Autoimmune and Immune mediated skin diseases Flashcards
Autoimmune, immune mediated,
When investigating a pruritic dog, in what order should which investigations take place?
1: Investigate cause of pruritus e.g. Malassezia dermatitis
2: Investigate potential underlying causes for this e.g. ectoparasites, environmental atopy, food atopy, endocrinopathy, immune mediated
3: If no ectoparasites found, carry out diet exclusion trial to rule in/out food atopy
4: If ineffective, and have ruled out all other causes, can diagnose as environmental atopy
5: Can investigate specific allergen or choose not to and control clinical signs
Describe the options for carrying out a food exclusion trial
- home cooked using novel proteins e.g. white fish, pork, rabbit etc., restricted to single protein source, single carbohydrate source and water. Start at 150% of original commercial diet, increase if weight loss. Minimum 3, up to 10 weeks
- OR commercial diets containing novel or hydrolysed proteins. Minimum 8 weeks. If no response try home cooked
What are the 2 methods for investigating allergens?
Intradermal allergy testing and serological tests
How does intradermal allergy testing work?
- shows type 1 hypersensitivities
- Tests capacity of skin to react to allergens
Discuss the disadvanages of intradermal allergy testing
- Time consuming
- Requires clipping and sedation
- Cannot be performed in lichenified, hyperpigmented, inflamed skin, widespread pyoderma or seborrhoea
- Allergens may be expensive to obtain
- Rare risk of anaphylaxis
- Harder in cats
Describe the method for intradermal allergy testing
- Introduce allergen into skin of animal, mark location on a sheet
- Measure degree of swelling, indicating inflammation and therefore allergic reaction to allergen to identify if reaction has occurred indicating allergy
How does serology testing for allergy work?
- Measure serum IgE alone, but may not correlate to levels in the skin
Compare the variations of serology testing for allergens
- Polyclonal: may measure trace IgG and give false positives
- Monoclonal: less sensitive, false negatives
- Mixed allergens: avoided as do not identify specific allergens
- Mast cell receptor molecule for specific IgE: better, but more expensive
What medical treatments are available for environmental atopy?
- Steroid creams
- Ciclosporin
- Glucocorticoids
- Lokivetmab
- Oclacitanib
- Immunotherapy/hyposensitisation
Identify actions an owner can take to avoid exposure of a dog to common allergens e.g. house dust mites
- Freeze bedding and any soft toys for 24 hours after washing
- Do not allow dogs in bedroom
- Hypoallergenic mattress and pillow covers for human bedding
- Wash human and dog bedding >70degressC
- Anti-dust mite sprays
- Remove carpets
- Socks for going on walks
Describe the immunotherapy/hyposensitisation protocol for an allergy
- Shots recommended if allergic to pollens, dust mites
- 17 injections at 3 day intervals, last 3 at 10, 20, 30 days intervals
- then injections every 2-3 weeks for 2-3 years
- High cost
What are the differentials for a dog with erythema, alopecia, hyperpigmentation on legs, crusting, lichenification
- Mange
- Fleas
- Bacterial skin infection
- Allergy
- Mites
In a case of environmental atopy where the owner has little money available for treatment, what actions would you advise?
- Glucocorticoids (short term)
- Anti-histamines e.g. piriton
- Good ectoparasite control
- Careful management of heat, humidity and stress
- Supplement EFAs, moisturisse
- Shampoo to remove allergens in coat
- Hypoallergenic diet may help
- Steroid cream in flare up areas
Outline an example of an immune mediated skin disease of cows
- Bovine leukocyte adhesion deficiency
- Genetic, and once gene identified was bred out
- Was due to BLAD gene, which led to a replacement of cytosine by a guanosine in the CD18 gene
Give examples of primary immunodeficiency disorders of the skin in small animals
- Severe combined immunodeficiency disease (SCID)
- Lethal acrodermatitis in English bull terriers
- Defective neutrophil function in Weimaraners
- Leukocyte adhesion deficiency in Irish setters
- Canine granulocytopathy syndrome in Irish setters with juvenile bacterial pyoderma
- Canine cyclic haematopoiesis of gray Collies
- Hypotrichosis and thymic aplasia in Birman kittens
- Chediak Higashi syndrome of cats
Identify the points in the immune system where development blocks may lead to immunodeficiencies
- Lymphoid precursor dysfunction can lead to combined immunodeficiency
- Myeloid precursor defects may lead to neutrophil defects
- Issues with “Bursal” processing may lead to agammaglobulinaemia
- Issues with B cells during development can lead to deficiencies in individual immunoglobulin classes
- Thymic aplasia leads to lack of thymic processing and T cell defects
Explain what is meant by a primary immuno-deficiency condition
A genetic defect in the immune system leading to clinical disease, rare
Explain what is meant by a secondary immuno-deficiency condition
Impairment of the immune system due to factors such as viral and other infections, endogenous hormones, drugs, age and malnutrition. Leads to the development of various uncommon conditions
Identify the general mechanisms that may cause autoimmune diseases
