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Background Syphilis is known as the “great imitator” because of its polymorphic clinical manifestations. Condyloma lata are an uncommon mucocutaneous manifestation of secondary syphilis, generally localized in intertriginous areas, such as the genitals and anus. Extragenital localization of condyloma lata is considered unusual. Methods A case study of extra-genital condylomata is presented. To contextualise the case, a literature review of extra-genital condylomata lata was subsequently undertaken. The authors searched MEDLINE/PubMed, Scopus and Excerpta Medica/EMBASE English-language sources using the following keywords: “condyloma lata”, “condylomata lata”, and “condyloma latum”. Results Thirty-five papers (from 1940 to 2021) describing an extra-anogenital localization of condyloma lata were found and are summarized in Table 1. Patients were mainly males (82.1%), with a mean age of 31.9 years. Most of them showed other manifestations of secondary syphilis (53.9%). In a minority of cases (39.0%), concomitant anogenital condyloma lata were present, thus making the diagnosis easier. The toe web localization was the most documented (26.2%) followed by the oral cavity (23.8%). Conclusion In the presence of extra-genital condyloma lata, the differential diagnosis is not always clear, especially when no other muco-cutaneous lesions are observed. In the case of eroded or wet lesions involving any cutaneous fold, associated or not with other cutaneous manifestations, a sexual history should be obtained, and syphilis must be considered.

Although primary syphilis generally involves the genitalia, literature reports that 12% of chancres are extragenital, with the anus and oral cavity as the most frequent locations. We present hereby a case series of four chancres of the finger observed at the sexually transmitted infection centre of Milan between 2010 and 2021.

Sequencing of most Treponema pallidum (T. pallidum) genomes excludes repeat regions in tp0470 and the tp0433 gene, encoding the acidic repeat protein (arp). As a first step to understanding the evolution and function of these genes and the proteins they encode, we developed a protocol to nanopore sequence tp0470 and arp genes from 212 clinical samples collected from ten countries on six continents. Both tp0470 and arp repeat structures recapitulate the whole genome phylogeny, with subclade-specific patterns emerging. The number of tp0470 repeats is on average appears to be higher in Nichols-like clade strains than in SS14-like clade strains. Consistent with previous studies, we found that 14-repeat arp sequences predominate across both major clades, but the combination and order of repeat type varies among subclades, with many arp sequence variants limited to a single subclade. Although strains that were closely related by whole genome sequencing frequently had the same arp repeat length, this was not always the case. Structural modelling of TP0470 suggested that the eight residue repeats form an extended α-helix, predicted to be periplasmic. Modeling of the ARP revealed a C-terminal sporulation-related repeat (SPOR) domain, predicted to bind denuded peptidoglycan, with repeat regions possibly incorporated into a highly charged β- sheet. Outside of the repeats, all TP0470 and ARP amino acid sequences were identical. Together, our data, along with functional considerations, suggests that both TP0470 and ARP proteins may be involved in T. pallidum cell envelope remodeling and homeostasis, with their highly plastic repeat regions playing as-yet-undetermined roles.

Loiasis is an infestation of the skin and eyes caused by the nematode Loa loa. We report a case of loiasis in a woman who contracted the infestation in Cameroon. The clinical picture was characterized by Calabar swellings on the upper limbs and axillary lymphadenopathy. Laboratory tests revealed persistent leucocytosis with neutropenia, lymphopenia, and eosinophilia. The search for microfilariae was always negative. The patient was successfully treated with ivermectin and albendazole. Follow-up (5 years) was negative for both clinical manifestations and laboratory tests.

