Rashes, ulcers, pigments and claws Flashcards
Where are melanosomes formed?
basal layer of epidermal structures, transferred to keratinocytes, then in anagen phase, transferred to hair matrix cells forming the hairs
What are the 2 types of melanin?
EUMELANIN: black, insoluble, oval melanosomes,
PHAEOMELANINS: red-brown/yellowish, soluble in alkali, round melanosomes,
How are melanins formed?
Tyrosine converted to dopaquinone by action of tyrosinase. Dopaquinone is converted into either eumelanin or phaemelanin
Define lichenification
an accentuation of the normal superficial skin markings
How do macules/patches changes clour?
can refer to an increase or decrease in size
How are diseases of pigmentation classifie?
genetic or acquired
- any disease affecting hair matrix or basal layer of epidermis may cause pigmentary changes
Name 2 dog breeds suscpetible to hyperpigmentation
WHWT and GSD
What can acquired hyperpigmentation be caused by?
Many factors:
- especially recent inflammation or endocrine disease
Define lentigo
- a macular melanosis in mature dogs
- no clinical consequences
- some cepidermal thickening may occur
What is lentigo simplex?
- condition of young orange cats
- small black spots appear on lips, gums, eyelids and nose at <1 year old
Causes - acquired hypopigmentation
- wider variety of factors causing damage to epidermis or hair follcile
- interface autoimmune diseases may cause depigmentation
- vitiligo is a disease with pigmentary loss as a consequence of an autoimmune attack directed specifically against melanocytes
Define photoallergy
reaction to chemical promoted by UV light
How can skin be damaged?
- excessive exposure of lightly pigmented skin (sunburn)
- photosensitivity
- photoallergy
What does photosensitivity involve?
the release of hydrolytic enzymes and other mediators following damage caused by the exposure of photodynamic agents in skin to UV light. Photodynamic agents may be administered (drugs), absorbed or fed (certain plants in grazing animals) or may accumulate as a consequence of abnormal metabolism due to hepatic disease or genetic abnormalities
What causes vasculitis?
immune complex deposition the most likely cause of autoimmune types of vasculitis.
Define vasculitis
the vessel is the target of inflammation rather than a participant.
- many cells are present in BV wall (versus dermis)
- occurs in haemorrhage and oedema
- degeneration of ECs
- can be presence of infarcts and adnexal atrophy
How easy is it to diagnose vasculitis in cats and dogs?
difficult
Define onychogryphosis
deformed overgrowth of nails
Define onychomadesis
complete shedding of nails
Define onychomycosis
fungal nail infection
Define onychorrhexis
a breakage or brittleness of a nail
What are the 4 main aetiologies of claw disease?
- trauma
- neoplasia
- paronychia
- symmetrical lupoid onychodystrophy (SLO) (lupoid onychitis)
Define paronychia
inflammation of the nail fold
When might an animal have paronychia?
- bacterial/fungal infection (check for immunosuppression)
- autoimmune diseases (esp. PF in cats)
Define PF
pemphigus foliaceous - an autoimmune disease
What is symmetrical lupoid onychodystrophy (SLO) / lupoid onychitis characterised by?
- dogs, 1-2 years, not uncommon
- sloughing claws
- regrowth of brittle, cracked short claws
- usually involves multiple claws on multiple feet
- without skin disease elsewhere
- this presentation should prompt consideration of SLO
- also an anti-inflammatory and immune-mediated disease (ophthalmology)
Histology - symmetrical lupoid onychodystrophy (SLO)
- Interface dermatitis at junction of clawbed and underlying dermis.
- amputation of P3 is needed for histopath. confirmation
- unless dewclaws are affected and available from excision, a clinical diagnosis followed by trial therapy (often OTC / nicotinamide) may be preferred
Define pustule
a small circumscribed fluid-filled elevation of the epidermis which contains pus, often transient
Where may pustules be found?
- centred on hair follicles (hair protrudes from lesion centre)
- interfollicular epidermis
What might the predominant lesions be in pustular diseases? 3
- pustules transient often
- predominant lesion may be crusts, epidermal collarettes or erosions.
Commonest cause of pustular lesions in dogs and cats
DOGS pyoderma caused by staph
CATS - pemphigus foliaceus (PF)
Causes of pustular diseases
- pyoderma caused by staph, dogs, rare in cats*
- some sterile inflammatory diseases (rare): drug eruptions, PF, subcorneal pustular dermatosis and sterile eosinophilic pustulosis
How can pustular diseases be diagnosed?
