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This article discusses the evaluation of routine molecular biology for the diagnosis of primary syphilis by assessing the serological status of patients with PCR-confirmed syphilitic ulcers. The study found that PCR analysis on lesions led to the diagnosis of primary syphilis in 64% of patients when serology was defective. This highlights the usefulness of PCR in detecting primary syphilis, especially in populations at risk of multiple reinfections or where follow-up is challenging. The article provides detailed clinical and epidemiological characteristics of patients with primary syphilis and emphasizes the importance of early detection for appropriate treatment and reducing transmission. [Extracted from the article]

SARS-CoV-2 vaccination is followed by cutaneous side effects in 2% of cases.[[1]] Some chronic dermatoses, more rarely oral lichen planus (LP), may be triggered or exacerbated after vaccination.[[1], [3], [5]] We report here 2 cases of multi-site mucosal LP that started after COVID-19 vaccination. SARS-CoV-2 vaccination may trigger and exacerbate mucosal lichen planus First, SARS-CoV-2 vaccination triggered LP although it is not possible to eliminate that LP was already present but quiescent before. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

In one case, skin biopsy displayed a superficial and deep perivascular and perieccrine lymphocytic infiltrate similar to those of chilblains or chilblain-like lesions. Relapse or new skin manifestations occurred in 2 patients following the second dose without worsening of symptoms. Patient 2 presented with 2 erythematous nodules 4 days after the first dose and chilblains 5 days after the second dose without nodules relapse. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Editor Skin manifestations have been increasingly reported in the setting of COVID-19. We retrieved six series, including ours, in which the numbers of both infected patients and patients with skin signs were available.4,6,7,9,10 Cutaneous lesions were observed in 38 patients over 2199 COVID-19 cases. In patients with rashes, severity was found in 64% of cases and death in 2%, while it was respectively found in 5% and 0% patients with chilblains. [Extracted from the article]

Immune checkpoint inhibitors (ICI) nivolumab and pembrolizumab, antiprogrammed cell death protein 1 antibodies, and ipilimumab, an anti-cytotoxic T-lymphocyte-associated antigen 4 antibody, are widely used in metastatic melanoma. Median time from ICI initiation to encephalitis onset was 42 days (range: 5-640) and was longer in patients receiving pembrolizumab than in patients receiving combined nivolumab and ipilimumab. Patients displaying ICI-induced encephalitis presented with a non-specific pattern of encephalitis with focal symptoms, confusion, meningeal syndrome, with exclusion of infectious or carcinomatous meningitis or new brain metastasis. [Extracted from the article]

The secondary syphilis (SS) is usually characterized by cutaneous eruptions sometimes atypical associated with unspecific symptoms.1 Serology is normally highly positive and reliable in diagnosis of SS.2 However, some issues of serological diagnosis have already been reported previously in human immunodeficiency virus-infected (HIV) patients.3 Here, we present an uncommon case of SS in a 33-year-old man treated with Rituximab (RTX) (for multiple sclerosis with last injection in May 2019) whose treponemal test (TT) was initially non-reactive even though a typical rash was observed since more than 12 days before. Despite inconclusive serological assays for syphilis, we suggested SS and the patient received three injections of benzathine penicillin (2.4 million units intramuscular weekly) with a dramatic improvement after the first injection. Physicians caring for RTX recipients or severe immunocompromised patients should be aware that some patients may present symptoms of SS with initial negative serology. [Extracted from the article]

SPCM specimen analysis by dermato-pathologists revealed four superficial spreading melanomas, including one invasive (Breslow thickness 0-3 mm) and three intraepidermal melanomas, which were subsequently surgically re-excised with lateral safety margins of 5 mm (for intraepidermal melanomas) or 10 mm (invasive melanoma). Second primary cutaneous melanoma in patients with advanced melanoma treated with anti-programmed-death-receptor-1 monoclonal antibodies Dear Editor, Cases of second primary cutaneous melanoma (SPCM), which were mostly BRAF-wildtype, have been reported in patients with BRAF-inhibitor-treated advanced cutaneous melanoma.1 Anti-programmed-death-receptor-1 (anti-PD-1) monoclonal antibodies (mAbs) nivolumab and pembrolizumab have also revolutionized the prognosis of these patients, but 10-15% of them experience grade 3-4 adverse events according to common terminology criteria for adverse events. [Extracted from the article]

