Veterinary Dermatology 2006, 17, 8592

Case report

Blackwell Publishing Ltd

Three cases of immune-mediated adnexal skin disease treated

with cyclosporin
CHIARA NOLI and STEFANO TOMA
Ospedale Veterinario Cuneese, Via Cuneo 52/N, 12011 Borgo S. Dalmazzo (CN), Italy
(Received 15 March 2005; accepted 15 August 2005)

Abstract Cyclosporin is currently considered a new and interesting drug in veterinary dermatology for the treatment of immune-mediated skin diseases, and a safe and effective alternative to immunosuppressive therapy with
glucocorticoids. The authors report a case of granulomatous folliculitis and furunculosis and of sebaceous adenitis
in two cats and a case of alopecia areata in a dog, successfully controlled with cyclosporin.

IN TRO D U CT I ON
Cyclosporin is a cyclic lipophilic endecapeptide with
important immune-modulating properties, used for
several years in human and veterinary dermatology for
the treatment of immunologic disorders.1,2 Its target
cells are mainly lymphocytes and its main mechanism
of action is to block the transcription of genes encoding for cytokines, in particular IL-2, thus inhibiting
antigen-induced activation of CD4+ T-helper cells.3
The inhibition of IL-2 production also prevents the
production of other cytokines, such as IL-4, IFNgamma and granulocyte-macrophage colony-stimulating
factor.3 As a result of its effect as a gene suppressor,
cyclosporin is also able to inhibit the activation of several other immune cells such as mast cells, eosinophils,
basophils, neutrophils, macrophages and Langerhans
cells.2,4,5
In veterinary dermatology, cyclosporin is used for
the treatment of immune-mediated dermatoses, especially atopic dermatitis4 and perianal fistulas.6 Some
published and anecdotal observations describe its
efficacy in dogs with sebaceous adenitis,7,8 pemphigus
foliaceus and cutaneous lupus,9 idiopathic sterile
nodular panniculitis,10 epitheliotropic lymphoma,9 endstage proliferative otitis externa,11 chronic pedal furunculosis, erythema multiforme, German Shepherd
pyoderma, metatarsal fistulae, sterile pyogranulomatous
syndrome and ulcerative dermatosis of the philtrum of
St. Bernards and Newfoundlands.1 In feline dermatology,
cyclosporin has been reported to be effective for the
treatment of manifestations of the eosinophilic
granuloma complex,12,13 miliary dermatitis,12 feline
urticaria pigmentosa,14 feline acquired alopecia (pseuCorrespondence: Chiara Noli, Ospedale Veterinario Cuneese, Via
Cuneo 52/N, 12011 Borgo S. Dalmazzo (CN), Italy. E-mail:
pitnoli@iol.it

dopelade),15 pemphigus erythematosus,9 feline atopic

dermatitis and dirty-face syndrome of Persian cats.1
The authors report here three cases of immunemediated adnexal disease successfully treated with
cyclosporin, in which, to our knowledge, the use of
this drug has never been previously reported.

C A SE R E P O RT S
Case 1
A 3-year-old neutered Domestic Shorthaired male cat
was referred for dermatological examination with a
6-month history of nonpruritic alopecia. Neither lumbosacral trauma nor pruritus was reported by the
owner. The cat had a history of dermatophytosis and
three negative fungal cultures had been obtained by the
referring veterinarian prior to referral. No improvement in the cats condition was noted after a 2-week
course of enrofloxacin at the standard dosage of
5 mg kg1 once daily. The cat was fed commercial dry
food, regularly vaccinated and treated against fleas.
Feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) status was negative.
On general examination, the cat appeared in excellent health. There was no sign of flea infestation on the
animal. On dermatological examination, three areas of
alopecia were observed on the back and flanks (Fig. 1).
A moderate erythema surrounding the alopecic areas
was observed. The skin of these areas was normal in
consistency, thickness and elasticity, and appeared
shiny. Differential diagnoses at this stage included
demodicosis, alopecia areata, pseudopelade, paraneoplastic alopecia, lymphocytic mural folliculitis, sebaceous adenitis, follicular dysplasia, self-inflicted alopecia
and hyperadrenocorticism.
Multiple, deep skin scrapings and trichoscopic examinations were performed to exclude dermatophytosis

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Figure 1. Case 1. Symmetric areas of complete alopecia on the back

of a cat affected with pyogranulomatous folliculitis and furunculosis.

