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The patched (PTCH) mutation rate in nevoid basal cell carcinoma syndrome (NBCCS) reported in various studies ranges from 40 to 80%. However, few studies have investigated the role of PTCH in clinical conditions suggesting an inherited predisposition to basal cell carcinoma (BCC), although it has been suggested that PTCH polymorphisms could predispose to multiple BCC (MBCC). In this study, we therefore performed an exhaustive analysis of PTCH (mutations detection and deletion analysis) in 17 patients with the full complement of criteria for NBCCS (14 sporadic and three familial cases), and in 48 patients suspected of having a genetic predisposition to BCC (MBCC and/or age at diagnosis < or =40 years and/or familial BCC). Eleven new germline alterations of the PTCH gene were characterised in 12 out of 17 patients harbouring the full complement of criteria for the syndrome (70%). These were frameshift mutations in five patients, nonsense mutations in five patients, a small inframe deletion in one patient, and a large germline deletion in another patient. Only one missense mutation (G774R) was found, and this was in a patient affected with MBCC, but without any other NBCCS criterion. We therefore suggest that patients harbouring the full complement of NBCCS criteria should as a priority be screened for PTCH mutations by sequencing, followed by a deletion analysis if no mutation is detected. In other clinical situations that suggest genetic predisposition to BCC, germline mutations of PTCH are not common. [ABSTRACT FROM AUTHOR]

Summary: Psoriasis is a common chronic inflammatory skin disease, affecting about 3% of the general population and approximately 2.5 million people in France, where this study took place. The genital area may be affected, however prevalence is poorly understood, meaning we do not know exactly how commonly this occurs. While it affects quality of life, genital psoriasis is under‐recognized, probably due to the reluctance of patients to discuss genital involvement and sexual quality of life. The aims of this study, called the GENIPSO study, were to determine the prevalence of genital psoriasis, its clinical characteristics (its symptoms), whether it is associated with a particular type of psoriasis, and its impact on quality of life. The study included 776 adults seeing their doctor for psoriasis between November 2016 and March 2017. Among them, 336 (43.2%) had genital psoriasis. All these patients were aware that they had psoriasis on their genitals (genital lesions) but only 135 (40%) had already had a genital medical examination. Genital lesions were associated with (linked to) male gender, more severe psoriasis, first developing psoriasis when aged over 20 years, psoriasis of the skin folds, psoriasis on the scalp, nail and external auditory (ear) canal, but they were not associated with obesity or psoriatic arthritis. Itching was the main symptom. Genital psoriasis was associated with reduced quality of life and sexual health. The study found that genital psoriasis has a high prevalence in patients seeing their doctors about their psoriasis generally, it affects quality of life and should be better taken into account by dermatologists for the best possible care for patients. Linked Article: Larsabal et al. Br J Dermatol 2019; 180:647–656 [ABSTRACT FROM AUTHOR]

Syphilis had almost disappeared in our country in the years 1995-1997 as a consequence of safer sexual behaviour. Since 1998, new diagnoses of early infectious syphilis (EIS) have consistently increased. In January 2000, a prospective national survey was initiated, collecting all cases of EIS. From January 2000 to September 2002, 468 cases have been reported (37 in 2000, 194 in 2001, 237 in 2002, provisional data). Most of the patients are men (97%) and 87% of them are homosexual-bisexual males (MSMs). 54% are HIV-seropositive (and 61% of the MSMs), most of them being aware of their serological status (85%) and receiving highly active antiretroviral therapy (57%). A self administered questionnaire points out that half of the cases of EIS could have been contracted by oral sex only. The syphilis epidemic reflects the relapse into unsafe sexual behaviour, as attested by two recent studies in gay venues. A national project has been implemented in May 2002 with educational programmes for practitioners, prevention actions in gay clubs, and free-anonymous serological tests for syphilis (STS) in Free and Anonymous HIV-testing Centers (FATC). From May to September 2002, 23 756 STS have been collected in FATC and 155 EIS were detected, mostly latent forms in MSMs (prevalence 2.4% positive STS in MSMs). [ABSTRACT FROM AUTHOR]

Abstract: Background. – Sexually transmitted infections (STI) in France are reported on a voluntary basis through several sentinel surveillance systems. Methods. – To monitor STI, sentinel laboratory- or clinician -based surveillance systems were set up by the Institut de Veille Sanitaire: gonorrhea surveillance (Renago) in 1986, Chlamydia infections surveillance (Renachla) in 1989, and more recently, syphilis surveillance in 2000 and rectal lymphogranuloma venereum (LGV) in 2004. Results. – From 2000 to 2003, 1,089 syphilis infections were reported. Most of the cases were diagnosed in men having sex with men (MSM) and were mainly reported by STI clinics located in the Paris area. From 1997 to 2000, an increase of gonorrhea was observed each year. After two years of stable trend, the prevalence of gonorrhea increased again in 2003. From 2002 to 2004, 123 LGV cases were diagnosed in France and were observed only in MSM. Since 2001, Chlamydia infections have steadily increased, particularly in women. Comments. – Because STI surveillance is based on a voluntary basis, the number of reported cases is probably lower than the number of STI diagnosed in France. However, the data provided by the different surveillance systems reveals that STI have been increasing in France since 1997. Moreover, the resurgence of syphilis in 2000 and the emergence of rectal LGV in 2004 indicate that these STI occur mainly in MSM. Trends on incidence and patients characteristics observed in France are similar to those of several Europeans countries. European Public Health interventions are becoming necessary to prevent and control STI. [Copyright &y& Elsevier]

BackgroundSyphilis in blood donors (BD) has increased in many countries.AimWe aimed to describe trends in syphilis seroposivity in BD in France, to identify risk factors and assess if a non-treponemic test (NTT) could define BD having recovered from syphilis for more than 1 year.MethodsThe analysis covered the period 2007 to 2022 and 45,875,939 donations. Of the 474 BD syphilis-positive in 2022, 429 underwent additional investigations with an NTT. History of syphilis was obtained at the post-donation interview or based on serology results for repeat donors.ResultsUntil 2021, positivity rates remained stable (mean: 1.18/10,000 donations, range: 1.01-1.38). An increased rate was observed in 2022 (1.74/10,000; p = 0.02). Over the whole study period, prevalence was 2.2 times higher in male than in female BD (4.1 times higher in 2022). The proportion of males with an identified risk factor who have sex with men increased from 16.7% in 2007 to 64.9% in 2022. Based on NTT, 79 (18%) of the donors who were seropositive in 2022 were classified as having been infected in the previous year. History of syphilis was available for 30 of them. All had an infection within the previous 3 years. Among seven donors with a syphilis < 12 months before testing, one had an NTT titre ≥ 8, three a titre between 1 and 4, three were negative.ConclusionSyphilis seropositivity increased considerably in BDs in 2022, mostly in males, notably MSM. Available data did not allow appropriate evaluation of the NTT to distinguish recent from past infection.

