Keeping owners of itchy allergic dogs happy: Treatment options (Proceedings)

Diagnosis of pruritic dermatopathies requires the dedication of collecting an historical account of the problem complete with all interrelationships of seasonality, in-contact animals, human disease and treatment, including specific drugs, treatment regimens and therapeutic outcome. Clinical examination with both general physical and dermatological examination is likewise important. Concepts important to identifying clinical aspects of the pruritic animal include pruritic threshold, allergic threshold, and summation effect.

Pruritic threshold is that level of pruritogenic factors (allergic or non-allergic) that is necessary to initiate itchiness in the animal. It often is the combination of a number of factors, some of which are represented by infectious or parasitic diseases. Staphylococcal pyoderma in combination with cutaneous malassezia complicating a case of canine atopy, flea allergy dermatitis and food allergy amplifies the individual effect on pruritius. The end result is referred to as the "summation effect" where each of the individual disease contributions additively increase the effect on pruritus. In other words, the pruritogenic factors now far exceed the pruritic threshold increasing the itch sensation to an all time high. Recognition of the contributing factors and their elimination is a cardinal principle of therapy. A large portion of these cases have already become refractory to glucocorticoid therapy. Principle II (after principle I, scrape pluck & smear) is elimination of recognized/suspected contributors to the overall summation of pruritus. Antibiotics for the pyoderma; anti-fungal therapy for the dermatophyte or yeast dermatitis; parasiticidal therapy for suspected or documented ectoparasites (acaricidal and insecticidal); dietary change for the suspected adverse reaction to food are all integral methods of evaluating/eliminating many of the possible conditions. The remaining pruritus may be related to the atopic component which can be addressed through symptomatic therapy or allergy testing and allergen immunotherapy or integration of cyclosporine A (Atopica, Novartis Animal Health). Persistent lesions may suggest the need for further diagnostic workup including acquistion of biopsies submitted to a reputable dermatohistopathologist.

Certain clues can be identified through lesion identification and distribution patterns. The presence of papules or pustules may be especially useful to relate diseases with the pruritic problem.

Causes of Papules

1. Staphylococcal pyoderma

2. Dermatophytosis

3. Demodicosis

4. Allergic contact dermatitis

5. Cutaneous Malassezia

6. Flea allergy dermatitis

7. Adverse reaction to food

8. Pemphigus foliaceous

9. Cutaneous drug eruption

10. Canine scabies

11. Cutaneous neoplasia (mastocytosis)

12. epitheliotrophic lymphoma

13. Arthropod reaction

14. +/- Atopy

Causes of Pustules'

