Immune-Mediated Skin Disease Flashcards
define autoimmune disease
specific humoral or cell mediated immune repsonse against autoantigens -> disease
define immune-mediated disease
mediated by the immune system - innappropriate inflammation or immune attack where specific humoral or cellular response to SELF AG NOT demonstrated.
- excludes hypersesntivities (even those these are immune mediated technically)
are immune mediated diseases common?
no
what type of immune assault leads to vesicles and bullae? what other lesions may be seen associated with these?
basement membrane or basal keratinocytes targetted
(epidermis separates from underlying tissue)
- erosions and ulcers more commonly seen as vesicles fragile
egs. of bullous or vesicular disease
- bullous pemphigoid
- pemphigous vulgaris
(NB: pempigous folacious = pustular disease)
what is targetted in subepidermal vesicular autoimmune disease?
- basememnt membrane
- accumulation of inflammatory cells (neutrophils, eosinophils) may be seen in conjunction with 1* lesions
where are subepidermal vesicular autoimmune disease lesions commonly seen?
mucocutaneous junction, axilla, groin, mucous membranes
Is bullous pemphigoid a single disease?
NO! recent molecular studies -> multiple types of subepidermal vesicular dermatitides eg.
- BP (bullous pemphigoid) dogs, cats, pigs, horses
- MMP (mucous membrane pemphigoid) dogs, cats
- EBA (epidermal bullosa acquisita) dogs
what is targetted in pemphigus vulgaris?
desmosomes
Ddx subepidermal vesicular autoimmune diseases?
- other ulcerative autoimmune diseases
- drug reactions
- epitheliotropic lymphoma
Dx of subepidermal vesicular autoimmune disease?
- hx, cs
- biopsy (cell rich or cell poor subepidermal vesic. dermatitis)
What occours with intraepidermal vesicular dermatitis?
- autoAb to desmosomal adhesion molecules (desmogleins)
- separation of keratinocyutes (acantholysis)
- blister/pustule formation
eg. of intraepidermal vesicular dermatitis? What is seen in this condition?
- pemphigus vulgaris
- suprabasilar clefting (“tombstone” appearance on histo as basal keratinocytes still attached to basement membrane)
- oral cavity affected in 90% cases
- mucocutaneous junction, claws, ears, axilla, grouin
- 2* bacterial infection common
- fever and depression severe
Dx of pemphigus vulgaris?
- h, cs
- skin biopsy: cupra basilar split, tombstones, FEW inflam cells)
Tx and prognosis of pemphigus vulgaris?
- suppress immune response (See later questinos on general tx principles)
- prognosis poor, needs agressive tx, difficult to get on top of
Most common pemphigus disease? What type of disease is this?
- pemphigus folaceous
- intraepidermal pustular disease
Which animals are affected by pemphigus folaceous?
- dogs cats horses
Clinical signs of pemphigus folaceous?
- pustules, crusts, scales, hair loss, erosions, epidermal collarettes
- face (ears first)
- feet inc foot pads
- groin
- becomes generalised (esp horses)
- fever and depression if severe
- may wax and wane with no new lesions for weeks
Dx pemphigus folaceous?
- hx, cs
- biopsy
- pustule smears (acantholytic cells and neutrophils, NO BACTERIA)
- histo of multiple intact 1* lesions or edge of recent lesion (less useful)
What is the only cause of interface dermatitis?
- AUTOIMMUNE OR IMMUNE MEDIATED DISEASE!!
- > Tx = antiinflam
Histo of interface dermatitis? Egs. of pathologies that show this?
- dermo-epidermal junction obscured by inflammatory cells or hydropic [swollen, vacuolated] degeneration (or combination)
eg. - discoid lupus erythematosus (nasal cutaneous lupus)
- erythema multiforme/toxic epidermal necrolysis (immune mediated often triggered by drugs not autoimmune)
Where should melanin be found/not be found?
should NOT be found deep to demo-epidermal junction
-> this would be seen as DEPIGEMNTATION of skin
Alternative name for discoid lupus erythematosus?
nasal cutaneous lupus erythematosus
- not a form of systemic lupus erythematosus
nasal cutaneous LE common?
uncommon dogs, v rare in cats
What may nasal cutaneous lupus erythematosus be exaccerbated by?
exposure to sunlight
clinical signs of nasal cutaneous lupus erythematosus? breed predisposition?
