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

Mortality may occur in 5% of cases of SJS, while 30% of cases of TEN may be fatal. The incidence of TEN and SJS have been estimated at 0.4 to 1.2 and 1.2 to 6 per million inhabitants per year, respectively (Roujeau 1994). SJS or TEN may also lead to significant morbidity. Eye involvement may result in visual impairment or permanent visual loss (de Felice 1987). Altered pigmentation and atrophic scars can also result after healing. Drugs are implicated in approximately 65% of cases (Auquier 2002); in general, the more severe the disease, the more likely a drug contributed to the development of the skin lesions. Sulfamethoxazole--trimethoprim and others sulfonamides antibiotics are associated with large increases in the risk of SJS or TEN as well as anticonvulsants agents, oxicam nonsteroidal antiinflammatory drugs (NSAIDs), allopurinol, chlormezanone and corticosteroids (Roujeau 1995) (Tablel 13). Cases of SJS and TEN caused by lamotrigine have been reported (Schlienger 1998). Penicillins and sulfonamide antibiotics were the drugs most commonly identified as etiological agents of SJS and TEN in a pediatrics population (Forman 2002). Other causes of the skin eruption that must be considered include infections, neoplasia and autoimmune disease.

The pathogenesis of these severe bullous cutaneous adverse drug reactions is unknown, although a metabolic basis similar to that of drug hypersensitivity syndrome has been hypothesized (Shear 1988). Sulfonamides and aromatic anticonvulsants are metabolized to toxic metabolites that are subsequently detoxified in most individuals. However, in predisposed patients with a genetic defect, the metabolite may bind covalently to proteins. These metabolites may trigger apoptosis resulting in severe cutaneous adverse reactions (Viard 1998).

Severe cutaneous insufficiency is a major acute complication of SJS or TEN. It can result in fluid loss, infections, impaired thermoregulation, altered immunologic functions and increased energy expenditure. Treatment of SJS--TEN starts with the early diagnosis and with the rapid withdrawal of the offending drug. Immediate measures like intravenous fluid replacement and transfer to an intensive care unit or a burn center are mandatory. Supportive treatment such as, nutritional support, careful wound care with bacterial sampling of the skin daily, anticoagulation and environmental temperature control is recommended (Ghislain 2002). Corticosteroids use is highly debated. Several articles reported the benefits of corticosteroids (Tegelberg-Stassen 1990, Patterson 1990,1994, Cheriyan 1995), but others studies claimed that corticosteroids use was detrimental (Halebian 1986, Kim 1983, Kelemen 1995). However, most authors now agree that systemic steroids should not be used. Other treatments like intravenous immunoglobulins (Viard 1998, TristaniFirouzi 2002), cyclophosphamide (Heng 1991, Trautmann 1998) and cyclosporin (Sullivan 1996, Arevalo 2000) have been reported to be useful.

Benign cutaneous pustular eruptions