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MK ACVD Exam > Immune-mediated diseases > Flashcards

Immune-mediated diseases Flashcards

Pemphigus complex, vasculitis, histiocytic, lupus, EM, SJS/TEN

1
Q

What is the most common antigen targeted in human PF?

A

Desmoglein-1

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2
Q

What is the most common antigen targeted in canine PF?

A

Desmocollin-1

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3
Q

What is the most common antibody isotype in canine and human PF?

A

IgG

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4
Q

What 4 insecticides have been implicated as a trigger in PF?

A

Metaflumizone-amitraz (Promeris)
Fipronil-amitraz-S-methoprene (Certifect)
Dinotefuran-pyriproxyfen-pyrethrin (Vectra 3D)
Afoxolaner (Nexgard)

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5
Q

What is the name of the endemic form of PF and where is it endemic?

A

Fogo selvagem, Brazil

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6
Q

What is the pathogenesis of fogo selvagem?

A

Sand fly salivary antigen LJM11
sand fly bites human –> antigen cross-reacts with Dsg-1 –> trigger PF

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7
Q

What are the 4 phenotypes of canine PF?

A

Facial-dominant
Truncal-dominant
Generalized
Foot pad-exclusive

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8
Q

What are two primary differentials for PF?

A

pustular dermatophytosis (Trichophyton)
superficial pyoderma

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9
Q

What is the antigen targeted in the mucosal-dominant variant of human PV?

A

Desmoglein-3

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10
Q

What is the antigen targeted in the mucocutaneous variant of human PV?

A

Desmoglein-1 and desmoglein-3

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11
Q

What is the antigen targeted in canine PV?

A

Desmoglein-3 (and less Dsg-1)

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12
Q

Histopathology of canine skin lesions reveals suprabasal keratinocyte acantholysis with basal cells remaining attached at the basement membrane, resembling tombstones. Which autoimmune disease is most likely?

A

PV

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13
Q

What desmosome is more prevalent in mucosa?

A

Dsg-3

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14
Q

What are the 3 types of deep pemphigus?

A

PV
Pemphigus vegetans
Paraneoplastic pemphigus

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15
Q

Besides anti-DSG3 antibodies, what other gene is suspected to be involved in canine PV?

A

c-Myc

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16
Q

What gender is more commonly affected by canine PV?

A

Males (opposite of human PV)

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17
Q

True or false: Pruritus is common in canine PV

A

False

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18
Q

What is the best area to biopsy for diagnosis of PV?

A

Margin of an erosion/ulcer (1/3 lesional skin, 2/3 perilesional skin)

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19
Q

What is the most common distribution of human Pveg?

A

Periorificial and intertriginous areas

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20
Q

Describe the Neumann-type vs. the Hallopeau-type of Pveg in humans

A

Neumann-type: starts with vesicles/blisters
Hallopeau-type: starts with pustules

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21
Q

What are the histopathologic features of Pveg?

A

PV (suprabasilar acantholysis) + hyperplastic PF

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22
Q

What subtype of human Pveg has a better prognosis?

A

Hallopeau-type

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23
Q

What neoplastic conditions have been associated with paraneoplastic pemphigus in dogs and cats?

A

Thymoma
Thymic lymphoma
Splenic sarcoma

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24
Q

What are the most consistent targets of paraneoplastic pemphigus?

A

Periplakin
Envoplakin
Desmoglein-3

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25
Q

What two immune-mediated conditions does histopath of paraneoplastic pemphigus resemble?

A

PV, EM

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26
Q

What are the most common lesions of canine paraneoplastic pemphigus?

A

Erosions and ulcers (oral cavity and lips most often)

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27
Q

Skin biopsies from a dog reveal features of both EM and PV. What is the most likely differential and what should be your next step?

A

Paraneoplastic pemphigus - start thorough workup for underlying neoplasia

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28
Q

What two breeds are overrepresented in canine PF?

A

Akita
Chow

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29
Q

Is there a sex predilection for canine or feline PF?

A

No

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30
Q

Apart from pustules and crusts, what other clinical feature is seen in horses with PF?

A

Ventral edema

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31
Q

What histopathologic features help differentiate PF from bacterial folliculitis?

A

PF pustules are large and span MULTIPLE follicular units
Recornification beneath the pustule

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32
Q

What is the major autoantigen of human PE?

A

Desmoglein-1

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33
Q

What are the histopathologic features of PE?