- cytology
- histopathology
- response to AB treatment
What would you see on cytology and biopsy for pyoderma?
- CYTOLOGY: neutrophils (sick) and cocci
- BIOPSY: neutrophilic folliculitis
Cytology and biopsy for pemphigus foliaceous (PF)
- CYTOLOGY: neutrophils, free epithelial cells
- BIOPSY: subcorneal pustules and acantholysis
Outline the approach to pustular disease in dogs
- Cytological exam - pustule contents - open with needle and smear on slide
- If cytology consistent with pyoderma, treat with ABs, re-examine after 10-20 days. Also take skin scrapings to Demodex to exlcude this as a cause of pyoderma
- If not AB reponse OR cytology not consistent with pyoderma:
- culture for bacteria (AR if tx failure)
- skin biopsy (to diagnose all sterile pustular diseases)
What is the approach to pustular disease in cats and horses?
Because pustules are so unusual in these species, biopsy all cases but consider treating with ABs pending biopsy results
Define ulcer
break in the continuity of epidermis so that underlying dermis is exposed.
Why do ulcers develop?
- self-trauma in pruritus *
- diseases that involve the epidermis or dermo-epidermal junction (infections, autoimmune diseases, drug reactions and neoplasia. Includes vesicular, interface, vascular and neoplastic types)
What might widespread ulceration reflect? 3
- progression from vesicles and bullae (intra-epidermal and superidermal vesicular dermatitides)
- epidermal separation (severe interface dermatitis)
- epitheliotropic lymphoma (epidermis damaged by invasion by neoplastic lymphocytes)
How do you approach cases of ulcerative skin disease?
Skin biopsies should be routinely obtained (often severe disease which needs aggressive, potentially hazardous treatments)
- ideally sample intact primary lesions
- if above not available, take excisional biopsies at lesion margency
Differentiate vesicle and bulla
= fluid filled elevations of the skin that contain clear fluid (vesicle 1cm diameter)
How long are vesicles present?
often transient lesions in haired skin due to the thin epidermis
Histology - vesicles
- intraepidermal or sub-epidermal vesicular dermatitis
- interface dermatitis (sometimes)
Aetiology - vesicles
- viral infection
- irritant chemicals and burns
- auto-immune or immune-mediated disease
What should vesicular lesions in farm animals prompt?
consider notifiable diseases (e.g. FMDV)
Describe the skin response to a drug reaction
- very wide range of CS
- can imitate any other skin disease
- often unusual or bizarre
What type of reaction are drug reactions?
immune-mediated reactions (don’t confuse with drug side effects which are direct effects induced by chemicals)
List possible drug reaction presentation
- urticaria / angioedema
- exfoliative erythroderma (i.e. red scaly skin)
- any autoimmune type of presentation
Dx - drug reaction
- hx of drug exposure
- CS of drug reaction
- consistent histopath (various patterns)
- rule out of other causes
- don’t rechallange with the offending drug!
Tx - drug reaction
- stop offending drug
- supportive/ symptomatic measures depending on presentation
- make case record for future
Define autoimmune disease
specific humoral or cell-mediated IR against auto(self)-antigens that results in disease
Define immune-mediated disease
= mediated by the immune system. usually used in instances where the skin disease is thought to result from inappropriate inflammation OR immune attack int eh skin, but where a specific humoral or cellular response against self-antigens has not been demonstrated. Hypersensitivities to external agents are not normally included in teh list of ‘immune-mediated’ diseases, although these are of course mediated by the immune system.
What are the 4 different histological patterns associated with autoimmune skin disease?
- INTRAEPIDERMAL PUSTULAR
- INTRAEPIDERMAL VESICULAR
- SUBEPIDERMAL VESICULAR
- INTERFACE
What autoimmune skin disease is an intra-epidermal pustular histology associated with?
Pemphigus foliaeceus (PF) - neutrophils and acanthocytes seen
What autoimmune skin disease is an intra-epidermal vesicular histology associated with?
Pemphigus vulgaris (PV) - suprabasalar split, cell poor
What autoimmune skin disease is a subepidermal vesicular histology associated with?
Bullous pemphigus (BP) + variants
- cell poor
- frequently associated with accumulation of inflammatory cells (neutrophils or eosinophils, usually mononuclear)
What autoimmune skin disease is an interface histology associated with?
