SAD - Ch 9 - Autoimmune Flashcards

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1
Q

What are the cutaneous signs associated with cryoglobulins and cryofibrinogens?

A

similar to vasculitis – pain, erythema, purpura, acrocyanosis, necrosis, ulceration; more commonly affects extremities and is precipitated by exposure to heat/cold

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2
Q

What are the most common clinical signs with feline SLE?

A

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

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3
Q

What is the distribution of lesions with CANINE pemphigus foliaceus?

A

head, face, ears; trunk, footpads

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4
Q

What lesions are typically seen with Equine Pemphigus foliaceus?

A

erosions, crusts, crust-scales, tufted crusts

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5
Q

What breed of dog is more likely to develop toxicityfrom azathioprine? Why?

A

Giant Schnauzers; lower levels of TMPT (thiopurine methyltransferase)

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6
Q

How soon after rabies vaccination can cutaneous vasculitis lesions appear? What are clinical signs?

A

2-6 months, can last for months to years; clinical signs are alopecia, hyperpigmentation, +/- scaling or erythema

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7
Q

What is the mechanism of action of tetracycline in treating autoimmune diseases?

A
  • 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
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8
Q

Paraneoplastic pemphigus has histopathological features of what two diseases?

A

pemphigus vulgaris + erythema multiforme

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9
Q

What should be monitored with leflunomide?

A

CBC, liver enzymes

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10
Q

What breed is over-represented with mucous membrane pemphigoid?

A

GSD

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11
Q

For what diseases has leflunomide been used?

A

systemic and cutaneous reactive histiocytosis, IMHA, IMPA, ITP, IBD, vasculitis, MUE

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12
Q

What are type I cryoglobulins? What are they also known as? What are they most commonly associated with?

A

monoclonal immunoglobulins or free light chains; AKA Bence Jones proteins; seen with lymphoproliferative disorders

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13
Q

What dermatophyte is the usual causative agent of pustular dermatophytosis in the dog?

A

Trichophyton mentagrophytes (T. terestrae, Microsporum persicolor also reported)

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14
Q

What interaction can occur between cyclosporine and macrocyclic lactones?

A

decreased efflux of macrocyclic lactones from blood-brain barrier cells and potential risk of CNS toxicity

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15
Q

What are the clinical features of bullous pemphigoid?

A

hair skin usually affected, mucosal lesions rarely, spares pads***

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16
Q

What is 6-mercaptopurine and how is it metabolized?

A

one of the active metabolites of azathioprine, metabolized by xanthine oxidase, thiopurine methyltransferase (TMPT)

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17
Q

What are the clinical features of canine discoid lupus erythematosus?

A

depigmentation of the nose, loss of normal cobblestone architecture, erythema, scaling –> erosions, ulcerations and crusting in chronic cases

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18
Q

What is the mechanism of action of niacinamide in treating autoimmune diseases?

A

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
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19
Q

T/F: Basal keratinocyte injury and loss is absent on histopathology of UV syndrome.

A

True - limited or absent

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20
Q

What are predictable adverse drug reactions?

A

usually dose dependent and related to the pharmacologic actions of the drugs

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21
Q

What cells are seen on histopathology with bullous systemic lupus erythematosus type 1?

A

neutrophils and histiocytes

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22
Q

Low levels of what enzyme are more likely to lead to myelotoxicity with azathioprine?

A

thiopurine methyltransferase (TMPT)

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23
Q

What class of drugs is dapsone a part of?

A

sulfone antimycobacterial and antiprotozoal

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24
Q

What AISBDs have been described in dogs and cats?

A

acquired junctional epidermolysis bullosa, bullous pemphigoid, epidermolysis bullosa acquisita, linear IgA bullous disease, mixed AISBC, mucous membrane pemphigoid, type 1 bullous systemic lupus erythematosus

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25
Q

Adverse effects of niacinamide?

A

vomiting, diarrhea, anorexia, increased liver enzymes, increased seizure activity

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26
Q

What is the target antigen of bullous pemphigoid?

A

collagen XVII

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27
Q

A familial cutaneous vasculopathy has been described in what breed? What is method of inheritance?

A

German shepherd dogs, autosomal recessive trait

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28
Q

What is the mechanism of action of chlorambucil?

A

cross-links DNA; cell cycle non-specific cytotoxic alkylating immunosuppressant and antineoplastic agent derived from nitrogen mustard

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29
Q

What drugs are the most commonly recognized agents responsible for idiosyncratic cutaneous adverse drug reactions?

A

topical agents, sulfonamides (especially potentiated), penicillins, cephalosporins, levamisole, diethylcarbamazine

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30
Q

Why are cats more susceptible to myelosuppression with azathioprine?

