Use and abuse of topical steroids Mrs Sue Paterson MA Vet MB DVD Dip ECVD MRCVS RCVS and European Specialist in Veterinary Dermatology Rutland House Referral Hospital St Helens

What do steroids do? Which steroids should we use in which situation? How can we use those properties to advantage and avoid side effects?

How do glucocorticoids affect the body? Liver – increased gluconeogenesis, increased glycogen stores Muscle – increased protein catabolism causing muscle wastage and weakness Bone – osteopaenia - increased protein catabolism & negative Ca balance Kidney – increased GFR, interference with vasopressin release or action, increased Ca excretion

How do steroids affect the skin ? Immune system – reduced inflammatory response, reduced immune response Skin – increased protein catabolism. Atrophic changes within the skin

Immune system Eosinophils – reduced formation in bone marrow, reduced survival time Mast cells – reduce mast cell numbers and histamine synthesis Neutrophils – increased release from bone marrow & neutrophilia - reduced margination & diapedesis into tissues. Reduction in chemotaxis, adherence & enzyme secretion Humural immunity – reduction in Ig production after high dose long term therapy

Skin Epidermal atrophy causing skin thinning, poor wound healing and poor scar formation, skin bruises easily Follicular keratosis, atrophy and telogenisation of hair follicles Sebaceous gland atrophy

Which topical steroids should we use ? Steroid absorption Steroid potency

Absorption of steroids Factors that influence absorption High concentrations Abraded or inflamed skin Occlusive dressings Steroid vehicle – gel v ointment

Shows adrenal suppression is concentration and vehicle dependent Aniya JS Griffin CE The effect of otic vehicle and conc of dexamethasone on liver enzyme activity and adrenal function in small breed healthy dogs Vet Derm 19(4) 226-231 2008 Comparison of liver function tests & ACTH stimulation tests in 3 groups of dogs treated over 2 weeks 2 x daily Grp 1 - 0.01% dexameth in saline, Grp 2 - 0.1% dexameth in saline, Grp 3 - 0.1% commercial otic prep. Group 1 – 6/6 dogs no changes on ACTH or liver tests Group 2 – 4/7 adrenal suppression but not liver enzymes Group 3 – 4/6 adrenal suppression & 3/6 marked suppression, 1 dog mild liver enzyme changes Shows adrenal suppression is concentration and vehicle dependent

Absorption of steroids Factors that influence absorption High concentrations Abraded or inflamed skin Occlusive dressings Steroid vehicle – gel v ointment

Thomas RC Logas D et al. Effects of a 1% hydrocortisone conditioner on haematological and biochemical parameters, adrenal function testing and cutaneous reactivity to histamine in normal and pruritic dogs Vet Derm 10(2), 109-116 1999 1% hydrocortisone leave on conditioner applied 2 x weekly for 6 weeks to normal and pruritic dogs In normal dogs – no changes were seen in haematology, biochemistry or ACTH stimulation tests In pruritic dogs – ACTH stimulation tests were depressed SAP was increased significantly but still in normal range Histamine reactivity unchanged in both groups Shows that topical steroid absorption is enhanced through inflamed skin

Which topical steroids should we use ? Steroid absorption Steroid potency

Classification of steroid potency UK system – 4 grps mild, moderate, potent, very potent USA system – 7 grps least potent (VII), low (VI), medium (V/IV), med/high (III), high (II), ultra-high (I)

Topical steroid potency Topical steroid potency is classified by the individual steroid molecule. Potency can be altered by the drug concentration and if the steroid has been halogenated, methylated, acetylated or esterified Potency can be altered by the vehicle e.g. ointment, cream or gel

Potency is an intrinsic property of the drug and is not the same as concentration Betamethasone dipropionate 0.05% is more potent than Hydrocortisone 1%. Betamethasone is a more potent steroid than hydrocortisone despite it only being 1/20 of the concentration Concentration is only important when the same molecules are compared Triamcinolone acetonide cream 0.5% is more potent than Triamcinolone acetonide cream 0.1%

