Abstract. Key Content

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1 Canine Alopecia: What s New Rod A.W. Rosychuk, DVM, Diplomate, ACVIM, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Ft. Collins, Colorado Abstract Alopecia is defined as a partial or complete lack of hair in areas where it would normally be present. The term is often used to describe complete hair loss, with a descriptor added to quantify the hair loss (e.g., partial alopecia). Hypotrichosis implies partial hair loss and is a form of alopecia. This article is an update on the diagnosis and management of various clinically nonpruritic, noninflammatory dermatoses in the dog, including select endocrine alopecias, alopecia X, color dilution alopecia, and sebaceous adenitis. Key Content Many differential diagnoses of alopecia are diagnosed on the basis of history and physical examination (cyclical flank alopecia, pattern baldness, post clipping alopecia, color dilution alopecia); screening laboratory work, including complete blood count, serum chemistry panel, and urinalysis; and more specific endocrinologic tests (hypothyroidism, hyperadrenocorticism) and/or response to trial therapy (e.g., hypothyroidism, Sertoli s cell tumor, alopecia X) or skin biopsy (e.g., sebaceous adenitis). Biopsies done to better define alopecic syndromes should be taken from maximally alopecic areas, ideally from the more dorsal areas of the thorax, abdomen and lumbar regions (if involved), and from a more normal area. The alopecia and lightening or bleaching of coat color associated with the more classic endocrinopathies (hypothyroidism, hyperadrenocorticism, sex hormone imbalances) and alopecia X all spare the head and distal extremities. The cutaneous signs associated with spontaneous hyperadrenocorticism may not all be solely related to overproduction of cortisol in affected individuals; it has been noted that sex hormones may also be produced in excess quantities. Cutaneous atrophy, cutaneous phlebectasias, perianal adenomas in neutered females, and calcinosis cutis suggest spontaneous hyperadrenocorticism. Alopecia X is typified by hair follicles that are arrested in the catagen or the early telogen stage of the hair follicle cycle. Many have concurrent adrenal sex hormone abnormalities. About 50% of patients may respond to melatonin therapy. When working up a patient presented for hair loss, it is important to recall that significant hair loss in dogs can be associated with self-trauma (e.g., pruritus associated with atopy; food sensitivity; flea bite hypersensitivity; and other ectoparasites, such as scabies) and Proceedings of a Symposium Held at the 2008 North American Veterinary Conference and the 2008 Western Veterinary Conference. Copyright 2008 Pfizer Inc. All rights reserved. The opinions expressed in the articles in this publication are those of the authors and do not necessarily reflect the official label recommendations and points of view of the company or companies that manufacture and/or market any of the pharmaceutical agents referred to. 1

2 any disease that is associated with folliculitis (e.g., bacterial pyoderma, dermatophytosis, demodicosis). Hair loss can also be encountered with diseases that are associated with significant cutaneous inflammation (e.g., autoimmune disease). In each case, a list of differentials is generated based on the major clinical problem--that is, pruritus or inflammation. For the purposes of this discussion, we will concentrate on the differential diagnoses for clinically noninflammatory, nonpruritic alopecias of the dog. Differential Diagnoses Classic endocrine alopecias--follicles telogenized, atrophic, hairless: Hypothyroidism, hyperadrenocorticism, sex hormone imbalances (Sertoli s cell tumor, testicular neoplasia, cystic ovaries, ovarian neoplasia), pituitary dwarfism (growth hormone deficiency). Hair cycle arrest syndromes--follicles in catagen or early telogen: Alopecia X (has been previously referred to as adrenal sex hormone imbalance, castration-responsive alopecia, sex hormone-responsive dermatosis, maturity-onset growth hormone responsive dermatosis), Siberian Husky follicular dysplasia (possibly), Malamute Coat Funk (possibly), postclipping alopecia, telogen defluxion. Follicular dysplasia--abnormal follicular morphology: cyclical flank alopecia, color dilution alopecia, black hair follicular dysplasia. Crossover syndromes (hair cycle arrest and follicular dysplasia)? Alopecia of the Irish Water Spaniel, Curly Coated Retriever, Chesapeake Bay Retriever, Portuguese Water Dog Others--Pattern baldness; sebaceous adenitis (clinically noninflammatory), alopecia areata (clinically noninflammatory); congenital alopecia The Role of Biopsy in Differentiating These Problems Many of the above problems are diagnosed on the basis of history; physical examination (cyclical flank alopecia, pattern baldness, postclipping alopecia, color dilution alopecia); screening laboratory work, including complete blood count, serum chemistry panel, and urinalysis; and more specific endocrinologic tests (hypothyroidism, hyperadrenocorticism) and/or response to trial therapy (e.g., hypothyroidism, Sertoli s cell tumor, alopecia X). Biopsies are most commonly considered once hypothyroidism and hyperadrenocorticism have been ruled out as likely causes of alopecia. Biopsies should be taken from areas that are most significantly alopecic and ideally from the more dorsal areas of the thorax, abdomen, and lumbar region (assuming affected) because the follicular units (follicles and adnexae) are largest here and easiest for a pathologist to assess. In skin over the ventrum, the epidermis tends to be thinner and sebaceous glands tend to be smaller than over the back. These characteristics could mimic endocrine changes. A sample should also be taken from a more normally haired area. Managing Microbes Symposium Proceedings 2

3 The sample can be marked before the biopsy is taken, which will allow for better visualization of the entire follicular unit from the epidermis to the deep dermis or subcutis. This is achieved by drawing a line with a permanent marker (i.e., a Sharpie) along the lay of the hair and then centering the biopsy punch on this. Make it known to the pathologist that you have marked the sample and ask to have it cut in along the line. Endocrinopathies Nonspecific Coat Changes Associated with Classic Endocrinopathies (Hypothyroidism, Spontaneous and Iatrogenic Hyperadrenocorticism) and Sex Hormone Imbalances (Sertoli s Cell Tumor, Testicular Neoplasia, Cystic Ovaries, and Ovarian Neoplasia) Failure of hair to regrow after clipping Irregular/abnormal shedding cycles Increased shedding; some breeds (e.g., plush-coated, such as the Arctic breeds) often initially lose primary hairs over truncal areas; other breeds initially lose secondary hairs Hairs more readily epilated In some, may see retention of hair (often long, frizzy hair) Initial loss of hair over areas of wear (e.g., dorsum of tail, axilla, inguinal area) with progression to a more classical bilaterally symmetrical truncal alopecia that spares the head and distal extremities (Figures 1 and 2) Figure 1 Pituitary hyperadrenocorticism showing symmetrical alopecia sparing head and distal extremities. Managing Microbes Symposium Proceedings 3

4 Figure 2 Patient seen in Figure 1 showing symmetric nature of alopecia. Some individuals initially lose hair in a symmetrical pattern --pericervical, shoulders, dorsolateral lumbar region, caudal thighs, tail, then hair loss in areas coalesce to become the more classic, symmetrical, truncal alopecia. Lightening or bleaching of truncal coat color is common, with a tendency to spare the head and distal extremities Changes in hair texture (coarse or frizzy hair) Skin Changes Associated with the above Classic Endocrinopathies Cutaneous hyperpigmentation (earliest in areas of alopecia) Comedones (most commonly over ventral abdomen) Seborrhea (sicca or oleosa) Patients with these endocrinopathies (especially hypothyroidism and hyperadrenocorticism) are often prone to recurrent/persistent bacterial pyoderma These skin/coat changes are nonpruritic unless complicated by secondary bacterial pyoderma or Malassezia infections; secondary seborrhea may also potentiate pruritus but is usually mild Coat/Skin Changes That May Suggest a Particular Classic Endocrinopathy Changes That Suggest Hypothyroidism Skin remains of normal thickness--may occasionally appear thicker than normal because of the presence of myxedema Facial myxedema-- tragic expression Managing Microbes Symposium Proceedings 4

5 Alopecia over the bridge of the nose (Figure 3) (which is an exception to the rule that the alopecia associated with endocrinopathies spares the head and distal extremities) Figure 3 Hypothyroidism--alopecia over the bridge of the nose. Changes That Suggest Hyperadrenocorticism Cutaneous atrophy» Earliest signs at sites of old scars» With iatrogenic hyperadrenocorticism--often see punched-out focal areas that are very atrophic (usually do not see this with spontaneous hyperadrenocorticism); primarily found over the medial thighs, groin, and ventral abdomen» Striae (fine folds of skin)--seen over the hairless areas of the ventral abdomen» Thinning often most readily seen over the ventral abdomen where vasculature becomes more readily visualized» Thin skin palpated over the back (reduction in dermal thickness and subcutaneous fat) Cutaneous phlebectasias--small, 2- to 6-mm blood blister -like vascular proliferations that can be seen with spontaneous or iatrogenic hyperadrenocorticism. Those related to iatrogenic hyperadrenocorticism usually do not resolve after discontinuation of steroids. The major differential diagnosis for these lesions is hemangioma or hemangiosarcoma. Perianal adenomas in neutered females--suggest an adrenal source of androgens Calcinosis cutis Thoughts on the Pathogenesis of the Coat/Skin Changes Associated with Spontaneous Hyperadrenocorticism The cutaneous signs associated with spontaneous hyperadrenocorticism may not all be solely related to overproduction of cortisol in affected individuals. It has been noted that other sex hormones may also be produced in excess quantities. In one study of 10 dogs with pituitary-dependent hyperadrenocorticism and elevated cortisol responses to adrenocorticotropic hormone (ACTH) stimulation, the following sex hormones were also elevated following ACTH stimulation: androstenedione (5 of 9), DHEAS (2 of 8), progesterone (6 of 10), and 17 hydroxyprogesterone (4 of 10). 1 Managing Microbes Symposium Proceedings 5

6 In dogs with so-called atypical Cushing s syndrome, affected individuals manifest many or all of the classic signs of spontaneous hyperadrenocorticism, including coat and skin changes, but routine screening tests for hyperadrenocorticism are normal (i.e., ACTHstimulation test, low-dose dexamethasone-suppression test, urine cortisol-creatinine ratio). Affected individuals often have abnormalities of adrenal sex hormone production (pre- and/or post-acth stimulation). The adrenal steroids involved include androstenedione, estradiol, 17-hydroxyprogesterone, progesterone, and/or aldosterone. 2,3 These observations also support the significance of sex hormones mediating some of the cutaneous changes seen in patients with hyperadrenocorticism. Sex Hormone Imbalances Only a few sex hormone dermatoses appear to be reasonably well documented in the dog. In the intact female dog, these include hyperestrogenism associated with ovarian cysts or granulosa cell tumors and in the intact male dog, hyperestrogenism associated with Sertoli's cell tumors and hyperandrogenism due to testicular neoplasia (usually interstitial cell tumors). Signs of hyperestrogenism have been noted in association with estrogen administration in both males and females. Hyperestrogenism (Sertoli's Cell Tumor) Alopecia and feminizing occurs in about one third of males with testicular Sertoli s cell tumor. Hyperestrogenism has been rarely associated with interstitial cell tumors or seminomas. Affected individuals are middle-aged to older. Incidence is higher in patients with retained testicles. Affected individuals often develop a pattern of alopecia (caudal thighs, perineum, pericervical, shoulders, dorsolateral lumbar region, and ventrum). Plush-coated individuals (e.g., Arctic working breeds) may initially loose primary hairs, leaving only a secondary coat (wooly coat syndrome). In all cases, the head and distal extremities are spared. The truncal coat lightens in color (also sparing the head and distal extremities). Coat changes are associated with varying degrees of hyperpigmentation and seborrhea. Affected individuals may occasionally develop linear preputial erythema (Figure 4) or hyperpigmentation (line of asymptomatic hyperemia or Figure 4 Linear preputial erythema--hyperestrogenism associated with Sertoli s cell tumor. Managing Microbes Symposium Proceedings 6

7 hyperpigmentation down the prepuce; may extend on to the scrotum). The cause of this change is not known, but it does appear to correlate well with the presence of hyperestrogenism. Blood estrogen concentrations are variable and may only be significantly elevated in 30% to 40% of cases. In advanced cases, preputial cytologic preparations may show cornification similar to that noted in a vaginal swab from a bitch estrus. The diagnosis is usually made by assessing response to therapy (castration). Recall that about 10% of Sertoli s cell tumors are malignant. Consideration should be given to presurgical thoracic and abdominal radiographs. Hyperandrogenism Hyperandrogenism associated with androgen-producing interstitial cell tumors of the testicles has been noted to produce perianal and/or tail gland hyperplasia, macular melanosis of the perianal tissue, and alopecia that targets the tail gland. Affected individuals have the potential to develop more generalized seborrhea oleosa. Affected patients often have prostatomegaly and are also more prone to perianal adenomas and adenocarcinomas. A testicular mass may or may not be palpable. The therapy is castration. Hair Cycle Arrest Syndromes The pathogenesis of hair cycle arrest syndromes is unclear. Alopecia X Alopecia X is typified by hair follicles that are arrested in the catagen or early telogen stage of the hair follicle cycle. For this reason, it has been suggested that the syndrome be referred to as hair cycle arrest. 4 Because of its clinical presentation and response to variable therapies, this syndrome has also been previously described as castrationresponsive dermatosis, estrogen- or testosterone-responsive dermatosis, maturity-onset growth hormone-responsive dermatosis, and pseudo-cushing s disease. It is most commonly seen in the Nordic or plush-coated breeds: Chow Chow, Pomeranian, Keeshond, Samoyed, Siberian Husky, Alaskan Malamute, American Eskimo dog, and Finnish Spitz. The Miniature Poodle also seems to be predisposed. Individuals of other breeds may also be affected. Some have suggested that Malamute coat "funk" and follicular dysplasia of the Siberian Husky may be manifestations of this syndrome. Affected dogs begin to lose hair as young, mature individuals, usually at 1 to 3 years of age. However, older individuals may also develop the syndrome. Although the problem is more common in intact males, both intact or neutered males and females may be affected. Alopecia is truncal, sparing the head and distal extremities (Figure 5). The truncal coat lightens in color, again sparing the head and distal extremities. There may be focal regrowth of hair at sites of trauma. The cause of alopecia X is controversial. Affected individuals often do regrow hair after neutering or administration of sex hormones or after administration of sex hormonealtering drugs. 4 Some but not all affected dogs have been noted to have elevated basal and/or ACTH-stimulated progesterone, 17-hydroxyprogesterone, androstenedione, Managing Microbes Symposium Proceedings 7

8 Figure 5 Four-year-old, spayed female Pomeranian--hair cycle arrest (alopecia X) showing truncal alopecia (sparing head and distal extremities) and truncal cutaneous hyperpigmentation. estradiol, or other sex hormone concentrations. This suggests an abnormality of adrenal sex hormone production. These hormones may have any one of a number of effects on local metabolism of sex hormones at the follicular level or on sex hormone receptors. Arguing against the importance of these elevated sex hormones and sex hormone intermediates is the observation that successful treatment with either melatonin or mitotane does not alter sex hormone profiles in affected individuals. 5 In some cases, sex hormone concentrations increase even further with trilostane therapy, despite hair regrowth. 6 In addition, after stimulating hair regrowth, hormone therapy may be stopped in some, and hair regrowth will continue for months to years. 4 Spontaneous resolution of the problem has also been noted. It has also been suggested that this syndrome is a mild form of pituitary hyperadrenocorticism. 4 However, the points noted above, such as the periodic observance of spontaneous regression, prolonged response to various therapies after discontinuation, and that individuals show no other signs of hyperadrenocorticism, argue against this. It would seem more likely that hair cycle arrest syndrome is a primary hair growth disorder--a genetic predisposition to the development of a local defect in the hair growth cycle that may involve local follicular hormonal metabolism abnormalities and/or hormone receptor abnormalities. The diagnosis is largely by history, physical findings, and ruleout (i.e., hypothyroidism, hyperadrenocorticism). Skin biopsies are suggestive, but not confirmatory. Hairs in most affected breeds tend to be in the early phase of telogen (so called "flame follicles"), with the "flame" description related to excessive trichilemmal keratinization. Sebaceous glands tend to be normal to slightly attenuated. In the Pomeranian, it has been noted that flame follicles do not tend to be as prominent, and instead more of a miniaturization of hair follicles may be found. Pomeranians and non-nordic breeds are also more likely to have dermal atrophy. It is important to note that once alopecia X is strongly considered as the most likely diagnosis, no further workup may be necessary, especially if the owners are willing to Managing Microbes Symposium Proceedings 8