A

they have lower levels of thiopurine methyltransferase (TMPT)

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31
Q

Against which cell types is cyclophosphamide most effective?

A

Lymphocytes – B cells > T cells (affects both humoral and cell-mediated immunity)

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32
Q

What is azathioprine metabolized to?

A

6-mercaptopurine

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33
Q

What are the proposed mechanisms for antibodies leading to acantholysis?

A

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

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34
Q

What infectious diseases can result in positive ANA titers?

A

Bartonella vinsonii, Ehrlichia canis, Leishmania infantum

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35
Q

What are the histopathological features of pemphigus erythematosus?

A

intragranular and subcorneal pustules (neuts + eos) plus a lichenoid-interface dermatitis

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36
Q

What is the usual presenting complaint for uveodermatologic syndrome?

A

acute bilateral uveitis, blindness or poor/decreased vision, conjunctivitis

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37
Q

What cutaneous adverse reactions have been reported with methimazole use?

A

pruritus and excoriations of face and neck

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38
Q

Where is collagen IV (top or bottom of blister) with acquired junctional epidermolysis bullosa?

A

Bottom of blister

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39
Q

What is the proposed pathomechanism of blister formation in bullous pemphigoid?

A

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

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40
Q

Adverse effects of tetracyclines?

A

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

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41
Q

What adjunctive therapies may be useful in treating ECLE?

A

hydroxychloroquine, IVIG (Fas/CD95 blockade)

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42
Q

How can drug metabolites contribute to toxicity?

A

drug metabolites generated by cytochrome p450 (oxidative metabolizing enzymes) which are chemically active AND/OR reduced detoxification of the reactive metabolites

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43
Q

What treatments other than traditional immunosuppressives have been shown to be effective in treating EBA?

A

colchicine (humans), IVIG

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44
Q

What are the histopathological features of vesicular cutaneous lupus erythematosus?

A

cell-rich interface dermatitis with some vesiculation at dermoepidermal junction; +/- apoptotic keratinocytes

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45
Q

For what diseases has colchicine been used in dogs?

A

Cutaneous amyloidosis, Familial Shar-pei fever, Shar-pei acute neutrophilic vasculitis or amyloidosis, epidermolysis bullosa acquisita, hepatocutaneous syndrome

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46
Q

Which AISBD typically has a blister with no or little inflammation?

A

mucous membrane pemphigoid

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47
Q

What should be monitored with dapsone therapy?

A

CBC (due to potential IMHA, leukopenia), Chemistry (hepatotoxicity)

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48
Q

What vector-borne infectious diseases are associated with cutaneous vasculitis?

A

Babesia, Ehrlichia/Anaplasma, Bartonella, Rickettsia rickettsii, Borrelia burgdorferi, Leishmania infantum

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49
Q

What is the major target antigen of pemphigus vegetans in dogs? Humans?

A

Dogs: DSG-1, Humans: DSG-3

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50
Q

What differentiates pseudopelade from alopecia areata?

A

lack of hair regrowth or poor hair regrowth

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51
Q

What sites are most commonly affected with pemphigus vulgaris?

A

mucosae/mucocutaneous junctions (oral cavity, nasal planum, lip margins, genitalia, anus & eyelids) & pinnae +/- haired skin

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52
Q

What is the target antigen of bullous systemic lupus erythematosus type 1?

A

collagen VII

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53
Q

What is the most common clinical sign of canine SLE?

A

joint disease (40-90% of patients)

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54
Q

What drugs can increase cyclosporine levels?

A

allopurinol, amiodarone, azole antifungals, bromocriptine, chloroquine, cimetidine, cisapride, corticosteroids, danazol, grapefruit juice, losartan, valsartan, macrolide antibiotics, metoclopramide, omeprazole, sertraline

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55
Q

What is the treatment for disease associated with cryoglobulinemia and cryofibrinogenemia?

A

1) correction of underlying cause if possible, 2) avoidance of cold, 3) immunosuppressive drugs

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56
Q

What is/are the target antigen(s) of mucus membrane pemphigoid?

A

BPAG-1, collagen XVII, laminin 332

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57
Q

What are the adverse effects reported with mycophenolate mofetil?

A

GI signs** (hemorrhagic diarrhea), secondary skin infections

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58
Q

What is the most common AISBD in dogs?

A

mucous membrane pemphigoid (>50% of cases of AISBD)

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59
Q

Other than biopsy with histopathological, what test may be useful for confirming a diagnosis of vasculitis? Why?

