Advances in Clinical Dermatology

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Recently Described Feline Dermatoses

Linda Medleau, DVM, MS*

FELINE IMMUNODEFICIENCY VIRUS INFECTION Feline immunodeficiency virus was first isolated from a cattery in California in 1986. 50 In this cattery, an outbreak of acquired immunodeficiency-like disease occurred in feline leukemia virus (FeLV)-negative cats shortly after the death of a recently obtained cat. Clinical signs included weight loss, unthriftiness, and a variety of chronic diseases, such as gingivitis, periodontitis, stomatitis, pustular dermatitis, bacterial otitis, rhinitis, conjunctivitis, and enteritis. A new feline retrovirus was isolated by coculturing lymphocytes from affected cats with feline T lymphocytes from normal cats. Initially designated feline T-lymphotropic lentivirus (FTLV), the virus is now called feline immunodeficiency virus (FIV), in accordance with internationally recognized nomenclature. Etiology There are three subgroups of retroviruses: the oncoviruses, spumaviruses, and lentiviruses. The oncoviruses include the cancer-causing viruses FeLVand feline sarcoma virus (FeSV), and endogenous type C oncornavirus. The spumaviruses, which have not been shown to cause disease, include syncytium-forming viruses such as feline syncytium-forming virus (FeSFV). The lentiviruses include nononcogenic exogenous retroviruses that are associated with chronic progressive diseases such as equine infectious anemia, caprine arthritis-encephalitis, progressive pneumonia of sheep, and human acquired immunodeficiency syndrome (AIDS). Feline immunodeficiency virus is a lentivirus that is morphologically and biochemically similar to human immunodeficiency virus (HIV) but is antigenically distinct. 50 That FIV has a worldwide distribution is supported by serologic studies identifying FlY-infected cats in the United States, Canada, Britain, Europe, Australia, and New Zealand. 2• 24 • 26 • 29 • 34 • 56 • 64 • 77 Depending on the geograph*Diplomate, American College of Veterinary Dermatology; and Associate Professor of Dermatology, University of Georgia College of Veterinary Medicine, Athens, Georgia Veterinary Clinics of North America: Small Animal Practice-Yo!. 20, No. 6, November 1990

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ical area studied, the infection rate among general cat populations ranges from less than 1% to 12%. In the United States, the infection rate among healthy or low~risk cats is 1.2%, and the infection rate among sick or highrisk (i.e., exposed) cats is 14%. 77 Transmission Feline immunodeficiency virus has been recovered from blood, serum, plasma, cerebrospinal fluid (CSF), and saliva, but not from milk or colostrum of infected cats. 77· 78 The virus is not easily transmitted by casual contact, through sexual contact, in utero, or lactogenically. 50• 77 • 78 The disease can be readily transmitted to susceptible cats with parental inoculation of infected blood or plasma. 77 • 78 Experimental studies have also shown that biting is a highly effective mode of transmitting FIV. 77 In naturally infected cats, the major mode of transmission is probably by territorial aggression and biting. 29 • 77 Clinical Signs

Feline immunodeficiency virus infection has been documented in cats ranging from less than 1 to 18 years old, but the incidence is highest in cats that are 6 years old or older. 77 Male cats, because they are territorially more aggressive and have a much higher incidence of cat bite wounds, are 2 to 3 times more likely to get infected than are female cats. 29 • 77 Cats that are kept strictly indoors are at the lowest risk, whereas free-roaming outdoor cats are at the highest risk. The incidence of FIV infection is greater in multiple-cat households than in single-cat- households, especially if the cats roam and fight. Feline immunodeficiency virus infection is most common in domestic shorthaired cats and is uncommon in purebred cats. 77 The lower incidence in purebred cats is probably because these cats are less likely to be allowed to roam freely than are domestic shorthaired cats. The clinical signs of FIV infection depend on what stage of the disease the cat is in. In experimentally infected cats, transient fever, neutropenia, and leukopenia lasting up to several weeks develops 4 to 6 weeks after FIV inoculation. 78 The initial phase of infection is also associated with generalized lymphadenopathy that lasts several months. This phase is followed by a period of relative clinical normality, which in turn is followed by appearance of chronic acquired immunodeficiency-like diseases. 51 · 78 The period between initial FIV infection and the development of acquired immunodeficiency-like diseases in naturally infected cats is unknown but may be more than 1 year. 29 Clinically ill FIV -infected cats may have one or more chronic diseases. The clinical signs may be episodic, with periods of apparent normality between bouts of illness, or they may be persistent. 27 The most common clinical signs are chronic oral disease (stomatitis, gingivitis, periodontitis), chronic diarrhea, chronic rhinitis, and upper respiratory tract infections. 77 Nonspecific signs, such as fever, lethargy, anorexia, and weight loss, are usually seen. Chronic or unusual skin diseases may be associated with FIV infection. Skin problems associated with FIV include recurring or persistent abscesses, bacterial pustular dermatitis, facial pyoderma, otitis externa, chronic miliary

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dermatitis, demodicosis, notoedric mange, and atypical mycobacteriosis (Fig. 1) (Stein B: Personal communication). 5 • 29• 50 • 77 Other clinical signs that may be observed include lymphadenopathy, ocular discharge, conjunctivitis, vomiting, and recurrent cystitis. 77 Central nervous system signs, seen in a small proportion of cats, include behavioral changes (hiding, rage, overaggression), dementia, inappropriate urination or defecation, and twitching movements of the face and tongue. 28 • 50 • 5 1· 77 Opportunistic infections such as hemobartonellosis, cryptococcosis, toxoplasmosis, and candidiasis may also occur in FlY-infected cats. 29 Neoplasia may be seen in a small proportion of FlY-infected cats, 29• 77 but the relationship of neoplasia to FlY may be coincidental because both tend to occur in older cats. 51 Hematologic abnormalities that may be seen in clinically ill cats include anemia or leukopenia. Leukopenia may be associated with neutropenia or lymphopenia. 77 Mild monocytosis may also be seen. 26 Serum biochemical values are usually within normal ranges. 26 There does not appear to be a relationship between Fe LV and FIV infections in cats. Although cats may be infected with both viruses, the incidence of FeLV in FlY-infected cats is the same as that in cats not infected with FlY. 29• 77 Diagnosis Because the clinical signs of FeLY and FlY infection are similar, sick cats should be tested for both viruses. Cats with opportunistic. infections, chronic and unusual skin diseases, or chronic oral cavity diseases should be tested for FlY infection. Also, all potential blood donor cats should be screened for FlY infection to avoia transfusing infected blood. Infection is

Figure l. Chronic facial dermatitis in a F lY-positive cat with otic demodicosis. The excoriations resulted from inte nse facial pruritus.

