Vet Dermatol 2021 DOI: 10.1111/vde.

12996

Clinical presentation, treatment and outcome in dogs

with pemphigus foliaceus with and without
vasculopathic lesions: an evaluation of 41 cases
Zijin Zhou*,1 , Sarah Corner†, Annette Petersen*, Edmund Rosser* and Erica L Noland‡
*Small Animal Clinical Sciences, †Veterinary Diagnostic Laboratory, ‡Pathobiology & Diagnostic Investigation, Michigan State University College
of Veterinary Medicine, East Lansing, MI, USA
1
Present address: BluePearl Pet Hospital – Levittown, 301 Veteran Hwy, Levittown, PA 19056, USA
Correspondence: Zijin Zhou, BluePearl Pet Hospital – Levittown, 301 Veteran Hwy, Levittown, PA 19056, USA. E-mail: zxz130@gmail.com

Background – Concurrent vasculopathic lesions in dogs with pemphigus foliaceus (PF) have been observed ane-
cdotally yet not reported in the literature. Any association with prognosis is unclear.
Hypothesis/Objectives – To compare clinical features and outcome of PF in dogs with and without vasculopa-
thic lesions.
Animals – Archived, formalin-fixed, paraffin-embedded biopsy samples of 41 dogs with PF.
Methods and materials – Archived, formalin-fixed, paraffin-embedded biopsy samples with a histological diag-
nosis of PF were selected and re-evaluated independently. Dogs were assigned to groups following histological
evaluation: Group 1 (no vasculopathic lesions) and Group 2 (vasculopathic lesions present). Group 2 was subdivi-
ded into Group 2a (vasculopathic lesions without vasculitis – i.e. vasculopathy) and Group 2b (overt vasculitis).
Medical records from identified cases were reviewed retrospectively for data on clinical presentation, treatment
and outcome.
Results – Time to remission was longer in Group 2b (93.8 days) compared to Group 1 (41.8 days) (P = 0.047).
Dogs in groups 2a and 2b were more likely to have systemic signs of illness at presentation (P = 0.028 and
P = 0.032, respectively) compared to Group 1. Dogs in Group 2b were more likely to have adverse effects asso-
ciated with treatment than dogs in Group 1 (P = 0.004). There were no significant differences in lesion type, dis-
tribution, rates of remission, recurrence or corticosteroid dosage between groups.
Conclusions and clinical importance – Dogs with PF and concurrent vasculitis took longer to achieve remis-
sion and were more likely to have systemic signs of illness or adverse effects associated with treatment than
dogs with PF without concurrent vasculopathic lesions.

