Review

Blackwell Publishing Ltd

A review of autoimmune skin diseases in domestic

animals: I Superficial pemphigus
Thierry Olivry
Center for Comparative Medicine and Translational Research and
Department of Clinical Sciences, College of Veterinary Medicine,
North Carolina State University, Raleigh, North Carolina, USA
Correspondence: Thierry Olivry, Department of Clinical Sciences,
North Carolina State University, College of Veterinary Medicine,
Research Building, 4700 Hillsborough Street, Raleigh, NC 27606,
USA. E-mail: Thierry_Olivry@ncsu.edu

Abstract
In humans, the pemphigus denomination encompasses
a group of autoimmune blistering skin diseases with
intraepidermal separation resulting from cellcell
detachment by acantholysis. Entities are classified
based on the level of blistering in the epidermis, and
both superficial (pemphigus foliaceus, IgA pemphigus)
and deep (pemphigus vulgaris, pemphigus vegetans
and paraneoplastic pemphigus) variants are recognized.
In domestic animals, subsets of pemphigus have been
recognized since the mid-1970s, and the disease classification resembles that used for human patients. This
article reviews up-to-date knowledge on the epidemiology, clinical signs, histopathology, immunopathology
and treatment outcome of superficial pemphigus in
domestic animals. Detailed information on canine,
feline, equine and caprine pemphigus foliaceus, canine
and feline pemphigus erythematosus and canine
panepidermal pustular pemphigus is provided.
Accepted 01 August 2006

Introduction
Epidermal cells possess structures that are involved
either in cellcell (desmosomes) or in cellmatrix adhesion
(hemidesmosomes-anchoring fibrils complex). Whenever
autoantibodies target proteins in these adhesion structures, intra- or sub-epidermal separation often occurs, and
clinical signs of an autoimmune blistering skin disease
usually develop.1 In the last 30 years, the identification of
antigens targeted by circulating autoantibodies has helped
reshape the classification of autoimmune blistering skin
diseases in humans. Based on clinical signs, histopathology
and immunological characteristics, several entities are now
well recognized. For example, the most common diseases
associated with autoantibodies against epidermal basement
membrane antigens are bullous pemphigoid (target: collagen
XVII), mucous membrane pemphigoid (laminin-5, collagen
XVII, integrin alpha-6 beta-4) and epidermolysis bullosa

acquisita (collagen VII).1 Similarly, autoantibodies targeting

desmosomal proteins in keratinocytes may result in
blistering diseases of the pemphigus group. This group
encompasses both deep (pemphigus vulgaris: desmoglein3 desmoglein-1; paraneoplastic pemphigus: desmoglein3, plakins) and superficial variants (pemphigus foliaceus:
desmoglein-1; IgA pemphigus, desmocollin-1 and 3).1
In animals, autoimmune blistering skin diseases were
first recognized 30 years ago, with the seminal description
of pemphigus vulgaris in dogs.2,3 Since then, most animal
homologues of the human entities have been identified. It
is the aim of the forthcoming series of reviews to compile
the latest knowledge on autoimmune skin diseases known
in domestic animal species. The first monograph of this
series covers information on the epidemiology, clinical
signs, treatment outcome, pathology and immunology of
superficial variants of pemphigus in dogs, cats, horses and
goats. Diseases highlighted herein are pemphigus foliaceus
(PF), pemphigus erythematosus (PE) and the so-called
panepidermal pustular pemphigus (PPP).

Pemphigus foliaceus
History
The first article describing the existence of PF in dogs was
published in 1977 by Halliwell and Goldschmidt.4 Since
then, this canine disease has been reported worldwide in
countless articles, each reporting one or few cases. Only
three retrospective studies of large series of subjects (37,
26 and 91 cases) have been published in English.5 7 The
first report of feline PF was in 1982,8 and there are only
two papers describing more than 10 cases each.6,9 Pemphigus foliaceus was recognized in horses in 1981,10 and
three articles report multiple patients.6,11,12 Finally, PF is a
rare autoimmune disease of goats and only scattered
reports exist.1316
Incidence and prevalence
Very little epidemiological information on canine PF is
available, unfortunately. In a veterinary teaching hospital
(New York State College of Veterinary Medicine at Cornell
University), PF was diagnosed in 26 of 9750 dogs between
1975 and 1984. This proportion results in an estimated
incidence of PF of approximately three per 1000 canine
patients referred for skin diseases per year.6 In another
institution (Michigan State University College of Veterinary
Medicine), PF was the diagnosis made in 1% of surgical
skin biopsies read by veterinary pathologists (R. W.
Dunstan, personal communication, WSAVA meeting, 1997).
Finally, in a retrospective study of 84 dogs with auto immune skin diseases, PF was the diagnosis given to
26 subjects, nearly one third of all dogs with autoimmune
skin diseases.17

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From data published in one article, the incidence of

feline and equine PF could be calculated as five and 10 per
1000 patients per 10 years, respectively.6 Pemphigus
foliaceus is too rare in goats to estimate its prevalence and
incidence.

studies found that PF could affect both very young (less

than 6 months) and ageing horses of up to 25 years old.6,11,12
Finally, there are too few cases of caprine PF for assembling relevant information on breed, sex and age predisposition to disease development.

