MISC Autoimmune Flashcards
What is the cell of origin of canine cutaneous histiocytoma?
Langerhans cells
What are the cell markers for Langerhans cells/
CD1a, CD11c/CD18, E-cadherin
T/F: Langerhans cell disorders have not been reported in feline skin.
TRUE - however they do get pulmonary Langerhans cell histiocytosis
What is the cell of origin of histiocytic sarcomas?
interstitial dendritic cells
_____ is an indolent form of localized histiocytic sarcoma that originates in the skin of cats
progressive histiocytosis
In what tissues are Langerhans cells found?
Epithelia of skin, alimentory, respiratory, and reproductive tracts
What is the only histiocytic disease of dogs and cats that originates in macrophages?
hemophagocytic histiocytic sarcoma
Blood monocytes can differentiate into Langerhans cells under the influence of what cytokines or growth factors?
granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4
What do keratinocytes secrete that promote differentiation of Langerhans cells from CD14+ precursor cells?
TGF-beta1
What are the two major locations of dendritic cells?
epidermis (Langerhans cells) and dermis (adjacent to postcapillary venules – dermal interstitial dendritic cells)
What are CD11/CD18 and what is their function?
beta-2 integrins, critically important adhesion molecules expressed by all leukocytes
What is the function of E-cadherin with respect to Langerhans cells?
LCs localize within epithelia via E-cadherin homotypic adhesion w/ E-cadherin expressed by epithelial cells
What is a marker for dermal interstitial dendritic cells?
Thy-1 (CD90), CD11c (a subset also express CD11b)
What are key morphological features of histiocytomas?
1) Lesions have an epidermal focus (top-heavy) and intraepidermal foci are common; 2) Histiocytes have diverse nuclear morphology (round, ovoid, indented, or compelx nuclear contours); 3) Multinucleated cells and cytologic atypia are rare.
Key morphologic features of cutaneous Langerhans cell histiocytosis?
1) Multiple cutaneous lesions are observed. Metastasis to lymph nodes and internal sites is possible. 2) Lesions are otherwise identical to histocytoma but may have a higher frequency of multinucleated cells and cellular atypia.
Cell markers for feline pulmonary Langerhans cell histiocytosis?
CD1a, CD18, E-cadherin
Morphological features of feline pulmonary Langerhans cell histiocytosis
Multinodular to diffuse involvement of all lung lobes. Lesions consist of cohseive histiocytic infiltrates, which obliterate terminal airways and extend to pleural surfaces. Birbecks granules observed by TEM.
What is the cell of origin of cutaneous histiocytosis?
interstitial dendritic cells
What are the cell markers for cutaneous histiocytosis?
CD1a, CD4, CD11c/CD18, CD90
Morphological features of cutaneous histiocytosis
Vasocentric lesions are focused on mid-dermis to subcutis (bottom heavy). Lesions are pleocellular but are dominated by histiocytes and lymphocytes. Lymphohistiocytic vasculitis is commonly osberved. Histiocytes lack cytologic atypia, multinucleated giant cells are rare. Skin draining lymph nodes may be infiltrated
What is the cell of origin of systemic histiocytosis?
interstitial dendritic cells
What are the cell markers for systemic histiocytosis?
CD1a, CD4, CD11c/CD18, CD90
Morphological features of systemic histiocytosis
Identical lesions to cutaneous histiocytosis in skin - lesions extend to lymph nodes, ocular and nasal mucosa and internal organs
What is the cell of origin of feline progressive histiocytosis?
interstitial dendritic cells
What are the cell markers for feline progressive histiocytosis?
CD1a, CD11b/CD18, CD5 (50%)
Morphological features of feline progressive histiocytosis
skin nodules and plaques. Lesions occupy the dermis with an epidermal focus - intraepidermal foci (40%) occur. In early lesions, histiocytes have minimal cytologic atypia. In later lesions, histiocytes manifest cytological atypia as described for histiocytic sarcoma
What is the most common histiocytic disease of cats?
feline progressive histiocytosis
What breeds are predisposed to histiocytomas?