Summary: 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. What's already known about this topic? Genital psoriasis is frequent but under‐recognized. What does this study add? The instantaneous prevalence of genital psoriasis in patients consulting for extragenital psoriasis was 43·2%.All patients were aware of their genital psoriasis but only 40% declared having had a previous examination of the genital area by a dermatologist. What are the clinical implications of this work? Owing to its frequency and impact on general and sexual quality of life, genital psoriasis should be screened in all patients, including those already receiving treatment for psoriasis. Respond to this article Linked Comment:Ryan. Br J Dermatol 2019; 180:460–461. Plain language summary available online [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Recent studies have independently implicated the chemokine CXCL12 and its receptors, CXCR4 and CXCR7, in the pathophysiology of Kaposi sarcoma ( KS). Objectives We investigated whether the CXCL12/ CXCR4- CXCR7 protein trio could constitute KS biomarkers. Methods Endothelial and spindle cells positive for CXCL12/ CXCR4- CXCR7, human herpesvirus-8 latency-associated nuclear antigen ( LANA), Ki67 antigen (proliferation) and vascular endothelial growth factor ( VEGF) were quantitated in skin lesions from patients with AIDS-associated KS, patients with classic KS and patients with angiomas, using immunohistochemistry and quantitative image analysis (16, 21 and 20 skin lesions, respectively). Plasma CXCL12 concentrations were measured by enzyme-linked immunosorbent assay from 20 patients with AIDS- KS, 12 HIV-infected patients without KS and 13 healthy donors' samples. Results Cells positive for CXCL12, CXCR4, CXCR7, LANA, Ki67 and VEGF were significantly enriched in patients with AIDS-associated KS and classic KS vs. angiomas ( P < 0·001), and in nodular vs. macular/papular KS lesions ( P < 0·05). CXCL12, CXCR4 and CXCR7 detection correlated with LANA, Ki67 and VEGF detection ( r > 0·4; P < 0·05). However, plasma CXCL12 concentrations did not differ between patients with AIDS-associated KS, HIV-infected patients without KS, and healthy donors. Conclusions The CXCL12/ CXCR4- CXCR7 trio is upregulated in KS and correlates with KS pathophysiological markers and the severity of skin lesions. Histological assessment of the CXCL12 axis could serve as a valuable biomarker for KS diagnosis and progression. [ABSTRACT FROM AUTHOR]

Background Merkel cell polyomavirus ( MCPyV) is the main aetiological agent of Merkel cell carcinoma ( MCC). Serum antibodies against the major MCPyV capsid protein ( VP1) are detected in the general population, whereas antibodies against MCPyV oncoproteins (T antigens) have been reported specifically in patients with MCC. Objectives The primary aim was to assess whether detection of serum antibodies against MCPyV proteins at baseline was associated with disease outcome in patients with MCC. The secondary aim was to establish whether evolution of these antibodies during follow-up was associated with the course of the disease. Methods Serum T-antigen and VP1 antibodies were assessed by enzyme-linked immunosorbent assay using recombinant proteins in a cohort of 143 patients with MCC, including 84 patients with serum samples available at baseline. Results Low titres of VP1 antibodies at baseline (< 10 000) were significantly and independently associated with increased risk of recurrence [hazard ratio ( HR) 2·71, 95% confidence interval ( CI) 1·13-6·53, P = 0·026] and death ( HR 3·74, 95% CI 1·53-9·18, P = 0·004), whereas T-antigen antibodies were not found to be associated with outcome. VP1 antibodies did not differ between patients in remission and those with recurrence or progression during follow-up. However, T-antigen antibodies were more frequently detected in patients with recurrence or progression at 12 months ( P = 0·020) and 24 months ( P = 0·016) after diagnosis. Conclusions VP1 antibodies constitute a prognostic marker at baseline, whereas T-antigen antibodies constitute a marker of disease recurrence or progression if detected > 12 months after diagnosis. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented concerning first-line treatment with paclitaxel for non- HIV-related Kaposi sarcoma.

