abordagem diagnóstica e terapêutica do prurido em gatos

Abordagem diagnóstica e terapêutica do prurido em

gatos

M.V., Phd., Alessandra Vieira PereiraRio de Janeiro- Brasil

Cães X Gatos

Gatos se lambem mais ( “Grooming”)

Infecções secundárias são menos frequentes

Alterações crônicas cutâneas são raras

Não deixam vestígios de pulgas

Diferentes apresentações clínicas

Triagem diagnóstica mais difícil

Se escondem para coçar!

Dermatopatias pruriginosas

Alergopatias

DAPE

HS alimentar

HS não induzida por pulgas e alimentos

HS picada de mosquito

Outras causas

Demodiciose (D.gatoi)

Sarna notoédrica

Otoacaríase

Pediculose/Lynksacaríase

Pênfigo Foliáceo

Clinical characteristics and causes of pruritus in cats:a multicentre study on feline hypersensitivity-associated dermatoses

Stefan Hobi*, Monika Linek†, GenevieveMarignac‡, Thierry Olivry§, Luc Beco¶, ClaudiaNett**, Jacques Fontaine††, Petra Roosje‡‡,Kerstin Bergvall§§, Sveta Belova¶¶, StefanieKoebrich***, DidierPin†††,MarcelKovalik‡‡‡,SabrinaMeury*,SylvieWilhelm*,1andClaudeFavrot*,1

*Dermatology Department, Clinic for Small Animal Internal Medicine,

Vetsuisse Faculty, University of Zurich, Zurich, Switzerland

†Tierarztliche Spezialisten, Hamburg, Germany

‡Unite de Parasitologie, Ecole Nationale Veterinaire d’Alfort,

Maisons-Alfort Cedex, France

§Department of Clinical Sciences and Center for Comparative

Medicine and Translational Research, North Carolina State

University, Raleigh, NC, USA

¶Clinique Veterinaire, Spa, Belgium

**Dermatologie und Allergologie fur Tieren, Kleintierklinik Rigiplatz,

Cham, Switzerland

††Clinique Veterinaire, Bruxelles, Belgium

‡‡Division of Clinical Dermatology, Department of Clinical Veterinary

Medicine, Vetsuisse Faculty, University of Bern, Bern, Switzerland

§§Department Clinical Sciences, Swedish University of Agricultural

Sciences, Uppsala, Sweden

¶¶Department of Therapy, Institute of Veterinary Medicine and

Animal Science, Estonian University of Life Sciences, Tartu, Estonia

***Bruchweg 3, D- 68809, Neulussheim, Germany

†††Unite de Dermatologie, VetAgro Sup Campus Veterinaire, Marcy

L’Etoile, France

‡‡‡The University of Edinburgh, Veterinary Dermatology Unit,

Division of Veterinary Clinical Sciences, The Hospital for Small Ani-

mals, The Royal (Dick) School of Veterinary Studies, Edinburgh, UK

Correspondence: Claude Favrot, Dermatology Department, Clinic for

Small Animal Internal Medicine, Vetsuisse Faculty, University of

Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland.

E-mail: [email protected] the authors contributed equally to this work.

Sources of Funding

Novartis Animal Health, Basel, Switzerland and research funds from

the University of Zurich financed this study.

Conflict of Interest

No conflicts of interest have been declared.

Abstract

Hypersensitivity dermatitides (HD) are often sus-pected in cats. Cats with HD are reported to presentwith one or more of the following patterns: miliarydermatitis, eosinophilic dermatitis, self-induced sym-metrical alopecia or head and/or neck excoriations.Previous reports on feline HD included small numbersof animals, took place in geographically restrictedareas or did not compare these conditions with othercauses of pruritus. The goal of the present study was

to analyse 72 parameters covering signalment, clini-cal, laboratory and treatment characteristics from alarge group of pruritic cats from different geographi-cal areas. Of the 502 cats, the following diagnoseswere made: flea HD (29% of cases), food HD (12%)nonflea ⁄ nonfood HD (20%) and other diseases inwhich pruritus was a feature (24%). Cats with signsconsistent with a HD but which did not complete afood trial were not analysed further (15% of cases).Most cats with nonflea HD exhibited signs compatiblewith one or more of the four typical lesional patterns,but none of these patterns was found to be patho-gnomonic for any specific diagnosis. Food HD andnonflea ⁄ nonfood HD were found to be clinicallyundistinguishable. Young adult, purebred and femalecats appeared predisposed to nonflea/nonfood HD.As many diagnoses presented with similar lesionalpatterns, a thorough clinical work-up is required forestablishment of a specific diagnosis.

Accepted 13 January 2011

Introduction

Hypersensitivity dermatitides (HD) are often suspected in

companion animals, and these include flea bite hypersen-

sitivity dermatitis, cutaneous adverse food reactions,

urticaria, angioedema and atopic dermatitis (AD).1 The

use of the term ‘feline AD’ remains debatable, however,

because its clinical presentation and histological features

differ markedly from those of its human and canine coun-

terparts. Furthermore, the use of the adjective ‘atopic’

(meaning ‘IgE-mediated’) itself is questionable for this

disease, because the importance of IgE in its pathogenesis

has not been firmly demonstrated.2,3 Very few studies

have investigated the role of IgE in the development of

HD in cats.2,4–6 Additionally, there is evidence suggesting

the heterogeneity of feline IgE and that allergen-specific

IgE serum levels do not correlate with clinical signs of HD

in cats.7–9 Finally, one study reported that up to 35% of

cats with HD have negative allergen-specific intradermal

and serological tests.2 Therefore, and following the current

nomenclature of human and canine allergic skin dis-

eases,10,11 as long as the importance of IgE has not been

firmly demonstrated in cats with pruritic allergic skin dis-

eases, the authors of this paper will not use the term ‘feline

AD’ and replace it with the more generic term of ‘HD’.

The diagnosis of feline nonflea HD (i.e. nonflea bite-

associated HD) is usually based on the exclusion of

ª 2011 The Authors. Veterinary Dermatology

406 ª 2011 ESVD and ACVD, Veterinary Dermatology, 22, 406–413.

DOI: 10.1111/j.1365-3164.2011.00962.x













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Abstract




Introduction




























DOI: 10.1111/j.1365-3164.2011.00962.x













Cham, Switzerland










L’Etoile, France








Sources of Funding





Abstract




Introduction




























DOI: 10.1111/j.1365-3164.2011.00962.x













Cham, Switzerland










L’Etoile, France








Sources of Funding





Abstract




Introduction




























DOI: 10.1111/j.1365-3164.2011.00962.x

Somali, sphinx, Chartreux and British blue were also repre-

sented but in low numbers. There were 225 male (45%)

and 277 female cats (55%).

One hundred and forty-six cats were diagnosed with

flea HD (29%), 61 with food HD (12%), 100 with non-

flea ⁄ nonfood HD (20%), 74 with an undetermined HD

(15%) and 121 (24%) with other diseases (Figure 2).

These pruritic cats with other diseases were diagnosed

as having one of 31 different conditions of the following

categories: parasitic (n = 35; 29%), autoimmune (15;

12%), fungal (13; 11%), neoplastic (8; 7%), psychogenic

(6; 5%), viral (5; 4%), isolated otitis externa (5; 4%) bacte-

rial (4; 3%), and miscellaneous or idiopathic conditions

(38; 31%). There were a total of 129 cats – some with

more than one disease.

Clinical features of cats with nonflea HDResults are presented in Tables 1–4 and Figure 3.

Forty-three of 161 cats with nonflea HD (27%) were

purebred cats; all Abyssinian cats included in this study

belonged to this group. Males represented 41% of cats

diagnosed with nonflea HD. The mean age of onset of

pruritus was 3.4 years, and 82 cats with nonflea HD

(51%) were younger than 3 years of age when they had

their first pruritic episode.

Most cats with nonflea HD exhibited one of the follow-

ing lesional patterns: self-induced symmetric alopecia

(83; 52%), head and neck pruritus (95; 59%), eosinophilic

diseases (41; 25%) or miliary dermatitis (30; 19%). Most

cats (152 of 161; 94%) were affected with at least one of

these patterns, while 74 (46%) presented with more than

one. In the remaining nine cats (5%), erythema, nonsym-

metrical alopecia and ⁄ or crusts were observed. Of cats

evaluated prospectively, the mean pruritus score was 6.4

of 10, and 119 of 136 cats (88%) had a pruritus score of 5

or greater [correction added on 1st April 2011 after online

publication: ‘119 of 161 cats (74%)’ changed to ‘119 of

136 cats (88%)’].

Interestingly, two body areas were affected in more

than half of the cats with nonflea HD: the head or face

and the abdomen (Table 3 and Figure 3). Additionally,

ears and neck were affected in more than one-third of

cats included in this group. Conversely, paws, sternum or

axilla and mouth were affected in <10% of these cats.

Sixty-seven cats with nonflea HD presented with non-

dermatological signs (42%). Among these 67 cats, 22

(33%) exhibited digestive signs (e.g. diarrhoea, vomiting,

soft tools or increased defecation), 24 (36%) had otitis

externa, 13 (19%) had conjunctivitis and 10 (15%) had

respiratory signs.

Comparisons between cats with nonflea HD andthose with flea HDFemale and purebred cats were over-represented in the

nonflea HD group compared with cats having flea HD

(P < 0.0001 and P = 0.003, respectively; Table 1). In fact,

How itchy is your cat?This scale is designed to measure the severity of itching in cats. Itching can include scratching, biting,licking, chewing, nibbling, rubbing and/or sudden run away. Read all the descriptions below starting from the bottomThen use a marker pen to place a mark anywhere on the vertical line that runs down the left hand side toIndicate the point at which you think your cat’s level of itchiness lies.

.

Extremely severe itching/almost continuous

Itching does not stop whatever is happening, even in the consulting room(needs to be physically restrained from itching)

Severe itching/prolonged episodesItching might occur at night (if observed) and also when eating, playing, exercising or being distracted

Moderate itching/regular episodesItching might occur at night (if observed), but not when eating, playing, exercising or being distracted

Mild itching/a bit more frequentWould not itch when sleeping, eating, playing, exercising or being distracted

Very mild itching/only occasional episodes

The cat is slightly more itchy than it was before the skin problem started

Normal cat – I don’t think itching is a problem

Figure 1. Pruritus scale.

588 pruritic cats

502 cats analysed86 cats excluded

235 nonflea HD cats 146 flea HD cats 121 other diseases

100 nonflea, nonfoodHD cats

74 undeterminedHD cats61 food HD cats

Figure 2. Assignment of cats into study groups.



Hobi et al.

Alergopatias381gatos













Cham, Switzerland










L’Etoile, France








Sources of Funding





Abstract




Introduction




























DOI: 10.1111/j.1365-3164.2011.00962.x

Infecciosas/A.I121gatos

Somali, sphinx, Chartreux and British blue were also repre-

sented but in low numbers. There were 225 male (45%)

and 277 female cats (55%).

One hundred and forty-six cats were diagnosed with

flea HD (29%), 61 with food HD (12%), 100 with non-

flea ⁄ nonfood HD (20%), 74 with an undetermined HD

(15%) and 121 (24%) with other diseases (Figure 2).

These pruritic cats with other diseases were diagnosed

as having one of 31 different conditions of the following

categories: parasitic (n = 35; 29%), autoimmune (15;

12%), fungal (13; 11%), neoplastic (8; 7%), psychogenic

(6; 5%), viral (5; 4%), isolated otitis externa (5; 4%) bacte-

rial (4; 3%), and miscellaneous or idiopathic conditions

(38; 31%). There were a total of 129 cats – some with

more than one disease.

Clinical features of cats with nonflea HDResults are presented in Tables 1–4 and Figure 3.

Forty-three of 161 cats with nonflea HD (27%) were

purebred cats; all Abyssinian cats included in this study

belonged to this group. Males represented 41% of cats

diagnosed with nonflea HD. The mean age of onset of

pruritus was 3.4 years, and 82 cats with nonflea HD

(51%) were younger than 3 years of age when they had

their first pruritic episode.

Most cats with nonflea HD exhibited one of the follow-

ing lesional patterns: self-induced symmetric alopecia

(83; 52%), head and neck pruritus (95; 59%), eosinophilic

diseases (41; 25%) or miliary dermatitis (30; 19%). Most

cats (152 of 161; 94%) were affected with at least one of

these patterns, while 74 (46%) presented with more than

one. In the remaining nine cats (5%), erythema, nonsym-

metrical alopecia and ⁄ or crusts were observed. Of cats

evaluated prospectively, the mean pruritus score was 6.4

of 10, and 119 of 136 cats (88%) had a pruritus score of 5

or greater [correction added on 1st April 2011 after online

publication: ‘119 of 161 cats (74%)’ changed to ‘119 of

136 cats (88%)’].