of skin disease, including adverse effects associated

Introduction
Pemphigus foliaceus (PF) is one of the most common
autoimmune skin diseases in dogs, characterised clini-
cally by large pustules and heavy crusting.1–3 Despite
being one of the more frequently encountered autoim-
mune diseases in dogs, there is limited information on
factors that predict or influence the outcome of individ-
ual cases. A proportion of dogs respond well to treat-
ment and can be maintained long-term with a good
quality of life.4–6 However, in one study including 43
dogs with PF, the case fatality rate was 60.5% (26 of
43).5 Patients that do survive face an array of adverse
effects resulting from treatment. In fact, in that same
study, among the dogs that died, 41.9% (18 of 43) were
euthanised as a consequence of the direct complications
Accepted 30 April 2021
Source of Funding: This study was funded in part by Paul Bloom
(Allergy, Skin and Ear Clinic for Pets, Bloom Animal Hospital,
Livonia, MI, USA).
Conflicts of Interest: No conflicts of interest have been
declared.
© 2021 the European Society of Veterinary Dermatology and the American College of Veterinary Dermatology.
with treatment.5 Based on the most recent report, 46%
(17 of 37) of dogs had some adverse effects associated
with treatment.7 Iatrogenic Cushing’s syndrome is espe-
cially common because glucocorticoids are a mainstay of
treatment. Identification of more prognostic indicators
may help to better predict which dogs with PF are likely
to respond favourably to treatment and to help guide
treatment.
There are rare reports on the variation in histopathologi-
cal findings in dogs with PF and association with out-
come. One study evaluated whether eosinophilic
infiltrates are associated with outcome, and there was no
difference in survival between those with an eosinophilic
infiltrate and those without.7 However, the study did indi-
cate that dogs with adverse effects associated with treat-
ment and those with concurrent diseases were more
likely to have an eosinophilic infiltrate.7
Based on the authors’ experience, there is a subset of
dogs with PF and histopathological evidence of vasculo-
pathic lesions. Concurrent vasculopathic lesions have
been reported in horses and cats, and not in dogs.1–3,8–10
Clinically, these dogs present with typical signs of PF, yet
anecdotally appear to be more refractory to treatment
1
Zhou et al.
and have poorer outcomes. However, to our knowledge,
this has not been reported previously, and therefore, the
primary aim of the study was to compare clinical presen-
tation, treatment and outcomes of canine PF cases with
and without vasculopathic lesions.
We hypothesised that dogs with PF and concurrent
vasculopathic lesions are more refractory to treatment
and have a poorer outcome.
Methods and materials
Case selection
Cases with a histopathological diagnosis of PF evaluated at a regional
veterinary diagnostic laboratory from 2014 to 2017 and submitted by
dermatology specialty practices were selected. Cases were included
if there was adequate tissue for examination, medical records were
available for analysis, and a diagnosis of PF could be confirmed on
histopathological evaluation.
Histopathological evaluation
Original paraffin-embedded blocks from identified cases were sec-
tioned at 5 lm and routinely stained with haematoxylin & eosin.
All cases underwent an independent re-evaluation by two diplo-
mates of the American College of Veterinary Pathologists (SC,EN).
At least two planes of section were evaluated from each case. All
cases were examined for the following histopathological features:
changes typical of PF, vasculopathic lesions, degree of inflamma-
tion, and presence or absence of epidermal disruption. Any cases
that were not histologically consistent with PF were excluded.
Histological criteria for PF included subcorneal and/or intraepider-
mal pustules or crusts containing rounded acantholytic cells. Some
cases also included pustules within follicle walls. In some cases,
rounding up of keratinocytes and rolling off the superficial viable
epidermis was observed. After evaluation, cases were grouped
based on the following histopathological criteria. Group 1 included
no vasculopathic changes, only focal changes observed, or
changes appreciated only under areas of extensive epidermal dis-
ruption. Group 2a cases were designated as vasculopathy and
included one or more of the following: excessive erythrocyte
extravasation not associated with furunculosis or ulceration,
smudging, pallor, and/or loss of cellular detail of vessel walls with-
out any additional criteria met for vasculitis. Group 2b cases were
designated as vasculitis and included one or more of the follow-
ing: fibrin replacing vessel walls, inflammatory cells infiltrating and/
or replacing vessel wall, and/or leukocytoclastic debris surrounding
necrotic vessels. Degree of inflammation was scored as absent to
minimal (0), mild (1), moderate (2) or severe (3). Degree of epider-
mal disruption was assessed as absent or present. Presence of
epidermal disruption included focal or multifocal epidermal erosion
(partial epidermal loss) and/or ulceration (full-thickness epidermal
loss).
Clinical data
Clinical information was evaluated retrospectively from the medical
records. Data collected included signalment, clinical signs at presen-
tation, types of lesions, distribution of lesions, initial treatment,
adverse effects of treatment, time to remission, recurrence, mainte-
nance treatment, follow-up time and survival. Distribution was
defined based on involvement of the head, trunk (sides and dorsum),
ventrum, limbs (including the dorsal aspect of the paws) and foot-
pads.
Statistics
For analysis, clinical and histopathological data from Group 2 were
compared to Group 1. Groups 2a and 2b then were compared sepa-
rately to Group 1. All categorical data were tested using Chi-squared
or Fisher’s exact test with a two-sided null hypothesis of no associa-
tion rejected at P < 0.05. Numerical data were assessed for
2 © 2021 the European Society of Veterinary Dermatology and the American College of Veterinary Dermatology.
normality using the Shapiro–Wilk test with acceptance of null hypoth-
esis of normal distribution at P > 0.05. Normal numerical data were
compared between groups with nonpaired Student’s t-tests with a
two-sided null hypothesis rejected at P < 0.05. Non-normal data
were compared between groups with Wilcoxon–Mann–Whitney U-
tests with a two-sided null hypothesis rejected at P < 0.05. All statis-
tical analyses were performed using PRISM v8 for Windows (Graph-
Pad Software; La Jolla, CA, USA; www.graphpad.com). Cases were
excluded from statistical analysis for parameters for which follow-up
information was not available.
Results
Study population
A total of 41 dogs were included in the final analysis. The
overall median age was 7 years (range 2–14 years). There
were 23 spayed females, 16 neutered males and two
intact male dogs. The mean length of follow-up data
obtained for surviving dogs was 379.6 days (range 30–
1,335 days).
Histopathological results
Vasculopathic lesions were observed only in the superfi-
cial and mid-dermis. There were 17 dogs in Group 1 (no
vasculopathic lesions) and 24 dogs in Group 2 (vasculo-
pathic lesions present). Within Group 2, 10 dogs had vas-
culopathic lesions without overt vasculitis (Group 2a) and
14 dogs had overt vasculitis (Group 2b) (Figure 1).
In dogs with vasculopathic lesions (Group 2), there was
no association between vasculopathic changes and epi-
dermal disruption or degree of inflammation (Table 1).
Clinical presentation
On clinical examination, lesion type and distribution at
presentation were similar between groups (see Tables S1
and S2).
On presentation, 21 of 41 dogs (51.2%) had reported
systemic signs of illness, including lethargy (n = 15),
hyporexia/anorexia (n = 11), fever (n = 11), lym-
phadenopathy (n = 2) and/or weight loss (n = 1). Within
groups, systemic signs of illness were observed in five of
14 dogs (29.4%) in Group 1 and 16 of 24 dogs (66.7%) in
Group 2 overall, and more specifically, six of 10 dogs in
Group 2a (60%) and 10 of 14 dogs (71.4%) in Group 2b.
At least one or more systemic signs were significantly
more common in dogs in Group 2 (P = 0.028) and Group
2b (P = 0.032) than in dogs in Group 1. There was no dif-
ference in pruritus between groups (Table 2). Based on
the clinical histories, drugs were not identified as a trigger
of PF in any dogs.
Treatment and outcome
At the time of the last communication, 26 of 41 dogs
(63.4%) were alive, eight of 41 dogs (19.5%) had died or
were euthanised due to pemphigus foliaceus (PF) or
adverse effects associated with treatment, and seven of
41 dogs (17.1%) had died or were euthanised for unre-
lated reasons. Survival was similar when compared
between all groups (1, 2, 2a and 2b). However, dogs in
Group 2b were more likely to die or be euthanised due to
PF or adverse effects associated with treatment com-
pared to those in Group 1 (P = 0.028). There were 28 of
41 dogs (68.3%) that achieved complete remission
 Dogs with pemphigus and vasculopathic lesions