Background: Intravenous benzylpenicillin is the gold-standard treatment for neurosyphilis, but it requires prolonged hospitalisation. Ceftriaxone is a possible alternative treatment, the effectiveness of which remains unclear. We aimed to assess the effectiveness of ceftriaxone compared with benzylpenicillin in the treatment of neurosyphilis., Methods: We did a retrospective multicentre study including patients with neurosyphilis who were treated at one of eight tertiary care centres in France, from Jan 1, 1997, to Dec 31, 2017. We defined neurosyphilis as positive treponemal and non-treponemal tests and at least one of otic syphilis, ocular syphilis, either neurological symptom with a positive result on cerebrospinal fluid (CSF)-VDRL or CSF-PCR tests, or more than five leukocytes in a CSF cell count. Patients with neurosyphilis were identified from the medical information department database of each centre and assigned to one of two groups on the basis of the initial treatment received (ie, benzylpenicillin group or ceftriaxone group). The primary outcome was the overall clinical response (ie, proportion of patients with a complete or partial response) 1 month after treatment initiation. The secondary endpoints were proportions of patients with a complete response at 1 month and serological response at 6 months, and length of hospital stay., Findings: Of 365 patients with a coded diagnosis of neurosyphilis in one of the eight care centres during 1997-2017, 208 were included in this study (42 in the ceftriaxone group and 166 in the benzylpenicillin group). The mean age of patients was 44·4 years (SD 13·4), and 193 (93%) were men. We observed 41 instances of overall clinical response (98%) in the ceftriaxone group versus 125 (76%) in the benzylpenicillin group (crude odds ratio [OR] 13·02 [95% CI 1·73-97·66], p=0·017). After propensity score weighting, overall clinical response rates remained different between the groups (OR 1·22 [95% CI 1·12-1·33], p<0·0001). 22 (52%) patients in the ceftriaxone group and 55 (33%) in the benzylpenicillin group had a complete response (crude OR 2·26 [95% CI 1·12-4·41], p=0·031), with no significant difference after propensity score weighting (OR 1·08 [95% CI 0·94-1·24], p=0·269). Serological response at 6 months did not differ between the groups (21 [88%] of 24 in the ceftriaxone group vs 76 [82%] of 93 in the benzylpenicillin group; crude OR 1·56 [95% CI 0·42-5·86], p=0·50), whereas hospital stay was shorter for patients in the ceftriaxone group than for those in the benzylpenicillin group (mean 13·8 days [95% CI 12·8-14·8] vs 8·9 days [5·7-12·0], p<0·0001). No major adverse effects were reported in either group., Interpretation: Our results suggest that ceftriaxone is similarly effective to benzylpenicillin for the treatment of neurosyphilis, potentially decreasing the length of hospital stay. Randomised, controlled trials should be done to confirm these results., Funding: None., Competing Interests: Declaration of interests JMM reports grants from Gilead, Merck, and Viiv Healthcare, outside the submitted work. JG reports grants from Gilead and ViiV Healthcare and personal fees from Gilead, ViiV Healthcare, Janssen, and Merck Sharp & Dohme, outside the submitted work. OR reports personal fees and non-financial support from ViiV, Merck Sharp & Dohme, and Gilead, and grants from Merck Sharp & Dohme, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Syphilis is reemerging in certain populations, such as in men who have sex with men in particular. Oral manifestations are not uncommon and can render diagnosis difficult, particularly if occurring in isolation., Materials and Methods: We recovered clinical data for all patients receiving a diagnosis of secondary syphilis who were referred to the National Reference Center for Syphilis in Paris, France, from January 2000 to July 2019. We selected patients presenting oral symptoms only and analyzed their general characteristics, time to diagnosis, and clinical presentations., Results: Secondary syphilis was diagnosed in 206 patients, 38 of whom (18%) presented oral manifestations, which were isolated in 14 patients (37%). The main oral manifestations were subacute erosive or ulcerative lesions (55%), mucous patches on the tongue (53%), and nodular (10%) and leukokeratotic lesions (5%). Mean time to diagnosis was 4.5 months, but was significantly longer for patients with isolated oral symptoms (8.8 vs 1.8 months; P = .02)., Conclusion: Oral presentations of secondary syphilis are frequent and challenging for diagnosis, even in patients with epidemiologic risk factors. Clinicians confronted with subacute oral lesions in such patients should bear in mind the possibility of this contagious, curable, and sometimes severe disease., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

We evaluated the utility of the commercial Allplex genital ulcer real-time PCR multiplex assay for detecting Treponema pallidum , herpes simplex virus 1 (HSV-1) and 2 (HSV-2), and Chlamydia trachomatis serovar L (lymphogranuloma venereum [LGV]) DNA in mucosal and genital ulcers in the context of suspected syphilis. In total, 374 documented genital and mucosal ulcers from patients with and without syphilis presenting at several sexually transmitted infection (STI) centers in France from October 2010 to December 2016 were analyzed at the National Reference Center (CNR) for Bacterial STIs at Cochin Hospital in Paris. T. pallidum subsp. pallidum detection results were compared with the final diagnosis based on a combination of clinical examination, serological results, and in-house nested PCR (nPCR). Detections of HSV and LGV were validated against reference methods. We found that 44.6% of the 374 samples tested were positive for T. pallidum subsp. pallidum , 21% for HSV, and 0.8% for LGV. No positive results were obtained for 30.7% of samples, and 4.8% presented coinfections. For T. pallidum subsp. pallidum detection, the overall sensitivity was 80% (95% confidence interval [CI], 76.1 to 84.1%), specificity was 98.8% (95% CI, 97.7 to 99.9%), positive predictive value was 98.8% (95% CI, 97.7 to 99.9%) and negative predictive value was 80.2% (95% CI, 76.2 to 84.2%), with a rate of concordance with the reference method of 92.5% ( k  = 0.85). This PCR multiplex assay is suitable for T. pallidum subsp. pallidum detection in routine use and facilitates the simultaneous rapid detection of a broad panel of pathogens relevant in a context of suspected syphilis lesions., (Copyright © 2021 American Society for Microbiology.)

