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
2
Q
What is the most common antigen targeted in canine PF?
A
Desmocollin-1
3
Q
What is the most common antibody isotype in canine and human PF?
A
IgG
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)
5
Q
What is the name of the endemic form of PF and where is it endemic?
A
Fogo selvagem, Brazil
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
7
Q
What are the 4 phenotypes of canine PF?
A
Facial-dominant
Truncal-dominant
Generalized
Foot pad-exclusive
8
Q
What are two primary differentials for PF?
A
pustular dermatophytosis (Trichophyton)
superficial pyoderma
9
Q
What is the antigen targeted in the mucosal-dominant variant of human PV?
A
Desmoglein-3
10
Q
What is the antigen targeted in the mucocutaneous variant of human PV?
A
Desmoglein-1 and desmoglein-3
11
Q
What is the antigen targeted in canine PV?
A
Desmoglein-3 (and less Dsg-1)
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
13
Q
What desmosome is more prevalent in mucosa?
A
Dsg-3
14
Q
What are the 3 types of deep pemphigus?
A
PV
Pemphigus vegetans
Paraneoplastic pemphigus
15
Q
Besides anti-DSG3 antibodies, what other gene is suspected to be involved in canine PV?
A
c-Myc
16
Q
What gender is more commonly affected by canine PV?
A
Males (opposite of human PV)
17
Q
True or false: Pruritus is common in canine PV
A
False
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)
19
Q
What is the most common distribution of human Pveg?
A
Periorificial and intertriginous areas
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
21
Q
What are the histopathologic features of Pveg?
A
PV (suprabasilar acantholysis) + hyperplastic PF
22
Q
What subtype of human Pveg has a better prognosis?
A
Hallopeau-type
23
Q
What neoplastic conditions have been associated with paraneoplastic pemphigus in dogs and cats?
A
Thymoma
Thymic lymphoma
Splenic sarcoma
24
Q
What are the most consistent targets of paraneoplastic pemphigus?
A
Periplakin
Envoplakin
Desmoglein-3
25
What two immune-mediated conditions does histopath of paraneoplastic pemphigus resemble?
PV, EM
26
What are the most common lesions of canine paraneoplastic pemphigus?
Erosions and ulcers (oral cavity and lips most often)
27
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?
Paraneoplastic pemphigus - start thorough workup for underlying neoplasia
28
What two breeds are overrepresented in canine PF?
Akita
Chow
29
Is there a sex predilection for canine or feline PF?
No
30
Apart from pustules and crusts, what other clinical feature is seen in horses with PF?
Ventral edema
31
What histopathologic features help differentiate PF from bacterial folliculitis?
PF pustules are large and span MULTIPLE follicular units
Recornification beneath the pustule
32
What is the major autoantigen of human PE?
Desmoglein-1
33
What are the histopathologic features of PE?
Intragranular or subcorneal neutrophilic/eosinophilic acantholytic pustules
Lichenoid interface dermatitis
34
What steroid has been associated with the highest rates of remission in feline PF?
Triamcinolone
35
Besides neutrophils, what inflammatory cell is often found in feline PF cases, differing from what is seen in canine PF?
Mast cells
36
Describe the pathogenesis of acantholysis in pemphigus
37
What pemphigus variants have been recognized in horses?
PF
PV
38
Describe the expression of desmosomal cadherins in haired skin/footpad/nasal planum
39
Describe the expression of desmosomal cadherins in the oral cavity/mucosa/esophagus
40
Besides genetics, what else may serve as a trigger/predisposing factor for PF?
Sun exposure
41
Are lesions of insecticide-triggered PF located at the site of application or distant from the site of application?
Both (though Vectra 3D has only been associated with distant lesions)
42
Cutaneous polyimmunity as been associated with PF and what other disease?
DLE
43
Is there a sex predilection in feline PF?
No
44
Is there a breed predisposition in feline PF?
No
45
Describe the lesion distribution of feline PF
46
In what condition may you see a "keratin ring" on histopathology?
PF
47
Are anti-DSC1 serum antibody titers related to PF severity?
Yes
48
Describe the glucocorticoid pulse regimen for treatment of PF
GC 10 mg/kg/day x3 days, then 1-2 mg/kg/day, repeat pulse if relapse occurs
49
What form of pemphigus is most common in humans?
PV
50
What is a primary difference between the vesicles seen in PV vs those seen in AISBDs?
PV vesicles are flaccid, not tense
51
What clinical test is pathognomonic for deep pemphigus?
