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Blackwell Science, Ltd

Putative drug-related pemphigus foliaceus in four dogs

STEPHEN D. WHITE*, DIDIER N. CARLOTTI, DIDIER PIN,
TERRI BONENBERGER, PETER J. IHRKE*, ERIC MONET, KOJI NISHIFUJI,
TOSHIROH IWASAKI and MARK G. PAPICH**
*Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis,
California 95616, USA
Cabinet de Dermatologie Vtrinaire, Hliopolis B3, Avenue de Magudas, F-33700 Bordeaux-Mrignac,
France
Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis,
California 95616, USA
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State
University, Fort Collins, Colorado 85023 USA
Department of Veterinary Internal Medicine, Tokyo University of Agriculture and Technology, Tokyo
1838509, Japan
**Department of Anatomy, Physiological Sciences and Radiology, College of Veterinary Medicine, North
Carolina State University, Raleigh, North Carolina 27606 USA
(Received 17 May 2001; accepted 31 January 2002)

Abstract Four dogs developed cutaneous lesions following the administration of various antibiotics. Histopathology of the lesions was compatible with pemphigus foliaceus, although apoptotic cells suggestive of erythema
multiforme were seen in two cases. In two dogs the lesions resolved after 7.58.5 months of immune-suppressive
treatment. No recurrence was seen during the follow-up period (3 and 4.5 years). The lesions in the other two
dogs resolved within 3 weeks to 3 months following discontinuation of the antibiotic. No recurrence of clinical
signs occurred during the follow-up period (1 and 4 years, respectively).
Keywords: adverse drug reaction, antibiotics, dogs, pemphigus foliaceus, skin lesions.

INTRODUCTION

CASE REPORTS

Canine pemphigus foliaceus is an autoimmune

antibody-mediated skin disease whose aetiology is
unknown, although a genetic predisposition in some
breeds has been noted.13 Circulating autoantibodies
have been recognized in dogs with pemphigus
foliaceus, and may share at least one of the same target
proteins (desmoglein 1) as in the disease in humans.4
Pemphigus foliaceus caused by the administration of
certain drugs has been a well-recognized disease entity
in humans but reports in dogs are rare.57 In people,
drug-related pemphigus may be categorized as
either drug-induced (in which case discontinuance of
the drug leads to regression of the disease) or drugtriggered (in which the drug is felt to have stimulated
an inherent predisposition to the disease).5,8 This
report describes four cases of putative drug-related
pemphigus foliaceus in dogs.

Case 1
A 4-year-old-male Cocker Spaniel weighing 15 kg was
examined at the Cabinet de Dermatologie Vtrinaire
(CDV) for a complaint of a severely pruritic dermatitis
of less than 3 weeks duration. Prior to the onset of
the dermatitis, the dog had developed a local pruritic
reaction to an antiparasitic collar of unknown composition. The referring veterinarian had treated the
dog with trimethoprimsulfamethoxypyridazine, griseofulvin, betamethasone, dexchlorpheniramine maleate
(an antihistamine) and dexamethasone. The dermatitis
started 45 days after these drugs were administered.
The latter two drugs caused some sedation and
improvement in the initial pruritus, but the dermatitis
itself continued to become generalized.
Physical examination showed a depressed dog with
generalized crusting, erythematous macules, arciform
and polycyclic plaques, papules, rare pustules and
truncal alopecia (Figs 13). Differential diagnoses
included erythema multiforme, pemphigus foliaceus,
cutaneous drug reaction, cutaneous neoplasia or
infectious folliculitis/furunculosis due to bacteria,
dermatophytes or Demodex canis mites. Skin biopsy
findings showed superficial pustules with acantholytic
keratinocytes, apoptosis throughout the epidermis,

Correspondence: Stephen D. White, Department of Medicine and

Epidemiology, School of Veterinary Medicine, University of
California, Davis, CA 95616, USA. Fax: +1 530 7520414; E-mail:
sdwhite@ucdavis.edu
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Figure 3. Case 1. Intact pustule, left lateral thorax.

