The use of oral cyclosporin to treat feline dermatoses:

a retrospective analysis of 23 cases

Blackwell Publishing Ltd

A. Vercelli*, G. Raviri and L. Cornegliani*

*Ambulatorio Veterinario Associato, C/so Traiano 99 /D, Torino, Italy
AmbulatorioVeterinario, P.za Vittorio Veneto 3, Venaria (Torino), Italy
Correspondence: L. Cornegliani, C.so Traiano 99/D, 10135 Torino,
Italy. Tel.: 0039-011-613987; Fax: 0039-011-3173763;
E-mail: gigiami@tin.it

Abstract
Limited information is available regarding the use of
cyclosporin A (CsA) for the treatment of feline dermatoses. The aim of this retrospective study was therefore to describe the efficacy of CsA for the therapy
of eosinophilic granuloma (EG), eosinophilic plaque,
indolent ulcer, linear granulomas, idiopathic pruritus
and stomatitis. A computer search for feline dermatological cases treated with CsA between 1999 and 2004
was performed. Based on history, clinical signs and
laboratory diagnostic tests, it was then possible to
divide cases into three groups and to select 23 cats.
Seven cats had one or more of the following conditions: EG, eosinophilic plaque, indolent ulcer and/or
linear granuloma (group A); eight cats had idiopathic
pruritus (group B) and eight cats had plasmacytic
stomatitis (group C). Doses ranged from 5.8 to
13.3 mg kg1 oral CsA. All cats were monitored, with
complete serum blood analysis and physical examination, monthly for a minimum of 6 months. Response to
therapy was scored (severity of lesions and pruritus)
with a 0 10 visual analogue scale at each visit (day 0,
day, 30, day 60, day 90). All cats in groups A and B were
cured and were maintained on alternate day therapy.
In group C, 4/8 patients went into remission, while
remaining cats have a fair to good improvement. Routine
haematological and biochemical examination failed to
reveal abnormalities related to CsA administration.
Accepted 6 March 2006

Introduction
Cyclosporin A (CsA) has been recently evaluated in numerous studies for the treatment of canine dermatoses.14
However, only limited information is available about the
use of CsA in cats. A couple of studies have investigated
the pharmacokinetics of CsA in cats.5 8 Bioavailability after
oral administration was found to be higher in cats than in
dogs, with a lower clearance and a slightly longer elimination half-life.6 Clinical efficacy of the drug has been tested

in feline dermatological diseases to control allergic pruritus or feline eosinophilic granuloma (EG) in anecdotal case
reports and in small-scale open label studies.9 12 More
specifically, CsA at 8.2 mg kg1 daily dose was effective
for the treatment of allergic pruritus in six cats.10 In
another trial, 12 cats with EG receiving the drug at a dose
ranging from 4.9 to 12.5 mg kg1 daily for 60 days markedly improved although indolent ulcer cases were not fully
resolved and a deterioration of the clinical signs was
observed after treatment interruption.11 Another prospective study on the use of daily CsA at 5 mg kg1 on feline
allergic diseases reported a reduction of pruritus and
improvement and/or resolution of the disease in more
than 50% of cases.12
Tolerability of CsA in cats has only been evaluated in one
study.6 Few and mild adverse events related to the drug
administration in cats (salivation, headshaking, intermittent soft faeces, gingival hyperplasia) were described.6
However, haematology and biochemical parameters
remained within normal values.6 The purposes of this
retrospective study were to collect and describe the therapeutic protocols using CsA in cats with EG, idiopathic
pruritus and plasmacytic stomatitis (previously unsuccessfully treated with steroids) and to evaluate the response
and possible side effects to the drug.

