Immune mediated skin disease Flashcards
What are the two broad categories of immune-mediated skin disease?
Allergic skin disease and autoimmune skin disease
What is a common factor in immune-mediated skin disease?
Breakdown of immune tolerance
What causes allergies?
external antigens called allergens
examples:
- Flea allergic dermatitis – allergy to flea saliva
- Atopic dermatitis – allergy to dust mites, pollens & moulds
What causes immune mediated disease?
self-antigens
examples:
- Pemphigus foliaceus – destruction of desmosomal proteins
- Discoid lupus – damage to epidermal cells
- Sebaceous adenitis – destruction of sebaceous glands
What are common allergens that can trigger allergies?
What are common self-antigens that can trigger immune mediated skin disease?
What are the main causes of allergic skin diseases?
Multifactorial causes including:
- Genetics (e.g. canine atopic dermatitis in Labrador retrievers)
- Microbiome & antibiotics effects
- Exposure frequency (e.g. intermittent exposure often induces hypersensitivity)
- Skin barrier function
- Environmental chemicals
How does the hygiene hypothesis relate to allergic diseases?
Reduced microbial exposure in early life may impair immune tolerance, increasing susceptibility to allergies and autoimmune diseases
What role does the epithelial barrier hypothesis play in allergic diseases?
Disruption of skin barrier by environmental factors like detergents & microplastics may increase allergen penetration & immune activation
Define canine atopic dermatitis
Hereditary, typically pruritic & predominantly T-cell driven inflammatory skin disease involving interplay between skin barrier abnormalities, allergen sensitisation & microbial dysbiosis
What are the three major clinical signs associated with allergic skin disease?
Pruritus
Urticaria
Plaque Formation
What are pruritogens, and how do they cause pruritus?
Pruritogens are itch-mediators produced by immune cells, including cytokines, chemokines & other mediators
They stimulate sensory nerves, leading to itching in allergic reactions
What type of hypersensitivity reaction is responsible for pruritus and urticaria in allergic skin disease, and which cells are involved?
Type I hypersensitivity, involving mast cells & basophils that release inflammatory mediators
What key mediators are released during a Type I hypersensitivity reaction, and what are their effects?
Histamine – Causes swelling & urticaria more than itch
Leukotriene B4, prostaglandins & proteases – Contribute to inflammation & itch
Nerve growth factor – Increases sensitivity to itch
IL-2 & IL-31 – Directly stimulate sensory nerves, enhancing pruritus
What is urticaria?
Skin reaction characterised by raised, swollen welts due to histamine release in Type I hypersensitivity response, commonly seen in allergic skin diseases
How does a type IV hypersensitivity lead to pruritus in allergic skin disease?
T-helper (Th2-biased) lymphocytes release IL-31 (major cytokine that stimulates sensory nerves & induces itching) & other pro-inflammatory cytokines
What are the key steps in allergen sensitisation in dogs?
- Allergen Exposure – Allergen enters through skin, inhalation, ingestion, or injection (e.g. pollen, dust mites, flea saliva)
- Antigen Capture – Langerhans cells (APCs) capture & process allergen
- T-Helper Cell Activation – Th2 cells trigger allergic response (IgE production), while Th1 cells lead to non-allergic response (IgG)
- B-Cell Activation – Th2 cytokines (IL-4, IL-5, IL-13) signal B-cells to produce IgE
- Mast Cell Sensitisation – IgE binds to mast cells, priming them for future allergic reactions
What happens when an animal is re-exposed to an allergen?
- Allergen Recognition – immune system remembers allergen from previous exposure, with IgE antibodies already bound to mast cells
- IgE Cross-Linking – allergen binds to IgE on mast cells, triggering cross-linking of FcεRI receptors
- Mast Cell Degranulation – Histamine, leukotrienes, prostaglandins & cytokines are released, leading to inflammation
- Inflammatory Effects:
- Vasodilation → Redness & swelling
- Increased vascular permeability → Oedema (fluid leakage)
- Smooth muscle contraction → Bronchoconstriction (e.g. coughing, wheezing)
- Pruritus (itching) → Common in allergic dermatitis
- Immune Cell Recruitment → More inflammation, eosinophil involvement
What causes plaque formation (induration) in allergic skin disease?