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diagnosed by detecting antibodies to FIV in the blood. Antibodies can be detected by an indirect fluorescent antibody assay, by ELISA, or by Western blotting. 48 · 50• 78 Commercially available tests include an ELISA kit for in-office veterinary testing (CITE, AgriTech) and an ELISA test for laboratory use that allows numerous samples to be tested at once (PetChek, AgriTech). Although very sensitive and specific, false-positive results may occur with practitioner-performed and laboratory-performed ELISA tests. 12 Thus, euthanasia should never be considered for a FlY-positive cat (especially asymptomatic healthy cats) unless the result has been confirmed with a Western blot test because the Western blot test is much more sensitive and specific than the ELISA tests. 12 False-negative ELISA test results may occur. In some cats, virus can be isolated from the blood although tests are negative for antibodies. 26 Validated assays for viral antigen are expected to be commercially available in the near future. Cats may be infected for several months before seroconversion occurs. 78 Thus, periodic retesting of antibody-negative cats is indicated if FIV infection is suspected. Treatment At this time there is no specific antiviral therapy for FIV infection. Affected cats should receive supportive and symptomatic therapy. Intravenous fluid therapy, blood transfusions, and good nutritional support (highcalorie diets) may be required. In anorectic cats, maintenance of nutritional requirements may be achieved using a gastrostomy tube. Antimicrobial therapy for secondary bacterial or fungal infections may be needed intermittently or on a long-term basis. In some cases the use of corticosteroids may result in clinical improvement in cats with stomatitis or gingivitis; but because of FIV' s immunosuppressant properties, corticosteroids should be used with caution in this diseaseY Because the immune status of a FlYinfected cat is not known, vaccination with a modified live vaccine is not recommended. 12 With good supportive care, FlY-positive cats may survive several years before succumbing to various terminal complications. 12 Nevertheless, owners of FlY-infected cats should be informed that their cats have a guarded prognosis and will likely develop illnesses in the future. Infected cats should be kept indoors to prevent transmission of FIV to other cats. Also, these cats are immunosuppressed, and by staying inside, they are less likely to contract potentially fatal infections from other cats. In multiple-cat households where the cats get along, casual contact with an infected cat is unlikely to result in disease transmission; however, if the cats fight, disease transmission is much more likely. 12 Public Health Significance There is no evidence that FIV is a health hazard for humans because FIV does not appear to be capable of infecting humans. The virus is antigenically distinct from HIV, is highly species specific, and cannot replicate in human cell cultures. 50• 78 Also, sera from humans with substantial exposure to FIV or FlY-infected cats have all tested negative for antibodies to FIV. 78

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CRYPTOCOCCOSIS Cryptococcosis, a systemic fungal infection of humans and animals, is caused by the round, yeastlike fungus Cryptococcus neoformans. It is the most common systemic fungal disease of cats. 61 Although cryptococcosis is not a newly recognized disease, the recent introduction of some newer classes of antifungal agents has made this disease more amenable to treatment. Etiology

Cryptococcus neofonnans is a saprophytic, yeastlike fungus that ranges from 3.5 to 7 1-L in diameter, with a capsule size that ranges from l to 30 1-L in diameter. 8 The fungus reproduces by budding. It is not a true yeast but is related to the rust and smut fungal pathogens of higher plants. 25 The organism is saprophytic and is usually associated with avian habitats, especially in pigeon droppings and accumulated filth of pigeon roosts. 16 Cryptococci may remain viable for at least 2 years in pigeon droppings, unless exposed to sunlight or drying. 54 In the hyperosmolar, alkaline environment of pigeon feces, C. neoformans is often shrunken and unencapsulated. However, it always produces a capsule in tissues. 8 Four serotypes of C. neofonnans have been identified. Serotypes A and D are found in pigeon feces. 10 The sour_ces of types B and C are unknown. Type A is most frequently associated with disease. in people, except in southern California where types B and C are also common. The serotypes associated with animal cryptococcosis have not been determined. Cryptococcus neoformans occurs commonly in nature, but the incidence of disease is low, suggesting that the organism is opportunistic. In people, the natural resistance to cryptococcosis is so strong that the presence of disease is a signal to look for an underlying cause. Immunosuppressive conditions such as lymphoreticular malignancies, sarcoidosis, acquired immunodeficiency syndrome, and long-term corticosteroid treatment are important predisposing factors for cryptococcosis in people. 25 • 58 In cats, infection with FeLV or FIV may increase susceptibility to cryptococcosis because these viruses have immunosuppressant properties. However, underlying immunosuppressive diseases have not been found in all cats with cryptococcosis. The exact mode of infection is not known. The infection in humans is thought to occur through inhalation of airborne organisms. 32 • 63 The resultant pulmonary infection may remain localized or may disseminate to other organs. Although the lungs may be the site of initial infection in cats, prominent lesions in the facial region and nose could be interpreted as cases of direct inoculation. 54 Cryptococcal organisms are not transmitted between animals or between animals and humans. Clinical Signs There is no sex or breed predilection for cryptococcosis in cats. 37 The age range of affected cats is broad (I to 13 years), but the disease is more common in middle-aged cats (average age: 5 years). 37 The infection is usually chronic, with one or more of the following organ systems affected: respira-

