Allergic skin disease Flashcards
Allergy definition
= a condition caused by a hypersensitivity response to allergens
- common cause of pruritus in dogs and cats
Triggers of allergic skin dz
- 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
Factors of allergic skin dz
- Environmental influences
- Immunological dysregulation
- Genetic background
Hypersensitivity involved
- Type I hypersensitivity most commonly involved
- But >1 type of hypersensitivity proposed for some conditions
- Picture is complex and incompletely understood
- But all require stages of:
– Sensitisation of individual by repeated exposure to allergen
– Subsequent exposure -> immunologically excessive/inappropriate response
-> clinical disease
Canine atopic dermatitis (CAD)
- A common chronic, relapsing, pruritic and inflammatory skin syndrome with characteristic clinical features
- Traditionally associated with IgE antibodies to environmental allergens BUT
- <30% cases have no evidence of IgE (’intrinsic atopics’) (based on serology/intradermal testing (IDT))
- <30% cases may have dietary trigger (not diagnosed by serology or IDT)
Environmental CAD pathogenesis
- Defective cutaneous barrier function
- Microbial dysbiosis/overgrowth/infection
- Hypersensitivity reaction
Common allergens associated with environmental CAD
- dust mites*
- pollen
- moulds
Hypersensivity/immunology associated with environmental CAD
- Type I hypersensitivity response is involved in most cases, but not all
- Adaptive immune response changes with chronicity
– Acute lesions: lymphocytes classically follow Th2 pathways -> IgE (Type I hypersensitivity)
– 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
- NB skin lesions sometimes accompanied by other manifestations of atopy (atopic conjunctivitis /rhinitis)
- Allergen specific IgE binds to tissue mast cells (+basophils + in circulation + Langerhans cells). IL31 is a major player in IgE allergic response
- Keratinocytes also cause substances that cause pruritus to be released in these cases
Type I HS overview (for environmental CAD)
- Initial sensitisation -> no clinical signs
- On re-exposure to the allergen:
– 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
-> itch/inflammation -> scratch
-> epidermal hyperplasia -> worsening epidermal barrier function
With chronicity of Type I HS reaction (for environmental CAD)
From scratching, toxins from skin microbes, continued exposure to allergens:
-> activate keratinocytes and other immune cells (eg macrophages) -> polarisation to Th1 phenotype
-> Increase monocyte/macrophage recruitment and activation
-> thickening of epidermis/ stratum corneum etc…
-> worsening epidermal barrier function
Favrot proposed diagnostic criteria for CAD
- 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
Other factors also involved
Environmental CAD: Signalment
Breed predisposition, varies with location.
Commonly, e.g.
- Golden/Labrador retriever
- WHWT/other terriers
- English/French bulldog, Pug, Boxer, Lhasa Apso, GSD, Shar Pei
Environmental CAD: History
- Nearly aways pruritic
– (v occasionally present as pyoderma that is 100% responsive to therapy) - Scratch, lick, rub, scoot
- Onset usually 6m-3y
- May start seasonally -> year round
Most will respond to anti-inflammatory dose of corticosteroids
Environmental CAD: Clinical signs
Affected areas commonly
- Face, ears (concave pinnae, ear canals)
- Axillae, ventral abdomen, inguinum, perineum
- Carpi/tarsi, feet
- Essentially most of the dog apart from the dorm and flank are commonly affected
Uncomplicated case
- Erythema
Self-induced alopecia, excoriations
- Primary papular eruption
With chronicity
- Lichenification, hyperpigmentation
NB Lesions of secondary infection often superimpose
CAD occasionally manifests as
- acral lick dermatitis (produce lesions by licking the same spot repeatedly)
- pyotraumatic dermatitis
Food-triggered AD: common reactions
- dogs: beef, dairy, chicken, wheat
- cats: beef, fish, chicken
Food-triggered AD (dog): 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
- affects <30% dogs with CAD
Food-triggered AD (dog): clinical signs
- 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?