- Normal responses that go awry or abnormal responses
- Immune dysfunction
- Genetics
- Environmental triggers
- Inflammation
- Trauma
- Infection
- Neoplasia
Give examples of ways in which a normal immune response can go awry and lead to autoimmune disease
- Immune response to previously hidden antigens, which may appear due to tissue damage, molecular alterations, or newly synthesised antigens
- Or response to molecular mimicry as a result of microbial cross reactions
Give an overview as to how an abnormal immune response may occur, leading to autoimmune disease
- Self reactive T cells and lymphoid tumours
- Failure of apoptosis, viral infections, microchimerism
- Hormonal influences, genetic predisposition
- Failure of regulatory control
Give an example how neoplasia can lead to autoimmune disease
Thymoma in cats, develop skin diseases, mechanism poorly understood, but removal of thymoma leads to resolution of skin disease
- T cells called to skin, target follicles leading to alopecia
Name the structures that act as autoantigens in the following conditions
a: Pemphigus
b: Pemphigoig
c: Linear IgA dermatitis
d: Epidermolysis bullosa acquista
a: Desmosomes
b: Hemidesmosomes
c: Lamina lucida
d: Type VII collagen fibres below the lamina densa
Which structure of the skin is a common target of immune disease and what is the result?
Desmosomes, leads to skin falling apart
Which forms of pemphigus are more, and which are less, common in dogs?
- Vulgaris rare in animals (common in people)
- Foliaceous common in dogs
- Also erthematosus more common in dogs
- Uncertain regardin vegetans
Describe the aetiology of pemphigus
- Usually unknown
- Associated wirh abnormal immune regulation or antigenic stimulation
List the factors that are recognised as causes of pemphigus in animals
- Neoplasia
- Infectious agents
- Drugs (antibiotics, vaccines, wormers)
- Chronic skin disease
- (In people: autoimmune disorders, certain haplotypes, pregnancy)
Compare the pathogenesis of pemphigus vularis and foliaceous
- Autoantibodies bind to all suprabasal layers of stratified squamous epithlium
- Desmoglein 3 mainly in lower layers (vulgaris, split near bottom of epiderms)
- Desmoglein 1 mainly in superficial layers (foliaceous, split near top)
- Desmocollin 1 is major autoantigen in canine pemhigus foliaceous
- Desmosome break apart = pustules, ulcerations
Describe the clinical signs of canine pemphigus foliaceous
- Leaf-like pustule appearance
- Erythema around pustules intense
- Sterile pus in skin
- Crusting occurs as pustule disappears
- Pyrexia, inappetance, depressed
- Lesions on face ad feet
- Pruritus is a major feature
- No response to antibactieral therapy
What is the signalment for canine pemphigus foliaceous?
- Any breed, but Cockers predisposed
- Onset from 2-7yrs
- Disease chronic in 75% of cases
Outline feline pemphigus foliaceous
- Little understood re. pathogenesis
- Assumed some features of canine apply
- PF is most common form of auto-immune skin condition in the cat
- Drug eruption documented as underlying case, incl. antibiotics
Describe the pathogenesis of pemphigus vulgaris
- Autoimmune blistering skin disease
- Generation of autoantibodies that target transmembrane desmosomal proteins in the epithlium
- Desmoglein 3 at the bottom of the epidermis affected, leading to lifting of the entire epidermis
Describe canine discoid lupus erythematosus (DLE) (appearance, prevalence, disease process, cause)
- Long nosed dogs
- Leads to crusty nosed appearnce, erythematous
- May be as common as pemphigus foliaceous
- Photosensitive dermatosis that involves the nasal planum
- Can be related to stress
Outline the pathogenesis of plasma cell pododermatitis
- Immune mediated? Aetiology unknown
- Leads to lymphocytosis of affected tissues and positive ANA titres
Give an example of a primary vasculitis in animals
Multisystemic necrotising vasculitis of small vessels in beagles = Juvenile Polyarteritis syndrome (JPS)
Compare the prevalence of primary and secondary cutaneous vasculopathies
Usually secondary to an underlying process
List potential causes of secondary vasculities in veterinary medicine
- Infection
- Vaccination
- Drugs:
- Allergy
- Immune mediated
- Other
- Idiopathic
- Sepsis and vascular toxins
Give examples of infections that may cause vasculitis
- Bacterial (incl. endocarditis via Staphylococus intermedius)
- Mycobacterial
- Funga
- Viral (FIP, FeLV, FIV, parvo)
- Protozoa (e.g. Leishmaniasis0
- Rickettshial (RMSF, Ehrlichia, Borrelia)
- Sarcocystis
Give examples of vaccinations that may cause vasculitis
- Rabies
- Hyposensitisation
- Sera
Give examples of drugs that may cause vasculitis
- Antibiotics
- Ivermectin
- Vaccines
- Metronidazole
- Phenobarbitol
- Frusemide
- Itraconazole
- Phenylbutazone
- Enalapril
- Imodium
- Metoclopramide
- Fenbendazole
Give examples of allergies that may cause vasculitis
- Food
- Insect/arthropod
- Eosinophilic granuloma
- Severe scabies
- Flea hypersensitivity
Give examples of immune mediated diseases that may cause vasculitis
- SE
- DLE
- Rheumatoid arthritis
Give examples of non-immune mediated conditions that may cause vasculitis
- Plasma cell pododermatitis
- malignancies
- Ulcerative colitis
- JPS of beagles
What is vasculitis?
