Efficacy of a soothing astringent topical spray Efficacy of a soothing astringent topical spray for the management of for the management of MalasseziaMalassezia

pododermatitis in dogspododermatitis in dogs

Dermacool®

A preliminary openA preliminary open--label clinical triallabel clinical trial

D.N.D.N. CarlottiCarlotti11, C.A., C.A. RèmeRème22

11DermatologyDermatology Veterinary Clinic, BordeauxVeterinary Clinic, Bordeaux--MerignacMerignac, France, France22VIRBACVIRBAC Laboratories, Carros, FranceLaboratories, Carros, France

47th BSAVA Congress, Birmingham, April 200447th BSAVA Congress, Birmingham, April 2004

Study rationale

Solutions for localised pedal dermatitisSolutions for localised pedal dermatitis

•• ≠≠ systemicsystemic azolesazoles (generalised, severe)(generalised, severe)•• azoleazole +/+/-- chlorhexidine shampoochlorhexidine shampoo•• azoleazole lotion, creamlotion, cream•• chlorhexidine soakschlorhexidine soaks

OpportunisticOpportunistic MalasseziaMalassezia

Primary diseasePrimary disease

Malassezia Malassezia overgrowthovergrowth

moisturemoisture, , surface lipidssurface lipidsepidermal barrierepidermal barrier

may prove may prove impractical orimpractical or

labourlabour--intensiveintensiveor shortor short--acting acting

Test an alternative “easy spot therapy” Test an alternative “easy spot therapy” using a leaveusing a leave--on residual spray, on residual spray, azoleazole-- && chlorhexchlorhex..--free, with both antiseptic and environment modifying propertiesfree, with both antiseptic and environment modifying properties

+ need to preserve + need to preserve sustained susceptibility sustained susceptibility to these key antifungal to these key antifungal

agents agents

P.J

asm

in

Animals

RecruitmentRecruitment•• Referral veterinary practice (Dr Carlotti,Referral veterinary practice (Dr Carlotti, DipDip ECVD)ECVD)

Inclusion criteriaInclusion criteria•• male & female dogs of any breed and agemale & female dogs of any breed and age•• presenting with presenting with erythematous feet (interdigital area)erythematous feet (interdigital area)•• MalasseziaMalassezia overgrowth evidenced by cytologyovergrowth evidenced by cytology

Exclusion criteriaExclusion criteria•• Parasitic pododermatitisParasitic pododermatitis•• Bacterial infectionBacterial infection•• ParonychiaParonychia•• Poor conformation, foreign body, granuloma, Poor conformation, foreign body, granuloma, neoplasianeoplasia•• Under or requiring immunomodulating therapyUnder or requiring immunomodulating therapy

Treatment

DermacoolDermacool®® BID for 15 daysBID for 15 days

spray on the lesionsspray on the lesions

contains:contains:•• PCMXPCMX & benzalkonium chloride& benzalkonium chloride

antisepticantiseptic•• MentholMenthol

soothing, relievingsoothing, relieving•• HamamelisHamamelis extractsextracts

drying, healingdrying, healing

D.N

. Car

lotti

NB: No other treatmentNB: No other treatment

Evaluation

D0 D7 D15

Scoring for pedal signsScoring for pedal signs

Lesions / signsLesions / signs•• erythemaerythema•• keratoseborrhoeic statuskeratoseborrhoeic status•• hyperpigmentationhyperpigmentation•• prurituspruritus

ScaleScale0/ none0/ none1/ mild1/ mild2/ moderate2/ moderate3/ severe3/ severe

Aggregate clinical scoreAggregate clinical score

ΣΣ scores / foot scores / foot (0(0--12)12)

Yeast quantitationYeast quantitation

Cellophane tape testCellophane tape test HeatHeat--fix,fix, DiffDiff--QuikQuik®® Counting / 30Counting / 30 hpfhpf (x1000, oil immersion)(x1000, oil immersion)

D. P

in

D. P

in

D. P

in

Results: baseline

•• Dog breeds: Labrador, West Highland White Terrier, BoxerDog breeds: Labrador, West Highland White Terrier, Boxer•• Age range: 2Age range: 2--8 years8 years•• Underlying disease: atopy, food allergy, idiopathicUnderlying disease: atopy, food allergy, idiopathic•• Statistical units of analysis: 16 feetStatistical units of analysis: 16 feet

0

4

8

12

16

erythema KSD Pigment Pruritus

Sign

Nb o

f fee

t 3210

Sign severity on D0Sign severity on D0

AggregAggreg. clinical score . clinical score ≥≥ 5 for 5 for 12 feet/16 12 feet/16

Yeast counts on D0Yeast counts on D0

0

10

20

30

40

50

60

70

80

90

Mea

nno

.of M

alas

sezi

a/ 3

0hp

f1 dot = 1 foot

Results: baseline

Variability of Variability of Malassezia Malassezia counts between microscopic fields on D0counts between microscopic fields on D0

0

10

20

30

40

50

60

70

80

90

100

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Foot

Num

ber o

f Mal

asse

zia

/hpf Need to count 30 Need to count 30

fields per foot to be fields per foot to be representativerepresentative…but tremendous work…but tremendous work

30 fields x 16 feet x 3 30 fields x 16 feet x 3 examination time points examination time points = 1440 fields counted !!!= 1440 fields counted !!!

