Multicentric evaluation of a specific intrathecal anti-Treponema pallidum IgG index as a diagnostic biomarker of neurosyphilis: results from a retro-prospective case-control study.

BACKGROUND AND OBJECTIVES: The diagnosis of neurosyphilis (NS) lacks a true 'gold standard', making the diagnosis challenging while consequences of a misdiagnosis are potentially severe. The aim of this study was to evaluate the diagnostic performance of measuring an antibody index (AI) for the intrathecal synthesis of specific anti-Treponema pallidum (T. pallidum) IgG for the diagnosis of NS. METHODS: Specific anti-T. pallidum IgG were measured simultaneously in paired cerebrospinal fluid (CSF)-serum samples collected retrospectively and prospectively between 2007 and 2022, from patients suspected of NS, in Switzerland. An AI was calculated to account for blood-brain barrier integrity. Area under the receiver operating characteristic curve, sensitivity/specificity and positive/negative predictive values of AI test were estimated. Two NS definitions were used: NS1 included patients with NS suspicion presenting with neurological symptoms and/or acute neurosensory signs, and positive T. Pallidum Hemagglutinations Assay (TPHA)/T. pallidum particle agglutination assay (TPPA) serology and CSF-TPHA/TPPA ≥320, and either CSF-leucocytes >5 cells/mm3 and/or CSF-protein >0.45 g/L and/or a reactive CSF-venereal disease research laboratory (VDRL)/rapid plasma reagin (RPR) test. NS2 included patients with suspected NS presenting with acute ocular and/or otologic symptoms, and positive TPHA/TPPA serology, and a favourable response to NS treatment. Controls were patients diagnosed with any other central nervous system (CNS) pathologies and with positive TPHA/TPPA serology. RESULTS: The study included 71 NS (43 NS1 and 28 NS2) and 110 controls. With a threshold of ≥1.7, sensitivity and specificity of the specific AI test were 90.7% (CI 77.7 to 97.4) and 100% (CI 96.7 to 100.0), respectively, for NS1 and 14.3% (CI 4 to 32.7) and 100% (CI 96.7 to 100.0) for NS2. In patients suspected of NS with a CNS involvement (NS1 group), NS could be confirmed by the positivity of this specific AI. CONCLUSIONS: Measurement of an intrathecal synthesis index of specific anti-T. pallidum IgG in patients with CSF inflammatory signs appears to be a valuable diagnostic test. However, in otic or ocular syphilis, presenting few CSF abnormalities, AI is not sufficient alone to confirm NS diagnosis. TRIAL REGISTRATION: Swiss Association of Research Ethics Committees number 2019-00232.

Evaluation of whole-genome enrichment and sequencing of T. pallidum from FFPE samples after 75 years.

The recent developments in genomic sequencing have permitted the publication of many new complete genome sequences of Treponema pallidum pallidum, the bacterium responsible for syphilis, which has led to a new understanding of its phylogeny and diversity. However, few archived samples are available, because of the degradability of the bacterium and the difficulties in preservation. We present a complete genome obtained from a Formalin-Fixed Paraffin-Embedded (FFPE) organ sample from 1947, kept at the Strasbourg Faculty of Medicine. This is the preliminary, proof-of concept study of this collection/biobank of more than 1.5 million FFPE samples and the evaluation of the feasibility of genomic analyses. We demonstrate here that even degraded DNA from fragile bacteria can be recovered from 75-year-old FFPE samples and therefore propose that such collections as this one can function as sources of biological material for genetic studies of pathogens, cancer, or even the historical human population itself.

Congenital syphilis in Switzerland: a retrospective cohort study, 2010 to 2019.

