Folliculitis decalvans is characterized by a persistent, abnormal subepidermal microbiota.

Folliculitis decalvans (FD) is a chronic inflammatory disease of unknown aetiology. Although Staphylococcus aureus, frequently found on lesional skin, is thought to play a causal role, the importance of its involvement remains controversial. To examine the role of S aureus, we compared superficial and subepidermal microbiota in 20 FD patients who had S aureus on lesional skin and in 20 healthy controls using culture techniques and genomic identification, before and after an anti-staphylococcal treatment; we also screened for S aureus virulence factors. When present on lesional skin, S aureus colonized non-lesional and subepidermal skin in 80% of cases. These data imply a break in the epidermal barrier integrity and that an abnormal non-lesional skin microbiota persists in FD. S aureus had no superantigenic toxin in 31% of cases and no toxin specificity. Clinical improvement obtained in most cases upon treatment was associated with the disappearance of S aureus in all studied areas, with an incomplete restoration of normal microbiota and a significant increase in negative bacterial samples. This persistent unbalanced, subepidermal microbiota may act as a reservoir of abnormal flora and explain the chronicity of FD, suggesting new avenues of research to restore normal microbiota.

Direct Approach to Quantum Tunneling.

The decay rates of quasistable states in quantum field theories are usually calculated using instanton methods. Standard derivations of these methods rely in a crucial way upon deformations and analytic continuations of the physical potential and on the saddle-point approximation. While the resulting procedure can be checked against other semiclassical approaches in some one-dimensional cases, it is challenging to trace the role of the relevant physical scales, and any intuitive handle on the precision of the approximations involved is at best obscure. In this Letter, we use a physical definition of the tunneling probability to derive a formula for the decay rate in both quantum mechanics and quantum field theory directly from the Minkowski path integral, without reference to unphysical deformations of the potential. There are numerous benefits to this approach, from nonperturbative applications to precision calculations and aesthetic simplicity.

Evolution in technique: use of hyalurostructure for lips rejuvenation as an alternative to needle injection without troncular anesthesia.

PURPOSE: To enhance lips ageing rejuvenation with specific microcannula and hyaluronic acid. METHOD: Clinical review was conducted from December 2010 to December 2011 among 46 patients complaining of predictable changes on lips and perioral region such as deficiency in contour definition, volume and projection. Lips rejuvenation injections were made using the hyalurostructure technique. RESULTS: Forty-two patients (92%) with a 6-month follow-up were satisfied or very satisfied with the aesthetic results after the hyalurostructure of the lips and the perioral region rejuvenation. The use of the specially designed cannula led to fewer complications. We noticed 40 oedemas (87%) that appeared 24-48 h after the injection and seven patients (15.2%) with haematomas. We noted fewer surface irregularities and a better distribution of the product. Patients' records showed the procedure was painless. CONCLUSION: The hyalurostructure technique reduces the number of punctures compared to that of the conventional method. The microcannula's blunt tip reduces the risks of intravascular injection of the substance and of reach and disruption of the key structures like vessels and nerves. Results revealed that the hyalurostructure used for lips rejuvenation and helps to maintain a natural effect and avoids pain.

The Emervel French survey: a prospective real-practice descriptive study of 1,822 patients treated for facial rejuvenation with a new hyaluronic acid filler.