Interestingly, two body areas were affected in more

than half of the cats with nonflea HD: the head or face

and the abdomen (Table 3 and Figure 3). Additionally,

ears and neck were affected in more than one-third of

cats included in this group. Conversely, paws, sternum or

axilla and mouth were affected in <10% of these cats.

Sixty-seven cats with nonflea HD presented with non-

dermatological signs (42%). Among these 67 cats, 22

(33%) exhibited digestive signs (e.g. diarrhoea, vomiting,

soft tools or increased defecation), 24 (36%) had otitis

externa, 13 (19%) had conjunctivitis and 10 (15%) had

respiratory signs.

Comparisons between cats with nonflea HD andthose with flea HDFemale and purebred cats were over-represented in the

nonflea HD group compared with cats having flea HD

(P < 0.0001 and P = 0.003, respectively; Table 1). In fact,

How itchy is your cat?This scale is designed to measure the severity of itching in cats. Itching can include scratching, biting,licking, chewing, nibbling, rubbing and/or sudden run away. Read all the descriptions below starting from the bottomThen use a marker pen to place a mark anywhere on the vertical line that runs down the left hand side toIndicate the point at which you think your cat’s level of itchiness lies.

.

Extremely severe itching/almost continuous

Itching does not stop whatever is happening, even in the consulting room(needs to be physically restrained from itching)

Severe itching/prolonged episodesItching might occur at night (if observed) and also when eating, playing, exercising or being distracted

Moderate itching/regular episodesItching might occur at night (if observed), but not when eating, playing, exercising or being distracted

Mild itching/a bit more frequentWould not itch when sleeping, eating, playing, exercising or being distracted

Very mild itching/only occasional episodes

The cat is slightly more itchy than it was before the skin problem started

Normal cat – I don’t think itching is a problem

Figure 1. Pruritus scale.

588 pruritic cats

502 cats analysed86 cats excluded

235 nonflea HD cats 146 flea HD cats 121 other diseases

100 nonflea, nonfoodHD cats

74 undeterminedHD cats61 food HD cats

Figure 2. Assignment of cats into study groups.



Hobi et al.

O quanto seu gato coça??

Extremamente severo/quase contínuoPrurido não cessa mesmo no consultório

Prurido severo/ episódios longosPrurido moderado/ episódios regulares

Prurido moderado/se mordiscam com frequênciaPrurido em episódios ocasionais

Não pensa que prurido é o problema0

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Abstract




Introduction




























DOI: 10.1111/j.1365-3164.2011.00962.x

Table 1. Signalment and history data

(1) Nonflea

HD

(2) Nonflea HD ⁄nonfood HD (3) Food HD (4) Flea HD (5) OD (1) versus (4) (1) versus (5) (2) versus (3)

n 161 100 61 146 121

Male cats (%) 66 (41) 42 (42) 24 (39) 83 (57) 48 (40) <0.0001 n.s. n.s.

Purebred cats (%) 43 (27) 22 (22) 21 (34) 22 (15) 35 (29) 0.003 n.s. n.s.

Siamese 8 (5) 5 3 5 3 n.s. n.s. n.s.

Persian 11 (7) 4 7 7 12 n.s. n.s. n.s.

Abyssinian 5 (3) 3 2 0 0 n.s. n.s. n.s.

Maine coon 4 (2) 2 2 3 3 n.s. n.s. n.s.

Mean age at onset (years) 3.4 3 4 4.4 4.9 0.001 0.001 n.s.

Indoor:outdoor ratio* 76 ⁄ 64 46 ⁄ 42 30 ⁄ 22 49 ⁄ 73 53 ⁄ 53 0.02 n.s. n.s.

Rural:urban ratio* 55/103 37/67 18/36 45/96 42/72 n.s. n.s. n.s.

Seasonality (%) 14 (9) 12 (12) 2 (3) 13 (9) 9 (7) n.s. n.s. n.s.

Pruritus mean 6.4 6.4 6.4 5.7 4.9 0.001 0.0001 n.s.

Pruritus < 5 (%) 17 (13) 10 (11) 7 (14) 32 (24) 45 (45) 0.008 <0.0001 n.s.

Pruritus > 5 (%) 98 (72) 64 (73) 34 (69) 79 (57) 42 (42) n.s. <0.0001 n.s.

Pruritus = 5 (%) 22 (16) 14 (16) 8 (16) 26 (19) 13 (13) n.s. n.s. n.s.

Means and proportions were analysed using Mann–Whitney U-test and Fisher’s exact test, respectively.

HD, hypersensitivity dermatis; n.s., not significant; OD, other disease.

*Cats living in both environments were not taken into account.

[Corrections to Table data added on 1st April 2011 after online publication: ‘Rural:urban ratio*’ row data were changed, as were data in the bottom

3 rows of ‘(1) Nonflea HD’ column].

Table 2. Pattern and pattern associations

(1) Nonflea

HD


n 161 100 61 146 121

Miliary dermatitis (%) 30 (19) 18 (18) 12 (20) 51 (35) 11 (9) 0.001 0.02 n.s.

Eosinophilic granuloma

complex (%)

41 (25) 26 (26) 15 (25) 20 (14) 3 (2) 0.01 <0.0001 n.s.

Erosions ⁄ ulcerations face

and neck (%)

95 (59) 56 (56) 39 (64) 55 (38) 66 (55) 0.0002 n.s. n.s.

Symmetrical alopecia (%) 83 (52) 57 (57) 26 (43) 57 (39) 22 (18) 0.02 <0.0001 n.s.

At least one of previous four

presentations (%)

152 (94) 95 (95) 57 (94) 133 (91) 90 (74) n.s. <0.0001 n.s.

Multiple patterns (%) 74 (46) 46 (46) 28 (46) 41 (28) 9 (7) 0.007 <0.0001 n.s.

Proportions were analysed using Fisher’s exact test.

[Correction to Table data added on 1st April 2011 after online publication: ‘At least one of previous four presentations (%)’ row data were changed

under column ‘(3) Food HD’].

Table 3. Localizations

(1) Nonflea HD


n 161 100 61 146 121

Head ⁄ face (%) 93 (58) 56 (56) 37 (61) 62 (42) 57 (47) 0.008 n.s. n.s.

Ears (%) 54 (34) 32 (32) 22 (36) 31 (21) 58 (48) 0.02 0.02 n.s.

Chin (%) 28 (17) 17 (17) 11 (18) 21 (14) 15 (12) n.s. n.s. n.s.

Lips (%) 23 (14) 15 (15) 8 (13) 8 (5) 7 (6) 0.01 0.05 n.s.

Oral ⁄ mouth (%) 11 (7) 2 (2) 9 (15) 6 (4) 3 (2) n.s. n.s. n.s.

Neck (%) 66 (40) 36 (36) 30 (50) 52 (36) 27 (22) n.s. 0.001 n.s.

Rump ⁄ tail (%) 24 (15) 18 (18) 6 (10) 78 (53) 10 (8) <0.0001 n.s. n.s.

Forelimbs (%) 42 (26) 34 (34) 8 (13) 30 (21) 18 (15) n.s. 0.03 0.003

Hindlimbs (%) 51 (32) 40 (40) 11 (18) 31 (21) 14 (12) 0.04 <0.0001 0.005

Forepaws (%) 11 (7) 6 (6) 5 (8) 5 (4) 14 (12) n.s. n.s. n.s.

Hindpaws (%) 9 (6) 1 (1) 8 (13) 6 (4) 9 (7) n.s. n.s. 0.002

Lateral thorax (%) 24 (15) 17 (17) 7 (11) 14 (10) 12 (10) n.s. n.s. n.s.

Sternum ⁄ axilla (%) 17 (11) 10 (10) 7 (11) 12 (8) 9 (7) n.s. n.s. n.s.

Flanks (%) 16 (10) 14 (14) 3 (5) 28 (20) 8 (7) 0.02 n.s. n.s.

Abdomen (%) 85 (53) 59 (59) 26 (43) 73 (50) 27 (22) n.s. <0.0001 0.05

Perineum (%) 20 (12) 14 (14) 6 (10) 18 (12) 5 (4) n.s. 0.02 n.s.

Dorsum (%) 30 (19) 23 (23) 7 (11) 61 (42) 18 (15) <0.0001 n.s. n.s.


[Correction to Table data added on 1st April 2011 after online publication: ‘Neck (%)’ row data were changed under column ‘(5) OD’].


ª 2011 ESVD and ACVD, Veterinary Dermatology, 22, 406–413. 409

Feline hypersensitivity dermatitisIntensidade do prurido













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Abstract




Introduction




























DOI: 10.1111/j.1365-3164.2011.00962.x

Como diagnosticar?

Procedência?

Idade do aparecimento das lesões

Tempo de evolução

Ambiente/Acesso a rua?/Contactantes?

Prurido?

Ectoparasitas?

Alimentação

Comorbidades

Banho? Produto?

Terapia prévia? CORTICOTERAPIA? Resposta?

História Clínica

História clínica

Filhotes

Parasitárias

Fúngicas

Alérgicas

História clínica

Adultos

Alérgicas

Parasitárias

Fúngicas

PF e psicogênicas e outras

! Derma&te(Miliar(

! Dermatoses(eosino/licas(

! Alopecia(Simétrica(auto(induzida(

! Lesões(erodo:(ulceradas(em(cabeça(e(

pescoço(

!

Exame Físico Padrões de reação cutânea

M.V . Tatiane Pirani

Pontos chave no Exame Físico

Paciência!!!

Inspeção da cavidade oral

Pente fino

Lâmpada de Wood

Ectoparasitas?

POSITIVO NEGATIVO

!!!NÃO SIM

RASPADO'TRICOGRAMA'

FITADE'ACETATO''SWABS'

CULTURA'FÚNGICA'HISTOPATO'

DAPE

ALERGIA ALIMENTAR DIETA!

"ATOPIA "

ESCABIOSE/DEMODICIOSE

OTOACARÍASE

CHEYLETIELLOSIS

DERMATOFITOSE

SIM

!!!NÃO

ESPOROTRICOSE

PÊNFIGO FOLIÁCEO

RESPOSTA'AO'TRATAMENTO?'

SIM!

PARCIAL!

Anti-ectop. a cd 15d/3aplic???

Research ArticleEfficacy of Spinosad Tablets Administered to a Colony of15 Indoor Cats Naturally Infested with Fleas

Marie-Christine Cadiergues and Charline Pressanti

INP-ENVT, 23 Chemin des Capelles, 31076 Toulouse Cedex 3, France

Correspondence should be addressed to Marie-Christine Cadiergues; [email protected]

Received 12 November 2013; Accepted 30 December 2013; Published 5 February 2014

Academic Editors: A. Anadon and K. Y. Mumcuoglu

Copyright © 2014 M.-C. Cadiergues and C. Pressanti. This is an open access article distributed under the Creative CommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work isproperly cited.

The aims of the study were (i) to describe adult fleas distribution in a strictly indoor cat colony composed of cats with flea allergydermatitis (FAD) and non-FAD cats and (ii) to evaluate the efficacy of spinosad used alone. Skin lesions were scored accordingto the SCORing Feline Allergic Dermatitis lesion severity scale (SCORFAD) on days 0, 15, 30, 45, 60, and 90. Cats were combedprior to the treatment (days 0, 30, and 60) and on days 15, 45, and 90; collected fleas were replaced on the animals. All cats receivedflavored spinosad tablets (Comfortis) at a dosage of 50–75mg/kg on days 0, 30, and 60. Cats were fed immediately afterwards. Onday 0, a total of 60 fleas were collected (mean: 4 ± 4). Cats with FAD had a SCORFAD of 6, 8, 12, and 13 and harbored 0, 2, 1, and0 fleas, respectively. Tablets were taken voluntarily by 8, 11, and 12 cats on days 0, 30, and 60, respectively. No adverse event wasrecorded. From day 15 to day 90, no fleas could be collected. SCORFAD was reduced by 40%, 71%, 80%, 89%, and 98% on days 15,30, 45, 60, and 90, respectively.