a b

c d

Figure 1. Haired skin of dogs with pemphigus foliaceus and concurrent vasculopathic lesions; vasculopathy (a, b) and vasculitis (c, d).
(a) In a case with vasculopathy, there is red blood cell extravasation in the superficial dermis underlying intact epidermis (arrow) adjacent to a
region of epidermis that has a subcorneal pustule (*) containing acantholytic cells. (b) Small-calibre blood vessels within regions of red blood cell
extravasation have thickened, hyalinised walls (arrow). (c) In a case with overt vasculitis, there is severe neutrophil infiltration of the wall of small-
calibre blood vessels and fibrinoid necrosis of vessel walls in the underlying intact epidermis. (d) In another case with overt vasculitis, there is fibri-
noid necrosis of small-calibre blood vessels and ischaemic necrosis of the overlying epidermis.

Table 1. Comparison of concurrent histological features in dogs with cases of pemphigus foliaceus with or without vasculopathic lesions.
Group

1 (n = 17) 2 (n = 24) 2a (n = 10) 2b (n = 14)

Epidermal disruption
Absent 7 (41.2%) 10 (41.7%) 4 (40.0%) 6 (42.9%)
Present 10 (58.8%) 14 (58.3%) 6 (60.0%) 8 (57.1%)
Degree of inflammation
0 (none to minimal) 1 (5.9%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
1 (mild) 8 (47.1%) 12 (50.0%) 6 (60.0%) 6 (42.9%)
2 (moderate) 7 (41.2%) 11 (45.8%) 4 (40.0%) 7 (50.0%)
3 (severe) 1 (5.9%) 1 (4.2%) 0 (0.0%) 1 (7.1%)

(Table 2). Of those dogs that had complete remission, 13
of 28 dogs (46.4%) had recurrence of clinical signs and
maintenance treatment was achieved in 20 of 28 dogs
(71.4%).
The mean corticosteroid dose needed to induce remis-
sion was 1.52 mg/kg/day of prednisone or equivalent. A
steroid-sparing agent was used in 26 of 41 dogs (63.4%).
This consisted of eight of 17 dogs (47.1%) in Group 1 and
18 of 24 dogs (75%) in Group 2 overall, and more specifi-
cally seven of 10 (70%) dogs in Group 2a and 11 of 14
dogs (78.6%) in Group 2b. Steroid-sparing agents
included azathioprine (n = 14), ciclosporin modified
(n = 13), mycophenolate mofetil (n = 4), chlorambucil
(n = 3), pentoxifylline (n = 2), doxycycline (n = 2) and
oclacitinib (n = 1). Two or more steroid-sparing agents
were used together or at different times during treatment
in nine dogs. There was no statistical difference in rates
of remission, recurrence, maintenance treatment, corti-
costeroid dose and use of a steroid-sparing agent
between groups. The mean time to remission was 56
days overall, including 41.8 for dogs in Group 1 and 66.6
days for dogs in Group 2. Within Group 2, the mean time
to remission was 35 days for dogs in Group 2a and 93.8
days for dogs in Group 2b. Dogs in Group 2b took more
than twice as long to achieve remission compared to
those in Group 1 (P = 0.047) (Table 3).
Adverse effects associated with treatment were
observed in 18 of 41 dogs (43.9%), including four of 17

© 2021 the European Society of Veterinary Dermatology and the American College of Veterinary Dermatology. 3
Zhou et al.