Figure 1. Case 1. Cocker Spaniel with generalized crusts, erythema
and truncal alopecia.

Figure 2. Case 1. Skin lesions from left lateral thorax, erythematous

macules and crusts.

neutrophilic satellitosis and a mild diffuse dermal

infiltrate of lymphocytes, plasma cells, neutrophils and
eosinophils (Fig. 4). No dermatophytes were detected
in periodic acid-Schiff (PAS) stained sections.
All systemic drugs were discontinued. Treatment
consisted of daily chlorhexidine soaks and prednisolone (2 mg kg1 q24 h for 7 weeks, then 1 mg kg1
q24 h for 3 weeks). The dog improved with treatment,
and the prednisolone was discontinued after a total
of 2.5 months. One month after prednisolone treatment
was discontinued, the dog developed hyperpigmentation,
lichenification and pustules; clinical signs had recurred.
Azathioprine treatment was started (1.7 mg kg1
q24 h) and continued for 4 months, at which time all
lesions had resolved and treatment was discontinued.
There has been no recurrence of clinical signs for
4.5 years.
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Figure 4. Case 1. Skin, left lateral thorax. Notice acantholytic

keratinocytes in the subcorneal pustule (H&E 400).

Case 2
A 5.5-year-old female Griffon Venden weighing 20 kg
had been presented at the referring veterinarian for
otitis, rhinitis and dysphagia. Cephalexin (15 mg kg1
PO, q12 h) had been prescribed (this drug had been
administered a few months before to the patient for the
same reason). After 8 days of cephalexin treatment, the
dog developed an erythematous, crusting dermatitis
of the face, ears, perineum and axillae. Over the next

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197

Figure 5. Case 2. Griffon Venden. Skin from dorsum. Notice apoptotic

keratinocytes at various levels in the epidermis (arrows) (H&E 250).

10 days, the condition became more generalized and

the dog developed oral mucosal ulcers.
On physical examination at the CDV the dog was
depressed and febrile (40.5 C, 105F). The dorsal muzzle,
periocular and perioral regions were erythematous
with encrusted erosions. Ulcers were present on the
oral mucosa, tongue, pinnae, and perianal and perineal
regions. Papules and follicular casts were seen on
thoracic and dorsal abdominal skin, and crusts were
noted in the axillae. The footpads were thickened. The
dermatitis was painful to the dog when touched.
Differential diagnoses included pemphigus foliaceus,
cutaneous drug reaction, infectious folliculitis/
furunculosis, erythema multiforme, cutaneous lymphoma
or sebaceous adenitis.
Due to an oversight, oral lesions were not biopsied.
Skin biopsy findings were similar to those of Case 1 as
well as showing mural follicular pustules with acantholytic keratinocytes (Fig. 5).
Cephalexin administration was discontinued and the
dog was treated with a keratolytic shampoo (SeboluxTM,
Virbac: Carros, France), a humectant (HumilacTM, Virbac:
Carros, France) and prednisolone (2 mg kg1 q24 h).
Complete healing of lesions was noted after 7 weeks of
treatment. The prednisolone dose was tapered slowly
over the course of the next 8.5 months, at which time it
was discontinued. The owners were concerned about
the possibility of a relapse and requested this slow
reduction of dosage. There has been no recurrence of
clinical signs for 3.5 years.
Case 3
A 1-year-old female spayed Labrador Retriever weighing 32 kg was examined at the referring veterinarian

Figure 6. Case 3. Labrador Retriever. Crusts on face and forelegs.

for multiple draining abscesses on the neck and face.