Signalment
Genetic factors are likely to predispose to the development
of canine PF. Indeed, data gathered from several studies
suggest that PF is more frequently diagnosed in dogs from
certain breeds. For example, in one group of 37 dogs with
PF, six breeds (bearded collie, Akita, Newfoundland,
Schipperke, Doberman and Finnish Spitz) exhibited a significant risk to develop the trait compared to the control
population.5 However, only two of these breeds (Dobermans
and Akitas) had more than one representative affected,
and both breeds exhibited a high odds ratio (OR) to develop
PF (OR = 29).5 In a second group of 26 dogs,6 Akitas and
dachshunds were the only breeds with more than one
individual diagnosed with PF. For dogs reported in this
article, we calculated the OR for PF development in Akitas
to be 3.0 with a large confidence interval (0.712.9).6 Using
data from the University of Pennsylvania Veterinary Hospital, breeds at significant risk of PF development included
Akitas (OR = 38; 95% confidence interval: 13 99), English
cocker spaniels (21; 888), chows (12; 4 49), shar-peis (8;
230) and collies (4; 214). Finally, in a University surgical
pathology service, three breeds of dogs accounted for one
third of all cases of PF, and OR for the diagnosis of PF were
23, 16 and 7 in Akitas, chows and Australian shepherds,
respectively (R. W. Dunstan, personal communication,
WSAVA meeting, 1997). Interestingly, two female Shetland
sheepdog littermates were reported to develop PF simultaneously at 6 months of age.18 In summary, over the years
and in various geographical locations in the USA, chows
and Akitas appear to be at high risk to develop PF. This
common predisposition may not be surprising in light of
the recent discovery that these two breeds exhibit closely
related genotypes and are in close phylogenetic linkage.19
In the three largest case series of dogs with PF, the
male to female sex ratios were 13:24 (0.5), 14:12 (1.2) and
46:45 (1.0), and these proportions suggest that a sex predisposition is unlikely to occur in this species.5 7 In these
reports, the age of onset of canine PF was very variable,
as it ranged from less than one up to 16 years (means: 4.2,
6 and 6 years).5 7
A breed predisposition for PF has not been reported
definitively in the feline species even though domestic
short-haired cats were found to be most commonly affected
with this disease in two case series.6,9 The male to female
sex ratios were 5:5 and 27:30, suggesting that a sex
predisposition for development of PF in cats also was
unlikely.6,9 In these two studies, the age of onset of feline
PF ranged from less than 1 to 9 and 17 years, respectively
(medians: 5 years).6,9
In the first study of equine PF, Appaloosas accounted for
one third of the patients, a proportion five times higher
than that of the general equine hospital population.6 However, such breed predisposition was not confirmed in the
other two case series.11,12 In none of these three papers
was a sex predisposition apparent.6,11,12 While no article
reported an age predilection for disease development, all

Triggering factors for PF

Environmental factors are suspected to induce flares of
canine PF. One of such factors may be sunlight exposure.
A decade ago, a book chapter reported a seasonal exacerbation of the disease with more active flares and requirement
for higher immunosuppressive drug dosages in warmer
months, but evidence to support such claims unfortunately
was not provided.20 In contrast to this assertion, a seasonal
pattern of PF development was not found in an epidemiological study regrouping 66 dogs with PF.21 More recently,
Japanese investigators reported that lesional scores of PF
worsened in the summer in 10/12 dogs studied, while values
improved in the winter.22 Experimentally, irradiation of
nonlesional skin from a dog with facial-predominant superficial pemphigus with 4590 kJ m2 of ultraviolet B (UVB)
led to epidermal acantholysis after 1 day. In vitro, incubation of pemphigus serum on UVB-irradiated skin explants
resulted in more intense intragranular acantholysis than on
non-irradiated cell cultures.23 The latter findings suggest
that additional studies on UV exacerbation of canine
superficial pemphigus are warranted.
In horses with PF, a higher risk for flares during fall and
winter months was reported in one study,12 but a clear
seasonal pattern was not observed in the second series of
cases.11 In two of these 15 horses, however, signs were
observed to recur each summer.11
A higher incidence of PF in dogs with allergic skin diseases has been mentioned, but evidence supporting such
an association was not given.20 Interestingly, a previous
history of flea allergy dermatitis was the most common
skin disease reported in dogs later diagnosed with PF in
one study from California.21 This observation must be
taken with caution because of the high prevalence of flea
allergy dermatitis in that particular geographical location.
In humans, several drugs are suspected to either cause
pharmacological acantholysis (i.e. drug-induced pemphigus)
while others can stimulate disease flares in patients already
predisposed to develop this illness (i.e. drug-triggered
pemphigus).24 Cases of drug-related PF have been suspected in several dogs and rare cats for 20 years.9,2529 A
recent paper provided information on four additional
patients.30 In these four dogs, the diagnosis of drug-related
PF was based on history, clinical signs, histopathology and
response to withdrawal of suspected causative drug(s). In
this paper, however, one subject (case 1) was treated with
immunosuppressive doses of prednisolone and azathioprine
for 7.5 months, another (case 2) was given high dosages
of prednisolone for 8.5 months, the last patient received
low dosages of prednisone for 7 months, whereas case 3
was not treated with anti-inflammatory medications.30 In
that report therefore two of four patients needed months
of immunosuppression to maintain remission before all
drugs were discontinued. While one cannot discount the
authors hypothesis that their patients were affected with
drug-related pemphigus, one cannot disprove the contrahypothesis either. Indeed, it is conceivable that the animals

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Superficial pemphigus in domestic animals

mentioned above could have suffered from natural autoimmune PF that went into prolonged remission after immunosuppression was discontinued, as has been shown
recently in several dogs with PF.31
To evaluate the probability of association between the
administration of a medication and the development of a
particular event, an assessment of likelihood of drug reaction must be made using adverse drug reaction probability
scales such as the one developed years ago by Naranjo
et al.32 When this scale is applied to all previous cases of
putative drug-related pemphigus in dogs and cats2530 only
low scores interpreted as possible probabilities of drug
reaction are obtained. Therefore, at this time, the strength
of evidence supporting drug causation for rare cases of PF
in dogs and cats is weak at best, and further documentation of canine and feline cases with highly probable drugrelated PF is critically needed.
Clinical signs
Clinical signs of PF appear to be similar across domestic
animal species. In most dogs, lesions initially appear on
the face, principally on the dorsal muzzle, planum nasale,
periocular skin and ears.5,6 In these areas, the pattern usually is strikingly bilateral and symmetrical (Fig. 1).5 In the
largest case series, lesions were restricted to the face in
15 of 91 dogs (16%) (Fig. 2).7 In rare canine patients, the
dermatosis exhibits a generalized distribution from the
onset, but in most cases, lesions will develop towards
regionalization (Fig. 3) or generalization (Fig. 4) over 3 to 12
months.5,7 In the largest retrospective study, generalized
skin lesions were present in 60/91 dogs (66%), and in
these dogs, crusts were most prevalent on the trunk (58%).7
A remarkable finding of canine PF is the predilection of
lesions for the footpads (Fig. 5).5 Indeed, footpad involve-

Figure 2. Canine facial PF. A 3-year-old Australian shepherd with

erythema, erosions, scaling and crusting at the time of initial
presentation to the dermatologist (left). Treatment with niacinamide
and tetracycline and intermittent oral prednisone led to minimal
remission with occasional recurrence of signs (right). During disease
flares, superficial pustules (top right; arrowheads) evolved rapidly into
crusts overlying erosions (bottom right).

