SAD - Ch 9 - Autoimmune Flashcards
What are the cutaneous signs associated with cryoglobulins and cryofibrinogens?
similar to vasculitis – pain, erythema, purpura, acrocyanosis, necrosis, ulceration; more commonly affects extremities and is precipitated by exposure to heat/cold
What are the most common clinical signs with feline SLE?
dermatological manifestations (generalized seborrheic skin disease, exfoliative erythroderma, erythematous crusting and scaling), glomerulonephritis, hemolytic anemia, neurological signs*** (more common than in the dog), fever less common than the dog
What is the distribution of lesions with CANINE pemphigus foliaceus?
head, face, ears; trunk, footpads
What lesions are typically seen with Equine Pemphigus foliaceus?
erosions, crusts, crust-scales, tufted crusts
What breed of dog is more likely to develop toxicityfrom azathioprine? Why?
Giant Schnauzers; lower levels of TMPT (thiopurine methyltransferase)
How soon after rabies vaccination can cutaneous vasculitis lesions appear? What are clinical signs?
2-6 months, can last for months to years; clinical signs are alopecia, hyperpigmentation, +/- scaling or erythema
What is the mechanism of action of tetracycline in treating autoimmune diseases?
- suppression of in vitro lymphocyte blastogenic transformation and antibody production
- inhibition of MMP
- downregulation of cytokines
- suppression of an in vivo leukocyte chemotactic responses
- inhibition of the activation of complement component 3
- inhibition of lipases and collagenases
- inhibition of prostaglandin synthesis
- antimicrobial effects due to reversible binding of tetracycline to the 30S ribosomal subunit of susceptible bacteria and inhibition of protein synthesis by interfering with the binding of aminoacyl-transfer RNA
Paraneoplastic pemphigus has histopathological features of what two diseases?
pemphigus vulgaris + erythema multiforme
What should be monitored with leflunomide?
CBC, liver enzymes
What breed is over-represented with mucous membrane pemphigoid?
GSD
For what diseases has leflunomide been used?
systemic and cutaneous reactive histiocytosis, IMHA, IMPA, ITP, IBD, vasculitis, MUE
What are type I cryoglobulins? What are they also known as? What are they most commonly associated with?
monoclonal immunoglobulins or free light chains; AKA Bence Jones proteins; seen with lymphoproliferative disorders
What dermatophyte is the usual causative agent of pustular dermatophytosis in the dog?
Trichophyton mentagrophytes (T. terestrae, Microsporum persicolor also reported)
What interaction can occur between cyclosporine and macrocyclic lactones?
decreased efflux of macrocyclic lactones from blood-brain barrier cells and potential risk of CNS toxicity
What are the clinical features of bullous pemphigoid?
hair skin usually affected, mucosal lesions rarely, spares pads***
What is 6-mercaptopurine and how is it metabolized?
one of the active metabolites of azathioprine, metabolized by xanthine oxidase, thiopurine methyltransferase (TMPT)
What are the clinical features of canine discoid lupus erythematosus?
depigmentation of the nose, loss of normal cobblestone architecture, erythema, scaling –> erosions, ulcerations and crusting in chronic cases
What is the mechanism of action of niacinamide in treating autoimmune diseases?
blocks antigen IgE-induced histamine release in vivo and vitro
- prevents degranulation of mast cells
- acts as a photoprotectants from inducing immunologic damage
- acts as a cytoprotectant that blocks inflammatory cell activation and apoptosis
- inhibits phosphodiesterases
- decreases protease release
T/F: Basal keratinocyte injury and loss is absent on histopathology of UV syndrome.
True - limited or absent
What are predictable adverse drug reactions?
usually dose dependent and related to the pharmacologic actions of the drugs
What cells are seen on histopathology with bullous systemic lupus erythematosus type 1?
neutrophils and histiocytes
Low levels of what enzyme are more likely to lead to myelotoxicity with azathioprine?
thiopurine methyltransferase (TMPT)
What class of drugs is dapsone a part of?
sulfone antimycobacterial and antiprotozoal
What AISBDs have been described in dogs and cats?
acquired junctional epidermolysis bullosa, bullous pemphigoid, epidermolysis bullosa acquisita, linear IgA bullous disease, mixed AISBC, mucous membrane pemphigoid, type 1 bullous systemic lupus erythematosus
Adverse effects of niacinamide?
vomiting, diarrhea, anorexia, increased liver enzymes, increased seizure activity
What is the target antigen of bullous pemphigoid?
collagen XVII
A familial cutaneous vasculopathy has been described in what breed? What is method of inheritance?
