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

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.