Veterinary Dermatology 2004, 15, 37 41

Eleven cases of vesicular cutaneous lupus erythematosus

in Shetland sheepdogs and rough collies: clinical management
and prognosis

Blackwell Publishing Ltd.

H. A. JACKSON
Department of Clinical Sciences, North Carolina State University, College of Veterinary Medicine, 4700
Hillsborough Street, Raleigh, NC 27606, USA
(Received 14 February 2003; accepted 15 July 2003)

Abstract A cutaneous ulcerative disease is recognized to affect the adult Shetland sheepdog and rough collie.
This has a distinct clinical and histological appearance consistent with a vesicular variant of cutaneous lupus erythematosus (VCLE). Retrospective information on the clinical outcome and response to therapy was collected
from 11 cases of histologically confirmed VCLE. In 8/11 dogs the onset of disease was in the summer; in three
dogs recrudescence occurred in subsequent summers. In eight dogs the skin disease was judged to be 75100%
controlled with therapy after a minimum follow-up of 9 months. Successful treatment in seven of these cases comprised immunosuppressive doses of oral glucocorticoids, alone (one dog), in combination with azathioprine (five
dogs) and doxycycline (one dog). One case responded to topical fluocinolone. Three dogs were euthanased for
reasons directly related to the disease, one prior to initiating any therapy. Vesicular cutaneous lupus erythematosus in the rough collie and Shetland sheepdog can be a debilitating skin disease which is best managed with
aggressive immunosuppressive therapy. Sun avoidance or the use of sunscreens is an important additional management recommendation.
Keywords: canine, collie, cutaneous lupus, Shetland sheepdog, therapy.

INTRODUCTION
In 2001 we reported on an ulcerative skin disease recognized in the rough collie and Shetland sheepdog.1
Clinical and histological features of this syndrome are
consistent with a vesicular variant of cutaneous lupus
erythematosus (VCLE). Briefly, VCLE affects adult
rough collie and Shetland sheepdogs. The onset of the
disease is usually in the summer months. Characteristic
cutaneous features are annular, polycyclic and serpigenous ulcerations distributed over sparsely haired areas
of the body, specifically the ventral abdomen, axilla,
groin, and concave aspects of the pinnae. Mucous
membranes may also be involved. Histological features
are a cell rich lymphocytic interface dermatitis and
folliculitis with vesiculation at the dermo-epidermal
junction.
There is little published information on prognosis
and response to therapy for this disease. It has been
suggested that prednisone, 12 mg kg1 twice daily,
should be used in the acute stages and that pentoxifylline 400 mg once daily and vitamin E supplementation
might have additional benefit.2 The purpose of this
retrospective study is to report on the outcome of 11
Correspondence: H. A. Jackson, Department of Clinical Sciences,
North Carolina State University, College of Veterinary Medicine,
4700 Hillsborough Street, Raleigh, NC 27606, USA. E-mail:
hilary_jackson@ncsu.edu
2004 European Society of Veterinary Dermatology

confirmed cases of VCLE, eight of which were described

in the original paper. The dogs were followed for a
minimum of 9 months post diagnosis or until death or
euthanasia supervened.
Selection criteria
Eleven dogs were included in the study. Preliminary
selection was made on the basis of skin biopsies which
were submitted to the author during a 2-year period
(199899). These were reviewed by the author and at
least two other Board certified dermatologists or pathologists with an interest in dermatology. Cases were only
included if the consensus histological diagnosis was
VCLE and the clinical description of the case, after discussion with the primary clinician, was consistent with
this diagnosis. A description of the initial clinical and
laboratory findings associated with eight of these cases
can be reviewed.1 Two of the dogs were managed by the
author. In eight cases the initial choice of therapy was
made by the primary clinician, five of whom were
board certified veterinary dermatologists; one dog was
euthanized without treatment. In three cases where the
response to initial treatment was poor the author was
consulted regarding therapeutic options, which may
have added bias to the ultimate choice of therapy.
Case management
Two questionnaires were sent to the primary veterinarian, the first when the case was initially identified and
37