9 live with an alopecic pet. To date, there have been no obvious systemic abnormalities associated with this disease and thus no need for further workup and therapy. In the author's hands, diagnostics from this point are usually based on assessing response to therapy. Neutering is recommended initially, but if neutering is not beneficial or the patient must be left intact, we generally try melatonin for a 3-month period The dosage is 3 to 6 mg BID to TID. The author routinely starts melatonin on a BID basis. In the United States, melatonin is readily available over-the-counter. Brand-name products, such as Nature s Bounty, have been proven to contain the amount of melatonin stated on the label. Melatonin is generally well tolerated by dogs; however, sedation is sometimes encountered and warrants a dosage reduction. Hair regrowth usually starts within 4 to 6 weeks. Therapy with melatonin is continued until maximal hair regrowth is noted, at which time melatonin is discontinued. Therapy is reinstituted if and when signs recur. This protocol has been suggested to circumvent intolerance to the drug with chronic administration, which has been noted by some. Melatonin is reported to produce partial or complete coat regrowth in 50% to 60% of cases. 5 If melatonin is not beneficial, consideration can be given to methyltestosterone therapy. The dosage is 1 mg/kg to a maximum dose of 30 mg, given once daily. Methyltestosterone is generally well tolerated but can cause hepatotoxicity, aggressive behavior, and/or seborrhea. It is recommended that baseline liver screening be done before administration, then 1 and 2 months after the start of therapy. Supplementation is stopped after maximal regrowth is noted. If methyltestosterone therapy fails, then measurement of sex hormones before and after ACTH stimulation (e.g., University of Tennessee sex hormone panel) is recommended. If abnormalities are noted, there is a rationale for treating with mitotane (op,ddd; Lysodren) or trilostane. Mitotane probably benefits affected individuals through its adrenolytic effect on the zona reticularis and fasciculata (from which sex hormones are produced). It may also have direct peripheral effects on follicle function. Induction is usually done at a more conservative dose of 15 to 25 mg/kg PO daily for 5 to 7 days. An ACTH-stimulation test is performed 24 hours after the induction dose is completed. The goal is to have preand poststimulation cortisol levels within the normal resting range for the laboratory being used (e.g., pre- and postcortisol levels should be 3 to 5 μg/dl). If cortisol values are as desired, the patient is placed on the daily induction dose (15 to 25 mg/kg), divided and given twice weekly. If the values are low, mitotane should be discontinued and started on a maintenance basis once cortisol levels have returned to the desired range. An ACTH-stimulation test is generally performed 4 to 6 weeks after adequate induction, 3 months after that, and then every 3 to 6 months thereafter. Consideration should be given to discontinuation of the mitotane therapy once full hair regrowth is noted (some will continue to grow hair for extended periods). In one study, 12 of 12 chows were noted to respond to mitotane therapy, and in another study, 4 of 6 dogs were noted to respond. Trilostane, a drug used to treat hyperadrenocorticism (a competitive inhibitor of 13 betahydroxysteroid dehydrogenase that interferes with adrenal steroidogenesis) promotes hair regrowth in dogs with hair cycle arrest. Interestingly, 17-hydroxyprogesterone concentrations consistently increase in treated individuals. 6 Therapy is given daily until maximal regrowth is noted. At that time, consideration should be given to discontinuing the drug and assessing for duration of response, which may be long-term, or the need to Managing Microbes Symposium Proceedings 9

10 establish a maintenance regimen (e.g., 2 to 3 treatments weekly). In one study, response was noted in 13 of 16 Pomeranians and 8 of 8 Miniature Poodles. 6 In another study, 3 of 3 Alaskan Malamutes responded to trilostane therapy. 7 Trilostane appears to be well tolerated but is expensive and must be ordered from abroad. A source (in the United Kingdom) and protocol for use and monitoring (cortisol levels are monitored by ACTH stimulation) are available at mastermarketing.com. Postclipping Alopecia Persistent alopecia is occasionally noted following clipping after, for example, surgical and epidural procedures. Areas predisposed include the lower back and dorsal pelvic region. This syndrome is seen most commonly in long-coated breeds (Norwegian, plush-coated breeds, such as the Samoyed and Chow Chow, and German Shepherds) but may also be seen in other breeds (e.g., Rottweilers). The skin in the clipped area tends to hyperpigment but is otherwise normal (Figure 6). Some tufts of hair may be Figure 6 German Shepherd--postclipping alopecia and hyperpigmentation of lower back. seen to regrow, especially at sites of trauma. The surrounding haircoat is normal. The cause of this syndrome is unknown. Some have hypothesized that it results from vascular perfusion changes in response to decreased temperature of the skin due to clipping. However, many believe that the prolonged time to hair regrowth is because the clipping happened to occur during the normal catagen stage of hair growth--that is, between losing and growing a new haircoat. This phase of the follicular cycle can be very long in some individuals. Hair does eventually regrow, but may take from 6 to 24 months. Managing Microbes Symposium Proceedings 10

11 Follicular Dysplasia Canine Recurrent Flank Alopecia Recurrent flank alopecia (also known as seasonal flank alopecia, canine idiopathic cyclical flank alopecia, cyclical follicular dysplasia) has a high incidence in Airedale Terriers, Boxers, English Bulldogs, Schnauzers, Griffon Korthals, Affenpinschers, and Bearded Collies (genetic predisposition). Well-demarcated, variably symmetrical alopecia and hyperpigmentation are noted over the flanks and lateral thoracoabdominal areas and may involve the dorsal and dorsolateral lumbar region (Figures 7 and 8). Although less Figure 7 Boxer--cyclical flank alopecia. Note well-demarcated areas of alopecia and hyperpigmentation. Figure 8 Cyclical flank alopecia wherein flank alopecia has extended over the back. Note well-demarcated areas of alopecia. Managing Microbes Symposium Proceedings 11

12 commonly encountered, some individuals have cyclical alopecia over the bridge of the nose or caudal thighs or ventral cervical region. Episodes of alopecia are often recurrent (i.e., hair loss in the fall and regrowth in the spring, or vice versa). The cycle may repeat itself annually or skip years. It has been hypothesized that the problem may be related to a genetically influenced melatonin deficiency, which may affect the skin either directly or indirectly through the effect of melatonin on prolactin, androgens, estrogens, and/or growth hormone. Melatonin can be used to shorten the duration of an alopecic episode or to prevent recurrence. Response to therapy is noted in about 50% to 75% of cases. Dosage is 3 to 6 mg given BID to TID for 2 months (until hair loss is not noted when expected as the season changes or until good hair regrowth is noted). Therapy is stopped once hair growth has been attained but is reinstituted for recurrences. Color-Dilution Alopecia Color-dilution alopecia is seen in bluecoated Doberman Pinschers, Great Danes, Whippets, Dachshunds, Standard Poodles, Chow Chows, fawn and some red Doberman Pinchers, and fawn Irish Setters. Affected individuals are born with a normal coat but gradually develop alopecia that only affects the color dilute (e.g., blue) areas of the coat (Figure 9). Hairs from affected individuals show large melanin clumps. Skin biopsies Figure 9 Color-dilution alopecia. Hair loss restricted to blue areas of coat--tan areas remain haired. also show melanin clumping in the epidermis, at all levels of the hair follicle, and in melanophages around the base of hair follicles. Hair follicles have varying degrees of dysplasia. In the past, treatments have been largely symptomatic (antiseborrheic shampoos, moisturizers, antibiotics for secondary infections). Oral synthetic retinoids (e.g., isotretinoin, acitretin) have been suggested to produce some partial regrowth. More recently, melatonin has been noted to benefit some individuals (hair regrowth) at a dosage of 3 to 6 mg BID to TID until maximal response is noted. Response is noted in 30% to 40% of patients. Follicular Dysplasia Other alopecic syndromes that have been thought to be follicular abnormalities with or without adrenal sex hormone abnormalities (perhaps similar to alopecia X in the Nordic Managing Microbes Symposium Proceedings 12

13 breeds and Miniature Poodles) include alopecias of the Irish Water Spaniel, Curly Coated Retriever, Chesapeake Bay Retriever, and Portuguese Water Dog. They often have abnormalities in sex hormone panels and histopathologic changes that suggest follicular dysplasia (clumped pigment in hair follicle and/or hair shaft). Irish Water Spaniels have hair loss over the ventral and lateral neck and distal tail, laterodorsal neck, flanks, dorsum, rump, and caudal thighs. The disorder is noted in both males and females. Alopecia in females may become progressively worse after each cycle. In males, the alopecia sometimes starts as early as 1 to 2 years of age, but most are 5 to 6 years of age at time of onset. The coat typically bleaches. Histopathology shows follicular dilatation and hyperkeratosis, pilosebaceous dysplasia, clumped pigment in the hair follicle and/or hair shaft, and some degree of pigmentary incontinence. Interestingly, some dogs showed significant regrowth of hair on a diet of high omega-3 fatty acids containing fish and corn. 8 Chesapeake Bay Retrievers have thinning to complete hair loss on the axillae, flanks, abdomen, and caudal thighs. Alopecia usually begins between 1 and 4 years of age; one reported case first developed alopecia at 5 months of age. It is common to see sex hormone abnormalities, pre- and post-acth stimulation, in affected individuals. Histopathology reveals follicular hyperkeratosis and plugging, follicular atrophy, and occasional melanin clumping within malformed hair shafts. There is a strong familial predisposition. Although melatonin has been reported not to be an effective treatment, the author has had some success with this drug (6 mg given 2 to 3 times per day). Portuguese Water Dogs have variable numbers of lost primary hairs and the undercoat changes to a dull, lighter color (black to reddish). Alopecia may also be noted in the periocular region. Other Disorders Canine Pattern Alopecia (Pattern Baldness) Symmetrical hair loss is noted behind the ears, ventral cervical, chest and abdomen, caudal thighs, and perianally, primarily in Dachshunds, Boston Terriers, Chihuahuas, Whippets, Italian Greyhounds, Greyhounds, Boxers, and Miniature Pinschers. Individuals begin to lose hair at about 6 months of age and gradually progress. Diagnosis is by biopsy (follicles are both shorter and thinner than normal hairs, and residual hair shafts are extremely fine). Melatonin has been shown to be effective in regrowing hair in 50% to 70% of cases (1.5 to 6 mg/dog BID or TID). Therapy is continued until good regrowth, then discontinued and reinstituted with recurrence. Sebaceous Adenitis Sebaceous adenitis is typified by an inflammatory destruction of the sebaceous glands accompanied by a defect in epidermal keratinization. The keratinization defect is seen as marked superficial and follicular hyperkeratosis. The cause is unknown. Studies done with the Standard Poodle and Akita suggest an autosomal recessive mode of inheritance in these breeds. Managing Microbes Symposium Proceedings 13

14 A focal form of this disease is most commonly seen in the Visla and occasionally in other short-coated breeds. Affected dogs are presented with focal areas of alopecia and scaling. These areas of alopecia may take on arciform shapes (Figure 10). Scale is very fine and whitish. The skin is variably erythematous. The head, back, and sides of the thorax, and abdomen are most commonly affected (Figure 11). Diagnosis is by skin biopsy. This manifestation of the disease may occasionally respond to glucocorticoids. Good-to-excellent responses have been noted with retinoid therapy (isotretinoin, starting at 1 to 2 mg/kg/day) or oral cyclosporine therapy (5 mg/kg/day). Once complete Figure 10 Visla with focal form of sebaceous adenitis showing areas of alopecia that have taken on arcuate patterns. Also note fine, white scale and mild inflammation in affected areas. Figure 11 Visla from Figure 10--focal areas of alopecia, becoming confluent to produce widespread alopecia over back. Managing Microbes Symposium Proceedings 14

15 remission has been achieved, retinoid or cyclosporine therapy can be discontinued in some dogs and the disease will go in to indefinite remission. Others require daily or every-other-day maintenance therapy to maintain remission. Topical therapy as outlined below for the generalized form of the disease may be tried, but it is usually not very effective. The so-called generalized form of the disease is the most common and tends to affect longer-haired breeds, including the Standard Poodle, Samoyed, and Akita and many other breeds (Old English Sheepdog, Toy Poodle, Lhasa Apso, Boxer, Chow Chow, German Shepherd, and crossbreeds, to mention just a few). Age of onset is usually 1 to 3 years, but the disease may develop at any age. Hair loss is often focal and asymmetrical initially (Figure 12), with progression to more symmetrical, generalized loss and scaling (Figures 13, 14, and 15). Primary areas of involvement are the head (including the face), neck, back, sides of the thorax and abdomen, and anterior aspect of the extremities. The ventrum is usually less affected. Scale is heavy and adheres to the base of the hairs ( follicular casting ). The medial aspect of the pinna and canals are dry and scaly; there is often mild to moderate inflammation in the canals. Affected individuals may be prone to secondary staphylococcal pyoderma. Sebaceous adenitis is usually nonpruritic. Development of pruritus is usually attributed to the presence of secondary pyoderma or concurrent allergic disease. The disease may wax and wane. When considering differential diagnoses for widespread nonpruritic, noninflammatory hair loss, the common involvement of the head and distal extremities seen with sebaceous adenitis is the opposite of that seen with endocrinopathies and alopecia X, in which these areas tend to be spared. Diagnosis is based on skin biopsy: There is usually moderate acanthosis and generally severe hyperkeratosis with follicular plugging, as well as perifollicular inflammation localized in the region of the sebaceous glands. The severity of the inflammation varies from scant to severe (scant in chronic lesions). Sebaceous glands are absent. Figure 12 Early generalized form of sebaceous adenitis with focal areas of hypotrichosis (dark-haired areas). Managing Microbes Symposium Proceedings 15

16 Figures 13 and 14 Standard poodle with sebaceous adenitis showing generalized hair loss (including head and distal extremities) and heavy, adherent scale. Figure 15 Hairs plucked from patient with sebaceous adenitis. Note heavy, adherent scale at base of hairs (follicular casting). Managing Microbes Symposium Proceedings 16

17 There are several options for treatment of this disease. With topical therapy, the overall goal is to remove scale. After scale removal, some hair usually regrows, although the coat generally does not return to its original fullness. Systemic therapy, specifically with oral cyclosporine, has been noted to be most successful in returning the haircoat to normal. 10 Option 1: Alpha Keri Bath Oil (or generic) is diluted 50:50 in water and applied over the entire coat/skin. It is left on for 1 to 3 hours, then removed with repeated shampooing (use a mild shampoo, such as Ivory dishwashing liquid; the last one or two shampoos can be with a veterinary sulfur/salicylic antiseborrheic shampoo). Repeat every 3 to 4 weeks until the scale is gone, then reduce frequency to maintenance (i.e., once every 6 to 8 weeks). If not too labor-intensive for the owners, bathe with an antiseborrheic shampoo once weekly between oil baths. Ideally, follow each of these antiseborrheic baths with a good conditioner (e.g., Resi conditioner, such as ResiSoothe [Allerderm/Virbac]). Between more intensive oil therapies, a propylene glycol (PG)- containing, commercial product (e.g., Humilac, used undiluted) or PG USP diluted 50:50 with water can be sprayed on the skin and left on once every day or every other day. Some use the PG regimen instead of the more intense oil therapy: PG sprays daily; shampoo with antiseborrheic shampoo every 3 to 7 days initially; once scale is gone, start to decrease frequency of bathings first, then topical sprays. Long-term maintenance is bathing every 2 weeks with PG sprays 2 times per week. If desired, the owner can use a more concentrated PG spray. To reduce the need for more aggressive topical therapy, patients are also treated with oral vitamin A 8,000 to 20,000 IU BID (50% show at least partial improvement) and fatty acids (Derm Caps ES [DVM] 1 capsule BID, or evening primrose oil 500 mg BID). Option 2: Oral tetracycline/niacinamide (500 mg of each/dog TID to initiate therapy) or tetracycline alone with or without the topical therapies noted above. Option 3: Cyclosporine (5 mg/kg PO one daily) has been reported to be effective in most treated dogs. 10 Following the attainment of maximal response (usually within the first 4 months after the start of therapy), the frequency or dose of cyclosporine is reduced. Topical cyclosporine (as a 1:10 dilution in water; used as a spray once daily to initiate therapy) has also been used effectively. Of all the therapies for sebaceous adenitis, oral cyclosporine therapy seems to result in hair regrowth that is closest to normal. This therapy is also noted to potentially result in the regrowth of sebaceous glands. 10 References 1. Frank LA, Schmeitzel LP, Oliver JW. Steroidogenic response of adrenal tissues after administration of ACTH to dogs with hypercortisolemia. J Am Vet Med Assoc. 2001;218: Ristic JME, Ramsey IK, Heath FM, Evans J, Herrtage ME. The use of 17- hydroxyprogesterone in the diagnosis of canine hyperadrenocorticism. J Vet Intern Med. 2002;16: Oliver JW. Steroid profiles in the diagnosis of canine adrenal disorders. Proc 25th ACVIM;2007: Frank LA. Growth hormone-responsive alopecia in dogs. J Am Vet Med Assoc. 2005;226: Managing Microbes Symposium Proceedings 17

