Topical polyhydroxy acid treatment for autosomalrecessive congenital ichthyosis in the golden retriever: aprospective pilot study

Anna Puigdemont* , Nicla Furiani† , Michela De Lucia‡ , Isaac Carrasco§ ,

Laura Ordeix¶ , Dolors Fondevila¶ , Laura Rami�o-Lluch** and Pilar Brazis**

*Facultat de Veterin�aria, Department of Pharmacology, Therapeutics and Toxicology, Edifici V, Universitat Aut�onoma de Barcelona, 08913

Bellaterra, Barcelona, Spain

†Studio di Dermatologia Veterinaria, via Morandi 7/C, 06083 Ospedalicchio di Bastia Umbra, Perugia, Italy

‡San Marco Veterinary Clinic, Via Sorio 114/C, 35141 Padova, Italy

§CNR Veterinaris, Riera Bast�e 22, 08830 Sant Boi de Llobregat, Barcelona, Spain

¶Facultat de Veterin�aria, Department of Animal Medicine and Surgery, Edifici V, Universitat Aut�onoma de Barcelona, 08913 Bellaterra,

Barcelona, Spain

**Laboratorios LETI, Edifici Astrolabio, Avinguda Cerdanyola 92, 08172 Sant Cugat del Vall�es, Barcelona, Spain

Correspondence: Anna Puigdemont, Department of Pharmacology, Therapeutics and Toxicology, Facultat de Veterin�aria, Edifici V, Universitat

Aut�onoma de Barcelona, 08913 Bellaterra, Barcelona, Spain. E-mail: anna.puigdemont@uab.cat

Background – Autosomal recessive congenital ichthyosis (ARCI) in golden retrievers is due to a PNPLA1 gene

mutation, which plays a role in epidermal lipid organization and metabolism. Topical therapies are used to reduce

scaling; however, there are few published efficacy studies.

Objectives – To examine the efficacy of topical treatment based on gluconolactone, a polyhydroxy acid with

known beneficial effects on stratum corneum structure.

Animals – Sixteen golden retriever dogs with clinical signs of ARCI and PCR-confirmed PNPLA1 gene mutation.

Methods – This was a prospective, multicentre, noncontrolled study. Dogs were treated with a shampoo and

lotion containing gluconolactone and other hydroxyl acids. Treatments were administered initially twice weekly

for two weeks, then once weekly for two weeks and finally once monthly. Examinations were performed prior

to and at 14 and 30 days of treatment to assess scaling, presence of other skin lesions and pruritus. In two dogs,

pre- and 30 day post-treatment, skin biopsies were obtained.

Results – The extent and size of the scales were reduced by 60% and 75% after 14 and 30 days of treatment,

respectively (P < 0.001). In 20% of the dogs, scaling was no longer observed after the first 30 days of treatment.

No other skin lesions or pruritus were observed in any dog. Post-treatment biopsies showed normalization of the

stratum corneummorphology and reduced hyperpigmentation.

Conclusion and clinical importance – The frequent use of a shampoo and lotion containing gluconolactone

may be an effective measure to improve skin scaling in golden retrievers with ARCI.

Introduction

Ichthyoses comprise a heterogeneous family of heredi-

tary cornification disorders caused by the abnormal differ-

entiation and shedding of keratinocytes (desquamation),

mainly in the outermost epidermal skin layer. The

described molecular mechanisms underlying ichthyosis

involve defects in the intracellular lipid barrier and corni-

fied cell envelope, and the abnormal deposition of keratin

or filaggrin degradation products, all of which play impor-

tant roles in skin barrier function.1–4 There are several rec-

ognized autosomal recessive congenital ichthyoses

(ARCI) disorders in dogs.5–8 The condition affecting

golden retrievers has been associated with mutations in

the PNPLA1 gene, which has a proposed role in epider-

mal lipid organization and metabolism.5 ARCI in golden

retrievers typically manifests as generalized skin scaling

giving rise to variably sized scales of different shades

ranging from white to black, mainly on the ventral and lat-

eral region of the neck and trunk. Occasionally, cerumi-

nous otitis and, rarely, hyperkeratosis of the paw pads

have been described.3

Suggested treatments for canine ichthyosis have

included a combination of topical keratolytic, keratoplastic

and moisturizer/humectant agents able to remove skin

scales and restore the epidermal barrier. These

Accepted 6 April 2018

Conflicts of interest: Laura Rami�o-Lluch and Pilar Brazis are

employees of Laboratorios LETI; they participated in the design

of the study and helped to the draft of the manuscript. No con-

flicts of interest have been declared by the other authors.