Background: Gonorrhoea is increasing in France since its resurgence in the late 1990's. Understanding trends of condomless sex is a requirement to tailor prevention toward most exposed individuals. This study aims to analyse trends and determinants of condomless penetrative sex (PS) in MSM and heterosexuals diagnosed with gonorrhoea in France., Methods: A standardized self-administered questionnaire filled by 3453 patients was used to monitor condomless sex through the sentinel surveillance network ResIST between 2005 and 2014. Trends were used to describe consistent condom use for penetrative sex (PS). A logistic regression model analysed patients' characteristics associated with condomless PS., Results: Between 2005 and 2014, condomless PS increased regardless of sexual orientation. Condomless PS was particularly common among HIV positive men who have sex with men (MSM (65%)). People living in metropolitan regions outside Paris area (adjusted odds-ratio (AOR) [95% CI] =1.33[1.12-1.58]) were more likely to engage in condomless PS. Conversely, MSM (AOR [95% CI] =0.21 [0.16-0.29]), HIV seronegative patients (AOR [95% CI] =0.68 [0.51-0.89]), patients diagnosed in hospital (AOR [95% CI] = 0.66 [0.45-0.97]) and multi-partners (≥ 10 partners, AOR [95% CI] = 0.54 [0.40-0.74]) were more likely to use condoms., Conclusions: These findings highlight a decreasing use of condom in MSM and heterosexuals diagnosed with gonorrhoea. Prevention strategies should take in account drivers of condomless sex in a context of uncontrolled STI epidemics.

Benzathine penicillin G (BPG) is the reference treatment for early syphilis, but shortages have recently been reported, highlighting a need for the validation of alternative treatments. The aim of this study was to evaluate the genomic resistance of Treponema pallidum subspecies pallidum (TPA) to macrolides and doxycycline in France. Swabs from genital, anal, oral and cutaneous lesions were obtained from 146 patients with early syphilis in France. They were screened for mutations conferring resistance to macrolides and doxycycline by nested PCR and sequencing. Resistance to macrolides was detected in 85% of the isolates, but no point mutations conferring doxycycline resistance were detected. These findings confirm that, in France, resistance to macrolides is widespread. Moreover, we confirmed the absence of genomic resistance to doxycycline in the TPA strains. Therefore, doxycycline could be safely recommended as an alternative to BPG for the treatment of early syphilis.

Introduction: Carney Complex (CNC) is a rare multiple endocrine and nonendocrine neoplasia syndrome. Manifestations and genotype-phenotype correlations have been described by retrospective studies, but no prospective study evaluating the occurrence of the different manifestations has been available so far., Methods: This multicenter national prospective study included patients with CNC, primary pigmented nodular adrenal disease (PPNAD), or a pathogenic PRKAR1A mutation; after a full initial workup, participants were followed for 3 years with annual standardized evaluation., Results: The cohort included 70 patients (50 female/20 male, mean age 35.4 ± 16.7 years, 81% carrying PRKAR1A mutation). The initial investigations allowed identification of several manifestations. At the end of the 3-year follow-up, the newly diagnosed manifestations of the disease were subclinical acromegaly in 6 patients, bilateral testicular calcifications in 1 patient, and cardiac myxomas in 2 patients. Recurrences of cardiac myxomas were diagnosed in 4 patients during the 3-year follow-up study period. Asymptomatic abnormalities of the corticotroph and somatotroph axis that did not meet criteria of PPNAD and acromegaly were observed in 11.4% and 30% of the patients, respectively. Patients carrying the PRKAR1A c.709-7del6 mutation had a mild phenotype., Conclusion: This study underlines the importance of a systematic follow-up of the CNC manifestations, especially a biannual screening for cardiac myxoma. By contrast, regular screening for the other manifestations after a first extensive workup could be spread out, leading to a lighter and more acceptable follow-up schedule for patients. These are important results for recommendations for long-term management of CNC patients., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Congenital syphilis (CS) is caused by Treponema pallidum infection in utero. There is a need to develop new tools to diagnose CS: the diagnostic value of PCR is difficult to assess. The aim of this study was to describe the clinical and laboratory characteristics of mothers and infants with CS as diagnosed by PCR tests on various maternal and neonatal samples., Patients and Methods: We included all infants epidemiologically linked to a mother diagnosed with syphilis whose samples were referred to the Syphilis Reference Center, and for whom at least one positive PCR result was obtained., Results: Twenty-two mother-infant pairs (8.3%) with assay performed on samples from one to four different anatomic sites were included between February 2011 and April 2018. Seven mothers (31.8%) were born abroad, fifteen (68.2%) presented psychological and/or social problems, eight (36.4%) had not been screened for syphilis prior to delivery, and eleven (50%) were referred from French overseas departments or territories, or from the Paris region. Six infants (27.3%) were stillborn and six were born preterm, while fifteen infants (68.2%) presented clinical features of CS. All infants born preterm were symptomatic. Infant VDRL/RPR titer was no greater than four times that in the mother's serum, except in two cases., Discussion: Lack of antenatal care, social disadvantage and psychological issues were common. There is a need for enhanced surveillance both in the French overseas departments/territories and in the Paris region. A larger study is required to assess the sensitivity and specificity of PCR. The best site for sampling has yet to be established. We recommend the collection of as many samples as possible to avoid underdiagnosis of CS., (Copyright © 2019. Published by Elsevier Masson SAS.)

