Keratinization Defects Flashcards
Ichthyosis
Several types of ichthytosis occur in animals and people. Clinical signs include accumulations of dead skin cells resulting in thick, dry scales that in the most severe forms resemble fish scales adherent to the skin surface.
Congenital forms of ichthyosis are due to primary defects in the formation of stratum corneum. Mutation in keratin genes result in epidermolytic forms of ichthyosis, while mutations affecting the production of lipids, non-keratin proteins or desquamation result in non-epidermolytic forms of ichthyosis.
Epidernolytic Ichthyosis
Light microscopy findings include vacuoles and lysis of keratinocytes in the stratum spinous and stratum granulosum, hypergranulosis and hyperkeratosis. Dog breeds reported to have epidermolytic forms of ichythyosis include Norfolk terriers, Rhodesian ridgebacks, Labrador retrievers and CKCS.
Ichthyosis: Norfolk Terriers
Identified as a mutation of keratin 10 production and a genetic test is available through PawPrint genetics. it is autosomal recessive and affect dogs have epidermal fragility that results in the superficial epidermis sloughing easily. Intertriginous areas may be severely affected. The food pads, hair and teeth are normal.
Non-epidermolytic Ichthyosis
Many dog breeds have been reported to have non-epidermolytic ichthyosis including Jack Russel terriers, Australian Terriers, Cairn Terriers, Norfolk terriers, American Bull Dogs, Golden Retreivers, Great Danes, and German Shepherds.
Ichthyosis: Jack Russel Terriers
Loss of function mutation in TGM1 that results in formation of a defective CE.
It is autosomal recessive and affected dogs have large, thick adherent scales on the body and in the ear canals, food pad hyperkeratosis, onychomalacia and a predisposition to secondary infections.
Genetic testing is available through University of Montreal.
Ichthyosis: American Bulldog
This is due to a mutation in NIPAL4 gene (nuclear interaction partner of ALK-like domain containing 4) that results in production of truncated protein = ichthyic protein with reduced lamellar body secretion, impaired formation of the confined envelope and accumulation of toxic metabolites in the skin. Affected puppies are noted as having a poor haricot shortly after birth, may have generalize white scales and the skin the ventral abdomen appears thickened with adherent brown scales.
Ichthyosis: Golden Retreiver
Due to a mutation in PNPLA1 (patina-lie phospholipase-1).
PNPLA1 codes for acylceramide and has a role in glycerophopholipid metabolism and cuteness barrier function. Affected puppies may have a rough haricot and scaling. The mutation has been found in over 50% of tested dogs in some countries (Switzerland).
Ichthyosis: GSD
Reprpoted in an intact female with scaling noted soon after birth. Genetic testing found a mutation in ASPRV1 gene that encodes aspartic peptize, retroviral-like1. Defects in ASPRV1 results in faulty processing of profilaggrin to filaggrin leading to wrinkled, dy, rough skin due to lack of normal aggression of keratin intermediate filaments and deficiency of natural moisturizing factors.
Ichthyosis: CKCS
Two types of ichthyosis has been reported.
Two littermates were reported with congenital ichthyosis in 1994.
More recently, a syndrome of Congenital Keratoconjunctivitis Sicca and Ichthyosiform Dermatatoses (CKCSID) has been reported in this breed.
Affected puppies have ‘dry eye’ from time of lid opening and frizzy haricoat. They also have dorsal scaling, footpad hyperkeratosis and deformed claw that may slough.
Genetic testing has identified a mutation of the FAM83H gene. Testing is available through Antagene.
Ichthyosis: Great Dane
Generalized gray to yellow scaling and skin wrinkles on their heads and legs.
Genetic testing found mutations of the SLC27A4 gene found on chromosome 9 affecting the proaction of fatty acid Transport Protein 4 (FATP4) that is an acyl-coat synthetase required for normal permeability barrier function.
Ichthyosis fetalis (Harlequin ichthyosis)
Several breeds of cattle have been reported with ichthyosis fettles. Affected calves are still-born or die within a few days following birth. Other features of this disease include microtia and eversion of the skin of the lips and eyelids.
Chianina
cattle with ichthyosis fettles have a H1935R substitution (mutation) gene ABA12. ABCA12 is an ATP-binding cassette transporter 12 protein and has a major role in transportation of lipids in the epidermis responsible for cholesterol efflux from keratinocytes.
