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Dermatology Rod A. W. Rosychuk, DVM, DACVIM Colorado State University Canine and Feline Dermatology - an Update CANINE ATOPY Important Points Regarding the Pathogenesis of Canine Atopy
Alternatives to prednisone /prednisolone include metylprednisolone (reduce incidence of PU/PD) or Temaril-P (5 mg of trimeprazine, an antihistamine and 2 mg of prednisone per tab); may allow for lesser dosages of glucocorticoid because of the antihistamine included. Prior to considering glucocorticoids for longer term maintenance, every effort should be given to provide glucocorticoid alternatives. When this is not possible, the author will usually try to maintain the patient on the lowest, once every other day dose of Temaril-P possible. This is often facilitated by using Temaril-P along with a full, daily dose of another antihistamine such as chlorpheniramine, diphenhydramine, hydroxyzine, amitriptyline, or clemastine. It is important, even at these low dosages to look for mild signs of iatrogenic hyperadrenocorticism (dry coat / skin; mild hair loss; gradual weight gain; increased propensity to develop bacterial pyoderma; increased propensity to develop urinary tract infections). Fatty Acids Controversy continues to exist as to which fatty acid and which ratio of fatty acid (omega 6:3) to use in optimizing anti-inflammatory, anti-pruritic effects. Products rich in n-3 fatty acids (cold water fish oils and flaxseed) appear to be favored. Our impression is that benefit is directly proportional to dose. In a study completed at CSU, dogs treated with about 85 mg/kg of a combination of Eicosapentanoic acid (EPA) and docsahexanoic acid (DHA) (equivalent to about 1 Giant breed 3V Cap per 5 kg body weight which is about 3 times the recommended bottle dose of about 20 - 30 mg/kg/day) or 200 - 335 mg/kg of flaxseed oil per day, 40 - 50% improved by greater than 50%. Complete remission was obtained in 10 - 20%. This suggests that higher dosages of omega 3 fatty acids should be used to initiate/assess therapy (e.g. 2 - 3 times the bottle dosages). Although it has been suggested that fatty acid containing products should be given at least a 12 week trial before they are critically evaluated, it was noted that many individuals had improved within the first 2-3 weeks of therapy in this study Research by Iams has shown that a 5:1 to 10:1 ratio of omega-6 to omega-3 fatty acid in the overall diet may be ideal for management of inflammatory skin disease in the dog. Their restrictive diets (e.g. Eukanuba TM Response Formula fish and potato and their kangaroo and oat diet) contain this ratio of fatty acids. Our own uncontrolled studies evaluating the efficacy of this diet in 47 atopic dogs showed a greater than 50% reduction in pruritus in 42% of dogs Antihistamines Antihistamines appear to benefit about 30% of our atopic patients. Both first generation H1 blockers (e.g. chlorpheniramine, diphenhydramine) and second generation products that fail to cross the blood brain barrier (e.g. loratidine, ceterizine) appear to have similar success rates. It is felt that one cannot predict which, if any antihistamine, will be of help in a given individual. We generally have the owner try several different antihistamines, each for 2 weeks (3 or 4 weeks if the owner is not very observant). The owner notes which antihistamine is being used and what degree of benefit, if any, it may produce. The following are the antihistamines used most frequently in our practice. Those with an asterisk tend to be most effective/cost effective (unless otherwise marked): * Hydroxyzine HCl - 2.2 mg/kg BID or TID ; * Chlorpheniramine .4 - .8 mg/kg BID to TID ; * Diphenhydramine - 2.2 mg/kg BID or TID; *Amitryptyline- 2.2 mg/kg BID; *Clemastine (Tavist or generic) - .05 mg/kg BID or for dogs under 10 kg 1/2 tab BID; 10 - 25 kg, 1 tab BID, bigger, 1 1/2 tab BID; Cyproheptadine - .25 - .5 mg/kg TID; Doxepin HCl-.5- 1.0 mg/kg BID; Trimeprazine tartrate - 2.5 - 5 mg/dog TID (expensive). Which is the most effective? Some studies have suggested clemastine; another recent study suggested hydroxyzine and diphenhydramine. The author has best results with hydroxyzine, with the next of the list being chlorpheniramine. H 1 blockers that have antihistaminic, antichollinergic, sedative and local anesthetic effects. They must be used with caution, if at all, in the presence of liver disease, glaucoma, urinary retention, gastrointestinal atony and pregnancy. The newer, non-sedating antihistamines include cetirizine. ( 10 mg/day/animal < 25 kg and 10 mg BID > 25 kg), loratidine (0.5-1.0 mg/kg/day) and astemazole (.25 mg/kg q24hr). It has been suggested that cetirizine may be the most effective of this group. Combinations of antihistamines may be of benefit when the individual antihistamines themselves appear to have failed. They are also considered in the initiation of therapy for those individuals who are more significantly pruritic (especially if glucocorticoids are not an option). The author has most commonly used chlorpheniramine along with hydroxyzine or chlorpheniramine and amitriptyline. The antihistamines are used at full dosages. Pentoxifylline Pentoxifylline (a phosphodiesterase inhibitor; Trental or generic) has been noted to reduce the pruritus and erythema associated with atopy at a dosage of 10 mg/kg BID, although TID administration at dosages as high as 20 - 25 mg/kg may be more beneficial. The author has, in general, been disappointed with this drug as a monotherapy for atopy. It may help to reduce steroid dosages in patients on glucocorticoids, and may work synergistically with antihistamines. It is therefore usually used as part of a combination therapy, especially when other more conventional therapies have failed. Cyclosporine Most commonly used at a dose of 5 mg/kg/day. Preferential forms based on bioavailability : Atopica, Novartis , Neoral ®, Novartis). It has been noted to produce good to excellent results in 70 - 80% of cases. The overall beneficial effects have been shown to be similar to those of prednisolone or methylprednisolone, without the attendant deleterious side effects of the steroid. The major side effect encountered is gastrointestinal upset (vomition, diarrhea, flatulence, abdominal cramping - with vomition being most common). The incidence of vomition may be minimized by gradually working up to the maintenance dose over several days. Cyclosporine should be given on an empty stomach (at least 2 hours before feeding) to enhance absorption. However, if vomition is noted, the drug should be stopped until this side effect has resolved and can be tried again with a small amount of food. Other uncommon to rare side effects reported in dogs include gingival hyperplasia, papillomatosis, bacteriuria, bacterial pyoderma, anorexia, nephropathies, bone marrow suppression and a lymphoplasmacytic dermatosis. Trial therapy should be at least one month. It may take longer to see the maximal benefit (45 - 60 days). Once the maximal benefit has been noted, The dose is reduced to every other day , then every 3rd day. If every other day dosing does not "hold" the problem, then return to daily dosing and once the problem is again quieted down, gradually reduce the once daily dose to the least amount required to control the problem. The daily dosage or frequency of administration can be reduced in about 80% of cases. It is very interesting to note that a significant number of patients may be able to have their oral cyclosporine eventually stopped, with a complete remission of disease (no recurrence; Olivry - 10% of cases; Radowiz - 24%). In that cyclosporine is expensive, it has been used in conjunction with ketoconazole to increase the blood concentrations of the cyclosporine. We start with 2.5 mg/kg cyclosporine per day along with 5.0 - 10 mg/kg ketoconazole once per day. A higher dose of ketoconazole (i.e. 10 mg/kg/day) may be associated with higher circulating cyclosporine concentrations and greater anti-pruritic benefits. The ketoconazole is usually given with a small amount of food, but the cyclosporine is usually given 2 hours before or after giving this small amount of food. Behavior Component to Atopic Pruritus? - There has been a suggestion that a subset of both atopic dogs may be pruritic in response to anxiety and/or another central trigger. Dextromethorphan is though to reduce pruritus is some dogs by blocking receptors for N-methyl-d-aspartate, which are found in the brain and spinal cord and mediate various sensations. In one study, 11 of 12 dogs had some degree of improvement (about 30 - 40%; 2 mg/kg PO q 12 hrs; low incidence of side effects - vomition, diarrhea, sedation). Dextromethorphan use should be reserved for