SA skin Flashcards
Definition of Canine Atopic Dermatitis (cAD)? Aetiology?
Genetically predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features, associated with IgE Abs most commonly to environmental allergens But 10-30% cases have no detectable allergen-specific IgE Allergens e.g. house dust mites, pollens, mould spores, food allergens High heritability (>0.5)
Define Atopic like dermatitis?
An inflammatory and pruritic skin disease with clinical features identical to those seen in CAD, in which an IgE response to environmental or otherallergens cannot be demonstrated
Pathogenesis of cAD?
Cutaneous inflammation and pruritus: - allergen sensitisation and Type I and IV hypersensitivity - the role of the T-cell - acute virus chronic inflammation Defective skin barrier function Microbial colonisation Other flare factors
Which types of hypersensitivity are involved in cAD?
Type 1 hypersensitivity:
- IgE bound to mast cells
- Allergen bound by IgE causes mast cell degranulation
- Products of mast cell degranulation cause tissue inflammation and pruritus
Type IV hypersensitivity (TH2 bias)
- Allergen peptides presented to T-cells by Langerhans cells
- Induce clonal expansion
- T-cells produce pro-inflammatory cytokines which cause tissue inflammation and pruritus (IL-4, IL-5, IL-13 and IL-31) - IL-31 most important
- T-cells produce cytokines which direct B-cells to produce IgE
What causes the subacute/chronic reaction of cAD? And what does it result in?
Influenced by secondary infection
TH2 bias reduced (e.g. IL-31, IL-4, IL-13)
Chronically TH1 cytokines also involved (e.g. IL-2, γ-IFN)
Tissue inflammation results in:
- Skin thickening through hyperplasia
- Increased numbers of Langerhans cells
- Reduced cutaneous barrier function
- Increased bacterial numbers on/in the skin
Why is there a defective barrier function in cAD?
Increased transepidermal water loss (TEWL)
Wide intercellular spaces between corneocytes
Disorganised & fragmented lipid matrix
Decreased levels of certain proteins and lipids in some breeds
n.b. can be primary or secondary
What microbial colonisation is seen with cAD? Why? What problems does this cause?
Increased carriage of Staphylococci
- Increased binding sites (due to inflammation)
- Reduced lipids and proteins (barrier function)
- Damage to skin surface (due to self trauma)
- Dysbiosis
- Reduced diversity
- Reduced balance between commensals and immune system
Very common to see secondary staphylococcal pyoderma and otitis and malassezial dermatitis in cAD = atopic flares
Induce further inflammation and pruritus - often not alleviated by specific anti-pruritics (e.g. Lokivetmab or oclacitinib)
Common causes of atopic flares?
Bacteria and yeast secondary infection Increases in allergens seasonally/changes to environment Fleas, scabies etc Reduction of therapy by owner/vet: - attempts to minimise treatment - cost - running out of meds - reducing meds through fears of adverse drug reactions
Treatment aims for cAD?
Improve skin barrier
Allergen avoidance and ASIT
Control inflammation and pruritus
Control flare factors
Diagnosis basis of cAD?
Compatible history Clinical signs Exclusion of differential diagnoses Once done these, can make diagnosis (don't need allergy testing esp as 20% may be negative) (Ie there are no pathognomonic signs)
Differential diagnoses for pruritus?
Ectoparasites - Sarcoptic mange, Cheyletiellosis, flea infestation and hypersensitivity, Trombiculiasis, pediculosis, Otodectic mange, Demodex canis/injai/gatoi
Allergic skin disease - cAD, contact dermatitis
Microbial infection - bacterial pyoderma, Malassezia dermatitis
Pemphigus foliaceus
Epitheliotropic lymphoma
Compatible history for cAD?
Pruritus seasonal or perennial or both
- pruritus precedes skin lesions
- 75% of dogs develop signs <3yo (up to 6yo)
- NB FIAD more commonly starts <1yo
Certain breeds predisposed (e.g. WHWT) but can be any breed
Certain breeds may have certain distribution
May have affected relatives
cAD: Signs of pruritus? Primary lesions? Secondary lesions? Distribution of lesions?