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tory, cutaneous, ocular, and central nervous system (CNS). Vague, nonspecific signs such as inappetance, weight loss, and depression may also be seen. The upper respiratory tract is most commonly affected. 37 Clinical signs include sneezing, snuffiing, unilateral or bilateral serosanguinous-to-mucopurulent nasal discharge, and respiratory difficulties. In many of these cases, a flesh-colored, granulomatous, polyplike mass is visible in one or both nostrils or a firm, hard swelling is evident over the bridge of the nose. Ulcerated or proliferative lesions in the oral cavity are also seen occasionally in conjunction with upper respiratory tract infections. Pulmonary involvement is rare. Cutaneous lesions are also common in cats with cryptococcosis. 37 Lesions may be single or multiple and usually involve the head, but they may be found anywhere on the body. Typically, there are papules and nodules that palpate as fluctuant or firm. Larger lesions tend to ulcerate, leaving a raw surface with a serous exudate (Fig. 2). Pruritus and pain are usually absent. If skin lesions are generalized, the disease is probably disseminated. Ocular abnormalities occur in some affected cats and include anterior uveitis ; dilated, unresponsive pupils ; and blindness due to exudative retinal detachment, granulomatous chorioretinitis, panopthalmitis, and optic neuritis. 37 The fundus can be affected without apparent visual loss. Chorioret-

Figure 2. Upper-respiratory and cutaneous cryptococcosis in a cat. The bridge of the nose is swollen and distorted, and there is a large ulcerated mass involving the side of the face .

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initis is probably a consequence of hematogenous spread and suggests that there is systemic involvement, whereas optic neuritis is usually associated with CNS involvement. 3 Neurologic signs, seen in a small proportion of cats, are variable and include depression, changes in temperament, seizures, circling, head pressing, ataxia, convulsions, paresis, and blindness. 37 Diagnosis

A diagnosis of cryptococcosis is made by demonstrating the organisms on cytology, in tissue biopsy specimens, by fungal culture, or serologically. The most rapid method of diagnosis is cytologic examination of nasal exudate, skin exudate, CSF, and tissue aspirates. Useful stains for cytology include Wright's stain, new methylene blue, Gram's stain, and India ink. The smear is examined for the presence of large, round, encapsulated, budding yeast. Because the buds may break off when quite small, the yeast tends to vary considerably in size. Wright's stain is most often used in diagnosing feline cases, but this stain can cause the organism to shrink and the capsule to become distorted. New methylene blue and Gram's stain are considered to be better than Wright's stain for this reason. India ink is not as definitive as the other stains unless budding is seen, because lymphocytes, fat droplets, yeast contaminants, and aggregated India ink particles may be confused with the organism. 8 Negative te~t results do not rule out cryptococcosis because if only a small number of organisms are present in the sample, they may be missed. Biopsies for histopathology should be performed on aspirated tissue masses that yield questionable or negative cytologic results. Because cytologic evaluation is easy and qu~k, impression smears should be made. If no organisms are seen, 'part of ~he biopsy specimen can be submitted for culture, and the rest processed for routine histologic examination. On hematoxylin and eosin (H&E) staining, the organisms stain as faint, roundto-oval eosinophilic· bodies surrounded by a clear halo. The organism is seen more easily with periodic acid-Schiff, Gomori' s methenamine silver, and Masson-Fontana stain. 8• 25 Mayer's mucicarmine stain is the definitive stain of choice because it stains the cryptococcal capsule rose red but does not stain other fungi that have similar morphologic characteristics. 8 For fungal culture, swabs of nasal or cutaneous exudate, tissue aspirates, biopsy specimens, CSF, or any other infected material can be submitted. Sabouraud' s dextrose agar is the best medium for fungal growth. It should contain antibiotics if bacterial contamination is suspected but should not contain cyclohexamide, which inhibits cryptococcal growth. 8 The organism should be cultured at 25° and 37°C; growth occurs in 2 days to 6 weeks, depending on the number of organisms in the inoculum. The organism forms white, creamy colonies that also have a mucoid appearance if a capsule is produced. Characteristics used to identify the organism are its morphology, growth at 37°C, hydrolysis of urea, response to various assimilation tests, and virulence for mice. 25 The cryptococcal antigen latex agglutination procedure is the only serologic test useful clinically on a routine basis. This test, which is commercially available (CALAS, Meridian Diagnostics), detects cryptococcal capsular antigen in serum and CSF and provides an easy, rapid, and

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reliable method of diagnosing cryptococcosis in cats. 40 The test detects cryptococcal antigen in the serum of the majority of cats with cryptococcosis but does not detect cryptococcal antigen in sera from healthy cats or cats with noncryptococcal diseases. 40 In our laboratory,* we have found that the test has a sensitivity of 95%, a specificity of 100%, and is highly reproducible. Treatment