Table 2. Presenting clinical signs, treatment and outcome for all groups of dogs with pemphigus foliaceus (PF) with or without vasculopathic
lesions.
Group
Overall
(n = 41) 1 (n = 17) 2 (n = 24) 2a (n = 10) 2b (n = 14)
Presenting signs
Systemic signs of illness 21 (51.2%) 5^,* (29.4%) 16^ (66.7%) 6 (60.0%) 10* (71.4%)
Pruritus on presentation 32 (78.0%) 12 (70.6%) 20 (83.3%) 7 (70.0%) 13 (92.9%)
Treatment
Adverse effects from treatment 18 (43.9%) 4* (23.5%) 14 (58.3%) 3 (30.0%) 11* (78.6%)
Complete remission achieved 28 (68.3%) 12 (70.6%) 16 (66.7%) 7 (63.6%) 9 (64.3%)
Steroid-sparing agent used 26 (63.4%) 8 (47.1%) 18 (75.0%) 7 (70.0%) 11 (78.6%)
Outcome
Alive 26 (63.4%) 11 (47.8%) 15 (62.5%) 7 (63.6%) 8 (61.5%)
Death related to PF 8 (19.5%) 1* (5.9%) 7 (29.2%) 1 (9.1%) 6* (46.2%)
Death unrelated to PF 7 (17.1%) 5 (29.4%) 2 (8.3%) 2 (18.2%) 0 (0.0%)
^
Significant difference between Group 1 and Group 2 (P < 0.05).
*Significant difference between Group 1 and Group 2b (P < 0.05).

Table 3. Long-term outcome, treatment, and remission times for dogs that achieved complete remission of pemphigus foliaceus with or without
vasculopathic lesions.
Group
Overall
(n = 28) 1 (n = 12) 2 (n = 16) 2a (n = 7) 2b (n = 9)
Recurrence 13 (46.4%) 5 (41.7%) 8 (50.0%) 3 (42.9%) 5 (55.6%)
Maintenance treatment achieved 20 (71.4%) 9 (75.0%) 11 (68.8%) 5 (71.4%) 6 (66.7%)
Corticosteroid dose for remission (mg/kg) 1.52 1.53 1.51 1.47 1.62
Time to remission (days) 56.0 41.8* 66.6 35 93.8*
*Significant difference between Group 1 and Group 2b (P < 0.05).

dogs (23.5%) in Group 1 and 14 of 24 dogs (58.3%) in
Group 2 overall, and more specifically three of 10 dogs
(30%) in Group 2a and 11 of 14 dogs (78.6%) in Group 2b
(Table 2). The most common adverse effects observed
were development of diabetes (n = 4), muscle wasting
(n = 3), weakness (n = 2) and calcinosis cutis (n = 2).
When groups were compared, adverse effects were
more common in dogs of Group 2b when compared to
those of Group 1 (P = 0.004).
Discussion
Based on our evaluation, vasculopathic lesions in dogs
with PF appeared to be relatively common, as 56% of
evaluated PF cases in this study had histological evidence
of vasculopathy or overt vasculitis. Given that the study
specifically evaluated for vasculopathy/vasculitis, it was
recognised more commonly than the initial assessments
of the biopsy [12 of 41 (29.2%) cases]. This suggests that
while this histological lesion could be present in more
than half of PF cases, it may be missed if not specifically
looked for.
Vasculopathic lesions associated with PF have not
been described previously in dogs, and they have been
observed concurrently with PF in cats and horses in one
study each.8,9 In those reports, eight of 46 (17.4%) cats
and three of 20 (15%) horses diagnosed with PF had vas-
culopathic lesions; however, the pathogenesis or signifi-
cance of these vasculopathic lesions was not definitively
known. Neither of these two studies correlated vasculo-
pathic lesions with systemic illness, treatment response,
or outcome, and one of the studies suggested a drug
4 © 2021 the European Society of Veterinary Dermatology and the American College of Veterinary Dermatology.
association.8 For that study, one of the eight cats with PF
and concurrent vasculopathic lesions developed PF two
weeks following a rabies vaccine, suggesting that these
two pathological changes may be associated with cuta-
neous drug reaction.8 In separate studies, two cats with
suspected drug-triggered PF also had concurrent vascu-
lopathy.11,12 The study evaluating PF in horses9 noted
those with vasculopathy had exfoliative dermatitis and
suggested that it may indicate an overall intense inflam-
matory state of the skin. In this state, the epidermis pro-
duces vascular endothelial growth factor and vascular
permeability factor resulting in vascular proliferation, vas-
cular permeability, and subsequent vessel wall degenera-
tion.
There are a few case reports of vasculitis and concur-
rent histological evidence of pemphigus or serological
results showing circulating pemphigus autoantibodies in
humans.13,14 In one case report of bullous pemphigoid, it
was suggested that the concurrent leukocytoclastic vas-
culitis may have been induced by compliment activation
secondary to cross-reactivity of anti-basement membrane
antibodies and vessel wall or blood-borne antigen.15 In a
study evaluating autoantibodies in people with pemphi-
gus vulgaris, anti-neutrophil cytoplasmic antibodies
(ANCA), a marker for vasculitis in humans, was reported
in a small proportion of PV patients.16 The pathogenesis
of this association is unclear. Leukocytoclastic vasculitis
also has been reported rarely with autoinflammatory dis-
orders in humans, a rare subset of autoimmune diseases
which are characterised by the presence of recurrent epi-
sodes of unprovoked inflammation due to a dysregulated
innate immune system in the absence of autoantibody