A

D-dimers; many vasculitis cases will have thrombus formations => fibrin in thrombus broken down => fibrin degradation products (D-dimers)

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60
Q

What cutaneous adverse reactions have been reported with cyclosporine use?

A

lymphoplasmacytoid dermatitis (plaque, nodules), gingival hyperplasia

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61
Q

T/F: With insecticide-triggered pemphigus foliaceus, lesions are only seen at the site of application.

A

False- predominantly at the site of application, but may be seen in other body areas typical of PF

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62
Q

What is the mechanism of action of dapsone?

A

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

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63
Q

What are the histopathological features of pemphigus vegetans?

A

epidermal hyperplasia (papillomatous or verrucous) + suprabasal acantholysis + intraepidermal “microabscesses” with mixed inflammation (neutrophils/eosinophils)

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64
Q

What are the most common clinical signs with SLE?

A

fever, joint disease, skin disease, glomerulonephritis

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65
Q

What are the dermatologic features of SLE? How common are they?

A

40-50% of cases of SLE have skin lesions; range from mild alopecia and scarring to widespread ulceration

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66
Q

What are the treatment principles for toxic epidermal necrolysis?

A

1) stop any suspected drug/correct underlying cause, 2) flud & electrolyte replacement, 3) ulcer wound management to prevent infections and sepsis

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67
Q

What clinical signs are typically seen with acute graft-versus-host disease (within 2 weeks)?

A

erythroderma, jaundice, diarrhea, gram-negative infections

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68
Q

What dermatophyte is the usual causative agent of pustular dermatophytosis in the horse?

A

Trichophyton equinum

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69
Q

What are the histopathological features of paraneoplastic pemphigus?

A

suprabasal acantholysis, transepidermal apoptotic keratinocytes, lymphocytic interface dermatitis

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70
Q

What areas are usually affected with Equine pemphigus foliaceus?

A

generalized, facial (pinnae, muzzle, eyelids), extremities (distal limbs, coronary bands), neck, trunk, ventral edema & systemic signs seen in about half of patients

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71
Q

A collection of fluid underneath the epidermis is known as what?

A

blister

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72
Q

What is the key event in initiation of toxic epidermal necrolysis in people?

A

massive keratinocyte apoptosis

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73
Q

What are the histopathological features of systemic lupus erythematosus?

A

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

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74
Q

Which AISBD(s) has/have NOT been reported in cats?

A

epidermolysis bullosa acquisita

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75
Q

T/F: Pruritus is more commonly seen with feline pemphigus foliaceus compared to canine.

A

True (~80% of cats can have pruritus, 17-36% of dogs)

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76
Q

What is a unique side effect of cyclophosphamide? How is this mitigated?

A

sterile hemorrhagic cystitis; decreased with concurrent furosemide therapy

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77
Q

What are the histopathological features of alopecia areata?

A

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

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78
Q

T/F: Idiosyncratic drug reactions are directly related to the dose of the medication.

A

False - dose independent, related to individual’s immunologic response or to genetic differences in patient susceptibility, related to metabolic or enzymatic deficiencies

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79
Q

Differentials for DLE in the dog

A

dermatomyositis, uveodermatologic syndrome, contact dermatitis, SLE

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80
Q

Amyloidosis is usually associated with what disease(s) in dogs & cats?

A

chronic inflammatory disease, neoplasia, accumulation of plasma cells

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81
Q

Proliferative arteritis of the nasal philtrum is common in what breed?

A

Saint Bernards

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82
Q

When is a nadir expected with chlorambucil?

A

7-14 days after the start of therapy

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83
Q

List 3 DDX for acantholytic pustular dermatitis in the cat. Horse?

A

pemphigus foliaceus, pustular dermatophytosis, impetigo (rare) – same for both species

84
Q

What are the clinical features of exfoliative cutaneous lupus erythematosus (breed, characteristic lesions, distribution)?

A

GSP; scaling and alopecia on the muzzle, pinnae, dorsal trunk –> limbs and ventral trunk, ulceration and crusting may develop; joint disease also a characteristic feature*

85
Q

What cells are seen on histopathology with mucous membrane pemphigoid?

A

variable – acellular or may have neutrophils and eosinophils, superficial dermis will have a lymphoplasmacytic bandlike infiltrate

86
Q

T/F: Females are more predisposed to develop pemphigus foliaceus than males.

A

false: no sex predilection in dogs. HOWEVER, female cats are 1.4x more frequent than males

87
Q

What cell types are different with graft-versus-host disease compared to erythema multiforme?

A

GVHD has fewer CD4+ T cells, CD1+ and CD11+ dendritic cells and no CD21+ B cells (all are present in EM)

88
Q

What are the clinical features of mixed AISBD?

