Diseases of the Skin

Pemphigus Foliaceus/Erythematosus

Karen A. Moriello, D.V.M.,
Diplomate, American College of Veterinary Dermatology

Pemphigus foliaceous and pemphigus erythernatosus are autoimmune skin diseases characteized by the development of autoantibodies against the intercellular cement (glycocalyx) of the stratified squamous epithelium.  When autoantibodies bind to the glycocalyx, a series of enzymatic reactions occur that destroy the adhesions of the epidermal cells to one another. The loss of intercellular cohesion leads to acantholysis and vesicle formation. The prematurely keratinized epidermal cells are shed into the vesicle in either singlets or rafts of cells commonly referred to as acantholytic cells. The release of inflammatory mediators is chemotactic for neutrophils, which quickly migrate into the vesicle. Clinically, these vesicles appear as pustules, which rupture very easily. The exudate in the vesicles quickly dries and is the source of the crusting so typical of these diseases.

Clinically, pemphigus foliaceus and pemphigus erythematosus are very similar. From a practical perspective, the principal difference is that pemphigus erythematosus is limited in distribution to head and face. Pemphigus foliaceus is more generalized and will involve the bead, face, ears, paws, and trunk. These diseases are characterized by the formation of pustules and vesicles in the haired and thinly haired areas. Lesions are usually symmetric; nasal crusting accompanied by periocular crusting is highly suggestive of pemphigus. Intact pustules are rarely observed in animals and are most likely to be seen in the inner pinnae and around the manimae. In practice, most cats with one or the other of these diseases have extensive crusting and exudation of the skin. Affected cats are often depressed and anorectic and may have a marked peripheral lymphadenopathy. Pruritus is variable. Some cats early in the course of pemphigus may present with only paronychia. The nail beds may exude a black- to green-colored exudate or may be thickly crusted. Some of these cats are lame. Finally, in rare instances, lesions may be present in the inner ear for months before becoming generalized. These cats are often presented for recurrent otitis externa.

Initial evaluation of these patients should include skin scrapings, flea combing, a dermatophyte culture (in some cats dermatophytosis is clinically indistinguishable from pemphigus foliaceus), and cytologic examination of exudate from the vesicles/pustules. Intact pustules are often difficult to find, but a thorough search of the ventral abdomen, especially around the nipples, is sometimes fruitful. If intact pustules cannot be found, impression smears of exudate from the inner pinnae or from debris from the nail beds may be very helpful in establishing a tentative diagnosis. Smears may be stained with DiffQuik or another suitable stain. Specimens should be examined for the presence of inflammatory cells, particularly neutrophils, the presence or absence of bacteria, and the presence or absence of acantholytic cells. Identification of the latter is particularly useful because acantbolytic cells are very suggestive of an autoimmune disease process.

Definitive diagnosis of pemphigus requires a skin biopsy. Under no circumstances should the skin be scrubbed, wiped, or aseptically prepared prior to harvesting the skin biopsy. The diagnostic findings for all the causes of exfoliative skin diseases are very superficial-any disruption of the surface may remove critical findings for making a definitive diagnosis, If an intact pustule is present, this should be submitted in 10 percent neutral buffered formalin for routine histologic examination. Because of the fragility of these lesions, the specimen should be collected via an elliptical skin incision, using a scalpel blade, rather than via punch biopsy. Cat skin is very thin and tends to curl when placed into formalin; therefore, the specimen should be blotted dry of blood and the subcutaneous side placed on a small piece of wood or cardboard. The specimen should be gently placed in the formalin; the bottle should not be agitated for at least several hours while the specimen fixes. These precautions are necessary to get a suitable sample for the dermatopathologist to examine. The use of direct immunofluorescence in the diagnosis of autoinimune skin diseases is very limited and not recommended on a routine basis. If the clinician wants to collect a sample for processing at a later time, the sample should be collected using the same method as the one for routine histopathology, except that it should be preserved in Michel's transport media. Specimens are stable in this media for months to years, depending on the pH value of the transport media. If intact pustules cannot be located, numerous skin biopsies of representative lesions should be submitted for histologic examination. In several cases of pemphigus foliaceus in cats in which gross lesions were not present, but histologic examination of skin biopsy specimens demonstrated classic findings present in the form of microvesicles/pustules with acantholytic cells. Confirmatory histologic findings for pemphigus foliaceus include subcorneal pustule formation with acantbolysis that may extend into the follicular epithelium. The histologic findings in pemphigus erythematostis are similar, except that a lichenoid band of inflammation may be present at the basement membrane. Direct immunofluorescence testing reveals intercellular deposition of antibody in pemphigus foliaceus, while in pemphigus erythematosus, intercellular and basement membrane deposition of antibody are classic findings.

