Chapter 9 - autoimmune Flashcards
(330 cards)
1
Q
What is the difference between auto-immune and immune-mediated disease?
A
Auto-immune = against self Immune-mediated = initial foreign trigger e.g. a drug or virus
2
Q
Azathioprine antagonises purine metabolism which interferes with the synthesis of what?
A
DNA and RNA
3
Q
Azathioprine is metabolised by which organ?
A
Liver
4
Q
Low thiopurine methyltransferase (TPMT) levels increases the risk of which adverse effect of Azathioprine?
A
Myelosuppression
5
Q
Which species has naturally low thiopurine methyltransferase (TPMT) levels?
A
Cats
6
Q
Name five adverse effects of Azathioprine
A
Anaemia Leukopaenia Thrombocytopaenia Vomiting Hypersensitivity reactions (liver) Pancreatitis Increased ALP Rashes Alopecia Diarrhoea
7
Q
How long can it take to see a clinical improvement with Azathioprine therapy?
A
3-6 weeks
8
Q
The cytotoxic effect of chlorambucil is due to cross-linking of what?
A
DNA
9
Q
Name three adverse effects of chlorambucil
A
Myelosuppresion Anorexia Vomiting Diarrhoea Alopecia Delayed hair growth
10
Q
How long can it take to see a clinical improvement with chlorambucil?
A
Several weeks
11
Q
Which inflammatory cell is most susceptible to cyclophosphamide?
A
Lymphocytes (B cells > T cells)
12
Q
Name five adverse effects of cyclophosphamide
A
Haemorrhagic cystitis Bladder fibrosis Teratogenesis Infertility Alopecia/poor hair growth Nausea Gastrointestinal inflammation Depression of bone marrow and haemopoesis Infections
13
Q
Mycophenolate mofetil suppresses which inflammatory cells?
A
B and T lymphocytes
14
Q
Which veterinary species are affected by pemphigus foliaceus?
A
Dogs, cats, horses and goats
15
Q
> 80% of PF cases have lesions at which body site?
A
Head, face and ears
16
Q
Which sites are typically affected with pemphigus vulgaris?
A
Oral cavity and MCJ
17
Q
What is the Nikolsky sign?
A
Peeling of the epidermis with a blunt instrument (lack of cohesion)
Epidermal detachment caused by mechanical pressure at the edge of a vesicle or normal skin
18
Q
Which antigen is targeted in bullous pemphigoid and where is it located?
A
Collagen XVII, basal cell hemidesmosomes
19
Q
Name two potential triggers of bullous pemphigoid
A
Drugs (sulfonamides, penicillins, furosemide)
UV light
20
Q
Do you see acanthocytes with bullous pemphigoid?
A
No
21
Q
Where does the cleft/vesicle form in bullous pemphigoid?
A
Subepidermal
22
Q
Which non-mucous membrane sites can be affected in MMP?
A
Ears, footpads (rarely) and claws
23
Q
What is the target antigen in epidermolysis bullosa acquisita?
A
Collagen VII (anchoring fibrils)
24
Q
Is epidermolysis bullosa acquisita acute or insidious in onset?
A
Acute
25
What is the target of IgG autoantibodies in acquired junctional epidermolysis bullosa?
Laminin 332
26
In what % of SLE cases do you see skin lesions?
40-50%
27
What is the most common presenting sign of SLE?
Joint disease
28
In DLE, which body sites are typically affected in cats?
Face and ears (nasal lesions are less prominent than in dogs)
29
What is the main target antigen in dogs with alopecia areata?
Trichohyalin
Many targets, often basement membrane and pre-cortex
Antibodies are secondary phenomenon and appear late in the course of disease
30
Which anatomical sites are typically affected with alopecia areata?
Head/face (muzzle, periocular)
| Also pinnae and limbs
31
Linear IgA pustular dermatosis is seen in which breed?
Dachshunds
32
Which organs are the principal targets in graft versus host disease?
Skin, liver, gastrointestinal
33
Histopathology of graft versus host disease is similar to which other disease?
Erythema multiforme
34
What are the typical skin signs in uveodermatologic syndrome?
What lesions were evident in the study by Zarfoss et al. (2018)?
Well demarcated depigmentation of hair and skin usually on the face (nose, lips, eyelids), pads, scrotum, anus and hard palate.
Dermatologic signs included leukoderma [56%]; scaling or erythema [24%]; alopecia [16%]; mucocutaneous erosions often centered around the nasal planum, mouth, eye-lids, or periocular skin [16%] and leukotrichia [14%].
35
Which histopathological pattern is seen in uveodermatologic syndrome?
Lichenoid interface granulomatous dermatitis with pigmentary incontinence and rare hydropic degeneration of epidermal basal cells
36
In pemphigus vulgaris, where are lesions most commonly found in dogs?
Lips and/or oral cavity 92%
| Gingivae and palate within the oral cavity
37
What is the reported distribution of ulcers in the four cases of feline pemphigus vulgaris?
Oral cavity, lips and nasal planum
38
What clinical sign do you see when pemphigus vulgaris affects the nails in dogs?
Onychomadesis
39
Pemphigus vulgaris has been reported in which species?
Human, dog, cat, horse, goat, monkey, and llama
40
Pemphigus erythematosus is considered a mild form of pemphigus foliaceus combined with which other disease?
Discoid (facial) lupus erythematosus
41
PNP has reportedly been associated with which types of neoplasia in dogs and one cat?
Thymoma, a thymic lymphoma and a splenic sarcoma, whereas the single cat with PNP had a lymphocytic thymoma
42
A combination of which two histopathological disease patterns is seen in cases of PNP?
Pemphigus vulgaris - suprabasal acantholysis
Erythema multiforme - apoptosis of individual keratinocytes at multiple epidermal levels, lymphocytic/vacuolar interface dermatitis, and leukocytic exocytosis
43
What are the histopathological findings in pemphigus vegetans?
Distinctly hyperplastic epidermal lesions (PF type) and a suprabasal acantholysis typical of PV
44
In the review by Tham et al. (2020), what % of treated dogs with PV reached complete remission?
65%
45
PV affecting only the nails/claws cannot be clinically distinguished from canine symmetric lupoid onychodystrophy (SLO) or idiopathic onychitis/onychomadesis, unless what is present?
An erosion/ulcer on the periungual region, which is rarely seen in canine SLO
46
True or false:
Human patients affected by mucosal-dominant PV only have detectable anti-DSG3 IgG AA, whereas those with mucocutaneous form of PV have both anti-DSG3 and DSG1 IgG AA
True
47
How does the base of an erosion associated with PV differ from erosions due to other causes?
Deep erosions from other causes can be lined by a single layer of epithelial cells, but these cells are usually flattened and elongated, and thus more typical of a wound healing response.
48
Which breeds of dog may be at higher risk of developing PF?
Akitas and Chows
| Possibly English cocker spaniels, Shar-peis and collies
49
```
In Mueller et al. study of 91 dogs with PF, what % had:
facial lesions only
generalised disease
footpad involvement
footpad lesions only
```
facial lesions only - 16%
generalised disease - 66%
footpad involvement - 33%
footpad lesions only - 2%
50
Roughly what % of dogs with PF are pruritic?