Nikolskiy sign (direct/marginal)
52
What clinical feature of paraneoplastic pemphigus helps differentiate it from PV?
Rapid progression of lesions
53
What is the target antigen in Pveg?
Dsg-1
54
What is the suspected antigen target in feline PF?
Dsg-1
55
What is the most common distribution of skin lesions associated with vasculopathy?
Bony prominences
Body extremities
56
What adhesion molecules are upregulated on endothelial cells during vasculitis?
E-selectin
ICAM-1
57
What are four mechanisms of immune-mediated vasculitis?
Immune complex deposition in vessel walls
Production of anti-neutrophil cytoplasmic antibodies (rare)
Anti-endothelial cell antibodies
Autoreactive T-cells, macs
58
What is the main cause of purpura hemorrhagica in horses?
Streptococcus equi
59
What is the hallmark feature of cutaneous vasculitis?
Palpable purpura
60
What are the histopathologic features of cutaneous vasculitis?
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
61
What triggers have been identified for cryoglobulinemia?
Lead poisoning
URI
Multiple myeloma
Lymphoma
62
A dog with urticarial vasculitis is biopsied and histopathology reveals primarily an eosinophilic infiltrate. What is your major differential?
CAFR
63
In cutaneous and renal glomerular vasculopathy, does the AKI usually occur before, simultaneously, or after skin lesions?
After skin lesions
64
What is the most important CBC finding in canine cutaneous and renal glomerular vasculopathy?
Thrombocytopenia (due to consumption from massive vessel thrombosis)
65
What are negative prognostic indicators for the development of AKI in canine cutaneous and renal glomerular vasculopathy?
Anemia
Neutrophilia
Thrombocytopenia
66
What is the gold standard for diagnosis of canine cutaneous and renal glomerular vasculopathy?
Kidney biopsy --> thrombotic microangiopathy of glomerular arterioles
67
What drug has been associated with proliferative thrombovascular necrosis of the pinnae?
Fenbendazole
68
What infectious diseases associated with vasculitis may preferentially affect the pinnae?
Leishmania
Bartonellosis
69
What oral medication has been shown to be effective for management of proliferative thrombovascular necrosis of the pinnae?
Oclacitinib (1-3 mo response times)
70
What breed is represented in familial necrotizing arteritis?
Beagles
71
What is the pathogenesis of familial necrotizing arteritis?
Anti-neutrophil cytoplasmic antibodies
72
What breeds are represented in familial cutaneous vasculopathy?
GSD
JRT
73
What is the suspected mode of inheritance of familial cutaneous vasculopathy in GSD?
autosomal recessive
74
What is the age of onset of familial cutaneous vasculopathy in GSD?
1-3 months of age
75
What are the most common areas affected in familial cutaneous vasculopathy in GSD?
Paw pads
Bridge of the nose
76
What is a potential trigger of familial cutaneous vasculopathy in GSD and JRT?
vaccination
77
What breed has a hereditary vasculitis that is restricted to the nasal planum?
Scottish Terriers
78
What is the suspected mode of inheritance of hereditary vasculitis in Scotties?
Autosomal dominant
79
What breed is predisposed to a life-threatening form of acute neutrophilic vasculitis seen in young puppies?
Shar Peis
80
Describe the 5 subsets of ischemic dermatopathy.
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
What is the main ddx for ischemic dermatopathy?
Cutaneous lupus erythematosus (hydropic degen of basal cells seen in both conditions)
82
What breeds are typical for familial dermatomyositis?
Rough Collies
Shelties
(Beauceron shepherds
Portuguese Water Dogs
Belgian Tervurens
Working Kelpies)
83
What 3 genes are associated with canine familial dermatomyositis?
PAN2
MAP3K7CL
FH3570
84
What 2 diagnostics could be used to confirm myositis in familial dermatomyositis?
Electromyography
Muscle biopsy
85
Name 2 triggers for familial dermatomyositis
Sun
Estrus
86
What are the main cytokines involved in canine familial dermatomyositis?
Type I interferons (this is why oclacitinib may be effective)
87
Is there a genetic test for canine familial dermatomyositis?
Yes
88
What is the typical time between Rabies vaccination and onset of localized vaccine-associated ischemia?
2-3 months (up to 8 months)
89
What is the typical age of onset of skin lesions in canine familial dermatomyositis?
<6 months (lesion peak by 12 months)
90
A horse is presented with signs of vasculitis. You want to rule out equine infectious anemia as a trigger. What test will you do?
