CLE (ECVD videos) Flashcards by Treasa Clifford

Which breeds develop VCLE

*Shelties
*Rough Collies
*Border collies

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Which body regions develop VCLE

*Sparsely haired skin (ventral abdomen, medial thighs, flanks)
*Mucocutaneous junctions, less (lipfolds, periocular, anus)

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Histopath pattern for VCLE

*Lymphocyte-rich interface dermatitis with keratinocyte vacuolation
*Confluent. vacuolation leading to intrabasal vesiculation

Lymphocytes kill keratinocytes via 1) apoptosis or 2) cell lysis and necrosis, which leads to hydropic degeneration, which leads to vacuolation

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Chronicity of VCLE (acute, subacute, chronic)

Subacute

(all other forms of CLE are chronic. No acute CLE in dogs)

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Which T cells are present in VCLE

CD4 and CD8

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Clinical signs of canine juvenile dermatomyositis

*Scarring alopecia w/ depigmentation and focal ulcers
*Facial predominant, ear tips, tail tips, joints

NOT THE SAME AS VCLE, just the same breeds!
*Interface dermatitis but CELL POOR
*ISCHEMIC FOLLICULAR ATROPHY

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Factor that can aggravate VCLE

UV light

Flares during summer, sunshine

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Where is IgG deposited in VCLE?

*Epidermal BMZ
*Vessel BMZ (possible vasculitic component)
*Intracytoplasmic basal cell (because IgG is attacking a part of basal cell, cytotoxic T cells also attack this antigen on basal keratinocyte –> induce vesiculation)

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What percent of dogs with VCLE have positive IgG against ANA in their skin?

Cannot find ANA

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What are the targets of IgG in VCLE on basal keratinocytes

Different nuclear antigens:
*SSA, SSB (also SLE in humans!)

Also
*Sm/RNP
*Jo1
*Scl70
*Sm

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Treatment for VCLE

BEST DRUG = CYCLOSPORINE (active on T cells!, which attack basal keratinocytes)
*Sun avoidance
*+/- Glucocorticoids tapered for 1 month
*+/- azathioprine if still unresponsive

PENTOXI IS NOT ENOUGH, because not related to dermatomyositis

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Prognosis VCLE

Complete remission in 100% with cyclosporine +/- GC

CR within 2 months in 73%

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T or F: Most dogs need GC in addition to cyclosporine to keep their VCLE in remission

FALSE. 100% of dogs could be on cyclosporine alone to maintain remission of VCLE

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Which disease causes macular and figurate erythema with superficial sloughing and erosions on lightly-haired body regions?

VCLE

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What is the lupus band test?

Positive IgG +/- complement against epidermal BMZ, vessel BMZ, and basal keratinocytes

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Which nuclear antigens are IgG targeting in VCLE

*Ro-SSA/SSB
*Other nuclear antibodies too

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Which version of canine CLE is most similar to human SCLE

VCLE is a close homologue of human (vesicular) SCLE

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Breeds ECLE

*German shorthaired pointers
*Vizsla

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Chronicity of ECLE (acute, subacute, chronic)

Chronic

(VCLE is only subacute form; all others are chronic)

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Sex overrepresented for ECLE

Females (2.1:1)

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Age for ECLE

Young! 10 month median

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Lesion distribution ECLE

Start on head, move to the back

Muzzle, pinnae, head –> dorsum

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Lesion type ECLE

Erythema, scaling (follicular casts), alopecia

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Mode of inheritance of ECLE

Autosomal recessive

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Gene associated with ECLE

UNC93B1 on chromosome 18

Function of UNC93B1

Function: Chaperone/Repressor for many TLRs With ECLE mutation: Continuous activation of TLRs by self and exogenous nucleic acids! Hyperactivation of innate immune system --> IFN --> autoimmunity

When syntenin-1 is bound to UNC93B1, what is the state of Myd88?

Myd88 is inactive when syntenin-1 is bound (from UNC93B1)

When syntenin-1 is ABSENT from UNC93B1, what is the state of Myd88?

Persistent activation of Myd88 --> hyperactive innate immune system. Self activation of TLR7/Myd88 --> autoimmunity

Which signaling pathways are increased in ECLE? (3)

*JAK-STAT *Interferon signaling *Innate immune response

Why does Apoquel work for ECLE?

Because increased JAK-STAT pathway signaling in ECLE

T or F: Sebaceous adenitis in vizsla may actually be a manifestation of ECLE

True Erythema, alopecia, scale, follicular casts

What are the concurrent systemic signs seen in ECLE? (6)

*Thrombocytopenia *Pain/lameness *Hunch back *Infections *Infertility *Lymphadenopathy

Which cells are targeted by T cells in ECLE

*Basal keratinocytes *Sebaceous glands

Which form of CLE has an associated sebaceous adenitis

ECLE

Which type of T cell is present in ECLE

Cytotoxic γδ T cells

Where can you find IgG in ECLE

*Epidermal BMZ *Hair follicle membrane *Sebaceous gland membrane

Is ECLE a true SLE?

