Genetic landscape of indolent and aggressive Kaposi sarcomas.

BACKGROUND: Kaposi sarcoma (KS) is a rare skin tumour caused by herpesvirus 8 infection and characterized by either indolence or an aggressive course necessitating systemic therapies. The genetic basis of this difference remains unknown. OBJECTIVES: To explore the tumour mutational burden in indolent and aggressive KS. METHODS: We performed whole-exome sequencing on a cohort of 21 KS patients. We compared genetic landscape including tumor mutational burden between the two forms of indolent and agressive KS. RESULTS: Aggressive KS tumours had a significantly higher TMB and a larger cumulative number of deleterious mutations than indolent KS tumours. In addition, all aggressive tumours had at least three deleterious mutations, whereas most indolent tumours harboured only one or no predicted deleterious mutations. Deleterious mutations listed in the Cancer Gene Census were detected exclusively in patients with aggressive disease. An analysis of somatic copy-number alterations (SCNA) revealed a tendency towards higher number of alterations in aggressive KS. CONCLUSIONS: These data suggest that SCNA alterations and an increase in mutational burden promote aggressive KS and that it might be more appropriate to consider indolent KS as an opportunistic skin disease rather than a cancer.

Use of a Multiplex PCR Assay To Assess the Presence of Treponema pallidum in Mucocutaneous Ulcerations in Patients with Suspected Syphilis.

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.

2020 European guideline on the management of syphilis.

The 2020 edition of the European guideline on the management of syphilis is an update of the 2014 edition. Main modifications and updates include: -The ongoing epidemics of early syphilis in Europe, particularly in men who have sex with men (MSM) -The development of dual treponemal and non-treponemal point-of-care (POC) tests -The progress in non-treponemal test (NTT) automatization -The regular episodic shortage of benzathine penicillin G (BPG) in some European countries -The exclusion of azithromycin as an alternative treatment at any stage of syphilis -The pre-exposure or immediate post-exposure prophylaxis with doxycycline in populations at high risk of acquiring syphilis.

High prevalence of syphilis in women, minors and precarious patients: a cross-sectional study in a Reunion Island sexually transmitted infection clinic, 2017-2020.

BACKGROUND: Syphilis is a sexually transmitted infection (STI) with a global prevalence estimated at 0.5% in 2012. Syphilis has been on the rise among men who have sex with men (MSM) in high-income countries and remains at endemic levels in low- and middle-income countries. This trend, however, has not been observed in Reunion Island. OBJECTIVES: To determine the prevalence, clinical characteristics and risk factors of syphilis in at-risk patients visiting the South Reunion STI clinic in Reunion Island. METHODS: This monocentric cross-sectional study included all patients who visited our STI clinic between 2017 and 2020. Syphilis serology was performed on all included patients, and data were collected using a standardized self-administered questionnaire. RESULTS: Over the 3-year study period, 2593 patients were enrolled. The prevalence of syphilis was 7.52% (n = 195, 95% CI, 6.50-8.65%) in the overall study population, 11.76% (n = 18, 95% CI, 6.97-18.59%) in minors (aged under 18 years) and 36.36% (n = 16, 95% CI, 21-59%) in pregnant women. The risk factors identified in multivariate analysis were being female [adjusted Prevalence Ratio (aPR) 1.85, 95% CI, 1.10-3.11], being MSM (aPR 2.87, 95% CI, 1.71-4.80), being aged under 18 years (aPR 3.54, 95% CI, 1.90-6.57), living in precarious conditions [aPR 3.12, 95% CI, 2.11-4.62] and being born in Reunion Island (aPR 2.43, 95% CI, 1.42-4.13). The clinical presentation was heterogeneous (plaques and papules, chancre, atypical ulcerations, multiple ulcerations, condyloma lata, etc.). CONCLUSIONS: These findings suggest a high prevalence of syphilis in at-risk patients visiting our STI clinic. Unlike the situation in other high-income countries, the people most at risk of syphilis in Reunion Island are local-born residents, minors, women and precarious patients. This is a source of concern, especially given the risk of resurgence of congenital syphilis on the island.

Benefits of simulation using standardized patients for training dermatology residents in breaking bad news.