How chemical changes in the steroid change potency Halogenation, methylation, acetylation or esterification of a steroid will increase its potency Hydrocortisone 1% spray VII least potent Hydrocortisone aceponate 0.0584% spray (HC ester) IV/V medium strength

How the vehicle changes the potency Ointments provide lubrication but are occlusive. Occlusion improves steroid absorption. Creams provide lubrication but are less occlusive than ointment. Creams are generally less potent than ointment of the same medication Lotion and gels are the least greasy & occlusive of all topical steroid vehicles. Betamethasone valerate ointment Grp III med/high potency Betamethasone valerate cream/gel Grp IV/V medium potency

Use of specific topical glucocorticoid products

Potency of some topical steroids VII Least potent 1% Hydrocortisone spray, gel* VI Low strength 0.1% dexameth lotion*, 0.015% triamcin acetonide spray* IV/V Mid-low strength 0.0584% HC aceponate spray*, 0.1% betameth valerate gel* 0.1% triamcin acetonide ointment* III Upper mid strength 0.1% Momet furoate oint* II Potent 0.05% betameth dipropionate ointment I Ultra potent 0.05% clobetasol propionate

Hydrocortisone aceponate IV/V Mid-low strength 0.0584% HC aceponate spray HCA is lipophilic diester of HC with enhanced skin penetration to produce local efficacy at low dose HCA is said to have high local activity with reduced systemic effects with minimal atrophogenic effects

Efficacy of a 0.584% HCA spray in the TX of CAD : a randomised, double blind placebo controlled trial Nuttall T Mueller R et al Vet Derm 20(3) 191-198 2009 Showed HCA significantly improved clinical signs including pruritus versus placebo. Showed no side effects used sid / 28 days then eod / twice wkly / 42 days Comparable efficacy of a topical 0.584% HCA spray and oral ciclosporin in tx CAD Nuttall T, McEwan NA et al Vet Derm Vol 23(1) 4-10 2012 Study compared HCA (2 sprays /100cm2 ) with ciclosporine (5mg/kg) sid over 84 day period. No significant difference in level of control in either grp. By day 84 13/24 HCA and 12/21 ciclosporine were tx eod or 2x wkly

General and local tolerance of a 0 General and local tolerance of a 0.584% HCA spray applied daily on dogs for 14 days Rey-Grobellet X et al Proc. 56th SCIVAC 2007 Repeated applications of a 0.584% HCA spray for 8 weeks in dogs, impact on skin thickness Reme C et al Vet Derm 19 (1) 47 2008 Both studies showed no cutaneous atrophy with repeated application of the spray Effect of a novel topical diester G/C spray on immediate and late phase cutaneous allergic reactions in Maltese beagles atopic dogs: a placebo controlled study Bizikova P Linder KE et al Vet Derm 21 (1) 70-79 2010 Showed atrophy occurred in axilla and inguinal areas with reduction in immediate and late phase IDT reactions. Ventral axilla, groin and flanks are areas more prone to topical G/C effects

Betamethasone valerate gel IV/V Mid-low strength 0.1% betamethasone valerate gel

In vitro percutaneous absorption of fusidic acid and betamethasone 17-valerate across canine skin Degim IT et al J.S.A.P. Vol 40, 11 515 -518 1999 Showed that 10% of betamethasone valerate and 1.3% of fusidic acid penetrated the skin over 24 hour period Topical fusidic acid / betamethasone containing gel compared to systemic therapy in the treatment of canine acute moist dermatitis Cobb MA et al Vet Journ. 169(2) 276-280 2005 Comparison of 0.5% fusidic acid and 0.1% betamethasone 17 valerate gel with systemic therapy (dexamethasone and clavamox) in the treatment of 104 dogs with AMD. Good response seen in both grps and no difference between them

2) produce changes in the skin How to use steroids effectively 1) to regulate the immune system 2) produce changes in the skin

1) Regulation of the immune system Immune system – reduced inflammatory response, reduced immune response Anti-inflammatory properties can be used to treat allergic and other inflammatory disease. A reduction in the immune response is useful in autoimmune and neoplastic disease

