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Immune Mediated Diseases
VM 610 Midterm
58
Veterinary Medicine
Professional
11/13/2012

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Term
Primary autoimmune disease
Definition
response directed against normal host constituents (self-antigens)
loss of tolerance to normal self antigens
Term
Secondary autoimmune diseases
Definition
destruction of normal host constituents secondary to immunolig event (foreign antigens)
bacteria, viruses, drugs
Term
Hormone Influences on Autoimmunity
Definition
predilection for females
female sex hormones may promote autoimmunity (estrogen and progesterone)
Term
Type II Direct Cytotoxicity
Definition
damage to target cells mediated by IgG, IgM, C2
examples: systemic lupus erythematosus, bullous pemphigoid, some drug reactions
Term
Type III Immune Complex
Definition
immune complexes are deposited in tissues and attract neutrophils that cause inflammation
Term
Type IV Delayed Hypersensitivity
Definition
tissue damage from activated T cells cytotoxic action
Term
Type V Antibody Activated Cell Damage
Definition
autoantibodies target desmogleins that are between cells in the juncions
cause destruction of cytoskeleton/desmosomes result in acantholysis
Term
Therapy for Immune Mediated Diseases
Definition
can be life threatening
treatments must be individualized
medication side effects are common
don't stop therapy abruptly
sunlight exacerbates condition
Term
Topical Therapy
Definition
supportive care with antiseptic and antiseborrheic
glucocorticoids and tacrolimus
Term
Systemic Glucocorticoids
Definition
most commonly used and highly effective
affect cell-mediated and humoral immunity
inhibits cytokines
inhibits chemotaxis
inhibits phagocytosis
Term
Glucocorticoids Side Effects
Definition
PU/PD
polyphagia
weight gin
dull hair coat
alopecia
muscle atrophy
thinning of skin
increased risk of infections
steroid hepatopathy
increased risk of diabetes mellitus
Term
Monitoring Glucocorticoids
Definition
monthly monitoring during induction
CBC and chemistry profiles
urinalysis and culture
watch for diabetes in cats
Term
Glucocorticoid Potency
Definition
dexamethasone > triamcinolone > Methylprednisolone > Prednisone > Hydrocortisone
Term
Azathioprine
Definition
antimetabolite
interferes with synthesis of nucleic acids
cytotoxic to T cells
slow onset of action
often combined with steroids to decrease the dose
do not use in cats
Term
Cyclophosphamide
Definition
alkalating agent
suppressed both humor and cell-mediated immunity
used for refractory cases of pemphigus
Term
Cyclophosphamide Side Effects
Definition
bone marrow suppression
sterile hemorrhagic cystitis
bladder fibrosis and neoplasia
vomiting/diarrhea, hair loss
infections
Term
Chorambucil
Definition
alkalating agent
suppresses both humoral and cell mediated immunity
may combine with steroids and/or azathioprine
Term
Tetracycline
Definition
antibiotic that has anti-inflammatory effects
decreases complement activation
decreases antibody production
decreases chemotaxis
decreases lymphocyte proliferation
decreases synthesis of prostaglandins, lipases, and collagenase
Term
Niacinamide
Definition
used in combination with tetracyclines for anti-inflammatory effects
blocks antigen and IgG-induced histamine released
inhibits mast cell degranulation and mediator release
Term
Cyclosporine
Definition
potent immunosuppressive
calineurin inhibitor which blocks gene transcription and alters mediator synthesis
targets T-cells and inhibits T helper cells and T cytotoxic cells
decreases cytokine production, antigen processing, macrophage activity, neutrophil adherence, mast cells in skin, eosinophil production, NK cell activity
Term
Cyclosporine Metabolism
Definition
metabolized by P450 enzymes in liver
need to consider other drugs that may increase/decrease P450 enzymes
Term
Cyclosporine Side Effects
Definition
anorexia, vomiting, diarrhea
gingival hyperplasia
cutaneous papillomas, hisutism
nephrotoxicity, hepatotoxicity, bone marrow suppression
secondary infections, neoplasia
Term
Tacrolimus/Pimecrolimus
Definition
topical calcineurin inhibitor
inhibits activation of T cells and mast cells in skin
useful for treating localized lesions
owners need to wear gloves when applying
Term
Mycophenolate Mofetil
Definition
inhibits purine synthesis
decrease DNA and RNA synthesis
cytotoxic to proliferating T and B cells
decreases antigen processing
decreases macrophage function
Term
Chrysotherapy
Definition
gold salts
Term
Dapsone
Definition
NOT FOR CATS
used when other treatments fail
decreases complement activation
decreases mast cell degranulation
decreases antibody production
decreases lysosomal enzyme synthesis
decreases neutrophil chemotaxis and respiratory burst
decreases leukotrienes
decreases bacterial growth
Term
Sulfsalazine
Definition
decreases neutrophil chemotaxis
decreases bacterial growth
decreases purine synthesis
anti-inflammatory
used to treat neutrophilic vasculitis
watch for KCS, drug allergies, hypothyroidism
used to treat colitis
Term
Human Immunologlobulin Therapy
Definition
used for serious diseases not for skin diseases
Term
Key Areas to Examine
Definition
around claw beds, foot pads, around the lips
around periocular region, nose and face
Term
History
Definition
predisposed breed
middle aged to older animals affected
other body system signs
