Almost
any drug can cause a cutaneous reaction, and many inflammatory skin conditions
can be caused or exacerbated by drugs. A drug reaction can reasonably be
included in the differential diagnosis of most skin diseases.
These
are many and various (Table 22.1), being related both to the properties of the
drug in question and to a variety of host factors. Indeed, pharmaceut-ical
companies study genes to predict responders and non-responders, and to detect
patients who may be unable to metabolize a drug normally. For example,
drug-induced lupus erythematosus occurs more com-monly among ‘slow acetylators’
who take hydralazine. However, not all adverse drug reactions have a genetic
basis; the excess of drug eruptions seen in the elderly may reflect drug
interactions associated with their high medication intake.
Not
all drug reactions are based on allergy. Some are a result of overdosage,
others to the accumulation of drugs, or to unwanted pharmacological effects,
e.g. stretch marks from systemic steroids (Fig. 22.1). Other reactions are
idiosyncratic (an odd reaction peculiar to one individual), or a result of
alterations of ecolo-gical balance .
Cutaneous reactions can be expected from the very nature of some drugs. These are normal but unwanted responses. Patients show them when a drug is given in a high dose, or even in a therapeutic dose. For example, mouth ulcers frequently occur as a result of the cytotoxicity of methotrexate. Silver-based pre-parations, given for prolonged periods, can lead to a slate-grey colour of the skin (argyria).
Acute vaginal candidiasis occurs when antibiotics
remove the normal resident bacteria from the female genital tract and so foster
colonization by yeasts. Dapsone or rifampicin, given to patients with
lepromatous leprosy, may cause erythema nodosum leprosum as the immune response
to the bacillus is re-established
Non-allergic
reactions are often predictable. They affect many, or even all, patients taking
the drug at a sufficient dosage for a sufficient time. Careful studies before
marketing should indicate the types of reaction that can be anticipated.
Allergic
drug reactions are less predictable. They occur in only a minority of patients
receiving a drug and can do so even with low doses. Allergic reactions are not
a normal biological effect of the drug and usually appear after the latent
period required for an immune response. Chemically related drugs may
cross-react.
Fortunately,
allergic drug reactions present in only a limited number of forms, namely
urticaria and angioedema, vasculitis, erythema multiforme, or a mor-billiform
erythema. Rarer allergic reactions include bullae, erythroderma, pruritus,
toxic epidermal nec-rolysis and the hypersensitivity syndrome reaction. This
syndrome includes the triad of fever, rash (from morbilliform to exfoliative
dermatitis) and internal involvement (hepatitis, pneumonitis, nephritis and
haematological abnormalities).
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