Treatment was started with trimethoprimsulfadiazine,
30 mg kg1 PO, q12 h. This had no effect on the abscesses,
but within 3 days the dog developed a generalized
crusting dermatosis. The referring veterinarian changed
the antibiotic treatment to doxycycline and ceftiofur
(doses unknown). This had no immediate effect on the
dermatitis and the case was referred to the Veterinary
Teaching Hospital at Colorado State University
(VTH-CSU).
Physical examination showed an alert dog with
multiple draining abscesses on the neck and face, and
generalized crusts of the skin surface, especially on the
face, dorsum and legs (Fig. 6). Differential diagnoses
included infectious folliculitis, cutaneous drug reaction
and pemphigus foliaceus. Cytology of the exudate under
the crusts showed multiple acantholytic keratinocytes
and neutrophils. Histology of the skin biopsy showed
subcorneal pustules with neutrophils and acantholytic
keratinocytes. A scattered dermal infiltrate of neutrophils
was present, with higher numbers noted around
sebaceous glands. No dermatophytes were detected in
PAS-stained sections.
While the dog was anaesthetized, the abscesses
were explored and surgically drained. Bacterial culture
of the abscesses grew Pseudomonas fluorescens; the
infection responded to the surgical drainage and
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S. D. White et al.

1 month of enrofloxacin at 10 mg kg1 PO, q24 h.

The crusting dermatitis resolved within 3 weeks
following the discontinuation of the trimethoprimsulfadiazine. No recurrence of clinical signs has been
noted in 4.5 years.
Case 4
A 4.5-year-old-male American Staffordshire Terrier
weighing 38 kg was examined by the referring
veterinarian for pododermatitis due to demodicosis;
multiple adult and juvenile Demodex canis mites were
demonstrated on skin scrapings. The dog was treated
with ivermectin (0.4 mg kg1 PO, q24 h) and enrofloxacin (dose unknown) for 4 months; during the
month prior to referral the antibiotic treatment had
been changed to trimethoprimsulfamethoxazole
(25 mg kg 1 q12 h). Physical examination at the
Veterinary Medical Teaching Hospital, University of
California, Davis (VMTH-UCD) revealed a severe
pododermatitis with haemorrhage and exudation of
all four paws. No Demodex canis mites were found
on skin scrapings. The owner did not feel that the
pododermatitis had improved in response to the referring veterinarians treatment regimen. The ivermectin
dose was increased to 0.6 mg kg1, and the antibiotic
treatment was changed to oxacillin (25 mg kg1,
q8 h) based on the results of a bacterial culture and
susceptibility performed previously by the referring
veterinarian (prior to the use of the trimethoprim
sulphonamide).
During the first month of treatment with oxacillin,
the owner reported by telephone that while the
pododermatitis was improving, the dog had developed
new lesions on the dorsal trunk. After 2 months of
treatment with oxacillin the dog was re-examined at
the VMTH-UCD. Physical examination revealed
generalized erythema with papules, pustules and
fistulas with purulent exudate and crusting involving
the entire dorsum and lateral thighs. Differential
diagnoses included pemphigus foliaceus, cutaneous
drug reaction and infectious folliculitis. A skin biopsy
specimen of the truncal lesions showed thick layered
serocellular crusts and pustules filled with intact
neutrophils, occasional eosinophils and small numbers
of both angular and rounded acantholytic keratinocytes.
In the superficial dermis, neutrophils were seen in the
lumen of vessels and migrating through the walls to
the overlying epidermis. There was vascular thickening
due to the intensity of the inflammation but no leucocytoclasia, actual vessel wall damage or thrombosis. A
skin biopsy of the pododermatitis showed severe
dermal fibrosis, chronic furunculosis and moderate,
multifocal panniculitis; no Demodex canis mites were
seen. No dermatophytes were detected in PAS-stained
sections. A bacterial culture and susceptibility of the
pododermatitis showed Staphylococcus intermedius
sensitive only to aminoglycosides and trimethoprim
sulphonamides.
A drug-related pemphigus foliaceus was suspected,
and the oxacillin and ivermectin treatment was
2002 Blackwell Science Ltd, Veterinary Dermatology, 13, 195 202

discontinued. The antibiotic was changed to trimethoprimsulfamethoxazole (40 mg kg1 q12 h), and pentoxifylline
(10 mg kg1 q12 h) was dispensed in order to increase
vascular flow to the affected paws.9 Over the next
3 months the truncal crusts and papules resolved. Two
months after resolution of the clinical signs of the
pemphigus foliaceus, the pododermatitis still had not
improved and a low dose of prednisone (0.5 mg kg1
q24 h for 14 d, then q48 h) was administered. This
resulted in an immediate improvement in clinical signs
of the pododermatitis. The dog was maintained on this
dose for 7 months at which time it was discontinued.
There has been no recurrence of the clinical signs of
either the pemphigus foliaceus or the pododermatitis
for 1.5 years.