The article discusses research that assessed the efficacy of anti-tumor necrosis factor (TNF)-alpha drugs in patients with hidradenitis suppurativa (HS). Topics covered include the initial characteristics of HS patients treated with an anti-TNF-alpha drug, factors associated with a complete or partial response to first-line anti-TNF-alpha therapy, and the modest and inconsistent efficacy of the therapy for moderate-to-severe HS.

Vemurafenib is a BRAF kinase inhibitor approved for first-line treatment of metastatic BRAF (V600) -mutant melanoma. However, data on the pharmacokinetic/pharmacodynamic (PK/PD) relationship are lacking. The aim of this prospective, multicenter study was to explore the PK/PD relationship for vemurafenib in outpatients with advanced BRAF-mutated melanoma. Fifty-nine patients treated with single-agent vemurafenib were prospectively analyzed. Vemurafenib plasma concentration (n = 159) was measured at days 15, 30, 60, and 90 after treatment initiation. Clinical and biological determinants (including plasma vemurafenib concentration) for efficacy and safety were assessed using Cox's model and multivariate stepwise logistic regression. Median progression-free survival (PFS) and overall survival were 5.0 (95 % confidence interval [95 % CI] 2.0-6.0) and 11.0 (95% CI 7.0-16.0) months, respectively. Twenty-nine patients (49 %) experienced any grade ≥3 toxicity and the most frequent grade ≥2 toxicity was skin rash (37 %). Severe toxicities led to definitive discontinuation in seven patients (12 %). Grade ≥2 skin rash was not statistically associated with better objective response at day 60 (p = 0.06) and longer PFS (hazard ratio 0.47; 95 % CI 0.21-1.08; p = 0.075). Grade ≥2 skin rash was statistically increased in patients with ECOG  ≥ 1 (odds ratio 4.67; 95 % CI 1.39-15.70; p = 0.012). Vemurafenib concentration below 40.4 mg/L at day 15 was significantly associated with a shorter PFS (1.5 [0.5-5.5] vs. 4.5 [2-undetermined] months, p = 0.029). Finally, vemurafenib concentration was significantly greater in patients developing grade ≥2 rash (61.7 ± 25.0 vs. 36.3 ± 17.9 mg/L, p < 0.0001). These results suggest that early plasma drug monitoring may help identify outpatients at high risk of non-response or grade ≥ 2 skin rash. [ABSTRACT FROM AUTHOR]

Mycobacterium avium-intracellulare complex ( MAC) infections are well known in immunocompromised patients, notably in human immunodeficiency virus infection, but remain scarcely described in kidney transplantation. Moreover, cutaneous involvement in this infection is very unusual. We describe here a disseminated infection caused by MAC in a kidney transplant recipient revealed by cutaneous lesions. This case highlights the need for an exhaustive, iterative microbiologic workup in the context of an atypical disease presentation in a renal transplant patient, regardless of the degree of immunosuppression. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Dermatological side-effects in hepatitis C infected patients under a triple regimen associating pegylated interferon, ribavirin and telaprevir," in the previous issue.

Background: The optimal management of Mycobacterium chelonae disease in immunocompromised patients remains unclear. A combination of antimicrobial agents is recommended as monotherapy with clarithromycin has been associated with clinical failures due to acquired resistance. Objectives: We aim to report the efficacy and tolerability of linezolid in association with clarithromycin for the treatment of M. chelonae infections in immunocompromised patients. Methods: We describe four immunocompromised patients treated by linezolid and clarithromycin for cutaneous M. chelonae disease. Results: This combination was associated with rapid clinical efficacy in all patients with no relapse observed after a median follow-up of 2.25 years (1.4 years). However, this treatment was responsible for frequent adverse events including thrombocytopaenia, myalgia and mitochondrial toxicity. All adverse effects were reversible after linezolid discontinuation. Conclusions: We therefore suggest linezolid/clarithromycin combination as the initial therapeutic strategy for M. chelonae skin infections in immunocompromised patients. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated the potential of everolimus, a mammalian target of rapamycin (mTOR) inhibitor approved in transplantation and oncology, as alternative treatment in Kaposi sarcoma (KS). Topics include a 6-month daily treatment with everolimus resulting in a clinical response and no correlation between clinical response and whole blood everolimus concentrations.

