Drug eruptions: approaching the diagnosis of drug-induced skin diseases

Journal of Drugs in Dermatology, June, 2003 by Simon Nigen, Sandra R. Knowles, Neil H. Shear

Discontinuation of the offending drug is usually sufficient in most patients with this self-healing disease. However, systemic corticosteroids (methylprednisolone 1 mg/kg/day) can be used in some patients depending on the extension and severity of the disease (Kempinaire 1997).

Table 15 summarizes the clinical features as well as the investigation and the management of these major drug-induced eruptions.

Other cutaneous eruptions

Lichenoid drug eruptions

Lichenoid drug eruptions mimic lichen planus clinically by their violaceous papular eruption, with or without oral involvement. However, the clinical presentation, as well as the distribution (generalized, photosensitive sites, flexural, extensor), the timing of the onset after administration of the offending drug (weeks to months) and the duration of the eruption are variable (Kanwar 1993, Firth 1989).

Resolution occurs usually within 2 to 4 months leaving post-inflammatory hyperpigmentation, particularly in dark-complexioned patients. Many drugs are implicated in lichenoid drug eruptions (Table 16).

Drug-induced photosensitivity

A photosensitive eruption is a broad term to describe a skin eruption that is due to the combined effect of sunlight on the skin and a chemical. It can manifest either by an inflammatory response of the skin to a harmless exposure of radiation or by an exaggerated response of the skin to inflammation-inducing levels. Although photosensitivity can be observed with visible light, most of the reactions occur upon exposure to radiation in the ultra-violet (UV) range (UVA: 320-400 nm and UVB: 290-320 nm). Furthermore, most of the drugs that have been associated with photosensitivity absorb in the UVA region.

Photosensitive eruptions constitute up to 8% of adverse cutaneous reactions in some series (Selvaag 1997). There are two types of photosensitive reactions: phototoxicity and photoallergy. Drugs reported to produce photosensitivity are listed in Table 17.

Phototoxic reactions are the most common and are dose dependent for both drug and UV light (mostly UVA), and any patient receiving a high enough dose of both is at risk of developing a phototoxic reaction. The pathophysiology of drug-induced phototoxic dermatitis begins with the passage of the UV or visible light through the skin. Absorption of the light by the drug present in the skin produces an excited state or a metabolite (photoactivated drug or photodegradation products) that then cause direct cellular damage.

A drug-induced phototoxic dermatitis is essentially and resembles an exaggerated sunburn with blistering, desquamation and hyperpigmentation. The eruption occurs exclusively on sun-exposed skin areas, giving a clear delineation of shading cause by clothing. Three different types of phototoxic eruptions have been described: 1) a strong delayed erythema and edema occurring 8 to 24 hours after sun exposure and lasting 2 to 4 days. This can be seen with the psoralens. 2) A more rapid, transient erythema with an immediate onset (30 minutes) lasting 1 to 2 days. There is no edema, but localized burning and itching are present. This can be seen with tetracyclines and tar derivatives. 3) A rapid, transient wheal and flare reaction with a burning sensation. (Moore 2002, Gould 1995, Epstein 1999).