Background: Genital psoriasis is often under-recognized., Objectives: To assess the instantaneous prevalence of genital psoriasis and describe its clinical features, association with a particular subtype of psoriasis and its impact on general and sexual quality of life (QoL)., Methods: GENIPSO is a prospective study conducted by private and hospital-based dermatologists. This study featured the consecutive inclusion of patients consulting for extragenital psoriasis. The clinical features of psoriasis and genital psoriasis were recorded and QoL and sexual health questionnaires were distributed to patients., Results: Overall, 335 of 776 patients (43·2%) included in the study had genital involvement. All were aware that they had genital lesions but only 135 patients (40%) declared that they had been previously examined. Genital lesions were associated with male sex, severity of psoriasis, age of onset > 20 years, inverse psoriasis and involvement of scalp, nail and external auditory canal, but were not associated with obesity, psoriatic arthritis and active sex life. Itching was the main symptom. Genital psoriasis was associated with impairment of QoL and sexual health according to the Dermatology Life Quality Index and the Female Sexual Function Index., Conclusions: Genital psoriasis has a high prevalence in patients consulting for extragenital psoriasis, which affects QoL, and should be taken into account by dermatologists in order to optimize global care., (© 2018 British Association of Dermatologists.)

Diagnoses of bacterial sexually transmitted infections (STI) have been increasing in France since their resurgence in the late 1990s. This article presents recent epidemiological trends until 2016 and the patients' characteristics. STI surveillance relies on sentinel networks: a clinician-based network RésIST (clinical, biological and behavioural data for early syphilis and gonorrhoea), the lymphogranuloma venereum (LGV) network (clinical, biological and behavioural data for rectal LGV, and the laboratory networks Rénachla and Rénago (demographic and biological data for chlamydial infections and gonorrhoea, respectively). Here we describe trends between 2014 and 2016, using data from diagnostic centres which participated regularly during the study period. The number of early syphilis, gonorrhoea and LGV diagnoses increased between 2014 and 2016, particularly in men who have sex with men. An increase in syphilis and gonorrhoea cases was also observed in heterosexuals. Nevertheless, we observed a drop in 2016 for syphilis and chlamydial infections after two decades of increases. Under-reporting and shortage of benzathine penicillin in 2016 may explain this latest evolution. Regular screening of patients and partners, followed by prompt treatment, remains essential to interrupt STI transmission in a context where human immunodeficiency virus (HIV) prevention has expanded towards biomedical prophylaxis.

Objective: In France, surveillance of early syphilis (primary, secondary and early latent) relies on the clinician-based ResIST sentinel network. Although ResIST enables the monitoring of trends, a complete picture of the syphilis epidemic is not possible. More specifically, cases reported by this network are mostly diagnosed in free sexually transmitted infection clinics and hospitals (75% and 24%, respectively). This study aims to estimate the number and rate of diagnoses made outside these health facilities by exploring health insurance data., Methods: An algorithm combining healthcare reimbursements for specific diagnostic tests and recommended treatment was fitted to identify syphilis cases. Sensitivity analyses were used to validate the algorithm. Age-standardised and gender-standardised diagnosis rates were estimated using census data., Results: Between 2011 and 2013, 12 644 (7.5 cases per 100 000 inhabitants) reimbursements were made for syphilis-related diagnoses. The annual number of cases increased by 22% from 2011 (n=3771, rate=6.7/100 000) to 2013 (n=4589, rate=8.2/100 000). The rate of syphilis diagnosis increased in men from 12.9/100 000 to 16.0/100 000, while it remained steady in women at approximately 1.8/100 000. The disease burden was greatest in French overseas territories (18.1/100 000) and in the Paris area (11.7 cases/100 000)., Conclusion: Despite the lack of data on the number of confirmed diagnoses and information on sexual behaviour, these findings demonstrate the relevance of analysing insurance data to help monitor the syphilis epidemic in patients who visit general practitioners and non-hospital-based specialists. Thus, reimbursement database might be a relevant alternative source of continuous information on syphilis in countries with similar insurance-based healthcare systems., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Treponema pallidum subsp. pallidum, the causative agent of sexually transmitted syphilis, detected in clinical samples from France, was subjected to molecular typing using the recently developed Multilocus Sequence Typing system. The samples (n = 133) used in this study were collected from 2010-2016 from patients with diagnosed primary or secondary syphilis attending outpatient centers or hospitals in several locations in France. Altogether, 18 different allelic profiles were found among the fully typed samples (n = 112). There were five allelic variants identified for TP0136, 12 for TP0548, and eight for TP0705. Out of the identified alleles, one, seven, and three novel alleles were identified in TP0136, TP0548, and TP0705, respectively. Partial allelic profiles were obtained from 6 samples. The majority of samples (n = 110) belonged to the SS14-like cluster of TPA isolates while 7 clustered with Nichols-like isolates. Patients infected with Nichols-like samples were more often older (p = 0.041) and more often diagnosed with secondary syphilis (p = 0.033) compared to patients infected with SS14-like samples. In addition, macrolide resistance caused by the A2058G mutation was found to be associated with allelic profile 1.3.1 or with strains belonging to the 1.3.1 lineage (p<0.001). The genetic diversity among TPA strains infecting the European population was surprisingly high, which suggests that additional studies are needed to reveal the full genetic diversity of TPA pathogens infecting humans., Competing Interests: The authors have declared that no competing interests exist.

