Surveillance of Antibiotic Resistance Genes in Treponema Pallidum Subspecies Pallidum from Patients with Early Syphilis in France.

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

Elvitegravir-Cobicistat-Emtricitabine-Tenofovir Alafenamide Single-tablet Regimen for Human Immunodeficiency Virus Postexposure Prophylaxis.

We evaluated an elvitegravir-cobicistat-emtricitabine-tenofovir alafenamide single-tablet regimen for human immunodeficiency virus postexposure prophylaxis. The completion rate and adherence were good, and the tolerance was acceptable; no seroconversion was observed. We confirm that this regimen could be appropriate for postexposure prophylaxis. CLINICAL TRIALS REGISTRATION: NCT02998320.

Impregnated acetate gauze compared with lipido-colloid contact layer at dressing removal pain: a single-blind cross-over randomised control trial.

OBJECTIVE: To evaluate the performance of Jelonet Plus (JP) and UrgoTul (UT), assessing pain at dressing removal when managing acute or chronic wounds at granulation and epithelialisation stages. METHODS: This was a randomised, multicentre, controlled single-blinded study using a cross-over design. Hospitalised and ambulatory patients presenting with non-infected acute or chronic wounds (at least 40% of wound area of ≤100cm2 covered with granulation tissue) were randomly allocated to be treated with either JP or UT dressings applied according to a standardised local care procedure for two days. At the following visit, patients received the other dressing for a second 2-day period. Pain was evaluated after two days of dressing application and immediately after its removal using a 100mm Visual Analog Scale (VAS). A pain level >30mm was considered as clinically relevant. A lower limit of -12% was determined as the threshold necessary to demonstrate the non-inferiority of JP compared to UT. RESULTS: For the 99 patients completing the study, a difference of 7.9% was observed in favour of JP (83.8% JP versus 75.9% UT) for pain immediately after dressing removal (VAS score < 30mm) with a confidence interval (CI) lower limit of -2.6%, demonstrating non-inferiority (pre-defined limit of -12%). Concerning pain at dressing removal, a difference of 19.6% was observed in favour of JP (81.6% versus 62.0%; p=0.029 for superiority analysis), with a CI lower limit ranging from 2.4% to 38.9%. Therefore, superiority could be concluded. A statistically significant period effect was detected (p=0.003) with fewer patients experiencing pain after the second period day 2 (D2) to day 4 (D4) than the first day 0 (D0) to D2. A statistically significant cross-over effect was also detected (p=0.047), with fewer patients experiencing pain when JP was applied first followed by UT. This suggests a carry-over effect thus preventing a full cross-over design analysis. Adherence of the dressing was less frequent with the JP than the UT dressing (2.0% JP versus 6.9% with UT). CONCLUSION: Non-inferiority of pain at dressing removal was demonstrated with JP. Superiority on this criteria was non-significant but we found adherence of the dressing to the wound bed to be more rare.

Multi-locus sequence typing of Treponema pallidum subsp. pallidum present in clinical samples from France: Infecting treponemes are genetically diverse and belong to 18 allelic profiles.

Treponema pallidum subsp. pallidum, the causative agent of sexually transmitted syphilis, detected in clinical samples from France, was subjected to molecular typing using the recently developed Multilocus Sequence Typing system. The samples (n = 133) used in this study were collected from 2010-2016 from patients with diagnosed primary or secondary syphilis attending outpatient centers or hospitals in several locations in France. Altogether, 18 different allelic profiles were found among the fully typed samples (n = 112). There were five allelic variants identified for TP0136, 12 for TP0548, and eight for TP0705. Out of the identified alleles, one, seven, and three novel alleles were identified in TP0136, TP0548, and TP0705, respectively. Partial allelic profiles were obtained from 6 samples. The majority of samples (n = 110) belonged to the SS14-like cluster of TPA isolates while 7 clustered with Nichols-like isolates. Patients infected with Nichols-like samples were more often older (p = 0.041) and more often diagnosed with secondary syphilis (p = 0.033) compared to patients infected with SS14-like samples. In addition, macrolide resistance caused by the A2058G mutation was found to be associated with allelic profile 1.3.1 or with strains belonging to the 1.3.1 lineage (p<0.001). The genetic diversity among TPA strains infecting the European population was surprisingly high, which suggests that additional studies are needed to reveal the full genetic diversity of TPA pathogens infecting humans.