Main sign is PRURITUS and precedes other lesions Signs of pruritus = scratching, rubbing, chewing, excessive grooming or licking, scooting, and/or head shaking Primary lesions may also include erythema +/- papules Secondary lesions due to pruritus: - alopecia - excoriations - salivary staining - lichenification - pustules, epidermal collarettes and crusts - hyperpigmentation - otitis Distribution: - face and chin - periorbital areas - ear pinna (not pineal margins) - elbow creases - feet (dorsal interdigital spaces and plantar/palmar) - ventral abdomen and axillae - perianal area Usually bilateral symmetrical
Favrot’s criteria (2010) for diagnosis of cAD?
- Onset of signs <3yo
- Dog mostly lives indoors
- Glucocorticoid-responsive pruritus
- Pruritus sine materia at onset
- Affected front feet and/or ear pinnae
- Non affected ear margins
- Non affected torso-lumbar area
5/7 signs = 85% se, 79% sp
How to exclude differential diagnoses for cAD?
Exclude ectoparasites:
- flea combing
- scale exam
- acetate tape strops
- hair plucks
- skin scrapes
- treatment trials needed for parasites that are in the environment or hard to find (scabies, fleas) and treat house
Identify and treat S.pseudointermedius and Malassezia pachydermatitis (commensals of skin, overgrow due to underlying allergic skin disease):
- cytology from impression smear and/or acetate tape impression
- fungal culture no value for Malassezia
Food hypersensitivity - Aetiology? History? Signs?
May be immune mediated, toxic, or non immunological
Most are food allergy and ‘atopy like’ or food-induced atopic dermatitis (FIAD)
15-60% have concurrent GI disease
Non seasonal, pruritic skin disorder associated with a new substance in the diet
Many cases are young dogs (<1yo) but not always
Pruritus is only consistent finding
May be associated with wheals, papules, erythema etc
Pruritus may be poorly responsive to steroids
Breeds predisposed: WHWT, boxer, Rhodesian ridgeback, pugs, GSD
Comparison between cAD and FIAD?
Clinical signs identical except
- Poss increased Malassezia overgrowth in FIAD
- No seasonality in FIAD
- Young age of onset for FIAD
- GI signs more common in FIAD
Food trials for FIAD/CAFR? How long for? Common allergens? Options?
Minimum 6 weeks (8 weeks better)
Common allergens: beef, lamb, milk (avoid these!)
Home cooked
- gold standard
- problems with identifying appropriate ingredients, unsuitable for long term use/growing animals, labour intensive, palatability, GIT upsets, cost
Commercial novel protein diets:
- nutritionally balanced
- improved owner compliance
- problems: availability of novel ingredients?, hidden allergens/additives? ‘Hypoallergenic’ means nothing on dog food so look for diets with research backing
Hydrolysed protein diets:
- assumes type I hypersensitivity so benefit for dogs with non-IgE mediated hypersensitivity unknown
- lowest allergenicity with more hydrolysation but gets expensive
Environmental allergen testing for cAD?
Not a diagnostic test (false positives and negatives)
Used to identify enviro allergen-specific IgE for use in management where cAD has been confirmed
Raised serum IgE in >75% of patients
IDT or IgE serology using FcER1 technology/dog specific monoclonal Ab
- serology measures circulating allergen-specific IgE
- IDT indirectly measures cutaneous mast cell reactivity due to the presence of IgE
- poor correlation between tests
- success of ASIT not significantly different using either test
- not useful for diagnosis of food allergy
Reasons for negative allergy testing with cAD?
Age of patient (<12mo often negative)
Improper technique/allergen concentration
Drug interference
Intrinsic host factors (breed differences in IgE production)
Incorrect selection of allergens
IDT performed too long after (>60d) or during peak allergy season
Atopic-like dermatitis
Aims to improve skin barrier function for cAD?
