Veterinary Dermatology 2003, 14, 313321

Feline pemphigus foliaceus: a retrospective analysis of 57 cases

Blackwell Publishing Ltd.

DIANE E. PREZIOSI*, MICHAEL H. GOLDSCHMIDT, JEAN S. GREEK,

JIM G. JEFFERS, KEVIN S. SHANLEY, KENNETH DROBATZ* and
ELIZABETH A. MAULDIN
Departments of *Clinical Studies and Pathobiology, University of Pennsylvania, School of
Veterinary Medicine, Philadelphia, PA, USA
Veterinary Specialists of Kansas City, Overland Park, Kansas, USA Animal Dermatology Clinic,
Rockville, MD, USA
Dermatology Clinic for Animals, Valley Forge, Pennsylvania, USA
(Received 13 January 2003; accepted 30 May 2003)

Abstract Fifty-seven cases of feline pemphigus foliaceus were identified from biopsy specimens submitted to
University of Pennsylvania School of Veterinary Medicines Laboratory of Pathology and Toxicology by veterinary dermatologists from 1991 to 2002. Age at onset ranged from less than 1 year to 17 years; median 5 years.
Eighty per cent of cats were reported to have been pruritic. At the time of biopsy, the distribution of lesions varied,
but included some combination of face / head, paws, dorsum or ventrum and consisted of crusts, erosions, scale
and alopecia. The histological features of 208 biopsy specimens were reviewed and included the following. Acantholytic cells were found in large numbers in both intact and degenerating pustules in most cases. Mast cells were
found in the dermal infiltrate more often than reported previously. Seventeen cases were receiving corticosteroids
at the time of biopsy; reducing the percentage of diagnostic biopsies per case. Forty-four cases were followed for
154 months (median 9 months). Triamcinolone was more successful at inducing remission without significant
adverse effects than prednisone or prednisone in combination with chlorambucil. Only 4/44 cats died from their
disease or therapy during the study period.
Keywords: acantholysis, feline, keratinocytes, pemphigus foliaceus, pustules, triamcinolone.

INTRODUCTION
Pemphigus foliaceus (PF) is the most common form
of pemphigus seen in domestic dogs and cats, as well
as the most common autoimmune dermatosis.1 The
pathogenesis involves targeting of a component of the
adhesion molecules on keratinocytes by autoantibodies. In humans and dogs this adhesion molecule has
been identified as a 150 KDa glycoprotein known as
desmoglein I.2,3 To the authors knowledge, the adhesion molecule has not been characterized in cats. Information about the pathogenesis of PF in cats is scant,
although drug eruptions resembling feline PF have
been reported.4,5 The clinical appearance of PF in cats
is most commonly described as a pustular eruption or
pustular dermatosis. Pustules are transient and crust,
scale, alopecia and erosions are commonly seen. The
distribution in cats includes a pattern involving the
dorsal nasal planum, periocular areas, pinnae, footpads
and claw folds; a more generalized form is not reported.1,6
Paronychia has been reported as a more common
finding in cats in one study.6 This study also noted
involvement of the trunk and legs in two cats and tail

Correspondence: Dr Diane E. Preziosi, Veterinary Specialists of

Alaska, 3330 Fairbanks St., Anchorage, AK 99503, USA. E-mail:
dermsurgAK@aol.com
2003 European Society of Veterinary Dermatology

involvement in a third cat. In addition, the periareolar

skin was reported as a common location in review on
PF in cats.7 A retrospective study presented at the
1993 American Academy of Veterinary Dermatology/
American College of Veterinary Dermatology (AAVD/
ACVD) meeting reported involvement of the trunk
(neck, dorsum and ventrum) as well as the head, ears
and feet. This study also noted that lesions were usually bilateral and cats were often pruritic.8 However,
information on the typical distribution pattern is
based on a total of 11 published cases of PF in cats
even though this is considered the most common
autoimmune skin disease of cats. The diagnosis of PF
in cats is based on clinical signs, ruling out other diseases
and supporting histological findings.
The purpose of this retrospective study was to
describe the history, clinical presentation and histopathological findings of 57 cases of feline PF. The
therapeutic protocols employed and their outcomes
are also characterized.

METHODS
A computer search for feline skin biopsies diagnosed
as PF from the University of Pennsylvania School of
Veterinary Medicines Laboratory of Pathology and
Toxicology between 1991 and 2002 was performed. From
313

