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Canine Pemphigus
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Pemphigus Foliaceus (PF)
results from the immune system "attacking" the adhesions between the
skin
cells. This results in several skin signs including pustules, scale,
crusts,
red skin, erosions, erosions and hair loss. Any part of the pet's skin
may
be affected. The footpads and mucous membranes are also sometimes
affected.
The PF lesions may be uncomfortable, itchy and/or painful. Sometimes
pets
with PF may be lethargic or depressed and/or have a fever and/or a poor
appetite.
Bacterial skin infections may be present concurrently. Definitive
diagnosis
requires tissue biopsies of the affected area(s). Therapies for
patients
with PF often often involve suppressing or modulating the immune
system.
The best therapies for your pet will be determined by our veterinary
dermatologist.
What is Pemphigus?
Canine Pemphigus Vulgaris
Pemphigus covers a group of
uncommon disorders that occur in dogs. With these conditions, there is
an abnormal immune response to normal components of the skin, resulting
in separation of cells. This leads to blisters, pustules, and crusting
erosions in the skin. There are some similarities to pemphigus in
humans, but many significant differences as well.
Breed predispositions are recognized for 2 forms - pemphigus foliaceus
and the milder pemphigus erythematosus. (There are no breed
predispositions recognized for the other 2 forms - p. vulgaris and p.
vegetans).
How is pemphigus inherited?
unknown
What breeds are affected by pemphigus?
pemphigus foliaceus: bearded collie, akita, Doberman
pinscher, Newfoundland, Schipperke
pemphigus erythematosus: collie, German shepherd and
German shepherd crosses
For many breeds and many disorders, the studies to determine the mode
of inheritance or the frequency in the breed have not been carried out,
or are inconclusive. We have listed breeds for which there is a
consensus among those investigating in this field and among veterinary
practitioners, that the condition is significant in this breed.
What does pemphigus mean to your dog & you?
Pemphigus foliaceus and erythematosus develop around 4 years of
age. P. erythematosus is thought to be a milder form of
p. foliaceus. Both conditions begin with pustular, crusty lesions on
the face and ears. However with p. foliaceus, the lesions spread to the
feet, the groin and other areas; there may be itching and pain; and
severely
affected dogs may lose their appetite and become depressed.
Loss of pigment in the nose is common with both forms of pemphigus, and
this results in photodermatitis - increased sensitivity to the
sun's rays so that the condition is worse in sunny weather.
How is pemphigus diagnosed?
P. foliaceus is the most commonly seen form of pemphigus; however it is
still uncommon. Your veterinarian will base the diagnosis on your
history of how the condition developed, physical examination of your
dog, and tests such as skin scrapings and smears, skin biopsy, and
immune testing to rule out other causes of similar skin lesions such as
a bacterial or fungal skin infection, mites, seborrhea,
dermatomyositis, and lupus erythematosus.
For the veterinarian: Multiple skin biopsies will increase the
chances of finding diagnostic histologic changes. Direct
immunofluorescence or immunohistochemical testing may or may not be
helpful. These tests have relatively low sensitivity and specificity.
How is pemphigus treated?
Treatment is based on suppressing the inappropriate immune response.
For pemphigus foliaceus, steroids (as a cream, or orally as a tablet -
prednisone) are used to accomplish this. Once the condition is under
control, your veterinarian will reduce the dosage to every second day
to avoid the side effects which can occur with these drugs. Long term
treatment
is generally necessary. Where prednisone is not effective (as is
sometimes
the case), your veterinarian will try other immunomodulating drugs or
chrysotherapy (gold salts).
For dogs that have lost pigment in the nose, protection against the sun
is important to prevent flare-ups of the condition. Keep your dog out
of the sun between 10:00 and 3:00 and/or use suncreens on the
nose with SPF of 15 or higher.
The milder form, pemphigus erythematosus, may be successfully treated
with sun avoidance and glucocorticoids applied to the skin.
