Veterinary Dermatology 2004, 15, 245 252

Blackwell Publishing, Ltd.

Prolonged remission after immunosuppressive therapy

in six dogs with pemphigus foliaceus
THIERRY OLIVRY*, KERSTIN E. BERGVALL, and BARBARA A. ATLEE
*Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University,
4700 Hillsborough Street, Raleigh, NC 27606, USA
Djur Akuten, Kungstensgatan, S-11329 Stockholm, Sweden
Department of Small Animal Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
Animal Dermatology & Allergy Clinic, 1204 Deboy Street, Raleigh, NC 27606, USA
(Received 23 August 2003; accepted 30 September 2003)

Abstract Limited information is available on the long-term outcome of treatment of pemphigus foliaceus in
dogs. The purpose of this study is to report that a prolonged remission can occur after discontinuation of immunosuppressive regimens in some animals with this disease. Six dogs were diagnosed with pemphigus foliaceus
based on suggestive clinical signs and histopathology. These patients were treated either with immunosuppressive
doses of oral glucocorticoids or with a combination of oral glucocorticoids and azathioprine. After clinical signs
underwent complete remission, which occurred 1.55 months after immunosuppression was initiated, the drugs
were tapered progressively and eventually withdrawn. The total duration of immunosuppressive therapy varied
between 3 and 22 months. Skin lesions of pemphigus foliaceus did not recur for 1.56 years after treatment was
stopped. These observations suggest that, in some dogs with pemphigus foliaceus, immunosuppression can lead
to long-term remission of skin lesions, and that discontinuation of treatment is not necessarily followed by a recurrence of clinical signs.
Keywords: autoimmunity, blistering dermatoses, canine, desmoglein, desmosome, epidermis, integument,
keratinocyte, skin.

IN TRO D U CT I ON
Pemphigus foliaceus (PF) represents the most common
autoimmune blistering skin disease of dogs.1,2 Its prevalence is estimated to be < 1% of cases presented for
skin diseases at university hospitals or examined as
surgical biopsy specimens at a university laboratory.14
Because the pathogenesis of human and canine PF
appears to involve autoantibodies targeting the keratinocyte
desmosomal cadherin desmoglein-157 standard-ofcare treatment typically consists of immunosuppressive protocols.8,9 Immunosuppression is achieved using
either oral glucocorticoids alone or in combination with
cytotoxic drugs that include azathioprine, chlorambucil
or cyclophosphamide.8,9 Upon remission of clinical
signs, the dosage and/or frequency of administration of
either glucocorticoids or cytotoxic drugs, or both, are
reduced gradually to decrease the risk of adverse drug
events.2,3
Information on long-term treatment outcome and
prognosis of large cohorts of dogs with PF has not
been published at this time. In the largest published
case series of dogs with PF, with follow-up of 17 years,
immunosuppressive therapy was deemed successful in
Correspondence: T. Olivry, DrVet, PhD, Department of Clinical
Sciences, North Carolina State University, College of Veterinary
Medicine, 4700 Hillsborough Street, Raleigh, NC 27606, USA. E-mail:
thierry_olivry@ncsu.edu
2004 European Society of Veterinary Dermatology

only 18 of 34 subjects (53%).3 Furthermore, other reports

provide evidence for a wide variation in prognosis
among patients. At one end of the disease spectrum,
some dogs with PF are killed because of a lack of response
of lesions to immunosuppression.2,10 In contrast, a single
dog with PF was reported to have remained free of lesions
for at least 1 year after discontinuation of prednisolone
administration (case 2 in Bensignor & Carlotti11).
The purpose of this study was to describe the clinical
course of PF lesions in six dogs in which discontinuation of immunosuppressive therapy led to long-term
remission with no recurrence of disease for at least
1.5 years after the cessation of treatment.

C A SE R E P O RT S
Selection
Medical records from three dermatology referral clinics
were searched for affected dogs that satisfied the following criteria during the period 19952001:
1 clinical signs suggestive of PF (pustules, erosions
and crusts with bilaterally symmetrical distribution
affecting primarily the face).
2 histopathological examination of lesional skin
biopsies diagnostic for PF (intraepidermal pustules rich in acantholytic keratinocytes).
245

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T Olivry et al.