Sources of funding: This study was supported in part by LETI,

this included provision of the therapies for free

Previous presentations The study was presented in part as a

poster at the 16th Congreso de Especialidades Veterinarias

(AVEPA), Bilbao, Spain, 2017.

Parts of this study were presented at the North American Veteri-

nary Dermatology Forum, 2018, Maui, Hawaii. Vet Dermatol

2018; 29: page number(s) (Abstract).

© 2018 ESVD and ACVD, Veterinary Dermatology 1

Vet Dermatol 2018 DOI: 10.1111/vde.12654

treatments have been shown to offer only partial bene-

fit.1,9 In a case report of a cross-bred golden retriever–poodle with ARCI, improvement occurred, although mild

visible scaling remained on the dorsum and lateral thighs,

after 18 months of oral fatty acid supplementation com-

bined with weekly shampooing followed by topical appli-

cation of an essential oil and fatty acid-based product.10

In human patients, polyhydroxy acids and a and bhydroxy acids, are able to improve epidermal barrier func-

tion through their actions on lipid-processing and desqua-

mation-regulating enzymes.9,11 Gluconolactone is highly

active at acidifying skin pH, which limits the growth of

pathogenic skin flora.12 It also improves lipid metabolism

and inhibits the breakdown of corneosomes, thus drasti-

cally reducing the presence of scales on the skin.9,11 In

addition, the chemical structure of this polyhydroxy acid

with multiple hydroxyl groups promotes the binding of

water molecules, improving skin hydration.

The aim of this study was to test the efficacy of a topi-

cal treatment regimen, over a three month period, based

on the polyhydroxy acid gluconolactone, a and b hydroxy

acids, and other active keratoplastic and keratolytic com-

pounds specifically formulated for the management of

ichthyosis in golden retrievers.

Material and methods

Study design, subjects and treatmentsThis prospective study was conducted at two university veterinary

teaching hospitals and two veterinary clinics in Spain and Italy. Six-

teen golden retriever dogs, aged 1–7 years of both genders with

mean weight of 33.9 � 6.3 kg, were enrolled. A clinical diagnosis of

ichthyosis was made for each dog before their enrolment in the

study. Inclusion criteria were a clinical presentation compatible with

ichthyosis and a positive PCR test for the PNPLA1 gene mutation

(Laboklin; Bad Kissingen, Germany). Exclusion criteria were other

concomitant diseases including bacterial or yeast skin infections and

concomitant treatments with other shampoos or drugs (including glu-

cocorticoids, retinoic acids, fatty acid supplements) that could inter-

fere with keratoseborrhoeic signs and affect the efficacy of the

products under investigation.

The treatment products included a lotion and two shampoos (con-

centrated and maintenance). These formulations are commercially

available products containing a combination of several active ingredi-

ents including gluconolactone, a and ß hydroxy acids, and urea at dif-

ferent concentrations (Table 1). The lotion contains higher

concentrations of the active ingredients (including 5% gluconolac-

tone and urea) and the two shampoos contain concentrated (2% glu-

conolactone) or maintenance (1% gluconolactone) levels of the

active ingredients (LETI+Derma, Kerato line, LETI Animal Health; Bar-

celona, Spain).

Study procedures and data collectionAt the time of inclusion (Day 0), a clinician performed a dermatologi-

cal examination to assess the severity of scaling, including distribu-

tion and size of scales, the presence and severity of pruritus, and

completed a data sheet for each dog (Table 2). The distribution and

extent of scaling were reported using a body map. An unvalidated

subjective visual scoring system from 0 to 3 (0 = none, 1 = small,

2 = medium and 3 = large) was used by the veterinarian to grade

scale size and the severity of pruritus. Skin lesions other than scales

were reported and graded using the same 0–3 scale (Table 2).

The dermatological examination was repeated by the same clini-

cian on days 14 and 30 after the beginning of treatment using the

same evaluation system. At the end of the study (Day 90), scaling

was assessed based on information provided by the owner to investi-

gators via telephone communication. Reductions in the extent and

size of the scales on days 14, 30 and 90 compared to Day 0 were

subjectively estimated and expressed as percentage improvements.

On Day 90 (end of the study), the pet owner was contacted by tele-

phone to ask about the severity of scaling (extent and size of the

scales) and the percentage reduction in both factors compared to

before treatment. General questions about how difficult or easy the

regimen had been and whether any adverse effects occurred also

were answered by the owner on Day 90. Moreover, on Day 90, a sat-

isfaction form regarding treatment ease was also completed by the

owner and directly delivered to the veterinarian or sent by email. Pho-

tographs of the most affected areas were obtained by the veterinar-

ian (0, 14 and 30 days) or by the owner (90 days) at each time point.