Materials and methods

Inclusion criteria
A computer search for feline dermatological cases treated with oral
administration of cyclosporin from Ambulatorio Veterinario Associato,
Turin (Italy), between 1999 and 2004 was performed.
Cases were selected based on the following criteria:
1 Cats had to have complete information with regard to signalment
and clinical presentation. Medical records had to provide full
information on weight, history of skin disease, previous medications, laboratory diagnostic tests (including skin or mucosal biopsies), initial treatment date, remission date, adverse events
and maintenance therapy; in all the selected cases a complete
dermatological work-up had been previously made (food trial,
parasitic control, etc.).
2 Topical and parenteral corticosteroids, essential fatty acids,
megestrol acetate administration had to be interrupted for 2
to 6 months before treatment with CsA was started.
3 Antibiotic treatment with either oral cefadroxyl at 25 mg kg1
(Cefacure tabs, Intervet, Peschiera Borromeo, Milano, Italy) or
enrofloxacin at 5 mg kg1 (Baytril, Bayer, Milan, Italy) had to
have been administered once a day for 4 weeks to eliminate
secondary infections; cytological examination was performed to
asses the lack of bacterial infections after antibiotic systemic
treatment.

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4 Elizabethan collars or bandages had not have been used;

5 Strict flea control with fipronil spot on monthly (Frontline spot on,
Merial spa, Milan, Italy) and oral or injectable lufenuron over a 6month period [Program, Novartis Animal Health, Origgio (VA), Italy];

A written consent was obtained prior to the beginning of the study

in all cases. Owners were provided with information regarding the
safety and efficacy of CsA in cats based on preliminary studies.59

Treatments
Initial therapy consisted of Sandimmune solution (100 mg mL1) or

6 Lack of response to an elimination diet performed with homemade horse and potatoes or feline Z/D low allergen (Hills pet
nutrition spa, Roma, Italy) or L/B dermatosis (Eukanuba, Borgo
Maggiore, Rep. S. Marino) for 12 weeks.

Sandimmune Neoral caps (25 mg) administered orally, respectively,

daily and twice a day, 2 h before or after meals, for 4 weeks. Details
of dose and treatment regimen are given in Table 1. The CsA was
continued every other day for 1 or 2 months until remission of the

Study population

symptom. A maintenance regimen was then installed with a twice-a-

A total of 24 cases could be selected. Five of these cats, with EG and

week administration of CsA for an unlimited duration.

pruritus, had been previously skin tested with a panel of 23 standard

allergens (Greer Laboratories, Lenoir, NC, USA). Even if some positive reactions (Dermatophagoides farinae, grass pollen mixture) were

Results

observed in two of them, no clinical amelioration could be detected in

Clinical signs

these cats following an 8-month-period immunotherapy. Serology for

Group A
Upon presentation all cases (n = 7) were affected by chronic
EG. Distribution of the lesions involved multiple sites in
four cats. Four cases had oral EG in the palate vault and/
or tongue and one of them had also a severe indolent ulcer
of the upper lips. Three cases had eosinophilic plaque on
the abdomen, and one of them had also an EG of the digit
and two of them had linear granuloma on the hind limbs.

IgE was not performed due to limited owner complaints. Duration of

clinical signs prior to CsA treatment ranged from 6 to 24 months in all
groups.

Complementary examinations
Diagnoses of EG, pyotraumatic dermatitis and plasmacytic stomatitis
had been previously confirmed by skin or mucosal biopsies. Skin
scrapings and fungal cultures were performed in groups A and B and
were negative in all cats.

Group allocation
Based on history, clinical signs and laboratory diagnostic tests, it was
then possible to divide cases into three groups: group A, chronic EG;
group B, idiopathic pruritus; group C, chronic plasmacytic stomatitis.
Groups A and B were further divided into two subgroups which
received CsA in an oil-based liquid formulation (Sandimmune
100 mg mL1, Novartis Farma spa, Origgio, Varese, Italy) or soft gelatine capsules containing a microemulsion proconcentrate formulation
(Sandimmune Neoral 25 mg and 50 mg, Novartis Farma spa, Origgio, Varese, Italy). Group C was not subdivided as cats were only
treated with the liquid formulation. This choice was made to ensure
better owner compliance when administering the drug to cats suffering from chronic stomatitis.