Figure 3. Canine PF (same dog as Figure 1). Skin lesions initially

appeared on the face (Figure 1), however, within one week of hair
clipping for cruciate ligament repair surgery and following intense sun
exposure, PF lesions (pustules, erosions and crusts) erupted on the
lateral aspect of the leg where hair had been clipped. Remarkably,
there were no lesions on the medial thigh, an area that had been
clipped also.

Figure 1. Canine PF. A 2-year-old chow crossbred dog exhibits crusting and erosions bilaterally and symmetrically distributed on the dorsal
muzzle, dorsal nasal planum and periocular areas.

ment is seen in one third of dogs with PF,7 and rare canine
patients exhibit lesions restricted solely to this location
(Fig. 5; right).6,7,3336 Of note is that mucosal lesions are
only rarely seen in dogs with PF (2/91; 2%).7 Pemphigus
foliaceus confined to the claws has been observed in one
dog.37

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Figure 4. Canine PF. This 3-year-old English bulldog was affected

with lesions that progressed rapidly from the face to cover most of the
body surface. Inset: details of rapidly drying pustules and crusts from
the lateral thigh.

The nature of skin lesions is comparable in most dogs

with PF: transient pustules evolve rapidly into erosions
and crusts, the latter being the lesions most commonly
seen.57 The pustules of PF are usually large and confluent
(Fig. 6), and they often exhibit polycyclic borders. Many
hair shafts can protrude from these pustules, in contrast
to the lesions of bacterial folliculitis where only a single
hair can be seen coming from each pustule.38 On rare
occasions, pustules, erosions and crusts are grouped in
a unique annular, or polycyclic pattern (Fig. 7).5,39 Alopecia
and generalized exfoliative erythroderma are seen
occasionally.5 Pruritus is present in one fourth to one
half of dogs with PF,5 whereas systemic symptoms consisting of anorexia, depression, fever and weight loss are
encountered usually in dogs with widespread erosive
lesions.6
The clinical signs of feline PF are reminiscent of those
seen in dogs with this disease. Pustules are extremely
transient, however, and the phenotype is dominated by
erosions and yellowish crusts on the face (Fig. 8), ears
(Fig. 9), and on the feet.6,8,9,40 Pedal lesions, consisting of
suppuration or crusts, can be seen on or around the footpads or ungual folds of claws (Fig. 10).6,8,9,35,40 The phenotype of feline PF is usually mild and fairly localized, but
generalized lesions can be seen also.9 The distribution of
lesions of feline PF is usually bilateral and symmetrical.9

Figure 6. Canine PF. Large, grouped and often coalescing superficial

pustules exhibit a peripheral erythematous halo. Multiple hair shafts
protrude from the roof of the pustule (case material: University of
California Davis).

Figure 7. Canine PF. Crusts overlie erosions with an erythematous

border in a grouped polycyclic arrangement.

Horses with PF usually are presented with multifocal to

generalized crusting, scaling and alopecia affecting the
face, neck, trunk and extremities (Fig. 11).6,11,12 Pustules
are observed rarely, and whenever present, they are

Figure 5. Canine PF. Footpad lesions

of canine PF vary with their chronicity.
Acute lesions (left) consist of pustules
(arrowheads; same dog as in Figure 4),
erosions and crusts. With time, crusts
coalesce (middle) and dry to form fissures
(right).

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Superficial pemphigus in domestic animals

Figure 8. Feline PF. Alopecia, erosions and crusts developed on the

face of a 1.5-year-old Siamese cat during a flare of PF (courtesy of
Dr Barbara Atlee).

Figure 11. Equine PF. A 12-year-old quarterhorse mare exhibits

erosions and crusts in a figurate pattern on the face and neck
(case material from the University of California Davis).

Figure 9. Feline PF. Yellowish crusts are present on the convex (left)
or concave aspects of the pinnae of two cats with PF (left: courtesy
of Dr Barbara Atlee; right: case material from the University of
California Davis).

Figure 12. Canine PF. Aspiration cytology from the content of a

superficial pustule reveals numerous neutrophils, some eosinophils
and scattered isolated or grouped acantholytic keratinocytes
(DiffQuick).

Figure 10. Feline PF. Crusting can be seen around footpads and
claws (left) or on pads themselves (right).

transient.6,11,12 Skin lesions may exhibit a unique annular

pattern as in dogs.41 Remarkably, ventral oedema is seen
in many horses with PF.12 Systemic symptoms, such as
depression and lethargy, were noticed in 50% of horses
with PF in one study6 but a similar observation was not
made in another retrospective study.11 Lesions of equine
PF are occasionally painful and /or pruritic.11,12

In goats, pustules, crusts, scales and alopecia predominate

on the face, ventral abdomen, limbs, perineum and tail. In
female animals, lesions may affect the udder and teats.13 16
Pemphigus foliaceus in animals has been reported in
association with systemic diseases such as hypothyroidism,42
leishmaniasis,43 thymoma44 and systemic lupus erythematosus.45 The relationship between PF and these entities
may be coincidental, or it could reflect a systemic disease
process leading to the induction of immunological imbalances and development of anti-keratinocyte autoimmunity.
Cytology
The diagnosis of PF in animals commences with the
demonstration of acantholytic keratinocytes in impression
smears of intact pustules (Fig. 12).57 Indeed, isolated to

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Figure 13. Canine (left) and feline (right) PF. In these early microscopic lesions, fluid-filled vesico-pustules contain few neutrophils and acantholytic
keratinocytes. The sample on the right was obtained as a shave biopsy from an auricular lesion not existing 2 h before (haematoxylin and eosin).