Background: The diagnosis of acrodermatitis chronica atrophicans (ACA), the late cutaneous manifestation of Lyme borreliosis, can be challenging. Histologic changes in ACA have been described in a few studies from endemic countries, relying on cases documented by serology only., Objectives: We sought to reassess the clinicopathological spectrum of ACA in a series of thoroughly documented cases., Methods: Patients prospectively included in a national prospective study were selected on the basis of positive culture and/or polymerase chain reaction of a skin biopsy sample. The diagnosis of ACA was confirmed by reviewing the clinical and serologic data. Histopathological samples were carefully reviewed., Results: Twenty patients were included. Unusual clinical features (ie, numerous small violaceous patches and equidistant small spinous papules with background faint erythema) were observed in 2 patients. Histopathological examination revealed a classic plasma cell-rich perivascular and interstitial pattern with telangiectases in 16 of 25 samples, whereas strikingly prominent granuloma annulare-like or lichenoid features were observed in 4 and 2 of 25 cases, respectively, and discrete nonspecific minor changes in 3 of 25 cases., Limitations: The small number of patients was a limitation., Conclusions: Genuine culture- and/or polymerase chain reaction-proven ACA can rarely present as numerous violaceous patches or cluster of spinous papules clinically, and as a granuloma annulare-like or lichenoid dermatosis histologically., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: A low 25-hydroxyvitamin D3 (25(OH)D3) serum concentration at melanoma diagnosis might be associated with worse survival. We prospectively studied the prognostic value of 25(OH)D3 at diagnosis and during follow-up., Methods: MelanCohort is a cohort of invasive melanoma patients. Serum 25(OH)D3 was measured by mass spectrometry and standardized on month of blood drawn, age, sex, and body mass index (BMI). Role of 25(OH)D3 levels and risk of relapse was analyzed in a Cox proportional hazards model adjusting for age, sex, BMI, and American Joint Committee on Cancer (AJCC) stage. All statistical tests were two-sided., Results: One thousand one hundred seventy-one patients were included. 25(OH)D3 levels at diagnosis (median = 49.0 nmol/L) were inversely correlated with prognostic factors such as AJCC stage (P < .001 Kruskal-Wallis), Breslow's thickness (P < .001 Spearman correlation), and ulceration (P < .001 Kruskal-Wallis), but not with risk of relapse. Changes in 25(OH)D3 levels during follow-up were associated with worse prognosis: With a third quartile Q3 of average change per year (-0.30 to 4.60 nmol/L/Y) used as reference, hazard ratios for the first, second, and fourth quarters were 1.94 (95% confidence interval [CI] = 1.36 to 2.76), 1.23 (95% CI = 0.85 to 1.78), and 1.61 (95% CI = 1.14 to 2.28), respectively. In sensitivity analyses, no changes were observed either by AJCC stage, number of 25(OH)D3 measures performed, or by 25(OH)D3 level at baseline. No evidence of reverse causation was identified. Analyses performed on overall survival yielded similar results., Conclusions: We show that 25(OH)D3 variation during follow-up is an independent melanoma prognostic marker, but not its level at diagnosis. Previously reported associations between low 25(OH)D3 level at diagnosis and poor prognosis seem to be due to insufficient adjustment for prognostic factors., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objective: Hypocomplementemic urticarial vasculitis (HUV) is an uncommon vasculitis of unknown etiology that is rarely described in the literature. We undertook this study to analyze the clinical spectrum and the therapeutic management of patients with HUV., Methods: We conducted a French nationwide retrospective study that included 57 patients with chronic urticaria, histologic leukocytoclastic vasculitis, and hypocomplementemia. We assessed clinical and laboratory data and evaluated the patients' cutaneous and immunologic responses to therapy. We evaluated treatment efficacy by measuring the time to treatment failure., Results: Urticarial lesions were typically more pruritic than painful and were associated with angioedema in 51% of patients, purpura in 35%, and livedo reticularis in 14%. Extracutaneous manifestations included constitutional symptoms (in 56% of patients) as well as musculoskeletal involvement (in 82%), ocular involvement (in 56%), pulmonary involvement (in 19%), gastrointestinal involvement (in 18%), and kidney involvement (in 14%). Patients with HUV typically presented with low C1q levels and normal C1 inhibitor levels, in association with anti-C1q antibodies in 55% of patients. Hydroxychloroquine or colchicine seemed to be as effective as corticosteroids as first-line therapy. In patients with relapsing and/or refractory disease, rates of cutaneous and immunologic response to therapy seemed to be higher with conventional immunosuppressive agents, in particular, azathioprine, mycophenolate mofetil, or cyclophosphamide, while a rituximab-based regimen tended to have higher efficacy. Finally, a cutaneous response to therapy was strongly associated with an immunologic response to therapy., Conclusion: HUV represents an uncommon systemic and relapsing vasculitis with various manifestations, mainly, musculoskeletal and ocular involvement associated with anti-C1q antibodies, which were found in approximately half of the patients. The best strategy for treating HUV has yet to be defined., (Copyright © 2015 by the American College of Rheumatology.)

Background: Thalidomide use in cutaneous sarcoidosis is based on data from small case series or case reports. The objective of this study was to evaluate the efficacy and safety of thalidomide in severe cutaneous sarcoidosis., Methods: This study consisted of a randomized, double-bind, parallel, placebo-controlled, investigator-masked, multicenter trial lasting 3 months and an open-label study from month 3 to month 6. Adults with a clinical and histologic diagnosis of cutaneous sarcoidosis were included in nine hospital centers in France. Patients were randomized 1:1 to oral thalidomide (100 mg once daily) or to a matching oral placebo for 3 months. In the course of an open-label follow-up from month 3 to month 6, all patients received thalidomide, 100 mg to 200 mg daily. The proportions of patients with a partial or complete cutaneous response at month 3, based on at least a 50% improvement in three target lesions scored for area and infiltration, were compared across randomization groups., Results: The intent-to-treat population included 39 patients. None of them had a complete cutaneous response. Four out of 20 patients in the thalidomide group (20%) vs four out of 19 patients in the placebo group (21%) had a partial cutaneous response at month 3 (difference in proportion of -1% [95% CI, -26% to +24%] for thalidomide vs placebo, P = 1.0). Eight patients with side effects were recorded in the thalidomide group vs three in the placebo group. We observed a large number of adverse event-related discontinuations in patients taking thalidomide in the first 3 months (four patients with thalidomide, zero with placebo) and in the 3 following months (five patients)., Conclusions: At a dose of 100 mg daily for 3 months, our results do not encourage thalidomide use in cutaneous sarcoidosis., Trial Registry: ClinicalTrials.gov; No.: NCT0030552; URL: www.clinicaltrials.gov.

