Desmosomes - Croatia Flashcards
Both Darier Disease and Hailey-Hailey Disease have what mode of inheritance?
autosomal dominant
Autoantibodies against periplakin can result in what clinical disease?
paraneoplastic pemphigus
Why are oral lesions not a feature of pemphigus foliaceus?
desmocollin-1 is not present in the oral mucosa
Why do autoantibodies against desmolgein-3 or desmocollin-3 result in more severe lesions?
These proteins are expressed in keratinocytes of stratum spinosum & stratum basale
What is the major antigen of pemphigus foliaceus in dogs?
desmocollin-1
Where are the most common areas to be affected with canine pemphigus foliaceus?
nasal planum and/or dorsal muzzle; trunk, pinnae, footpads
ExpA and ExpB toxins of S. pseudintermedius target what structure in the canine desmosome?
DSG-1
Is desmoglein-1 present in the superficial epidermis (corneum/granulosum) or deep epidermis (spinosum/basale)?
Both – but more present in superficial epidermis
What species of dermatophytes has been demonstrated to cause superficial acantholytic pustular dermatophytosis? In what animal species has this been reported?
Trichophyton spp., dogs and horses
In superficial pustular dermatophytosis, what structures of the epidermis are invaded by dermatophytes?
stratum corneum, follicular infundibula, subcorneal pustules
To what does desmoglein-3 bind?
amino-terminus is heterophilic binds to DSC1, DSC2, DSC3; carboxy-terminus: plakophilin-3, plakoglobin
T/F: Trichograms from animals suspected to have superficial pustular dermatophytosis are the best sample for fungal culture.
False – do NOT invade the hair shaft, need the scale (i.e. the stratum corneum)
What is the target autoantigen in pemphigus foliaceus in dogs?
DSC-1 (major), DSG-1 (minor) - dogs
What are the two main members of the desmosomal cadherin family?
desmogleins and desmocolins
T/F: Many dogs with pemphigus foliaceus also suffer from a concurrent autoimmune disease.
True - up to 19% have a concurrent autoimmune disease (IMHA, ITP, KCS, thyroiditis)
T/F: The exfoliatin toxin of both S. aureus and S. hyicus cleave canine DSG-1.
False – different attachment site in the dog
Histological features of Darier disease?
acanthosis with orthokeratotic and parakeratotic hyperkeratosis; marked, diffuse, multifocal areas of acantholysis of the lower and middle portions of the epidrmis and follicular outer root sheet; acantholytic dyskeratotic keratinocytes (corps ronds) may be visible
T/F: Gram-positive cocci are usually present in the subcorneal pustules seen with exudative epidermitis.
True– though you usually need special stains to see it
Median age of onset for Pemphigus foliaceus in dogs? Cats? Horses? Small Ruminants?
Dogs: middle-aged (6 years), Cats: middle aged (6.5 years), Horses: 7 years, Small ruminants: young (median 1.5 years)
To what does plakophilin-1 bind?
cytoplasmic segment of desmogleins and desmocollins; desmoplakin, plakoglobin, keratins
What the clinical signs of pemphigus vegetans?
flaccid blister –> widespread erosions –> heal with excessive proliferation –> verrucous plaques, especially in areas of friction
To what does desmoplakin-1/2 bind?
amino-terminus: plakoglobin, plakophilins, DSC1, DSG1; carboxy-terminus: keratins
T/F: Desmogleins only bind to other desmogleins.
False - desmogleins DO NOT bind to each other, they ONLY bind to desmocolins
What type of T cells help naïve B cells differentiate into plasma cells? Through what cytokines?
Th2 helper cells; IL-5, IL-13, IL-6, IL-10
What are the primary lesions of pemphigus vulgaris?
flaccid vesicle rapidly progressing to an erosion, crusts can develop over lesions at mucocutaneous junctions or haired skin
Mutations in the gene that encodes for plakophilin-1 (PKP1) has been described in what breed?
Chesapeake Bay retrievers
What is the target autoantigen in pemphigus vegetans (dog)?
DSG1
Do dogs or cats more commonly exhibit signs of systemic illness with pemphigus foliaceus?
Cats – up to 50% of cats have non-dermatological signs (lethargy, fever, anorexia), reported in ~30% of dogs; cats and dogs both can exhibit pruritus
What are the plakins present in the epidermis?