clustered (e.g. rafts) free-floating rounded keratinocytes

admixed with nondegenerated neutrophils and rarer eosinophils are seen usually.57 Acantholytic keratinocytes
exhibit either microscopic characteristics of normal differentiated spinous or granular layer epithelial cells, or they
present signs of apoptosis with eosinophilic cytoplasm,
condensed chromatin or karyorrhexis. Occasionally, neutrophils can be seen in close apposition to detached keratinocytes. The presence of acantholytic keratinocytes and
neutrophils is not specific of PF, however. Similar microscopical findings have been found in canine and equine
cases of pustular dermatophytosis, a PF mimicker in
which Trichophyton fungi invade the stratum corneum and
induce subcorneal acantholytic neutrophilic pustules.46 48
Keratinocyte acantholysis has been reported also in dogs
with bacterial skin infections.38
Histopathology
In dogs, cats, horses and goats with PF, histological examination of lesional skin reveals similar findings. Very early
lesions may be vesicles with acantholytic keratinocytes
and scarce neutrophils (Fig. 13). However, these lesions
rapidly evolve into intragranular (Fig. 14) or subcorneal
pustules (Figs 13,14,15) with isolated and /or clustered
acantholytic cells.5,6,38,39 In these lesions, neutrophils predominate, but variable numbers of eosinophils may be
found.57,38,39 Pustules commonly invade the epithelium
and /or the lumen of the follicular infundibulum.5,38 In general, the pustules are large and span the length of multiple
follicular units, a finding that differentiates these lesions
from those of bacterial folliculitis.12,38 Similarly, recornification, defined as newly reformed stratum corneum at the
base of neutrophilic pustules, is more suggestive of PF
(Fig. 16) than bacterial folliculitis.38 Microscopic characteristics of acantholytic keratinocytes mirror those observed
with cytology. Epidermal cells that recently detached from
their neighbours usually appear similar to differentiated
keratinocytes whilst other cells exhibit cytological characteristics of apoptosis.5 Apoptotic keratinocytes are seen
often in the epidermis of dogs with PF,49 and as a result
these apoptotic epidermal cells cannot be taken for bona
fide markers of underlying drug reactions. The induction of
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Figure 14. Canine PF. Intraepidermal vesico-pustule in the granular

layer of footpad epidermis (haematoxylin and eosin).

Figure 15. Canine PF. Intraepidermal to subcorneal neutrophilic

and eosinophilic pustule with single and clustered acantholytic
keratinocytes. Of interest is the keratin filament ring that can be
seen in acantholytic or pre-acantholytic keratinocytes (arrowheads)
from the presumed detachment of keratin filaments from
desmosomes (haematoxylin and eosin).

apoptosis may reflect the phenomenon of anoikis that follows the rupture of desmosomal cadherin adhesion during
acantholysis.50 Alternatively, activation of the apoptotic
pathway could be an early consequence of the binding of

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Superficial pemphigus in domestic animals

Figure 16. Feline PF. Large subcorneal neutrophilic acantholytic pustule

with underlying epidermal recornification (haematoxylin and eosin).

Figure 17. Canine PF. Direct IF performed on a frozen skin section

reveals intercellular epidermal IgG in the stratum spinosum and
granulosum (anticanine IgG fluorescein).

autoantibodies to keratinocytes as shown recently in humans

with pemphigus.51 Even though acantholytic keratinocytes can be seen in pyogenic skin bacterial infections38
and pustular dermatophytoses,46 48 the presence of a
high number of free-floating epidermal cells, often seen in
clusters, may be more suggestive of PF than other infectious dermatoses.38
In one study, immunostaining for desmogleins was
altered in skin biopsies of dogs with PF compared to those
of normal individuals.52 In canine PF skin, desmoglein
staining appeared as distinct clumped deposits at the
periphery of keratinocytes and /or dark cytoplasmic staining of acantholytic cells consistent with internalization of
these molecules.52

Direct immunofluorescence
Direct immunofluorescence (IF) or immunoperoxidase
have been used to detect antikeratinocyte autoantibodies
deposited in vivo in the skin of animals with PF. Skin-fixed
intercellular epidermal IgGs were found in most cats,
horses and goats with PF.6,15 Similarly, intercellular epidermal IgG autoantibodies were detected in 66 80% of
canine specimens examined (Fig. 17).5,6,17,39,53 One study
established that, in some dogs with PF, skin-fixed autoantibodies belonged to IgG2 and/or IgG4 subclasses.54 In rare
instances, intercellular deposits of IgA or IgM and activated
complement (C3 fraction) were observed.6,39 In one third
of canine specimens, intercellular fluorescence was
restricted to the upper half of the epithelium.5 In some
dogs with PF, direct IF testing of skin biopsy specimens
has remained negative, and these results were attributed
to glucocorticoid therapy administered prior to specimen
collection.6 Unfortunately, intercellular epidermal IgG also
can be found in biopsy specimens obtained from dogs with
dermatoses other than PF.6,17 These findings markedly
reduce the specificity of direct IF testing for the diagnosis
of canine PF.

nique was deemed unreliable for the diagnosis of animal

pemphigus, as circulating IgG autoantibodies rarely were
found in canine, feline or equine sera.6,39 When antikeratinocyte antibodies were detected in canine PF sera, the
titre was usually inferior to 1 : 40.5,6 A recent study provided information suggesting that indirect IF results will
vary according to the substrate utilized for autoantibody
detection. When normal bovine oesophagus substrate
was used, circulating antibodies were detected in 65% of
affected patients.55 Similarly, indirect IF was positive for all
canine PF sera tested on cultured canine keratinocytes.56,57
When other epidermal substrates were employed, however, the frequency of detection of circulating autoantibodies
was usually lower.55 Unfortunately, the skin of the nasal
planum exhibits physiological intercellular IgG, rendering
indirect IF testing positive using this substrate and normal
dog sera.55 At North Carolina State University, indirect IF
testing performed using normal canine footpad revealed
antikeratinocyte autoantibody titres superior to 1 : 50 in
the serum of 73 of 87 dogs with PF (84%).58 Using this
substrate, nearly half of canine PF sera tested were
shown to contain IgG that bound to keratinocytes of both
stratum spinosum and granulosum, but additional IF
patterns also were uncovered.58 These results provided
evidence of immunological heterogeneity of canine PF.58
Using neonatal mouse skin as substrates, canine PF
serum autoantibodies were detected in 36 of 44 dogs with
PF (82%) (Fig. 18), and they were found to be of either
IgG1 (30/44; 68%) or IgG4 (35/44; 80%) isotypes.59 Similar
findings were reported by other investigators.22 In six
dogs, immunosuppression led to a reduction in clinical
scores with serum IgG, IgG1 and IgG4 autoantibody titres
decreasing in four, one and four patients, respectively.59
Similarly, serum titres of IgG autoantibodies correlated
with the severity of clinical signs of canine PF in two
recent reports from the same group.22,60
Finally, in one retrospective study, indirect IF testing
revealed circulating antikeratinocyte autoantibodies in 0/9
(0%) and 5/9 (56%) cats and horses with PF, respectively.6

Indirect immunofluorescence
The identification of circulating pemphigus autoantibodies
has been performed historically by means of indirect IF
testing of the animals sera. For many years, this tech-

Advanced immunological tests

Unfortunately, at this time, studies investigating the nature of
autoantigens and pathogenicity of circulating autoantibodies
of feline, equine and caprine PF have not been reported.