Two major Treponema pallidum subtypes, 14 d/g and 14 d/f, were identified in a population of 119 patients with syphilis in Paris, France, characterized by a high proportion of men who have sex with men. A new subtype named 11 q/j was characterized, and a reinfection case was determined in 1 patient having consecuitve syphilis infection at 19-month interval.

Sexually transmitted infections (STIs) remains a major problem of public health in France. Voluntary networks of physicians (RésIST) and laboratories (Rénago, Rénachla, lymphogranuloma venereum: LGV network) produce indicators showing the evolution of the main bacterial STIs. In 2010, the main findings were the following. The number of gonococcal infections has increased throughout the decade 2000 to 2010. The decrease in susceptibility of gonococcal strains to first-line antibiotics (extended-spectrum cephalosporins) needs to keep great attention. The number of screening and diagnosis of chlamydial urogenital infections also continues to rise in both sexes, particularly due to increased screening among young people. The relatively stable number of cases of early syphilis and of rectal LGV needs to be confirmed over the coming years. Both of these STIs affect overwhelmingly homo/bisexual men. There is still a high level of HIV co-infection with LGV and syphilis, and to a lesser extent with gonorrhea. We observe that condom use is still inadequate, especially during oral sex., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background: Day hospital is a unit allowing the provision of several services together in a single day such as complex or specific therapy, or investigations requiring the services of different technical departments. This paper describes the structure and activity of dermatological day hospitals within French university hospitals (CHU)., Patients and Methods: A transverse prospective study was performed over a 2-week period in 2009 based on a first questionnaire which assessed the organisation and structure of the day hospitals (one questionnaire per day hospital unit), while the second assessed the activity of the day hospitals (one questionnaire for each patient attending day hospitals) throughout the period covered by the survey., Results: Twenty-eight of the 44 dermatology French university hospital day centres responded to the survey (participation rate: 63 %). Six had access to shared day hospital facilities while the 22 others had dedicated dermatology facilities. The day hospital unit was part of a national reference centre in 13 of 24 cases. The median number of beds per day-hospital structure was six for a median of eight patients admitted per day and 1500 sessions recorded each year. On average, the teams comprised two full-time doctors, two nurses, 1.25 hospital workers and one secretary. The mean number of administrative documents generated per unit each week was 57. There were 793 admissions to day hospitals throughout the survey period, for examinations in 61 % of cases and for treatment in 37 % of cases. Fifteen percent of patients were seen without prior arrangement for a variety of intercurrent events. The mean amount of doctor's time devoted to each patient was 25 min. Among the main diseases seen at dermatology day hospitals, we noted cancer (44 % of admissions, 322 cases), psoriasis (7 % of admissions, 54 cases) and chronic wounds (5 % of admissions, 43 cases)., Discussion: Dermatology day hospitals serve to provide treatment for complex or costly diseases requiring a variety of specialised laboratory examinations in a single unit all at one time. A considerable workload is generated, particularly in medical and administrative terms. These are well-adapted structures with their own staff, a selection of technical means and upstream scheduling allowing multidisciplinary patient management. Day hospitals meet a real need in dermatology., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: EDNRB gene variants were reported to be associated with melanoma risk in French patients, with the S305N variant showing the highest frequency., Aim: To verify the S305N association with melanoma risk in an independent larger French population (378 patients, 389 controls); to investigate the role of EDNRB variants in melanoma risk in an Italian population (133 patients, 118 controls); and to explore the association of CDKN2A or CDK4 mutations with the S305N EDNRB variant in a subgroup of patients (59 French, 12 Italian) with a suspected hereditary predisposition to melanoma (familial melanoma, sporadic multiple primary melanoma or melanoma associated with pancreatic cancer)., Methods: The S305N variant was genotyped in the French population, while the EDNRB gene in the Italian population was entirely sequenced., Results: Overall, there was no significant difference in the frequency of the S305N variant between patients with sporadic melanoma and controls in either the French or the Italian population. However, a significantly higher S305N allele frequency was detected in French patients with a suspected hereditary predisposition to melanoma compared with controls (P = 0.04). In addition, in this subgroup of patients, the S305N allele was also significantly associated with the presence of CDKN2A mutations (P = 0.04)., Conclusions: Our results showed no evidence of association of the S305N EDNRB polymorphism with sporadic melanoma risk in either the French or Italian populations, but there was an indication that EDNRB might be a melanoma-predisposing gene in French patients with a suspected hereditary predisposition to melanoma., (© The Author(s). CED © 2011 British Association of Dermatologists.)

Sexually transmitted infections (STI) or diseases (STD) are sociologic markers reflecting sexual behaviours of individuals belonging to this society. Since 2000, the evolution of STI has been characterized by the recrudescence of syphilis, the appearance of resistance of gonococcus to fluoroquinolones and the emergence of lymphogranuloma venereum. These STI are nearly exclusively observed in men and predominantly in men having sex with men with a high proportion of HIV infected individuals from 15% in those consulting for gonococcemia to 100% in those diagnosed with lymphogranuloma venereum. The epidemic is relatively stable since 2007 which suggest that it could decline in the next future. Relapse of these STI suggests a relapse of high risks sexual practices in group of patients historically exposed to HIV and that control measures for prevention of STI targeting men having sex with men should be reinforced for controlling the incidence of classical STI and of HIV.

Purpose: Xeroderma pigmentosum variant (XPV) is a rare recessive autosomal genodermatosis predisposing to multiple early onset skin cancers, including melanoma. XPV results from mutations of the POLH gene that encodes a DNA translesion polymerase. In this work, we tested the hypothesis that POLH variants could be associated with melanoma risk., Experimental Design: A common non-synonymous POLH variant, c.1783A>G p.M595V, was genotyped in 1075 melanoma patients and in 1091 ethnic-matched controls from France. In addition, we searched for rare POLH variants by sequencing the entire coding sequence in 201 patients having a familial history of melanoma (n=123), sporadic multiple melanomas (n=65) and a melanoma associated with a skin carcinoma (n=13)., Results: Overall, the c.1783G, p.595V allele was statistically associated with melanoma (respective allelic frequencies, 0.040 versus 0.022, P-value=1.17 x 10(-3), odds ratio (OR)=1.86 [1.27-2.71]), which was further confirmed by a meta-analysis including 274 patients and 174 matched controls from Italy (P-value=7.7 x 10(-4), OR=1.84 [1.29-2.63]). Interestingly, three non-synonymous POLH variants were identified in three patients (c.295G>A p.V99M, c.815T>C p.I272T and c.1745C>T p.S582L) which were absent in 352 chromosome controls from healthy subjects., Conclusions: Besides severe deficiencies in translesion synthesis which are major risks factors for skin carcinomas and melanomas, less deleterious POLH variants could act as low penetrance melanoma predisposing alleles. The ongoing identification of genetic markers implied in skin cancer predisposition could help to identify high-risk subjects as targets for clinical follow-up. Replication studies in other populations are awaited to assess these data.