Boxers, Dachshunds
Cutaneous Langerhans cell histiocytosis has been reported in what breed?
Shar Peis
Histiocytomas are progressively infiltrated by what cell type?
CD8+ T cells
What IHC markers are necessary to differentiate histiocytomas from epitheliotropic T-cell lymphoma?
CD3 (T-cells) and CD18 (dendritic cells)
What cell markers are useful to differentiate interstitial dendritic cells and Langerhans cells?
interstitial dendritic cells (CD90+), Langerhans cells (E-cadherin+)
What are the cell markers for histiocytic sarcoma?
CD1a, CD11c/CD18
Morphological features of histiocytic sarcoma
mass lesions are observed in spleen, lung, lymph node, and other primary tissue sites. Histiocytes are pleomorphic, mononuclear, and multinucleated giant cells with marked cytological atypia
What cell type other than interstitial dendritic cells is common to find with canine reactive histiocytosis?
T-cells (CD8+)
What test is necessary to differentiate canine reactive histiocytosis from non-epitheliotropic T-cell lymphoma?
T-cell receptor gamma gene rearrangement analysis – detects clonal T-cell expansion of lymphoma cells
Which has raised lesions: erythema multiforme, Stevens-Johnson syndrome, or Toxic epidermal necrolysis?
Erythema multiforme - SJS and TEN are almost always flat
Erythema multiforme minor in humans is almost always caused by what?
herpes simplex virus
What are known triggers for classical drug-induced EM in dogs?
sulphonamides, antibiotics, and levamisole; other triggers = diet, neutraceuticals, infections, neoplasia
What are reported triggers for classical drug-induced EM in cats?
antibacterial drugs, aurothioglucose
T/F: Drugs are the main precipitating factors for EM, SJS, and TEN.
False - not for EM, but for SJS/TEN
What are reported triggers for SJS/TEN in animals?
sulphonamides, antibiotics (cephalosporins and penicillins), levamisole, diethylcarbamazine, phenobarbital
What is the target of the immune response in EM, SJS, and TEN?
keratinocytes
What is the major mediator of keratinocyte injury in EM?
lymphocyte-mediated direct cytotoxicity of target keratinocytes (CD8+ lymphocytes)
What is the major mediator of keratinocyte injury in SJS/TEN?
granulysin released from cytotoxic T lymphocytes and NK cells; other soluble mediators of cell death include Fas ligand, granzymes, and perforin
What type of immune response predominates with EM? What is the major cytokine released?
Th1 response; interferon-gamma
Distribution of lesions with EM
trunk, glabrous skin of groin and axilla, inner pinna, footpads, and mucocutaneous junctions
Clinical presentation of SJS/TEN
sudden disease onset with severe systemic signs (anorexia, lethargy, depression) and widespread, usually painful skin and mucosal lesions
Lesions associated with SJS/TEN
macules/patches –> coalesce into arciform or serpiginous shapes –> epidermal detachment –> widespread ulceration
Histopathological findings with EM
cytotoxic (interface) dermatitis, with keratinocyte apoptosis in the basal cell layer as well as suprabasilar, mild lymphocytic infiltration in the interface
What conditions could be confused with EM based on histopathological findings alone?
ciclosporin-responsive “proliferative, lymphocytic, infundibular mural folliculitis and dermatitis with prominent follicular apoptosis and parakeratotic casts” (PLIMF), superficial nerolytic dermatitis, proliferative and necrotizing otitis externa
How is toxic epidermal necrolysis distinguished from a burn histologically?
lack of dermal necrosis
What are the main clinical differentials for SJS/TEN in people?
staphylococcal scalded skin syndrome, acute generalized exanthematous pustulosis, severe cases of EM major, generalized fixed drug eruptions
What are the main clinical differentials for SJS/TEN in animals?
burns, bullous autoimmune diseases, SLE, superficial suppurative dermatitis of miniature schnauzers, vasculitis, epitheliotropic lymphoma
What is the proposed mechanism for IVIG in SJS/TEN?
counteract cell death by high concentrations of anti-Fas antibodies in the immunoglobulin fraction; however, granulysin is more likely than Fas-L to be the main effector molecule so efficacy is questionable
T/F: Histopathology can distinguish between EM and SJS/TEN.
