Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: Assessment of Medication Risks with Emphasis on Recently Marketed Drugs. The EuroSCAR-Study

Abstract

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe cutaneous adverse reactions (SCAR) related to a variety of medications. They have a significant public health impact because of high mortality and morbidity. A multinational case-control study conducted in Europe between 1997 and 2001 evaluated the risk of medications to induce SCAR. Cases were actively detected through a hospital network covering more than 100 million inhabitants. Three hospitalized patients per case matched on age, gender, and date of interview were enrolled as controls. After validation by an expert committee blinded to exposures, 379 SCAR cases and 1,505 controls were included. Among drugs recently introduced into the market, strong associations were documented for nevirapine (relative risk (RR)>22) and lamotrigine (RR>14), and weaker associations for sertraline (RR=11 [2.7-46]), pantoprazole (RR=18 [3.9-85]), and tramadol (RR=20 [4.4-93]). Strong associations were confirmed for anti-infective sulfonamides, allopurinol, carbamazapine, phenobarbital, phenytoin, and oxicam-NSAIDs , with some changes in relative numbers of exposed cases. Thus, many cases were still related to a few "old" drugs with a known high risk. Risk was restricted to the first few weeks of drug intake. The use of such drugs as first-line therapies should be considered carefully, especially when safer alternative treatments exist. A number of widely used drugs did not show any risk for SJS and TEN.

Clinical, Etiologic, and Histopathologic Features of Stevens-Johnson Syndrome During an 8-Year Period at Mayo Clinic

“…Previous reports in the medical literature describe similar intervals, with the greatest risk of development of SJS occurring in the first 2 months of drug treatment 1 and an interval of 4 to 28 days being the most suggestive of drug causality in SJS. 13 We found that antibiotics and anticonvulsants were the most common medications causing SJS, with trimethoprim-sulfamethoxazole and phenytoin the most common culprits in each drug class, respectively. Previous studies enumerating medications specifically associated with SJS have identified antibiotics, anticonvulsants, and nonsteroidal anti-inflammatory drugs.…”

“…13 Among recently marketed drugs, nevirapine and lamotrigine were strongly associated with SJS, with sertraline showing a lower but still significant risk as well. 13 Our study reflects these findings, with 2 cases secondary to lamotrigine therapy and 1 case secondary to sertraline therapy. Moreover, recently reported data from the EuroSCAR study indicated that al- a BVac = basal vacuolar change; eos = eosinophils; epi = epidermis; FTN = full-thickness necrosis; HFN = hair follicle necrosis; INK = individual necrotic keratinocytes; intra = intraepidermal; lymph = lymphocytes; neut = neutrophils; mod = moderate; PA = periadnexal; PI = pigment incontinence; PK = parakeratosis; plasma = plasma cells; PTN = partial-thickness necrosis; RBC ext = red blood cell extravasation; RE = regenerating epidermis; SPV = superficial perivascular; SPVI = superficial perivascular and interstitial; sub = subepidermal.…”

“…10,11,[13][14][15][16] A recent multinational case-control study in Europe called EuroSCAR (European Study of Severe Cutaneous Adverse Reactions) showed a high risk of SJS with the following medications: trimethoprim-sulfamethoxazole and other anti-infective sulfonamides, lamotrigine, carbamazepine, phenytoin, phenobarbital, allopurinol, nevirapine, and oxicam nonsteroidal anti-inflammatory drugs. 13 Among recently marketed drugs, nevirapine and lamotrigine were strongly associated with SJS, with sertraline showing a lower but still significant risk as well. 13 Our study reflects these findings, with 2 cases secondary to lamotrigine therapy and 1 case secondary to sertraline therapy.…”

Risk evaluation and mitigation strategy assessments: Social science methodologies to assess goals related to knowledge

“…This information is supported by a multinational case-control study, 12 in which the numbers of individuals taking specific medications was low among 1,500 control patients hospitalized for acute conditions. Because the control patients were hospitalized, the prevalence of medication use among the controls in this study may very well have overestimated the prevalence among the general population.…”

Genetic and immune predictors for hypersensitivity syndrome to antiepileptic drugs

“…[11][12][13] Most HSR cases occur during the first eight weeks of treatment. [14][15][16][17] HSRs refer to dose-independent, idiosyncratic, severe adverse drug reactions (ADR). 18,19 Clinically, a triad of fever, rash and organ manifestation defines a "true" HSR.…”