Is a specific eyelid patch test series useful? Results of a French prospective study.

BACKGROUND: Eyelids are frequent sites of contact dermatitis. No prospective study focused on eyelid allergic contact dermatitis (EACD) has yet been published, and this topic has never been studied in French patients. OBJECTIVES: To prospectively evaluate the usefulness of an eyelid series in French patients patch tested because of EACD, and to describe these patients. METHODS: We prospectively analysed standardized data for all patients referred to our departments between September 2014 and August 2016 for patch testing for suspected EACD as the main reason. All patients were patch tested with an eyelid series, the European baseline series (EBS), the French additional series, and their personal products. Patch testing with additional series and repeated open application tests (ROATs) or open tests were performed if necessary. A standardized assessment of the relevance was used, and the analysis of the results was focused on patients having positive test results with a current certain relevance. RESULTS: Two-hundred and sixty-four patients (238 women and 26 men) were included. Three-hundred and twenty-two tests gave positive results in 167 patients, 84 of whom had currently relevant reactions: 56 had currently relevant positive test reactions to the EBS, 16 had currently relevant positive test reactions to their personal products, 8 had currently relevant positive test reactions to the French additional series, and 4 had currently relevant positive test reactions to the eyelid series. Sixty-seven per cent of all relevant cases were related to cosmetic products. The most frequent allergens with current relevance were methylisothiazolinone (10.2%), fragrance mix I (3%), nickel (2.7%), hydroxyperoxides of linalool (2.7%) and limonene (2.3%), and Myroxylon pereirae (2.3%). Current atopic dermatitis was found in 9.5% of patients. The duration of dermatitis was shorter (23.2 vs 34.2 months; P = .035) in patients with currently relevant test reactions. The percentage of currently relevant tests remained the same when atopic patients or dermatitis localized only on the eyelids were taken into account. CONCLUSION: In French patients, testing for EACD with the extended baseline series and personal products, also including ROATs and use tests, appears to be adequate, considering the currently relevant positive test reactions. The regular addition of an eyelid series does not seem to be necessary.

Clinicopathologic analysis of atypical hand, foot, and mouth disease in adult patients.

BACKGROUND: Hand, foot, and mouth disease is a contagious viral infection usually affecting children. A resurgence of cases in adults, mainly caused by coxsackievirus A6 and with an atypical and more severe presentation, has taken place. OBJECTIVE: The goal was to examine the clinical, histologic, and immunohistochemical features of this disease in adults. METHODS: This is a retrospective study on documented cases of adult hand, foot, and mouth disease from France's Dermatology Department of Strasbourg University Hospital and Bel-Air Hospital in Thionville. RESULTS: Six patients with severe and atypical presentation were included, 4 caused by coxsackievirus A6. The histologic features were: spongiosis, neutrophilic exocytosis, massive keratinocyte necrosis, shadow cells in the upper epidermis, vacuolization of basal cells, necrotic cells in follicles and sweat glands, dense superficial dermal infiltrate of CD3+ lymphocytes, and strong granulysin expression. LIMITATIONS: This is a retrospective case series. CONCLUSION: In adult patients presenting with atypical hand, foot, and mouth disease caused by coxsackievirus A6, biopsy specimens show distinctive changes in the epidermis but also in adnexal structures. The inflammatory infiltrate is made of T cells with a cytotoxic profile, with numerous granulysin-positive cells, as observed in severe drug-induced eruption with necrosis of keratinocytes.

Histopathological study of six types of adverse cutaneous drug reactions using granulysin expression.

BACKGROUND: Few studies have been published on the histopathology of cutaneous adverse drug reactions (CADR), and most of these lack information on skin allergological tests. The histopathology of drug reaction with eosinophilia and systemic symptoms (DRESS) is also seldom described. The purpose of our study was to examine six types of well-documented CADR (maculopapular exanthema, DRESS, fixed drug eruption, Stevens-Johnson syndrome, toxic epidermal necrolysis [TEN], and acute generalized exanthematous pustulosis) using histopathology and immunohistochemistry to evaluate the expression of granulysin, a key molecule in TEN. METHODS: We retrospectively included 106 skin biopsies performed in proven cases of CADR (by chronological investigation, single attributable drug, or/and skin tests). All slides were reviewed, and microscopic changes were analyzed using a standardized form. Granulysin expression was studied by immunohistochemistry. RESULTS: In DRESS, we observed spongiosis, edema, and basal vacuolization, with rare necrotic keratinocytes and constant lymphocytic infiltrate in the superficial dermis. Eosinophils were often present, and pustules were found in 15% of cases. Necrotic keratinocytes are often absent in maculopapular exanthema. Granulysin was expressed in six types of CADR with a trend toward more intense expression in DRESS and TEN. CONCLUSION: We detailed further about the histopathology of DRESS. Granulysin expression was observed in all CADR with a marked overlap of expression pattern between the six types.

