Cutaneous Vessels (including diseases) Flashcards
1
Q
What are the three intercommunicating plexuses of arteries and veins?
A
1) Deep plexus (interface of dermis and subcutis - some branches supply lower hair follicle and epitrichial sweat glands)
2) Middle plexus (level of the sebaceous gland and supplies arrector pili, middle hair follicle, and sebaceous glands)
3) Superficial plexus (capillary loops just below the epidermis - supplies upper hair follicle and epidermis)
2
Q
Describe arterioles
A
endothelial cells surrounded by smooth muscle cells, most likely function as part of the resistance vessels in skin
3
Q
How do capillaries differ from arterioles?
A
Smaller and lack surrounding smooth muscle cells
4
Q
Describe venules
A
A majority of dermal vessels are post-capillary venules
Most physiologically reactive segment of the microcirculation, are where inflammatory cells migrate from the vasculature to the tissue and where endothelial cells develop gaps due to inflammation which increases vascular permeability
5
Q
What are the three sections of the microcirculatory bed?
A
Arterioles, capillaries, and venules
6
Q
What IHC stain is useful for diagnosis of vascular neoplasms and for identification of vascular invasion by neoplasms?
A
Factor VIII-related antigen
7
Q
What happens to selectins and members of the immunoglobulin superfamily on endothelial cells with inflammation?
A
E- and P-selectin as well as ICAM-1/VCAM-1 are upregulated and mediate rolling, adhesion, and transmigration of leukocytes (ex. neutrophils) from the blood
8
Q
What are the 3 main functions of the endothelium?
A
1) maintain homeostasis of the blood
2) separate blood from tissues
3) regulate blood flow
9
Q
Name 3 signaling molecules that regulate dermal angiogenesis.
A
1) Mast cells (histamine)
2) Macrophages (TNF-α)
3) TGF-β
10
Q
Describe pericytes
A
- Aligned parallel to the blood vessels and vary in appearance from club-like to fusiform
- Contractile cells that contain actin-like and myosin-like filaments and regulate capillary flow
- Unknown origin
- Integral part of vessel wall and enmeshed in mural basement membrane material
11
Q
Describe veil cells
A
- Flat, advential, fibroblast-like cells that surround all dermal microvessels
- exact function and nature are undetermined
- entirely external to vessel wall and demarcates it from the surrounding dermis
- perivascular mast cells are usually present in the space between the walls and the veil cells
12
Q
What IHC stain would you use to identify veil cells?
A
Factor XIIIa (indicates that it is part of the dermal dendrocyte system)
13
Q
Describe arteriovenous anastomoses
A
Normal connections between arteries and veins that allow arterial blood to enter the veins and bypass the capillaries
- associated with thermoregulation (ex. waterbird feet)
- occur in all areas but more common in extremities
- occur at all layers of the dermis but especially the deep dermis
- vary in structure from simple to the glomus
- can be pathologic
14
Q
What causes dilation of arteriovenous anastomoses?
A
Acetylcholine and histamine
15
Q
What causes constriction of arteriovenous anastomoses?
A
Epinephrine and norepinephrine
16
Q
What is a glomus?
A
- A special AV shunt located in the deep dermis
- Consists of an arterial section (Sucquet-Hoyer canal) which branches from an arteriole and a venous section that is thin-walled with a wide lumen
- Has a tunica media that is densley packed with 4-6 layers of golmus cells that are large and pump, have clear cytoplasm, and resemble epithelial cells
- the glomus cells are generally regard as modified smooth muscle cells
17
Q
Describe pathologic AV anastomoses/fistulae
A
- Can be congenital or acquired through trauma
- Hard to treat, surgery is frequently recommended
- Frequently in legs/limbs
- Arteriography can visualize them
18
Q
Where do the cutaneous lymphatics arise from?
A
Capillary networks in the superficial dermis (though not usually seen in routine histopath preparations above the mid-dermis)
19
Q
What are the functions of the dermal lymphatics?
