Immune-mediated diseases Flashcards
Pemphigus complex, vasculitis, histiocytic, lupus, EM, SJS/TEN
What is the most common antigen targeted in human PF?
Desmoglein-1
What is the most common antigen targeted in canine PF?
Desmocollin-1
What is the most common antibody isotype in canine and human PF?
IgG
What 4 insecticides have been implicated as a trigger in PF?
Metaflumizone-amitraz (Promeris)
Fipronil-amitraz-S-methoprene (Certifect)
Dinotefuran-pyriproxyfen-pyrethrin (Vectra 3D)
Afoxolaner (Nexgard)
What is the name of the endemic form of PF and where is it endemic?
Fogo selvagem, Brazil
What is the pathogenesis of fogo selvagem?
Sand fly salivary antigen LJM11
sand fly bites human –> antigen cross-reacts with Dsg-1 –> trigger PF
What are the 4 phenotypes of canine PF?
Facial-dominant
Truncal-dominant
Generalized
Foot pad-exclusive
What are two primary differentials for PF?
pustular dermatophytosis (Trichophyton)
superficial pyoderma
What is the antigen targeted in the mucosal-dominant variant of human PV?
Desmoglein-3
What is the antigen targeted in the mucocutaneous variant of human PV?
Desmoglein-1 and desmoglein-3
What is the antigen targeted in canine PV?
Desmoglein-3 (and less Dsg-1)
Histopathology of canine skin lesions reveals suprabasal keratinocyte acantholysis with basal cells remaining attached at the basement membrane, resembling tombstones. Which autoimmune disease is most likely?
PV
What desmosome is more prevalent in mucosa?
Dsg-3
What are the 3 types of deep pemphigus?
PV
Pemphigus vegetans
Paraneoplastic pemphigus
Besides anti-DSG3 antibodies, what other gene is suspected to be involved in canine PV?
c-Myc
What gender is more commonly affected by canine PV?
Males (opposite of human PV)
True or false: Pruritus is common in canine PV
False
What is the best area to biopsy for diagnosis of PV?
Margin of an erosion/ulcer (1/3 lesional skin, 2/3 perilesional skin)
What is the most common distribution of human Pveg?
Periorificial and intertriginous areas
Describe the Neumann-type vs. the Hallopeau-type of Pveg in humans
Neumann-type: starts with vesicles/blisters
Hallopeau-type: starts with pustules
What are the histopathologic features of Pveg?
PV (suprabasilar acantholysis) + hyperplastic PF
What subtype of human Pveg has a better prognosis?
Hallopeau-type
What neoplastic conditions have been associated with paraneoplastic pemphigus in dogs and cats?
Thymoma
Thymic lymphoma
Splenic sarcoma
What are the most consistent targets of paraneoplastic pemphigus?
Periplakin
Envoplakin
Desmoglein-3
What two immune-mediated conditions does histopath of paraneoplastic pemphigus resemble?
PV, EM
What are the most common lesions of canine paraneoplastic pemphigus?
Erosions and ulcers (oral cavity and lips most often)
Skin biopsies from a dog reveal features of both EM and PV. What is the most likely differential and what should be your next step?
Paraneoplastic pemphigus - start thorough workup for underlying neoplasia
What two breeds are overrepresented in canine PF?
Akita
Chow
Is there a sex predilection for canine or feline PF?
No
Apart from pustules and crusts, what other clinical feature is seen in horses with PF?
Ventral edema
What histopathologic features help differentiate PF from bacterial folliculitis?
PF pustules are large and span MULTIPLE follicular units
Recornification beneath the pustule
What is the major autoantigen of human PE?
Desmoglein-1
What are the histopathologic features of PE?
Intragranular or subcorneal neutrophilic/eosinophilic acantholytic pustules
Lichenoid interface dermatitis
What steroid has been associated with the highest rates of remission in feline PF?
Triamcinolone
Besides neutrophils, what inflammatory cell is often found in feline PF cases, differing from what is seen in canine PF?
