I ve tried X, Y & Z Why is nothing working? Common Reasons for Dermatologic Treatment Failures. Charlie Pye BSc, DVM, DVSc, Diplomate ACVD

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1 + I ve tried X, Y & Z Why is nothing working? Common Reasons for Dermatologic Treatment Failures Charlie Pye BSc, DVM, DVSc, Diplomate ACVD

2 + Overview Frustrating when treatment does not improve condition Frustrating when cases initially improve but then decline rapidly Require diagnostic steps to be revisited Further diagnostics

3 + Treatment Failure Atopic dermatitis Treatment failure Lack of response of presumed atopic patient to glucocorticoids or Atopica Previously controlled allergic patients pruritus Time of year Dietary indiscretion Consider the following: Secondary infections with yeast or bacteria Food allergy Sarcoptic mange Cutaneous epitheliotrophic T cell lymphoma

4 + Malassezia dermatitis Malassezia = normal cutaneous microflora Surface infection, principally skin folds Overgrowth of Malassezia pachydermatis leads to dz Secondary to predisposing factor Highly pruritic Erythema, brown discolouration, crusting, lichenification, hyperpigmentation Interdigital region, ears, nail beds, peri-anal region, lip folds Odour don t be fooled Minimal response to steroids ventrum,

5 + Malassezia dermatitis Often under diagnosed in dogs Cytology using acetate tape or swab Treat with oral or topical antifungals Treat for days Clinical and cytological resolution Bloodwork prior to azole therapy Fluconazole if liver disease Consider Malassezia hypersensitivity Allergy to organisms Pulse dosing?

6 + Malassezia Topical therapy Miconazole and chlorhexidine Miconazole 1% Chlorhexidine 2-4 % Shampoo 2-3 x weekly until a clinical improvement is seen Can be used more often Spot treatments Use COOL water Contact time of 5-10 minutes

7 + Malassezia Oral therapy Drug Ketoconazole Itraconazole Terbinafine Class Azole Azole Allylamine How supplied Species 200 mg tablets Human Several generic brands 10 mg/ml solution Veterinary Itrafungol (Vetoquinol) 52 ml bottle Sporonox tablets/liquid (human) 250 mg tablets Human Several generic brands Dose 5-10 mg kg 1 q12-24h days 5 mg kg 1 q24h days mg kg 1 q24h 28 days or twice weekly Side effects Vomiting, diarrhea, anorexia, lethargy Ptyalism, vomiting, diarrhea, anorexia, lethargy Vomiting

8 + Canine pyoderma S. pseudintermedius: normal cutaneous microflora Colonizes skin, hair follicles, mucocutaneous sites Primary No identifiable cause Secondary Underlying cause Chronic recurrent pyoderma therapy? underlying dz? Superficial pyoderma (aka folliculitis) Papule Pustule Crust Epidermal collarette

9 + Cytology Determine what bacteria are present Guide antimicrobial therapy Also important for otitis externa Cotton tipped applicator Swab over lesions Pustules are the best 25 gauge needle to open pustule Impression smear under crust Helps Interpret culture findings Determine if resistance is present/developing

10 + Bacterial culture When to culture? 1. If rods noted on skin cytology in large numbers 2. If deep bacterial pyoderma or furunculosis 3. If resistant bacterial population suspected Clues: Animal on antibiotics for appropriate length of time, appropriate dose, good compliance and no resolution of lesions

11 + Bacterial pyoderma - treatment Antibiotic appropriate for bacteria Staphylococcal species Consider topical versus systemic Surface versus deep Choice based on culture results Treat for minimum of 3-4 weeks 7-14 days past resolution Deep pyoderma weeks

12 + Topical Treatment Daily to 1-2 times weekly Mupirocin Fusidic acid Silver sulfadiazine cream Other antibiotic ointments/creams Antibacterial shampoo Chlorhexidine 2-4% Benzoyl peroxide

13 + Systemic Treatment Hillier A, Lloyd DH, Weese JS, et al. Guidelines for the diagnosis and antimicrobial therapy of canine superficial bacterial folliculitis. Veterinary Dermatology, 2014; 25: 163-e43. First tier (empirical selection) Clindamycin First generation cephalosporins e.g. cephalexin Clavulanted amoxicillin Trimethoprim-potentiated sulphonamides First or second tier Third generation cephalosporins e.g. cefovecin, cefpodoxime