25-50%
51
Pemphigus foliaceus in animals has been reported in association with which systemic diseases?
Hypothyroidism
Leishmaniasis
Thymoma
Systemic lupus erythematosus
52
Can intercellular epidermal IgG be found in biopsy specimens obtained from dogs with dermatoses other than PF?
Yes - direct IF is not a specific test
53
Vasculitis is most often regarded as an immune-mediated, type III hypersensitivity response, resulting in excessive antigen-antibody immune complex deposition in vessel walls. Describe how it occurs?
1. Antigen-antibody complexes become trapped in blood vessel walls as a result of incomplete clearance, which activates the complement cascade and inflammatory cell recruitment to the vessel wall.
2. The cells then infiltrate vessel walls and release lysosomal con-tents (collagenase and elastase) and reactive oxygen species which damage endothelial cells.
3. Over time, this damage results in fibrin deposition, endothelial necrosis, extravasation of erythrocytes and formation of thrombi.
54
What are the main triggers of vasculitis in dogs?
Drugs, vaccinations, infections and neoplasia
55
In dogs with PF, do those with vasculopathic lesions present differently in terms of clinical lesions and distribution?
No - some may present with oedema or non-blanching erythema but in most cases, the vascular changes on histopathological evaluation were not sufficiently severe to cause clinical manifestations.
56
In dogs with PF, do those with vasculopathic lesions present differently in terms of systemic clinical signs?
Dogs with vasculopathic lesions on histopathological evaluation were more likely to present with one or more systemic signs of illness than those without.
57
In dogs with PF, do vasculopathic lesions affect outcome?
PF and concurrent vasculitis may be more refractory to treatment and take longer to achieve remission than PF without concurrent vascular changes.
58
What are the major targets of autoantibodies in human and canine PF?
Human - desmoglein-1(Dsg-1)
| Canine - desmocollin-1 (Dsc-1)
59
Mycophenolate mofetil may be more likely to cause GI adverse effects at what dose?
> 30 mg/kg/day
60
Rank the AISBD in order of prevalence in dogs:
Bullous pemphigoid
Epidermolysis bullosa aquisita
Junctional epidermolysis bullosa aquisita
Linear IgA disease
Mixed AISBD
Mucous membrane pemphigoid
Pemphigoid of gestation
Type 1 bullous systemic lupus erythematosus
1. Mucous membrane pemphigoid (48 %)
2. Epidermolysis bullosa aquisita (26 %)
3. Bullous pemphigoid (10 %)
4. Junctional epidermolysis bullosa aquisita (6 %)
5. Mixed AISBD (4 %)
6. Linear IgA disease (3 %)
7. Pemphigoid of gestation and Type 1 bullous systemic lupus erythematosus (1 % each)
61
In the paper by Tham et al. (2016), what body areas were first affected in dogs with mucous membrane pemphigoid?
Oral/perioral (75 %)
Ocular/periocular (38 %)
Nasal (25 %)
Genital (13 %) and / or concave pinnae (13 %)
62
In the paper by Tham et al. (2016), what were the clinical signs of mucous membrane pemphigoid?
Skin lesions were symmetrical in 88% and they consisted of erosions and ulcers 100% – an inclusion criterion, crusting 56%, erythema 31%, vesicles/bullae 31%, scarring 19% and hypopigmentation 13%
63
In the paper by Tham et al. (2016), at presentation 100% of dogs with mucous membrane pemphigoid had lesions on mucosae and MCJ (the nasal planum is a modified mucosa), what % had lesions on haired skin?
38 %
64
In the paper by Tham et al. (2016), how many dogs with mucous membrane pemphigoid had lesions at more than one mucosal/MCJ site?
94 %
65
In the paper by Tham et al. (2016), complete remission was achieved in what % of dogs with mucous membrane pemphigoid and in what time frame?
91 % in median of 33 weeks (6-64 weeks)
66
How can you differentiate DLE and MCLE from MMP?
DLE and MCLE rarely affect the oral cavity and oral lesions are present in the vast majority of dogs with MMP
67
In the paper by Tham et al. (2016), what treatment was recommended as first line for MMP and which was reportedly the least successful at inducing remission?
- Tetracycline and niacinamide with or without additional immunosuppressive drugs
- Glucocorticoid monotherapy was the most frequent treatment regimen that failed to induce CR
68
What is anoikis?
Anoikis is a form of apoptosis triggered by a loss of the cell attachment to the appropriate matrix
69
What are the reportedly targeted antigens in dogs with mucous membrane pemphigoid?
Collagen XVII
BP230
Laminin-332
70
Which antigen has been shown to be targeted in a cat with mucous membrane pemphigoid?
Laminin-332
71
What % of epidermal detachment is seen in SJS and TEN?
SJS < 10%
| TEN > 30%
72
Which body areas are typically affected in SJS and TEN in dogs and cats?
Trunk, often axillary and inguinal, mucocutaneous junctions, concave pinnae, pads
Can be generalised
Mucosal involvement is severe – more than one mucosal site affected
73
How many mucosal sites are affected in EM minor and EM major in cats and dogs?
EM minor – none or 1 site
| EM major > 1 site
74
According to Yager et al. (2014), which ‘drug’ causes of EM in dogs have been confirmed?
Those triggered by beef/soy, commercial dog food and a nutraceutical product have been proved through (unintentional) rechallenge
75
In SJS/TEN, mucosal lesions typically affect the oral cavity but can be seen at which other mucosal sites?
Tracheobronchial, urogenital and oesophageal mucosae are susceptible.
Corneal involvement occurs in people and animals.
76
True or false:
| In dogs and cats, the follicular infundibular epithelium is usually affected concurrently in EM, SJS and TEN.
True
77
Toxic epidermal necrolysis is distinguished from a burn by the lack of what histopathological findings?
Dermal necrosis
78
What are the differential diagnoses for SJS/TEN in dogs?
```
Burns
Bullous autoimmune diseases
SLE
Superficial suppurative dermatitis of miniature schnauzers
Vasculitis
Epitheliotropic lymphoma
```
79
What novel treatment for hyperkeratotic (old dog) EM was presented by High et al. (2020)?
Oclacitinib 0.6-0.9 mg/kg BID
80
Which other diseases in cats can present with similar histological signs to EM?
Proliferative and necrotizing otitis externa (PNOE) also has significant outer epidermal apoptosis, which can be confused with lesions of EM.
The microscopic lesions of thymoma-associated paraneoplastic exfoliative dermatosis in cats are EM like, in that they represent an epidermal cytotoxicity reaction pattern. In addition to marked hyperkeratosis, sebaceous glands are targeted and maybe absent in some cases. Similar lesions of exfoliative dermatitis, with no accompanying thymoma, have been characterized as a form of feline EM.
81
Which other diseases in dogs can present with similar histological signs to EM?
- Ciclosporin-responsive ‘proliferative, lymphocytic, infundibular mural folliculitis and dermatitis with prominent follicular apoptosis and parakeratotic casts’ (PLIMFD), typically in young Labrador retrievers.