Gonorrhoea is a major public health concern globally. Increasing incidence and sporadic ceftriaxone-resistant cases, including treatment failures, are growing concerns. The 2020 European gonorrhoea guideline provides up-to-date evidence-based guidance regarding the diagnosis and treatment of gonorrhoea. The updates and recommendations emphasize significantly increasing gonorrhoea incidence; broad indications for increased testing with validated and quality-assured nucleic acid amplification tests (NAATs) and culture; dual antimicrobial therapy including high-dose ceftriaxone and azithromycin (ceftriaxone 1 g plus azithromycin 2 g) OR ceftriaxone 1 g monotherapy (ONLY in well-controlled settings, see guideline for details) for uncomplicated gonorrhoea when the antimicrobial susceptibility is unknown; recommendation of test of cure (TOC) in all gonorrhoea cases to ensure eradication of infection and identify resistance; and enhanced surveillance of treatment failures when recommended treatment regimens have been used. Improvements in access to appropriate testing, test performance, diagnostics, antimicrobial susceptibility surveillance and treatment, and follow-up of gonorrhoea patients are essential in controlling gonorrhoea and to mitigate the emergence and/or spread of ceftriaxone resistance and multidrug-resistant and extensively drug-resistant gonorrhoea. This review provides the detailed background, evidence base and discussions, for the 2020 European guideline for the diagnosis and treatment of gonorrhoea in adults (Unemo M, et al. Int J STD AIDS. 2020).

Hyperkeratosis lenticularis perstans (HLP), or Flegel's disease (FD), is a rare disorder of keratinization first described in 1958 by Flegel. HLP is characterized by asymptomatic small papules distributed symmetrically on the dorsal feet and lower part of the legs. It typically presents in the fourth or fifth decade of life. FD has been reported more commonly in women, and little is known about the pathogenesis of this rare dermatosis. Histological examination is mandatory to confirm the diagnosis, and the characteristic features are: focal compact hyperkeratosis, thinned stratum malpighii, epidermal atrophy, and a dense, band-like lymphocytic infiltrate in the papillary dermis. The treatment of FD is challenging, and a fully effective standard therapy does not exist. We report four cases of HLP that have been diagnosed at the Dermatology Unit of IRCCS Ca' Granda Ospedale Maggiore Policlinico in Milan, Italy, and a literature review is enclosed.

In spite of its immutable susceptibility to penicillin, Treponema pallidum (T. pallidum) subsp. pallidum continues to cause millions of cases of syphilis each year worldwide, resulting in significant morbidity and mortality and underscoring the urgency of developing an effective vaccine to curtail the spread of the infection. Several technical challenges, including absence of an in vitro culture system until very recently, have hampered efforts to catalog the diversity of strains collected worldwide. Here, we provide near-complete genomes from 196 T. pallidum strains – including 191 T. pallidum subsp. pallidum – sequenced directly from patient samples collected from 8 countries and 6 continents. Maximum likelihood phylogeny revealed that samples from most sites were predominantly SS14 clade. However, 99% (84/85) of the samples from Madagascar formed two of the five distinct Nichols subclades. Although recombination was uncommon in the evolution of modern circulating strains, we found multiple putative recombination events between T. pallidum subsp. pallidum and subsp. endemicum, shaping the genomes of several subclades. Temporal analysis dated the most recent common ancestor of Nichols and SS14 clades to 1717 (95% HPD: 1543-1869), in agreement with other recent studies. Rates of SNP accumulation varied significantly among subclades, particularly among different Nichols subclades, and was associated in the Nichols A subclade with a C394F substitution in TP0380, a ERCC3-like DNA repair helicase. Our data highlight the role played by variation in genes encoding putative surface-exposed outer membrane proteins in defining separate lineages, and provide a critical resource for the design of broadly protective syphilis vaccines targeting surface antigens.Author SummaryEach year, millions of new cases of venereal and congenital syphilis, caused by the bacterium Treponema pallidum (T. pallidum) subsp. pallidum, are diagnosed worldwide, resulting in significant morbidity and mortality. Alongside endemic circulation of syphilis in low-income countries, disease resurgence in high-income nations has underscored the need for a vaccine. Due to prior technological limitations in culturing and sequencing the organism, the extent of the genetic diversity within modern strains of T. pallidum subsp. pallidum remains poorly understood, hampering development of a broadly protective vaccine. In this study, we obtained 196 near-complete T. pallidum genomes directly from clinical swabs from eight countries across six continents. Of these, 191 were identified as T. pallidum subsp. pallidum, including 90 Nichols clade genomes. Bayesian analysis revealed a high degree of variance in mutation rate among subclades. Interestingly, a Nichols subclade with a particularly high mutation rate harbors a non-synonymous mutation in a putative DNA repair helicase. Coupling sequencing data with protein structure prediction, we identified multiple novel amino acid variants in several proteins previously identified as potential vaccine candidates. Our data help inform current efforts to develop a broadly protective syphilis vaccine.

