By Dr Anita Patel, BVM, DVD, FRCVS, RCVS recognised specialist in Veterinary Dermatology

Cutaneous adverse reactions are uncommon to rare, unintended effects to drugs that result in skin lesions. One type of adverse reactions may be a predictable consequence of the drug which have been reported during the clinical trial and are documented in the data sheet. They are associated with the pharmacologic action of the drug and may be dose dependent. In many cases dose adjustments reverse the cutaneous signs. The other type of adverse reaction is an unpredictable effect that causes skin disease. Unpredictable consequences of drugs are related to the individual’s immune response to the drug, or genetic susceptibility. Some of these reactions can be life threatening, and in these cases it is important to recognise the potential cause and cease administering the drug. In many cases there may be several drugs being administered at the time of presentation, making it difficult to pin the reaction down to just one of them. In other cases, the drugs although different, belong to the same class and therefore changing to another in the same class will have the same and probably worsening consequence. It is therefore paramount that a full history of the medical problem, including all the various drugs dispensed and responses to them, is properly taken. 

Predictable cutaneous adverse drug reactions 

These reactions are generally non-immunological and are associated with inappropriate choice of drug, overdosing, cumulative effects, or a drug interacting with another drug. 

Glucocorticoids 

Cutaneous reactions to both systemic and topical glucocorticoids are associated with long-term use, inappropriate use or with high dosages. They include alopecia, thinning of skin, loss of elasticity, scarring, comedones, striae formation, and calcinosis cutis. Seconding infections (pyodermas and Malassezia infections) and generalised demodicosis can occur with prolonged use. 

Ciclosporin 

Adverse reactions to ciclosporin includes hirsutism, gingival hyperplasia and papillomatosis. Cases of cutaneous tumours and cysts have been observed in some individuals on higher doses or long-term usage. 

Unpredictable cutaneous adverse drug reactions 

Unpredictable reactions can immunological or non-immunological. These are dose independent and can be associated with the individual’s immunologic response or to genetic susceptibility associated with metabolic or enzymatic deficiencies. 

Immunological reactions 

The exact immunologic process that results in the condition is not known in most cases, but may include hypersensitivities type I – IV, as well as FAS ligand activation that can induce apoptosis. 

Almost any drug can cause an unpredictable reaction. In people adverse reactions become more likely as the number of drugs taken increases demonstrating that drug to drug interaction has a role to play. Type I reactions include urticaria, angioedema, pruritus and sometimes shock. Type II reactions that are associated with cytotoxicity include thrombocytopenic purpura. Type III hypersensitivity reactions are associated with the formation of immune-complexes and include vasculitis. Type IV are cell-mediated hypersensitivity reactions which include maculopapular lesions and erythroderma. Autoimmune-like conditions (pemphigus complex), erythema multiforme and toxic epidermal necrolysis have complex poorly understood mechanisms. (Table 1) 

The clinical signs of cutaneous adverse drug reactions can mimic almost any lesion or any skin condition. Unpredictable cutaneous adverse drug reactions are generally uncommon to rare but when they do occur, they are to drugs commonly used in small animal practice. They can include drugs prescribed for any medical condition. 

The diagnosis of a drug reaction requires careful history taking, and looking at how the clinical signs relate to the lesions chronologically. If the initial diagnosis is correct where the prescribed drug is expected to have a beneficial effect for the condition. but skin lesions appear in an animal with no history of previous dermatological disease or if the lesions in animals being treated for a dermatological disease continue to worsen, suspicion of a cutaneous drug reaction should be raised immediately. 

Histopathological findings can support the diagnosis of specific syndromes such as pemphigus complex, erythema multiforme, ischaemic dermatopathy, toxic epidermal necrolysis, sterile neutrophilic dermatosis, eosinophilic dermatitis and oedema (Well’s like syndrome) and superficial necrolytic dermatitis. 

Clinical management and prognosis depend on the extent of the reaction and particularly if there is systemic involvement. The management includes ceasing the drug, treating the clinical signs with unrelated systemic or topic treatments and making sure that related classes of drugs are not used specially where antimicrobials are concerned. 

The prognosis is poor if there is extensive cutaneous necrosis and systemic involvement. Each individual should have treatment tailored to their needs.