A

Intragranular or subcorneal neutrophilic/eosinophilic acantholytic pustules
Lichenoid interface dermatitis

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34
Q

What steroid has been associated with the highest rates of remission in feline PF?

A

Triamcinolone

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35
Q

Besides neutrophils, what inflammatory cell is often found in feline PF cases, differing from what is seen in canine PF?

A

Mast cells

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36
Q

Describe the pathogenesis of acantholysis in pemphigus

A
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37
Q

What pemphigus variants have been recognized in horses?

A

PF
PV

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38
Q

Describe the expression of desmosomal cadherins in haired skin/footpad/nasal planum

A
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39
Q

Describe the expression of desmosomal cadherins in the oral cavity/mucosa/esophagus

A
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40
Q

Besides genetics, what else may serve as a trigger/predisposing factor for PF?

A

Sun exposure

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41
Q

Are lesions of insecticide-triggered PF located at the site of application or distant from the site of application?

A

Both (though Vectra 3D has only been associated with distant lesions)

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42
Q

Cutaneous polyimmunity as been associated with PF and what other disease?

A

DLE

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43
Q

Is there a sex predilection in feline PF?

A

No

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44
Q

Is there a breed predisposition in feline PF?

A

No

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45
Q

Describe the lesion distribution of feline PF

A
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46
Q

In what condition may you see a “keratin ring” on histopathology?

A

PF

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47
Q

Are anti-DSC1 serum antibody titers related to PF severity?

A

Yes

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48
Q

Describe the glucocorticoid pulse regimen for treatment of PF

A

GC 10 mg/kg/day x3 days, then 1-2 mg/kg/day, repeat pulse if relapse occurs

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49
Q

What form of pemphigus is most common in humans?

A

PV

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50
Q

What is a primary difference between the vesicles seen in PV vs those seen in AISBDs?

A

PV vesicles are flaccid, not tense

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51
Q

What clinical test is pathognomonic for deep pemphigus?

A

Nikolskiy sign (direct/marginal)

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52
Q

What clinical feature of paraneoplastic pemphigus helps differentiate it from PV?

A

Rapid progression of lesions

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53
Q

What is the target antigen in Pveg?

A

Dsg-1

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54
Q

What is the suspected antigen target in feline PF?

A

Dsg-1

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55
Q

What is the most common distribution of skin lesions associated with vasculopathy?

A

Bony prominences
Body extremities

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56
Q

What adhesion molecules are upregulated on endothelial cells during vasculitis?

A

E-selectin
ICAM-1

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57
Q

What are four mechanisms of immune-mediated vasculitis?

A

Immune complex deposition in vessel walls
Production of anti-neutrophil cytoplasmic antibodies (rare)
Anti-endothelial cell antibodies
Autoreactive T-cells, macs

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58
Q

What is the main cause of purpura hemorrhagica in horses?

A

Streptococcus equi

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59
Q

What is the hallmark feature of cutaneous vasculitis?

A

Palpable purpura

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60
Q

What are the histopathologic features of cutaneous vasculitis?

A

Hyalinization/fibrinoid necrosis of vessel wall
Inflammatory cells in vessel wall
Swollen endothelial cells
Edema, hemorrhage
Ischemia: pale collagen, follicular atrophy, cell-poor interface dermatitis

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61
Q

What triggers have been identified for cryoglobulinemia?

A

Lead poisoning
URI
Multiple myeloma
Lymphoma

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62
Q

A dog with urticarial vasculitis is biopsied and histopathology reveals primarily an eosinophilic infiltrate. What is your major differential?

A

CAFR

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63
Q

In cutaneous and renal glomerular vasculopathy, does the AKI usually occur before, simultaneously, or after skin lesions?

A

After skin lesions

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64
Q

What is the most important CBC finding in canine cutaneous and renal glomerular vasculopathy?

A

Thrombocytopenia (due to consumption from massive vessel thrombosis)

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65
Q

What are negative prognostic indicators for the development of AKI in canine cutaneous and renal glomerular vasculopathy?

A

Anemia
Neutrophilia
Thrombocytopenia

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66
Q

What is the gold standard for diagnosis of canine cutaneous and renal glomerular vasculopathy?

A

Kidney biopsy –> thrombotic microangiopathy of glomerular arterioles

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67
Q

What drug has been associated with proliferative thrombovascular necrosis of the pinnae?