A
- Control movement of interstitial tissue fluid so are essential for nutrition and control the true microcirculation of the skin
- Drain and take away material that arises through daily wear and tear so are important for the recycling of protein and cellular debris as well as removing topical medications/toxins, injected medications, etc
- Link skin to lymph nodes for immune regulation
20
Q
Describe lymph formation and the removal via contractions
A
- Initial collector system is non-contractile, have an attenuated endothelial layer, discontinuous BMZ, and non-continuous cell junctions
- Lymph formation depends on periodic expansion of the lymphatics and compression (caused muscle contractions and physical motion) which causes emptying of the initial lymphatics to contractile lymphatics that have smooth muscle and exhibit peristalsis
21
Q
How do you distinguish lymphatics from capillaries on H&E?
A
- Lymphatics have a wider/more angular lumen, more attenuated and flattened endothelial cells, no pericytes, shouldn’t have blood (but might with injury or inflammation)
22
Q
What are Voight lines?
A
Boundaries of areas of distribution of the main cutaneous nerve stems
23
Q
What are Langers lines?
A
Reflect the course of blood vessels or lymphatics
24
Q
What are Blaschko’s lines?
A
- Lines follow a V-shape over the spine, S-shape on the abdomen, axial distribution on limbs, wavy on the face
- Reflect a mosaic condition
25
What are cleavage lines?
Same as tension lines
26
What is the pathogenesis of cutaneous vasculitis?
- Non-immunopathic (endotoxins or hemodynamic factors)
- Immunopathic
- Type III hypersensitivity
- Infectious pathogens initiating specific immune response
- Secondary vasculitis from local bacteria or septicemia
- Immune-mediated to drugs or underlying diseases
- Auto-immune disease
27
What are some causes of vasculitis?
Immunologic response
Food hypersensitivity – eos vasculitis
Insect bites – eos vasculitis
Neoplasia
--> MCT – eos vasculitis
Lupus erythematosus (or other connective tissue disorders)
Drug induced – many drugs including dexamethasone, prednisone
--> Itraconazole (dose dependent at 10mg/kg/d but not 5)
Vaccines esp rabies
Other – bacteria, protozoa, viruses
Canine eosinophilic dermatitis – eos vasculitis
PF
Cryoglobulinemia
Idiopathic
28
What are the clinical features of acute vasculitis?
- Skin is typically only organ system affected but not always
--> may also have other signs of illness
--> systemic vasculitis may lead to shock and DIC
- Usually dependent areas, pressure points, extremities
- Purpura, purpuric plaques, hemorrhagic bullae, eschar, crateriform ulcers, pitting edematous areas, occasional acrocyanosis, petechia, erythematous urticaria, plaques, papules, pustules
--> Does not blanch with diascopy
29
What is lupus vasculitis?
Form of lupus associated with systemic or cutaneous lupus erythematosus
30
What is cryoglobulinemia/cryofibrinogenemia?
Vasculitis associated with precipitation of cold reactive immunoglobulins or immune complexes which affects the distal extremities
31
What is vaccine-associated vasculitis?
Lesions develop 2-6 months following vaccination at the site
- the pinnal apex is most common non-injected site
32
What is the most common vaccine associated with vasculitis?
Rabies
33
When breeds have a higher risk of rabies vaccine-associated vasculitis?
Yorkies, miniature poodles, Bichon Frise, other long-haired small breeds
34
What are the clinical signs of rabies vaccine-associated vasculitis?
Focal alopecia at the site (or dependent to it) with minimal inflammation
- Plaque, +/- hyperpigmentation
- 2-3 months later (or longer)
Usually asymptomatic
- Lethargy, fever, generalized alopecia may happen
35
What are the histopathologic findings of rabies vaccine-associated vasculitis?
* Lymphocytic vasculitis and cuffs in subcutis
Cell-poor interface dermatitis, vacuolation in basal cell layer, pigmentary incontinence, and mural folliculitis
* Amorphous blue-to-gray granules (vaccine material)
Macrophages or free in matrix
Atrophy and hyalinization of the dermis with mucin (pallor & smudgy)
Marked atrophy and pale staining of hair follicle
36
From a hyperpigmented patch on the right hip of a Yorkshire terrier
Post-rabies vaccination vasculitis/panniculitis
37
What is septic vasculitis?