Figure 2. Case 1. Histological appearance of pyogranulomatous

folliculitis and furunculosis, A nodular dense infiltrate of
macrophages, with few neutrophils, is centred on the hair follicles,
sparing the sebaceous glands (haematoxylin and eosin, 4).

and demodicosis, with negative results. A complete

blood count and serum biochemical analysis yielded
normal results.
Multiple biopsies from lesional and perilesional skin
were taken under general anaesthesia for histological
examination. Samples were processed, cut in 5-m
sections and stained with haematoxylin and eosin
following standard procedures. On histological examination, a normal epidermis was observed. In the
dermis, nodular granulomatous infiltrates, with a few
neutrophils, were observed centred on the hair follicles,

Figure 3. Case 1. A closer view of the pyogranulomatous

furunculosis shown in Figure 2 (H&E, 10).

causing furunculosis but sparing sebaceous glands

(Figs 2 and 3). A special stain (periodic acid of Schiff)
for fungi was negative, and Demodex spp. mites were not
observed in any of the sections examined. Histological and
clinical findings were not compatible with any disease
previously described in cats. An immune-mediated
follicular disease was suspected.
The cat was treated with cyclosporin at a dosage
of 5 mg kg1 PO every 24 h (one 25-mg capsule of
Sandimmune Neoral, Novartis, Origgio, Italy), after
having confirmed its negative status for toxoplasmosis
with both serum IgG and IgM measurement. After 1
month of drug administration, hair growth was evident
in most of the affected areas and the erythema had
totally resolved. The therapy was continued at the same
dosage for another month. After 2 months of once-daily
cyclosporin administration, the clinical signs dramatically improved in the affected areas, with exception of a
small area on the tail that was still alopecic. The dosage
was then lowered to an alternate-day dosage of 5 mg kg1
for another 3 months, after which, the clinical signs
had nearly completely resolved (Fig. 4). Alternate-day
administration of cyclosporin was continued for another
month and then discontinued. Six months after therapy
was stopped, no relapses were observed. No side effects
were observed during cyclosporin treatment.

Case 2
A 3-year-old neutered Oriental female cat was referred
for dermatological examination with a 3-month history

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Adnexal skin diseases treated with cyclosporin

Figure 4. Case 1. A visible improvement of the alopecia is noticeable

after 4 months of cyclosporin treatment.

Figure 5. Case 2. Black-brown exudate on the eyelids and follicular

casts on the back in a cat affected by sebaceous adenitis. The hair on
the back has been clipped in order to better observe the lesions.

of crusts and pruritus on the face and body. The cat

was acquired at 1 year of age, had free access to the
house and outdoors and was fed with commercial dry
and wet food. It was regularly vaccinated and treated
against fleas. Dermatophytosis had been suspected by
the referring veterinarian who had treated the cat with
griseofulvin at a dosage of 50 mg kg1 PO once daily
for a month and 5 days of itraconazole at a dosage of

87

Figure 6. Case 2. Histological appearance of sebaceous adenitis.

There is complete lack of sebaceous glands and a nodular mononuclear
cell infiltrate is visible at their usual location (haematoxylin and
eosin, 10).