38

H. A. Jackson

Case number

Breed

Age onset (years)

Gender

1
2
3
4
5
6
7
8
9
10
11

Shetland sheepdog cross

Shetland sheepdog
Shetland sheepdog
Rough collie
Shetland sheepdog
Shetland sheepdog
Rough collie
Shetland sheepdog
Shetland sheepdog
Shetland sheepdog
Rough collie

11
4
6
5
8
7
6
4
5
4
7

FS
F
FS
F
M
M
FS
FS
FS
MN
F

Table 1. Details of the case signalment for

individual dogs

FS, female spayed; F, female; M, male; MN, male neutered.

the second 2 years after the first case was collected.

This resulted in variable follow-up intervals. The initial
questionnaire requested details regarding the signalment, month of onset of clinical signs, previous therapy (including routine prophylactics), history of
previous skin disease, date of diagnosis and details of
any laboratory investigations which had been performed. This information is summarized in the initial
paper.1 The second questionnaire concerned therapeutic strategies employed subsequent to diagnosis. The
clinician was asked to give details of the dose (mg kg1),
frequency and length of treatment for each drug or
combination of drugs employed. Details of any side
effects of therapy, concurrent diseases, or relapse of the
initial disease were also requested. Additionally, clinicians were asked to grade the response to therapy using
the following scale; deterioration, no improvement,
25%, 50%, 75% improvement or complete remission.
Seven Shetland sheepdogs, three rough collies and one
Shetland sheepdog cross were included in the case
series. Details of the signalment are given in Table 1.
There were eight females (five spayed) and three males
(one neutered). The mean age of onset of the disease
was 6 years (median 6 years, range 411). In eight of
the 11 dogs the clinical signs were first noted between
June and September; two started in February and one
in March.
Previous or concurrent diseases
One rough collie (dog 7) had been diagnosed with
hypothyroidism prior to the onset of VCLE and was
euthyroid on replacement therapy at the time of diagnosis; this dog also had a previous history of episodes
of superficial pyoderma. One Shetland sheepdog (dog
9) had concurrent rheumatoid arthritis.
Treatment
In all cases systemic treatment with a minimum of a
4-week course of a systemic bacteriocidal antibiotic
(cephalexin, oxacillin, potentiated amoxicillin, enrofloxacin) and a topical antibacterial agent (benzoyl
peroxide, chlorhexidine or ethyl lactate) was initiated
at the time of first presentation. Case 4 was septicaemic
necessitating treatment in intensive care. In this dog
and case 3, rods and cocci were identified on skin surface cytology at presentation. Silver sulfadiazine was

applied topically until surface cytology was clear in

these two cases. Systemic antibiotics were continued
for a variable period of time after diagnosis (range 4
16 weeks). Three dogs required additional intermittent
treatment with systemic antibacterial agents for superficial pyoderma during the course of their disease and
one individual (dog 9) received long-term pulse therapy (cephalexin, one dose twice weekly). In six cases
regular (weekly or biweekly) shampooing with an antibacterial (benzoyl peroxide, chlorhexidine or ethyl lactate) was a component of maintenance therapy.
Details of immunosuppressive treatment are given in
Table 2. In 10 of the 11 cases immunosuppressive treatment was initiated after a confirmed histological diagnosis. Dog 11 was euthanized at the owners request
after a guarded prognosis for complete recovery was
given.
The initial treatment for six dogs (14, 6, 9) was
immunosuppressive doses of prednisone (1.72 mg kg1
daily), which was tapered according to the clinical
response observed. In only one dog (case 2) was this the
sole final treatment given. This dog was reportedly in
remission after 50 days of therapy and treatment was
discontinued. The dog was clinically normal 9 months
after diagnosis. Case 9 was tapered to 0.5 mg kg1
every third day and the cutaneous lesions were well
controlled after 2 years with the addition of a oncedaily dose of 5.5 mg kg1 doxycycline. Oral prednisone
caused haematemesis in case 3 and it was therefore
discontinued. In the remaining three dogs which had
started on prednisone alone, azathioprine was added
to the treatment regime due to an unsatisfactory
response to the single therapeutic agent after 6
12 weeks. In case 1, prednisone was replaced with
methylprednisolone to minimize side effects of polyuria and polydipsia. The therapy for case 8 was changed
to methylprednisolone and azathioprine after an initial
poor response to alternative immunomodulating
agents. Thus, in five dogs the final treatment was a combination of an oral glucocorticoid and azathioprine, in
one dog, prednisone in combination with doxycycline
and in another dog, prednisone alone, which was discontinued after an excellent response after 50 days of
therapy.
Four dogs were treated with pentoxifylline. In three
dogs this was the initial drug of choice and in the other