Vasculitis that occurs following severe bacterial infection, deep pyoderma or secondary to severe generalized Demodex with cellulitis
38
What is the pathogenesis of septic vasculitis?
Pathogenesis is complex and includes five main mechanisms:
1) disseminated intravascular coagulation
2) direct invasion and occlusion of blood vessel walls by microorganisms
3) hypersensitivity reaction with immune complex deposition into blood vessel walls
4) embolism from a distant infectious site
5) vascular effects of toxins
39
What is eosinophilic vasculitis associated with?
Type I hypersensitivities:
arthropod rxn
adverse food rxn
canine eosinophilic dermatitis
40
What is familiar cutaneous vasculopathy of German shepherd dogs?
Pedigree analysis showed autosomal recessive inheritance pattern
Swollen, depigmented paw pads; crusting and ulceration of ear tips and tail tips; and focal depigmentation of the nasal planum
May have pyrexia and lethargy
Young puppies 4 to 6 weeks
Typically occurs 7 to 10 days after first vaccination and get worse with more
41
What is cutaneous and renal glomerular vasculopathy?
AKA Alabama Rot AKA vasculitis of greyhounds (b/c first in racing greyhounds)
- causes cutaneous lesions and acute kidney injury
--> PU/PD/vomiting, dark stools, acute renal failure
--> Palpable edematous purpura (go from red to purple to sloughing)
--> Limbs and less commonly groin and trunk affected
--> Leaves well-demarcated, slow-healing ulcers behind
- Etiology not completely known
--> most but not all are associated with E. coli shigalike toxin from bad meat
42
What is solar vasculopathy?
Severe erythema, swelling, exudation, erosions and ulcerations are limited to non-pigmented glabrous or poorly haired areas of the skin
- may develop secondarily to acquired depigmentation
- may develop secondary to photosensitizing drugs/plants.
Mainly seen in dogs
Etiology: UV light induces formation of thymidine dimmers, increase of nitric oxide as well as damage of the DNA repair system.
43
Which rickettsial disease is most closely associated with vasculitis in veterinary medicine?
Erlichia
44
Which parasitic diseases are most closely associated with vasculitis in veterinary medicine?
dirofilariasis
babesiosis
leishmaniasis
trypanosomiasis
45
Which viral diseases are most closely associated with vasculitis in veterinary medicine?
Herpes virus
FIP
FIV
FeLV
46
Which exogenous antigens are closely associated with vasculitis in veterinary medicine?
drugs (including vaccines), food additives
47
Which endogenous antigens are closely associated with vasculitis in veterinary medicine?
neoplasia, connective tissue diseases
48
What how can idiopathic vasculitis be subdivided?
--1st by vessel type, size and location
--2nd by inflammatory infiltrate
49
What type of vasculitis is type III hypersensitivity reaction generally associated with?
Neutrophilic vasculitis and fibrinoid necrosis of the vascular wall
Immune-complexes attract complement factors and activate the complement cascade which recruit neutrophils
50
How do cytotoxic T cell cause vasculitis?
CD8+ cytotoxic T cells can recognize haptens, such as drug metabolites, bound to components of the vascular wall, initiating immunologic reactions resulting in vasculitis
Can also be directed against structural components of vascular wall
51
What is the common clinical presentation of chronic vasculitis?
Less severe or slowly progressive vasculitis results in low-grade ischemia Patchy alopecia, scaling, erythema and hyperpigmentation are seen
Lesions typically distally +/- over pressure points.
52
What are some clinicopathologic findings associated with vasculitis?
Anemia, thrombocytopenia, lymphopenia, eosinophilia, neutrophilia with a left shift and toxic changes, hypoalbuminemia, and elevated liver enzymes may be seen with systemic vasculitis.
Circulating immune complexes, diminished complement factors and hypergammaglobulinemia may be present with immune-mediated vasculitis.
53
What is the most common form of vasculitis?
Predominantly neutrophilic
--> non-leukoclastic
--> leukoclastic = (degenerative neutrophils, nuclear dusts)
54
What is typical of histopathology of acute and sub-acute vasculitis?
