Incidence of and mortality from epidermal necrolysis (Stevens-Johnson syndrome/toxic epidermal necrolysis) in France during 2003-16: a four-source capture-recapture estimate.

BACKGROUND: Because of its rarity, the exact incidence of and mortality from epidermal necrolysis (Stevens-Johnson syndrome/toxic epidermal necrolysis) is difficult to establish and closely depends on the size and type of the data source. OBJECTIVES: To estimate the incidence of and mortality due to epidermal necrolysis in France over a 14-year period. METHODS: Data from four national databases were analysed. A capture-recapture analysis was performed. RESULTS: A total of 2635 incident cases of epidermal necrolysis were recorded in at least one of the four databases during the study period [males: 47·9%; median age: 52 (interquartile range 25-72) years]. On capture-recapture analysis, the estimated total number of cases was 5686, for an overall estimated annual incidence of 6·5 (95% confidence interval 4·1-8·9) cases per million inhabitants. The estimated annual incidence rates were 4·1 (0·3-7·9) cases per million inhabitants < 20 years of age, 3·9 (1·5-6·3) cases per million inhabitants aged 20-64 years and 13·7 (5·4-22·0) cases per million inhabitants ≥ 65 years of age. The estimated overall annual mortality rate from epidermal necrolysis was 0·9 (0·1-1·8) case per million inhabitants. It was 0·6 (0·1-1·5) case per million inhabitants aged 20-64 years and 2·8 (0·9-6·6) cases per million inhabitants ≥ 65 years of age (deaths in people < 20 years old were too rare to provide an accurate estimate). CONCLUSIONS: The annual incidence of epidermal necrolysis is higher than the one to five cases per million inhabitants usually reported. Such estimations could be helpful in establishing appropriate healthcare plans for people with epidermal necrolysis, in particular the need for specialized care units. What's already known about this topic? Few data are available regarding incidence of and mortality from epidermal necrolysis in the general population. Experts in epidermal necrolysis have recently proposed an annual incidence of one to five cases per million individuals. The overall mortality rate is usually reported to be between 10% and 20%. What does this study add? Using a four-source capture-recapture method and data from a 14-year period (2003-16), the annual incidence of and mortality from epidermal necrolysis were estimated to be 6·5 (95% confidence interval 4·1-8·9) and 0·9 (0·1-1·8) cases per million French inhabitants, respectively. Such estimations could be helpful in establishing appropriate healthcare plans, in particular the need for specialized care units.

Severe cutaneous adverse reactions due to inappropriate medication use.

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.

Relative risk of and determinants for adverse events of methotrexate prescribed at a low dose: a systematic review and meta-analysis of randomized placebo-controlled trials.

Low-dose (i.e. ≤ 30 mg per week) methotrexate is widely prescribed by dermatologists. However, there is limited evidence-based information regarding the relative risk of and determinants for adverse events associated with this treatment. The aims of this review were to assess the relative risk of and the determinants for adverse events associated with low-dose methotrexate exposure. A systematic review was undertaken using the MEDLINE, Embase and CENTRAL databases. Randomized controlled trials comparing low-dose methotrexate with placebo were eligible. Random effect meta-analyses were conducted to assess the risk ratios (RRs) of adverse events associated with methotrexate exposure. Subgroup analyses and random effect meta-regressions were performed to examine the determinants of adverse events. In total, 68 trials (6938 participants) were included. Compared with placebo, low-dose methotrexate slightly increased the risk of adverse events (mean number per individual: 1·78 ± 2·00 in the methotrexate group, 1·53 ± 1·89 in the placebo group; P < 0·001), including nausea/vomiting, elevated transaminase levels, mucosal ulcerations, leucopenia, thrombopenia and infectious events, but not the risk of serious adverse events or death. Low-dose methotrexate also increased the number of withdrawals from studies because of adverse events [RR 1·32 (1·13-1·53)]. The concomitant prescription of folic/folinic acid was associated with a significant lower risk of any adverse events, and methotrexate prescribed orally was associated with a higher risk of abdominal pain than when prescribed subcutaneously or by intramuscular injection. On the other hand, the risk of adverse events did not increase with the weekly dose or with duration of exposure. Similar studies comparing methotrexate with other systemic/biological treatments are needed.

