Autoimmune Dermatoses Flashcards
As a review, what disease should you think with lesions on the ventrum?
- Pyoderma
As a review, what disease should you think with lesions on the head/legs/paws?
Demodicosis
As a review, what disease should you think with lesions on the pinnae?
- Scabies or notoedres
As a review, what disease should you think with lesions on the flanks and tail tip?
- Endocrine
Autoimmune diseases definition
- Implies the body is attacking a self-antigen
- Antibodies or activated lymphocytes develop against itself and cause lesions
What is an immune-mediated disease?
- Implies a foreign antigen (protein) triggers an immunological reaction
Antigens that can cause immune-mediated disease?
- Drugs!
- Bacteria!
- Viruses
What are lymphocytes involved in?
- Surveilling things
- Allergies and cytokines
- Antigens and immune responses
How are activated lymphocytes generally cleared?
- In the thymus of normal individuals (tolerance)
- Breakdown in regulation of these may lead to activation of self-reactive lymphocytes
What breakdown leads to increased activated lymphocytes?
- Breakdown in TOLERANCE
- Cross reactivity with self and foreign antigen (e.g. drugs or infectious agents)
What is the target organ in true autoimmune dermatoses?
- SKin
What hypersensitivity reactions are involved with autoimmune disease?
- Type II and Type III
Age of animals with autoimmune disease in general?
- Middle-aged most often
Pemphigus definition?
- Autoimmune vesicuobullous to pustular skin disease characterized by acantholysis***
What are the two main subtypes of pemphigus, and which is most common?
- Pemphigus foliaceus (MOST COMMON)
2. Pemphigus vulgaris
Other types of pemphigus
- Pemphigus erythematosus
- Paraneoplastic pemphigus
Pathogenesis of pemphigus
- Autoantibodies (usually IgG) are directed against components of the epidermal cell membrane (desmosomes)
- Binding of the antibodies initiates cellular events that eventually degrades the desmosomal components and results in aacantholysis (release of the cellular attachments allowing the cell to separate, float, roundup, and subsequent cleft formation)
What are acantholytic keratinocytes, and how do they appear on cytology?
- Large round cells that look like “fried eggs” on cytology
- Immature detached keratinocytes that are the hallmark of pemphigus
What are the primary two adhesion structures involved in holding the skin together? Where are they in the layers of the epidermis?
- Desmosomes (more superficial)
- Hemidesmosomes (attach keratinocytes to basal cell layer)
Which two proteins mediate adhesions of desmosomes?
- Desmogleins (Dsg)
- Desmocollins (Dsc)
- Three isoforms of Dsc and four isoforms of Dsg
In people, which protein is the most common target in pemphigus?
- Desmoglein 1 glycoprotein in the desmosome
In dogs, what does the autoantibody response primarily involve? What about in people?
- In dogs, it’s primarily IgG
- In people it’s primarily IgG also
In dogs, which protein is the most common target in pemphigus?
- Dsc 1 glycoprotein in the desmosome
What often plays a role in development of canine pemphigus foliaceus?
- Genetic factors
Dog breeds that most often get PF?
- Akitas and Chows
Age or sex predisposition for PF in dogs
- No age or sex predisposition, but usually middle-aged
Signalment of cats that get PF?
- No sex or breed predisposition
- Median age is 5 years, but ranges from 1 to 17 years
Triggering factors for PF IN DOGS?
- Ultraviolet light (exposure from the sun suspected to induce flares)
- Lesions can worsen in the summer and improve in the winter
- Allergies (higher incidences of cPF with allergic skin diseases, but not really proven)
- Drug induced (activation of proteolytic enzymes in the skin and autoantibodies against desmosomes)
Medications associated with PF
- Cephalexin
- Clavamox
- TMS
- Promeris (Metafluminzone and amitraz) - not on the market anymore
- Certifect (not on the market)
Triggering factors for PF in cats?
- Usually idiopathic
- Drugs: sulfas, penicillins, cephalosporins, fenbendazole, vaccines
Clinical signs of PF in dogs
- Pustules, crusts, erosions (looks like pyoderma)
Location of PF lesions in dogs?
- Face/muzzle
- Bridge of nose
- Periocular skin
- Ears
- Paw pads (may JUST see this)
- Generalized
- More symmetrical and distributed over the body than pyoderma
Major differentials for pustules in canines?