1. Introduction

Fleas remain the most common parasites in cats [1–4]. Inaddition to potentially carry zoonotic diseases [5], fleas causeskin irritations due to their bites, including in some animalsan allergic dermatitis (the so-called flea allergic dermatitis orFAD) [6, 7]. FAD is the most common allergic skin diseaseof dogs and cats, although its frequency varies according togeographical location. The past twenty years have broughtimportant advances in flea biology as well as better insec-ticides [8]. Nevertheless, flea control in general, and morespecifically in cats with FAD, remains a real challenge forveterinarians and owners. The goal is to minimize flea bites,that is, to minimize the amount of saliva injected by fleas inorder to be under the allergic threshold.

Spinosad is an aerobic fermentation product of the soilbacterium, Saccharopolyspora spinosa. Spinosad kills insectsthrough activation of the acetylcholine nervous systemthrough nicotinic receptors. A chewable tablet is indicatedfor the treatment and prevention of flea infestations causedby Ctenocephalides felis; it was first introduced for dogs tothe USA market in 2007 after approval by the Food and

Drug Administration. The European Commission granteda marketing authorisation valid throughout the EuropeanUnion in 2011 after approval by the European MedicinesAgency. Subsequently, it was approved for cats in USA,Canada, and Japan in 2012 and in the European Union in2013. Its excellent efficacy against fleas and its rapid killingeffect that are observed in dogs [9–12] are also reported incats [13, 14].

We had the opportunity to observe a colony of fifteencats, housed strictly indoors and naturally infested with fleas;it included cats with clinical signs of FAD. We aimed todescribe the distribution of fleas in a strictly indoor cat colonycomposed of FAD cats and non-FAD cats. We also aimed toevaluate the efficacy of spinosad used alone, both on the adultflea population and on the skin lesions.

2. Materials and Methods

Within a laboratory colony of fifteen strictly indoor, adultdomestic shorthair cats, receiving no ectoparasiticide, fourof them presented with excessive licking and alopecia, which

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2 ISRN Veterinary Science

had progressed over the past month. Advice was sought fromthe dermatology clinics of the Small Animal Hospital ofthe Toulouse Veterinary School. Clinical examination, testprocedures, treatment, and followup of the cats were doneafter obtaining a written consent from the people responsibleof the cat colony.

Coat brushing had allowed demonstration of flea infes-tation (adult fleas and/or flea dirt). Ctenocephalides feliswas identified after microscopical examination of severaladult specimens [15]. Skin scrapings and hair plucks hadbeen negative for Demodex mites and dermatophytes. Tapeimpressions from the skin surface had not shown evidence ofsecondary bacterial or yeast infections.

Domestic shorthair cats (7 females spayed and 8 malesneutered) between 4.7 and 6.7 years of age andweighing from3 to 4.7 kg were housed in a stone-floored four-room space,measuring 23m2 and having an additional surface of 8m2of cat tree furniture. No outdoor access was allowed. Theyhad been living in this space for more than one year. Theywere fed a commercial cat diet and water was supplied adlibitum. Temperature was maintained at 19 ± 2∘C and airwas renewed 20 times per hour. Cats were vaccinated againstfeline panleukopenia virus, feline herpesvirus 1 (FHV-1), andfeline calicivirus (FCV) and had no medical history.

Each animal was submitted to a full clinical exami-nation on days 0, 15, 30, 45, 60, and 90. Skin lesionswere scored according to the SCORing Feline Allergic Der-matitis lesion severity scale (SCORFAD) [16]. SCORFADreduction was calculated at each time point ! using thearithmetic mean of SCORFAD according to the followingformula: SCORFAD reduction (%) = 100 × (meanday 0 −mean")/meanday 0.

Cats were combed for 10 minutes prior to the treatment(days 0, 30, and 60) and additionally on days 15, 45, and90. The combing procedure was standardized and appliedsimilarly to every single cat. Two operators were involvedin the assessment of a specific animal. One person handledand restrained gently the cat; the second combed the cat,quantified the fleas recovered from each comb, and recordedthe data. During combing, an extra-fine flea comb (11.4teeth/cm, http://www.easypets.fr) was used to recover fleaspresent in the cat’s fur. The method of combing includedseveral strokes of the comb in each area of the animal, eachtime moving in the same direction, following the pattern ofthe hair coat. Movement from one part of the cat’s fur to thenext was via strokes overlapping each other, so that no area offur was missed. After completion of the combing procedurefor all body areas, the whole procedure was repeated so thatall areas were combed twice [17]. Fleas which were collectedwere counted and were replaced on the animal. Efficacywas calculated at each time point ! using the arithmeticmean numbers of fleas according to the following formula:Efficacy (%) = 100 × (meanday 0 −mean")/meanday 0.

All cats received flavored spinosad tablets (Comfortis, EliLilly and Company Ltd., Basingstoke, UK) at a dosage of 50–75mg/kg on days 0, 30, and 60. The tablet was first offeredto the cat; in case of nonimmediate voluntary reception, thetablet was given with a pilling device. Cats were fed their

60

50

40

30

20

10

0D0 D15 D30 D45 D60 D90

Total number of fleas in non-FAD catsTotal number of fleas in FAD catsTotal SCORFAD of non-FAD catsTotal SCORFAD of FAD cats

Figure 1: Progression of the total number of fleas (pale blue: non-FAD cats, pink: FAD cats) and the total SCORFAD (blue: non-FADcats, red: FAD cats) over time.

usual ration immediately afterwards. All cats were observedfor 2 hours posttreatment to record any adverse event.The environment was routinely cleaned, but no insecticideor insect growth regulator was applied. No inflammatorytreatment was prescribed.

3. Results

On day 0, prior to the initial treatment, a total of 60 fleaswere collected (mean: 4 ± 4, min: 0, max: 12). Two catshad self-induced alopecia, mainly on the dorsolumbar anddorsal tail regions. Two cats suffered frommiliary dermatitis,principally of the dorsum and self-induced alopecia. Thefour cats with FAD had a SCORFAD of 6, 8, 12, and 13 andharbored 0, 2, 1, and 0 fleas, respectively. Additionally, verymild lesions were observed on five other cats (SCORFAD of1 or 2) (Figure 1). Non-FAD cats harbored a total of 57 fleas(mean: 5.2 ± 4.1, min: 0, max: 12).

Tablets were taken immediately and voluntarily by 8, 11,and 12 cats on days 0, 30, and 60, respectively. No adverseevent was recorded. From D15 to D90, no fleas could becollected (100% efficacy). SCORFAD was reduced by 40%,71%, 80%, 89%, and 98% on days 15, 30, 45, 60, and 90,respectively (Figure 1).

4. Discussion

Flea infestation in strictly indoor animals, particularly cats, isfrequently overlooked, possibly denied. In a study conductedin 2007 in UK, 48% of the owners whose pets had signs of anactive flea infestation were unaware that their pet had fleas[1]. Cat owners may think that because they have an indoor-only cat, it is impossible for their pet to get fleas. Initiallyone or two fleas may be introduced from a pant leg, sock,

Cura clínica leva tempo!!!0,75 pulgas/gato DAPP

5,2 pulgas/gato sem DAPP

Ectoparasitas?

POSITIVO NEGATIVO

!!!NÃO SIM

RASPADO'TRICOGRAMA'

FITADE'ACETATO''SWABS'

CULTURA'FÚNGICA'HISTOPATO'

DAPE

ALERGIA ALIMENTAR DIETA!

"ATOPIA "

ESCABIOSE/DEMODICIOSE

OTOACARÍASE

CHEYLETIELLOSIS

DERMATOFITOSE

SIM

!!!NÃO

ESPOROTRICOSE

PÊNFIGO FOLIÁCEO

RESPOSTA'AO'TRATAMENTO?'

SIM!

PARCIAL!

Anti-ectop. a cd 15d/30 dias /90 dias!!

Excluindo parasitárias, fúngicas, dermatofitose...

Alergopatias (DAPE/H.A./“Atopia”)

Responsivo a corticoterapia...

Possuem os mesmos sinais clínicos... Mas não na mesma frequência!!!













Cham, Switzerland










L’Etoile, France








Sources of Funding





Abstract




Introduction




























DOI: 10.1111/j.1365-3164.2011.00962.x













Cham, Switzerland










L’Etoile, France








Sources of Funding





Abstract




Introduction




























DOI: 10.1111/j.1365-3164.2011.00962.x













Cham, Switzerland










L’Etoile, France








Sources of Funding





Abstract




Introduction




























DOI: 10.1111/j.1365-3164.2011.00962.x













Cham, Switzerland










L’Etoile, France








Sources of Funding





Abstract




Introduction




























DOI: 10.1111/j.1365-3164.2011.00962.x

when compared with the rest of the study population,

males were over-represented in the flea HD group, while

females dominated the nonflea HD group. Among pure-

bred cats, Abyssinians were only present in the nonflea

HD group. The mean age at onset was also lower in the

nonflea HD group (3.4 years) when compared with the

flea HD group (4.4 years; P = 0.001). The pruritus was

also more intense in cats with nonflea HD (6.4 versus 5.7

grade; P = 0.001).

Cats from both groups presented with one of the four

main lesional patterns, but the frequencies of each

pattern varied significantly between groups (Table 2);

cats with flea HD presented more frequently than cats

with nonflea HD with miliary dermatitis (35 versus 19%;

P = 0.001) and less commonly with eosinophilic diseases

(14 versus 25%; P = 0.01), head and neck excoriations

(38 versus 59%; P = 0.0002) and symmetrical alopecia

(39 versus 52%; P = 0.02). Interestingly, cats with

nonflea HD (46%) presented more often with two or

more lesional patterns compared with cats having flea

HD (46 versus 28%; P = 0.007).

The distribution of skin lesions was also different

between groups (Table 3). The head or face (P = 0.008),

the ears (P = 0.02), the lips (P = 0.01) and the hindlimbs

(P = 0.04) were more frequently affected in cats with non-

flea HD, while those with flea HD presented more often

with changes affecting the rump or tail (P < 0.0001), the

flanks (P = 0.02) or the dorsum (P < 0.0001).

Comparisons between cats with food HD and thosewith nonflea ⁄ nonfood HDThere were few significant differences between cats of

these two groups. The mean ages of pruritus onset were

similar in both groups; 72 cats with nonflea ⁄ nonfood HD

(72%) and 32 cats with food HD (52%) exhibited their first

pruritus manifestation before 3 years of age (P = 0.04). In

Table 4. Associated clinical signs

(1) Nonflea

HD

(2) Nonflea HD ⁄nonfood (3) Food HD (4) Flea HD (5) OD

(1) versus

(4)

(1) versus

(5)

(2) versus

(3)

n 161 100 61 146 121

Nondermatological signs (%) 67 (42) 42 (42) 25 (41) 44 (30) 49 (40) 0.02 n.s. n.s.

Digestive signs (%) 22 (14) 9 (9) 13 (21) 17 (12) 10 (8) n.s. n.s. 0.03

Respiratory signs (%) 10 (6) 6 (6) 4 (7) 5 (3) 5 (4) n.s. n.s. n.s.

Otitis (%) 24 (15) 20 (20) 4 (7) 4 (3) 23 (19) 0.0002 n.s. 0.02

Conjunctivitis (%) 13 (8) 8 (8) 5 (8) 4 (3) 8 (7) 0.04 n.s. n.s.


Figure 3. Silhouettes depicting the proportion of distribution of lesions in cats with nonflea HD, nonfood HD, food HD and flea HD. NFIHD, non

food induced hypersensitivity dermatitis; NFNFIHD, non flea, non food induced hypersensitivity dermatitis; FIHD, food induced hypersensitivity

dermatitis; FBH, flea bite hypersensitivity.



Hobi et al.

Como tratar?

Tratar ou controlar a causa base

Terapia Tópica Terapia Sistêmica

ConsideraçõesTerapia Tópica?

Terapia Sistêmica?

Proprietário X Gato

Comorbidades?

Obeso?

Glicocorticóides

Prednisolona oral (1 a 3 mg/kg/SID/ 7 a 30 dias)

Deflazacort oral (0,3 mg/kg/ cada 48h/ 7 a 30 dias

Acetato de metil prednisolona I.M. (4 mg/kg)

Grupos de risco

Sobrepeso

Idosos a partir de 10 anos

Nefropatas

Anormalidades na ausculta cardíaca

FiV e FelV ??

