Immune mediated dermis dz (ECVD video) Flashcards
1
Q
Common precursor of DCs and macrophages
A
Blood monocytes (CD18+, CD45+)
2
Q
Cell surface markers of Interstitial DC (in dermis)
A
CD4+, CD90+
3
Q
Cell surface markers of LCs
A
CD4-, CD90-
4
Q
Which type of cell is responsible for reactive histiocytosis?
A
Interstitial DCs
5
Q
Which cell type is responsible for sterile granulomatous pyogranuloma syndrome; + cell surface markers
A
Macrophages (CD1a, CD11d)
6
Q
Which of the below DOES express CD4? Interstitial DCs or LCs?
A
Interstitial DCs
LCs do NOT express CD4
7
Q
CD11d is suggestive of which cell
A
Macrophage
8
Q
CD18 is suggestive of which cell
A
Blood monocyte
9
Q
Reactive cutaneous histiocytosis breeds
A
Collie, Shetland sheepdog
10
Q
Reactive systemic histiocytosis breeds
A
Bernese mountain dogs > Irish wolfhounds, golden retrievers, lab retriever, rottweiler
11
Q
Age for reactive histiocytosis
A
Cutaneous: 4 yr median
Systemic: 1-9 yr range
12
Q
Cytokine profile of cutaneous reactive histiocytosis
A
Th1 (IL-6, IL-12, IFNg, TNFa)
13
Q
Etiology of cutaneous reactive histiocytosis
A
*Persistent antigen stimulation
*Immunologic dysregulation
14
Q
Cells of cutaneous reactive histiocytosis
A
Dendritic cels
T cells (CD8>CD4)
15
Q
Clinical lesions of cutaneous histiocytosis
A
Papules, plaques, nodules
Alopecia, erythema, depigmentation, ulcers, crusts
16
Q
Body region of cutaneous histiocytosis
A
Haired skin
Nasal planum (clown nose)
Foot pads
Linear
Regional LN
17
Q
Organ systems affected in systemic histiocytosis
A
Everywhere :)
Skin, mucosa
Liver, spleen
LN
BM
Lungs, eyes, kidneys, testes, muscles, nasal cavity
Systemically ill
18
Q
Labwork findings with systemic histiocytosis
A
Anemia
Monocytosis
Lymphopenia
Hypercalcemia
19
Q
Cutaneous reactive histiocytosis is DIFFERENT than histiocytoma because ______-
A
Reactive histiocytosis is BOTTOM HEAVY (not affected epidermis
Histiocytoma is TOP HEAVY
20
Q
Sterile pyogranuloma syndrome breeds
A
Boxer
Collie
Dachshund
Doberman pinscher
English Bulldog
Golden Retriever
Great Dane
Weimeraner
21
Q
Pathogenesis of sterile pyogranuloma syndrome
A
*Aberrant inflammatory response
*Immune dysfunction
*Infectious agents: low numbers (Leishmania) or incomplete clearance of their antigens –> using PCR may help us find these organisms better!
22
Q
Body region sterile pyogranuloma syndrome
A
Dog: Head (muzzle, periocular, pinnae), neck, trunk, legs, paws
-Hypercalcemia in dogs!
-Regional lymphadenopathy in 30%
Cat: Muzzle>pinnae, extremities > trunk
23
Q
Causes of infectious granulomatous diseases
A
*Protozoa
-Leishmania
-Neospora
*Bacteria
-Actinomyces
-Nocardia
-Mycobacteria
-Actinobacillus
*Fungal
-Cryptococcus neoformans
-Coccidiodes immitis
-Histoplasma capsulatum
-Blastomyces dermititidis
-Sporotrixhum schenckii
*Oomyces
-Lagenidium
-Pythium insidiosum
*Pheohyphomycosis
-Alternaria
-Curvularia
*Algae
-Prototheca
24
Q
Causes of NONinfectious granulomatous diseases
A
*Foreign body
*Endogenous material
-Hair
-Sebum
-Keratin etc
*Sterile granuloma and pyogranuloma syndrome
*Reactive histiocytosis
*Juvenile sterile granulomatous dermatitis and lymphadenitis
*Cutaneous xanthoma
*Canine sarcoidosis
25
Sarcoidosis gene predisposition (humans)
MHC cl II
26
Sarcoidosis pathogenesis in humans
Th1 immune response to infectious agents, allergens
ie: Mycobacterium >> minerals (cat litter), chemicals (insecticides)
27
Other organs affected by sarcoidosis in humans
Lungs> skin > eyes, liver > other
28
Sarcoidosis (human) prognosis)
Good
May self-cure.