Results: baseline

Correlation between clinical signs and Correlation between clinical signs and Malassezia Malassezia counts on D0counts on D0

0

10

20

30

40

50

60

70

80

90

0 2 4 6 8 10 12

Aggregate clinical scoreAggregate clinical score

Mea

nM

ean

no.

no. o

f of M

alas

sezi

aM

alas

sezi

a/ 3

0/ 3

0hp

fhp

f

Pearson r² = 0.2, NSPearson r² = 0.2, NS

Weak correlationWeak correlation

Signs also depend Signs also depend on underlying disease on underlying disease (allergy), reaction of the (allergy), reaction of the animal (foot licking)animal (foot licking)

Yeast overgrowth Yeast overgrowth depends on microdepends on micro--ecosystem conditionsecosystem conditions

Results over the study period

Clinical signs: globalClinical signs: global

Examination time point (day)Examination time point (day)

Mea

n ag

greg

ate

clin

ical

sco

re (

Mea

n ag

greg

ate

clin

ical

sco

re ( ±±

SE)

SE)

012345678

0 7 15

RM ANOVARM ANOVA, p < 0.0003, p < 0.0003

Decrease from D7 onwardDecrease from D7 onward

Clinical score Clinical score ≥≥ 55

•• D0: 12 feet /16D0: 12 feet /16

•• D7: 1 foot /16D7: 1 foot /16

•• D15: 3 feet /16D15: 3 feet /16

Mean reduction: 43%Mean reduction: 43%

Results over the study period

Clinical signs: splitClinical signs: split

0

4

8

12

16

D0 D7 D15

3210

0

4

8

12

16

D0 D7 D15

No.No.

of fe

etof

feet

PruritusPruritusErythemaErythema

SeveritySeverity

Erythema: progressive reduction, still 6 feet / 16 with high scoErythema: progressive reduction, still 6 feet / 16 with high score on D15re on D15

Pruritus: rapid reduction, still significant for 3 feet / 16 onlPruritus: rapid reduction, still significant for 3 feet / 16 onlyy

Results over the study period

Clinical signs: splitClinical signs: split

KSDKSDHyperpigmentationHyperpigmentation

HyperpigmHyperpigm.: progressive reduction (chronicity).: progressive reduction (chronicity)

KSDKSD: low incidence and severity, little affected: low incidence and severity, little affected

0

4

8

12

16

D0 D7 D150

4

8

12

16

D0 D7 D15

3210

No.No.

of fe

etof

feet

SeveritySeverity

Results over the study period

MalasseziaMalassezia countscounts

0

10

20

30

40

50

60

70

80

90

100

0 7 15

Mal

asse

zia

Mal

asse

zia

coun

t /co

unt /

hpf

hpf

Pooled data (16 feet x 30 microscopic fields / time )Pooled data (16 feet x 30 microscopic fields / time )

Examination time point (day)Examination time point (day)

RM ANOVARM ANOVA, p < 0.0001, p < 0.0001

Huge decrease from D7Huge decrease from D7

Mean counts (±Mean counts (± SDSD) / 16 feet) / 16 feet

•• D0: 22.3 (± 21.5)D0: 22.3 (± 21.5)

•• D7: 0.8 (± 1.2)D7: 0.8 (± 1.2)

•• D15: 0.1 (± 0.1)D15: 0.1 (± 0.1)

No. of feet for which mean No. of feet for which mean yeast count < 1yeast count < 1 hpfhpf / 30 fields/ 30 fields

•• D0: 0 / 16D0: 0 / 16

•• D7: 13 / 16D7: 13 / 16

•• D15: 16 / 16D15: 16 / 16

ConclusionsDermacoolDermacool®® spot therapy proved valuable spot therapy proved valuable in vivoin vivo to control signs and yeast to control signs and yeast proliferation associated with proliferation associated with MalasseziaMalassezia pododermatitispododermatitis

Convenient, well tolerated (no adverse event)Convenient, well tolerated (no adverse event)

MultiMulti--targeting: yeast killing + soothing, drying effects (“ seed & grtargeting: yeast killing + soothing, drying effects (“ seed & ground”)ound”)

Sustained release (Sustained release (encapsulationencapsulation technology: Spherulitestechnology: Spherulites®®) )

Need to address underlying allergic condition to achieve completNeed to address underlying allergic condition to achieve complete efficacye efficacy

OpportunisticOpportunistic MalasseziaMalassezia

AllergyAllergy

Malassezia Malassezia overgrowthovergrowth

epidermal lipidsepidermal lipidsTEWL TEWL moisturemoisture

inflammation, scratching inflammation, scratching epidermal barrierepidermal barrier

HamamelisHamamelis extractsextracts

MentholMenthol

PCMXPCMX ++ BenzalkBenzalk.. ChlChl..

DermacoolDermacool®® sprayspray