18 5. Frank LA, Hnilica KA, Oliver JW. Adrenal steroid hormone concentrations in dogs with hair cycle arrest (alopecia X) before and during treatment with melatonin and mitotane. Vet Dermatol. 2004;15: Cerundolo R et al. Treatment of canine alopecia X with trilostane. Vet Dermatol. 2004;15: Leone F, Cerundolo R, Vercelli A, LLloyd DH, The use of trilostane for the treatment of alopecia X in Alaskan Malamutes. J Am Anim Hosp Assoc. 2005;41: Cerundolo R, Lloyd DH, McNeil PE, Evans H. An analysis of factors underlying hypotrichosis and alopecia in Irish Water Spaniels in the United Kingdom. Vet Dermatol. 2000; 11: Cerundolo R, Mauldin EA, Goldschmidt MH, et al. Adult-onset hair loss in Chesapeake Bay retrievers: a clinical and histological study. Vet Dermatol. 2005;16: Linek M, Boss C, Haemmerling R, Hewicker-Trautwein M, Mecklenburg L. Effects of cyclosporine A on clinical and histologic abnormalities in dogs with sebaceous adenitis. J Am Vet Med Assoc. 2005;226: Managing Microbes Symposium Proceedings 18

19 Dogs That Itch: Determining the Cause and Stopping the Frenzy! Valerie A. Fadok, DVM, PhD, Diplomate, ACVD, Gulf Coast Veterinary Dermatology, Gulf Coast Veterinary Specialists, Houston, Texas Abstract Pruritus is among the most common and frustrating aspects of canine dermatologic disorders. Each of us is very familiar with the physical damage caused by constant scratching, and controlling itching is a critical part of the successful management of dogs with dermatologic diseases. It is also important to realize that, with few exceptions, most itchy dogs have manageable but chronic problems. One of our most important duties is to acknowledge this fact ourselves and share it with our clients. Frequent follow-ups and a sense of teamwork between client and veterinarian are the keys to success in managing itchy dogs. Key Content A standardized history is very important; to this end, a dermatology history questionnaire is immensely helpful. Treating for parasitic diseases (fleas, scabies, cheyletiellosis, demodicosis), treating infections (staphylococcal pyoderma, Malassezia dermatitis), and ruling out food allergies are advocated before a diagnosis of canine atopic dermatitis is made. Sarcoptic mange and flea and food allergy are the three most itchy disorders in dogs. Most pruritic skin disease in dogs is manageable, not curable, and for most dogs, we can decrease itching but not ablate it. Each client and itchy pet should be approached individually, as there is great variation in how much itching clients and pets can tolerate. Most pruritic skin disease in dogs is manageable, not curable, and for most dogs, we can decrease itching but not ablate it. Acknowledging these facts ourselves and helping our clients to accept them allows us to have an impact on canine pruritus, one patient at a time. Triaging your dermatology patients requires a good grasp of each dog s history. Taking a standardized history is very important. Because some owners are better oral historians than others, a dermatology history questionnaire is immensely helpful (Figure 1). If you have a clinic Web site, you can have these forms available online and ask your clients to download and fill them out before their appointment; alternatively, the clients can fill them out while they wait to be seen. You can make this task easy by asking your client to circle the appropriate responses. This format pleases the minimalist. I do recommend having spaces to write in extra information for detail-oriented clients who like to be complete. This questionnaire can easily fit on one side of a page, allowing you to scan it before your examination. Proceedings of a Symposium Held at the 2008 North American Veterinary Conference and the 2008 Western Veterinary Conference. Copyright 2008 Pfizer Inc. All rights reserved. The opinions expressed in the articles in this publication are those of the authors and do not necessarily reflect the official label recommendations and points of view of the company or companies that manufacture and/or market any of the pharmaceutical agents referred to. 1

20 Figure 1. Sample questionnaire for veterinary dermatology. Managing Microbes Symposium Proceedings 2

21 The next step is a good dermatologic examination, which requires good light and, when necessary, magnification. I often use the little magnifier on the otoscope to look closely at lesions. Rolling the dog over and looking at the bottoms of the feet, as well as under the tail is important, as is riffling the coat to see the skin over the back. You will be looking for primary lesions, such as papules, wheals, pustules, macules, or nodules. You will also be looking for identifying and describing these lesions will make consultations you have with veterinary secondary lesions, such as excoriations, crusts, scale, lichenification, and alopecia. Correctly identifying and describing these lesions will make consultations you have with veterinary dermatologists much more productive; descriptions and definitions are found in Muller and Kirk s Small Animal Dermatology. 1 Gentle otoscopy should also be performed to determine if the dog has an ear infection or whether the ear canals are merely red, the latter suggesting an allergic ear. During the examination, you can ask the owner which came first, the itching or the lesions. This information is useful, as atopic dermatitis has often been termed an itch that rashes, 2 whereas a disease like scabies is a rash that itches. The next step is to develop a list of differential diagnoses and a plan by which to sort them out. I usually tell the client that we will develop a short-term plan and a long-term plan. The short-term diagnostic plan consists of skin scrapings and cytologies, and maybe a dermatophyte culture if the history and physical examination support it. If you live in a flea-ridden area, using a flea comb during the examination can be very helpful. The skin scrapings will help us determine whether Demodex mites are present. If done properly, negative skin scrapings rule out demodicosis in most cases; however, negative skin scrapings never rule out scabies or cheyletiellosis. Skin cytologies help characterize the microbial infections that are present: bacteria, yeast, or both. The short-term treatment plan is to rule out scabies or cheyletiellosis if indicated, to control fleas if indicated, and to eliminate all microbial infections. If pruritus is severe, a short course of glucocorticoids is very helpful. In 1 month, I meet with the patient and client again to determine how much itching has been resolved by treating ectoparasites and microbial infections. Then we develop the long-term plan. The long-term diagnostic plan might be to perform elimination diet testing to rule out food allergy or to perform intradermal skin testing or serum allergy testing to discover which antigens are contributing to atopic dermatitis/atopy. Alternatively, we might develop a long-term steroid treatment regimen or suggest use of cyclosporine. Diagnostic tests, such as bacterial culture and sensitivity or biopsy, could be part of either the short-term or the long-term plan, depending on the appearance of the disorder during the first examination. The Dermatologic Toolbox Diagnostic techniques for dermatology are simple and cost-effective. Skin scrapings and cytologies should be part of the evaluation of every dermatologic patient, and they should be used during follow-up visits to assess progress. These techniques are well-described in current veterinary dermatology textbooks. 3.4 Placing the materials to take samples (glass slides, no. 10 blades, mineral oil, clear tape) in each exam room makes it quick and easy to do these tests. There are two types of skin scrapings: broad superficial scrapings, which are used to detect sarcoptic mange mites or Cheyletiella mites, and focal deep scrapings to detect Demodex mites. For the former, apply a film of oil to the skin first to facilitate uptake of all the crust and scale; then separate this matter among several slides for examination. For the latter, be sure to scrape deeply enough to cause capillary ooze. I often apply a thin film of mupirocin ointment after deep skin scraping for hemostasis and soothing. During evaluation for Demodex mites, it can also help to pluck several hairs for examination because mites are often found at the roots of hairs. 3,4 This technique may be safer for alopecic areas around the eyes. Managing Microbes Symposium Proceedings 3

22 Skin cytologies can be done in several ways, but I prefer to use clear acetate tape or clear packing tape. Press the tape to the surface of the skin, and then remove it. It will pick up surface corneocytes, on which bacteria and yeast are usually found. Stain the tape with a modified Giemsa/Romanowsky stain, such as Diff-Quick or Leukostat, avoiding the first in the series of 3, which is the methanol fix. Alternatively, glass slides coated with an adhesive, such as Duratak, Can be used; again, avoid the use of the methanol fix, which will melt the adhesive off of the slide. Cotton-tipped swabs are useful for ears and folds; smear or roll the matter onto glass slides. Slides made from ear swabs should be heat-fixed before staining. There are some key points for success with skin cytologies. First, examine the slides by microscopy using the oil-immersion lens, so you can differentiate among the types of bacteria. Second, be sure to maintain the microscope regularly to avoid artifacts and so it focuses properly. Third, change the stain solutions at least once weekly or more often if it is used heavily. A simple semiquantitative scoring system can be used to estimate the numbers of yeast and bacteria on slides (e.g., 1+ to 4+); scoring can be helpful when you are monitoring response to therapy. A flea comb can be a useful tool in areas where fleas are a significant cause of skin disease. The metal combs are very durable and can be used on each patient to help find and identify adult fleas, eggs, or flea dirt. Keep in mind, however, that flea allergic animals may find and remove fleas before we can, so not finding fleas on a dog does not rule them out as a cause of significant itching. Dermatophyte cultures should be used when dermatophytosis is suspected. Ringworm is less common than bacterial pyoderma or Malassezia yeast, but can be a cause of itching in some dogs. Many dermatologists advocate adding fungal culture to the minimum data base for each dermatologic patient. The major question is whether to set up these cultures in house or to send them out. Unless you are prepared to examine the cultures on a daily basis and perform microscopic analysis of fungal colonies, it probably makes more sense to send them out. If you culture them in-house, the cultures should be examined daily for development of red color as the colony grows. Also, dermatophyte colonies are not heavily pigmented--colonies usually appear white or light-colored. Bacterial culture and sensitivity are becoming more important, particularly for areas in which methicillin-resistant Staphylococcus intermedius are being identified. Biopsy can be a useful tool for selected dermatoses; however, most of the diseases that cause itching can be diagnosed without it. Histopathologic examination of tissue will not help to differentiate among the various allergies--it will only suggest that a hypersensitivity disorder is present. Most of the time you know this before you submit the biopsy. Things That Make Dogs Itch Many things make a dog itch (Table 1); thus, having a standard approach to itchy dogs is helpful. There are several recommendations available, but I favor the 4-step program advocated by Michele Rosenbaum and colleagues (Rosenbaum et al., personal communication, 2007). This approach allows you to diagnose most of the common things that make dogs itch as well as to exclude several causes of itching before making a diagnosis of canine atopy, which is a disease requiring chronic management and which you may wish to refer for skin testing and hyposensitization therapy. Dr. Rosenbaum advocates treating for parasitic diseases (fleas, Managing Microbes Symposium Proceedings 4

23 scabies, cheyletiellosis, demodicosis), treating infections (staphylococcal pyoderma, Malassezia dermatitis), and ruling out food allergies before making a diagnosis of canine atopic dermatitis. This approach is likely to identify the cause of more than 90% of the pruritus you will see and will make managing atopic dermatitis much easier. There are a few unusual skin diseases associated with itching; these disease look unusual, and a good rule of thumb is to biopsy anything that looks weird! Table 1. A Partial List of Pruritic Skin Diseases in Dogs on a Scale from 1 to 10 Intensely Itchy 8-10/10 Moderately Itchy 4-7/10 Mildly Itchy 1-3/10 Variably Itchy 1-10/10 Sarcoptic mange* Early uncomplicated Dry skin Cheyletiellosis atopy Food allergy (some)* Food allergy (most) Pyoderma (some) Demodicosis Flea allergy (most)* Flea allergy (some) Atopy (few) Pemphigus foliaceus Atopy (chronic Pyoderma (many) Dermatophytosis and/or infected Malassezia dermatitis Contact allergy Mycosis fungoides Pyoderma ( staphylococcal hypersensitivity )/ staphylococcal colonization Acral pruritic nodule/lick granuloma * The three most itchy skin diseases. Parasitic Disease The major parasitic causes of itching include fleas and flea allergy dermatitis, scabies, cheyletiellosis, and demodicosis. 5,6 The contribution of fleas to canine pruritus cannot be underestimated. Fleas have been acknowledged by veterinarians as a cause of itching in dogs since the early 1900s. 7 Dr. George Waterman noted that fleas are very troublesome to dogs, and occasion him and others a great deal of regret. Dogs may be allergic to fleas alone (simple flea allergy dermatitis) or an allergy to fleas can accompany food allergy or atopic dermatitis. Because dogs with flea allergies often remove the parasites themselves, they may have fewer fleas on them than their nonallergic cohorts. I think the best diagnostic tool for flea allergy is a trial with nitenpyram (Capstar, Novartis) for 1 month. This oral medication not only kills adult fleas rapidly, 8 it seems to prevent them from feeding. It is extremely safe and can be used in puppies 4 weeks of age or older weighing 2 or more pounds (see Novartis Web site, Capstar can be used safely with other methods of flea control. The only negative aspect is a very short duration. Dogs with flea problems will improve when Capstar is used every other day or 3 days a week (e.g., Monday, Wednesday, Friday of every week). Once the diagnosis is made, integrated pest management should be put into place for affected dogs and their cohorts, to include treatment with an adulticide and an insect growth regulator/insect development inhibitor, and environmental Managing Microbes Symposium Proceedings 5

24 treatment initially to reduce the environmental burden. Products containing selamectin, imidacloprid, and fipronil have been shown to be effective against the fleas that infest dogs and cats They are also easy for clients to use. Because flea allergy dermatitis is one of the three most itchy skin diseases of dogs, a short course of glucocorticoids may be needed to make the patient more comfortable. Scabies, or sarcoptic mange, is another of the top three most itchy diseases that can afflict dogs. In its classic presentation, it is easy to diagnose. It occurs in young dogs acquired from pet shops, shelters, or flea markets and is characterized by intense pruritus associated with a papular eruption. Crusts accumulate on the lateral margins of the ears and the elbows. Diagnosis is made by superficial skin scrapings, but it is critical to remember that negative skin scrapings do not rule out the diagnosis. In fact, in my experience skin scrapings are positive in fewer than 50% of cases. Diagnosis is confirmed by response to treatment, although modern acaricides kill many different types of parasites. 13 Selamectin (Revolution, Pfizer) can be applied every 2 weeks for three to four treatments to the patient and all animals with which the patient has contact. This topical parasiticide is approved for use in puppies as young as 6 weeks of age (see Pfizer Web site, Other treatments include lime sulfur, ivermectin, fipronil (although its efficacy has been disputed, moxidectin, and amitraz. 13 Because scabies occurs in older dogs, especially those that with a history of allergies, your level of suspicion should be raised in any allergic dog that has a sudden relapse that is intensely pruritic. These dogs may not show classical symptoms because they are bathed frequently for their allergies. Scabies should always be ruled out in these patients by treatment. In addition, keep in mind that not all dogs in the house will necessarily be itchy and it is not always easy to find an identifiable source of infestation in these older dogs. Urban wildlife may represent one source, 14 as the mites can live off the host for hours to days, depending on environmental conditions. 15,16 Cheyletiella infestation is not common in areas where fleas are prevalent, because many flea treatments kill these mites. 17 Cheyletiella infestation is more common in northern states and western states like Colorado, where fleas are less common. The pruritus caused by Cheyletiella is quite variable, but it can be intense. This mite can be transmitted to humans. These mites may also be difficult to document on skin scrapings; other recommended methods include flea combing, fecal analysis, and acetate tape preparations. 13,17,18 Cheyletiella mites are reported to be susceptible to many insecticides, although that has been disputed 19 ; however, the variation may result from geographic differences. I prefer to use selamectin every 2 weeks for three or four treatments, as I do for scabies. Exterminating mites in the environment is important because they can remain viable away from a host for several days. 13,17.18 Although the belief that demodicosis is not pruritic is widespread, many veterinarians have observed pruritus in some dogs infected with this hair follicle mite, even in the absence of bacterial and yeast infections. Concurrent allergies may be present in some of these patients. In addition, the pruritus may be associated with dying mites, as I have observed that the pruritus can intensify once treatment for mites is started. Steroids are not an option for dogs with demodicosis; the pruritus will have to be controlled by diagnosing and treating secondary infections and by diagnosing underlying allergies. Antihistamines can sometimes be helpful. Diagnosis is best made by deep skin scraping; however, it has recently been reported that hair pluckings and exudate cytology can also be diagnostic, although less sensitive than deep skin scraping. 20 The only approved treatment for demodicosis is amitraz (Mitaban, Pfizer), which is labeled for use at 250 ppm as a whole-body dip every other week. Some dermatologists have advocated weekly dips; others have advocated doubling the concentration to 500 ppm. 5,6 Because of the Managing Microbes Symposium Proceedings 6