In the past, the treatment of choice for cats with cryptococcosis was the use of flucytosine and/or amphotericin B. 1· 11 • 22 • 42 • 49· 53• 66· 71 · 74 • 75 However, drug resistance may develop when flucytosine is used alone. 1 The disadvantages of amphotericin B are that it must be given intravenously and is potentially nephrotoxic to cats. 11 • 49 • 66 Thus, long-term hospitalization and constant monitoring are necessary during treatment with amphotericin. Since its development in the late 1970s, ketoconazole has become the most important imidazole antifungal drug in veterinary medicine. Ketoconazole (Nizoral, Janssen Pharmaceutica, Piscataway, NJ) is a broad-spectrum antifungal agent that is given orally. At therapeutic doses it is fungistatic. It interferes with the synthesis of ergosterol, a sterol necessary for fungal · cell wall integrity. 71 In the presence of ketoconazole, ergosterol precursors accumulate. The lack of ergosterol and the buildup of precursor sterols result in permeability changes and fungal growth stops. 70 Ketoconazole has been used alone to successfully treat cats with cryptococcosis. A dosage of 10 to 24 mglkg once daily or divided into two doses was usually effective, 13• 17• 33• 39• 46 • 52• 59 although .one cat required a very high dosage of ketoconazole (72 mg/kg/d) to resolve the infectitm. 23 If ketoconazole is effective, long-term therapy (several months) is usually needed to resolve cryptococcosis in cats. Unfortunately, some cats do not improve even with high doses of ketoconazole or cannot tolerate the drug without developing side effects. Side effects of ketoconazole are common in cat~ and include anorexia, vomiting,. diarrhea, elevated serum liver enzyme (ALT) levels, and icterus. 17• 20• 45• 46• 52• 59 If the cat becomes anorectic, depressed, or icteric, the ketoconazole therapy should be halted and the ALT levels should be measured. Ketoconazole can be reinstituted at a lower dosage or given on an alternate-day basis once the cat is eating normally and ALT levels normalize. Giving ketoconazole with food and dividing the daily dose to two to four times may also help alleviate signs of anorexia and vomiting. 46 The search for improved antifungal azole agents has continued, in part because of ketoconazole's potential toxicity. Recently, itraconazole, a new investigational triazole compound, has shown promise as a systemic antifungal agent. As with ketoconazole, itraconazole inhibits the synthesis of ergosterol. 55 It is well absorbed orally and achieves high tissue levels. 69 Itraconazole has fungicidal or fungistatic activity against dermatophytes, yeasts, aspergilli, cryptococci, and various other pathogenic fungi. 30 In *Infectious Disease Laboratory, Department of Small Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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general, the concentrations of itraconazole needed to inhibit fungal growth are much lower than those needed with ketoconazole. 30 Itraconazole appears to have fewer side effects in people than ketoconazole. Only nausea, headache, and mild elevations in serum ALT have been reported. 65 Side effects in cats are similar to those seen with ketoconazole but occur less frequently (Medleau L: unpublished data). In cats, side effects are probably dose related and to date have included anorexia, weight loss, elevated serum ALT levels, icterus, and hepatotoxicity (Medleau L: Unpublished data). As for ketoconazole, therapy with itraconazole is temporarily halted until side effects abate, and then reinstituted at a lower or less frequent dosage. However, many cats that do not tolerate ketoconazole because of its side effects tolerate treatment with itraconazole (Medleau L: unpublished data). Twenty-five cats with naturally occurring cryptococcosis have been treated with itraconazole (Medleau L: unpublished data). Dosage ranged from 50 mg on an alternate-day basis· to 100 mg daily. Most cats have been treated with 50 to 100 mg of itraconazole per day. Seven cats appear to be in clinical remission (follow-up periods of 4 to 14 months). Duration of treatment ranged from 5 to 10 months in these cats. Ten cats died during treatment. Three of the cats died from cryptococcosis, 6 cats died of other diseases or unrelated causes, and one cat died of itraconazole-induced hepatitis. Eight cats are currently being treated with itraoonazole, and all but one are responding well. Regardless of whether ketoconazole or itraconazole is used, treatment should be continued until all lesions have resolved, plus 2 or more months for insurance. In addition to monitoring the cat clinically, serum samples should be obtained monthly durii'lg treatment so that the cryptococcal antigen titer can be assessed. A persistently high titer suggests active cryptococcosis, whereas a decrease in titer suggests treatment response (Medleau L: Unpubiished data). In some cats, the titer remains elevated or even increases during the first few months of treatment before starting to fall (Medleau L: Unpublished data). However, if the titer does not fall and no clinical improvement is noted, a change in drug therapy (i.e., higher dosage or different drug) is indicated. Public Health Significance Cryptococcosis is not a public health hazard because the organism does not aerosolize from culture media or from sites of tissue infection. Transmission of this disease from animal to animal or from animal to humans has never been reported. The major public health significance is that the environmental source of infection for infected pets is also a potential source of infection for associated humans. DERMATOPHYTE PSEUDOMYCETOMAS Dermatophytosis in cats is usually characterized by a superficial infection of the keratinized layers of skin and hair. In dermatophyte pseudomycetomas, the dermatophyte infection involves the deep dermal and subcutaneous tissues. Dermatophyte pseudomycetomas are rare in cats.

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Etiology All reported cases of dermatophyte pseudomycetomas in cats have been caused by subcutaneous infection with Microsporum canis. 4 • 41• 68 • 76 Microsporum canis is zoonotic for cats and normally does not elicit much dermal or follicular inflammation. In severe infections, perifolliculitis, folliculitis, and furunculosis may be seen. A dermatophyte pseudomycetoma is an atypical form of dermatophytosis because there is no perifollicular of follicular inflammation. In pseudomycetomas, fungal hyphae may extend from the base of hair follicles into the subcutaneous fat. 76 The presence of hyphae within the panniculus results in myce tomalike granulomas. It has been speculated that cats develop dermatophyte pseudomycetomas because they are immune incompetent.41 Clinical Signs There have been four published reports of dermatophyte pseudomycetomas in cats. 4 • 41 • 68• 76 All cats were Persian. Ages ranged from 4 to 14 years, and both males and females were affected. The author is also aware of two other cats (both Persians) with dermatophyte pseudomycetomas (Mundell A: Personal communication; Medleau L: Unpublished data). Affected cats present with firm nodules that may ulcerate and drain (Fig. 3). Usually, the dorsum of the trunk or base of the tail is affected. In some cats, the re is a history of superficial dermatophyte infection prior to development of pseudomycetomas. 4 Affected cats may also be asymptomatic carriers of Microsporum canis (Medleau L: Unpublished data). 68• ; 6

Figure 3. De rmatophyte pseudomycetoma on the flank of a cat. The nodule is ulcerated and draining.