1. Staphylococcal pyoderma

2. Pemphigus foliaceous

3. Subcorneal pustular dermatosis

4. Sterile eosinophilic dermatosis

5. Drug reaction

While the list of causes of papules is long, the most common causes include infectious or parasitic etiologies and are frequently observed in the pruritic patient. Papules are most often related to folliculitis and the three most common causes of folliculitis are 1. bacterial (Staphyloccocal infection), 2. dermatophytosis, 3. demodicosis. Although malassezia does not always have papules associated with the disease their presence with well demarcated lesions could be suggestive. In general, when papules are present in the pruritic dog, think bacterial folliculitis first but be sure to do cytology for malassezia, a fungal culture (DTM) and perform deep skin scrapings. The most prominent cause of pustules is once again staphylococcal pyoderma although pemphigus foliaceous is the second most common cause. Simple cytology of the pustule contents should provide differentiation of the two; PMN's with intracellular cocci for the pyoderma and PMN's without cocci but with acantholytic cells in PF. These two problems represent greater than 90% of the pustules found on dogs. Patterns of pruritus are likewise beneficial in development of a differential diagnostic list. Pruritus affecting the head (face &/or ears), ventrum and extremities include three prominent differentials: 1. Canine atopy 2. Adverse reaction to food (food allergy) and 3. Canine scabies. These diseases provide the basis for the evolvement of a basic working list of diseases to initiate diagnostic evaluation. Canine scabies can be easily ruled out despite the lack of disease confirmation from multiple skin scrapings. Dietary trials are usually successful in identifying a diet related problem (remember that the vast majority of food related allergy animals also have concurrent canine atopy. Another concurrent allergic relationship is the presence of flea allergy in greater than 75% of the atopic dogs. The distribution pattern of flea allergy dermatitis in the dog specifically affects the pelvic region with the dorsal lumbar sacral involvement as well as caudo-medial thighs and inguinal area quite unique compared to canine atopy. Occasionally food allergy may have the same pattern as flea allergy. Canine atopy does not typically have papules so when you see an animal with the suspicion of canine atopy and papular dermatitis it is always best to think of concurrent infection first (staphylococcal pyoderma). As many as 75% of the atopic dogs examined through referral dermatology specialty clinics have a concurrent pyoderma upon presentation! Although demodicosis is commonly associated with young dogs, adult onset demodicosis can occur later in life and is most commonly associated with glucocorticoid therapy commonly used in the management of the allergic animal. Demodicosis further potentiates the likelihood of secondary pyoderma also increasing the level of pruritus. Dermatophytosis is also a juvenile problem and is not commonly associated with disease in the mature adult dog unless some immuno-compromising factors may be present. These may include allergic dermatopathies and glucocorticoid therapy. The Yorkshire terrier and Jack Russell Terrier are breeds that tend to be more vulnerable for fungal complications. Minimal data base acquisition can identify the co-existing complicating problems. Routine specimen acquisition is mandatory for successful management. The "pluck, scrape and smear" procedures are universally the cardinal basis of the meaning of fundamental dermatological diagnosis. Scrape for mites; smear ears and skin for infectious agents and pluck hair for fungal culture.

Symptomatic antipruritic therapy is almost always utilized in the treatment regimen for the pruritic animal. Prioritization of non-steroidal therapy (anti-histamines, essential fatty acids and antipruritic topicals should be made over the empirical use of glucocorticoids. The therapeutic premise then is 1. to eliminate all diseases that can be eliminated 2. utilize non-steroidal therapy 3. Use glucocorticoids topical if possible 4. Integrate low dose, short acting, low potency glucocorticoid therapy as the remaining therapy. Often times these are integrated with allergen immunotherapy for the atopic dog with constant surveillance for recurrent infections, dietary management and intermittent chronic parasiticidal therapy. Routine shampooing and ear rinses are part of the total control elements. The "ounce of prevention is worth a pound of cure" philosophy prevails.

Anti-pruritic therapy is an essential aspect of daily treatment of many dermatologic diseases and often involves the combination of several therapeutic products. Treatment options include the use of products containing glucocorticoids and those that do not (steroidal vs. non-steroidal) and systemic vs. topical treatment. Non-steroidal anti-pruritic therapy includes antihistamines and fatty acid

supplementation in addition to shampoos & rinses not containing glucocorticoids. Antihistamines or antihistamine like compounds are certainly less reliable than glucocorticoids but recently have resurfaced in popularity for symptomatic treatment of the pruritic patient. They are particularly useful in conjunction with allergen immunotherapy or to simply decrease the requirement of glucocorticoid therapy. Synergism has been demonstrated between some antihistamines and prednisone as well as essential fatty acids. In general, approximately 30% response rate is observed with the treatment of an antihistamine. Some guidelines concerning the use of antihistamines include the following:

1. Antihistamines should be used at the recommended dosage and for a period of 14-21 days to adequately evaluate response. Each antihistamine requires individual evaluation to determine response.

2. Antihistamine therapy is only expected to partially control pruritus unless the intensity is mild as in the early symptoms of an atopic patient.

3. The presence of co-existing pruritic conditions dramatically influence the response observed to antihistamines. Elimination of as many of these factors as possible (fleas, food, pyoderma, malassezia etc.) is necessary for representative evaluation.