25 potential toxicity to humans, most veterinarians prefer to apply the dip in their practices. I rarely use amitraz dips and prefer oral ivermectin. Many dermatologists are using ivermectin (300 to 600 micrograms/kg/day) in nonherding breeds and milbemycin (1 to 2 mg/kg/day) in herding breeds. It is worth considering performing genetic testing for MDR1 mutation in dogs before using ivermectin, as this mutation has been shown to be the cause of increased ivermectin sensitivity in collies. 21,22 The test is commercially available and reasonably priced (see Infectious Disease The major infectious causes of itching in dogs include staphylococcal pyodermas and Malassezia dermatitis. Dermatophytosis is less common but can cause itching in dogs, especially when the disease is caused by Trichophyton mentagrophytes. Most itchy pyodermas are caused by Staphylococcus intermedius and present as staphylococcal surface overcolonization 23 or folliculitis. Diagnosis can be made by skin cytology in most cases. Treatment requires good antistaphylococcal antibiotics for 3 to 4 weeks (or longer depending on the depth of the pyoderma), along with appropriate topical therapy. Avoid penicillin, amoxicillin, ampicillin, or tetracycline because they are rarely effective. Amoxicillin potentiated by clavulanic acid (Clavamox, Pfizer) remains a good choice, as do the cephalosporins. Cefpodoxime (Simplicef, Pfizer) in particular is handy because of its once-daily dosing at 5 to 7 mg/kg/day. Fluoroquinolones are usually a poor choice for superficial pyodermas, particularly since they are usually underdosed. Enrofloxacin is currently recommended to be given at 20 mg/kg once daily for pyodermas, which makes it quite expensive. Useful shampoos contain chlorhexidine, ethyl lactate, or benzoyl peroxide. Dogs that do not respond within 10 to 14 days to appropriate antibiotic therapy should have a bacterial culture and sensitivity performed. Methicillin-resistant S. intermedius seem to be increasing. 24 Overcolonization or infection of the skin by Pseudomonas species, usually P. Aeruginosa, has been documented. 25 Dogs with colonization by rods can be very itchy, although they are sometimes painful. In dogs with these infections or mixed infections with cocci and rods, marbofloxacin (Zeniquin, Pfizer) at 5.5 mg/kg/day may be useful. Silver sulfadiazine topically for localized infections can also be helpful. Malassezia pachydermatis is a significant cause of itching in dogs. 26, 27 It can be the sole infection present, but is more often combined with S. intermedius. Diagnosis is made best by skin cytology. Treatment for most dogs is best accomplished by oral antifungal therapy, either ketoconazole or fluconazole at 5 mg/kg/day for 3 to 4 weeks, or longer if necessary. Topical therapy alone can be successful, but it requires that the dogs be bathed every day and most owners will not be able to do so. A combination of systemic and topical therapy is ideal. Shampoos containing miconazole (Malaseb, IVX) or ketoconazole (Ketochlor, Virbac; Mal-A- Ket, Derm-A-Pet) are useful. The Malaseb line is particularly useful because it contains shampoo, ear flush, spray, pledgets, a rinse, and now towelettes. The pledgets and towelettes are helpful for maintenance treatment. Food Allergy/Food Intolerance/Adverse Reaction to Food It is very clear that some itchy dogs respond to elimination diet testing; however, the exact mechanism by which food causes itching remains a mystery. True food allergy probably does exist in some dogs; other dogs may be responsive because of idiosyncratic intolerances or adverse reactions. For our intents and purposes, it is probably not necessary to differentiate among these. It remains true that there is no effective way to diagnose food reactions in dogs except by elimination diet testing. While skin-testing extracts and blood allergy testing are Managing Microbes Symposium Proceedings 7

26 available, they do not seem to be specific or sensitive 28,29 and therefore are not cost-effective for clients. Everyone has his or her favorite elimination diets, and there is little hard evidence that one is better than another, although home-cooked diets appear to be the gold standard. I favor the use of novel protein/novel carbohydrate diets, which contain ingredients to which the dog has not previously been exposed and thus should not be reactive. However, the choice of protein and carbohydrate can be problematic. Some dermatologists believe that there is potential cross reaction between venison and beef, and among chicken, turkey, and duck. There is some evidence that IgG is a major food allergen for meat-allergic humans and that their beefreactive IgE cross-reacts with venison and lamb, but not pork or turkey. 30 We do not have this information available for dogs. So perhaps the safest choice is rabbit and potato, or kangaroo and oatmeal. Fish-based diets seem to be less useful. 31 That food allergic dogs can be managed successfully using commercial diets has been shown by Leistra and colleagues. 32 The newest trend is toward hydrolysis of proteins into peptides of fewer than 10,000 daltons; this size is based on the observation that food allergens tend to be 10,000 to 70,000 daltons. 33 Feeding hydrolyzed diets has been shown to be successful in the diagnosis and management of canine food allergy. 34 However, there are anecdotal reports of dogs with chicken allergies becoming symptomatic when placed on hydrolyzed chicken diets (Linda Messinger, et al., personal communication, 2005). Hill s makes z/d Ultra, which contains hydrolyzed chicken/chicken liver with an average molecular weight of less than 3000 daltons. Purina s HA is based on hydrolyzed soy. I believe that if we use commercial diets to diagnose of food allergy, at least two diets should be tried before ruling out the diagnosis. The diagnosis is the cure; avoidance is the best way to manage food allergy. However, food allergic dogs may also have atopic dermatitis. Atopic Dermatitis/Atopy Atopy is the genetic tendency to produce IgE in response to several environmental allergens, including pollen, dust, mold, dander, mite, and certain foods. In humans, three major clinical syndromes have been identified, including atopic dermatitis, allergic rhinitis/conjunctivitis, and asthma. These three classic allergic diseases occur in veterinary species; however, the prevalence of each varies among species. Allergic rhinitis has been identified in cattle; reactive airway disease has been identified in horses and cats, and atopic dermatitis (or at least skin manifestations of atopy) has been identified in dogs, cats, and horses. Most dogs with atopy have dermatitis as the major clinical manifestation of disease. There is some dissension among veterinary dermatologists about whether overproduction of IgE is a primary or secondary cause of atopic dermatitis. The disease is quite complex, and it is likely that as the involved genes are multifactorial, so are the pathogenetic mechanisms. 35 Recent and very preliminary studies of canine atopic dermatitis have suggested lipid barrier dysfunction in the skin 36 and that immune derangements, such as those seen in humans, may be present in dogs, at least at the RNA level. 37,38 Clinical sings of atopy manifest when the dog is between the ages of 2 and 4 years, although depending on their genetic background and environmental exposure, they may have signs when they are younger than 1 year of age. The major clinical sign is pruritus; however, secondary skin and ear infections with bacteria and yeast often follow. The itching may be seasonal or nonseasonal, depending on the allergens to which the dog reacts. Diagnosis is made by eliminating other causes of pruritus and by history and clinical signs. Ideally, specific treatment with immunotherapy is instituted early in life. Selection of allergens is based on immunologic testing. The test of choice is the intradermal skin test. 39 This test involves Managing Microbes Symposium Proceedings 8

27 intradermal injection of allergenic extracts of pollen, dust, mold, mites, and dander and is best done by veterinarians who are trained and experienced in allergy diagnosis and management. The specific choice of allergens varies according to location. If intradermal skin testing is not available, then blood allergy testing is recommended. Blood allergy testing in dogs has improved over the past couple of decades, but for most dogs, it remains less sensitive and less specific than skin testing. 40,41 I have no doubt that blood allergy testing can be a useful tool and have used it myself for patients that cannot be withdrawn from steroids or that could not physically tolerate the procedure. I have found that patients with positive blood allergy tests and appropriate symptoms have responded well to immunotherapy; however, I have made the allergy vaccines myself and used my own schedules. Treatment of atopic dermatitis is, in general, lifelong. Dogs with this disorder are high maintenance for veterinarian and client alike. Managing these patients requires realism, patience, commitment, and time. Recurrent bacterial and yeast infections will need to be identified and treated. Itching will need to be controlled, but with realistic goals in mind. Ideally, immunotherapy is used and adjusted specifically for each patient as needed. Even so, it is likely that these dogs will need adjunctive therapy during the first year of their vaccine. 42 There are many pharmacologic options for treating itching associated with atopic dermatitis. However, good published evidence exists only for glucocorticoids and cyclosporine, 43 and it is important to note that the study evaluated the use of each drug as a sole treatment, not as part of a comprehensive treatment program. Thus, if immunotherapy is used, it may be beneficial to use fatty acids and antihistamines as part of the whole treatment package, but we don t know that for certain. Some owners report success with fatty acids and/or antihistamines so it may be worthwhile to try these agents because they have few side effects. Most of the commercial fatty acid supplements contain fish oil, although flaxseed oil has also been suggested to be effective in canine atopic dermatitis. 44 Unfortunately, the choice of antihistamine is empirical. Each dog seems to respond differently, so it has been popular for veterinary dermatologists to advise trying 3 or 4 sequentially, with each drug given for 2 weeks. The owner then picks the one that works best. I think that a small subset of dogs with mild atopic dermatitis can be managed in this way. For dogs with more intense itching, glucocorticoids may be required. My experience suggests that at least some atopic dogs can be managed with low alternate-day doses of glucocorticoids alone; however, many dogs require increasing doses of steroids, making these drugs less desirable as the sole treatment. Low doses of glucocorticoids may be helpful in combination with immunotherapy. I favor using low doses of steroids either on an alternate-day basis, or as pulse therapy, early in the course of immunotherapy as we wait for the positive benefits to kick in. I really like using the veterinary product Temaril-P (Pfizer), each tablet of which contains the antihistamine trimeprazine and 2 mg prednisone. This combination helps to keep the total steroid dose quite low. My protocol has been to place dogs beginning immunotherapy on this drug, then try to withdraw it in 2 to 3 months. If the dogs relapse, continue for another 2 to 3 months, then try to withdraw it again. Many dogs will be able to stop the drug in 6 to 12 months of immunotherapy. Candace Sousa has developed what she has termed her safe annual dose of prednisone, which is based on the normal annual cortisol production by dogs. 45 Using the assessment that prednisone is about 4 times as potent as endogenous cortisol, she has developed an easy-to-use equation to estimate this safe annual dose: body (lbs) x 15, or body weight (kg) x 30, = safe annual dose of prednisone. 45 Through use of this formula, dogs in which itching is controlled by this dose of prednisone are at lower risk for steroid side effects; if dogs require more than this dose, then other means of itching control need to be sought. Using Temaril-P makes achieving this safe dose very easy once infections are controlled and other causes of pruritus have been addressed. Managing Microbes Symposium Proceedings 9

28 Designing and using immunotherapy is the ultimate goal of performing an intradermal skin test or blood allergy test. It is highly desirable as a treatment because it has few side effects, is individualized for each patient, and has the potential to retrain the immune system and inhibit its overreactivity. Estimates vary, but most veterinary dermatologists report success rates of about 60% to 70%. 46 Successful immunotherapy requires extensive client communication and fairly frequent monitoring, at least by phone. This is not a one-size-fits-all treatment. Proper selection of allergens is important and should be made by someone familiar with interpreting skin test or blood allergy test results. Dosages and frequency of injections must be adjusted as needed, so that each program is individualized according to each patient s needs. 46 In general, we find that persisting with weekly allergy injections through the first year is very helpful for most patients. Therefore, some of the schedules provided by the serum allergy companies that suggest rapidly decreasing injections to once a month may not be effective for some of your atopic patients. Bathing is underestimated as a tool in the treatment of atopic dogs. 47 Frequent bathing can often reduce allergens from the surface of the skin, as well as help keep the numbers of bacteria and yeast low. Newer shampoos have been designed to help restore the defective barrier of the skin (e.g., Douxo, Sogeval; see as well as inhibit colonization of the skin by bacteria and yeast (Virbac glycotechnology; see Topical therapy should always be used in atopic patients and the shampoo chosen specifically for each individual patient according to their needs. In my view, cyclosporine as a treatment for atopy should be reserved for patients in which immunotherapy has failed or for elderly patients that may not live long enough to experience the benefits of immunotherapy. It is fair to say that we know little about how this drug really works in atopic dogs. What we do know is that it is expensive, has a short half-life, and has been used for such a relatively few number of years that potential side effects are probably underappreciated. That said, cyclosporine has been an effective treatment for many atopic dogs and has substantially improved their quality of life. 43 Estimates of efficacy have been about 60%. As near as we know now, long-term use of cyclosporine is associated with much fewer side effects than long-term use of glucocorticoids. Unusual Causes of Itching A few other causes of itching should be mentioned. One of these is trivial: dry skin. Dry skin is easily treated by enriching the diet with essential fatty acids, usually at doses lower than those required to reduce atopic pruritus, and by the use of emollient shampoos and rinses. The other two are usually unusual enough that a biopsy will be required to make the diagnosis. The autoimmune skin disease pemphigus foliaceus can sometimes cause pruritus in affected dogs. Pemphigus foliaceus is relatively common in dogs and often requires lifelong immunosuppressive therapy. The neoplastic skin disease mycosis fungoides (epitheliotropic T- cell lymphoma) can sometimes cause itching. There is no cure for this disease; however, many oncologists have found that lomustine can provide short-term palliation. Managing Microbes Symposium Proceedings 10

29 Putting It All Together In summary, managing pruritus in dogs involves the following steps: 1. Rule out parasitic causes of itching. 2. Rule out infectious causes of itching. 3. Rule out food allergy. 4. Diagnose and manage atopic dermatitis, or refer the patient for such diagnosis and management. At any step along the way if the dermatitis is unusual or response to therapy is not appropriate, then a biopsy must be done to rule out unusual causes. Up to step 4, steroids should not be used until a diagnosis has been made. When steroids are used, use Candace Sousa s equation for determining safe annual doses. The following section provides case examples of common pruritic diseases. Using these scenarios, we will work through a series of patients with pruritic skin disease, discussing the key historical and clinical features as well as the diagnostic and treatment plans for each. Patient 1: Mr. Big, 3-Month-Old Male Poodle Key historical features: Young, intensely itchy dog purchased at roadside stand. Key diagnostic features: Erythematous papular rash, positive pinnal-pedal reflex, scale and crust on ears, positive cytologies for cocci/yeast, negative skin scrapings a red herring. Treatment: Topical selamectin every 2 weeks for 3 treatments, oral cefpodoxime and fluconazole, antiseborrheic shampoos; methylprednisolone for pruritus. Final diagnosis: Sarcoptic mange, with secondary pyoderma and Malassezia dermatitis. Important points: Negative skin scrapings do not rule out sarcoptic mange. It is important to treat the bacterial and yeast infections associated with mange. Because Sarcoptes induce a hypersensitivity reaction, corticosteroids may be helpful in ameliorating the itching. Managing Microbes Symposium Proceedings 11