Treatment of pemphigus in cats should be individualized for the patient.. If there is extensive crusting, the cat should be bathed in a mild cleansing shampoo to remove the crust and scale. If the cat is a longhair cat and is severely matted, clipping of the hair coat may be necessary.  Removal of the crusting prior to the initiation of therapy makes it easier to determine whether new lesions are developing during induction therapy. Cats are considered to be "in remission" when old lesions resolve and new lesions no longer develop. Glucocorticoids are almost always used as the firstchoice immunosuppressive drugs. They may be used alone or in combination with another immunosuppressive drug, but glucocorticoids alone are rarely adequate to maintain the patient in a state of clinical remission. Oral prednisolone or prednisone (4 to 6 mg/kg/day) is most commonly used as initial glucocorticoid therapy. This dose may be given as a single dose once daily or in two equal divided doses. Most cats will achieve clinical remission in 1 to 3 weeks. The dose of glucocorticoid therapy can gradually be reduced to an alternate-day scheduling of prednisolone in the range of I to 2 mg/kg PO q48h. Most veterinarians prefer to begin therapy with a glucocorticoid alone and determine whether the patient can be maintained in remission using only this drug. If lesions begin to develop when the dose is reduced or at a later date, if needed, adjuvant therapy is added to the glucocorticoid therapy. The two Most commonly used drugs are aurothioglucose (Solganol; 1 to 2 mg/ kg IM weekly) or chlorambucil (Leukeran; 0. 1 to 0.2 mg/kg PO q24h). Although azathioprine (Imuran) is related to chlorambucil, it is extremely myelotoxic in cats and should be avoided. If aurothioglucose is used, it is important to remember that significant benefit may not be noticed for up to 12 weeks. Once the cat responds to the aurothioglucose, the dosage schedule can be lengthened to once every 2 to 4 weeks. Chlorambucil has a lag period of 2 to 3 weeks. Both drugs can cause severe side effects, including drug eruptions, erythema multiforme, proteinuria, and bone marrow suppression. Complete blood counts should be monitored every 2 to 4 weeks for the first several months of therapy. Regardless of the drugs used to treat a particular patient, it is important to remember that the autoimmune disease is still present and that only the clinical signs are suppressed. Relapses are common and are best managed by increasing the dosage of glucocorticoid for a period of several weeks until remission is reestablished. Some cats develop steroid tachyphylaxis or steroid resistance if they receive a particular steroid for long periods. This is due to the development of autoantibodies against the particular drug. Changing the type of glucocorticoid from prednisolone or prednisone to dexamethasone (Azium), triamcinolone (Vetalog), or betamethasone (Celestone) may be beneficial. Spontaneous resolution of the disease in cats has been reported.

The prognosis for cats with pemphigus diseases is good with respect to quality of life. Most cats tolerate therapy very well and suffer only minor and acceptable side effects of therapy, such as polyuria and polydipsia. Cats receiving chronic glucocorticoid therapy may develop diabetes mellitus, but in most cases this is transient. Most veterinary dermatologists caution owners that the cat's life span may be shortened by the disease or its treatment; however, this may not always be true. Some cats with pemphigus foliaceus have lived until they were 17 years of age. The cats had received glucocorticoids and azathioprine for the last 12 years of life and died from an unrelated diseases.

Pemphigus Vulgaris

Pemphigus vulgaris is a very rare autoimmune skin disease of cats. The disease is caused by the development of autoantibodies against the intercellular substance of the stratified squamous epithelium. Pemphigus vulgaris is characterized by a lack of cohesion of epidermal cells and by an inflammatory response in the deeper layers of the epidermis, accounting for the different clinical signs observed in pemphigus vulgaris versus pemphigus foliaceous.

Clinically, cats with pemphigus vulgaris present with vesicles, ulceration, erosions, and crusts on the mucocutaneous junctions. Cats are often anorectic, febrile, and depressed. Definitive diagnosis may be very difficult as the most revealing lesions to biopsy are vesicles, which are extremely transient. Cats with suspected autoimmune skin diseases should be hospitalized and examined every few hours for the development of vesicles or pustules. This is time-consuming but very cost effective when the costs of inappropriate diagnostics and therapy are considered. The classic histologic findings in pemphigus vulgaris include suprabasilar pustules with acantholytic cells. The prognosis for cats with pemphigus vulgaris is guarded.

Systemic Lupus Erythematosus

Systemic lupus erythernatosus is a rare multisystemic autoirnmune disease of cats. The etiology of the disease is unknown and may be multifactorial. The cutaneous signs of SLE in cats are variable and include any combination of the following: erythema, scaling, erosions, mucocutaneous ulceration, crusts, alopecia, and depigmentation. The face, ears, and paws appear to be most commonly affected. Vesicles and ulcers of the mucocutaneous junctions, palate, and nail bed may be seen. Systemic signs include anorexia, depression, weight loss, fever, and weakness. Immune-mediated hernolytic anemia, thrombocytopenia, glomerulonephritis, and polyarthritis may also be present. Definitive diagnosis of SLE is rarely based on just one diagnostic finding. Hematologic evaluations, antinuclear antibody tests, and skin biopsies provide the most useful diagnostic information in SLE. Skin biopsy may reveal classic lesions of SLE-hydropic interface dermatitis and intraepidermal vesicular dermatitis. The prognosis for cats with SLE is guarded. Treatment is similar to that for pemphigus foliaceus.

Discoid Lupus Erythematosus

Discoid lupus erythernatosus (DLE) is an autoimmune skin disease that is considered very rare in the cat as compared with the dog; however, this may be due to a marked difference in clinical appearance of the disease. I am aware of a cat with DLE that had a I-year history of nasal depigmentation, erythema, erosions, and crusting; similar to signs seen in dogs with DLE (Kahaler KM, Scott SW; personal communication, 1989). Nasal biopsies showed interface dermatitis and direct immunofluorescence testing showed immunoglobulin deposition at the basement membrane. The condition was successfully managed with oral vitamin E, topical glucocorticoids, and avoidance of sunlight. Recently, cats with histologic, immunologic, and serologic findings consistent with DLE were described. (Vet Dermatol 1:19, 1989)  These cats had variable pruritus marked truncal exfoliation, and vesicles and papules on the periocular margins and mucocutaneous junctions. Treatment with systemic glucocorticoids produced variable improvement. If these cases truly represent feline DLE, there are distinctly different manifestations from canine DLE.

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