those atopic patients that fail more traditional anti-pruritic therapy and (ideally), where there is suggestion that the behaviors are repetitive and anxiety-induced. Hyposensitization Hyposensitization is noted to benefit 60 - 70% of cases (good to excellent results). Over the long term, 50 - 70% of our patients on hyposensitization require additional medication (antihistamine steroids and/or fatty acids) to control allergic signs during part or all of the year. The majority of our patients on maintenance hyposensitiztion get their shots every 1-2 weeks during the allergy season. For patients who derive only transient benefits from a given shot (2-3 days), we divide our solutions and give .5 cc twice weekly, or even smaller volumes up to three times a week (e.g. .2 cc three times weekly). "Rush" immunotherarpy, which involves giving all the induction dosages in the hyposensitizing protocol in one day appears has been shown to produce both a more rapid onset of benefit from hyposensitization and an overall higher success rate. The incidence of significant side effects from this protocol has been very low. Once the "Rush" is completed, the patient is placed on the 1 cc per week maintenance dose of solution until the maximal benefit of the solutions is noted. It is also very important to monitor for increased pruritus following a given shot. Affected individuals may actually have their allergy signs significantly worsened if they react to the hyposensitization solution. If such is the case, we reduce the volume of solution to that which did not produce a reaction. Patients noted to have reactions to shots appear to have an overall better chance of deriving benefit from the shots, assuming the volume and frequency of solution is managed appropriately. It is interesting to note that in one recent study (Power H et al,), 29% of patients who discontinued hyposensitization shots did so because the atopy went in to spontaneous remission. We quote a 20 - 30% chance that individuals with come off hyposensitization after at least 2-3 years on the desensitizing protocol. UPDATE ON THE MANAGEMENT OF FELINE ATOPY In the older Veterinary literature, it has often been suggested that the incidence of atopy is similar to that of food sensitivity in the cat. However, in our clinic, for cats showing the clinical signs listed below, about 80% are noted to be atopic and 20% food sensitive. Feline atopy is associated with a myriad of clinical signs. These may include:
The therapy of feline atopy should always include the documentation and treatment of secondary bacterial or Malassezia infections. These are best defined by cytologic examination. Because glucocorticoids are well tolerated in the cat, they tend to be the cornerstone of therapy. However, as the disease becomes more chronic and severe, it is not uncommon to have the patient require higher dosages, more frequent dosage administrations or more potent glucocorticoids to maintain comfort. It has been shown that prednisolone is more bioavailable and has improved drug kinetics when compared to prednisone in cats and therefore prednisolone is the drug of choice in cats. Cats are often started on 1 - 2 mg/kg/day of prednisolone. "Depo" steroids are acceptable for periodic administration (ideally keep frequency of administration to less than once every 6-8 weeks - methylprednisolone acetate or triamcinolone acetonide). For patients refractory to prednisolone consideration should be given to using the longer acting, more potent oral dexamethasone (.1 - .2 m/kg/day) or triancinolone acetonide (.5 - 1 mg/kg/day). Emphasis should always be placed on reducing dosages to the least frequent administration possible. Fatty acids (omega 3 and 6) such as DVM Derm Caps Liquid or 3V caps (omega 3) benefit approximately 20 - 30% of cases (some quote 30 - 50%). Many cats, however, refuse to eat the fatty acids. The antihistamines that have been of most benefit for in our hands for treating feline atopy are chlorpheniramine (2-4 mg/cat q 12 hrs) or amitriptyline ( 5 mg/cat q 12 - 24 hrs). Amitriptyline may cause significant sedation, ataxia etc.; cats may salivate excessively when it is given. To minimize the chances of encountering this side effect, the author starts at 2.5 mg total dose in the evening. If this is tolerated, the dose is 2.5 in the AM and 2.5 mg in the PM. If this is tolerated, but is not beneficial to the pruritus, the dose is increased to 5 mg in the evening, 2.5 mg in the morning, then 5 mg BID if necessary. Problems with palatability can be circumvented by using amitriptyline powder mixed in fish/cod liver oil. Other antihistamines to be tried include clemastine fumarate (.34 - .68 mg/cat BID), ceterizine (.5 - 1 mg/kg or 5 mg/cat) or cyproheptadine (2 mg/cat BID; may cause polyphagia and behavioral effects). Each is tried for 3 weeks. Hyposensitization has been reported to benefit anywhere from 45% to 75% of cases. Our success rate has been in the 60 -70% range. Protocols using aqueous allegens are similar to those used for the dog. The author uses the same frequency of administration, but only 1/2 the volumes. One recently published study reported the benefits of hyposensitized based on RAST data. The numbers of patients with various manifestations of atopy and the percentage of patients who improve by greater than 50% included : hair loss - 29cats/53%; military dermatitis - 23cats/76%; eosinophilic plaque - 10 cats/ 73%; indolent ulcer - 6 cats/95%; linear granuloma - 3 cast/100%; otitis externa - 4 cats/65%; Asthma - 4 cats/90%. Oral cyclosporine has been noted to work well in the management of atopic dermatitis in the cat. Cats are generally treated with 5 - 7 1/2 mg/kg/day. In one study, eosinophilic plaques and eosinophilic granulomas were put in to remission within 30 - 60 days. 3 cats with indolent ulcers had only partial responses. Cyclosporin at this dosage appears to be tolerated reasonably well . GI upsets (nausea, vomition, inappetence, anorhexia) are relatively common. If possible, we gradually increase our dosages over several days, prior to getting to our maintenance dose (above). If GI problems are encountered, the drug is stopped until the signs have abated and it is then re-instituted … given with a small amount of food. We have seen apparently latent toxoplasmosis exacerbated while on this therapy (likely because of the immunosuppressive effect of cyclosporine -- something to be aware of! Chlorambucil has also been of benefit (usually along with steroids) in treating refractory atopy. Recommended dose is 0.1 - 0.2 mg/kg q 24 hrs until 75% improvement in clinical signs, then this dose every other day. Adverse effects to be monitored for include hepatotoxicity and bone marrow suppression. Megestrol acetate may be considered a "last ditch" alternative for treating feline atopy, in light of potential side effects ( polyphagia / weight gain, PU/PD, personality and behavioral changes, pyometra or stump pyometra, mammary hyperplasia, mammary neoplasia, diabetes mellitus and adrenal suppression). Remission of clinical signs can often be achieved with an oral dose of 2.5 - 5.0 mg/cat every 48 hours for 1-3 weeks. This is followed by weekly maintenance dosages. SUNDRE FELINE DERMATOSES THAT MAY MIMIC FELINE ATOPY FELINE ATOPY MIMICKERS: IDIOPATHIC ULCERATIVE DERMATITIS OF THE SHOULDER AREA Lesions are focal, usually singular, intensely pruritic, erosive to ulcerative and most commonly located over the dorsal interscapular region. Lesions will resolve if protected (e.g. e-collar). Histopathologic findings are nonspecific. Response to antibiotics, glucocorticoids and psychoactive drugs (e.g. clomipramine) is poor. More recently, dramatic responses have been noted to oral cyclosporine (beginning at 5 mg/kg/day). HERPESVIRUS 1 - ASSOCIATED DERMATITIS AND STOMATITIS Facial Dermatitis and stomatitis has been associated with Herpesvirus 1 in domestic cats. In a report of 10 cats (Hargis A. et al, 14th Proceedings of AAVC/ACVD, 1998), 5 cats had histories of recurrent or persistent mild upper respiratory tract infection. Six cats had been treated systemically with glucocorticoids or drugs with glucocorticid activity (Ovaban) prior to lesion development, suggesting exacerbation of a latent viral infection. Lesions are located on the nasal planum or haired skin of the face and are vesicular, ulcerated and crusted. Histologically, there is ulceration, crusting, necrosis and a mixed dermal inflammatory infiltrate including many eosinophils. Intranuclear inclusion bodies are present in surface and adnexal epithelium. Due to the prominent eosinophilic inflammation and low numbers of inclusion bodies, the cutaneous or oral lesions may be misinterpreted as allergic dermatitis or lesions