- A very similar case, also in a Labrador retriever puppy, was reported in 1983; this showed a rapid clinical response to oral vitamin A (40,000 IU twice daily); treatment was required for life.
- A significantly large subset of canine superficial necrolytic dermatitis cases show prominent single cell death in the outer stratum spinosum.
82
In Banovic et al. (2015); canine TEN signs were irregular erythematous and purpuric macules that evolved into widespread and severely painful erosions. The number of eroded mucosae varied; however, which mucocutaneous junctions frequently were affected?
Periocular and perilabial
83
In the study by Banovic et al. (2015) on canine TEN, what was the most common pattern of epidermal necrosis?
Apoptosis at multiple epidermal levels was the most common pattern of epidermal necrosis (12/13 biopsies, 92%). In contrast, full-thickness coagulation necrosis was present less often (7/13 biopsies, 52%).
84
In uveodermatological syndrome, can dogs develop ophthalmic signs before dermatological signs?
Yes, this occurred in 66% of dogs in the study by Zarfoss et al. (2018)
85
Which breeds of dog are over-represented in cases of uveodermatological syndrome and which gene mutation is associated?
```
American Akitas (Siberian Huskies, Samoyeds)
Dog leukocyte haplotype (DLA)-DQA1*00201
```
86
Has alopecia areata universalis been reported in the dog?
Yes - complete hair loss included eyelashes and vibrissae
Also a report of AAU in a dog with testicular neoplasia; signs worsened following castration and resolved with ciclosporin therapy
87
Can the nails be affected in dogs with alopecia areata?
Yes - roughening, ridging, and vertical striations (trachyonychia) have been reported
The claw matrix is also an immune-privileged site
88
Septic vasculitis can be seen with which ectoparasite infestation?
Generalised demodicosis with cellulitis
89
Familial cutaneous vasculopathy affects which breed of dog?
GSD
| Also reported in fox terriers and miniature schnauzers
90
Proliferative arteritis of the nasal planum classically affects which breed of dog?
Which part of the nose is affected?
St. Bernard (also giant schnauzer, basset hound, Labradors, Newfies and Samoyeds)
Nasal philtrum - often symmetrically
91
What are the clinical signs of familial cutaneous vasculopathy?
```
Pyrexia
Lethargy
Swollen, depigmented footpads
Alopecia, crusts and ulceration may also occur - pinnae, tail and nasal planum
Usually by seven weeks old
```
92
What are the five clinical presentations of ischaemic dermatopathy?
1. Familial dermatomyositis
2. Juvenile onset dermatomyositis in other breeds
3. Post-rabies vaccination panniculitis
4. Generalised vaccine-induced ischaemic dermatopathy
5. Adult onset with no temporal association with vaccination
93
Vaccine associated ischaemic dermatopathy lesions occur when?
2-8 months after vaccination
94
Which vector-borne infectious diseases can be associated with vasculitis?
```
Babesia
Ehrlichia/Anaplasma
Bartonella
Rickettsia rickettsia
Borrelia burgdorferi
Leishmania infantum
```
95
What is a key histopathological feature of pseudopelade?
Lymphocytic infiltration that targets the mid-isthmus of the hair follicle where the follicular bulge cells (stem cells for hair growth) are present. Destruction of these stem cells results in permanent scarring alopecia.
96
Is auricular chondritis in dogs and cats painful?
Reports are variable but often considered painful (some are asymptomatic)
97
Bilateral auricular chondritis may be a manifestation of relapsing polychondritis; which other organs can be affected with this disease?
```
Nonerosive seronegative inflammatory polyarthritis
Nasal chondritis
Ocular inflammation
Respiratory tract chondritis
Cochlear and/or vestibular signs
```
98
What are the differentials for the clinical signs of vasculitis?
Sepsis (can cause thrombosis and / or vasculopathy)
Disseminated intravascular coagulation
Cryoglobulinaemia / Cryofibrinogenaemia (cold agglutinin disease)
Frostbite
SLE
Lymphoreticular neoplasia
Subepidermal bullous diseases and burns if ulceration is present
99
What are the underlying causes of vasculitis in dogs?
```
Drugs
Insect bites
Food
Infections (viral, bacterial, mycobacterial, fungal, protozoal and rickettsial)
Neoplasia, autoimmune disease
Genetic/familial
Idiopathic
```
100
Which antifungal drug is known to trigger vasculitis in dogs and at what dose?
Itraconazole at 10 mg/kg
101
The case of urticarial vasculitis in a three year old FB reported in Vet Derm by Jan Declerq (2014) was suspected to be triggered by what?
Food
ECVD abstracts - cold urticarial vasculitis and drug (amoxicillin/clavulanic acid)
102
Which other drugs have reportedly been associated with cutaneous vasculitis in dogs and cats?
```
Antibiotics
Ivermectin
Vaccines
Itraconazole
Metronidazole
Phenobarbital
Furosemide
Enalapril
Phenylbutazone
Imodium
Metoclopramide
Fenbendazole
Acepromazine
NSAIDs (Meloxicam)
```
103
Which bacteria has been associated with idiopathic cutaneous renal glomerular vasculopathy in Greyhounds (‘Alabama rot’)?
Verotoxin-producing strains of Escherichia coli O157:H7 – this disease is not thought to be purely infectious and genetic factors may be involved
104
CRGV in dogs in the UK affects a variety of breeds. What are the clinical signs?
- Skin lesions affecting the limbs (77-81%), body (20%), face/muzzle (7%) and tongue (4%) – usually precede systemic signs
- Vary from small, superficial abrasions (0.5 cm), to large areas of full-thickness ulceration and necrosis (>30 cm), with surrounding bruising and edema. Lesions are commonly circular and erythematous.
- Oligoanuric acute kidney injury – high mortality rate associated with this
- AKI developed on average 3 days after skin lesions (97.6% within 13 days)
105
In the study by Souza et al. (2019) on dermal arteritis of the nasal planum, which breeds were most commonly affected?
Saint Bernard > bloodhound, great Dane, German shorthaired pointer
106
In the study by Souza et al. (2019) on dermal arteritis of the nasal planum, what was the mean age of onset?
5.3 years
107
In the study by Souza et al. (2019) on dermal arteritis of the nasal planum, what treatment did they recommend?
0.1% tacrolimus ointment
108
Which diseases have reportedly been associated with ear tip ulcerative dermatitis in dogs?
Leishmaniosis, bartonellosis, Rickettsia rickettsia experimental infection, frostbite, cryoglobulinaemia and familiar vasculitides
109
Which treatment reported by Colombo et al. (2021) was effective in 22/25 dogs with ear tip ulcerative dermatitis?
Oclacitinib 0.4-0.6 mg/kg BID or SID
110
Proliferative thrombovascular necrosis of the pinna is considered idiopathic; which vessels are targeted?
Small dermal arterioles - fibrinoid degeneration and thickening of small dermal arteriole walls, and fibrin thrombi.
111
Which breeds of dog are considered to be predisposed to ear tip ulcerative dermatitis?
Dachshunds and Rhodesian Ridgebacks
112
Which breeds of dog are reportedly predisposed to vaccine associated vasculitis?
Yorkshire terriers, Poodles, Silky terriers, Pekingese and Maltese
113
Which breeds of dog have familial vasculitides been reported in?