30 Patient 2: Koby, 9-Year-Old Male Malamute Mix Key historical features: Partial response to antibiotics, steroids; mild pruritus a red herring? Key diagnostic features: Crusting on ear margins, positive pinnal-pedal reflex, skin scrapings positive for mites, cytology positive for cocci, low thyroid hormone levels. Treatment: Oral ivermectin, oral cephalexin, antiseborrheic shampoos, thyroid supplementation. Final diagnosis: Sarcoptic mange, hypothyroidism, secondary pyoderma. Important points: Older dogs can get scabies. Although no other dogs in the house were itchy, they may have been asymptomatic carriers and possible sources of infection for our patient; all in-contact animals should be treated. Large numbers of mites may be present in debilitated dogs: Norwegian scabies. An underlying metabolic disease may predispose to large numbers of mites; the depression associated with hypothyroidism may have made him less itchy with the disease. Prolonged treatment times may be required for dogs with large numbers of mites. Managing Microbes Symposium Proceedings 12

31 Patient 3: Bonnie, 3-Year-Old Female Spayed West Highland White Terrier Key historical features: Owners observations of fleas, short-term response to steroids, insufficient flea control for patient and her housemates. Key diagnostic feature: Presence of fleas on patient, pattern of alopecia, response to treatment. Treatment: Oral Capstar and increased frequency of topical Advantage for patient, oral lufenuron and topical selamectin for cats, treatment of house and yard. Final diagnosis: Flea allergy dermatitis. Important points: Flea allergy dermatitis requires integrated pest management on all animals in the house. Controlling itching sometimes requires only increasing awareness of the flea life cycle and increasing vigor of flea control. Steroids not required for this dog. Managing Microbes Symposium Proceedings 13

32 Patient 4: Ingrid, 3-Year-Old Female Spayed Shepherd Cross Key historical features: Pruritus at a young age, inappropriate dietary trials, variable response to steroids, no response to treatment for scabies. Key diagnostic features: Failure to respond to treatment for scabies, cytologies positive for cocci and yeast, response to treatment for infections, eventual response to strict dietary trial and food challenges. Final diagnosis: Food allergy, with secondary pyoderma and Malassezia dermatitis. Important points: Dietary trials must be complete. All edible treats and toys must be stopped. Infection control can improve the comfort level of food allergic dogs. Food challenges can enable the dog to go back on a commercial diet. Not all food-allergic dogs are refractory to steroids. It may be important to try more than one diet if food allergy is highly suspected. Managing Microbes Symposium Proceedings 14

33 Patient 5: Schotze, 4-Year-Old Female Spayed Shih Tzu Key historical features: Nonseasonal pruritus with seasonal flares, exacerbation following move to warmer climate. Key diagnostic features: Skin cytology, response to flea control, response to dietary trial, intradermal skin testing. Final diagnosis: Flea allergy dermatitis, food allergy, atopic dermatitis with secondary pyoderma and Malassezia dermatitis. Important points: Dogs can have multiple allergies. Observing response to flea control and food trials requires that the infections be managed. Controlling fleas and elimination diet testing revealed that atopic dermatitis was still a possibility, so skin testing and immunotherapy were pursued. Managing Microbes Symposium Proceedings 15

34 Patient 6: Tessie Belle, 1-Year-Old Female Spayed West Highland White Terrier Key historical features: Moderate to severe pruritus with no response to treatment for scabies, relinquished to breed rescue society. Key diagnostic features: No response to treatment for scabies, skin cytologies positive for cocci and yeast, response to infection control, positive blood allergy test, positive intradermal skin test. Final diagnosis: Flea allergy dermatitis and atopy with secondary pyoderma and Malassezia dermatitis. Important points: Malassezia is an intensely pruritic disorder. Malassezia can be brought under control with topical therapy but requires daily bathing for several weeks. Infection control can reduce itching dramatically in atopic dogs. Managing Microbes Symposium Proceedings 16

35 Patient 7: Boudreaux, 5-Year-Old Male Castrated Labrador Cross Key historical features: Poor response to antibiotics, poor response to Depo Medrol, nonseasonal pruritus with waxing and waning nature. Key diagnostic features: Distribution of primary lesions on face, ears, and footpads Final diagnosis: Pemphigus foliaceus with secondary bacterial pyoderma. Important points: Historical ringer was the seasonal nature of the disease: This dog s pemphigus flares every summer. Primary lesions of pustules and crusted papules on face and ears very suggestive of pemphigus foliaceus. If skin disease looks strange, biopsy it! Managing Microbes Symposium Proceedings 17

36 Patient 8: Clancy, 6-Year-Old Male Castrated English Bulldog Key historical features: Atopic dog on immunotherapy well regulated for 3 years; relapsing pruritus and erythematous plaques, collarettes over past 6 months; poor response to antibiotics and steroids. Key diagnostic features: Negative cytology, skin biopsy, distribution of the lesions on top of the head, and the indurated character of the lesions (if it s weird, biopsy it). Final diagnosis: Epitheliotropic T-cell lymphoma (mycosis fungoides). Important points: Relapsing itching after years of good control on immunotherapy. Poor response to antibiotics and steroids. Unusual distribution, appearance, and feel of lesions. References 1. Scott DW, Miller WH, Griffin CE. Muller and Kirk s Small Animal Dermatology, ed. 6. Philadelphia: WB Saunders;2001: Boguniewicz M. Atopic dermatitis: beyond the itch that rashes. Immunol Allergy Clin North Am. 2005;25: Scott DW, Miller WH, Griffin CE. Muller and Kirk s Small Animal Dermatology, ed. 6. Philadelphia: WB Saunders;2001: Medleau L, Hnilica KA. Small Animal Dermatology. A Color Atlas and Therapeutic Guide, ed. 2. Philadelphia: Elsevier;2006: Scott DW, Miller WH, Griffin CE. Muller and Kirk s Small Animal Dermatology, ed. 6. Philadelphia: WB Saunders;2001: Medleau L, Hnilica KA. Small Animal Dermatology. A Color Atlas and Therapeutic Guide, ed. 2. Philadelphia: Elsevier;2006: Managing Microbes Symposium Proceedings 18

37 7. Waterman GA. The Practical Stock Doctor. HL Baldwin;1909: Schenker R, Tinembart O, Humbert-Droz E, Cavaliero T, Yerly B. Comparative speed of kill between nitenpyram, fipronil, imidacloprid, selamectin and cythioate against adult Ctenocephalides felis (Bouche) on cats and dogs. Vet. Parasitol. 2003;112: Franc M, Yao KP. Comparison of the activity of selamectin, imidacloprid and fipronil for the treatment of cats infested experimentally with Ctenocephalides felis felis and Ctenocephalides felis strongylus. Vet. Parasitol. 2007;143: Cadiergues MC, Caubet C, Franc M. Comparison of the activity of selamectin, imidacloprid and fipronil for the treatment of dogs infested experimentally with Ctenocephalides canis and Ctenocephalides felis felis. Vet. Rec. 2001;149: Dryden MW, Smith V, Payne PA, McTier TL. Comparative speed of kill of selamectin, imidacloprid, and fipronil-(s)-methoprene spot-on formulations against fleas on cats. Vet Ther. 2005;6: Dryden MW, Denenberg TM, Bunch S. Control of fleas on naturally infested dogs and cats and in private residences with topical spot applications of fipronil or imidacloprid. Vet Parasitol. 2000;93: Curtis CF. Current trends in the treatment of Sarcoptes, Cheyletiella and Otodectes mite infestations in dogs and cats. Vet Dermatol. 2004;15: Pence DB, Ueckermann E. Sarcoptic mange in wildlife. Rev Sci Tech. 2002:21: Arlian LG, Vyszenski-Moher DL, Pole MJ. Survival of adults and development stages of Sarcoptes scabiei var.canis when off the host. Exp Appl Acarol. 1989;6: Arlian LG, Runyan RA, Achar S, Estes SA. Survival and infectivity of Sarcoptes scabiei var. canis and var. hominis. J Am Acad. Dermatol. 1984;11: Scott DW, Miller WH, Griffin CE. Muller and Kirk s Small Animal Dermatology, ed. 6. Philadelphia: WB Saunders;2001: Medleau L, Hnilica KA. Small Animal Dermatology. A Color Atlas and Therapeutic Guide, ed. 2. Philadelphia: Elsevier;2006: Moriello KA. Treatment of Sarcoptes and Cheyletiella infestations. In: Krik RW, Bonagura JD (eds): Kirk s Current Veterinary Therapy XI: Small Animal Practice. Philadelphia: WB Saunders Co;1992: Saridomichelakis M, Koutinas AF, Farmaki R, Leontides LS, Kasabalis. Relative sensitivity of hair pluckings and exudate microscopy for the diagnosis of canine demodicosis. Vet. Dermatol. 2007;18: Mealey KL, Bentjen SA, Gay JM, Cantor GH. Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene. Pharmacogenetics. 2001;11: Managing Microbes Symposium Proceedings 19

38 22. Mealey KL. Therapeutic implications of the MDR-1 gene. J Vet Pharmacol Ther. 2004;27: Pin D, Carlotti DN, Jasmin P, DeBoer DJ, Prelaud P. Prospective study of bacterial overgrowth syndrome in eight dogs. Vet. Rec. 2006;158: Morris DO, Rook KA, Shofer FS, Rankin SC. Screening of Staphylococcus aureus, Staphylococcus intermedius, and Staphylococcus schleiferi isolates obtained from small companion animals for antimicrobial resistance: a retrospective review of 749 isolates ( ). Vet Dermatol. 2006;17: Hillier A, Alcorn JR, Cole LK, Kowalski JJ. Pyoderma caused by Pseudomonas aeruginosa infection in dogs: 20 cases. Vet. Dermatol. 2006; Morris DO Malassezia dermatitis and otitis. Vet Clin North Am Small Anim Pract. 1999;29: Medleau L, Hnilica KA. Small Animal Dermatology. A Color Atlas and Therapeutic Guide, ed. 2. Philadelphia: Elsevier;2006: Jeffers JG, Shanley KJ, Meyer EK. Diagnostic testing of dogs for food hypersensitivity. J Am Vet Med Assoc. 1991;198: Kunkle G, Horner S. Validity of skin testing for diagnosis of food allergy in dogs. J Am Vet Med Assoc. 1991;200: , 30. Ayuso R, Lehrer SB, Lopez M. et al. Identification of bovine IgG as a major cross-reactive vertebrate meat allergen. Allergy. 2000;55; Tapp T, Griffin C, Rosencrantz W, Muse R, Boord M. Comparison of a commercial limitedantigen diet vs home-prepared diets in the diagnosis of canine adverse food reaction. Vet Ther. 2002;3: Leistra MH, Markwell PJ, Willemse T Evaluatiion of selected-protein-source diets for management of dogs with adverse reactions to foods. J Am Vet Med Assoc. 219: Lehrer SB, Horner WE, Reese G. Why are some proteins allergenic? Implications for biotechnology. Crit Rev Food Sci Nutr. 1996; Loeffler A, Soares-Magalhaes R, Bond R, Lloyd DH. A retrospective analysis of case series using home-prepared and chicken hydrolysate diets in the diagnosis of adverse food reactions in 181 pruritic dogs. Vet Dermatol. 2006;17: DeBoer DJ. Canine atopic dermatitis: new targets, new therapies. J Nutr. 2004;134:S2056- S Inman AO, Olivry T, Dunstan SM, Monteiro-Riviere A, Gatto H. Electron microscopic observations of stratum corneum intercellular lipids in normal and atopic dogs. Vet Pathol. 2001;38: Managing Microbes Symposium Proceedings 20

39 37. Nuttall TJ, Knight PA, McAleese SM, Lamb JR, Hill PB. Expression of Th1, Th2 and immunosuppressive cytokine gene transcripts in canine atopic dermatitis. Clin. Exp.Allergy.2002;32: Marsella R, Olivry T, Maeda S. Cellular and cytokine kinetics after epicutaneous allergen challenge (atopy patch testing) with house dust mites in high-ige beagles. Vet Dermatol. 2006;17: Hillier A, DeBoer DJ. The ACVD task force on canine atopic dermatitis (XVII): intradermal testing. Vet Immunol Immunopathol. 2001;81: DeBoer DJ, Hillier A. The ACVD task force on canine atopic dermatitis (XVI): laboratory evaluation of dogs with atopic dermatitis with serum-based allergy tests. Vet Immunol Immunopathol. 2001;81: Foster AP, Littlewood JD, Webb P, Wood JL, Rogers K, Shaw SE. Comparison of intradermal and serum testing for allergen-specific IgE using a Fc epsilon R alpha-based assay in atopic dogs in the UK. Vet Immunol Immunopathol. 2003;93: Colombo S, Hill PB, Shaw DJ, Thoday KL. Requirement for additional treatment for dogs with atopic dermatitis undergoing allergen-specific immunotherapy. Vet Rec. 2007;160: Olivry T, Mueller RS. Evidence-based veterinary dermatology: a systematic review of the pharmacotherapy of canine atopic dermatitis. Vet Dermatol. 2003;14; Mueller RS, Fieseler KV, Fettman ML, et al. Effect of omega-3 fatty acids on canine atopic dermatitis. J Small Anim Pract. 2004;45: Sousa C. Glucocorticoids in veterinary dermatology. Current Veterinary Therapy XIV; in press. 46. Griffin CE. Allergen-specific immunotherapy for canine atopic dermatitis: making it work. Vet Med. 2006;101: Rosencrantz W. Practical applications of topical therapy for allergic, infectious, and seborrheic disorders. Clin Tech Small Anim Pract. 2006;21: Managing Microbes Symposium Proceedings 21

40 Feline Alopecia Jenise Coyne Daigle, DVM, Diplomate, ACVD, Austin Veterinary Dermatology and Allergy, Austin, Texas Abstract Feline alopecia is a common problem seen in everyday veterinary medicine. Alopecia is defined as loss of hair and may vary from partial to complete. Various patterns can occur, such as focal, multifocal, diffuse, or symmetrical. Alopecia can be congenital or acquired. It can be a primary disorder, such as is seen with endocrine disorders and follicular dysplasias, or secondary to trauma or inflammation (e.g., dermatophytosis, Demodex, allergies). It is important to formulate an organized history and diagnostic plan to limit potential differential diagnoses. An accurate diagnosis is imperative to successfully treat the alopecia. This article discusses the appropriate steps for diagnosis and treatment of pruritic and nonpruritic causes of feline alopecia. Key Content Feline alopecia can have many potential causes; a systematic approach to diagnosis is essential. A trichogram is used to visualize the hair for evidence of pruritus (self-inflicted alopecia), dermatophytosis, endocrine alopecia, pigmentation defects, and growth phase. Skin scraping is an underutilized diagnostic tool in feline dermatology; deep skin scraping is used to check for Demodex cati and superficial skin scraping is used to identify D. gatoi. A biopsy may provide useful information in identifying the cause of the alopecia. Feline allergies to fleas, inhaled allergens, and food allergens are among the most common causes of alopecia. Diagnostics The most important factor before the workup is started is to determine whether the alopecia is self-inflicted from overgrooming or if the hair has simply fallen out. This can be determined by placement of an Elizabethan collar or the use of a trichogram. Regrowth of hair with the cat wearing an Elizabethan collar confirms that the alopecia is self-inflicted. A trichogram is used to visualize the hair for evidence of pruritus (selfinflicted alopecia), dermatophytosis, endocrine alopecia, pigmentation defects, and growth phase. Proceedings of a Symposium Held at the 2008 North American Veterinary Conference and the 2008 Western Veterinary Conference. Copyright 2008 Pfizer Inc. All rights reserved. The opinions expressed in the articles in this publication are those of the authors and do not necessarily reflect the official label recommendations and points of view of the company or companies that manufacture and/or market any of the pharmaceutical agents referred to. 1