Use of topical glucocorticoids: a population-based cohort study.

BACKGROUND: Little is known about the prescriptions of topical glucocorticoids in the general population. OBJECTIVES: To report an overall picture of topical glucocorticoid prescriptions in France. METHODS: This study used the Echantillon Généraliste de Bénéficiaires (EGB) database, a 1/97th random sampling of the French population covered by the main national healthcare insurance system (approximately 90% of the whole population). All patients prescribed topical glucocorticoids over a 5-year period (1 January 2011 to 31 December 2015) were identified using a specific code list for topical glucocorticoids. RESULTS: Over the 5-year study period, 662 531 individuals were recorded for at least 1 day in the EGB. Among them, 220 345 (33.3%) were prescribed at least once topical glucocorticoid. The prevalence of topical glucocorticoid prescription increased regularly from 2011 (11.7%) to 2015 (12.5%). A total of 922 026 tubes of topical glucocorticoids were dispensed, mainly high-potency glucocorticoids, and were mainly prescribed by general practitioners (73.1%). A total of 1713 (0.8%) patients were prescribed at least 24 tubes over a calendar year. These patients were more frequently men (P < 0.001) and older (P < 0.001) than the overall population of patients prescribed topical glucocorticoids. The 124 844 tubes prescribed to these patients had stronger potency than those prescribed to the overall population (P < 0.001) and were mostly prescribed by general practitioners (68.1%). The reasons for prescription were available for only 371 patients (21.7%) and were mainly psoriasis, auto-immune bullous dermatoses and eczema. CONCLUSION: About 12% of the French general population is prescribed topical glucocorticoids at least once each year. Most prescriptions are issued by general practitioners, dermatologists being the prescribers in less than one-quarter of cases.

Dermatological emergencies: evolution from 2008 to 2014 and perspectives.

BACKGROUND: Our dermatological department includes a dermatological emergency unit (DEU) whose activity has grown in recent years. OBJECTIVES: An audit to characterize the activity of our DEU and its evolution in terms of medical demographics of the area. METHODS: We collected the following data from administrative services: number of patients consulting each year in the DEU and in the general emergency unit (GEU) of our hospital between 2008 and 2014; daily and seasonal activity of the DEU; occurrence of a second event in the department and proportion of patients from the DEU who were hospitalized and why. From the medical charts of a random sample of patients consulting in the first 15 days of January and August 2014, we studied the epidemiological profile, time to consultation and diagnoses. Data related to medical demographics (number of general practitioners and dermatologists) between 2007 and 2014 and projections were obtained. RESULTS: The activity in the DEU increased by 67% between 2008 and 2014 but remained stable in the GEU over the same period. The activity was higher on Mondays and in the summer (+30%). More than 15% of the patients were seen a second time in outpatient consultation; 1.2% were hospitalized. Infectious dermatosis was the main reason for consultation; seasonal-disease consultations were more frequent in the summer. Less than 40% of patients consulted in the first week after disease onset. Medical demographics continually decreased since 2007 in Paris and suburbs and will continue to decrease in the next years. CONCLUSION: The increasing activity of our DEU parallels the decrease in medical demographics in Paris. The proportion of patients hospitalized was low, in part due to specific healthcare networks implemented for some life-threatening dermatoses independent of the DEU. A better coordination between hospital and private practitioners for managing dermatologic emergencies, taking into account the decrease in medical demographics, is warranted.

[What's new in internal medicine?] / Quoi de neuf en médecine interne ?

As it is practiced in France, internal medicine meets the Anglo-Saxon definition of the specialty, ie doctors "equipped to handle the broad and comprehensive spectrum of illnesses that affect adults, and are recognized as experts in diagnosis, in treatment of chronic illness, and in health promotion and disease prevention - they are not limited to one type of medical problem or organ system". This 2017 "What's new in internal medicine" will consist of 2 parts, a first part on significant publications in the field of systemic and autoimmune diseases and a second part on more diverse publications (HIV, cancer, pregnancy, well-being...) important for medicine in general and its different specialties.