Topical treatment was applied by the owner according to the fol-

lowing protocol: from Day 0 to Day 14, the concentrated shampoo

formulation and lotion (Kerato, Leti Animal Health) (Table 1) were

used twice a week. From Day 14 to Day 30, the maintenance sham-

poo formulation and lotion (Kerato, Leti Animal Health) were used

once a week, and finally from Day 30 to Day 90, the maintenance

shampoo was applied monthly. Owners were instructed to apply the

shampoo and wait for 10 min before rinsing. The lotion was sprayed

immediately after a bath 10–20 cm from the skin. The recommended

dose was two sprays per 100 cm2 (a 10 9 10 cm square). In the

most affected areas, owners were told that the lotion should be

applied until the zone was completely wet.

Histological examinationIn two of the dogs, two biopsy samples of the ventro-lateral aspect

of the thorax just behind the tip of the elbow were taken before and

30 days after starting the treatment. Skin samples (6 mm biopsy

punch) were collected under local anaesthesia by subcutaneous

injection of lidocaine hydrochloride 2% (B. Braun; Rubi, Spain). Skin

biopsies were fixed in 5% neutral buffered-formalin for 24 h and then

embedded in paraffin wax and processed routinely; sections were

stained with haematoxylin and eosin. The study was conducted fol-

lowing approval from the UAB Institutional Animal Care and Use

Committee requirements.

Statistical analysisResults are expressed as the mean � standard error (mean � SEM).

Differences between means were tested, using Microsoft� excel,

Table 1. Active components of the Kerato (Leti Animal Health) topical formulations used to treat golden retriever dogs with ichthyosis

Active ingredients Concentrated shampoo (%) Maintenance shampoo (%) Lotion (%)

Gluconolatone 2 1 5

Salicylic acid <1 <1 <1Glycolic acid <1 - <1Lactic acid <1 - <1Citric acid <1 - <1Malic acid <1 - <1Tartaric acid <1 - <1Urea - - 5

Aloe <1 <1 <1

© 2018 ESVD and ACVD, Veterinary Dermatology2

Puigdemont et al.

for significance using the Student’s t-test for unpaired data with sig-

nificance set at a P < 0.05.

Results

Sixteen golden retriever dogs with a clinical and genetic

diagnosis of ARCI underwent the 90-day topical glucono-

lactone-based treatment regimen. One dog was with-

drawn from the study on Day 22 for reasons unrelated to

treatment.

All of the animals enrolled showed mild to severe gen-

eralized skin scaling distributed over the body including

the lateral and ventral aspects of the neck, the trunk,

rump and ventral folds (inguinal and axillary areas). Large

white or black scales were adhered to the skin and hair

shafts (Figure 1). Pruritus or skin lesions other than scal-

ing were not observed in any of the participants.

At the end of the three month treatment period, a satis-

factory decrease in skin scaling (extent and size of the

scales) was observed in all dogs, although the response

was different in time and magnitude in each animal. A

mean reduction in the extent and size of the scales (gen-

eral improvement) of 60% was observed after 14 days of

the initiation regimen (shampoo containing a high concen-

tration of active compounds). This improvement contin-

ued until an average reduction of scaling of 75% was

recorded after 30 days of treatment, and this percentage

reduction remained stable until the Day 90 time point (re-

ported by the owner) in response to the maintenance

treatment protocol (shampoo containing a lower concen-

tration of active compounds; Figures 1 and 2).

A reduction in the size of the scales (0–3 score) also

was observed over the course of the study, as shown in

Figures 1 and 3. The dog owners reported a significant

improvement in clinical signs in most cases and an

improvement in skin and hair condition in all dogs. After

30 days of treatment, lesions were completely resolved

in 20% of dogs, in 13% no improvement was observed,

and in the remaining 67% of the dogs, scaling was

reduced by 75%. The products were well-tolerated and

no adverse effects (erythema or pruritus) were observed

either during the initiation or maintenance therapy. The

mean owner satisfaction score regarding ease of treat-

ment was 7.2 on a scale of 1–10.Histological findings in two dogs before and after treat-

ment are illustrated in Figure 4. Before treatment, a com-

pact orthokeratotic hyperkeratosis was present and the

epidermis showed a pleated appearance (Figure 4a,c).