65 mutations in this gene have been identified in people with harlequin ichthyosis. A mutation in ABCA12 was also identified in Shorthorn cattle affected with ichthyosis fetalis.
Ichthyosis congenita
Several breeds of cattle have been identified as suffering from a less severe form of ichthyosis termed ichthyosis congenita. Signs may be present at birth or appear within a few weeks with generalized hyperkeratosis and occasionally microtia, cataracts and thyroid abnormalities.
Naked foal syndrome
Akhal-Teke horses have been reported to have an autosomal recessive condition in which affected foals lack hair and have mild ichthyosis. Death occurs by 3 years of age. Genetic testing has found a nonsense variant of ST14 gene, which is serine protease involved in epidermal development.
Congenital ichthyosis in alpacas
One study of 68 alpacas with skin disease reported that 4.5% were diagnosed with ichthyosis.
Porcine model of harlequin ichthyosis
Ethylnitrosourea was used to create a pig model of harlequin ichthyosis with a mutation of the ABCA12 gene. Affected piglets have a severe hyperkeratosis and fail to thrive. This model has been used to study treatments.
Feeding acitretin to pregnant sows and newborn piglets results in improved phenotype and longer survival.
Treatments of Ichthyosis
Survival of children with ichthyosis has increased to 80% with the use of retinoids in treatment. Acitrentin has multiple effects on epidermal cell growth and differentiation and can up regulate the activity of ABCA6 to partially compensate for a lack of ABCA12. Other treatments that may help lessen the severity of clinical lesions include topical keratolytic, keratoplastic and emollient shampoos and sprays, topical retinoids, topical fatty acids and essential oils, topical retinoids and topical use of polyhydroxyacid gluconolacctone.
X-linked Cornification Defects
X-linked cornification defects have a dominant or semi-dominant phenotype. The skin lesions follow lines of Blaschko and may be more severe on one side of the body. Affected breeds have included Rottweilers, Siberian huskies and Labrador retrievers. Genetic analysis of an affect Labrador and her daughter found a structural defect in the NSDHL gene. Mutations in this gene are associated with CHILD syndrome (congenital hemidysplasia with ichthyosiform nevus and limb defects) in people.
X-inked hypohidrotic ectodermal dysplasia
This has been reported in dachshunds - this is an X-linked recessive condition that results in mild clinical signs in heterozygous females and more severe signs in X-recessive male puppies.
This disease has been repotted in several breeds of dogs including miniature poodles, Belgian shepherds, Labrador retrievers, Bischon fries, GSD, whippet, cocker spaniel and mixed breeds.
Genetic analysis found a mutation of EDA gene (ectodysplasin A) - affected puppies and the dam had one base paid deletion in the EDA gene.
Follicular Parakeratosis and Mural Folliculitis
Follicular parakeratosis and mural folliculitis have been repotted in Labrador retrievers resulting in multifocal verruvous paupers and plaques, follicular cast formation , hair loss and comedones on the head, ears, abdomen, trunk and limbs. Some affected dogs improved following treatment with CSA and suggesting an immune-mediated disease.
Genetic testing was negative for NSDHL mutation.
Hereditary Nasal Parakeratosis
Labrador retrievers and greyhounds have been described with heredity nasal parakeratosis. Biopsy findings include marked parakeratosis with serum lakes between cell slayers of the nose.
Genetic studies have found a mutation in SUV39H2.
Familial Paw Pad Hyperkeratosis
Severe hyperkeratosis of pads of all feet develops in affected dogs by 9 months of age. Claws are very hard and fast growing and the haricot may be dull, dogs and less wooly than normal in affected Dromfohrlander dogs. This condition has also been reported in Irish terriers and Dogue de Bordeaux.
Genetic testingg has found a mutation in the FAM83G gene - other disease associated with this genetic mutation include mice with wooly haricots and CKCS with KCS and curly haricots
Antigen offers a genetic test for familial paw pad hyperkeratosis.
Primary seborrhea
It has been reported in American Coker spaniels, English singer spaniels, West highland white terriers, basset hounds, golden retrievers, American bulldogs ad Persian Cats. Epidermal cell kinetics were studied in cocker spaniels with affected dogs having epidermal turnover times of 8 days (normal is 21) and 3 to 4 times higher basal mitotic index. Autosomal recessive.
