JPC SYSTEMIC PATHOLOGY
Signalment (JPC# 2367492): Pig
HISTORY: This pig had been on an experimental zinc deficient diet since weaning.
HISTOPATHOLOGIC DESCRIPTION: Haired skin: Diffusely, the stratum corneum is expanded up to 200 µm by lamellations of keratin with retained nuclei (parakeratotic hyperkeratosis). There is marked epidermal hyperplasia with anastomosing rete ridges and projections that interdigitate with the corneal layer (papillated hyperplasia); thickening of the stratum spinosum (acanthosis); and intercellular edema with prominent intercellular bridges (spongiosis). Multifocally, hair follicles exhibit similar changes including epithelial hyperplasia and parakeratotic hyperkeratosis. Follicular ostia and infundibula are often ectatic and variably filled with lamellations of keratin admixed with many viable and degenerate neutrophils, eosinophils, fragmented hair shafts, necrotic debris and few 1-2 µm cocci (luminal folliculitis). Occasionally inflammatory cells transmigrate the follicular epithelium (mural folliculitis). Multifocally within the superficial dermis there are low numbers of lymphocytes, plasma cells and macrophages with fewer eosinophils and neutrophils. There is mild, periadnexal and perivascular edema and mildly ectatic apocrine glands.
MORPHOLOGIC DIAGNOSIS: Haired skin: Hyperkeratosis, parakeratotic, epidermal and follicular, diffuse, marked, with epidermal and follicular hyperplasia, and mild lymphoplasmacytic dermatitis and folliculitis, breed unspecified, porcine.
ETIOLOGIC DIAGNOSIS: Zinc-responsive parakeratosis or dermatoses
CAUSE: Zinc deficient diet, impaired zinc absorption / metabolism
CONDITION: Zinc deficiency
- Zinc (Zn) is a component of >70 metalloenzymes and a cofactor for other enzymes that regulates RNA and DNA metabolism
- Zn is needed for bone and muscle growth, reproductive function, feed utilization, vitamin A absorption, normal leukocyte function, keratogenesis, and wound healing
- Zn deficiency can occur in any domestic species;
- Most often manifests as parakeratosis in pigs and dogs
- Diffuse parakeratosis can be seen in many chronic dermatoses; zinc-responsive dermatosis, dermatophilosis, superficial necrolytic dermatitis, and thallotoxicosis
- Zn is important in skin protection against free radical-induced oxidative damage
- Possible deficiency of Zn ligands necessary for intestinal transport of Zn
- Two biochemical pathways exist for absorption of Zn:
- Nonsaturable system involves passive diffusion of Zn into enterocytes
- Transporter-dependent saturable system (impaired in the cattle disease)
- Low concentrations of dietary Zn
- Alterations of intestinal flora, enteric bacterial or viral infections, resulting in malabsorption of Zn and other nutrients
- Excess phytates binds Zn (i.e. soybean phytic acid or high cereal diets)
- Excess calcium, metals (i.e. iron), or vitamins chelate impairing Zn absorption
- Low concentration of dietary free fatty acids
TYPICAL CLINICAL FINDINGS:
- Growing pigs (2-4 months of age) can exhibit parakeratosis
- Decreased appetite, decreased growth rate, listlessness, shivering, stiff or swollen joints, increased susceptibility to infections, inflamed nasal and/or oral mucosa
TYPICAL GROSS FINDINGS:
- Initial cutaneous lesions are usually symmetrical, erythematous macules on the lower limbs (particularly over joints), face (ears, eyes, snout), scrotum, tail
- Cutaneous lesions may develop into papules, covered with a dry brown crust up to 2-3 mm thick, may be penetrated by deep fissures
- Tongue may appear "furred"
- Esophageal mucosa appears dull and white not glistening and smooth
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Diffuse epidermal and follicular parakeratotic hyperkeratosis is the hallmark of Zn responsive dermatoses, but is not present in all cases
- Hyperplastic superficial perivascular dermatitis; often eosinophilic and lymphocytic
- Hypergranulosis, acanthosis
- Intraepidermal pustular dermatitis and folliculitis with secondary bacterial infection
ADDITIONAL DIAGNOSTIC TESTS:
- History, examination, skin biopsy and response to Zn therapy add to final diagnosis
- Plasma or serum Zn levels are usually low; but results may not be accurate due to sampling, physiologic, and environmental factors
Gross differentials in the pig:
- Sarcoptic mange: Usually intensely pruritic; skin scrape for mites
- Exudative epidermitis, Staphylococcus hyicus: Usually younger age group, predominately greasy crust
- Dermatosis vegetans: Hereditary disease of Landrace pigs with foot lesions; including rings parallel to coronary grove
- Porcine juvenile pustular psoriasiform dermatitis (pityriasis rosea): Lesions on ventral abdomen are symmetrical, forming mosaic or serpiginous pattern