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Kaposi sarcoma (KS) and primary effusion lymphoma (PEL) are two pathologies associated with KS herpes virus (KSHV/HHV-8) infection. KSHV genome contains several oncogenes, among which, the viral G-protein-coupled receptor (vGPCR open reading frame 74) has emerged as a major factor in KS pathogenicity. Indeed, vGPCR is a constitutively active receptor, whose expression is sufficient to drive cell transformation in vitro and tumour development in mice. However, neither the role of vGPCR in KSHV-infected B-lymphocytes nor the molecular basis for its constitutive activation is well understood. Here, we show that vGPCR expression contributes to nuclear factor-κB (NF-κB)-dependent cellular survival in both PEL cells and primary B cells from HIV-negative KS patients. We further identified within vGPCR an AP2 consensus binding motif, Y326GLF, that directs its localization between the plasma membrane and clathrin-coated vesicles. The introduction of a mutation in this site (Y326A) increased NF-κB activity and proinflammatory cytokines production. This correlated with exacerbated morphological rearrangement, migration and proliferation of non-infected monocytes. Collectively, our work raises the possibility that KSHV-infected B-lymphocytes use vGPCR to impact ultimately the immune response and communication within the tumour microenvironment in KSHV-associated pathologies. [ABSTRACT FROM AUTHOR]

Background Syphilis remains a major public health problem in Europe (both in Eastern Europe since the 1990's and in Western Europe since the re-emergence of the disease in the late 1990's-early 2000's). Methods This guideline is an update of the IUSTI: 2008 European guideline on the management of syphilis and is produced by the European Guideline Editorial Board () and EDF Guideline Committee. Results It provides recommendations concerning the diagnosis and management of syphilis in Europe. Major advances include (1) broader use of PCR, immunohistochemistry, subtyping of the etiological agent Treponema pallidum subspecies pallidum, new treponemal tests, and rapid-point-of-care ( POC) tests detecting both treponemal and non-treponemal antibodies, (2) more flexible options for screening ( TT- treponemal test- first or NTT - non treponemal test- first or both TT and NTT), and (3) procaine penicillin is no longer the first line therapy option in any phase of the disease, i.e. long acting penicillin G (i.e. benzathine penicillin G- BPG) is the only first line therapy regimen in early syphilis and in late latent syphilis. Conclusions Syphilis is a disease that is relatively easy to detect by appropriate serological tests, however, all laboratory results should be considered together with clinical data and sexual risk anamnesis. Syphilis is also easy to treat with BPG. A major concern about the supply of BPG in many European countries could threaten the efficacy of the policies of eradication of the disease in Europe. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Merkel cell polyomavirus has been recognized to be associated with Merkel cell carcinoma ( MCC), but the evolution of this cancer probably depends on various factors. Vitamin D deficiency, defined by serum 25-hydroxyvitamin D levels <50 nmol/L, seems to influence cancer behavior and progression, but has never been assessed in MCC patients. Objectives First, to evaluate whether vitamin D deficiency was associated with tumor characteristics and prognosis in a cohort of MCC patients. Second, to assess expression of the vitamin D receptor ( VDR) in MCC tumors. Methods Clinical findings, Merkel cell polyomavirus markers and vitamin D status were assessed in a cohort of French MCC patients. The study was limited to the 89 patients for whom the serum sample had been collected within 3 years after the diagnosis of MCC. Correlation between vitamin D deficiency and MCC characteristics and outcome were determined in regression analyses. VDR expression in MCC tumours was assessed by immunohistochemistry. Results Vitamin D deficiency was noted in 65.1% of the patients and was independently associated with greater tumor size at diagnosis ( P = 0.006) and with metastasis recurrence ( HR, 2.89; 95% CI, 1.03 to 8.13; P = 0.043), but not with death from MCC, although there was a trend ( HR, 5.28; 95% CI, 0.75 to 36.96; P = 0.093). VDR was found to be strongly expressed in all 28 MCC tumor specimens investigated. Conclusion The association between vitamin D deficiency and MCC characteristics and outcome, together with detection of the VDR in MCC cells, suggest that vitamin D could influence the biology of MCC. [ABSTRACT FROM AUTHOR]