A

Fenbendazole

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68
Q

What infectious diseases associated with vasculitis may preferentially affect the pinnae?

A

Leishmania
Bartonellosis

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69
Q

What oral medication has been shown to be effective for management of proliferative thrombovascular necrosis of the pinnae?

A

Oclacitinib (1-3 mo response times)

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70
Q

What breed is represented in familial necrotizing arteritis?

A

Beagles

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71
Q

What is the pathogenesis of familial necrotizing arteritis?

A

Anti-neutrophil cytoplasmic antibodies

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72
Q

What breeds are represented in familial cutaneous vasculopathy?

A

GSD
JRT

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73
Q

What is the suspected mode of inheritance of familial cutaneous vasculopathy in GSD?

A

autosomal recessive

74
Q

What is the age of onset of familial cutaneous vasculopathy in GSD?

A

1-3 months of age

75
Q

What are the most common areas affected in familial cutaneous vasculopathy in GSD?

A

Paw pads
Bridge of the nose

76
Q

What is a potential trigger of familial cutaneous vasculopathy in GSD and JRT?

A

vaccination

77
Q

What breed has a hereditary vasculitis that is restricted to the nasal planum?

A

Scottish Terriers

78
Q

What is the suspected mode of inheritance of hereditary vasculitis in Scotties?

A

Autosomal dominant

79
Q

What breed is predisposed to a life-threatening form of acute neutrophilic vasculitis seen in young puppies?

80
Q

Describe the 5 subsets of ischemic dermatopathy.

A

1) Familial dermatomyositis
2) Dermatomyositis-like disease in atypical breeds (juvenile-onset ischemic dermatopathy)
3) Post-Rabies vaccine vasculitis and panniculitis
4) Generalized vaccine-associated ischemic dermatopathy
5) Adult-onset generalized idiopathic ischemic dermatopathy

81
Q

What is the main ddx for ischemic dermatopathy?

A

Cutaneous lupus erythematosus (hydropic degen of basal cells seen in both conditions)

82
Q

What breeds are typical for familial dermatomyositis?

A

Rough Collies
Shelties
(Beauceron shepherds
Portuguese Water Dogs
Belgian Tervurens
Working Kelpies)

83
Q

What 3 genes are associated with canine familial dermatomyositis?

A

PAN2
MAP3K7CL
FH3570

84
Q

What 2 diagnostics could be used to confirm myositis in familial dermatomyositis?

A

Electromyography
Muscle biopsy

85
Q

Name 2 triggers for familial dermatomyositis

86
Q

What are the main cytokines involved in canine familial dermatomyositis?

A

Type I interferons (this is why oclacitinib may be effective)

87
Q

Is there a genetic test for canine familial dermatomyositis?

88
Q

What is the typical time between Rabies vaccination and onset of localized vaccine-associated ischemia?

A

2-3 months (up to 8 months)

89
Q

What is the typical age of onset of skin lesions in canine familial dermatomyositis?

A

<6 months (lesion peak by 12 months)

90
Q

A horse is presented with signs of vasculitis. You want to rule out equine infectious anemia as a trigger. What test will you do?

91
Q

Besides type III HST, what type of hypersensitivity may be expected in a case of eosinophilic vasculitis?

92
Q

What types of triggers might be expected in eosinophilic vasculitis?

A

Arthropod
Food
Mast cell tumor

93
Q

Besides type III HST, what type of hypersensitivity may be expected in a case of granulomatous vasculitis?

94
Q

What is the most common vaccine implicated in purpura hemorrhagica?

A

Strangles vax (S. equi)

95
Q

What is the mode of inheritance of familial cutaneous vasculopathy in GSD?

A

autosomal recessive

96
Q

What is the primary area of the skin affected in familial cutaneous vasculopathy in GSDs?

97
Q

Type I cryoglobulinemia is most commonly associated with what disease?

A

B cell malignancy (B-cell lymphoma, multiple myeloma)

98
Q

What is the most common inflammatory cell found in vasculitis?

A

Neutrophils

99
Q

What breed is predisposed to dermal arteritis of the nasal philtrum?

A

Saint Bernard

100
Q

What is a common non-injected lesional site in vaccine-associated vasculitis?

A

Apex of pinna

101
Q

What is the presumed causative agent in cutaneous and renal glomerular vasculopathy in Greyhounds?

