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Diagnosis and management of cutaneous drug reactions in dogs and cats (Proceedings)
Observed reaction does not resemble pharmacologic action.
Pathogenesis
Immunologic
- Type I, II, III, IV hypersensitivity reactions
Nonimmunologic
- Related to pharmacology of the drug
- Predictable, dose dependent
Route of administration
- Oral, Topical, Injectable, Inhalation
Clinical presentations:
- Erythema multiforme, Toxic epidermal necrolysis
- Pemphigus foliaceus
- Vaccine reaction
- Cutaneous vasculitis
- Lichenoid Drug Eruption
Unique feline reactions:
- Miliary dermatitis reaction
- Vaccine reaction - Injection site fibrosarcomas
Erythema multiforme
- Drug-induced apoptosis - Programmed cell death
- Acute onset of lesions, Erythematous macules, “Target lesions”, Urticarial plaques, Vesicles and bullae, Concurrent systemic illness, Fever, depression, anorexia
- Mucous membrane involvement - Vesicles, bullae, ulcers
- Erythema multiforme major or Stevens-Johnson syndrome - Can be life threatening
Drugs implicated
- Aurothioglucose, Cephalexin, chloramphenicol, gentamicin, trimethoprim sulfas, ormetoprim sulfas, tetracycline, Diethylcarbamazine, levamisole, L- thyroxine, phenobarbitol
Toxic epidermal necrolysis
- Severe erythema multiforme?
- Massive and sudden apoptosis
- Diffuse erythematous rash, Vesicles and bullae, Full thickness skin sloughing and ulcers
- May affect footpads, mucous membranes
- Lesions usually painful, Concurrent fever, anorexia, lethargy, depression
- Secondary sepsis a problem, Often a fatal disease
Drugs implicated
- Penicillins, cephalosporins, trimethoprim sulfas, Griseofulvin, Levamisole, 5- fluorocytosine, Topical flea dips (D-limonene)
Drug-induced pemphigus
- Mimics Pemphigus foliaceus
- Acute, transient pustular eruptions, Subsequent crusts, scales, erosions, epidermal collarettes, Variable distribution patterns
- Systemic illness rare
Drugs implicated
- Ampicillin, cephalosporins, sulfonamides, Diethylcarbamazine, thiabendazole, Cimetidine, procainamide
Vaccine reactions
- Most commonly observed at site of a subQ or IM vaccination - Rabies, DHLP- Parvo
- Can occur from weeks to months post-vaccination
- Focal area of alopecia and hyperpigmentation
Breed predisposition
- Poodle, Bichon Frise, Shih Tzu, Lhasa Apso, Miniature Schnauzer, Yorkshire Terrier, Bedlington Terrier, Silky Terrier
- Most spontaneously resolve over several months, Lesion may remain static
- Area of alopecia and hyperpigmentation can gradually enlarge over months to years
Treatment
- Tincture of time, Surgical excision, Pentoxifylline (Trental) - 15 mg/kg TID x 3 months
Cutaneous vasculitis
- Palpable purpura, hemorrhagic bullae, Craterform ulcers, full thickness skin sloughing
- Acrocyanosis of distal extremities, Large areas of erythematous or purplish skin (Does not blanch on dioscopy)
- Lesion often painful, Pitting edema of distal extremities
- Concurrent systemic illness - Anorexia, depression, fever
Drugs implicated
- Penicillins, sulfonamides, cephalosporins, dexamethasone, DHLP- Parvo vaccine
Lichenoid drug eruption
- Solitary to multiple papillomatous or plaque-like lesions
- Drugs implicated: Cyclosporine (Atopica, Neoral, Gengraf)
Miliary dermatitis reaction
- Miliary lesions - Affects head, face, neck regions
- Intense pruritus, Mimics “food allergy”
- Drugs implicated: Methimazole (Tapazol), Propranolol
Vaccine reaction
Injection site fibrosarcomas
- Interscapular and femoral regions - Associated with either subQ or IM injections
- Tumor may develop 1-2 years post -vaccination
- Vaccines implicated: FeLV, Rabies, FVRCP
Diagnosis of cutaneous drug reactions
History
- Observed reaction does not resemble pharmacologic action
- Prior exposure to drug may have been well tolerated
- Reaction can be reproduced by small amounts of drug
- Reaction consistent with a known hypersensitivity response
- Reaction occurs within several days of drug exposure
- Resolution within several days of drug withdrawal
Drug rechallenge
- Proves cause and effect relationship, Clinical signs often more severe, Outcome can be fatal
Erythema Multiforme
- Histopathology- Hydropic interface dermatitis, Dyskeratotic keratinocytes with satellitosis, Superficial perivascular infiltrates with mononuclear cells
Toxic Epidermal Necrolysis
- Histopathology - Hydropic degeneration of basal cells, Coagulation necrosis of epidermis, Absence of dermal inflammation, Dermoepidermal separation and bullae formation
Pemphigus Foliaceus
- Histopathology - Subcorneal pustules, Acantholytic cells, Neutrophils, eosinophils, Involvement of hair follicles
Vaccine Reaction
- Histopathology - Vasculitis, panniculitis, Dermal edema, Atrophic hair follicles, Hydropic degeneration of basal cells
Cutaneous Vasculitis
- Histopathology - Most commonly leukocytoclastic, Neutrophils in vessel walls, “Nuclear dust”, Fibrinoid degeneration, thrombi, Perivascular hemorrhage and edema
Lichenoid drug eruption
- Histopathology - Psoriasiform lichenoid dermatosis – with or without papillomavirus
Unique feline reactions
Miliary dermatitis
- Histopathology - Epidermal crusts, spongiosis, Neutrophilic, eosinophilic vesicopustules, Eosinophilic perivascular infiltrates
Vaccine Reactions
- Histopathology - Fibrosarcoma
Treatment
- Discontinue suspected drug
- Avoid chemically related or similar drugs
- When multiple drugs are present: all should be discontinued
- Best advice: “Do no harm!”
- For Idiopathic cases (Erythema multiforme, cutaneous vasculitis, miliary dermatitis) – consider hydrolysate treated or home-cooked elimination diet trial
Supportive Therapy - IV Fluids
- Systemic antibiotics in septic patients
- Broad spectrum initially - Cephalexin - 10 mg/lb TID or Based on culture and sensitivity
- Gram negative organisms - Ciprofloxacin - 22 mg/kg SID
Immunosuppressive drugs
- Extremely controversial - May actually be contraindicated, Increased risk of infections, delayed healing
- Indicated in drug induced Erythema Multiforme major
- Corticosteroids: Prednisolone - 1 mg/lb SID-BID
- Immune Modulating Drugs: Cyclophosphamide - 1 mg/lb SID, Cyclosporine (Neoral, Gengraf, Atopica) - 5 mg/kg SID-BID, Azathioprine (Imuran) - 1 mg/lb SID, Pentoxifylline (Trental) – 15 mg/kg TID
Clinical criteria EMM EMM SJS OVE TEN
Flat or raised, focal
or multifocal, target lesions Yes Yes No No No Number of mucosa involved <1 >1 >1 >1 >1
Erythematous or purpuric,
macular or patchy eruption <50% <50% >50% >50% >50% Epidermal detachment <10% <10% <10% 10-30 >30%
Olivry T et al: Erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis in the dog: Clinical classification, drug exposure, and histopathological correlations. Proceedings of the Autumn Meeting of the British Veterinary Dermatology Study Group, 1998, York, United Kingdom.