In the setting of protein C deficiency, skin necrosis, which occurs most often at the initial phase of oral anticoagulants therapy, is a rare side effect. Six cases have previously been reported in the literature. In this case report, we present a protein C deficient 42-year-old woman who was being treated for venous thrombosis. Five days after the initiation of oral anticoagulant treatment, she developed extensive skin necrosis on her left calf, followed by a painful leg ulcer. The pathogenesis underlying skin necrosis caused by anticoagulation therapy is still not clear. Despite only a few cases being reported in the literature, it is important to recognise this complication since adequate therapeutic approaches leading to a stable anticoagulation state may prevent it. [ABSTRACT FROM AUTHOR]

Vemurafenib, a selective BRAF (v-raf murine sarcoma viral oncogene homologue B1) kinase inhibitor, is a new targeted biotherapy that improves survival in patients with metastatic melanomas harbouring the BRAF V600E mutation. However, this drug has significant dermatological adverse effects. We report a new severe cutaneous reaction to this drug associated with acute kidney injury ( AKI). Four patients presented a generalized grade 3 ( Common Terminology Criteria for Adverse Events) erythematous eruption with hyperkeratosis pilaris, 5-14 days after the introduction of vemurafenib. These symptoms were associated with AKI in all cases and transitory hypereosinophilia in two cases. Vemurafenib treatment was stopped in three patients and the dose was reduced in the fourth, leading to a gradual improvement of skin symptoms and renal function. Positron-emission tomography scans showed a complete response in three cases and a major response in one case. Vemurafenib was reintroduced at a lower dose, without a relapse of the rash, but renal function again deteriorated. Thus, we report a cluster of four cases of AKI associated with similar, severe, grade 3 cutaneous drug reactions related to vemurafenib. [ABSTRACT FROM AUTHOR]

We report the observation of cutaneous Kaposi's sarcoma (KS) worsening during the second trimester of pregnancy in 2 African women. Both patients were tested seronegative for HIV. They had no complication during their pregnancy, and no evidence of extracutaneous disease was found, allowing therapeutic abstention. They gave birth to healthy children showing no clinical evidence of human herpesvirus 8 (HHV-8) infection. Based on these observations and on the review of the literature, we discuss the risk of vertical transmission of HHV-8 as well as the impact of pregnancy on KS. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The incidence of severe infections is increased under biologic therapies and the skin is the second localization. Objective: To appraise the factors associated with severe skin infections (SSI) in patients under biologic therapies for inflammatory rheumatic diseases (IRD). Methods: We performed a case-control (ratio 1:3) study nested in a prospective cohort of patients with IRD. SSI was defined as requiring hospitalization or intravenous anti-infectious therapy. We defined two imbedded periods: period A was the time window between the first biologic therapy and the SSI; period B was the last 3 or 12 months (for tumor necrosis factor blockers or rituximab, respectively) before the SSI. Results: Among 4,361 patients with IRD, 29 had a SSI under biologic therapy. In multivariate analyses, SSI were significantly associated with smoking, baseline C-reactive protein and gammaglobulinemia, non-steroidal anti-inflammatory drugs before biologic therapy, cumulative dose of steroids, concomitant steroids during period A, number of different biologic therapies during period A, treatment with infliximab during period A, period B or as first biologic therapy and treatment at high dose during period B. Conclusion: In patients under biologic therapies for IRD, the risk of SSI is associated with several factors including tobacco, treatment with infliximab or high dose range. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Summary 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. [ABSTRACT FROM AUTHOR]