314

D. E. Preziosi et al.

this search, 262 cases with the diagnosis of PF were

identified. To be included in the study, cases had to
have been submitted by clinicians at the Veterinary
Hospital of the University of Pennsylvania (VHUP) or
one of three board-certified veterinary dermatologists
(JSG, KSS, JGJ) in private referral practices. Each case
had to have complete information with regard to signalment and clinical presentation; 57 cases met these
criteria.
Medical records from all cases were reviewed for the
following information: signalment, history of skin disease, clinical signs when the disease was first noted and
at presentation, medication used at the time of biopsy,
laboratory tests analysed prior to treatment, initial
treatment, remission, complications and maintenance
treatment. Four treatment groups were formed based
on initial therapy to aid in assessing effectiveness and
side effects of these treatments: those treated with triamcinolone, prednisone, prednisone and chlorambucil
and those treated with other protocols.
Two of the authors, DEP and EAM, evaluated a
total of 208 skin biopsy specimens that had been submitted from the 57 selected cases. The authors were
blinded to prior pathology findings and case information. On average, three to four, 46-mm skin biopsy
specimens were evaluated per case. All samples were
routinely fixed and stained with haematoxylin and eosin
(H&E) at the time of submission. The original samples
were reviewed for the presence and location of pustules, external root sheath involvement, number of hair
follicles spanned in haired samples, cellular infiltrate of
the dermis, intraepidermal pustules and the presence
or absence of bacteria. Numbers of acantholytic cells
in the pustules were estimated per high-power field and
the presence of waves of pustules (re-cornification
with new pustule formation underneath older pustules), rafts of acantholytic cells (four or more acantholytic cells adhered together), and acantholytic cells
adhered to the overlying stratum corneum of a pustule
(cling-ons) were recorded for each case. To compare
numbers of acantholytic cells statistically, acantholytic
cells were counted in three nonrandomly selected 400
fields (hpf); the first field being selected on the basis of
the presence of acantholytic cells and the next two
being randomly selected. A range was determined for
each biopsy sample to account for samples with multiple pustules with variable numbers of acantholytic
cells present per hpf, as well as pustules with differing
counts depending on location within the pustule.
Biopsies were considered diagnostic for PF based
on the criteria established for dogs.9 Criteria included
pustules (newly formed or older degenerative pustules)
pustules spanning several hair follicles in haired samples,
evidence of acantholytic cells within a pustule or
degenerating pustule along with granulocytic cells. The
presence of rafts or acantholytic cells clinging to the
overlying stratum corneum was considered helpful but
not required for diagnosis. Biopsies were considered
suggestive of PF if there were pustules with a cornified
base that spanned more than two hair follicles and had

five or fewer acantholytic cells with no active acantholysis. All 57 cases had a least one biopsy sample that
was clearly diagnostic of PF.
Records were reviewed in conjunction with histopathological findings to determine the effect of corticosteroids on biopsy findings, such as the number of
diagnostic samples per case, the frequency of rafts
and the number of acantholytic cells per biopsy sample.
In addition, the biopsies from cats with a diagnosis
of allergy either on previous biopsy or clinically, were
compared with the rest of the biopsies for differences in
inflammatory infiltrate.
Statistical analysis
Data distribution for continuous variables was determined using the ShapiroWilks test. Median and range
or mean SD were used to describe continuous
variables that were nonparametric or parametric,
respectively. Proportions for categorical variables
were described using percentage. One-way or
KruskalWallis test was used to initially compare multiple groups of continuous variables depending upon
data distribution. If significant (P < 0.05), these tests
were then followed by pairwise comparisons between
groups using the Wilcoxon rank sum test or unpaired
t-test where appropriate. Categorical variables were
compared using the 2 test or Fishers exact test where
appropriate. A P-value of < 0.05 was considered significant. All statistical evaluations were performed using
a statistical software program ( 7.0
for Windows 98/85/NT, Stata Corporation, College
Station, TX).

RESULTS
History and signalment
The duration of clinical signs prior to diagnosis ranged
from 0.25 to 36 months with a median of 4 months.
Eleven cats had a history of previous dermatological
problems separate from their presenting complaint,
including presumed allergic dermatitis (5), indolent
ulcer (2), otitis (1), feline acne (1), pyoderma (1) and an
unspecified pruritic skin infection (1). The two cats
with a history of indolent ulcer were from the same
litter. Ten other cats had skin biopsies performed 1
10 months prior to a diagnosis of PF. The histological
diagnosis six of these cats was consistent with allergic
dermatitis, biopsies from two cats had an acute erosive
dermatitis, one cat was diagnosed with a pyoderma
and one biopsy taken by the referring veterinarian was
reported as nondiagnostic by the dermatologist in the
record. In three cases the onset of PF was thought to be
related to the administration of one of the following:
on-going administration of itraconazole and/or lime
sulfur dip, methimazole or ipodate.
Domestic Short Hair cats were the most commonly
affected breed (34/57 or 59.6%). The other cats were of
various breeds including Domestic Long Hair (4),
Siamese (4), Himalayan (4), Persian (3), Maine Coon

2003 European Society of Veterinary Dermatology, Veterinary Dermatology, 14, 313321

Feline pemphigus foliaceus

(3), and 1 each of PersianHimalayan cross, American
Blue, Somali, Scottish Fold and Ragamuffin. Thirty
cats (52.6%) were female (4 intact) and 27 cats (47.4%)
were male (1 intact). The median age of onset was
5 years, range < 117 years.