41 Performing a trichogram: 1. Grasp individual hair with hemostatic forceps and pluck completely (approximately 20). 2. Lay hair on microscope slide (with mineral oil) with hair oriented in the same direction. 3. Examine hairs at low power for morphology, concentrating on hair bulb, shaft, and pigmentation. Examine the hairs for integrity of the shaft, stage (anagen, catagen, or telogen), and pigmentation. If most of the hairs have been sheared off, this is probably the result of licking, as seen in cats that excessively groom. Hair breakage is also seen in coatdilution alopecia and traction alopecia. Damage to the shaft can be seen with several uncommon conditions, but dermatophytosis is the most common cause. When a hair bulb is present, it is important to document whether the follicles are predominantly in anagen, telogen, or catagen. Anagen bulbs are round, while telogen bulbs are often spear-shaped. Predominance of telogen follicles can be indicative of endocrinopathies, nutritional disorders, and metabolic diseases. This is not an exact science, however, and there is a great deal of breed variability. Skin scrapings are an underutilized diagnostic tool in feline dermatology. Demodex mites are an important cause of alopecia. Deep skin scraping is used to check for D. cati, and superficial skin scraping is used to try to identify D. gatoi (Figure 1). Figure 1 Skin scraping from a cat with generalized alopecia revealing Demodex gatoi. D. cati is a follicular dwelling mite that has a long slender tail, similar to canine Demodex mites. These mites are usually seen affecting a single pet in the household. Immunocompromising diseases, such as hyperthyroidism, FIV, FeLV, and cancer, should be sought as the cause of demodicosis. Treatment for the cause of Demodex is more important than resolving the mites. Other parasitic causes of alopecia include chiggers, lice, Notoedres cati, and Lynxacarus radovski (cat fur mite). Diagnosis is usually straightforward by use of tape preparations, magnifying lens examination, and skin scrapings. The diagnostic value of the Wood's lamp is limited to a screening test for Microsporum canis. Negative fluorescence does not rule out M. canis because fewer than 50% of these infections routinely fluoresce, and the Wood s lamp is not useful for diagnosis of Managing Microbes Symposium Proceedings 2

42 dermatophytosis caused by other organisms, including M. gypseum and Trichophyton mentagrophytes. A Wood's lamp uses ultraviolet light filtered through cobalt or nickel oxide to cause some fungi to glow green in a darkened room. A tryptophan metabolite is the fluorescing material, not the fungi or spores themselves. This metabolite is only seen when the fungus is growing on hair shafts; it is noticeably absent on scale, claws, or culture plate matter. Only M. canis fluoresces (also M. distortum, M. adouinii, and T. schoenleinii in humans), and then only about 50% of the time. Whereas dermatophytes fluoresce an apple-green color, most scales and medications have a bluish or violet hue. The examination must be done in a darkened room. A complete examination of the skin surface requires almost 5 minutes. If positive hairs are present, these should be plucked and used for a dermatophyte test medium (DTM) culture. Remember that fluorescence seen on surface scale, crusts, or on claws are false-positives. Also, since fluorescence is caused by metabolites, not viable spores or fungi, fluorescence might persist even in conjunction with successful systemic therapy. DTM fungal cultures are used to isolate and identify dermatophyte organisms. DTM is made with special ingredients that inhibit bacterial growth and turn red when dermatophytes grow. Performing a DTM culture: 1. Select samples for culture. A Wood's lamp can be used to help select contaminated hairs or scales. 2. Longer hairs should be clipped short and the area cleaned with alcohol to decrease contaminants. 3. Inoculate material onto DTM. I prefer the DermDuets by Bacti-lab. 4. If media are in capped vials, be sure the caps are not tightened. 5. Keep at room temperature but in a darkened environment (some recommend incubating). 6. Check cultures daily for evidence of fungal growth and color change of DTM from amber to red. A daily log should be kept. Most dermatophytes grow as fluffy white colonies. Ignore any color change that occurs after 2 weeks. 7. Examine microscopically all fungal growth for purposes of identification. A biopsy may provide useful information in identifying the cause of the alopecia. It is essential to provide a thorough history and description of physical findings to the pathologist. Provide both lesions and normal-haired skin, and make certain that they are identified correctly. Histopathology can be helpful in differentiating congenital/hereditary, endocrine, and telogen defluxion from allergic causes. However, in mildly inflamed, trauma-induced alopecic skin, the results may appear "normal." A complete blood count with serum chemistry profile is sometimes useful as a diagnostic tool for feline alopecia. Most allergic causes result in changes in eosinophilic counts but are not diagnostic alone. If there is any clinical evidence of systemic illness associated with the alopecia, then laboratory blood work is indicated. Managing Microbes Symposium Proceedings 3

43 Miscellaneous Diseases Bacterial folliculitis is an uncommon cause of feline alopecia. Severe traumatic alopecia may be accompanied by bacterial overgrowth. Cytologic examination and bacterial culture provide a definitive diagnosis. A positive response to antibacterial therapy can be a helpful diagnostic tool. Feline allergies to fleas, inhaled allergens, and food allergens are among the most common causes of alopecia. A thorough history can help to differentiate self-inflicted alopecia from spontaneous alopecia. However, some cats are secretive groomers and the owner many not see the cat lick or pluck at the hairs. Many times there is a concurrent increase in hairballs because of hair consumption. If onset of alopecia is sudden and other causes of alopecia are ruled out, some uncommon circumstances should be considered. Cats with urinary tract cystitis may suddenly lick exuberantly at the caudal abdominal region. Similar findings may also be seen in cats with impacted anal sacs. For both of these disorders, the traumatic alopecia may extend to the caudal hindlimbs, perianal region, and proximal aspect of the tail head. Hair Cycle Abnormalities Several causes of alopecia are related to hair cycle abnormalities. Congenital hypotrichosis and alopecia universalis (Sphinx cat) is usually a simple diagnosis to make and can be confirmed with histopathology. Feline Preauricular Alopecia This is a normal condition and is not considered pathologic. The hair on the temporal region between the ears is often sparse compared with other areas of the head. There is no effective treatment, but no treatment is required anyway. Sebaceous Adenitis Cats present clinically with patchy alopecia; easily epilated hair; and various amounts of erythema, scales, follicular casts, and pruritus. The definitive diagnosis is obtained only with a skin biopsy. A pyogranulomatous infiltrate invades the sebaceous glands. In some cases there may be systemic disease. Cyclosporine at 5 mg/kg may be beneficial. The author has had one case that responded to cyclosporine. Alopecia Areata and Pseudopelade This rare disease is characterized by patchy (alopecia areata) to diffuse (pseudopelade), usually noninflammatory nonpruritic alopecia. The diagnosis is made by biopsy and histopathology. In alopecia areata, lymphocytes invade the bulbus and in pseudopelade they invade the isthmic region. Alopecia areata may spontaneously regress. Therapy (immunosuppressive drugs) is usually not attempted and is not effective. Managing Microbes Symposium Proceedings 4

44 Mural Lymphocytic Folliculitis The clinical picture of mural lymphocytic folliculitis varies, from mild alopecic patches to severe hair loss, erythema, and variable amounts of pruritus. It is possible that this histologic pattern reflects several different diseases: initial epitheliotropic lymphoma, drug reaction, sebaceous adenitis, dermatophytosis, demodicosis, pseudopelade, FIV infection, and even food allergy. The severity of the clinical picture, response to treatment, and the prognosis depend on the underlying cause. Idiopathic forms of mural lymphocytic folliculitis have been described in middle-aged to old cats. Therapy with steroids or cyclosporine may be beneficial. Prognosis is poor in severely affected animals. Hyperadrenocorticism Hyperadrenocorticism, both naturally occurring and iatrogenic, is rare in cats. Clinical signs are similar to those of dogs, with the exception of polyuria and polydipsia, which are usually absent. Cutaneous lesions include patchy alopecia, easily epilated hair, dry seborrhea with dull hair, and in some cases increased fragility of the skin, which can be torn with minor traction (Figure 2). Figure 2 Skin fragility in a cat with hyperadrenocorticism. Increased skin fragility can occur in over 50% of cases. 1 Muscle wasting and a pot belly may be present on physical examination. Diagnosis can be difficult, and adrenal function tests are usually recommended. Abdominal ultrasonography may be beneficial in the diagnosis of adrenal neoplasia or bilateral enlargement of the adrenal glands. Treatment of secondary infections is important. Surgery for adrenal neoplasia is the treatment of choice. Medical therapy for pituitary-dependent disease can be considered but success rates are low. Hypothyroidism Spontaneous hypothyroidism is very rare in cats. The author has seen one confirmed case in a middle-age cat that had a generally poor haircoat and chronic decubital ulcers (Figure 3). Haircoat and wound healing properties improved with thyroid supplementation. Managing Microbes Symposium Proceedings 5

45 Figure 3 Generalized poor haircoat in a cat diagnosed with primary hypothyroidism. Paraneoplastic Alopecia This is rarely seen in cats affected by pancreatic carcinoma or, less frequently, bile duct adenocarcinoma. These patients usually have systemic illness and are anorexic and may present with vomiting, diarrhea, lethargy, and weight loss. Results of biochemical blood analysis are usually within the normal range. Radiography and ultrasonography usually fail to identify the tumor. The alopecia usually involves the ventrum and legs. The hair is easily epilated and leaves a typically smooth, glistening skin (Figure 4). Figure 4 Paraneoplastic alopecia in a cat with pancreatic adenocarcinoma. (Courtesy of Carol Foil, DVM, Diplomate ACVD, Baton Rouge, La.) The nail beds may contain thick black wax, and footpads may also become affected. In some cases pruritus and excessive grooming, which exacerbates the alopecia, occur. Secondary Malassezia infection may be seen in the nail beds. Histologically, there is profound atrophy and miniaturization of hair follicles and mild hyperkeratotic hyperplasia of the epidermis, with occasionally mild lymphocytic exocytosis. The prognosis is usually poor. Injection Site Alopecia Alopecia can result from various subcutaneous injections. Reactions have been associated with vaccines, ivermectin, praziquantel, antibiotics, and glucocorticoids. Alopecia develops at the site of the injection and can present initially as an erythematous nonpruritic plaque. Diagnosis is based on history, lesion, and Managing Microbes Symposium Proceedings 6

46 histopathology. Therapy is usually not necessary nor helpful. Hair regrowth may take several months to a year; however, alopecia sometimes is permanent. Summary Feline alopecia is a clinical reaction pattern with many potential causes. It is important to systematically work through these cases and to begin with a basic dermatologic database for diagnosis and to successfully manage the alopecia if applicable. References 1. Scott DW, Miller WH, Griffin CE. Muller & Kirk s Small Animal Dermatology, 6th ed. Philadelphia: WB Saunders Co, 2000, pp Managing Microbes Symposium Proceedings 7

47 Feline Pruritus--Scratch It Like Mad! John C. Angus, DVM, Diplomate, ACVD, The Animal Dermatology Clinic, Pasadena, California Abstract Feline pruritus can be a source of frustration for both owners and veterinarians and misery for the cat if not diagnosed and managed adequately. Sometimes even recognizing that a cat is pruritic can be challenging. If characterized by active scratching or accompanied by visible evidence of inflammation, such as scale, crust, erythema, papules, plaques, or erosion, then clients and veterinarians are more likely to think of pruritus; however, in some cats the only evidence of pruritic disease is symmetrical alopecia subsequent to excessive grooming. Sadly, this manifestation is more commonly attributed to psychogenic disease than pruritus. There is a long list of diseases that cause pruritus in cats; however, the vast majority of cases will result from a smaller, more manageable list best remembered by the acronym PAIN: Parasite, Allergy, Infection, Neoplasia. Of these parasite hypersensitivity and food allergy are the easiest to treat, but unfortunately the most underdiagnosed. No patient with symmetrical alopecia, pruritus, miliary dermatitis, or eosinophilic granuloma complex should ever leave the clinic without aggressive, comprehensive flea and mite control. Similarly, any pruritic cat without overt parasitism should experience a good-quality diet trial early in the diagnostic work-up. Key Content Excessive grooming and subsequent alopecia is a manifestation of pruritus in greater than 90% of cases referred for psychogenic alopecia. The top three causes of pruritus in cats are atopy, food allergy, and parasite hypersensitivity. The initial battery of diagnostic tests is aimed at identifying parasites, thus eliminating the need to pursue other tests. No cat with alopecia, facial pruritus, miliary dermatitis, or eosinophilic granuloma should leave the veterinarian without an aggressive and comprehensive flea and mite control protocol. Corticosteroids are useful in managing pruritus in cats, but should never be used as a substitute for diagnosis or treatment of underlying diseases. Pruritus is medical term derived from the latin prurire, meaning itch. Three hundred forty years ago, Samuel Hafenreffer defined pruritus as an unpleasant sensation provoking the desire to scratch. In other words, if you feel an itchy sensation, your brain tells you to scratch near it, activating competing sensations, which change your perception of the Proceedings of a Symposium Held at the 2008 North American Veterinary Conference and the 2008 Western Veterinary Conference. Copyright 2008 Pfizer Inc. All rights reserved. The opinions expressed in the articles in this publication are those of the authors and do not necessarily reflect the official label recommendations and points of view of the company or companies that manufacture and/or market any of the pharmaceutical agents referred to. 1

48 itch. This is a protective mechanism, like other cutaneous sensations, such as heat, cold, or pain, which elicit a specific response to help avoid harm. Because feline patients might also rub, lick, scoot, chew, roll, or shake, as well as scratch, we must expand the definition to include these clinical signs. Indeed, one of the most common expression of pruritus for cats is obsessive grooming, not classic scratching. Physiology of Pruritus Dozens of pruritic mediators have been discovered to produce the sensation of itch-- histamine, serotonin, prostaglandins, leukotrienes, inflammatory products of the complement cascade, neurotransmitters, and various peptides and proteolytic enzymes. 1,2 Some of these mediators are activated by the body in response to mast cell degranulation, inflammation, trauma, or even the gentle touch and movement of parasites and insects on the skin surface. Other mediators are produced directly by bacteria, fungi, and plants in our environment. Mediators act on free nerve endings, transmitting sensation along C-fibers to the dorsal horn of the spinal cord and then to the cerebral cortex via the spinothalamic tract. 1-3 Much has been made of the fact that pruritus and pain share many of the same neural pathways; however, recent studies have demonstrated that pruritic sensation uses unique neural pathways not shared with pain sensation. 4 Further evidence to support separation of pain from pruritus is the observation that pain relievers do not influence pruritus. Indeed, opioids induce pruritus in 90% of patients receiving them for pain. Nonsteroidal antiinflammatory drugs have been shown to have no more effect on pruritus than placebo, which incidentally, can be effective in up to 20% of pruritic human patients. Similarly, owners perceive a beneficial response in 15% to 25% of veterinary patients given placebo. 5 Concepts in Management of Pruritus Why is this important to veterinarians? Understanding the physiology of itch gives us an opportunity to influence the sensation in our patients by intervening at various points along the way. At the level of peripheral mediators we can block or change mediator actions. We can give medications that block transmission of that sensation to the cerebral cortex. Or we can modulate the cerebral cortexes interpretation of pruritic stimuli. There are three clinically relevant concepts that can help veterinarians improve management of pruritic patients: threshold, modulation, and summation. 1,6 Threshold Pruritic mediators or sensations are not equal in their ability to elicit itch. A certain level of sensation is required before itch is recognized by the patient. If sensation exceeds threshold you itch, otherwise you don t. The same stimulus may or may not induce a response depending on individual threshold and the circumstances that influence the threshold at that moment. Modulation Psychological state can raise or lower threshold. Competing stimuli, such as noise, food, or presence of other animals or humans, can distract a patient from scratching without actually changing intensity of pruritic stimulation. For example, when left alone in a quiet house, an atopic cat may lick rhythmically for hours, but when the family comes home Managing Microbes Symposium Proceedings 2