3 positive clinical response to immunosuppressive

protocols that included glucocorticoids with or
without cytotoxic drugs.
4 lack of recurrence of clinical signs of PF for at least
1 year after discontinuation of immunosuppressive medications.
At the North Carolina State University College of
Veterinary Medicine (Raleigh, NC, USA), 27 dogs
were diagnosed with PF based on criteria 1 and 2 during the study period. Two of these subjects (7%) fulfilled additional criteria 3 and 4.
At the Animal Dermatology and Allergy Clinic (Cary/
Durham, NC, USA), 15 dogs were diagnosed with PF.
Two dogs (13%) fulfilled all four criteria necessary for
inclusion in this report.
At the Djur Akuten specialty clinic (Stockholm,
Sweden), nine dogs were diagnosed with PF per criteria
1 and 2. Two dogs (22%) also satisfied inclusion criteria
3 and 4. In all, six dogs with PF in long-term remission
without treatment are reported herein.

Case 1
A 1.5 year-old female spayed Doberman pincher dog
was presented with a 2-month history of generalized
pustular eruption, scaling and crusting that initially
affected the face, limbs and abdomen. Drugs had not
been administered prior to the appearance of the first
skin lesions. Superficial pyoderma was diagnosed by
the general practitioner based on a culture of Staphylococcus intermedius (location of sampling unknown).
Owing to a lack of improvement after successive prescriptions of cephalexin, amoxicillinclavulanate, oxacillin, prednisone and griseofulvin, the dog was referred
to a dermatologist.
On clinical presentation, the dog was febrile (40.5 C).
Large irregular pustules were found on the ventral
abdomen, axillae and near auditory orifices. Scattered
eroded and crusted lesions were present at various locations on the body, especially on the dorsal and lateral
muzzle and around the eyes, where the lesions exhibited
a bilateral symmetry (Fig. 1a,b).
Aspiration cytology of pustule content revealed intact
neutrophils and numerous acantholytic keratinocytes.
Histopathological examination of skin biopsy specimens exposed subcorneal neutrophilic pustules with

Figure 2. Skin; case 1: a subcorneal pustule contains neutrophils

and acantholytic keratinocytes. Haematoxylin and eosin,
bar = 75 m, inset = 50 m.

isolated and clustered acantholytic keratinocytes (Fig. 2).

periodic acid Schiff (PAS) staining of skin sections was
unremarkable. A fungal culture of crusts and hair was
negative. Direct immunofluorescence (IF) testing, performed as described previously,12 confirmed the presence of intercellular immunoglobulin (Ig)G and IgA
deposited in the upper half of the epidermis. Indirect
IF testing was negative on canine lip and tongue substrates.12 A diagnosis of PF was made based on clinical
signs, histopathology results and direct IF testing.
Treatment was initiated with prednisone at 60 mg
(2.0 mg/kg) twice daily. After 3 weeks, new pustules
erupted, and erosions and crusts appeared on the
footpads. Azathioprine was added at 50 mg (1.5 mg/ kg)
once daily, and the dose of prednisone was decreased to
40 mg (1.3 mg/kg) twice daily to reduce side effects of
glucocorticoid therapy. Because of a lack of perceived
efficacy after 2 weeks, the dose of azathioprine was
doubled to 100 mg (3.3 mg/kg) once daily. Complete
remission of skin lesions occurred within 2 months,
and the dose of prednisone was tapered to 40 mg
once daily. During the following 5 months, the dose of
prednisone was decreased by 25% every 2 weeks, on an
alternate-day basis, and the lesions remained in complete

Figure 1. Case 1: bilaterally symmetrical

erosions and crusts can be seen around the
eyes (a) and on the dorsal (a) and lateral
muzzle (b).
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247

remission. During the ensuing 2 months, azathioprine

was administered on an every other day basis at the
same dose. All medications were discontinued eventually
after 10 months of immunosuppression. Skin lesions of
PF did not recur during the subsequent 6 years.

