Signalment:  

7-year-old, female, Thoroughbred, equine (Equus caballus).The horse was referred with a two-month history of multiple papules, round elevated cutaneous lesions with central crusts on the trunk and limbs, and associated scaling and crusting on the head and neck. The lesions were secondarily pruritic. The animal had also reluctance to move associated with distal limb edema. No parasite, bacteria or fungus was identified on skin scrapings, and cytology of the crust revealed the presence of many acantholytic cells and numerous filamentous bacteria consistent with Dermatophilus congolensis. The cutaneous lesion quickly spread to the whole body and the animal was euthanized due to progressive loss of body condition and hindlimb pain.

Gross Description:  

The mare had generalized chronic severe crusting, scaling and exfoliative dermatitis except in the pasterns, associated with emaciation and pitting edema of the hindlimbs. 

Morphologic Diagnosis:  

Skin : Subcorneal acantholytic vesiculo-pustular dermatitis, chronic severe, characteristic of pemphigus foliaceus in a horse, Equus caballus.

Condition:  

Pemphigus foliaceus

Contributor Comment:  

Pemphigus foliaceus (PF) is the most common autoimmune skin disease in horses, first described in this species in 1981. Pemphigus foliaceus has also been reported in the dog, cat and goat. There is a lack of breed or sex predilection in horses, even if one case study suggested Appaloosas to be predisposed.(3,4) The disease can occur at any age from few months-old foals to aging horses up to 25 years old. A higher risk in winter and fall have been observed in one case study, but this seasonal pattern was not confirmed in a second one.(3,4) Lesions are generalized crusting, scaling and alopecia first affecting the face, neck, trunk and extremities but often spreading in a few months to involve the whole body. Equine PF can be painful and pruritic. The lower extremities and ventral abdomen often develop edema; the exact pathogenesis of this remains unknown. Systemic signs such as weight loss, anorexia, fever, anemia, neutrophilia and hypoalbuminemia have been reported.(2,4). The primary lesion consists of fragile and transient intraepidermal and follicular vesicles evolving into crusting so that the lack of intact pustules in some cases can be a diagnostic challenge.

Diagnosis of PF in horse is based on histologic features and by ruling out differential diagnoses, such as dermatophytosis in the horse. This fungal infection caused by Trichophyton spp. has been reported to cause generalized pustular and crusting exfoliative dermatitis with the presence of many acantholytic cells. Acantholysis is thought to be mediated by fungal proteolytic enzymes. A PAS stain can help to exclude such infection from cases of pemphigus foliaceus lacking characteristic subcorneal pustules. Deposition of IgG at epidermal intercellular bridges can be demonstrated by immunofluorescence (IF) or immunohistochemistry (IHC) but is not specific of PF.(2)

Pemphigus encompasses a group of blistering skin diseases caused by a type II hypersensitivity response involving production of circulating autoantibodies directed against cellular adhesion proteins of desmosomes. Different forms of pemphigus are recognized based on the level at which the acantholysis occurs within the epidermis according to the location of target antigen (cf. Table I). In human beings, PF autoantibodies target the desmosomal protein desmoglein 1 (Dsg1) which is expressed more intensely in the upper layer, explaining the formation of superficial epidermal cleft. Autoantibodies against desmoglein 1 have been reported only in few cases of canine PF where others antibodies are involved.(1) In domestic animals PF seems to be an immunologically heteregenous disease.

Table I: Autoimmune acantholytic dermatoses in animals

Disease	Species	Distribution	Target	Location of vesicles
Pemphigus foliaceus (PF)	Dog, Cat, Horse, Goat	Skin	Dsg 1 in human and dog (<10%)	subcorneal
Pemphigus vulgaris	Dog, Cat, Horse, Goat, Llama, Monkey	Oral mucosa, skin	Dsg 3	Suprabasal
Paraneoplasic pemphigus	Dog	Oral mucosa, skin and non stratified squamous epithelia	Dsg 3 and plakins	suprabasal
Pemphigus erythematous (variant of PF)	Dog, Cat	Skin (face and feet)		Subcorneal, lichenoid infiltrate
Panepidermal Pustular Pemphigus (PF subtype)	Dog	Oral mucosa, skin		All epidermal layers
Pemphigus vegetans	Dog (one case)	Skin, oral mucosa	Dsg 1	Suprabasal, exophytic hyperplasia

Acantholysis can result from mechanisms other than autoimmunity;(1) mutations involving genes encoding desmosomal adhesion proteins (genetic acantholytic dermatoses) or infectious proteases produced by some strains of fungus or bacteria can cleave desmosomes (proteolytic acantholytic dermatoses). The following acantholytic dermatoses are described in various species: dermatophytosis caused by Tricophyton spp; some staphylococcal infections of dog and swine (such as exfoliative epidermitis caused by Staphylococcus hyicus in swine); and bullous impetigo in the dog caused by Staphylococcus pseudointermedius. This bacterium (which produces a circulating exfoliative toxin specific for desmoglein-1) induces blisters locally and at sites distant from primary infection. In human beings, a third group of acantholytic dermatoses is recognized as genetic diseases involving mutations in genes encoding desmosomal adhesion proteins. Such genetic acantholysis has rarely been described in the dog and cattle.

JPC Diagnosis:  

Haired skin: Dermatitis, superficial, histiocytic and lymphoplasmacytic, diffuse, mild with intra-epidermal pustules, acantholytic keratinocytes, acanthosis, parakeratosis, and pigmentary incontinence.

Conference Comment:  

The moderator and participants commented on the excellent quality of the specimen. The moderator noted that it is rare to observe such well developed pustules as seen in this case. Additionally, the large size of the biopsy specimen reduces the chances of tissue loss during processing. The contributor provides an excellent review of the pemphigus complex of diseases in veterinary species, with due attention to pathogenesis as well as the disease manifestation in horses. 

References:

1. Olivry T, Linder KE. Dermatoses affecting desmosomes in animals: a mechanistic review of acantholytic blistering skin diseases. Vet Dermatol. 2009;20:313-326. 

2. Olivry T. A review of autoimmune skin diseases in domestic animals: I Superficial pemphigus. Vet Dermatol. 2006;17:291-305. 

3. Vandenabeele SI, White SD, Affolter VK, Kass PH, Ihrke PJ. Pemphigus foliaceus in the horse: a retrospective study of 20 cases. Vet Dermatol. 2004;15:381-388.

4. Zabel S, Mueller RS, Fieseler KV, Bettenay SV, Littlewood JD, Wagner R. Review of 15 cases of pemphigus foliaceus in horses and a survey of the literature. Vet Rec. 2005;157:505-509.

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