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Diagnosis

A diagnosis of dermatophyte pseudomycetoma is made by histopathologic examination of skin biopsy specimens and by fungal culture of the lesions. Histologically, the lesions are characterized by a pyogranulomatous to granulomatous panniculitis. Granulomas are usually composed of an amorphous eosinophilic material (Splendori-Hoeppli reaction) in which irregularly shaped aggregates of distorted septate hyphae and thick-walled fungal cells are embedded. The inflammatory response is usually characterized by the presence of neutrophils, macrophages, epithelioid cells, and multinucleated cells. Fibroplasia may surround the granulomas. Often, fungal elements are not detected in the hair shafts or epidermis of the overlying skin. 41 • 68 Fungal cultures of dermatophyte pseudomycetomas have yielded Microsporum canis in all cats to date. Because asymptomatic infection of hairs is likely, the haircoat should be examined carefully for stubbled or broken-off hairs. A Wood's-light examination as well as fungal culture of suspect hairs should be performed. If no fluorescence is seen and the coat appears normal, hairs should be collected for fungal culture, using a sterile toothbrush technique. 44 To rule out the possibility of an underlying disease, a complete blood count (CBC), serum biochemical profile, and urinalysis should be evaluated. Testing for FeLV and FIV infection is also suggested. Therapy

Surgical excision of the lesions does not result in cure because lesions tend to recur at the surgical site. 4~ 41 · 68 Because so few cats have been studied, the medical treatment of choice is not yet known. Two cats have been treated with griseofulvin. In one cat, lesions resolved after treatment with griseofulvin, 30 mg/kg once daily for 2 months. 4 Another cat did not improve when treated with griseofulvin, 65 mg/kg daily for 2 months. This cat also failed to respond to treatment with ketoconazole, 37 mg/kg daily. 41 Two cats are currently being treated with the investigational antifungal drug itraconazole. One cat had multiple subcutaneous masses over his trunk, yet results offungal cultures of hairs were negative for dermatophyte growth. This cat' s infection remains clinically controlled, but not cured, after 18 months of therapy with itraconazole, 25 mg/d (Mundell A: Personal communication). Because the eat's serum ALT level increased after 5 months of therapy, a higher dose of itraconazole has not been used for fear that clinical side effects might occur. In the other cat, marked clinical improvement has been seen after 2 months of treatment with itraconazole, 50 mg/d (Medleau L: Unpublished data). This cat was also diagnosed an asymptomatic carrier (normal haircoat, multifocal areas fluoresced on Wood's-light examination, Microsporum canis cultured from fluorescing hairs). Therefore, his coat has been clipped short and he is being dipped with 2% lime sulfur solution once weekly. Should this eat's condition continue to improve, he will be treated with itraconazole and lime sulfur dips 2 months past clinical resolution oflesions and negative fungal cultures.

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DEMODICOSIS Although demodicosis has been thought to occur rarely in cats, there are several recent reports of this disease in the veterinary literature. 5• 7• 36• 36• 72

Etiology Two species of Demodex cause demodicosis in cats. 6• 9 • 36• 38• 73 One species, Demodex cati, may be a normal inhabitant of feline skin. 60 This mite is morphologically similar to Demodex canis except that it is narrower, the anterior portion of the vulva is positioned more posterior in D. cati females, and D. cati males have an opisthosomal invagination, whereas D. canis males do not. 47 Although the life cycle and mode of transmission for D. cati are not well understood, it probably spends its entire life cycle on the cat. Demodex cati may be found in hair follicles, in hair follicle infundibula, or in stratum corneum. The other species of Demodex is unnamed. This species is shorter than D. cati and has a broad, blunt abdomen. 6 • 36• 38• 73 These demodectic mites have only been found in stratum corneum. 6 • 36• 73 They are morphologically similar to, yet distinct from, D. criceti, a species that is found in the stratum corneum of hamsters. 6 Although the life cycle of this mite is unknown, transmission between unrelated cats has been speculated to occur. 38

Clinical Signs There have been 21 cases of feline demodicosis-reported in the North American veterinary literature. s-?, 9 • 19• 36• 38• 43· 60• 62 • 67• 72 • 73 Age of affected cats was indicated in 16 of the reports and ranged from 1 to 14 years; 12 cats were aged 5 years or older at !he time of presentation. Thus, older cats are predisposed to demodicosis. There does not appear to be a breed or sex predisposition. Demodicosis in cats 'may be localized or generalized. Localized lesions usually involve the face or ears. Typically, there are focal patches of alopecia that may also be erythematous and crusty. 19• 60 • 67 • 73 Localized demodicosis is usually not pruritic. Ceruminous otitis is another clinical manifestation of demodicosis in cats. Affected cats may present with only otitis9 or may have concurrent demodectic skin lesions. 5• 7• 38• 72 The clinical signs of generalized demodicosis in cats are extremely variable and include exudative dermatitis, ceruminous otitis, and multifocal-to-generalized patches of alopecia with variable degrees of scaling, erythema, hyperpigmentation, and crusting (Fig. 4). Generalized lesions may be papulocrustous and resemble miliary dermatitis. 5 Bilaterally symmetric alopecia has also been reported. 38 • 62 Pruritus, if present, varies from being intermittent or mild to intense (see Fig. 1). The development of generalized demodicosis may be a signal that the cat has an underlying disease. Of 15 cats with generalized demodicosis, 10 had concurrent systemic disease, including diabetes mellitus (n = 3), FeLV infection (n = 3), FIV infection (n = 2), systemic lupus erythematosus (n = 1), and toxoplasmosis (n = 1). 5 • 38 • 60 • 72

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Figure 4. Generalized demodicosis in a cat. There are generalized patches of alopecia involving the ventral aspects of the chest and abdomen.