Gomberg, Mikhail/0000-0002-1070-5229; Nicolaidou, Electra/0000-0002-8221-0217 WOS:000468972400005 PubMed ID: 30968980 Background Anogenital warts (AGW) can cause economic burden on healthcare systems and are associated with emotional, psychological and physical issues. Objective To provide guidance to physicians on the diagnosis and management of AGW. Methods Fourteen global experts on AGW developed guidance on the diagnosis and management of AGW in an effort to unify international recommendations. Guidance was developed based on published international and national AGW guidelines and an evaluation of relevant literature published up to August 2016. Authors provided expert opinion based on their clinical experiences. Results A checklist for a patient's initial consultation is provided to help physicians when diagnosing AGW to get the relevant information from the patient in order to manage and treat the AGW effectively. A number of frequently asked questions are also provided to aid physicians when communicating with patients about AGW. Treatment of AGW should be individualized and selected based on the number, size, morphology, location, and keratinization of warts, and whether they are new or recurrent. Different techniques can be used to treat AGW including ablation, immunotherapy and other topical therapies. Combinations of these techniques are thought to be more effective at reducing AGW recurrence than monotherapy. A simplified algorithm was created suggesting patients with 1-5 warts should be treated with ablation followed by immunotherapy. Patients with >5 warts should use immunotherapy for 2 months followed by ablation and a second 2-month course of immunotherapy. Guidance for daily practice situations and the subsequent action that can be taken, as well as an algorithm for treatment of large warts, were also created. Conclusion The guidance provided will help physicians with the diagnosis and management of AGW in order to improve the health and quality of life of patients with AGW. Meda Pharma S.p.A. a Mylan Company Medical writing support was funded by Meda Pharma S.p.A. a Mylan Company.

The outbreak of the COVID-19 pandemic (caused by SARS-CoV-2) is a public health emergency of magnitude.1 The rapid spread of the novel coronavirus in such a densely populated area as Lombardy threatened the capacity of the health system. All health facilities were reorganised to contain the spread of the virus. Unprecedented social isolation measures (lockdown) were adopted to control the epidemic.2 In relation to sexual health, one would assume that the lockdown should reduce the opportunity for sexual encounters and acquisition opportunities for STIs. In Milan, the main city of the Lombardy region, there are two main STI centres which account for about 80% of STI diagnosis. On 8 March, regional ordinance limited outpatient activity to acute cases only. The two STI centres remained open for ‘emergencies’. Patients …