Coggins
91
Besides type III HST, what type of hypersensitivity may be expected in a case of eosinophilic vasculitis?
Type I
92
What types of triggers might be expected in eosinophilic vasculitis?
Arthropod
Food
Mast cell tumor
93
Besides type III HST, what type of hypersensitivity may be expected in a case of granulomatous vasculitis?
Type IV
94
What is the most common vaccine implicated in purpura hemorrhagica?
Strangles vax (S. equi)
95
What is the mode of inheritance of familial cutaneous vasculopathy in GSD?
autosomal recessive
96
What is the primary area of the skin affected in familial cutaneous vasculopathy in GSDs?
Paw pads
97
Type I cryoglobulinemia is most commonly associated with what disease?
B cell malignancy (B-cell lymphoma, multiple myeloma)
98
What is the most common inflammatory cell found in vasculitis?
Neutrophils
99
What breed is predisposed to dermal arteritis of the nasal philtrum?
Saint Bernard
100
What is a common non-injected lesional site in vaccine-associated vasculitis?
Apex of pinna
101
What is the presumed causative agent in cutaneous and renal glomerular vasculopathy in Greyhounds?
Shiga-like toxin from E. coli in contaminated raw meat
102
Is ischemic dermatopathy cell-rich of cell-poor?
Cell poor
103
What is the most common inciting cause of purpura hemorrhagica in horses?
Streptococcus equi (strangles)
104
Where are vasculitis lesions typically found?
Dependent areas, extremities, pressure points
105
What is the typical age of onset of familial cutaneous vasculopathy in GSDs?
Young, within 7 weeks of age
106
What type of hypersensitivity reaction is vasculitis?
Type III
107
What cell type is affected in reactive histiocytosis?
Interstitial dendritic cells
108
What breed predisposition exists for systemic histiocytosis?
Large breeds especially Bernese Mt Dog
109
What are the primary cytokines involved in reactive histiocytosis?
Th1 cytokines (IL-6, IL-12, IFN-gamma, TNF-a)
110
What condition is associated with a "clown nose" in dogs?
Cutaneous reactive histiocytosis
111
What ion may be elevated on labwork in systemic histiocytosis?
Calcium
112
In addition to histiocytes, what inflammatory cell is common on histopathology of cutaneous reactive histiocytosis?
Lymphocytes
113
Is reactive histiocytosis "top-heavy" or "bottom-heavy" on histopath?
Bottom-heavy (dermis, panniculus)
114
CD4 staining is performed on fresh-frozen tissue and is positive. Is this most consistent with reactive histiocytosis or histiocytic sarcoma?
Reactive histiocytosis
115
What IHC marker would be used to differentiate dendritic cells from macrophages?
CD1a (+ in DCs --> reactive histiocytosis)
CD204 (+ in macs, usually - in DCs)
116
True or false: systemic reactive histiocytosis can evolve to histiocytic sarcoma
False
117
True or false: Cutaneous reactive histiocytosis can evolve to systemic histiocytosis
True
118
In humans, where are sarcoidal granulomas usually found?
Lungs
119
What are the typical lesions of sarcoidosis in horses?
exfoliative dermatitis/scale>
nodules
alopecia
120
Is equine sarcoidosis usually progressive or acute?
Progressive
121
What is a potential environmental trigger for equine sarcoidosis?
Hairy vetch
122
What breed is at increased risk for sterile nodular panniculitis?
Dachshunds
123
What antibodies are increased in canine sterile nodular panniculitis?
Anti-neutrophil cytoplasmic antibodies (ANCAs)
124
A case of panniculitis reveals numerous eosinophils on cytology. What are the primary causes to consider for the panniculitis in this case?
FB
Injection reaction
Insect bite
125
What is the first-line treatment for sterile granulomatous dermatitis and lymphadenitis?
Glucocorticoids
126
What are the 3 subtypes of chronic cutaneous lupus erythematosus?
Exfoliative
Mucocutaneous
Discoid (facial or generalized)
127
What breeds are predisposed to canine VCLE?
Shelties
Rough Collies
128
What parts of the body are usually affected by VCLE?
Sparsely haired areas>
Mucocutaneous junctions
129
What condition is typified by figurate erythema?
Canine VCLE
130
What treatment combination has been shown to be highly effective in maintaining remission for VCLE?
Oral CsA + sun avoidance
131
What breeds are predisposed to exfoliative cutaneous lupus erythematosus?
GSP
Viszla
132
What gender is overrepresented in ECLE?
Female
133
What is the typical age of onset of ECLE?