Clinical monitoring
Clinical monitoring was based on a score ranging from 1 to 10 reflecting the extension of the lesional surfaces (skin, oral mucosa).
Response to treatment was measured monthly (day 30, day 60, day 90)
by the improvement over baseline of the lesions (0% = no amelioration,
100% = complete resolution). Pruritus was subjectively judged by the
owner with the same score system (from 1 to 10) at each consultation.
Complete blood count (CBC), biochemical profile, urine analysis, feline
leukaemia virus (FeLV)/feline immunodeficiency virus (FIV), toxoplamosis tests were performed in all cases before CsA administration.

Table 1. Dose, dosing regimen and duration of follow-up by group

Group

CsA dosage administered to cats

Three cats received 50 mg daily of Sandimmun solution;

medium dosage 11.2 mg kg1 (range 1012.5 mg kg1)
Four cats received 25 mg Neoral capsules twice a day;
medium dosage 6.4 mg kg1 (range 5 8.3 mg kg1)
Three cats received 50 mg daily of Sandimmun solution;
medium dosage 12.3 mg kg1 (range 1014.2 mg kg1)
Five cats received 25 mg Neoral capsule twice a day;
medium dosage 10.3 mg kg1 (range 8.312.5 mg kg1)
Eight cats received from 30 to 50 mg daily of
Sandimmun solution; mean dosage 10.3 mg kg1
(range 5.813.3 mg kg1)

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Figure 1. 1a and 1b: improvement of the skin lesions during the

treatment. On day 0, day 30, day 60 and day 90 severity of lesions was
scored with numeric points (range 010). 1c: improvement of oral
lesions during the treatment. On day 0, day 30, day 60 and day 90
severity of lesions was scored with numeric points (range 010).

2006 The Authors. Journal compilation 2006 European Society of Veterinary Dermatology.

Cyclosporin in feline allergic dermatosis

Figure 2. The photographs show the improvement of indolent ulcer during treatment with CsA. The controls were performed at day 0 (a), day 30
(b), day 60 (c), day 90 (d).

Group B
All cases (n = 9) were affected by idiopathic pruritus with
autotraumatic skin lesions of variable severity and distribution. Four cats had severe pyotraumatic dermatitis of the
face and neck, three cats had less severe lesions on the
limbs or the abdomen. Symmetric ventral alopecia associated with alopecia of the limbs was found in four cats. Symmetric auto-induced alopecia (ventral abdomen and limbs)
was the only clinical sign in the two remaining cats.
Group C
All cats (n = 8) had severe chronic plasmacytic stomatitis
with ulcerative and proliferative features.
Clinical monitoring performed based on a score from
1 to 10 to assess the severity of pruritus; the extension
of skin and/or mucosal lesions on days 0, 30, 60 and 90
is reported in Fig. 1 (a, b, c).
Biochemistry, haematology, urinanalysis and
serodiagnostics
At the time of referral, all cats had received several treatments. Antibiotics had been given for 1 to 3 weeks followed
with long-lasting injectable corticosteroids (methylprednisolone acetate), oral prednisone or megestrol acetate for
several months. One cat was affected by secondary diabetes.
CBC revealed the following abnormalities in 22/24 cats:
leucocytosis neutrophilia (12/24), lymphopenia (6/24),
monocytosis (4/24), eosinophilia (10/24). Twenty-one of

the 24 cats had biochemical profiles within normal values;

3/24 cats that had previously received repeated methylprednisolone acetate injections had hyperglycaemia and
elevated ALP (alkaline phosphatase). Urine analyses were
in the normal range for 23/24 cats, mild glucosuria was
present in one cat. Regarding serodiagnostic tests, 22/24
cats were negative for both FeLV and FIV, 2/24 cats were
positive for FIV, but negative for FeLV and all cases (24/24)
were negative for toxoplasmosis test.
Only one case (group B) could not be followed up;
euthanasia was required after 2 weeks of CsA treatment
because of the worsening of the poor patient condition (weight
loss, anorexia, depression and weakness). Post-mortem
examination was not allowed by the owner, and for this
reason further investigations were not carried out.
During CsA administration, serum biochemical analyses
were performed in 20/24 cases every 3 to 6 months and
did no show abnormalities regarding glycaemia, hepatic
enzymes, creatinine, blood urea nitrogen and electrolytes.
The hyperglycaemia and abnormal ALP value found in 3/24
cats at the beginning of the study went under normalization
within day 30 and day 60. Information regarding treatment
with CsA was available for 23 cats for at least 3 months.
Decrease of pruritus in both groups (A, B) was followed
by improvement of skin lesions (Figs 2 & 3).
In group A during the third month, two cases continued
on alternate day treatments (case 1 and 5) whereas the
other five cases, which were in clinical remission, started