Diagnosis Diagnosis of demodicosis is based on clinical signs and identification of the mites. Demodectic mites are readily recovered by s.kin scrapings from cats with skin lesions and by ear swab specimens from cats with otitis. Histologically, Demodex catt may be found deep within hair follicles , within hair follicle infundibula, or in surface keratin. Associated inflammation may be nonexistent or may be characterized by pyogranulomatous-togranulomatous perifolliculitis and folliculitis .5 • 7 • 38· 72 Histologically, mild acanthosis and hyperkeratosis, nonexistent-to-mild superficial dermal inflammation , and mites on and within the stratum corneum have been reported for the unnamed Denwdex species. 6 • 36• 36 Because mites were not demonstrated in multiple biopsy specimens from two cats with generalized demodicosis,36· 62 skin scrapings are the diagnostic test of choice for ruling out demodicosis in cats with skin disease. In cats with generalized demodicosis, the diagnostic workup should also include a complete blood count, biochemical profile, urinalysis, FeLV test, and FIV test because concurrent systemic disease is common. Therapy Topical treatments that have been used to treat localized demodicosis in cats include 0.025% amitraz solution on lesions twice weekly (one cat) and rotenone on lesions once daily (four cats).5 · 19• 36· 73 Lesions resolved in the cat treated with amitraz and in only one of the cats treated with rotenone. 19• 73 One cat with localized demodicosis recovered spontaneously with no treatment. 60 However, progression to the generalized form of the disease despite local topical treatment has also been reported. 5 • 38 Successful treatment regimens for demodex otitis in cats have included

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the otic application of rotenone (Canex, Pitman-Moore, Mundalein, IL) in mineral oil (1:3) and lime sulfur solution. 5• 60 Another otic preparation that is effective is amitraz (Mitaban, Upjohn Co., Kalamazoo, MI) in mineral oil (1:9) (Medleau L: Unpublished data). Otic preparations are instilled in the ears daily or every other day until no mites are found in ear swab specimens. If the cat is also being dipped for demodectic skin lesions, otic treatment is continued once weekly for the duration of the dips. Both rotenone and amitraz can cause an allergic or irritant contact dermatitis or otitis when used in the ears of cats (Medleau L: Unpublished data). 35 Topical products that have been used to successfully treat cats with generalized demodicosis include 2% to 3% lime sulfur solution and phosmet (Paramite, Vet-Kern, Dallas, TX). 5· 6 · 36· 38 The latter product is not approved for use in cats. Cats with generalized demodicosis should be dipped weekly until results of skin scrapings are negative for Derrwdex and then treated for 2 to 4 more weeks for insurance. If no improvement is seen, the owner's compliance should be assessed. Also, the cat should be evaluated for the presence of an underlying disease, and biopsies should be performed on its skin lesions for histopathologic examination. Mites located within the stratum corneum or hair follicle infundibula are usually eradicated with the topical application of lime sulfur solution or phosmet. If the mites are deep seated in hair follicles, however, resistance to lime sulfur and phosmet dips is possible. 7• 38 Amitraz is the drug most used in dogs with generalized demodicosis. 44 However, it is not approved for use in cats. Also, cats are more likely to show side effects from amitraz than are dogs. Mild side effects consisting of anorexia, diarrhea, and sedation were reported in normal cats treated with 0. 025% or 0. 0125% amitraz solution. 21 N evertlieless, amitraz should be considered a treatment option for cats with generalized demodicosis that fail to respond to conventional therapies and for whom the potential benefits of using amitraz outweigh its. risk. Weekly dips with 0.0125% amitraz solution (Mitaban, 2.5 mUgal water) were used successfully to treat a cat with deep-seated generalized demodicosis that failed to respond to weekly lime sulfur dips. 7 Side. effects of treatment were transient in this cat and included mild sedation, ptyalism, and hiding under the furniture for about 12 hours after being dipped.

MISCELLANEOUS DISEASES Sezary-like Syndrome Cutaneous T-celllymphomas in people include the leukemic exfoliative erythroderma commonly referred to as Sezary syndrome and the nonleukemic disorder known as mycosis fungoides. In the Sezary syndrome, atypical lymphocytes (Sezary cells) are found in the skin and peripheral blood. 14 These cells are characterized in blood smears as having a large, grooved nucleus that occupies most of the cell. 18 The Sezary syndrome differs from other forms of leukemia because the Sezary cells do not appear to originate from the bone marrow. 15

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A Sezary-like syndrome was described in a 5-year-old male castrated domestic shorthair cat. 57 Clinical signs included intense pruritus, alopecia, erythroderma, and diffuse exfoliative dermatitis of the head, trunk, and limbs. All peripheral lymph nodes were enlarged. The cat tested negative for FeLV and FIV virus infection. A CBC showed a white blood cell count of 46,000 cells/cm3 ' 43,000 cells/cm3 were lymphocytes. On electron microscopy, the lymphocytes morphologically resembled Sezary cells. Epidermotropic lymphosarcoma and perinodallymphosarcoma were diagnosed on histologic examination of skin and lymph node biopsy specimens, respectively. The cat was euthanatized. On necropsy, lymphosarcoma involving the skin, peripheral lymph nodes, and sternal lymph nodes was found. Discoid Lupus Erythematosus Discoid lupus erythematosus was diagnosed in a 2-year-old male castrated domestic medium-haired cat. 31 The cat had a 1-year history of nasal depigmentation, erythema, erosions, and crusting. The cat tested negative for FeLV and FIV infection and for antinuclear antibodies. On histologic examination of a skin biopsy specimen, there was interface dermatitis, with hydropic degeneration of basal cells in some areas and hyperplastic superficial and deep perivascular dermatitis in other areas. On direct immunofluorescent testing, granular deposition of IgM at the basement membrane zone was seen. The condition was succe~sfully managed with avoidance of sunlight, topical application of a preparation containing fluocinolone and dimethyl sulfoxide (Synotic, Syntex Animal Health, West Des Moines, IA) every 1 to 3 days, and the oral administration ·of vitamin E, 100 IU twice daily.