Anti-histamínicos

Hidroxizine (2,0 mg/kg ou 10 mg/gato BID)

Cetirizina (1,0 mg/Kg ou 5mg/gato SID)

Ciproheptadina (1,0-2,0 mg/sid/gato)

Loratidina (5 mg/gato)

The efficacy of cetirizine hydrochloride on the pruritusof cats with atopic dermatitis: a randomized, double-blind, placebo-controlled, crossover study

Kerstin Wildermuth*,†, Sonja Zabel‡ and Rod A. W. Rosychuk*

*Department of Clinical Sciences, Colorado State University College of Veterinary Medicine and Biomedical Sciences, 300 West Drake, Fort

Collins, CO 80523, USA

†Tierdermatologie Dr. Wildermuth, Borsigstraße 7a, 65205 Wiesbaden, Germany

‡Department of Small Animal Medicine and Surgery, University of Georgia College of Veterinary Medicine, 501 DW Brooks Drive, Athens, GA

30602, USA

Correspondence: Kerstin Wildermuth, Tierdermatologie Dr. Wildermuth, Borsigstraße 7a, 65205 Wiesbaden, Germany. E-mail: kerstinw@

tierdermatologie-wildermuth.de

Background – Various antihistamines have been used in the management of feline atopic dermatitis, with vari-

able reported benefit. To date, there have been no randomized, double-blind, placebo-controlled, crossover clini-

cal trials on the use of this drug class in cats.

Hypothesis/Objectives – To evaluate the clinical efficacy of cetirizine hydrochloride for the control of pruritus

and dermatitis in cats diagnosed with atopic dermatitis.

Methods – In this randomized, double-blind, placebo-controlled crossover clinical trial, 21 client-owned cats diag-

nosed with mild to moderate nonseasonal atopic dermatitis were randomly assigned to two groups. Cats in each

group received either 1 mg/kg cetirizine hydrochloride or placebo once daily per os for 28 days followed by a

14 day wash-out period. Treatments were then crossed over, and cats received placebo or cetirizine hydrochlor-

ide for another 28 days. Owners marked a pruritus severity scale before inclusion in the study and weekly

throughout the entire study period. Lesions were scored by the clinician using a Canine Atopic Dermatitis Extent

and Severity Index (CADESI)-03 modified for the cat before enrolment and at day 28 of each treatment.

Results – Nineteen cats completed the study. There were no statistically significant differences between treat-

ment with cetirizine hydrochloride and placebo for modified CADESI-03 or pruritus scores.

Conclusion and clinical importance – This study suggests that cetirizine hydrochloride cannot be recom-

mended for the management of feline atopic dermatitis.

Introduction

Atopic dermatitis (AD) is a common skin disorder in cats,

with pruritus being one of the most characteristic signs.1

Glucocorticoids are commonly used for the management

of feline AD. Although glucocorticoid therapy is effective,

high-dose or long-term therapy may be associated with

adverse effects, including diabetes mellitus or skin atro-

phy.2 Ciclosporin has been shown to be effective but is

also potentially associated with significant adverse

effects and is relatively expensive.3 Allergen-specific

immunotherapy is considered to be a safe treatment in

cats but may take several months before obvious benefit

is noted, is relatively expensive and is usually given by

subcutaneous administration.4 Essential fatty acids are

also a safe alternative but have not been shown to be

effective as a single treatment.5 Antihistamines have

been used to treat feline AD.6–8 Histamine receptors, spe-

cifically H1 receptors, are found on mast cells, basophils,

macrophage/dendritic cells, T lymphocytes, neutrophils,

eosinophils, blood vessel endothelial cells and airway epi-

thelial and smooth muscle cells.9 The H1 antihistamines

stabilize the inactive configuration of H1 receptors and

thus inhibit histamine binding to the receptor and mast

cell degranulation.10 They appear to be well tolerated in

cats and are relatively affordable for pet owners.6–8,11

There are only a few open clinical trials investigating the

efficacy of antihistamines in cats with allergic pruritus.

These clinical trials showed an improvement of pruritus in

50% of the cats treated with clemastine, 45% of cats

treated with cyproheptadine and 77% of cats treated with

chlorpheniramine.6–8

Cetirizine is a second-generation antihistamine and an

active metabolite of hydroxyzine. Second-generation anti-

histamines do not cross the blood–brain barrier and, in

humans, are associated with less potential for sedation.12

A recent pharmacokinetic study in cats has shown that a

single dose of cetirizine of approximately 1 mg/kg results

in high plasma concentrations and a long half-life, compat-

ible with once daily dosing.11 In a recent open clinical trial,

Accepted 25 June 2013

Sources of Funding: This study was funded by the American

College of Veterinary Dermatology (ACVD) Resident’s Research

Award, Royal Canin USA Inc. and Heska Corporation.

Conflict of Interest: No conflicts of interest have been declared.

Results of this study were presented as a poster at the 7th World

Congress of Veterinary Dermatology (WCVD) 2012; Vancouver,

Canada. Vet Dermatol 2012; 23 Suppl 1: 66.

© 2013 ESVD and ACVD, Veterinary Dermatology , 24, 576–e138.576

Vet Dermatol 2013; 24: 576–e138 DOI: 10.1111/vde.12067

The efficacy of cetirizine hydrochloride on the pruritusof cats with atopic dermatitis: a randomized, double-blind, placebo-controlled, crossover study

Kerstin Wildermuth*,†, Sonja Zabel‡ and Rod A. W. Rosychuk*

*Department of Clinical Sciences, Colorado State University College of Veterinary Medicine and Biomedical Sciences, 300 West Drake, Fort

Collins, CO 80523, USA

†Tierdermatologie Dr. Wildermuth, Borsigstraße 7a, 65205 Wiesbaden, Germany

‡Department of Small Animal Medicine and Surgery, University of Georgia College of Veterinary Medicine, 501 DW Brooks Drive, Athens, GA

30602, USA

Correspondence: Kerstin Wildermuth, Tierdermatologie Dr. Wildermuth, Borsigstraße 7a, 65205 Wiesbaden, Germany. E-mail: kerstinw@

tierdermatologie-wildermuth.de

Background – Various antihistamines have been used in the management of feline atopic dermatitis, with vari-

able reported benefit. To date, there have been no randomized, double-blind, placebo-controlled, crossover clini-

cal trials on the use of this drug class in cats.

Hypothesis/Objectives – To evaluate the clinical efficacy of cetirizine hydrochloride for the control of pruritus

and dermatitis in cats diagnosed with atopic dermatitis.

Methods – In this randomized, double-blind, placebo-controlled crossover clinical trial, 21 client-owned cats diag-

nosed with mild to moderate nonseasonal atopic dermatitis were randomly assigned to two groups. Cats in each

group received either 1 mg/kg cetirizine hydrochloride or placebo once daily per os for 28 days followed by a

14 day wash-out period. Treatments were then crossed over, and cats received placebo or cetirizine hydrochlor-

ide for another 28 days. Owners marked a pruritus severity scale before inclusion in the study and weekly

throughout the entire study period. Lesions were scored by the clinician using a Canine Atopic Dermatitis Extent

and Severity Index (CADESI)-03 modified for the cat before enrolment and at day 28 of each treatment.

Results – Nineteen cats completed the study. There were no statistically significant differences between treat-

ment with cetirizine hydrochloride and placebo for modified CADESI-03 or pruritus scores.

Conclusion and clinical importance – This study suggests that cetirizine hydrochloride cannot be recom-

mended for the management of feline atopic dermatitis.

Introduction

Atopic dermatitis (AD) is a common skin disorder in cats,

with pruritus being one of the most characteristic signs.1

Glucocorticoids are commonly used for the management

of feline AD. Although glucocorticoid therapy is effective,

high-dose or long-term therapy may be associated with

adverse effects, including diabetes mellitus or skin atro-

phy.2 Ciclosporin has been shown to be effective but is

also potentially associated with significant adverse

effects and is relatively expensive.3 Allergen-specific

immunotherapy is considered to be a safe treatment in

cats but may take several months before obvious benefit

is noted, is relatively expensive and is usually given by

subcutaneous administration.4 Essential fatty acids are

also a safe alternative but have not been shown to be

effective as a single treatment.5 Antihistamines have

been used to treat feline AD.6–8 Histamine receptors, spe-

cifically H1 receptors, are found on mast cells, basophils,

macrophage/dendritic cells, T lymphocytes, neutrophils,

eosinophils, blood vessel endothelial cells and airway epi-

thelial and smooth muscle cells.9 The H1 antihistamines

stabilize the inactive configuration of H1 receptors and

thus inhibit histamine binding to the receptor and mast

cell degranulation.10 They appear to be well tolerated in

cats and are relatively affordable for pet owners.6–8,11

There are only a few open clinical trials investigating the

efficacy of antihistamines in cats with allergic pruritus.

These clinical trials showed an improvement of pruritus in

50% of the cats treated with clemastine, 45% of cats

treated with cyproheptadine and 77% of cats treated with

chlorpheniramine.6–8

Cetirizine is a second-generation antihistamine and an

active metabolite of hydroxyzine. Second-generation anti-

histamines do not cross the blood–brain barrier and, in

humans, are associated with less potential for sedation.12

A recent pharmacokinetic study in cats has shown that a

single dose of cetirizine of approximately 1 mg/kg results

in high plasma concentrations and a long half-life, compat-

ible with once daily dosing.11 In a recent open clinical trial,


Sources of Funding: This study was funded by the American

College of Veterinary Dermatology (ACVD) Resident’s Research

Award, Royal Canin USA Inc. and Heska Corporation.


Results of this study were presented as a poster at the 7th World

Congress of Veterinary Dermatology (WCVD) 2012; Vancouver,

Canada. Vet Dermatol 2012; 23 Suppl 1: 66.

© 2013 ESVD and ACVD, Veterinary Dermatology , 24, 576–e138.576


19 gatos1 mg/kg/dia/28 dias

Ausência de efeitos adversos

Results

CatsTwenty-one cats (10 male castrated and 11 female

spayed) met the inclusion criteria and were enrolled in

the study. They showed the following clinical signs in

addition to pruritus: self-induced alopecia (10 of 21

cats), self-induced alopecia with dermatitis (7 of 21

cats), facial dermatitis (2 of 21 cats) and self-induced

alopecia with facial dermatitis (2 of 21 cats). Nineteen

cats completed the study. One cat was excluded after

day 28 of the first treatment period due to severity of

clinical signs. One cat was lost to follow-up after

day 28 of the first treatment period for unknown

reasons. The owners of this cat did not return the

forms with the pruritus scales for any of the visits and

therefore only the modified CADESI-03 data on days 0

and 28 of the first treatment period were available for

analysis.

The age range of the study cats was 2–16 years (mean

7.9 years, median 7 years). The cats weighed between

3.1 and 6.6 kg (mean 5.8 kg, median 5.5 kg).

Modified CADESI-03 and pruritus scoresUpon inclusion in the study, the modified CADESI-03scores ranged from 26 to 112 (mean 45.5). Two of the 19

cats (10.5%) showed a modified CADESI-03 score

improvement of >50% at day 28 of treatment with CTZ.

In one cat (5.3%), the modified CADESI score worsened

by >50% at day 28 of treatment with CTZ. Four of 19 pla-

cebo-treated cats (21%) showed improvement of >50%at day 28. In one placebo-treated cat (5.3%), the modified

CADESI-03 score worsened by >50% at day 28. There

were no statistical differences in modified CADESI-03scores between the CTZ- or PBO-treated cats when data

were either evaluated continuously or dichotomized.

Pruritus scores at the beginning of the study ranged

from 4.0 to 7.5 (mean 5.1). In two of 19 CTZ-treated cats

(10.5%), pruritus scores improved by >50% at day 28.

None of the CTZ-treated cats had an increase in pruritus

score of >50%.

One PBO-treated cat (5.2%) showed an improvement

of >50% at day 28. One PBO-treated cat (5.2%) showed

an increase of pruritus score by >50% at day 28; this cat

was one of the patients that showed a > 50% improve-

ment in pruritus score and also a > 50% improvement in

the modified CADESI-03 score while being treated with

CTZ.

There were no significant statistical differences

between the CTZ- and PBO-treated cat pruritus scores

when the data were considered continuously or dichoto-

mized. Changes in modified CADESI-03 and pruritus

scores over time are shown in Figures 3 and 4.

Adverse eventsNone of the cats showed adverse effects to CTZ during

the study period.

Discussion

In this study, CTZ-treated cats showed a >50% improve-

ment of modified CADESI-03 scores and pruritus scores

Extremely severe itching/ almost continuous. Itching doesn't stop whatever is happening, even inexam room (needs to be physically restrained from itching)

Severe itching/ prolonged episodes. Itching might occur at night (if observed) and also when eating,playing, exercising or being distracted

Moderate itching/ regular episodes. Itching might occur at night (if observed) and also when eating,playing, exercising or being distracted

Mild itching/ a bit more frequent. Wouldn't itch when sleeping, eating, playing, exercising or beingdistracted

Very mild itching/ only occasional episodes. The cat is slightly more itchy than before the skinproblem started

Normal cat - I don't think itching is a problem

Figure 2. Scale used by owners to evaluate level of pruritus.