There are well circumscribed dermal and epidermal areas of coagulation necrosis, micro-hemorrhages, marked protein-rich edema and deposition of fibrin
The vessel walls are thickened and edematous with hyalinization and fibrinoid necrosis; the endothelial cells are swollen and necrotic (cell-poor vasculitis or vasculopathy)
Degenerative changes may be associated with intramural inflammation. The presence of degenerative neutrophils, referred to as leukocytoclasia, is pathognomonic for vasculitis
Presence of inflammatory cells within arterial and venous walls indicates vasculitis, as leukocyte migration does not occur through arteries and veins
The nature of the inflammatory infiltrate may change over time.
There may be deposition of PAS-positive material within the vessel walls
55
What is seen on histopathology of lymphocytic vasculitis?
tight cuffs of small CD8+ lymphocytes surrounding primarily small arterioles
56
When is lymphocytic vasculitis typically seen on histopathology?
chronic resolving stages of immune-complex vasculitis (vaccine-induced panniculitis, vasculopathy of German Shepherds, drug reactions)
57
What is granulomatous vasculitis?
Is usually a subacute to chronic stage of primary fibrinoid necrosis that may occur with neutrophilic, leukocytoclastic vasculitis
58
What is typical of histopathology of chronic vasculitis?
Predominant changes are atrophy of the hair follicles and adnexal glands
The subepidermal collagen is homogenized and pale
Newly formed, arborizing thin collagen btw preexisting dermal collagen
Mucin deposition may be present
The number of small dermal vessels may be decreased
The vascular walls appear thickened and hyalinized and a decrease of factor VIII+ endothelial cells is apparent
The overlying epidermis may be atrophic
Features of cell-poor interface dermatitis are common
Larger areas of scaring may be present
59
What is vasculitis with cartilage necrosis of the pinnal fold in dogs?
Crusting, exudative, ulcerating linear lesions develop on the medial aspect of the pinna, along the fold of the ear pinna in dogs
More frequent in dogs that traditionally had ears cropped (example: Boxers)
Etiology--Unknown.
60
What is thrombovascular necrosis of the pinna?
wedge-shaped, usually bilateral symmetrical, necrosis of the distal ear pinna in dogs
Typically progressive syndrome, lesions are painful
Etiology--unknown
May have to remove ear pinna
61
5-year old male Labrador Retriever that presented with bilateral ulceration and necrosis of its ear tips
Thrombovascular necrosis of pinnae (pinnal margin vasculopathy aka ischemic necrosis of pinnae)
62
What is dermal arteritis of the nasal philtrum?
a condition that selectively targets large vessels of the nasal philtrum of dogs and presents as a characteristically well-demarcated linear to oval ulcer that spans the short axis of the nasal philtrum
- large breeds may be predisposed (St. Bernard)
- treatment is prednisolone, doxycycline/niacinamide, tacrolimus, pentox, surgery was previously tried
63
What is rostrolateral nasal alar arteriopathy?
a vasculopathy observed primarily in middle-aged German shepherd dogs, characterized by a linear ulcer/fissure on the rostrolateral alar fold
- etiology is unknown but it is suspected to be immune-mediated
- strong breed predisposition to GSD
- empirical treatment with topical and/or systemic immunomodulatory drugs can be considered.
64
Nasal philtrum arteritis
65
Nasal alar arteriopathy
66
Arteriopathy, nose
(a) discrete linear epidermal ulceration (arrow) and underlying dermal arteriopathy (arrowhead); (b) marked acanthosis with underlying dermal arteriopathy (arrowheads). (c–e) High-power fields showing a dermal arteriole: (c) with a markedly expanded tunica intima/media and no adjacent vessel-oriented inflammation; (d) with strong Alcian blue uptake within the tunica intima/media, consistent with mucin deposition; (e) with strong tunica intima/media basophilic staining using Masson's trichrome, consistent with collagen deposition.
67
What is ischemic dermatopathy?
Not typically inflammatory, characterized by alopecia, scale and scarring
- Results from loss of blood supply from vasculitis or vasculopathy
- “cell poor vasculitis”
- dogs <10 kg may be predisposed
68
What are the 5 classic types of ischemic dermatopathy?