If this is ineffective, oral glucocorticoids or other drugs may be
required.
For the veterinarian: A combination of tetracycline and
niacinamide has been used with some success in dogs with p.
erythematosus (Scott, 1995 below).
Breeding advice
It is advisable not to use affected dogs in breeding programmes, even
though inheritance for these conditions has not been worked out.
FOR MORE
INFORMATION ABOUT THIS DISORDER, PLEASE SEE YOUR VETERINARIAN.
Resources
Scott, D.W., Miller, W.H., Griffin, C.E. 1995. Immunologic Skin
Diseases. In Muller and Kirk's Small Animal Dermatology. p. 500-518.
W.B. Saunders Co., Toronto.
Copyright © 1998 Canine Inherited Disorders Database. All rights
reserved.Revised: July 23, 2001.
This database is a joint initiative of the Sir James Dunn Animal
Welfare Centre at the Atlantic Veterinary College, University of Prince
Edward Island, and the Canadian Veterinary Medical Association.reprinted with kind
permission from:-
Alice
Crook, DVM,Coordinator, Sir James Dunn Animal
Welfare Centre, Atlantic Veterinary College,University of Prince Edward
Island, 550 University Ave.Charlottetown, PEI C1A 4P3
http://www.upei.ca/cidd
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Canine pemphigus vulgaris
Autoimmune mediated
skin diseases can be classified in two major groups, bullous processes
and non-bullous ones (Carlotti 1989, Halliwell and Gorman 1989),
including the first group the pemphigus complex -pemphigus vulgaris,
pemphigus foliaceus, pemphigus erythematosus and pemphigus vegetans-
and the bullous pemphigoid. According to Muller and others (1989)
canine and feline pemphigus represented about 0.3% of the skin diseases
observed at the New York State College of Veterinary Medicine being
consequently uncommon in domestic animals.
The present report describes a case of canine pemphigus vulgaris. Some
points of the difficulty for the practitioner to get a definitive
diagnosis in autoimmune skin diseases, and its possible treatment are
discussed.
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Pododermatitis
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Pinna: crusts
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Case report
The dog was a female spanish mastiff aged three years, weighing 45 kg.
Her owner had observed that she was apathetic and anorectic one week
ago, and that she had non-pruritic skin lesions.
We observed a depressed animal, with a rectal temperature of 41°C,
and skin lesions involving nasal and submandibular areas, pinna,
breast, axillae and abdomen.
Skin lesions included escoriations, pustules, most of them broken,
appearing consequently epidermal collarettes and yellowish crusts;
occasionally, there were some vesicle among the lesions mentioned
above. In oral mucosa it was observed some vesicle localized on lips,
without any other lesions.
At otoscopy exploration no lesions were observed on the external ear
mucosa. Retropharyngeal and submandibular lymph nodes were slightly
enlarged.
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Axillae: exudative lesion
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On the other hand, the animal
denied walking due to a severe lameness of the different extremities,
being her pads hot, edematous and painful, with a reddish colour in
her interdigital spaces. The four pads had a intense keratinization
and exudation, and their nails were longer and fragile.
At that moment a systemic antibiotic treatment with cephadroxil (500 mg
every 8 hours PO) was initiated. After 48 hours she was still
depressed, anorectic and febrile, skin lesions had been extended and
pododermatitis was more intense.
Then a corticosteroid therapy was started (20 mg prednisone every 12
hours PO) and cephadroxil administration was maintained. After 72
hours she recuperated her appetite (she ate 1 kg of meat daily without
being forced) and responded adequately to external stimuli. The active
skin lesions started to get dry and she walked more confidently,
although
she still preferred to be laid down.
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Abdomen: epidermal
collaretes
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During this period she received two weekly baths with a 1% selenium
sulphide solution, rubbing intensely her pads and removing big rests
of their horny layer.