315

in five cases. Intact pustules were rarely observed; predominant lesions were serous or haemorrhagic crusts
with associated scale and alopecia. In the cats that had
claw fold involvement, paronychia with purulent exudate was observed.
Other clinical signs were reported in a variable
number of cats. Pruritus was noted as mild to severe in
42 (80%) of the 52 cats for which this finding was
recorded. Lethargy was reported in 20 (47.6%) of
42 cats. An elevated rectal temperature was noted in 13
(35%) of 37 cats. Anorexia occurred in 14 (32.5%) of

Clinical signs
The initial distribution of lesions was known for 51
cats. The most common initially affected area was the
head. In 17 cats (33%) this was specified as the pinnae,
as the face/head in 13 cats (25%) and the nose, chin or
periocular area in 4 cats (8%). Seven cats (14%) had
lesions on their feet (5) or claw folds (2). Other areas
reported for initial involvement included the dorsum in
five cats (10%), ventrum in four cats (8%) and legs or
tail in one cat each (2%). Eleven cats (21%) had multiple
sites affected initially. Of these 51 cats, only 5 (10%)
had lesions that remained localized to the initial distribution sites compared with the distribution at referral.
The distribution of lesions upon presentation to the
veterinary dermatologist was known for all 57 cases
and involved multiple sites in 51 (89.5%) cats. The most
common site affected was the head or face, noted in
45 cats (78.9%) (Figs 1, 2), and included cases designated as head/face (28 cats, 49%), nose (11 cats, 19%)
and periocular region (6 cats, 10%). The pinnae were
involved in 39 cases (68.4%). Paws were involved in 31
(54.4%) cases with claw folds being specified in 18 cases
(31.6%) (Figs 3, 4). The dorsum and ventrum were
commonly affected, being reported in 26 (45.6%) and
22 (38.6%) of the cases, respectively. Periareolar
involvement was noted in one case. Other areas less
commonly involved included the legs in six cats
(10.5%), chin in five cats (8.7%) and tail in four cats
(7%). Ten cats (17.5%) had a distribution involving the
face, ears and feet. Three cats had lesions confined to
the paws, two cats had lesions involving the face and
ears or face and paws only, and one cat had lesions limited to the face. Lesions were bilaterally symmetrical in
distribution in 49 of 52 cases (94%) and asymmetrical
in 3 cases (6%). The symmetry of lesions was not noted

Figure 2. Pinna; close up of cat in Figure 1. Crusted lesions with

associated alopecia.

Figure 1. Face; cat with pemphigus foliaceus. Crusts and erosions

can be seen on the face, margins of the pinnae, dorsal nose and
periocular area.

Figure 3. Paw; same cat as Figure 1. Alopecia, erythema and

erosions on the dorsum of the paw along with paronychia and
crusting at the claw folds.

2003 European Society of Veterinary Dermatology, Veterinary Dermatology, 14, 313321

316

D. E. Preziosi et al.

Figure 4. Paw; palmer surface of the paw in Figure 3. Thick crusts

are seen at the margins of the pads as well as in the interdigital spaces
along with scaling of the surface of the pads.

43 cats and was usually described as mild to moderate.

Other systemic signs infrequently reported included
weight loss (8 cats), lymphadenopathy (5), otitis
externa (2), cystitis (1) and seborrhea sicca (1).
Complete blood count (CBC), biochemical profile,
feline leukaemia virus (FeLV) or feline leukaemia
virus/feline immunodeficiency virus (FeLV/FIV) testing were performed on a variable number of cats.
Twenty-seven cats had a CBC performed prior to
beginning treatment. Sixteen cats had values within
reference parameters. Eleven cats had the following
abnormalities: leukocytosis (11), neutrophilia (7),
lymphopenia (3), monocytosis (7), eosinophilia (8),
basophilia (3) and mild normocytic, normochromic
anaemia (3). Serum biochemical profiles were performed
on 25 cats. The profiles of four cats were within reference
parameters. The abnormalities noted in the remaining cats were mild and nonspecific. Twenty-one cats
had viral testing performed. Eighteen cats were
negative for both FeLV and FIV. Three cats were tested
for FeLV only and were also negative. Fungal cultures
were performed on 18/57 cats by either the referring
veterinarian or the veterinary dermatologist and were
negative in all cases.
Histopathology
A total of 208 biopsy specimens were reviewed by
two of the authors, DEP and EAM. Between 1 and
8 samples were submitted per case with an average of
3.6 biopsy specimens per case. Of the 208 samples
reviewed, 11 (5.3%) were considered suggestive of PF
and 175 (84.1%) were considered diagnostic of PF as
determined by DEP and EAM. Results for the previously mentioned criteria were tabulated for those
samples deemed diagnostic or suggestive. A Periodic
acid-Schiff stain was applied to the biopsy samples of
two cats with a history of possible fungal infections
and to the samples of the cats from the same litter; all
were negative for arthrospores or fungal hyphae.
The epidermis in most samples was mildly to
severely hyperplastic, due primarily to acanthosis (166/

Figure 5. Feline dermis. A diffuse dermal infiltrate consisting

predominately of mast cells and neutrophils are seen in the
superficial dermis (H&E, 20, bar = 42.7 m).