Plaque formation is caused by Type IV hypersensitivity, where T-helper lymphocytes release cytokines:
Th1-biased response: IFNγ, TNFβ, IL-2, IL-3 → cellular infiltration, swelling & skin thickening
Th2 & Th17-biased response: IL-4, IL-5, IL-17 → eosinophilic granuloma complex
Lesions are usually pruritic
What role do haptens play in allergic skin disease?
Haptens are small molecules that, when bound to body proteins, create new immune targets, triggering contact hypersensitivity reactions
How does classical contact hypersensitivity present clinically?
It causes pruritic inflamed skin lesions that appear where allergen contacts body
Rare in small animals but seen in horses (e.g. from tack materials)
What are the subdivisions of allergic skin disease in dogs?
Food and environmental induced-atopic dermatitis
- e.g. house dust mites or food proteins
Flea allergy
Contact allergy
- e.g. drugs
How can food and environmental allergies be distinguished in dogs?
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
Flea allergy
Insect and mite hypersensitivity
Food allergy
What are the clinical signs of CRP (feline cutaneous reaction patterns)?
Self-induced alopecia
Miliary dermatitis
Head and neck pruritus
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
Alopecia, depigmentation & ulcerations
Peripheral lymphadenomegaly
What are the subdivisions of allergic skin disease in horses?
Insect bite hypersensitivity
Equine atopic skin disease
Contact allergy
- e.g. tack
What are common clinical signs of allergic skin disease in horses?
Urticaria, pruritus, secondary infection, behavioural changes
Describe the mechanism of action of arthropod bite hypersensitivity in horses
Mixed IgE mediated – type I hypersensitivity reaction => pruritus
What is parasite-induced hypersensitivity in farm animals?
Allergic reaction to parasites such as sheep scab, scabies, sheep ked biting lice & Dermanyssus gallinae (bird mites)
Hypersensitivity is major part of clinical signs & can be protective or unhelpful to host
What can cause parasite-induced hypersensitivity in exotic species?
Scabies
Describe fly-bite hypersensitivity, caused by Culicoides spp in horses
AKA sweet itch
Allergic reaction to Culicoides spp. midge bites, causing Type I (± Type IV) hypersensitivity
Clinical Signs:
- Affects mane, tail, ears, face & sometimes ventral abdomen
- Papules, secondary alopecia, infections, excoriations
- Severe pruritus, leading to agitation and self-trauma
Common in UK, esp. in pastured horses during midge season
What are the two main types of hypersensitivity reactions in allergic skin disease?
Type I hypersensitivity (IgE-mediated, mast cell activation)
Type IV hypersensitivity (T-cell-mediated, delayed response)
How does Type IV hypersensitivity contribute to contact allergies?
TH-1 responses release IFN-γ & cytokines that lead to macrophage-rich inflammation & cellular infiltration
What role does IL-31 play in allergic reactions?
IL-31 is potent pruritogen, released by allergen-specific T cells, causing pruritus & eosinophilic inflammation
What are the predominant hypersensitivity types in CIMDs (Cutaneous Immune-Mediated Disease)?
Type II hypersensitivity – antibody-mediated
Type III hypersensitivity – immune-complex disease (often in vasculitis)
Type IV hypersensitivity – T-cell-mediated
What is pemphigus foliaceus?
Autoimmune skin disease where antibodies (Type II hypersensitivity) attack desmosomes, leading to pustules, crusting & hair loss
Antibodies cause opsonisation & trigger neutrophilic migration to target site, worsening skin damage
What is the target of Pemphigus foliaceus?
Desmosomal proteins in the upper part of the epidermis
What is main differential diagnosis for Pemphigus foliaceus?