production or infections. The review was unable to deter-
mine the pathogenesis of this association.17
The pathogenesis and possible triggers for concurrent
vasculopathic lesions in animals with PF is still undeter-
mined. Vasculitis is most often regarded as an immune-
mediated, type III hypersensitivity response, resulting in
excessive antigen-antibody immune complex deposition
in vessel walls. Antigen-antibody complexes become
trapped in blood vessel walls as a result of incomplete
clearance, which activates the complement cascade and
inflammatory cell recruitment to the vessel wall. The cells
then infiltrate vessel walls and release lysosomal con-
tents (collagenase and elastase) and reactive oxygen spe-
cies which damage endothelial cells. Over time, this
damage results in fibrin deposition, endothelial necrosis,
extravasation of erythrocytes and formation of thrombi.18
The main triggers reported for vasculitis in dogs include
drugs, vaccinations, infections and neoplasia.19 There
was no known association with vaccinations in our study.
A strong temporal association between drugs precipitat-
ing clinical lesions was not appreciated in any of the
cases. Therefore, drugs also do not appear to be associ-
ated with vasculitis in our study. In one of our cases with
concurrent vasculitis, the dog was found to have low–
moderate titres for Borellia burgdorferi and subsequently
was treated with doxycycline, yet still needed prednisone
to achieve and maintain remission. In other cases, there
was no obvious association with systemic illness includ-
ing tick-borne disease, systemic infection or neoplasia.
Although it could be considered that the vasculitis
observed in the superficial dermis in some cases of PF
may be secondary to local changes such as epidermal dis-
ruption or severe dermal inflammation, there was no obvi-
ous correlation between histological evidence of
epidermal disruption or severity of inflammation and vas-
culopathic lesions in our study. It is possible that the vas-
culopathic lesions observed are secondary to the primary
immunological reaction caused by PF. While PF is con-
ventionally characterised as a type II hypersensitivity, it is
possible that elements of a type III hypersensitivity con-
tribute to lesions as well.
Overall, dogs with PF and vasculopathic lesions on
histopathological evaluation presented in a similar way
clinically to those cases of PF without vasculopathic
lesions, including lesion types and distribution. We were
expecting more cases with identified vasculopathic
lesions to have oedema and/or nonblanching erythema as
those are clinical findings associated with vascular dam-
age.19 However, only two of our cases had reported
oedema. This may suggest that in most cases, the vascu-
lar changes on histopathological evaluation were not suffi-
ciently severe to cause clinical manifestations. As would
be expected, both dogs presenting with oedema had vas-
culopathic lesions: one with vasculopathy and one with
vasculitis. One dog was euthanised owing to lack of dis-
ease control, while the other achieved remission yet had
recurrence of lesions, developed gastric ulcers and
required mycophenolate for disease control. For these
two dogs, the oedema may have indicated more severe
vascular damage, leading to a reduced response to treat-
ment. However, the numbers are too low to make any
significant conclusions and owing to the retrospective
© 2021 the European Society of Veterinary Dermatology and the American College of Veterinary Dermatology.
Dogs with pemphigus and vasculopathic lesions
nature of the study, clinical lesions of vasculopathic dis-
ease may have been under-reported.
The similarity in lesions makes clinical distinction
between PF cases with or without vasculopathic
changes difficult without the aid of histopathological eval-
uation. However, dogs with vasculopathic lesions on
histopathological evaluation were more likely to present
with one or more systemic signs of illness than those
without. It can be hypothesised that vasculopathic
lesions are indicative of a more severe systemic
immunological and inflammatory reaction.20 A systemic
inflammatory response would result in the release of
inflammatory cytokines such as tumor necrosis factor
alpha, which can cause general lethargy.21 While concur-
rent underlying systemic disease causing vasculopathic
changes cannot be completely ruled out as a contributing
factor to the more severe disease presentation in the
presented PF cases with vasculopathic lesions, we were
not able to identify any in our cases. The retrospective
nature of this study could have made it more difficult to
identify concurrent diseases.
Even though dosages of glucocorticoids and use of
steroid-sparing agents were similar, dogs with concurrent
vasculitis took longer to achieve remission and had a
wider range of adverse effects from treatment. Although
there was no difference in survival, dogs with vasculitis
were more likely to be euthanised due to PF or related
adverse effects. Taken together, this suggests that PF
and concurrent vasculitis may be more refractory to treat-
ment than PF without concurrent vascular changes. This
significant difference in prognosis will be helpful when
advising clients and managing expectations. Further stud-
ies assessing modification of treatment protocols, such
as adding treatment for the concurrent vasculitis like pen-
toxifylline and/or sulfasalazine, may be helpful in improv-
ing outcome.19 Interestingly, the corticosteroid dose
needed to induce remission was noticeably lower than
reported in other studies. Previous studies report average
prednisone or equivalent dosages of around 2 mg/kg/day
versus a mean of 1.52 mg/kg/day in our cases.4,5,22 This
is likely a result of regional differences in practice. All clini-
cians submitting cases for our study had trained at one
point in the same dermatology programme which has
used lower dosages of prednisone or prednisolone for
the treatment of canine PF in the past two decades. How-
ever, based on our subset of cases, remission is possible
with a dose lower than what has been recommended
traditionally.
To the best of the authors’ knowledge, this is the first
report to describe PF with concurrent vasculopathic
lesions in dogs, and the first report in domestic animals to
evaluate its associations with clinical presentation, treat-
ment and outcome.
In summary, dogs with PF and concurrent vasculitis on
histopathological evaluation present more frequently with
systemic signs of illness. These cases take longer to
achieve remission and are more likely to be euthanised
due to their disease, suggesting that they are more diffi-
cult to manage. As such, histological identification of vas-
culopathic lesions may be a useful prognostic indicator in
dogs with PF. Further prospective studies would be bene-
ficial to help identify possible triggers and evaluate
5
Zhou et al.