Lupus erythematous (LE)
- cell rich
- lymphocyte
What dictates the type of lesion seen in autoimmune skin conditions?
the nature and location of the autoantigen and associated inflammatory response
Generally, what are immune-mediated assaults on the basement membrane or basal keratinocytes characterised by?
vesicles and bullae (which form as the epidermis separates from the underlying tissues). Since these lesions are fragile, erosions and ulcers usually dominate the clinical presentation
Name 2 autoimmune conditions where the skin and MM are both affected
- bullous pemphigoid (BP)
- pemphigus vulgaris (PV)
Where is the target autoantigen located in subepidermal vesicular autoimmune diseases?
in basement membrane thus immune attack –> loss of cohesion between epidermis and dermis.
What are the primary and secondary lesions in subepidermal vesicular autoimmune diseases
- PRIMARY: vesicles or bullae, rupture to:
- SECONDARY: erosions or ulcers
CS - subepidermal vesicular autoimmune diseases
- phenotype variable
- lesions often around mucocutaneous junctions, axillae, groin, may involve MM too.
Name 3 different subepidermal vesicular dermatitides and the species they affect
- Bullous pemphigoid (BP) - dogs, cats, pigs, horses
- Mucous membrane pemphigoid (MMP) - dogs, cats
- Epidermolysis bullosa acquisita (EBA) - dogs
What are the 4 mechanisms of subepidermal vesicular autoantigen diseases?
- genetic defect (SP)
- immune attack (SP)
- severe epidermal oedema
- keratinocyte degeneration
Summarise the clinical patterns of autoimmune skin diseases
- PUSTULAR (CRUSTS) - PF, intraepidermal pustular
- VESICLES + BULLAE (erosions, ulcers) - PV, BP, intra or subepidermal vesicular, skin and mucosae often
- ERYTHEMA VESICLES (erosions, depigmentation) - LE, interface, widespread of confined to nasal planum
What does pigmentary incontinence reflect?
reflects previous interface dermatitis
Define pigmentary incontinence
loss of melanin from the epidermis and accumulation in melanophages in upper dermis. seen in some inflammatory diseases and incontentia pigmenti
Ddx for subepidermal vesicular autoimmune skin diseases?
- other ulcerative autoimmune diseases
- drug reactions
- epitheliotropic lymphoma
Dx - subepidermal vesicular autoimmune disease
- hx
- CS
- biopsy (cell rich or cell poor subepidermal vesicular dermatitis)
Define dermatitides
the plural of dermatitis
Pathomechanism - intraepidermal vesicular dermatitis
AutoAb to desmosomal adhesion molecules (desmogleins) in the epidermis leads to separation of keratinocytes from each other (acantholysis) and blister or pustule formation. The dermoepidermal junction is obscured
What is pemphigus vulgaris?
- a type of intraepidermal vesicular dermatitis
- associated with suprabasilar clefting as a consequence of acantholysis
- very rare
- CS: vesicles, bullae, erosions, ulcers
- oral cavity (90%)
- mucocutaeneous junctions, ears, claw, axilla, groun
- secondary bacterial infection common
- fever and depression (severe)
What is suprabasilar clefting?
a pattern of acantholysis seen in P.V. where the acantholysis occurs just above the basal layer of the epidermis but the basal layer remains intact. In P.F., the acantholysis is higher up, just below the stratum corneum.
Diagnosis - intrapeidermal vesicular dermatitis (PV)
- hx
- CS
- skin biopsy (suprabasilar split with ‘tombstones’ = the row of basal cells forming the base of the blister. and a few inflammatory cells)
- histopath. - essential for diagnsis
Tx - intraepidermal vesicular dermatitis (PV)
- often severe and difficult so aggressive therapy
Name 3 intraepidermal pustular diseases
- PF
- Interface dermatitis
- Discoid lupus erythematous
What is the commonest pemphigus disease?
PF - dogs, cats, horses
Lesions - PF
- transient pustules (–> crust) and may not be seen
- crusts, scales, hair loss, erosions and epidermal collarettes affect face (ears first), feet including footpads, neck and groin.
- tends to become generalised and widespread (horses)
- fever, depression (severe)
Dx - PF
- hx
- CS
- biopsy
- pustule smears - look for acatholytic cells and neutrophils in the absence of bacteria
- histopath - essential
What happens histologically in interface dermatitis? 3
- the dermo-epidermal junction is obscured by inflammatory cells OR hydropic degeneration OR a combination of these features.
- I.e. it is cell-rich OR cell-poor.