GSD – young puppies with foot pad lesions
Scottish terriers – litter of puppies with nasal lesions of leukocytoclastic vasculitis and pyogranulomatous inflammation
114
Measurement of which substance in the blood can aid diagnosis of vasculitis?
D-dimers - fibrin degradation product, associated with thrombus formation
115
Neutrophilic vasculitis can be suggestive of which diseases?
Type III immune-complex hypersensitivity e.g. Staphylococcal dermatitis, SLE, some drug eruptions and septicaemia
116
Eosinophilic vasculitis can be suggestive of which diseases?
Type I hypersensitivity reactions e.g. arthropod bites, mast cell tumours, EGC in cats, drug and food reactions, canine eosinophilic dermatitis
117
Lymphocytic vasculitis can be suggestive of which diseases?
Suggests a cell-mediated immune response e.g. rabies vaccine, some drug eruptions
118
Pruritic, papular lesions on the dorsal head and back of a 19 week old male DSH kitten with concurrent pyrexia showed nodular pyogranulomatous dermatitis with vasculitis and necrosis on histopathology associated with which virus?
Feline coronavirus (FIP)
119
Do cats with auricular chondritis have lesions in other cartilagenous tissues?
Not usually - one case report of lesions in the sternum, joints, tracheal and laryngeal cartilages
120
Has auricular chondritis been reported in the dog
Yes - rarely
121
How do you treat auricular chondritis?
```
Variable response reported to steroids and ciclosporin
Dapsone has been effective in some cases
Pinnectomy
Spontaneous remission has been reported
No treatment if not painful
```
122
What are the clinical differences in signs of pseudopelade in dogs and cats?
- In the dog head and neck are sparred
- In the cat the alopecia may begin from the face and then spread to ventrum, legs and paws
- In the cat onychomadesis and onychorrexis can be present
123
Metatarsal fistulation has been reported in GSDs and which other breeds?
Weimeraner and Greyhound
124
What are the histopathological findings with metatarsal fistulation in GSDs?
- Nodular to diffuse predominantly pyogranulomatous dermatitis
with fibrosis and fistulous tracts
- Hair follicle rupture with endogenous foreign body reaction to keratin and hair shaft is common
125
What are the three suspected pathomechanisms of sebaceous adenitis?
1. Developmental and inherited defect that leads to sebaceous gland destruction
2. Abnormality in lipid metabolism or storage
3. Keratinisation abnormality that leads to obstruction of the sebaceous ducts, resulting to the inflammation of the sebaceous glands
126
How does sebaceous adenitis presentin short-coated breeds?
- Annular areas of scaling and alopecia that coalesce
White, fine scales that do not attach to hair
- Moth-eaten appearance
127
Which gene is responsible for perianal fistulas in GSDs?
DLA-DRB1*00101
128
Perianal fistulas have been reported in GSDs and which other breeds?
Irish Setter, Collie, Border collie, Old English sheepdog, Labrador retriever, English bulldog, Bouvier de Flandres, Spaniels, Beagles
129
In canine perianal fistulas, what bacterial dysbiosis is reported?
- Increased abundance of Bacteroides vulgatus and Escherichia coli
- Decreased abundance of Megamonas species and Prevotella copri
130
Which diseases have been linked to cold agglutinin disease in the dog and cat?
Dog: Idiopathic, lead poisoning, infection
Cat: Respiratory infection, idiopathic, lead poisoning
131
How frequent is hair regrowth in cases of alopecia areata and why does it occur?
39%
| Stem cells localized in the HF bulge are usually not targeted
132
In which dog and cat breeds is there a familial predisposition for amyloidosis?
Shar-Pei, Beagle
Abyssinian, Siamese
Cocker spaniel (may be predisposed to primary cutaneous amyloidosis and extramedullary plasmacytoma resulting in cutaneous amyloidosis
133
Which stain can be used to identify amyloidosis on histopathology?
Congo red
134
HCA has been used topically to treat which autoimmune disease in cats?
PF – BID application (Hobi et al., 2022; De Bellis et al., 2008)
135
Can histopathology of crust, without skin biopsy, aid diagnosis of PF?
Hobi et al. (2022) demonstrated acantholytic keratinocytes in crust on histopathology when biopsy could not be performed in cats
136
Ciclosporin enters the T cell and forms a physical complex with _________ that inhibits calcineurin, an intracellular phosphatase without which the cell cannot activate the gene transcription factor nuclear factor of activated T cells, leading to decreased production of IL-2 and IFN-gamma.
Cyclophilin
137
In uveodermatological syndrome, at which body site do skin lesions occur?
Head/face
| Nasal planum > periocular > lips
138
What skin lesions are seen with uveodermatological syndrome?
Leukoderma and/or leukotrichia, erosions/ulcerations, alopecia, crust and erythema
139
Which autoimmune/immune-mediated disease target cause mural folliculitis of the isthmus?
- Pseudopelade
- Mucinotic m.f. of lundehunds
- Degenerative mucinotic m.f.
- Cutaneous and systemic LE
- Granulomatous m.f
140
What are differential diagnoses for mural folliculitis targeting the infundibulum?
- Demodectic m.f. *
- Dermatophytic m.f. *
- Cutaneous and systemic LE*
- Thymoma-associated exfoliative dermatitis *
- Proliferative lymphocytic m.f with apoptosis
- Proliferative and necrotizing otitis externa in cats
- Granulomatous m.f
141
Which autoimmune/immune-mediated disease target cause mural folliculitis of the inferior portion of the HF?
Alopecia areata
142
Which breeds of dog are commonly affected by alopecia areata?
GSD
Dachshund
Beagle
143
Which inflammatory cells predominate in alopecia areata?
CD8+ T cells
144
A mucinotic, mural isthmic folliculitis is seen in which breed of dog?
Lundehunds
145
Which treatment is effective for mural isthmic folliculitis of Lundehunds?
Ciclosporin
146
Feline degenerative mucinotic mural folliculitis has clinical signs of generalized alopecia with more pronounced lesions affecting the face, head, neck and shoulders, variable pruritus and which other sign?
The skin of the face of all cats had a thickened and swollen appearance, particularly on the muzzle. The eye openings were often narrowed to just slits.
There was accompanying scaling and/or crusting,
and variable hyperpigmentation.
147
Which cadherins are present in haired skin and which layers are the most abundant?
DSC1 - superficial > deep
DSG1 - superficial > deep
DSG3 - sparse, deep
DSC3 - sparse, deep
148
Which cadherins are present in mucous membranes and which layers are the most abundant?
DSC1 - NO
DSG1 - sparse, superficial > deep
DSG3 - deep > superficial
DSC3 - deep > superficial
149
Which antibody predominates in PF?
IgG4
150
What are the proposed mechanisms for acantholysis in PF?
1. Steric hindrance
2. Signaling disruption
3. Inhibition of desmosome assembly and promotion of its disassembly by clustering and/or endocytosis of
cadherins
151
People with active PF produce pathogenic IgG4
| targeting which epitopes of DSG1?
EC1 and EC2 (extracellular) domains
152
What is the suspected target of Ab in feline PF?