An accumulation of cells within the vessel wall, causing injury with necrosis and degeneration of endothelial smooth muscle cells and fibrin deposition
What is fibrinoid necrosis in vasculitis?
Association of complement, fibrin, immunoglobulins, platelets within vessel wall and lumen, that appears as an eosinophilic mush
Describe the histological changes that occur with vasculitis
- Frequently transient and are followed by signs of vasculopathy where tissue changes suggest vascular compromise
- Variety of distinct histological changes
What therapy is required in cases of auto-immune and immune mediated skin disease?
Immunosuppressives
List the methods used in the diagnosis of canine pemphigus foliaceous
- Tzanck prep of pustule
- Bacterial swab and culture and sensitivity testing
- Skin biopsy for histopathology
What results would be expected in a Tzanck prep of a pustule in the case of canine pemphigus foliaceous?
- Numerous acantholytic keratinocytes
- Neutrophils
- Eosinophils in some cases
- No cocci should be observed
What may complicate the diagnosis of pemphigus foliaceous and what should be done to avoid this?
- PF lesions can involve substantial secondary bacterial infection, so cocci may be seen
- Treat for microbial infection first, then collect samples
Explain the use of a skin biopsy for the diagnosis of canine pemphigus foliaceous
- For histopath, bacterial and fungal culture
- Use punch, may require 8mm to encompass pustule
- Pustules delicate and readily traumatised by biopsy collection, may need several samples
Describe the clinical signs of feline pemphigus foliaceous
- Very similar to dermatophytosis
- Involvement of claw beds of several feeet, also pinnae
- May wax and wane
List the methods used for the diagnosis of feline pemphigus foliaceous
- Haematology
- ANA
- Fungal culture
- Skin biopsies
- Cytology from undisturbed neutrophils
What results would be expected for all diagnostic tests carried out in the investigation of feline pemphigus foliaceous?
- Haematology: eosinophilia
- ANA: negative
- Fungal culture: negative
- Cytology: neutrophils, sometimes eosinophils, acantholytic keratinocytes
From what area are pustules likely to be most useful in the diagnosis of feline pemphigus foliaceous
From top of head or base of pinnae, require punch or excision, will require anaesthesia
Ideally multiple samples and 6mm punch
List the differential diagnoses for pemphigus vulgaris
- Cutaneous manifestations of lupus erythemotus
- Epitheliotropic lymphosarcoma (T cell lymphoma)
- Uveodermatological syndrome (Japanese Akitas)
- Nasal aspergillosis
- Erythema multiforme
- Mucous membrane pemphigoid
What histological pattern is seen in canine DLE?
Interface dermatitis, hydropic/lichenoid
In what conditions is an interface dermatitis pattern seen on histology?
- Muco-cutaneous lupus
- Pemphigu erythematosus
- P. foliaceous
- Mucocutaneous pyoderma
What is required for the diagnosis of canine DLE?
- NOT ANA; non-specific, raised in systemic disease
- Diagnosis based on assessment of response to antibacterial agents
What are the differentials for plasma cell pododermatitis in the cat?
- Eosinophilic granuloma complex
- Pemphigus foliaceous
- Viral infection with cowpox
- Multicentric tumours
- Contact dermatitis (rare in cats)
- metabolic deposits
- Vasculitis
How would you go about making a diagnosis of feline plasma cell pododermatitis?