IMMUNOLOGICAL STUDIES
Serum collected at initial presentation was available
from Cases 2 and 4 and was tested for the presence of
immunoreactivity (autoantibodies) against the surface
of living canine keratinocytes (IgG, IgM, IgA and
C3).4 No antibodies were detected in either dogs sera.
Paraffin-embedded sections of Cases 1, 3 and 4 were
available for direct immunofluorescence (DIF) testing
for the presence of immunoglobulin (Ig)G, IgM, IgA
and C3, using a previously described method.10 In
Case 1, DIF testing showed diffuse intercellular faint
deposition in 2 out of 4 sections for IgG. Testing in Case
3 showed diffuse intercellular moderate deposition in
2 out of 6 sections for IgG (with occasional dotted
intrakeratinocyte fluorescence), diffuse intercellular
faint deposition in 2 out of 6 sections for IgM, and diffuse intercellular faint deposition, with an occasional
dotted pattern, in 2 out of 6 sections for C3. Case 4
showed diffuse intercellular faint to strong (most
marked in the stratum spinosum) deposition in 8 out of
8 sections for IgG (with occasional dotted intrakeratinocyte fluorescence) (Fig. 7), multifocal to diffuse
intercellular faint deposition in 3 out of 8 sections for
IgM, and multifocal to diffuse intercellular faint
deposition in 3 out of 8 sections for C3.

DISCUSSION
Drug-related pemphigus in people may be either pemphigus foliaceus or pemphigus vulgaris; it is uncertain
which form may be the more common.5,11,12 Most
implicated drugs such as penicillamine contain a thiol
group ( SH), or are drugs such as gold that contain a
disulphide bond which readily releases SH groups.8,11
Some nonthiol drugs contain sulphur in their molecule;
in some of these drugs the sulphur may undergo
metabolic transformation to form thiol groups. Such
drugs have been termed masked thiols and include
the penicillins and cephalosporins.5,8,11 Increasingly,
nonthiol drugs, especially enalapril, which lack sulphur
also have been implicated.13

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Drug-related pemphigus in dogs

Figure 7. Case 4. American Staffordshire Terrier. Skin from dorsal

trunk. Notice diffuse intercellular immunofluorescence, faint to
strong deposition for IgG, most marked in the stratum spinosum.
Direct
immunofluorescence
with
anticanine
IgG-FITC,
bar = 25 m. Courtesy of Dr Thierry Olivry.

The primary hypothetical mechanism by which the

thiol groups are thought to cause acantholysis is the
binding of the drugs to the cell membrane. This is
followed by the formation of anomalous disulphides
that are inadequate for maintenance of normal cell
cell adhesion; these anomalous disulphides may also
change the conformation of cellsurface antigens,
leading to autoantibody production.14 Autoantibodies,
in the skin or in the serum, have been noted in some
but not all cases in humans with drug-related pemphigus.5,10,1518 These antibodies recognize antigens that
are identical to those in the idiopathic forms of pemphigus foliaceus or pemphigus vulgaris.15 The presence
of autoantibodies is not dependent on the presence of
a thiol group in the offending drug.8
Experimental data have indicated other potential
mechanisms of thiol group acantholysis, including
impairment of plasminogen activator inhibitors and
inhibition of enzymes necessary for the process of
keratogenesis.18,19 This latter mechanism has also
been shown to be a likely method by which enalapril (a
nonthiol drug) causes acantholysis. In both nonthiol
and some thiol drugs, the presence of an active amide
group has also been hypothesized to contribute to the
induction of pemphigus.20 Humans with drug-related
pemphigus may have received the suspect drug 12 days
to as long as 10 months prior to the onset of the disease;
thiol drugs may have longer incubation time.8,11
Diagnosis is based on a thorough history, but may be
augmented with in vitro tests that demonstrate a hypersensitivity response to the inducing drug, such as the
mast cell degranulation and the macrophage migration
inhibition tests.5,8,11
Reports of drug-related pemphigus foliaceus are
rare in small animals: four cases have been reported