Tx: GCs +/- 2' steroid sparing agents
29
Sarcoidosis, Systemic Granulomatous Disease in horses: age of onset
Usually > 3 years old, wide range
30
Sarcoidosis, Systemic Granulomatous Disease in horses: etiology
*Idiopathic
>>
*Infectious agents
-Mycobacterium
-Borrelia burgdorferi
-EHV-2
*Toxins
-Hairy vetch
31
Which infectious agents may cause Sarcoidosis, Systemic Granulomatous Disease in horses
*Infectious agents
-Mycobacterium
-Borrelia burgdorferi
-EHV-2
*Toxins
-Hairy vetch
BUT USUALLY IDIOPATHIC
32
Other organs affected by Sarcoidosis in horses
*Skin
*Lungs
>>
*Internal LN
*Liver
*GI
*Spleen
*Kidney, bone, CNS, Heart, Adrenal, Thyroid, Thymus, Pancreas, Muscles, BM
33
3 clinical forms of Sarcoidosis in horses
*Localized (focal exfoliative dermatitis, ie lower limb)
*Partially Generalized (Exfoliative dermatitis, nodules that progress from a focal area. LN+ --> generalized)
*Generalized (internal organs +/- cutaneous)
34
Lab findings with Sarcoidosis in horses
*Anemia
*Leukocytosis
-Neutrophilia
*Hyperfibrinogenemia
*Hypoalbuminemia
*Hyperglobulinemia
*Hyperbilirubinemia
35
Sarcoidosis in horses histopath
-Nodular, interstitial granulomatous inflammation with multinucleated giant cells
-Superficial, dermis > panniculus
36
Prognosis Sarcoidosis in horses
*Cutaneous only: RARELY self cure
Variable response
-Relapse with tx discontinued, or seasonal flares, training/competition stress
*Systemic: Often euthanized
37
Treatment Sarcoidosis in horses
*Remove hair vetch from diet
*GC (1-4mg/kg/d prednisolone)
*OFA
*Pentoxifylline
38
Breed, age for canine Sarcoidosis
Shetland sheepdogs
Middle aged
39
Clinical lesions for canine sarcoidosis
Papules, plaques, nodules
*Possibly the same as sterile granuloma/pyogran syndrome
40
Histopath difference between SGPS and sarcoidosis in dogs
*No neutrophils in sarcoidosis
*Sarcoidosis does not affect adnexa or extend to panniculus
41
Histopath difference between reactive histiocytosis and sarcoidosis in dogs
Reactive histiocytosis is bottom heavy
Sarcoidosis is top heavy
42
T or F: Sarcoidosis in dogs usually progresses to systemic involvement
FALSE
Systemic involvement not yet reported in dogs
(It does happen in horses, humans)
43
Treatment sarcoidosis dogs
*GC
*Cyclosporine
44
Breed predisposed to SNP
Dachshunds!!!!
*Australian shepherd
*Brittany spaniel
*Chihuahua
*Collie
*Dalmatian
*English bulldog
*Pomeranian
*Poodle
45
Species w/SNP
*Dog
*Cat
*Horse, donkey
*Bovine
*Human
46
Pseudomonas panniculitis has been reported in which species
*Cats
*Ferrets
47
Causes of panniculitis
*Infections (Bartonella, Serratia, Myobacteria, Nocardia, etc
*Physical (trauma, injections, foreign bodies, burns)
*Nutritional (pansteatitis)
*Pancreatic (inflammation, neoplasia)
*alpha1-antitrypsinase deficiency??
*Immune mediated (vasculopathy--ischemic/rabies, KBr, SLE, IMPA, IBD, arthropods)
*Idiopathic
48
Which drug most often causes panniculitis
KBr
49
T or F: anti-neutrophil antibodies have been reported in dogs with sterile panniculitis
True!! Most!
*Can be perinuclear or cytoplasmic antibodies
*Unknown if this is a cause or a result of SNP
50
In which immune mediated disease has anti-neutrophil cytoplasmic antibodies been reported
Sterile nodular panniculitis
51
Septal panniculitis-- pyogranulomatous infiltrate among _____ neoplastic cells
T cell lymphoma!!
Be cautious not to misdiagnose as SNP
52
Juvenile cellulitis age
USUALLY 3w-4mo
BUT case reports of adult onset!!!
53
Sterile granulomatous dermatitis and lymphadenitis other name
Juvenile cellulitis
BUT many adult onset cases
54
Sterile granulomatous dermatitis and lymphadenitis clinical signs
*Edema of facial MC junctions
*Papules, pustules on face, pinnae
*Nodules, fistulous dracts
*SUBMANDIBULAR lymphadenopathy
*Neuro signs from spinal cord compression or inflammation of CSF
55
Sterile granulomatous dermatitis and lymphadenitis histopath
Nodular pyogranulomatous inflammation
Effacement of hair follicles
r/o sterile pyogranuloma granuloma syndrome-- looks the same on histopath
56
Sterile granulomatous dermatitis and lymphadenitis treatment
May self cure in 1-3 months, but TREAT because might die!!
