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Background The proportion of severe cutaneous adverse reactions (SCARs) that could be avoided if medication use was consistent with good medical practice is unknown. Objectives To estimate the proportion of SCARs related to inappropriate medication use. Methods We carried out a retrospective study of all validated SCARs collected in a French registry between 2003 and 2016. For each case, all plausible drugs suspected of inducing SCARs (i.e. not just the drug regarded as 'the most probable') were considered with regard to (i) prescription for an inappropriate indication, (ii) unintentional rechallenge despite a previous allergy to the drug or (iii) self-medication with prescription medicines. Results In total, 602 cases were included in the analyses. Antibiotics, anticonvulsants and allopurinol were the drugs most frequently involved, accounting for more than 50% of all cases. All suspected medications were considered to have been appropriately used for 417 of the 602 individuals included in the study population [69·3%, 95% confidence interval (CI) 65·6-73·0] and inappropriately used for 144 individuals (23·9%, 95% CI 20·5-27·3). These inappropriate uses were due mainly to prescriptions for an inappropriate indication (65·8%, 95% CI 58·4-73·2) or unintentional rechallenge (20·9%, 95% CI 14·6-27·2). Allopurinol and co-trimoxazole were the drugs most frequently involved in inappropriate indications. Antibiotics were the largest group involved in unintentional rechallenge. Nonsteroidal anti-inflammatory drugs, available on prescription, were most frequently involved in inappropriate self-medication. Conclusions Our results underline the need for respecting the appropriate indication for drugs in order to reduce the incidence of SCARs. Reducing unintentional rechallenge also seems to be a necessary preventive measure.

SummaryBackground The histopathological features of drug rash with eosinophilia and systemic symptoms (DRESS) syndrome remain poorly characterized. Objectives To better characterize the histopathological features of DRESS syndrome, and define the phenotype of the effector cells in the skin and compare it with maculopapular rash (MPR). Methods We conducted a retrospective study on 50 skin biopsies from patients with DRESS syndrome (n = 36). Histopathological and immunophenotypical features were studied and compared with a series of MPRs (n = 20). Results Foci of interface dermatitis, involving cutaneous adnexae, were frequently seen in cases of DRESS. Eosinophils were seen in only 20% of cases and neutrophils in 42%. Eczematous (40%), interface dermatitis (74%), acute generalized exanthematic pustulosis-like (20%) and erythema multiforme-like (24%) patterns were observed. The association of two or three of these patterns in a single biopsy was significantly more frequent in cases of DRESS than in a series of nondrug-induced dermatoses (P

Summary Background Acute-stage specific bronchial epithelial detachment has been described in 27% of patients with Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Objectives To assess the pulmonary function of patients with SJS/TEN after remission. Methods Analysis of pulmonary function tests (PFTs) performed during the usual follow-up of patients with SJS/TEN managed in a referral centre from April 2007 to January 2010. Results Of 58 patients admitted, 32 underwent PFTs (17 male, 15 female). The median time from the acute stage to PFTs was 3 months (interquartile range 1–18). Three patients had grade 2 dyspnoea. Eighteen patients (56%) had abnormal PFTs, including 13 patients (41%) with moderately altered diffusion capacity for carbon monoxide (DLCO) normalized by the alveolar volume (VA) (giving the ratio KCO, which equals DLCO/VA) and five patients with decreased total lung capacity. No airway obstruction was observed. Patients with decreased KCO had higher initial detached body surface area than others (30% vs. 10%, P = 0·006), as did those with decreased DLCO (25% vs. 10%; P = 0·054). There were correlations between detached body surface area and both KCO (r = −0·41, P = 0·026) and DLCO (r = −0·47, P = 0·011). Among 10 patients with decreased KCO on the first PFT, eight patients had a sustained decrease in KCO on a second PFT. Conclusions More than half of patients with SJS/TEN displayed abnormalities on PFTs, mainly diffusion impairment, which was associated with higher initial skin surface detachment. These abnormalities were mostly asymptomatic and remained stable over time.

Summary Background Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction characterized by rash with sterile pustules, high fever and elevated circulating neutrophil counts. Objectives To investigate the frequency and clinical features of AGEP systemic involvement. Methods This retrospective study included all patients hospitalized in our department between 2000 and 2010 with a discharge diagnosis of AGEP. Patients had to fulfil the following criteria: (i) a specific EuroSCAR score > 4 and (ii) biological and radiological work-up available. Results Among the 58 patients enrolled, 10 had at least one systemic involvement: hepatic function test results were abnormal for seven; six had renal insufficiency; two developed acute respiratory distress, with one patient's bronchoalveolar lavage fluid containing many neutrophils but no microorganisms; one was agranulocytotic. Mean peripheral neutrophil counts and mean C-reactive protein levels were elevated significantly in patients with systemic involvement. Amoxicillin rechallenge and hospitalization duration were associated with systemic involvement. AGEP systemic involvement was observed in 17% of cases studied, including liver, kidney, bone-marrow and lung involvement. Outcomes were favourable after drug withdrawal, and symptomatic and topical steroid treatments. Conclusions The neutrophil count–systemic involvement association may suggest a role for neutrophils in AGEP systemic involvement. Physicians should be aware of the possibility of systemic involvement in AGEP and should actively look for signs of extracutaneous reactions.

SummaryBackground Linear IgA bullous dermatosis (LABD) is a rare autoimmune blistering skin disorder characterized by linear deposits of IgA along the dermoepidermal junction, visualized by direct immunofluorescence (DIF). It is usually spontaneous and drug induced. Objectives To compare the clinical and histological forms of LABD. Methods This retrospective single-centre cohort study concerned 28 patients diagnosed with LABD between 1 January 1995 and 31 December 2010. Imputability, determined according to the French imputability method (modified Begaud score) and Naranjo score, enabled classification into drug-induced and spontaneous LABD groups. Clinical and histological features were compared by blinded analysis of images and histological patterns. Results Sixteen patients had spontaneous LABD and 12 had drug-induced LABD. Nikolsky sign and large erosions were significantly more frequent in drug-induced than spontaneous LABD (P = 0·003 and P = 0·03, respectively), with no between-group differences for erythematous plaques, target or target-like lesions, string of pearls, location, mucosal involvement or histological features. Conclusions Drug-induced LABD was more severe than the spontaneous form, with lesions mimicking toxic epidermal necrolysis. Because LABD may be polymorphic and sometimes life threatening, DIF assay is recommended for all patients with Nikolsky sign and large erosions.