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Drug use must be weighed against risk of dangerous skin reactions, study shows

Drug use must be weighed against risk of dangerous skin reactions, study shows

Stevens-Johnson syndrome

Source: Dr P Marazzi / Science Photo Library

The high recurrence rate for Stevens-Johnson syndrome points to a genetic susceptibility in affected individuals

Two potentially fatal and rare cutaneous adverse reactions — Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) — have a significant likelihood of recurrence, researchers have found.

In a Canadian cohort study reported in JAMA (4 June 2014), among people admitted to hospital with a first episode of SJS or TEN, in which patients suffer extensive skin loss, 7.2% of those who survived after being discharged from hospital were readmitted with a recurrence.

Most episodes of SJS and TEN are drug-induced, so, according to the researchers, led by Yaron Finkelstein, from the Hospital for Sick Children in Toronto, Ontario, the use of these medicines — including allopurinol, sulphonamide antibiotics, aminopenicillins, cephalosporins, quinolones, carbamazepine, phenytoin and non-steroidal anti-inflammatory drugs — should be considered in light of the risk of SJS and TEN.

Finkelstein says that the high-risk finding is novel. “Recurrence had previously been shown in few isolated cases, but the phenomenon had not been studied on a large scale,” he says. “We advise clinicians to use even more discretion than usual when prescribing to this population [patients who have experienced a previous episode of SJS or TEN].”

Finkelstein’s group analysed data on all Ontario residents admitted to hospital with a first episode of SJS or TEN between April 2002 and March 2011. There were 567 cases of SJS and 141 of TEN; 17.9% of affected individuals were under 18 years of age and the same percentage died either in hospital or within 60 days of discharge.

Among the remaining 581 patients, 42 experienced a recurrence during a median of 1,283 days of follow-up, giving an incidence rate of 16 episodes per 1,000 person–years. The median time to recurrence was 315 days and eight patients experienced multiple recurrences.

Being male, being treated in a rural location and treatment at an academic hospital for the index episode were significant risk factors for recurrence, with hazard ratios of 1.94 (95% confidence interval 1.01–3.73), 2.28 (1.02–5.05) and 4.00 (2.04–7.85), respectively.

The recurrence rate is several thousand times higher than would be expected based on the incidence of these conditions in the general population, which points to a genetic susceptibility in affected individuals, say the investigators.

“Genetic predisposition has been identified for several medications in association with specific genotypes, such as carbamazepine-induced SJS in Chinese patients carrying HLA-B*1502 alleles,” Finkelstein and co-authors remark. “Additionally, SJS and TEN recurrence has been reported after exposure to structurally dissimilar drugs, such as carbamazepine and zonisamide.”

Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2014.11139056

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