Integrating longitudinal serum IL-17 and IL-23 follow-up, along with autoantibodies variation, contributes to predict bullous pemphigoid outcome.

Bullous pemphigoid (BP) is an inflammatory autoimmune bullous disease involving cytokines and proteases in the process of blister formation. Recently, IL-17 and IL-23 were evidenced in lesional skin and serum of BP patients at time of diagnosis, but their involvement in disease outcome has still not been investigated yet. We then analysed IL-17 and IL-23 serum levels during the first months of follow-up upon treatment. Compared with age- and sex- matched controls, high levels of IL-23 were observed at baseline in BP patients serum (P < 0.01), while IL-17 levels was not. However, some BP patients expressed high IL-17 serum level, independently of disease severity. In these patients, those with ongoing remission reduced IL-17 concentration upon treatment (P < 0.001), whereas IL-17 level remained elevated in patients who relapsed. Meanwhile, IL-23 serum levels increased during the first month of treatment in BP patients who later relapsed (P < 0.01) and MMP-9 serum level was not controlled. Accordingly, we found that both IL-17 and IL-23 increased MMP-9 secretion from leukocytes in-vitro. Then, we showed that elevated IL-17/IL-23 serum concentrations helped to discriminate BP patients who later relapsed. Such uncontrolled inflammatory response raises the question whether these molecules could become biological target for BP patients resistant to steroid treatment.

Brain endothelial TAK1 and NEMO safeguard the neurovascular unit.

Inactivating mutations of the NF-κB essential modulator (NEMO), a key component of NF-κB signaling, cause the genetic disease incontinentia pigmenti (IP). This leads to severe neurological symptoms, but the mechanisms underlying brain involvement were unclear. Here, we show that selectively deleting Nemo or the upstream kinase Tak1 in brain endothelial cells resulted in death of endothelial cells, a rarefaction of brain microvessels, cerebral hypoperfusion, a disrupted blood-brain barrier (BBB), and epileptic seizures. TAK1 and NEMO protected the BBB by activating the transcription factor NF-κB and stabilizing the tight junction protein occludin. They also prevented brain endothelial cell death in a NF-κB-independent manner by reducing oxidative damage. Our data identify crucial functions of inflammatory TAK1-NEMO signaling in protecting the brain endothelium and maintaining normal brain function, thus explaining the neurological symptoms associated with IP.

Contact sensitization to modern dressings: a multicentre study on 354 patients with chronic leg ulcers.

BACKGROUND: Modern dressings (MDs) may have a low sensitization rate, but there is a lack of prospective studies in patients with chronic leg ulcers (CLUs) to evaluate this. OBJECTIVES: To determine the rate of sensitization (contact allergy) to MDs and substances present in dressings. PATIENTS AND METHODS: A prospective multicentre study was carried out in patients with CLUs at five French dermatology departments; patch tests were performed with the European baseline series and with an additional 27 individual allergens and 10 MDs. RESULTS: Among 354 patients (226 women and 128 men) with CLUs, 59.6% had at least one positive patch test reaction to an MD and 19% had at least one sensitization to an MD. The number of positive test reactions per patient was correlated with the duration of ulcerative disease, but not with ulcer duration, the cause of the ulcer, or the presence of surrounding eczematous lesions. For 11 of 45 patients sensitized to Ialuset cream®, more detailed information could be obtained with sensitization to sodium dehydroacetate (5 cases) or Lanette SX® (3 cases). CONCLUSIONS: Sensitization to MDs is not rare. It is absolutely necessary to label all components of MDs on their packaging and to avoid some sensitizing molecules, such as colophonium derivatives or any strong sensitizers.

Clinical impact of negative-pressure wound therapy: a 1,126-patient observational prospective study.