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Figure 3. The photographs show the progressive resolution of crusting and ulcerated dermatitis of the face in a cat with EG under CsA therapy.
The controls were performed at day 0 (a), day 30 (b), day 60 (c), day 90 (d).

maintenance therapy with twice-a-week CsA administration. In group B, two cases were maintained on alternate
day treatment whereas the other six cases in clinical
remission started maintenance twice a week. In group C,
all cats were maintained on alternate day treatments. At
day 90 complete remission was obtained in all cases in
groups A and B, whereas in group C remission was
observed in only 4/8 cats, in the other four cases there
was a partial to fairly good improvement of clinical signs
(from 40% to 70%) (Fig. 4). Relapse occurred in 6/23 cats
(four cases from group A and two case from Group B) when
maintenance therapy was arbitrary interrupted by the
owners after several months. No relapse was observed in
the other cases (17/23) that continued the maintenance
therapy twice a week during the follow-up. In groups A
and B, the response was almost identical at 30, 60 and
90 days in cats treated with the solution or the capsules,
although the mean dose administered with capsule was
lower (8.6 mg kg1 vs. 11.8 mg kg1).
Adverse effects
Adverse reactions were minimal and included mild gastrointestinal signs (intermittent soft faeces or occasional
vomiting) in 4/23 cats during the first week of treatment.
One cat (group A) had an episode of FUS (feline urinary
syndrome), which was treated with antibiotics and diet
204

and underwent remission in few days. No secondary

infections were detected in 22/24 cases during follow-up.

Discussion
In this retrospective study, CsA appeared to be effective
for the management of feline allergic dermatitis. In groups
A and B all cats were successfully managed on alternate
day CsA therapy, and in group C 50% of patients went into
remission, while the remaining showed fair to good
improvement. In all 23 cases routine haematological and
biochemical examination failed to reveal abnormalities
related to administration suggesting safety of this treatment modality.
In cats, EG, idiopathic pruritus and plasmacytic stomatitis often are difficult disease to control. Steroids are
generally used to treat all the cases where a definitive
diagnosis or response to correct therapy fails. These drugs
can potentially induce severe side effects such as iatrogenic Cushing or diabetes mellitus.13 For these reasons,
clinicians have recently introduced the use of CsA, based
on anecdotal reports.6,8,1012 CsA inhibits the functions of
cells that initiate immune reactions and of effector cells
of the allergic response in human and dogs. This drug
produces alterations in eosinophils, keratinocytes, Langerhans cells, lymphocytes, mast cells and macrophages

2006 The Authors. Journal compilation 2006 European Society of Veterinary Dermatology.

Cyclosporin in feline allergic dermatosis

Figure 4. Plasmacytic stomatitis in a cat, on day 0 (a) and after CsA

administration on day 90 (b).