186 samples, 89%) with 16/186 (8%) samples also

demonstrating hypergranulosis. In general, the stratum
corneum exhibited orthokeratotic hyperkeratosis
(143/186 samples, 76%) and was seen admixed with focal
parakeratosis in seven samples. Coccoid bacteria were
found in the crust of 29/186 (15%) samples from 15/57
cases. Malassezia spp. was found in the stratum corneum of one biopsy sample. The dermal infiltrate was
perivascular to interstitial in most cases and varied
from mild to severe. Neutrophils were the most prevalent cell type but mast cells were found in almost all
samples diagnostic for PF. Only 12/186 (6%) samples
had rare or no mast cells present in the dermis. Mast
cells were a prominent cell type in the dermis of 38/186
(20%) samples and mild to moderate in number in the
130/186 (70%) biopsies (Fig. 5). Six samples (3%) had
mast cells present in the epidermis. Eosinophils were
noted either marginating in dermal blood vessels or
within the dermis in 119/186 (64%) samples and were
generally mild to moderate in number. In no samples
were eosinophils the predominant cell type. There was
no difference in the type or intensity of dermal infiltrate in the biopsies of cats that had a prior diagnosis
of allergic dermatitis or acute inflammatory dermatitis.
Pustules, either newly formed or degenerative (i.e.
crusts), were found in all cases that were considered
diagnostic. In 79 (45.1%) samples the location was
within the stratum corneum, i.e. the pustule had
acquired a cornified base. In 32 (18.3%) samples, pustules were subcorneal, acantholysis occurring at the
level of the stratum spinosum or granulosum. In 64
(36.6%) samples both subcorneal and intracorneal
pustules were seen. Some of these represented waves of
pustules (Figs 6, 7), and some represented partial recornification of the base of at least 5075% the length
of the pustule. Intact pustules (Fig. 8) with no overlying degenerating pustule were found in 28/186 (16%)
samples. Rafts of acantholytic cells (Fig. 9) were
present in 103/186 (58.8%) biopsy samples. Acantholytic cells adhered to the overlying stratum corneum
were found in 37/186 (21%) biopsy samples.
Pustules were composed primarily of neutrophils
and acantholytic cells but eosinophils were noted in 53

2003 European Society of Veterinary Dermatology, Veterinary Dermatology, 14, 313321

Feline pemphigus foliaceus

Figure 6. Feline epidermis. An active area of acantholysis located

within the stratum spinosum is forming beneath an older recornified
pustule (H&E, 10, bar = 86.2 m).

Figure 7. Feline epidermis, same slide as Figure 6. At higher

magnification, acantholytic cells can be seen springing up from the
stratum spinosum (H&E, 20, bar = 43.3 m).

samples from 26 cases, although in no case were

they the predominant granulocytic cell. External root
sheath involvement was present in 20 samples from
15 cases. Pustules spanned 215 follicular units (mean
3.91) depending on the density of hair in the region
biopsied and the size of the pustule. The number of
acantholytic cells ranged from < 5 in an entire pustule
to > 50 per hpf. Thirty-two samples had pustules or
degenerating pustules containing fewer than 5 acantholytic cells per hpf, 70 samples had 515 acantholytic
cells per hpf, 34 had 1020+ acantholytic cells per hpf
and 39 samples had > 20 acantholytic cells per hpf.
Seventeen cats were on some form of corticosteroid at the time of biopsy that ranged from topical
thiabendazoledexamethasoneneomycin sulfate or
nystatinneomycin sulfatethiostreptontraimcinaolone
acetonide to oral prednisone or triamcinolone to a
repository steroid, Methylprednisolone acetate that was
given within days to 1 month prior to biopsy. The absolute number of biopsy samples in cats that were
receiving corticosteroids and cats that were not, was
not significantly different but the proportion of diagnostic samples was significantly higher (P = 0.0027) in
the animals that were not receiving corticosteroids
(median 100%, range 40100%) compared with the

317

Figure 8. Feline epidermis. An intact pustule from the footpad

containing granulocytes and acantholytic cells (H&E, 10,
bar = 76.3 m).

Figure 9. Feline epidermis. Rafts of acantholytic cells within a

pustule (H&E, 20, bar = 36.7 m).

ones that were (median 62.5%, range 20100%). There

was no significant difference between the groups
regarding the absolute number of acantholytic cells or
number of rafts of acantholytic cells seen in the biopsies. Subjectively, there was no difference in the type or
intensity of the dermal infiltrate.
Treatment
Information regarding treatment for at least 1 month
following biopsy was available for 46/57 cases. Eleven
cases had either no follow up or no record available.
One cat was not treated and was euthanized due to the
disease 1 month after diagnosis. One cat was not
treated due to the high degree of suspicion of a druginduced PF caused by itraconazole and/or lime sulfur
dip. Lesions resolved within a few weeks of discontinuing the drugs and have remained resolved for 4 years.
One of the other suspected drug-induced PF (ipodate)
required treatment to induce remission and remained
on therapy. No follow-up was available for the third
case of suspected methimazole-induced PF.
For the 44 cases that were treated, the median length
of follow up was 9 months (range 154 months). Initial
therapy consisted of triamcinolone, oral suspension