199

in dogs and three in cats. 6,7,2123 In all four dogs,

trimethoprim-sulphonamides (sulfadiazine in three
cases, sulfamethoxazole in one case) were implicated,
although this may reflect the bias of the reports, which
dealt solely with trimethoprimsulphonamide-induced
drug reactions. In the cats, doxycycline, ampicillin and
cimetidine were implicated. Skin lesions regressed in all
animals following discontinuation of the suspect drug;
in three dogs and one cat, a short course (1 week to
1 month) of corticosteroid treatment was also given. In
one of the dogs given sulfadiazine, and in the two cats
given doxycyline or cimedatine, inadvertent readministration of the suspect drug, which varied from 10 days
to 6 months after initial drug withdrawal, resulted in a
recurrence of clinical signs. Direct immunofluorescence
was performed on the skin of two of the dogs and two
of the cats. Only the cat with the suspected drug
reaction to ampicillin had findings consistent with
pemphigus foliaceus, with IgG binding to the cell
membranes in the superficial layers of the epidermis,
although one dog had deposition of IgG antibodies
along the dermalepidermal junction which has been
noted in a small percentage of drug-induced pemphigus
cases in humans.6,8,22 The cat with the reaction to
doxycycline had evidence of hypersensitivity to the
drug utilizing a basophil degranulation test.23
The drug-induced aetiology for the four dogs reported
here must be regarded as putative, as no rechallenge
using the suspect medications was attempted. A
drug exposure scoring system for diagnosis of a
drug-induced aetiology has been adapted for dogs.24
This assessment scheme relies heavily on recurrence of
lesions on rechallenge as well as resolution of lesions
upon discontinuation of the drug (without using other
medications).24 These criteria were not applicable in
our cases for humane considerations.
Our diagnoses were based on history (especially
temporal association between the administration of
the suspect drug and the onset of the dermatitis), clinical signs, histopathology and response to withdrawal of
the suspect drug. Cephalexin, trimethoprimsulfadiazine
and oxacillin are strongly suspected in Cases 2, 3 and 4,
respectively, as these are the drugs whose administration
was rapidly (3 days to 1 month) followed by the occurrence
of the skin disease. To our knowledge, Cases 3 and 4
had not received these drugs previously. In Case 4, the
increase in ivermectin dosage could also be implicated,
but seems less likely, as the dog had already been
exposed to this medication over the course of several
years with no adverse reactions reported. The suspect
drug in Case 1 is less clear, but is probably trimethoprim
sulfamethoxypyridazine, griseofulvin being less likely
for reasons to be discussed.
Assessment of the suspect drugs in our cases plus
those of dogs and cats in previous reports reveals that
all the suspect drugs have either a sulphur atom (and
presumably subsequent thiol group formation) and/or
an amide group. The sulphonamides, ampicillin, oxacillin
and cephalexin have both sulphur atoms and at least
one amide group in their structure; cimetidine has a
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S. D. White et al.