Kaposi Sarcoma (KS) are opportunistic tumors, associated with human herpes virus 8 (HHV8) infection. KS development is highly favored by immune-depression and remains the second most frequent tumor in acquired immune deficiency syndrome patients. Although it has been shown that experimental expression of the HHV8 G-protein-coupled receptor (vGPCR) in the endothelial compartment is alone sufficient to recapitulate the formation and progression of KS-like lesions, its functional effects on endothelial homeostasis are not fully understood. Here we show that vGPCR expression in endothelial cells induces an increase in paracellular permeability both in vivo and in vitro. By using pharmacological inhibitors and small interference RNA-based knockdown, we demonstrate an essential role for the PI(3)Kinase-γ/Rac nexus in vGPCR-mediated permeability. This was further accompanied by dramatic remodeling of VE-cadherin-dependent cell-cell junctions. Importantly, this in vitro vGPCR-initiated signaling signature was observed in a large panel of human KS. Altogether, our results support the hypothesis that endothelial vGPCR signaling is co-opted in KS, and unveil new key cellular targets for therapeutic intervention. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented that discusses development of classical Kaposi sarcoma through anti-hypertensive renin-angiotensin system inhibitors.

The article presents a case study of a 38 year old woman who received Subcutaneous (SC) injection of Bortezomib for multiple myeloma (MM). Topics discussed include histology showing fibrinoid necrosis of capillaries with thrombosis, presence of eccrine ischaemia compatible with diagnosis of Nicolau vasculitis and Bortezomib being reintroduced intravenously with no signs of relapse after skin was completely healed.

Background Human immunodeficiency virus (HIV)+ patients have an increased risk of anogenital warts. High-risk (HR) human papillomaviruses (HPVs), especially types 16 and 18, are major risk factors for precancerous and cancerous lesions of the anogenital tract, while low-risk (LR) HPVs are associated with benign lesions. Cure of genital warts with ablative techniques, surgical excision, podophyllotoxin or trichloroacetic acid is frequently difficult. Treatment with imiquimod cream showed a total clearance of external genital or perianal warts in about 50% of immunocompetent subjects. However, total clearance was reduced in HIV+ subjects not treated with highly active antiretroviral therapy (HAART). Objectives To assess clinically and by monitoring HPV content the efficacy of 5% topical imiquimod to treat anogenital warts in HIV+ subjects with at least partially restored immune functions. Methods Fifty HIV+ patients successfully treated with HAART (total CD4+ cells ≥ 200 cells mm−3 and plasma HIV RNA load < 104 copies mL−1) with anogenital warts were included. Imiquimod 5% cream was applied on external genital or perianal warts three times weekly for up to 16 weeks. Warts were tested at entry and after treatment for human LR- and HR-HPV DNA. Results Total wart clearance was observed in 16 of 50 (32%) patients at week 16. At enrolment, HPV DNA was present in more than 90% of lesions with a majority of lesions co-infected by HR- and LR-HPV. At study end, the HPV load decreased or became undetectable in 40% of cases studied. Conclusions Imiquimod 5% cream did not show safety concerns and is suitable for use in HIV+ subjects with anogenital warts and successful HAART treatment. [ABSTRACT FROM AUTHOR]

Background Among heterosexuals, the sexual transmission of human herpesvirus 8 (HHV8) has not been established. Objectives To assess HHV8 seroprevalence in spouses of patients with classic and endemic Kaposi sarcoma (KS) and to suggest possible routes of transmission. Methods A case–control study was carried out in a teaching hospital among spouses of human immunodeficiency virus-negative patients with KS (cases – exposed subjects) and controls who did not have KS nor were related to patients with KS (nonexposed subjects). HHV8 seroprevalence in spouses of patients with KS was compared with HHV8 seroprevalence in controls matched for age, gender and place of birth. Other serology tests were compared between cases and controls. Among heterosexual couples, HHV8-seropositive and HHV8-seronegative spouses were compared for possible risk factors for virus transmission. Results HHV8 seroprevalence was significantly higher among spouses of patients with KS (13 of 22; 59%) than among matched controls (19 of 58; 33%; P = 0·043). Among heterosexual couples, five of five (100%) male spouses were HHV8 positive vs. six of 15 (40%) female spouses ( P = 0·04). There was no significant difference between HHV8-seropositive and HHV8-seronegative spouses for all other factors screened for among heterosexual couples. Conclusions Being a spouse of a patient with KS is a risk factor for HHV8 seropositivity. Our results suggest that female-to-male HHV8 transmission could be more efficient than male-to-female transmission among couples including a patient with KS. Transmission could involve distinctive behaviours, or currently unknown biological properties of HHV8. [ABSTRACT FROM AUTHOR]

A letter to the editor offering information on the testing for levamisole and diagnosis of levamisole-related panniculitis is presented.