Negative-pressure wound therapy (NPWT) was developed in the early 1990s and reported in 1997 by Argenta and Morykwas. Ignored at first, this technique progressively came to be considered as an outstanding advancement in reconstructive surgery. Several randomized controlled studies produced evidence for the effect of NPWT on promotion of granulation tissue formation and prevention of tissue damage and amputation. However, no important longitudinal study has yet produced clinical and economic data on the consequences of integrating NPWT into practice in multiple institutions. This prospective, comparative longitudinal study of NPWT as a clinical-practice innovation was conducted in 1,126 patients between March 2006 and June 2009 in 30 university and nonuniversity public and private hospitals in France. NPWT was proposed in a nonrandomized fashion for various clinical indications, and the patients were divided into two groups, one using NPWT, the second using standard care. Efficacy criteria were spontaneous closure, closure after surgical coverage using skin grafts or flaps, or achievement of 40% wound area regression. The results, observed in a pragmatic but not randomized study, are suggestive of a favorable impact of NPWT in multiple clinical situations. The significance of differences between surgical patients who underwent NPWT and those who did not was unclear, as NPWT had already been adopted by most of the surgical wards.

Clinical and immunologic factors associated with bullous pemphigoid relapse during the first year of treatment: a multicenter, prospective study.

IMPORTANCE: Although predisposing factors for bullous pemphigoid (BP) have been recently established, no clinical or immunologic factors have yet been identified to predict disease outcome. OBJECTIVE: To identify risk factors for BP relapse during the first year of treatment. DESIGN, SETTING, AND PARTICIPANTS: Multicenter prospective study of 120 consecutive patients with newly diagnosed BP in 8 French dermatology departments. Baseline and 6 follow-up visits were planned to record disease activity and collect blood samples for measurement of serum anti-BP180 and anti-BP230 levels by means of enzyme-linked immunosorbent assay (ELISA). MAIN OUTCOMES AND MEASURES: The end point was clinical relapse within the first year of therapy. Associations of clinical and immunologic (including serum levels of anti-BP180 and anti-BP230 autoantibodies) parameters with clinical relapse were assessed using univariate and multivariate analyses. RESULTS: During the 1-year follow-up, 35 patients (29.2%) experienced relapse, whereas anti-BP180 and anti-BP230 ELISA results were similar at baseline between patients who did and did not experience relapse. Factors at baseline independently associated with relapse were extensive disease at inclusion (hazard ratio [HR], 2.37 [95% CI, 1.2-4.8]) and an associated dementia (HR, 2.09 [95% CI, 1.0-4.2]). Use of superpotent topical corticosteroids alone (by 100 patients [83.3%]) induced a dramatic, early decrease in serum levels of anti-BP180 and anti-BP230 autoantibodies. Mean early decreases in autoantibody levels between baseline and day 60 were lower in patients with relapse compared with patients with ongoing remission (-10.0% and -45.2%, respectively, for anti-BP180 levels [P < .001] and -11.8% and -35.4%, respectively, for anti-BP230 levels [P = .046]). A higher serum level of anti-BP180 at day 150, with a cutoff of 23 U/mL, provided 84.2% sensitivity, 44.8% specificity, 33.3% positive predictive value, and 89.7% negative predictive value for the occurrence of relapses between days 150 and 360. CONCLUSIONS AND RELEVANCE: The pronounced decrease in the level of anti-BP180 autoantibodies and, to a lesser extent, those directed against BP230 confirmed the use of superpotent topical corticosteroids alone as a reference BP treatment. Furthermore, our study suggests that neurological diseases play a major role in BP, not only as a predisposing but also as a prognostic factor.

Retronychia : four new cases.

Retronychia (RN) refers to the incarnation of the nail plate in the proximal nail fold. We report four clinical cases of this little-known pathology, where there may be a long delay in diagnosis. RN exhibits a triad of clinical features, which are chronic paronychia, liquid discharge from under the nail fold and disruption of the linear nail growth. Chronic paronychia is often confused with bacterial or fungal infection. Empirical antibiotic treatment is not useful. Nail plate avulsion is the diagnostic and curative procedure of choice. Subsequent nail growth is normal without dystrophia and no recurrences are observed. Knowledge of this pathology avoids misdiagnosis, unnecessary antibiotic or local treatments and allows adequate surgical management.

Distinctive features of melanoma and its management in elderly patients: a population-based study in France.

