Skin Pathology 6 Flashcards
THE SKIN IN SYSTEMIC DISEASE. -Name the types of systemic disease that may affect the skin. -Outline various ways in which nutritional disturbances may affect the skin -Describe the various syndromes in which zinc deficiency is considered to play a role and briefly explain the mechanisms thought to be involved. -Define the terms anagen, catagen, telogen, effluvium. -Give an account of endocrine related alopecia, including specific examples in dogs and cats. -Briefly describe other ca
NON INFECTIOUS SYSTEMIC DISEASES THAT AFFECT THE SKIN
Skin changes may be the presenting sign of internal disease or a complication of ongoing disease and/or it’s treatment- side effects!
(Immune and autoimmune diseases, haematological and circulatory diseases already covered)
-DRUG ERUPTIONS
-GENETIC DISORDERS
-METABOLIC, ENDOCRINE AND NUTRITIONAL DISTURBANCES
-NEOPLASIA AND PARANEOPLASTIC SYNDROMES.
DRUG ERUPTIONS
Common. Mimic a wide variety of other skin conditions.
Skin lesions are the most common signs seen with drug eruptions.
IMMUNE MEDIATED- drug hypersensitivity (eg. penicillin- common)
NON-IMMUNE- predictable drug side effect/toxicity/interaction.
-Unpredictable idiosyncratic reaction- pseudoallergic response, individual intolerance.
GENETIC DISORDERS OF THE SKIN
Onset of signs may be congenital or tardive.
Skin changes may be a direct result of the genetic alteration eg. EPIDERMOLYSIS BULLA- not immune mediated- a congenital condition (immune mediated form can be seen).
eg. EPITHELIOGENESIS IMPERFECTA- similar congenital condition. Parts of skin (eg. band round middle) are missing.
Skin changes may be a reflection of pathology elsewhere eg. porphyria- chromatic pigment accumulates in teeth (yellow, pink under UV lamp), but the pathology is seen in the blood and bone marrow.
NUTRITIONAL SKIN DISEASE
Unlikely in healthy animals eating an appropriate, balanced diet.
Disease results from- Dietary lack of nutrient
-Malabsorption
-Antimetabolites
-Defective utilisation.
SIGNS OF NUTRITIONAL SKIN DISEASE
PROTEIN DEFICIENCY- poor hair coat- economic impact in wool/hide producing animals, cosmetic in small animals.
Moving sheep from low to high protein diet improves wool quality.
Protein deficiency also increases susceptibility to infection.
FATTY ACID DEFICIENCY- diffuse scaling. Mechanisms are not well understood; presumed role of prostaglandins influencing epidermal cell turnover.
Alopecia.
VITAMIN DEFICIENCY- scaling and/or alopecia, dermatitis.
MINERAL IMBALANCE- eg. ZINC RESPONSIVE DERMATOSIS- especially seen in pigs, dogs. Can be due to absolute deficiency, relative deficiency (increased phytate) or impaired uptake/utilisation.
Decreased wound healing.
Keratinisation effects in epidermis, hair and horn- parakeratosis (nucleated keratinocytes due to high cell turnover).
ZINC
AN ESSENTIAL TRACE ELEMENT. Component of important metalloenzymes and a cofactor for others.
Zinc dependent enzymes regulate DNA and RNA expression.
-Zinc has a role in all metabolic processes involved with tissue growth, maturation and repair.
-Involved in vitamin A metabolism
-Involved in enzymes needed for free radical scavenging
-Modulates aspects of inflammatory and immune responses.
ZINC DEFICIENCY SYNDROMES
-TRUE zinc deficiency- rare. Pigs- SWINE PARAKERATOSIS. Dietary availability is adversely affected by phytate, high Ca and low fatty acids in cereal based diets.
Not problematic with improved management and dietary supplementation.
Occasionally seen in ruminants, can affect forestomachs as well as skin.
-ZINC RESPONSIVE DERMATOSIS- reported in goats in USA, Europe, Australia. Mechanism uncertain, may involve high Ca diets, hereditary malabsorption.
-Dogs- two syndromes recognised- NORDIC BREEDS- presumed hereditary malabsorption.
Nordic breeds should be fed on high zinc diets.
See peaks of parakeratotic hyperkeratosis, minimal hyperplasia. Scaling and crusting dermatitis shows particular distribution pattern- face, pressure points, footpads.
-PUPPIES/YOUNG DOGS- any breed, on generic/cereal based dog food.