Immunopathology

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Figure 19. Canine PF. Only rare sera from dogs with PF recognize
canine dsg1 expressed ectopically on the surface of transfected 293T
human kidney cells. These results indicate that dsg1 is only a minor
antigen in dogs with PF (indirect IF, anticanine IgG-fluorescein).66

Figure 18. Canine PF. Serum IgG recognize antigen(s) present on the
membrane of superficial epidermal keratinocytes (arrowheads), and
also, in some patients, in the cytoplasm of basal and follicular
keratinocytes (arrows, bottom) (indirect IF, neonatal mouse skin
substrate).59

In contrast, the search for canine PF autoantigens has

been ongoing for over 15 years. Limited immunoblotting
studies first revealed that serum IgG autoantibodies from
two of two dogs with PF bound to a 148 kDa antigen
extracted from lip epithelium.61 In another study, autoantibodies from eight of 16 dogs were found to bind a 160 kDa
protein extracted from cultured normal canine keratinocytes.56,62 This 160 kDa antigen was identified also by the
serum of a human patient with PF.56 At first, these 148 and
160 kDa antigens were suspected to represent different
glycosylation states of canine desmoglein-1 (dsg1), the
homologue of the major PF antigen in humans.
From the late 1990s to mid-2000s, numerous attempts
were made to determine whether dsg1 was, indeed, the
main antigen in dogs with PF. The canine dsg1 gene was
cloned and sequenced, and it was found to encode a
peptide of 1055 amino acid identical in organization to the
human and bovine genes with highest homology existing
in the sequences of the aminoterminal EC1 and EC2
segments.63 The extracellular segment of canine dsg1
was produced using the baculovirus expression system.64
Remarkably, this recombinant protein was recognized by
sera from human patients with PF, but it was not identified
by IgG from any of the canine PF sera tested.62,65
Recently, human 293T kidney cells were transfected to
express ectopically membrane-bound canine dsg1. Indirect
IF staining established that only five of 83 canine PF sera
(6%) recognized canine dsg1-transfected human cells
(Fig. 19).66 When present, antidsg1 IgG autoantibodies
were found to target calcium and glycosylation-dependent
epitopes.66 In summary, at the time of this writing and in
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contrary to previous beliefs, dsg1 appears to be only a

minor autoantigen for canine PF.
A second desmosomal cadherin, desmocollin-1, was
pursued as a tentative autoantigen for PF in dogs. Canine
desmocollin-1 was cloned, sequenced and produced
ectopically in transiently transfected Chinese hamster
ovary cells.67 Unfortunately, sera from six dogs with PF did
not recognize canine desmocollin-1 isolated from transfected cells using immunoprecipitationimmunoblotting.67
Finally, two recent studies provided additional information relevant to the localization of putative canine PF antigen(s). In one dog with nondsg1-specific antikeratinocyte
autoantibodies, post-embedding immunoelectron microscopy confirmed the binding of IgG to the extracellular section of desmosomes.65 Finally, whatever the autoantigens
are, there is evidence for pathogenicity of canine PF IgG.
Indeed, the intradermal injection into neonatal mouse skin
of IgG isolated from the serum of three dogs with PF led
to acantholytic blistering below the stratum granulosum
(Fig. 20).68 Remarkably, acantholysis occurred in the
absence of neutrophil granulocytes in the vesicles.
In summary, at the time of this writing, the identity of
major canine PF antigen(s) remains unknown. The identification of these antigen(s) may lead to a more precise
reclassification of superficial pemphigus in dogs based on
clinical, histopathological and immunological knowledge.
Treatment and outcome
To date, immune suppression remains the initial therapeutic intervention of choice for PF in domestic animals. Of
note is that all recommendations for immunosuppression
initially were based on interventions used for treatment of
the human disease, and prospective clinical trials were not
performed to optimize protocols for animals. As a result,
information in the following paragraphs was collated almost
exclusively from retrospective case series. Historically,
standard-of-care treatment of canine PF relied on the
induction of immunosuppression with oral glucocorticoids,
such as prednisone or prednisolone, at daily dosages varying from 2 to 6.6 mg kg1 divided in one or two administrations.57,69 If lesions decreased in extent and severity
with this regimen, then the dose and /or administration

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

Superficial pemphigus in domestic animals

Figure 20. Canine PF. The intradermal injection of IgG from dogs with
PF into neonatal mouse skin results in subgranular blister formation,
thereby confirming the pathogenicity of serum autoantibodies
(haematoxylin and eosin).68

frequency of glucocorticoids was reduced with the goal of

rapidly achieving alternate day intake.5,69 In many canine
patients, however, glucocorticoid therapy alone appears
incapable in halting or slowing the progression of skin
lesions.5 In these cases, cytotoxic drugs are usually
added.5,6,69 Azathioprine (22.5 mg kg1, orally, once daily),
cyclophosphamide (25 mg m2, orally, once daily) or chlorambucil (0.2 mg kg1 every 24 48 h) have been proposed
as adjunct cytotoxic drugs.5,6,69 Alternatively, immune modulation with injectable aurothioglucose (1 mg kg1 week1)
was used two decades ago to treat dogs with unacceptable
side-effects of immune suppressive medications.5,6
Finally, rare dogs with PF exhibit lesions that respond to
tetracycline and niacinamide (250500 mg of each, three
times daily).7,70
In recent years, two small prospective open clinical trials
explored the efficacy of novel drugs for treatment of dogs
with PF. In a 16-week pilot study, eight subjects were
treated with mycophenolate mofetil at 20 40 mg kg1 per
day, divided in three daily doses.71 In three dogs, a reduction of lesional area and /or severity were seen. Four subjects
did not complete the study and two were euthanized.
Additionally, all dogs required concurrent glucocorticoid
therapy to control the severity of skin lesions.71 As a result
of high cost and limited proven benefit, there is currently
insufficient evidence for recommending this drug for treatment of canine PF.
Recently, a small pilot study evaluating the efficacy of
oral cyclosporin (5 10 mg kg1 once daily) in five dogs with
PF was reported.72 Four dogs did not complete the trial
because of perceived lack of efficacy. In one dog, there was
a transient reduction in lesional scores.72 Future studies
should evaluate whether this drug could be used as a
glucocorticoid-sparing agent, or whether higher dosages
are needed to induce lesion remission.
The treatment outcome of canine PF appears to be
variable, presumably because of variations in treatment
protocols and /or disease subtypes. In articles describing
cases seen in the 1970s and 1980s, 18 of 34 (53%)5 and
23 of 26 (88%) dogs with PF6 were reported to have been
managed successfully with the interventions mentioned
above.