10 mg kg1 PO once daily. No improvement in the clinical signs had been observed with these treatments.
On general examination, the cat appeared in good
health. On dermatological examination, a diffuse scaly
dermatitis, alopecia with follicular casts and a brown
exudation around the eyes and vulva were observed
(Fig. 5). Differential diagnoses were dermatophytosis,
demodicosis, sebaceous adenitis, paraneoplastic
syndromes, metabolic epidermal necrosis and skin
tumour. Multiple deep skin scrapings and trichoscopic
examinations were performed to exclude dermatophytosis and demodicosis. The trichoscopic examination
revealed the presence of follicular casts. A complete
blood count and serum biochemical analysis were
unremarkable.
Multiple biopsies from lesional skin were obtained
under general anaesthesia for histological examination. Samples were processed, cut in 5-m sections and
stained with haematoxylin and eosin following standard
procedures. On histological examination of the epidermis,
laminated orthokeratotic hyperkeratosis was observed.
In the dermis, a mild superficial perivascular mononuclear
infiltrate was present, whereas the hair follicles were
affected by a mild mural lymphocytic folliculitis. The
sebaceous glands were completely absent in the sections examined, but a nodular lymphocytic infiltrate
was present in the area where the sebaceous glands
would normally be found (Fig. 6). A diagnosis of sebaceous adenitis was made.

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Figure 7. Case 2. Complete remission of clinical lesions of sebaceous

adenitis around the eyes after 3 months of cyclosporin administration.

Serological tests for the assessment of IgM and IgG

titres for toxoplasmosis and a FIV/FeLV test were performed and were negative. Treatment with cyclosporin
at a dosage of 5 mg kg1 every 24 h was initiated (one
25 mg capsule of Sandimmune Neoral, Novartis).
After 1 month of cyclosporin administration, the
clinical picture greatly improved and treatment with
daily cyclosporin was continued for a further 2 months.
After 3 months of once-daily administration, the
lesions were in complete remission (Fig. 7). The
cyclosporin was then administered at the same dosage
on alternate days for a further 2 months. At the end of
the second month of alternate-day therapy, no relapse
was observed, and cyclosporin was administered at
the same dose every 72 h. After 20 days of treatment at
this lower dosage, a relapse of the disease was observed,
starting with the production of a brown exudate
around the eyes and the development of some crust on
the face. In order to rapidly control the new relapse,
prednisolone was administered orally at a dosage of
2 mg kg1 once daily for a week, and then once every other
day for another week, together with every other day
administration of cyclosporin at a dosage of 5 mg kg1
and a daily dexamethasone/tobramicine eyedrop
(Tobradex, Alcon Italia, Milano, Italy) for 2 weeks.
After 2 weeks of prednisolone and eye drop therapy,
the clinical signs had resolved. The disease remained in
remission with the administration of cyclosporin every
other day at a dose of 5 mg kg1. After 3 months, no
relapses were observed. There were no side effects
observed during cyclosporin treatment, and monthly
complete blood cell counts and serum biochemistry
remained within normal limits.

Case 3
A 4-year-old intact male pincher was referred for dermatological examination with a 7-month history of
nonpruritic patchy alopecia on the neck. The dog had
been bought in a pet shop at the age of 3 months, and
there was no previous history of systemic or dermatological disease. The dog lived indoors and there were

Figure 8. Case 3. Photomicrograph of alopecia areata on the neck

and cheeks in a dog.

no other pets in the household. It was fed a wellbalanced home-cooked diet, was regularly vaccinated and
treated for fleas. The dog had previously been treated
with weekly ivermectin injections (dosage unknown)
for 2 months and twice weekly topical application of
0.1% amitraz for 4 months. No improvement of the
lesions had been noted. On general examination, the
dog appeared in good health. On dermatological
examination, patches of noninflammatory alopecia
were observed on the ventral neck and on both cheeks
(Fig. 8). Differential diagnoses included demodicosis,
dermatophytosis, bacterial folliculitis, alopecia areata,
follicular pemphigus foliaceus and other follicular
diseases. Multiple deep skin scrapings were negative for
Demodex mites and fungi, and a fungal culture was
negative. Cefalexin was administered at a dosage of
25 mg kg1 twice daily for 3 weeks while waiting for the
fungal culture results, in order to exclude bacterial
folliculitis as a cause for the clinical signs, but no improvement was noted.
Two skin biopsies were taken from alopecic areas
under general anaesthesia for histological examination.
Samples were processed, cut in 5-m sections and stained
with haematoxylin and eosin following standard procedures. On histological examination, a normal epidermis
and a mild periadnexial mononuclear infiltrate were
observed. In several hair follicles, a lymphocytic
bulbitis with perifollicular pigmentary incontinence
was evident. The histological lesions were diagnostic of
alopecia areata (Fig. 9).