2004 European Society of Veterinary Dermatology, Veterinary Dermatology, 15, 37 41

Management of vesicular cutaneous lupus erythematosus

39

Table 2. Summary of the therapeutic management of 11 dogs diagnosed with VCLE

Case Initial treatment

Response after
6 12 weeks

2
3
4

Prednisone 1.7 mg kg1 QD

Topical steroids
Prednisone 2 mg kg1 QD
Prednisone 2 mg kg1 QD
Prednisone 2 mg kg1 QD

5
6

Topical fluocinolone as needed Excellent

Prednisone 2 mg kg1 QD
Poor

Pentoxifylline*

Poor

Poor

Pentoxifylline 3 mg kg1 BID

Tetracycline 500 mg TID
Niacinamide 500 mg TID
Vitamin E 400 IU BID
Prednisone 2.2 mg kg1 QD

10

Pentoxifylline 30 mg kg1 QD

Good initially

11

No treatment

Poor
Excellent
Not tolerated
Poor

Outcome
Follow-up (months) (% improvement)

Final treatment
1.4 mg kg1 azathioprine QOD
0.7 mg kg1 methylprednisolone QD
none
Pentoxifylline 16 mg kg1 TID
Prednisone 0.6 mg kg1 QD
Azathioprine 1.6 mg kg1 QD
Prednisone 0.8 mg kg1 QOD
Azathioprine mg kg1 QOD
Prednisone 0.1 mg kg1 QOD
Azathioprine 0.6 mg kg1 twice weekly
Methylprednisone*
0.4 mg kg1
Azathioprine* 1.1 mg kg1

Poor

48

100%

9
3
15

100%
0%, died
75% Euthanized

12
42
18

100%
75%
Died
75%

15

75%

Prednisone 0.5 mg kg1 every 3rd day

24
Doxycycline mg kg1 SID 5.5 mg kg1 QD
Azathioprine mg kg1 SID 2 mg kg1 QD 10
Pentoxifylline mg kg1 SID 30 mg kg1 QD

100%
0% euthanized
0% euthanized

*Dose or frequency not given.