2003 European Society of Veterinary Dermatology, Veterinary Dermatology, 14, 313321

318

D. E. Preziosi et al.

(Aristocort Fujisawa Healthcare, Deerfield, IL,

USA) in 14 cats and the tablet form in 1 cat (n = 15),
prednisone (n = 13), prednisone and chlorambucil
(n = 11), triamcinolone and chlorambucil (n = 2), dexamethasone (n = 2) and prednisone and injectable gold
salts (n = 1). Dosages for triamcinolone ranged from
0.6 to 2 mg kg1 daily. Prednisone dosages were generally 45 mg kg1 daily.
Remission occurred in 15/15 (100%) in the triamcinolone group, 8/13 (61.5%) of the prednisone group,
9/11 (81.8%) in the prednisone/chlorambucil group
and 5/5 (100%) cats in the other therapies combined.
Cats receiving triamcinolone had a significantly higher
remission rate (P = 0.023) than those receiving prednisone. Cats that responded to prednisone were not on
a significantly higher dose than the cats that did not
respond. Adverse effects from the initial treatment
occurred in 22.7% of all cases and prompted a change
in therapy in 9%. The triamcinolone group had significantly (P = 0.044) fewer adverse effects (2/15, 13%)
than the prednisone/chlorambucil group (6/12 and
50%). Adverse effects reported in cats receiving triamcinolone included diarrhoea in one cat and lethargy
and partial anorexia in a second cat. For the cats
receiving prednisone, adverse effects reported include
polydypsia and polyuria (PU/PD) in two cats, decreased
appetite in one and lethargy in another. Adverse effects
reported for the prednisone/chlorambucil group included
PU/PD in three cats, and otitis externa, decreased platelets, localized deep pyoderma of the foot and weight
gain in one cat each. Lethargy and an increase in liver
enzymes were reported in the cat receiving triamcinolone and chlorambucil.
In addition, six cats whose therapies were altered
had adverse effects with their second therapeutic protocol. Therapy in two cats was changed to triamcinolone/chlorambucil, one became anaemic, the other
leukopenic. Chlorambucil was added to the initial
therapy of prednisone in one cat that also experienced
leukopenia. Chlorambucil was also added to the initial
therapy with dexamethasone of another cat that
became mildly thrombocytopenic. Following a therapy
change from prednisone/chlorambucil to methylprednisolone/chlorambucil, one cat experienced diarrhoea,
lethargy and anorexia. The sixth cat had PU/PD and
soft stools when receiving methylprednisolone and
gold salts. All six cats had a change in therapy due to
these adverse effects and a third protocol was chosen.
One additional cat that had been receiving prednisone/
chlorambucil and was changed to dexamethasone/
chlorambucil in an effort to induce remission was
euthanized 4 months later with severe gastrointestinal
problems.
Twelve cats (27%) relapsed at some point but only
eight were changed to a new therapy. Therapy was
changed in 20 cats either due to lack of remission,
undesirable adverse effects, both or because a decrease
in therapy frequency or dose caused a relapse. Therapeutic changes were made more frequently in the prednisone group (10/12, 83%) than the triamcinolone

group (2/16, 12.5%). This was statistically significant

(P < 0.001)
Maintenance therapy was known for 30 of 44 cases.
Four cases were lost to follow-up before a maintenance
therapy was known, three died due to their disease or
from complications of therapy and three were treated
and did not have a recurrence of their disease when
treatment was discontinued (one treated with prednisone, two treated with triamcinolone). Four cases
were still having the dosage of their drugs decreased
when last seen (two on triamcinolone, one on prednisone and one on triamcinolone and gold salts).
Thirteen cats were being maintained on triamcinolone,
dosage ranging from 0.6 to 1 mg kg1, every 27 days.
Four cats were taking prednisone, 2.55 mg kg1, every
23 days. Three cats received chlorambucil alone at
0.5 mg cat1, every 23 days, and one cat received
chlorambucil at a similar dose but was also managed
with topical betamethasone as needed. Three cats were
managed with dexamethasone, 1.5 mg cat1, every 2
7 days. Two cats each were managed on chlorambucil
combined with prednisone or dexamethasone and two
with methylprednisolone. More cats were managed on
triamcinolone than any other therapy. Only four cats
were euthanized due to their disease or due to treatment complications. Three cats died within 1 month of
diagnosis and one cat died 5 months after diagnosis.
One died due to cardiac arrest, one was euthanized
without treatment, another never went into remission
and the last cat was euthanized due to severe gastrointestinal problems 5 months into treatment. No necropsies were performed.