4. Antihistamine therapy should be trialed at different times of the year when there is a difference of allergen load and the summation of pruritogenic factors.

5. Side effects of antihistamines are variable but usually not a major concern. They include somnolence, CNS excitation, teratogenecity, anti-cholinergic-atropine actions and agranulocytosis (rare).

The following drugs are commonly available and may be used to evaluate responsiveness. It usually takes some experimentation to determine the most beneficial product or in some instances combination of drugs.

1. Diphenhydramine (Benadryl) 2.2 mg/kg TID

Available as 25 & 50 mg capsules or tablets and 12.5mg/5ml elixer.

2. Hydroxyzine HCl (Atarax) 2.2 mg/kg TID (Hydroxyzine pamoate may be substituted for hydrocholoride for cost savings.

Available as 10, 25, 50, 100 mg tablets. Generic appears to be as effective and less expensive. There are less side effects than classic antihistamines. This drug has also been used in cats with some success at 2 mg/kg twice daily.

3. Chlorpheniramine (Chlortrimeton) 4-12 mg two - three times daily. Available as 4 mg tablets or liquid at 0.5 mg/ml. The dosage most frequently used in cats is 2 mg. per cat two - three times daily.

4. Trimeprazine (Temaril) 1-2 mg/kg, three times daily.

It is available in 25 mg size and in a liquid at a concentration of 2.5 mg/ml

Prednisone 2mg is combined with trimeprazine in Temaril P (Pfizer)

5. Doxepin HCl 3-5 mg/kg twice daily.

6. Fluoxetine (Prozac) 1 mg/kg once daily P.O. 4 weeks then adjust. ( Controversial results with limited response in many)

7. Amitryptyline 1-2 mg/kg BID (Good choice for large breed dogs for convenience and cost effectiveness; variable response noted)

8. Cyproheptadine, 0.3-2.0 mg/kg, BID, PO

9. Astemizole, (Hismanal) 0.25 mg/kg, BID, PO

10. Clemastine (Tavist), 0.05 mg/kg, BID, PO; 0.125 mg/kg BID in cats

11. Loratadine (Clariton) 0.25 mg/kg - 0.50 mg/kg orally every 24 hours

12. Cetirizine (Zyrtec) 0.5 – 1.0 mg/kg or 5-10 mg qd – bid in the dog 2.5-5.0 mg per cat qd

Fatty Acid Therapy

Fatty acid therapy has been popular as adjunctive therapy for the pruritic patient (primarily allergic) with the expectation of 25-35% response rate. As a non-steroidal therapy, essential fatty acids are often combined with antihistamines for additive effect or used with low dose oral glucocorticoid treatment. Essential fatty acids are used because of their affect on the arachidonic acid cascade which results in pro-inflammatory mediators of pruritus. Therapeutic effect (according to some manufacturers) requires 45-60 days to achieve optimal response. Both omega 6 & omega 3 fatty acids may be helpful to reduce inflammation although it is generally accepted that emphasis of omega 3 fatty acids are the primary choice for pruritus whereas omega 6 fatty acids are indicated for scaling disorders. Eicosapentanoic acid (EPA) is a common supplement included in commercial products and has been used at a dosage of 180 mg per 10 pounds body weight. High dose fatty acids should be used with caution in dogs with tendency toward pancreatitis, diarrhea or bleeding disorders. Essential fatty acids are incorporated in some of the specialty diets used in dermatology and may be another source of them. The amount of fatty acid in these feeds may not provide the level of eicosapentanoic acid suggested as the ideal amount. Supplementation with additional n-3 fatty acids has not been deleterious in dogs on a diet containing essential fatty acids although reports indicating that the amount of fatty acids in the selective diets may not warrant additional supplementation. A variety of commercial products are available with omega-3 fatty acids or some pet owners elect to acquire them from a retail store.

Topical Anti-pruritic Therapy

Topical anti-pruritics are likewise beneficial to augment systemic therapy or at times to allow elimination of systemics. The following represent methods of topical anti-pruritic management.

