Autoimmune and immune mediated diseases of the skin Flashcards
Outline at what points in the immune system immuno-deficiency can occur?
What is a primary immuno-deficiency?
Primary condition
- Genetic defect in the immune system leads to clinical disease
- Rare!
Primary immuno-deficiency disorders – skin disease
- Severe combined immunodeficiency disease
- Lethal acrodermatitis in English bull terriers# (acro= at ends, near feet)
- Defective neutrophil function in Weimaraner’s
- Leukocyte adhesion deficiency of Irish setters (CLAD)
- Canine granulocytopathy syndrome of Irish setters with juvenile bacterial pyoderma
- Canine cyclic haematopoiesis of gray collies
- Hypotrichosis and thymic aplasia in Birman kittens
- Chédiak Higashi syndrome of Persian cats
What is a secondary immuno-deficiency condition?
Secondary condition
- Associated with factors such as viral and other infections, endogenous hormones, drugs (steroids), age and malnutrition – leads to impairment of the immune system
- Development of various uncommon conditions
What is the pathogenesis of auto-immune conditions?
Name a variety of mechanisms that might be involved when an autoimmune disease develops?
- Over expression of self antigen
- Exposure of cryptic/sequestered self antigens
- Epitope spreading
- Molecular mimicry
- Failure of central tolerance
- Auto activation of T cells
Why do some animals get these immuno deficiency diseases?
- Genetics
- Collies, shepherds
- Environmental triggers
- UV light / drugs
- Inflammation
- Existing disease
- Trauma
- Infection
- Neoplasia
- e.g. thymoma (particular issue in cats. T cells are called to skin and target hair follicles, take thymoma away and hair grows back)
What is the pathogenesis of pemphigus?
Aetiology usually unknown
Associated with abnormal immune regulation or antigenic stimulation:
- Neoplasia *
- Infectious agents *
- Drugs *
- Autoimmune disorders
- Certain haplotypes
- Pregnancy
- Chronic skin disease *
*recognised in animals
What are the clinical signs of Canine Pemphigus foliaceus?
Clinical signs
- Any breed of dog (cockers classic breed that get it)
- Onset of signs can be from two to seven years
- Disease is chronic in 75% of cases
- Primary lesions include vesicles and pustules although they are transient because the canine epidermis is comparatively thin and trauma readily leads to crusting and erosions
- Footpads often involved and may be the only area affected
- Skin lesions are usually generalised with scaling, crusting and alopecia
- Large pustules on the trunk, head and pinnae that look like a bacterial infection but do not respond to appropriate antibacterial therapy should be serious candidates for PF
- Pruritus can be a major feature
How is Canine Pemphigus foliaceus diagnosed?
Diagnosis
- Tzanck prep of the pustule - cytology reveals numerous acantholytic keratinocytes, neutrophils (eosinophils in some cases), no cocci should be observed
- Bacterial swab and culture & sensitivity testing –
- should be sterile
- Unfortunately Pf lesions can involve substantial secondary bacterial infection and so cocci may also be a feature
- Treat first for microbial infection then collect samples
- Skin biopsy for histopathology (& bacterial & fungal culture)
- using a punch tool - may require 8 mm diameter to encompass the pustule
- Beware: these pustules are very delicate and readily traumatized by the act of collecting a biopsy – you may need several samples!
Acantholytic keratinocytes look like fried eggs (large blue cells with nucleus meaning the layers off skin have broken down and come away from a stratum too early)
How does histopathology and immunopathology of pemphigus foliaceus appear?
Histopathology of pemphigus foliaceus:
- Intraepidermal and/or intrafollicular pustules with abundant acantholytic keratinocytes in the granular or upper spinous cell layers
Immunopathology:
- Anti-keratinocyte membrane auto-antibodies demonstrated by direct immunofluorescence in up to 80% of cases
- Usually IgG, occasionally IgM or IgA or C3 associated
What is the pathogenesis of feline pemphigus foliaceus?
- Little understood about the pathogenesis
- Assumed that some of the features of canine pemphigus may apply
- Pf is the most common form of auto-immune skin condition in the cat
- Drug eruption has been documented as an underlying cause
What are the clinical signs of Feline pemphigus foliaceus (Pf)?
- There are no breed, sex or age predilections
- Skin lesions are usually observed around the head, especially the pinnae, planum nasale and the claw beds
- Can be extension to the face (bridge of the nose, muzzle, around the eyes), tail, ventral abdomen including around the nipples
- Claw beds can have a thick caseous green purulent discharge - multiple digits and feet even the dew claw
- Claws are usually normal in appearance
- Skin lesions consist of pustules and vesicles
- Transient and readily replaced by erosions and overlying crusts
- Pyoniciar = pus around nail bed
Picture shows before and after steroid therapy
Feline pemphigus foliaceus diagnosis?