Name 2 examples of interface dermatitis (a type of intraepidermal pustular disease)
- Discoid lupus erythematous (nasal cutaneous lupus)
- Erythema multiforme/ toxic epidermal necrolysis (immune-mediated rather than autoimmune, often triggered by drugs)
What is another name for discoid lupus erythematous (DLE)?
nasal cutaneous lupus erythematous
n.b. it is a type of interface dermatitis, it is NOT a form os systemic lupus
How common is DLE?
DOGS - uncommon
CATS - very rare
What aggravates DLE in 50% cases?
sunlight exposure
DLE breed predispositions
Collies, Shelties, GSDs, huskies
CS - DLE
- no systemic signs
- depigmentation
- scaling and erythema of nose extending to the bridge of the nose, sometimes affects ears and periorbital areas
- early sign is loss of cobblestone appearance of the nasal planum, subsequent erosion and crusting
- small oral ulcers
Histopathology - DLE
cell-rich, lymphocytic interface dermatitis
Tx - DLE - 5
- avoid sunlight (exacerbates)
- consider topical fluorinated glucocorticoids twice daily intially then reduce to every 2 days and switch to less potent preparations such as 1-2% hydrocortisone. Some pets lick this off! Alternative topical is tacrolimus.
- combined TC and niacinamide
- vitamin E or combiinations of n-3 and n-6 EFAs (adjunctive agents)
- systemic prednisolone (severe cases, combine with other immunosuppressants if necessary, balance side effects)
Principles of therapy for autoimmune skin conditions
- suppress autoimmune reaction
- anti-inflammatories and immunosuppressants used singly or in combination
- dose for each animal
- monitor animal for side effects
- balance severity of disease with side effects
Outline general treatment options for mild autoimmune and immune-mediated disease
- topical steroids
- vit E
- TC/ niacinamide
- low doses of steroids
Outline general treatment options for severe autoimmune and immune-mediated disease
- high dose steroids
- oral prednisolone
- oral dexamethasone
- azathioprine (NOT CATS)
- chlorambucil
Dose - prednisolone - autoimmune conditions
DOGS: 2-4mg/kg every 24 hours initially, maintain on every other day dosing, reduce gradually with signs
CATS: double the dog dose (for allergy much lower doses are used).
Outline azathioprine in the tx of autoimmune conditions
- useful in dogs, NOT IN CATS
- combine with systemic predisolone, either as a first line combination or after it has been shown that prednisolone by itself is not sufficient
- initial dose: 2mg/kd/d orally until response then every other day for 4-6 weeks, then reduce dose and interal
- cost is a factor
- regular haematology to check for myelosuppression
Outline chlorambucil in tx of autoimmune conditions
- often combined with prednisolone
- useful in PF cats that don’t respond to steroids alone
- dog/cat: 0.1-0.2 mg/kg every 24-48 hours
- monitor haematology twice/month
Outline ciclosporin in tx of autoimmune conditions
- v expensive
- efficacy to be established in next few years
- prelim data suggests poor efficacy in canine PF
- sometimes used with azathioprine for refractory cases
Outline TC and niacinamide in tx of autoimmune conditions
- this combination of AB and B-vitamin is known to have an anti-inflammatory action
- good for milk autoimmune diseases where the risk of side-effects of more potent drugs cannot be justified.
Aetiology/ pathogenesis - feline cowpox
- an orthopox virus
- zoonotic
- rodents (voles and woodmice are RH)
- affected cats normally rural hunters
- characteristic CS
- mostly autumn (when RH most active)
CS - feline cowpox
- initial lesion: small ulcer or larger area of abscessation or cellulitis often on face or distal limb
- after 7-10d, multiple nodular lesions develop in skin due to viral replication in the draining node and white-cell associated viraemia
- lesions are typically well-demarcated, raised, erythemaotus, vesicular top, rapidly develops into crust
- some lesions have central depression or crater
- lesions generally resolve after 4-6 weeks in cats which are otherwise healthy
- pneumonia (occasionally)
Dx - feline cowpox
- virus isolation
- EM of crusts
- serology (early seroconversion)
- skin biopsy (histopath)
Histopathology - feline cowpox - 3
- degenerative changes in surface and follicular epithelium (incl. adnexal glands)
- marked dermal infiltrate of inflammatory cells
- intracytoplasmic eosinophilic inclusion bodies (epidermal areas that aren’t necrotic)
Management - feline cowpox
- no specific antiviral
- supportive symptomatic therapy
- avoid steroids (worsen disease)
- ZOONOTIC (standard hygiene)
