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Flashcards in Small Animal Deck (97):
1

What sites contain Igs normally, and should therefore not be collected for immunofluorescence testing?

nasal planum of dogs and cats, footpads of dogs

2

What is Michel fixative?

fixative used for samples submitted for direct immunofluorescence testing. Samples can be held in this for up to 2 weeks. pH: 7.0-7.2

3

immunoperoxidase testing can yield false POSITIVE or false NEGATIVE results?

false positive

4

What are the phases of treatment as it relates to immune-mediated dermatoses?

(1) induction of remission, (2) transition, (3) maintenance, and (4) determining cure

5

Goal of Induction phase:

avoid bad side effects; can take days to weeks

6

goal of transition phase:

get to lowest effective dose, takes weeks to months

7

goal of maintenance phase:

maintain dose for duration of disease with monitoring to avoid adverse effects, takes 6 mos to years

8

goal determining cures:

stop drugs after complete remission has been maintained and observe for recurrence of disease; may take several attempts

9

Azathioprine is what kind of drug?

Synthetic modification of 6-mercaptopurine; antagonizes purine metabolism and interferes with DNA/RNA synthesis.

metabolized in the liver to 6-mercaptopurine and other active metabolites.

6-Mercaptopurine is then metabolized by three enzyme systems. 1) Xanthine oxidase and
2) thiopurine methyltransferase (TPMT) produce inactive metabolites. Humans and possibly dogs that have absent (homozygous) or low (het- erozygous) TPMT activity are more likely to experience myelo- suppression; cats have lower levels, making them more susceptible to toxicity
3) hypoxanthine phosphoribosyltransferase

10

What is azathioprine metabolized to and by which enzyme system?

Metabolized to 6-mercaptopurine (and other active metabolites)

-Xanthine oxidase and thiopurine methyltransferase (TPMT) produce inactive metabolites - if TMPT is low, can have more myelosuppression

11

what drugs do you NOT want to use with azathioprine?

allopurinol

12

what are potential side effects of azathioprine?

bone marrow suppression! hepatotoxicity (but rare, and usually in combo)
(CEG: as long as acting normal, and bilirubin not up, ok to see some liver values change)

anemia, leukopenia (lymphopenia**), demodicosis, thrombocytopenia, vomiting, hypersensitivity reactions (especially of the liver), pancreatitis (esp if also on steroids), elevated serum alkaline phosphatase concentrations, rashes, and alopecia, diarrhea (hemorrhagic) - most respond to drug reductions,

13

How long is the lag time for azathioprine?

There is often a lag phase, with clinical improvement occurring in 3 to 6 weeks

14

What are adverse effects of azathioprine in cats (and why should AZA NOT BE USED IN CATS)?

fatal leukopenia and thrombocytopenia)

15

what is chlorambucil?

alkylating agent derived from nitrogen mustard. Its cytotoxic effect is due to cross-linking of DNA

16

what are potential side effects of chlorambucil?

v/d, anorexia, alopecia and delayed hair growth after clipping have been reported, (poodles and Kerry blue terriers are reported to be at greater risk)

17

what's a potential side effect of cyclophosphamide?

STERILE HEMORRHAGIC CYSTITIS (30% of dogs on it for >2 mos), bladder fibrosis, teratogenesis, infertility, alopecia and poor hair growth, nausea, GI inflammation, bone marrow suppression

18

what is colchicine?

alkaloid that suppresses neu- trophil chemotactic and phagocytic functions via disruption of microtubule assembly and elongation, increasing cellular cyclic adenosine monophosphate (cAMP) levels and inhibiting lysosomal degranulation
-It also inhibits immunoglobulin secretion, interleukin (IL)-1 production, histamine release, and human leukocyte antigen (HLA)-DR expression.
-inhibits cell division during metaphase by interfering with sol-gel formation and the mitotic spindle.
**antifibrotic**

19

What drugs should not generally be used with colchicine?

NSAIDs - concern with concurrent use and bone marrow suppression

don't use with azathioprine or chlorambucil

20

What is cyclophosphamide?

nitrogen mustard alkylating agent metabolized to agents that inhibit mitosis via interferring with DNA replication and RNA transcription and replication

21

what cell line is most sensitive to cyclophosphamide?

lymphocytes - especially b cells

suppresses antibody production

22

What is the MOA of mycophenolate mofetil?

=prodrug is antiproliferative agent mycophenolic acid (MPA) and specifically and reversibly inhibits inosine monophosphate dehydrogenase --> thereby inhibits purine (guanine) synthesis and prevents maturation of B and T lymphocytes

-inhibits de novo synthesis of purine
-suppresses T and B lymphocytes
-induces lymphocyte apoptosis
-induced dendritic cell maturation
-decreases IL-1 expression
-enhances expression of IL-1R antagonist

23

Mycophenolate mofetil has a synergitic effect with which other immune suppressive drug?