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Adnexal skin diseases treated with cyclosporin

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Figure 10. Case 3. Visible hair re-growth after 1 month of

cyclosporin treatment.

Figure 9. Case 3. Histological appearance of alopecia areata

demonstrating a lymphocytic bulbitis (H&E, 10).

Therapy with cyclosporin (5 mg kg1 every 24 h, one

25-mg capsule of Sandimmune Neoral, Novartis)
was prescribed to treat the alopecia areata, and it led to
a visible improvement of lesions within 1 month
(Fig. 10). The therapy was continued for a further
2 months at a dosage of 5 mg kg1 orally every other
day, with complete remission of the clinical lesions.
Unfortunately, the dog was then lost to follow-up.
During cyclosporin treatment, no side effects were
observed. Blood cell counts and serum biochemical
analysis performed before and after 1 month of
cyclosporin administration gave normal results.

D ISCU SSION
The clinical and histological findings of case 1 were
very unusual and, to the authors knowledge, not compatible with any previously described skin disease in cats.
Dorsolumbar alopecia is a common finding in cats.
The most important cause is self-trauma caused by
pruritus (allergies, ectoparasites) or psychogenic
factors. Other, non-selfinduced, causes of feline alopecia are alopecia areata, pseudopelade, telogen effluvium, congenital hypotrichosis, paraneoplastic alopecia
associated with pancreatic tumour, epitheliotropic
lymphoma, hyperadrenocorticism, dermatophytosis,
demodicosis and bacterial folliculitis. In this case,
the clinical and histological examinations excluded
causes of alopecia as a result of self-licking, endocrin-

opathies, telogen effluvium, congenital hypotrichosis,

neoplastic and paraneoplastic diseases, demodicosis
and dermatophytosis. It was thus considered to be
an immune-mediated process focused on the hair
follicle.
Immune-mediated folliculitides described in the cat
are lymphocytic mural folliculitis,16 with a mucinous
degenerative variant,17 alopecia areata,18 pseudopelade15
and sebaceous adenitis.19
Lymphocytic mural folliculitis is characterized
clinically by patchy or diffuse alopecia and exfoliation
(which was absent in our cat), and histologically by a
lymphocytic and histiocytic infiltrate in the follicular
infundibular and isthmic wall.16 Neutrophils, as seen in
our case, are not observed. A mucinous degenerative
variant of this disease has also been described,17 which
is characterized histologically by an infundibular and
isthmic infiltrate of lymphocytes, macrophages, plasma
cells and neutrophils, with presence of multinucleated
giant cells and follicular mucinous degeneration. This
histological picture is similar to what was observed in
this case, in particular the presence of macrophages
and neutrophils. However, we did not observe any
follicular mucinous degeneration in our case. Furthermore, cats with this particular disease show severe clinical signs of pruritus, erythema, exfoliation and crusts,
which were absent in our cat. Other forms of lymphocytic mural folliculitis have been associated with
dermatophyte infections, which could not be observed
on histological examination, but could be confirmed
by fungal culture. In our case, fungal cultures were
performed multiple times and were always negative. The
cat did not respond to oral antifungal therapy with
griseofulvin and itraconazole.
Alopecia areata is a mildly inflammatory form of
alopecia, characterized by a perifollicular and intrabulbar lymphocytic infiltrate. An antifollicular cellmediated and humoral immunological response has
been demonstrated in canine alopecia areata.20 Certainly, the clinical appearance of our case resembles
alopecia areata but the histological features are different: the infiltrate is strictly lymphocytic in alopecia