Keratin was hypereosinophilic and multifocal hyperpig-

mentation also was noted. Vacuolated single ker-

atinocytes were observed in the upper stratum

spinosum-granulosum (Figure 4, black arrows). After

treatment, the stratum corneum still showed orthokera-

totic hyperkeratosis although keratin was organized as a

laminated basket weave mesh and hyperpigmentation

was reduced. Vacuolated cells were still present in the

samples examined.

Discussion

Our findings indicate that treatment with a shampoo and

lotion containing gluconolactone and a and ß hydroxy

acids were effective at improving the skin condition of

golden retrievers with ichthyosis caused by a mutation in

the PNPLA1 gene. To the best of the authors’ knowledge,

this is the first prospective study to assess the efficacy of

topical treatment to control this chronic disease. As

ichthyoses are hereditary epidermal cornification disor-

ders that normally appear at a very young age and are life-

long, in human patients finding an effective and easily

applied treatment that can improve the health and appear-

ance of the skin would be worthwhile.13

In this study, treatment efficacy was assessed based

only on the extent and size of the scales. None of the

Table 2. Clinical scores and data collection sheet from Day 0 to Day 90 of treatment for golden retrievers with ichthyosis, treated with topical

therapies

Day 0 Day 14 Day 30 Day 90

Affected area

Dorsal

Ventral

Size of skin flakes* 0 - 1 - 2 - 3 0 - 1 - 2 - 3 0 - 1 - 2 - 3 0 - 1 - 2 - 3

Pruritus ** 0 - 1 - 2 - 3 0 - 1 - 2 - 3 0 - 1 - 2 - 3 0 - 1 - 2 - 3

Other skin lesions (e.g. excoriations, erosions) ** 0 - 1 - 2 - 3 0 - 1 - 2 - 3 0 - 1 - 2 - 3 0 - 1 - 2 - 3

General improvement (%)

Adverse effects after treatment?

Pictures of dog obtained

*0: none/ 1:small/ 2: medium/ 3: large.

**0: none/ 1: mild/ 2: moderate/ 3: severe.

© 2018 ESVD and ACVD, Veterinary Dermatology 3

Topical therapy for canine ichthyosis

a b

c d

Figure 1. Clinical response to topical therapy observed in two golden retriever dogs with autosomal recessive congenital ichthyosis (ARCI).

Pictures obtained before (a, c) and after one month of treatment (b, d).

Figure 2. Scores obtained for scale size (X � SEM) over the

30 days of topical treatment with polyhydroxy acids in golden retriev-

ers with ichthyosis.

All data points are veterinary evaluations except that at Day 90 which

denotes owner asessment. (n = 15) Scoring system 0 = none,

1 = small, 2 = medium and 3 = large. **P < 0.001 versus baseline

value.

Figure 3. Average percentage of general clinical signs reduction

(X � SEM) observed over the 30 days of treatment of golden retriev-

ers receiving topical therapy for ichthyosis.

All data points are veterinary evaluations except that at Day 90 which

denotes owner asessment (n = 15).

© 2018 ESVD and ACVD, Veterinary Dermatology4

Puigdemont et al.

dogs showed pruritus or lesions other than scales

supporting the absence of concomitant dermatological

diseases that could have confounded the results of our

trial. Although hyperpigmentation has been frequently

reported in golden retrievers suffering from this condition

we did not consider this factor useful to evaluate the

response to treatment. According to a previous report,

the presence and degree of hyperpigmentation may vary

according to the examination site and even if it generally

correlates fairly well with scaling there can be some dis-

crepancies in certain areas of the body between the two

lesion types (e.g. axillary and inguinal regions).2

The histopathological lesions observed in the selected

animals were characteristic of the disease.1 Due to the

genetic origin of the disease, medical treatments are not

expected to completely resolve both the macroscopic

and microscopic lesions. In fact, 30 days after the begin-

ning of treatment vacuolated keratinocytes were still pre-

sent in the upper stratum spinosum-granulosum, but

evident changes were produced in the organization of

keratin. In the stratum corneum, hyperkeratosis remained

but the keratin took on a more laminated, less compact

and woven appearance. These observations, albeit in only

two dogs, may help to explain the improvement observed

in clinical signs after one month of treatment and the lack

of recurrence of these signs noted in the following two

months of maintenance treatment.

One factor to consider when reviewing the results of

this trial is the lack of a control group. This means we

could not distinguish possible benefits attributable simply

to frequent bathing and hydration of the skin, which is

very important in this type of clinical disorder. Moreover,

due to the subjective nature of the scoring system used

to assess the extent and size of the scales, as well as the

rough estimation of the percentage reduction of scaling,

future clinical trials with validated scoring systems are

needed to confirm the results of this pilot study.