Usually no relapse if juvenile. May relapse if adult (30%!)
GC +/- cyclosporine
Analgesics
57
Canine pyoderma gangrenosum breed
American staffordshire terrier
58
Canine pyoderma gangrenosum: Pathogenesis, Cytokines
Autoimmune?
IL-1b, IL-8, IL-17a, TNF-a
59
Canine pyoderma gangrenosum: triggers, concurrent dz
Neoplasia
IMPA
Surgery (pathergy)
Idiopathic
60
Canine pyoderma gangrenosum pathomechanism
1) Apoptosis of keratinocytes, release DAMPs,PAMPS
2) Innate immune system activated
3) Neutrophils recruited
4) T cells activated
5) Macrophages and neutrophils come to the skin
61
Clinical signs, body distribution: Canine pyoderma gangrenosum
Deep pustules, hemorrhagic bullae -> Ulcers (undermined borders), pain
Multiple sites: face, trunk, legs
62
Canine pyoderma gangrenosum: Internal organs
*Pancreatitis
*Neutrophilic splenitis
Fever, lameness
*Increased C-reactive protein on labwork
63
Bromodera
Drug reaction from contact or systemic bromide administration
-Hemorrhagic bullae, crusted nodules, deep ulcers
Looks similar to Canine pyoderma gangrenosum
-Resolves with KBr discontinued
64
Clinical difference between Sweets and Canine pyoderma gangrenosum
Gangrenosum has ulcers
Sweets is more papules/plaques w/o ulcers
Look the same on histopath, so need to differentiate clinically
65
Canine pyoderma gangrenosum Treatment
Treat inciting disease (if it exists)
*Pain management
*Prednisolone, cyclosporine vs azathioprine
*CAN do cyclosporine monotherapy
Prognosis: Good
66
Triggers for Sweets-like
*Carprofen
*Firocoxib
*Plant-oil containing flea preventative in cats
*IMPA
(In humans, infections, vaccines, immune-mediated dz, neoplasia, pathergy, pregnancy)
67
Immune response to Sweets-like Syndrome
*Th1 OR Th17 in different patients
*Aberrant neutrophil proliferation, maturation, and dermal infiltration. Increased G-CSF to promote neutrophils
*IL-1b, IL-8, IL-33, IFNg, TNFa, CCL2, CXCL10
68
Clinical signs Sweets-like syndrome
*Edema, erythema
*Macules, papules, plaques
*Vesicles
*PAIN
*Generalized. Haired skin and MM
69
Lab findings with Sweets-like syndrome
*IMHA
*IMTP
*Decreased albumin
*Neutrophilia
*Increased c-reactive protein
70
Which special stain can help determine CAEDE vs Sweets-like?
Luna stain (eosinophilic infiltration amount)
71
Treatment Sweets-like syndrome
*Drug withdrawal
*Pain management
*GC, cyclosporine, azathioprine, MMP
72
Which species have CAEDE
*Dogs
*Horses
73
What other organ system is affected in CAEDE
GI in 80% of cases
Usually before skin lesions (60%), but can be concurrent (15%)
74
Pathogenesis of CAEDE
*GI dz
*Drugs
*Insects
75
Clinical signs of CAEDE
*Erythema (macular, diffuse)
*Wheals
*Edema (pitting, face/legs).
*Pruritus in 30%
Face, pinnae, ventrum > extremities
76
Lab findings CAEDE
RARE to have peripheral eosinophilia
*Low TP
*Low Cholesterol
77
Difference between Pattern 1, 2, 3 of CAEDE
1: Superficial
3: Diffuse eos inflammation with flame figures, edema, ulcers
78
Treatment for CAEDE
*Hospitalized for severe GI signs
*Skin disease may wax/wane
*Rare for skin signs to relapse once treatment discontinued. BUT GI signs often do relapse
GLUCOCORTICOIDS + CETIRIZINE!!!
79
Species with Hypereosinophilic syndrome
*Dogs (no skin involvement)
*Cat
*Horse
*Ferret
*Human
80
Pathogenesis Hypereosinophilic syndrome
*Idiopathic
*Paraneoplastic (lymphoma in a cat!)
81
Clinical signs Hypereosinophilic syndrome
*Macules, papules, plaques, edema-wheals, pruritus
*Oral cavity, LN, BM, liver, spleen, GI heart, lung involvement possible
*Eosinophilia on labwork!!!