of the eosinophilic granuloma group of disorders. Lesions usually persist and do not respond to glucocorticoids. Treatment options include L-lysine, 250 mg (1/2 tab) BID (make sure it is form without propylene glycol); response usually seen within two to four weeks or Alpha interferon, 1.0 - 1.5 million units / m2 SubQ three times weekly for 4-8 weeks. IDIOPATHIC FACIAL DERMATITIS OF PERSIAN AND HIMALAYAN CATS An idopathic facial dermatitis has been described by Bond et al (Veterinary Dermatology, 1:3541,2000) affecting Persian cats. Age of onset was 4 months to 5 years (median 12 months). The first abnormality noted was the presence of black material which matted the hairs of the periocular, perioral and/or chin areas. Although pruritus was not reported early in the course of the disease, it did develop. and became moderate to severe. Affected skin became progressively inflamed. A bilateral erythematous otitis externa with accumulation of black waxy material within the ear canals was common. Some cats had secondary Malassezia infections. Biopsies showed marked acanthosis, hydropic degeneration of basal cells, occasional dyskeratotic keratinocytes and a superficial dermal infiltrate comprised of eosinophils, neutrophils, mast cells, macrophages and occasional melanophages. Sebaceous glands appeared enlarged. Ectoparasites and allergies were ruled out. Response to glucocorticoids was variable and often poor. The cause of the disorder is unknown although a genetic basis is possible. More recently, this disease has shown response to oral cyclosporine (5 mg/kg/day). Allergic Otitis Externa in the Dog and Cat: Current Management Strategies Atopy and, to a lesser degree, food sensitivity are without question the most common primary factors noted to initiate inflammation within the ears of the dog. It is uncommon to see otitis as a manifestation of flea bite hypersensitivity. In one study (Muse R, Proc. AAVD/ACVD, 1996) 4 of 17 dogs had a concurrent otitis externa. While allergies are comparatively less common in the cat, they are an underdiagnosed reason for chronic otitis externa in the cat. Malassezia pachydermatis is the most common secondary colonization and infection problem encountered in atopic and food sensitive dogs and cats. It is important to note that dogs may develop hypersensitivies to Malassezia and its by-products, and as such, relatively few organisms may contribute significantly to inflammation and pruritus in the ear. Secondary bacterial infections are less commonly encountered in allergic ears. Staphylococcus intermedius is most commonly encountered in both acute and chronic cases. Gram negative infections (Pseudomonas, E.coli, Kleb siella etc.) are more likely to develop in more chronic cases or those that have been intermittently treated with antibiotics in the past. Other perpetuators of otitis that are commonly encountered in allergic otitis externa include:
In the dog, allergic otitis externa with secondary Malassezia infections commonly results in the production of large amounts of waxy debris within the ears. This waxy debris may slowly put pressure on the tympanum and push it partially into the tympanic cavity (so called "false middle ear"). Even with chronic otitis, the tympanum is usually still intact in these ears. Perforation tends to become more likely in the presence of severe proliferative changes. The tympanum of the cat does not tend to have as much "give" (less likely to develop a "false middle ear") and is more likely to perforate with the longer term accumulation of debris. Routine Treatment of Acute and Infrequently Recurrent Allergic Otitis Externa In many cases seen in clinical practice, such cases are often readily managed with topical products that contain a combination of an antibiotic, anti-fungal and glucocorticoid. Although there have been differing reports as to the efficacy of various anti-fungal ingredients against Malassezia, the author adheres to one report that listed the various products (most to least effective) as follows: ketoconazole, clotrimazole, miconazole, nystatin and thiabendazole. The thiabendazole in Tresaderm and the nystatin in Panalog provide reasonable anti-Malassezia therapy, but the clotrimazole in Otomax is superior. Otomax might be the preferred medication for a more severe Malassezia problem. The neomycin in products such as Tresaderm and Panalog provide reasonable, broad spectrum gram positive and gram negative coverage. The gentamicin in Otomax provides a broader spectrum gram negative effect (picking up even 50 - 60% of Pseudomonas) and is therefore possibly the antibiotic of choice when rods (usually gram negative organisms) are seen to predominate on an ear cytology. The potency of the triamcinolone in Panalog, the dexamethasone in Tresaderm and the betamethasone in Otomax, clinically seem to be quite similar, although the betamethasone in the Otomax formulation appears superior. "At home" ear flushes are prescribed for ears with significant debris. Cleanser/dryers such as EpiOtic (Virbac) or Malacetic Otic (DermaPet) are used most routinely. These products have good germicidal activity against both Malassezia and bacteria. They are usually initiated 2-4 days after starting "drops", to allow the ears to quiet down (flush is more irritating than drops for most dogs). Heavier oil products are used for more dry, tenacious debris (e.g. Cerumene; squalane; Vetiquino).For more tenacious debris, consider OtiFoam (DVM), followed by OtiRinse (DVM). For ears with a history of sensitivity to other flushes, consider dilute vinegar and water (1:2). For ears that are severely inflamed, a short course of oral glucocorticoid is readily rationalized to more quickly reduce the inflammation and pain, open up the canals to facilitate medication getting to where it needs to get in the ear and to allow the owners to more readily medicate the ears. Dosages used to initiate therapy are anti-inflammatory - i.e. 0.5 - 1.0 mg/kg/day of prednisone or prendisolone in the dog and 1.0 - 2.0 mg/kg/day prednisolone in the cat. Systemic antibiotics are used in more severe otitis presentations where neutrophils are present in the cytology along with bacteria (suggesting a deeper seated infection). The author tends to start with cephalexin for cocci, marbofloxacin for rods (gram negative organisms). Duration of therapy is usually 3 weeks. Differentiating Otitis Externa due to Food Sensitivity vs Atopy This is best done by assessing response to a restrictive diet trial. As much as possible, secondary ear infections and proliferative changes should be resolved prior to or during the earlier stages of the trial restrictive diet. Clinical/otoscopic/cytologic examinations should be repeated every 3 weeks during the diet trial. As the ears come under control, gradually drop out of the various anti-inflammatory medications (oral steroids first, then topical steroid containing product) until the ear is controlled with flush alone. This will allow for interpretation of what the diet alone is capable of doing. It appears to take longer to see the onset of benefit of a restrictive diet when evaluating otitis externa as compared to evaluating more generalized pruritus/dermatitis (e.g. 3-4 months). The patient is challenged with his/her regular diet at that time to prove the presence of a food sensitivity. Long Term Management of Allergic Otitis Externa
True refractory infections with Malassezia appear to be rare. Recurrent infections, however, are common (i.e. secondary to atopy). When Malassezia appears to be refractory, factors that may affect the efficacy of conventional therapies include:
Diseases of the Canine Nasal Planum - What's New? The differential diagnoses for diseases of the canal nasal planum, beginning with those most commonly seen in practice would include idiopathic nasal hypopigmentation, idiopathic nasal hyperkeratosis, discoid lupus erythematosus, chronic nasal discharge, bacterial dermatitis, the pemphigus complex, vitiligo, solar dermatitis, hereditary parakeratotic hyperkeratosis, nasal hyperkeratosis associated with xeromycteria, idiopathic granulomatous/pyogranulomatous dermatitis, dermatophytosis, vasculitis, ulcerative dermatosis of the St. Bernard, leukocytoclastic vasculitits of the Scottish Terrier, cutaneous lymphoma (mycosis fungoides or epitheliotropic lymphoma), distemper and squamous cell carcinoma. This list is not intended to be entirely complete, but instead emphasizes those diseases which may be restricted to the planum. Idiopathic Nasal hypopigmentation (Dudley nose, snow nose) - most commonly seen in Golden retrievers, yellow Labrador retrievers, white German shepherds, poodles, Doberman pinschers, Irish setters, pointers, Samoyeds Siberian huskies, Malamutes, and Afghan hounds. The planum is normal at birth, but the black gradually fades to a light brown or whitish color. The hypopigmentation may wax and wane, sometimes seasonally (worse in winter). This problem does not sun sensitize the planum. No therapy is necessary. There is an anecdotal suggestion that therapy with oral melatonin (3 - 6 mg BID) may benefit those individuals with a more seasonal tendency (i.e. snow nose). Vitiligo is thought to involve autoimmunity to melanocytes. Breeds predisposed include the Belgian Tervuren, German Shepherd dog, Rottweiler and Doberman Pinscher. Non-inflammatory asymptomatic depigmentation is most commonly noted on the planum, lips, muzzle, and buccal mucosa. There may be focal or widespread leukotrichia and/or depigmentation of the nails. The natural course of the disease may wax and wane. Histology shows a lack of melanin in affected areas. On occasion, a mild superficial dermal accumulation of lymphocytes may be noted. References generally state that there is no therapy but for preventing/managing solar damage. However, there are anecdotal reports of using a combination of oral folic acid, Vitamin C and injectable Vitamin B12. An 80 lb dog was given 1 mg folic acid PO BID, 50 microgram B12 IM every 14 days and 500 mg Vitamin C PO BID. Others have reported some success with 10 drops of stock solution of an alcoholic extract of blueberry. We have had some success in treating mildly inflammatory forms of the disease with the combination of tetracycline and niacinamide or oral glucocorticoids or topical tacrolimus (see below under "discoid lupus erythematosus"). Bacterial dermatitis of the planum nasale tends to be under-diagnosed in clinical practice. Crusting, loss of the normal reticular pattern of the planum and depigmentation may all be caused by bacterial infection. The German Shepherd dog appears to be uniquely predisposed to type of problem. In this breed, dermatitis is most commonly noted over the lateral nares, but may extend up and over the planum. It is also important to note that chronic nasal discharge in any breed may result in the creation of a micro-environment that may predispose to secondary bacterial infections of the planum. Biopsies may be suggestive (epidermitis, changes consistent with a mucocutaneous pyoderma - predominance of plasma cells in the superficial epidermis), but may also show changes indistinguishable from discoid lupus erythematosus. The diagnosis is supported by assessing response to systemic and/or topical antibiotics. Discoid Lupus Erythematosus is the most common inflammatory disease of the nasal planum in the dog. Lesions are generally restricted to the head. Lesions of the planum consist of variable degrees of loss of the normal cobblestone appearance, depigmentation, inflammation, crusting, atrophy and erosion. Erosive nasal lesions can be profound, resulting in significant hemorrhage. There is variable involvement of the bridge of the nose, lip margins, periocular region and medial aspect of the pinna. It is not uncommon to see inflammation of the third eyelids (plasma cell infiltrate). The Collie, Shetland Sheepdog, Australian Shepherd, German Shepherd dog and Siberian Husky exhibit a breed predilection for this disease. There is no systemic symptomatology. ANA titers are negative. The lesions are variably photo-aggravated. Histopathologic changes suggestive of this disease include vacuolar degeneration of the basal cell layer, single cell necrosis of keratinocytes (mostly in basal cell layer), pigmentary incontinence and an accumulation of predominantly mononuclear cells in the superficial dermis. These histopathologic changes are as those for Systemic Lupus Erythematosus. Differentiation between these diseases must therefore be made on the basis of assessing systemic involvement and ANA titer. In our clinic, as many as half of the cases that meet the clinical criteria of DLE have moderate to severe superficial lymphocytic/plasmacytic infiltrates and marked pigmentary incontinence in their biopsies, but fail to meet several of the other criteria required for a histologic diagnosis of DLE. These dogs appear to respond to therapy as for DLE. Whether these dogs suffer from a variant of DLE or some other immune mediated disease is not known. For all manifestations of DLE or DLE - like disease, sun restriction and the use of topical sun screens are strongly advocated. Mild disease is treated with topical glucocorticoids (Betamethasone valerate 0.1% or Betamethasone diproprionate 0.5% or fluocinolone acetonide 0.01% - Synotic) BID initially, then back off to q 48 to q 72 hours maintenance, usually used with oral Vitamin E and essential fatty acids PO (but marginal responses to these therapies in our regional area). Mild to moderate cases are treated with either topical tacrolimus or tetracycline and niacinamide. Topical Tacrolimus (0.1%, Protopic, Fujisawa; available in 30 and 60 gm tubes; expensive but a little goes a long way). Tacrolimus inhibits T-lymphocyte activation and is 10 - 100 times as immunosuppressive as cyclosporine. It is minimally absorbed. Lesions are initially treated BID. Once maximal benefit is noted the frequency is reduced to once daily for 1-2 months, then once every other day. Maintenance is usually achieved with once daily or once every other day regimens. It is suggested that the product be applied with a gloved finger although absorption through the skin is minimal. The product may prove irritating on affected skin but this is rare. Overall response to therapy occurs in about 75 - 80% of patients. Tetracycline and niacinamide are noted to benefit approximately 50 - 60% of patients (500 mg of each tetracycline and niacinamide given TID until maximal benefit noted, then reduce to BID for couple of months, then q 24 hours). Doxycycline has been used to replace TID tetracycline (doxycycline 5 mg/kg BID). If the lesions are moderate to severe , therapy is usually initiated with glucocortiocids and tetracycline/niacinamide, then maintenance is attempted with tetracycline/niacinamide alone. Tacrolimus and tetracycline/niacinamide failures have generally been treated with glucocorticoid monotherapy (usually starting at 2-4 mg/kg/day; dosage dictated by severity of lesions. Refractory DLE cases are treated with glucocorticoids and azathioprine (must wait at least 3 months to assess effects of azatioprine). Alternate therapies include glucocorticoids with gold salts or chlorambucil. Dapsone has also been used. Pemphigus erythematosus may closely mimic the clinical presentation of DLE. The diseases are differentiated histologically. Therapies are as for DLE with similar response rates. Pemphigus foliaceus also commonly affects the planum (inflammation, depigmentation, crusting, erosion/ulceration, pustules) although other areas of the body are usually involved early in the course of the disease (bridge of nose, medial pinna, periocular, pad/skin junction and foot pads. Variants of the disease include a form restricted to the feet and a chronic facial form. Breeds that appear to be more prone to secondary bacterial infections associated with PF include the Chow Chow and German Shepherd. Infections may complicate histopathologic interpretation. Especially in these breeds, consideration should be given to treating with systemic antibiotics prior to biopsy. A diagnosis is supported by finding acantholytic keratinocytes in unbroken pustules or impression smears and confirmed by biopsy. In our clinic, mild to moderate, chronic facial forms of this disease are treated with tetracycline/niacinamide. Approximately 30% of these cases respond. Only about 10 - 20% of our generalized cases respond to tetracycline/niacinamide. Mild cases of generalized disease that fail tet./niac. are treated with glucocorticoids alone. Moderate to severe cases are started on glucocorticoids and azathioprine. We feel that 65% of our cases in this category do well and have minimal complications related to the medications. Glucocorticoid/azathioprine failures are treated with glucocorticoids and chlorambucil, gold salts or dapsone. Topical tacrolimus is a "newer" therapy that may significantly benefit lesions. Because of its expense and the relative widespread areas of involvement associated with the disease, tacrolimus is usually used to "top off" other therapies to produce a more rapid resolution or help with the treatment of more refractory lesions. Therapy is generally initiated on a BID basis. It should be noted that Pemphigus vulgaris and Bullous Pemphigoid may also affect the planum. These diseases are comparatively rarely encountered in clinical practice. Proliferative arteritis restricted to the planum has been noted in the