SUPERFICIAL NECROLYTIC DERMATITIS
aka. Metabolic Epidermal Necrosis (MEN), Necrolytic Migratory Erythema (NME, humans).
DIFFUSE PARAKERATOSIS
UPPER EPIDERMAL OEDEMA/LYSIS
BASAL HYPERPLASIA
A postulated mechanism involves a combination of deficiencies- zinc, amino acid, fatty acid.
Deficiencies arise from a wide variety of sources- dietary insufficiency, malabsorption syndromes, disorders of metabolism, liver disease, elevated glucagon levels.
SUPERFICIAL NECROLYTIC DERMATITIS- KEY FEATURES
Uncommon in dogs, rare in cats.
May present as pedal or scrotal dermatitis.
Associated most often with a HEPATOPATHY or (less often) a GLUCAGONOMA.
HYPOaminoacidaemia appears to be a consistent feature- irrespective of cause.
Possibly seen due to increased hepatic catabolism, or because proteins play a role in zinc transport.
HEPATOCUTANEOUS SYNDROME
SKIN- Lesions seen on feet, face, pressure points (same distribution as with zinc responsive dermatosis).
Superficial pallor, occasionally lysis.
Massive, diffuse parakeratosis plus hydropic degeneration of upper epidermis.
LIVER- Macronodular cirrhosis- small, nodular liver, vacuolar change, fibrosis.
*Debate as to the nature of liver disease- vacuolar hepatopathy vs. cirrhosis- may not be mutually exclusive. Ballooned hepatocytes contain glycogen or fat (can’t see difference).
GLUCAGONOMA SYNDROME
Underlying pathology- glucagon-producing tumour in pancreas (a cells)
Up to 90% of glucagonoma patients are DIABETIC- diabetes mellitus also present in some animals with hepatocutaneous syndrome.
Some cases reported as ‘diabetic dermatosis’
Pancreatic neuroendocrine tumours may be benign or malignant and metastasis (eg. to liver) may have already occurred by the time the animal presents clinically.
Rarely, surgical excision can be curative.
Clinically- crusted, fissured footpads, nodular growth in pancreas (look for metastases also)
LETHAL ACRODERMATITIS OF BULL TERRIERS
Inherited autosomal recessive trait, disorder is presumed to be due to an unidentified defect in zinc metabolism.
Similar to acrodermatitis enterohepatica in humans and lethal trait A46 in black pied Danish cattle (except zinc treatment does NOT reverse clinical signs)
Affected pups are stunted and have a small/absent thymus- susceptible to skin/lung/intestinal infections.
Distorted, swollen feet/face, crusting lesions, erythema, alopecia.
Most cases are fatal by 2 years of age.
CUTANEOUS MANIFESTATIONS OF INTERNAL DISEASE
Changes in the skin can be critical sentinels for internal disease, as skin appearance and integrity are influenced by internal factors, including hormone levels and overall health.
Recognising those skin changes can accelerate diagnosis and management of systemic disease.
(systemic disease eg. endocrine disorders, paraneoplastic skin diseases, systemic infections)
Skin biopsies can, in some cases, provide sufficient information to make/confirm a diagnosis.
ENDOCRINE RELATED ALOPECIA
Atrophic dermatitis with hair cycle arrest- hairless telogen follicles often predominate. Exaggerated catagen follicles may be seen.
Definitive diagnosis depends on clinical data including endocrine assays, function tests.
Hormones that may affect hair growth- GLUCOCORTICOIDS, OESTROGEN- SUPPRESSION
THYROID HORMONE- ACCELERATION (hirsutism)
HAIR PHASES
ANAGEN- growth phase
CATAGEN- transitional phase (club hair produced)
TELOGEN- resting phase- old club hair falls out.
-> ANAGEN etc.
TELOGEN EFFLUVIUM
Temporary hair loss due to shedding of resting/telogen hair after some shock to the system. New hair continues to grow.
Loss of normal club hairs from normal resting follicles is accelerated or early.
Hair loss occurs some time after the initiating event, as regrowth begins and pushes out the old hair.
May follow cytotoxic therapy or other stress. Hairs are abruptly shifted from anagen to telogen phase then shed as regrowth occurs, weeks to months after the event. The mechanism is not fully understood.
ANAGEN EFFLUVIUM- Similar to the above, but hair sheds due to interruption of active/anagen hair growth by drugs/toxins/inflammation- damage to hair matrix, loss may be sudden and extensive, due to inhibition of cell proliferation.