YES, with time Develop + ANA with AGE

Prognosis ECLE

Poor. 44% euthanized, 31% achieve CR

Most effective ECLE therapy

High dose glucocorticoids + cytotoxic drug combo to induce remission Other reported tx: mycophenolate

Which genes are overexpressed in ECLE

IFNg Decreases with successful therapy

Types of CLE that responds to Apoquel (oclacitinib)

*MCLE (100%) *ECLE (100%) *FDLE (75%) 0.45mg/kg BID

Breed MCLE

*GSD *Belgian Shepherd

Sex MCLE

Females Female:Male 1.7:1

Age MCLE

Median 6 years

Clinical lesions MCLE

*Erosions, ulcers (perianal, perigenital) *Pain (+/- pruritus?) *Dyschezia *Dysuria

Lesion distribution MCLE

*Perianal *Perigenital *Perioral Less common: *Periocular *Perinasal MOST DOGS have lesions at 2-3 MC regions

Do MCLE lesions typically scar?

MCLE vs MMP similarities

*Both affect GSD, near MC junctions

MCLE vs MMP differences

*MMP affects lip, but not surrounding skin *MCLE affects perioral skin, but not lip mucosa itself *MCLE: erosions/exudation *MMP: ulcers, scars, blister formation

Histopath MCLE

*Lymphocyte-rich interface dermatitis *Thick, irregular BMZ (immune complex deposition)

What type of Ig do you find at BMZ in MCLE

Mostly IgG (83%) --> Positive "lupus band test" Also IgM (44%), C3 (33%), IgA (17%)

Treatments MCLE

*Oral glucocorticoid *Cyclosporine *Doxy/niacinamide

Prognosis MCLE

Good! CR within 3 months

T or F: spontaneous remission can occur in MCLE

False. Usually, need lifelong meds

Treatment with fastest time to CR in MCLE

Oral glucocorticoids (1 month vs 2 months w/o)

How do you differentiate MCLE from mucocutaneous pyoderma

No response to topical/oral antibiotics

T or F: recurrence/relapses are common in MCLE if you taper immunosuppressive medication

True

Clinical signs of FDLE

*Depigmentation *Erythema *Scarring *Loss of architecture *Crusting *Alopecia

Main differential diagnosis for FDLE

MMP (Can affect nose, cause scarring) (Less likely, nasal PV)

Histopath for FDLE

*Lymphocytic interface dermatitis w/BMZ thickening, keratinocyte damage **Lymphocytes and plasma cells are NORMAL in mucosa, which are not present on haired skin. Can make lymphocytic interface and basal cell apoptosis harder to see**

T or F: lymphoplasmacytic lichenoid dermatitis is specific to FDLE

FALSE. NONSPECIFIC lesion of mucosal and MC inflammation!!!

Treatment FDLE

*Doxy/niacinamide *Partial improvement with tacrolimus

Overrepresented breeds GDLE

*Chinese crested dogs (lack of hair, more UV light exposure) *Labrador retrievers

Sex GDLE

Equal M:F

Age GDLE

Older. 9 year median

Body distribution GDLE

*Lateral thorax *Dorsum *Neck *Abdomen *Proximal limbs

Clinical lesions GDLE

*Polycyclic plaques with central atrophic scarring *Pigmentation changes *Variable scaling *Reticulated hyperpigmentation (raised if active, flat if inactive) *MC junction involvement Less common: *Deep erosions, ulcers *Hypertrophic crusting, scaling *Scarring alopecia

Histopath GDLE

Lymphocyte rich interface dermatitis

Which Ig are present at Dermo-Epidermal junction for GDLE

*IgG (90%) *IgA (80%)

What is UNIQUE about GDLE deposits of immunoreagents

IgG AND IgA!!

Can GDLE become SLE?

Yes, reported in 1 dog

Does GDLE have + ANA in serum?

Yes, 88% dogs But most dogs do NOT progress to SLE

Which forms of CLE have reported SLE later?

ECLE GDLE (not typical though!!)

Does GDLE have spontaneous remission reported

Treatment GDLE

*Glucocorticoids + Cyclosporine (PR) *Doxycycline/Niacinamide (n=1, but CR) *Tacrolimus + hydroxychloroquine

Do lesions usually recur with medication taper for GDLE?

Yes

What is unique about the immunopathology of GDLE?

*Positive low titers of ANA, without progression to SLE *IgG and IgA antibodies

Which form of CLE is reported in cats

GDLE *DLE

Which form of CLE is reported in donkeys

GDLE

What species have GDLE been reported in

Dogs Humans Cats Donkeys

Which form of canine CLE is most similar to human DDLE

GDLE. Plaques, scarring, dyspigmentation (more similar than FDLE)

What are the lupus-nonspecific skin diseases?

*Vasculitis (lupus panniculitis?) *Autoimmune BM disease (BSLE-1)

Skin clinical signs of SLE

*Skin lesions (50-60%) *MC ulcers + basal cell vacuolation = **vasculitis?** *oral ulcers *Hyperkeratotic paw pads

Bullous SLE Type 1

SLE + EBA

Clinical signs of SLE

*Fever *Non-erosive Polyarthritis *Proteinuria *IMHA *Leukopenia *Thrombocytopenia *Mouth ulcers *Skin lesions (crusts, ulcers, scars) *Internal organ involvement: thyroid gland, spleen, or kidneys.

UV-A vs UV-B differences (relevant bc UV radiation can trigger lupus)

UV-A = longer waves, affects dermis, causes reactive oxygen species UV-B = shorter waves, affects epidermis, causes DNA breakage Both damage basal keratinocytes