AIMS OF THE STUDY: We previously reported a re-emergence of syphilis from 2006 to 2009 with detection of congenital syphilis in Switzerland. This study aimed to reassess the incidence of children exposed to maternal syphilis during pregnancy and congenital syphilis in a following 10-year period in the canton of Zurich, the most populous canton in Switzerland with the highest incidences of syphilis. METHODS: Children were identified both by reviewing medical records at the four major neonatal and paediatric hospitals providing acute care in the canton of Zurich and by the serological database of the syphilis reference laboratory. Inclusion criteria for children were (a) date of birth in the period 2010-2019, (b) place of birth in the canton of Zurich, (c) evaluation for syphilis due to positive syphilis pregnancy screening and (d) age <1 year at diagnosis. Results were compared with epidemiological data provided by the Federal Office of Public Health (FOPH). RESULTS: We identified and evaluated 17 children after potential exposure to maternal syphilis. Residual antibodies of a past infection were found in 11 mothers. Six children were identified as having had real exposure to asymptomatic maternal syphilis. From an epidemiological perspective, the distribution of the cases followed a similar pattern as confirmed syphilis cases in women of childbearing age reported to the FOPH. No cases of congenital syphilis were observed. CONCLUSIONS: In contrast to the rise in syphilis infections, this study identified no cases of congenital syphilis in the canton of Zurich, Switzerland, in the period 2010-2019. Syphilis pregnancy screening may have prevented congenital syphilis by diagnosing and allowing adequate treatment of asymptomatic maternal syphilis.

Congenital syphilis in Switzerland: a marker of inequality? A mini-review.

Syphilis remains a global public health problem, with growing incidence in most regions of the world, particularly among women of childbearing age. This alarming trend has led to an increase in cases of congenital syphilis, resulting in devastating consequences. While the implementation of measures by the World Health Organization (WHO) and various governments has contributed to a decline in the global incidence of congenital syphilis, many countries are facing an escalating crisis, as incidence continues to rise. This mini-review aims to provide an overview of the current state of this disease in different parts of the world, focusing on the most affected populations and highlighting congenital syphilis as a marker of vulnerability. It also focuses on Switzerland, a country with a robust economy, to identify shortcomings in the healthcare system that contribute to the persistence of congenital syphilis, even though the infection is easily detectable and treatable. In conclusion, this mini-review highlights the persistent risk of congenital syphilis worldwide, regardless of country prevalence or economic status, and underscores the need for sustained efforts to reach underserved women, emphasizing the vital role of comprehensive training for healthcare professionals.

Towards an Early Clinical and Biological Resistance Detection in Dermatophytosis: About 2 Cases of Trichophyton indotineae.

Trichophyton indotineae causes resistant dermatophytosis to terbinafine. The global spread of terbinafine-resistant Trichophyton indotineae strains with mutations in the squalene epoxidase gene is a major issue. This emerging species is now more frequently isolated in Europe and we report here two cases of T. indotineae tinea corporis in Switzerland, one with in vitro resistance to terbinafine and a second with in vitro susceptibility but a clinical resistance. Mycology isolation from cultures and sequencing ITS gene were used to confirm T. indotineae infection. In vitro antifungal susceptibility was tested in a microplate with a colorimetric detection of fungal viability for the determination of the minimal inhibitory concentration (MIC). Facing these emerging resistances and since there are a limited number of antifungal agents available to treat dermatophytosis, the early detection of terbinafine resistance should be a prerequisite in the management of T. indotineae infections.

[Mpox (Monkeypox): from a dermatologist's point of view]. / Mpox (variole du singe) : l'œil du dermatologue.

Mpox (Monkeypox) was largely unknown in Switzerland before the outbreak that started in May 2022 and spread worldwide, including Europe and the Americas. This article reviews the clinical manifestations and treatment of this infection while emphasizing the importance of clinical observation. Rapid identification and diagnosis of cases allow a more efficient application of sanitary measures in order to prevent further spreading of the disease.

La mpox (variole du singe) était une maladie largement méconnue dans notre pays avant la poussée épidémique de mai 2022. Cette dernière a essaimé dans plusieurs pays, notamment en Europe et aux Amériques. Nous abordons ici les symptômes et signes cliniques ainsi que le traitement de cette maladie, tout en rappelant l'importance de l'observation clinique en médecine. Un diagnostic précoce des patients infectés permet une application plus efficace des mesures sanitaires afin de limiter la propagation.