In the next days the skin lesions remised; there was an improvement of
the pododermatitis, and she walked normally. Consequently, three
weeks after the beginning of the cephalosporin therapy this was
suppressed. In that moment prednisone treatment is on alternate day
schedule, having reduced the dose to 15 mg every other morning.
After one week we observed a complete remission of the skin lesions and
pododermatitis, but some vesicle (never more than four together)
appeared in abdomen, which immediately remitted. Then we developed some
skin biopsies, covering these vesicles of recent appearance.
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Histologic picture: suprabasilar
vesicles
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Histologically it was observed vesicular lesions with suprabasilar
localization, being in different evolutive phases, appearing broken the
oldest ones. In all cases it was seen the presence of a dense cellular
infiltrate (neutrophils, lymphocytes and plasma cells) as well as an
important number of eosinophils; this cellular infiltrate was located
predominantly in the papilar dermis, reaching the deep layers, without
affecting the hypodermis.
The histopathologic picture was typical of a pemphigus vulgaris; this
disorder was compatible with the signs and lesions observed in the
physical examination of the animal, although mucosa lesions were not
numerous.
As a result of the diagnosis we tried to maintain the animal
immunosuppressed with the lowest possible glucocorticoid dose. Two
months after the beginning of the disease, azathioprine (100 mg daily
PO) was added to the treatment.
One week after there was a relapse of the animal with similar
skin lesions and their distribution, the presence of pododermatitis,
and the dog appeared apathetic, anorectic and febrile.
Consequently, we suppressed the administration of azathioprine, and we
increased prednisone dose to 20 mg each 12 hours PO. She was
treated with 500 mg cephadroxil every 8 hours PO, during 15 days too.
The dog responded well to the therapy and then prednisone therapy was
administered in alternate day basis.
Now, 8 months after the beginning of the disease, she is being
maintained adequately with 15 mg prednisone every other morning PO,
although
when weather is wet she suffers a light process, which consists of a
mild pododermatitis without any other sign, remitting when weather is
sunny.
Discussion
Autoimmune mediated skin diseases have two points of great interest for
the practitioner; their definitive diagnosis and their therapeutic
considerations.
The diagnosis of pemphigus is based on the history, the physical
exploration of the animal and some complementary tests, including
direct smears from intact vesicles, and skin biopsy for
histopathological examination and for direct immunofluorescence testing
(DIT) (Muller and others 1989).
The clinical features of our case were very similar to those described
by the different authors (Halliwell and Gorman 1989, Muller and others
1989, Thompson 1989). These include vesiculobullous lesions which are
quickly transformed in pustules, most of them very transient due to the
thin epidermis of the dogs. This fact provokes the apparition of
yellowish crusts. The distribution of skin lesions were similar to the
pemphigus vulgaris
ones. These authors report that severely affected dogs can be
anorectic,
depressed or febrile, and that nails may be affected, signs that
appeared
in our case.
The little extension of lesions in oral mucosa and the absence of
lesions in other mucocutaneus junctions were the least coincident
features when, according to Muller and others (1989), there are oral
lesions in
about 90% of the animals at the time of diagnosis.
The most effective diagnostic test for autoimmune skin diseases is,
according to Schmeitzel (1991), their histopathologic examination,
which can be diagnosed, in many cases, through this test alone. Thus,
in different autoimmune mediated disorders there are diagnostic or
highly suggestive lesions in about a 70- 80% of the cases (Werner and
others 1983, Ackerman 1986), although Werner and others (1983) had
reported
about a 20% of false positive results in animals affected by non
autoimmune
diseases.
Several authors recommend to develop both DIT and histopathological
evaluation because, according to Halliwell and Gorman (1989), it
increases the probability of reaching a correct diagnosis. However,
different
studies have reported that DIT has about a 50% of false negatives in
autoimmune disorders (Werner and others 1983, Ackerman 1986, Bradley
and others 1990). In addition, false positives are frequent, varying
depending on the study and the skin area where biopsy was effected,
between
a 20% (Werner and others 1983), a 45% at paw area (Scott and others
1983b),
a 73% at nose one (Scott and others 1983a), or without any false
positive
if labial mucosa was studied (Scott and others 1983a).