BPAG1-e (BP230), plectin, desmoplakin 1/2, envoplakin, periplakin, epiplakin
Clincal presentation of exfoliative superficial pyoderma
superficial spreading pyoderma – rapidly expanding epidermal collarettes that can coalesce to cover large areas with a polycyclic pattern; staphyloccal scalded skin syndrome – erythema with overlying scaling composed of large sheets of stratum corneum
What virulence factor of Staph. Aureus results in subcorneal pustules?
exfoliatin toxin A, B, D (proteases that can bind to and cleave DSG-1)
What are the typical lesions of canine Darier disease?
nonpruritic alopecic, scaly and crusted plaques –> hyperplastic
What is the target autoantigen in paraneoplastic pemphigus? In what species?
described in dogs & cats; autoantigen known for dogs only: DSG3, plakins (evoplakin, periplakin)
T/F: With insecticide-triggered pemphigus foliaceus, lesions were localized to the site of application of the product in most cases.
False – over 70% of cases were generalized (head, face, paws, trunk affected) in addition to site of application
At what age does Darier disease usually become apparent?
during puberty
T/F: The autoantigen of pemphigus vegetans is the same in dogs and people, DSG-1.
FALSE – DSG-1 is the target in DOGS, but DSG-3 is the major antigen in people (few cases of DSG-1 and desmocollin in people)
To what does plakoglobin bind?
desmogleins and desmocolins, desmoplakins, plakophilins, keratins
T/F: The feet and coronary bands are usually NOT affected with exudative epidermitis in pigs.
False - usually bear similar lesions (erythema, brown exudation, crusting)
What are the histological characteristics of bullous impetigo?
large subcorneal or intragranular pustules, containing neutrophils and variable numbers of acantholytic keratinocytes, gram+ cocci may be seen in pustules
What body sites are affected “atypical” canine pemphigus foliaceus?
trunk-predominant without nasal planum/muzzle involvement
T/F: In bullous impetigo, it is common to see spreading collarettes along with follicular papules and pustules.
False – these lesions do not typically coexist with lesions typical of bacterial folliculitis
Typical clinical presentation of superficial pustular dermatophytosis
localized papules/pustules/scaling/crusts –> spread centrifugally to affect larger areas (expansion is a sign of proteolysis)
What is distribution of lesions in cats with pemphigus foliaceus?
face (pinnae, eyelids, nasal planum/dorsal muzzle), feet (claw folds and/or footpads), perioral, mammary papillae
Autoantibodies against desmoglein-3 can result in what clinical disease?
mucosal pemphigus vulgaris, mucocutaneous pemphigus vulgaris, paraneoplastic pemphigus (rare in dogs)
To what does periplakin bind?
amino-terminus: envoplakin, involucrin; carboxy-terminus: keratins
T/F: Acantholytic keratinocytes are commonly identified with exfoliative superficial pyoderma.
FALSE
Non-dermatological signs in equine pemphigus foliaceus
pruritus (~50% of horses), pain, swelling/edema, lethargy, fever (30-50%)
To what does desmocollin-1 bind?
amino-terminus heterophilic, binds to DSG1/DSG2/DSG3/DSG4, carboxy-terminus: PKP1/PKP2/PKP3 (plakophilin), PG (plakoglobin), desmoplakin
What is the characteristic lesion of pemphigus foliaceus?
subcorneal pustule (rapidly progresses into an erosion, crust, scale-crust, alopecia)
T/F: Circulating antikeratinocyte IgG has been demonstrated in dogs, cats, and horses, but not other species.
True –has not been demonstrated in goats and sheep with PF
What is the major antigen of paraneoplastic pemphigus in dogs?
DSG-3, plakins
What molecule is important for cadherin conformation and the strength of intermolecular adhesions?
calcium
T/F: Autoreactive T cells are the primary mediator of pemphigus diseases.
False - they play a role, but is primarily an antibody-mediated disease
What strains of bacteria have been associated with exudative epidermitis in pigs?
Staph. Hyicus, S. chromogenes, S. sciuri
Differentials for acantholytic pustular dermatitis in the dog
pemphigus foliaceus, superficial pyoderma (impetigo), pustular dermatophytosis, pustular dermatitis associated with leishmaniosis
Histopathology characteristics of pemphigus foliaceus
subcorneal to intragranular pustule containing individualized or clustered acantholytic keratinocytes; pustules may span several hair follicles & may extend into infundibula; neutrophils are predominant inflammatory cell type +/- eosinophils; multilayered neutrophilic or eosinophilic crusts with ghost acantholytic cells may be seen in cats & horses
Distribution of lesions of equine pemphigus foliaceus
symmetrical and generalized: face (pinnae, muzzle, eyelids), extremities (distal limbs, coronary bands), neck, and/or trunk
What are the exfoliatin-toxins of S. pseudintermedius?
EXPA and EXPB
In what species has pemphigus vulgaris been described?
dogs, horses, cats, primates, humans
T/F: Desmocollin-3 is the major antigen of pemphigus vulgaris in dogs.