We report the case of an 83-year-old French woman with multiple melanomas showing a severe DNA repair deficiency, corrected after transfection by XPC cDNA. Two biallelic mutations in the XPC gene are reported: an inactivating frameshift mutation in exon 15 (c.2544delG, p.W848X) and a missense mutation in exon 11 (c.2108 C>T, P703L). We demonstrate that these new mutations are involved in the DNA repair deficiency and confirm the diagnosis of xeroderma pigmentosum from complementation group C (XP-C). We speculate that the coexistence of a MC1R variant may be involved in the phenotype of multiple melanomas and that the unusual long-term survival may be related to a lower ultraviolet radiation exposure and to a regular clinical follow-up. This patient appears to be the first French Caucasian XP-C case and one of the oldest living patients with XP reported worldwide. [ABSTRACT FROM AUTHOR]

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Background Quinolone-resistant Neisseria gonorrhoeae (QRNG) rates are increasing worldwide. Objectives (i) To assess the rate of QRNG among patients referred to a venereology clinic in Paris between 2000 and 2004; and (ii) to assess associated epidemiological factors. Methods Retrospective study of consecutive cases over 2000–2004. Indications and techniques of swabbing and culture were constant over 2000–2004. Susceptibility of N. gonorrhoeae was tested to six antibiotics: ciprofloxacin, amoxicillin, cefotaxime, tetracycline, erythromycin, and spectinomycin. Epidemiological data and anatomical site of N. gonorrhoeae infection were collected. Results Annual numbers of cases decreased ( P < 10−4) from 2000 ( n = 41) to 2002 ( n = 12), then increased ( P < 10−4) in 2004 ( n = 60). Anorectal gonorrhoea was more frequent in 2003–2004 (22.0%, n = 18/82) than in 2000–2002 (3.9%, n = 3/76). QRNG rates increased from the period 2000–2002 (1.3%) to 2003 (22.7%, P < 0.01), and 2004 (30.2%, P < 0.005). All QRNG strains had a minimal inhibitory concentration of ciprofloxacin > 1.0 mg/L, thus fitting the international definition of quinolone resistance. There were no significant changes in rates of N. gonorrhoeae resistance to the five other antibiotics. QRNG tended to be more frequent among men who have sex with men (MSM; 16.7% vs. 7.1%), HIV-infected patient (20.5% vs. 11.9%), and patients having more than five partners during the last year (24.4% vs. 17.1%), but statistical significance was not reached in multivariate analyses. Conclusion We recommend (i) avoiding fluoroquinolones as first-line treatment for N. gonorrhoeae infections in Paris; (ii) that first-line treatment relies on third-generation cephalosporins or spectinomycin; and (iii) reinforcing targeted screening and prevention of gonorrhoea, especially among HIV-positive patients and MSM. [ABSTRACT FROM AUTHOR]

Background. Kaposi sarcoma (KS) occurs mainly in immunocompromised patients and is strongly associated with infection with human herpesvirus 8 (HHV-8; also known as 'KS-associated herpesvirus'). We hypothesized that KS is linked to deficiencies in specific anti-HHV-8 T cell immunity. Methods. We studied asymptomatic HHV-8 carriers coinfected with human immunodeficiency virus (HIV; n=23) and patients with HIV-related or classic KS (n=29). We used an interferon-gamma enzyme-linked immunospot assay with 56 specific peptides distributed on 6 HHV-8 proteins (glycoprotein [gp] B, gpH, gp35/37, latent nuclear antigen 1 [LANA-1], K12, and K15) to detect HHV-8-specific T cell responses. Results. We found that patients with KS responded to these peptides less often and had much lower HHV-8-specific T cells counts than did asymptomatic HHV-8 carriers (P=.001 and P=.0004, respectively), regardless of CD4 T cell count or HHV-8 load. The frequency of Epstein-Barr virus-specific T cells was similar in both groups. Conclusions. Our results suggest that HIV-related and classic KS are associated with a lack of HHV-8-specific T cells. Also, we have described 8 new HHV-8 T cell epitopes in LANA-1, K12, and K15, including 2 CD4 T cell epitopes. These data provide new insight into HHV-8 cellular immunity. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

