topical polyhydroxy acid treatment for autosomal recessive
TRANSCRIPT
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: [email protected]
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.