Reduce transepidermal water loss
Reduce exposure to environmental allergens and irritants
Reduce microbial colonisation
Reduce cutaneous inflammation
Treatments for improving the skin barrier function of cAD?
Non irritating shampoos
- emollient shampoos likely to be most soothing
- anti-seborrheic for skin greasiness or scaling
- antiseptics for infections
- add topical moisturisers to prevent excessive drying
- intensity and frequency of bathing may be most important factor
- consider impact on topical flea products (use tablets if poss)
Oral EFAs supplements/enriched diet:
- omega 3 and 6 oils
- safe
- take 8-12 weeks
- glucocorticoid and small cyclosporin sparing effect
Topical EFA-containing formulations:
- help to normalise existing stratum corner defects
- likely no benefit compared to oral supplement
Anti-inflammatory and anti-pruritic therapies for cAD?
Glucoroticoids: - systemic (pred, methyl pred, dex) - topical (betamethasone, hydrocortisone aceponate) Calcineurin inhibitors - systemic (ciclosporin) - topical (tacrolimus ointment) Novel Janus Kinase inhibitor - Oclacitinib Biologics - Lokivetmab Antihistamines
Systemic glucocorticoids for cAD - Advs? Adverse signs? When to avoid? How best used?
Advs - consistent efficacy with minor and predictable adverse effects
Adberse effects - polypagia, PUPD, panting, behaviour changes, iatrogenic HAC, increased UTI risk
Avoid as sole therapy in young dogs and perennial clinical signs
Good used as ‘crisis busters’:
- maintain on non-GC baseline therapy
- treat acute exacerbations with systemic GCs for 3-5 days
- if flares too frequent then need more aggressive baseline therapy
Topical glucocorticoids for cAD - How works? Side effects? How to use?
Hydrocortisone aceponate
Topical diester glucocorticoid
Potent anti-inflammatory effect
Metabolised within the dermis - very little active drug reaches circulation so minimal systemic effects
Effective
Major safety risk is skin thinning with prolonged use - prevented by intermittent application
E.g. use twice weekly - delays recurrence of flares
Oral clacineurin inhibitors for cAD? - How does it work? Adverse effects?
Ciclosporin
Inhibits T lymphocyte function via blocking calcineurin
Adverse effects:
- GI signs
- gingival hyperplasia
- viral papillomas
- hirsutism
Effective and adverse effects usually minor
Comparable efficacy to oral GCs but slower onset of action (4-8 weeks for full response) so often start with steroids then taper off
Topical calcineurin inhibitors for cAD - what is available?
Tacrolimus ointment Suggested efficacy Expensive Not licensed Valuable in dogs with skin atrophy 'Burning sensation' reported in people
Janus Kinase Inhibitor for cAD - How does it work? Adverse reactions? Contraindications?
Oclacitinib
JAK1-enzymes involved in signal transduction of pro-inflammatory, pro-allergic and pruritogenic cytokines (IL-2, IL-4, IL-6, IL-13, IL-31)
JAK2 - dependent signally associated with changes in the haematopoetic system
Preferential inhibitor of JAK1
Effective and safe
Rare adverse effects - mainly mild GI signs
Haematological/biochem changes - significance?
Haematology/biochemistry/urinalysis recommended regularly on data sheet (usually before, 6-8 weeks after and then 6 monthly)
May increase susceptibility to infection and exacerbate neoplastic conditions
Contraindications: <12mo or <3kg BW, breeding dogs, dogs with serious infections, underlying neoplasia, immune suppression
Quick onset of action
What is Lokivetmab for cAD? How does it work? Contraindications?
Anti-canine IL-31 monoclonal antibody
Caninised monoclonal antibody that specifically targets and neutralises canine IL-31 (pruritogenic cytokine)
Highly targeted -> minimal impact on normal immune functions
Eliminated via normal protein degradation pathways (minimal involvement of liver or kidneys)
Contraindicated <3kg BW
Antihistamines for cAD?
Poor efficacy, good safety
Chlorpheniramine and hydroxyzine may have medium efficacy combined - best used as preventative before flare occurs (continuous daily basis)
Allergen avoidance for cAD?