Feline atopic syndrome (FAS): 4 feline cutaneous reaction patterns
- Face, head, neck pruritus (FHN)
- Self-induced alopecia (SIA)
- Miliary dermatitis (MD)
- Eosinophilic granuloma complex (EGC)
(eosinophilic granulomas/ulcers/plaques)
- Can show 1 or more simultaneously
Adverse food reactions:
Food allergy: - Hypersensitivity reaction
(likely Types I, III +/or IV)
- immunological reaction
Food intolerance:
- Metabolic reaction
- Pharmacologic reaction
- Idiosyncratic reaction
- Non-immunological reaction
Intoxication:
- Bacterial/ fungal/ other toxins
- Non-immunological reaction
Most common causes for feline cutaneous reaction patterns
- FASS
- FFA
- Flea allergic dermatitis (FAD)
Causes of FAS
- Feline atopic skin syndrome (FASS)
- Feline food allergy (FFA)
- Feline asthma
FASS (& FAD) clinical signs
- 4 feline cutaneous reaction patterns
FFA cutaneous clinical signs
- 4 feline cutaneous reaction patterns
- urticaria
- non-pruritic nodules
- plasma cell pododermatitis
FASS: Signalment, history, clinical signs
- Inflammatory/pruritic skin syndrome, likely associated with IgE to environmental allergens
- Usually young adult – 6mo-5y onset (occasionally older)
- Seasonal/ non-seasonal
FFA: Signalment, history, clinical signs
- Can occur at any age (3mo+) but 27% cats <1yo
- Non-seasonal
- +/- GI/conjunctivitis/respiratory signs
FAS diagnosis in most cases
- Eliminate ectoparasites and bacterial/fungal infections
2.-> Exclusion diet trial -> FFA - -> FASS
Contact hypersensitivity
- Very uncommon
- Type IV reaction: affects isolated individual
- Sensitisation usually over prolonged period, eg to:
– Plants, topical drugs/shampoos
– Chemicals, cleaning products, rubber, plastic, leather, metal etc - Lesions in areas of contact only
- Particularly affects sparsely haired regions
2 types of contact dermatitis
- Contact irritant dermatitis (due to irritant nature of substance (not hypersensitivity) – often affects >1 animal)
- Contact hypersensitivity
Patch testing
- For contact hypersensitivity
- Can be undertaken but rarely performed
Drug eruptions
- 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
- Antibiotics most frequently implicated
– Especially potentiated sulphonamides
What dermatological drug eruption can a vaccine reaction cause?
- Vasculitis (type III HS)
( = blocking of the blood vessels, so get necrosis of the downstream skin)
Parasitic arthropod hypersensitivities
- Insect bite HS
- Mite HS
- Eosinophilic folliculitis/furunculosis
Insect bite HS
- FAD (dogs & cats)*
- Mosquitoes (uncommon, especially non-haired skin of cats)
- Flies
Mite HS
- 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
What are the two established types of allergy test used for canine atopic dermatitis?
- IgE serology and intradermal testing (IDT)
- No role in initial diagnosis of food-triggered or environmental allergies
IgE serology for environmental allergens
- Tests detect IgE using an anti-canine IgE antibody. Most sensitive and specific tests based on
– a monoclonal anti-IgE or
–a recombinant fragment of the human IgE receptor subunit that has a high affinity for canine IgE - Best to use a test with CCD (cross-reactive carbohydrate determinant) blockers
– Avoids false positives caused by detection of clinically irrelevant IgE to carbohydrates (not proteins) on the allergen surface being detected - The first molecular serum IgE-specific test for pets is now commercially available
– This is a new technology called ‘molecular allergology’ in which antibodies to specific allergen molecules (not the whole antigen) are detected. This should make the test more specific and sensitive than traditional technologies.
