Cutaneous Adverse Drug Reactions in Domestic Animals Katherine Doerr, DVM, Dip. ACVD Veterinary Dermatology Center Maitland, Rockledge, Waterford Lakes, FL Not highly studied in veterinary medicine Unknown frequency of occurrence Reaction patters- pleomorphic (mimic anything) Diagnosis- increased risk of future drug reactions? Humans- Genetic Role HLA Type Slow N- acetylation, slow hydroxylamine detoxification Drug Reaction Increased likelihood of future reactions with similar drugs Atopics Increased risk of drug induced anaphylaxis? Pathogenesis 1. Non-immunologic mechanisms Related to pharmacologic action NOT related to pharmacologic action 2. Immunologic mechanisms Type I, II, II, IV reactions Non-Immunologic Mechanisms 1. Predicatable, dose-dependent 2. Anti-metabolites, other immunomodulators 3. Alopecia, purpura, poor wound healing, infection
Immunologic Mechanisms 1. NOT predictable 2. Relatively dose INDEPENDENT 3. Abnormal production of IgE, IgA, IgG, IgM; cytotoxic, immune complex, delayed hypersensitivity Clinical Features Maculopapular rash, urticaria, angioedema, erythroderma, exfoliative dermatitis, alopecia, pruritus/self trauma, purpura, altered pigmentation, erosions, ulcers, target lesions = ANYTHING Clinical Features Lesions often involve: Concave pinnae Ventrum Distribution: Generalized Oral cavity/mucous membranes Clinical Features Lesions often involve: Concave pinnae Ventrum Distribution: Generalized Oral cavity/mucous membranes
Reactions to Systemic Medications Specific clinical syndromes or diseases may be linked to cutaneous adverse drug reactions: Toxic epidermal necrolysis Erythema multiforme (minor & major) Vasculitis Pemphigus foliaceus/ Pemphigus vulgaris ERYTHEMA MULTIFORME & TOXIC EPIDERMAL NECROLYSIS NOT diseases SYNDROMES Distinct reaction patterns (clinically & histologically Drugs- Most common initiator Other Triggers Neoplasia Infection Idiopathic ERYTHEMA MULTIFORME Erythematous macules & papules, target lesions, erosions, ulcers, collarettes Sites Truncal (ventrum), mucocutaneous junctions, face, ears TOXIC EPIDERMAL NECROLYSIS Macular erythema Confluent erythema, ulceration, pain Sites Face, trunk, mucocutaneous junctions, pawpads OTHER REACTION PATTERNS Urticaria Maculopapular eruptions
Injection site drug reactions Erythroderma Exfoliative dermatitis CUTANEOUS ADVERSE REACTIONS TO THERAPY Worsening clinical lesions or acute onset of new lesions could be due to a cutaneous adverse drug reaction Can occur at ANY time Typically within 14 days of initiating the causative drug Can be due to BOTH systemic medications and/or topical products COMMON DRUGS to TRIGGER CUTANEOUS (Systemic) Dogs, cats, horses, humans: Antibiotics: Sulfonamides (TMS, Primor) Penicillins Cephalosporins/b- lactams NSAIDS/Anxiety medications: Dogs Carprofen (?) Horses Phenylbutazone Acepromazine COMMON DRUGS to TRIGGER CUTANEOUS (Topical) Ointments, salves, lotions, shampoo, sprays, etc. Occurs at SITE of application Cats, dogs
Topical flea control products Promeris - may cause DISTANT reaction (PF) Topical otic medications/rinses Neomycin Shampoos/sprays - typically most severe in dorsal linear pattern Corticosteroids thinning Chlorhexidine DRUG REACTIONS Diagnosis Previous experience HISTORY! Timing: 1-2 weeks Rule out other differential diagnosis Response to de-challenge Skin biopsy EM, TEN, PF, Vasculitis, mixed histologic reaction Re-challenge Not recommended Management WITHDRAW suspected drug Avoid suspect drug + all RELATED drugs in the future Supportive care +- Immunosuppressive therapy Prognosis MOST- self limiting after drug withdrawal (2-14 days) Requires drug avoidance
If immunosuppressive therapy- watch for side effects Erythema multiforme Potentially life-threatening Toxic epidermal necrolysis ALWAYS life-threatening Pemphigus vulgaris ALWAYS life-threatening Reactions to Systemic Drugs Non-immunologic reactions are dose related & predictable Glucocorticoids Immmunologic drug reactions are unpredicatable & NOT dose dependent Cutaneous lesions are often pleomorphic & may mimc other skin diseases Angioedema, urticaria, macules, papules, erythema, erosions, ulcers Thank you!