it was administered after an immunosuppressive dose

of prednisone was poorly tolerated. The dose and frequency of administration varied. The total dose given
in a 24-h period ranged from 9 to 30 mg kg1. In one
case the dose was not documented (no. 7) and in
another (no. 8) this was administered concurrently
with tetracycline, niacinamide and vitamin E. The
response to pentoxifylline therapy was poor in all
cases, prompting a change in the therapeutic regime.
An initial improvement was seen in one dog (case 10),
followed by deterioration of clinical signs.
Adverse effects of therapy
Adverse side effects were reported in all dogs which
were prescribed systemic glucocorticoids. These
included acute haematemesis, polyuria and polydipsia,
polyphagia, weight gain, thinning of the hair coat and
calcinosis cutis. In two dogs treated with azathioprine,
in addition to glucocorticoids marked elevation of liver
enzymes was reported.
Outcome
A complete response to therapy was reported in four
dogs (1, 2, 5 and 9). In two of these cases (1 and 2), therapy was discontinued after 2.5 years and 9 months,
respectively. Case 1 was still in remission 18 months
later, case two was lost to follow-up, and the other two
cases were still receiving treatment after 1 (case 5) and
2 years (case 9). Four dogs were reportedly 75%
improved with treatment (cases 4, 6, 7 and 8) after
15 months to 3.5 years of therapy. Case 4 was euthanized after 15 months of treatment at the owners
request due to financial constraints on continuing therapy, and case 6 died of unknown causes after 3.5 years,
aged 10.5 years. Of these eight dogs with 75100%
improvement in clinical signs, five were treated with
prednisone or methylprednisolone in combination

with azathioprine, one was maintained on prednisone

and doxycycline, one on prednisone alone and the final
case was treated with topical fluocinolone. A poor
response to therapy was reported in two dogs; case 10
was euthanased at 10 months after failure to respond
to azathioprine and pentoxifylline and case 3 died of
unknown causes 3 months after diagnosis on treatment
with pentoxifylline and a poor response to therapy.
Case 11 did not receive treatment and was euthanized.
In three cases (4, 6 and 7), recrudescence of clinical signs
occurred in the summer months.
In this series of 11 cases of VCLE, the best long-term
therapeutic outcome was achieved with the oral
administration of short acting glucocorticoids starting
at an immunosuppressive dose and tapered, either
alone or in combination with azathioprine. Treatment
of any immune-mediated disease with immunosuppressive therapy is ultimately achieving a balance
between minimizing the severity of the disease and the
side effects of therapeutic agents. Although 100%
remission was not achieved with therapy in all cases,
quality of life was judged to be good by the attending
veterinarian. It should be noted, however, that many of
these dogs required intermittent topical or systemic
antibacterial therapy during the course of treatment as
a consequence of the residual active skin lesions, and
additionally developed adverse clinical signs associated with the therapy itself.
Canine VCLE has clinical and histological similarities to subacute cutaneous lupus erythematosus
(SCLE) in humans, a cutaneous autoimmune disease
occurring on skin exposed to ultraviolet radiation.
Subacute cutaneous lupus usually responds to topical
glucocorticoids and/or therapy with systemic antimalarials. Systemic glucocorticoid therapy is usually only
required to control acute flares or in the treatment of
systemic lupus erythematosus.3 In the majority of these

2004 European Society of Veterinary Dermatology, Veterinary Dermatology, 15, 3741

40

H. A. Jackson

canine cases the lesions were too extensive and severe

to consider using only topical treatment. In case 5,
however, application of a potent synthetic glucocorticoid to localized lesions on the abdomen resulted in
remission of clinical signs.
Four dogs were treated with pentoxifylline either
alone (three dogs) or in combination with other therapeutic agents. A poor response to this therapy was
reported. Pentoxifylline has diverse modes of action,4
but in the context of canine VCLE the immunomodulatory properties such as inhibition of the synthesis of
pro-inflammatory cytokines and B- and T-cell activation would make it an appropriate therapeutic choice.
The doses used in this study were variable and were
antecedent to any pharmokinectic study of this drug in
dogs. It has subsequently been shown that a 15-mg kg1
dose in the dog, three times daily, achieves plasma
concentrations similar to therapeutic levels in
humans.5 As none of the dogs in this case series were
administered the drug at this dose and frequency, it
cannot be dismissed as a therapeutic agent for canine
VCLE based on this report.
Tetracycline or doxycycline in combination with
niacinamide has been reported as an effective treatment in cutaneous autoimmune skin diseases in both
humans6 and dogs.7 As only two dogs received these
drugs in combination with another therapeutic agent
the author cannot comment on the suitability of this
choice for canine VCLE, although additional improvement in case 9 was noted when doxycycline was added
to the initial prednisone therapy.
Many human patients with SCLE have concurrent
immune-mediated systemic disorders although these
are not as frequent or as severe as those seen with systemic lupus erythematosus (SLE).8 In this canine case
series only two dogs had concurrent immune-mediated
diseases, namely hypothyroidism and rheumatoid
arthritis. Due to the small number of cases in this series
conclusions as to concurrent immune-mediated problems cannot be drawn from the incidence reported here.
Photosensitivity is a marked feature of SCLE in
humans, and management with sunscreens and sun
avoidance is a key to minimizing relapses. It is interesting
to note in this context that, not only did the majority of
these dogs (8/11) first manifest clinical signs between June
and September but additionally in three cases followed
for over 12 months, the attending veterinarians noted a
definite flare of clinical signs in subsequent summers.