Figure 3. Modified CADESI-03 scores before and after treatment

with cetirizine hydrochloride (CTZ; n = 19) and placebo (PBO;

n = 21). Values are means ! SD.

© 2013 ESVD and ACVD, Veterinary Dermatology , 24, 576–e138. 579

Cetirizine in feline atopic dermatitis

Não é recomendada para controle de prurido em gatos atópicos!

Feline atopic dermatitis: a retrospective study of 45cases (2001–2012)Philippa A. Ravens*, Bei J. Xu† and Linda J. Vogelnest*

*Small Animal Specialist Hospital, Level 1, 1 Richardson Place, North Ryde, NSW 2113, Australia

†University of Sydney Veterinary Teaching Hospital, 410 Werombi Road, Brownlow Hill, NSW 2570, Australia

Correspondence: Philippa A. Ravens, Small Animal Specialist Hospital, Level 1, 1 Richardson Place, North Ryde, NSW 2135, Australia.

E-mail:[email protected]

Background – Atopic dermatitis (AD) is recognized as a common cause of pruritus in cats, but it remains incom-

pletely characterized.

Hypothesis/Objectives – The aim of the study was to evaluate cases of confirmed feline AD.

Animals – Fourty-five cats from a dermatology referral practice (2001–2012).

Methods – A retrospective case record review was carried out using strict diagnostic criteria, including exclusion

of flea-bite hypersensitivity and adverse food reaction.

Results – Disease prevalence was 12.5%, with domestic mixed (n = 24), Abyssinian (n = 6) and Devon rex

(n = 3) cat breeds predisposed. Median age of onset was 2 years (62% <3 years; 22% >7 years; range

3 months to 12 years). Common presentations were severe (82%), nonseasonal (82%), waxing/waning (36%)

pruritus, with alopecia/crusting/excoriations and/or erosions/ulceration (73%). Miliary dermatitis (20%) and eosin-

ophilic granuloma complex lesions (27%) occurred. The face/head (71%), ventral abdomen (51%), neck (51%),

limbs (38%), pinnae (31%), dorsum/rump (31%) and feet (16%) were frequently affected sites; lesions were

restricted to the head/neck in only five cats (11%). Concurrent otitis externa (16%), superficial bacterial pyo-

derma (49%), Malassezia dermatitis (7%), flea-bite hypersensitivity (24%) and adverse food reaction (13%)

occurred. Strong reactions on intradermal allergen testing were common (68%; 19 of 30), most frequently to pol-

lens (61%) and/or insects (46%). Good response to ciclosporin (100%; 10 of 10), systemic glucocorticoids (55%;

22 of 40) and allergen-specific immunotherapy (57%; 13 of 23) and good/partial response to antihistamines

(67%; 22 of 33) were reported.

Conclusions and clinical importance – The prevalence of feline AD was higher than previously suggested, and

breed predispositions were confirmed. Severe nonseasonal pruritus was most common, with a varied spectrum

of lesions affecting a range of body areas.

Introduction

Feline atopic dermatitis (AD) is suggested to be the sec-

ond most common allergic dermatosis in cats.1 Despite

reported clinical similarities to canine and human AD and

being referenced as feline AD in textbooks2 and reviews,3

there is some recent disagreement on nomenclature due

to limited current understanding of the pathogenesis.4

Increased CD4+ T cells, interleukin-4+ cells and CD1a+dendritic cells in lesional and/or nonlesional skin and in

affected compared with healthy cats are similar to findings

in canine and human AD, supporting a role for T-helper 2-

mediated immune dysfunction.3 However, a confirmed

role for immunoglobulin E (IgE) in feline AD is more con-

troversial,5 and despite numerous recent advancements

in the understanding of canine AD, very little research has

focused on the pathogenesis of feline AD to date.

Feline AD is anecdotally characterized by seasonal or

nonseasonal pruritus, and affected cats are reported com-

monly to exhibit one or more lesional patterns, including

symmetrical alopecia, miliary dermatitis, focused head

and neck pruritus and eosinophilic granuloma complex

(EGC) lesions.2,4 Young cats are reported to be predis-

posed, with clinical signs often developing before 3 years

of age, although a wide age range is noted.2,6 No sex or

breed predilections have been identified, and evidence of

inheritance is restricted to a single report of AD occurring

in three domestic short hair (DSH) littermates,7 in

contrast to canine and human AD, for which there are

well-established genetic links.2

The disease is currently diagnosed based upon a com-

patible history and clinical presentation, with exclusion of

other pruritic dermatoses.2 However, there are no widely

established clinical diagnostic criteria as there are in

dogs.8 Studies and case reports focusing on detailed

descriptions of feline AD are also limited,4,7,9,10 with only

one report of three cats that provides trial details for

exclusion of both flea-bite hypersensitivity (FBH) and

adverse food reactions (AFRs),7 which are recognized as

Accepted 28 November 2013

Sources of Funding: This study was self-funded.


© 2014 ESVD and ACVD, Veterinary Dermatology 1

Vet Dermatol 2014 DOI: 10.1111/vde.12109

BOA$RESPOSTA=$6%$

RESPOSTA$PARCIAL=$59%$

RESPOSTA$POBRE=$34%$

n=19=>$Lora:dina$$5$mg/gato$ n=18=>$Ce:rizina$5$mg/gato$

Ciclosporina

Dose: 7mg/kg/sid/VO

Pode ser administrado junto a refeição!

Ciclosporina

CONTRA'INDICAÇÕES.!  Gatos.com.histórico.de.doença.crônica.ou.

suspeita.de.malignidade.(neoplasia).

!  Gatos.FIV.ou.FeLV.++.!  Dermatofitose/Esporotricose.

INDICAÇÕES*!  Controle*de*prurido*a*longo*prazo*!  Refratários*a*corticoterapia*!  Diabéticos**

Ciclosporina

INTERAÇÕES*MEDICAMENTOSAS*!  Cetoconazol*!  Itraconazol*!  Claritromicina*

A randomized double-blinded placebo-controlled studyto evaluate an effective ciclosporin dose for thetreatment of feline hypersensitivity dermatitis

Stephen King*, Claude Favrot†, Linda Messinger‡, Tim Nuttall§, Jean Steffan*, Sophie Forster*and Wolfgang Seewald*

*Novartis Animal Health, Schwarzwaldallee 214, Basel, Switzerland

†Dermatology Department, Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland

‡Veterinary Referral Center of Colorado – Dermatology ⁄ Allergy, 3550 South Jason Street, Englewood, CO 80110, USA

§Department of Infection Biology, School of Veterinary Science, The University of Liverpool, Leahurst Campus, Neston, UK

Correspondence: Stephen King, Novartis Animal Health, Schwarzwaldallee 214, Basel, Switzerland. E-mail: [email protected]

Background – Hypersensitivity dermatitides (HD) are frequently suspected in cats, but there are few clinical

studies on safe and effective treatments in the published literature.

Objectives – To establish a safe and effective dose of ciclosporin in the treatment of feline HD.

Animals – One hundred client-owned cats with feline HD.

Methods – Double-blind study, with cats randomly assigned to receive ciclosporin at either 7.0 mg ⁄ kg once daily

(n = 33) or 2.5 mg ⁄ kg once daily (n = 32) or a placebo (n = 35) for 6 weeks.

Results – Mean Total Lesion Scores with 7.0 mg ⁄ kg ciclosporin were significantly lower than with 2.5 mg ⁄ kg

ciclosporin (P = 0.0047) or placebo (P = 0.0003) at study end. Individual Total Lesion Scores improved by >50%

in 70% of the 7.0 mg ⁄ kg group, compared with 47% in the 2.5 mg ⁄ kg group and 23% in the placebo group

(P = 0.0006). The investigators’ Global Assessment of Improvement was ‘excellent’ or ‘good’ in 61% of cats

treated with 7.0 mg ⁄ kg ciclosporin, compared with 47% of cats given 2.5 mg ⁄ kg and 23% given placebo. The

improvement in Investigator Pruritus Scores was significantly greater in cats treated with 7.0 mg ⁄ kg ciclosporin

(54%) compared with both 2.5 mg ⁄ kg ciclosporin (32%; P = 0.0232) and placebo (21%; P = 0.0063). Mild gas-

trointestinal disorders were the most common adverse events, but these did not require cessation of therapy.

Conclusions and clinical importance – Results suggest that 7.0 mg ⁄ kg ciclosporin once daily in food or per os

for 6 weeks is effective and well tolerated in feline HD.

Introduction

Hypersensitivity dermatitides (HD) are frequently sus-

pected in cats, but there are few published clinical studies

and most of the data have been drawn from the

observations of individual dermatologists.1–4 Hypersensi-

tivity dermatitis is a general term that usually encom-

passes flea-bite hypersensitivity, urticaria, angioedema,

food-induced hypersensitivity dermatitis, contact dermati-

tis and atopic dermatitis.4 It is usually accepted that aller-

gic cats exhibit pruritus and at least one of the following

pattern of lesions: head and neck excoriations or ulcer-

ations; self-induced alopecia; eosinophilic granuloma

complex (eosinophilic plaque, eosinophilic granuloma,

indolent ulcers and fat chin); and miliary dermatitis. It is,

however, worth noting that none of these signs or pat-

terns is pathognomonic of an allergic disease.2,5

Treatment of HD in cats generally relies on glucocortic-

oids, antihistamines, allergen-specific immunotherapy,

fatty acids, special diets selected following food elimina-

tion diet trials, flea control ⁄ avoidance and, more

infrequently, megestrol acetate.1 Treatment with corti-

costeroids and megestrol acetate is not always satisfac-

tory because adverse effects are not uncommon. The

efficacy of antihistamines has not been clearly demon-

strated, having been assessed only in an open single-arm

study.6 Hyposensitization has been evaluated in several

open studies, and success has been reported in 50–75%

of cases.7,8 Despite this, hyposensitization may not com-

monly be used, because identification of the offending

allergens can be difficult. The use of ciclosporin in the

treatment of feline HD with clinical signs of pruritus,

excoriation ⁄ ulceration, self-induced alopecia and eosino-

philic granuloma complex has been reported in small

uncontrolled pilot studies9 and retrospective studies.10 In

these studies, feline HD-associated pruritus and lesions

responded well (improvement in the range of 50–75%

after 30–60 days) to ciclosporin with greater than half of


Sources of Funding: This study was funded by Novartis Animal

Health, Basel, Switzerland.

Conflict of Interest: Stephen King, Jean Steffan, Sophie Forster

and Wolfgang Seewald are full-time employees of Novartis Ani-

mal Health. Tim Nuttall and Claude Favrot have received related

and unrelated consultancy fees, lecture fees and funding from

Novartis Animal Health.


440 ª 2012 ESVD and ACVD, Veterinary Dermatology, 23, 440–e84.

Vet Dermatol 2012; 23: 440–e84 DOI: 10.1111/j.1365-3164.2012.01086.x

7 mg/kg/dia

Dose tapering for ciclosporin in cats withnonflea-induced hypersensitivity dermatitis

Jean Steffan*, Elizabeth Roberts†, Andrea Cannon‡, Pascal Pr!elaud§, Peter Forsythe¶, JacquesFontaine**, Stephen King† and Wolfgang Seewald*

*Novartis Animal Health, Schwarzwaldallee 214, Basel, Switzerland

†Novartis Animal Health US, Inc., 3200, Northline Ave., Greensboro, NC 27408, USA

‡Animal Dermatology & Allergy, 3924 Oakdale Road, Modesto, CA 95357, USA

§Clinique Advetia, 5 rue Dubrunfaut, 75012, Paris, France

¶Veterinary Dermatology Referrals, Glasgow, G51 1RN, UK

**Animalclinic, Avenue Brugmann 425, Brussels, 1180, Belgium

Correspondence: Jean Steffan, Novartis Animal Health, Schwarzwaldallee 214, Basel, Switzerland. E-mail: [email protected]

Background – Little information is available on the ciclosporin dose-tapering regimen and clinical response in

the treatment of feline hypersensitivity dermatitis.

Hypothesis/Objectives – To test a dose-tapering regimen and assess efficacy and clinical safety for up to

18 weeks.

Animals – Eighty-eight client-owned cats with feline hypersensitivity dermatitis.