DSG1
153
Name the superficial types of pemphigus in dogs and their targets
PF
Pemphigus erythematosus
DSC1 +/- DSG1
154
Name the deep types of pemphigus in dogs and their targets
PV
PNP
Pemphigus vegetans
DSG3 +/- DSG1
155
What is the odds ratio for PF in Chows?
13
156
Which environmental factor may be a trigger for PF?
UV exposure
157
What do PF pustules look like?
Non-expanding, irregular and confluent
158
Can you see clustering of lesions in PF with an annular to polycyclic arrangement and clear center?
Yes - these do not expand cf Staph collarettes
159
What are the phenotypes of PF?
1. Classical: facial predominant +/- trunk and feet, nasal or pedal
2. Atypical: truncal but not facial
3. Insecticide triggered: application site plus classical
160
Which insecticides have triggered PF in dogs?
Promeris - metaflumizone
Vectra 3D - dinotefuran, pyriproxyfen and permethrin.
Certifect - fipronil, s-methoprene, amitraz
161
Which diseases can mimic signs of PF in dogs?
1. Pustular dermatophytosis
2. Eosinophilic furunculosis
3. Aspergillosis (nasal lesions)
4. Zinc responsive dermatosis
5. EM
6. SND
162
What are the common systemic signs of PF in dogs and how often are they seen?
Pruritus 22%
Pain 35% (especially pedal)
Pyrexia and lethargy 45%
163
What are the common systemic signs of PF in the cat and how often are they seen?
1. Pruritus 64%
2. Pyrexia 27%
3. Lethargy 50%
164
Which diseases can mimic PF in cats?
1. Thymoma
2. FASS
3. Notoedric mange
4. Herpes
5. Acantholytic dermatitis of unknown origin
165
What is a keratin ring?
Condensation of keratin filaments after separation from the desmosome
166
Why don't you see MM lesions in PF when DSG1 is targeted? E.g. in people and cats
DSG3 may keep keratinocytes bound together (present in large amounts in MMs)
167
When can you start tapering steroids in PF treatment?
When no new lesions have been seen for 2 weeks and 80% of lesions have healed
168
When should you add a lymphocyte immunosuppressant in PF treatment?
If a relapse occurs before the end of the consolidation phase or the end of the consolidation phase cannot be reached in 1 month
Consolidation phase = no new lesions and healing begins
It ends when no new lesions have been seen for 2 weeks and 80% of lesions have healed
169
What dose of prednisolone is used for pulse dosing in PF?
10 mg/kg for 3 days followed by 1-2 mg/kg/d
| Repeat pulse if new lesions appear (no more than SIW)
170
What is the benefit of pulse steroid therapy for PF in dogs?
Significantly more dogs achieved complete remission
Time to CR, adjunct therapy and severe a/e were not statistically different
171
Can steroids prevent keratinocyte acantholysis?
Yes, in vitro
172
Which adverse events have been reported with pulse steroid therapy for PF?
Diarrhoea
Melaena
Aggression
173
What % of dogs can remain in remission for >12 months when treatment for PF is stopped?
12%
174
Can insecticide triggered PF spontaneously resolve?
No
175
What is the median time to complete remission of PF in dogs and cats?
Dogs 12 months
| Cats 21 days! 90% in < 30 days
176
How common is PV in dogs?
0.1-0.2% of dogs with skin disease
177
How do vesicles in deep pemphigus differ from subepidermal AIBD?
Deep pemphigus = flacid, rupture easily
| SAIBD = tense +/- haemorhage
178
Do you see significant Erythema associated with erosions in PV?
No (cf EM)
179
What are the three types of Nikolsky sign?
```
Marginal = rub normal marginal skin (PV)
Direct = rub distant normal skin (PV)
Pseudo = rub erythematosus skin (SJS/TEN)
```
180
Which disease is identified by this classical sign?
PV
181
Can suprabasal clefting in PV also occur around hair follicles?
Yes
182
Has spontaneous remission been reported in dogs with PV?
Yes, extremely rare
183
What % of dogs with PV achieve complete remission and in what time frame?
65%
| 0.5-9 months
184
What % of dogs with PV are euthanized (a/e treatment or lack of response)?
38%
185
In a horse with mucocutaneous PV, what did antibodies target?
DSG3 and DSG1
186
In a dog with pemphigus vegetans, what did antibodies target?
DSG1 (not DSG3 as in people!)
187
In cats with PF, what % have generalised or localised disease?
Generalised 81%
| Localised 19%
188
In cats with PF, what % have lesions on the head/face?
85%
Pinnae 80%
Nose 37%
Periocular 20%
189
In cats with PF, what % have lesions on the limbs/feet?
73%
Footpads 23%
Claw folds 56%
Claws only 11%
190
In cats with PF, what % have lesions on the neck or trunk?
45%
| Aerola/periareolar 10%
191
In cats with PF, what % have lesions on the perianal/perigenital skin?
4%
192
In the review by Bizikova (2019), which drugs were triggers of PF In cats?
Cimetidine and doxycycline were proven with rechallenge
| Lime sulfur/itraconazole, antibiotics, carprofen suspected
193
In the review by Bizikova (2019), which disease were associated with PF in cats?
Leishmaniosis
| Thymoma
194
In human endemic PF in Brazil, what has been suggested as an antigenic trigger of PF?
A sand fly salivary antigen via molecular mimicry
195
Does pulse steroid therapy reduce time to remission in cats with PF as it can in dogs?
No - but cats with PF respond rapidly to steroids
196
Adverse effects were reported in 1/3rd of cats treated for PF; name the more severe a/e seen
Diabetes mellitus
UTIs
Hepatopathy
Bone marrow suppression (chlorambucil, azathioprine)
197
Death or euthansia associated with PF was reported in what % of cats?
10%
198
Is ciclosporin an effective treatment for PF?
Used alongside GCs can achieve clinical remission (median of 57 days with ~6 mg/kg CsA in Chong et al.)
~50% could be maintained in ciclosporin alone
199
Is MMF an effective treatment for PF?
May have a steroid sparing effect but remission cannot be maintained on MMF alone
200
Has oclacitinib been reported as a treatment for PV in dogs?
Yes, starting at 0.5 mg/kg BID
201
Has oclacitinib been reported as a treatment for PF in cats?
Yes, starting at 1mg/kg BID
202
Can Bruton's tyrosine kinase inhibitors be used to treat PF in dogs?
They may have some benefit (45-75% of dogs >90% of lesions resolved)
203
Are anti-keratinocyte antibodies specific for PF in dogs and cats?
No - they can be found in healthy animals too (although at lower levels)
204
PF has been reported in combination with which other autoimmune skin disease in dogs?
GDLE
205
What is the difference between direct and indirect IF?
Does indirect or direct immunofluorescence recognise antikeratinocyte autoantibodies in tissue?
- Direct = a single antibody directed against the target of interest. Reduces risk of non-specific binding.
- Indirect = a primary unconjugated antibody and a fluorophore-conjugated secondary antibody directed against the primary antibody. Several secondary antibodies will bind to the primary antibody resulting in an amplified signal.
