Pathogenesis and clinical signs of allergic skin disease Flashcards
What are triggers of allergic skin disease?
-
Environmental allergens
- Environmental atopic dermatitis - dog
- Feline atopic skin syndrome (FASS) – cat
-
Foods
- Food-induced atopic dermatitis (‘food allergy’)– dog
- Feline food allergy (FFA) – cat
-
Ectoparasites
- Flea allergic dermatitis
- Insect bite hypersensitivity
- Mite hypersensitivity – especially Sarcoptes
- Contact allergens
- Micro-organisms, e.g. Malassezia hypersensitivity
- Drugs
What hypersensitivity types are associated with allergic skin disease?
Types I & IV hypersensitivity involved
I - Immediate
Cross-linking of IgE molecules on mast cell surface by allergen -> degranulation -> tissue inflammation. IgE on Langerhans cells increased T-cell sensitivity to allergen
IV - Cell-mediated
T-helper 2 cells produce inflammatory and pruritic cytokines and promote class-switching from IgG to IgE
What are the 2 stages leading to allergic skin disease?
Sensitisation of individual by repeated exposure to allergen
Subsequent exposure - immunologically excessive/inappropriate response -> clinical disease
What is canine atopic dermatitis? What allergens cause it?
- Environmental &/or food-associated AD
- 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.
- Allergens include house dust mites, pollens and mould spores in the environment and food allergens fed to the dog
- but 10-30% of cases have NO detectable allergen-specific IgE (IDT or ELISA)
Describe the clinical syndrome of environmental canine atopic dermatitis
- Type I hypersensitivity responses are involved in most cases, but not all
- Adaptive immune response changes with chronicity
- Acute lesions: lymphocytes classically follow Th2 pathways -> IgE / TH-2 cytokines
- Chronic lesions: more complex pattern - include Th1, Th2 and other T-cell responses
- Cells/mediators of innate immune system (including keratinocytes) play a role in initiating/maintaining inflammation
- Skin lesions sometimes accompanied by other manifestations of atopy called the atopic triad in people (asthma, hayfever and atopic eczema) – seen as allergic conjunctivitis and rhinitis in dogs
What occurs on re-exposure to allergen in environmental CAD?
- degranulation of mast cells -> release of inflammatory mediators
- keratinocytes/activated T-cells -> cytokines
- All recruit inflammatory cells (esp neutrophils, then eosinophils) to dermis
Inflammatory cells activated and proliferate via Janus kinase (JAK) pathways on cell surface
Signs
* itch / inflammation -> scratch
* epidermal hyperplasia -> worsening epidermal barrier
What role does the cytokine interleukin 31 have in allergy?
Drives itchyness, inflammation, impaired barrier function and neurogenic inflammation
How can you diagnose CAD?
- A diagnosis of elimination
- No single clinical or lab test
- In the face of typical history and clinical signs
- Remove and control secondary infection (TTP)
- Eliminate parasitic disease that may mimic allergic disease
- Consider the role of food
- Make a diagnosis
- Allergy testing: e.g. intradermal allergy testing or allergen-specific in vitro testing is used for treatment design and NEVER for diagnosis.
What are the 7 diagnostic criteria for CAD? How are they used?
- Age at onset <3 years
- Living mostly indoors
- Glucocorticoid-responsive pruritus
- Non-lesional pruritus
- Affected front feet and/or pinnae
- Unaffected ear margins
- Unaffected dorsal/lumbar area
If 5 positive criteria…
- Sensitivity 85%
- Specificity 79%
May help, but cannot be used in isolation
Often better for rule outs – i.e. ear margin and dorsolumbar disease strong indicators for scabies and fleas respectively
What signalment is often associated with CAD?
Breed predisposition – varies with location.
Commonly, examples:
* Golden/Labrador retriever
* WHWT/other terriers
* English/French bulldog
* Pug
* Boxer
* Lhasa Apso
* GSD
* Shar Pei
What history is often associated with environmental CAD?
- Nearly aways pruritic
- Occasionally see pyoderma as presenting sign - 2˚ to skin inflammation and dysbiosis with little itch (e,g. Golden retrievers)
- Scratch, lick, rub, scoot
- Onset usually 6 months to 3 years
- May start seasonally (80% start in the summer and 20% in the winter but usually a year round in the UK)
- Most will respond to anti-inflammatory dose of corticosteroids
What clinical signs are associated to CAD?