Exfoliative Cutaneous Lupus Erythematosus
GSHP have a hereditary condition termed ECLE that is inherited as a single nucleotide polymorphism on chromosome 18. Severe scaling starts o the face and ears and may become generalized. Affected dogs are painful and pruritus While early attempted at treatment were unrewarding, a case report showed a favorable response to treatment with mycophenolate. You could also try hydrocholoquine.
Lethal Acrodermatitis
Bull Terriers and miniature bull terriers may be affected with an autosomal recessive form of lethal acrodermatitis. Affected puppies have growth retardation, progressive acrodermatitis, pyoderma, paronychia, diarrhea and pneumonia. Most died by 7 months of age.
Genetic studies showed a mutation of the MKLN1 gene that encodes intracellular protein muslin 1 and functions in cell adhesion and intracellular transport processes.
A litter of Pharaoh hounds was reported to have a similar lesions. unlike bull terriers, the Pharaoh hounds had a favorable response to intravenous zinc.
Bovine Hereditary Zinc Deficiency
Also known as lethal trait A46, bovine hereditary zinc deficiency is an autosomal recessive disease in black pied Fresian cattle, Holstein-Fresians, shorthorns and Angus. it is similar to acrodermatitis eneteropathica in people. Affected cattle improve when treated with high doses of zinc.
A slice mutation in SLC39A4 was found in frisians.
Cornification Disorder of Flechvieh Cattle
Flechvieh cattle have an autosomal recessive cornification disorder that is due to a mutation of PLD4 (a phospholipase encoding gene). Affected cattle do not improve following treatment with zinc.
The pathogenesis may be similar to the congenital parakeratosis of Labrador retrievers with mutations of PNPLA1.
Zinc Deficiency Type 1 in Dogs
Samoyeds, Siberian Huskies, and Alaskan malamutes have been reported to develop parakeratotic hyperkeratosis of the skin on their face that usually improves following zinc supplementation. These dogs may have inherited impaired zinc absorption or metabolism.
Zn Meth + Zn Gluc > Zn Sulfate
GC increase synthesis of metallothionine which is essential for Zn transport and increases Zn absorption.
Symptoms develop between 1 to 43 years of age. Clinical signs include erythema, alpaca, scales, and thick adherent crusts involving mucocutaneous junctions and pressure points. Differential diagnoses include immune-mediated daises, demodicosis, dermatophytosis and other causes of seborrhea.
Localized Parakeratotic Hyperkeratosis
Boston terrier dogs have been reported to develop a localized parakeratotic hyperkeratosis with scaling affecting the face and/or pressure points. Some dogs improved following zinc supplementation although a zinc deficiency was not proven.
Vitamin-A Responsive Dermatosis
Cocker Spaniels, miniature schnauzers and Labrador Retrievers develop lesions as adult dogs. Clinical signs include follicular papules, follicular casts and mutlfdocal erythematous alopeic plaques that re most prominent on the ventral and lateral chest and abdomen.
Treatment with Vitamin A 1000-1200 IU/kg/day + FA
Sebaceous identities
This has been reported in cats, rabbits, and man breeds of dogs including standard poodles, Samoyed, Akita, Vizlas, dachshunds, beagles, Old English sheepdogs, toy poodles, springer spaniel, Lhasa aposos, boxers, chow chows, collies, German shepherd dogs, miniature pinschers, Plott hounds and MBD.
An autosomal recessive inheritance is proposed the standard poodles and Akitas. Clinical signs include adherent scales, follicular casts and poor hair coat. Lesions are often most severe on the dorsal drunk, temporal region , face and pinnae with some dogs developing a ‘rat tail’. Less common are focal coalescing firm nodules, annular plaques and/or facial swelling.
Epidermal dysplasia
Controversial condition occurs in Westies. Debate exists as to whether this is a primary condition of it lesions develop secondary to Malassezia.
American Hairless Terrier
Hairlessness in the American hairless terrier is an autosomal recessive trait due to a frameshift deletion of SGK3 (serum glucocorticoid regulated kinase family member 3 gene). Puppies are born with thin coat of hair lost within the first months of life.
This gene is involved in postnatal hair follicle development.