German shepherd dogs, autosomal recessive trait
What is the mechanism of action of chlorambucil?
cross-links DNA; cell cycle non-specific cytotoxic alkylating immunosuppressant and antineoplastic agent derived from nitrogen mustard
What drugs are the most commonly recognized agents responsible for idiosyncratic cutaneous adverse drug reactions?
topical agents, sulfonamides (especially potentiated), penicillins, cephalosporins, levamisole, diethylcarbamazine
Why are cats more susceptible to myelosuppression with azathioprine?
they have lower levels of thiopurine methyltransferase (TMPT)
Against which cell types is cyclophosphamide most effective?
Lymphocytes – B cells > T cells (affects both humoral and cell-mediated immunity)
What is azathioprine metabolized to?
6-mercaptopurine
What are the proposed mechanisms for antibodies leading to acantholysis?
1) steric hindrance - physically prevents binding from occurring; 2) Signaling disruption - inhibition of desmosome assembly and promotion of its disassembly by clustering and/or endocytosis of cadherins
What infectious diseases can result in positive ANA titers?
Bartonella vinsonii, Ehrlichia canis, Leishmania infantum
What are the histopathological features of pemphigus erythematosus?
intragranular and subcorneal pustules (neuts + eos) plus a lichenoid-interface dermatitis
What is the usual presenting complaint for uveodermatologic syndrome?
acute bilateral uveitis, blindness or poor/decreased vision, conjunctivitis
What cutaneous adverse reactions have been reported with methimazole use?
pruritus and excoriations of face and neck
Where is collagen IV (top or bottom of blister) with acquired junctional epidermolysis bullosa?
Bottom of blister
What is the proposed pathomechanism of blister formation in bullous pemphigoid?
1) binding of complement-fixin pemphigoid antibody to noncollagenous domain NC16A of collagen XVII
2) complement fixation and activation
3) activation of mast cells, chemotactic cytokines
4) chemoattraction of neuts and eos
5) release of proteolytic enzymes from leukocytes –> disruption of dermo-epdermal cohesion –> vesicle
Adverse effects of tetracyclines?
GI signs (vomiting, nausea, diarrhea, lethargy), renal tubular necrosis and hepatotoxicity; may aggravate azotemia in renal failure; urolith formation with long-term use; affects tooth formation in young animals; phototoxic reactions such as cutaneous edema and erythema after sun exposure; **false-positive glucose urine test results when copper sulfate reagents are used and false negative results when glucose oxidase reagants are used
What adjunctive therapies may be useful in treating ECLE?
hydroxychloroquine, IVIG (Fas/CD95 blockade)
How can drug metabolites contribute to toxicity?
drug metabolites generated by cytochrome p450 (oxidative metabolizing enzymes) which are chemically active AND/OR reduced detoxification of the reactive metabolites
What treatments other than traditional immunosuppressives have been shown to be effective in treating EBA?
colchicine (humans), IVIG
What are the histopathological features of vesicular cutaneous lupus erythematosus?
cell-rich interface dermatitis with some vesiculation at dermoepidermal junction; +/- apoptotic keratinocytes
For what diseases has colchicine been used in dogs?
Cutaneous amyloidosis, Familial Shar-pei fever, Shar-pei acute neutrophilic vasculitis or amyloidosis, epidermolysis bullosa acquisita, hepatocutaneous syndrome
Which AISBD typically has a blister with no or little inflammation?
mucous membrane pemphigoid
What should be monitored with dapsone therapy?
CBC (due to potential IMHA, leukopenia), Chemistry (hepatotoxicity)
What vector-borne infectious diseases are associated with cutaneous vasculitis?
Babesia, Ehrlichia/Anaplasma, Bartonella, Rickettsia rickettsii, Borrelia burgdorferi, Leishmania infantum
What is the major target antigen of pemphigus vegetans in dogs? Humans?
Dogs: DSG-1, Humans: DSG-3
What differentiates pseudopelade from alopecia areata?
lack of hair regrowth or poor hair regrowth
What sites are most commonly affected with pemphigus vulgaris?
mucosae/mucocutaneous junctions (oral cavity, nasal planum, lip margins, genitalia, anus & eyelids) & pinnae +/- haired skin
What is the target antigen of bullous systemic lupus erythematosus type 1?
collagen VII
What is the most common clinical sign of canine SLE?
joint disease (40-90% of patients)
What drugs can increase cyclosporine levels?
allopurinol, amiodarone, azole antifungals, bromocriptine, chloroquine, cimetidine, cisapride, corticosteroids, danazol, grapefruit juice, losartan, valsartan, macrolide antibiotics, metoclopramide, omeprazole, sertraline
What is the treatment for disease associated with cryoglobulinemia and cryofibrinogenemia?