A

Shiga-like toxin from E. coli in contaminated raw meat

102
Q

Is ischemic dermatopathy cell-rich of cell-poor?

103
Q

What is the most common inciting cause of purpura hemorrhagica in horses?

A

Streptococcus equi (strangles)

104
Q

Where are vasculitis lesions typically found?

A

Dependent areas, extremities, pressure points

105
Q

What is the typical age of onset of familial cutaneous vasculopathy in GSDs?

A

Young, within 7 weeks of age

106
Q

What type of hypersensitivity reaction is vasculitis?

107
Q

What cell type is affected in reactive histiocytosis?

A

Interstitial dendritic cells

108
Q

What breed predisposition exists for systemic histiocytosis?

A

Large breeds especially Bernese Mt Dog

109
Q

What are the primary cytokines involved in reactive histiocytosis?

A

Th1 cytokines (IL-6, IL-12, IFN-gamma, TNF-a)

110
Q

What condition is associated with a “clown nose” in dogs?

A

Cutaneous reactive histiocytosis

111
Q

What ion may be elevated on labwork in systemic histiocytosis?

112
Q

In addition to histiocytes, what inflammatory cell is common on histopathology of cutaneous reactive histiocytosis?

A

Lymphocytes

113
Q

Is reactive histiocytosis “top-heavy” or “bottom-heavy” on histopath?

A

Bottom-heavy (dermis, panniculus)

114
Q

CD4 staining is performed on fresh-frozen tissue and is positive. Is this most consistent with reactive histiocytosis or histiocytic sarcoma?

A

Reactive histiocytosis

115
Q

What IHC marker would be used to differentiate dendritic cells from macrophages?

A

CD1a (+ in DCs –> reactive histiocytosis)
CD204 (+ in macs, usually - in DCs)

116
Q

True or false: systemic reactive histiocytosis can evolve to histiocytic sarcoma

117
Q

True or false: Cutaneous reactive histiocytosis can evolve to systemic histiocytosis

118
Q

In humans, where are sarcoidal granulomas usually found?

119
Q

What are the typical lesions of sarcoidosis in horses?

A

exfoliative dermatitis/scale>
nodules
alopecia

120
Q

Is equine sarcoidosis usually progressive or acute?

A

Progressive

121
Q

What is a potential environmental trigger for equine sarcoidosis?

A

Hairy vetch

122
Q

What breed is at increased risk for sterile nodular panniculitis?

A

Dachshunds

123
Q

What antibodies are increased in canine sterile nodular panniculitis?

A

Anti-neutrophil cytoplasmic antibodies (ANCAs)

124
Q

A case of panniculitis reveals numerous eosinophils on cytology. What are the primary causes to consider for the panniculitis in this case?

A

FB
Injection reaction
Insect bite

125
Q

What is the first-line treatment for sterile granulomatous dermatitis and lymphadenitis?

A

Glucocorticoids

126
Q

What are the 3 subtypes of chronic cutaneous lupus erythematosus?

A

Exfoliative
Mucocutaneous
Discoid (facial or generalized)

127
Q

What breeds are predisposed to canine VCLE?

A

Shelties
Rough Collies

128
Q

What parts of the body are usually affected by VCLE?

A

Sparsely haired areas>
Mucocutaneous junctions

129
Q

What condition is typified by figurate erythema?

A

Canine VCLE

130
Q

What treatment combination has been shown to be highly effective in maintaining remission for VCLE?

A

Oral CsA + sun avoidance

131
Q

What breeds are predisposed to exfoliative cutaneous lupus erythematosus?

132
Q

What gender is overrepresented in ECLE?

133
Q

What is the typical age of onset of ECLE?

A

~10 months

134
Q

Where do lesions of ECLE typically start?

135
Q

What mutation is associated with canine ECLE in GSP?

A

UNC93B1 –> activation of innate immune system –> chronic interferon production

136
Q

What systemic signs can be seen with ECLE?

A

Thrombocytopenia
Lymphadenopathy
Lameness
Pain
Infertility

137
Q

What therapy is most effective for treatment of ECLE?

A

High dose glucocorticoid + other immunosuppressant

138
Q

What is the prognosis for ECLE?

A

Poor to fair (hardest cutaneous lupus to treat)

139
Q

What is the typical clinical appearance of ECLE?

A

Scaling, follicular casts, erythema, alopecia

140
Q

What breeds are predisposed to MCLE?