CsA

24

What are some side effects of mycophenolate mofetil?

bone marrow suppression, nausea, vomiting, diarrhea, increased incidence of infections
-GI side effects more common when drug is given as sodium enteric-coated tablet

25

MOA of tetracycline/niacinamide for immune-mediated or inflammatory disease treatment?

unknown

26

properties of tetracycline?

-suppression of in vitro lymphocyte blastogenic transformation and antibody formation
-inhibits matrix metalloproteinases**
-inhibits prostaglandin synthesis

27

properties of Niacinamide?

-block antigen IgE-induced histamine release in vivo and in vitro
-prevents mast cell degranulation
-photoprotectants from inducing immunologic damage
-cytoprotectant that blocks inflammatory cell activation and apoptosis
-inhibits phosphodiesterase
-decreases protease release

-ANTIOXIDANT
-ALSO AVAILABLE TOPICALLY

28

which has a longer half-life: doxycycline or tetracycline?

doxycycline - can use lower dose and longer interval between doses (tetracycline TID)

29

what does "panepidermal pustular pemphigus" refer to?

cases that have acantholysios, neutrophilic and eosinophilic infiltrate throughout the epidermis (i.e. PVeg and PEryth)

30

What are primary targets in PF?

Desmocollin 1 and Desmoglein 1

31

what are primary targets in PV?

Desmoglein 3 (deeper, mucosal involvement)

32

what are the primary targets in paraneoplastic pemphigus?

plakin famaily antigens: envoplakin and periplakin

33

what subclasses of immunoglobulin deposits are seen in pemphigus?

IgG2 and IgG4
-intraepidermal Ig deposits are not specific for pemphigus and may be found in 20% of other dermatoses

34

indirect immunofluorescence is most reliable on which types of tissue for PF and PV?

PF: neonatal mouse skin
PV: canine gingival mucosa

35

What are three possible immunopathogenic pathways proposed for mechanism by which autoantigens exert their effects?

1) antibodies act by steric hindrance
2) antibody binding triggers intracellular signaling events leading to aberrant phosphorylation of Dsg3 and depleted desmosome formation. protein kinases are modulated by protein kinase inhibitors here.
3) intercellular cohesion is dependent on cholinergic mechanisms with Acetylcholine receptor playing a role in controlling phosphorylation of adhesion molecules:
--atropine and muscarinic Ach antagonists decrease Dsg phosphorylation --> abnormal desmosome formation

36

T/F: urokinase plasminogen activator (uPA) plays a pivotal role in acantholysis.

F

37

what are some drugs that have been involved with drug-induced pemphigus?

PF: cimetidine, itraconazole or Lime sulfur, amitraz/metaflumizone (Promeris) - promeris may have triggered it vs induced
PV: polymyxin-B

38

What breeds are overrepresented in cases of PF?

akitas, chow chows
also: cockers, dachshunds, labrador retrievers, english bulldogs

39

What is the inciting cause of PF?

usually idiopathic, but possible drug-induced or drug-triggered, a subset may develop subsequent to chronic skin disease (allergies), possibly UV light can exacerbate?

40

which body sites are predisposed to PF lesions?

head, face, ears - often bilaterally symmetric
nasal depigmentation later in disease
footpads too

41

which disease shows nasal depigmentation 1st: DLE or PF?

DLE; usually a later event in PF

42

What is the target antigen for Acquired junctional epidermolysis bulls (AJEB)?

Target antigen: laminin 332

histo: may be acellular

Features: ears, oral cavity, pads, nasal or perinasal

Collagen IV location: 100% bottom of blisters

Salt split IF deposition: both or bottom

43

What is the target antigen for Bullous Pemphigoid (BP)?

Target antigen: Collagen XVII

Histo: eosinophils intact or degranulated; sub epidermal cleft and vesicle formation

Features: haired skin usually affected, occasional mucosal lesions likely - SPARES PAW PADS

Collagen IV location: both

Salt split IF deposition: top

IgG and IgM are most commonly detected, with some C3

44

What is the target antigen for Bullous Systemic Lupus Erythematosus type I (BSLE-I)

Target antigen: Collagen VII

Histo: Neutros and histiocytes

Collagen IV location: suspected like EBA (mostly above)

Salt split deposition: bottom

45

What is the target antigen for Epidermolysis Bullosa acquisitor (EBA)?