Pseudo-Pemphigoid Gestationis Eruption Following SARS-CoV-2 Vaccination with mRNA Vaccine.

Auto-immune reactions, including auto-immune bullous disease, have been reported following SARS-CoV-2 virus vaccination. Few cases of bullous pemphigoid are described, but there has been no case of pemphigoid gestationis. We report the first case here.

[Urethritis in the context of risk of sexually transmitted infections : update!] / Urétrites en contexte de risque d'infections sexuellement transmises : actualités.

Urethritis of infectious origin are part of the sexually transmitted diseases (STD) that represent a major public health problem in terms of costs and morbidity. The incidence of urethritis has been increasing for several years and the diagnosis and management must be carried out as soon as possible to avoid complications that may arise and that are sometimes irreversible, but also to limit contamination chains. The difficulties of diagnosis lie in the numerous asymptomatic cases and the management of sexual partners who may be multiple and difficult to identify. The constantly changing epidemiology and resistance to antibiotics guide new developments in their management.

Les urétrites d'origine infectieuse font partie des IST et représentent un problème majeur de santé publique en termes de coûts et de morbidités. Depuis plusieurs années, leur incidence ne cesse d'augmenter et le diagnostic ainsi que la prise en charge doivent être réalisés dans les meilleurs délais afin d'éviter des complications parfois irréversibles, mais aussi de limiter la chaîne de contamination. Les difficultés du diagnostic résident dans les nombreux cas asymptomatiques et la prise en charge des partenaires sexuels qui peuvent être multiples et difficiles à identifier. L'épidémiologie et la résistance aux antibiotiques en constante évolution guident les nouveautés de leur prise en charge.

Intrathecal Synthesis Index of Specific Anti-Treponema IgG: a New Tool for the Diagnosis of Neurosyphilis.

Neurosyphilis (NS) diagnosis is challenging because clinical signs are diverse and unspecific, and a sensitive and specific laboratory test is lacking. We tested the performance of an antibody index (AI) for intrathecal synthesis of specific anti-Treponema IgG by enzyme-linked immunosorbent assay (ELISA) for NS diagnosis. We conducted a retroprospective monocentric study including adults with neurological symptoms who had serum and cerebral spinal fluid (CSF) samples collected between 2006 and 2021. Two NS definitions were used. NS1 included patients with neurological symptoms, positive Treponema pallidum particle agglutination (TPPA) serology, and CSF-TPPA of ≥320, as well as CSF-leukocytes of >5 cells/mm3 and/or CSF-protein of >0.45 g/L and/or a reactive CSF-VDRL/RPR test. NS2 included patients with acute ocular and/or otologic symptoms, positive TPPA serology, and a response to NS treatment. Controls were patients with central nervous system disorders other than neurosyphilis. Anti-Treponema pallidum IgG were measured simultaneously in serum and CSF, and AI was calculated according to Reiber diagram. We assessed the AI test area under the curve (AUC), sensitivity/specificity, and estimated positive and negative predictive values. In total, 16 NS1 patients, 11 NS2 patients, and 71 controls were included. With an AI of ≥1.7 as a positive test for NS diagnostic, specificity was 98.6% (95% confidence interval [CI 95%] of 92.4 to 100.0) and sensitivity was 81.3% (CI 95% of 54.4 to 96.0) for NS1 and 98.6% (CI 95% 92.4 to 100.0) and 27.3% (CI 95% 6.0 to 61.0), respectively, for NS2. Positive and negative predictive values were >95% for NS1 and >85% for NS2, for prevalence above and below 20%. Measuring an AI for intrathecal synthesis of specific anti-Treponema pallidum IgG is a new promising tool highly specific for NS diagnosis. IMPORTANCE In the context of a lack of a gold standard for the diagnosis of neurosyphilis due to either nonspecific or nonsensitive tests, we present in this article a new promising tool highly specific for NS diagnosis. This new test involves measuring an intrathecal synthesis index of specific anti-Treponema IgG by ELISA.