REFERENCES l. Barrett RE, Scott DW: Treatment of feline cryptococcosis: Literature review and case

report. J Am Anim Hosp Assoc 11:511, 1975 2. Bennett M, McCracken C, Lutz H, et al: Prevalence of antibody to feline immunodeficiency virus in some cat populations. Vet Rec 124:397, 1989 3. Blouin P, Conner MW: Cryptococcosis. In Holzworth J (ed): Diseases of the Cat: Medicine and Surgery. Philadelphia, WB Saunders, 1987, p 332 4. Bourdin M, Destombes P, Parodi AL, et al: Premiere observation d'un mycetome a Microsporum canis chez un chat. Rec Med Vet 151:475, 1975 5. Chalmers S, Schick RO, Jeffers J: Demodicosis in two cats seropositive for feline immunodeficiency virus. JAm Vet Med Assoc 194:256, 1989 6. Conroy JD, Healey MC, Bane AG: New Demodex sp. infesting a cat: A case report. J Am Anim Hosp Assoc 18:405, 1982 7. Cowan LA, Campbell K: Generalized demodicosis in a cat responsive to amitraz. J Am Vet Med Assoc 192:1442, 1988 8. Davis CE: Cryptococcus. In Braude AI, Davis CE, Fierer J (eds): Medical Microbiology and Infectious Diseases. Philadelphia, WB Saunders, 1986, p 564 9. Desch C, Nutting WB: Demodex cati Hirst 1919: A redescription. Cornell Vet 69:280, 1979 10. Diamond RD: Cryptococcus neoformans. In Mandell GL, Douglas RG, Bennett JE (eds): Principles and Practice of Infectious Diseases. New York, John Wiley and Sons, 1985, p 1460

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11. Duckworth RH, Taylor DES, Julian AF: Cryptococcus neoformans infection in a cat. Vet Rec 96:48, 1975 12. DVM Roundtable: Experts discuss clinical, biological consequences of FIV infection; unanswered questions remain. DVM 20(4):18, 1989 13. Dye JA, Campbell KL: Cutaneous and ocular cryptococcosis in a cat: Case report and literature review. Comp Anim Pract 2:34, 1988 14. Edelson RL: Cutaneous T cell lymphoma: Mycosis fungoides, Sezary syndrome, and other variants. J Am Acad Dermatol 2:89, 1980 15. Edelson RL, Kirkpatrick CH, Shevach EM, et al: Preferential cutaneous infiltration by neoplastic thymus-derived lymphocytes. Ann Intern Med 80:685, 1974 16. Emmons CW: Isolation of Cryptococcus neoformans from soil. J Bacterial 62:685, 1951 17. Emms SG: Ketoconazole in the treatment of cryptococcosis in cats. Aust Vet J 64:276, 1987 18. Flandrin G, Brouet JC: The Sezary cell: Cytology, cytochemical, and immunological studies. Mayo Clin Proc 49:575, 1974 19. Gabbert N, Feldman BF: Feline demodex. Feline Pract 6:32, 1976 20. Greene CE, Miller OM, Blue J: Trichosporon infection in a cat. J Am Vet Med Assoc 117:946, 1985 21. Gunaratnam P, Wilkinson GT, Seawright AA: A study of amitraz toxicity in cats. Aust Vet J 60:278, 1983 22. Gwin RM, Gelatt KN, Hardy R, et al: Ocular cryptococcosis in a cat. J Am Anim Hosp Assoc 13:680, 1977 23. Hansen BL: Successful treatment of severe feline cryptococcosis with long-term high doses of ketoconazole. J Am Anim Hosp Assoc 23:193, 1987 24. Harbour DA, Williams PO, Gruffydd-Jones TJ, et al: Isolation of a T-lymphotropic lentivirus from a persistently leucopenic domestic cat. Vet Rec 122:84, 1988 25. Hoeprich PO: Cryptococcosis. In Hoep~ich PO (ed): Infectious Diseases. Philadelphia, Harper and Row, 1983, p 1053 26. Hopper CD, Sparkers AH, Gruffydd-Jones TJ, et al: Clinical and laboratory findings in cats infected with feline immunodeficiency virus. Vet Rec 12p:341, 1989 27. Hosie M, Sparkes A, Hopper C: Feline immunodeficiency virus. In Pract 11:87, 1989 28. Ishida T, Washizu T, Toriyabe K, et al: Detection of feline T-lymphotropic lentivirus (FTLV) infection in Japanese domestic cats. Jpn J Vet Sci 50:39, 1988 29. Ishida T, Washizu T, Toriyabe K, et al: Felipe immunodeficiency virus infection in cats of Japan. JAm Vet Med Assoc•194:221, 1989 30. Itraconazole: Basic medical information brochure. Janssen Pharmaceutica, 1984 31. Kalaher KM, Scott OW: Discoid lupus erythematosus in a cat. Comp Anim Pract, in press 32. Khan ZU, PalM, Randhawn HS, et al: Carriage of Cryptococcus neoformans in the crops of pigeons. J Med Microbial 11:125, 1978 33. Legendre AM, Gompf R, Bone 0: Treatment of feline cryptococcosis with ketoconazole. JAm Vet Med Assoc 181:1541, 1982 34. Lutz H, Egberink H, Arnold P, et al: Felines T-lymphotropes lentivirus (FTLV): Experimentelle Infektion und Vorkommen in einigen Landern Europas. Kleinter-Praxis 33:455, 1988 35. Mansfield PO: Preventative ear care for dogs and cats. Vet Clin North Am [Small Anim Pract] 18:845, 1988 36. McDougal BJ, Novak CP: Feline demodicosis caused by an unnamed demodex mite. Comp Cont Ed Pract Vet 8:820, 1986 37. Medleau L, Barsanti JA: Cryptococcosis. In Greene CE (ed): Infectious Diseases of the Dog and Cat. Philadelphia, WB Saunders, 1990, p 687 38. Medleau L, Brown CA, Brown SA, et al: Demodicosis in cats. J Am Anim Hosp Assoc 24:85, 1986 39. Medleau L, Hall EJ, Goldschmidt MH, et al: Cutaneous cryptococcosis in three cats. J Am Vet Med Assoc 187:169, 1985 40. Medleau L, Marks MA, Brown J, et al: Clinical evaluation of a cryptococcal antigen latex agglutination test for diagnosis of cryptococcosis in cats. J Am Vet Med As soc, 196:1470, 1990 41. Miller WH Jr, Goldschmidt MH: Mycetomas in the cat caused by a dermatophyte: A case report. J Am Anim Hosp Assoc 22:255, 1986