A

affects haired skin and mucosal sites

89
Q

What is the target antigen of epidermolysis bullosa acquisita?

A

collagen VII

90
Q

What are the histopathological features of UV syndrome?

A

lichenoid interface granulomatous dermatitis with large histiocytes present; pronounced pigmentary incontinence

91
Q

What hematologic changes can be present with SLE? How common are these changes?

A

anemia (30-60%) – IMHA or anemia of chronic disease; thrombocytopenia (10-25%); leukopenia or leukocytosis (20-30%)

92
Q

List 4 DDX for acantholytic pustular dermatitis in the dog

A

pemphigus foliaceus, superficial pyoderma (impetigo), pustular dermatophytosis, pustular dermatitis due to leishmaniosis

93
Q

What breed is predisposed to Linear Immunoglobulin A Pustular Dermatosis?

A

Dachshunds

94
Q

What are the histopathological features of exfoliative cutaneous lupus erythematosus?

A

interface dermatitis composed of T lymphocytes extending to the infundibulum of the hair follicles as a mural folliculitis; +/- apoptosis of basal keratinocytes, sebaceous and sweat glands may be destroyed

95
Q

What are the clinical features of auricular chondritis?

A

swollen, erythematous, deformed, and often painful pinna

96
Q

What are the gold salts used in veterinary medicine?

A

aurothioglucose, sodium aurothiomalate, auranofin

97
Q

What is the most common treatment-related adverse event with pemphigus foliaceus?

A

development of diabetes mellitus (due to corticosteroid use)

98
Q

Granulomatous mural folliculitis has been reported as a cutaneous reaction pattern associated with what drugs?

A

amitraz, cefadroxil, topicals, L-thyroxine

99
Q

What chemotherapeutic agent is known to cause alopecia that begins on the head and extends to ventral neck, thorax, and abdomen?

A

doxorubicin

100
Q

What is the primary lesion of pemphigus vulgaris?

A

flaccid vesicle –> erosion

101
Q

What are the clinical features of alopecia areata?

A

focal or multifocal patches of asymptomatic noninflammatory alopecia (most common on head or face), leukotrichia, chronic lesions may become hyperpigmented

102
Q

What is the classic lesion of autoimmune subepidermal blistering diseases?

A

vesicle - clear, fluid-filled, small (<1 cm) blister

103
Q

IVIG has been shown to be of benefit for what immune-mediated skin disease?

A

Erythema multiforme

104
Q

T/F: The erythematous plaques of vasculitis blanch with diascopy.

A

false - confirms its purpuric nature

105
Q

What are the adverse effects reported with colchicine?

A

GI signs; rare - abdominal pain, malabsoprtion, increased liver enzymes, hair loss, bone marrow suppression, renal damage, neuromuscular side effects

106
Q

What breed is predisposed to uveodermatologic syndrome?

A

Akitas

107
Q

What are the clinical features of mucous membrane pemphigoid?

A

haired skin sparsely affected – mostly mucosal or mucocutaneous junctions, spares pads**

108
Q

What drugs should be avoided to give concurrently with colchicine? Why?

A

NSAIDs; increased risk of bone marrow suppression (thrombocytopenia, leukopenia)

109
Q

What is the major antigen in dogs with pemphigus foliaceus?

A

desmocollin-1

110
Q

What are cyroglobulins and cryofibrinogens?

A

proteins that preciptate from serum (globulins) and plasma (fibrinogens) by cooling and redissolve on warming

111
Q

What is the primary lesion of pemphigus foliaceus?

A

pustule –> erosion –> crust

112
Q

What diseases other than AISBDs can create subepidermal vesicles but also affect other parts of the skin (epidermis and hair follicles)?

A

erythema multiforme, TEN, dermatomyositis, vesicular cutaneous lupus erythematosus

113
Q

What is the distribution of lesions with pemphigus vegetans?

A

Mucosal lesions (oral & genital mucosae), flexural areas (groin, axilla, inter-gluteal folds, umbilicus or interdigital folds)

114
Q

What breeds of dog are over-represented with pemphigus vulgaris?

A

GSD and collies

115
Q

What monitoring parameters are recommending when using gold salts? Why?

A

CBC every 2 weeks - blood dyscrasias, eosinophilia may precede development of adverse reactions; Chemistry - nephro- and hepatotoxicity; Urinalysis - nephrotoxicity (proteinuria)

116
Q

What is the target antigen of linear IgA bullous disease?

A

shed collagen XVII

117
Q

What is the clinical presentation of familial cutaneous vasculopathy of German Shepherd dogs? Age of onset?