[Amiodarone-induced immune complex cutaneous vasculitis]. / Vascularite cutanée induite par l'amiodarone.

BACKGROUND: A wide variety of drugs can cause cutaneous vasculitis. Herein we report a case of immune complex vasculitis induced by amiodarone. PATIENTS AND METHODS: A 57-year-old patient reported a recent history of pruritus associated with large erythematous, inflammatory, necrotic plaques localized on the lower limbs and back. These cutaneous lesions had appeared less than 2 months after initiation of amiodarone for supra-ventricular arrhythmia. Histological and direct immunofluorescence examinations of a skin biopsy sample revealed vasculitis with the presence of IgM and C3 immune complexes in vessels. The remaining laboratory tests were unremarkable (in particular, cryoglobulin and autoantibody tests were negative). The patient himself attributed his symptoms to the recent administration of amiodarone and spontaneously stopped the drug without medical advice. No other therapy was prescribed. Following drug withdrawal, the lesions that had been present for more than 4 months completely disappeared. No recurrence occurred after follow-up of over 6 months. The diagnosis of amiodarone-induced vasculitis was retained. DISCUSSION: Fewer than 10 cases of amiodarone-induced vasculitis have been reported in the medical literature. It is not known whether this entity is rare, under-diagnosed or under-reported.

[Paroxysmal finger haematoma (Achenbach syndrome)]. / Hématomes digitaux spontanés paroxystiques (syndrome d'Achenbach).

BACKGROUND: Paroxysmal finger haematoma (also known as "Achenbach syndrome") is a benign condition resulting in the sudden appearance of bruising on one or more fingers, either spontaneously or after minimal trauma, and resolving without treatment. To date, less than 40 cases have been reported. PATIENTS AND METHODS: We report two cases of women aged over 50 years presenting for sudden onset of digital haematomas occurring spontaneously without any prior trauma. Laboratory and radiological tests appeared to be normal for both patients. History-taking and clinical and laboratory data pointed towards a diagnosis of spontaneous paroxysmal finger haematoma. Each episode resolved spontaneously but, as is generally seen, recurrences occurred during follow-up. DISCUSSION: In the absence of known aetiologies and/or treatments for spontaneous paroxysmal finger haematomas, a knowledge of this rare condition can at least help doctors reassure their patients by diagnosing their condition and pointing out the benign nature thereof. It also helps avoid costly and unwarranted additional investigations.

[Purpura in a young woman with hyperthyroidism]. / Purpura chez une jeune femme hyperthyroïdienne.

INTRODUCTION: Propylthiouracil (PTU) is a synthetic antithyroid drug that can induce ANCA-associated vasculitis. OBSERVATION: A 27-year-old woman diagnosed with Graves' disease was on PTU for the past 10 years. She developed purpuric lesions of the legs and on the tip of the nose diagnosed as vasculitis. ANCAs were positive, with anti-MPO and anti-PR3 on blood ELISA. After discontinuation of PTU, she was able to fully recover. CONCLUSION: All synthetic antithyroid drugs can induce ANCA-associated vasculitis, more often PTU. In most cases, antibodies are directed against MPO. Dual anti-MPO and anti-PR3 positivity is possible, but rare. The mechanism could be through an accumulation of PTU in neutrophils, altering the structure of MPO and making it immunogenic. PTU can also induce ANCA-free or lupus vasculitis, maculopapular rashes or urticaria. Many other drugs can induce ANCA-associated vasculitis.

Impact of glucocorticoid-induced adverse events on adherence in patients receiving long-term systemic glucocorticoid therapy.