House dust mires most important source of allergens - environmental flea sprays can reduce levels
Sleep in cages etc
What is allergen specific immunotherapy for cAD (ASIT)? How is it made? How quick does it work?
= administering gradually increasing quantities of an allergen extract to ameliorate symptoms associated with subsequent exposure to the causative agent.
Use allergen specific intradermal testing or IgE serology to identify specific hypersensitivities
Must be based on these results and history
Slow onset: 4-6 months (trial for 12 months)
Uncommon adverse effects but serious if occurs
Controlling flare factors for cAD?
Control parasites - topical monthly treatment, treat house q4-6 months
Antimicrobials (topical if poss) if signs of infection or colonisation are present
Avoid known flare factors
Treat secondary infections
Chlorhexidine shampoos to avoid infection
Stress - work related pressure, behavioural therapy, adaptil
Environment - irritants, temperature, humidity
Food allergens
Monitoring of cAD therapy?
Assess every 2-6 weeks until stable
Continue to assess every 6-12mo if good control, more frequently if poor control
Tailor to individual
What is the middle ear lined by?
Modified respiratory epithelium
Some ciliated and secretory cells (mucus)
Ear margin seborrhoea - Breeds? Signs? Treatment?
Relatively uncommon
Marked breed predilection in Dachshunds
Can be a feature of hypothyroidism
Adherent keratin on both medial and lateral sides of the pinna
Follicular casts and plugs may trap hair
Rubbing produces erosions and ulceration
Pruritus is variable
Fissuring and secondary infection can be problematic
Treatment: emollient rinses, vaseline, propylene glycol, surgery
Ear physiology?
Temp 38-2-38.4C
Humidity 88.5C
pH 6.2
Sebaceous glands
Ceruminous glands (modified sweat glands)
Lipids and sloughed keratinocytes form cerumen - traps small FB, anti-bacterial/yeast, epithelial migration moves wax from TM to external space
Normal ear canal flora?
Gram +ve cocci predominate (but no growth in some dog’s ears)
Similar species to those found on the skin
Micrococcus spp.
Coagulase negative staphylococci, Staphylococcus schleiferi and Staphylococcus pseudintermedius
Streptococcus species
Malassezia
Otitis externa pathophysiology?
Most important factor is humidity - this changes the epithelial defences and microbiological proliferation
Predisposing factors for otitis externa?
Conformation: - Excessive hair growth in canals (e.g. poodle) - Hairy concave pinna (e.g. cocker spaniel) - Pendulous pinna (e.g. basset hound) - Stenotic canals (e.g. shar pei) Excessive moisture: - Environment (heat & high humidity) - Water (swimmer’s ear, grooming, cleaners) Obstructive ear disease: - Feline apocrine cystadenomatosis - Neoplasia - Polyps Primary otitis media - PSOM in CKCS, tumour or sepsis Treatment effects - Altered normal microflora (e.g. inappropriate cleaner) - Trauma from cleaning or plucking
Primary causes of otitis externa?
Parasites: - Otodectes cynotis - Demodex spp. - Scabies Foreign bodies: - Grass awns Hypersensitivity: - Atopic dermatitis - Food hypersensitivity - Medications Keratinisation disorders: - Primary idiopathic seborrhoea - Hypothyroidism Glandular disorders: - Cocker spaniels, English springer spaniels & Labrador retrievers have increased ceruminous glands Miscellaneous: - e.g. feline proliferative & necrotising otitis externa
Otodected cynotis (ear mites) - Signs? Treatment?
Common cause of otitis
Dark wax, small white mites (photophobic)
Hypersensitivity disease
Most ear creams are effective with localised disease
Selamectin or moxidectin spot-on
Evidence that the isoxazoline group are effective
May need a cleaner ± steroids for secondary disease
Grass seeds causing otitis - Signs?
Late spring to end of summer
Often stimulate violent response in the affected individual - sudden onset
Check the other ear!