The author concludes that a diagnosis of VCLE in the

rough collie, Shetland sheepdog or their crosses should
carry a guarded prognosis for complete remission,
although clinical signs can be controlled with immunosuppressive doses of short acting oral glucocorticoids,
often with the addition of azathioprine. Given the
marked seasonality of onset of this disease and distribution of lesions on less haired areas of the body, sun
avoidance or the use of sunscreens should be an important management recommendation.

ACKNOWLEDGEMENTS
The author wishes to thank all the veterinarians who
provided information on these cases, in addition to
those individuals who sent biopsy material from
affected dogs.

REFERENCES
1. Jackson, H.A., Olivry, T. Ulcerative dermatosis of the
Shetland sheepdog and rough collie dog may represent a
novel vesicular variant of cutaneous lupus erythematosus.
Veterinary Dermatology 2001; 12: 1927.
2. Irkhe, P.J., Gross, T.L. Ulcerative dermatosis of Shetland
sheepdogs and collies. Bonagura, J.D., Kirk, R.W. eds.
Current Veterinary Therapy XII. Small Animal Practice.
Philadelphia: W B Saunders, 1995: 63970.
3. Callen, J.P. Management of skin disease in patients with
lupus erythematosus. Best Practice and Research in Clinical Rheumatology 2002; 16 (2): 24564.
4. Samlaska, C.P., Winfield, E.A. Pentoxifylline. Journal of
the American Academy of Dermatology 1994; 30: 60321.
5. Marsella, R., Nicklin, D.F., Munson, J.W. et al. Pharmokinetics of pentoxifylline in dogs after oral and intravenous
administration. American Journal of Veterinary Research
2000; 61: 6317.
6. Fivenson, D.P., Breneman, D.L., Rosen, G.B. Nicotinamide and tetracycline therapy of bullous pemphigoid.
Archives of Dermatology 1994; 130: 7538.
7. White, S.D., Rosychuck, R.A.W., Reinke, S.L. Use of tetracycline and niacinamide for the treatment of autoimmune skin disease in 31 dogs. Journal of the American
Veterinary Medical Association 1992; 200: 1497500.
8. Black, D.R., Hornung, C.A., Schneider, P.D. et al. Frequency and severity of systemic disease in patients with
subacute cutaneous lupus erythematosus. Archives of Dermatology 2002; 138: 11758.

Rsum Une maladie cutane ulcrative est rapporte chez le Colley et le Shetland. Il sagit dune entit prsentant des caractristiques cliniques et histologiques compatibles avec une forme vsiculeuse de lupus cutan
(VCLE). Une valuation rtrospective des donnes cliniques et de la rponse au traitement a t obtenue chez
11 chiens pour lesquels le diagnostic histopathologique tait celui de VCLE. Pour 8/11 cas, la maladie est apparue
pendant lt, et pour les trois autres cas une recrudescence de la dermatose a t observe pendant lt. Pour
huit chiens, un contrle de 75 100% a t obtenu avec le traitement, avec un suivi minimum de 9 mois. Le traitement tait dans 7 cas lutilisation de doses immunosuppressives de glucocorticodes par voie orale, seule (1 chien)
ou en association avec lazathioprine (5 cas) ou la doxycycline (un cas). Un cas a rpondu lapplication topique
de fluocinolone. Trois chiens ont t euthanasis pour des raisons directement lies la maladie, un avant tout
2004 European Society of Veterinary Dermatology, Veterinary Dermatology, 15, 37 41