Case 2
A 4 year-old female intact German shepherd crossbred dog was presented with a 1-month history of
pruritic facial lesions. Medications had not been given
before cutaneous signs were observed. One week prior
to presentation to the dermatologist, lethargy, depression and fever (40 C), arose, and skin lesions spread to
the limbs. The dog walked reluctantly. Dermatological
examination revealed large flaccid pustules with a
peripheral erythematous halo on the abdomen. Erosions
and crusts were generalized, and they were present in
highest numbers on the face, ears, genitalia and tail. The
periphery of most footpads was crusted and fissured.
Fine-needle aspiration of the content of abdominal
pustules revealed numerous intact neutrophils and
isolated or clustered acantholytic keratinocytes. Histopathological examination of pustular skin lesions
uncovered the presence of large subcorneal pustules
with numerous acantholytic keratinocytes. Staining with
PAS did not reveal corneophilic dermatophytes. A
dermatophyte culture of scales and crusts was unremarkable after 2 weeks. Indirect IF on mouse skin was
negative at 1:50 dilution. The diagnosis of PF was
based on clinical and histopathological findings.
Prednisone was prescribed at 40 mg (2.0 mg/kg)
twice daily. Two weeks later, a marked improvement in
the severity of skin lesions was seen, and the dose of
prednisone was decreased to 30 mg (1.5 mg/kg) twice
daily for 2 weeks, then to 20 mg (1.0 mg/ kg) twice daily
for another 2 weeks. At that time, complete clinical
remission was achieved and prednisone was administered at 20 mg once daily for 1 month. Because of persistent remission, prednisone was given on alternate
days with decreasing dosages, and it was discontinued
after 6 months. Almost 2 years after cessation of glucocorticoid therapy, the disease remains in complete
remission.

Case 3
A 4 year-old Australian shepherd dog had a 1-year history of depigmentation, erosions and crusting of the
nasal planum and dorsal muzzle. The patient was receiving no medications when skin lesions were noticed first.
Prednisone (uncertain dosage) was administered for
suspected discoid lupus erythematosus, and this treatment resulted in temporary remission of skin lesions.
Because of adverse effects of glucocorticoids, therapy
was switched to a niacinamidetetracycline combination, topical hydrocortisone cream, sun avoidance and
a diet change. When skin lesions worsened, the dog was
referred. Upon presentation to the dermatologist, the
nasal planum had lost its normal cobblestone surface
architecture; it was depigmented, erythematous, eroded
and crusted (Fig. 3 and inset). Scales and crusts

Figure 3. Case 3: depigmentation, erythema, scales and crusts are

visible on the dorsal muzzle (a), while the dorsal and frontal aspects
of the nasal planum are depigmented, erythematous, eroded and
crusted (b).

Figure 4. Skin; case 3: IgG is deposited around keratinocytes of

perilesional skin. The intensity of staining is strongest in the stratum
spinosum. Direct IF, anticanine IgG-fluorescein (green colour),
Evans blue and propidium iodide (red nuclear colour)
counterstains, bar = 25 m.

covered the dorsal muzzle (Fig. 3). Several large erythematous, oedematous and crusted plaques were present
on the lateral trunk.
A Woods lamp examination was unremarkable. A
dermatophyte culture of hair and crusts did not yield
any growth. Antinuclear antibodies were not detected
at 1:40 dilution. Microscopic examination of skin biopsies
revealed subcorneal pustules rich in neutrophils and
acantholytic keratinocytes. Direct IF confirmed the
presence of IgG surrounding epidermal keratinocytes,
especially those of the stratum spinosum (Fig. 4). Indirect IF, performed on neonatal mouse skin, revealed
antikeratinocyte IgG auto-antibodies at up to 1:250
dilution. The diagnosis of PF was made based on
clinical signs, as well as results of histopathology and
IF assays.
Pending reception of test results, oral cephalexin, a
topical glucocorticoid solution and fatty acid supplements were prescribed. Because skin lesions did not
respond to this regimen, immunosuppression was
initiated with prednisone at 20 mg (0.8 mg/kg) twice
daily and azathioprine 50 mg (1.9 mg/kg) once daily.