INTRODUCTION: Simulation in healthcare is a rapidly developing teaching method in the training of technical procedures. It is also used to enable caregivers to learn how to inform patients of serious illness and complex health status. However, its use is not widespread in the field of dermatology. This study investigated the utility of simulation as regards disclosing melanoma diagnosis, taking resident physician satisfaction as a primary endpoint. MATERIALS AND METHODS: Fifteen dermatology residents were recruited as trainees. Four scenarios were allocated based on length of residency. An introductory briefing was held prior to the training sessions. Debriefing took place on completion of the diagnosis disclosure consultation. The participants completed questionnaires after the simulation session, after debriefing, and 3 months after the simulation session. The primary endpoint was usefulness of the session felt by trainees several months after the simulation. RESULTS: The majority of participants (93.3%) thought the session helped with stress management, improved their attitude and control over their reaction (86.6%), and improved their communication skills (100%). They rated the usefulness of the simulation at 7.79/10 on average (range: 5-10). DISCUSSION: According to our findings the resident physicians involved, particularly those with the least experience, were satisfied with this type of learning technique. Any difficulties encountered by these residents were brought to light and addressed during debriefing. CONCLUSION: There would appear to be real benefits to be reaped from simulation, whatever the stage of medical training at which it takes place. Simulation should become an increasingly important part of contemporary pregraduate specialty programs.

Azithromycin resistance in Treponema pallidum in Reunion Island: A cross-sectional study.

OBJECTIVE: Since the beginning of the 21st century, Reunion Island has experienced a syphilis epidemic. Infected patients are mostly heterosexual, with a high proportion of women, suggesting that congenital syphilis is present on the island. To determine whether azithromycin can be used for mass treatment of syphilis on Reunion Island, we assessed the prevalence of macrolide resistance in Treponema pallidum (TP). METHODS: This monocentric cross-sectional study was conducted at the Reunion Island University Hospital. Samples were collected from lesions suggestive of primary or secondary syphilis. Samples positive for TP by multiplex polymerase chain reaction (PCR) were sent to the French National Reference Centre (NRC) for further analysis. Nested PCR-tpp47 was performed on these samples for detection of TP-DNA; 23s rRNA was amplified by PCR in confirmed positive samples. The Restriction Fragment Length Polymorphism (RFLP) technique was performed on samples with amplified 23s rRNA for detection of the A2058G mutation. RESULTS: A total of 129 samples were collected from 119 patients. Of these, 18 tested positive for TP using multiplex PCR and were sent to the NRC. Fifteen (83.3%) of the 18 samples were confirmed positive by nested PCR-tpp47, and 23s rRNA was amplified in only 7 (38.9%) samples. Azithromycin resistance was detected in all TP strains with amplified 23s rRNA. CONCLUSION: Amplification of 23s rRNA was successful in only 7 TP strains, all of which displayed resistance to macrolides. Keeping in mind the small sample size of our study, this suggests that azithromycin should not be used for mass treatment of syphilis in Reunion Island.

Rituximab is an effective treatment in patients with pemphigus vulgaris and demonstrates a steroid-sparing effect.

BACKGROUND: Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing steroid-related adverse events (AEs) is unproven. OBJECTIVES: To utilize data collected in a French investigator-initiated, phase III, open-label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV. METHODS: This was an independently conducted post hoc analysis of the moderate-to-severe PV subset enrolled in the Ritux 3 study. Patients were randomized to rituximab plus 0·5 or 1·0 mg kg-1 per day prednisone tapered over 3 or 6 months, or 1·0 or 1·5 mg kg-1 per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for ≥ 2 months, and 24-month efficacy and safety results were also reported. RESULTS: At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff ≥ 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one rituximab-plus-prednisone patient withdrew due to pregnancy. Overall, 24 of 36 patients (67%) on prednisone alone experienced a grade 3/4 CS-related AE vs. 13 of 38 patients (34%) on rituximab plus prednisone. CONCLUSIONS: In patients with moderate-to-severe PV, rituximab plus short-term prednisone was more effective than prednisone alone. Patients treated with rituximab had less CS exposure and were less likely to experience severe or life-threatening CS-related AEs. What's already known about this topic? Pemphigus vulgaris (PV) is the most common type of pemphigus. Corticosteroids, a standard first-line treatment for PV, have significant side-effects. Although their effects are unproven, adjuvant corticosteroid-sparing agents are routinely used to minimize steroid exposure and corticosteroid-related side-effects. There is evidence that the anti-CD20 antibody rituximab is effective in the treatment of patients with severe recalcitrant pemphigus and in patients with newly diagnosed pemphigus. What does this study add? This study provides a more detailed analysis of patients with PV enrolled in an investigator-initiated trial. Rituximab plus prednisone had a steroid-sparing effect and more patients achieved complete remission off prednisone. Fewer patients experienced grade 3 or grade 4 steroid-related adverse events than those on prednisone alone. This collaboration between academia and industry, utilizing independent post hoc analyses, led to regulatory authority approvals of rituximab in moderate-to-severe PV.

