JPC SYSTEMIC PATHOLOGY
Signalment (JPC #2152K): Dog
HISTORY: This dog had multifocal alopecia, crusting, and hyperpigmentation of the skin of the head and trunk.
HISTOPATHOLOGIC DESCRIPTION: Haired skin: Multifocally expanding the hyperplastic epidermis are subcorneal pustules that span several hair follicles and are filled with numerous neutrophils, few eosinophils and moderate numbers of individualized acantholytic keratinocytes with a central nucleus and a condensed eosinophilic cytoplasm. The underlying epidermis is acanthotic and keratinocytes exhibit prominent intercellular bridging (spongiosis) and also contain vacuoles within their cytoplasm (intracellular edema). There is a moderate neutrophilic exocytosis. The remaining adjacent epidermis is characterized by mild acanthosis, spongiosis and orthokeratotic hyperkeratosis. Diffusely at the dermal-epidermal junction there is a lichenoid band of inflammation characterized by moderate numbers of neutrophils and lymphocytes, with fewer plasma cells, eosinophils, and macrophages, which occasionally infiltrate the deeper dermis and surround adnexae. Rare neutrophils are also within follicular epithelium. Collagen bundles are separated by clear space and there are dilated lymphatics (edema) and apocrine glands are mildly ectatic.
MORPHOLOGIC DIAGNOSIS: Haired skin: Subcorneal pustules with acantholysis, multifocal, moderate, with moderate neutrophilic dermatitis, breed unspecified, canine.
ETIOLOGIC DIAGNOSIS: Autoimmune dermatitis
CONDITION: Pemphigus foliaceus
- Pemphigus: A group of autoimmune skin diseases characterized grossly by the formation of pustules, vesicles, bullae, erosions, ulcers and histologically by acantholysis (loss of adhesion between epithelial cells)
- Pemphigus foliaceus (PF), although uncommon, is the most common form of pemphigus in domestic animals
- Typically occurs in middle-aged dogs, with no sex predilection
- Genetic predisposition in Akita, bearded collie, chow chow, dachshund, Doberman pinscher, Finnish spitz, Newfoundland, Chinese shar-pei, English springer spaniel and schipperke
- There are three forms:
- Spontaneous: Akitas and chow chows
- Drug induced: Labrador retrievers and Doberman pinschers
- Disease associated: Dogs with chronic allergic or pruritic skin disease
- Circulating pemphigus autoantibodies target cell-adhesion molecules which assists in binding keratinocytes together at the desmosome
- Pemphigus foliaceus lesions occur only on haired skin, and the antibody targets a desmosomal glycoprotein which resides in the upper layers of the epidermis
- The major autoantigen in dogs is desmocollin-1 (DSC1)
- Desmocollin 1 is a transmembrane calcium-dependent desmosomal glycoprotein involved in intracellular adhesions
- Only a minority of dogs with PF will have against another desmosomal cadherin, desmoglein-1 (DSG1), which is the autoantigen in humans
- Often arises spontaneously, but can be triggered by adverse drug reactions as well as topical flea and tick preventatives
- Mechanisms leading to acantholysis:
- Autoantibody binding to DSC1> antibody-induced cleavage of extracellular domain DSC1 > loss of cohesion between keratinocytes (acantholysis)
- It is also thought that autoantibody binding to adhesion molecules may stimulate the secretion of urokinase-type plasminogen activator (uPa) > activates plasminogen> loss of cohesion between keratinocytes
TYPICAL GROSS FINDINGS:
- Pustules and crusting of the face (especially nasal planum), ears, footpads, clawbeds, groin that is often bilaterally symmetrical
- Pustules are transient and lead to thick crusts with variable scaling, alopecia and erosions
- Nasal depigmentation leads to photosensitization
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Superficial intraepidermal pustular dermatitis that typically involves the corneal layer and granular cell layer
- Ruptured pustules can form a thick inflammatory crust that contains acantholytic cells
- Pustules contain numerous acantholytic keratinocytes that are free, partially adherent or adhered to the overlying stratum corneum. These “cling-ons” are only seen in PF
- Pustules often span several follicles and contain myriad neutrophils and often eosinophils
- External root sheath of hair follicle can have acantholytic keratinocytes
- Lichenoid (band-like) inflammation possible
- Footpad lesions include villous hyperkeratosis, swelling, and fissures
ADDITIONAL DIAGNOSTIC TESTS:
- Immunofluorescence or Immunohistochemistry (IHC) may demonstrate immunoglobulin (IgG) in the intercellular space in all layers of the suprabasilar epidermis or in the superficial epidermis
For gross findings (pustular and crusting dermatitis):
- Superficial bacterial folliculitis is the top differential diagnosis for PF
- In PF the pustules span multiple hair follicles whereas in bacterial folliculitis are usually centered on single follicles
- Acantholytic cells are more numerous in PF than in superficial folliculitis
- “Cling-on” stratum granulosum cells are only present in PF
- Bullous impetigo: Usually ventral abdominal in pubescent dogs
- Impetigo does not involve hair follicles
- Superficial spreading pyoderma: Smaller pustules and Dunstan's blue line of basophilic debris in superficial keratin layers
- Superficial pustular dermatophytosis: Usually young animals
- Discoid and systemic lupus erythematosus
- Zinc responsive dermatosis
- Sebaceous adenitis
- Mycosis fungoides: Less symmetry
For microscopic findings (subcorneal pustules):
- Bullous impetigo: Cocci; no active acantholysis
- Pemphigus erythematosus: Milder form usually limited to facial lesions (not footpads); deposits of IgG/IgM along the basement membrane and intercellular spaces; basal cell damage (interface dermatitis) is prominent
- Acantholytic dermatophytosis - GMS, PAS reveals hyphae
- Cat – thick crusts are often bilaterally symmetrical on the face and ears (pinnal margin)
- Horse – PF is the most common autoimmune skin disease in equids; begins on the face or distal extremities, or may be localized to coronets; no age or sex predilections; Appaloosas may be predisposed; over 50% have concurrent systemic clinical signs
- Goat – limbs, perineal region, ventrum
- Barbary sheep
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- Bizikova P, Olivry T, Mamo LB, Dunston SM. Serum autoantibody profiles of IgA, IgE and IgM in canine pemphigus foliaceus. Vet Derm. 2014;25:471-475.
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- Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Saunders Elsevier; 2016: 601-602.
- Peters J, Scott DW, Erb HN, Miller WH Jr: Comparative analysis of canine dermatophytosis and superficial pemphigus for the prevalence of dermatophytes and acantholytic keratinocytes: A histopathological and clinical retrospective study. Vet Dermatol. 2007;18(4):234-240.