A

young puppies (usually by 7 weeks of age) - pyrexia, lethargy, swollen, depigmented footpads; alopecia, crusts, ulcerations of pinnae, tail, nasal planum

118
Q

What is the target cell of the autoimmune process associated with UV syndrome?

A

melanocytses or melanocyte-associated antigens (tyrosinase and gp100)

119
Q

What is the mechanism of action of colchicine?

A

disrupts microtubular proteins, alters cell functions such as mitosis, chemotaxis and cell adhesion; inhibits lysosomal degranulation, IL-1 production, secretion of immunoglobulins, histamine release, human leukocyte antigen (HLA)-DR expression, synthesis of collagen by stimulating the activity of collagenases; blocks secretion and synthesis of serum amyloid A by hepatocytes; inhibits the expression of leukocyte vascular endothelial growth factor

120
Q

Mechanism of action of oclacitinib?

A

janus kinase inhibitor - selectively binds/blocks JAK1 and JAK3. JAKs play roles in cytokine signaling and are involved in signal transduction of many pro-inflammatory, pro-allergic, and pruritogenic cytokines: reduces IL-31, IL-2, IL-4, IL-6, IL-13

121
Q

A familial tendency towards amyloidosis has been reported in what breed(s)?

A

Chinese Shar-Pei, beagles, Abyssinian & Siamese cats

122
Q

What is the mechanism of action of azathioprine?

A

antagonizes purine metabolism (interferes with DNA and RNA synthesis)

123
Q

What is the mechanism of action of mycophenolate mofetil?

A

prodrug, metabolized to active antiproliferative agent mycophenolic acid (MPA); specifically and reversibly inhibits the enzyme inosine monophosphate dehydrogenase, which is important for the de-novo syntehsis of guanine in T and B lymphocytes, blocks synthesis of purine, and prevents maturation of T and B lymphocytes; suppresses lymphocyte proliferation and reduces antibody production by B cells; induces T-lymphocyte apoptosis, dendritic cell maturation, decreases expression of IL-1 and enhances expression of IL-1 receptor antagonist

124
Q

Does epidermolysis bullosa acquisita progress slowly or quickly?

A

quickly

125
Q

What is the target antigen for mixed AISBD?

A

laminin 332 and collagen VII

126
Q

What cytokine is elevated in TEN but NOT erythema multiforme?

A

IL-13

127
Q

What breed of dog may need a higher dose of azathioprine? Why?

A

Alaskan malamutes; higher enzyme activity of TMPT (thiopurine methyltransferase)

128
Q

What bloodwork abnormalities can be seen with cyclosporine?

A

elevated creatinine, hyperglobulinemia, hyperphosphatemia, hyperproteinemia, hyperchloesterolemia, hypoalbuminemia, hypocalcemia, elevated BUN; hypernatremia, hyperkalemia, elevated ALP, elevated ALT, hypercalcemia, and hyperchloremia

129
Q

In humans with toxic epidermal necrolysis what is the leading cause of death?

A

sepsis

130
Q

T/F: Once the primary cause is identified and controlled, vasculitis is usually resolved.

A

FALSE -once immune complexes & immune system has been stimulated, resolution of the primary cause may not immediately resolve the vasculitis

131
Q

What side effect is noted in dogs treated with 10 mg/kg/day of itraconazole for blastomycosis?

A

cutaneous vasculitis –> lymphedema, necrotizing lesions on one or more limbs

132
Q

T/F: Dogs with pemphigus foliaceus may have other concurrent autoimmune diseases.

A

True: approximately 19% may have another autoimmune disease (IMHA, ITP, KCS, thyroiditis, etc.)

133
Q

What are the adverse effects reported with dapsone?

A

non-regenerative anemia, leukopenia, ALT elevations, GI signs, hepatotoxicity, neuropathies, photosensitivities, cutaneous eruptions, carcinogenicity

134
Q

Vaccine reactions are more commonly reported in what breeds?

A

poodles, silky terriers, Yorkies, Pekingese, Maltese

135
Q

With salt-split skin, what structures are on the “roof” and what structures are on the “floor”?

A

epidermis and lamina lucida = roof/top; dermis and lamina densa = floor/bottom

136
Q

Auricular chondritis usually involves autoantibodies to what?

A

collagen, usually collagen type II (a cartilage component)

137
Q

How common is glomerulonephritis with SLE?

A

proteinuira present in 50% of cases

138
Q

What are the reported toxicities associated with azathioprine?

A

anemia, leukopenia, thrombocytopenia, vomiting, pancreatitis, elevated ALP, hypersensitivity reactions, rashes, alopecia, diarrhea*

139
Q

What are the histopathological features of toxic epidermal necrolysis?