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]

Results of first-principles (FP) total energy calculations for 32 different configurations of the μ phase in the binary system Nb–Ni are used in the compound energy formalism (CEF) to model finite-temperature thermodynamic properties. A comparison with Cluster Expansion Hamiltonian–Cluster Variation Method (CEH-CVM) calculations indicates that the CEF describes temperature-dependent site occupancies as well as the CEH-CVM within the temperature range of interest for applications. This suggests that the Bragg–Williams–Gorsky approximation (BWGA) used in the CEF is sufficient to describe site occupancies and thermodynamics of the μ phase. A phase diagram is calculated using the μ phase description derived in the present work together with a previous Calphad description for the other phases of this system. The FP-CEF approach significantly improves the description of the thermodynamic properties as a function of composition compared to the Calphad procedure generally used up to now. [ABSTRACT FROM AUTHOR]

Highly active antiretroviral therapy (HAART) reduces the incidence and improves the prognosis of Kaposi's sarcoma (KS). This study was designed to identify factors associated with KS clinical responses in HIV-infected patients during HAART. We reviewed the files of 138 HIV-1-infected patients with KS. Epidemiologic and HIV-related clinical and biological parameters were recorded at KS diagnosis (baseline) and every 6 months thereafter. In a subset of 73 antiretroviral-naive patients, we compared the clinical outcome of KS according to the use or nonuse of protease inhibitors (PI). After 6 months of follow-up, KS remission was more frequent in patients who were naive of HAART and who were at ACTG stage S0 at baseline (P=0.03 and 0.02). Undetectable HIV viral load was strongly associated with KS remission (P0.004 at all time points), while CD4 cell count was not. Among the 73 antiretroviral-naive patients at baseline, and who were studied for 24 months, KS outcome did not differ between patients who were prescribed PI-containing and PI-sparing regimens. Intercurrent multicentric Castleman's disease was associated with poor outcome after 60 months of follow-up (P0.0001). Fourteen deaths occurred after a median follow-up of 37.5 months, eight of which were KS related. Suppression of HIV replication appears to be crucial to control KS. Non-PI-based regimens were equivalent to PI-based regimens as regards the clinical and virological outcome of antiretroviral-naive HIV-infected patients with KS.British Journal of Cancer (2006) 94, 1000–1006. doi:10.1038/sj.bjc.6603056 www.bjcancer.com Published online 28 March 2006 [ABSTRACT FROM AUTHOR]

To study the possible influence of patient characteristics on abacavir pharmacokinetics.A population pharmacokinetic model for abacavir was developed using data from 188 adult patients by the use of a nonlinear mixed effects modelling method performed with NONMEM.Abacavir pharmacokinetics was well described by a two-compartment open model with linear absorption and elimination. Typical population estimates for the absorption rate constant (Ka), the apparent central distribution volume (Vc/F), the apparent peripheral distribution volume (Vp/F), the apparent intercompartmental clearance (Q/F) and the apparent plasma clearance (CL/F) were 1.8 h−1, 75 l, 23.6 l, 10 l h−1 and 47.5 l h−1, respectively. Apparent plasma clearance was positively related to bodyweight. Individual Bayesian estimates of CL/F were used to calculate abacavir AUC. The latter decreased from 10.7 ± 5.0 to 5.7 ± 1.6 mgh l−1 when bodyweight increased from 36 to 102 kg. This drop in abacavir exposure could lead to suboptimal treatment for the heaviest patients, as antiviral efficacy of abacavir is known to be related to its AUC. A 400 mg abacavir dose would be necessary to achieve adequate exposure to abacavir in patients weighing more than 60 kg.The apparent plasma clearance of abacavir was positively related to bodyweight. The efficacy of the current recommended abacavir dosage for patients with high bodyweight should be evaluated in further studies. [ABSTRACT FROM AUTHOR]