49 and activity in the environment increases, they stop grooming immediately. When the house becomes quiet and dark at night, the cat returns to licking or scratching. However, some patients itch so intensely that no amount of stimulation or physical restraint distracts them. Parasites, herpes, and food allergy can stimulate self-mutilating pruritus. For more mild cases, we can modulate psychological states to reduce pruritus by recommending environmental enrichment, such as toys, an oscillating fan, a fish tank, or additional house mates. Summation Multiple pruritic stimuli can add up to exceed threshold and worsen severity of pruritus. For example, an atopic cat may not itch when exposed to ragweed pollen alone, but becomes clinically pruritic when secondary factors, such as dry skin, fleas, or bacterial infection, are added to the atopic stimulus. By preventing fleas and treating infection, pruritus is more easily controlled. Conversely, failure to manage these amplifying factors may require high-dose steroids to control pruritus or may result in treatment failure no matter how aggressively or appropriately the primary disease is treated. Our job is to identify and manage as many primary and secondary causes for itch as possible, do our best to raise the threshold, modulate sensation, and eliminate factors that contribute to summation. Recognizing Pruritus in Cats Some clinical signs of pruritus are obvious--for example, scratching the face, head, ears, and neck with hind claws to the point of excoriation and self-mutilation (Figure 1). Figure 1 Cat exhibiting extreme pruritus, active scratching, and self-trauma. Cats that chew, corn-cob, or pull hair with their teeth are also easily recognized as having pruritus. If pruritus is accompanied by visible evidence of inflammation or dermatitis, such as scaling, crust, erythema, papules, plaques, or erosions, then clients and veterinarians are much more likely to think of pruritus. The difficulty arises when the only evidence of a pruritic disease is alopecia subsequent to excessive grooming, Managing Microbes Symposium Proceedings 3

50 especially when the cats do not groom in front of owners. In many cases symmetrical alopecia of the flanks, ventral abdomen, limbs or tail, is the only sign of significant pruritus In addition, such dermatologic lesions as miliary dermatitis; eosinophilic ulcers, plaques, or granulomas of the lips or haired skin; alopecia and scaling on pinna; and facial seborrhea are often associated with diseases that cause pruritus, but the patient never appears to be itchy (Table 1). The diagnostic approach to these lesions is the same as that for pruritus, even if itch is not the most prominent clinical sign. Table 1. Clinical Manifestations of Pruritus Primary Clinical Signs Secondary Lesions Associated with Pruritus Scratching Excoriation Erythema Chewing Scaling Seborrhea Corn-cobbing Crust Miliary dermatitis Licking Erosion Eosinophilic plaque Excessive grooming Hypotrichosis Eosinophilic granuloma Hyperesthesia Symmetrical alopecia Eosinophilic ulcer Differential Diagnoses There are dozens of diseases that can cause cats to itch; however, 95% of cases will result from a smaller, more manageable list best remembered by the acronym PAIN: Parasite, Allergy, Infection, Neoplasia. Parasite: Notoedres, Cheyletiella, Otodectes, fleas, Demodex gatoi, lice, chiggers. Allergy: Atopy, food, contact, mosquito bite hypersensitivity, eosinophilic granuloma complex Infection: Bacteria, Malassezia, dermatophytes, herpesvirus dermatitis Neoplasia: T-cell lymphoma Less common primary causes of pruritus that should be included on a list of differentials for unusual cases or when more common causes have been eliminated include intestinal parasitism, hyperthyroidism, drug eruption, vasculitis, erythema multiforme, urticaria pigmentosa, pemphigus foliaceus, hypereosinophilic syndrome, and cholestasis. 7-9 Symmetrical Alopecia A common clinical syndrome that can be used to illustrate a thorough yet practical approach to feline pruritus is symmetrical alopecia secondary to excessive grooming (Figure 2). The management techniques discussed here can be applied to cats with intense facial pruritus, miliary dermatitis, eosinophilic granuloma complex, or pruritic exfoliative erythroderma. The principals of diagnosis and therapy are the same. Managing Microbes Symposium Proceedings 4

51 Figure 2 Symmetrical alopecia of ventral abdomen and limbs in a cat with atopy. Clinical Presentation A cat tongue is very efficient for breaking off and removing hair shafts at the surface of the skin. The broken hair shaft remains in the hair follicle and is easily visible on physical examination. Examination of hair shafts under the microscope demonstrates fractured ends that are easily differentiated from the tapered end of a normal hair. Owners may or may not observe the patient grooming excessively. Swallowed hair may manifest as hairballs, frequent regurgitation, vomiting, or hair in the stool. Scaling, crust, and other evidence of a primary disease may be effectively removed by the patient. In most cases, skin is quiescent. This presentation of pruritus is frequently misdiagnosed as psychogenic alopecia based solely on clinical appearance. Excessive grooming is much more likely the result of underlying pruritic diseases than social anxiety or obsessive-compulsive behavior. In a recent study evaluating 21 adult cats referred to a behavioral service with a presumptive diagnosis of psychogenic alopecia, a biological cause for pruritus was identified in 19 cats and only 2 cats were found to have psychogenic disease. 10 Adverse food reaction was the most common diagnosis, with 12 of 21 cats confirmed by challenge feeding and 2 additional cats suspected but not confirmed. Other causes identified in this population included parasitism, flea allergy dermatitis, atopy, and hyperthyroidism. Psychogenic alopecia should only be diagnosed when all causes of pruritus have been eliminated from the list of differential diagnoses This list can be intimidating and the ability to arrive at a definitive diagnosis can be difficult; however, achieving a final diagnosis and directing therapy at the cause of the itch is much more rewarding for the patient, owner, and veterinarian than treating all causes of itch symptomatically with frequent steroid injections or worse, failing to recognize pruritus in the first place. Managing Microbes Symposium Proceedings 5

52 Diagnosis History History is useful to rank differential diagnoses but rarely provides a definite diagnosis. First, determine the age of onset of clinical signs. If the patient is younger than 6 months of age, consider parasite hypersensitivity and dermatophytes as the most likely cause of disease. If onset occurs between 6 months and 6 years of age, any cause for pruritus is possible; however, ectoparasitism, atopy, and food allergy are the most likely differentials. If the patient is older than 8 years of age, add cutaneous T-cell lymphoma or hyperthyroidism to the list. Second, determine whether the condition is predominantly seasonal. If pruritus is evident year round, you cannot eliminate or even move atopy down on the list, since it may be nonseasonal; however, if the condition seems to be seasonal with extended periods of normalcy during predictable and repeatable cycles, then atopy is most likely, followed by seasonal insect triggers, such as fleas and mosquitoes. Third, determine whether the condition is responsive to corticosteroid therapy. Atopy is generally very responsive to steroids, parasite hypersensitivity is partially or temporarily responsive, and food allergy tends to exhibit a poor response. Also be sure to determine whether the lifestyle of the patient increases risk for contagious causes of pruritus, such as Notoedres, Otodectes, Cheyletiella, fleas, or dermatophytes. Examples include adoption from a shelter, rescue, or multiple-cat household; a recently introduced animal; recent travel; or access to the outdoors. Initial Diagnostic Approach The initial battery of diagnostic tests is aimed at finding parasites early, thus eliminating the need to pursue other tests. Start with flea combing, ear swabs, acetate tape preparations, skin scraping, and hair plucking in mineral oil to evaluate for fleas, Demodex gatoi, Otodectes, and Cheyletiella. D. gatoi mites are the most elusive. Target your search by hair plucks, deep and superficial scrapings on any area with inflammation, or easily epilated hairs. If no areas exist, sample broadly across several regions, including areas the cat cannot reach easily, such as the back of the head and neck. If the cat cannot groom an area of skin, they cannot remove and swallow the evidence. Since affected cats efficiently groom mites from the skin, efforts to find mites frequently yield negative results. If you are unsuccessful in finding mites on the clinically affected cats, samples of skin scrapings from nonpruritic cats in the same household may be positive, since these cats are not affected by their parasite burden and are not grooming and removing mites as efficiently. In addition, fecal flotation can evaluate for mites swallowed during grooming. When examining mineral oil preparations, be sure to lower the condenser on the microscope to increase refraction and to avoid blasting light through the unstained mites. If no mites or fleas are found, perform a Wood s lamp examination and collect a dermatophyte culture. Begin to discuss food allergies and environmental allergies with the owner, as these diseases will be the next focus if parasitism and dermatophytosis are definitively ruled out. Managing Microbes Symposium Proceedings 6

53 Parasite Treatment Trial A parasite treatment trial is recommended for all pruritic cats. Remind owners that the absence of parasites on initial samples does not eliminate ectoparasites from the list of differential diagnoses. Selamectin applied topically every 2 weeks for three treatments is a protocol commonly used by dermatologists. 13,14 Selamectin is labeled for treatment of fleas and Otodectes 15 and is anecdotally beneficial for management of Notoedres and Cheyletiella, although it has not been rigorously evaluated. 13,14,16,17 Oral or injectable ivermectin has no substantial advantages over selamectin and is not effective against fleas. Fipronil spray is effective against Cheyletiella, as well as fleas, but not Otodectes. 13,18 Unfortunately, no avermectin or other easy parasiticide is consistently effective against D. gatoi. For D. gatoi use lime sulfur dip (8 oz /1 gallon) once weekly for 4 to 6 weeks. 9,19,20 Use an Elizabethan collar to prevent removal and ingestion of product and allow to air dry. Although time-consuming to apply and malodorous, lime sulfur is safe, effective, mildly antipruritic, and has the added benefit of efficacy against dermatophytosis. A treatment trial with lime sulfur is the only way to rule out D. gatoi. Regardless of the drug used during the treatment trial, treat all animals in a multicat household to eliminate the possibility of repeated infestation during the trial. If this is impossible, then the patient should be quarantined for the duration of the trial. Food Trials A comprehensive elimination diet trial should be implemented as a diagnostic test in any pruritic cat with no evidence of parasitism or dermatophytosis. 9,21 For a minimum of 8 to 12 weeks, the patient should be given only an appropriate novel protein or hydrolyzed protein diagnostic test diet. Other pets may need to be isolated and dishes removed, since even licking empty food dishes could provide enough of the offending protein to perpetuate pruritus and invalidate the diet trial. Be sure the owner understands that the diet food is not what makes their cat better--the absence of offending proteins is what is necessary for improvement. Further, the diagnostic value of a diet trial is not the extent of improvement while the cat is on the food but whether clinical signs return when the cat is challenge-fed with the original diet. Food trials can be performed concurrent with parasite treatment trials, since the diagnostic test for food allergy is response to provocative challenge. Allergen Testing The purpose of allergen testing is to identify environmental allergens for inclusion in immunotherapy injections, not to diagnose atopy. Most healthy cats have a few positive reactors by intradermal allergy testing or IgE allergy serology, but that does not mean that those environmental allergens cause disease. 22,23 In cats with distinct seasonal pruritus or cats where other causes, such as parasites, dermatophyte, and food allergy, have been eliminated, intradermal allergy testing or IgE allergy serology is appropriate. Which test to use depends on access to intradermal testing, ability to remove the patient from medications that inhibit intradermal testings (antihistamines, corticosteroids), and the safety of sedating the patient. Serology is an acceptable substitute for intradermal allergy testing if conditions for intradermal allergy testing cannot be met. Regardless of method, immunotherapy should be instituted with the understanding that this therapy is not immediately antipruritic. Rather, immunotherapy modulates response to allergens, decreasing the severity of hypersensitivity reactions. This is a long-term therapy that Managing Microbes Symposium Proceedings 7

54 diminishes clinical signs, but may not eliminate all manifestations of disease. The safety record of immunotherapy is excellent Therapy In addition to attempting to identify and manage the primary cause, symptomatic therapy can be instituted to provide temporary relief of clinical signs. Basic therapies include cooling, topical sprays/lotions, omega-3 fatty acids, antihistamines, corticosteroids, and cyclosporine. 26,27 Cooling methods commonly used in dogs, such as frequent cool water baths, menthol, or witch-hazel sprays, are less useful for cats because they may not be readily accepted by the patient. Topical sprays and lotions may also be resisted, but they can be beneficial if the cat is not permitted to groom after application. Prolonged use of potent topical steroids (betamethasone, dexamethasone, triamcinolone) can have severe adverse effects, including permanent skin thinning and hyperfragility. Topical steroids should only be used for short periods. 26,28,29 Oral omega-3 fatty acids and antihistamines may be beneficial in mild pruritus but are less likely to provide satisfactory results in severely affected patients. Data on use in cats is woefully inadequate. Omega-3 fatty acids, should not be used during a food trial, since fish is a common dietary protein in cats. The dosage of EPA (eicosapentaenoic acid) should be approximately 180 to 200mg/day. 26,30 Fatty acids alone are not likely to substantially reduce pruritus; however, they may be beneficial in combination with other therapies, perhaps even reducing the amount of corticosteroid required Antihistamines are most useful for pruritus secondary to atopy; little if any benefit is noted with other pruritic diseases. Table 2 provides a list and suggested doses of antihistamines used in cats. Antihistamines are very safe, with minimal side effects or contraindications. Failure to respond to one antihistamine does not mean that the patient will not respond to another antihistamine. 5,26,27 Try several antihistamines in 2-week trials before considering treatment a failure. Table 2. Suggested Antihistamine Dosages for Cats Chlorpheniramine maleate 0.25 mg/kg up to TID Clemastine (Tavist ) 0.05 to 0.1 mg/kg BID Cyproheptadine (Periactin ) 0.5 to 1.0 mg/kg up to TID Hydroxyzine HCl (or pamoate) (Atarax ) 1.0 to 2.0 mg/kg up to TID Amitriptyline 5 to 10 mg/cat SID or divided BID Corticosteroids are the most effective method of providing immediate and substantial relief from symptoms. Therapy protocols should be designed to provide temporary humane relief from refractory pruritus, but corticosteroids should never be used as a substitute for appropriate diagnosis and management of primary disease and secondary infections. Long-term glucocorticoids can have adverse consequences, including increased risk for secondary infections; diabetes; and feline cutaneous hyperfragility syndrome, which is a terrible disorder characterized by thin, fragile skin that tears easily and does not repair itself. 26,27,29 When glucocorticoids are being used to manage pruritus, the rule of thumb is to use the lowest dose needed to provide relief for the shortest period. Because cats are slow to Managing Microbes Symposium Proceedings 8

55 convert prednisone to metabolically active forms, always use prednisolone or methylprednisolone. If an appropriate prescribed dosage is being used and there is no response, verify that prednisone was not dispensed inadvertently. Oral triamcinolone and dexamethasone are acceptable for short-term use in cats. Our knowledge of the metabolism of the various synthetic corticosteroids in veterinary patients is not adequate. Most information on absorption, half-life, and relative potency is extrapolated from human literature. A recent study comparing glucocorticoids at immune-suppressive doses in cats supported the hypothesis that dexamethasone had higher diabetogenic effects than prednisolone. 34 This may be due to a variety of factors, but suggests that if long-term high-dose steroids are necessary for managing a feline patient, prednisolone is preferred over dexamethasone. In general, initially prescribe oral steroids at high daily dosage to suppress pruritus, and then diminish to the lowest alternate day dose that maintains control of symptoms. Use of steroids in combination with oral antihistamines may extend the time between doses or lower the overall amount of steroid necessary to maintain satisfactory clinical response. Depo-medrol (methylprednisolone acetate) is recommended primarily for management of eosinophilic granuloma complex or in atopic cats. 30,35 Long term use of glucocorticoids in any form should be viewed as a last resort for humane management of refractory pruritus when all other diagnostic and therapeutic options have been exhausted. Microemulsified cyclosporine provides an alternative to corticosteroids for cats that require long-term symptomatic management, or who do not respond satisfactorily to management of the primary disease. Anecdotally, cyclosporine is effective at 5.0 to 7.5 mg/kg daily for pruritus and eosinophilic granuloma complex, but this drug and protocol has not been rigorously evaluated in cats In general, cyclosporine does not provide the rapid cessation of pruritus achieved with corticosteroids, but can be used for longterm treatment with relatively fewer adverse consequences. Diarrhea, inappetence, and vomiting are the most common side effects Fatal systemic toxoplasmosis has been reported Avoid use in cats at high risk for toxoplasmosis, such as hunters. Toxoplasmosis titers can be performed before administration. Allergen-specific immunotherapy (ASIT) provides a nondrug option for long-term treatment of atopy. While not directly antipruritic, ASIT modulates response to allergens and diminishes the severity of hypersensitivity reactions. The precise mechanism of action is not known; however, the safety record is very good and there is excellent evidence of efficacy. Response rates as high as 70% have been reported for ASIT in feline patients. 22,24,25 Cats may require adjunctive therapy, such as antihistamines or intermittent corticosteroids, for maximum benefit. Either intradermal allergy testing or serum IgE allergy serology are appropriate methods for determining which allergens should be included in therapy. The progestational compounds megestrol acetate and medroxyprogesterone acetate have been used to relieve pruritus in cats. 27 However, the author strongly recommends strict avoidance of these products except in the most dire cases of inhumane, selfmutilating pruritus that is refractory to glucocorticoids, cyclosporine; all other options for management of primary disease have been tried; and the owners are considering euthanasia rather than continuing with any other form of therapy. Progestational compounds are associated with prolonged suppression of adrenocortical function, diabetes mellitus, and catastrophic cutaneous hyperfragility syndrome (Figure 3). Managing Microbes Symposium Proceedings 9