Methods – Cats that received either a placebo or ciclosporin at 2.5 mg/kg or 7 mg/kg daily for 6 weeks were

given 7 mg/kg ciclosporin daily for 4 weeks. Depending on the clinical response, the dose was tapered from daily

to every other day over the next 4 weeks and further to twice a week for an additional 4 weeks.

Results – After all cats received 7 mg/kg for 4 weeks, the dose could be tapered to every other day for the

next 4 weeks in 70% of cats remaining in the study. During the next 4 weeks, 57, 15 and 22% of cats

remaining in the study could be treated at twice a week, every other day or daily, respectively. After the

first 4 weeks, the mean lesion score and owner-assessed pruritus improved over baseline by 69 and 61%,

respectively, and remained stable during the following 8 weeks. Approximately 65% of the cats in the study

were reported to have an adverse event (AE), very often mild and resolving spontaneously. The most fre-

quent AEs were gastrointestinal and included primarily vomiting and diarrhoea. Eighty per cent of AEs

occurred when cats were on daily treatment.

Conclusions and clinical importance – Results suggest that the induction dose of 7 mg/kg ciclosporin can be

tapered as soon as 4 weeks without deterioration of the clinical response. Establishment of the lowest effective

dosing regimen of ciclosporin reduced the frequency of AEs.

Introduction

Ciclosporin has been used for many years in the treat-

ment of feline hypersensitivity dermatitis at various

doses, generally ranging from 5 to 10 mg/kg.1–4 The dose

of 7 mg/kg given daily has recently been tested in a ran-

domized, blinded parallel group, placebo-controlled study

and was shown to be efficacious and well tolerated.5 In

cats with head and neck excoriations, self-induced alope-

cia, eosinophilic plaque and/or miliary dermatitis, the

administration of 7 mg/kg ciclosporin daily for 6 weeks

resulted in a decrease in total lesion and owner-assessed

pruritus severity scores. In cats receiving the 7 mg/kg

daily dose, the most common adverse events were mild

gastrointestinal disorders. That dose-determination study

was aimed at establishing an efficacious and safe dose.

Dosing duration was limited to 6 weeks and did not

address the long-term use of ciclosporin to treat feline

hypersensitivity dermatitis.

In cats, limited information is available about long-

term efficacy and safety of ciclosporin. Studies suggest

that feline hypersensitivity dermatitis can be well con-

trolled with dose tapering;2,6 however, the frequency

and response to dose tapering has not been docu-

mented in cats. The present study was designed to

assess the clinical response to a dose-tapering regimen

and the tolerability to ciclosporin administered for up to

18 weeks.

Materials and methods

Study designThe study was conducted in two phases. The first phase established

7 mg/kg as an effective dose of ciclosporin for the treatment of

hypersensitivity dermatitis.5 The present study presents the out-

come of the second phase, in which a dose-tapering regimen was

examined.


Sources of Funding: This study was funded by Novartis Animal

Health, Basel, Switzerland.

Conflict of Interest: J.S., E.R., S.K. and W.S. are full-time

employees of Novartis Animal Health. A.C., P.P., P.F. and J.F.

have received related and unrelated consultancy fees, lecture

fees or investigator fees from Novartis Animal Health.

© 2013 The Authors. Veterinary Dermatology



Dose: 7 mg/kg/SID/ 4 semanas

7 mg/kg/48h/4 sem (em15%)

7 mg/kg/ 2x/sem (em 57%)

88 gatos

Em até 70%

Veterinary Dermatology 2013; 24: 315–e70.

Adverse events in 50 cats with allergic dermatitisreceiving ciclosporin

Nicole A. Heinrich, Patrick J. McKeever andMelissa C. Eisenschenk

McKeever Dermatology Clinics, Inc., Eden Prairie,

MN, USA

Correspondence: Nicole A. Heinrich, McKeever Dermatology

Clinics, Inc. 7723 Flying Cloud Drive Eden Prairie, MN 55344, USA.

E-mail: [email protected]

Sources of Funding

This study is self-funded.



Parts of this study were published as an abstract from the 25th North

American Veterinary Dermatology Forum in Portland, OR, USA; Vet-

erinary Dermatology 2010; 21: 326.

Abstract

Ciclosporin is an immunosuppressive drug thathas been used to treat allergies and other immune-mediated diseases in cats, dogs and humans. Infor-mation about the adverse effects of ciclosporin in catshas been limited to smaller studies and case reports.Adverse effects in dogs are mainly gastrointestinal innature, but humans can also experience hypertensionand altered renal function. The aim of this retrospec-tive case series study was to document the occur-rence and clinical appearance of adverse events incats receiving ciclosporin to treat allergic skin disease.The medical records of 50 cats with allergic dermatitistreated with oral ciclosporin (1.9–7.3 mg ⁄ kg ⁄ day)were reviewed. Adverse events occurred in 66% (33cats). Adverse events likely to be associated withciclosporin included the following: vomiting or diar-rhoea within 1–8 weeks of receiving ciclosporin(24%), weight loss (16%), anorexia and subsequenthepatic lipidosis (2%) and gingival hyperplasia (2%).Other adverse events less likely to be associated withciclosporin therapy included the following: weightgain (14%), dental tartar and gingivitis (10%), otitis(4%), chronic diarrhoea (4%), inflammatory boweldisease with indolent gastrointestinal lymphoma(2%), urinary tract infection (2%), cataract (2%), ele-vated liver enzymes (2%), hyperthyroidism and renalfailure (2%) and transient inappropriate urination(2%). Some cats experienced multiple adverse events.Case–control studies are needed to prove cause andeffect of ciclosporin with regard to these adverseevents.

Accepted 30 March 2011

Introduction

Feline allergic dermatitis is characterized by pruritus and

varying degrees of alopecia, erythema and crusting.1

These lesions generally affect the head, neck, forelegs,

groin, lateral thorax and caudal thighs.1 Feline allergic

dermatitis varies in severity; some cats require minimal

or no treatment, while other cats require intensive, daily

therapy.

Corticosteroids are often used to treat feline allergic

dermatitis, but adverse effects (such as diabetes mell-

itus2) associated with this therapy have stimulated inter-

est in alternative treatments.

The use of ciclosporin is gaining acceptance for treat-

ment of feline allergic dermatitis, as several studies and

anecdotal reports have demonstrated efficacy and appar-

ent safety.3,4 The true safety of this drug is of concern, as

only limited data are available that specifically address the

adverse effects of ciclosporin in cats.5–7

Ciclosporin treatment in cats has been associated with

toxoplasmosis,6,7 post-transplant malignant neoplasia,8,9

diarrhoea,3,4 vomiting, hyperactivity, increased appetite,4

anorexia10 and gingival hyperplasia.11 This is similar to

dogs, in which gingival hyperplasia12 and gastrointestinal

(GI) upsets13 have also been described. Humans have

also developed gingival hyperplasia, GI upsets and malig-

nancy in association with ciclosporin.14

In contrast to cats, dogs can also develop hirsutism, cuta-

neous papillomatous hyperplasia, hyperkeratosis of the

footpads, increase in nail growth and lymphoplasmatoid

dermatitis in association with ciclosporin.5 Adverse effects

associated with ciclosporin use in humans include hirsut-

ism, skin rash, neurological signs, hypertension, hepatic

dysfunction, impaired renal function and musculoskeletal

pain.5Theseadverseeffectshavenotbeenreported incats.

Ciclosporin affects a number of cells in the skin, includ-

ing T cells, dendritic cells and keratinocytes. Ciclosporin

is a calcineurin inhibitor;15 calcineurin causes dephosphor-

ylation of nuclear factor of activated T cells (NFAT). NFAT

promotes transcription of genes that encode for proin-

flammatory cytokines, including interleukin (IL)-2, IL-4,

interferon (IFN)-c and tumour necrosis factor (TNF)-a.16

Ciclosporin inhibition of gene transcription for these cyto-

kines has been specifically demonstrated in cats.17 These

cytokines lead to activation and proliferation of T cells.

Ciclosporin also specifically impairs the ability of dendritic

cells to stimulate proliferation of T cells,18 and blocks

calcineurin and NFAT in epidermal keratinocytes.19

Cats with allergic dermatitis have been shown to have

higher numbers of T cells (both CD4+ and CD8+) in

lesional skin compared with healthy cats.20 It has also

been demonstrated that these CD4+ T cells are the pri-

mary producers of IL-4.21



DOI: 10.1111/j.1365-3164.2011.00983.xAdverse events in 50 cats with allergic dermatitisreceiving ciclosporin



MN, USA




Sources of Funding







Abstract



Introduction







therapy.















































DOI: 10.1111/j.1365-3164.2011.00983.x

Adverse events in 50 cats with allergic dermatitisreceiving ciclosporin



MN, USA




Sources of Funding







Abstract



Introduction







therapy.















































DOI: 10.1111/j.1365-3164.2011.00983.x

One cat developed gingival hyperplasia after 1 year of

receiving generic modified ciclosporin daily. All three

raters agreed that the probability of an adverse drug

reaction was ‘probable’.

The authors all considered the next group of adverse

events unlikely to be caused by ciclosporin administration

and classified them as having ‘doubtful’ probability.

Seven cats (14%) developed dental tartar and gingivitis.

Five cats (10%) experienced 14–42% weight gain over

varying lengths of time. Two cats developed diabetes

mellitus while concurrently receiving oral dexametha-

sone, and two cats developed otitis. The following

adverse events were reported once each: transient

inappropriate urination, urinary tract infection (one author

rated this event as a ‘possible’ drug reaction), corneal

ulcer, constipation, transient coughing and sneezing, and

hyperthyroidism with subsequent chronic renal failure.

Discussion

This paper describes a case series, which is a study

design that cannot formally investigate causality. Case

series are important for detecting potential safety signals,

which need to be tested with more rigorous study

designs such as case–control or cohort studies.25

This case series lists every adverse event that occurred

in a population of 50 cats receiving ciclosporin to treat

allergic skin disease. Table 3 summarizes these events.

The authors offer expert opinion regarding causality usingTab

le1.

(Continued)

Cat

Age

star

ted

CS

A

Dia

gnose

sprior

tost

arting

CS

A

Typ

eof

CS

AD

ose

Initia

l

concu

rrent

medic

atio

ns

Mai

nte

nan

ce

dose

and

oth

er

medic

atio

ns

Tim

eon

CS

AFollo

wup

Adve

rse

eve

nts

and

dia

gnose

saf

ter

star

ting

CS

A

46

13

year

sA

DA

topic

a!

6m

g⁄k

gD

exa

meth

asone,1.5

mg

6m

g⁄k

geve

ry2

day

san

d

inte

rmitte

nt

ora

l

dexa

meth

asone

18

month

sA

nnual

exa

min

atio

n,

CB

C⁄c

hem

⁄tota

l

thyr

oxi

ne

Chro

nic

dia

rrhoea

1ye

ar

late

r

47

1ye

arA

DA

topic

a!

4.6

mg

⁄kg

None

4.6

mg

⁄kg

eve

ry2

day

san

d

inte

rmitte

nt

ora

l

dexa

meth

asone

3ye

ars

Annual

exa

min

atio

nD

iarr

hoea

3ye

ars

late

r

48

10

year

sA

D,eosi

nophili

c

pla

que

Ato

pic

a!

25

mg

per

cat

Dexa

meth

asone,1.5

mg

4.4

mg

⁄kg

eve

ry2

day

s2

year

sA

nnual

exa

min

atio

nU

rinar

ytr

act

infe

ctio

nonce

2ye

ars

late

r

49

11

year

sA

DA

topic

a!

3.4

mg

⁄kg

None

3.4

mg

⁄kg

eve

ry3–4

day

s14

month

sA

nnual

exa

min

atio

n,

CB

C⁄c

hem

Ele

vate

dliv

er

enzy

mes,

pro

gre

ssiv

ew

eig

ht

loss

1ye

arla

ter

50

12

year

sA

DA

topic

a!

25

mg

per

cat

Dexa

meth

asone,1.5

mg

25

mg

eve

ry2

day

s17

month

sA

nnual

exa

min

atio

n,

CB

C⁄c

hem

⁄to

talt

hyr

oxi

ne

Hyp

ert

hyr

oid

ism

,ch

ronic

renal

failu

re2

year

sla

ter

AD

,at

opic

derm

atitis

;A

DE

,ad

vers

eeve

nts

;A

FR

,ad

vers

efo

od

reac

tion;C

BC

,co

mple

teblo

od

count;

chem

,se

rum

chem

istr

y;C

SA

,ci

closp

orin;H

CM

,hyp

ert

rophic

card

iom

yopat

hy;

IBD

,in

flam

mat

ory

bow

eld

iseas

e;

UA

,urinal

ysis

.