A

full-thickness devitalization of the epidermis = hypereosinophilic cytoplasm, plae/hyperchromatic nuclei, minimal dermal inflammation*; subepidermal vesicles/bullae

140
Q

What breeds are predisposed to the focal cutaneous vasculitis and alopecia at the site of rabies vaccination?

A

Poodles, Yorkies, silky terriers

141
Q

To what class of drugs does cyclophosphamide belong?

A

nitrogen mustard alkylating agent (similar to chlorambucil)

142
Q

What are the histopathological features of graft-versus-host disease? What other disease shares these features?

A

dermal lymphoid infiltrates, interface dermatitis (hydropic or lichenoid) with apoptosis and satellitosis, lymphocytic exocytosis and apoptosis can also target the follicular epithelium; Similar to Erythema Multiforme

143
Q

What class of drugs is chlorambucil a part of?

A

nitrogen mustard - alkylating agent

144
Q

what is the distribution of lesions with FELINE pemphigus foliaceus?

A

facial (pinnae, eyelids, nasal planum/dorsal muzzle), feet (claw folds and/or footpads), mammary papillae

145
Q

What are the clinical features of acquired junctional epidermolysis bullosa?

A

ears, oral cavity, pads, nasal or perinasal

146
Q

T/F: Skin lesions usually resolve before ocular changes with treatment of UV syndrome.

A

True – skin lesions may respond while eye disease remains active

147
Q

What antigens have been reported with canine paraneoplastic pemphigus?

A

DSG-3, plakins (periplakin and envoplakin)

148
Q

Mutations in what gene can increase an Akita’s odds of developing VKH/UV syndrome?

A

DLA class II (encodes for part of MHC)

149
Q

What drugs are most commonly associated with toxic epidermal necrolysis in dogs?

A

TMS, cephalosporins and penicillins

150
Q

What are the histopathological features of pemphigus foliaceus?

A

subcorneal to intragranular pustule containing individualized or clustered acantholytic keratinocytes; may span several hair follicles and extend into infundibula; neutrophils +/- eosinophils

151
Q

What cells are seen on histopathology with epidermolysis bullosa acquisita?

A

neutrophils +/- eos +/- subepidermal microabscesses

152
Q

T/F: In the dog, cat, and horse, anti-keratinocyte IgG can be found in circulation with pemphigus foliaceus.

A

TRUE

153
Q

What treatments have been used for treatment of toxic epidermal necrolysis? What drugs should be avoided?

A

glucocorticoids are controversial because they may increase the risk of sepsis; cyclosporine, plasmapheresis, IVIG, anti-TNF antibodies, N-acetylcysteine (to counteract drug-induced reactive oxygen species)

154
Q

What are the histopathological features of auricular chondritis?

A

lymphoplasmacytic inflammation, loss of cartilage basophilia, cartilage necrosis

155
Q

What is the most common histopathological finding of Erythema Multiforme?

A

keratinocyte apoptosis with lymphocytic satellitosis

156
Q

What are the clinical features of epidermolysis bullosa acquisita?

A

concave pinna, oral cavity/pads/sites of friction; generally multiple sites to generalized disease & rapid progression

157
Q

What is a key feature of pseudopelade identified on histopathology?

A

lymphocytic inflammation that targets the mid-isthmus of the hair follicle, where the follicular bulge cells (stem cells for hair growth) are present

158
Q

How long does it take for chlorambucil to result in clinical response?

A

4-8 weeks

159
Q

What are indications for using dapsone?

A

mycobacterial infections, autoimmune skin diseases, vasculitis, brown recluse spider bite (Loxosceles)

160
Q

What cells are seen on histopathology with bullous pemphigoid?

A

eosinophils

161
Q

What changes are seen with melanin granules on histopathology of UV syndrome?

A

melanin granules are found in melanophages in the dermis & appear as a finely granular, dusted, cytoplasmic pigment

162
Q

What are the clinical features of cutaneous vasculitis?

A

palpable purpura, erythematous to purpuric plaques, hemorrhagic bullae, eschar, crateriform ulcers, pitting edema, acrocyanosis, urticaria

163
Q

What areas of haired skin are more commonly affected with pemphigus vulgaris?

A

areas of friction or pressure (leading to rupture of vesicles) - footpads, clawbeds, perineum

164
Q

What breed is predisposed to SLE?

A

GSD

165
Q

Adverse effects of cyclosporine?

A

GI signs (vomiting, diarrhea, anorexia), lethargy, gingival hyperplasia, lymphadenopathy, UTI; Rare: viral papillomatosis, hepatotoxicity, nephrotoxicity, bone marrow suppression, hypertrichosis, excessive shedding, infections, corneal opacity, neurotoxicity, neoplasia, glucose homeostasis alterations

166
Q

What are the most common lesions with feline pemphigus? What is the distribution of lesions?