Direct IF = tissue
Indirect IF = serum
206
Is CRP affected in cases of canine PF? Can it be used to distinguish PF from Staph. pyoderma?
- CRP levels are increased beyond normal in dogs with PF
| - Dogs with CRP 10.6lg/ mL were 5.5 times more likely to have PF than Staph. pyoderma.
207
What are the early signs of PV on histopathology?
1. Spongiosis and vacuolation of the suprabasilar epidermis
2. Progresses to suprabasilar acantholysis with intraepidermal clefts, vesicles, or bullae between the stratum basale and the stratum spinosum
208
What types of dermal inflammatory patterns can accompany the epidermal changes seen in pemphigus vulgaris?
1. A perivascular-to-interstitial pattern of inflammation predominates (neutrophils, lymphocytes, and plasma cells and in some dogs, eosinophils)
2. A band-like (lichenoid) inflammatory cell infiltrate may occur just below the epithelium. Stereotypic tissue response in mucosal, perimucosal, and nasal planum
209
Is scarring a typical feature of PV?
No
210
What dose of prednisolone is recommended to treat PV in dogs and cats?
Dogs: at least 3 mg/kg/day
Cats: up to 3 mg/kg twice daily
211
What are the clinical signs of pemphigus vegetans?
1. Blistering acantholytic dermatosis that combines unusually hyperplastic and verrucous pustular skin lesions and mucosal erosions.
2. Tends to affect the periorificial regions (e.g., the vermilion border of the lips) or large skin fold areas and the oral cavity (vegetative lesions rare in oral cavity)
212
What are the suggested mechanisms of PNP in people?
Tumor-induced production of AA, the cross-reactivity of tumor and epithelial antigens, as well as epitope spreading
213
Which isoxazoline has been suspected as a trigger of PF in dogs?
Afoxolaner
214
Polysulphated GAGs have been used alongside immunosuppressive medication to treat refractory cases of which disease in dogs?
PF
215
Pemphigus erythematosus has been reported with which neoplasia in the dog?
Epitheliotropic (T cell) lymphoma
216
In cats with PF, vasculopathological changes were noted in what % of cats? Demonstrated by varying degrees of microhaemorrhage, leucocytoclasia, necrotic dermal components within crusts and fibrin leakage
17%
217
In Jorden et al. (2019); which inflammatory cells predominated in the dermis of cats with PF?
Neutrophils > mast cells and plasma cells
218
Acantholytic dermatitis of unknown origin in cats, which presents with progressive, well-demarcated, crusting dermatitis with variable pruritus, differs from PF in what way?
- It does not respond to immunosuppression
- Lesions are asymmetrical originating in one (or two) body location: digits, paw or legs, face or head
- Lesions are progressive
- All affected cats were from the same state in the US
219
PNP has been reported in a cat associated with which neoplasia and which other disease?
Thymoma
| Myasthenia gravis
220
Which breed of dog is reportedly over-represented in cases of MMP?
GSD
221
Does MMP have a slow or acute progression?
Slow
222
What were the non-dermatological clinical signs of MMP?
Oral malodour, pain when eating, excessive salivation/drooling
223
Collagen XVII, BP230 and laminin-332 are targeted in canine MMP; which other antigens are reportedly targeted in people?
Integrin alpha-6 beta-4 and more rarely, collagen VII
224
Name dog breeds with high prevalence of SLO
```
Bearded Collie
GSD
Gordon Setter
English Setter
Giant Schnauzer
Rottweilers
```
225
Which gene has been suggested for developing of SLO in Bearded collie, Gordon setters , Giant Schnauzers
DLA class II alleles
226
Name three differential diagnoses for SLO
```
Bacterial paronychia
Onychomycosis
Nailbed keratoacanthoma
Nailbed epithelial inclusion cyst
Claw bed SCC
```
227
What is average healthy CLAW GROWTH ?
0.7 to 2.1 mm/week
228
What are listed underlying causes of SLO?
Adverse food reaction
Hypothyroidism
Idiopathic
229
Name four treatment options for SLO
```
OIL SUPPLEMENTS containing omega3 and omega6
-especially gamma-LINOLENIC ACID
-effective in multiple reports
FA+ PENTOXYFYLLINE
TOPICAL GCs
TETRACYCLINE/NIACINAMIDE
SYSTEMIC GCs
AZATHIPRINE
CICLOSPORIN
SURGICAL ONYCHECTOMY
```
230
What is proposed MOA why fatty acids work in SLO?
1. Neutrophils and macrophages obtain higher concentration of EPA and DHA in cell membranes
2. It is thought that it contributes to modulating immune response so that less potent inflammatory mediators are produced
3. Expression of MHC class I and II on cell surface decreases in animals fed a diet rich in omega-3 fatty acids
231
Which two diagnostic methods can be used to help diagnose SLO?
1. Amputation of P3
| 2. Onychobiopsy using 8 mm punch (claw may not regrow normally as removing claw matrix!)
232
In canine bullous SLE, which antigen is targeted?
Collagen VII
233
Which type of hypersensitivities are involved in pathogenesis of SLE?
Type III-most common
Type II and IV also occur
Effectors:
1. Pathogenic antibodies
2. Pathogenic immune complexes (glomeruli, synovia, choroid plexus)
3. Autoreactive T cells (dermatologic lesions, polymyositis and vasculitis)
234
Which genes has SLE has been associated with?
DLA A7 allele
| DLA A1 and B5
235
Name criteria for SLE
1. ANA titre- in absence of drugs, infections, or neoplastic conditions
2. Cutaneous lesions - depigmentation, erythema, erosions, ulcerations, crusts, and/or scaling, biopsy consistent with SLE
3. Oral ulcers- oral or nasopharyngeal ulceration, usually painless
4. Arthritis -nonerosive, non-septic involving 2 or more peripheral joints
5. Renal disorders - glomerulonephritis or persistent proteinuria in absence of UTI
6. Anemia and/or thrombocytopenia - no offending drugs
7. Leukopenia
8. Polymyositis or myocarditis
9. Serositis –presence of non-septic inflammatory cavity effusion
10. Neurologic disorders –seizures or psychosis in absence of known disorders
11. Antiphospholid antibodies- prolongation of activated partial thromboplastin time
2 criteria and positive ANA !
3 or more, but without ANA are considered positive for SLE
236
Is there a sex predisposition for vasculitis?
Yes - females 4x more likely to have primary vasculitis
- Immune mediated diseases are related to effects of oestrogens
- Oestrogens are associated with active Th1 responses, greater numbers of CD4+ T cells and higher Ig concentrations
237
What is the mean age of onset of bullous pemphigoid in dogs?
5 years
238
How frequent is skin involvement and how frequent is mucocutaneous involvement in canine BP?
Skin lesions very common, 89%
| Mucosal/MCJ lesions, common 67%
239
What are the most common BP lesions and which two body sites are most affected?
