[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.

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+.

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.

[Association between prescription of long-term systemic glucocorticoid therapy associated measures and prescriber's medical speciality]. / Prescription des mesures adjuvantes aux corticothérapies systémiques prolongées en fonction de la spécialité du prescripteur.

INTRODUCTION: In order to prevent some glucocorticoid-induced adverse events, adjuvant measures are often associated with prescription of long-term (≥3 months) systemic glucocorticoid therapy. The main objective of this study was to study the association between prescription of these measures and the medical specialty of the prescriber. METHODS: A cross-sectional study was conducted through the website www.cortisone-info.fr. Patients visiting this website and receiving long-term glucocorticoid therapy were asked to fill a questionnaire asking them, among other things, the specialty of the physician who initiated glucocorticoids and the adjuvant measures they were prescribed at treatment initiation. RESULTS: In all, 1383 patients answered the questionnaire and 843 (61%) questionnaires were analyzed (women: 70.6%, median age: 59 [44-70] years, current glucocorticoid dosage: 12.5 [5-30] mg/day, maximum dose: 42 [20-60] mg/day). The main prescribers were rheumatologists (30.5%) and internists (17.3%). Most adjuvant measures were heterogeneously prescribed and depended largely on the specialty of the prescribing physician. Some probably unnecessary measures in most patients (potassium supplementation, prevention of peptic ulcer, low-sodium diet) were frequently prescribed while other consensual measures (prevention of osteoporosis, vaccinations) were prescribed to less than half of patients. In multivariable analyses, most of the studied measures were more frequently prescribed by internists than by colleagues of other specialties. Pneumologists more often vaccinated patients against influenza or pneumococcus than their colleagues. CONCLUSION: Adjuvant measures to long-term glucocorticoid therapy are heterogeneously prescribed. The prescriptions depend largely on the medical specialty of the prescribing physician.

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.

[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.

Effects of chronic exposure of hydroxychloroquine/chloroquine on the risk of cancer, metastasis, and death: a population-based cohort study on patients with connective tissue diseases.

BACKGROUND: Hydroxychloroquine and chloroquine may reduce the risk of cancer as they inhibit autophagy, in particular, in people with connective tissue diseases. METHODS: The hazard ratios of cancers, metastases, and death were assessed in adults with connective tissue diseases prescribed hydroxychloroquine/chloroquine for at least 1 year in comparison with unexposed individuals with the same underlying conditions. A competing risk survival regression analysis was performed. Data were extracted from the Health Improvement Network UK primary care database. RESULTS: Eight thousand nine hundred and ninety-nine individuals exposed to hydroxychloroquine (98.6%) or chloroquine (1.4%) and 24,118 unexposed individuals were included in the study (median age: 56 [45-66] years, women: 76.8%). When compared to the unexposed group, individuals exposed to hydroxychloroquine/chloroquine were not at lower risk of non-skin cancers (adjusted sub-distribution hazard ratio [sHR]: 1.04 [0.92-1.18], p=0.54), hematological malignancies (adjusted sHR: 1.00 [0.73-1.38], p=0.99), or skin cancers (adjusted sHR: 0.92 [0.78-1.07], p=0.26). The risk of metastasis was not significantly different between the two groups. However, it was significantly lower during the exposure period when compared with the unexposed (adjusted sHR: 0.64 [0.44-0.95] for the overall population and 0.61 [0.38-1.00] for those diagnosed with incident cancers). The risk of death was also significantly lower in those exposed to hydroxychloroquine/chloroquine (adjusted HR: 0.90 [0.81-1.00] in the overall population and 0.78 [0.64-0.96] in those diagnosed with incident cancer). CONCLUSION: Individuals on long-term exposure to hydroxychloroquine/chloroquine are not at lower risk of cancer. However, hydroxychloroquine/chloroquine may lower the risk of metastatic cancer and death.

[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.

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.

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.

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.

[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.

Diversity and combinations of infectious agents in 38 adults with an infection-triggered reactive haemophagocytic syndrome: a multicenter study.

Reactive haemophagocytic syndrome (HS) is a rare condition that occurs in patients with infections, haematological malignancies or autoimmune diseases. Although various microorganisms are thought to trigger HS, most of the literature data on this topic have been gathered in single-centre case series. Here, we sought to characterize infectious triggers in a large, multicentre cohort of patients with HS. Patients were included in the present study if HS was solely due to one or more infections. Detailed microbiological data were recorded. Of the 162 patients with HS in the cohort, 40 (25%) had at least one infection and 38 of the latter (including 14 women, 36.8%) were included. The median age was 46 years. Seven patients were presumed to be immunocompetent (18.4%), whereas 19 patients (50%) were infected with human immunodeficiency virus and 12 patients (31.6%) were immunocompromised for other reasons. Twenty-seven patients (71.1%) had a single infection, whereas six (15.8%) and five (13.1%) patients had, respectively, two and three concomitant infections. We observed pyogenic bacterial infections (n = 7), tuberculosis (n = 10), non-tuberculous mycobacteriosis (n = 3), viral infections (n = 17: 11 cytomegalovirus, three Epstein-Barr virus, two human herpesvirus 8, one herpes simplex virus 2), parasitic infections (n = 8: four disseminated toxoplasmosis, one leishmaniasis, three malaria), fungal infections (n = 5: four pulmonary pneumocystosis and one candidaemia). Eighteen patients (47.4%) received corticosteroids and/or etoposide. Twelve patients died (31.6%). All multiple infections and all deaths occurred in immunocompromised patients. When compared with patients suffering from malignancy-associated HS, patients with infection-triggered HS were younger and more likely to be immunocompromised, and had a better outcome.

[Cardiovascular pathologies and referrals for hospitalization by general practitioners: factors influencing the choice of a private or public hospital]. / Pathologies cardiovasculaires et recours à l'hospitalisation par le médecin généraliste : facteurs influençant le choix du secteur d'hospitalisation.

OBJECTIVES: When a hospitalisation is required in France, the general practitioner has the choice between public or private hospitals. The reasons for this choice are poorly known. METHODS: All the cases of hospitalisation requirement reported between 1997 and 2001 by the general practitioners involved in the Réseau Sentinelles(®) were included in this study. The cardiovascular reasons were extracted from all these declarations. Factors influencing the general practitioners' choice between public and private sector were assessed by using logistic regression. RESULTS: During the study period, 45,960 cases of hospitalisation requirement were reported. Amongst these cases, 4475 (10.8%) were made for clearly defined cardivoascular diseases (cardiac failure 38.0%, coronary heart disease 24.7%, atrial fibrillation 11.7%, pulmonary embolism 8.4%, hypertension 3.6%, pericarditis 1.6%, cardiovascular check-up 1.5%). Referrals to private sector depended on the reason for hospitalisation, cardiovascular check-up being the reasons the most referred to a private institution (33.8% of patients) and cardiac insufficiency the less referred to private institution (17.2% of patients). Referral to private sector was also associated with physician (patient's usual general practitioner) and consultation (consultation outside of a context of emergency) characteristics. CONCLUSION: Whether patients suffering from cardiovascular diseases are sent to a public or private sector is not completely haphazard. Further analyses are needed in the context of new French health policies.