In addition, according to Tizard (1987) DIT is limited in pemphigus
diagnosis because of the difficulties in locating precisely the lesions
in the different layers of the epidermis and dermis.
These facts make that Carlotti (1989) and Schmeitzel (1991) consider
that DIT may be unnecessary when the histopathologic examination proves
diagnostic. In addition, as a result of the many difficulties in DIT
execution, Kalaher (1992) concludes that skin biopsies must be sent to
a reputable laboratory with a proved record in veterinary
immunopathology. This is a new problem for the practitioner. The last
author considers that
it may be prudent to use DIT as a confirmatory rather than a screening
method.
There are different opinions about the use of other easier
complementary tests as immunoperoxidase methods to replace DIT. In one
hand, Kalaher (1992) thinks that immunoperoxidase method has too many
false positives, and she prefers nowadays the use of DIT; on the other
hand, Bradley and others (1990) report that immunoperoxidase methods
can be superior to DIT in the diagnosis of different canine autoimmune
mediated skin diseases.
It is important to differentiate between the different forms of
pemphigus due to prognostic reasons (Tizard, 1987), being pemphigus
vulgaris the one which has worst prognosis. Clinical differentiation
is mainly based on lesions distribution, affecting both to skin and
mucosas,
while the other forms of pemphigus affect only to skin. Definitive
diagnosis
is based in histopathologic examination locating the site of vesicle
formation
in epidermis, having a good illustration in Halliwell and Gorman
(1989).
Once a definitive diagnosis of autoimmune mediated skin disease is
made, the difficulty is which the most successful therapeutic
management is. Autoimmune skin disorders require large doses of
systemic glucocorticoids, with or without other immunosuppressive drugs
(Muller and others 1989). In addition, secondary complications must be
treated. On one hand topically, using 1% selenium sulphide champus, as
a intense keratolytic agent which removes crusts and it is drying
(Halliwell 1991, Harvey 1991). On the other hand, a systemic antibiotic
therapy must be administered.
Glucocorticoid therapy has an induction phase, variable in time, and a
maintenance phase, on an every other day basis if possible. It must be
maintained for life, ant it must be used a short- acting
corticosteroid, as prednisone PO. The recommended daily induction dose
varies between 1.5-2.5 mg/kg for Bourdeau (1992), 2-4 mg/kg for
Halliwell and Gorman (1989) and Muller and others (1989), and 4-6 mg/kg
according to Thompson (1989). The main side-effect of large doses of
corticosteroids is the development
of an acute exocrine pancreatitis (Muller and others 1989).
Later the dose will be decreased as much as possible, and the
animals are usually adequately maintained with 1 mg/kg prednisone every
other morning PO (Bourdeau 1992).
Muller and others (1989) report that only about 50% of pemphigus
responds adequately to corticosteroids, and that it is necessary in the
other cases to administer some immunosuppressive drug, alone or
combined with corticosteroids.
The use of other immunomodulating drugs may allow significant
reduction or termination of glucocorticoid dose; it can be used
azathioprine,
chlorambucil, dapsone, cyclosporine and chrysotherapy (Muller and
others
1989).
When using both corticosteroid on alternate day schedule and a
cytostatic drug, Bourdeau (1992) recommends to administer the last one
in the alternate day.
Luckily, our dog has been maintained with a relative low prednisone
dose, and no intense side-effects to glucocorticoid therapy have been
observed.
On the other hand, we do not know if the relapse of the dog was induced
or not by azathioprine when this immunosuppressive drug was
administered. We consider that if an increase of prednisone dose is
not necessary, we must not try to administer any cytostatic again.
Finally, most of the authors advocate for a specific therapy in drug
and doses for each individual patient (Halliwell and Gorman 1989,
Muller and others 1989).