Familial dermatomyositis
Juvenile onset dermatomyositis/ischemic disease
- Jack Russells may be at risk
Post rabies vaccine panniculitis
Generalized vaccine induced ischemic dermatopathy
Adult onset ischemic dermatopathy with no association with vaccines
69
Young collie-mix
Familial dermatomyositis
70
What breeds are predisposed to canine familial dermatomyositis?
Collies **
Shetland Sheepdogs **
Beaucerons
Belgian Tervurens
Portuguese Water Dogs
71
What is the clinical manifestation of canine familial dermatomyositis?
- 1.5 to 6 months of age
- alopecia, erythema, crusting, erosions, ulcerations, progressing to scarring +/- sloughing of skin, usually on the bony prominences
- not often associated with myositis, but when present, the masticatory muscles are most commonly affected
- megaesophagus rarely occurs
- peripheral muscle involvement can lead to generalized weakness
- can get secondary infections
72
What is the etiology of canine familial dermatomyositis?
- a genetic component to this disease is believed to be present
- pathogenesis of dermatomyositis remains unknown
--> presence of antigen-antibody complexes in the vessel walls suggests a type III hypersensitivity reaction
--> elevated serum complement levels and class G immunoglobulins have also been demonstrated
--> can get worse with photo-aggravation, trauma, estrus
73
What are the histopathologic features of canine ischemic dermatopathy?
cell-poor vasculitis (causes vascular compromise and cutaneous ischemia)
- loss of endothelial cells, with hyalinization and occasional leukocytoclasia
- Altered staining of the collagen (pale and smudgy)
- fading atrophy of the follicles
- mucin and edema
- basal apoptosis in the follicular isthmus > epidermis
potential myositis if biopsy deep enough on the face
advanced case: dermal-epidermal vacolation, pigmentary incontinence and artefactual lifting of the epidermis could occur (subepidermal vesicles esp collies)
74
What is the prognosis of canine familial dermatomyositis?
It can wax and wane but usually poor
Can try immunomodulators
75
What causes linear vascular patterns on histopathology?
DIC, lymphoreticular neoplasia, SLE, cold agglutinin disease, frostbite
76
What is pastern leukocytoclastic vasculitis?
Pastern dermatitis in mature horses, unilateral or bilaterally symmetrical
Hind legs are more commonly affected
Affected non-pigmented area on distal extremities (legs, sometimes muzzle)
Gets worse in summertime (photo aggravation)
Thought to be an immune complex disease with deposition in distal limb
Well demarcated circular, painful erythematous crusts on medial and lateral pastern
Painful with edema and lameness common
Dx on histopath
Tx by avoiding light, can use steroids and pentoxy +/- abx
77
pastern leukocytoclastic vasculitis
78
What are the histopathologic findings for leukocytoclastic vasculitis?
intramural inflammatory cells (blood vessels)
leukocytoclasia with nuclear dust
microhaemorrhages
thickening of the vessel wall
79
What are the potential etiologies of leukocytoclastic vasculitis on the distal part of the equine leg?
idiopathic pastern leukocytoclastic vasculitis
leukocytoclastic vasculitis due to photosensitisation or bacteria
trauma-induced vasculitis
systemic vasculitis
80
What is chronic progressive lymphedema?
- swelling/pitting edema (lymph fluid), hyperkeratosis and fibrosis (nodules, skin folds, ulcerations) of distal limbs (hind>front) in draft horses
- starts at a relatively early age and is progressive
- frequent bacterial and chorioptic mange infections --> more lymphedema
- histopath shows Increased elastin degradation, abnormal elastin network, increase elastin antibodies in serum
o defect in elastin leads to dilated lymph vessels and lymph retention
o changes are more evident in very deep dermis
- supportive care, no treatment known
81
What are the names of the 3 parallel skin vacular networks in the dermis?
- Subcutaneous plexus: derived from arterial branches to superficial cutaneous structures
- Cutaneous plexus: supplies hair follicles and sweat glands, arises from branches of subcutaneous
- Superficial plexus: supplies papillary processes, arises from branches of the cutaneous