3 main types of diets used for the elimination diet trial
- Hydrolysed diets
- Limited antigen diets
- Home-cooked diets
Hydrolysed diets (description, pros, cons, other comments)
Description of constituents:
- Diet undergone enzymatic hydrolysis to reduce its allergenicity
Advantages:
- Commercial food -> convenient
- Most accurate commercial diet (if chicken hydrolysate avoided) irrespective of previous diet
Disadvantages:
- Level of hydrolysis varies – if incomplete, some allergenicity may remain
Suitable for growth?
- Some
Other points:
- Use a fully hydrolysed diet.
- Avoid chicken hydrolysate diets in case parent molecules remain (NB chicken feather hydrolysate diet OK)
Limited antigen diets (description, pros, cons)
Description of constituents:
- Novel protein and carbohydrate source
Advantages:
- Commercial food -> convenient
Disadvantages:
- Undeclared ingredients in normal food makes accurate knowledge of what eaten before difficult
- May contain undeclared proteins
Suitable for growth?
- Some
Home-cooked diets (description, pros, cons, other comments)
Description of constituents:
- Home-cooked novel protein and carbohydrate
Advantages:
- Most accurate
Disadvantages:
- Labour-intensive, costly, not balanced for long term use
Suitable for growth?
- No
Other points:
- Infrequently used
Elimination diet trial
How to introduce the diet: gradually, e.g. over 7-10 days
How long to feed it exclusively: minimum 8 weeks
How to control pruritus during the trial: with oclacitinib or prednisolone in initial stages
Treats? No
What should he drink? Water only
Owner communication
Once diagnosis made, important that owner knows the facts re AD
It’s not their fault - there’s nothing they could have done to avoid it
Disease will persist life long and will need ongoing management to control
Lots of treatment options
- No guaranteed successful treatment and no ‘one size fits all’
- Usually need combination of therapies
- Need to establish tailor-made regime dependent on patient/owner factors
Once regime established, changes may be needed as
- Disease not static – may have temporary flare-ups -> short-term adjustments
- Disease severity may generally increase with age -> adapt core regime long term
AD partly heritable so should not breed
Treatment of AD – important considerations
- Multiple pruritic problems may coexist: need to identify each and treat
- Need to control inflammation, infection & itch
- Need to find a balance:
– Product efficacy/ speed of onset
– Risk side effects
– Treatment feasibility/ owner compliance
keep regime as simple as possible
– Cost
Multi-modal tx
- Control inflammation + pruritus
- Allergen avoidance & allergen-specific immunotherapy
- Control flare factors
- Improve skin barrier
Control of inflammation & pruritus
- Glucocorticoids/corticosteroids - systemic or topical
- Oclacitinib (JAK inhibitor)
- Lokivetmab (anti- IL-31 monoclonal antibody)
- Ciclosporin (calcineurin inhibitor -> T-cell suppression)
- Antihistamines (e.g. Puritan
Glucocorticoids
- highly effective re inflammation and pruritus
- rapid onset (24h)
- inexpensive
- but significant risk of side effects, esp with long term use
- vary in anti-inflammatory potency and duration of action, dependent on drug/ester/formulation
- also vary in mineralocorticoid action
- 6-monthly serum biochemistry and urinalysis advised if used long term
Approx GCC potency (from low to high)
- Hydrocortisone
- Prednisolone/methylprednisolone/triamcinolone
- Dexamethasone/ beta-methasone/ hydrocortisone aceponate
- Mometasone
GCC potential side effects
- tend to increase with steroid potency, dose, duration
Short term:
- Polydipsia, polyuria, polyphagia
- Panting, lethargy
Long term:
- Systemic immunosuppression
-> infections (often undetected in bladder)
-> failed wound healing
- GI haemorrhage/ gastric ulcers
- Iatrogenic HAC
- Diabetes mellitus
- HPA axis suppression -> Addison’s disease
GCC use (aims)
- lowest potency product
- lowest dose
- shortest time
that will be effective