treatment regimens of canine PF with added treatment of
the vasculopathic lesions.
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Supporting Information
Additional Supporting Information may be found in the
online version of this article.
Table S1. Lesion types for all groups.
Table S2. Lesion distribution for all groups.

RESUM

E
Contexte – Les le
sions vasculopathiques concomitantes des pemphigus foliace
(PF) chez le chien ont e
te


observe
es anecdotiquement dans la litte
rature. Une association avec un pronostic n’est pas claire.
Hypothe ses/Objectifs – Comparer les donne
es cliniques et l’e
volution des PF chez le chien avec et sans

sions vasculopathiques.
le
Sujets – Des biopsies dans la paraffine, fixe
es dans le formol paraffine, archive
es de 41 chiens avec PF.
Me
thodes – Les biopsies avec diagnostic de PF ont e
te

se

lectionne
es et re
e

value
es de facßon inde
pen-
dante. Les chiens ont e
te

assigne
s aux groupes selon l’e
valuation histologique: Groupe 1 (pas de vasculo-
pathie) et Groupe 2 (pre
sence de le
sion de vasculopathie). Le Groupe 2 a e
te

divise

en Groupe 2a (le
sions
vasculopathiques sans vascularite - i.e. vasculopathie) et Groupe 2b (nette vascularite). Les donne
es me
di-
cales des cas identifie
s ont e

te

revues re

trospectivement pour les donne
es de pre
sentation clinique, le trai-
tement et le suivi.
Re
sultats – Le temps de re
mission e
tait plus long dans le Groupe 2b (93.8 jours) compare
au Groupe 1
(41.8 jours) (P = 0.047). Les chiens des groupes 2a et 2b de
veloppaient davantage de signes syste
miques
(P = 0.028 et P = 0.032, respectivement) compare
au Groupe 1. Les chiens du Groupe 2b pre
sentaient
davantage d’effets secondaires associe
s au traitement que les chiens du Groupe 1 (P = 0.004). Il n’y avait

rence significative dans le type de le
pas de diffe
sion, la distribution, les taux de re
mission, les re
cidives ou
les dosages de cortico€ıdes entre les groupes.
Conclusions et importance clinique – Les chiens avec PF et vascularite concomitante prennent plus de
temps pour atteindre une re
mission et e
taient plus prompts 
velopper des signes syste
a de
miques ou des

sirables lie
effets inde
s aux traitements que les chiens avec PF sans le
sion de vasculopathie associe
e.

RESUMEN

n – de forma anecdo
Introduccio
tica, se han observado lesiones vasculop
aticas concurrentes en perros

nfigo foli
aceo (PF), pero no se han descrito en la literatura. No est

con pe
n con el
a clara ninguna asociacio

6 © 2021 the European Society of Veterinary Dermatology and the American College of Veterinary Dermatology.
 Dogs with pemphigus and vasculopathic lesions

prono
stico.
Hipo
tesis/Objetivos – Comparar las caracter
ısticas cl
ınicas y la progresio
n de PF en perros con y sin lesio-
nes vasculop
aticas.
Animales – muestras de biopsia archivadas, fijadas en formalina e incluidas en parafina de 41 perros con
PF.
Me
todos – se seleccionaron y reevaluaron de forma independiente muestras de biopsia archivadas, fijadas
en formalina e incluidas en parafina con un diagno
stico histolo

gico de PF. Los perros se asignaron a los gru-
pos siguiendo la evaluacio
n histolo

