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Companion Animals, Too, Can Get Pemphigus

by Thierry Olivry, DrVet, PhD, DipACVD, DipECVD,
Associate Professor of Dermatology, Department of Clinical Sciences,
College of Veterinary Medicine, NC State University,
Raleigh, North Carolina,
and Adjunct Clinical Associate Professor of Dermatology, Department of Dermatology,
School of Medicine, University of North Carolina,
Chapel Hill, North Carolina

Autoimmune blistering skin diseases first were identified in companion animals twenty five years ago, with the description of two dogs affected with pemphigus vulgaris (PV). Two years later, the first cases of pemphigus foliaceus (PF) were recognized in canine patients. These two diseases represent the main forms of animal pemphigus being diagnosed by veterinarians.

Surprisingly, whereas the main form of pemphigus affecting human individuals is pemphigus vulgaris (PV), this entity is extremely rare in dogs with less than 50 cases being reported in veterinary medical journals. This deep pemphigus variant also has been recognized, albeit very sporadically, in rare cats and horses.

Clinically, dogs and cats with PV will present with blisters and ulcers that affect the oral cavity and skin areas bordering the mouth, nose, eyes, ears, anus and genitalia. The lesions often progress to involve the skin, especially in areas of frictions such as the groin and armpits. In rare dogs, the ulcers are restricted to the skin, or to the nose, or to the borders of the nails. Ulcerated skin and mucosal lesions generally are painful; the pets thus are reluctant to eat, and they will begin to lose weight. Deep skin lesions commonly become infected with skin bacteria.

The diagnostic methodology for animal PV is similar to that used for human patients. Skin biopsies are taken and examined by a pathologist. Microscopic lesions of canine and feline PV include cleavage that occurs in the deepest part of the epidermis, identically to that which is seen in human beings with PV. Immunological tests are not done routinely. When performed, these tests will reveal the presence of skin-fixed and serum IgG autoantibodies that recognize desmoglein-3, the same autoantigen as is found in human individuals with mucosal-predominant PV.

Canine PV reportedly is very difficult to treat. Veterinarians will attempt to control the disease with high doses of prednisone, and when not sufficient, will add immune-suppressive chemotherapeutic drugs such as azathioprine (IMURAN), cyclophosphamide (CYTOXAN) or chlorambucil (LEUKERAN).

Pemphigus foliaceus is, by far, the most common variant of pemphigus in all animal species, and it has been recognized in dogs, cats, horses and goats. In North America, there is a remarkable breed predisposition for PF in dogs of the Chow and Akita breeds. This predilection suggests that genetic factors could be very important in increasing the sensitivity of dogs to develop the disease. Pemphigus foliaceus usually affects adult dogs, but some animals can develop the disease around puberty, which occurs usually before one year of age.

The first skin lesions of canine PF will usually appear on the top of the nose, either on the haired part, or on the nose pad itself. From there, they will spread to the skin around the eyes, the ears and, in some patients, to the rest of the body. Interestingly, the footpads, and more rarely the nails, can be affected as well. In contrast to those of PV, skin lesions of PF are not found in the oral cavity or on other mucosal surfaces. In most cases, the skin lesions are seen bilaterally and symmetrically on the skin. The main difference between animal and human PF is the nature of the skin lesions themselves. Human patients with PF usually will present superficial clear blisters that rupture easily leaving shallow erosions and marked dandruff formation. The earliest lesions of PF in dogs and other animals are pustules, which are blisters filled with pus (e.g. pimples). The pustules can be quite large, and clustered in groups of variable numbers. The pustules always will dry into crusts (scabs), which, if removed, will leave superficial erosions. In many dogs with PF, the skin of the nose can show a loss of the normal black pigment. Because lesions of PF are more superficial than those of PV, there is usually less pain than in deep pemphigus.

The skin lesions of feline PF are very similar to those seen in dogs, except that the disease will be usually less severe than in canine patients. The lesions can be restricted to the face. In horses and goats, the skin lesions consist primarily of large crusts, and the distribution is more generalized than in small animals.

In all animal species, PF is diagnosed primarily by microscopic examination of skin biopsies. The veterinary pathologists will look for superficial pustules, rich in neutrophils and free-floating clustered or individual epidermal cells (“acantholytic cells”). Care is taken to look for skin fungal infections that can cause lesions resembling to those of PF. At this time, there are very few laboratories that perform immunological tests for confirming the diagnosis of animal PF. In our laboratory, immunofluorescence tests are used to demonstrate IgG autoantibodies in the skin and serum of affected patients. Recently, the canine PF autoantigen has been identified as desmoglein-1, the same that is being targeted in human individuals with the same disease.

The prognosis of animal PF is highly variable, lesions responding to low doses of prednisone in some patients, while others will need very high doses of this medication to enter remission. When the lesions persist in spite of the glucocorticoids, the veterinarians will prescribe chemotherapeutic drugs as done for PV. In rare cases, response of skin lesions to dapsone, gold salts, or niacinamide-tetracycline has been reported.

Recent investigations have established that canine PV is remarkably similar to the disease that affects human patients, both at the lesional, microscopic and immunological level. Canine PF, even though the autoantigen is desmoglein-1, is different at the clinical and histological level because primary lesions consist of pustules (pimples) instead of vesicles (blisters). A pustular variant of PF has been recognized recently in human patients, however. Because PF is not uncommon in dogs, studies on genetic factors and mechanisms of lesion formation in the canine disease could further the knowledge on various aspects of human pemphigus. Moreover, novel treatment strategies could be tested on canine patients, especially when standard-of-care therapy has failed to induce lesion remission.

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