Systemic GCCs - injections:
Short-acting solutions
- Useful for rapid onset short-acting effect – some licensed iv
- Occasionally dexamethasone solution used orally for fractious cats – off label - use with care and informed consent – see literature for dose/frequency
Depot suspensions
- Some products (methylprednisolone acetate) with action <4-8 weeks but poor dose control. Most commonly used in fractious cats, ?never in dogs
- Diabetogenic and risk hypothalamic-pituitary-adrenal axis suppression with long term use
Systemic GCCs - oral
- mainstay of dermatological GCCs
- Usually prednisolone
- Occasionally methylprednisolone (more expensive but less MCC effects)
Dose: anti-inflammatory dose needed for allergic disease
- Start daily (eg 0.5-1mg/kg prednisolone q24h for dogs)
- Taper to lowest effective alternate day dose if needed for maintenance (e.g. aim for 0.3mg/kg prednisolone q48h or lower)
- Taper gradually – never stop suddenly (risk of iatrogenic Addisonian crisis)
Topical GCCs
- Useful for focal treatment and to reduce use of systemic GCC
- Risk of systemic absorption and skin thinning with long term use
– Gloves must be worn
– Advise owner re licensed maximum duration of therapy, especially on thin-skinned areas - NB Some products also contain antibiotic (e.g. fusidic acid) – use only if antibiotic action actually required
NB Hydrocortisone aceponate spray
- Steroid-only
- Potency equivalent to betamethasone but stated to cause less systemic absorption/skin thinning (still exercise caution)
Oclacitinib
- Very commonly used drug for CAD – dogs only, minimum 1yo
- Effective in approx. 70% cases
- Rapid-onset effect (24h), considered safe for long term use
- Excellent antipruritic, some anti-inflammatory effect
- NB for treatment of allergic pruritus and dermatitis only, not for pruritus of non allergic origin
- Minimal interaction with other drugs, though unlicensed for concurrent use with prednisolone or ciclosporin (additive depressive effect on aspects of immune system)
- Dose orally q24h
– If needed, can commence at q12h for 2 weeks, then reduce – NB may experience rebound pruritus when dose reduced – usually abates
– Do not exceed labelled dose - Not if patient immunosuppressed, has renal/liver impairment or suffering progressive neoplasia
Lokivetmab
- Specific action (selective blocking of IL-31) ->
– Good safety profile and no effect on general immunity
– Rare anaphylaxis
– Excellent antipruritic but minimal anti-inflammatory effect
– NB for treatment of allergic pruritus and dermatitis only, not for pruritus of non allergic origin - s/c injection q4 weeks; DOGS ONLY!
- Rapid onset of action, effective in 75% dogs
- Occasionally efficacy lost with time (pts body produces antibodies against the antibody of the drug)
- Can use
– in any age of dog
– with impaired liver/kidney function and neoplasia (cf many alternatives)
– in conjunction with the other therapies (steroids, ciclosporin, oclacitinib) if necessary – others not licensed to combine
Ciclosporin
- Excellent anti-inflammatory and antipruritic
- Licensed for dogs and cats, but costly
- Effective (80% cases) but slow to work (1-2mo)
-> initial concurrent use with 2-3 week of prednisolone or oclacitinib (off label) - Oral product – q24h initially, but many can taper to q48-72h once stable
- T-cell suppressor
– Avoid use 2 weeks before/after vaccination
– Test cats for FeLV/FIV/toxoplasmosis before commencing
-> needs to be FeLV/FIV negative
-> needs immunity against toxoplasma before commencing (i.e. not a naive animal as would be greatly affected if did get it) - Not <6 months old or with neoplasia
- Side effects
– Most commonly diarrhoea/vomiting, usually transient
– Others, e.g. anorexia, gingival hyperplasia, hirsuitism
Antihistamines
- Block H1 histamine receptors of C neurones (+/- some central sedative effect) – but histamine has limited role in canine allergy
- Efficacy low (?20%), but may allow reduction of dose of other drugs?
- May provide small and limited benefit if given before flare?