> collies, shelties, gsd, huskies
- no systemic signs
- depigmentation, scaling and erythema of the nose (+- ears and periobribatal areas)
- loss of cobblestone appearance of nasal planum
- erosion and crusting
- small oral ulcers
- histo: cell rich, lymphocytic interface dermatitis
Tx discoid lupus erythematosus?
- avoid sunlight
- initial topical fluorinated GCs BID tapered to EOD
- switch to less potent 1-2% hydrocortisone or tacrolimus
- tetracycline/niacinamide tx combination
- Vit E and EFAs
- systemic prednisolone +- immunosuppressants if severity ^
Tx mild cases of immune mediated/autoimmune disease
- topical steroids
- vit E
- oxytet/niacinamide
- low dose steroids
Tx more severe autoimune disease
High dose steroid (pred or dexomethosone)
+ azathioprene (NOT CATS) - chlorambucil good for cats
- monitor for myelosuppression fortnightly
Dosage prednisolone? Actions?
- fast
> dogs: 2-4mg/kg SID -> EOD -> taper
> cats: double dosage required and tolerated - lower doses used for allergy tx
Dosage azathioprine? Actions?
- combination with systemic presnisolone (first line tx or if pred alone does not work)
- NOT FOR CATS
> dogs: 2-4mg/kg/d PO until response seen then EOD for 4-6 weeks -> taper - NB. cost
- monitor myeolosuppression ~ few weeks
What alternative drug to azathioprine can be given to cats? Dosage?
- Chlorambucil (good for cats with PF unresponisve to steroids alone)
> dogs and cats: 0.1-0.2 mg/kg q24-48hrs - monitor haem 2x monthly
Speed of action ciclopsporin? Efficacy and usefulness?
- works slow
- $$$
- poor efficacy in canine PF
- azathioprine for refrctory cases may be useful
What cases is tetracycline and niacinamide indicated for? Dose? When are effects ecpected to be seen?
- Abx + Vit B -> anti-inflam
- good for mild autoimmune diseases (risks of more potent drugs not justified)
> dogs>10kg = 500mg each substance q8hrs
> dogs<10kg 250mg TID - expect effects in 8 weeks
Is feline cowpox zoonotic? What type of virus is this and which animals acct as reservoir hosts? Which animals are susceptible?
- YES
- orthopoxvirus
- voles and woodmice reservoir -> hunting cats esp in rural environment
- esp seen in autumn when reservoir hosts most active
Clinical signs of feline cowpox? Ddx?
> Ddx = cat bite abscess/RTA
- small ulcer/abscessation/cellulitis face or distal limb
- 7-10d later, (viral replication in raining node and white cell assoc viraemia stage) multiple nodular lesions develop
- histo: inclusion bodies
- lesions well demarkated, raised, erthematous, vesicular top -> crust +- central depression or crater
Prognosis of pathgenesis of feline cowpox?
- spontaneously resolves after 4-6 weeks
- cats otherwise healthy
Dx feilne cowpox?
- virus isolation
- electron miccroscopy of crusts
- serology (cats seroconvert early)
- skin biopsy
> degernative changes in surface and follicular epithelium inc adnexal glands + marked dermal infiltrate of inflam cells. Characteristic intracytoplasmic eosinophilic inclusion bodies in non-necrotic epidermis
Tx feline cowpox?
NOT STEROIDS!!! -> pneumonia
- supportive symptomatic tx
- cowpox is a zoonosis but standard hygeine measured should prevent spread (beware immunosuppressed people)
How is vasculitis characterised?
- many cells in the vessel walls cf. dermis
- haemorrhage and oedema
- degeneration of endothelial cells
- +- infarcts and adnexal atrophy
> difficult dx in cats and dgos
where should inflammatory cells not be seen?
near an arteriole
Where may vasculitis be seen?
- extremitis (pinna, distal limb)
- immune complex deposition/infectious disease/idiopathic
Outline 3 main immune mediated clinical patterns and associated histological patterns.
> pustular crusts (PF)
- intraepidermal pustular
- neutrophils and acanthocytes
vesicles and bulla, erosions and ulcers (PV + BP +BP variants)
- intra/subepidermal vesicular, skin and mms
- suprabasalar split (PV), both cell poor
erythema, vesicles, erosions and depigmentation (LE)
- interface, widespread or confined nasal planum
- cell rich, lymphocytic