1) correction of underlying cause if possible, 2) avoidance of cold, 3) immunosuppressive drugs
What is/are the target antigen(s) of mucus membrane pemphigoid?
BPAG-1, collagen XVII, laminin 332
What are the adverse effects reported with mycophenolate mofetil?
GI signs** (hemorrhagic diarrhea), secondary skin infections
What is the most common AISBD in dogs?
mucous membrane pemphigoid (>50% of cases of AISBD)
Other than biopsy with histopathological, what test may be useful for confirming a diagnosis of vasculitis? Why?
D-dimers; many vasculitis cases will have thrombus formations => fibrin in thrombus broken down => fibrin degradation products (D-dimers)
What cutaneous adverse reactions have been reported with cyclosporine use?
lymphoplasmacytoid dermatitis (plaque, nodules), gingival hyperplasia
T/F: With insecticide-triggered pemphigus foliaceus, lesions are only seen at the site of application.
False- predominantly at the site of application, but may be seen in other body areas typical of PF
What is the mechanism of action of dapsone?
sulfone with bacteriostatic and bactericidal activities; affects folic acid synthesis; anti-inflammatory properties by decreasing neutrophil chemotaxis, complement activation, antibody production, and lysosomal enzyme synthesis
What are the histopathological features of pemphigus vegetans?
epidermal hyperplasia (papillomatous or verrucous) + suprabasal acantholysis + intraepidermal “microabscesses” with mixed inflammation (neutrophils/eosinophils)
What are the most common clinical signs with SLE?
fever, joint disease, skin disease, glomerulonephritis
What are the dermatologic features of SLE? How common are they?
40-50% of cases of SLE have skin lesions; range from mild alopecia and scarring to widespread ulceration
What are the treatment principles for toxic epidermal necrolysis?
1) stop any suspected drug/correct underlying cause, 2) flud & electrolyte replacement, 3) ulcer wound management to prevent infections and sepsis
What clinical signs are typically seen with acute graft-versus-host disease (within 2 weeks)?
erythroderma, jaundice, diarrhea, gram-negative infections
What dermatophyte is the usual causative agent of pustular dermatophytosis in the horse?
Trichophyton equinum
What are the histopathological features of paraneoplastic pemphigus?
suprabasal acantholysis, transepidermal apoptotic keratinocytes, lymphocytic interface dermatitis
What areas are usually affected with Equine pemphigus foliaceus?
generalized, facial (pinnae, muzzle, eyelids), extremities (distal limbs, coronary bands), neck, trunk, ventral edema & systemic signs seen in about half of patients
A collection of fluid underneath the epidermis is known as what?
blister
What is the key event in initiation of toxic epidermal necrolysis in people?
massive keratinocyte apoptosis
What are the histopathological features of systemic lupus erythematosus?
lichenoid or hydropic interface dermatitis - may extend to hair follicle and outer root sheath; +/- apoptosis of basal or suprabasal cells; +/- subepidermal vacuolar lateration; +/- pigmentary incontinence
Which AISBD(s) has/have NOT been reported in cats?
epidermolysis bullosa acquisita
T/F: Pruritus is more commonly seen with feline pemphigus foliaceus compared to canine.
True (~80% of cats can have pruritus, 17-36% of dogs)
What is a unique side effect of cyclophosphamide? How is this mitigated?
sterile hemorrhagic cystitis; decreased with concurrent furosemide therapy
What are the histopathological features of alopecia areata?
peribulbar to inferior hair follicle accumulation of lymphocytes, macrophages or dendritic cells +/- plasma cells; chronic lesions – follicular and hair shaft dysplasia, predominance of catagen and telogen hair follicles, follicular atrophy
T/F: Idiosyncratic drug reactions are directly related to the dose of the medication.
False - dose independent, related to individual’s immunologic response or to genetic differences in patient susceptibility, related to metabolic or enzymatic deficiencies
Differentials for DLE in the dog
dermatomyositis, uveodermatologic syndrome, contact dermatitis, SLE
Amyloidosis is usually associated with what disease(s) in dogs & cats?
chronic inflammatory disease, neoplasia, accumulation of plasma cells
Proliferative arteritis of the nasal philtrum is common in what breed?
Saint Bernards
When is a nadir expected with chlorambucil?
7-14 days after the start of therapy