Diagnosis and management of cutaneous drug reactions in dogs and cats (Proceedings)


Observed reaction does not resemble pharmacologic action.



  • Type I, II, III, IV hypersensitivity reactions


  • 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


  • 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


  • 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


  • 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.

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