JPC SYSTEMIC PATHOLOGY
Signalment (JPC# 2017878): One-day-old Angus-cross calf
HISTORY: The entire skin had a thick horny epidermis that was divided into large plates by deep fissures.
HISTOPATHOLOGIC DESCRIPTION: Haired skin: Diffusely the stratum corneum is severely thickened (up to 2 mm) by laminated anuclear keratin (orthokeratotic hyperkeratosis), which entraps hair shafts; the follicular epithelium is also mildly hyperkeratotic. The subcorneal epidermis is mildly hyperplastic forming projections that interdigitate with the corneal layer (papillated hyperplasia). Keratinocytes in the stratum granulosum and spinosum are occasionally degenerate with indistinct cell borders and a prominent perinuclear clear vacuole. Several follicles are mildly ectatic with loss of hair shafts, while hair follicles within the deeper dermis often appear dysplastic. The superficial dermis is mildly expanded by increased clear space (edema) and contains low numbers of neutrophils, lymphocytes, and plasma cells. Diffusely, there is sebaceous gland atrophy. Many apocrine glands are ectatic and lined by attenuated epithelium.
MORPHOLOGIC DIAGNOSIS: Haired skin, epidermis and follicular epithelium: Hyperkeratosis, orthokeratotic, diffuse, severe, with sebaceous gland atrophy, Angus‑cross, bovine.
ETIOLOGIC DIAGNOSIS: Hereditary congenital hyperkeratosis
CAUSE: Autosomal recessive genetic defect (presumed)
CONDITION: Ichthyosis fetalis
SYNONYM: Fish scale disease
- Heterogeneous group of rare congenital, often autosomal recessive, dermatoses reported in cattle, dogs, humans, cats, mice, chickens, pigs, llamas, alpacas, and greater kudus
- Congenital and/or hereditary defect in the formation of the stratum corneum
- Hallmark lesion is marked lamellar hyperkeratosis (scales)
- Classification is complex with four major and several minor types described in humans
- Epidermolytic: Vacuolation and lysis of keratinocytes together with hypergranulosis and hyperkeratosis within the within the spinous and granular cell layers
- Nonepidermolytic subtype is gaining favor in veterinary medicine in that most ichthyoses in veterinary species are nonepidermolytic: Marked lamellar orthokeratotic hyperkeratosis and mild acanthosis
- The underlying biochemical defect in most cases is unknown and probably varies among different forms of the disease
- Pathogenesis involves either increased cohesion or defective dishesion (retention hyperkeratosis) of keratinocytes associated with either a short epidermal turnover time and/or disruption of the normal desquamative process or possibly alteration of lipid metabolism
- In severe forms of the disease, fissuring leads to exudation of protein and secondary bacterial and/or fungal infections which may lead to death
TYPICAL CLINICAL FINDINGS:
Cattle (both forms inherited as simple autosomal recessive traits):
- Ichthyosis fetalis:
- Most severe form; incompatible with life, and affected animals are aborted or survive only a few days after birth
- Most analogous to harlequin ichthyosis in man, a rare fatal autosomal recessive disorder
- Norwegian red poll, Friesian, and brown Swiss calves
- Skin is covered by large horny plates separated by deep fissures corresponding to normal cutaneous cleavage lines
- Hair is either absent or present as short stubble trapped in the thick hyperkeratotic plaques or lining the bottom of the fissures
- Skin is tight and inelastic causing tension and eversion of eyelids (ectropion), lips (eclabium), and/or other mucocutaneous junctions
- Ear pinnae are often small (microtia)
- Ichthyosis congenita:
- Less severe form reported in Jerseys, Pinzgauer, Chianina, and Holstein‑Friesian calves which live longer
- Most analogous to lamellar ichthyosis in man, an autosomal recessive ichthyosis thought to be caused by defective keratinocyte transglutaminase
- Lesions similar to but less severe than those of ichthyosis fetalis; most severe on the limbs, abdomen, and muzzle
- Alopecia is not an initial feature; may develop over time
- Thick hyperkeratotic and curling scales in areas where hair is short, i.e. behind the muzzle and in the axilla
- Pinzgauer calves also have an associated microtia, cataracts and thyroid abnormalities
TYPICAL GROSS FINDINGS:
- Lichenification and crusting; deep (ichthyosis fetalis) or shallow (ichthyosis congenita) fissures
- Alopecia, hyperpigmentation, and lymphadenopathy are possible
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- The stratum corneum is markedly thickened by laminated orthokeratotic and occasional parakeratotic hyperkeratosis affecting both surface and follicular epithelia