A

German and Belgian shepherds

141
Q

What gender is overrepresented in canine MCLE?

142
Q

What is the lesion distribution for canine MCLE?

A

Anal/perianal and genital most common (perioral, periocular, perinasal also seen)

143
Q

How can MMP be clinically differentiated from MCLE?

A

MCLE: erosion > ulceration, little scarring, typically affects haired skin first with less involvement of mucous membranes
MMP: ulcers, scarring, blisters > erosion; typically affects mucous membranes and less haired skin

144
Q

What is the typical finding of lupus erythematosus on direct immunofluorescence?

A

IgG deposition at basement membrane (positive “lupus band” test)

145
Q

What is the recommended tx for MCLE?

A

oral GC alone or with doxy/niacinamide

146
Q

What breed may be predisposed to GDLE?

A

Chinese Crested

147
Q

What is the gender predisposition for GDLE?

148
Q

What form of lupus has been reported in cats?

A

discoid lupus erythematosus

149
Q

What organ system has been demonstrated to be affected in GSPs with ECLE?

A

Kidneys (immune-complex membranous glomerulonephritis)

150
Q

True or false: Most dogs with ECLE are ANA-positive

151
Q

What receptor is impacted in canine ECLE?

152
Q

What is considered a subacute type of canine CLE?

153
Q

What breed is predisposed to FDLE?

154
Q

In what subtype(s) of cutaneous lupus are female dogs overrepresented?

155
Q

What triggers the majority of human cases of EM minor?

A

Herpesvirus (HSV1>HSV2)

156
Q

What is the main precipitating factor for SJS/TEN in humans and animals?

A

Drugs (sulfonamides, cephalosporins, penicillins, zonisamide, levamisole, phenobarb)

157
Q

What is the pathogenesis of EM?

A

Keratinocytes express antigen –> lymphocyte-mediated direct cytotoxicity of keratinocytes

158
Q

What is the suspected pathogenesis of SJS/TEN?

A

Granulysin, TNF-alpha release from cytotoxic T-cells (CD8+) and NK cells –> cell death –> epidermal necrosis

159
Q

What is the dominant cytokine in herpes-associated EM in humans?

160
Q

What is the dominant cytokine in drug-induced EM in humans?

161
Q

What is the typical lesion distribution of canine EM?

A

Trunk (esp glabrous skin)

162
Q

What feature about the clinical course of EM in dogs differs significantly from EM in humans?

A

Canine EM is often chronic or relapsing

163
Q

What is primarily responsible for the high mortality rate of SJS/TEN in humans and animals?

164
Q

What is a major ddx for SJS/TEN in dogs?

165
Q

What is the typical lesion of EM in humans?

A

Raised, target lesions with at least 3 different zones of color

166
Q

What subset of T cells predominates in the skin in EM in dogs?

A

Cytotoxic/CD8+ (though T helper/CD4+ cells present in lower numbers)

167
Q

What infectious agent has been associated with feline cases of EM?

A

Feline herpesvirus

168
Q

Is canine EM usually associated with systemic symptoms?

169
Q

Can EM resolve on its own?

170
Q

What is an infectious trigger of TEN in cattle?

A

Mycoplasma bovis

171
Q

What percentage of the body surface area should be ulcerated to make a diagnosis of TEN?

172
Q

Does TEN typically have palpable edema?

A

No – helps differentiate it clinically from EM

173
Q

What breeds are predisposed to cutaneous reactive histiocytosis/

A

Shelties
Collies

174
Q

What markers help differentiate cutaneous reactive histiocytosis from other similar diseases?

A

Expression of Thy-1 and CD4

175
Q

What is the inheritance pattern of canine familial dermatomyositis?

A

Autosomal dominant

176
Q

True or false: hyperkeratotic EM has been associated with both drug and viral triggers

A

False (no triggers were identified)

177
Q

Based on current data, what treatments are most likely to be successful for treatment of hyperkeratotic EM?

A

Cyclosporine
Oclacitinib

178
Q

What percent of skin detachment occurs in SJS?

179
Q

What percent of the body is involved but NOT ulcerated in SJS?

A

> 50% (<10% detachment)

180
Q

What clinical feature separates EM-minor from EM-major?

A

EM minor: <=1 mucosal surface
EM major: >1 mucosal surface

MK ACVD Exam (17 decks)

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