IMPORTANCE: Life expectancy is increasing in most developed countries, and elderly people have the highest incidence of melanoma. OBJECTIVE: To identify characteristics of melanoma and its management in the elderly compared with younger patients. DESIGN, SETTING, AND PARTICIPANTS: Retrospective population-based study of incident cases of primary melanoma in 1621 patients with stage I or II melanoma in 2004 and 2008. Questionnaires administered to physicians and a survey of cancer registries and pathology laboratories were used to obtain data. The study was conducted in 5 regions in northeastern France. MAIN OUTCOMES AND MEASURES: Characteristics of patients and tumors, circumstances of diagnosis, and further management in older patients (≥70 years, 487 patients [30.0%]) compared with younger ones (<70 years, 1134 [70.0%]). RESULTS: Older patients had more frequent melanomas of the head and neck (29.4% vs 8.7%; P < .001) and of the nodular, lentigo maligna, or acral lentiginous histologic subtypes. They had thicker and more frequently ulcerated tumors, categorized as T3 or T4 in 36.7% of cases vs 20.1% in younger patients. Diagnosis of melanoma occurred more frequently in a general practice setting and less frequently in direct consultation with a dermatologist or regular screening for skin cancer. Time to definitive excision was longer in older patients, and 16.8% of them compared with 5.0% of the younger population had insufficient excision margins (P < .001). A sentinel lymph node biopsy was performed in 23.3% of the older patients with melanoma thicker than 1 mm vs 41.4% in the younger patients (P < .001). Adjuvant therapy was less frequently started in older patients and was prematurely stopped in a higher proportion of that population. CONCLUSIONS AND RELEVANCE: Age-related variations are observed at every step of melanoma management. The most important concerns are access of elderly people to settings for early diagnosis and excision with appropriate margins.

A case of cutaneous lichen sclerosus et atrophicus effectively treated by extracorporeal photochemotherapy.

Lichen sclerosus et atrophicus (LSA) is an inflammatory disease that affects the genitals, which was first described by Hallopeau in 1887 and is of unknown etiology. Only 15% of patients have an associated extra-genital form, and 2.5% have an isolated extra-genital form. LSA treatment remains poorly codified and mostly empirical. Here, we report a case of LSA, of mainly cutaneous form, which was effectively treated using extracorporeal photochemotherapy (ECP). Remission was achieved quickly, after the fourth session, with excellent treatment tolerance. ECP is now recognized as an effective treatment for erosive lichen planus, graft-versus-host disease (GVHD), and scleroderma. Thus, we began ECP treatment for our cases of LSA based on clinical and/or anatomopathological similarities between LSA and these commonly ECP-treated disorders. The fact that ECP is effective in LSA, GVHD, erosive lichen planus, and scleroderma strengthen the hypothesis that there is a common link between these four conditions.

Clinical and sociodemographic characteristics associated with thick melanomas. A population-based, case-case study in France.

OBJECTIVE: To identify clinical and sociodemographic factors associated with very thick melanoma (VTM) (Breslow thickness, 3 mm) in France. DESIGN: Retrospective, population-based, case-case study using a survey of cancer registries and questionnaires to practitioners. SETTING: Five regions covering 19.2% of the French territory and 8.2 million inhabitants. CASES: Cases included all incident melanomas with a Breslow thickness of 3 mm or greater (ie, VTM), diagnosed between January 1 and December 31, 2008, in residents of the study area (Alsace, Bourgogne, Champagne-Ardenne, Franche-Comte', and Lorraine, France), and a randomly selected sample of melanomas thinner than 3 mm. MAIN OUTCOME MEASURES: Circumstances of diagnosis,clinical and pathological characteristics of melanomas,and sociodemographic characteristics of patients(age, sex, residence, home and family life conditions, educational level, and smoking habits). RESULTS: Among 898 melanomas, 149 (16.6%) were VTMs. Very thick melanomas were more often diagnosed in a general-practice setting than thinner melanomas.The rate of immediate clinical recognition by dermatologists was lower for VTMs than for thinner melanomas. In a multivariate logistic regression analysis,factors associated with VTM were the nodular and acrolentiginous types; the head and neck and lower limb locations; older age; male sex; and being single, separated,divorced, or widowed. When only factors related to patients were taken into account, older age, male sex,and living alone were independent risk factors for VTM.The most significant risk was observed for patients living alone. CONCLUSIONS: Intrinsic factors related to the tumor and socio demographic characteristics of patients contribute to the occurrence of VTM. These factors should be better targeted in future secondary prevention programs.