- Collection of deep biopsies from pads
- Demonstration of numerous plasma cells and lymphocytes in the dermis
What methods are used in the diagnosis of Idiopathic Symmetric Lupoid Onychodystrophy (ILSO)?
- Histopathology: dew claw easiest to amputate, submit whole nail and third distal phalanx for histology
- Bacterial and fungal cultures carried out
List the differentials for vasculitis
- Cold agglutinin disease
- DIC
- Coagulopathy
- SLE
- Lymphoreticular neoplasia
- Frostbite
Why does vasculitis present a diagnostic challenge?
- Small blood vessel damage is a consequence of a variety of disease processes
- Vasculitis often transient, followed by more chronic change aka vasculopathy, biopsy may not show active inflammation
What samples are required for the diagnosis of vasculitis?
- Skin, organ, lymph node biopsies
- Blood samples
What blood findings would be consistent with vasculitis?
- Lymphopaenia, eosinopaenia, leukopaenia, neutropaenia, monocytosis
- Leukocytosis with left shift
- Normochromic, normocytic anaemia
- Thrombocytopaenia
- Increased serum liver enzymes, TAGs
- Hypoalbuminaemia
- Hyperglobulinaemia
- Hyperfibrinogenaemia
Describe the clinical signs of feline pemphigus foliaceous
- Skin lesions usually observeed around head, esp. pinnae, planum nasale, also claw beds
- Pustules and vesicles, transient and replaced by erosions and overlying crusts
- Nail beds have thick caseous green purulent discharge (paronychia) on multiple digits and feet, claws themselves are normal appearance
- Lesions can extend to rest of face, tail, ventral abdomen, incl around nipples
Describe the clinical signs of equine pemphigus foliaceous
- Covered in scale and crusting
- Histology shows acantholytic keratinocytes
Describe the histological appearance of canine pemphigus foliaceous
Intraepidermal and/or intrafollicular pustules with abundant acantholytic keratinocytes in granular or upper spinous cell layers
What is meant by acantholytic?
Loss of intercellular connections
How can keratinocytes be identified as acantholytic?
- Think fried eggs
- Large blue cells with nuclei normal for keratinocytes in stratum granulosum and spinosum
- In stratum corneum, normal keratinocytes have no nuclei
- Presence of nucleus shows that these have shed too early, and desmosomal connections have broken
Describe the results of direct immunofluorescence in canine pemphigus foliaceous, and state where immunopathology would be used
- Anti-keratinocyte membrane auto-antibodies demonstrated
- Usually IgG, occasionally IgM or IgA or C3 associated, target desmocollin 1
- Only used in reaserch, not a diagnostic tool
Describe the clinical signs of canine pemphigus vulgaris
- Lesions (pustules, vesicles, erosions, ulcers) at mucosal and mucocutaneous junctions (eyes, lips, nose, pepuce, anus)
- Rare cases affected with varient of PV without oral or mucosal involvement
- May also see inside mouth
- Paronychia sometimes seen
Describe the clinical appearance of canine discoid lupus erythematosus
- Hypopigmentation
- Erythema
- Scaling
- Erosions
- Very similar appearance to pemphigus erythematosus, little importance, treat the same
Describe the histological appearance of canine DLE
- Lymphoplasmacytic
- Lichenoid pattern
- Interface dermatitis
Describe the clinical signs of plasma cell pododermatitis
- Gross swelling of multiple metacarpal/tarsal pads, occasionally foot pads
- Ulceration, lameness, pain, occasionally pruritus
- Occasionally pad ulceration
Describe the histological appearance of plasma cell pododermatitis
Full of plasma cells
Describe the clinical signs of idiopathic symmetric lupod onychodystrophy
- Typical history of naisl progressive becoming loose or splitting, incl, dew claws
- Some nairls lost altogether
- Extremely painful when nails start to lift off
Describe the histological appearance of vasculitis
- Dermal oedema
- Collagen smudging
- Hair follicle atrophy
- Degeneration of vessel walls
- Perivascular cuffing with mononuclear cells
Describe the clinical appearance of vasculitis
- Skin becomes necrotic, hair follicles shut down, crusting, ulceration
- Skin affected in dependent areas and extremities, esp. paws (incl. sloughing pads), claws, pinnae, lips, tail, scrotum, oral mucosa
- Skin lesions include purpura, macules, plaques, haemorrhagic bullae, papules, pustules, necrosis, ulcers, acrocyanosis
- oedematous plaques, urticaria, lymphoedema, pain , erythema
- Septa vasculitis and panniculitis
- Pitting oedema of limbs, ventral trunk, head and scrotum
- Anorexia, depression, pyrexia, pain, pruritus
- Polyarthropathy, myopathy, neuropathy,, hepatopathy, thrombocytopaenia, anaemia, lymphadenopathy
- Change in skin colour to blue, black, red
Discuss the management of feline pemphigus foliaceous (licensing, side effects, other difficulties)
- Ciclosporin off license
- Licensed in cats for allergy
- Side effects: GI disruption (V/D)
- Only for use where are confident will see patient regularly
- Very expensive
List the treatment options for pemphigus
- Glucocorticoids
- Ciclosporin
- Azathioprine
- Gold salts (aurothioglucose)
- Chlorambucil (cats)
- Oclacitanib (Apoquel)
- Adjunctive therapy
Outline the use of glucocorticoids in the treatment of pemphigus
- Pred/methylpred
- <2mg/kg/day divided until in remission (care re. doses >2mg/kg)
- Then alternate day therapy
- Slowly reduce dose
What considerations should be taken into account when using glucocorticoids inthe treatment of pemphigus?