sulphur atom and doxycycline has an amide group.25

Griseofulvin has none of these attributes, and thus
according to the aforementioned hypotheses, is less
likely to be the causative drug in Case 1.25
Interestingly, despite the predominance of the
trimethoprimsulphonamide combinations as potential
or proven pemphigus-inducing drugs in the dogs of
this and earlier reports, they are not mentioned in three
lists of drugs implicated in causing pemphigus in
humans.5,8,11 The reason for this is unclear, but may be
due to differing metabolism between the two species. In
humans, sulphonamide drugs are metabolized in the
liver by three mechanisms: N-acetylation, glucuronide
conjugation and aromatic hydroxylation. Dogs and
wild canids are unable to detoxify by N-acetylation, and
other metabolic routes therefore become more important.26
This leads to increased formation of sulphonamide
hydroxylamine, a cytotoxic metabolite, which can in turn
degrade to an even more reactive molecule, the nitroso
metabolite.27 Nitroso metabolites of sulphonamides
bind to tissue proteins forming drugprotein complexes.
Antibodies to these drugtissue protein complexes have
been found in human patients with sulphonamide
hypersensitivity.28 Oxidation of sulphonamides to
hydroxylamine and subsequently the nitroso metabolite
thus increases the immunogenicity of these drugs.27
The clinical signs of our cases are similar to those
reported previously, consisting of papules, pustules,
crusts and erythema, which rapidly became generalized.6,7
Histopathology showed subcorneal or follicular lumen
pustules with neutrophils and acantholytic keratinocytes.
While other diseases may cause acantholysis, it is the
pemphigus group of diseases that has this finding as its
hallmark.18 Our cases were judged to be more typical of
pemphigus foliaceus than of bacterial infection by
previously reported guidelines: larger number of acantholytic keratinocytes, larger pustules bridging multiple
hair follicles, recornification and reformation of pustules,
and occasional rafts of acantholytic keratinocytes.29
Infection with a Trichophyton species, which have been
reported to cause acantholysis in the dog, was less
likely because of the absence of fungi in PAS-stained
sections, as well as the response to treatment.30,31
The finding of apoptosis in all levels of the epidermis, suggestive of erythema multiforme in Cases 1
and 2, may be another histological manifestation of a
drug reaction.32 Alternatively, in humans, necrotic foci
of keratinocytes may be seen in both drug-induced and
idiopathic pemphigus; in general, histopathology
can not distinguish between the two aetiologies.33
Pemphigus foliaceus in dogs may also show apoptotic
keratinocytes (Gross, personal communication 2001).
Interestingly, pemphigus-like IgG autoantibodies were
found in a dog that had both clinical and histological
diagnoses of erythema multiforme due to treatment
with trimethoprimsulfamethoxazole.34 It seems likely
that the unbiopsied oral lesions in Case 2 are more
suggestive of erythema multiforme, as pemphigus foliaceus in dogs seldom, if ever, involves the oral cavity.2
Further, an emerging concept in the study of human
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pemphigus termed the desmoglein compensation hypothesis holds that antibodies to desmoglein 1 can only
disrupt the epidermis in places that desmoglein 3 (the
target protein of pemphigus vulgaris) are not expressed,
such as the superficial epidermis.35 As desmoglein 3 is
expressed throughout the human oral mucosal epithelium, the hypothesis maintains that oral lesions would
not occur due to antibodies to desmoglein 1.35,36 The applicability of this hypothesis in dogs remains to be proven.
A recent report states that exfoliative toxin A,
produced by Staphylococcus aureus in humans with
bullous impetigo and staphylococcal-scalded-skin
syndrome, also targets desmoglein 1.37 None of our
cases exhibited clinical or histological signs consistent
with these diseases, as reported in dogs.38 40
There are several possible reasons for the fact that
the sera obtained from Cases 2 and 4 did not show
antibodies to the surface of living canine keratinocytes.
The sera from Case 2 was stored for 3 years, which may
have adversely affected the antibodies survival. In
Case 4, the serum was not obtained until 9 months
after resolution of clinical signs. The concentration of
antibodies at that point may have been too low to
detect. The low dose of prednisone that Case 4 was
receiving may also have interfered with the test. As
mentioned previously, not all cases of drug-induced
pemphigus in humans have autoantibodies and, when
present, the titres may not parallel the severity and
extent of disease activity.17 However, it is interesting
that of the three dogs whose paraffin blocks were tested
for the presence of tissue-bound autoantibodies, all
three had varying degrees of positive IgG staining, and
two also had IgM and C3 deposition. Whether these
autoantibodies are a response to the unmasking of
the cellular antigens by the drug-caused acantholysis
as hypothesized in humans is unknown.14
In humans, drug-related pemphigus is further
categorized as either drug-induced pemphigus or drugtriggered pemphigus. In patients with drug-induced
pemphigus the drug plays the major role and the disease
regresses once the drug is discontinued.5,8 In contrast,
in drug-triggered pemphigus the drug is felt to have
stimulated a predisposition (endogenous, genetic, hereditary and/or immunological); in such cases the disease
usually does not spontaneously resolve following withdrawal of the triggering drug, rather it has the same
course as spontaneously occurring pemphigus.5,8,11
Cases 3 and 4 are clearly in the drug-induced category,
as the lesions spontaneously resolved once the offending
drug was discontinued. Cases 1 and 2 are more problematic
to classify, as they required the continual treatment of
immune-suppressive medication for 7.58.5 months in
order to control the disease; however, after this period
of time, the medications were discontinued and the
disease did not recur. Such a nonrecurrence of spontaneously occurring generalized pemphigus foliaceus can
occur, albeit rarely, in the dog (Olivry, personal communication 2001). At this time, details of such cases
have not been reported in the veterinary literature.
Perhaps in dogs the triggering mechanism may be