Can be hidden in discharge and migrate into middle ear
Grass seeds causing otitis - Signs?
Late spring to end of summer
Often stimulate violent response in the affected individual - sudden onset
Check the other ear!
Can be hidden in discharge and migrate into middle ear
Painful - chemical restraint essential in most to remove
Which bacteria tend to cause secondary acute and chronic otitis externa?
Acute: gram positive: - Staph - Strep - Corynebacterium Chronic: gram positive: - Enterococcus Chronic: gram negative: - Pseudomona - Proteus - E.coli
What pathological changes can happen to the external ear canal as a result of otitis externa? Acute and chronic changes?
Inflammation causing failure of epithelial migration
Acute change: oedema, hyperplasia
Chronic change: proliferative change, canal stenosis, calcification of pericartilaginous fibrous tissue
Hyperplasia of ceruminous and sebaceous glands
Hidradenitis
Changes to the tympanum as a result of otitis externa?
Dilation, rupture, diverticulum
Clinical signs of otitis externa?
Aural pruritus or head shaking Mild to marked exudate Malodour Head tilt Deafness Erythema, swelling, scaling, discharge Pain Secondary pineal lesions, pyotraumatic dermatitis, haematoma
How does otitis externa progress from primary to secondary disease?
Often Malassezia -> Staph -> Gram negative rods
If treated inadequately, potential for antimicrobial resistance
In many cases, Pseudomonas aeruginosa is end point
Progressive pathoglocial changes:
- Epidermal hyperkeratosis and hyperplasia
- Dermal oedema
- Fibrosis
- Ceruminal gland hyperplasia and dilation
- Abnormal epithelial cell migration
- Tympanic membrane alterations
- Otitis media (16% of acute OE, 50–80 % of chronic OE)
Consequences of Otitis media?
Conductive deafness:
- Loss of drum
- High pressure fluid/mucous in the middle ear
- Chronic OE or OM ± cholesteatoma
Horner’s syndrome/facial paralysis:
- Ear and lip droop, asymmetrical lips, dribbling
- Keratoconjunctivitis sicca, neurogenic dry nose
- Anisocoria with ipsilateral miosis, ptosis of the upper eyelid etc.
Vestibular syndrome (otitis interna [OI])
Horner’s syndrome - Signs?
Drooping of eyelid on affected side (ptosis)
Pupil of affected eye will be constricted (miosis), or smaller than usual
Affected eye often appears sunken (enophthalmos)
Third eyelid of affected eye may appear red and raised or protruded (conjunctival hyperemia)
Primary secretory otitis media (PSOM)? Which breeds? Signs? Treatment?
CKCS and brachycephalic breeds
Presented for deafness or neck pain!
Marked mucoid build-up in the middle ear
Bulging middle ear noted on otoscopy
Repeated flushing and myringotomy (3-5 times)
Sputolysin (mucolytic) has been used by some
Steroids are used to reduce mucous production
Clinical signs of otitis media?
Pain - often localised to head/neck, with spontaneous episodes of vocalisation and a guarded and horizontal neck
Neurological signs: ataxia, facial paralysis, nystagmus, head tilt or seizures
Pruritus around ears without external otitis
Otitis externa
Deafness
Fatigue
Signs of OI if progression
How to investigate otitis media?
Appearance of the drum on video otoscopy Sampling of the middle ear for Bacteriology Fungal culture Cytology via myringotomy or ruptured TM Palpation of granulation tissue in the middle ear BAER (hearing testing) Imaging
When is myringotomy used?
Bulging TM with pain or neurological signs (Horner’s, vestibular signs, facial paresis)
Radiographic/MRI bulla changes and intact TM
Evidence of tissue or fluid behind the TM
Medically unresponsive vestibular disease with an intact TM
Chronic otitis cases longer than 6 months that have not responded to treatment for otitis externa (requires judgement)
How is myringotomy done?