BACKGROUND: Emervel consists of a range of 5 hyaluronic acid (HA) fillers (Touch, Classic, Lips, Deep, and Volume), with a fixed HA concentration (20 mg/mL), and various degrees of cross-linking and calibration. OBJECTIVES: To describe the current use of Emervel fillers in France. METHODS: Prospective multicenter, cross-sectional, real-practice, descriptive survey, including 1,822 patients injected with Emervel fillers for face rejuvenation by 58 French physicians between September 2010 and July 2011. The injection modalities were left to the respective physician's discretion. RESULTS: The physicians were dermatologists (52.3%), surgeons (43.8%), or general practitioners (14.1%). Nasolabial folds (NLF) with a mean severity 2.4 were mainly injected with Emervel Deep (51.0%) and Emervel Classic (36.0%) (mean volume: 1.0 mL), and primarily with the linear retrograde (LR) technique (89.3%). Marionette lines (ML), with a mean severity 2.6 were mainly injected with Emervel Deep (52.5%) and Emervel Classic (34.6%) (mean volume: 0.8 mL), and mainly with the LR technique (79.5%). More than 90% of patients had scores of 0 or 1 for erythema, bruising, edema, and pain. No serious adverse events were reported up to 15 months after the injection. CONCLUSION: These data could contribute to upcoming international consensus on optimal injection modalities of the Emervel range of HA fillers.

The France-PDT study: a national prospective observational cohort survey on the use of methyl-aminolevulinate photodynamic therapy in France, with up to 6-month follow-up.

BACKGROUND: The efficacy and safety of MAL-PDT have been shown in actinic keratoses (AK), basal cell carcinoma (BCC), and Bowen's disease (BD). OBJECTIVES: To appraise the current use of MAL-PDT in France. METHODS: National prospective cohort survey, including 583 patients treated for the first time with MAL-PDT. Clinical and treatment data were collected at baseline, month 3, and month 6 if applicable. The primary objective was to estimate the rate of misuse of MAL, defined as divergence from the French Summary of Product Characteristics. RESULTS: Of 174 contacted physicians, 66 agreed to participate in the study, and 56 included at least one patient. Among the 456 patients included in the observational cohort, 203 had AK, 130 had BCC, and 63 had BD. Referring to the French SPC of Metvixia®, the MAL-PDT was misused in 48.7% of BCC, 25.6% of AK and 23.4% of BD. The main criteria for misuse in BCC were the performance of two rather than one lighting sessions at baseline cure. The main criteria for misuse in AK were the duration of lighting and the performance of 2 rather than 1 lighting sessions at baseline cure. The main criteria for misuse in BD were the performance of 1 rather than 2 lighting sessions at baseline cure and the duration of illumination. CONCLUSION: Contrasting with the French label, nearly one third of French dermatologists treat BCC with two sessions, as recommended at European level and in Australia. International consensus guidelines are needed to homogenize and rationalize current use of MAL-PDT.

[Syphilis]. / Syphilis.

Syphilis is back since 2000. Early syphilis comprises primary syphilis, secondary syphilis and early latent syphilis (less than 1 year duration). During early phases of syphilis, patients are more contagious and neurologic complications are rare. Early neurosyphilis are mostly represented by uveitis or cranial nerves lesions. Treatment of non-neurologic syphilis are based on intramusculary injection of benzathine-penicilline G: one injection in case of early syphilis, three injections in case of late syphilis. The follow-up after treatment is based on clinical evolution and the titer of VDRL. Intravenously infusion of penicillin G is the only treatment recommended for neurosyphilis.

Effect of early syphilis infection on plasma viral load and CD4 cell count in human immunodeficiency virus-infected men: results from the FHDH-ANRS CO4 cohort.