St. Bernard and Giant Schnauzer. It is an ulcerative dermatitis of the anterior aspect (philtrum) of the planum. Ulceration, when severe, may result in significant hemorrhage from the site. There appears to be a familial tendency for this disease. Histologic examination shows an arteritis. Lesions do not appear to respond to antibiotics. Response to glucocorticoids is variable (topical or systemic) as is response to tetracycline and niacinamide. We have had some success in managing affected individuals with topical cyclosporine (as noted above under Discoid Lupus Erythematosus) or topical tacrolimus. Hereditary nasal parakeratosis has been noted in Labrador retrievers and crosses. An autosomal recessive mode of inheritance is suspected. Lesions are first noted between 6 and 12 months of age. They consisted of grayish or brownish adherent accumulations of dry and rough keratin. In more severe cases, fissures and erosions develope. Some dogs experience depigmentation of the remaining nasal planum. The dermatitis does not appear to be exacerbated by UV light exposure. Histopathology shoes parakeratotic hyperkeratosis and a sub-basal lympho-plasmacytic infiltration within the superficial dermis. Zinc methionine, cephalexin, Vitamin A alcohol and topical tretinoin have failed to be of benefit. Improvement of the lesions was obtained with topical vitamin E, petrolatum and propylene glycol. Idiopathic nasal hyperkeratosis is most commonly noted in middle aged to older dogs with the Cocker spaniel being over represented. It has also been suggested that it is a senile change. It may be concurrently associated with pad hyperkeratosis. The nose becomes dry, rough and hyperkeratotic, especially on the dorsum of the nose. Fissures, erosions and ulcers are only occasionally noted. There is no depigmentation or inflammation. This is an important observation which helps to clinically differentiate the lupus or pemphigus group of diseases (which may also be hyperkeratotic). The diagnosis is generally made on a clinical basis. Therapeutic considerations include the daily topical administration of Kerasolv (DVM pharmaceuticals; salicylic acid, sodium lactate and urea in propylene glycol), Bag Balm or tretinoin gel (Retin-A;Ortho). Petrolatum may also be used. More rapid removal of the hyperkeratotic debris may be facilitated by pre-hydrating the planum (water compresses for 5-10 minutes) prior to application. Oral vitamin A may also be of benefit. Dosages are usually in the range of 8,000 to 20,000 Units BID. Although there is nothing "new" about this disease, it must be differentiated from a disease that not as well recognized by most - nasal hyperkeratosis associated with xeromycteria. Nasal Hyperkeratosis Associated with Xeromycteria ("Parasympathetic" nose)- The lateral nasal gland of the dog is located in the mucosa of the maxillary recess, near the opening of this recess into the nasal cavity. This gland is mostly responsible for the moisture of the nasal mucosa and the moisture observed at the external nares of the dog. Moisture from here is thought to translocate over the surface of the planum. This gland receives parasympathetic innervation with its fibers coursing with the facial nerve through the petrous temporal bone. Lacrimal glands also receive parasympathetic innervation. Xeromycteria associated with KCS may suggest that the preganglionic parasympathetic fibers proximal to the pterygopalatine ganglion are likely to have been damaged. Clinically, the petrous temporal bone should be examined for evidence of disease. In the dog, this warrants the evaluation of the patient for otitis media. Lesions may be either unilateral or bilateral. In affected dogs, resolution of otitis media may result in spontaneous improvements in nasal secretions and hyperkeratosis of the planum. In those cases in which an association with otitis media is not noted, or where resolution of the otitis media does not improve the planum, topical therapy is as for idiopathic nasal hyperkeratosis. Pilocarpine therapy has also been noted to be of benefit. Idiopathic, sterile, granulomatous and pyogranulomatous dermatoses may also be restricted to the planum at presentation. In general, lesions are usually multiple, firm, papular, nodular or plaquiform, variably haired and variably inflamed. On occasion, they may ulcerate. Areas of predilection include the head (especially the bridge of the nose and muzzle) and distal extremities. Less frequently, lesions can also develop on the pinnae, eyes, trunk and abdomen. When restricted to the planum, the syndrome has been called "clown nose". These lesions must be differentiated from the canine histiocytosis which can have similar presentations. Diagnosis is by rule out (bacterial and fungal cultures), and biopsy. In the dog, therapy is with topical tacrolimus, oral glucocorticoids, tetracycline/niacinamide or glucocortioids and azathioprine. After achieving remission for prolonged periods, some cases will be able to have medications discontinued. Cutaneous T-cell lymphoma, usually seen in older dogs, may have a multitude of various clinical presentations, one of which periocular, perioral and/or planum nasale inflammation / depigmentaiton. MF may look very much like an immune mediated disease. Canine and Feline Alopecia Syndromes: Where Are We Now? The differential diagnoses usually given for non pruritic, non inflammatory alopecia in the dog include classic endocrinopathies (hypothyroidism, hyperadrenocorticism, Sertoli's cell tumor , hyperestrogenism due to cystic ovaries or ovarian tumors, pituitary dwarfism), several disorders where endocrine imbalances may play a role (Alopecia X, maturity onset growth hormone responsive alopecia, cyclic flank alopecia), disorders thought to be related to follicular dysfunction (follicular dysplasias of the Irish water spaniel, Curly coated retriever, Portuguese water dog, Siberian Husky and Alaskan Malamute ), disorders thought to be related to morphologic follicular abnormalities (Color dilution alopecia, black hair follicular dysplasia), disorders that are histologically inflammatory but are usually not clinically inflammatory (alopecia areata, sebaceous adenitis) and congenital alopecias. Where are we now with respect to utilizing skin biopsies to better differentiate these problems? Many of the above problems are diagnosed on the basis of history, physical examination (cyclic flank alopecia, pattern baldness), screening laboratory work (CBC, serum chemistry panel) and more specific endocrinologic tests (e.g. hypothyroidism, hyperadrenocorticism) and/or response to trial therapy (e.g. hypothyroidism, sertoli's cell tumor). Biopsies are most commonly considered once hypothyroidism and hyperadrenocorticism have been ruled out as likely causes of alopecia. Biopsies often help to put one in the right "camp" with respect to causes of alopecia (e.g. endocrinopathy versus non-endocrine alopecia such as sebaceous adenitis or color dilution alopecia). Biopsies will usually not differentiate which endocrinopathy is present (nonspecific endocrine changes include hyperkeratosis, follicular atrophy, telogenization of hairs, sebaceous gland atrophy, hyperpigmentation. However, there may be changes that suggest a particular endocrinopathy (i.e. cutaneous atrophy suggesting hyperadrenocorticism; calcinosis cutis consistent with hyperadrenocorticism or a predominance of "flame follicles - follicles that are in catagen or early telogen suggesting Alopecia X). Where and what to biopsy: areas that are most significantly alopecic; more normal area; ideally, take samples from the more dorsal areas of the thorax, abdomen, lumbar region (assuming affected) because pilosebaceous structures are largest here and most consistent with normal; over the ventrum, the epidermis tends to thin, sebaceous glands are smaller - which could mimic endocrine changes. To better assure the pathologists ability to view the entire follicle (from epidermis to deep dermis or subcutis) along with adnexal glands (sebaceous and apocrine), draw a line along the lay of the hair and centre your biopsy on this. Tell the pathologist you have marked the sample and have it cut in along the line. Where are we now with respect to specific syndromes characterized by non pruritic, non inflammatory alopecia? Canine Recurrent Flank Alopecia (Seasonal flank alopecia, canine idiopathic cyclic flank alopecia, cyclic follicular dysplasia) High incidence in Airedale terriers, Boxers, English bulldogs, Schnauzers, Griffon Korthals, Affenpinscher, Bearded Collie (genetic predisposition). Well demarcated, variably symmetric alopecia and hyperpigmentation noted over the flanks, lateral thoracoabdominal area and may involve the dorsal and dorsolateral