Sustained Trichodysplasia Spinulosa Polyomavirus Viremia Illustrating a Primary Disseminated Infection in a Kidney Transplant Recipient.

Novel human polyomaviruses (HPyV) have been recently identified in solid organ transplant recipients. Trichodysplasia spinulosa (TS) is a rare disease associated with immunosuppression and induced by a polyomavirus (TSPyV). We report here a case of primary and disseminated TSPyV infection after kidney transplantation with extensive skin lesions, sustained viremia, and high viral loads in urine specimens, anal, nasal and throat swabs, assessed via specific real-time PCR for TSPyV during a follow-up period of 32 months after transplantation. The detection of TSPyV with a high viral load in respiratory and anal swab samples is compatible with viral replication and thus may suggest potential respiratory and oro-fecal routes of transmission.

[SARS-COV-2 infection and skin manifestations]. / Infection par le SARS-CoV-2 et manifestations cutanées.

With the COVID-19 emergence, came the description of large cutaneous rash variety. Although nonspecific and rarer than respiratory symptoms, many case reports emerged on 2020 and can be classified into 3 categories. Histopathological analysis associated with microbiological samples can guide the diagnosis. Knowledge of these cutaneous rash can help diagnosis and allow precocious detection of COVID 19, especially with patients without other systemic symptoms.

Avec l'émergence du Covid-19 est apparue la description de différentes manifestations cutanées. Bien qu'aspécifiques et plus rares que les symptômes respiratoires, de nombreux rapports de cas ont été publiés durant l'année 2020, pouvant être classés en 3 catégories. L'analyse histopathologique associée aux prélèvements microbiologiques peut orienter le diagnostic. Les connaissances de ces manifestations cutanées peuvent parfois aider au diagnostic et permettre une détection plus précoce de l'infection par le SARS-CoV-2, notamment chez les patients ne présentant pas d'autres symptômes systémiques.

An Unusual Case of Cocaine-induced Neutrophilic Systemic Disease.

is missing (Short communication).

[Rubor, calor, dolor, tumor†: skin and soft tissue infections]. / Rubor, calor, dolor, tumor†: infections de la peau et des tissus mous.

Skin infections are a frequent cause of consultation, yet the diagnosis can be challenging for physicians. Microbiological documentation is rare, and empiric antibiotic regimens should cover the most commonly identified bacteria, i.e. streptococci Staphylococcus aureus. Other pathogens should be considered in case of immunosuppression or certain exposures. Necrotizing fasciitis (NF) is a severe but rare infection. Early surgical management in parallel with antibiotics is the cornerstone of treatment. Despite the high incidence of these infections, little progress has been made in their management and some areas of uncertainty exist, especially regarding the optimal duration of treatment, the prevention of recurrences and the use of polyclonal immunoglobulins for NF. This article reviews the main aspects of diagnosis and treatment of these infections.

Les infections de la peau sont fréquentes mais leur diagnostic peut représenter un défi pour le clinicien. La documentation de l'étiologie microbiologique est rare et le traitement empirique doit couvrir les germes fréquents, notamment Streptococcus spp. et Staphylococcus aureus. Des bactéries inhabituelles peuvent être retrouvées lors d'immunosuppression ou exposition spéciale. La fasciite nécrosante (FN) est une infection sévère mais rare, dont le traitement repose sur la chirurgie rapide et l'antibiothérapie. Malgré leur fréquence, peu de progrès ont été réalisés dans la prise en charge de ces infections et des incertitudes persistent par rapport à la durée optimale de traitement, la prophylaxie pour les récurrences ou l'utilité des immunoglobulines polyclonales intraveineuses pour la FN. Cet article aborde les aspects diagnostiques et thérapeutiques de ces infections.

[Lyme Borreliosis in 2020 practice, from a dermatological point of view]. / Borréliose de Lyme vue par le dermatologue, en pratique en 2020.