- Pyoderma, demodex, dermatophytosis
Can dogs with PF be pruritic?
- yes
Clinical signs of PF in cats
- Crusts, pustules, erosions, alopecia
Locations of PF lesions in the cat?
- head
- Face
- Ears
- Claw folds (always look here; caseous material when retracting the claw)
- Peri-areolar (crusting around the nipple; very bizarre)
Systemic signs associated with PF
- Fever
- Lethargy
- Anorexia
- Lymphadenopathy
Is PF pruritic?
- Up to 50% of dogs and 80% of cats
- He tends to find that they’re not
What differential diagnoses must always be considered with pemphigus foliaceus?
- Superficial pustular dermatophytosis (Trichophyton)
- Bacterial (Staph; different distribution but a LOT of bacteria found); produce toxins that target desmosomes and mimic canine PF
- Demodex/Scabies/Notoedres
- Other autoimmune mediated diseases
- Zinc responsive dermatosis
- Cutaneous lymphoma
Other autoimmune or immune-mediated diseases that are dfdx for pemphigus foliaceus?
- Pemphigus erythematosus (considered relatively benign and only affects the face)
- Discoid lupus erythematosus (generally affects only the nose)
Diagnosis of PF
- History
- PE
- Dermatologic exam (pustules and crust around the face and head)
- Rule out folliculitis
- Cytology
- negative skin scrapings
- Histopathology (ultimately this is required; you could guess and mostly be right, but the consequences of being wrong are horrible)
Cytology of PF?
- Evidence of acantholytic keratinocytes (look like fried eggs)
- Non-degenerate neutrophils
- Absence of organisms
Biopsy signs of PF?
- Evidence of subcorneal or intracorneal disease
- Acantholytic keratinocytes
- Pustules
- Absence of organisms
What is important to do prior to biopsy of PF?
- Discontinue oral steroids 2-3 weeks; repository steroids 6-8 weeks
- Treat secondary infections
- Sample active lesions (pustules are the key; important area is intact crust and don’t prepare the surface)
- Take multiple samples
- Trim away hairs but don’t scrub
- They want a lesional area
- Provide detailed informations and Ddx to pathologist
How common is pemphigus erythematosus?
- Uncommon
What is pemphigus erythematosus? What is the distribution?
- Benign variant of pemphigus foliaceus with a facial distribution primarily
Clinical lesions with pemphigus erythematosus
- Pustules
- Crust
- Alopecia
- Erosions
- Oozing
- Primarily around the face and not involving body or feet
What is the most severe form of pemphigus? How common?
- Pemphigus vulgaris
- Fortunately it’s rare
Prognosis for pemphigus vulgaris
- Rare
Dfdx for pemphigus erythematosus
- Facial pyoderma
- Dermatophytosis
- Demodicosis
- Discoid lupus erythematosus
Diagnosis of pemphigus erythematosus
- Clinical signs and distribution
- Rule out causes of folliculitis
- Cytology (evidence of neutrophils +/- eosinophils with acantholytic cells! and no bacteria)
- Biopsy and histopath (Subcorneal and intraepidermal pustules containing acantholytic cells)
Clinical lesions of pemphigus vulgaris
- Vesicles (primary)
- Bullae (primary)
- Ulcers (secondary)
- Crusting (secondary)
Distribution of lesions with pemphigus vulgaris?
- Ears
- Foot pads
- Mucocutaneous junctions
Ear pinnae - Nasal planum
- oral cavity (80%)
What is the target in pemphigus vulgaris vs foliaceus?
- Desmoglein 3 in PV
- Desmoglein 1 in PF
Dfdx for pemphigus vulgaris
- Other severe autoimmune diseases (mucous membrane pemphigoid, bullous pemphigoid, epidermolysis bullosa)
- Cutaneous lymphoma
- Deep pyoderma
- Deep mycoses
Diagnosis of pemphigus vulgaris
- Clinical signs and severity of ulcers
- Cytology of vesicle showing acantholytic cells, neutrophils, no bacteria
- Biopsy and histopathology (evidence of suprabasilar vesicles or pustules containing acantholytic cells and neutorphils; row of basal cells often remain attached to basement membrane resembling tombstone cells)
Treatment of pemphigus
- Suppress the immune system
- Induce remission
- Taper to lowest dose (anti-inflammatory)
- Taper to lowest frequency (e.g. EOD)
Glucocorticoid protocol with pemphigus
- Immune-suppressive dose (2mg/kg in 14 days)
- Usually goes away
- Recheck
- Begin slow tapering
- Taper to lowest dose every other day
- NO DAILY STEROIDS
Effects of glucocorticoids
- Decrease arachidonic acid
- inhibit inflammatory cytokines
- Decrease chemotactic factors and inflammatory cells
- Suppress T cell function
- Induce apoptosis of T cells
- Suppress B cell antibody production (IgG mainly)
- Side effects are common with long-term use
What are other immune-modulatory drugs?