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T Olivry et al.

Three weeks later, the lesions had markedly decreased

in severity, and the dose of prednisone was reduced to
30 mg (1.1 mg/kg) one day and 20 mg the next, whereas
that of azathioprine remained at 50 mg once daily. One
month later, the skin lesions were almost in complete
remission. During the following 17 months, as all skin
lesions had regressed completely, the dosage of both
drugs was reduced progressively. All medications were
discontinued eventually 22 months after immunosuppression was initiated. Three and a half years later,
the disease has remained in complete remission without any treatment.

Case 4
A 2.5 year-old female intact Irish wolfhound was presented to the referring veterinarian with a 1-month
history of multifocal erythematous and crusted papules
on the trunk, erythematous pododermatitis and lameness. Medications had not been administered before
the owner noticed skin lesions. Cephalexin was prescribed for 14 days, and upon observation of footpad
exfoliation, this antibiotic was changed to trimethoprimsulfamethoxazole, then to enrofloxacin. Despite
therapy, lesions continued to worsen, and pruritus
became more severe.
Upon referral to the dermatologist, the dog was
depressed. The pinnae were oedematous, erythematous,
excoriated and painful. The ear canals were eroded and
filled with purulent fluid. Large dried erythematous
pustules and crusts, often overlying an erythematous
base, were present over the entire body, including the
head and muzzle. The footpads were hyperkeratotic
and fissured. Erythema and erosions were noticed in
intertriginous areas of the abdomen, inguinal region
and perineum. Lesions were not observed on mucosal
surfaces.
Impression smears of pus collected under dried
crusts revealed few cocci and neutrophils, but no
obvious acantholytic keratinocytes. Ear cytology was
consistent with suppurative bacterial and yeast otitis
externa. Skin biopsies were collected from four crusted
pustules and microscopic examination of sections
revealed epidermal hyperplasia, hyperkeratosis and
subcorneal neutrophilic pustules with acantholytic
keratinocytes. Scattered bacterial colonies were seen
on the skin surface. Neutrophils, lymphocytes, plasma
cells and macrophages surrounded superficial dermal
blood vessels. Additional staining with PAS did not
reveal any dermatophytes. Examination with a Woods
lamp and a dermatophyte culture of hair and scales
were unremarkable. Indirect IF, performed on neonatal mouse skin, uncovered the presence of circulating
antikeratinocyte IgG auto-antibodies (1:500 titre).
Pemphigus foliaceus, secondary pyoderma and mixed
suppurative mixed bacterial and yeast otitis externa
were diagnosed from clinical signs and results of cytological, histological and IF tests.
Pemphigus skin lesions were treated with prednisone
at 40 mg (0.7 mg/kg) twice daily to be reduced to once
daily administration after clinical remission was

obtained. Clindamycin was given at 300 mg (5.5 mg/ kg)

twice daily for 3 weeks. Baths with ethyl lactate (Etiderm,
Virbac, Fort Worth, TX, USA) were recommended.
Ear flushes and a topical antibioticantifungalglucocorticoid formulation were prescribed (Otomax, ScheringPlough Animal Health, Union, NJ, USA) for treatment
of the otitis externa. Flea control was implemented.
After 3 weeks of antibiotic and glucocorticoid administration, most lesions had begun to heal, but new
pustules continued to erupt. Remaining crusts were
large, thick and often confluent. Large pustules,
evolving from an erythematous base, were present
over the sternum and axillae. The footpads remained
hyperkeratotic.
Cytological examination of the pustules revealed
neutrophils, cocci and acantholytic keratinocytes.
Because clinical signs were deemed most consistent
with the diagnosis of PF, azathioprine was added at
75 mg (1.4 mg/kg) once daily and the dose of prednisone was decreased to 40 mg (0.7 mg/kg) once daily
to reduce the occurrence of adverse side effects. Also,
oral clindamycin and ethyl lactate shampoos were to be
continued for an additional 10 days.
Two weeks later, all pustules had healed, and new
lesions had not developed. The footpads were affected
less severely than before. The dose of prednisone was
decreased to 30 mg (0.6 mg/kg) once daily, whereas
azathioprine was continued at the same dose. After
2 weeks, the owner reported that remission was complete. The owner had independently reduced the dose
of prednisone to 20 mg (0.4 mg/kg) in the last week,
but skin lesions had not recurred. During the ensuing
months, the dose of both drugs was reduced progressively by the referring veterinarian, and treatment was
discontinued eventually after 6 months of immunosuppression. Skin lesions did not recur during the subsequent 2 years.