Superficial pyoderma
What is Facial Cutaneous Lupus Erythematosus?
Autoimmune disease where T-cells attack epithelial cells via Type IV hypersensitivity, leading to apoptosis (programmed cell death) of keratinocytes
What is the target of facial Cutaneous Lupus Erythematosus?
Epithelial cells
What are the clinical signs of facial Cutaneous Lupus Erythematosus?
Damaged epithelium with ulceration & depigmentation
What are the main differential diagnoses for Facial Cutaneous Lupus Erythematosus?
Mucocutaneous pyoderma
Epitheliotropic lymphoma
What is the target of Vitiligo?
Melanocytes
What is the main differential diagnosis for Vitiligo?
Any inflammatory disease that causes depigmentation
What is the immune mechanism behind vitiligo in animals?
Autoimmune disease targeting melanocytes, mediated by Type IV & Type II hypersensitivity, involving T-cells &, to a lesser extent, antibodies
What are the clinical signs of vitiligo?
Removal of pigment from epithelium, with minimal inflammation
What are the key dermal targets in immune-mediated skin diseases?
Hair follicles → Pseudopelade (scarring alopecia)
Hair bulb → Alopecia areata (alopecia, sometimes regrowth without pigment)
Sebaceous glands → Sebaceous adenitis (scale & alopecia)
Blood vessels → Vasculitis (signs depend on damage severity)
Dermal proteins → Epidermolysis bullosa acquisita (vesicles & ulcers due to collagen VII damage)
What is the target for sebaceous adenitis?
Sebaceous glands
What are the main differential diagnoses for sebaceous adenitis?
Superficial pyoderma
Dermatophytosis
Many scaling diseases
What is sebaceous adenitis?
Immune-mediated disease targeting sebaceous glands, leading to gland destruction
Caused by T-cell-mediated (Type IV hypersensitivity) apoptosis
What are the clinical signs of sebaceous adenitis?
Broken hair, scale & alopecia
What is the target of vasculitis?
Dermal blood vessels
What are the main differential diagnoses for vasculitis?
Causes of alopecia (numerous!)
Tumours
Trauma
What is vasculitis?
Immune-mediated disease targeting dermal blood vessels, caused by Type III hypersensitivity.
Pathophysiology:
- Immune complexes deposit in capillary beds, causing ischemia & reduced blood supply
- Leads to tissue death & loss in affected area
What is the target of panniculitis?
Subcuticular fat
What are the main differential diagnoses for panniculitis?
Tumours
Deep infections (e.g. M. bovis)
What is panniculitis?
Immune-mediated condition targeting subcutaneous fat, Th1-like T-cell hypersensitivity causing pyogranulomatous inflammation
What are the clinical signs of panniculitis?
Soft, fluctuating nodules in skin
Nodules may rupture & discharge
How can cutaneous immune-mediated diseases (IMDs) relate to systemic disease?
Cutaneous IMDs can be:
- Cutaneous marker of systemic disease
- Part of systemic disease
- Accompanied by other unrelated IMDs, as autoimmune conditions often occur together
What systemic diseases can be associated with sterile pyogranulomatous dermatitis and panniculitis (SPDP)?
Pancreatic neoplasia
Pancreatitis
Polyarthritis
Systemic lupus erythematosus
How can vasculitis impact other organs beyond the skin?
Kidneys (causing glomerulonephropathy)
Joints (leading to immune-mediated arthropathy)
Eyes (causing retinal hemorrhage)
Why do some autoimmune conditions occur together?
Some immune-mediated diseases share common pathogenic mechanisms, leading to multiple conditions in one animal
Example: Addison’s disease often coexists with sebaceous adenitis in poodles
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 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
- Always select several sites
- Avoid areas of ulceration, self trauma or other secondary disease
- Consider test treatment with antibiotics in cases of cutaneous lupus
Routine bloods
- Check for other immune-mediated disease
- Prepare for treatment