In human patients,11 polyhydroxy acids, such as

gluconolactone, can reduce skin pH and create a “super-

barrier” due to their effects on lipid-processing desqua-

mation enzymes produced through reduced serine pro-

tease-dependent desmoglein-1 degradation and induced

desmoglein-3 expression in the lower stratum corneum.

This effect has been demonstrated in a mouse model,11

and in human patients with acne,14 and could perhaps

explain the effect observed here in dogs with ichthyosis.

Through the capacity of gluconolactone to acidify skin pH,

lipid metabolism is improved and the breakdown of

a b

c d

Figure 4. Histopathological changes in skin biopsies obtained in two golden retrievers with autosomal recessive congenital ichthyosis (ARCI),

before and after topical treatment.

Note the diffuse laminar orthokeratotic hyperkeratosis in the stratum corneum and scattered vacuolated keratinocytes (arrows) in the stratum

granulosum and spinosum before treatment (a, c). In response to treatment, the keratin has a typical basket weave appearance but vacuolated

cells were still present (arrow) (b, d). Haematoxylin and eosin.

© 2018 ESVD and ACVD, Veterinary Dermatology 5

Topical therapy for canine ichthyosis

corneodesmosomes is impaired, thus drastically reducing

the presence of scales on the skin.11 In addition, the

chemical structure of gluconolactone includes several

hydroxide groups that form hydrogen bonds with water

molecules allowing the retention of water around glu-

conolactone and consequently improving skin hydration.

Hence, gluconolactone has a mechanism of action that

specifically addresses the main factors involved in cornifi-

cation disorders.

Other described topical treatments in dogs include the

use of emollients, moisturizers and essential oils, some-

times combined with oral fatty acid. Despite some benefi-

cial effects on the animal, no such treatment has served

to satisfactorily resolve the signs of this disease.1,10

Because of the genetic origin of ARCI, treatment can only

be targeted at controlling signs and attenuating typical

manifestations as much as possible. Congenital ichthyo-

sis cannot be cured and not all treatments achieve satis-

factory results for the owner and veterinarian.

In conclusion, this pilot study found topical gluconolac-

tone therapy to be a simple effective treatment for con-

genital ichthyosis in the golden retriever. Further

controlled studies are needed to confirm the beneficial

impacts of the active components tested here and to

assess their efficacy in other keratoseborrhoeic/kera-

tinization disorders that affect dogs.5–8

References

1. Mauldin EA, Credille KM, Dunstan RW et al. The clinical and

morphologic features of nonepidermolytic ichthyosis in the

golden retriever. Vet Pathol 2008; 45: 174–180.2. Cadi�ergues MC, Patel A, Shearer DH et al. Cornification defect

in the golden retriever: clinical, histopathological, ultrastructural

and genetic characterisation. Vet Dermatol 2008; 19: 120–129.3. Guaguere E, Bensignor E, Kuryy S et al. Clinical, histopathologi-

cal and genetic data of ichthyosis in the golden retriever: a

prospective study. J Small Anim Pract 2009; 50: 227–235.

4. Fleckman P, DiGiovanna JJ. The ichthyoses. In Goldsmith LA,

Katz SI, Gilchrest BA et al., eds. Fitzpatrick’s Dermatology in

General Medicine. 8th edition. New York, NY: McGraw Hill,

2012; 507–538.5. Grall A, Guagu�ere E, Planchais S et al. PNPLA1 mutations cause

autosomal recessive congenital ichthyosis in golden retriever

dogs and humans. Nat Genet 2012; 44: 140–147.6. Jagannathan V, Bannoehr J, Plattet P et al. A mutation in the

SUV39H2 gene in Labrador Retrievers with hereditary nasal

parakeratosis (HNPK) provides insights into the epigenetics of

keratinocyte differentiation. PLoS Genet 2013; 9(10): e1003848.

7. Casal ML, Wang P, Mauldin EA et al. A defect in NIPAL4 is asso-

ciated with autosomal recessive congenital ichthyosis in Ameri-

can bulldogs. PLoS ONE 2017; 12(1): e0170708.

8. Bauer A, Waluk DP, Galichet A et al. A de novo variant in the

ASPRV1 gene in a dog with ichthyosis. PLoS Genet 2017; 13(3):

e1006651.