BACKGROUND: Concomitant syphilis and human immunodeficiency virus (HIV) infection is increasingly frequent in industrialized countries. METHODS: From a large hospital cohort of HIV-infected patients followed up in the Paris area between 1998 and 2006, we examined the effect of early syphilis on plasma HIV-1 RNA levels and CD4 cell counts. We compared 282 HIV-1-infected men diagnosed as having incident primary or secondary syphilis with 1233 syphilis-free men matched for age (±5 years), sexual orientation, participating center, length of follow-up (±6 months), and immunologic and virologic status before the date of syphilis diagnosis (index date). Increase in viral load (VL) (plasma HIV-1 RNA) of at least 0.5 log or a rise to greater than 500 copies/mL in patients with previously controlled VL during the 6 months after the index date was analyzed, as were CD4 cell count variations and CD4 slope after the index date. RESULTS: During the 6 months after the index date, VL increase was observed in 77 men with syphilis (27.3%) and in 205 syphilis-free men (16.6%) (adjusted odds ratio [aOR], 1.87; 95% CI, 1.40-2.49). Even in men with a VL of less than 500 copies/mL undergoing antiretroviral therapy, syphilis was associated with a higher risk of VL increase (aOR, 1.52; 95% CI, 1.02-2.26). The CD4 cell count decreased significantly (mean, -28/µL) compared with the syphilis-free group during the syphilis episode (P = .001) but returned to previous levels thereafter. CONCLUSIONS: In HIV-infected men, syphilis was associated with a slight and transient decrease in the CD4 cell count and with an increase in VL, which implies that syphilis may increase the risk of HIV transmission, even in patients receiving antiretroviral therapy and with a VL of less than 500 copies/mL.

Oculofacial contour asymmetries: Management of combined treatment with hyalurostructure and botulinum toxin injections.

PURPOSE: To assess the long-term results of the treatment of oculofacial asymmetries using a combined injection schedule for injections of hyaluronic acid, with a specific micro cannula and botulinum toxin. METHOD: A retrospective study was conducted from January 2009 to January 2010. Patients were treated in the Alcazar Eye Clinic and Oculoplastic Department in Princess Grace Hospital, Monaco. We selected patients complaining of asymmetrical periorbital features who received treatment with hyalurostructure and botulinum toxin injection in one or more sessions. Nine patients were selected and presented with the following symptoms: asymmetry of eyebrow position (2 patients), superior orbital hollow (2 patients), tear trough (2 patients) and orbital volume (ocular prosthesis) (3 patients). The objective was to evaluate the efficiency of combined treatment in one or more sessions on these oculofacial asymmetries. Hyaluronic acid injections were done using hyalurostructure. Hyaluronic acid gel (Restylane Lidocaine) was used with a 25 gauge reinforced micro-cannula (pix'l +, Thiebaud). This was combined with injections of botulinum toxin (azzalure*) to areas of muscular hyperaction. Follow-up was done at 1 year by clinical examination, photography and patient satisfaction. Complications of this combined treatment have been identified. RESULTS: At 1-year follow-up, 88% of patients were satisfied or very satisfied with their results. There were no more complications secondary to both treatments in the same session. It was not noticed more hematomas and bruises than in classical injection method. The action of toxin is constant over time despite the association of hyaluronic acid injections. CONCLUSION: Combined treatments with toxin and hyaluronic acid in oculofacial asymmetries are efficient and can be proposed in the same session. These treatments must be repeated to maintain and optimize muscle contraction and volume loss. Use of hyalurostructure and botulinum toxin treatment in the same session is effective and safe.

Progressive upregulation of PD-1 in primary and metastatic melanomas associated with blunted TCR signaling in infiltrating T lymphocytes.

Programmed death-1 (PD-1) is involved in T-cell tolerance to self-antigens. For some cancers, it has been suggested that the expression of a ligand of PD-1, namely PD-L1, could contribute to tumor escape from immune destruction. Nevertheless, the relationship between PD-1 expression on tumor-infiltrating T lymphocytes (TILs), disease stage, and TIL responsiveness is still poorly documented. In this study, we show that freshly isolated CD4(+) and CD8(+) TILs express substantial levels of PD-1 in primary melanomas. The expression of PD-1 was further increased at later stages in distant cutaneous metastases, especially on CD8(+) TILs. The expression of PD-1 ligands was frequent only in metastases, on both tumor cells and tumor-derived myeloid cells. TILs isolated from these cutaneous tumors are poorly reactive ex vivo, with blunted calcium response and IFN-γ production after TCR stimulation. Surprisingly, in distinct parts of a primary melanoma, either invasive or regressing, we show that TILs similarly express PD-1 and remain dysfunctional. The expressions of PD-1 and PD-L1 in metastatic melanoma lesions could be considered as witnesses of an unsuccessful anti-tumoral immune response, but the direct involvement of PD-1 in the severity of the disease, and the importance of TILs in tumor regression, remain to be established.