More recently, 43 dogs with PF were seen at the University of Pennsylvania between 1994 and 2000.73 Of these
patients, only 17 of 43 subjects (40%) were still alive at the
end of the study period. Most dogs died during the first
year of treatment. Of the dogs that died, 18 of 26 (69%)
were euthanized because of lack of response of lesions to
therapy, poor quality of life or adverse effects of treatment.73 Interestingly, the addition of antibiotics during the
induction of immunosuppression was associated with a
significant improvement in survival rate in this cohort of
patients.73
In contrast to such results that suggest a poor outcome
following standard-of-care therapy with combined oral
immunosuppression, Rosenkrantz reported a 71% survival
rate after one year in 31 dogs with PF with only four dogs
euthanized because of poor response to therapy or treatment discontinuation with subsequent relapses.69 Similarly,
the latest series of 91 dogs with PF reported by Mueller
and colleagues provided additional data on favourable
treatment outcome.7 Of 88 dogs treated for PF, 46 underwent complete remission (52%), 31 (35%) achieved
partial remission of lesions, and only 11 (13%) were euthanized.7 Reasons for euthanasia included lack of response
to treatment (4/11; 36%), unacceptable side-effects of
medications used (2/11; 18%) and unrelated or unknown
causes.7 Complete remission was achieved with oral glucocorticoids in 15 of 39 dogs (38%) within 1.512 months
of treatment initiation (average: 7 months), and this occurred
with a glucocorticoidazathioprine combination in 18 of 33
dogs (55%) within 229 months (average: 12 months) of
starting therapy. Therefore, the addition of azathioprine did
not lead to a significant difference in the time needed to
achieve remission compared to the use of glucocorticoids
alone.7 In five dogs, however, the sole administration of
prednisolone was unsuccessful, and the addition of azathioprine led to complete lesion remission.7 Remarkably,
adverse drug events occurred significantly more often with
prednisoloneazathioprine combination than glucocorticoids
alone. These observations suggest that a prospective
study must be undertaken to determine whether or not
the addition of azathioprine offers any benefit to glucocorticoid monotherapy in dogs with PF.
In this series of dogs with PF, there were no significant
differences in either rate of complete remission or death
between dogs with facial localized vs. generalized lesions,
dogs treated with prednisolone alone vs. prednisolone and
azathioprine combination, or dogs treated with immunosuppression with or without antibiotics.7 In summary, the
review of treatment outcome in this cohort of dogs with
PF suggests that the benefit of azathioprine addition to
oral glucocorticoid regimens must be weighed carefully
against the cost of treatment monitoring and additional
risk to patients.
Finally, the persistence of long-term remission of canine
PF after discontinuation of immunomodulating therapy
has been reported in 722% of dogs with PF.31 Similar
results were obtained in two of 88 dogs (2%) in the most
recent case series. 7
In cats with PF, glucocorticoid monotherapy usually is
effective for achieving clinical remission. Historically, the
oral glucocorticoids of choice have been prednisone (4
5 mg kg1 daily) and triamcinolone (0.62 mg kg1 daily).9

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Olivry

Recent pharmacological data, however, have shown that

oral prednisone is not very well absorbed and /or converted into prednisolone in cats, therefore suggesting that
oral prednisolone is a better choice than prednisone in this
species.74 In cats whose PF lesions fail to respond to glucocorticoids, chlorambucil (0.2 mg kg1, orally, once daily)
is the cytotoxic drug most commonly used.9,75 Even though
azathioprine has been used successfully to treat cats with
PF40 this drug is no longer used widely as it is known to
cause profound neutropenia and thrombocytopenia in
feline patients.76 This abnormal sensitivity to azathioprine
may be due to their recently discovered lower activity of
thiopurine methyltransferase, an enzyme that metabolizes
azathioprine and whose deficiency can cause severe
myelosuppression.77,78 Sometimes, lesions of feline PF
respond to aurothioglucose.6
In one study, complete remission of PF lesions occurred
in 15 of 15 cats (100%) using triamcinolone alone, in eight
of 13 (62%) using prednisone alone, and in nine of 11
(82%) using a prednisone/chlorambucil combination.9 In
that series of cases, cats receiving triamcinolone exhibited
a higher rate of complete remission and a lower rate of
adverse drug events than those receiving a prednisone/
chlorambucil combination.9 Only four of 30 cats (13%) for
which long-term treatment outcome was known were
euthanized because of their disease or to treatment complications.9 In an older series of 10 cats with PF, treatment
with prednisolone was reported to be effective in six subjects
(60%) and with aurothioglucose in four patients (40%).6
Similarly to dogs and cats with this disease, lesions of
PF can be treated successfully in horses and goats with
either prednisolone or dexamethasone alone or in combination with aurothioglucose.6,12,15 As is seen in cats, prednisone may be of limited efficacy in horses due to its poor
absorption and/or biotransformation into prednisolone.79
In one of the retrospective studies, five of 13 horses
(38%) were euthanized for either lack of response of
lesions to treatment or development of steroid-induced
acute laminitis.12 Four of 11 horses (36%) remained in
remission for more than one year after immunosuppression lasting from three to 12 months was discontinued.12
In the second study, follow-up information was reported
for seven of 15 horses.11 Only one subject was euthanized
due to financial constraints, while the other horses achieved
remission with prednisone, prednisolone or aurothioglucose.11 In one horse, long-term remission was maintained
in the absence of treatment.11 Of note is that none of the
three published case series provided information substantiating the previously held belief that equine PF is of better
prognosis in young horses than in old subjects.
Conclusions: diagnosing pemphigus foliaceus in
domestic animals
In summary, at the time of this writing (June 2006), it is
apparent that canine PF appears to be clinically, histologically and immunologically heterogeneous with only rare
patients having autoantibodies targeting dsg1, the canine
homologue of the major human PF antigen. It is likely
therefore that the entity currently called canine PF may
not be a single disease, but a clinicopathological syndrome
regrouping several immunological variants. In many ways,
this situation is similar to the recent reclassification of
300

human cicatricial pemphigoid within the spectrum of

mucous membrane pemphigoid.80 Whether feline, equine
and caprine PF are immunologically heterogeneous currently remains unknown.
As a result, and until further studies allow a refinement
in the nosology of this syndrome, we propose that the
diagnosis of PF be based principally on clinico-pathological
grounds. Therefore, it is suggested that, at this time, the
diagnosis of PF be given to animals that suffer from a skin
disease satisfying ALL three criteria below:
1 Clinical examination: pustules rapidly evolving in
shallow erosions and crusts with predominance to
the face and feet
2 Histopathology: superficial epidermal or follicular
pustules rich in neutrophils and often-clustered
acantholytic keratinocytes
3 Differential diagnoses: rule out of other acantholytic
neutrophilic pustular diseases, especially exfoliatinassociated staphylococcal pyodermas and pustular
dermatophytosis due to corneophilic dermatophytes.