Deep erosions/ulcers the commonest (89%)
Erythematous macules, papules, plaques and crusts (67%)
Trunk (67%)
Ear pinnae (56%)
240
Describe the proposed pathomechanism of blister formation in BP
1) Binding of complement-fixing pemphigoid antibody to the noncollagenous domain NC16A of collagen XVII (+rarely BP 230)
2) Complement fixation and activation
3) Activation of mast cells and release of chemotactic cytokines (IL-1, IL-5, IL-6, IL-8)
4) Chemoattraction of neutrophils and eosinophils
5) Release of proteolytic enzymes from the infiltrating leukocytes, whichdisrupt dermo-epidermal cohesion
241
Where is NC16A of collagen XVII located in BMZ?
Anchoring filaments (lamina lucida)
242
What is the target molecule in linear bullous IgA? Where it is located in the BMZ?
Collagen XVII, the processed (shed)extracellular segment, also called LAD-1
Anchoring fibrils, lamina lucida
243
Why does linear bullous IgA occur in the processed segment of collagen XVII?
Following proteolytic cleavage of collagen XVII NC16A ectodomain, new conformational epitopes are revealed and targeted
244
When using collagen IV IHC to diagnose EBA, what do we expect to see?
- Collagen IV IHC predominantly on the roof of the split
| - Sens 71%, spec 90%
245
Which are the main anatomic locations affected by EBA and JEBA?
```
Concave pinnae
Oral cavity and lips
Footpads
Friction areas
Can also see on nasal planum
```
246
Is there a clinical feature that can help us distinguish EBA/JEBA from MMP and BP?
Footpad sloughing is reported in 70% of EBA cases
247
Apart from Great Danes, which other breed of dog is more often affected with EBA?
```
Great Dane (55%)
GSHP (15%)
```
248
Is there a sex predilection in EBA?
Male to female ratio 2.3
249
How many dogs with EBA had clinical signs before 1 year of age?
45%
250
What antigen is targeted in EBA?
NC1 domain of collagen VII (anchoring fibrils)
251
What are the early histopathological lesions we expect to see in EBA?
- Alignment of neutrophils in the dermoepidermal junction
- Perivascular to interstitial dermatitis
- Formation of vesicles (intravesicular neutrophils 94%, eos. 53%)
252
What is the median time to remission with treatment for EBA?
58 days
253
Did any of the dogs with EBA achieved remission and medication was discontinued without relapse?
Yes 6/14 (43%)
254
What are the targeted antigens in mixed AISBD?
```
Laminin 332
Collagen VII (NC1 segment)
```
255
The pathomechanisms are different in EM and SJS/TEN. Lymphocyte-mediated direct cytotoxicity of target keratinocytes occurs in EM, but in SJS/TEN there is little evidence of cell–cell contact in fully developed lesions. While a role for soluble Fas ligand (FasL) has been proposed, what appears to be the major mediator of the widespread cell death in SJS/TEN?
Granulysin released from cytotoxic T lymphocytes and natural killer (NK) cells
Macrophages and dendritic cells may contribute by secreting apoptosis-triggering molecules, such TNF-related apoptosis-inducing ligand (TRAIL; extrinsic pathway) and TNF-like weak inducer of apoptosis (TWEAK; intrinsic pathway)
256
Can salt split IF be performed on skin with a vesicle?
No - needs to be unsplit skin
257
In people, which type of cutaneous lupus is most often associated with SLE?
Acute CLE > subacute CLE > chronic CLE
258
Which forms of canine cutaneous lupus are classified as subacute and chronic?
```
Subacute = VCLE
Chronic = ECLE, MCLE, DLE, FDLE, GDLE
```
259
What are the lupus-nonspecific skin diseases in dogs?
Vasculitis and bullous SLE-1
260
VCLE is seen in which breeds and at what age?
Shelties, rough collies and border collies
| Mean 5.5 years
261
Is VCLE photoactivated?
Yes
262
Where do you seen lesions in VCLE?
Sparsely haired areas predominantly and MCJ
263
What do lesions look like in VCLE?
Erythematous macules, target and polycyclic lesions (figurate) that become eroded
264
Where in the epidermis do vesicles form in VCLE?
Intrabasal
265
How does VCLE differ from dermatomyositis histologically?
Dermatomyositis is a cell poor interface dermatitis with ischaemic follicular atrophy
266
Which treatment is most effective at inducing and maintaining remission of VCLE in dogs?
Ciclosporin
267
Which drugs can be used for more rapid induction of remission if VCLE than ciclosporin?
Prednisolone 2 mg/kg/d
+/- topical steroids/tacrolimus
Oclacitinib 0.5 mg/kg BID
268
In VCLE there is a deposition of Igs +/- complement at the dermoepidermal junction, basal keratinocytes and where else?
Blood vessels
269
What do IgG target in VCLE?
Ro-SSA/SSB
| Other nuclear antigens
270
What is the inheritance pattern in ECLE of GSHP?
Autosomal recessive
271
Which gene mutation is associated with ECLE in GSHP and Viszlas?
UNC93B1
A chaperone/repressor for several TLRs
Leads to hyperactivation of the immune system and autoimmunity (increased IFN signalling, innate immune response and JAK-STAT pathway)
Change in conserved amino acid
272
What are the clinical signs of ECLE?
Scaling (100%), alopecia (76%), erythema, dyspigmented plaques, follicular casts (28%), pruritus (28%), thrombopaenia (24%), pain/lameness (28%), lymphadenopathy, infertility
273
Do you see sebaceous adenitis with ECLE?
Yes
274
Which T cell is involved in ECLE?
Cytotoxic T cells
274
Can ECLE progress to SLE?
Yes, with advancing age
275
What is the most effective treatment for ECLE?
Immunosuppressive doses of steroids +/- other cytotoxic drugs (eg MMF)
Use cytotoxic eg MMF for maintenance
276
Which breeds are reported with MCLE?
GSD and Belgian shepherds (and crosses)
277
What is the median age of onset for MCLE?
6 years
278
Where do you see lesions in MCLE?
1. Anal/perianal (60%)
2. Genital/perigenital (57%)
3. Oral/perioral (48%)
4. Ocular/periocular (29%)
5. Nasal/perinasal (19%)
Lesions do not usually affect the mucosa itself!
279
What can be seen surrounding erosions and ulcers in MCLE?
Perilesional hyperpigmentation
280
How can you clinically differentiate MCLE from MMP? Both affect GSDs
MMP affects the lip mucosa and rarely affects haired skin
| MMP has ulcers, scars and blister formation
281
True or false, a lymphoplasmacytic lichenoid dermatitis is a non-specific findings in mucosal and mucocutaneous inflammation
True
282
How long does it take to induce remission when treating MCLE and what are the treatment options?
~3 months
Can be as quick as 14-30 days with oral steroids eg prednisolone 1-2 mg/kg
Pred +/- ciclosporin/MMF/tacrolimus/topical steroids
Nicotinamide and tetracyclines
283
Which treatments are effective for FDLE?
Nicotinamide and tetracyclines
| Topical tacrolimus
284
Does GDLE affect the face?
Not usually
285
What are the lesions of GDLE?
Plaques centred on atrophic scars, pigmentation changes (peripheral hyperpigmentation) and variable scaling
Occasional deep erosions and ulceration
Hyperpigmented areas may be palpably thickened in active disease
286
Has GDLE been seen in association with SLE?
Yes
287
How well does GDLE respond to treatment?