14 + Systemic Treatment Second tier (culture) Doxycycline Chloramphenicol Fluoroquinolones Rifampin Aminoglycosides Third tier (culture) - discouraged Linezolid, vancomycin

15 + Methicillin Resistant Staphylococcus Pseudintermedius Common reason for txt failure Resistant to most cephalosporins Variable resistance to tetracyclines, fluoroquinolones Can be transmitted between dogs Important if wounds, surgery, immunocompromised Information on this subject Possible for dogs to transmit to humans relevance? Important if immunocompromised or have surgical implant

16 + Food Allergy Underlying food allergy Ears, feet, rears along dorsum Erythema, pruritus, alopecia GI signs 30% Consider novel protein or hydrolyzed diet Restricted diet No treats, table scraps, pilling vehicles, flavoured medications Period of 8-12 weeks Reaction to multiple food items

17 + Sarcoptic Mange Sudden onset, Exposure to wildlife Pinnal margins, elbows, hocks, ventral abdomen Erythema, papules, thick yellow crusts, Pruritic! Pinnal-pedal reflex Specificity: 93.8%, sensitivity: 81.8% Diagnosed via superficial skin scrapings Treatment with Revolution (Pfizer) or Advantage Multi (Bayer) 3 treatments at 14 day intervals May need course of steroids Hypersensitivity Mueller RS, Bettenay SV, Shipstone M. Vet Rec 2001; 148:

18 + Epitheliotrophic T cell lymphoma Infiltration of T lymphocytes into epidermis (CD8+) Systemic involvement rare Older animals Erythema and scales Plaques and erosions thickened skin Pruritic 50% cases mucosal involvement The great mimicker! Consider if non-responsive to antipruritic therapy Fontaine J, Heimann M, Day MJ. Vet Dermatol 2010; 21:

19 + Epitheliotrophic T cell lymphoma Study determined that a number of dogs with this disease had previously had chronic allergic skin disease Diagnosis via skin biopsy 40% no changes on bloodwork Txt: Lomustine, retinoids, steroids, other chemotherapeutic agents Guarded to poor prognosis 6 months- 2 years Fontaine J, Heimann M, Day MJ. Vet Dermatol 2010; 21:

20 + Treatment Failure Skin biopsies provide further information Azathioprine for refractory canine atopic dermatitis Dose of mg/kg once daily Bloodwork q 2-4 weeks Myelosuppression and hepatic toxicity (increase in ALT, ALP) Full bloodwork and urinalysis for systemic immunosuppressive therapy

21 + Treatment Failure Alternative Medications Pentoxifylline (synthetic xanthine) Vasculitis, dermatomyositis Anti-inflammatory, rheologic agent Suppress pro-inflammatory IL-1, IL-6 and TNF-α 10 mg/kg BID for 4 weeks significantly decreased pruritus and erythema Residual pruritus Higher dose more effective? Short half life so TID more beneficial Safe no crushing of tablets Marsella R, Nicklin CF. Vet Dermatol 2000; 11:

22 + Alternative Medications Pruritus pain or neuropathic Gabapentin mg/kg TID BID Sedation and ataxia Maropitant (neurokinin-1 receptor antagonist) Cerenia (Zoetis) Reduced ulcerative lesions in mice Blocks action of substance P Licensed at 2 mg/kg daily for vomiting For itch: 1-2 mg/kg daily for 4 days then decrease to 2-3 x weekly?

23 + Alternative Medications Oclacitinib (Apoquel, Zoetis) Janus Kinase Inhibitor (JAK1) IL-31 (inhibits function) pruritogenic cytokine Also inhibits function of IL-2,4,6,13 (all pro-inflammatory) Available in US (currently not Canada) mg, 5.4 mg and 16 mg tablets Not in dogs younger than 1 yr or < 3Kg Not in immunosuppressed or dogs with cancer Cosgrove S, Wren JA, Cleaver DM. Vet Dermatol 2013; 24: 587-e142. Open access.

24 + Take Home Points In cases of treatment failure perform cytology and skin scrapings, verify compliance Antibiotic resistance for patient on antibiotics who continues to have bacterial pyoderma Skin biopsies further information Alternative therapies in pruritic patients Patient non responsive to therapy for atopic dermatitis, consider food allergies or cutaneous epitheliotropic T cell lymphoma

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