Since 2000, the incidence of syphilis has risen in developed countries. An updated knowledge of syphilis features is the key for early diagnosis and treatment. Our objective was to appraise the clinical and epidemiological presentation of syphilis in Paris, France. A retrospective monocentric descriptive study of 284 consecutive syphilis cases was conducted in a venereal disease centre (Paris, France), over the period 2000-2007. Epidemiological, clinical and microbiological data were systematically collected, using standardized medical forms. Overall, 95% of the cases occurred in men (271/284), 83% in men having sex with men (MSM) (231/278), 58% in patients having more than 10 partners/year (138/240) and 19% in patients who never use a condom (49/253). At least one STD has been previously diagnosed in 79% (220/279) of the cases. In 50.5% of the cases (142/281), HIV serology was positive. Most patients had primary (82/279, 29%) or secondary (125/279, 45%) syphilis. The most frequent physical signs in primary and secondary syphilis were, respectively, a genital chancre (63/82, 77%) and a diffuse exanthema (108/125, 86%). Syphilis occurs chiefly in MSM, often in HIV-positive patients. Many patients never use condoms. These data will help provide the basis for the development of national information and screening campaigns.

In this study, we investigated whether variants in three key pigmentation genes-MC1R, MATP/SLC45A2, and OCA2--were involved in melanoma predisposition. A cohort comprising 1,019 melanoma patients (MelanCohort) and 1,466 Caucasian controls without skin cancers were studied. A total of 10 polymorphisms, including five functional MC1R alleles (p.Asp84Glu, p.Arg142His, p.Arg151Cys, p.Arg160Trp, and p.Asp294His), two nonsynonymous SLC45A2 variants (p.Phe374Leu and p.Glu272Lys), and three intronic OCA2 variants previously shown to be strongly associated with eye color (rs7495174 T>C, rs4778241 G>T, and rs4778138 T>C) were genotyped. As expected, MC1R variants were closely associated with melanoma risk (P value <2.20.10(-16); odds ratio [OR]=2.29 [95% confidence interval, CI=1.85-2.82 and OR=3.3 [95% CI=2.00-5.45], for the presence of one or two variants, respectively). Interestingly, the SLC45A2 variant p.Phe374Leu was significantly and strongly protective for melanoma (P-value=2.12.10(-15); OR=0.35 [95% CI=0.26-0.46] and OR=0.32 [95% CI=0.24-0.43], considering the genotypes Phe/Leu and Leu/Leu, respectively). MC1R and SLC45A2 variants had additive effects on melanoma risk, and after adjusting for pigmentation characteristics, the risk was persistent, even though both genes had a strong impact on pigmentation. Future studies may show whether genetic information could provide a useful complement to physical examination in predicting melanoma risk.

Background: Four epidemiologic forms of Kaposi's sarcoma have been described, all of which are associated with the human herpesvirus-8. In western countries, human herpesvirus-8 is more prevalent in homosexual men than in the general population, and anecdotal cases of Kaposi's sarcoma in HIV-negative homosexual men have been reported., Patients and Methods: We included HIV-negative homosexual and bisexual male patients with histologically proven Kaposi's sarcoma in a retrospective study. Clinical data were collected using a standardized form. Risk factors for human herpesvirus-8 infection and for the development of Kaposi's sarcoma were systematically recorded., Results: Between 1995 and 2007, 28 men met the defined inclusion criteria. Mean age at first symptoms of Kaposi's sarcoma was 53 years. Clinical presentation resembled classical Kaposi's sarcoma, with limited disease in most patients. No cellular or humoral immunodeficiency was observed. Serologic tests for human herpesvirus-8 (latent immunofluorescence assay) were positive in 88% of patients, and only two patients displayed human herpesvirus-8 viremia at the time of Kaposi's sarcoma diagnosis. Three patients developed lymphoproliferative disorders (Castleman disease, follicular lymphoma and Burkitt lymphoma). In this population, alpha-interferon was well tolerated and gave a complete response, but most patients require only local treatment, if any., Conclusion: Kaposi's sarcoma may develop in homosexual or bisexual men without HIV infection. This type of Kaposi's sarcoma has clinical features in common with classical Kaposi's sarcoma but occurs in younger patients. Its prognosis is good, as Kaposi's sarcoma is generally limited, but clinicians should be aware of the association with lymphoproliferative diseases, which may affect prognosis.

Our aim was to evaluate remission and relapse rates and the number of laser sessions necessary for treatment. Among the relapses observed, we sought to differentiate between the persistence and recurrence of an HPV-induced lesion. This retrospective study was performed in patients, immunocompetent or not, treated with CO2 laser for condylomatous or neoplastic anogenital lesions by the same operator over a period of 12 months. 106 treated patients were followed for 6 months. Three groups of patients were analysed: HIV(+) patients, patients with therapeutic immunosuppression (ImST) and immunocompetent patients (ImC). Twenty-seven (25.5%) patients presented with high-grade intraepithelial neoplasms (IEN III). IEN III lesions were more common in the HIV(+) group than in immunocompetent patients (47.4% versus 20.2%, p = 0.015). The development of HPV-induced lesions at several sites on the body was also more common in HIV(+) patients. Post-laser controls at one month demonstrated a clinical absence of HPV-induced lesions in 81.2% of cases, recurrence in 12.6% of cases and persistence in 6.6% of cases. Remission rates at one month did not differ significantly between the three groups. 93% of patients in remission at one month were still in remission at three months. IEN III neoplasms in remission at one month remained so at six months. ImC and ImST patients presented more frequently with recurrence than persistence, when compared with HIV(+) patients. At six months, 83% of patients were in remission after 1.4 laser treatments. The excision of HPV-induced anogenital lesions using CO2 laser remains an efficient treatment, even if it needs to be repeated if lesions recur or persist. CO2 laser treatment under colposcopic guidance can achieve remission in both immunocompromised and non-compromised patients with longstanding lesions.