Case 5
A 5-year-old female intact akita inu dog was presented
to the dermatologist with a 4-month history of facial
crusting and alopecia. The dog had not been given any
drugs in the period immediately preceding the onset of
skin lesions. A 1-month course of cephalexin was not
followed by any noticeable decrease or worsening in
extent or severity of cutaneous signs.
On clinical examination by the dermatologist, the
dog was alert, normothermic and appeared in good
general health. Easily removed crusts were found on
the concave aspect of the pinnae, dorsal muzzle, nasal
planum and around the eyes. Skin lesions exhibited a
bilateral symmetry. A few intact pustules were observed
on the concave aspect of both pinnae.
Fine-needle aspiration of intact pustules, as well as
imprints of the underside of exfoliated crusts, revealed
intact neutrophils and either isolated or clustered acantholytic keratinocytes. Fungal culture of hairs and
crusts was unremarkable. Histopathological examination of skin biopsy specimens revealed subcorneal pustular dermatitis with acantholytic keratinocytes. A

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Remission of canine pemphigus foliaceus

diagnosis of PF was made based on clinical signs, results
of histopathology and exclusion of corneophilic dermatophyte infestation.
Treatment was initiated with prednisolone at the
dose of 35 mg (1.0 mg/kg) twice daily and topical
application of 0.1% betamethasone valerate cream
(Celeston Valerat, Schering-Plough AB, Stockholm,
Sweden). After 3 weeks, owing to unacceptable adverse
effects, the dosage of prednisolone was reduced to
17.5 mg (0.5 mg/kg) twice daily, and azathioprine was
added at 50 mg (1.4 mg/kg) every other day. One week
later, the severity of skin lesions had improved markedly, but lesions still persisted on the nose and around
the eyes. Prednisolone was no longer administered on
the days when the patient received azathioprine. Betamethasone valerate cream was still used topically as
needed to control the remaining skin lesions. After an
additional 3 weeks, the disease was considered to be in
complete remission. Topical therapy was discontinued,
and prednisolone was tapered to 35 mg (1.0 mg/kg)
every other day; azathioprine was continued at 50 mg
(1.4 mg/kg) every other day. Two weeks later, the disease remained in remission and hair began to regrow.
The dosage of prednisolone was decreased to 15 mg
(0.4 mg/kg) every other day. Azathioprine was continued as before. Ten days later, after 3 months of immunosuppression, the owner discontinued all medications
without instructions, and skin lesions of PF did not
recur during the following 18 months.

Case 6
A 7.5-year-old intact male Eurasier dog, a breed related
to the chow-chow, was presented to the dermatologist
with a 6-month history of dermatitis. There was no history of drug administration prior to the development
of skin lesions. Preputial erythema and facial crusting
were the first skin lesions observed. Treatment with
cephalexin and prednisolone (dosages unknown) for
2 weeks led to partial improvement, but clinical signs
worsened after discontinuation of the drugs.
On physical examination, the dog appeared in good
general health. Mild hyperthermia was attributed to
excitement. Alopecia and nonadherent crusts were
seen, in a bilateral and symmetrical pattern, around the
eyes, dorsal muzzle (Fig. 5), ear pinnae, prepuce and
scrotum. The footpads were dry, fissured and crusted.
Crusts were also seen around the base of few claws.
Cytological examination of impression smears revealed
neutrophils and acantholytic keratinocytes. A dermatophyte culture, performed on both hair shafts and
crusts, was negative. Histopathological examination of
lesional skin biopsies uncovered a neutrophilic subcorneal pustular dermatitis with acantholytic keratinocytes.
A diagnosis of PF was made from clinical, histological
and cytological findings
Immunosuppression was initiated with prednisolone
at 30 mg (1.2 mg/kg) twice daily. Five days later, the
owner reported unacceptable adverse effects from this
treatment, so the dose of prednisolone was reduced to
50 mg (2.0 mg/kg) every other day. Azathioprine was