lumbar region. Affected skin may be somewhat scaly and thin. Affected individuals are prone to episodes of alopecia that are often recurrent. Hair loss may occur in the fall, only to regrow in the spring or vice versa. The cycle may repeat itself yearly or skin years. Regrown hairs may be normal or have different colors and/or texture. The syndrome is much more common in higher latitudes (above 450 parallel). The etiology for this syndrome remains unclear. It has been hypothesizeed that the problem is related to a genetically influenced melatonin deficiency. This deficiency may affect the skin either directly or indirectly through melatonin's effects 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 - 75% of cases. Dosage is 3 - 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 at this time and used for future prophylaxis or treatment of recurrences. Canine Pattern Alopecia (Pattern baldness) Symmetrical hair loss behind the ears, ventral cervical, chest and abdomen, caudal thighs and perianally. Seen primarily in Dachshund, Boston Terrier, Chihuahua, Whippet, Italian Greyhound, greyhound, Boxer and miniature pinschers. Individuals begin to loose hair about 6 months of age and gradually progress. Diagnosis by biopsy (follicles are both shorter and thinner than normal and residual hair shafts are extremely fine). Small rudimentary hair bulbs are present and hair follicles continue to cycle. Melatonin has been shown to be effective in regrowing hair in 50 - 70% of cases (2-6 mg/dog given BID or TID). Therapy is again used until good regrowth, then discontinued and re-instituted with recurrence of the problem. Color Dilution Alopecia Blue Doberman, Great Dane, whippet, dachshund, standard poodle, chow chow, red and fawn Doberman, fawn Irish setters. Born with a normal coat; gradually develop a patchy alopecia and seborrhea sicca. By 2-3 years of age, may be a profound alopecia affecting all color dilute areas. May see papule formation due to cystic hair follicles. Changes usually only affect the 'blue' parts of the coat. Nonpruritic unless develops secondary pyoderma (which they are prone to do). Diagnosis based on breed, color, cytological examination of hairs and skin biopsy. Cytologically (direct examination of hairs mounted in mineral oil) see numerous melanin aggregates within hair shafts. They have been associated with deformation and fracture of the hair cortex. Biopsy of the skin: superficial and follicular hyperkeratosis, follicular dilatation, normal to decreased size and number of sebaceous glands, large aggregates of melanin within the hair cortex and medulla, large melanin-containing macrophages within the dermis. In the past, treatments have been largely symptomatic (antiseborrheic shampoos, moisturizers; antibiotics for secondary infections). Oral synthetic retinoids (e.g. isotretinoin, acetretin) have been suggested to produce some partial regrowth. More recently, melatonin (as a nonspecific stimulator of follicle function) has been noted to benefit a significant number of individuals (hair regrowth); dosage: 3 - 6 mg BID to TID until maximal response is noted. Alopecia X Most commonly seen in the Nordic breeds or "plush coated" breeds: chow chow, pomerainian, keeshound, samoyed, Siberian husky, Alaskan Malamute, American Eskimo dog and Finnish spitz The miniature poodle also appears to be predisposed. Other individuals in other breeds may also be affected . To date, because of signalment, history, physical findings, laboratory findings and response to various therapies, dogs with this syndrome have been diagnosed as castration responsive alopecia, testosterone responsive alopecia, ovariohysterectomy responsive alopecia, estrogen responsive alopecia, congenital-adrenal hyperplasia-like syndrome, Pseudo-Cushing's disease, maturity onset growth hormone responsive dermatosis, malamute coat "funk", and follicular dysplasia of the Siberian husky and malamute. Affected dogs begin to develop hair loss as young, mature individuals, usually at 1-3 years of age. However, alopecia may develop at any age. Both males and females are affected. They may be intact or neutered. Primary hairs are usually lost first, with progression to loss of secondary hairs. Hair re-growth following clipping is slow or absent. Alopecia tends to initially develop in certain areas (peri-cervical, caudal shoulder, dorso-lateral lumbar, tail, perineum, caudal thigh) with progression to a more generalized truncal alopecia. The head and distal extremities are spared. Hairs tend to become bleached, dry and may break easily. The skin may become somewhat dry and mildly scaly and variably hyperpigmented. Hyperpigmentation may be profound in some individuals. The skin may become thin, especially in the pomeranian and in other non-Nordic breeds. Hair regrowth may be seen at sites of trauma (e.g. biopsy site). Comedo formation may be noted, but is usually mild and predominantly ventral in distribution. There is no pruritus. The alopecia is usually not complicated by secondary infections (e.g. bacterial pyoderma, Malassezia). Spontaneous resolution has been occasionally noted with this disease. The etiology of Alopecia X is very controvercial. Affected individuals often do re-grow hair following neutering or the administration of sex hormones, or the administration of sex hormone altering drugs. Some, but not all, affected dogs have been noted to have elevated basal and/or ACTH stimulated progesterone, 17 hydroxyprogesterone, androstenedione, 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 affect in the local metabolism of sex hormones at the follicular level, or on sex hormone receptors. Arguing against the importance of these sex hormones and sex hormone intermediates is the observation in more recent studies showing the treatments that result in hair regrowth do not alter sex hormone profiles in affected individuals and, in some cases the sex hormone concentrations even worsen with therapy, in spite of hair re growth (Frank L et al, Vet Dermatology 2004 - no change in sex hormones in melatonin and mitotane treated individuals; Cerundolo R et al, Vet Dermatology 2004 - sex hormones worsened with trilostane therapy). There is more data to suggest that this may be a primary hair growth disorder : a genetic predisposition to the development of a local defect in the hair growth cycle (e.g. local follicular horonal metabolism abnormality, hormoe receptor abnormality). In support of this argument is the observation that after stimulating hair re-growth in some individuals, hormonal therapy may be stopped and hair re-growth will continue to persist for many months to years after discontinuation. The observation of hair regrowth at sites of trauma and the fact that hair re-growth may be influenced by many different therapies (i.e. sex hormones, growth hormone or sex hormone altering drugs) also supports this argument. Interestingly even more non-specific therapies have also been noted to promote hair regrowth in affected dogs (Pomeranians) - Dl-alfa-tocopheryl nicotinate, 100 mg SID to BID and/or L-cysteine. How does one then diagnose Alopecia X? The diagnosis is largely by history, physical findings, and rule out (i.e. hypothyroidism , hyperadrenocorticism etc.). Skin biopsies are suggestive, but not confirmatory. There is usually variable degrees of orthokeratotic hyperkeratosis. The epidermis is of normal to decreased thickness. The pomeranian and non-Nordic breeds appear to be more likely to have epidermal atrophy . 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 tricholemmal 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, there may be more of a miniturization of hair follicles. 