Epidemiology of cutaneous adverse drug reactions

Epidemiologic investigations of cutaneous adverse drug reactions (cADR) are important to evaluate their impact in dermatology and health care in general as well as their burden for affected patients. Few epidemiologic studies have been performed on frequent non-life-threatening cADR including reactions of both delayed and immediate hypersensitivity, such as maculopapular exanthema, fixed drug eruption and urticaria. Concerning rare but life-threatening severe cutaneous adverse reactions, e.g. toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), acute generalized exanthematous pustulosis and drug reaction with eosinophilia and systemic symptoms, several epidemiologic studies have been performed to date, some of which are still ongoing. Such studies enabled the calculation of reliable incidence rates and demographic data, but also allowed to perform risk estimation for drugs. The spectrum of drugs causing cADR differs substantially when separating the various clinical conditions. Whereas antibiotics are by far the most frequent inducers of milder cADR like maculopapular exanthema, they have a much lower risk to induce SJS/TEN, for which high-risk drugs are anti-infective sulfonamides, allopurinol, certain anti-epileptic drugs, nevirapine and nonsteroidal anti-inflammatory drugs (NSAIDS) of the oxicam type. In contrast, acute generalized exanthematous pustulosis is predominantly caused by the antibiotics pristinamycin and aminopenicillins, followed by quinolones, (hydroxy-)chloroquine and sulfonamides. Drug reaction with eosinophilia and systemic symptoms can be induced by a number of drugs known to cause SJS/TEN, such as certain antiepileptics and allopurinol, but also other medications (e.g. minocyclin).