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areata and was pyogranulomatous in our case. Pseudopelade, an immune-mediated alopecia characterized
by a lymphocytic infiltrate in the follicular isthmus, has
been described in the cat.15 As for alopecia areata, the
granulomatous folliculitis and furunculosis observed
in our case is not compatible with the histologic
appearance of pseudopelade, in which neutrophils
are absent. Sebaceous adenitis is characterized by a
granulomatous inflammation centred on the sebaceous
glands. Clinically, exfoliation, crusts, follicular casts
and alopecia are usually observed.19 Neither the clinical nor the histological lesions seen in our cat were
compatible with sebaceous adenitis, because in our
case, the sebaceous glands were spared by the nodular
granulomatous inflammatory reaction.
A rare form of granulomatous folliculitis has been
described in dogs18 and in horses,21 but not in cats. The
canine and equine cases were thought to be related to
drug administration. The clinical picture was characterized by large, well-circumscribed areas of alopecia,
exfoliation and hyperkeratosis. Chronic lesions had a
smooth, shiny appearance, similar to that observed in
our case. However, there was no history of drug administration in our case prior to the onset of the lesions.
Finally, it seems very unlikely that this cat was suffering from a mycobacterial or other acid-fast bacterial
infection due to the strictly follicular localization of
the infiltrate, the absence of clinical symptomatology
and the improvement with the administration of an
immune-suppressive drug. However, special stains for
acid-fast bacteria or polymerase chain reaction for their
detection were not performed and we cannot exclude
with certainty the presence of these microorganisms.
Cyclosporin was used in this case because an
immune-mediated alopecia was suspected, and there
are anecdotal reports of its efficacy for other immunemediated skin diseases, and in particular those affecting the adnexa, such as canine granulomatous
sebaceous adenitis7 or feline pseudopelade.15 There was
only a partial (i.e. not complete) response to treatment
and it could be speculated that this was caused by the
presence of an inflammation of pyogranulomatous
nature. There were only small numbers of lymphocytes
present, the main target of cyclosporin.
As the case went into long-term remission, it could
have been a spontaneous resolution rather than an
effect of the cyclosporin. However, the alopecia had
been present and stable for several months prior to
therapy, and it improved dramatically as soon as the
drug was administered. Furthermore, complete remission was never achieved as it would be normally
expected in case of a spontaneous resolution. In conclusion, we believe that the clinical improvement was
an effect of the cyclosporin administration.
Case 2 showed classical clinical and histological
features of sebaceous adenitis, a rare disease in cats.19
The usual treatment of this condition, based on keratolytic shampoos, emollient rinses or topical application
of diluted propylene glycol,18 is generally difficult to
apply in cats. An alternative therapy with long-term