Lyme borreliosis is a frequent disease in Switzerland. Due to the increasing number of symptoms attributed to this infection, the diagnostic is often controversy between different specialists and is often a subject of discussion. The diagnostic of Lyme disease lays particularly on the knowledge of cutaneous signs which are the only specific. Despite recent scientific progress, microbiological diagnostic is still delicate and serological tests currently used do not differentiate between an active infection versus a serological marker. Here we describe the different clinical presentations of Lyme disease diagnosis and management procedures according to stages of evolution.

La borréliose de Lyme est une maladie fréquente en Suisse. Elle a beaucoup fait parler d'elle ces dernières années en raison d'un nombre croissant de symptômes qui lui ont été attribués, faisant polémique auprès des spécialistes. Le diagnostic de la maladie de Lyme repose en grande partie sur la reconnaissance des signes cutanés qui seuls sont spécifiques. Malgré les progrès scientifiques, le diagnostic microbiologique reste toujours délicat, et les tests sérologiques utilisés actuellement ne permettent pas de faire la distinction entre une infection active et une cicatrice sérologique. Dans cet article, nous décrivons les différentes manifestations cliniques et la prise en charge diagnostique et thérapeutique selon les stades d'évolution de la maladie.

[Martorell hypertensive ischemic ulcer: an atypical wound to know]. / Angiodermite nécrotique†: un ulcère à connaître.

Martorell hypertensive ischemic ulcer is often an unrecognized cause of chronic leg ulcer and may result in a delayed management. We describe a typical case report with clinical key features for diagnosis and therapeutic management. Pathophysiology and main differential diagnosis are discussed. Skin biopsy can be used to rule out differential diagnosis. Management should be focused on pain control, evaluation and treatment of cardiovascular risks before performing a skin graft.

L'angiodermite nécrotique ou ulcère de Martorell est une cause souvent méconnue d'ulcère chronique des membres inférieurs, pouvant conduire à un retard de prise en charge. Au travers d'un cas clinique typique, nous discutons des hypothèses physiopathologiques et de la prise en charge diagnostique et thérapeutique. La biopsie cutanée permet d'éliminer les diagnostics différentiels. Le traitement est spécifique et repose sur un contrôle de la douleur, la recherche et le traitement des facteurs de risque cardiovasculaire avant d'entreprendre une greffe cutanée de peau mince.

Diagnostic Value of Histological Analysis of Punch Biopsies in Suspected Cutaneous Buruli Ulcer: A Study on 32 Cases of Confirmed Buruli Ulcer in Cameroon.

BACKGROUND: Buruli ulcer (BU) is a cutaneous infectious disease caused by Mycobacterium ulcerans. In this prospective study, we aim to clarify the main histopathological features of cutaneous BU based on 4-mm skin punch biopsies and to evaluate the diagnostic value of this method. METHODS: Between 2011 and 2013, a prospective study was conducted in Cameroon. Dry swabs from ulcerative lesions and fine-needle aspirates of nonulcerative lesions were examined for Ziehl-Neelsen (ZN) staining, followed by PCR targeting IS2404 and culture. Two 4-mm punch biopsies were performed in the center and in the periphery of each lesion. RESULTS: The 364 patients included in the study had 422 lesions (381 were ulcerative and 357 lesions were biopsied). Among the 99 ulcerated lesions with a final diagnosis of BU, histological features for BU were fulfilled in 32 lesions. 32/32 showed subcutaneous necrosis with a neutrophilic inflammatory infiltrate. 26/32 presented alcohol-resistant bacilli confirmed by ZN stain on histology. CONCLUSION: Punch biopsies help in establishing the correct diagnosis of BU and also in the differential diagnosis of chronic ulcers. The main histological feature for BU is diffuse coagulative necrosis of subcutaneous tissue, with acid-fast bacilli detected by ZN stain.

[A new life for old anatomical wakes]. / Nouvelle vie pour les moulages anatomiques anciens.

Wax mouldings exemplifying human body and cutaneous diseases were produced and used from the 18th to the 20th century. They were mainly used for teaching and also for exhibitions to prevent sexually transmitted diseases. Many medical mouldings are still shown in European museums. Their originality and their artistic value encourage us to preserve them and also benefit of them as a new old tool to teach. Thanks to modern applications of imagery we show here how such historical pieces find a new life.