Mast cells
Describe the pathogenesis of acantholysis in pemphigus
What pemphigus variants have been recognized in horses?
PF
PV
Describe the expression of desmosomal cadherins in haired skin/footpad/nasal planum
Describe the expression of desmosomal cadherins in the oral cavity/mucosa/esophagus
Besides genetics, what else may serve as a trigger/predisposing factor for PF?
Sun exposure
Are lesions of insecticide-triggered PF located at the site of application or distant from the site of application?
Both (though Vectra 3D has only been associated with distant lesions)
Cutaneous polyimmunity as been associated with PF and what other disease?
DLE
Is there a sex predilection in feline PF?
No
Is there a breed predisposition in feline PF?
No
Describe the lesion distribution of feline PF
In what condition may you see a “keratin ring” on histopathology?
PF
Are anti-DSC1 serum antibody titers related to PF severity?
Yes
Describe the glucocorticoid pulse regimen for treatment of PF
GC 10 mg/kg/day x3 days, then 1-2 mg/kg/day, repeat pulse if relapse occurs
What form of pemphigus is most common in humans?
PV
What is a primary difference between the vesicles seen in PV vs those seen in AISBDs?
PV vesicles are flaccid, not tense
What clinical test is pathognomonic for deep pemphigus?
Nikolskiy sign (direct/marginal)
What clinical feature of paraneoplastic pemphigus helps differentiate it from PV?
Rapid progression of lesions
What is the target antigen in Pveg?
Dsg-1
What is the suspected antigen target in feline PF?
Dsg-1
What is the most common distribution of skin lesions associated with vasculopathy?
Bony prominences
Body extremities
What adhesion molecules are upregulated on endothelial cells during vasculitis?
E-selectin
ICAM-1
What are four mechanisms of immune-mediated vasculitis?
Immune complex deposition in vessel walls
Production of anti-neutrophil cytoplasmic antibodies (rare)
Anti-endothelial cell antibodies
Autoreactive T-cells, macs
What is the main cause of purpura hemorrhagica in horses?
Streptococcus equi
What is the hallmark feature of cutaneous vasculitis?
Palpable purpura
What are the histopathologic features of cutaneous vasculitis?
Hyalinization/fibrinoid necrosis of vessel wall
Inflammatory cells in vessel wall
Swollen endothelial cells
Edema, hemorrhage
Ischemia: pale collagen, follicular atrophy, cell-poor interface dermatitis
What triggers have been identified for cryoglobulinemia?
Lead poisoning
URI
Multiple myeloma
Lymphoma
A dog with urticarial vasculitis is biopsied and histopathology reveals primarily an eosinophilic infiltrate. What is your major differential?
CAFR
In cutaneous and renal glomerular vasculopathy, does the AKI usually occur before, simultaneously, or after skin lesions?
After skin lesions
What is the most important CBC finding in canine cutaneous and renal glomerular vasculopathy?
Thrombocytopenia (due to consumption from massive vessel thrombosis)
What are negative prognostic indicators for the development of AKI in canine cutaneous and renal glomerular vasculopathy?
Anemia
Neutrophilia
Thrombocytopenia
What is the gold standard for diagnosis of canine cutaneous and renal glomerular vasculopathy?
Kidney biopsy –> thrombotic microangiopathy of glomerular arterioles
What drug has been associated with proliferative thrombovascular necrosis of the pinnae?
Fenbendazole
What infectious diseases associated with vasculitis may preferentially affect the pinnae?
Leishmania
Bartonellosis
What oral medication has been shown to be effective for management of proliferative thrombovascular necrosis of the pinnae?
Oclacitinib (1-3 mo response times)
What breed is represented in familial necrotizing arteritis?
Beagles
What is the pathogenesis of familial necrotizing arteritis?
Anti-neutrophil cytoplasmic antibodies
What breeds are represented in familial cutaneous vasculopathy?
GSD
JRT