E. Sbidian

Methotrexate in psoriasis: a systematic review of treatment modalities, incidence, risk factors and monitoring of liver toxicity.

Background/Aim  To define practical use and to specify the ideal method for monitoring the liver toxicity of MTX in the management of psoriasis.

Oral cyclosporin in psoriasis: a systematic review on treatment modalities, risk of kidney toxicity and evidence for use in non-plaque psoriasis.

Background  Although cyclosporin (CyA) has been in use in psoriasis for more than 20 years, there is still controversy regarding treatment strategy, monitoring of kidney function and utility in non‐plaque psoriasis.

Mortality associated with neurofibromatosis 1: a cohort study of 1895 patients in 1980-2006 in France.

BackgroundNeurofibromatosis 1 (NF1), a common autosomal dominant disorder, was shown in one study to be associated with a 15-year decrease in life expectancy. However, data on mortality in NF1 are limited. Our aim was to evaluate mortality in a large retrospective cohort of NF1 patients seen in France between 1980 and 2006.MethodsConsecutive NF1 patients referred to the National French Referral Center for Neurofibromatoses were included. The standardized mortality ratio (SMR) with its 95% confidence interval (CI) was calculated as the ratio of observed over expected numbers of deaths. We studied factors associated with death and causes of death.ResultsBetween 1980 and 2006, 1895 NF1 patients were seen. Median follow-up was 6.8 years (range, 0.4-20.6). Vital status was available for 1226 (65%) patients, of whom 1159 (94.5%) survived and 67 (5.5%) died. Overall mortality was significantly increased in the NF1 cohort (SMR, 2.02; CI, 1.6-2.6; P < 10-4). The excess mortality occurred among patients aged 10 to 20 years (SMR, 5.2; CI, 2.6-9.3; P < 10-4) and 20 to 40 years (SMR, 4.1; 2.8-5.8; P < 10-4). Significant excess mortality was found in both males and females. In the 10-20 year age group, females had a significant increase in mortality compared to males (SMR, 12.6; CI, 5.7-23.9; and SMR, 1.8; CI, 0.2-6.4; respectively). The cause of death was available for 58 (86.6%) patients; malignant nerve sheath tumor was the main cause of death (60%).ConclusionsWe found significantly increased SMRs indicating excess mortality in NF1 patients compared to the general population. The definitive diagnosis of NF1 in all patients is a strength of our study, and the high rate of death related to malignant transformation is consistent with previous work. The retrospective design and hospital-based recruitment are limitations of our study. Mortality was significantly increased in NF1 patients aged 10 to 40 years and tended to be higher in females than in males.

Evidence-based recommendations on conventional systemic treatments in psoriasis: systematic review and expert opinion of a panel of dermatologists.

Background  There is a high level of heterogeneity regarding the practical use of conventional systemic treatment in psoriasis.

Impact of STROBE Statement Publication on Quality of Observational Study Reporting: Interrupted Time Series versus Before-After Analysis

Background In uncontrolled before-after studies, CONSORT was shown to improve the reporting of randomised trials. Before-after studies ignore underlying secular trends and may overestimate the impact of interventions. Our aim was to assess the impact of the 2007 STROBE statement publication on the quality of observational study reporting, using both uncontrolled before-after analyses and interrupted time series. Methods For this quasi-experimental study, original articles reporting cohort, case-control, and cross-sectional studies published between 2004 and 2010 in the four dermatological journals having the highest 5-year impact factors (≥4) were selected. We compared the proportions of STROBE items (STROBE score) adequately reported in each article during three periods, two pre STROBE period (2004–2005 and 2006–2007) and one post STROBE period (2008–2010). Segmented regression analysis of interrupted time series was also performed. Results Of the 456 included articles, 187 (41%) reported cohort studies, 166 (36.4%) cross-sectional studies, and 103 (22.6%) case-control studies. The median STROBE score was 57% (range, 18%–98%). Before-after analysis evidenced significant STROBE score increases between the two pre-STROBE periods and between the earliest pre-STROBE period and the post-STROBE period (median score2004–05 48% versus median score2008–10 58%, p<0.001) but not between the immediate pre-STROBE period and the post-STROBE period (median score2006–07 58% versus median score2008–10 58%, p = 0.42). In the pre STROBE period, the six-monthly mean STROBE score increased significantly, by 1.19% per six-month period (absolute increase 95%CI, 0.26% to 2.11%, p = 0.016). By segmented analysis, no significant changes in STROBE score trends occurred (−0.40%; 95%CI, −2.20 to 1.41; p = 0.64) in the post STROBE statement publication. Interpretation The quality of reports increased over time but was not affected by STROBE. Our findings raise concerns about the relevance of uncontrolled before-after analysis for estimating the impact of guidelines.

Efficacy and safety of oral retinoids in different psoriasis subtypes: a systematic literature review.

Background  There is limited evidence regarding the efficacy and safety of retinoids in different psoriasis subtypes.