BackgroundSyphilis incidence has exponentially increased in recent decades, particularly among men who have sex with men (MSM). Primary syphilis is characterised by a chancre appearing at the site of Treponema pallidum (TP) inoculation. Atypical morphological variants of syphilitic chancre are frequent. Clinical suspicion must be confirmed either by the demonstration of TP within the lesion through direct tests, such as dark field microscopy (DFM) or T. pallidum nucleic acid amplification technique (TP-NAAT), or by serological tests.ObjectivesTo analyse the clinical features, the sexual behaviour and the role of diagnostic tests in a cohort of men with primary syphilis in Milan.MethodsEpidemiological, clinical and laboratory data of male patients with primary syphilis seen at the STI Center of the University of Milan between 2015 and 2019 were retrospectively evaluated. Diagnosis was confirmed by at least one positive diagnostic test of either DFM, TP-NAAT or serology.ResultsAmong a total of 244 patients, 160 (65.6%) were MSM and 32 (13.1%) were living with HIV. One hundred twenty-four (50.8%) patients had a clinically atypical chancre. Chancres were exclusively extragenital in 30 (12.3%) patients, with MSM being more commonly affected (MSM vs heterosexuals: 16.3% vs 4.8%, respectively; p=0.012), and anal region the most frequently involved site. Chancres were multiple in 68/242 (28.1%) patients and morphologically atypical in 76/244 (31.1%). Diagnosis was obtained by (1) both serology and direct methods in 158/244 patients (64.7%), (2) serology solely in 47/244 (19.3%) and (3) direct methods solely in 39/244 (16%). DFM yielded positive results in 83/139 (59.7%) patients, while TP-NAAT gave positive results in 114/121 (94.2%) patients.ConclusionsPatients with primary syphilis frequently present with morphologically atypical chancres. Furthermore, MSM commonly exhibit extragenital involvement. A combined diagnostic approach including both direct and indirect tests is needed.

The authors describe an atypical case of primary syphilis of the neck. The unusual clinical presentation and localization led to an initial diagnostic mistake. This case confirms the polymorphic character of syphilis. Considering the increased incidence of sexually transmitted infections worldwide, a high index of suspicion should be maintained by physicians.

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Mesotherapy is sometimes responsible for dermal and subcutaneous infections caused by nontuberculous mycobacteria. Mycobacterium chelonae, M abscessus, and M fortuitum are usually involved. We present two cases of deep skin infections caused by M chelonae following mesotherapy. A review of the literature is included.

At present, we have no evidence that we are doing more good than harm detecting and subsequently treating Mycoplasma hominis, Ureaplasma parvum and Ureaplasma urealyticum colonizations/infections. Consequently, routine testing and treatment of asymptomatic or symptomatic men and women for M. hominis, U. urealyticum and U. parvum are not recommended. Asymptomatic carriage of these bacteria is common, and the majority of individuals do not develop any disease. Although U. urealyticum has been associated with urethritis in men, it is probably not causal unless a high load is present (likely carriage in 40-80% of detected cases). The extensive testing, detection and subsequent antimicrobial treatment of these bacteria performed in some settings may result in the selection of antimicrobial resistance, in these bacteria, true' STI agents, as well as in the general microbiota, and substantial economic cost for society and individuals, particularly women. The commercialization of many particularly multiplex PCR assays detecting traditional non-viral STIs together with M. hominis, U. parvum and/or U. urealyticum has worsened this situation. Thus, routine screening of asymptomatic men and women or routine testing of symptomatic individuals for M. hominis, U. urealyticum and U. parvum is not recommended. If testing of men with symptomatic urethritis is undertaken, traditional STI urethritis agents such as Neisseria gonorrhoeae, Chlamydia trachomatis, M. genitalium and, in settings where relevant, Trichomonas vaginalis should be excluded prior to U. urealyticum testing and quantitative species-specific molecular diagnostic tests should be used. Only men with high U. urealyticum load should be considered for treatment; however, appropriate evidence for effective treatment regimens is lacking. In symptomatic women, bacterial vaginosis (BV) should always be tested for and treated if detected.

Hepatitis E virus (HEV) is a feco-orally transmitted pathogen and one of the most common cause of acute hepatitis worldwide. Recent studies in developed countries suggested that a direct human-to-human contact such as for sexually transmitted diseases may play a significant role in the HEV spread. The aim of this study was to investigate the seroprevalence of HEV and HAV in a group of MSM, including subjects HIV, and Treponema infected, in Milan, Italy. The overall anti HEV IgG seroprevalence in MSM was 10.2% (65/636), instead in the control group the detection rate was 5.2% (15/288) (P

The European guideline for the management of pelvic inflammatory disease includes evidence-based advice on the investigation and treatment of pelvic inflammatory disease (PID). It has been updated to acknowledge the role of Mycoplasma genitalium as an important cause of PID with testing now recommended for women presenting with possible PID and for the male partners of women with confirmed M. genitalium infection. Recent evidence suggests that serious adverse events are uncommon when using moxifloxacin and its use is now recommended as a first-line therapy, especially in those women with M. genitalium PID. The potential utility of MRI scanning of the pelvis in excluding differential diagnoses has been highlighted. The use of doxycycline is now suggested as empirical treatment for male partners of women with PID to reduce exposure to macrolide antibiotics, which has been associated with increased resistance in M. genitalium.