Les moulages en cire étaient largement utilisés dans les facultés de médecine entre le XVIIIe et le début du XXe siècle pour l'enseignement de l'anatomie et des dermatoses. Mais on pouvait également les voir dans certaines expositions itinérantes, dont l'objectif était d'informer un public large sur les maladies sexuellement transmises. De nos jours, de nombreuses pièces sont exposées dans différents musées en Europe. La qualité technique et artistique et l'originalité des moulages en cire motivent non seulement leur conservation mais aussi la redécouverte de leur potentiel de nouveau-vieil outil d'enseignement. Grâce aux applications modernes de l'imagerie, nous montrons ici comment de telles pièces historiques trouvent une nouvelle vie.

[Update on Mycoplasma genitalium among women]. / Le point sur Mycoplasma genitalium chez la femme.

Mycoplasma genitalium (MG) is a sexually transmitted pathogen with a poorly understood natural history. Often asymptomatic, it has been associated with urogenital conditions. The implementation of NAAT (Nucleic Acide Amplification Test) has not only improved the detection of MG, but also brought to light the emergence of antibiotic resistances, hence challenging the proposed treatment strategies and questioning the indication for systematic screening. This article summarizes current knowledge on MG among women, over viewing incidence, prevalence and clinical implications. It resumes the last guidelines in terms of screening and treatment.

Mycoplasma genitalium (MG) est un pathogène sexuellement transmissible souvent asymptomatique, dont la pathogénicité est méconnue. Source croissante d'intérêt car mieux détecté depuis l'implémentation des NAAT (Nucleic Acide Amplification Test), MG serait incriminé dans diverses pathologies uro-génitales. L'émergence des résistances aux antibiotiques est un enjeu de taille dans le traitement de l'infection et soulève le débat sur l'utilité d'un dépistage systématique. Cet article résume l'état des connaissances actuelles au sujet de MG chez la femme : son incidence, sa prévalence ainsi que ses implications cliniques. Il fait la synthèse des dernières recommandations en termes de dépistage et de traitement.

Sign of Leser-Trélat and Cutaneous T-Cell Lymphoma: A Rare Association.

Sign of Leser-Trélat is a rare paraneoplastic cutaneous manifestation, characterized by the sudden appearance and rapid increase in size and number of seborrheic keratoses, accompanied by pruritus. Edmund Leser and Ulysse Trélat described this sign in 1890. Since their first description, their conclusions have been considered controversial and some authors assert the absence of a causal link. It seems to be frequently associated with solid tumors and in particular gastrointestinal cancer. Here, we describe a new case associated with a cutaneous T-cell lymphoma and a partial response to extracorporeal photopheresis.

Chronic Prurigo: An Unusual Presentation of Hodgkin Lymphoma.

BACKGROUND: Prurigo nodularis is a condition of unknown origin defined by papulonodular eruption and intense pruritus. Hodgkin lymphoma often presents nonspecific initial symptoms. An association between systemic malignancy and cutaneous manifestations has long been documented. We report a case of prurigo nodularis as a first presentation of Hodgkin lymphoma. CASE: A 35-year-old woman presented with a 2-year history of pruritus. Previously diagnosed with bedbugs, the pruritus persisted even after insect eradication, with the appearance of papulonodular lesions consistent with chronic prurigo. The pruritus and the pain were refractory to all treatments. She had no past medical history or clinical, radiological, or laboratory findings. A lymphadenopathy was revealed 2 years after onset of the symptoms. Lymph node biopsy showed a nodular sclerosis Hodgkin lymphoma. The patient was initiated on chemotherapy and the skin lesions decreased. CONCLUSION: This case report of chronic prurigo as the first manifestation of a systemic malignancy reminds us of the importance of a systematic diagnostic approach to this kind of patients initially and throughout time, especially if the symptoms do not respond to treatment. Our case may question the role of imaging examinations in the management and follow-up of a persistent prurigo nodularis.