions lead to high suspicion for feline PF, although lesions are less commonly found in this area than in other areas.1,18<\/sup><\/span><\/p>\n

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\"FigureFigure 3. (A) Diffuse alopecia with crusting and erosions on the face of a cat.<\/span><\/a><\/div>
\"FigureFigure 3. (B) Multifocal erythematous patches, crusts, small pustules, and erosions on the face of a French bulldog.<\/span><\/a><\/div>
\"FigureFigure 3. (C) Severe crusting on footpads with plantar erythema, erosions, and pustules on the left hind foot of the same French bulldog.<\/span><\/a><\/div>
\"FigureFigure 3. (D) Multifocal crusts with peripheral erythema and alopecia on the trunk of a dog.<\/span><\/a><\/div>
\"FigureFigure 4. (A) Crusting and hyperkeratosis on footpad as the sole clinical presentation in an adult cat with pemphigus foliaceus.<\/span><\/a><\/div>
\"FigureFigure 4. (B) Severe crusting on ungual folds in a cat.<\/span><\/a><\/div>
<\/div><\/div><\/p>\n

Diagnostic Investigations<\/h2>\n

In brief, diagnosis of PF is based on compatible clinical presentation, confirmation of superficial pustular acantholysis, and exclusion of relevant differential diagnoses (<\/span>FIGURE 5<\/span><\/strong>).3<\/sup> Diagnostic investigation of PF begins, as for every disease, with consideration of the patient\u2019s signalment (e.g., breed predisposition) and a detailed history. Careful questioning should reveal the patient\u2019s therapeutic history (responses to antibiotics, ectoparasiticides, immunosuppressants) and exposure to other drugs or toxins. PF typically affects the face first. The course of the disease might be progressive with either a rapid (within days or weeks) or slow (within months or years) onset of clinical signs, or it may wax and wane with waves of pustule formation.5,21,22<\/sup> Clinical suspicion of PF can be elicited by the classic clinical features of superficial pustular dermatitis (pustules, erosions, crusts, alopecia, scales) affecting the face, pinnae, and feet\/footpads (including ungual folds and\/or periareolar regions in cats) and sparing the mucosae (<\/span>TABLE 1<\/span><\/strong>). For patients, the next recommended diagnostic step is cytology to detect acantholytic keratinocytes (<\/span>FIGURE 6<\/span><\/strong>). Also helpful is <\/span>evaluating whether the patient has concurrent pyoderma.<\/p>\n

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Figure 6. Microscopic view of an impression smear made from under a crust from a dog with suspected pemphigus foliaceus. Several acantholytic keratinocytes (round, deep basophilic, large nucleus) are surrounded by numerous nondegenerate neutrophils.<\/p><\/div>\n

Cytology<\/h3>\n

The best lesions to sample are pustules. However, when pustules are not evident, the authors use a dermatoscope (a handheld device that emits high-quality light coupled with a magnifying lens), which increases the sensitivity for identifying small or early-forming pustules. If an intact pustule is found, it can be sampled by puncturing the pustule with a needle and lifting the keratinocyte scaffold to expose the pus and gently placing a slide against it.23<\/sup> Most clinicians, however, will see patients with secondary crust formation; for these patients, sampling can be performed by removing the superficial crust and obtaining an impression smear of the exudative lesion underneath.23<\/sup> Once the sample on the slide is dried, it is then fixed and stained using the 3-solution Diff-Quik method. The sample should then be examined in 100\u00d7 high-powered oil field using immersion oil. Acantholytic keratinocytes have reportedly been captured in cytologic samples from approximately 77% of dogs2<\/sup> and 74% of cats.18<\/sup> However, presence of acantholytic keratinocytes is not pathognomonic for PF because pyoderma (particularly that caused by some strains of Staphylococcus<\/i> pseudintermedius<\/i>), dermatophytosis caused by Trichophyton <\/i>species, and canine leishmaniasis can also produce acantholytic keratinocytes.1-3,24<\/sup> Impression smears may reveal nondegenerate neutrophils and, to a lesser extent, eosinophils and bacteria (intracellular and extracellular).1-3<\/sup><\/span><\/p>\n

Ancillary Testing\u00a0<\/span><\/h3>\n

In dogs and cats for which PF is clinically suspected and acantholytic keratinocytes have been identified, superficial pyoderma (impetigo) and pustular dermatophytosis should be ruled out. Useful for ruling out superficial pyoderma is ancillary testing via cytology and\/or aerobic bacterial culture with sensitivity testing. Pustular dermatophytosis is rarer than impetigo but still warrants investigation. Ancillary tests to rule out pustular dermatophytosis include Wood\u2019s lamp examination, trichoscopy, molecular testing (e.g., polymerase chain reaction), and fungal culture. When PF and concurrent superficial pyoderma are suspected, it should be determined whether the superficial pyoderma is secondary to PF or causal to the clinicopathologic features. Regardless, a systemic antibiotic should be given, either guided by sensitivity testing or empirically chosen if no test is done. If there is partial or no clinical improvement, then superficial pyoderma is not likely to be the final diagnosis. In areas where Leishmania <\/i>are endemic or emerging, the authors also recommend ruling out canine leishmaniasis.\u00a0<\/span><\/span><\/p>\n

Histopathology<\/h3>\n

After superficial pyoderma and pustular dermatophytosis have been ruled out, the next diagnostic step is skin biopsy.3<\/sup> A representative biopsy sample is critical for an accurate diagnosis of PF (<\/span>BOX\u00a01<\/span><\/strong>). Classic histopathologic features of PF are superficial epidermal and follicular (subcorneal or intragranular) pustules with acantholytic keratinocytes in the absence of infectious pathogens (<\/span>FIGURE 8<\/span><\/strong>). These pustules are often large and span several hair follicles.3<\/sup> Special stains (i.e., Gram, periodic acid\u2013Schiff) can be used to detect bacteria or fungi and thus increase the sensitivity of histopathology. Neutrophils are usually found in large numbers within pustules, and most appear intact (nondegenerate or nontoxic). Eosinophils can also be a prominent cytologic and histopathologic finding.3,20<\/sup> Eosinophilic infiltration is reportedly more likely in patients with concurrent systemic disease.20<\/sup> In a recent study, histopathologic findings consistent with vasculopathy or vasculitis were more likely to occur in dogs with systemic signs and for which clinical remission took longer to achieve.25<\/sup>\u00a0<\/span><\/span><\/p>\n

BOX 1 Tips for Performing a Skin Biopsy for Suspected Pemphigus Foliaceus Cases <\/div>
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