False - although there are some differences, there are enough similarities that it is impossible to distinguish on histopathology alone
Histopathological findings with cutaneous lymphocytosis
monomorphic population of small lymphocytes forming a diffuse infiltrate in the superficial and deep dermis with smaller numbers of lymphocytes in the epidermis and occasionally within the follicular epithelium; no mitotic figures; lymphocytes have sparse to mildly expanded pale cytoplasm surrounding ovoid nuclei
What is the typical clinical presentation of feline cutaneous lymphocytosis?
solitary lesion showing alopecia, erythema, scaling, with or without crusting - most commonly on the thorax. Most cats do not become systemically ill
Is feline cutaneous lymphocytosis a disease of B or T lymphocytes?
T lymphocytes (CD3+)
What histopathological findings differ between feline cutaneous lymphocytosis and epitheliotropic T-cell lymphoma?
ETCL has significant involvement of the epidermis, nulear atypia, and Pautrier’s microabscesses
Histopathologic features of canine perianal fistulas
periadnexal inflammation +/- furunculosis, pronounded hidradenitis, periadnexal fibrosis, ulceration, formation of epithelial-lined sinus tracts within the dermis
What is the main differential diagnosis for canine perianal fistuals?
mucocutaneous lupus erythematosus
Mechanism of action of cyclosporin A
binds to intracellular protein cyclophilin-1, which inhibits calcineurin –> prevents dephosphorylation of nuclear factor of activated T cells and subsequent production of pro-inflammatory cytokines such as IL-2 –> decreased IL-2 leads to decreased growth and activation of T lymphocytes
Why is tacrolimus more suited for topical application compared to cyclosporin A?
smaller molecular weight –> better absorption through epidermis
What are the primary lesions of generalized discoid lupus erythematosus?
annular (discoid) to polycyclic plaques with dyspigmentation (depigmentation and hyperpigmentation), an erythematous margin, adherent scaling, follicular plugging, and central alopecia
Histopathologic features of generalized discoid lupus erythematosus?
cell-rich, lymphocytic interface dermatitis and folliculitis; in chronic lesions with scarring - dermal fibrosis occasionally displaces the cell-rich inflammatory infiltrate from the superficial dermis
What breed is over-represented with mucocutaneous lupus erythematosus?
German shepherd dogs
Differentials for mucocutaneous lupus erythematosus skin lesions?
mucocutaneous pyoderma and mucous membrane pemphigoid
Most relevant clinical ddx for vesicular cutaneous lupus erythematosus
erythema multiforme
Most relevant clinical ddx for exfoliative cutaneous lupus erythematosus
sebaceous adenitis
Most relevant clinical ddx for facial discoid lupus erythematosus
mucocutaneous pyoderma, epitheliotropic T cell lymphoma, UV syndrome
Most relevant clinical ddx for generalized discoid lupus erythematosus
hyperkeratotic erythema multiforme, generalized ischemic dermatopathies
Histopathologic feature of vesicular cutaneous lupus erythematosus?
lymphocyte cell-rich interface dermatitis with prominent basal keratinocyte vacuolation, apoptosis and loss –> intrabasal clefts and epidermal vesiculation
For what variant of lupus is sun avoidance crucial?
vesicular cutaneous lupus erythematosus – shown to be induced and/or worsened by UV light; facial discoid LE
Exfoliative cutaneous lupus erythematosus has been reported in GSP’s and what other breed?
Magyar viszlas
What autoimmune subepidermal blistering disease has been reported in horses?
bullous pemphigoid
Humoral and cellular immune responses against keratinocyte-keratinocyte adhesion molecules result in what diseases?
pemphigus
Autoimmune diseases directed against keratinocyte-basement membrane attachment proteins result in what clinical diseases?
subepidermal blistering diseases (pemphigoid, EBA)
What stain would be useful in highlighting eosinophils in bullous pemphigoid?
Luna stain
On salt split skin, where does IgG deposit with bullous pemphigoid (epidermis or dermis)?
epidermis