DISCUSSION
This study represents the largest reported collection
of feline PF cases to date. In reviewing the pertinent
aspects of this disease such as history and clinical signs,
it is clear that this disease can be more variable in presentation and progression than previously reported. In
dogs it has been theorized that autoantibody formation in PF can occur as a result of a drug reaction,
chronic skin disease or it can be idiopathic.1,10 The role
of genetics has not been definitively proven in dogs but
is thought to play a role due to breed predilection. It is
not clear historically, what role, if any, previous skin
disease plays in the development of PF in cats. However, it is noteworthy that two cases had a history of
chronic allergic skin disease for several years prior to
developing PF. This may suggest a causative role for
chronic inflammatory skin disease inducing PF in cats,
although this cannot be proven from these cases. As
reported previously, drug-induced PF can occur in
cats.4,5 Only one case in this study could be considered
highly suggestive of drug-induced PF, because the clinical signs resolved upon discontinuation of the itraconazole and lime sulfur. The case believed to be induced
by ipodate resolved with therapy although therapy
could not be discontinued without a relapse. If this case

2003 European Society of Veterinary Dermatology, Veterinary Dermatology, 14, 313321

Feline pemphigus foliaceus

of PF was indeed due to the ipodate, it may represent
a drug-triggered PF as reported in people and recently
in dogs.10,11 It is also interesting to speculate about the
possible role of genetics in cats. Two cases were from
the same litter, had previous histories of indolent
ulcers, had identical distribution, lesions and large,
acantholytic cell-filled pustules on histopathology. The
lesions in both cats resolved with therapy and have not
recurred.
The classic clinical distribution of feline PF has
been reported as involving the head (periocular, auricular and planum nasale) paws, claw folds and periareolar area.7,12 This study found involvement of other
areas of the body trunk, tail, legs and chin. This most
closely matches the distribution reported by Caciolo
et al.6 as well as Greek.8 The periareolar area was not
commonly affected but may be underrepresented due
to the retrospective nature of the study. Three cats
had lesions confined to the feet, which has not been
reported previously. In this study cats were often noted
to be pruritic and have bilaterally symmetrical lesions,
a finding also reported by Greek. Cats can also be
adversely affected with systemic signs such as lethargy,
anorexia and fever. Blood work abnormalities are
nonspecific, although mild neutrophilia was found in
all cases that had abnormal CBCs and eosinophilia was
common.
Histopatholgical findings were similar to those
reported in dogs.9,12,13 A previous report specified
similar pathological changes with regard to epidermal
hyperplasia due to acanthosis, follicular infundibulum
involvement and a perivascular infiltrate of a mixed
population of cells.6 Although neutrophils were the
most common cell type in this study as in others, the
dermal infiltrate often contained a large proportion of
mast cells. This finding represents a marked difference
in the dermal infiltrate found in cats as compared to
dogs with PF, but is most likely due to the cats propensity to have mast cells within the dermis in any
inflammatory dermatoses.1,12,13 This finding is also in
agreement with a previous abstract.8 The presence of
mast cells in the dermal infiltrate of cats with PF might
account for the allergic biopsy diagnosis in six cats of
this study. If no intact pustule or degenerating pustule
is sampled or the degenerating pustule is removed and
lost in the process of procuring, transporting or processing the skin sample, the resulting specimen may
only show an inflammatory dermal infiltrate leading to
an incorrect diagnosis.
Even though subcorneal pustules were a relatively
rare finding in this study, diagnosis could be made
based on examination of degenerating pustules (i.e.
crust). This indicates that waiting for pustules to arise
in order to secure a diagnosis is not necessary. However, if pustules are present they should be considered
the most diagnostic lesion to biopsy. Crusted lesions, if
obtained, should be as fresh as possible and care must
be taken in the processing of the sample to preserve any
degenerating pustule present, even if it separates from
the underlying tissue.

319

In this study the use of corticosteroids prior to or at

the time of biopsy affected the percentage of diagnostic
samples. However, with appropriate lesion selection
and the submission of multiple sites, a diagnosis was
still possible. Although corticosteroid use at the time of
biopsy did not statistically change the number of acantholytic cells seen in samples that had them, it still produced more nondiagnostic samples that did not exhibit
active acantholysis under crusts or have recognizable
acantholytic cells in the degenerating pustule. Therefore, it seems prudent to avoid corticosteroid use, if
possible, at the time of biopsy to increase diagnostic
yield. Because only cases that received a diagnosis of
PF were selected, it is not known how many samples
were submitted to the biopsy service that were actually
PF but did not receive that diagnosis due to corticosteroid use. It also probable that the overall diagnostic
percentage was higher due to the selection bias created
by only using cases seen by veterinary dermatologists.
Various treatments have been recommended for
feline PF. Treatment must not only induce remission,
but must do so without significant side effects. The
dose and frequency of administration needs to be
reduced from initial levels to avoid undesirable side
effects associated with long-term treatment while still
controlling the disease. In this study, treatment protocols were altered frequently due to lack of remission,
side effects of treatment, or because the dosage of the
drugs used could not be decreased without causing a
relapse.
Monotherapy with prednisone is often advocated as
an effective treatment for PF in cats.1,14,15 In this study,
the use of a triamcinolone suspension was found to be
more likely to induce remission than prednisone alone.
Treatment with prednisone combined with chlorambucil was effective as reported previously.16 However,
the cats treated with triamcinolone had a decreased
number of adverse effects when compared with the
prednisone/chlorambucil group. Although the combination of prednisone with an induction dose of
azathioprine was reported to be effective in eight cats,
a later study demonstrated frequent leukopenia and
thrombocytopenia secondary to azathioprine administration, thus this protocol can no longer be recommended.6,17 Prednisone in combination with gold
salts is an alternative to monotherapy with a corticosteroid or a steroid in combination with chlorambucil, but the discomfort inherent in the intramuscular
administration of gold salts and the risk of serious side
effects make this a secondary choice for therapy.1,7,14
When maintenance therapy was reviewed, it was
evident that more cats were controlled long-term on
triamcinolone alone than other therapies. Based on
this study, the use of an oral triamcinolone suspension
can be advocated as a safe and effective therapy for
feline PF.
Overall, cats with PF seem to have fewer problems
with therapy than do dogs. As reported in a retrospective
study presented at the 2001 AAVD/ACVD meeting, a
significant number of dogs die or are euthanized within