responses.14,15 CsA inhibits eosinophil release of toxic

granules, survival, cytokine secretion and recruitment to
the sites of allergic inflammation. It also inhibits mast cell
survival, secretory response, histamine release, prostaglandin production and cytokine secretion.14,15 Based on all
these properties, it has been hypothesized that CsA could
be effective in the treatment of feline pruritic dermatosis.
All cats in this study had previously been treated with
injectable steroids and an incomplete response or a
marked reduction in efficacy over time was obtained. One
cats (1/24) had also developed secondary corticosteroid
induced diabetes mellitus, which resolved with a hypocaloric diet, during the treatment course with CsA. In 2/3
cats, hyperglycaemia was considered related to stress
(normal urine exams) while abnormal ALP values were
ascripted to steroid administration and resolved with
hypocaloric diet too. Because of the limited number of
cases in each group and the absence of control treatment,
this study did not allow a direct comparison with corticosteroids. The response to CsA therapy appeared better in
groups A and B than in group C. In groups A and B, 11/16
cases completely resolved after 2 months and all cases
after 3 months. In comparison, in group C, after 3 months,
the clinical improvement of stomatitis was incomplete
(ranging from 40% to 70%) in 4/8 cats. Although the
response was incomplete in four cats, it was considered
acceptable or fairly good by the owners because the
patients improved their quality of life (e.g. normal appetite,

no salivation). For this reason, maintenance CsA therapy

twice weekly was continued.
Our data are in agreement with previous clinical
studies1012 that reported a good clinical control of cases
of idiopathic pruritus and EG, and a partial improvement of
oral lesions, particularly indolent ulcer. In our limited series
of cases oral EG and indolent ulcer seemed to be more
refractory to CsA treatment as they required longer treatment duration to resolve. The same observation was
made on two cases in group B affected by severe pyotraumatic dermatitis of the face. No difference in clinical
response was detected between the solution and the capsules, although cats given capsules received a lower dose.
The minimal effective dose in the treatment of these conditions has not been yet established. Maintenance therapy
with increasing intervals between administrations was
able to maintain clinical improvement.
CsA treatment was well tolerated in most cats. In one
cat, capsules caused diarrhoea whereas the same dose
administered as liquid formulation did not produce any
adverse reaction. It is possible that an excipient of the capsules was responsible for this gastro-intestinal disorder.
No clinical expression of viral disease was manifested in
the two cats found to be FIV positive before CsA therapy.
The use of CsA in the treatment of FIV-infected cats is still
controversial.16 Biochemical analyses did not reveal any
sign of renal impairment or hepatotoxicity even if the drug
is administered for extended periods of time at doses
ranging from 5.8 to 13.3 mg kg1. This is consistent with
an earlier retrospective study in kidney-transplanted cats.7
In summary, CsA is considered safe and effective for
the treatment of feline allergic dermatoses. Additional
large-scale prospective randomised and controlled studies
are warranted to better assess the effective inducing dose
and maintenance-dosing regimen for treatment of feline
dermatological diseases.12