~10 months
134
Where do lesions of ECLE typically start?
Head
135
What mutation is associated with canine ECLE in GSP?
UNC93B1 --> activation of innate immune system --> chronic interferon production
136
What systemic signs can be seen with ECLE?
Thrombocytopenia
Lymphadenopathy
Lameness
Pain
Infertility
137
What therapy is most effective for treatment of ECLE?
High dose glucocorticoid + other immunosuppressant
138
What is the prognosis for ECLE?
Poor to fair (hardest cutaneous lupus to treat)
139
What is the typical clinical appearance of ECLE?
Scaling, follicular casts, erythema, alopecia
140
What breeds are predisposed to MCLE?
German and Belgian shepherds
141
What gender is overrepresented in canine MCLE?
Female
142
What is the lesion distribution for canine MCLE?
Anal/perianal and genital most common (perioral, periocular, perinasal also seen)
143
How can MMP be clinically differentiated from MCLE?
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
What is the typical finding of lupus erythematosus on direct immunofluorescence?
IgG deposition at basement membrane (positive "lupus band" test)
145
What is the recommended tx for MCLE?
oral GC alone or with doxy/niacinamide
146
What breed may be predisposed to GDLE?
Chinese Crested
147
What is the gender predisposition for GDLE?
None
148
What form of lupus has been reported in cats?
discoid lupus erythematosus
149
What organ system has been demonstrated to be affected in GSPs with ECLE?
Kidneys (immune-complex membranous glomerulonephritis)
150
True or false: Most dogs with ECLE are ANA-positive
False
151
What receptor is impacted in canine ECLE?
TLR7
152
What is considered a subacute type of canine CLE?
VCLE
153
What breed is predisposed to FDLE?
GSD
154
In what subtype(s) of cutaneous lupus are female dogs overrepresented?
ECLE
MCLE
155
What triggers the majority of human cases of EM minor?
Herpesvirus (HSV1>HSV2)
156
What is the main precipitating factor for SJS/TEN in humans and animals?
Drugs (sulfonamides, cephalosporins, penicillins, zonisamide, levamisole, phenobarb)
157
What is the pathogenesis of EM?
Keratinocytes express antigen --> lymphocyte-mediated direct cytotoxicity of keratinocytes
158
What is the suspected pathogenesis of SJS/TEN?
Granulysin, TNF-alpha release from cytotoxic T-cells (CD8+) and NK cells --> cell death --> epidermal necrosis
159
What is the dominant cytokine in herpes-associated EM in humans?
IFN-gamma
160
What is the dominant cytokine in drug-induced EM in humans?
TNF-alpha
161
What is the typical lesion distribution of canine EM?
Trunk (esp glabrous skin)
162
What feature about the clinical course of EM in dogs differs significantly from EM in humans?
Canine EM is often chronic or relapsing
163
What is primarily responsible for the high mortality rate of SJS/TEN in humans and animals?
Sepsis
164
What is a major ddx for SJS/TEN in dogs?
CETL
165
What is the typical lesion of EM in humans?
Raised, target lesions with at least 3 different zones of color
166
What subset of T cells predominates in the skin in EM in dogs?
Cytotoxic/CD8+ (though T helper/CD4+ cells present in lower numbers)
167
What infectious agent has been associated with feline cases of EM?
Feline herpesvirus
168
Is canine EM usually associated with systemic symptoms?
No
169
Can EM resolve on its own?
Yes
170
What is an infectious trigger of TEN in cattle?
Mycoplasma bovis
171
What percentage of the body surface area should be ulcerated to make a diagnosis of TEN?
>30%
172
Does TEN typically have palpable edema?
No -- helps differentiate it clinically from EM
173
What breeds are predisposed to cutaneous reactive histiocytosis/
Shelties
Collies
174
What markers help differentiate cutaneous reactive histiocytosis from other similar diseases?
Expression of Thy-1 and CD4
175
What is the inheritance pattern of canine familial dermatomyositis?
Autosomal dominant
176
True or false: hyperkeratotic EM has been associated with both drug and viral triggers
False (no triggers were identified)
177
Based on current data, what treatments are most likely to be successful for treatment of hyperkeratotic EM?
Cyclosporine
Oclacitinib
178
What percent of skin detachment occurs in SJS?
<10%
179
What percent of the body is involved but NOT ulcerated in SJS?
>50% (<10% detachment)
180
What clinical feature separates EM-minor from EM-major?
EM minor: <=1 mucosal surface
EM major: >1 mucosal surface