Affected areas
* Face
* Ears (concave pinnae, ear canals)
* Axillae, ventral abdomen, inguinum, perineum
* Carpi/tarsi, feet (including plantar/palmar skin)
Uncomplicated cases
* Erythema
* Self-induced alopecia, excoriations
* Primary papular eruption (rare)
With chronicity
* Lichenification
* hyperpigmentation
* Lesions of secondary infection often superimpose
Occasional manifests as
* acral lick dermatitis (see Deep pyoderma)
* pyotraumatic dermatitis (see Microbial infections)
What secondary lesions occur with CAD?
- Alopecia
- Excoriations
- Salivary staining
- Lichenification
- Pustules, epidermal collarettes and crusts
- Hyperpigmentation
- Chronic otitis
What are common causes of food triggered atopic dermatitis in dogs and cats?
Dogs: beef, dairy, chicken, wheat
Cats: beef, fish, chicken
What signalment, history and clinical signs are associated with food allergies?
Affects <30% dogs with CAD
Age of onset:
* Can develop at any age
* 30-50% start at <1yo
* More likely than environmental CAD if onset <6mo?
* Sensitisation not associated with diet change!
Skin signs clinically indistinguishable from environmental CAD
+/- Concurrent clinical signs, e.g.
* GI signs
* Urticaria/angioedema
* Malassezia dermatitis
Less responsive to steroid anti-inflammatories than environmental CAD?
Which of the four feline reaction patterns are pictured? Which three conditions are the most common cause for all?
1 - Eosinophilic granuloma complex
2 - Face, head, neck pruritus
3 - Miliary dermatitis
4 - Self induced alopecia
Can show 1 or more simultaneously
FASS, FFA and flea allergic dermatitis (FAD) can cause any/all – so can look identical
What clinical signs are associated with feline food allergy?
4 cutaneous reaction patterns
Other cutaneous signs
- urticaria
- non pruritic nodules
- plasma cell pododermatitis
Gastrointestinal signs
- vomiting
- diarrhoea
- weight loss
- poor appetite
How does the signalment vary between feline atopic skin syndrome and feline food allergy?
Feline atopic skin syndrome (FASS)
* Inflammatory/pruritic skin syndrome, likely associated with IgE to environmental allergens
* Usually young adult – 6mo-5y onset (occasionally older)
* Seasonal/ non-seasonal
Feline food allergy (FFA)
* Can occur at any age (3mo+) but 27% cats <1yo
* Non-seasonal
* +/- GI/conjunctivitis/respiratory signs
Both most commonly present with one or more of the four feline reaction patterns…
How would you work up a feline case to establish the underlying cause of skin disease?
- Eliminate ectoparasites and bacterial/fungal (dermatophytosis) infections
- Exclusion diet trial -> FFA
- FASS
WHat are the 3 common types of parasitic arthropod hypersensitivities?
Insect bite hypersensitivity
* FAD – dogs and cats – see previous notes
* Mosquitoes – uncommon. Especially non-haired skin of cats
* Flies
Mite hypersensitivity
* In affected individuals -> increase pruritus from infestation
* Potential reason for persistence of pruritus after parasite killed
* E.g. Sarcoptes (dog), D gatoi? (cats), Cheyletiella, Otodectes
Eosinophilic folliculitis/ furunculosis
* Reaction to presumed arthropod bite
* Acute onset, highly pruritic
* Often affects dorsal muzzle +/- other sites
* Cytology shows eosinophils and little or no infection
* Treat aggressively with steroids to avoid scarring
What type of hypersensitivity is caused by contact hypersensitivity? How does it occur?
- Type IV reaction – affects isolated individual
- Th1 reactivity (classical delated hypersensitivity)
- Often haptens
- Sensitisation usually over prolonged period, eg to:
- Plants, topical drugs/shampoos (e.g. neomycin)
- Chemicals, cleaning products, rubber, plastic, leather, metal etc
- Lesions in areas of contact only!
- Particularly affects sparsely haired regions
How can drug eruptions present? What drugs often cause them?
- Can manifest as almost any type of cutaneous lesion or reaction pattern
- Should be remembered but are rare!
- Any of Type I, II, III, IV hypersensitivity mechanisms can be involved
- Variable pruritus
- Antibiotic commonly implicated
- Especially potentiated sulphonamides
- Also
- Methimazole (anti-thyroid drug)
- Itraconazole (antifungal drug)
- Frunevetmab (Arthritis drug)
An 18-month-old Jack Russell terrier, treated monthly with afoxolaner, presents with ventral and pedal pruritus of 2 months’ duration. The dog is otherwise well. What is your top differential diagnosis?
Environmental atopic dermatitis