- Zinc-responsive dermatosis (presents as one of two clinical syndromes):
- Syndrome I:
- Almost exclusively Siberian huskies and Alaskan malamutes:
- Inherited defect of Zn absorption or metabolism
- Crusting, scaling, alopecia of periorbital skin, ears, genitals and perineum
- Parakeratosis extends into hyperplastic follicular infundibula; +/- dyskeratosis, spongiosis, dermatitis, hypogranulosis
- Hyperpigmentation with chronicity
- Hyperkeratotic footpads (DDx: canine distemper virus)
- Lifelong supplementation required
- Syndrome II:
- Occurs in rapidly growing, large breed dogs fed zinc deficient diet, or over-supplemented with chelating minerals (calcium inhibits Zn absorption)
- Less common due to balanced commercial dog foods
- Similar lesions but more severe lesions than syndrome I
- Only transient Zn supplementation required
- Hereditary nasal hyperkeratosis of the Labrador retrievers
- Autosomal recessive inheritance
Gross differentials of diffuse hyperkeratosis in the dog:
- Dermatophytosis, pemphigus foliaceus, and pyoderma
Histological differentials of diffuse hyperkeratosis in the dog:
- Lethal acrodermatitis of bull terriers: Autosomal recessive inheritance; not responsive to oral Zn supplementation; pathogenesis of low plasma Zn disease is unknown, copper deficiency (presumed); causes growth retardation, progressive dermatopathy, paronychia, diarrhea, bronchopneumonia, and death by 18 months of age; thymic and lymph node hypoplasia and giant cell bronchopneumonia seen postmortem
- Superficial necrolytic dermatitis: Distinct band of hydropic, pale keratinocytes within the stratum spinosum
- Vitamin A responsive dermatosis: Predominantly marked follicular keratosis on chest and abdomen; histologically there is
- Generic dog food dermatosis: Rapid onset; systemic illness is common
- Thallium toxicosis (very rare, thallium banned in the U.S.): brick red mucous membranes; epithelial necrosis is common
- Canine distemper virus: Hyperkeratotic foot pads
- Sarcoptic mange and flea-hypersensitivity dermatitis: Diffuse parakeratosis, with increased lymphocytes, eosinophils, plasma cells, and mast cells
- Perivascular dermatitis with hyperkeratosis: various degrees of orthokeratosis and/or parakeratosis
- Congenital follicular parakeratosis: cornification disorder of Rottweilers and Labrador retrievers; X-linked dominant inheritance; epidermis is acanthotic, hair follicles have marked papillated parakeratotic hyperkeratosis that forms conically shaped projections
Ruminants (goats, sheep, cattle, alpacas, llamas):
- Dietary deficiency or diets with Zn high chelating agents (calcium, iron, phytates)
- Alopecia, scaling, crusting of skin on face, neck, distal extremities, and mucocutaneous junctions
- Histopathologic: Papillated epidermal hyperplasia, spongiosis, superficial perivascular lymphoeosinophilic dermatitis, with parakeratotic hyperkeratosis
- Parakeratosis also affects forestomachs
- Wool-eating and drooling
- Orthokeratotic hyperkeratosis predominates
- Thin wool that loses its crimp and epilates easily; entire fleece can shed
- Normal ringed structure of the horns is lost; horns can shed
- Nose, muzzle, and periocular region may also be affected.
- Breeding females and those with darker fleeces are more susceptible to zinc-responsive dermatosis because of a higher demand for zinc
- Hereditary zinc deficiency (HZD)
- Also called: lethal trait A46, hereditary parakeratosis, hereditary thymic aplasia, and edema disease
- Commonly affected are young Fresian and black pied Danish calves of Friesian descent in Europe and shorthorn cattle in the U.S.
- Crusting and alopecia on muzzle, eye, base of ears, ventral mandible
- Lesions eventually spread to neck and skin over joints
- Resolves with Zn supplementation
- Defects in SLC39A4 gene
- Intestinal malabsorption of zinc is the cause of the disorder in cattle
- Calves may develop conjunctivitis, rhinitis, bronchopneumonia or diarrhea
- Thymic hypoplasia with depletion of other lymphoid organs
- Hereditary zinc deficiency (HZD)
- Reported in foals with a Zn deficient diet
- Alopecia and scaling of the limbs, ventral abdomen, and thorax
- Campbell GA, Crow D. Severe zinc responsive dermatosis in a litter of pharaoh hounds. J Vet Diagn Invest. 2010;22(4):663-666.
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- Romanucci M, Bongiovanni L, et al. Oxidative stress in the pathogenesis of canine zinc-responsive dermatosis. Vet Dermatol. 2011(1):31-38.
- Scott DW, Vogel JW, Fleis RI, Miller WH Jr, Smith MC. Skin diseases in the alpaca (Vicugna pacos): a literature review and retrospective analysis of 68 cases (Cornell university 1997-2006). Vet Dermatol. 2011; 22(1):2-16.