BACKGROUND: Factors influencing adherence to long-term (i.e. ≥ 3 months) systemic glucocorticoid therapy are poorly understood. OBJECTIVE: To evaluate the relationship between glucocorticoid-induced adverse events and therapeutic adherence in patients on long-term glucocorticoid treatment. METHODS: A cross-sectional survey was conducted in three departments of dermatology/internal medicine between April and September 2008. Patients were asked to provide data regarding symptoms they attributed to glucocorticoids, and adherence to treatment was measured using the four-item Morisky-Green adherence scale. Logistic regression analyses were used to assess the association between reported adverse events and adherence to glucocorticoids. RESULTS: A total of 255 questionnaires were completed and analysed [women 78%; median age 48 years (interquartile range (IQR) 34-65); connective tissue diseases 59%; median duration of treatment 24 months (IQR 8-72); median daily dose 10 mg (IQR 6-20)]. Among these 255 patients, 199 (78%) reported themselves as 'good adherents' and 56 (22%) as 'poor adherents' to treatment. Poor adherence was associated with younger age [odds ratio (OR) 0·97, 95% confidence interval (CI) 0·95-0·99, per increasing year; P < 0·01], presence of glucocorticoid-induced epigastralgia (OR 4·02, 95% CI 2·00-8·09; P < 0·01) and presence of glucocorticoid-induced morphological changes (OR 2·49, 95% CI 1·19-5·21; P = 0·02). Moreover, patients with poor adherence were likely to report concomitantly poor adherence to dietary advice associated with glucocorticoid therapy (OR 2·44, 95% CI 1·12-5·26; P = 0·02). CONCLUSIONS: As with other chronic therapies, the presence of glucocorticoid-induced adverse events is associated with an altered self-reported adherence to glucocorticoids. Patients who report epigastric pain or morphological changes that they associate with glucocorticoid therapy are particularly at risk of poor adherence. Adherence to dietary advice associated with glucocorticoid therapy may be an indirect measure of treatment adherence.

Frequency, clinical features and prognosis of cutaneous manifestations in adult patients with reactive haemophagocytic syndrome.

BACKGROUND: Cutaneous involvement has been reported in 30-40% of children with the familial form of haemophagocytic syndrome. However, few studies have focused on cutaneous manifestations in patients with reactive haemophagocytic syndrome (RHS). OBJECTIVES: To describe the frequency, clinical features and prognosis of skin involvement in adult patients with RHS. METHODS: We conducted a retrospective study in a French university-based tertiary centre. The medical records of all adult patients with a suspected or confirmed diagnosis of RHS during a 2-year period were reviewed. Demographic, clinical, biological and histological data of patients were compared using nonparametric tests. RESULTS: The medical charts of 151 patients were reviewed, 69 of whom had a definite diagnosis of RHS (35% women; mean +/- SD age 49 +/- 17 years). The aetiology of RHS was mainly B-cell or T-cell lymphoma (n = 33) or herpesvirus infection (n = 19). Cutaneous manifestations were observed in 32 (46%) patients and were of three types: (i) specific to the underlying malignancy (Kaposi sarcoma n = 8, cutaneous lymphoma n = 4), (ii) reflecting the biological consequences of RHS (thrombopenic purpura n = 10, conjunctival jaundice n = 7), and (iii) a generalized, transient, nonpruriginous maculopapular rash (n = 18). None presented with erythroderma, or with eczematiform, ichthyosiform, psoriasiform or bullous lesions. One patient had cytophagic histiocytic panniculitis. Histological features of maculopapular rash biopsies were usually nonspecific. The rate of in-hospital death was not significantly associated with cutaneous involvement. CONCLUSIONS: A generalized, nonpruriginous, transient, maculopapular rash is frequently observed in patients with RHS. Although nonspecific, awareness of this cutaneous involvement may assist physicians in the initial diagnosis of RHS.

Factors associated with tuberculosis-associated haemophagocytic syndrome: a multicentre case-control study.

SETTING: Tuberculosis (TB) is a potential trigger of haemophagocytic syndrome (HS) but little is known about the features of TB-associated HS.OBJECTIVE: To assess the risk factors associated with HS in patients with TB.DESIGN: We performed a multicentre case-control study assessing the medical records of adult patients diagnosed with proven TB with (TB/HS+) or without (TB/HS-) associated HS.RESULTS: Twenty-one patients with TB/HS+ (24% women, median age, 37 years [IQR 30-48]) were included in the study. Eleven patients (52%) were infected with human immunodeficiency virus and seven patients (33%) were immunocompromised due to other reasons. TB was disseminated in 17 patients (81%). Compared with 50 control TB patients (TB/HS-), patients with TB/HS+ were more likely to be immunocompromised (86% vs. 18%; P < 0.001) and to present with disseminated TB (80% vs. 12%; P < 0.001). The outcome was poorer in patients with TB/HS+, with a higher admission rate to intensive care (71% vs. 0%; P < 0.001) and a higher risk of death (38% vs. 7%; P = 0.005).CONCLUSION: TB/HS+ occurred more likely in immunocompromised patients and severely impaired the prognosis of TB. Further studies are needed to devise therapeutic strategies for patients with TB/HS+.