Pemphigus erythematosus
In humans, PE is a controversial clinically heterogeneous
entity that has been historically linked to both discoid
lupus erythematosus (DLE) and superficial pemphigus.81
Supporting the current concept that human PE in fact represents a variant of PF, immunological investigations have
confirmed the identity of the main human PE autoantigen
as dsg1, the major PF antigen.82,83 Additionally, serum
autoantibodies targeting the basement membrane zone
antigens bullous pemphigoid antigen 1 (230 kDa) and periplakin (190 kDa) have been identified in rare patients.83
The first mention of the existence of PE in animals was
in a general review article of immunological skin diseases
by Scott in 1978.84 Two years later, the same author included
previously reported cases in an article describing clinical,
histopathological and immunological characteristics of
four dogs and one cat with PE.85 In June 2006, the search
of several reference databases identified in addition to
the original princeps descriptions only one case series of
nine dogs6 and scattered case reports of canine39,86 90
and feline PE.91
In the largest case series, PE was reported to be the
third most common form of pemphigus seen at Cornell
University Veterinary Teaching Hospital, yet patients with
PE only accounted for less than one of 1000 dogs and cats
presented with skin diseases over 10 years.6 Unfortunately,
due to the scarcity of information on canine and feline PE,
detailed information on any breed, age and sex predisposition for this disease cannot be provided.
Clinically, dogs and cats with PE are reported to present
with pustules erosions and crusts localized to the face
and pinnae along with depigmentation, erythema and
erosion/ulceration of the nasal planum and dorsal muzzle
(Fig. 21).6,39,8591 Only rare patients exhibit nonfacial lesions.6
Microscopic examination of skin biopsies of dogs and cats
with PE reveals intragranular to subcorneal neutrophilic
and eosinophilic acantholytic pustules suggestive of PF
along with a lichenoid interface dermatitis that resembles
that of DLE.6,39,8591

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

Superficial pemphigus in domestic animals

Figure 21. canine PE. A 2-year-old collie

presented with a pustular, erosive and
crusting dermatosis bilaterally and
symmetrically distributed to the face (left)
and ears. Additionally, there were
depigmenting atrophic scars, erosions and
crusts on the dorsal nasal planum (right,
top) as well as depigmentation, scarring
and deep erosions/ulcers on the ventral
nares (right, middle and bottom).
Histological and immunological
characteristics resembled those previously
reported for canine PE.

On direct IF examination, skin biopsy specimens of

canine and feline PE uniquely exhibit both intercellular
epidermal pemphigus-like and basement membrane
lupus-like depositions of immunoglobulins with or without
activated complement.6 Of note is that not all dogs with
PE will have this basement membrane immunoreagent
deposition.6,85 Indirect IF performed with canine and feline
PE sera has remained negative for all patients tested.6,85
In contrast, low serum titres of antinuclear antibodies
(1 : 10 1 : 40) have been identified in approximately half
of sera from dogs with PE.6,85
The treatment outcome of canine and feline PE is
reported to be good, with lesions responding to immunosuppressive regimens used to treat patients with PF.6 In
one of two dogs with PE, the administration of a tetracycline
and niacinamide regimen resulted in a partial resolution of
clinical signs.70 The use of sun avoidance and sunscreens
has been advocated.6 Finally, topical treatment with 0.1%
tacrolimus ointment was reported to be of benefit, as an
adjunct medication, in two dogs with PE.89
In summary, the rare descriptions of canine and feline
PE published since 1980 have implied that this disease
represented an unusual facial-predominant dermatosis with
clinical, histopathological and immunopathological characteristics of both PF and DLE. As a result, the current dogma
is that PE might be a crossover between these two entities.
This concept must be considered controversial, however. Indeed, the rationale for previous individualization
of canine PE as an entity distinct from PF needs to be reexamined in light of recent knowledge suggesting that
both diseases exhibit very similar characteristics:
1 The predominance of skin lesions to the face is not
unique to PE, as facial lesions are identified also in
most dogs with PF, and they are restricted to this area
in 16% of canine patients with this disease.7
2 Photosensitivity is not specific for canine PE, as preliminary evidence suggests that this phenomenon
exists also for canine PF (see discussion in the PF
section).

3 Superficial acantholytic epidermal pustules are seen

in both canine PF and PE, while the presence of a
lichenoid interface dermatitis in the latter may only
reflect the nasal/paranasal location of skin biopsies in
dogs with PE. Indeed, dogs with various nasal dermatoses often exhibit a band-like diffuse superficial
plasmacytic to lymphoplasmacytic dermatitis with or
without basal cell damage.92
4 The observation of immunoglobulins and complement
at the basement membrane zone by direct IF is not
specific for lupus, as it is seen also in canine PF and
numerous other immune-mediated skin diseases.53,93
Moreover, serum antibasement membrane autoantibodies can be detected in some dogs with PF.58
5 The presence of low serum titres of antinuclear antibodies in dogs with PE is not unique to this entity
because of the recent observation that nearly 30% of
dogs with various phenotypes of PF also exhibit low
titres of serum IgG targeting nuclear antigens.58
6 Finally, PE cannot be individualized from PF on the
basis of differing treatment outcomes as a favourable
response to treatment is seen both in dogs with PE and
in canine patients with localized or generalized PF.7
In summary, at this time, there is insufficient evidence
supporting that canine PE is markedly different from localized facial PF either clinically, histologically, immunologically or prognostically. Additional studies are needed to
determine whether there would be any value for either
patients or clinicians in individualizing canine PE as a
separate entity, whether it should be reclassified as a
localized variant of PF, or whether it is a genuine crossover
between PF and DLE or other entities. Similarly, there is
not enough information on feline PE and PF to permit an
accurate separation between these two diseases.