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Drug-related pemphigus in dogs

permanently disengaged after a sufficient period of
immune-suppressive treatment; alternatively, some
cases of canine drug-induced pemphigus may need
such treatment, but only for a limited time. Similar
cases have been reported in humans.41
In conclusion, this report provides further evidence
that some cases of pemphigus in dogs may be drug
related. Future studies are needed to delineate the
existence and specificity of autoantibodies and to define
the relevance of individual necrotic keratinocytes in
pemphigus foliaceus lesions as a possible indicator of a
drug-related aetiology.

ACKNOWLEDGEMENTS
The authors thank Dr Thierry Olivry for performing
the immunohistology studies and Dr Kimberly
Boyanowski for obtaining the serum of Case 4.

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Rsum Quatre chiens ont t prsents pour des lesions cutanes apparues aprs ladministration de divers
antibiotiques. Lexamen histopathologique des lsions tait compatible avec un pemphigus foliac, bien que dans
deux cas des cellules apoptotiques suggraient un rythme polymorphe. Les lesions ont disparu chez deux chiens
aprs 7.5 8.5 mois de traitement immunosuppresseur. Aucune rcidive na t note durant le suivi (3 et 4.5 ans).
Pour les deux autres chiens, les lesions ont disparu entre 3 semaines et 3 mois aprs larrt de ladministration de
lantibiotique. Aucune rcidive na t observe pendant la priode de suivi (1 an et 4 ans respectivement).
Resumen Cuatro perros desarrollaron lesiones cutneas despus de la administracin de diferentes antibiticos.
La histopatologa de las lesiones era compatible con pnfigo foliceo, aunque tambin se observaron en dos casos
clulas apoptticas sugestivas de eritema multiforme. En dos perros, las lesiones se resolvieron despus de
7.58.5 meses de terapia inmunosupresora. No se observaron recidivas durante el seguimiento (3 y 4.5 aos). Las
lesiones en los dos perros restantes se resolvieron en 3 semanas a 3 meses despus de retirar la antibioterapia.
No se produjeron recidivas de los sntomas clnicos durante el seguimiento (1 y 4 aos, respectivamente).
Zusammenfassung Vier Hunde entwickelten Hautlsionen nach der Gabe unterschiedlicher Antibiotika. Die
histopathologischen Befunde waren kompatibel mit einer Diagnose von Pemphigus foliaceus, obwohl in zwei
Fllen apoptotische Zellen auffielen, die auf Erythema multiforme hindeuteten. Bei zwei Hunden verschwanden
die Lsionen nach 7,5 bis 8,5 Monaten immunosuppressiver Behandlung. Whrend des weiteren Beobachtungszeitraums von 3, beziehungsweise 4,5 Jahren trat kein Rezidiv auf. Die Lsionen der beiden anderen Hunde
gingen innerhalb von 3 Wochen bis 3 Monaten nach dem Absetzen des Antibiotikums zurck. Innerhalb des
weiteren Beobachtungszeitraums von einem Jahr, beziehungsweise 4 Jahren trat kein Rezidiv auf.

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