Diseases where topical steroids may be useful Inflammatory diseases Hypersensitivity – flea allergy, atopic dermatitis, adverse food reactions Pyotraumatic dermatitis (hot spots) Contact dermatitis ( irritant or allergy) Immune / neoplastic diseases Immune mediated dermatoses – pemphigus, pemphigoid, DLE) Neoplasia – epitheliotropic lymphoma

Use in inflammatory diseases Hypersensitivity – flea allergy, atopic dermatitis, adverse food reactions Pyotraumatic dermatitis (hot spots) Contact dermatitis ( irritant or allergy) Aim to use the weakness topical steroid possible. In acute flares use a potent steroid and aim to reduce or withdraw as soon as possible

Use in immune mediated or neoplastic disease Immune mediated dermatoses – pemphigus, pemphigoid, DLE Neoplasia – epitheliotropic lymphoma Use a potent topical steroid and taper as quickly as possible

When does steroid use become steroid abuse ?

How can those properties causes problems ? Immune system – reduced inflammatory response, reduced immune response Where the inflammatory or immune response is protective then prevention of this can lead to problems with secondary infection (bacteria, yeast) or parasites (demodex)

How can problems be avoided in inflammatory skin disease? Hypersensitivity – flea allergy, atopic dermatitis, adverse food reactions Pyotraumatic dermatitis (hot spots) Contact dermatitis (irritant or allergy) Questions to ask Are there any primary lesions? What does cytology show? Have the signs improved as expected?

Presence of primary lesions Pustules – evidence of infection ? Often difficult to find but secondary lesions may be present – crust, scale epidermal collarettes Papules – evidence of infection or ectoparasites ? Satellite lesions useful to differentiate surface from deep infection in cases of AMD

Satellite lesions to help differentiate AMD from deep pyoderma Satellite lesions never present Cytology - non degenerate polymorphs – rare bacteria Deep Pyoderma Satellite lesions present Cytology degenerate neutrophils + bacteria Topical steroids contraindicated Topical steroids part of therapy

What does cytology show? Is there just an inflammatory infiltrate present ? Is there evidence of bacteria ? Is there evidence of yeast ? Is there evidence of parasites? If in doubt use an anti-pathogenic wipe/spray/wash before using topical steroid

Have the signs improved as expected? Has rational topical steroid therapy improved the animal as predicted ? If therapy is being used excessively e.g. HCA is being used daily to control pruritus suggests it is not appropriate therapy or other causes of pruritus present

How can problems be avoided in immune mediated and neoplastic skin disease? Immune mediated dermatoses – pemphigus, pemphigoid, DLE) Neoplasia – epitheliotropic lymphoma Questions to ask Are there compatible clinical signs? What does cytology show? Is it definitely an immune mediated disease?

2) produce changes in the skin How to use steroids effectively 1) to regulate the immune system 2) produce changes in the skin

To produce changes in the skin Skin – increased protein catabolism causing thin skin. Hair growth and glandular tissue in skin affected Thinning of the skin is useful where there is chronic hyperproliferative changes. Reduction in glandular secretion useful where there is over production

Diseases where topical steroids may be useful Proliferative otitis – hyperplasia of the wall of the canal with ceruminous and sebaceous gland hyperplasia Chronic skin change where the skin is lichenified and hyperplastic

When does steroid use become steroid abuse ?

How can those properties causes problems ? Skin – thin skin, poor wound healing, poor scar formation, skin bruises easily The ability of a topical steroid to thin the skin is not useful if the skin is normal and increased fragility is a disadvantage

How can those properties cause problems ? Skin – Atrophic changes to hair follicles, skin and sebaceous glands Excessive topical steroids can lead to hair loss and over drying of the skin

Take home messages Use the most appropriate topical steroid based on the case Allergy - use the weakest steroid and increase potency if required tapering asap Immune mediated disease - use a potent steroid and taper asap Use cytology to assess for infection and parasites before starting steroid therapy Use topical antibacterial and anti-yeast therapy prior to starting topical steroids if necessary