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 if the owners are willing to live with an alopecic pet. Do date, there are no obvious systemic abnormalities associated with this disease, and there is therefore no need to do further work-up and therapy. In the author's hands, diagnostics from this point are usually based on assessing response to therapy. Neutering is recommended initially; if this fails to be of benefit (or the patient must be left intact), we generally try melatonin for a 3 month period (3 - 6 mg BID to TID; treat until maximal response and discontinue; re institute therapy if and when signs recur; this protocol has been suggested to circumvent what some have noted as the development of an intolerance to the drug with chronic administration). Meltaonin is noted to produce partial or complete coat regrowth in 50 - 60% of cases (Frank L et al, Vet. Dermatology 2004). . Should this fail to be of benefit, we try methyltestosterone therapy (1 mg/kg to a maximum dose of 30 mg, once daily; generally tolerated well, but can cause hepatotoxicity, aggressive behavior and/or seborrhea; recommend a baseline liver profile prior to administration, then one and two months after initiating therapy. Supplementation is stopped after maximal re-growth is noted. If melatonin or methyltestosterone fail to be of benefit, then we tend to recommend measuring sex hormones pre and post ACTH stimulation (University of Tennessee; blood collected in a 5.0 clot tube, centrifuged and > 0.5 ml serum is frozen immediately; synthetic ACTH as Cosyntropin, Organon Inc. is given IV at a dose of 0.5 IU/KG and a post-ACTH stimulation serum sample, > 0.5 ml. is collected 1 hour later and frozen. The samples are sent on ice. If abnormalities are noted, there is rational for treating with mitotane (op,DDD; Lysodren) or trilostane. Mitotane likely benefits affected individuals through its adrenolytic effect on the zona reticularis and fasiculata (from which sex hormones are produced) although it may also have direct peripheral effects on follicle function. Induction is usually done at a more conservative dose of 15-25 mg/kg PO daily for 5-7 days. An ACTH stimulation is performed 24 hours after the induction dose is completed. The goal is to have the pre and post stimulation cortisols within the normal resting range for the laboratory being used (e.g. pre and post cortisol should be 3 - 5 micrograms/dl). If cortisol values are as desired, the patient is placed on the daily induction dose (15-25 mg/kg) divided and given twice weekly. If the values are low, mitotane should be discontinued and started, on a maintenance basis once cortisols have returned to the desired range. An ACTH stimulation test is generally performed 4-6 weeks after adequate induction, 3 months after this, then every 3-6 months thereafter. Owner's must appreciate the potential for the development of hypoadrenocorticism on this therapy. Success rates: in one study, 12 of 12 chows were noted to respond (Rosenkrantz WS, Proc. 2nd World Congress of Vet Derm, 1992), in another study, 4 of 6 dogs were noted to respond. Trilostane, a drug used to treat hyperadrenocorticism (competitive inhibitor of 13 Beta-hydroxysteroid dehydrogenase which interferes with adrenal steroidogenesis ) promotes hair regrowth in non-Cushingoid individuals, but 17 hydroxyprogesterone concentrations consistently go up in treated individuals (Cerundolo R et al. Vet Dermatology 2004). 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 (may be long term) or the need to establish a maintenance regimen (e.g. 2-3 treatments weekly). In the Cerundolo study, response was noted in 13 of 16 Pomeranians responded, 8 of 8 miniature poodles responded (Cerundolo R, Vet. Dermatology 2004) . Triostane appears to be well tolerated but is expensive and must be ordered from abroad at present. A source and protocol for use and monitoring (cortisols are monitored by ACTH stimulation) is available at Follicular Dysplasias? Other alopecic syndromes which have been thought to be follicular abnormalities +/- adrenal sex hormone abnormalities (perhaps similar to Alopecia X in the Nordic breeds and miniature poodle) include alopecias of :
Alopecia tends to take on a pattern distribution (pericervical, dorsolateral lumbar, shoulder, tail, then becomes generalized and truncal. It has been suggested that an important part of the pathogenesis of these disorders relates to weakening of the hairs. Individuals frequently have abnormalities of adrenal sex hormone production (as assessed by ACTH stimulation), but the significance of these findings is unknown. Affected individuals have been noted to respond to therapies outlined for Alopecia X (especially melatonin and trilostane). FELINE ALOPECIA FELINE SYMMETRICAL ALOPECIA Differential diagnoses for feline symmetrical alopecia - due to self truama
Several techniques may be used to help determine the mechanism of hair loss:
In that pruritic causes of hair loss are much more common than psychogenic causes, we emphasize elimination of all the potential causes of pruritus in the cat before returning to a tentative diagnosis of psychogenic dermatitis. Techniques used to differentiate pruritic from psychogenic causes of alopecia:
Alopecia +/- dermatitis due to behavioral problems are quite uncommon in the cat as a sole cause of alopecia due to self trauma. It is difficult to estimate how many cats with primary pruritic disease develop a stereotypic component to their overgroomig (5 - 10%?). Cats with alopecia due to self trauma are often considered to have anxiety neuroses caused by such things as changes in the cats environment (new family member, new cat or dog in the house or neighborhood). Historical features that may suggest a psychogenic etiology:
Treatment:
If no obvious psychogenic stress, consider workup for allergies first (trial steroid regimen : 2 mg/kg/day prednisolone for 1 week, then 1 mg/kg/day for 1-2 weeks; hypoallergenic food trial, skin testing), then trial psychoactive drug therapy if this fails. FELINE ALOPECIA UNASSOCIATED WITH SELF TRAUMA
The predominant feline cutaneous changes associated with hyperadrenocorticism included (25 cases):
Serum chemistry abnormalities include increased serum activities of alkaline phosphatase (although less common and much less severe as compared to the dog) , ALT, hypercholesterolemia, hyperglycemia and hypokalemia (especially if concurrently diabetic). The reader is referred to other sources for a discussion of confirmatory diagnostics and therapies. Paraneoplastic Alopecia and Internal Malignancies in the Cat Cats with pancreatic adenocarcinoma or bile duct carcinomas may present with a symmetric alopecia involving the ventrum and extremities. Hairs are usually readily epilated. The footpads/, footpad/skin junctions may be dry and scaly/crusty and occasionally fissured and painful. The alopecic skin is often smooth and "glistening" and occasionally mildly scaly and erythematous. Pruritus is usually absent. All cats manifest varying degrees of weight loss, inappetence and lethargy. Diagnosis is by skin biopsy (severe follicular and adnexal atrophy with follicular miniaturization and mild perivascular inflammation) and workup to document visceral neoplasia. The prognosis is grave. Newer Diseases and Therapies in Veterinary Dermatology WHAT'S NEW IN THE DEMODEX WORLD? Therapeutic alternatives for the management of canine juvenile onset, generalized demodex: The therapeutic alternatives for the treatment of juvenile onset, generalized demodex remain unchanged over the last few years, including topical amitraz , oral ivermectin and oral milbemycin oxime. In a recently review of 53 publications related to demodex therapy, overall cure rates associated with any of these therapies are reported to be about 60%. Interestingly, another course of therapy for those cases that recurred after the fist course of therapy was noted to put another 25% of cases in to remission (overall cure rate of 85% with 2 treatment courses). Because of the recent problem with availability of amitraz (the only approved therapy for this disease), oral ivermectin became the most popular, routinely used therapy. It is generally used at an initial dose of 0.3 - 0.4 mg/kg PO once daily. It has been suggested by some that a gradual work-up to this dosage be enacted over several days (such that if neurotoxicity noted, it will hopefully be at a lower dosage). If no significant improvement is noted in 4-6 weeks, we increase the dosage to 0.6 mg/kg PO once daily. Treatment is continued until 2 months beyond resolution. Oral ivermectin is not to be used in herding breeds (e.g. Collie, Shetland sheepdog, Australian Shepherd, Old English Sheepdog, crosses). Idiosyncratic reactions (neurotoxicity) can be seen in other breeds (at any time during therapy). It is now possible to screen individuals for potential to develop ivermectin related, CNS toxicity. It has been noted that p-glycoprotein functions as an important component of the blood brain barrier (drug efflux pump which prevents ivermectin from accumulating within the brain). The mdr1 gene codes for this protein synthesis. Mutation of the mdr1 gene results in incomplete p-glycoprotein synthesis. Patients with this mutation are noted to accumulate excessive amounts of ivermectin in the CNS, culminating in neurotoxicity. Individuals who are homozygous for the dilution experience toxicity. Those that are heterozygous or homozygous for wild type do not experience toxicity. The genotype of an individual can be assessed by submitting a cheek swab sample. This test is currently being offered by Washington State University for a cost of about $60.00. More information regarding this test and the rational for its use can be obtained at www.vetmed.wsu.edu/depts-VCPL/ .