To evaluate the oncological and functional outcomes of patients diagnosed with penile cancer undergoing conservative treatment through thulium–yttrium–aluminium–garnet (Tm:YAG) laser ablation. Twenty-six patients with a penile lesion underwent ablation with a RevoLix 200 W continuous-wave laser. The procedure was carried out with a pen-like laser hand piece, using a 360 μm laser fiber and 15–20 W of power. Median (IQR) follow-up time was 24 (15–30) months. Recurrence rate and post-operative sexual function were assessed. Median age at surgery was 61 years. Median (inter quartile range) size of the lesions was 15 [10–20] mm. Overall, 11 (47.8%) and 12 (52.2%) at the final pathology presented in situ and invasive squamous cell carcinoma (SCC), respectively. The final pathological stage was pTis, pT1a, pT2, and pT3 in 11 (47.8%), 7 (30.4%), 3 (13.0%), and 2 (8.7%) patients, respectively. Moreover, four (17.4%) patients had a recurrence of which three (13.0%) and one (4.3%) patients developed an invasive or in situ recurrence, respectively. After treatment 6 (26.1%) patients reported a conserved penile sensitivity, while 13 (56.5%) and 4 (17.4%) patients experienced a better or worse sensitivity after ablation, respectively. Post-treatment sexual activity was achieved within the first month after laser ablation in 82.6% of the patients. Early stage penile carcinomas can be effectively treated with an organ preservation strategy. Tm:YAG conservative laser treatment is easy, safe and offers good functional outcome, with a minor impact on patient’s quality of life.

Immune evasion and disease progression of Treponema pallidum subspecies pallidum are associated with sequence diversity in the hypervariable, putative outer membrane protein TprK. Previous attempts to study variation within TprK have sequenced at depths insufficient to fully appreciate the hypervariable nature of the protein, failed to establish linkage between the protein’s 7 variable regions, or were conducted on strains passed through rabbits. As a consequence, a complete profiling of tprK during infection in the human host is still lacking. Furthermore, prior studies examining how T. pallidum uses its repertoire of genomic donor sites to generate diversity within the V regions of the tprK also yielded a partial understanding of this process, due to the limited number of tprK alleles examined. In this study, we used short- and long-read deep sequencing to directly characterize full-length tprK alleles from T. pallidum collected from early lesions of patients attending two STD clinics in Italy. Our data, combined with recent data available on Chinese T. pallidum strains, show the near complete absence of overlap in TprK sequences among the 41 strains profiled to date. Moreover, our data allowed us to redefine the boundaries of tprK V regions, identify 55 donor sites, and estimate the total number of TprK variants that T. pallidum can potentially generate. Altogether, our results support how T. pallidum TprK antigenic variation system is an unsurmountable obstacle for the human immune system to naturally achieve infection eradication, and reiterate the importance of this mechanism for pathogen persistence in the host.ImportanceSyphilis continues to be a significant public health issue in both low- and high-income nations, including the United States, where the number of infectious syphilis cases has increased dramatically over the past five years. T. pallidum, the causative agent of syphilis, encodes an outer membrane protein TprK that undergoes segmental gene conversion to constantly create new sequences. We performed deep TprK profiling to understand full-length TprK diversity in T. pallidum-positive clinical specimens and compared these to all samples for which TprK deep sequencing is available. We found almost no overlap in TprK sequences between different patients. We further estimate that the total baseline junctional diversity of full-length TprK rivals that of current estimates of the human adaptive immune system. These data underscore the immunoevasive ability of TprK that allows T. pallidum to establish lifelong infection.