Clean and dry the external ear canal
Incision made
Passed through either hand held or video otoscope
Position:
- caudoventral aspect of the pars tensa to avoid damaging the tympanic germinal epithelium and the structures of the middle ear
Sampling:
- Pass swab(s) for cytology and bacteriology
- instilling and then withdrawing a small amount of sterile saline solution
Flush with saline (± other agents depending on the cytology results)
BAER for otitis media? What is it?
Brainstem auditory evoked response
Click applied to tested ear (white noise to other)
Peaks of response respond to transition through differing structures (e.g. peak I = vestibulocochlear nerve)
Normal dog – threshold <10dB
Otitis interna: Aetiology? Clinical signs? Treatment?
May develop from OM extension (majority) or haematogenous and ascending infection via auditory tube Clinical signs: - head tilt to affected side - spontaneous or rotatory nystagmus - assymetric limb ataxia with preservation of strength - falling - V+ and/or anorexia Long term systemic antibiotics
Options for otoscope if ear very painful?
Don’t look
Admit for chemical restraint
Treat for short period and then reassess
Examination of the ear canal with an otoscope - What to look for?
Is the surface of the epithelium smooth?
Is the surface of the canal red?
Is the lumen open and consistently so?
Nature of discharge?
Epithelial migration?
Check for swelling, ulceration, hyperplasia, hair, masses
Check for wax, pus, ear mites, foreign bodies and occlusion in lumen
Drum present or absent, changes in colour, bulging?
No wax in unusual, heaped or spread along canal? (Crude measure of epithelial migration)
What does the nature of the ear canal exudate in otitis suggest for possible pathogens:
- dry coffee granules?
- moist brown?
- purulent yellow/green (malodorous)
- ceruminous discharge (often little smell)
Dry coffee granules - Otodectes cynotis
Moist brown - Staph, Malassezia
Purulent yellow/green (malodorous) - Gram -ves (esp. Pseudomonas)
Ceruminous discharge (often little smell) - allergy, endocrine (esp hypothyroidism), keratinisation defects, bacteroides
What must always be done for an otitis??
Cytology!
+/- bacteriology and susceptibility - affected by previous antibiotic ear creams and cleaners - flawed when considering topical treatment!!!
Indications to flush an ear?
Diagnostic:
- To see epithelium of ear canal (hyperplasia, ulceration, masses etc)
- Check integrity of drum
Therapeutic:
- Dilutes and removes, bacteria, yeasts and inflammatory mediators
- Antimicrobial effects of some cleaners
- Removes pus which may inactivate antibiotics
- Removes old treatments
Anaesthesia needed for adequate flushing of severe/chronic otitis (Et tube protects aspiration, hearing often present with sedation)
What should be used to flush ears?
Normal saline (most often used) - safe, sterile, widely available
Dilute povidine iodine - some recommend, some think ototoxicity
Chlorhexidine - problematic at higher concentrations, 0.15% safe in dogs (not cat)
Others for use after drum known to be intact:
- cerumolytics emulsify ear wax for easy removal e.g. squalene, alcohols
- aqueous solutions aid in removing pus, mucus and serum
- drying agents decrease moisture and desiccate surface keratinocytes e.g. boric acid
What are the 3 principles for treating otitis? What do medications contain?
- Remove/reduce microbes
2/ Reduce swelling, discomfort or pain - Normalise canal lumen and function
Polypharmacy - antibiotic, antifungal, anti-inflammatory agent
How to decide with otitis ear cream/ointment to use?
Potency of steroid:
- highly inflamed ear -> need greater potency (dexamethasone)
- diabetic -> low systemic absorption (hydrocortisone aceponate)
Antibiotic:
- correct for cytological organisms sean
- potential for ototoxicity (e.g. not gentamycin)
- antibiotic stewardship (e.g. fucidic acid)
Antifungal - less need for choice
Ease of use - e.g. Osurnia
Which drugs are ototoxic?
Gentamicin Polymixin B Ticarcillin and imipenem Propylene glycol Chlorhexidine at moderate concentrations If have to use, avoid concurrent use of drugs which may increase ototoxicity: - frusemide and other loop diuretics - cis-platin - erythromycin - NSAIDs
