Cutaneous Lupus Erythematosus Flashcards
What are the main histological findings with cutaneous lupus erythematosus?
lymphocytic interface dermatitis with hydropic degeneration of the basal epidermal layer accompanied by a dense perivascular inflammatory infiltrate adjacent to the epidermal membrane
What is an interface dermatitis?
immune cell infiltrate close to the basal membrane of the epidermis and cell swelling and death of the basal keratinocytes
What diseases in dogs are characterized by an interface dermatitis?
erythema multiforme, dermatomyositis, toxic epidermal necrolysis, Stevens-Johnson syndrome, VKH, feline thymoma-associated exfoliative dermatitis, cutaneous lupoid variants
What is necroptosis?
programmed formed of necrosis/inflammatory cell death
What two cytokines are known inducers of necroptosis?
IFN-gamma and TNF-alpha
What receptor is expressed in lesions of necroptosis?
RIP3: receptor-interacting serine/threonine-protein kinase 3
What is a positive lupus band test?
linear deposition of immunoglobulins and complement components at the dermoepidermal junction detected by immunofluorescence
What is the most important exogenous trigger for development of lesions in CLE?
UV light –> leads to apoptosis
What is the function of type I interferons?
promote differentiation of naïve T cells to effector CD4 or CD8 T cells, reduce proliferation of Treg cells, drive expression of MHC class I & II and costimulatory molecules on dendritic cells and monocytes
What cytokine is released by keratinocytes and is believed to play an important role in CLE?
IFN-kappa
What are the IFN-inducible chemokines that lead to recruitment of T cells and plasmacytoid dendritic cells into skin lesions of CLE?
CXCL9, CXCL10, CXCL11
The inflammatory infiltrate in CLE is composed of primarily what cells: T cells or B cells?
T cells - CD4+ > CD8+ T cells (all are CD3+)
What nucleic acid recognition mechanisms are activated in CLE?
TLR signaling, cytosolic DNA sensing, RIG-I-like receptor
T/F: The JAK-STAT pathway is activated in CLE.
TRUE
What is the mechanism of action of hydroxychloroquine?
binds nucleic acid complexes (leads to inhibition of TLR signaling, inhibition of endolysosomal acidification, phagocytosis, and Ag presentation; inhibition of proinflammatory cytokines & calcium signaing in B and T cells)
What is the mechanism of action of tetracyclines in CLE?
inhibition of MMP 2, 9, 13; inhibition of proinflammatory cytokines; inhibition of neutrophil chemotaxis/activation
Vesicular CLE is reported most commonly in what breeds?
Shelties & their crosses, Collies & their crosses
What are the clinical signs associated with vesicular CLE?
erythematous macules –> annular to polycyclic lesions with vesiculation –> erosions to ulcerations and peripheral erythema
What areas are most commonly affected with lesions of vesicular CLE?
glabrous skin of abdomen, axillae, groin, and medial thighs; +/- minor ulceration of mucocutaneous junctions, concave pinnae and oral cavity
How can you differentiate between cell-poor vesicular CLE and dermatomyositis on histopathology?
dermatomyositis: cell-poor interface dermatitis and ischemic follicular atrophy; vesicular CLE: more lymhocyte exocytosis into basal epidermal layer, with lymphocytic satellitosis of apoptotic basal keratinocytes
What are typical histologic findings of vesicular CLE?
lymphocyte cell-rich interface dermatitis with prominent basal keratinocyte vacuolation, apoptosis and loss –> intrabasal clefts and epidermal vesiculation; can have mural folliculitis
T/F: Most dogs with vesicular CLE will have antinuculear IgG antibodies.
true (reported in 55% of dogs with VCLE)
What are the clinical signs associated with facially-dominant discoid lupus erythematous?
erythema, loss of cobblestone appearance, depigmentation, erosion/ulceration, crusting/scarring** (DLE scars more than MCLE), loss of tissue architecture
What breeds are over-represented with facial DLE?
GSDs, Shelties, Collies, all of their crosses
What are the clinical signs associated with generalized DLE?
macules and plaques with central scarring, pigmentation changes, erosions, scaling, alopecia
What is a potential neoplasm associated with facial DLE?
squamous cell carcinoma (also reported in humans with DLE)
DDX for localized depigmentation of nose
T-cell lymphoma, facial DLE, MCP, UDS
DDX for generalized DLE
generalized ischemic dermatopathy, hyperkeratotic EM (“old dog” EM)
T/F: Animals with generalized DLE are at high risk for developing SLE.
False - reported in people with generalized DLE with a positive ANA titer – at risk for development of SLE; only reported in one dog
Histologic changes with DLE
lichenoid cell-rich, lymphocytic interface dermatitis reaction pattern with basal keratinocyte vacuolar degeneration, apoptosis, loss of basal cells and BMZ thickening
Exfoliative CLE has been reported in what breeds?
GSP, Magyar viszlas (common ancestry with GSP)
What is the mode of inheritance of ECLE?
autosomal recessive
What are the predominant skin lesions associated with ECLE?
scaling and alopecia, follicular casting
What are the systemic signs associated with ECLE?
lymphadenomegaly, arthralgia/lameness, lethargy, CBC abnormalities (lymphs, platelets decreased)
Histologic changes with ECLE
cell-rich interface dermatitis, dermal lymphocyte infiltrate; apoptosis of basal keratinocytes was accompanied by moderate to marked lymphocytic exocytosis in lower epidermis; diffuse orthokeratotic hyperkeratosis; lymphocytic interface mural folliculitis present in infundibulum; periglandular lymphocytic infiltrate
What breeds are over-represented with MCLE?
GSDs & their crosses
Clinical signs of MCLE?
perimucosal ulcerative skin lesions with vocalization while urinating or defecating, pain, dyschezia, dysuria, pruritus
Lesions are most commonly found in what locations with MCLE?
anus, genitalia or perigenital region, less commonly, perioral and periorbital, nasal
What are the characteristic skin lesions of MCLE?
erosions and ulcers – do not tend to heal with scarring (as in DLE), crusting present when lesions extend into haired skin, hyperpigmentation
DDX for MCLE
MCP, MMP, EM variant
Histologic changes with MCLE
cell-rich lymphocytic interface dermatitis with basal keratinocyte damage, extended to infundibula of hair follicles, granulation tissue was limited and fibrosis was not seen