NF-1Score: A Prediction Score for Internal Neurofibromas in Neurofibromatosis-1

NF-1 is associated with a 15-year decrease in life expectancy. Internal neurofibromas are associated with increased morbidity and mortality through malignant transformation and compression of neighboring organs. Our purpose was to develop and to validate a clinical score for predicting internal neurofibromas in adults. The development sample comprised 208 patients and the validation sample 191 patients. The score was developed using logistic regression. Discrimination and calibration of the model were evaluated. Four variables were independently associated with internal neurofibromas: at least two subcutaneous neurofibromas (odds ratio (OR)=4.7, [2.1-10.5]), age < or =30 years (OR=3.1, [1.4-6.8]), absence of cutaneous neurofibromas (OR=2.6, [0.9-7.5]), and fewer than six café-au-lait spots (OR=2.0 [0.9-4.6]). The score computed by linear combination of the rounded coefficients of these four variables ranged from 0 to 40 (mean, 12.8+/-10.8). The probability of internal neurofibromas was computed as exp (-2.93+0.11Score)/exp (1+(-2.93+0.11Score)). Probabilities agreed well with the observed frequencies indicating good calibration, and discrimination was adequate (AUC-ROC, 0.75) in both data sets. The presence of internal neurofibromas can be accurately predicted using a simple clinical score. Further work will establish the score threshold that identifies patients at high risk for complications.

Kawasaki disease in adults: Observations in France and literature review.

OBJECTIVE Kawasaki disease (KD) is a vasculitis that mostly occurs in young children and rarely in adults. We analyzed the characteristics of adult-onset KD (AKD) in France. METHODS We collected retrospective and prospective data for patients with a diagnosis of KD occurring after the age of 18 years. Cases were obtained via various French medical networks and identified from the international literature. RESULTS We included 43 patients of AKD at 26 institution from 1992 to 2015, with mean (SD) age 30 (11) years (range 18-68) and sex ratio (M/F) 1.2; 34 patients met the American Heart Association criteria and 9 were incomplete AKD. The median time to diagnosis was 13 days (interquartile range 8-21). The main symptoms were fever (100%), exanthema (98%), changes in the extremities (91%), conjunctivitis (77%), oral cavity changes (89%), cervical adenitis (55%) and cardiac abnormalities (45%). Overall, 35% of patients showed large-vessel vasculitis: coronary vasculitis (26%) and coronary aneurysm (19%). Treatment was mostly intravenous immunoglobulins (79%) and aspirin (81%). Four patients showed myocardial infarction due to coronary vasculitis, but none were treated with IVIg because of late diagnosis. After a median follow-up of 5 months (range 1-117), persistent aneurysm was noted in 9% of cases. Damage was significantly lower with early treatment than late or no treatment (p=0.01). CONCLUSION Given the high frequency of cardiac involvement and complications in this series of AKD, diagnosis and treatment should not be delayed, and early IVIg treatment seems to improve the outcome.

Acute generalized exanthematous pustulosis: a retrospective audit of practice between 1994 and 2011 at a single centre

tosensitive rash that did not warrant vemurafenib withdrawal. This highlights the importance of careful patient monitoring, even though most vemurafenib-induced rashes resolve spontaneously. We chose to switch to dabrafenib because no crossreaction with vemurafenib had previously been described. Also, although this BRAF inhibitor has been used more recently than vemurafenib, cutaneous side-effects appear less frequent and less severe. Indeed, to our knowledge, no cases of TEN or DRESS have hitherto been reported with dabrafenib. To conclude, BRAF inhibitor molecules appear to have different skin toxicity profiles. When permanent discontinuation of vemurafenib is required after TEN, drug switching to dabrafenib appears to be a useful alternative treatment option.

At-Risk Phenotype of Neurofibromatose-1 Patients: A Multicentre Case-Control Study

ObjectivesTo assess associations between subcutaneous neurofibromas (SC-NFs) and internal neurofibromas in patients with neurofibromatosis type 1 (NF-1) and to determine whether the association between SC-NFs and peripheral neuropathy was ascribable to internal neurofibromas.Patients and methodsProspective multicentre case-control study. Between 2005 and 2008, 110 NF-1 adults having two or more SC-NFs were individually matched for age, sex and hospital with 110 controls who had no SC-NF. Patients underwent standardized MRI of the spinal cord, nerve roots and sciatic nerves and an electrophysiological study. Analyses used adjusted multinomial logistic regression (ORa) to estimate the risk of the presence of internal neurofibromas or peripheral neuropathies associated with patients presented 2 to 9 SC-NFs, at least 10 SC-NFs as compared to patients without any (referential category).ResultsCases had a mean age of 41 (± 13) years; 85 (80%) had two to nine SC-NFs and 21 (19%) at least ten SC-NFs. SC-NFs were more strongly associated with internal neurofibromas in patients with ten or more SC-NFs than in patients with fewer NF-SCs (e.g., sciatic nerve, aOR = 29.1 [8.5 to 100] vs. 4.3 [2.1 to 9.0]). The association with SC-NFs was stronger for diffuse, intradural, and > 3 cm internal neurofibromas than with other internal neurofibromas. Axonal neuropathy with slowed conduction velocities (SCV) was more strongly associated with having at least ten SC-NFs (aOR = 29.9, 5.5 to 162.3) than with having fewer SC-NFs (aOR = 4.4, 0.9 to 22.0). Bivariate analyses showed that the association between axonal neuropathy with SCV and sciatic neurofibromas was mediated by the association between SC-NFs and sciatic neurofibromas.ConclusionThe at-risk phenotype of NF-1 patients (i.e. NF-1 patients with SC-NFs) is ascribable to associations linking SC-NFs to internal neurofibromas at risk for malignant transformation and to axonal neuropathies with slowed conduction velocities. Axonal neuropathies with SCV are particularly common in patients with at least ten SC-NFs.Registration detailsORPHA86301