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Rsum Peu de donnes sont disponibles quant lutilisation de la cyclosporine (CsA) pour le traitement
des dermatoses flines. Le but de cette tude rtrospective tait de dcrire lefficacit de la CsA pour
le traitement de lsions de granulome osinophilique (EG), de plaque osinophilique, dulcre atone, de
granulomes linaires, de prurit idiopathique et de stomatite. Une tude par ordinateur des cas de dermatologie fline traits avec la CsA entre 1999 et 2004 a t ralise. En se basant sur lanamnse, les signes
cliniques et les rsultats des examens complmentaires, il a t possible de diviser les cas en trois groupes,
pour un total de vingt trois chats. Sept chats avaient une ou plusieurs des dermatoses suivantes: granulome
osinophilique, plaque osinophilique, ulcre atone et/ou granulome linaire (groupe A); 8 chats avaient un
prurit idiopathique (groupe B); et 8 chats avaient une stomatite plasmocytaire (groupe C). Les doses variaient
entre 5.8 et 13.3 mg kg1 de CsA. Tous les chats ont t surveills, avec numration formule, biochimie
sanguine et examen clinique tous les mois pendant au moins 6 mois. La rponse au traitement (svrit
des lsions et du prurit) a t cte de 0 10 chaque visite (jours 0, 30, 60, et 90). Tous les chats des
groupes A et B ont t guris et on pu tre maintenus en traitement par jour altern. Dans le groupe C, 4/8
patients parvinrent une rmission alors que les autres prsentrent une amlioration mdiocre bonne.
Aucun effet secondaire, notamment sanguin, ne fut observ.
Resumen Actualmente existe poca informacin acerca del uso de Ciclosporina A (CsA) en el tratamiento
de dermatosis felinas. El objetivo de este estudio retrospectivo fue, por lo tanto, describir la eficacia de CsA
en el tratamiento de granuloma eosinoflico (EG), placa eosinoflica, lcera indolente, granulomas lineales,
prurito idioptico y estomatitis. Se realiz una busqueda al ordenador de casos de dermatosis felinas tratados
con CsA entre 1999 y 2004. Basndonos en la historia clnica, signos clnicos y en pruebas de diagnstico
laboratorial fue posible dividir los casos en tres grupos y seleccionar un total de 23 gatos. Siete de ellos
presentaron al menos una de las condiciones siguientes: granuloma eosinoflico, placa eosinoflica, lcera
indolente y/o granuloma linear (grupo A); 8 gatos presentaron prurito idioptico (grupo B); y 8 gatos tenan
estomatitis plasmactica (grupo C). Las dosis variaron entre 5.8 y 13.3 mg kg1 de CsA va oral. Todos los gatos
fueron controlados mensualmente por un mnimo de 6 meses, con completo anlisis serolgico y examen
fsico. La respuesta al tratamiento se valor entre 0 y 10 (basado en severidad de lesiones y prurito) siguiendo
una escala visual en cada visita (das 0, 30, 60 y 90). Todos los gatos en los grupos A y B se curaron y se
mantuvieron con tratamiento a das alternos. En el grupo C, 4/8 gatos progresaron a remisin de las lesiones,
mientras que los gatos restantes presentaron moderada a buena mejora. El examen hematolgico y
bioqumico no revel ninguna anormalidad relacionada con la administracin de CsA.
Zusammenfassung Es gibt nur limitierte Informationen bezglich der Verwendung von Cyclosporin (CsA)
zur Behandlung von felinen Dermatosen. Das Ziel dieser retrospektiven Studie war es daher, die Wirksamkeit von CsA fr die Therapie von eosinophilen Granulomen (EG), eosinophilem Plaque, indolentem Ulkus,
linearen Granulomen, idiopathischem Juckreiz und Stomatitis zu beschreiben. Eine Computersuche nach
felinen Hautfllen, welche mit CsA zwischen 1999 und 2004 behandelt worden waren, wurde durchgefhrt.
Basierend auf der Anamnese, den klinischen Symptomen und den diagnostischen Labortests, war es dann
mglich die Flle in drei Gruppen einzuteilen und dreiundzwanzig Katzen auszuwhlen. Sieben Katzen hatten
einen oder mehrere der folgenden Zustnde: eosinophile Granulome, eosinophiles Plaque, indolentes Ulkus
und/oder lineare Granulome (Gruppe A); 8 Katzen hatten idiopathischen Juckreiz (Gruppe B); und 8 Katzen
hatten plasmazytre Stomatitis (Gruppe C). Die Dosierungen von oralem CsA reichten von 5.8 bis 13.3 mg kg1.
Fr die Dauer von mindestens 6 Monaten wurden die Katzen monatlich mittels kompletter Blutanalyse
und physischer Untersuchung berwacht. Die Antwort auf die Therapie wurde bei jeder Prsentation (Tag
0, Tag 30, Tag 60, Tag 90) mittels einer visuellen analogen Gradeinteilung von 0 bis 10 bewertet (Schweregrad der Lsionen und des Pruritus). Alle Katzen in Gruppe A und B wurden geheilt und auf einer
Erhaltungsdosis von jedem zweiten Tag kontrolliert. In Gruppe C gingen 4/8 Patienten in Remission,
whrend die brigen Katzen eine mig bis gute Verbesserung zeigten. Die routinemssig durchgefhrten
hmatologischen und biochemischen Untersuchungen konnten keine Abnormalitten aufzeigen, die auf die
CsA Gabe zurckzufhren gewesen wren.
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2006 The Authors. Journal compilation 2006 European Society of Veterinary Dermatology.