82
Prognosis Hypereosinophilic syndrome
Usually fatal if systemic involvement
Cats with skin only: live 2-4 years
83
Hypereosinophilic syndrome Treatment
Glucocorticoids-- only temporary response
Hydroxyurea (block bone marrow production of eos, but general BM suppression)
Cyclosporine
84
Perianal fistula breed
MI GSD > MN GSD
GSD (80%), but other large/medium breeds possible.
85
Perianal fistula genetics predisposition
MHC cl II
Potentially also intestinal bacterial dysbiosis
86
Which type of T cell is more common in Perianal fistula
CD4+ cells
B cells, plasma cells, macrophages
(Cells that respond to MHC cl II)
87
Cytokines upregulated in Perianal fistula
Mostly Th1 cytokines (IL-2, IFNg >>>>)
*IL-1b
*IL-2
*IL-6
*IL-8
*IL-10
*IFNg
*TNFa
*TGFb
88
What human disease is potentially related to Perianal fistula
Crohns
89
Which MMPs are upregulated in Perianal fistula
MMP 9, MMP 13
*Implicates macrophages in pathogenesis
*Explains extensive tissue destruction
90
What non-skin clinical sign is present in 42-100% of dogs with Perianal fistula
Colitis
91
What comorbidities can accompany Perianal fistula
CAFR
Metatarsal sinuses
Chronic superficial keratitis
92
Which MMPs are upregulated in Perianal fistula
MMP 9, MMP 13
*Implicates macrophages in pathogenesis
*Explains extensive tissue destruction
93
Treatment for Perianal fistula
Cyclosporine + topical tacrolimus (96% of dogs respond)
*Higher dose SID is best to achieve remission
-Prednisone
-Aza
-MMP
-Apoquel (2 cases)
-Stem cell injection
-Phovia
-Elimination diet?
-Sx?
-Tx 2' infections
Some people use metronidazole too
94
Metatarsal fistula breed
GSD
95
Metatarsal fistula sex
Males
96
Metatarsal fistula age of onset
Middle-aged
97
Metatarsal fistula pathogenesis
Focal panniculitis
-Mechanical stress?
-Anticollagen antibodies?
98
Are front or hind limbs more often affected in Metatarsal fistula
Metatarsus > Metacarpus
99
Is Metatarsal fistula usually bilateral or unilateral
Bilateral
100
Non-GSD breed w/ reported Metatarsal fistula
Grey hound
Cleared with topical tacrolimus
101
Treatment Metatarsal fistula
-GC (topical, oral)
- Cyclosporine
-Tacrolimus (use for maintenance once in remission)
-Vitamin E
- Doxy/niacinamide
May self cure, with recurrences common
102
Metatarsal fistula histopath
Pyogranulomatous inflammation of panniculus, deep dermis
Sinus formation
Fibrosis in necrotic areas
103
Feline plasma cell pododermatitis: Sex
Males (esp neutered)
104
Feline plasma cell pododermatitis: Age, breed
None reported
105
Feline plasma cell pododermatitis: pathogenesis
**Immune mediated**
*plasma cells *increased g-globulins in serum
*response to immunosuppression tx
**Allergic**
**Contact (perfumed litter)**
**Structural (localization, response to sx)**
**Infection (FIV/FeLV)**
106
Are plasma cells monoclonal in Feline plasma cell pododermatitis?
NO. They are polyclonal
107
Which Ig are the plasma cells secreting in Feline plasma cell pododermatitis
IgG mostly
A little IgA
108
Does Bartonella cause Feline plasma cell pododermatitis
No
But study was used on formalin-fixed tissue.
Was studied because cats respond to doxycycline
109
What viruses implicated in Feline plasma cell pododermatitis
FIV (60% are +)
FeLV less common, but reported in 2 cats
110
Feline plasma cell pododermatitis: Sex
Males (esp neutered)
111
Lab findings from Feline plasma cell pododermatitis
Increased g-globulins, thrombocytopenia
112
Feline plasma cell pododermatitis: other body sites
*Stomatitis
*Bridge of nose
*Glomerulonephritis
*Amyloidosis
-from hyperactive plasma cells
113
Plasma cell special stain
Methyl Green-Pyronin (MGP)
-Nucleus: dark blue
-Cytoplasm: pink (stains mRNA for Ig synthesis)
114
Feline plasma cell pododermatitis: treatment
Mild: allow to self-cure. Change litter, doxycycline x3-10w
Severe: glucocorticoids, cyclosporine
Very severe (nodules, ulcers, hemorrhages): surgery
115
Clinical course of cutaneous histiocytosis
Waxes/wanes
Consider maintenance therapy to minimize recurrence
116
Body location with more aggressive cutaneous histiocytosis
Nasal planum lesions