Distinguish between the 2 by examining roots of dropped hairs to determine anagen:telogen ration. Can also biopsy skin, but hairs may have already returned to growth phase by the time biopsy is taken.
JUVENILE ONSET PANHYPOPITUITARISM
PITUITARY DWARFISM.
Simple autosomal recessive trait produces an individual with a malformed/cystic pituitary gland.
Dwarf pups are indistinguishable from normal until around 2 months of age, when slower growth rate, retention of puppy coat and lack of primary hairs and gradual development of bilateral symmetrical alopecia are seen.
Histology- atrophic dermatosis, hairless telogen follicles.
HYPERADRENOCORTICISM
Canine Cushing’s Syndrome.
Produces bilateral symmetrical alopecia, comedones and pot bellied appearance (due to muscle wasting).
Atrophic dermatosis visible histologically.
CALCINOSIS CUTIS
DYSTROPHIC CALCIFICATION in Cushingoid patients.
Seen mainly in adult or aged dogs.
Majority are pituitary dependent (ACTH-producing adenoma). Others are iatrogenic (steroid therapy- fragile skin syndrome in cats- withdraw steroids), or due to functional adrenocortical tumours.
Signs- thin skin with ulcerated plaques, mineral deposits on dermal collagen- relate to gluconeogenic, lipolytic, protein catabolic and anti inflammatory effects of the glucocorticoid hormones.
Calcinosis cutis is an uncommon by CHARACTERISTIC feature.
ENDOCRINE RELATED ALOPECIA- HYPOTHYROIDISM
Said to be the commonest endocrine disorder in dogs.
HOWEVER, is also one of the most commonly over-diagnosed diseases; the frequency of cutaneous signs is controversial.
Hypothyroidism seen due to lymphocytic thyroiditis or idiopathic thyroid atrophy.
Signs include decreased appetite, weight gain and lethargy.
Skin changes may be subtle- hair loss, dry skin/coat, skin thickening due to increased mucin- puffy face.
ENDOCRINE RELATED ALOPECIA- SERTOLI CELL TUMOUR
Feminisation of affected animal, with alopecia and hyperpigmentation of flank, caudal thigh and peritoneum.
Histology- hairless telogen follicles with epithelial streamers.
CATEGORIES OF ALOPECIA
- ENDOCRINE RELATED- follicle keratosis, dilation and atrophy. eg. canine Cushing’s syndrome.
- GENETIC- follicle dysplasia. eg. colour dilution alopecia.
- IMMUNE MEDIATED/AUTOIMMUNE- mononuclear cell infiltrate. eg. alopecia areata (idiopathic/autoimmune)
- PARANEOPLASTIC- variable eg. feline pancreatic carcinoma
- NEOPLASTIC- atypical cell infiltrate eg. cutaneous lymphoma
- INFLAMMATORY- common. Dermal inflammation and/or scarring. eg. Leishmaniasis
BREED ASSOCIATED ALOPECIA
- CANINE CYCLIC FLANK ALOPECIA, aka. seasonal flank alopecia, recurrent flank alopecia.
Seen in Boxers, Bulldogs, Airedale terriers, Schnauzer etc.
Tardive onset, most cases will regrow hair, but condition is progressive in some individuals.
Hair loss due to exaggerated manifestation of normal moulting schedule in affected individuals.
Photoperiod- pineal gland- melatonin may influence development.
Histology- hair cycle arrest/hair follicle dysplasia- ‘big foot’ follicles have truncated ‘toes’ on bottom. - CANINE FOLLICULAR DYSPLASIA, aka. hair follicle dysplasia.
Affects Siberian huskies, Irish water spaniels, Portuguese water dogs etc. Features vary between breeds, but alopecia is non cyclical- tends to persist once it has appeared.
Pathogenesis uncertain- may be linked to steroidogenesis.
Histology- variable hair cycle arrest, follicle atrophy/dysplasia, pigmentary incontinence, pigment clumping.
COLOUR DILUTION ALOPECIA
aka. ‘Blue Doberman/Whippet Syndrome’, colour mutant alopecia. Affects animals with dilute coat colour; dilute areas become alopecic. Seen in various dog breeds with dilute coats.
Partial alopecia of dilute areas occurs via hereditary follicle dysplasia- distorted follicles, abnormal clumped pigment, pigmentary incontinence.
Role of pigment uncertain.
Tardive onset- breeding control difficult.
BLACK HAIR FOLLICULAR DYSPLASIA- similar, a different mutation causes loss of only black hair.