Mediastinal tuberculosis in an adult patient with cystic fibrosis.

Tuberculosis (TB) is rarely observed in cystic fibrosis (CF) patients. We report the first case of mediastinal TB, associated with leg pain and skin rash, in an adult patient with CF, and discuss factors suggestive of TB in the course of CF.

Origins of syphilis and management in the immunocompetent patient: facts and controversies.

Despite the continued efficacy of penicillin since the 1940s, many aspects of the natural history, diagnosis, and management of syphilis remain controversial. A key factor among the numerous factors explaining the persistence of significant areas of controversies is the absence of a gold standard direct method for distinguishing between the different stages of syphilis and appraising treatment response. This contribution presents an overview of some of the most debated aspects of the origins, diagnosis, and management of syphilis in immunocompetent patients. The two main current hypotheses on the origins of Treponema pallidum are the "Columbian" and the "Pre-Columbian" hypotheses. Strong evidence supports that Columbus' crew brought T pallidum to Europe at the time of discovery of the New World. Because T pallidum culture and inoculation to animals are not readily available methods, the gold standard method for the diagnosis of syphilis is the direct identification of T pallidum by dark field microscopy or direct fluorescent antibody tests. These methods, however, are inapplicable in many patients, and thus the diagnosis of syphilis is usually based on the clinical and serologic picture. Serologic tests should only be considered as surrogate markers of the disease and do not provide definite distinction between syphilis stages. The optimal combination of serologic tests is still undefined. Other areas of controversy include the identification of patients who would benefit from a lumbar puncture, the diagnostic criteria of neurosyphilis, and the most relevant markers of treatment response.

Management of syphilis in the HIV-infected patient: facts and controversies.

After reaching an all time low at the turn of the millennium in several industrialized countries, the syphilis incidence is rising again, perhaps as a consequence of unsafe sexual behavior in response to improved antiretroviral therapeutic options for HIV. Since the beginning of the HIV pandemic, numerous reports on the various aspects of the interaction between syphilis and HIV have been published. Controversies persist on many issues of the management of coinfected patients. This contribution presents a critical appraisal of the available literature. Few large-scale, properly designed, controlled studies have compared syphilis baseline presentation and treatment response according to HIV status. Among the weakness are (1) high rates of patients lost to follow-up, (2) lack of long-term follow-up, (3) lack of gold standard criteria for treatment response, (4) small sample size, and (5) lack of stratification according to syphilis stage, ongoing antiretroviral treatment, CD4 cell count and HIV viral load. From the available data, and given the ever-possible publication bias, we conclude that if HIV has an effect on the course of syphilis, it is small and clinically manageable in most cases. The controversial issues discussed should furnish the rational for clinical research during the forthcoming decade.

Ustekinumab for the treatment of psoriasis: review of three multicenter clinical trials.

Ustekinumab, a fully human monoclonal antibody that binds to the p40 subunit of IL-12 and IL-23, has been recently approved in Europe and the U.S. for the treatment of moderate to severe plaque psoriasis. The efficacy and safety of ustekinumab have been demonstrated in three randomized phase III clinical trials, which are reviewed herein. In the PHOENIX 1 and 2 trials, significantly more patients achieved a PASI 75 response at week 12 on ustekinumab 45 mg (67.1% and 66.7%, respectively) or 90 mg (66.4% and 75.7%, respectively) than on placebo (3.1% and 3.7%, respectively; P < 0.0001 for each comparison versus placebo, in both trials). In the ACCEPT trial, PASI 75 was achieved at week 12 by 67.5% of patients on ustekinumab 45 mg, 73.8% on ustekinumab 90 mg and 56.8% on etanercept (comparison versus etanercept: P = 0.01 and P < 0.001, respectively). Injection-site reactions were significantly more common on etanercept than on ustekinumab. These results show that ustekinumab is significantly more effective than placebo and etanercept in the short-term treatment of moderate to severe psoriasis. Its safety has also been demonstrated during 76 weeks in patients without active infection or malignancy. Long-term safety data should be provided by the ongoing follow-up of the PHOENIX 1 and 2 cohorts.