9. Berardesca E, Distante F, Vignoli GP et al. Alpha hydroxyacids

modulate stratum corneum barrier function. Br J Dermatol 1997;

137: 934–938.10. Tamamoto-Mochizuki C, Banovic F, Bizikova P et al. Autosomal

recessive congenital ichthyosis due to PNPLA1 mutation in a

golden retriever-poodle crossbred dog and the effect of topical

therapy. Vet Dermatol 2016; 27: 306–e75.11. Hachem JP, Roelandt T, Sch€urer N et al. Acute acidification of

stratum corneum membrane domains using polyhydroxyl acids

improves lipid processing and inhibits degradation of cor-

neodesmosomes. J Invest Dermatol 2010; 130: 500–510.12. Korting HC, Kober M, Mueller M et al. Influence of repeated

washing with soap and synthetic detergents on pH and resident

flora of the skin of forehead and forearm. Results of a cross-over

trial in health probationers. Acta Derm Venereol 1987; 67: 41–47.

13. Hohl D. Les ichtyoses. In Saura JH, Grosshans E, Laugier P et al.

eds. Dermatologie et infections sexuellement transmissibles.

3rd edition. Paris, France: Masson. 2004; 207–214.14. Hunt MJ, Barnetson RS. A comparative study of gluconolactone

versus benzoyl peroxide in the treatment of acne. Australas J

Dermatol 1992; 33: 131–134.

R�esum�e

Contexte – L’ichtyose cong�enitale r�ecessive autosomale (ARCI) des golden retrievers est due �a une muta-

tion du g�ene PNPLA1 qui joue un role dans l’organisation et le m�etabolisme des lipides �epidermiques. Les

traitements topiques sont utilis�es pour r�eduire le squamosis, cependant, il existe peu d’�etudes d’efficacit�e

publi�ees.

Objectifs – Examiner l’efficacit�e d’un traitement topique compos�e de gluconolactone, un polyhydroxy-

acide, ayant des effets b�en�efiques connus sur la structure du stratum cormeum.

Sujets – Seize golden retrievers pr�esentant des signes cliniques d’ARCI et une mutation confirm�ee par

PCR du g�ene PNPLA1.

M�ethodes – Cette �etude est prospective, multicentrique et non control�ee. Les chiens ont �et�e trait�es avec

un shampooing et une lotion contenant du gluconolactone et d’autres acides hydroxyls. Les traitements

ont �et�e administr�es deux fois par semaine pendant 2 semaines et une fois par semaine pendant 2 semai-

nes puis une fois par mois. Les examens ont �et�e r�ealis�es avant, �a jour 14 et �a jour 30 du traitement pout

�evaluer le squamosis, la pr�esence d’autres l�esions cutan�ees et le prurit. Pour deux chiens, des biopsies

cutan�ees ont �et�e r�ealis�ees �a J0 et �a J30.

R�esultats – L’�etendue et la taille des squames �etaient r�eduites de 60% et 75% apr�es 14 et 30 jours res-

pectivement (P < 0.001). Dans 20% des cas, le squamosis n’�etaient plus observ�e apr�es les 30 premiers

jours de traitement. Aucune autre l�esion cutan�ee ou prurit n’�etait observ�e pour aucun chien. Des biopsies

post-traitement ont montr�e une normalisation de la morphologie du stratum corneum et une diminution de

l’hyperpigmentation.

Conclusion et importance clinique – L’utilisation fr�equente de shampoing et de lotion contenant du glu-

conolactone peut etre efficace pour am�eliorer le squamosis des golden retrievers atteints d’ARCI.

© 2018 ESVD and ACVD, Veterinary Dermatology6

Puigdemont et al.

Resumen

Introducci�on – la ictiosis cong�enita autos�omica recesiva (ARCI) en Golden Retrievers se debe a una

mutaci�on del gen PNPLA1, que desempe~na un papel en la organizaci�on y el metabolismo de los l�ıpidos

epid�ermicos. Se utilizan terapias t�opicas para reducir la descamaci�on; sin embargo, hay pocos estudios de

eficacia publicados.

Objetivos – Examinar la eficacia del tratamiento t�opico basado en gluconolactona, un polihidroxi�acido con

efectos beneficiosos conocidos sobre la estructura del estrato c�orneo.

Animales – Diecis�eis perros Golden Retriever con signos cl�ınicos de ARCI y mutaci�on del gen PNPLA1

confirmado por PCR.

M�etodos – este fue un estudio prospectivo, multic�entrico y no controlado. Los perros fueron tratados con

un champ�u y una loci�on que contienen gluconolactona y otros �acidos hidrox�ılicos. Los tratamientos se

administraron inicialmente dos veces por semana durante 2 semanas, luego una vez a la semana durante 2

semanas y finalmente una vez al mes. Los ex�amenes se realizaron antes y a los 14 y 30 d�ıas de tratamiento

para evaluar la descamaci�on, la presencia de otras lesiones cut�aneas y el prurito. En dos perros, antes y 30

d�ıas despu�es del tratamiento, se obtuvieron biopsias de piel.