- Feline pemphigus foliaceus diagnosis
- Fairly straightforward with involvement of the claw beds of several feet; or the pinnae
- Other clinical signs may lead to confusion with dermatophytosis
- Hence some cats receive antifungal therapy
- Cats treated with antibiotics for paronychia
- Contains cocci but these organisms are secondary
- Some cases wax and wane
- May suggest a positive response to antimicrobial therapy
- Haematology may show eosinophilia
- ANA (anti nuclear antibody) will usually be negative
- A fungal culture will (usually) be negative
- Cytology from an undisturbed pustule will reveal numerous neutrophils (eosinophils) with acantholytic keratinocytes
- Skin biopsies may be collected with a punch tool, some lesions are best excised
- Cat should be sedated or undergo general anaesthesia
- Pustules are extremely delicate and readily damaged when incised
- Lesions on the top of the head or from the base of the pinnae may be most fruitful
How is feline pemphigus foliaceus managed?
- Prednisolone?
- Ciclosporin (tradename atopica) very expensive? Can cause diarrhoea and sickness
What is this?
Equine pemphigus foliaceus
Not very common in horses. Can be dramatic in horses. Can see epidermis here massive amount of crusting.
What is this?
Pemphigus vulgaris (PV)
- Rare autoimmune blistering skin disease associated with the generation of autoantibodies that target transmembrane desmosomal proteins in the epithelium
- Autoantibodies looking for DSG 3
- First cases of canine PV were reported in 1975 since then a small number of cases have been described
- Most dogs exhibit lesions at the mucosal and
- Mucocutaneous junctions (eyes, anus, lips, nose and prepuce)
- Rare cases are affected with a variant of PV without oral or mucosal involvement
- GSD predisposed
What are the differential diagnosis for pemphigus vulgaris?
- Cutaneous manifestations of lupus erythematosus (systemic lupus rare in dogs)
- Epitheliotropic lymphosarcoma
- Uveodermatological syndrome (Japanese akitas)
- Nasal aspergillosis (nose reflects what is going on further up in nasal passages)
- Erythema multiforme (go into mouth as well)
- Mucous membrane pemphigoid
What are the treatments for pemphigus?
Treatment of pemphigus:
- Glucocorticoids
- Prednisolone / methylprednisolone
- <2 mg / kg per day divided until in remission
- Care with doses > 2 mg / kg
- Go to alternate day therapy
- Slowly reduce dose to avoid relapse (every 2-3 weeks)
- Ciclosporin
- Azathioprine (historically)
- not recommended for cats
- Gold salts
- Chlorambucil (old drug occasionally used)
- Apoquel (oclacitinib) No studies probably doesn’t help as it is meant to block IL-31 seen in allergies.
Adjunct therapy
- Chlorhexidine-based shampoo / product for the secondary bacterial component and to remove crust/scale
- Antibiotics for three weeks e.g. cefalexin 20 mg/kg BID
- Gut protectants (e.g. cimetidine omeprazole) to reduce risk of side effects of such therapy
- Methylprednisolone equivalent dose of 0.8 to 1 mg of prednisolone
When giving steroids what advice do you provide the owner?
Steroids can make them lethargic and depressed. PU/PD, polyphagic, weight gain, diabetic.
Discuss azathioprine Imuran (sometime used for heamolytic anaemia) as a treatment for PF in more detail?
- Dog - dose of 2 mg/kg orally every 24-48 hours
- Cat – no!
- Severe bone marrow suppression
- Adverse effects
- Myelosuppression, pancreatitis and hepatotoxicity
- Complete blood & platelet count initially monitored every two weeks for two months and then every 2 - 3 months
- Slow onset of action - three to six weeks to produce clinical effects
Discuss in more detail the use of Chlorambucil in cats to treat PF?
Action: Alkylating agent that inhibits DNA synthesis and function
through cross-linking with cellular DNA. Cell cycle non-specific.
Use: Management of some malignancies, lymphoproliferative, myeloproliferative and immune-mediated diseases. Immunosuppressive effect is not well defined and therefore it should
only be considered where more established therapies such as
prednisolone and azathioprine have failed. May be useful in the
treatment of feline pemphigus foliaceus and severe feline eosinophilic
granuloma complex. Has been used in lymphosarcoma in cockatoos.
- Daily therapy or every other day, in combination with steroids, using 0.1 to 0.2 mg/kg
- Tablet size is 2 mg so most cats receive half a tablet per day
- Therapy given for 4-8 weeks, side effects may include vomiting, diarrhoea, anorexia & bone marrow suppression
- Monitor haematology every two weeks
Discuss Aurothioglucose (Gold salt) as a treatment for PF?
- Influences neutrophil migration, lymphocyte function and immunoglobulin production
- Weekly dose of 1.0 mg/kg (by intramuscular injection) to once every two or four weeks. May take 6 - 12 weeks to see the full response
- Adverse effects may include glomerulonephritis, bone marrow suppression, thrombocytopenia, and cutaneous eruptions
- Monitoring every two weeks with haematology, serum biochemistry and urinalysis
What is Canine Lupus Erythematosus?
Discoid lupus erythematosus (DLE) is a relatively common autoimmune skin disease of dogs. Autoimmune disease occurs when the immune system targets harmless cells of the body resulting in inflammation and disease. In DLE, skin disease tends to occur around the nose, but can extend to include areas around the eyes, lips and ears. It is distinct from other forms of lupus in dogs that can cause systemic or internal disease along with more widespread skin disease.
What causes DLE?
The exact causes of DLE are not known, although genetic, hormonal and environmental factors are likely to be involved as they are in the human disease. In particular, sun exposure is likely to exacerbate or even induce the lesions of DLE.