[Clinical presentation of syphilis]. / Circonstances de découverte de la syphilis.

Since the turn of the millennium, the incidence of syphilis is on the rise in France and in other developed countries. The majority of syphilis cases currently occur in men having sex with men and half of the cases occur in HIV-positive patients. Multiple partners and non protected intercourses are frequently reported. About 80% of syphilis recently diagnosed in France are symptomatic and correspond to primary or secondary syphilis. The other potential circumstances of diagnosis of syphilis include the presence of risk factors, an intercourse with an infected partner, the serological follow-up of a previous syphilis and a systematic screening during pregnancy. Clinical features are mainly represented by skin and mucosal lesions. However, extra-cutaneous involvement and biological abnormalities are quite frequent during secondary syphilis especially ophthalmic complications which are source of sequelae due to the delay for diagnosis. In the post-HAART era, it seems that clinical presentation and serological response after treatment is similar in HIV infected patients in comparison to HIV uninfected patients and that patients with early syphilis shoud be treated with one dose of benzathine penicillin G while the unique treatment for neurosyphilis is intravenous penicilline G.

The historical basis of a misconception leading to undertreating atopic dermatitis (eczema): facts and controversies.

The quest for clarifying the pathophysiology of atopic dermatitis (eczema) has lasted for 25 centuries. Yearning to discern the primum movens of atopic dermatitis, physicians aimed to identify the curative therapy. Recent scientific efforts has brought to the light an ever-growing amount of interplaying pathophysiologic factors, including the epidermal barrier, the digestive flora, food, early infections and antigenic stimulations, and innate and adaptive immune response; however, overfocusing on some of these factors, along with misconceptions about the benefit/risk balance of topical therapies, has sometimes led topical therapies being disregarded. Reviewing the history of pathophysiologic concepts, we aim to return topical therapies to the center of the clinical management of atopic dermatitis.

Pathophysiology, etiologic factors, and clinical management of oral lichen planus, part I: facts and controversies.

Lichen planus (LP) is an inflammatory disease of the stratified squamous epithelia of unknown etiology. LP affects most frequently the oral mucosa, but it may also involve other mucosa and the skin. Oral LP (OLP) most frequently affects woman aged between 30 and 60 years. Histopathologic examination typically shows orthokeratotic hyperkeratosis, basal cell degeneration, and a dense well-defined infiltrate of lymphocytes in the superficial dermis. OLP lesions may result from the induction of keratinocytes apoptosis by cytotoxic CD8+ T cells stimulated by a yet unidentified self-antigen on a genetically predisposed patient. The association of OLP with hepatitis C virus (HCV) has been more consistently demonstrated in the Mediterranean area. Although HCV RNA and HCV-specific CD4+ and CD8+ T cells have been retrieved in the mucosal lesions of patients with chronic HCV infection and OLP, the eventual pathophysiology of HCV in OLP lesions remains unclear. Available treatments of OLP are not curative, and many have potentially prominent side effects. The objectives of OLP management should be to prevent and screen for malignant transformation and alleviate symptoms on the long-term. Avoidance of potential precipitating drugs, tobacco, alcohol, and local trauma, as well as strict oral hygiene, is essential. The first-line pharmacologic treatment relies on topical steroids. Systemic steroids should be limited to the short-term cure of severe refractory OLP. Life-long clinical follow-up, at least annually, is fundamental.

Clinical and serologic baseline and follow-up features of syphilis according to HIV status in the post-HAART era.