Table 2. Statistical inter-rater agreement for gastrointestinal events

Gastrointestinal events j-value P-value Agreement

Overall 0.52 0.0001 Moderate

Definite reactions )0.09 0.59 Low

Probable reactions 0.48 0.004 Moderate

Possible reactions 0.84 <0.0001 High

Table 3. Number of adverse events by category

Adverse event

Number

of cats

Vomiting, diarrhoea and ⁄ or anorexia within 1–8 weeks

of starting ciclosporin

12

Weight loss 8

Dental tartar and gingivitis 7

Weight gain 5

Chronic diarrhoea after receiving ciclosporin for

12 months or more

2

Diabetes mellitus 2

Otitis 2

Severe inflammatory bowel disease, indolent

gastrointestinal lymphoma and mild hypertrophic

cardiomyopathy

1

Hepatic lipidosis 1

Elevated liver enzymes 1

Gingival hyperplasia 1

Transient inappropriate urination 1

Urinary tract infection 1

Corneal ulcer 1

Constipation 1

Transient coughing and sneezing 1

Hyperthyroidism with subsequent chronic renal failure 1



Heinrich et al.

Subcutaneous administration of ciclosporin in 11allergic cats – a pilot open-label uncontrolled clinicaltrial

Sandra N. Koch* , Sheila M. F. Torres*, Sandra Diaz†, Sophie Gilbert§ and Aaron Rendahl‡

*Department of Veterinary Clinical Sciences, University of Minnesota, 1365 Gortner Avenue, Saint Paul, MN 55018, USA

†Department of Veterinary Clinical Sciences, The Ohio State University, 601 Vernon Tharp Street, Columbus, OH 43210, USA,

§Centre V!et!erinaire Laval, 4530 Highway 440, Laval, Quebec Canada, H7T 2P7 and

‡Department of Veterinary and Biomedical Sciences, University of Minnesota, 1365 Gortner Avenue, Saint Paul, MN 55018, USA

Correspondence: Sheila M. F. Torres, Department of Veterinary Clinical Sciences, University of Minnesota, 1365 Gortner Avenue, Saint Paul, MN

55018, USA. E-mail: [email protected]

Background – Oral ciclosporin has been reported to be efficacious for feline inflammatory skin diseases; how-

ever, cats are often difficult to medicate orally.

Hypothesis/Objective – To evaluate the efficacy and tolerability of subcutaneous ciclosporin administered to

cats with allergic skin disease.

Animals – Eleven client-owned cats with nonseasonal clinical signs.

Methods – Prospective open label trial. Ciclosporin 50 mg/mL solution for injection (Sandimune!, Novartis; NJ,

USA) was administered subcutaneously for 60 days with initial doses ranging from 2.5 mg/kg once daily (one

cat) to every other day (five cats) and 5 mg/kg once daily (four cats) to every other day (one cat). Dosages

were adjusted monthly if needed based on clinical response. Clinical response was assessed using a modified

FeDESI (feline Dermatitis Extent and Severity Index) and PVAS (pruritus Visual Analog Scale) between days (D)

0, 30 and 60.

Results – Six cats completed the study and four of five cats withdrawn from the study were included in an inten-

tion-to-treat analysis. There was significant decrease in FeDESI and PVAS scores between D0 and D30, D0 and

D60 and D30 and D60 (P < 0.05) in all ten cats.

Conclusions and clinical importance – Ciclosporin administered subcutaneously at initial doses of 2.5-5 mg/

kg, once daily to alternate days, appears to be an efficacious therapy for feline allergic dermatitis and may be an

alternative therapy for cats that cannot be treated orally. Randomized and controlled long term studies which

include a larger number of cats are needed to confirm these findings.

Introduction

Feline dermatoses, including allergic diseases, are often

challenging to manage. Topical therapies are frequently

not well tolerated by cats, may pose risk of systemic

adverse effects due to drug ingestion and are typically

used as adjunctive therapies.1 Antihistamines and essen-

tial fatty acids are treatment options but the success rate

is variable and often low.1 Oral and injectable glucocorti-

coids are quite effective but have the potential for severe

long-term adverse effects, including diabetes mellitus.1

Oclacitinib maleate may be an alternative treatment for

cats with allergic skin disease, although in one pilot

study only five of 12 (41.6%) cats with nonflea- and

nonfood-induced hypersensitivity dermatitis treated

with oclacitinib, at the doses recommended for dogs,

showed good improvement after 30 days of therapy.2

Several studies have investigated the use of oral ciclos-

porin A (CsA) in cats with various skin disorders; the effi-

cacy and safety of CsA for the treatment of feline allergic

dermatoses has been reported in double-blinded and ran-

domized controlled trials.3–9 Additionally, CsA has been

reported in retrospective and case series reports to

be effective for other feline dermatological conditions

including eosinophilic granuloma complex, urticaria pig-

mentosa, plasmacytic stomatitis, acquired alopecia (pseu-

dopelade), pemphigus complex, idiopathic pruritus and

dirty face syndrome of Persian cats.7–9 Mild adverse

effects have been reported with oral CsA administration

in cats, including hypersalivation, headshaking, vomiting,

soft faeces, diarrhoea and gingival hyperplasia.10,11 Given

the reported efficacy and minimal adverse effects, oral

CsA appears to be a valid therapeutic approach for the

long-term control of feline allergic skin diseases. How-

ever, cats are often difficult to medicate orally which

could interfere with the efficacy of CsA and result in treat-

ment discontinuation by the owners. In addition, oral CsA

Abbreviations: CsA, ciclosporin; sCsA, subcutaneous injectedciclosporin.

Accepted 31 August 2017

Sources of funding: This study was self-funded

Conflict of interest: No conflicts of interest have been declared.





















0, 30 and 60.








Introduction










































Ciclosporina 50 mg/ml SC

Dose: 2.5 a 5.0 mg /Kg/SID ou EDA

the study were 2.5 mg/kg every third day (two cats),

5 mg/kg once daily (two cats) and 5 mg/kg every other

day (four cats). Only six of 11 cats completed the study

and their dosages included 2.5 mg/kg every third day

(one cat), 5 mg/kg every 36 to 48 h (one cat), 5 mg/kg

every other day (three cats) and 5 mg/kg every third day

(one cat), (Table S1).

WithdrawalFive (45.45%) cats (cases 7, 8, 9, 10 and 11) were with-

drawn from the study per owners’ requests prior to trial

completion (D60). One cat (Case 8) was withdrawn due

to behaviour changes reported by the owner and lack of

response to therapy. Two cats (cases 9 and 11), although

improved, were withdrawn because of adverse effects at

injection sites reported by the owners. Two cats (cases 7

and 10) were withdrawn because the owners were not

comfortable to continue administering the injections.

Table S1 shows details of withdrawal times and reasons

for each cat.

Assessment of skin lesions (FeDESI)The Friedman test showed a significant (P = 0.0002)

impact of therapy on skin lesions. Pairwise analyses

showed significant skin lesion improvement between D0

and D30 (P = 0.008), D0 and D60 (P = 0.006) and D30

and D60 (P = 0.02). Figure 1 and Table S2 show the indi-

vidual scores. Figure S1 and Figure S2 show pictures of

two cats that completed the study.

Assessment of pruritus (PVAS)The Friedman test showed a significant (P = 0.0003)

impact of therapy on pruritus. Pairwise analyses showed

significant pruritus decrease between D0 and D30

(P = 0.028), D0 and D60 (P = 0.026) and D30 and D60

(P = 0.034). Figure 1 and Table S2 show the individual

scores.

Adverse effects and laboratory testsA total of six (54.5%) cats (4, 5, 6, 8, 9 and 11) devel-

oped adverse effects reported by the owners. Five cats

(4, 5, 6, 9 and 11) developed lesions associated with the

injection sites, seven to 10 days after starting therapy

(Table S1). Owners described the lesions as focal hair

loss, crusts, abscesses or swellings with or without ooz-

ing. These resolved in three of five cats (cases 4, 5 and

11) after changing the injection site, reviewing injection

administration instructions or discontinuing therapy.

Cases 4 and 11 had focal alopecia at the injection sites

observed by the investigators on D30 and presumed to

be sequelae of previous lesions. One cat (Case 8) devel-

oped behaviour changes and another cat (Case 9) was

licking the injection site and twitching her back after

each injection. None of the cats developed systemic

signs during the study duration or follow-up period. In

one cat (Case 4) the pre-diagnosed diabetes mellitus

remained clinically controlled during the follow-up period.

Table S1 shows details on adverse events for each cat.

Ten (90.9%) cats had chemistry profiles, complete CBC,

urinalyses and urine cultures before starting sCsA ther-

apy. Six (60%) cats had these tests repeated on D60.

There were no significant abnormalities reported at any

time for any of the cats.

Follow-up of cats after completion of the studySix cats (cases 1, 2, 3, 4, 5 and 6) continued to receive

sCsA therapy beyond D60, with therapy duration rang-

ing from three to 18 months (mean: 9.8 months). The

maintenance sCsA dose for these cases ranged from

2.5 to 5 mg/kg every two to three days. Any further

attempt to taper the frequency of injections failed with

recurrence of pruritus with or without skin lesions and

alopecia. No adverse reactions were reported during the

follow-up visits. Table S1 provides further details on

treatment duration.

Figure 1. Feline Dermatitis Extent and Severity Index and pruritus Visual Analog Scale (range 0-10) scores on days (D) 0, 30 and 60 in 10 cats with

allergic skin disease (Cat 10 not included).


Subcutaneous CsA for feline skin disease



















0, 30 and 60.








Introduction










































Efeitos adversos em54.5% dos casos

5 gatos => lesões no local da aplicação 7 a 10 dias após.

1 gato => alteração comportamental

OclacitinibApoquel®

Oclacitinib in feline nonflea-, nonfood-inducedhypersensitivity dermatitis: results of a smallprospective pilot study of client-owned cats

Christian Ortalda*, Chiara Noli†, Silvia Colombo‡ and Stefano Borio§

*Servizi Dermatologici Veterinari, Strada Revigliasco 11, Moncalieri, 10024, Italy

†Servizi Dermatologici Veterinari, Strada Bedale della Ressia 2, Peveragno, 12016, Italy

‡Servizi Dermatologici Veterinari, via Felice Musazzi 24, Legnano, 20025, Italy

§Servizi Dermatologici Veterinari, via Italia 12, San Mauro Torinese, 10099, Italy

Correspondence: Chiara Noli, Servizi Dermatologici Veterinari, Strada Bedale della Ressia 2, 12016 Peveragno (CN), Italy. E-mail: info@dermatologia

veterinaria.it

Background – Oclacitinib is a Janus kinase inhibitor that decreases pruritus and lesions in allergic dogs. In cats,

it is able to inhibit interleukin-31-induced pruritus; no information is available on its clinical effectiveness.

Hypothesis/Objectives – To evaluate the efficacy, ease of administration and tolerability of oclacitinib in feline

nonflea-, nonfood-induced hypersensitivity dermatitis.

Methods – Cats >12 months of age and >3 kg body weight with a diagnosis of nonflea-, nonfood-induced hyper-

sensitivity dermatitis were treated with oclacitinib, 0.4–0.6 mg/kg orally (p.o.) twice daily for 2 weeks, then once

daily for an additional 14 days. Clinical lesions were evaluated with the Scoring Feline Allergic Dermatitis (SCOR-

FAD) system and pruritus was evaluated with a 10-cm-long visual analog scale (VAS) before and at the end of the

study. Owners assessed global efficacy, ease of administration and tolerability with a four-point scale.

Results – Twelve cats were treated with a mean initial oclacitinib dose of 0.47 mg/kg p.o. twice daily. There was

good improvement in SCORFAD and VAS pruritus scores in five of 12 cases, while the other cats were

unchanged, deteriorated or dropped out due to treatment failure. Owners scored global efficacy as good/excel-

lent in four of 12 cases and ease of administration and tolerability as good/excellent in 10 of 12.

Conclusions and clinical importance – Oclacitinib at 0.4–0.6 mg/kg p.o. may be an effective and safe drug for

some cats with nonflea-, nonfood-induced hypersensitivity dermatitis. Further studies are needed to identify the

most effective dose range for this species.