gica: Grupo 1 (sin lesiones vasculop
aticas) y Grupo 2 (lesiones vascu-
lop
aticas presentes). El grupo 2 se subdividio
en el grupo 2a (lesiones vasculop
aticas sin vasculitis, es
decir, vasculopat
ıa) y el grupo 2b (vasculitis manifiesta). Los historiales cl
ınicos de los casos identificados
se revisaron retrospectivamente para obtener datos sobre la presentacio
n cl
ınica, el tratamiento y el resul-
tado.
Resultados – el tiempo para obtener remisio
n fue mayor en el Grupo 2b (93,8 d
ıas) en comparacio
n con el
Grupo 1 (41,8 d
ıas) (P = 0,047). Los perros de los grupos 2a y 2b ten
ıan m
as probabilidades de presentar
signos siste
micos de enfermedad en el momento de la presentacio
n (P = 0,028 y P = 0,032, respectiva-
mente) en comparacio
n con el Grupo 1. Los perros del Grupo 2b ten
ıan m
as probabilidades de tener efec-
tos adversos asociados con el tratamiento que los perros del Grupo 1 (P = 0,004). No hubo diferencias

n, distribucio
significativas en el tipo de lesio
n, tasas de remisio
n, recurrencia o dosis de corticosteroides
entre los grupos.
Conclusiones e importancia cl
ınica – los perros con PF y vasculitis concurrente tardaron m
as en lograr la
remisio
n y ten
ıan m
as probabilidades de presentar signos siste
micos de enfermedad o efectos adversos
asociados con el tratamiento que los perros con PF sin lesiones vasculop
aticas concurrentes.

Zusammenfassung
Hintergrund – Gleichzeitig auftretende pathologische Gef€ aßl€
asionen bei Hunden mit Pemphigus foliaceus
(PF) sind anekdotisch beobachtet, aber in der Literatur noch nicht beschrieben worden. Ein Zusammen-
hang mit der Prognose ist unklar.
Hypothese/Ziele – Ein Vergleich der klinischen Merkmale und das Ergebnis von PF bei Hunden mit und
ohne pathologischen Gef€aßl€asionen.
Tiere – Archivierte, in Formalin-fixierte und in Paraffin eingebettete Biopsieproben von 41 Hunden mit PF.
Methoden – Archivierte, in Formalin-fixierte und in Paraffin eingebettete Biopsieproben mit der histopatho-
logischen Diagnose eines PF wurde ausgesucht und unabh€ angig re-evaluiert. Die Hunde wurden nach his-
tologischer Evaluierung in Gruppen eingeteilt: Gruppe 1 (keine pathologischen Gef€ aßver€anderungen) und
Gruppe 2 (pathologische Gef€aßver€anderungen). Gruppe 2 wurde unterteilt in Gruppe 2a (pathologischen
Gef€aßver€anderungen ohne Vasculitis – i.e. Vaskulopathie) und Gruppe 2b (deutliche Vaskulitis). Die medizi-
nischen Patientendaten von identifizierten F€ allen wurden retrospektiv in Bezug auf klinische Pr€asentation,
Behandlung und Endergebnis durchgesehen.
Ergebnisse – Die Zeit bis zur Remission war in Gruppe 2b (93,8 Tage) im Vergleich zu Gruppe 1 (41,8 Tage)
l€anger. Bei Hunden in Gruppe 2a und 2b waren systemische Anzeichen von Erkrankung zum Zeitpunkt der
Pr€asentation wahrscheinlicher (P = 0,028 bzw P = 0,032) als in Gruppe 1. Hunde in Gruppe 2b hatten h€ aufi-
ger Nebenwirkungen im Zusammenhang mit der Behandlung als Hunde in Gruppe 1 (P = 0,004). Zwischen
den Gruppen bestanden keine signifikanten Unterschiede beim Typ der L€ asionen, ihrer Verteilung, der
Remissionsraten, dem Wiederauftreten oder der verabreichten Cortisondosis.
Schlussfolgerungen und klinische Bedeutung – Hunde mit PF und gleichzeitigen pathologischen
Gef€aßver€anderungen beno €tigten eine l€angere Zeit, um eine Remission zu erzielen und hatten h€ aufiger sys-
temische Anzeichen von Erkrankung oder Nebenwirkungen im Zusammenhang mit der Behandlung als
Hunde mit PF ohne gleichzeitige pathologische Gef€ aßver€anderungen.

要約
背景 – 落葉状天疱瘡 (PF) の犬における血管病変の併発は、逸話的に観察されているが、文献的には報告
されていない。また、予後との関連も不明である。
仮説・目的 – 本研究の目的は、PF犬において血管病変のある犬とない犬の臨床的特徴および予後を比較
することであった。
供試動物 – PFを発症した41頭の保存されたホルマリン固定、パラフィン包埋バイオプシーサンプル。
方法 – PFの組織学的診断を受けた保存されたホルマリン固定、パラフィン包埋生検サンプルを選択し、
独立して再評価した。組織学的評価の後、グループ1 (血管病変なし) およびグループ2 (血管病変あり) に
犬を分けた。グループ2は、グループ2a (血管炎を伴わない血管病変、すなわち血管障害) およびグループ
2b (顕在化した血管炎) に細分化された。同定された症例の医療記録を回顧的にレビューし、臨床症状、
治療、転帰に関するデータを得た。
結果 – 寛解までの期間は、グループ1(41.8日) に比べ、グループ2b(93.8日) の方が長かった (P = 0.047) 。グ
ループ2aおよび2bの犬は、グループ1の犬と比較して、来院時に全身性の病気の兆候がある可能性が高
かった (それぞれP = 0.028およびP = 0.032) 。 グループ2bの犬は、グループ1の犬と比較して、治療に伴う
© 2021 the European Society of Veterinary Dermatology and the American College of Veterinary Dermatology. 7
Zhou et al.