- Elongation of rete pegs and secondary bacterial infections
- Histologic changes in the subcorneal epidermis vary between different anatomic locations and different forms, but it may be thin, acanthotic, or edematous, and is often extremely folded on itself
- Cattle: Hyperkeratotic lesions in calves
- Mycotic dermatitis: In fetal calves; observed with mycotic abortions (Aspergillus, Absidia, Mucor, Rhizopus); irregular, multifocal to coalescing elevated plaques about the periorbit, occiput, shoulders, back, and sides
- Cutaneous dermatophytosis/ringworm (Trichophyton , Microsporum sp.): Well-circumscribed, alopecic, roughly circular lesions with a thick layer of gray-white scale-crust; periocular region and other parts of the head most common in calves
- Dogs: Most cornification disorders are secondary to other diseases; differential diagnosis for hyperkeratosis of the nasal planum or footpads
- Immune-mediated: Pemphigus foliaceus, lupus erythematosus, drug reaction
- Metabolic/endocrine: Hypothyroidism, hyperadrenocorticism, sex hormone imbalance/deficiency, superficial necrolytic dermatitis, zinc-responsive dermatosis, generic dog food dermatosis
- Infectious: Canine distemper, leishmaniasis, papillomavirus, ectoparasites (demodicosis), dermatophytosis
- Neoplastic: Exfoliative form of cutaneous lymphoma
- Inherited: Familial footpad hyperkeratosis, familial nasal hyperkeratosis, nasal parakeratosis of the Labrador retriever, hyperplastic dermatosis of the West Highland white terrier
- Idiopathic: Primary seborrhea, nasodigital hyperkeratosis, sebaceous adenitis
- Dogs: Nonepidermolytic subtype
- Best characterized in the golden retriever and West Highland white terrier; also noted in Doberman pinscher, Irish setter, collie, American bulldog, pitbull, Boston terrier, Labrador retriever, Jack Russell terrier, Manchester terrier, Australian terrier, Cairn terrier, Norfolk terrier, Yorkshire terrier, soft coated Wheaton terrier and mixed breeds
- Golden retriever ichthyosis: Mutation in the PNPLA1 gene responsible for lipid metabolism in outer epidermis
- Gross: Generally mild scaling on the dorsum and hyperpigmentation ventrally
- Histo: Diffuse lamellar orthokeratotic hyperkeratosis without epidermal hyperplasia or dermatitis, prominent granular layer which contains keratinocytes with distinct perinuclear clear spaces
- American bulldogs: Similar to golden retriever but more severe; NIPAL4 (ICHTHYIN) deficiency leads to alteration of lipid metabolism
- Jack Russel terriers: Loss of function mutation in TGM1 gene which mediates calcium dependent cross linking of peptides
- Great Danes: Epidermal and follicular orthokeratotic hyperkeratosis, enlarged keratohyaline granules, vacuolated keratinocytes, and accumulations of eosinophilic lipid-rich material within dilated hair follicles and sebocyte cytoplasm
- Heterogenous causes: Defects in stratum corneum components such as intercellular lipids, cornified envelope, keratins or internal desmosomal components
- Gross: Tightly adherent, parchment-like, gray or light brown scales over most body regions including pawpads and planum nasale with sparse hair coat bound to keratinous deposits
- Histology: Mild to severe laminar (“basket weave”) to compact orthokeratotic hyperkeratosis; variable acanthosis with variable granular layer; focal parakeratosis has been described; condition in golden retrievers characterized by laminar orthokeratotic hyperkeratosis without epidermal hyperplasia or dermal inflammation and ultrastructurally, retained and convoluted membranes with crystalline structures in the stratum corneum
- Dogs: Epidermolytic subtype
- Defect in K1 and K10 genes
- Reported in Rhodesian ridgeback, Norfolk terrier, Labrador retriever cross
- Probably an autosomal recessive trait (parents of affected animals appear normal)
- Lesions are congenital and generalized, but are most severe on the flexural surfaces and footpads
- Gross: Dry, gray scales, sometimes forming verrucous or feather‑like projections, tightly adherent to the underlying, sometimes hyperpigmented skin; alopecia and lichenification
- Histologic (consistent findings): Marked orthokeratotic hyperkeratosis, follicular plugging, hypergranulosis, with or without an accompanying perivascular dermatitis, vacuolation of keratinocytes (intracellular edema) and reticular degeneration may occur along with mitotic figures in keratinocytes
- Alpacas: Rare reports of congenital ichthyosis; r/o zinc responsive dermatitis
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