1. Routine bathing

2. Lime sulfur rinses at 2-2.5% concentration (LymDyp,

3. Colloidal oatmeal shampoos, rinses or lotions(Relief, DVM Pharmaceuticals, Inc., EpisootheR, Virbac, Ft. Worth, TX; Aveeno Colloidal Oatmeal, Rydelle Laboratories, Racine, WI; Oatmeal Shampoo, Veterinary Solutions

4. Humectant (HumilacR, Virbac, Ft. Worth, TX) or emollient therapy (HyLyt EFA, DVM Pharmaceuticals, Inc., Miami, FL)

5. Medicated shampoos: antihistamine (HistacalmR, Virbac, Ft. Worth, TX), glucocorticoid (hydrocortisone - CortisootheR, Virbac), menthol (NuSal-TR DVM Pharmaceuticals, Inc.).

6. Antipruritic solutions & sprays: Hydrocortisone (CortisprayR DVM Pharmaceuticals, Inc., Miami, FL), hammamelis extract (DermacoolR, Dermacool with LidocaineR,or Dermacool HCR, Allerderm/Virbac, Fort Worth, TX); Triamcinolone 0.015% GenesisR (Virbac), Dermal Soothe Spray (1% pramoxine, Evsco);

7. Cream rinses: Dermal-Soothe cream rinse [1% pramoxine (Evsco)], Allerspray (Evsco), Relief cream rinse [1% Pramoxine, (DVM)], HyLyt cream rinse (DVM), Epi-Soothe cream rinse (Virbac), Oatmeal Rinse, (Veterinary Solutions), Histacalm [Diphenhydramine (Virbac)], Relief Spray [1% Pramoxine(DVM)],

8. Leave on conditioners/rinses:Examples include ResisootheR,Allerderm/Virbac, Ft. Worth, TX (colloidal oatmeal), ResicortR, Allerderm/Virbac (1% hydrocortisone), ResihistR , Allerderm/Virbac, (diphenhydramine) and ResiProxR , Allerderm/Virbac, (1.5 % pramoxine).

Anti-pruritic Glucocorticoid Therapy

Induction therapy of an oral glucocorticoid is usually 1.1 mg prednisolone or prednisone per kg per day. This may be given once daily or divided bid for 5-7 days. The anti-inflammatory maintenance dosage is usually 0.55 to 1.1 mg per kg every other day but may be administered to a maximum of 2.2 mg/kg every other day. In general, cats usually require 2-3 times the glucocorticoid dose for both induction and maintenance regimen of anti-pruritic / anti-inflammatory therapy. Methylprednisolone provides effective control of the pruritic dog at a dosage of 1 mg per 10-20 pounds body weight and can be given daily for induction with conversion to alternate day for maintenance. There appears to be less polydipsia and polyuria with methylprednisilone compare to prednisone or prednisolone. Oral triamcinolone has also been used to treat pruritus and may be effective at a dosage of 0.2 mg/kg. Since triamcinolone is rated as an intermediate glucocorticoid it has been advised to use every three days for maintenance regimens. The veterinary source of oral triamcionone is no longer available but can be acquired as Aristocort through pharmacies.

The ideal anti-pruritic therapy incorporates the use of topical treatment, systemic non-steroidal therapy (antihistamines or antihistamine like drugs and essential fatty acids) with the reservation of systemic glucocorticoid therapy as needed using the least amount necessary for control of the pruritus. This integrated approach to the treatment regimen, although more complex, time consuming and expensive, usually produces the optimal control of the pruritic condition with maximal owner satisfaction. Development of a treatment plan ideal for the individual pet and pet owner can be a challenge but well worth the time and effort.

1. Anti-pruritic therapy is essential in treating many common allergic, parasitic or infectious dermatologic diseases. 2. Integrated therapy is most often utilized to provide optimal response of the pruritic patient. 3. Principles of glucocorticoid therapy should be followed when treating the pruritic patient.