Canine "Long Bodied" demodex mite (Demodex injai) Presented as mature dogs with a focal area of seborrhea oleosa over the mid back region. Variable pruritus. Diagnosis: multiple scrapings. Therapy: aggressive antiseoborrheic topical therapy (e.g. benzoyl peroxide shampoo), systemic antibiotic for secondary bacterial pyoderma and oral ivermectin as for juvenile onset demodicosis. Feline Demodex Demodex cati - the classic demodex mite that lives in the hair follicles and is most commonly seen in immunocompromised individuals (FIV, FelV, uncontrolled diabetes etc) Produces focal to widespread areas of alopecia, variable degrees of pruritus, inflammation and scaling,crusting Demodex gatoi - short bodied mite that lives on the surface of the epidermis. Affected individuals may have history of glucocorticoid administration or underlying allergies but it is uncommon to see other more serious, intercurrent immunocompromising diseases. This mite is communicable. Produces variable degrees of alopecia (without dermatitis) or alopecia and variable degrees of focal or more generalized dermatitis. Degree of pruritus is also variable. Therapy: Both Demodex cati or Demodex gatoi have been most responsive to lime sulfur dips once every 5-7 days. Ivermectin - starting at 0.3 mg/kg PO once daily is only variably effective and selamectin (selamectin used once weekly for 6 weeks in one study) is usually not effective. FELINE DERMATOPHYTOSIS : An Update Therapeutic considerations:
Tacrolimus is a macrolide produced by Streptomyces tsukabaensis. It's mode of action is very simlar to that of cyclosporine (potent inhibiotor of T cell function), but is 10 - 100 times as potent as cyclosporine. I is available as Protopic (Fugisawa) in both .03 and .1% strengths. The 0.1% concentration has been used most effectively in Veterinary medicine. Although expensive (cost to the client for a 30 gm tube is about $80.00), a little has been shown to go a long way!. Slight moistening of the skin prior to application may help with dispersion of the ointment, thereby facilitating more wide spread coverage of lesions. When administered parenterally in humans, tacrolimus has the potential to be nephrotoxic. Topical application, however, has been associated with minimal absorption in both humans and dogs. In dogs, blood concentrations achieved with widespread topical administration, even with injestion through licking, has not been noted to produce systemic effects. Mild irritation of lesional skin may be noted in a small number of cases. Therapy is usually initiated on a BID basis, decreasing to once daily once the lesions have significantly improved. Maintenance is usually achieved with once daily or once every other day application. Topical tacroimus has been shown to be effective in the management of the following dermatoses:
IMIQUIMOD Imiquimod (Aldara) is a topical immune response modifier that has been noted to have both antiviral and anti-tumor effects, likely through its ability to affect the production of several cytokines and through its enhancement of cell-mediated cytolytic anti-viral activity. In humans, it has been used most commonly to treat viral induced papillomas, but has also been used to treat pre-malignant or neoplastic diseases such as actinic dermatitis, squamous cell carcinoma in situ and basal carcinoma. In Veterinary medicine, it has also been used to treat canine viral induced papilloma, feline papilloma, feline Bowens disease (squamous cell carcinoma in situ) and actinic dermatitis (solar induced dermatitis) in both dogs and cats. This is an expensive therapy. It is common to see irritation at the sites of application (erythema, edema, crusting, erision). Frequency of application is usually 2-4 consecutive days of each week. Others have used the product three times weekly. Frequency of application appears to be directly correlated with the incidence of topical side effects. If irritation is noted, consideration should be given to reducing the frequency of administration. Cats appear to be more sensitive than dogs to the topical side effects of imiquimod. INTERFERON (IFN) Interferons are a group of cytokines that are produced by various inflammatory cells and fibroblasts. They are noted to have antiviral, antimicrobial, antiproliferative and immunomodulating effects. Enhancement of anti-microbial effects are thought to occur through IFNs ability to enhance macrophage activity. Direct anti-viral, anti-proliferative and anti-allergy effects appear to be more consistently associated with higher dose therapy. Certain interferons may be more suited to producing certain beneficial effects (i.e. one interferon source may be of more benefit as an immunomodulator when compared to another). In Veterinary medicine, three interferon sources have received most attention: Interferon Alfa -2A (human recombinant, Intron-A, Schering), feline recombinant (Virbagen Omega, Virbac; available only in Europe and Canada at this time) or canine recombinant (available in Japan). Efficacy has been supported in non dermatologic diseases, including canine parvovirus and feline Felv and FIV infections. Immunomodulatory effects: low dose, daily oral therapy (1000 units human interferon; total dose for all sized dogs) is suggested to have some benefit in reducing the incidence of infections in atopic dogs. This and even lower dosages (30 - 60 units per day) have been noted to be of some value in treating indolent ulcers in cats. Anti-viral, anti-proliferative and anti-allergy effects: higher dosages (1 to 1.5 million units per m2 body surface area given SubQ three times weekly) have been used effectively in treating both canine and feline papilloma virus lesions, feline herpesvirus lesions, the idiopathic facial dermatitis of Persian cats and as adjunctive treatment in the management of canine mycosis fungoides (epitheliotropic lymphoma) . Lesser dosages have been used for these purposes (e.g. 100,000 units total dose per os per dog per day) but responses have been more erratic. 10,000 U / Kg canine interferon or 1 million units feline recombinant SubQ, three times weekly have been noted to have some beneficial effects in reducing the signs of atopy (through altered cytokine release and decreased IgE production). Once re-constituted and frozen, interferon is good for at least 2-3 months (some say 1 year???). Once thawed, efficacy appears to be maintained for one month (refrigerated). When formulating low dose protocols, a 3 million IU/ml vial can be diluted in 999ml lactated Ringers (1000 units/ml) and then divided into 30 ml aliquots for freezing. A new aliquot is thawed out on a once per month basis. Interferon therapy appears to be well tolerated. More aggressive, higher dose parenteral therapies have occasionally been associated with some transient malaise. |