RECENTLY DESCRIBED FELINE DERMATOSES

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42. Moore R: Treatment of feline nasal cryptococcosis with 5-flucytosine. J Am Vet Med Assoc 181:816, 1982 43. Muller GH: Feline demodicosis. In Kirk RW (ed): Current Veterinary Therapy VIII. Philadelphia, WB Saunders, 1983, p 487 44. Muller GH, Kirk RW, Scott DW: Small Animal Dermatology. Philadelphia, WB Saunders, 1989 45. Noxon JO, Diglio K, Schmidt DA: Disseminated histoplasmosis in a cat: Successful treatment with ketoconazole. JAm Vet Med Assoc 181:817, 1982 46. Noxon JO, Monroe WE, Chinn DR: Ketoconazole therapy in canine and feline cryptococcosis. JAm Anim Hasp Assoc 22:179, 1986 47. Nutting WB: Hair follicle mites (Dernodex spp.) of medical and veterinary concern. Cornell Vet 66:214, 1976 48. O'Conner TP, Tanguay S, Steinman R, eta!: Development and evaluation of immunoassay for detection of antibodies to feline T-lymphotropic lentivirus (feline immunodeficiency virus). J Clin Microbial 27:474, 1989 49. Palumbo NE, Perri S: Amphotericin B therapy in two cases of feline cryptococcosis. Vet Med [Small Anim Clin] 70:553, 1975 50. Pedersen NC, Ho EW, Brown ML, et a!: Isolation of a T-lymphotropic virus from domestic cats with an immunodeficiency-like syndrome. Science 235:790, 1987 51. Pedersen NC, Yamamoto JK, Ishida T, et a!: Feline immunodeficiency virus infection. Vet Immunol Immunopathol 21:ll1, 1989 52. Pentlarge VW, Martin RA: Treatment of cryptococcosis in three cats, using ketoconazole. JAm Vet Med Assoc 188:536, 1986 53. Prevost E, McKee JM, Crawford P: Successful medical management of severe feline cryptococcosis. JAm Anim Hasp Assoc 18:ll1, 1982 54. Rippon JW: Medical Mycology: The Pathogenic Fungi and the Pathogenic Actinomycetes. Philadelphia, WB Saunders, 1982, p 532 55. Saag MS, Dismukes WE: Azole antifungal agents: Emphasis on new triazoles. Antimicrob Agents Chemother 32:1, 1988 56. Sabine M, Michelson J, Thomas F, eta!: Feline AIDS. Aust Vet Pract 18:105, 1988 57. Schick RO: Sezary syndrome in a cat. In Proceedings. Am Acad Vet Dermatol, 1989, p 57 58. Schimpf£ SC, Bennett JE: Abnormalities in cell-mediated immunity in patients with Cryptococcus neoformans infection. J Allergy Clin lmmunol 55:430, 1975 59. Schulman J: Ketoconazole for successful treatment of cryptococcosis in a cat. J Am Vet Med Assoc 187:508, 1985 60. Scott DW: Feline dermatology 1900-1978: A monograph. JAm Anim Hasp Assoc 16:331, 1980 61. Soltys MA, Sumner-Smith G: Systemic mycoses in dogs and cats. Can Vet J 12:191, 1971 62. Stogdale L, Moore DJ: Feline demodicosis. J Am Anim Hasp Assoc 18:427, 1982 63. Swinne-Desgain D: Cryptococcus neoformans of saprophytic origin. Sabouraudia 13:303, 1975 64. Swinney GR, Pauli JV, Jones BR, et a!: Feline T-lymphotropic virus (FTLV) (feline immunodeficiency virus infection) in cats in New Zealand. NZ Vet J 37:41, 1989 65. Terrell CL, Hermans PE: Antifungal agents used for deep-seated mycotic infections. Mayo Clin Proc 62:ll16, 1987 66. Thrall MA, Rich LJ, Freemyer FG: Feline cryptococcosis treatment with amphotericin B. Feline Pract 6:15, 1976 67. Trimmier BR: Demodicidosis in a cat. Southwest Vet 20:57, 1966 68. Tuttle PA, Chandler FW: Deep dermatophytosis in a cat. JAm Vet Med Assoc 183:106, 1983 69. Van Cauteren H, Heykants J, DeCoster R, et a!: Itraconazole: Pharmacologic studies in animals and humans. Rev Infect Dis 9:S43, 1987 70. Van den Bossche H, Willemsen G, Cools W, et a!: In vitro and in vivo effects of the antimycotic drug ketoconazole on sterol synthesis. Antimicrob Agents Chemother 17:922, 1980 71. Weir EC, Schwartz A, Buergelt CD: Short-term combination chemotherapy for treatment offeline cryptococcosis. JAm Vet Med Assoc 174:507, 1979 72. White SD, Carpenter JL, Moore FM, et a!: Generalized demodicosis associated with diabetes mellitus in two cats. JAm Vet Med Assoc 191:448, 1987

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73. Wilkinson GT: Demodicosis in a cat due to a new mite species. Feline Pract 13:32, 1983 74. Wilkinson GT, Bate MJ, Robbins GM, eta!: Successful treatment of four cases of feline cryptococcosis. J Small Anim Pract 24:507, 1983 75. Willard MD: Cryptococcosis. California Vet 12:13, 1982 76. Yager JA, Wilcock BP, Lynch JA, et a!: Mycetoma-like granuloma in a cat caused by Microsporum canis. J Comp Pathol 96:171, 1986 77. Yamamoto JK, Hansen H, Ho EW, et a!: Epidemiologic and clinical aspects of feline immunodeficiency virus infection in cats from the continental United States and Canada and possible mode of transmission. J Am Vet Med Assoc 194:213, 1989 78. Yamamoto JK, Sparger E, Ho EW, et a!: Pathogenesis of experimentally induced feline immunodeficiency virus infection in cats. Am J Vet Res 49:1246, 1989

Address reprint requests to: Linda Medleau, DVM, MS College of Veterinary Medicine University of Georgia Athens, GA 30602