249

Figure 5. Case 6: depigmentation, erythema, erosions, scales and

crusts are distributed bilaterally and symmetrically on the dorsal
muzzle, around the eyes and on the pinnae.

given at 50 mg (2.0 mg/kg) on the days without prednisolone. After 3 weeks of this regimen, few crusts
remained, but the footpads were still fissured. Prednisolone
was given at 25 mg (1.0 mg/kg) every other day,
whereas the prescription of azathioprine was unchanged.
Three weeks later, the owner elected to discontinue
glucocorticoid administration because of persisting
polyuria and polydipsia. At that time, however, the disease was considered to be in complete remission. After
2 weeks, the dose of azathioprine was reduced to 25 mg
(1.0 mg/kg) every other day, and the hair began to
regrow in previously alopecic areas. Five weeks later,
3.5 months after initiation of immunosuppression, the
administration of azathioprine was discontinued. Except
for persistent mild alopecia on the dorsal muzzle, as
well as dry footpads, the disease has been considered
to be in remission without treatment for the last 18
months.

D IS C U S S IO N
Here, we report the evolution of PF in six dogs for
which immunosuppression led to complete remission
of skin lesions, and discontinuation of treatment was
not followed by a recrudescence of the disease for
follow-up periods varying from 1.5 to 6 years. In total,
51 dogs seen at three dermatology clinics met the study
criteria for a diagnosis of PF, and 6 of the 51 (12%)
experienced a long-term remission after discontinuation of immunosuppressive drugs. To the authors
knowledge, such a remarkable long-term treatment
outcome had been reported only once before (case 2 in
Bensignor & Carlotti11).

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T Olivry et al.

In the six dogs described here, the diagnosis of PF

was made from collation of clinical signs along with
typical histopathological findings.3,9 Moreover, in
three of four patients (75%), immunological tests
revealed the presence of skin-fixed or circulating antikeratinocyte IgG auto-antibodies, supporting the diagnosis of PF. Also, pustular dermatophytosis, a PF-like
eruption caused by corneophilic dermatophytosis13,14
was ruled out in all patients based on results from histopathology and dermatophyte cultures. In only one
patient (dog no. 4), was the existence of concurrent
bacterial impetigo, a known PF-mimicker, considered
possible. In this dog, bacteria were seen on microscopic
examination of cytology specimens and at the surface
of sections of skin biopsies. However, lesions failed to
respond to the administration of three different antibiotics, and they did not recur after antibiotics were discontinued, a noticeable finding in light of continuing
glucocorticoid administration.
To determine with certainty whether or not a disease
is caused by pre-existing drug administration is almost
impossible short of re-challenging the subjects with the
suspected medication(s). However, such drug provocation is rarely performed for ethical reasons and to
decrease harm to patients. Therefore, for most human
and animal individuals, the diagnosis of drug-induced
skin disease usually remains speculative. Because four
of six of the patients reported herein had been treated
at some points with cephalexin for the suspected initial
diagnosis of pyoderma, one could hypothesize that these
dogs were affected with cephalexin-induced or -triggered
PF. Indeed, cephalosporins exhibit the potential to
induce pemphigus lesions, not due to the presence of
thiol (sulfhydryl) radicals, but because they possess an
active amide group.15 As an anecdotal proof of such
capability, cefadroxil has been reported to induce pemphigus vulgaris (PV) in a human patient.16
We do not consider as valid the hypothesis that PF
was induced or triggered by cephalexin in our patients
for the following reasons: (i) four of our five dogs were
affected with facial lesions prior to the prescription of
cephalexin, and facial lesions are seen more commonly
during PF than superficial pyoderma; (ii) in four dogs
that received cephalexin (cases 1, 3, 5 and 6), cephalexin
administration did not result in a worsening of skin
lesions, as would be expected in cephalexin-induced
PF; (iii) in human individuals, beta-lactamin antibiotic
administration triggers the deeper form of pemphigus
(PV) instead of the superficial variant reported here.17
Finally, (iv) the incubation period for nonthiol drugtriggered human PV is reported to be greater than
4 months, a duration not compatible with the histories
recorded for our patients.17
Recently, PF suspected to be associated to previous
drug administration was reported in four dogs.18 In
these subjects, the diagnosis of drug-related PF was
based on history, clinical signs, histopathology and
response to withdrawal of suspected causative drug(s).
In this study, however, one subject (case 1) was treated
with immunosuppressive doses of prednisolone and