[General practitioners' perception of the impact of corticosteroid-induced adverse events]. / Perception par les médecins généralistes de la gêne induite par les effets indésirables d'une corticothérapie systémique prolongée.

BACKGROUND: General practitioners' perception of the discomfort their patients experience because of corticosteroid-induced adverse events is unknown. METHODS: An observational epidemiological study was conducted in September 2007. Eight hundred and sixty general practitioners belonging to the réseau Sentinelles were asked to complete an electronical questionnaire. The questionnaire aimed to assess their perception of discomfort induced by adverse events induced by a long-term (i.e.,>or=3 months) corticosteroid therapy among their patients. Results were compared with the declaration made by 115 long-term corticosteroid treated patients followed in an internal medicine department. RESULTS: Two hundred and ninety-three general practitioners responded to the questionnaire (response rate: 34%). They were predominantly male (87%). Forty-eight percent of them reported 400 to 600 monthly visits. The mean length of corticosteroid therapy for patients was 44+/-38 months and the mean daily dosage was 15+/-14 mg. They suffered mainly from lupus erythematosus (33%) or giant cell arteritis (15%). The adverse events considered to be the most disturbing by patients were lipodystrophy (25%), followed by weight gain (18%) and neuropsychiatric complaints (16%). Physicians widely overestimated the discomfort caused by weight gain cited as the most disturbing adverse event by 59% of them and underestimated that induced by mood disorders cited as the most disturbing by only 3% of them. CONCLUSION: The discomfort caused by corticosteroid-induced neuropsychiatric adverse events are underestimated by general practitioners.

[Short-term effect of dietary-sodium intake on arterial blood pressure of patients treated with systemic corticosteroids: a prospective, randomised, crossover study]. / Effet à court terme des apports sodés sur la pression artérielle des patients recevant une corticothérapie systémique: étude prospective, randomisée, croisée.

INTRODUCTION: It is unknown if the level of dietary-sodium intake influences blood pressure in patients receiving systemic corticosteroids. METHODS: Randomized, single centre, crossover trial involving patients starting systemic corticosteroid therapy and having initial blood pressure less or equals to 159/99 mm Hg. The first period of sodium regimen was randomized (<3 g/j versus >6 g/j) and each period of sodium regimen lasted 3 weeks. No washout period was performed. Blood pressure was recorded for each patient at inclusion and after 3 weeks and 6 weeks. Moreover, all patients were asked to record on a standardized questionnaire everything they ate during 1 week of each period regimen. Questionnaires were analysed by a dietician for mean daily energy and sodium intakes during each period. Mixed models were used to estimate the relationship between sodium intake and blood pressure variations. RESULTS: Between June 2006 and June 2008, 49 patients were randomized, 24 in group 1 (first period regimen=salt<3g/day; women: 63%; mean age: 56+/-21 years; baseline prednisone dosage: 54+/-19 mg/day) and 25 in group 2 (first period regimen=salt>6g/day; women: 56%; mean age: 60+/-19 years; baseline prednisone dosage: 56+/-16 mg/day). Mean daily salt intakes were 2.5+/-1.8 and 9.3+/-1.9 g/day during the first period and 7.8+/-3.2 and 3.8+/-2.9 g/day during the second period, respectively for group 1 and group 2. Blood pressure variations were not significantly associated with daily salt intakes or with randomisation group. No order effect was evidenced. By comparison with baseline, systolic blood pressure increased by greater than 20 mm Hg at week 6 in five patients (2 in group 1 and 3 in group 2). CONCLUSION: At short-term, sodium intake does not seem to influence blood pressure variations in patients starting systemic corticosteroids therapy.