Target antigen: Collagen VII

Histo: neutrophils +/- Eos, sub epidermal micro abscesses

Features: concave pinnae, oral cavity, pads and friction sites, multifocal-generalized

Collagen IV location: 43% above, 29% below, 29% both

Salt split deposition: bottom

46

What is the target antigen for Linear IgA Disease?

Target antigen: Shed collagen XVII

Histo: mild to no inflammation

Features: one case report only

Collagen IV location: below

Salt split deposition: top

47

What is the target antigen for Mixed AISBD?

Target antigen: Laminin 332 and collagen VII

Histo: cellular vesicles, dermal neuts and eos

Features: affects haired skin and mucosal sites, 2/3 erythematous base to vesicles

Collagen IV location: 100% below

Salt split deposition: bottom

48

What is the target antigen for Mucus membrane pemphigoid (MMP)?

Target antigen: BPAG 1 (BP230), Collagen XVII, laminin 332

Histo: acellular or. neuts/eos, beta-lichenoid

Features: mostly mucosal or MC Jxn; haired skin sparsely affected, spares pads

Collagen IV location: 91% below, 9% both

Salt split deposition: top more but some bottom or both

49

Describe Salt-split indirect immunofluorescence testing:

used in indirect immunofluorescence testing with patient's serum.

a 1-molar NaCl solution splits canine lip or gingival skin through lamina Lucida, allowing recognition of autoantibodies that bind to the top (epidermal side of lamina lucida) or bottom (dermal and lamina dense side) or both

50

what are the autoantibodies in bullous pemphigoid?

Mainly IgG, with subtypes G1 and G4 predominating, but low titers of IgM and IgE have also been detected

Canine and feline cases of BP exhibit antibodies against multiple epitopes of the NC16A collagen XVII molecule

51

What is another term for BPAG-1?

BP230

52

What is another term for BPAG-2?

BP180 aka Collagen XVII
180 kDa hemidesmosomal transmembranous molecule, target of BP in animals.

53

What AISBD targets the NC16A domain of collagen XVII molecule?

Bullous pemphigoid

54

What is the proposed pathomechanism of blister formation in BP?

(1) binding of complement-fixing pemphigoid anti- body to the noncollagenous domain NC16A of collagen XVII
(2) complement fixation and activation
(3) activation of mast cells and release of chemotactic cytokines, which may be partly mediated or facilitated better by IgE autoantibodies
(4) che- moattraction of neutrophils and eosinophils
(5) release of proteolytic enzymes from the infiltrating leukocytes, which disrupt dermo-epidermal cohesion, resulting in dermo- epidermal separation and vesicle formation

55

Which proteins were elevated in human blister fluid, suggesting that the release of these from activated granulocytes are important in blister formation?

eosinophil cationic protein, major basic protein, and neutrophil-derived myeloperoxidase and elastase

56

Which drugs may provoke development of bullous pemphigoid?

sulfonamides, penicillins, and furosemide, UV light

57

target antigen for BP?

Collagen XVII

58

T/f: footpads are generally affected with BP

false, lesions mainly affect skin, oral cavity, LC junctions

59

T/F: footpads are generally affected with EBA

true

60

Compare the main cell types seen histologically for BP, MMP, EBA

BP: eosinophils

MMP: noninflammatory blisters

EBA: neutrophil-rich vesicles

61

Which AISBD is most common in dogs?

MMP

62

Primary target of MMP?

NC16A domain of collagen XVII; most dogs react to BPAG-2 and many reacting to BPAG-1

63

Which breeds are overrepresented with BP?

GSD; mature dogs

64

Clinical signs of Bullous Pemphigoid?

erythema, tense vesicles, hypo pigmentation, erosions/ulcers, SCARRING PREDOMINANTLY

65

What is the primary target of EBA?

NC1 domain of collagen VII, an adhesion molecule and main component of anchoring fibrils

66

What is Collagen VII?

An adhesion molecule and main component of anchoring fibrils.

67

What contributes to blister formation in EBA (and also likely BP)?

granulocyte-derived nicotinamide adenine dinucleotide phosphate (NADPH), oxidase

68

What breed is overrepresented in cases of EBA?

Great Dane - young dogs

69

EBA affects paw pads: t/f?

T: over 75% of cases have pads sloughing or ulcerated

70

EBA affects oral cavity: t/f?

T - oral cavity is always involved

rapid progression to generalized

71

EBA does not exhibit systemic signs: t/f?

F: pyrexia, depression, lethargy are often present and anemia and thrombocytopenia may be seen

72

Which AISBD vesicle is acellular?

EBA; can also see neutrophilic microabcesses

AJEB also had reports of acellular vesicles

73

Which immunoglobulin is most common in EBA?