There is a lack of large studies appraising the effect of the human immunodeficiency virus (HIV) on the course of syphilis since the advent of highly active antiretroviral therapy (HAART). We aimed to appraise the effect of HIV on clinical and serologic features of syphilis at baseline and during follow-up in the post-HAART era.We designed a retrospective cohort study of consecutive syphilis cases, diagnosed between 2000 and 2007, in an academic venereal disease center. Data were collected using standardized medical forms. Patients were treated according to the European guidelines. Serologic failure was defined as either a 4-fold rise in Venereal Disease Research Laboratory (VDRL) titers 30-400 days posttreatment or a lack of 4-fold drop in VDRL titers at 270-400 days posttreatment.Among 279 syphilis cases with informative baseline clinical and serologic data, HIV infection was significantly associated with men having sex with men, French origin, multiple partners, lesser usage of condom, history of sexually transmitted disease, early syphilis, anal primary chancre, and cutaneous eruption. Median baseline titer from the Treponema pallidum hemagglutination assay (TPHA) was higher in HIV-infected patients (p = 0.02).Among 144 informative syphilis cases, there was a nonsignificant trend for a lower rate of serologic response among HIV-positive patients (91.8% vs. 98.3%, p = 0.14). Serologic failure was significantly associated with a history of previous syphilis (p < 0.05). The median delay to serologic response was similar in HIV-positive (117 d) and in HIV-negative (123 d) patients (p = 0.44).We conclude that for patients under HAART treatment, the effect of HIV on serologic response to syphilis treatment is likely minimal or absent.

Neisseria gonorrhoeae antibiotic resistance in Paris, 2005 to 2007: implications for treatment guidelines.

Quinolone-resistant Neisseria gonorrhoeae rates have increased worldwide since 1994. The objective of this study was to appraise: (i) the antimicrobial susceptibility of Neisseria gonorrhoeae in a venereology clinic in Paris, between 2005 and 2007; and (ii) the factors associated with quinolone-resistant N. gonorrhoeae. A prospective study of consecutive cases was performed for the period 2005 to 2007. Susceptibility of N. gonorrhoeae to five antibiotics (ciprofloxacin, ceftriaxone, spectinomycin, penicillin G and tetracycline) was tested systematically. Clinical and epidemiological data were collected using a standardized form. Male-to-female sex ratio was 22.0. Median age was 30.0 years. Of 115 cases, 84 occurred in men having sex with men (72.6%) and 22 involved the anorectal area (19.1%). The rate of quinolone-resistant N. gonorrhoeae was 37.4% (43/115), without significant association with gender, age, sexual behaviour, past history of sexually transmitted diseases and susceptibility to other antibiotics. All N. gonorrhoeae were susceptible to ceftriaxone and spectinomycin. The rate of quinolone-resistant N. gonorrhoeae in Paris has been increasing since 2004. Ceftriaxone remains the gold standard treatment.

Predictive factors of eczema-like eruptions among patients without cutaneous psoriasis receiving infliximab: a cohort study of 92 patients.

BACKGROUND: Anti-tumor-necrosis-factor-alpha agents are limited by their side effects. Eczema is one of the most frequent adverse reactions affecting quality of life. OBJECTIVE: To assess potential predictive risk factors for eczema in patients receiving infliximab. METHODS: We conducted a prospective cohort study including patients treated with infliximab for a variety of disorders with the exception of cutaneous psoriasis. Clinical features were compared among patients with and without eczema under therapy. RESULTS: 92 consecutive patients were included; 15 developed eczema after the initiation of infliximab. In univariate analyses, a personal history of atopic symptoms was the only predictive factor for the occurrence of eczema (odds ratio = 3.6). Sex, age, principal diagnosis, dose and duration of infliximab and concomitant use of other immunosuppressors had no influence on the occurrence of eczema. CONCLUSIONS: A personal history of atopic symptoms is predictive of eczema under infliximab. Specific information should be provided to atopic patients starting such a treatment.