- Reduce slowly to avoid relapse (every 2-3 weeks)
- Inform owners of risk of iatrogenic Cushings or Addison’s, as well as risk of diabetes
Outline the use of ciclosporin in the treatment of pemphigus
- Dose required unclear
- Use 5mg/kg/day for allergies
- Good to minimise side effects from treatment
Outline the use of azathioprine inthe treatment of pemphigus
- Not recommended in cats
- Historical treatment
- In dogs: 3mg/kg orally q24-48 hours
- Frequent monitoring required
- Slow onset of action (3-6 weeks for clinical effects)
What are the potential adverse effects of azathioprine treatment for pemphigus?
- Myelosuppression
- Pancreatitis (may lead to diabetes)
- Panniculitis
- Hepatotoxicity
Describe the monitoring required when using azathioprine as a treatment for pemphigus
- CBC and platelet count initially q2 weeks for 2 months
- Then q2-3 months
Explain the mechanism of action of Gold salts (Aurothioglucose) for the treatment of pemphigus
Influences neutrophil migration, lymphocyte function and immunoglobulin production
Describe the protocol for the use gold salts in the treatment of pemphigus
- Weekly dose of 1.0mg/kg IM, to once every 2 or 4 weeks
- May take 6-12 weeks to see full response
- Monitoring every 2 weeks
List the adverse effects of gold salts in the treatment of pemphigus
- Glomerulonephritis
- Bone marrow suppression
- Thrombocytopaenia
- Cutaneous eruptions
- Injections themselves are painful
What monitoring is required during the use of gold salts for pemphigus?
- Every 2 weeks require haematology, serum biochem, urinalysis
- This is the expensive part, not the drug
Describe the use of chlorambucil for the treatment of feline pemphigus
- Daily or every other day therapy, in combination with steroids
- 0.1-0.2mg/kg, tablet is 2mg so most cats receive half a tablet/day
- Therapy for 4-8 weeks
- Regular monitoring required
Describe the adverse effects of chlorambucil
- Vomiting
- Diarrhoea
- Anorexia
- Bone marrow suppression
What monitoring is required while using chlorambucil?
Haematology every 2 weeks
Discuss the use of oclacitanib in the treatment of pemphigus
- Suggested, but no studies
- Only effective against the pruritus via IL-13 block (is an allergy medication)
Explain the adjunctive therapies used for pemphigus
- Chlorhexidine based shampoo to prevent secondary bacterial component and remove crust/scale
- Antibiotics for 3 weeks e.g. cefalexin 20mg/kg BID
- Gut protectants to e.g. cimetidine omeprazole to reduce risk of side effects
- Methylprednisolone equivalent dose of 0.8-1mg of prednisolone
Outline the treatment options for CLE/DLE
- Topical glucocorticoids
- Topical ciclosporin (Tacrolimus)
- Topical sunblockers
- Vitamine E 400-800mg/day
- Essential fatty acids
- Niacinamide and tetracycline
- Oral glucocorticoids
- Azathioprine
- Chlorambucil
- Nasal flap plastic surgery
Discuss the use of topical ciclosporin in the treatment of CLE/DLE
- Not licensed in animals
- Protopic ointment
- used for perianal fistulas/anal furunculosis, CLE/DLE, pemphigus erythematosus
- Apply once/twice daily for 4-8 weeks
- Burns in humans, none noted in aanimals
- No significant toxic absorption and no side effects in animals
Outline the use of niacinamide in the treatment of CLE/DLE
- Aka nicotinamide (vit B3)
- mode of action and efficacy unsure
- No side effects
- Dose: 3xdaily, 250mg<10kg or 500mg>10kg for 6-8 weeks