Panepidermal pustular pemphigus

In 1994, Wurm, Mattise and Dunstan proposed the creation of a new entity named canine panepidermal pustular

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pemphigus to regroup cases previously diagnosed as

pemphigus vegetans and PE.94 The main criteria for diagnosing canine PPP were the demonstration of neutrophilrich and eosinophil-rich acantholytic pustules at all layers
of the epidermis and the suprabasal infundibular outer root
sheath epithelium.94 A considerable morphologic overlap
between PPP and PF in dogs was noted to exist, but the
main difference between these two entities was the
observation of pustules in the granular and upper spinous
layers in PF and the occurrence of these lesions throughout the epidermis in PPP.94
The rationale for creating an entity solely based on
histological grounds is subject to controversy. Indeed, as
noted above, there is current evidence of clinical, histopathological and immunological heterogeneity among
dogs diagnosed with PF, and the individualization of distinct
subsets of canine pemphigus must await the determination whether the identification of the various autoantigens
targeted provides a rationale for a revision of disease classification. Indeed, the observation of microscopic lesions
arising at different epithelial depth simply could be due to
variability in distribution of antigens targeted by autoantibodies at different body locations. This concept is best
illustrated by the recent discovery that, for example, dsg1
can be detected on keratinocytes of all epidermal layers in
the dorsal muzzle, pinna and footpads of dogs.95 In contrast,
dsg1 is visible only in the upper layers of canine shoulder,
groin or abdomen epidermis.95 Therefore, dogs with antidsg1
associated pemphigus would be more likely to exhibit
superficial lesions on the abdomen and groin and more
panepidermal lesions on the muzzle, ears and footpads.
In summary, at the time of this writing, there is little
evidence supporting the separation of canine PPP from the
main superficial pemphigus group (e.g. PF). Further studies
are needed to determine whether clinical, treatment
outcome and immunological information warrants the
individualization of PPP as a bona fide entity.

Conclusions
The last decades have seen the discovery of canine, feline,
equine and caprine homologues of superficial pemphigus
in humans. The 1980s and early 1990s saw the separation
of several subtypes of pemphigus (PF, PE and PPP)
because of minor differences in gross and microscopic
lesions. However, the recent observation of clinical, histological or immunological overlap between these three
entities and the discovery of marked heterogeneity among
dogs with PF suggests that, until further investigations
have characterized the major autoantigens in this group of
diseases, there is not enough evidence to warrant individualizing subsets within the superficial pemphigus group in
animals. The terminology of PF remains most appropriate
at this time, keeping in mind that this denomination might
represent a syndrome rather than a homogeneous entity.

Acknowledgements and funding

The author is grateful to Drs Gregg Dean, Luis Diaz, Toshiroh
Iwasaki, Eliane Mueller, Koji Nishifuji, Maja Suter, Simon
Warren and Zhi Liu for their past and current collaborations
in the field of canine pemphigus foliaceus research. Twelve
302

years of continuous technical support by Stan Dunston

also is acknowledged.

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Rsum Chez lhomme, la dnomination pemphigus regroupe un ensemble de dermatoses autoimmunes caractrises
par une sparation intrapidermique rsultant dun dtachement cellulaire par acantholyse. Ces entits sont classes en
se basant sur la profondeur du clivage pidermique, et des formes superficielles (pemphigus foliac, pemphigus IgA) et
des formes profondes (pemphigus vulgaire, pemphigus vegetant et pemphigus paranoplasique) sont dcrites. Chez les
animaux domestiques, des formes de pemphigus ont t rapportes depuis le milieu des annes 70 et la classification
animale ressemble celle utilise chez lhomme. Cet article dcrit les donnes rcentes sur lpidmiologie, les signes
cliniques, lhistopathologie, limmunopathologie et le traitement des pemphigus superficiels chez les animaux domestiques. Des donnes dtailles sur le pemphigus foliac canin, flin, quin et caprin, sur le pemphigus rythmateux canin
et flin et sur le pemphigus panpidermique pustuleux canin sont prsentes.
Resumen En humanos la denominacin pnfigo engloba un grupo de enfermedades vesiculares de la piel con separacin intraepidermal resultando en desunin intercelular y acantolisis. Las entidades se clasifican en base al nivel de formacin de vesculas en la epidermis, y tanto variantes superficiales (pnfigo foliceo, pnfigo con deposicin de IgA) como
profundas (pnfigo vulgar, pnfigo vegetativo y pnfigo paraneoplstico) son reconocidas. En animales domsticos,
variantes de pnfigo han sido reconocidas desde la mitad de la dcada de 1970, y la clasificacin de las enfermedades se
asemeja a la utilizada en seres humanos. Este artculo revisa el conocimiento actual sobre la epidemiologa, signos clnicos,
304

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Superficial pemphigus in domestic animals

histopatologa, inmunopatologa y resultados del tratamiento de las variantes de pnfigo superficial en animales domsticos.
Se ofrece asmismo una informacin detallada sobre pnfigo foliceo en perros, gatos, caballos y cabras, pnfigo eritematoso
en perros y gatos, y pnfigo pustuloso panepidermal en perros.
Zusammenfassung Beim Menschen umfasst die Pemphigus-Bezeichnung eine Gruppe von autoimmunen blasenbildenden Hauterkrankungen mit intraepidermaler Separation, welche aus einer Zell-Zell Loslsung durch Akantholyse
resultiert. Die Gruppen werden nach dem Ausma der Blasenbildung in der Epidermis eingeteilt, wobei sowohl oberflchliche
(Pemphigus foliaceus, IgA Pemphigus) als auch tiefe (Pemphigus vulgaris, Pemphigus vegetans und paraneoplastischer
Pemphigus) Varianten anerkannt sind. Bei Haustieren sind Untergruppen von Pemphigus seit der Mitte der 1970er Jahre
bekannt, und die Klassifizierung der Erkrankung ist jener hnlich, die fr humane Patienten verwendet wird. Dieser Artikel
berarbeitet das neueste Wissen in bezug auf Epidemiologie, klinische Symptome, Histopathologie, Immunpathologie und
Behandlungserfolge von oberflchlichem Pemphigus bei Haustieren. Detaillierte Informationen ber Pemphigus foliaceus
beim Hund, bei der Katze, beim Pferd und bei der Ziege, ber Pemphigus erythematosus beim Hund und bei der Katze,
sowie ber den panepidermalen pustulsen Pemphigus beim Hund werden geliefert.

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