Introduction

Feline allergic dermatitis is a common disease in veteri-

nary dermatology and is the result of a cutaneous

hypersensitivity reaction to environmental, food and/or

flea allergens. Current therapies include allergen-spe-

cific immunotherapy, antihistamines, essential fatty

acids, palmitoylethanolamide, glucocorticoids and ciclo-

sporin.1,2 Oclacitinib (Apoquel; Zoetis, Rome, Italy) is a

Janus kinase inhibitor which has been registered for

the treatment of allergic pruritus and atopic dermatitis

in the dog. It may be an option for the treatment of

feline allergic diseases. When administered orally (p.o.)

to cats at a dose of 0.4 mg/kg it was able to reduce

pruritus induced by interleukin-31 significantly.3,4 There

is scant information about the use of oclacitinib in cats

and it is limited to experimentally induced asthma.5

Results of this preliminary trial demonstrated that a

dose of 0.5–1.0 mg/kg p.o. twice daily for 28 days was

safe and effective; serial clinical examinations and com-

plete blood count, serum biochemical profile and urinal-

ysis were performed; no adverse clinical signs or

clinically relevant laboratory abnormalities were

observed. The only report about the use of oclacitinib

in a cat with a dermatological condition described a lab-

oratory cat affected with mastocytosis that was suc-

cessfully treated with oclacitinib at 1 mg/kg p.o. twice

daily for 1 month.6

The aim of this small pilot study was to evaluate the

response to and safety of oclacitinib in cats with nonflea-,

nonfood-induced hypersensitivity dermatitis (NFNFIHD).

Primary outcome measures were changes in pruritus and

lesion scores. Secondary outcome measures were ease

of administration, tolerability and development of adverse

effects.

Materials and methods

This was an open multicentre study involving four clinics.

AnimalsCats >12 months of age and >3 kg body weight, diagnosed with

NFNFIHD following the standard procedures and fulfilling Favrot’s

feline allergy diagnostic criteria, were included in the study.7 Cats

were not included if ectoparasitic infestations, bacterial or fungal

infections, flea-allergy dermatitis or other diseases were diagnosed.


Sources of Funding: This study was self-funded.

Conflict of Interest: The authors have consulted for Zoetis and

for several other pharmaceutical companies. The drug manufac-

turer was not involved in the design or support of this study.

© 2015 ESVD and ACVD, Veterinary Dermatology, 26, 235–e52. 235


Melhora em 5/12 gatosDose: 04-0.6 mg/kg/bid

Abstracts of the 29th Annual Congressof the ECVD-ESVD, 7-9th September 2015,

Lausanne, Switzerland

Novel serum biomarkers of oxidativestress in canine atopic dermatitis

R. M. ALMELA*, U. MAYER*, C. P. RUBIO†,A. ANS!ON‡, A. TICHY‡ and J. J. CER!ON†

*Kleintierspezialisten Augsburg €Uberweisungszentrum,Augsburg, Germany†Interdisciplinary Laboratory of Clinical Analysis, CampusExcellence Mare Nostrum, Murcia, Spain‡Veterin€armedizinische Universit€at Wien, Vienna, Austria

Atopic dermatitis (AD) is a disease with a highly complex

and not fully understood pathophysiology. Oxidative

stress (OS) has been shown to be involved in the patho-

genesis of human and canine AD by several distinct

mechanisms. Recently, novel serum biomarkers of OS

(sbOS) have been validated in normal dogs; they do not

appear to have been studied in dogs with AD, however.

The aim of this prospective, cohort-controlled study was

to compare a panel of novel sbOS (thiol [THIOL], ferric

reducing ability of the plasma [FRAP], cupric reducing

antioxidant capacity [CUPRAC], trolox equivalent antioxi-

dant capacity [TEAC], trolox equivalent antioxidant capac-

ity-B [TEAC-B], and ferrous oxidation-xylenol orange

[FOX]) in normal and atopic dogs. To evaluate the antioxi-

dant response, we assessed the levels of the THIOL,

FRAP, CUPRAC, TEAC and TEAC-B parameters, while

that of FOX was measured as a biomarker of oxidative

damage. We included 46 healthy dogs, nine client owned

dogs with nonfood-induced and three with food-induced

AD. The mean serum levels for THIOL, CUPRAC, TEAC

and TEAC-B were significantly lower in all categories of

dogs with AD (NFIAD + FIAD; NFIAD; FIAD) compared to

those of healthy dogs; whereas FOX and FRAP values

were significantly higher in the atopic group (two-tailed t-

tests/Mann–Whitney test, P < 0.05 for all). These find-

ings suggest that oxidative stress could play an important

role in the pathogenesis of canine AD. In addition, the

evaluation of sbOS could be useful to help detect subsets

of atopic dogs who might benefit of antioxidant therapies.

Source of funding: Self-funded.

Conflict of interest: None declared.

Use of RNAScope in situ hybridizationto assess the context-specificexpression of genes in canine tissues

G. BAMMERT, S. DUNHAM, C. HEDKE andA. GONZALESZoetis, Kalamazoo, MI, USA

Understanding disease pathogenesis often involves mon-

itoring differential gene expression through comparison

of RNA from healthy, model and diseased cell popula-

tions; such studies eventually lead to the examination of

protein-based cellular imbalances that are fundamental to

better understand disease mechanism. RNAScope in situ

hybridization (RNA-ISH) overcomes the technical chal-

lenges involved with signal amplification, as it allows sin-

gle gene expression to be monitored in the context of

cellular and tissue morphological changes. We describe

the use of RNA-ISH to probe the expression of selected

genes (il4r, il13ra1, il31ra, trpv1 and ntrk1) in normal bea-

gle skin, dorsal root ganglia (DRG) and spinal cord tissues:

these genes were chosen for their association with atopic

dermatitis or the neuronal signal transduction of itch and

pain sensations. Formalin-fixed, paraffin-embedded

(FFPE) tissues were probed using the Leica Bond Rx with

haematoxylin counter-staining to define nuclei, while

proximal sections were H&E-stained to capture cellular

and tissue morphology. Staining was qualified with a con-

stitutive positive (PPIB) and negative (DapB) controls. All

genes appeared similarly expressed in canine skin. While,

Il4r and il13ra1 were absent from dog DRGs, there was a

robust expression of il31ra, trpv1 and ntrk1 in these neu-

rons. Our results describe a step forward in understand-

ing a context-specific expression of genes relevant to

canine atopic dermatitis. These methods will likely play

an important role in understanding how a clinical disease

relates to tissue gene expression, and they may allow for

the development of relevant cellular models for assess-

ment of drug safety and efficacy.

Source of funding: Zoetis Global Therapeutics Research.

Conflict of interest: GB, SD, CH and AG are employees of

Zoetis.

© 2017 ESVD and ACVD, Veterinary Dermatology

1


their clinical manifestations of atopic dermatitis (AD).

Eighty one dogs that responded positively to the initial

three month lokivetmab treatment in a positive-controlled

field study were enrolled into this trial. These dogs were

continued on monthly subcutaneous injections with loki-

vetmab for up to six additional administrations at the mini-

mum dosage of 1 mg/kg. Prior to each monthly

treatment, the dog owners assessed pruritus levels using

a visual analog scale (VAS) while investigators assessed

skin lesions using the CADESI-03. Blood was drawn

monthly (clinical pathology, drug exposures) and urine col-

lected every three months (urinalysis). At the end of this

study, after nine months, the mean VAS (which reached

a low of 14) and CADESI-03 (reduced to 32) remained

similar to their respective values at the start of this exten-

sion trial. After nine months of lokivetmab injections, 45/

59 dogs (76%) were assessed as being “normal” with

regards to their pruritus levels (VAS score ≤ 19) and 35 of

these (59%) were deemed with skin lesions “in remis-

sion” (CADESI-03 ≤ 15). None of the observed adverse

events were attributable to lokivetmab; treatment-

induced immunogenicity (i.e. anti-lokivetmab antibody

development) was not seen in any dog. This study

demonstrated that lokivetmab injections were well toler-

ated for up to 9 months at a monthly minimum dose of

1 mg/kg, and it provided a continuous and robust efficacy

against both pruritus and skin lesions in dogs with AD.

Source of funding: Zoetis.

Conflict of interest: All authors are employees of Zoetis.

Laboratory evaluation of the speed ofkill of lotilaner against Ixodes ricinusticks on dogs

M. G. MURPHY, D. A. CAVALLERI, W. SEEWALD,J. J. DRAKE and S. NANCHENElanco, Basel, Switzerland

The novel isoxazoline lotilaner is rapidly absorbed follow-

ing administration of a chewable tablet formulation (Cre-

delio, Elanco, Greenfield, IN, USA) to dogs, and it

provides efficacy for a minimum of 1 month against fleas

and ticks. This study was conducted to determine its

speed of kill against ticks. Thirty two dogs were random-

ized to four groups: two received lotilaner tablets at a min-

imum dose rate of 20 mg/kg and two were left untreated.

Infestations with Ixodes ricinus were performed on Days

-2, 7, 14, 21, 28 and 35. Counts were completed 4 and

8 h on Day 0, and 8 and 12 h following the subsequent

infestations. All live ticks were incubated, without loti-

laner, for 24 h following removal. At 4 h post-treatment,

there was a 70% reduction in geometric mean live tick

counts in treated dogs compared to controls. After incu-

bation, this reduction increased to 97%. At 8 h after treat-

ment, pre- and post-incubation reductions were 99% and

100%, respectively. Following post-treatment challenges,

the post-incubation efficacy through Day 28 (at 8 and

12 h) was at least 94% and 98%, respectively, and 86

and 94% at 8 and 12 h after the last challenge on Day 35.

There were no treatment-related adverse events.Loti-

laner, at a minimum dose rate of 20 mg/kg, was well tol-

erated and began to kill ticks on dogs within 4 h of

treatment; its efficacy was 100% within 8 h. Lotilaner

sustained a rapid kill of I. ricinus ticks throughout this

35 day study.

Source of funding: Elanco.

Conflicts of interest: All authors are employed by Elanco.

Efficacy of oclacitinib in allergic cats: amulticentre randomised, blinded,methylprednisolone-controlled study

C. NOLI*, I. MATRICOTI* and C. SCHIEVANO†

*Servizi Dermatologici Veterinari, Peveragno, Italy†Universit!a di Padova, Padova, Italy

Oclacitinib is a Janus kinase inhibitor that decreases inter-

leukin-31-induced pruritus in cats. At 0.4-0.6 mg/kg/day

orally, it relieves pruritus and skin lesions in less than half

of allergic cats. We aimed to evaluate the efficacy and

safety of a higher dosage of oclacitinib in feline non-flea-

non-food-induced hypersensitivity dermatitis (NFNFIHD).

Affected cats were randomly assigned to receive oclac-

itinib (group A, 18 cats, 0.8–1.3 mg/kg) or methylpred-

nisolone (group B, 14, 0.5–1 mg/kg) orally, twice daily for

28 days. On Day 1 and 28, veterinarians evaluated lesions

with the Scoring Feline Allergic Dermatitis (SCORFAD)

scale, while owners assessed pruritus with a 10-cm

visual analogue scale (VAS) and quality of life (QoL) with a

validated questionnaire. Haematochemical tests were

performed before and after treatment. Results were anal-

ysed with a General Linear Mixed Model (significance:

P < 0.05). There were no significant differences between

parameters at baseline. In both groups, values improved

significantly over time. In cats treated with oclacitinib, the

mean percentage reduction in SCORFAD and VAS was

62 and 51%, respectively. In those treated with methyl-

prednisolone, decreases were 77% and 74%, respec-

tively; there was no significant difference between

groups at study end. No response was seen in five and

one cat from groups A and B, respectively. Scores of QoL

improved similarly in both groups (26 versus 23%). Hae-

matochemical changes were not noted on any cat. In con-

clusion, oclacitinib at 0.8–1.3 mg/kg twice daily orally

appears safe for 28 days, and it is as effective as methyl-

prednisolone for the treatment of feline NFNFIHD.

Source of funding: European Society of Veterinary Der-

matology.

Conflict of interest: None declared.

© 2017 ESVD and ACVD, Veterinary Dermatology

16

Abstracts ECVD-ESVD 2017

18 gatos tratados com 0.8 a 1.3 mg/kg /sid/28 dias

Redução lesões=> 62%Redução prurido =>51%

Conclusões

Necessidade de mais estudos na dermatologia felina

Sempre buscar a causa base

O sucesso do tratamento depende da cooperação do gato e seu serviçal

[email protected] Obrigada!!

mailto:[email protected]

abordagem diagnóstica e terapêutica do prurido em gatos

Education