Background: Reported rates of incomplete excision of basal cell carcinoma (BCC) range from 4% to 16.6%., Objective: The objective was to assess, in clinical practice, the rate and the factors associated with pathologically reported incomplete excision of BCC., Methods: In this retrospective monocentric study, data from all surgically excised BCCs during the year 2004 were computerized. Age, sex, number of BCC excised during the same surgical session, BCC location, pathologic types, and involvement of surgical margins were analyzed., Results: Mean age of the 284 patients was 67.4+/-14.9 (SD) years (range, 27-96 years). A total of 52.7% of the 362 BCCs were located on the face (including nose, 10%; eyelids, 4.2%; lips, 2%; and ears, 2.2%). Incomplete excisions occurred in 10.3% of the cases including 8.6% of positive lateral margins and 2.5% of positive deep margins. In the multivariate analysis, incomplete excision was independently associated with location on the nasal ala (p<.02), other parts of the nose (p=.02), and inner canthus (p=.01) and with infiltrative (p<.0001) and multifocal (p<.0001) types., Conclusion: Pathologically reported incomplete excision rate was comparable to that of other studies and was significantly associated with the location on the face, particularly on the nose and inner canthus, and with infiltrative and multifocal histologic types.

In this study, we assessed the role of melanocortin 1 receptor (MC1R) variants and of two patched (PTCH) polymorphisms (c.3944C>T (P1315L), insertion 18 bp IVS1-83) as risk factors for basal cell carcinoma (BCC) in the French population. The population investigated comprised 126 BCC patients who were enrolled on the basis of specific criteria (multiple and/or familial BCC and/or onset before the age of 40 years and/or association with another tumor)--and 151 controls matched for ethnicity, age, and sex. MC1R variants appeared as a moderate risk factor for BCC (odds ratio (OR) for one and two variants, 2.17 [1.28-3.68] and 7.72 [3.42-17.38], respectively), independently of pigmentation characteristics (OR = 2.53 [1.34-4.8]). Interestingly, in addition to the predictable red hair color (RHC) alleles, two non-RHC alleles (V60L and V92M) were also closely associated with BCC risk (OR 3.21 [1.91-5.38] and 2.87 [1.5-5.48], respectively), which differs from the situation in the Celtic population. In addition, the PTCH c.3944C/C genotype was also associated with BCC risk (OR 1.94 [1.2-3.1]), especially in the subgroup of patients with multiple tumors (OR 2.16 [1.3-3.6]). Thus, our data show that MC1R and PTCH variants are associated with BCC risk in the French population. We further suggest that assessing MC1R and PTCH status could be useful, combined with the assessment of clinical risk factors, in identifying high-risk patients to be targeted for prevention or more rigorous surveillance.

Background: Sexually transmitted infections (STI) in France are reported on a voluntary basis through several sentinel surveillance systems., Methods: To monitor STI, sentinel laboratory- or clinician-based surveillance systems were set up by the Institut de Veille Sanitaire: gonorrhea surveillance (Renago) in 1986, Chlamydia infections surveillance (Renachla) in 1989, and more recently, syphilis surveillance in 2000 and rectal lymphogranuloma venereum (LGV) in 2004., Results: From 2000 to 2003, 1,089 syphilis infections were reported. Most of the cases were diagnosed in men having sex with men (MSM) and were mainly reported by STI clinics located in the Paris area. From 1997 to 2000, an increase of gonorrhea was observed each year. After two years of stable trend, the prevalence of gonorrhea increased again in 2003. From 2002 to 2004, 123 LGV cases were diagnosed in France and were observed only in MSM. Since 2001, Chlamydia infections have steadily increased, particularly in women., Comments: Because STI surveillance is based on a voluntary basis, the number of reported cases is probably lower than the number of STI diagnosed in France. However, the data provided by the different surveillance systems reveals that STI have been increasing in France since 1997. Moreover, the resurgence of syphilis in 2000 and the emergence of rectal LGV in 2004 indicate that these STI occur mainly in MSM. Trends on incidence and patients characteristics observed in France are similar to those of several Europeans countries. European Public Health interventions are becoming necessary to prevent and control STI.

This article describes syphilis trends, characteristics of patients from 2000 to 2003 in France and trends of the benzylpenicillin benzathine 2.4 million UI sales from 2001 to 2003. The ongoing surveillance system for syphilis case reporting since 2001 has been set up in volunteer settings, mostly public settings where STI treatment is offered. Clinical case reporting is complemented by sexual behavioural data based on a self-administered questionnaire. From 2000 to 2003, 1089 syphilis cases were reported in France, increasing from 37 cases in 2000 to 428 in 2003. Overall, 96% of syphilis cases were in men with a mean age of 36.5 years and 70% of whom were born in France. The proportion of syphilis cases with HIV co-infection decreased over time from 60% in 2000 to 33% in 2003. The most affected area by the syphilis epidemic is the Ile-de-France region, mainly the city of Paris. The greatest proportion of syphilis cases diagnosed in men who have sex with men (MSM) were in the Ile-de-France region, where they made up 87% of cases, compared with 75% in other regions. Among the patients who completed the self-administered questionnaire on sexual behaviour, 83% reported having casual sex partners in the 3 months prior to their syphilis diagnosis. Trends in the sales of benzylpenicillin benzathine 2.4 million UI in private pharmacies are similar to those observed in the surveillance system, and increased between 2001 and 2003. In conclusion, syphilis transmission is still ongoing in France in 2003 and the role of unprotected oral sex in the transmission of syphilis should be emphasised.