Can be difficult to achieve complete remission, lesions often recur
- prednisolone, ciclosporin, tacrolimus and hydroxychloroquine, tetracyclines and nicotinamide all reported
288
Has GDLE been reported in cats and equids?
Rarely
289
Bullous SLE type 1 in a dog was a combination of SLE and which other disease?
Epidermolysis bullosa acquisita
290
Which breeds of dog are reportedly over represented in cases of adult onset sterile granulomatous dermatitis and lymphadenitis?
```
Havanese
Australian shepherd
Irish setter
Dachshund
Bichon frise
Maltese dog
```
291
Juvenile sterile granulomatous dermatitis and lymphadenitis is an uncommon lymphocutaneous disease seen in puppies of what age?
From just a few weeks to four months
292
Juvenile sterile granulomatous dermatitis and lymphadenitis presents with what clinical signs?
- Facial swelling with pustular dermatitis affecting the peri-ocular skin, muzzle and pinnae.
- Lesions on the feet, abdomen, thorax, perianal or genital skin are less commonly reported.
- Fever, lethargy, hyporexia and lameness.
- +/- Mandibular, prescapular or generalized lymphadenopathy
293
Which breeds of dog are reportedly over represented in cases of juvenile sterile granulomatous dermatitis and lymphadenitis?
Golden retriever, Dachshund, Labrador retriever and Gordon setter
294
What is the average age of onset of sterile granulomatous dermatitis and lymphadenitis in adult dogs?
3.5 years
| Dogs up to 5 years of age over-represented
295
Which body sites were most commonly affected in adult onset sterile granulomatous dermatitis and lymphadenitis?
1. Periocular (72.2%)
2. Muzzle (55.5%)
3. Lips (38.8%)
4. Pinna (37.7%)
5. Nose (34.4%)
6. Chin (25.5%)
Lymphadenomegaly (33.3%)
296
What systemic signs were seen with adult onset sterile granulomatous dermatitis?
1. Lethargy (45.7%)
2. Fever (40%)
3. Hyporexia (40%)
4. Pain (40%)
5. Vomiting, diarrhoea, lameness or coughing
297
Treatment of adult onset sterile granulomatous dermatitis involves prednisolone (1-2 mg/kg/d) +/- ciclosporin/MMF etc.; how long does it take to achieve remission?
Average of 28 days
298
Idiopathic pyogranulomatous lymphadenitis is more commonly seen in which breed of dog?
English springer spaniels
299
Idiopathic pyogranulomatous lymphadenitis can be accompanied by what skin lesions?
- cutaneous masses
- oral ulcers
- facial or ventral cervical swelling
- cutaneous pustules of ulcers
- otitis
300
Bullous pemphigoid has been reported in dogs and cats and which other veterinary species?
Horses, pigs
301
~75% of AISBD in dogs are which two diseases?
MMP
| EBA
302
MMP most commonly affects GSD, what is the mean age of onset?
6 years
303
What % of dogs with MMP present with ulcers?
98%
304
Which part of the oral cavity is most affected in dogs with MMP?
Gingivae > palate
305
Dogs with this type of lesions are most likely to have which disease?
MMP
306
Which is the most common AISBD of cats?
MMP
307
Haemorrhagic vesicles suggests what depth of separation?
Subepidermal
308
Pemphigoid of gestation has been reported in which veterinary species?
Dog
309
Briefly describe the pathogenesis of EBA
1. Loss of central tolerance leads to activation of autoreactive T and subsequently B cells
2. Produce auto antibodies
3. Binding of Ab to collagen VII activates complement and mast cells
4. Cytokine production recruits neutrophils
5. Neutrophil elastases activate matrix metalloproteinases that digest ECM leading to dermoepidermal separation
310
An epidermal pattern in salt split IF is seen with which diseases?
BP
MMP
LAD
Pemphigus of gestation
BPAG1e, plectin, intergrin a6b4, collagen XVII NC 16A
311
A dermal pattern in salt split IF is seen with which diseases?
EBA
MMP
JEBA
MAISBD
collagen VII, IV, XVII C terminus
Laminin 332
312
Alopecia areata has been reported in dogs, horses and which other veterinary species?
Cats
Cows (Eringer)
Donkeys
313
In alopecia areata, ectopic expression of hair follicle antigens, autoreactive CD8 T cells and insufficient Treg activity leads to ____ signalling and collapse of immune privilege
IFN-gamma
314
Is alopecia areata acute or slowly progressive?
Can be both
315
What is a prodromal sign of alopecia areata?
Leukotrichia (bulbar melanocyte attack?)
316
Has seasonal alopecia areata been reported?
Yes in a dog
317
Can lesions of alopecia areata be restricted to dark haired areas of skin?
Yes
318
Has alopecia areata been reported in association with atopy in dogs and in people?
Yes - rarely
319
Where should you biopsy in cases of suspected alopecia areata?
From alopecic areas not adjacent haired skin!
320
Why may JAK/STAT inhibitors be useful for alopecia areata?
IFN-gamma, a major cytokine in breakdown of immune privilege in alopecia areata, uses the JAK-1 pathway
321
Name three diseases associated with lymphocytic mural folliculitis in the cat
```
Dermatophytosis
ADR
Allergic skin disease
Systemic disease/neoplasia
Epitheliotropic lymphoma
```
322
What clinical signs are seen with lymphocytic mural folliculitis in the cat?
```
Alopecia
Erythema
Scaling
Crusting
Follicular casts (concurrent sebaceous adenitis)
Ulcers
Shiny skin
Leukoderma and leukotrichia
```
323
What are the clinical signs of degenerative mucinotic mural folliculitis in cats?
- Generalised alopecia
- Variable pruritus
- Scaling and crusting
- Thick facial skin (characteristic)
- Can be associated with systemic disease and FIV
- Lethargy > weight loss, polyarthritis, fever, diarrhoea, PUPD
324
Which region of the hair follicle is primarily targeted in degenerative mucinotic mural folliculitis in cats?
Isthmus > infundibulum
325
Which part of the hair follicle is targeted in pseudopelade?
Isthmus
326
What are the clinical signs of pseudopelade?
- Well demarcated alopecia, scales and hyperpigmentation
- Can be localised to diffuse
- Progressive
- Onychomadesis/onychorrhexis in a cat
327
Can treatment resolve alopecia in pseudopelade in people?
No, the stem cell bulge is destroyed = scarring alopecia
Did resolve in one cat treated with ciclosporin as stem cells are present in other areas not just the bulge
328
In SJS/TEN, which mechanisms may be involved in keratinocyte apoptosis?
- Granulysin direct cellular toxicity (may also amplify the inflammatory/immune response by activating antigen-presenting cells through Toll-like receptor 4)
- TNF-alpha and Fas-ligand
- Keratinocyte inducible nitric oxide, stimulated by TNF-alpha and IFN-gamma, upregulates Fas-L production and as keratinocytes already express Fas, a wave of keratinocyte-to-keratinocyte apoptosis would follow activation of the extrinsic pathway
329
Urticarial vasculitis (UV) is a subtype of vasculitis, clinically defined by urticarial and purpuric lesions and histopathologically characterised by what type of vasculitis?
leucocytoclastic