- No use for chronic disease
- Unlicensed in animals
Examples
- Dogs: chlorpheniramine, hydroxyzine, cetirizine
- Cats: chlorpheniramine, hydroxyzine
Side effects
- Rare except drowsiness – care especially with cats
Acute situation drug at best
Good for acute urticarial reaction but not for average atopic scenario
Piriton = Chlorepheniramine
Clinical implications of more targeted drugs (oclacitinib/lokivetmab)
- have rapid effect and best safety profile (use whenever possible)
- may not provide adequate control in situations where inflammatory component high, eg
– In the initial stage of treatment if inflammation +++
– otitis, pedal inflammation
-> may need to add topical corticosteroid or change to drug with higher anti-inflammatory action
Allergen avoidance
- Need to have established allergens involved
- Avoidance feasible for food
- Unlikely feasible as sole strategy for environmental allergens
– House dust mite reduction measures?
– Prevent patient contact with dust?
–Decrease mites/their secretions/excretions? (Allergone®)
– Washing after walk to remove outdoor allergens from coat?>
Allergen-specific immunotherapy
- Administer small amounts of relevant allergen to try to induce tolerance
- Only treatment that can potentially alter the long term course of the disease
- Immunotherapy vaccines made by selecting clinically relevant allergens
– Based on positive results from IDT or serum IgE testing
– Administration: subcutaneous, sublingual, intralymphatic
– Unlicensed in UK – import licence required
Allergen-specific immunotherapy: Use
- Environmental allergens (not food/fleas)
- Malassezia (Malassezia hypersensitivity recognised in some individuals)
Allergen-specific immunotherapy: Efficacy
- Slow onset – trial 12mo+
- 20% highly effective (use as sole therapy)
- 50% helped but require other concurrent treatment
- 30% ineffective
- If effective, can taper to lowest effective frequency – usually lifelong treatment but can occasionally withdraw
Allergen-specific immunotherapy: Side effects
- Increased pruritus for few days after injection in ?10%
- Rare local injection reactions
- Systemic reactions <1%
- Anaphylaxis very rare (initial course given in surgery)
How to improve the skin barrier
- Topical moisturisers, e.g.
– Colloidal oatmeal, aloe vera, glycerin, urea, propylene glycol, ophytrium, lactic acid, sodium or ammonium lactate - Systemic essential fatty acids
– Supplements or high EFA diets
– NB 2-3 months to effect - Essential oils
Control of flare factors
- Good ectoparasite control
- Avoid overheating
- Control microbial populations
– e.g. antimicrobial shampoos/wipes/foams
->For treatment and prevention
NB good control of underlying CAD is best way to prevent recurrent secondary infection
Particular challenges with cats
- Allergic skin disease less commonly presented than dogs but has particular challenges
- Few licensed products
– GCCs and ciclosporin licensed
– Oclacitinib and lokivetmab unlicensed in cats (NB Oclacitinib not recommended; NEVER lokivetmab to cats) - Administration of oral and topical treatments generally more difficult than dogs
- Vet visits more stressful
- Scratching can cause rapid and severe damage
Short-term physical prevention of self-trauma
- Collars
- Shirts
- Soft-claws (useful short-term, cat must not go out)
Factors affecting product choice
- Patient
– Species, age
– Clinical signs
->Area of body affected
->Level of inflammation vs pruritus
– Systemic health - Drug
– Speed of response required
– Product efficacy, safety - Owner
– Expected compliance
– Cost (including of monitoring)
Consider phase of treatment that patient is in (for decision-making when prescribing)
- Reactive – initial rapid control of clinical signs required
– May require initial course of corticosteroids (oral +/-topical) if inflammation +++. Then change to more targeted therapy for longer term use - Proactive – ongoing maintenance therapy to prevent recurrence
– Use safest drug/regime that is effective
– Remember to consider all aspects of multimodal therapy - Avoid systemic corticosteroids if possible
– But if needed, taper to lowest effective alternate day dose
Why eventually aim to give steroids every other day?
- Gives HPA axis chance to recover
- Reduces renal suppression
- Much less likely to get Addisonian crisis