A

focal crusting lesions > pustules; head, face & ears most commonly affected, claw folds affected in 30% of cases

167
Q

For what disease does IVIg have the best evidence for use?

A

ITP

168
Q

What are the histopathological features of pemphigus vulgaris?

A

suprabasal acantholysis (may extend into hair follicle infundibuli) –> blister formation (usually free of inflammatory cells); ** suprabasilar intraepidermal cleft with remaining basal cells exhibiting a tombstone appearance

169
Q

What are the features of feline DLE?

A

**nasal involvement less prominent than the dog; lesions commonly involve face and ears

170
Q

What are type II cryoglobulins? What diseases are they most commonly associated with?

A

monoclonal and polyclonal immunoglobulins; most commonly associated with autoimmune and connective tissue disease

171
Q

Is systemic lupus erythematosus more of a T-cell mediated or B-cell mediated disease?

A

Both - but more B-cell driven - main immunologic event is B-cell overactivity, also reduced numbers of T lymphocytes

172
Q

What cells are seen on histopathology with mixed AISBD?

A

cellular vesicles and dermal neuts and eos

173
Q

What are the clinical features of vesicular cutaneous lupus erythematosus (breed, characteristic lesions, distribution)?

A

Shelties and rough collies; focal to confluent serpiginous areas of ulceration on ventral abdomen, groin, and medial thighs; mucocutaneous junctions and concave pinna and buccal mucosa may be affected

174
Q

What breeds are predisposed to UV syndrom?

A

Akitas, Samoyeds, Siberian Huskies

175
Q

What are the reported toxicities associated with cyclophosphamide?

A

myelosuppression, GI toxicity, alopecia and poor hair regrowth, infertility, bladder fibrosis; cats may lose whiskers

176
Q

What are the adverse effects reported with gold salts (aurothioglucose, sodium aurothiomalate, auranofin)?

A

blood dyscrasias (ITP, IMHA, or leukopenia); GI disturbances (diarrhea** – due to alterations in fecal electrolyte concentrations from inhibition of Na+/K+ adenosine triphosphate => increased fluid volume in intestines); rare - nephrotoxicity (proteinuria), hepatotoxicity (increased liver enzymes), dermatosis, corneal and oral ulcers

177
Q

What are the clinical features of paraneoplastic pemphigus?

A

erosions/ulcers affected mucosae, mucocutaneous junctions, nasal planum, and/or haired skin

178
Q

What should you monitor when starting chlorambucil? When and why?

A

Complete blood count - starting 2 weeks after initiation of therapy due to potential myelosuppression (nadir at 7-14 days after starting)

179
Q

Mechanism of action of cyclosporine?

A

binds to specific cellular receptor on calcineurin and inhibits the T-cell receptor-activated transduction pathway, therefore blocking the gene transcription of T-cell cytokines, esp IL-2, which is essential for T-cell proliferation. Potent inhibitor of cell-mediated immunity and less so of humoral immunity. Depresses the induction and proliferation of cytotoxic T cells, antibody production by help-T-cell-dependent B cells, proliferation of activated T cells, and the activation of mononuclear phagocytes and helper T cells; anti-inflammatory effects on mast cells, eos, Langerhans, endothelial cells, keratinocyes, cytostatic effect on keratinocytes

180
Q

What are type III cryoglobulins? What diseases are they most commonly associated with?

A

polyclonal immunoglobulins; occur with infections, autoimmune diseases, and connective tissue diseases

181
Q

What is the target antigen of acquired junctional epidermolysis bullosa?

A

Laminin 332

182
Q

What is the mechanism of action of cyclophosphamide?

A

non-specific cell cycle inhibitor; metabolites (phosphoramide and acrolein) are alkylating agents that interfere with DNA synthesis and function (as well as RNA transcription and replication)

183
Q

What is the typical disease progression with mucous membrane pemphigoid?

A

usually a slowly progressive disease

184
Q

Adverse effects of leflunomide?

A

lethargy, anorexia, liver enzyme elevations (transient), respiratory symptoms, vomiting, anemia, lymphopenia, thrombocytopenia, hemorrhagic colitis; GI toxicity may occur as a result of accumulation of the metabolite trimethylfluoroanaline; reported in humans: diarrhea, nausea, alopecia, CLE, TEN, SJS, hypertension, hepatotoxicity, myelosuppression, peripheral neuropathy

185
Q

What subclass of immunoglobulins has been identified to be circulating in cases of pemphigus foliaceus?