Autosomal dominant Hairlessness
Hairlessness in Chines creste, Mexican xoloitcuintle and Peruvian Inca orchid dogs is autosomal dominant due to a mutation in Fox13 (forehead box transcription factor 13), which regulated ectodermal development, post-natal hair growth and hair regeneration; hairless dogs may also have problems with dentition and malformed ears.
Homozygous presence of this mutation is fatal.
Schnauzer Comedo Syndrome
Miniature schnauzers may develop comedones in a band along the dorsal midline. Hairs in affected areas may appear darker and more erect with crusted papules and distended follicular ostia.
Canine Ear Margin Seborrhea
Dachshunds and other dogs with pendulous ears are predisposed to developing ear margin seborrhea with adherent keratinous deposits on the medial and lateral margins of pinnae, partial alopecia and occasionally a seborrheic odor.
Acanthosis Nigricans
This has been reported as a genodermatoses affecting dachshunds. Most cases occur secondary to other causes of cutaneous hyperpigmentation and hyperkeratosis including allergies, intertrigo, endocrinopathies and Malassezia infections.
Equine Linear Keratosis
Vertical bands of hyperkeratosis and thickened skin appear not eh neck, body or limbs of QH.
Equine Cannon Keratosis
Focal areas of scaling, crusting and alopecia appear on anterior skin over the rear cannon bones of horses.
Equine Photosensitization
scaling and crusting develop follow-ing UV light interacting with photoactive agents in the skin that may be primary (ingested from plans or drugs); hematogenous (inefficient breakdown of phylloerythrin due to liver disease) or to abnormal pigment production (occurs in cattle with porphyria).
The optimal stratum corneum water concentration to promote softness and pliability is what percent?
20% to 35%.
What is the different between keratolytic and keratoplasic ingredients?
Keratolytic agents facilitate decreased cohesion among corneocytes, desquamation, and shedding, resulting in a softening of the stratum corneum with easy removal of scale. They do not dissolve keratin.
Keratoplastic agents attempt to renormalize the keratinization and abnormal epithelialization that is present in keratinization disorders.
- The complete mechanism of these effects is not known, although some keratoplastic agents (particularly tar) are believed to normalize epidermal proliferation by decreasing deoxyribonucleic acid (DNA) production with a resultant decrease in the mitotic index of the epidermal basal cells.
What are the most common ingredients in anti-sebboreic shampoos?
Tars, sulfur, salicylic acid, benzoyl peroxide, and selenium sulfide.
o Other commonly included active agents are urea, glycerine, and lactic acid.
Sulfur is both keratoplastic and keratolytic, probably through the interaction of sulfur with _____ in keratinocytes.
cysteine
Sulfur is also antibacterial, antifungal, and antiparasitic, and these actions are attributed to the formation of what two compounds?
pentathionic acid and hydrogen sulfide
Thymoma Associated Exfoliative Dermatitis
A generalized exfoliative dermatitis has been described in cats with thymoma.
o Thymoma is usually located in the cranial thoracic cavity, but had ectopic thymic tissue in its neck.
o Affected cats are middle-aged to older.
o Lethargy, weight loss and anorexia are common findings.
o Some cats will develop signs of myasthenia gravis, polymyositis, or mycarditis before or after a thymectomy.
o Lesions are first noted on the head and pinna. Pruritus usually is minimal or absent, but may be intense. Despite treatment with steroids, antibiotics, or other agents, lesions spread and involve the entire body in a matter of weeks to several months. Hair loss can accompany the exfoliation.
o Skin biopsies will show a cell-poor hydropic interface dermatitis with exocytosis of CD3 or CD8 lymphocytes into the surface and or follicular epithelium. Apoptotic keratinocytes are seen in the basal layer, and to a lesser extent in the SS. Sebaceus glands may be absent.
Gordon setters with a vitamin A- responsive condition that differs in its clinical presentation. How?
Instead of a seborrheic presentation, these dogs have a pruritic disorder, especially over their dorsum, with a papular dermatitis in the pruritic regions.
Treatment with antibiotics resolves the papular dermatitis and lessens the pruritus but a relapse can be expected when the antibiotic is withdrawn.
Treatment with vitamin A alcohol results in resolution of the rash and pruritus, and the dog remains normal with continued treatment. The marked follicular plugging that occurs in these dogs is highly suggestive of this disease.