56 Figure 3 Catastrophic, full-thickness degloving wound on neck following simple restraint in cat with cutaneous hyperfragility syndrome. Specific Conditions In addition to symmetrical alopecia and excessive grooming due to underlying atopy, food allergy, or parasite hypersensitivity, there are several specific conditions associated with feline pruritus that warrant additional attention. Because all of these conditions cause pruritus, the basic approach to diagnosis and management should fundamentally be the same as that for excessive grooming. However, veterinarians should be aware of special features for each of these conditions that may affect early recognition, selection of diagnostic tests, and therapeutic considerations. Intense Facial/Head Pruritus While some cats manifest pruritus with excessive grooming, other cats may engage in extreme self-mutilating pruritus of the face, head, pinna, and neck (Figures 4 and 5). Managing Microbes Symposium Proceedings 10

57 Figure 4 Same cat as in Figure 1, with intense facial and head pruritus in cat with adverse food reaction. Note facial excoriations. Figure 5 Same cat after elimination diet trial. This presentation is exceptionally alarming to owners and equally frustrating to veterinarians. Top differential diagnoses remain the same: atopy, food allergy, and parasite hypersensitivity, although Otodectes hypersensitivity and food allergy may be considered ahead of atopy due to the intensity of the itch. Some dermatologists consider food allergy to be the most common cause of intense facial pruritus of cats. 7,9,21 Additional conditions to consider include mosquito bite hypersensitivity, Trichophyton mentagrophytes, Microsporum canis, herpes viral dermatitis, Malassezia dermatitis, epitheliotropic T-cell lymphoma, pemphigus foliaceus, adverse drug reaction, and idiopathic facial dermatitis of Persian and Himalayan cats (Figure 6). Managing Microbes Symposium Proceedings 11

58 Figure 6 Mosquito bite hypersensitivity reaction. The diagnostic approach should be aggressive and comprehensive early on in the course of disease and should include skin scraping, ear mite preparation, cytology for bacteria and yeast, dermatophyte culture, fecal flotation, parasite treatment trial, food trial, intradermal allergy testing or allergy serology, and biopsy. Early biopsy may be especially important in these cases. Because secondary trauma and infection may mask histopathologic evidence of primary disease, consider placing an Elizabethan collar on the patient and treating with systemic antibiotics before biopsy. Miliary Dermatitis/Eosinophilic Granuloma Complex Miliary dermatitis is not a separate, specific disease, but rather should be thought of as a reaction pattern associated with hypersensitivity of any cause (Figures 7 and 8). Figure 7 Miliary dermatitis on dorsum. Managing Microbes Symposium Proceedings 12

59 Figure 8 Close-up of miliary dermatitis. Characterized by tiny, brown crusts over erythematous papules, miliary dermatitis can be distributed over any region of the body, although clusters on the head, neck, and tail base are most common.,43 Alopecia varies, depending on how much hair removal the patient engages in. In many cases, the milia are felt before they are seen. Most often the cat is moderately to severely pruritic. Whenever miliary dermatitis is seen, veterinarians should suspect allergic triggers, with flea allergy dermatitis placed highest on the list of differentials, followed by other ectoparasites (Otodectes, Cheyletiella, chiggers, lice), atopy, and food allergy. Less commonly, primary infectious conditions that cause folliculitis, such as dermatophytosis of staphylococcus, can present as miliary dermatitis. Interestingly, this is the same list of differential diagnoses for feline eosinophilic granuloma complex (ECG), including indolent ulcers of the lip, eosinophilic plaques, eosinophilic granulomas, and eosinophilic ulcer 7,9,30,35 (Figures 9 and 10). Like Figure 9 Eosinophilic granuloma of upper lip. Managing Microbes Symposium Proceedings 13

60 Figure 10 Eosinophilic ulcer with secondary bacterial infection. miliary dermatitis, these clinical syndromes are reaction patterns to hypersensitivity disorders rather than specific diseases. The diagnostic approach should include skin scraping, ear mite preparation, and cytology. If no obvious parasites are found, collect hairs for a dermatophyte culture, perform a fecal flotation to examine for evidence of ingested mites or fleas, and lay the ground work for an elimination diet trial and testing for environmental allergens. Most important, no patient with miliary dermatitis or ECG should ever leave the clinic without an aggressive, comprehensive flea and mite control protocol. Do not succumb to arguments that the other cats in the household are fine or that this couldn t be fleas because the owner always gets bit, too. Miliary dermatitis is a hypersensitivity disorder; therefore, very low parasite burdens can create severe disease in one cat, while other animals coexist peacefully with parasites and exhibit no clinical signs. Do not let your clients convince themselves or you that they don t have to treat for fleas. Stand firm. Insist on comprehensive flea control in any household with a cat with miliary dermatitis or ECG. If it would help, show the owner the cost of allergy testing or feeding their 18 cats a prescription elimination diet. Use all communication skills to convince them that a flea problem in their house is actually much easier to address than any other cause. Of course, any comprehensive parasite treatment trial must include adequate treatment for Otodectes, the second most common parasitic cause of miliary dermatitis in cats. 7 Demodex gatoi Demodex gatoi is a short-form Demodex mite of cats. Unlike the classic follicular Demodex mite, this mite is a primary cause of pruritus that is also highly contagious among cats. Although details of the life cycle are not known, one report states that live mites were present on recently shed hairs, supporting the observation that mites can be spread without direct cat-to-cat contact. 20 Duration of survival off the cat or ability to infest from a fomite is not known. Pruritus in infested cats can vary, from mild scaling; to excessive-grooming presentation resembling psychogenic alopecia ; to the more Managing Microbes Symposium Proceedings 14

61 severe, acute onset mad itchy cat syndrome described by Sandra Newbury and Karen Moriello. 20 Mad itchy cats are intensely pruritic, have hair that is easily epilated in sheets with gentle traction, profound follicular plugs, and cutaneous erythema and inflammation between follicles (Figure 11). Figure 11 Symmetrical alopecia in cat with Demodex gatoi. (Photograph courtesy of Karen Campbell) Mites can be found on superficial or deep skin scrapings, hair pluck preparations, and fecal flotations. Fecal examination is important in the diagnostic approach to any cat with suspected parasite dermatitis, especially D. gatoi. Cats are very efficient at removing mites from the skin, decreasing the likelihood of discovery on skin scrapings, but since cats swallow the evidence, mite bodies may be present in the stool. When examining for Demodex mites on scrape or fecal samples, scan the entire slide at 10x in a regular back-and-forth pattern. Lower the condenser away from the stage to increase refraction as light passes through the colorless mites. The head and thorax of the mite is similar to traditionally recognized Demodex mites, but the tail is much shorter--approximately equal in length to the thorax. In addition, the tail has a rounded end and a serrated edge 20,44 (Figure 12). Managing Microbes Symposium Proceedings 15

62 Figure 12 Demodex gatoi. Note short, rounded tail. Treatment consists of weekly lime sulfur dip for 4 to 6 weeks. In most cases, pruritus is reduced rapidly. Ivermectin, fipronil, and other parasite therapies are ineffective for management of D. gatoi and cannot be relied on for an effective parasite treatment trial to rule out the presence of mites in a highly suspicious mad itchy cat situation. 20 Dermatophytosis Microsporum canis is the most common dermatophyte of cats. 45 Clinical signs are highly variable, including alopecia, folliculitis, crust, comedones, hyperpigmentation, and erythema. Pruritus is also highly variable. Many cats seem unaware of the folliculitis and do not exhibit excessive grooming or pruritus, while other cats may manifest itch through grooming, chewing, hair pulling, or self-mutilation. 45,46 Trichophyton mentagrophytes is a less commonly isolated organism but has been a subject of great interest in several recent surveys of dermatophytosis in stray cats and animal shelters The clinical presentation described is pruritus, alopecia, and crust limited to the ear margins. The condition may be subtle enough to escape recognition by cat owners and veterinarians, appearing as mild ear margin seborrhea. Because the reservoir for this organism is rodents and large animal species, cats with access to outdoors have increased risk. Interestingly, in shelter surveys this organism is more commonly isolated in winter months. T. mentagrophytes is more fastidious on culture media than M. canis and may require a longer period to incubate. 45,46 Any cat with ear margin seborrhea, face or body folliculitis, alopecia, scaling, hyperpigmentation, or pruritus should have a DTM performed. Cats with high-risk lifestyles, such as those from shelters, multiple-cat households, and breeding facilities; those with outdoor access; and show animals, should have multiple negative cultures before ruling out dermatophytosis in any pruritic cat. Managing Microbes Symposium Proceedings 16

63 Herpesvirus Dermatitis Veterinarians are most familiar with upper respiratory infections, conjunctivitis, and keratitis caused by feline herpesvirus 1; however, this virus can also cause severe facial pruritus and dermatitis. 49 In most cases, cats have a history of respiratory and ocular disease or may even have concurrent classic disease. Characteristic dermatologic lesions affect the nasal planum, bridge of nose, or periocular skin. Lesions are often unilateral (Figure 13). During the acute phase vesicles may be seen, with or without erythema, alopecia, and intense pruritus. Chronic cases are characterized by ulcerative, crusting lesions with a predominantly eosinophilic inflammatory infiltrate on cytology that strongly resemble eosinophilic granuloma complex. 9,30 Figure 13 Herpesvirus dermatitis with unilateral erythema, induration, and alopecia. Definite diagnosis is made by biopsy. Ideally, biopsy is taken from an intact vesicle. In cases with only ulceration, the tissue adjacent to the ulcer is preferred rather than the ulcer itself. Histopathologic identification of viral inclusion bodies is conclusive. Unfortunately, since viral replication is intermittent, intranuclear inclusions are not always present. Supportive histopathologic findings include multinucleated giant cells and mixed inflammatory infiltrates with high numbers of eosinophils. Polymerase chain reaction techniques for amplification of viral DNA are now available; however, interpretation can be difficult, since cats may have herpesvirus DNA present from past exposure, without the virus being the cause of current disease. Treatment for herpesvirus dermatitis is similar to that recommended for herpesvirus keratitis. Cats may respond to lysine 500mg/cat BID. 50 Lysine is available as granules, capsules or oral gels Lysine interferes with viral metabolism during replication and therefore suppresses viral replication. Idoxuridine can be compounded as a 1% solution or ointment and should be applied topically once a day. Off-label use of human oral antiherpes medications can be beneficial. Famciclovir has been used successfully by the author for herpesvirus dermatitis and by ophthalmologists for viral keratitis with minimal adverse reactions (Reuben Meredith, DVM, DACVO, personal communication) (Figures 14 and 15). Use with caution in older patients or animals with compromised renal Managing Microbes Symposium Proceedings 17

64 Figure 14 Herpesvirus dermatitis with unilateral alopecia and punctuate erosions similar to miliary dermatitis. Figure 15 Same cat as Figure 14 after treatment with famciclovir and lysine. function. Your local ophthalmologist is likely to have the most current information, recommendations, and accepted dosages for managing feline herpesvirus diseases with or without oral antiherpetic medications. Because these diseases can wax and wane, judging response to therapy versus cyclic improvement is difficult. Hyperthyroidism The classic presentation of a hyperthyroid cat is profound weight loss, polyphagia, and palpable thyroid nodule in an older adult cat. Additional clinical signs that might lead a veterinarian to check a resting T 4 include polyuria/polydipsia, restlessness, vomiting, diarrhea, and hypertrophic claws. However, some cats present to veterinarians with only Managing Microbes Symposium Proceedings 18

65 dermatologic signs, including excess scaling, pruritus, and alopecia focused on the trunk. This is not the classic noninflammatory, bilateral symmetrical alopecia associated with other endocrine disorders in dogs the condition in cats is pruritic and scaly. In an older adult cat with no prior history of dermatitis or pruritus, hyperthyroidism should be considered a differential for any coat abnormality or excessive grooming. Differential diagnoses for this particular clinical presentation include Cheyletiella, food allergy, and epitheliotropic T-cell lymphoma (ECTCL). Epitheliotropic Cutaneous T-Cell Lymphoma Clinical signs of ECTCL are highly variable in the cat. The classic clinical presentation is exfoliative erythroderma, a term used to describe generalized pruritus, exfoliation, and erythema. However, before progression to generalized disease, the early lesions can be very subtle and easily missed by owners and veterinarians. Early lesions include scaling, folliculitis, mild erythema, or mild pruritus. These lesions may exhibit sharp demarcation between normal and abnormal skin. ECTCL can be easily misdiagnosed as miliary dermatitis, chin acne, psychogenic alopecia, or virtually any other dermatologic disease. Plaques, nodules, and ulcers are less common in cats than in other species. 9,51,52 Differential diagnosis should include all common causes of folliculitis, scaling, alopecia, or pruritus, including dermatophytosis, bacterial folliculitis, atopy, food allergy, D. gatoi, Cheyletiella, Otodectes, other ectoparasites. Less common differentials include sebaceous adenitis, pemphigus foliaceus, exfoliative viral dermatitides, and paraneoplastic syndromes. In most cases of feline ECTCL, patients have been treated empirically for other, more common diseases for months or years before being diagnosed correctly. Early biopsy should be considered in any older cat with excessive scaling, alopecia, or pruritus that does not respond to therapy for the more common conditions. Progression of ECTCL is unpredictable, but usually slow. Patients may live for years with active clinical disease before progressing to significant morbidity or mortality. Treatment options exist to provide long-term relief in most cases, but complete remission and cure are unlikely. 53 Published data on treatment protocols and outcome are limited for feline ECTCL. Oral lomustine (CCNU) alone or in combination is a common choice. Synthetic retinoids can also be used, but cost and potential vitamin A toxicity-like syndromes in cats may limit usefulness. Check with your local oncologist for the latest treatment options and recommendations. Dirty Face Syndrome Idiopathic facial dermatitis of Persian and Himalayan cats is a frustrating and poorly understood condition, characterized by adherent, black exudate on the skin and hair of the face folds, periocular, and perioral regions. 54,55 Initial onset can occur between 4 months and 5 years and is typically progressive, from nonpruritic dirty face to intense, and nonresponsive pruritus. Secondary infection with bacteria and Malassezia are common. The underlying cause is unknown but may be a manifestation of hypersensitivity, idiopathic seborrhea, or some other process; a genetic basis is hypothesized. The diagnostic approach should include cytology to determine whether secondary bacterial or yeast infections are contributing to severity of the pruritus, skin scraping, parasite treatment trial, food trial, allergen-specific testing, and biopsy. Managing Microbes Symposium Proceedings 19

66 Treatment goals are management of secondary infections and pruritus. Partial response to corticosteroids and cyclosporine has been reported. 9,37 Urticaria Pigmentosa Urticaria pigmentosa is an uncommon disease characterized by pruritus and papules that occasionally coalesce into plaques with superficial crusts. Lesions may involve any body region and are often generalized (Figures 16 and 17). Sphinx and Rex cats are predisposed; however, the disease has also been described in Siamese and Himalayan cats The cause is unknown, but appears to be a manifestation of extreme mast cell Figure 16 Sphinx with generalized urticaria pigmentosa. Figure 17 Close-up of urticaria pigmentosa of patient in Figure 16. Managing Microbes Symposium Proceedings 20