azathioprine for 7.5 months, one (case 2) was given

high dosages of prednisolone for 8.5 months, the
last patient received only low dosages of prednisone
for 7 months, and case 3 was not treated with antiinflammatory medications.18 In that study, therefore,
two of four patients had needed months of immunosuppression before all treatment was discontinued. Although
one cannot discount the authors hypothesis that their
patients were affected with drug-associated pemphigus, one cannot disprove the contra-hypothesis either.
Indeed, it is conceivable that these animals could have
suffered from natural autoimmune PF similarly to the
six dogs reported here. If this alternative hypothesis
were to be considered, then the administration and
subsequent withdrawal of culprit drug(s) would have
had no influence on disease evolution in at least two
of four dogs diagnosed with drug-related PF. Unfortunately, the question of which hypothesis to accept
will remain unanswered as drug re-challenges were
not performed in any of these dogs for valid ethical
reasons.
Nevertheless, our observations suggest that the lack
of recurrence of pemphigus lesions after discontinuation of immunosuppression cannot be used as a criterion for diagnosing drug-related PF in dogs.
A retrospective cohort study recently investigated
the long-term outcome of treatment in human beings
with PV.19 Among other valuable follow-up information, the authors reported rates of complete remission,
defined by a period of more than one month during
which the patient was receiving no systemic therapy
and was lesion free. Complete and long-lasting remissions were induced in 25, 50 and 75% of 40 patients
2, 5 and 10 years after diagnosis, respectively. Two
factors were identified to predict the course of PV in
these subjects. The first parameters were the initial
severity and extent of the disease, with patients affected
with mild to moderate PV being twice as likely to enter
complete remission than those with severe phenotype.
The other factor was a rapid response to immunosuppression. Patients whose lesions responded early to
therapy were more than twice as likely to enter prolonged remission than those with delayed response to
treatment.
The six dogs described in this report exhibited variable phenotypes of PF, with lesional extent ranging
from localized to the face (case 5) to generalized (cases
1, 3 and 4), and severity varying from mild (case 5) to
severe (case 4). Such observations suggest that extent
and severity of skin lesions are unlikely to be useful factors for predicting long-term remission in dogs with
PF. In contrast, and similarly to observations reported
by Herbst & Bystryn in human beings with PV19 a
rapid response of skin lesions to immunosuppression
might be a factor helpful for predicting long-term
treatment evolution of canine PF. Indeed, complete
remission of skin lesions occurred shortly after immunosuppression was initiated in the six patients described
herein (median: 2 months; range: 1.54.7 months).
Such short durations could empirically qualify as

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rapid remissions. Nonetheless, a cohort study is
needed to validate whether time to complete remission is
a parameter useful for predicting the evolution of PF in
dogs.
In conclusion, our observations suggest that, in
some dogs with PF, immunosuppression can lead to
rapid remission of skin lesions, and signs will not recur
for at least 1.5 years after discontinuation of treatment.
This anecdotal report supports the recommendation
for dose reduction and eventual discontinuation of
immunosuppressive drugs after achieving complete
remission of PF skin lesions. Such practice should result
in maximal benefit from immunosuppressive regimens
while minimizing harm associated with prolonged use
of these drugs.