- Mycophenolate
- Azathioprine
- Cyclosporine
Mycophenolate MOA
- Inhibits DNA synthesis (purine synthesis)
- Inosine monophosphate dehydrogenase inhibitor which is necessary for de novo purine synthesis
- Inhibits Macrophages, and T and B cell proliferation
- Induces apoptosis of T cells
- Suppresses B cell antibody production
Onset of action of mycophenolate
- Rapid onset of action
- Often used in conjunction with corticosteroids if they aren’t enough when tapered down to every other day
Azathioprine MOA
- Purine analog (pro-drug)
- interferes with nucleic acid snthesis
- read the image or something?
- Cytotoxic to T cell
How quickly does azathioprine work?
- Slow onset of action (1-2 weeks)
Side effects with azathioprine
- Fulminant hepatic necrosis with increases of ALT
- Bone marrow suppression
- Increased risk of infections
- DO NOT USE IN Cats
Why shouldn’t you use azathioprine in cats?
- Cats lack thiopurine methyltransferase and can’t convert azathioprine to its inactive form
- Results in severe myelotoxicity
Cyclosporine MOA
- Cyclosporine binds cyclophilin which inhibits calcineurin
- Inhibition works upstream blocking pro-inflammatory cytokines such as IL-2 and pro-inflammatory pathways
- See the slide
- prevents activation of T cells
Cyclosporine usefulness in pemphigus?
- May be more beneficial in maintaining remission vs inducing remission
What is the second most common auto-immune disease?
- Discoid lupus erythematosus
Where are the lesions with DLE?
- Limited to nose
Severity of DLE
- it’s benign
- can be aggravated and/or induced by UV light
- pet feels good otherwise
Clinical lesions of DLE
- Depigmentation of nose
- Gray/bluish color
- Loss of cobblestone appearance
- Erosion
- ulcers
- Crusting
Distribution of DLE
- Nose
- Can extend to eyes and ears
- Bridge of nose
Diagnosis of DLE
- Rule out mucocutaneous pyoderma and lymphoma
- Pemphigus erythameatosus doesn’t affect the nose itself and neither does pemphigus foliaceus
- Cytology
- Biopsy pathologist cannot differentiate MCP vs DLE)
- Treat for pyoderma first
Treatment of DLE
- Tacrolimus (effective)
- Calcineurin inhibitor that penetrates the epidermis because it’s smaller than cyclosporine
- Avoid sunlight (sunscreens SPF 15 or greater; zinc oxide works)
- Doxycycline/niacinamide
MOA of doxycycline/niacinamide
- How long for it to be effective?
- Inhibits matrix metalloproteases
- Anti-inflammatory properties
- Can take approximately 6-8weeks to be effective
Biopsy of DLE
- Cannot differentiate MCP vs DLE
- Variable changes can be seen. The most consistent findings include hydropic degeneration of basal cells, basal cell apoptosis, lichenoid dermatitis, subepidermal vacules (bubbles) and pigmentary incontinence (pigment that leaks from the epidermis into the underlying dermis)
Why is tacrolimus the treatment of choice for DLE?
- Molecule is small enough to pass through the epidermis and into the dermis
Prognosis for most autoimmune skin disorders
- Variable, but generally guarded until you know how they will respond to treatment
- Some patients don’t respond at all
- Patients require lifelong therapy
- Relapses are common
Topical treatments for localized autoimmune disease
- Steroids (betamethasone or mometasone)
- Ear meds
- Tacrolimus 0.1% (great for DLE and PE)
Cyclosporine for PF
- Not useful for inducing remission of PF, but can be used to maintain remission
- Commonly used in allergies, so understand the MOA
Severe side effects of prednisone/prednisolone
- Calcinosis cutis with daily dosing
How much more potent than prednisone is dexamethasone?
- 10x more potent