IgG

74

What treatment options are recommended for EBA?

colchicine, glucocorticoids, IVIg

75

What kind of autoantibodies do patients with Acquired junctional epidermolysis bulls have?

IgG autoantibodies to laminin 332

76

What are other names for Laminin 332?

laminin 5, epiligrin, kalinin

77

What are the targets of Linear IgA disease? and what times of autoantibodies do these patients have in addition to IgA?

IgA and sometimes IgG autoantibodies against processed extracellular components of collagen XVII (including LAD-1 protein)

78

What are the three troikas of lupus?

The 3 troikas idea is comparing the pathogenesis of Lupus to a traditional Russian 3-horse carriage, where each horse pulls independently but each contributes to the final outcome.



1. Etiology
a. Genetic factors
b. Hormonal factors
c. Environmental factors

2. Etiopathogenesis
a. T-cell dysfunction
b. Polyclonal B-cell activation
c. Cytokines

3. Pathogenesis
a. Immune-complex mediated damage
b. Direct damaging effects by autoantibodies
c. Functional effects of antibodies

79

What dog breed has a predisposition for SLE?

GSD

80

What are signs of SLE-like disease in Nova Scotia Duck Tollers?

Polyarthritis and meningitis/arteritis

Frequently positive ANA titers.


This is a highly inbred breed that can have an MHC II polymorphism. Five loci on chromosomes 3, 8, 11, 24 and 32 were strongly associated with the disease.

81

What MHC haplotype is associated with SLE in dogs?

MHC I haplotype DLA-A7

82

environmental factors for SLE?

-UVA/UVB
Can induce or exacerbate symptoms!
-Drugs
hydralazine, isoniazid, phenytoin, procainamide, chlorpromazine in people
-Infection
Epstein-barr virus in people

83

hormonal factors for SLE?

More of a big deal for people. Woman are more affected than men (6:1 to 15:1) and especially at higher estrogen periods of their lives. Symptoms can abate around menopause.

Increased estrogen, decreased androgens are risk factors for SLE in people.

Controversial if any sex bias exists for SLE in the dog (2 studies have actually identifed more males) but a lot of pet dogs are neutered so this is more difficult to determine.

No sex predilection reported for the horse.

84

genetic factors for lupus?

Really complex and multifactorial.

GSD breed disposition for SLE
Association with the DLA-A7 MHC I haplotype in the dog
Nova Scotia duck trolling retrievers that develop an SLE-like disease also have a MHC class 11 polymorphism.

85

Antibodies against ___ have been reported in cases of VCLE.

Ro/SSA and/or La/SSB in sera from 55% of cases

86

VCLE has similarities to ___ form of lupus in humans?

SCLE

87

What are antibody targets seen in alopecia areata?

bulbar and inferior part of hair follicle with TRICHOHYALIN as major antigen in dogs

-also hair bulb melanocytes?

88

CD8+ cells are responsible for inducing hair loss in humans. t/f?

T; more CD8+ cells found within hair bulbs in dogs and humans

CD1+ dendritic APCs present in perifollicular dermis

89

What observations have been seen in humans to support an immunologic basis in Alopecia Areata?

-autoimmune thyroid disease
-increased incidence of autoantibodies
-decreased numbers of circulating T cells
-abnormal presence of Langerhans cells in follicular bulb
-increased MHC class I and MHC Class II expression
-C3 or IgG and IgM deposition at BMZ
-Therapeutic benefit with altering cytokines similar to what's seen by inducing delayed type hypersensitivity
-response to immunosuppressive tx

90

Breeds predisposed to developing alopecia areata?

GSD, dachshund, beagles

91

What sites aside from the head and trunk can be affected by alopecia areata?

claws (trachyonychia = roughening, ridging, vertical striations); also see leukotrichia and melanoderma

can be confined to dark-haired areas

92

Describe trichographic and histopathologic findings of alopecia areata

"exclamation point" hairs, normal telogen, dysplastic hairs

histo: peribulbar to inferior hair follicle accumulation of lymphocytes, macrophages, or dendritic cells with some plasma cells (swarm of bees)
-peribulbar mucin, pigment incontinence
-follicular dysplasia, atrophy in later lesions

93

in humans, diphenylcyclopropenone (DPCP) is used to treat which disease?

alopecia areata

94

What breed is overrepresented in linear IgA pustular dermatosis?

dachschunds

95

You have an adult dachshund with multifocal pustular dermatitis on trunk, minimal pruritus. what are your ddx?

linear IgA pustular dermatosis, dermatophyte, folliculitis, demodicosis, PF

96

What is the half life of IgG?

IgG half life is 23 days (longest)

97

What is the half life of IgE?

2-3 days (shortest)