Stevens–Johnson syndrome/toxic epidermal necrolysis and erythema multiforme drug-related hospitalisations in a national administrative database

Abstract

BackgroundStevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and erythema multiforme (EM) are immunologically-mediated dermatological disorders commonly triggered by drug exposure and/or other external agents. We aimed to characterise SJS/TEN- and EM-drug-related hospitalisations in a nationwide administrative database, focusing on demographic and clinical characteristics, and in the most frequently implicated drug classes.MethodsWe analysed all drug-related hospitalisations with associated diagnosis of SJS/TEN or EM in Portuguese hospitals between 2009 and 2014. We compared gender, age, comorbidities, length of stay, and in-hospital mortality and estimated the number of episodes per million packages sold of drug classes. Predictors of in-hospital mortality were investigated in both conditions by logistic regression.ResultsThere were 132 SJS/TEN-related and 122 EM-related hospitalisations. Incidence and in-hospital mortality of SJS/TEN episodes (24.2%) were consistent with previous studies. HIV co-infection was more common among SJS/TEN hospitalisations (9 vs. 2% with EM; P = 0.009). Liver disease, advanced age, and a TEN diagnosis, were significantly associated with higher risk of mortality in patients with SJS/TEN. The highest numbers of SJS/TEN and EM episodes per million drug packages sold were observed for antivirals (8.7 and 1.5, respectively), antineoplastic/immunosuppressive drugs (5.6 and 3.9, respectively) and hypouricaemic drugs (5.0 and 2.4, respectively).ConclusionsSJS/TEN in-hospital mortality is high, and its risk factors include advanced age, liver disease, and TEN diagnosis. The drug classes most frequently associated with these conditions include antivirals, hypouricaemic drugs and antineoplastic/immunosuppressive drugs. Administrative databases seem useful in the study of SJS/TEN drug-related hospitalisations, yielding results consistent with previous studies and on a nationwide basis.Electronic supplementary materialThe online version of this article (10.1186/s13601-017-0188-1) contains supplementary material, which is available to authorized users.

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“…Lichenoid eruptions: resolve by ceasing the drug. They appear as flat mauve lesions, but they can be scaly and may flow into each other, e. g. gold salts, imatinib, interferon-α [10,11]. Erythema multiforme is an eruption of target-like lesions and in severe cases the center blisters.…”

“…The condition is reversible on ceasing the medication. Topical corticosteroids can be used for limbs, paracetamol for pain and fever and topical treatment can be used for oral, ocular and genital symptoms [10,11]. blistering and epidermal sloughing occur.…”

Rechallenge of lamotrigine after development of rash

“…The rate of rash increased when the rechallenge began within 4 weeks of the initial rash (36% vs 7%, P  = .002) and diminished when the initial rash had no signs of potential seriousness (0% vs 23%, P  = .01), which was defined using a rating scale developed by the research team 12. This scale ranged from 0 to 8 with higher scores indicating more serious symptoms including the following: exfoliation or erythroderma; purpura, tenderness, or blistering; facial or mucous membrane involvement; lymphadenopathy; hematological abnormalities (eg, eosinophilia) or elevated transaminase enzymes; and constitutional symptoms (fever, malaise, arthralgia, pharyngitis, cough) 11. For patients who underwent rechallenge, the average rash-severity rating was 1.2 12.…”

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“…Current recommendations therefore include genetic testing for people in at‐risk populations prior to commencing carbamazepine . A retrospective analysis of drug‐related hospitalisations in Portugal from 2009 to 2014 found that the most frequently associated drug classes with SJS/TEN included antibiotics, antivirals, anticonvulsants and uric acid metabolism drugs, and in particular allopurinol and lamotrigine . A systematic review of drug‐induced SJS and TEN in the Indian population showed carbamazepine, phenytoin, fluoroquinolones (gatifloxacin, ciprofloxacin, ofloxacin and levofloxacin) and paracetamol as being strongly associated with SJS/TEN .…”

“…96 antibiotics, antivirals, anticonvulsants and uric acid metabolism drugs, and in particular allopurinol and lamotrigine. 95 A systematic review of drug-induced SJS and TEN in the Indian population showed carbamazepine, phenytoin, fluoroquinolones (gatifloxacin, ciprofloxacin, ofloxacin and levofloxacin) and paracetamol as being strongly associated with SJS/TEN. 83,96 Other studies 92 have also suspected paracetamol while others still have questioned its association due to confounding by indication or other concurrent medication.…”