[A case of "early" syphilis]. / Une syphilis « précoce ¼.

INTRODUCTION: Syphilis mainly affects men who have sex with men (MSM) between the ages of 20 and 49. Herein we report a case in a teenager illustrating extension of the epidemic to other populations. PATIENTS AND METHODS: A 15-year-old boy consulted in May 2018 for an anal fissure and painful oral erosions. He reported having had unprotected anal sex with another male teenager of the same age three months earlier. Syphilis serology was positive, with a positive treponemal test (TT) and non-treponemal test (VDRL) at 1/128. A treponemal bacterial DNA PCR assay was also positive for swabs obtained from the oral erosions and anal fissure. Due to a history of allergy to penicillin the patient was treated with doxycycline 200mg daily for 14 days. One month later, the mucosal lesions had subsided, and 3 months later the VDRL titer had decreased by 2 dilutions. CONCLUSION: This case of "early" syphilis illustrates a change in the French epidemiology of sexually transmitted diseases (STIs). STIs currently affect very young and previously unexposed metropolitan French populations. These infections are increasing in teenagers due to an increase in high-risk sexual behavior associated with a lack of knowledge of STIs. This case is a reminder of the current decline in the level of knowledge about STIs among teenagers as compared to young people of the same age in the 1990s.

GENIPSO: a French prospective study assessing instantaneous prevalence, clinical features and impact on quality of life of genital psoriasis among patients consulting for psoriasis.

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.

Congenital syphilis: A prospective study of 22 cases diagnosed by PCR.

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.

A fifth subtype of Kaposi's sarcoma, classic Kaposi's sarcoma in men who have sex with men: a cohort study in Paris.

BACKGROUND: Classic Kaposi's sarcoma (CKS) occurs predominantly among elderly men and is associated with Kaposi's sarcoma-associated herpesvirus (KSHV). In low-endemic countries, KSHV infects predominantly men having sex with men (MSM). OBJECTIVES: To describe a cohort of classic Kaposi sarcoma in a low-endemic area for KSHV, to highlight the features of CKS in MSM and identify prognostic factors. METHODS: Retrospective single-centre study of CKS cases. We compared MSM to heterosexual patients. Then, we divided the patients into two subgroups, those requiring a systemic treatment and the others, and we performed univariate and multivariate analyses to determine aggressiveness of CKS. RESULTS: Between 2006 and 2015, seventy-four patients were included. Mean age at diagnosis was 68.9 years; sex ratio (M/F) was 6.4, and 28% were MSM; MSM patients were younger (P = 0.02), less often originated from endemic areas (P < 0.0001). KS was less severe (P = 0.04), required more often a local treatment than a systemic one (P = 0.03). On multivariate analysis, CD4 T-cell count > 500/mm3 at baseline was associated with a reduced risk of severe evolution. CONCLUSION: First CKS cohort in low-endemic zone. We describe a fifth subtype of KS: KS in MSM. The CD4 T-cell count was found to correlate with prognosis.

[Dermatologic surgery, hemophilia and Von Willebrand disease]. / Risques en dermatologie interventionnelle chez les patients hémophiles ou atteints de la maladie de Willebrand.

BACKGROUND: Von Willebrand disease (VWD) and hemophilia A and B are the most common types of hereditary coagulation-factor deficiencies. The frequency and type of complications of skin surgery in these patients are unknown. The increasing incidence of skin cancer prompted us to reflect upon this issue. While the incidence of skin cancer is increasing, the complications of skin surgery or ablative laser treatment remain unknown in this population. AIM: The aim of this study was to determine the frequency of bleeding complications during and after skin surgery in patients with a hereditary coagulation-factor deficiency (hemophilia or VWD). PATIENTS AND METHODS: We conducted a retrospective study in patients with hemophilia A or B or VWD undergoing skin surgery or ablative laser treatment at the Dermatology Department of the Cochin Hospital in Paris, France. RESULTS: Fourteen procedures were performed in 8 patients. Three episodes of bleeding occurred (n=3/14, 21.4%): one hematoma, one delayed bleed and one immediate bleed. None of these complications required surgical revision or resuscitation. DISCUSSION: The rate of hemorrhagic complications was higher than in the general population. However, these complications can be considered non-serious and the risk-benefit ratio remains favorable. Multidisciplinary management and coordination with the reference hemophilia center are mandatory in this population to establish a coagulation-factor (CF) substitution protocol suited to the disease characteristics and the surgical procedure.