oral retinoids may be associated with side effects.18

Cyclosporin has been reported to be successful in
canine sebadenitis,7,8 but to the authors knowledge,
there is no report of its use in the feline form. In the
case described, the disease was well controlled with
cyclosporin, although the dosage could not be reduced
to less than 5 mg kg1 every other day. More cases are
needed to confirm the efficacy of cyclosporin in feline
sebaceous adenitis.
In case 3, the clinical and histological lesions were
typical of canine alopecia areata.18 Alopecia areata is a
T-cell immune-mediated disease against autoantigens
of the hair follicle.20 Because of the important
involvement of T cells in the pathogenesis of this
disease, cyclosporin should be an effective drug to
treat this condition. Reports on its efficacy in human
alopecia areata are very contradictory.2225 Because of
its high systemic toxicity in man, the majority of studies
conducted in human medicine were performed with
topical solutions and gave partial or no results.24,25
However, being a very large molecule, cyclosporin is
not well absorbed through the epidermis,5 and it may
be that the clinical failure was the result of the low drug
concentration achieved in the deep dermis. Future
therapeutic approaches of alopecia areata in humans
include the incorporation of immunomodulatory
agents into liposomes as an improved vehicle.26
Cyclosporin administered systemically was successful
in our case of alopecia areata. In canine dermatology,
there is only anecdotal evidence suggesting that
topical, intralesional or systemic treatment with glucocorticoids may be beneficial.18 The use of cyclosporin
to treat canine alopecia areata, to our knowledge, has
not been described, and could thus represent an
interesting option.
Reported side effects of cyclosporin in cats are intermittent soft faeces, salivation, head shaking and gingival
hyperplasia.27 In dogs, gingival hyperplasia, papillomatosis, vomiting, diarrhoea, bacteriuria, pyoderma,
poor appetite, hirsutism, renal disease, bone marrow
suppression and lymphoplasmacytoid dermatosis have
been described.1 No side effects were observed in our
cases. Blood cell counts and biochemical serum analysis in this study remained within normal values.
A recently recognized severe complication of
cyclosporin administration in cats is the development
of systemic toxoplasmosis, which can have a fatal
outcome.28,29 Cats are the definitive hosts of Toxoplasma
gondii, which they ingest by eating raw (prey) meat containing tissue cysts. Immunocompetent cats develop an
effective cell-mediated immunity, which protects the
animal from the development of systemic disease.
Immune suppression, either as the result of viral
infections30,31 or of iatrogenic causes,32 can lead to the
development of an acute systemic disease, caused by
the reactivation of dormant tissue cysts. Before
cyclosporin treatment, it is thus mandatory to test for
toxoplasmosis and to advise the owner to feed cooked
or commercial food only.29 IgG and IgM serum titles
tested negative in both cats of this report.

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Adnexal skin diseases treated with cyclosporin

In conclusion, these cases suggested that cyclosporin can
be a useful tool in the treatment of selected immunemediated diseases of the hair follicle and adnexa.

ACKN OWLEDGE ME NT S
The authors would like to thank the colleagues of the
Veterinary Clinic S. Giorgio (Montecchio Emilia, RE)
for referring case 1, Dr Paolo Corsaletti for referring
case 2 and the Veterinary Hospital Anubi for referring
case 3. We are also thankful to Ms. Natalie Perrins for
the English editing of the manuscript.

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Rsum La cyclosporine est actuellement considre comme une molcule nouvelle et intressante en dermatologie
vtrinaire pour le traitements des dermatoses immunologiques, et une alternative sre et efficace au traitement
immunosuppresseur avec les glucocorticoides. Les auteurs rapportent un cas de folliculite/furonculose granulomateuse chez un chat, un cas dadnite sbace chez un chat et un cas dalopecia areata chez un chien contrls
par la cyclosporine.
Resumen La ciclosporina es considerada actualmente una medicina novedosa y de inters en dermatologa
veterinaria para el tratamiento de enfermedades inmunomediadas de la piel, as como una alternativa segura y
eficaz al tradicional tratamiento inmunosupresor con glucocorticoides. En este articulo los autores exponen un
caso de foliculitis y furunculosis granulomatosa en un gato; un caso de adenitis de glndulas sebceas en otro
gato; y un caso de alopecia areata en un perro, todos ellos controlados con xito tras tratamiento con ciclosporina.
Zusammenfassung Cyclosporin wird zur Zeit als neues und interessantes Medikament in der Veterinrdermatologie fr die Behandlung von immun-mediierten Hauterkrankungen betrachtet. Es gilt als eine sichere und
effektive Alternative zu immunsupprimierender Therapie mit Glukokortikoiden. Die Autoren beschreiben einen
Fall einer granulomatsen Follikulitis und Furunkulose bei einer Katze, einen Fall von Sebadenitis bei einer
Katze sowie einen Fall einer Alopecia areata bei einem Hund, die alle erfolgreich mit Cyclosporin kontrolliert
wurden.

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