References
Ackerman, L. Pemphigus and pemphigoid in dogs and cats. 2. A clinical
survey. Modern Vet. Pract. 67: 358-360. 1986.
Bourdeau, P. La córticothérapie en dermatologie
des carnivores. Rec. Méd. Vét. 168: 627-644. 1992.
Bradley, G.A., Mays, M.B.C. y Calderwood-Mays, M.B. Immunoperoxidase
staining for the detection of autoantibodies in canine autoimmune skin
disease; comparison to immunofluorescence results. Vet. Immunol.
Immunopathol. 26: 105-113. 1990.
Carlotti, D. Autoimmune mediated skin diseases. J. Small Anim. Pract.
30: 223-227. 1989.
Halliwell, R.E.W. Rational use of shampoos in veterinary dermatology.
J. Small Anim. Pract. 32: 401-407. 1991.
Halliwell, R.E.W. y Gorman, N.T. Autoimmune and other immune-mediated
skin diseases. En: Veterinary clinical immunology, pp. 285-307. W.B.
Saunders, Philadelphia. 1989.
Harvey, R. Introduction to topical therapy. In practice 13: 208-211.
1991.
Kalaher, K.M. The value of immunofluorescence testing. En: Kirk, R.W. y
Bonagura, J.D. (Eds). Current veterinary therapy. Small animal
practice. (XI), pp. 503-505. W.B. Saunders, Philadelphia. 1992.
Muller, G.H., Kirk, R.W. y Scott, D.W. Immunologic diseases. En: Small
animal dermatology, pp. 427-574. 4ª ed. W.B. Saunders,
Philadelphia. 1989.
Schmeitzel, L.P. Recognizing the cutaneous signs of immune-mediated
diseases. Vet. Med. 86: 138-163. 1991.
Scott, D.W., Walton, D.K., Lewis, R.M. y Smith, C.A. Pitfalls
in immunofluorescence testing in dermatology. II. Pemphigus-like
antibodies in the cat, and direct immunofluorescence testing of normal
dog nose and lip. Cornell Vet. 73: 275-279. 1983.
Scott, D.W., Walton, D.K., Manning, T.O., Lewis, R.M. y Smith, C.A.
Pitfalls in immunofluorescence testing in canine dermatology. Cornell
Vet. 73: 131-136. 1983.
Thompson, J.P. Immunologic diseases. En: Ettinger S.J. (Ed). Textbook
of veterinary internal medicine. Diseases of the dog and cat, pp.
2297-2328. 3ª ed. Vol 2. W.B. Saunders, Philadelphia. 1989.
Tizard, I. Autoimmunity: specific diseases. En: Veterinary immunology,
pp. 337-355. 3ª ed. W.B. Saunders, Philadelphia. 1987.
Werner, L.L., Brown, K.A. y Halliwell, R.E.W. Diagnosis
of autoimmune skin disease in the dog: correlation between
histopathologic, direct immunofluorescent and clinical findings. Vet.
Immunol. Immunopathol. 5: 47- 64. 1983.
J Rejas López, A J Alonso
Díez, J R González Montaña, P Alonso Alonso, J
Martínez Martínez
La información contenida en este documento
puede ser impresa para uso personal, pero no reproducida ni distribuida
sin el consentimiento por escrito de los autores. Derechos reservados
©, 1997.
Juan Rejas López dmvjrl@unileon.es
Fecha de actualización: Febrero '97
reprinted with kind permission from Juan Rejas López
Dpto. Medicina, Cirugía y Anatomía Veterinaria,
Universidad de León
Campus de Vegazana s/n. 24007 León (España), Tfno: 987
291 216 - Fax: 987 291 270
http://www3.unileon.es/personal/wwdmvjrl/
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The above information is simply
informational. It's intent is not to replace the advice of a
veterinarian nor to assist you in making a diagnosis of your pet.
Please consult with your own veterinarian for confirmation of any
diagnosis. Your pets life may depend on it.