A

IgG4 (anti-keratinocyte)

186
Q

What are nonimmunologic mechanisms of cutaneous adverse drug reactions?

A

predictable reactions related to known activities of the drug that are not intended effects or related to overdose or drug-drug interactions and unpredictable reactions (idiosyncratic, pseudoallergic, intolerance)

187
Q

What are the clinical features of pseudopelade?

A

well circumscribed areas of non-inflammatory alopecia to diffuse alopecia, +/- scale, +/- hyperpigmentation, no pruritus

188
Q

What breed is over-represented in the United States with cutaneous and renal glomerular vasculopathy (Alabama rot)?

A

greyhounds

189
Q

What are the dermatological lesions associated with UV syndrome/VKH in dogs? Where are they located?

A

depigmentation +/- erythema and scale of skin=> erosion=> ulceration & crusting; depigmentation of hair; lesions usually occur on face (all cases), nose/nasal planum, eyelids/periorbital skin, lips, occasionally on the footpads, scrotum, anus and hard palate

190
Q

What areas of the body are typically affected with vasculitis? Why?

A

dependent areas of the body, pressure points, extremities (pinnae, tip of tail, pads, elbows); hypothesized that increased trauma, more susceptibility to cold temperatures, and sparse collateral vascular supply

191
Q

Adverse effects of IVIg?

A

acute hypersensitivity, anaphylaxis, acute renal failure, aseptic meningitis, may promote hypercoagulability and an inflammatory state

192
Q

What is the mechanism of action of gold salts (aurothioglucose, sodium aurothiomalate, auranofin)?

A

inhibit macrophage phagocytosis, reduce release of inflammatory mediators such as lysosomal enzymes, histamine and prostaglandin, inactivate complement components, interfere with immunoglobulin-synthesizing cells, inhibit antigen- and mitogen-induced T-cell proliferation, and suppress IL-2 and IL-2 receptor synthesis; in vitro has an inhibitory effect on DNA, RNA, and protein synthesis

193
Q

What AISBDs usually spare the footpads?

A

bullous pemphigoid and mucus membrane pemphigoid

194
Q

_______ is a form of programmed cell death that results in cell shrinkage, nuclear pyknosis, then karyorrhexis and formation of plasma membrane-bound apoptotic bodies.

A

Apoptosis

195
Q

T/F: Bullous pemphigoid in animals has been shown to be exacerbated by UV exposure.

A

False - though true in people, has not been demonstrated in animals

196
Q

VKH is a multisystem autoimmune disease that can afffect what organ systems?

A

eye, ear, nervous system, skin and hair

197
Q

What breed is over-represented with epidermolysis bullosa acquisita?

A

Great Dane

198
Q

What is the clinical presentation of toxic epidermal necrolysis?

A

systemic signs (pyrexia, anorexia, lethargy, depression) and multifocal/generalized erythematous macules/patches on haired skin and mucosal surfaces => ulcerative and necrotic, rapid progression

199
Q

Pemphigus erythematosus has features of what two diseases?

A

pemphigus foliaceus + discoid lupus erythematosus

200
Q

What is the mechanism of action of leflunomide?

A

reversibly inhibits the enzyme dihydroorotate dehydrogenase involved in de-novo pathway of pyrimidine synthesis –> results in decreased DNA and RNA synthesis and inhibition of cell proliferation; antiproliferative effect involves T and B lymphocytes, smooth muscle cells, and fibroblasts. Metabolized to active form teriflunomide by the intestinal mucosa; inhibits COX-2, inhibits tyrosine kinase (decreases activation of signaling pathways leading to DNA repair, apoptosis, and cell proliferation)

201
Q

What are the reported adverse effects of chlorambucil?

A

myelosuppression, GI signs, alopecia and delayed hair regrowth after clipping (Kerry blue terriers and poodles)

202
Q

What clinical signs are typically seen with chronic graft-versus-host disease? How quickly do they occur?

A

Occurs 3-4 months after grafting: exfoliative erythroderma, ulcerative dermatitis, ascites, gram-positive infections.

203
Q

What breeds are predisposed to pemphigus foliaceus?

A

Akita, Chow-Chow

204
Q

What stain is used to identify amyloid on biopsy?

A

Congo red

205
Q

What cells are seen on histopathology with acquired junctional epidermolysis bullosa?

A

may be acellular

206
Q

What is the mechanism of action of IVIg?

A

immune globulin binds Fc receptors on mononuclear phagocytes, downregulates immunoglobulin production, eliminates pathogenic autoantibodies, modulates cytokine synthesis, inhibits complement, mediates Fas-Fas ligand interactions