sunlight exposure is an environmental factor that can affect these
often not pruritic
many are chronic and slowly progressing
may be brought on by drugs or vaccines
Term
Types of Lesions
Definition
alopecia, pustules/blisters
crust/scale, erosions/ulcers
nodules/papillomas
depigmentation
loss of normal texture of nose
hyperkeratosis
nail abnormalities
Term
Pemphigus
Definition
pemphigus foliaceus is the most common
primary target of autoantibodies are desmoglein 3 in lower epidermis and desmoglein 1 in upper epidermis
desmoglein 3 is most common at mucocutaneous junctions and in oral cavity
desmoglein 1 is highest in skin on face
Pemphigus vulgaris - attacks desmoglein 3
Term
Pemphigus Pathogenesis
Definition
pemphigus antibodies bind to pemphigus antigens (desmosomes) on keratinocytes
internalization of antibody
activation and release of proteolytic enzymes (plasmingogen activator)
plasminogen converted to plasmin
plasmin hydrolyzes cell adhesion molecules and causes acantholysis
acantholysis: loss of intercellular connections
Term
Pemphigus foliaceus
Definition
most common pemphigus disease
affects many species
any age possible although more common as middle aged
Term
Pemphigus foliaceus cause
Definition
underlying cause may be spontaneous, secondary to trichophyton
drug induced
paraneoplastic
some breeds are predisposed (chows and cocker spaniels)
Term
Pemphigus foliaceus Signs
Definition
alopecia, scale, erythema
erosions, nasal depigmentation
hyperkeratosis of pads
+/- pruritis, otitis externa
papules, pustules, vesciles, ulcers
may have fever/anorexia
distributed on faces, ears, feet/pads, nails(cats), around nipples (cats), generalized
Term
Pemphigus foliaceus Diagnosis
Definition
impression smear, skin scraping, DTM culture, biopsy
will see acantholytic keratinocytes
immunofluroescence
Term
Pemphigus foliaceus Treatment
Definition
need to treat many months past clinical resolution or for life
induction phase includes immunosuppressive doses of glucocorticoids
may need to add other immunosuppressive drugs for induction phase
then gradually taper dose during maintenance phase to lowest effective dose
antibiotics and topicals also
Term
Pemphigus erythematosus
Definition
Collies and German Shepherds are predisposed
sunlight exacerbates condition
Term
Pemphigus erythematosus Signs
Definition
most of the lesions are on the face and start on the nose
pustules with oozing crusts, erythema, alopecia
erosions, nasal depigmenttion, hyperkeratosis
distributed on face, ears, nose, paws, genitalia
Term
Pemphigus erythematosus Treatment
Definition
photoprotection
topical glucocorticoids/tacrolimus
tetracycline/niacinamide
omega 3 FA
glucocorticoids
rarely more potent immunosuppressive drugs
Term
Pemphigus vulgaris
Definition
no age or breed predilections
dogs and cats
Term
Pemphigus vulgaris Signs
Definition
vesicles/bulla
erosions and ulcers
may have pruritis
oral and mucocutaneous lesions common
axilla, groin, clawbed, paw pad, concave pinna
fever, anorexia, depression, lymphadenopathy, pain
Term
Pemphigus vulgaris Diagnosis
Definition
biopsy and signs
Term
Pemphigus vulgaris Management
Definition
corticosteroids
supportive care
Term
Pemphigoid Diseases
Definition
autantibodies are different than pemphgius diseases
antibodies directed to hemidesmosomes in basement membrane zone
creates separation between epidermis and dermis
don't see acantholytic keratinocytes
clefts and vesicles form below stratum basale
Term
Mucous Membrane Pemphigoid
Definition
rare
autoantibodies against collagen and laminin 5
around mucous membranes
Term
Discoid Lupus Erythematosus
Definition
common in dogs
young to middle aged
affects long nosed dogs
especially areas of white around their nose or muzzle
Term
Discoid Lupus Erythematosus Signs
Definition
nose, muzzle, face, ears, lips
depigmentation, erythema, alopecia, scaling, crusting
loss of cobblestone texture of nasal planum
erosions, ulcers, scars
Term
Discoid Lupus Erythematosus Management
Definition
sun avoidance
topical gluocorticoids or tacrolimus
topical antibiotics
tetracycline/niacinamide
omega 3 FA
vitamin E
oral corticosteroids
Term
Uveodermatologic Syndrome
Definition
antibodies attack melanin and melanocytes
causes depigmentation of the nose
predisposed breeds are arctic breeds
Term
Uveodermatologic Syndrome Signs
Definition
uveitis, photophobia
depigmentation of planum nasale, lips, eyelids
erosions/ulcers
Term
Uveodermatologic Syndrome Diagnosis
Definition
biopsy
rule out other causes of uveitis
Term
Uveodermatologic Syndrome Management
Definition
topical corticosteroids, tropine
systemic corticosteroids, azathioprine
cyclophosphamide
Term
Symmetric Lupoid Onychodystrophy
Definition
German Shepherds, Rottwielers
3-8 years old
antigen unknown
may have underlying food allergy, drug reaction, immune mediated disease
Term
Symmetric Lupoid Onychodystrophy Signs
Definition
may initially involve one claw and later multiple ones
secondary paronychia
misshapen, brittle claws, pain on palpation
Term
Symmetric Lupoid Onychodystrophy Diagnosis
Definition
biopsy or P3 removal
Term
Symmetric Lupoid Onychodystrophy Management
Definition
avulse loose nails
keep nails trimmed short
pain management
omega 3 fatty acids
novel protein diet tril
vitamin E
tetracyline + niacinamide
glucocorticoids
declawing
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