[Pemphigus and herpes: Multicentre survey and literature review]. / Pemphigus et herpès : enquête multicentrique et revue de la littérature.

BACKGROUND: Although herpes superinfection is a well-known complication of pemphigus, it has not been widely investigated. AIM: To investigate the frequency and features of herpes infection in patients with ongoing pemphigus. PATIENTS AND METHODS: We carried out a multicenter retrospective study between 2008 and 2016 in patients with newly diagnosed pemphigus presenting active herpes infection. Clinical, virological, immunological and therapeutic data were collated. We performed a literature review for pemphigus and herpes. RESULTS: Among the 191 pemphigus patients, screening for herpes (PCR or culture) was carried out in 11 to 71 % of subjects, depending on the center in question. Twenty-four patients (12 women, mean age 58 years) presented at least one episode of herpes infection. The frequency of positivity ranged from 0 to 42 % by center. Twenty-one cases consisted of pemphigus vulgaris and infection occurred at a mucosal site in 19 patients. Herpes infection was identified at the time of diagnosis in 15 patients and 17 patients received no specific treatment for their pemphigus. The virus was identified using PCR in 23 cases. Ten patients subsequently received prophylactic treatment for herpes. The mean duration of follow-up was 36 months (0-89 months). Thirteen of the 24 patients had 23 relapses of pemphigus; PCR testing for herpes was performed 19 times and was positive in 6 cases (31.5 %). CONCLUSION: Our study showed wide variation in the incidence of herpes superinfection in patients with pemphigus, reflecting the different screening approach at each center (being performed either routinely or only in the event of strong suspicion). The prognostic value of routine screening for herpes in patients with active pemphigus lesions remains to be demonstrated by further prospective investigations.

Anaplastic Kaposi's sarcoma: 5 cases of a rare and aggressive type of Kaposi's sarcoma.

BACKGROUND: Anaplastic Kaposi's sarcoma (KS) is a rare form of KS characterized clinically by the development of a tumour mass with unusual local aggressiveness and histologically by a specific architecture and cytological morphology. A very small number of limited series in endemic countries have established characteristics common to these anaplastic forms of KS. We present five patients with an anaplastic form in a context of KS ongoing for several years in a non-endemic country. MATERIALS AND METHODS: We collected 5 cases of anaplastic KS followed in our department over a period of 20years. We describe the main developmental, clinical, virological and histological features. RESULTS: The cases involved 4 men and 1 woman whose mean age at diagnosis of anaplastic KD was 70years, with an average time of 25years between initial diagnosis of KD and anaplastic transformation. Our patients were all treated with chemotherapy and/or radiotherapy (RT) prior to diagnosis of anaplastic transformation. All patients had a tumour mass of the lower limbs developing in classically indolent KS with associated chronic lymphoedema. Progression was very aggressive locally with deep invasion of the soft tissues as well as osteoarticular involvement, without visceral dissemination. At present, three patients are dead, one patient is showing partial response, and one patient is in locoregional progression. Diagnosis of the disease was based on histopathological findings. The tumour cells were undifferentiated, pseudo-cohesive, and chiefly organized in sheets. The mitotic count was high (27 mitoses per 10 fields at high magnification). Necrosis was constant. DISCUSSION: To our knowledge, this is the first series describing anaplastic Kaposi's sarcoma in a non-endemic country. The severity of the prognosis, despite the absence of visceral dissemination, is related to the local aggressiveness of anaplastic KS and to its resistance to radiotherapy and chemotherapy, with amputation being required in certain cases.

Extensive levamisole-induced vasculitis.

Levamisole (an increasingly frequent contaminant of cocaine) can cause antineutrophil cytoplasmic antibody-associated vasculitis. Dermatologists should consider a diagnosis of cocaine/levamisole-associated cutaneous vasculopathy syndrome in cases of purpura of the ears and/or extensive retiform purpura in drug users. We report a case of particularly severe levamisole-induced necrotic purpura and immunological abnormalities in a 40-year-old woman.