Immune mediated skin disease Flashcards
What triggers and allergic response? give examples
External antigens (allergens)
Flea allergic dermatitis – allergy to flea saliva
Atopic dermatitis – allergy to dust mites, pollens and moulds
Give examples of immune mediated diseases
Pemphigus foliaceus – destruction of desmosomal proteins
Discoid lupus – damage to epidermal cells
Sebaceous adenitis – destruction of sebaceous glands
Fill in the blanks describing the self-antigens causing immune-mediated disease
What are the causes of allergic disease?
Genetic
Microbiome and antibiotic effects
Exposure
Skin damage and chemical exposure
Species differences in immunological response
give an example of genetics causing allergy
Culicoides hypersensitivity (sweet-itch) in Icelandic horses or canine atopic dermatitis in Labrador retrievers
Define cAD (canine atopic dermatitis)
Canine atopic dermatitis is a hereditary, typically pruritic and predominantly T-cell driven inflammatory skin disease involving interplay between skin barrier abnormalities, allergen sensitization and microbial dysbiosis
What are the major clinical signs of allergy?
Pruritis => secondary lesions
Urticaria (rash)
Plaque Formation (relatively uncommon)
Describe pruritus and urticaria as an allergic reaction
Immune cells produce pruritogens - cytokines, chemokines etc stimulate sensory nerves => itch
Type I hypersensitivity - mast cells and basophils release histamine, leukotriene B4, prostaglandins, proteases, nerve growth factor, IL-2 and IL-31
Type IV hypersensitivity - T-helper lymphocytes release IL-31 and other pro-inflammatory cytokines
What is the effect of histamine in an allergic reaction?
causing swelling and urticaria more than itch
What is the effect of nerve growth factor in allergic reactions?
increases sensitivity to itch
Describe the sensitisation phase producing an allergy
Allergen Exposure – The allergen enters the body through inhalation, ingestion, skin contact, or injection (e.g., insect stings, vaccines, or drugs). Common allergens in veterinary medicine include pollen, dust mites, food proteins, flea saliva, and certain medications.
Antigen Presentation – Antigen-presenting cells (APCs), such as dendritic cells and macrophages, capture the allergen and process it.
Activation of T-Helper Cells – The APCs present the processed allergen to naïve T-helper (Th) cells, specifically Th2 cells, in lymphoid tissues.
B-Cell Activation and IgE Production – Th2 cells release cytokines (e.g., IL-4, IL-5, IL-13) that stimulate B cells to produce allergen-specific immunoglobulin E (IgE) antibodies.
Binding to Mast Cells and Basophils – The produced IgE antibodies bind to receptors on mast cells and basophils, “arming” these cells.
Describe the provocation phase of an allergic response
Re-exposure to Allergen – After the initial sensitization, the animal encounters the same allergen again (through inhalation, ingestion, or contact). The immune system “remembers” the allergen due to the previously produced allergen-specific IgE antibodies bound to mast cells and basophils.
Allergen Binding to IgE – On re-exposure, the allergen binds to the IgE antibodies that are now bound to the surface of mast cells and basophils.
Mast Cell and Basophil Degranulation – The binding of the allergen to IgE on the surface of these cells cross-links the IgE receptors (FcεRI), triggering the degranulation of mast cells and basophils. This results in the release of histamine, leukotrienes, prostaglandins, cytokines, and other inflammatory mediators.
Inflammatory Response – These mediators cause a variety of effects, such as:
Vasodilation: leads to redness and swelling in the affected tissue.
Increased vascular permeability: causes fluid to leak into tissues, leading to edema.
Smooth muscle contraction: can cause bronchoconstriction (leading to symptoms like coughing, wheezing, or difficulty breathing) in cases like asthma or bronchitis.
Pruritus: itching, commonly seen in allergic dermatitis.
Inflammation: the local immune response results in the recruitment of more immune cells (e.g., eosinophils), which exacerbate the inflammation.
Describe plaque formation (induration) as an allergic reaction
Type IV hypersensitivity:
- T helper cells release IFNg, TNFb IL-2 and IL-3 => cause cellular infiltration
- T helper cells release IL-4, IL-5 and IL-17 => eosinophilic plaque formation
- usually pruritic
What are the subdivisions of allergic skin disease in dogs?
Food and environmental induced-atopic dermatitis
Flea allergy
Contact allergy
Describe the differences between environmental and food allergies
Malassezia increased in food allergy
Seasonality not seen in food allergy
Young age of onset for food
More compact age of onset for environmental allergy
GI signs more common in food allergy
What are the subdivisions of allergic skin disease in cats?
Feline atopic skin syndrome (House dust mites, Pollens & mould)
Flea allergy
Insect and mite hypersensitivity
Food allegy
What are the clinical signs of CRP (feline cutaneous reaction patterns)
self-induced alopecia, miliary dermatitis, head and neck pruritus and eosinophilic granuloma
What are the clinical signs of mosquito-bite hypersensitivity in cats?
Type I hypersensitivity:
Nose, ears and feet (thin or sparsely haired)
Papules rapidly developing into small crusts
May be alopecia, depigmentation and ulcerations
Peripheral lymphadenomegaly
What are the subdivisions of allergic skin disease in horses?