Resultados – la extensi�on y el tama~no de las escamas se redujeron en un 60% y un 75% despu�es de 14 y

30 d�ıas de tratamiento, respectivamente (P < 001). En el 20% de los perros, ya no se observ�o desca-

maci�on despu�es de los primeros 30 d�ıas de tratamiento. No se observaron otras lesiones cut�aneas o pru-

rito en ning�un perro. Las biopsias postratamiento mostraron una normalizaci�on de la morfolog�ıa del estrato

c�orneo y una hiperpigmentaci�on reducida.

Conclusi�on e importancia cl�ınica – el uso frecuente de un champ�u y una loci�on que contiene gluconolac-

tona puede ser un tratamiento eficaz para mejorar la descamaci�on de la piel en Golden Retrievers con

ARCI.

Zusammenfassung

Hintergrund – Eine autosomal rezessive kongentiale Ichthose (ARCI) des Golden Retrievers wird durch

eine Mutation des PNPLA1 Gens verursacht, welches bei dem epidermalen Lipidaufbau und Metabolismus

eine Rolle spielt. Topische Therapien werden dabei zur Reduzierung der Schuppenbildung eingesetzt; es

gibt jedoch nur wenige publizierte Wirksamkeitsstudien.

Ziele – Eine Untersuchung der Wirksamkeit der topischen Behandlung, die auf Gluconolacton, einer Poly-

hydroxys€aure basiert, die bekanntermaßen positive Auswirkungen auf die Struktur des Stratum corneum

aufweist.

Tiere – Sechzehn Golden Retriever mit klinischen Zeichen von ARCI und PCR-best€atigter PNPLA1 Gen

Mutation.

Methoden – Es handelte sich hierbei um eine prospektive, Multizenter, nicht-kontrollierte Studie. Die

Hunde wurden mit einem Shampoo und einer Lotion behandelt, welche Gluconolacton und andere Hydr-

xyls€auren enthielten. Die Behandlungen wurden anfangs zweimal w€ochentlich, dann einmal w€ochentlich

f€ur 2 Wochen und schließlich einmal monatlich durchgef€uhrt. Es wurden Untersuchungen bis zum und am

14. und 30. Tag nach der Behandlung durchgef€uhrt, um die Schuppenbildung, das Auftreten anderer Haut-

ver€anderungen und des Juckreizes festzuhalten. Bei zwei Hunden, vor und 30 Tage nach der Behandlung

wurden Hautbiopsien entnommen.

Ergebnisse – Das Ausmaß und die Gr€oße der Schuppen wurde auf 60% bzw 75% nach 14 bzw 30 Tagen

der Behandlung reduziert (P < 0,001). Bei 20% der Hunde wurden nach den ersten 30 Tagen der Behand-

lung keine weiteren Schuppen festgestellt. Es bestanden bei keinem Hund anderweitige Hautver€anderun-

gen oder Juckreiz. Biopsien nach der Behandlung zeigten eine Normalisierung der Morphologie des

Stratum corneum und reduzierten die Hyperpigmentierung.

Schlussfolgerung und klinische Bedeutung – Der h€aufige Einsatz eines Shampoos und einer Lotion, die

Gluconolacton enthielten, kann eine wirksame Maßnahme zur Verbesserung der Schuppenbildung der

Haut beim Golden Retriever mit ARCI sein.

要約

背景 – ゴールデンレトリバーの常染色体劣性先天性魚鱗癬(ARCI)は、表皮脂質組織および代謝において

役割を果たすPNPLA1遺伝子の突然変異によるものである。外用療法は、落屑を減少させるために使用さ

れるが、有効性を示した研究はほとんどない。

目的 – 本研究の目的は、角質層構造に有益な効果をもたらすことで知られるポリヒドロキシ酸の一つで

あるグルコノラクトンに基づく外用療法の有効性を調べることである。

被験動物 – ARCIの臨床徴候を有し、PNPLA1遺伝子の突然変異がPCRで確認されたゴールデンレトリー

バー16頭。方法 – 本研究は前向き、他施設共同、無制御研究であった。犬は、グルコノラクトンおよびその他のヒ

ドロキシル酸を含有したシャンプーおよびローションによって処置した。処置は、最初は毎週2回/2週間、その後は毎週1回/2週間、そして最後には1回/1ヶ月で実施した。試験は、落屑、他の皮膚病変および

