Transcript Which topical steroids should we use

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
1
 What
do steroids do?
 Which steroids should we use
in which situation?
 How can we use those
properties to advantage and
avoid side effects?
2
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
3
How do steroids affect the skin ?
Immune system – reduced
inflammatory response, reduced
immune response
 Skin – increased protein
catabolism. Atrophic changes
within the skin

4
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
5
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

6
Which topical steroids should
we use ?
 Steroid
absorption
 Steroid potency
7
Absorption of steroids
Factors that influence absorption
 High concentrations
 Abraded or inflamed skin
 Occlusive dressings
 Steroid vehicle – gel v ointment
8
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
9
Absorption of steroids
Factors that influence absorption
 High concentrations
 Abraded or inflamed skin
 Occlusive dressings
 Steroid vehicle – gel v ointment
10
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
11
Which topical steroids should
we use ?
 Steroid
absorption
 Steroid potency
12
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)

13
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
14
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%
15
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
16
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
17
Use of specific topical
glucocorticoid products
18
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
20
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
21
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
22
topical G/C effects
Betamethasone valerate gel

IV/V Mid-low strength
0.1% betamethasone valerate gel
23
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
24
How to use steroids
effectively
1) to regulate the immune
system
2) produce changes in the skin
25
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
26
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
27
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
28
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

29
When does steroid use
become steroid abuse ?
30
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)
31
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?
32
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
33
Satellite lesions to help differentiate
AMD from deep pyoderma
AMD
Deep Pyoderma
Satellite lesions
never present
Cytology non degenerate
polymorphs –
rare bacteria
Satellite lesions
present
Cytology
degenerate
neutrophils
+ bacteria
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
35
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
36
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?

37
How to use steroids
effectively
1) to regulate the immune
system
2) produce changes in the skin
38
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
39
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
40
When does steroid use
become steroid abuse ?
41
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
42
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

43
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
44