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Rsum Peu de donnes sont disponibles sur le pronostic au long cours du pemphigus foliac (PF) chez le chien.
Le but de cet article est de rapporter quune rmission prolonge peut survenir chez certains animaux souffrant
de cette maladie aprs arrt des traitements immunosuppresseurs. Six chiens prsentant un PF (diagnostic clinique et histopathologique) ont t traits avec soit des doses immunosuppressives de glucocorticodes oraux soit
avec lassociation de corticodes et dazathioprine. Aprs disparition des signes cliniques, soit 1.5 5 mois aprs
la mise en place du traitement, les doses ont t progressivement diminues et ventuellement stoppes. La dure
totale du traitement immunosuppresseur a vari entre 3 et 22 mois. Les lsions de PF nont pas rechut 1.5 6
ans aprs cessation de la thrapeutique. Ces observations suggrent que dans certains cas de PF, limmunosuppression peut permettre une rmission prolonge des lsions cutanes, et que larrt de la thrapeutique nest
pas ncessairement suivi par une rechute.
Resumen La informacin existente sobre el resultado a largo plazo del tratamiento del pnfigo foliceo (PF)
en perros es escasa. El propsito de este artculo es mostrar que se puede producir una remisin prolongada
despus de retirar la terapia inmunosupresora en algunos animales con esta enfermedad. Se haban diagnosticado seis perros con PF, basado en sntomas clnicos indicativos y en la histopatologa. Estos pacientes fueron
tratados con dosis inmunosupresoras de glucocorticoides orales, o con una combinacin de glucocorticoides
orales y azatioprina. Despus de la completa remisin de los sntomas clnicos, lo que se produjo entre 1.5 y 5
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T Olivry et al.
meses despus de iniciarse la inmunosupresin, la medicacin fue reducida progresivamente y eventualmente retirada. La duracin total de la terapia inmunosupresora vari entre 3 y 22 meses. Las lesiones cutneas de PF
no recidivaron en 1.5 a 6 aos despus de finalizar el tratamiento. Estas observaciones sugieren que, en algunos
perros con PF, la inmunosupresin puede llevar a una remisin de las lesiones cutneas a largo plazo, y la retirada
del tratamiento no necesariamente es seguida por una recidiva de los signos clnicos.
Zusammenfassung ber die Langzeitergebnisse der Behandlung von Pemphigus foliaceus (PF) bei Hunden
sind nur begrenzt Informationen verfgbar. Zweck dieses Artikels ist es, darber zu berichten, dass bei einigen
Tieren mit dieser Erkrankung eine anhaltende Remission nach Beendigung von immunsuppressiven Behandlungen auftreten kann. Bei sechs Hunden wurde PF aufgrund von entsprechenden klinischen Anzeichen und
Histopathologie diagnostiziert. Diese Patienten wurden entweder mit immunsuppressiven Dosen oraler Glukokortikoide oder mit einer Kombination von oralen Glukokorticoiden und Azathioprine behandelt. Nachdem
die klinischen Anzeichen in vollstndige Remission gegangen waren, was zwischen 1,5 und 5 Monaten nach Einleitung der Immunsuppression eintrat, wurden die Medikamente nach und nach reduziert und schlielich abgesetzt. Die Gesamtdauer immunsuppressiver Therapie variierte zwischen 3 und 22 Monaten. Hautlsionen durch
PF kehrten fr 1,5 bis 6 Jahre nach Absetzen der Therapie nicht wieder. Diese Beobachtungen lassen vermuten,
da bei einigen Hunden mit PF die Immunsuppression zu einer Langzeitremission der Hautlsionen fhren kann
und da eine Beendigung der Behandlung nicht notwendigerweise ein Wiederauftreten der klinischen Anzeichen
nach sich zieht.

2004 European Society of Veterinary Dermatology, Veterinary Dermatology, 15, 245 252