False - desmoglein-3
Suprabasal Acantholytic Epidermolysis Bullosa in cattle has what mode of inheritance?
autosomal recessive
How can bacterial or fungal (dermatophyte) diseases results in acantholysis?
proteases degrade the proteins in the desmosomes –> resulting in acantholysis
What are the clinical features of bullous impetigo?
nonfollicular flaccid or tense pustules, which rupture and become overlain with yellow crusts –> expanding epidermal collarettes
Paraneoplastic pemphigus clinically resembles what other form of pemphigus?
Pemphigus vulgaris
What is the target autoantigen in pemphigus vulgaris in the dog? Horse?
dog: DSG3, DSG1 (mucocutaneous form); horses: DSG3, DSG1
Histopathology characteristics of pemphigus vegetans
suprabasal acantholysis, papillomatous or verrucous proliferation of epithelium; intraepithelial microabscesses containing neutrophils and eosinophils +/- apoptotic or necrotic keratinocytes
Histopathology characteristics of pemphigus vulgaris
suprabasal acantholysis –> blister formation, usually free of inflammatory cells; submucosal and dermal inflammation from mucocutaneous junctions is superficial lymphomasmacytic band-like infiltrrate, which is a nonspecific inflammatory response in these anatomic locations
What are the members of the armadillo family?
plakoglobin, plakophilins
What is the distribution of lesions of pemphigus vulgaris?
mucosae/mucocutaneous junctions (oral cavity, nasal planum, lip margins, genitalia, anus, eyelids) & pinnae; haired skin may or may not be involved**
Histologically, paraneoplastic pemphigus resembles what other disease processes?
pemphigus vulgaris: suprabasal acantholysis; erythema multiforme: apoptotic keratinocytes and mononuclear interface dermatitis; dermo-epidermal separation: bullous pemphigoid
T/F: Paraneoplastic pemphigus can affect both mucosae/mucocutaneous junctions and haired skin
TRUE
Canine Darier Disease is reported in what breed?
English setter
Autoantibodies against desmoglein-1 can result in what clinical disease?
rare in dogs (not most common antigen)– pemphigus foliaceus, mucocutaneous pemphigus vulgaris, pemphigus vulgaris (rare)
What is the most common pemphigus variant in people? In dogs?
pemphigus vulgaris in people, pemphigus foliaceus in dogs
Why can animals with pemphigus foliaceus have thick, multilayered crusts?
repeated waves of pustule formation
Autoantibodies against desmoplakin-1/2 result in what clinical disease?
Paraneoplastic pemphigus
Clinical lesions of equine pemphigus foliaceus
intact pustules are very rarely seen; common lesions are shallow erosions, crusts, scrust-scales, and/or tufted crusts
Differentials for acantholytic pustular dermatitis in the horse & cat
pemphigus foliaceus, pustular dermatophytosis, impetigo (rare)
Autoantibodies against envoplakin can result in what clinical disease?
paraneoplastic pemphigus
T/F: The autoantigen of pemphigus vulgaris is the same in dogs and humans, DSG-3.
True, DSG-1 is detected in a minority of dogs with PV
What breeds of dog are over-represented with pemphigus foliaceus?
Chow-Chow and Akita
Darier disease likely results from mutations in genes that encode what structures?
calcium pumps – impair desmosomal function
What breeds of dog are over-represented with pemphigus vulgaris?
German Shepherd, collie
Mutations in the gene that encodes for plakophilin-1 (PKP1) result in what clinical disease?
Ectodermal dysplasia/skin fragility syndrome (Suprabasal Epidermolysis bullosa Simplex) – recognized in one line of Chesapeake bay retrievers
What structure is suspected to be targeted in exfoliative superficial pyoderma leading to crust formation
corneodesmosin
Is desmoglein-3 present in the superficial epidermis (corneum/granulosum) or deep epidermis (spinosum/basale)?
both – but more present in deep epidermis (stratum basale)
To what does desmoglein-1 bind?
amino-terminus is heterophilic binds to DSC1, DSC2, DSC3; carboxy-terminus: desmoplakin, plakophilins, plakoglobin, keratin-5
T/F: A negative anti-keratinocyte IgG assay rules out a diagnosis of atypical pemphigus foliaceus.
False – positive result supports the diagnosis but negative does not rule it out (up to 50% can test negative)
T/F: Subcorneal pustules with acantholytic keratinocytes and lymphocytic interface dermatitis are features of superficial pustular dermatophytosis.
TRUE
Pemphigus vegetans is considered to be a variant of which other disease?
Pemphigus vulgaris
Mutations in the gene that encodes for what results in lethal acantholytic epidermolysis bullosa simplex?
desmoplakin (DSP)