2003 European Society of Veterinary Dermatology, Veterinary Dermatology, 14, 313321

320

D. E. Preziosi et al.

10 months of being diagnosed with PF. In this study,

only four cats died or were euthanized due to an inability
to control the disease or from side effects of treatment
in this study. However, follow-up information was not
available on all cases. Despite this, the majority of cats
were alive and their disease controlled at their last
recorded visit or phone contact. This may reflect a
better tolerance to side effects of the medication or an
inherent difference in this disease in felines that makes
it easier to treat or perhaps both factors.
REFERENCES
1. Scott, D.W., Miller, W.H., Griffin, C.E. Small Animal
Dermatology, 6th edn. Philadelphia: W.B. Saunders,
2001: 686 90.
2. Suter, M.M., Ziegra, C.J., Cayatte, S.M. et al. Identification of canine pemphigus antigens. In: Ihrke, P.J.,
Mason, I.S., White, S.D., eds. Advances in Veterinary
Dermatology II. New York: Pergamon Press, 1993: 367
80.
3. Rubenstein, N., Stanley, J.R. Pemphigus foliaceus antibodies to desmogein I demonstrate stratified squamous
epithelia-specific epitopes of desmosomes. American
Journal of Dermatopathology 1987; 9: 510 14.
4. McEwan, N.A., McNeil, P.E., Kirkham, D. et al. Drugeruption in a cat resembling pemphigus foliaceus. Journal of Small Animal Practice 1987; 28: 713 20.
5. Mason, K.V., Day, M.J. A pemphigus foliaceous-like
eruption associated with the use of ampicillin in a cat.
Australian Veterinary Journal 1987; 64: 223 4.
6. Caciolo, P.L., Nesbitt, G.H., Hurvitz, A.I. Pemphigus
foliaceus in eight cats and results of induction therapy
using azathioprine. Journal of the American Animal Hospital Association 1984; 20: 5717.

7. Griffin, C.E. Recognizing and treating pemphigus

foliaceus in cats. Veterinary Medicine 1991; 86: 51316.
8. Greek, J.S. Feline pemphigus foliaceus: a retrospective
of 23 cases. Proceedings of the 8th Annual AAVD/ACVD
Meeting, San Diego, California, 1993: 27.
9. Kuhl, K.A., Shofer, F.S., Goldschmidt, M.H. Comparative histopathology of pemphigus foliaceus and superficial folliculitis in the dog. Veterinary Pathology 1994; 31
(1): 1927.
10. White, S.D., Carlotti, D.N., Pin, D. et al. Putative drugrelated pemphigus foliaceus in four dogs. Veterinary
Dermatology 2002; 13 (4): 195202.
11. Wolfe, R., Tamir, A., Brenner, S. Drug-induced versus
drug-triggered pemphigus. Dermatologica 1991; 182:
20710.
12. Gross, T.L., Irhke, P.J., Walder, E.J. Veterinary Dermatopathology: A Macroscopic and Microscopic Evaluation
of Canine and Feline Skin Disease. St. Louis, MO:
Mosby, 1992: 1618.
13. Ihrke, P.J., Stannard, A.A., Ardens, A.A. et al. Pemphigus foliaceus in dogs. A review of 37 cases. Journal of the
American Veterinary Medical Association 1985; 186 (1):
5966.
14. Manning, T.O., Scott, D.W., Smith, C.A. et al. Pemphigus diseases in the feline: seven case reports and discussion. Journal of the American Animal Hospital
Association 1982; 18: 43343.
15. Olivry, T., Chan, L.S. Autoimmune blistering dermatoses in domestic animals. Clinics in Dermatology 2001;
19: 75060.
16. Rhodes, K.H., Shoulberg, N. Chlorambucil. Effective
therapeutic options for the treatment of feline immunemediated dermatoses. Feline Practice 1992; 20 (3): 58.
17. Beale, K.M., Altman, D., Clemmons, R.R. et al. Systemic toxicosis associated with azathioprine administration in domestic cats. American Journal of Veterinary
Research 1992; 53 (7): 123640.

