Cutaneous Lupus Erythematosus

Question 1

What are the main histological findings with cutaneous lupus erythematosus?

Answer 1

lymphocytic interface dermatitis with hydropic degeneration of the basal epidermal layer accompanied by a dense perivascular inflammatory infiltrate adjacent to the epidermal membrane

Question 2

What is an interface dermatitis?

Answer 2

immune cell infiltrate close to the basal membrane of the epidermis and cell swelling and death of the basal keratinocytes

Question 3

What diseases in dogs are characterized by an interface dermatitis?

Answer 3

erythema multiforme, dermatomyositis, toxic epidermal necrolysis, Stevens-Johnson syndrome, VKH, feline thymoma-associated exfoliative dermatitis, cutaneous lupoid variants

Question 4

What is necroptosis?

Answer 4

programmed formed of necrosis/inflammatory cell death

Question 5

What two cytokines are known inducers of necroptosis?

Answer 5

IFN-gamma and TNF-alpha

Question 6

What receptor is expressed in lesions of necroptosis?

Answer 6

RIP3: receptor-interacting serine/threonine-protein kinase 3

Question 7

What is a positive lupus band test?

Answer 7

linear deposition of immunoglobulins and complement components at the dermoepidermal junction detected by immunofluorescence

Question 8

What is the most important exogenous trigger for development of lesions in CLE?

Answer 8

UV light –> leads to apoptosis

Question 9

What is the function of type I interferons?

Answer 9

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

Question 10

What cytokine is released by keratinocytes and is believed to play an important role in CLE?

Answer 10

IFN-kappa

Question 11

What are the IFN-inducible chemokines that lead to recruitment of T cells and plasmacytoid dendritic cells into skin lesions of CLE?

Answer 11

CXCL9, CXCL10, CXCL11

Question 12

The inflammatory infiltrate in CLE is composed of primarily what cells: T cells or B cells?

Answer 12

T cells - CD4+ > CD8+ T cells (all are CD3+)

Question 13

What nucleic acid recognition mechanisms are activated in CLE?

Answer 13

TLR signaling, cytosolic DNA sensing, RIG-I-like receptor

Question 14

T/F: The JAK-STAT pathway is activated in CLE.

Answer 14

TRUE

Question 15

What is the mechanism of action of hydroxychloroquine?

Answer 15

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)

Question 16

What is the mechanism of action of tetracyclines in CLE?

Answer 16

inhibition of MMP 2, 9, 13; inhibition of proinflammatory cytokines; inhibition of neutrophil chemotaxis/activation

Question 17

Vesicular CLE is reported most commonly in what breeds?

Answer 17

Shelties & their crosses, Collies & their crosses

Question 18

What are the clinical signs associated with vesicular CLE?

Answer 18

erythematous macules –> annular to polycyclic lesions with vesiculation –> erosions to ulcerations and peripheral erythema

Question 19

What areas are most commonly affected with lesions of vesicular CLE?

Answer 19

glabrous skin of abdomen, axillae, groin, and medial thighs; +/- minor ulceration of mucocutaneous junctions, concave pinnae and oral cavity

Question 20

How can you differentiate between cell-poor vesicular CLE and dermatomyositis on histopathology?

Answer 20

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

Question 21

What are typical histologic findings of vesicular CLE?

Answer 21

lymphocyte cell-rich interface dermatitis with prominent basal keratinocyte vacuolation, apoptosis and loss –> intrabasal clefts and epidermal vesiculation; can have mural folliculitis

Question 22

T/F: Most dogs with vesicular CLE will have antinuculear IgG antibodies.

Answer 22

true (reported in 55% of dogs with VCLE)

Question 23

What are the clinical signs associated with facially-dominant discoid lupus erythematous?

Answer 23

erythema, loss of cobblestone appearance, depigmentation, erosion/ulceration, crusting/scarring** (DLE scars more than MCLE), loss of tissue architecture

Question 24

What breeds are over-represented with facial DLE?

Answer 24

GSDs, Shelties, Collies, all of their crosses

Question 25

What are the clinical signs associated with generalized DLE?

Answer 25

macules and plaques with central scarring, pigmentation changes, erosions, scaling, alopecia

Question 26

What is a potential neoplasm associated with facial DLE?

Answer 26

squamous cell carcinoma (also reported in humans with DLE)

Question 27

DDX for localized depigmentation of nose

Answer 27

T-cell lymphoma, facial DLE, MCP, UDS

Question 28

DDX for generalized DLE

Answer 28

generalized ischemic dermatopathy, hyperkeratotic EM (“old dog” EM)

Question 29

T/F: Animals with generalized DLE are at high risk for developing SLE.

Answer 29

False - reported in people with generalized DLE with a positive ANA titer – at risk for development of SLE; only reported in one dog

Question 30

Histologic changes with DLE

Answer 30

lichenoid cell-rich, lymphocytic interface dermatitis reaction pattern with basal keratinocyte vacuolar degeneration, apoptosis, loss of basal cells and BMZ thickening

Question 31

Exfoliative CLE has been reported in what breeds?

Answer 31

GSP, Magyar viszlas (common ancestry with GSP)

Question 32

What is the mode of inheritance of ECLE?

Answer 32

autosomal recessive

Question 33

What are the predominant skin lesions associated with ECLE?

Answer 33

scaling and alopecia, follicular casting

Question 34

What are the systemic signs associated with ECLE?

Answer 34

lymphadenomegaly, arthralgia/lameness, lethargy, CBC abnormalities (lymphs, platelets decreased)

Question 35

Histologic changes with ECLE

Answer 35

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

Question 36

What breeds are over-represented with MCLE?

Answer 36

GSDs & their crosses

Question 37

Clinical signs of MCLE?

Answer 37

perimucosal ulcerative skin lesions with vocalization while urinating or defecating, pain, dyschezia, dysuria, pruritus

Question 38

Lesions are most commonly found in what locations with MCLE?

Answer 38

anus, genitalia or perigenital region, less commonly, perioral and periorbital, nasal

Question 39

What are the characteristic skin lesions of MCLE?

Answer 39

erosions and ulcers – do not tend to heal with scarring (as in DLE), crusting present when lesions extend into haired skin, hyperpigmentation

Question 40

DDX for MCLE

Answer 40

MCP, MMP, EM variant

Question 41

Histologic changes with MCLE

Answer 41

cell-rich lymphocytic interface dermatitis with basal keratinocyte damage, extended to infundibula of hair follicles, granulation tissue was limited and fibrosis was not seen