副作用がある可能性が高かった (P = 0.004) 。病変の種類、分布、寛解率、再発率、副腎皮質ステロイド

の投与量にはグループ間で有意な差はなかった。
結論と臨床上の重要性 – PFと血管炎を併発している犬は、血管病変を併発していないPFの犬に比べて、
寛解に至るまでに時間がかかり、全身性の病気の兆候や治療に伴う副作用が出やすかった。

摘要
背景 – 在落叶型天疱疮(PF)犬中观察到并发血管病变, 但文献中未见报告。与预后的任何相关性尚不清楚。
假设/目的 – 比较有和无血管病变的PF患犬的临床特征和结果。
动物 – 被存档的41只PF犬的福尔马林固定、石蜡包埋活检样本。
方法 – 存档的福尔马林固定、石蜡包埋活检标本, 组织学诊断为PF, 被独立选择并重新评价。根据组织学评
价将犬分组: 组1 (无血管病变) 和组2 (存在血管病变) 。第2组又分为第2a组 (无血管炎的血管病变-即血管病)
和第2b组 (明显血管炎) 。对选出病例的病历记录进行回顾性审查, 以获得关于临床表现、治疗和结果的数
据。
结果 – 与第1组 (41.8天) 相比, 第2b组 (93.8天) 的至缓解时间更长(P = 0.047)。与第1组相比, 第2a组和第2b
组中的犬在就诊时更可能出现全身性疾病体征 (分别为P = 0.028和P = 0.032) 。第2b组中的犬比第1组中的犬
更可能出现与治疗相关的不良反应(P = 0.004)。组间病灶类型、分布、缓解率、复发或皮质类固醇剂量差异
均无统计学意义。
结论和临床重要性 – 与未并发血管病变的PF犬相比, 并发血管炎的PF犬需要更长的时间才能达到缓解, 并
且更可能出现与治疗相关的全身性疾病体征或不良反应。

Resumo
Contexto – A presencßa de leso ~es causadas por vasculopatia concomitantemente com o pe ^nfigo foli

aceo
(PF) em c~aes j
a foi observada de forma anedo
tica, mas ainda n~ ao relatada na literatura. N~ao est

a claro se h
a
associacß~ao disto com o progno
stico.
Hipo
tese/Objetivos – Comparar as caracter
ısticas cl
ınicas e a evolucß~ ao do PF em c~ aes com e sem leso ~es
de vasculopatia.
Animais – Foram analisadas 41 amostras arquivadas de bio
psia cut^ anea de c~aes com PF parafinadas e fixa-
das em formol.
Me
todos – Amostras de bio
psia cut^anea parafinadas e fixadas em formol arquivadas com o diagno
stico
histolo
gico de PF foram selecionadas e reavaliadas de forma independente. Os c~ aes foram divididos em
grupos de acordo com a avaliacß~ao histolo
gica: Grupo 1 (sem leso ~es vasculop
aticas) e Grupo 2 (presencßa de
leso~es vasculop
aticas). O Grupo 2 foi subdividido em Grupo 2ª (leso ~es vasculop
aticas sem vasculite – vas-
culopatia) e Grupo 2b (vasculite evidente). Os prontu
arios dos casos identificados foram revisados retros-
pectivamente e foram registrados os dados de apresentacß~ ao cl
ınica, tratamento e evolucß~ao.
Resultados – O tempo ate
a remiss~ao foi maior no Grupo 2b (93,8 dias) em comparacß~ ao com o Grupo 1
(41,8 dias) (P=0,047). Os c~aes dos grupos 2a e 2b foram mais propensos a apresentar sinais siste ^micos
~ ~
(P=0,028 e P=0,032, respectivamente) em comparacßao com o Grupo 1. Os caes do Grupo 2b foram mais
propensos a ter efeitos adversos associados ao tratamento do que os c~ aes do Grupo 1 (P=0,004). N~ ao
houve diferencßas significativas no tipo de les~ ao, distribuicß~
ao, freque ^ncia de remiss~ ^ncia ou dosa-
ao, recorre
gem de corticosteroide entre os grupos.
Concluso ~ es e importa ^ncia cl
ınica – C~aes com PF e vasculite concomitante demoraram mais para atingir
a remiss~ao e foram mais propensos a ter sinais siste ^micos ou efeitos adversos associados ao tratamento
do que c~aes com PF sem leso ~es vasculop
aticas concomitantes.

8 © 2021 the European Society of Veterinary Dermatology and the American College of Veterinary Dermatology.