Rsum Cinquante sept cas de pemphigus foliac flin ont t diagnostiqus par examen histopathologique au
laboratoire de pathologie et de toxicologie de l'Ecole de Mdecine Vtrinaire de l'Universit de Pennsylvanie
entre 1991 et 2002. L'ge l'apparition des lsions variait de moins d'un an 17 ans, avec une moyenne de 5 ans.
Quatre-vingt pour cent des chats prsentaient un prurit. Au moment de la biopsie, la distribution des lsions tait
varie, mais la face, les coussinets, le dos ou le ventre taient majoritairement atteints. Les lsions regroupaient
des crotes, des rosions, des squames et de l'alopcie. Les signes histopathologiques de 208 biopsies ont t
tudis. Des cellules acantholytiques ont t retrouves en grand nombre dans des pustules intactes ou dgnres
sur la plupart des prlvements. Des mastocytes ont t retrouvs plus frquemment dans l'infiltrat dermique que
prcdemment rapport. Dix-sept chats recevaient des corticodes au moment des biopsies, ce qui a diminu le
pourcentage de biopsies permettant le diagnostic par cas. Quarante quatre chats ont t suivis pendant 154 mois
(moyenne de 9 mois). La triamcinolone tait plus efficace pour induire une rmission sans effet secondaire que
la prednisolone ou la prednisone en association avec le chlorambucil. Seulement 4/44 chats sont morts de leur
maladie ou du traitement pendant la priode de suivi.
Resumen Se identificaron cincuenta y siete casos de pnfigo foliceo felino en muestras de biopsias remitidas
por dermatlogos al Laboratorio de Patologa y toxicologa de la Facultad de Veterinaria de la Universidad de
Pennsylvania entre 1991 y 2002. La edad de presentacin se encontraba entre el ao y los 17 aos, media = 5
aos. El ochenta por ciento de los gatos figuraban como prurticos. En el momento de la biopsia, la distribucin
de las lesiones variaba, pero inclua alguna combinacin de cara/cabeza, garras, reas dorsales o ventrales y consistan en costras, erosiones, escamas y alopecia. Se revisaron las caractersticas histolgicas de 208 muestras de
biopsia e incluan las siguientes. Se encontraron un nmero elevado de clulas acantolticas tanto en pstulas
degeneradas como intactas, en la mayora de casos. Se encontraron mastocitos con ms frecuencia de lo que
se haba descrito anteriormente. Diecisiete casos estaban recibiendo corticoterapia en el momento de la toma
de biopsia, reduciendo el nmero de biopsias diagnsticas por caso. Se realiz un seguimiento de cuarenta y
cuatro casos durante 1 54 meses (media=9 meses). La triamcinolona consigui una remisin ms efectiva que
2003 European Society of Veterinary Dermatology, Veterinary Dermatology, 14, 313321

Feline pemphigus foliaceus

321

la prednisona o la prednisona combinada con cloranbucil, sin los efectos negativos de estas ltimas. Slo 4/44
gatos murieron de la enfermedad o de la terapia durante el periodo de estudio.
Zusammenfassung Von den von Veterindermatologen an das Labor fuer Pathologie und Toxikologie der
Veterinrmedizinischen Hochschule an der Universitt von Pennsylvania im Zeitraum von 19992002 eingesandten Biopsien wurden 75 Flle als feliner Pemphigus foliaceus diagnostiziert. Das Alter zu Beginn der
Erkrankung rangierte von einem Jahr bis zu 17 Jahren und betrug durchschnittlich 5 Jahre. Entsprechend den
Berichten zeigten 80% der Katzen Juckreiz. Die Verteilung der Lsionen bei Biopsieentnahme variiert, umfasst
verschiedene Kombinationen von Regionen wie Gesicht/Kopf, Pfoten, Dorsum oder Ventrum, wobei Krusten,
Erosionen, Schuppen und Alopezie beschrieben werden. Die histologischen Vernderungen von 208 Biopsien
werden berprft und im Folgenden beschrieben. Sowohl in intakten als auch in degenerierenden Pusteln werden
in den meisten Fllen akantholytische Zellen in grosser Anzahl gefunden. Im dermalen Infiltrat werden hufiger
Mastzellen gefunden als bisher berichtet. Da 17 Flle zum Zeitpunkt der Biopsieentnahme Kortikosteroide
erhielten, reduziert sich die Anzahl der aussagefhigen Biopsien um diese Anzahl. 44 Flle wurden ber einen
Zeitraum von 1-54 Monaten (durchschnittlich 9 Monate) verfolgt. Triamcinolon wurde hufiger erfolgreich
ohne bedeutende Nebenwirkungen zur Erzielung einer Remission eingesetzt als Prednisolon allein oder in
Kombination mit Chlorambucil. Whrend des Zeitraumes der Studie starben nur 4 von 44 Katzen aufgrund ihrer
Erkrankung.

2003 European Society of Veterinary Dermatology, Veterinary Dermatology, 14, 313321