© 2018 ESVD and ACVD, Veterinary Dermatology 7

Topical therapy for canine ichthyosis

掻痒の評価をするため、処置前、処置後14日および30日後に実施した。処置前および処置後30日後に2頭の犬において、皮膚生検を実施した。

結果 – 落屑の程度およびサイズは、処置後14および30日後にそれぞれ60%および75%に減少した

(P <0.001)。20%の被験犬において、治療開始30日後に落屑はもはや観察されなかった。いずれの犬にお

いても、他の皮膚病変または掻痒は観察されなかった。治療後の生検では、角質層の形態が正常化し、

色素沈着が改善していた。

結論と臨床的重要性 – グルコノラクトン含有シャンプー及びローションの頻回使用は、ARCIのゴールデンレトリバーの皮膚落屑を改善する有効な手段となり得る。

摘要

背景 – 金毛犬的常染色体隐性遗传性鱼鳞病,是由PNPLA1基因突变引起的,这种基因在表皮脂质组成和代

谢中起着重要作用。外部治疗可以减少皮屑;然而,已发表的功效性研究较少。目的 – 研究葡萄糖酸内酯的外部治疗效果,已知葡萄糖酸内酯是一种多羟基酸,可改善角质层结构。动物 – 16只有ACRI临床症状的金毛犬,经PCR确认具有PNPLA1基因突变。方法 – 这是一个前瞻性、多中心、无对照研究。犬使用含有葡萄糖酸内酯和其他羟基酸的浴液。最初两周,每周进行两次治疗,然后每周一次,持续两周,最后每月一次。分别在治疗前、治疗后14天、治疗后30天进行

检查,以评估皮屑,是否有其他皮肤病变和瘙痒。其中两只犬,在治疗前和治疗后30天进行皮肤活检。结果 – 在治疗14天和30天后,皮屑的范围和大小分别降低了60%和75% (P < 0.001)。在治疗30天后,20%的犬

未观察到皮屑。全部犬只均未见其他皮肤病变或瘙痒。治疗后活检显示,角质层形态更加正常,且色素沉着减

少。结论和临床意义 – 给患有ARCI的金毛犬经常使用葡聚糖酸内酯香波和乳液,可以有效地改善脱皮屑状况。

Resumo

Contexto – A ictiose autossomica recessiva congenita (IARC) em golden retrievers ocorre devido �a

mutac�~ao no gene PNPLA1, que participa da organizac�~ao e metabolizac�~ao de lip�ıdeos epid�ermicos. Terapias

t�opicas s~ao utilizadas para reduzir a descamac�~ao; entretanto, poucos estudos foram publicados relatando a

sua efic�acia.

Objetivos – Avaliar a efic�acia de um tratamento t�opico baseado em gluconolactona, um �acido polihidr�oxido

com efeitos ben�eficos j�a relatados na estrutura do estrato c�orneo.

Animais – Dezesseis c~aes da rac�a golden retriever com sinais cl�ınicos de IARC e mutac�~ao do gene

PNPLA1 confirmada por PCR.

M�etodos – Este estudo foi prospectivo, multicentrico e n~ao controlado. Os c~aes foram tratados com um

shampoo e uma loc�~ao contendo gluconolactona e outros �acidos hidrox�ılicos. Os tratamentos foram admi-

nistrados inicialmente duas vezes por semana por duas semanas, depois uma vez por semana por duas

semanas e, finalmente, uma vez por mes. As avaliac�~oes foram realizadas antes do in�ıcio do tratamento,

em 14 e em 30 dias de tratamento, e inclu�ıram an�alise de descamac�~ao, presenc�a de outras les~oes

cutaneas e prurido. Em dois c~aes, bi�opsias antes e 30 dias ap�os o tratamento foram coletadas.

Resultados – A extens~ao e o tamanho das escamas foram reduzidos em 60% e 75% ap�os 14 e 30 dias de

tratamento, respectivamente (P < 0.001). Em 20% dos c~aes, a descamac�~ao n~ao foi mais observada ap�os

os primeiros 30 dias de tratamento. N~ao foram observadas outras les~oes cutaneas ou prurido em nenhum

dos c~aes. As bi�opsias cutaneas p�os-tratamento demonstraram normalizac�~ao da morfologia do estrato

c�orneo e reduc�~ao da hiperpigmentac�~ao.Conclus~ao e importancia cl�ınica – O uso frequente de um shampoo e uma loc�~ao contendo gluconolac-

tona pode ser uma medida eficaz para melhorar a descamac�~ao cutanea de golden retrievers com IARC.

© 2018 ESVD and ACVD, Veterinary Dermatology8

Puigdemont et al.