Drug hypersensitivity syndrome: drug rash with eosinophila and systemic symptoms (DRESS)

The term “drug hypersensitivity syndrome” (DHS) refers to a specific severe drug reaction typically including skin rash and systemic involvement. The skin rash lasts 5 days or more with fever, is usually morbilliform, sometimes with bullous or purpuric lesions, and is often accompanied by hypereosinophilia, hepatitis and lymphadenopathy. DHS has been associated with anticonvulsants, ACE inhibitors, β-blockers, dapsone, allopurinol, sulphonamides, gold salts and minocycline, the majority of which may cause drug-induced lymphadenopathy. The differential diagnosis of DHS includes maculopapular rash and exfoliative dermatitis not associated with systemic involvement, Sézary syndrome and angioimmuno-blastic lymphoma, and sometimes acute generalized exan-thematous pustulosis. The pathogenesis is largely unknown. Because the typical interval from beginning drug therapy to onset of the cutaneous reaction is 2 to 6 weeks, and because positivity after rechallenge occurs more quickly than after the initial challenge, a delayed cutaneous hypersensitivity has been suggested. The involvement of drug-specific CD8+ T lymphocytes has also been suggested. A genetic inability to detoxify the toxic arene oxide metabolic products and cross-sensitivity between the various aromatic antiepileptic drugs have been observed. There may be susceptibility of leucocytes to toxic metabolites in vitro and slow N-acetylation of sulphonamides in vivo. An immune reaction against drug-reactive metabolites produced in excess may be involved. Because the pathogenesis is not fully understood treatment is uncertain. Recovery is usually total and spontaneous in a few weeks. Treatment with corticosteroids is used empirically for life-threatening systemic involvement but there are no controlled studies.