Management of vesicular cutaneous lupus erythematosus

41

traitement. Le lupus rythmateux cutan vsiculeux du Colley et du Shetland peut tre une maladie grave, et
doit tre trait avec un traitement immunosuppresseur aggressif. Lviction solaire, ou lutilisation de photoprotecteurs est galement raliser systmatiquement.
Resumen Se identifica una enfermedad ulcerativa cutnea que afecta el perro pastor de Shetland adulto y el Collie de pelo duro. sta muestra una apariencia clnica e histolgica compatible con una variante vesicular del lupus
eritematoso cutneo (VCLE). Se recopil informacin sobre la evolucin clnica y la respuesta a la terapia de 11
casos de VCLE confirmados histolgicamente. En 8/11 perros la enfermedad se inici en verano, y en tres perros
se produjo una recada los veranos siguientes. En ocho perros se estim que la enfermedad cutnea poda controlarse en un 75 100% mediante terapia despus de un seguimiento mnimo de nueve meses. El tratamiento con
xito en siete de estos casos comprenda dosis inmunosupresoras de glucocorticoides orales, solos (un perro), en
combinacin con azatioprina (cinco perros) y doxiciclina (un perro). Un caso respondi a la fluocinolona tpica.
Se eutanasiaron tres perros por razones directamente relacionadas con la enfermedad, uno antes de iniciar
cualquier tipo de terapia.
El lupus eritematoso vesicular cutneo en el pastor de Shetland y en el Collie de pelo duro puede ser una
enfermedad cutnea debilitante controlada con terapia inmunosupresora agresiva. Evitar la exposicin solar o
utilizar pantallas solares son medidas adicionales recomendadas.
Zusammenfassung Beim erwachsenen Sheltie und Rough Collie wurde eine kutane ulcerative Erkrankung
entdeckt. Diese hat ein deutlich ausgepgtes klinisches und histologisches Erscheinungsbild, das im Einklang mit
einer vesikulren Variante des kutanen Lupus erythematodes (VKLE) steht. Retrospektive Informationen bezglich des klinischen Verlaufes und Therapieerfolges wurden von 11 Fllen mit histologisch besttigtem VKLE
gesammelt. Bei 8/11 Hunden begann die Erkrankung im Sommer, bei 3 Hunden trat sie in folgenden Sommern
wieder auf. Bei acht Hunden wurde die Hauterkrankung zu 75100% therapeutisch unter Kontrolle gebracht mit
einem Mindest-follow-up on 9 Monaten. Erfolgreiche Behandlung bei sieben dieser Flle umfasste immunsuppressive Dosen oraler Glukokortikoide als alleinige Therapie (ein Hund), in Kombination mit Azathioprin (fnf
Hunde) oder Doxycyclin (ein Hund). Ein Hund reagierte auf topisches Floucinolon.
Drei Hunde wurden aus Grnden euthanasiert, die direkt mit der Erkrankung im Zusammenhang standen,
einer vor Einleitung irgendeiner Therapie.
Vesikulrer kutaner Lupus erythematodes bei Rough Collies und Shelties kann eine schwchende Hauterkrankung sein, die am besten mit aggressiver immunsuppressiver Therapie behandelt wird. Vermeidung von
Sonne oder die Verwendung von Sonnenschutzmitteln ist eine wichtige zustzliche Behandlungsempfehlung.

2004 European Society of Veterinary Dermatology, Veterinary Dermatology, 15, 3741