Insect bite hypersensitivity (Biting flies, including Culicoides spp.)
Equine atopic skin disease (Stable mites, pollens and fungal spores)
Contact allergy (tack)
What are the common clinical signs of allergic skin disease in horses?
Urticaria (hives), pruritus commonly seen, with secondary infection and behavioural changes
Describe the mechanism of action of arthropod bite hypersensitivity in horses
Mixed IgE mediated – type I hypersensitivity reaction => pruritus
Describe allergic skin disease in farm animals
Parasite induced hypersensitivity
Atopic dermatitis diagnosed in sheep & goats
Describe allergic skin disease of exotic species
Parasite induced hypersensitivity
Describe the clinical signs of fly-bite hypersensitivity (Culicoides spp) in horses
Type I hypersensitivity (± Type IV HS):
Mane, tail, ears and face most commonly
ventral abdominal form (different midge sp?)
Papules may be present, secondary alopecia, infections and accompanying excoriations are common
Marked pruritus – agitation
Describe the hypersensitivity response seen in contact allergies
, TH-1-like responses are noted, characterised by IFN-g and other cytokines that cause cellular (usually macrophage-rich) inflammation
Describe the allergic reaction seen in non-contact allergies
, allergen-specific IgE bound to mast cells and allergen-specific T-cells producing cytokines such as IL–31 (a potent pruritogen) and other (TH-2-like) proinflammatory cytokines cause pruritus and eosinophilic inflammation.
What is the target in pemphigus foliaceus?
desmosomal proteins in upper part of epidermis
What is the immune mechanism in Pemphigus foliaceus
type II HS (antibody)
Antibodies => opsonisation and neutrophilic migration to target
Describe the clinical signs of Pemphigus foliaceus
pustules rapidly developing into crusts, leaving erosions
What are the other differential diagnosis when an animal presents with Pemphigus foliaceus?
superficial pyoderma
What is the target of Facial cutaneous lupus erythematosus?
epithelial cells
what is the immune mechanism in Facial cutaneous lupus erythematosus
T cells (type IV HS)
Apoptosis of keratinocytes
What are the clinical signs of Facial cutaneous lupus erythematosus
damaged epithelium with ulceration and depigmentation
What are the other possible differential diagnoses when an animal presents with Facial cutaneous lupus erythematosus?
Mucocutaneous pyoderma
Epitheliotropic lymphoma
What is the target of vitiligo?
melanocytes
what is the immune mechanism of vitiligo?
T-cells (+ antibodies)
Type IV and II HS
What is the presentation of vitiligo?
Removal of pigment from the epithelium, with minimal inflammation
What are the other possible differential diagnoses when an animal presents with vitiligo?
any other inflammatory disease that causes depigmentation
Give examples of possible allergic dermal targets
What is the target of sebaceous adenitis
sebaceous glands
What is the immune mechanism of sebaceous adenitis?
T-cells
Type IV HS
Apoptosis of sebaceous glands, causing destruction of glands.
What is the presentation of sebaceous adenitis
broken hair, scale and alopecia
What are the other possible differential diagnoses when an animal has sebaceous adenitis?
Superficial pyoderma
Dermatophytosis
Many scaling diseases
What is the target of vasculitis?
dermal blood vessels
What is the immune mechanism of vasculitis?
antibody (± antibody–immune complexes)
Type III hypersensitivity
Immune-complexes become entrapped in capillary beds causing ischaemia and reduced blood supply
What is the presentation of vasculitis?
tissue death and loss in the area supplied
What are the other possible differential diagnoses when an animal has vasculitis?
Causes of alopecia (numerous)
Tumours
Trauma
What is the target of panniculitis?
subcuticular fat
What is the immune mechanism of panniculitis?
unclear (pyogranulomatous inflammation – likely Th1-like T-cell hypersensitivity
What is the presentation of panniculitis?
soft-fluctuating nodules that may rupture
What are the other possible differential diagnoses when an animal has panniculitis?
Tumours
Deep infections (e.g., M bovis)
What other conditions cause sterile pyogranulomatous dermatitis and panniculitis?
pancreatic neoplasia
pancreatitis
polyarthritis
systemic lupus erythematosus
What other areas of the body can vasculitis effect?
Kidneys (glomerulonephropathy)
joints (immune-mediated arthropathy)
eyes (retinal haemorrhage)
Why is an accurate diagnosis of cutaneous immune mediated diseases important?
Adverse effects are common
Incorrect treatment for CIMDs may worsen or fail to resolve many infectious diseases
What diagnostic tests can be done to exclude cutaneous immune mediated diseases?
Careful history taking:
- First lesions
- Speed of onset
- Comorbidity
Rule out the common differential diagnoses:
- Skin scrapes & hair plucks
- Dermatophyte culture
- Cytology ± culture
- Test treatment (e.g. some parasites)
What diagnostic tests can be used to confirm cutaneous immune mediated diseases
Cytology
Biopsy of typical lesions
Routine bloods:
- Check for other immune-mediated disease
- Prepare for treatment
Describe the important things to do when collecting biopsies of cutaneous lesions
Always select several sites
Avoid areas of ulceration, self trauma or other secondary disease
Consider test treatment with antibiotics in cases of cutaneous lupus