Varicella-like exanthem as a specific COVID-19-associated skin manifestation: Multicenter case series of 22 patients

Syphilis is a systemic disease that initially usually involves the skin and may subsequently spread to almost all internal organs. It has polymorphous manifestations and has been defined by French Dermatologists “la grande mime” because of its ability to mimic many other diseases. If untreated syphilis can be a cause of death many years after infection. Penicillin is still the drug of choice and no documented cases of clinical resistance have been reported.

We report a case of secondary syphilis mimicking lupus vulgaris in an HIV-infected patient. A 21-year-old Brazilian man presented with a two-month history of asymptomatic cutaneous lesions accompanied by fever and fatigue. Dermatological evaluation revealed an erythematous, crusted, large plaque on the neck with the ‘apple jelly’ sign on diascopy and two smaller scaly elements on the trunk and left palm. Bacteriological examinations for bacteria and mycobacteria gave negative results. Histology revealed psoriasiform epidermal hyperplasia and dermal lymphoplasmacytic infiltrate. Serology for syphilis was positive, and immunohistochemistry confirmed the presence of Treponema pallidum in lesional skin. A diagnosis of secondary syphilis was made, and the patient was successfully treated with benzathine penicillin G. Cutaneous manifestations of secondary syphilis are protean and skin tuberculosis may be considered in the differential diagnosis, especially in HIV-infected patients. In the current case, clinical examination, and particularly, ‘apple jelly’ sign positivity, was suggestive of lupus vulgaris, but only typical histopathology and immunohistochemistry led to the correct diagnosis of secondary syphilis.

BACKGROUND: Although syphilis rates have been relatively high in Italy for over 15 years, no data on the molecular types of Treponema pallidum subsp. pallidum (T. pallidum) circulating in this country are yet available. Likewise, no data exist on how widespread is resistance to macrolide or tetracycline antibiotics in these strains. Such data would however promote comprehensive studies on the molecular epidemiology of syphilis infections in Italy and inform future interventions aiming at syphilis control in this and other European countries. GOALS AND STUDY DESIGN: Swabs from oral, genital, cutaneous, or anal lesions were obtained from 60 syphilis patients attending dermatology clinics in Milan, Turin, Genoa, and Bologna. Molecular typing of T. pallidum DNA was performed to provide a snapshot of the genetic diversity of strains circulating in Northern Italy. Samples were also screened for mutations conferring resistance to macrolides and tetracyclines. RESULTS: T. pallidum DNA was detected in 88.3% of the specimens (53/60) analyzed. Complete and partial T. pallidum typing data were obtained for 77.3% (41/53) and 15.0% (8/53) of samples, respectively, while four samples could not be typed despite T. pallidum DNA being detected. The highest strain type heterogeneity was seen in samples from Bologna and Milan, followed by Genoa. Minimal diversity was detected in samples from Turin, in spite of the highest number of typeable samples collected there. Resistance to macrolides was detected in 94.3% (50/53) of the strains, but no known mutations associated with tetracycline resistance were found. CONCLUSIONS: Genetic diversity among T. pallidum strains circulating in Northern Italy varies significantly among geographical areas regardless of physical distance. Resistance to macrolides is widespread.

The emergence of antibiotic resistant strains poses a great concern for gonorrhea treatment. The aim of this study was to characterize penicillinase–producing Neisseria gonorrhoeae (PPNG) isolates collected in Italy in two time frames, 2003–2004 and 2014–2015. A total of 80 PPNG were characterized for the blaTEM gene variant and the plasmid type. Furthermore, gonococci were typed using Neisseria gonorrhoeae multiantigen sequence typing. Antibiotic susceptibility assay was performed for penicillin, ciprofloxacin, ceftriaxone, and spectinomycin by Etest and minimum inhibitory concentration (MIC) test strip methods. The β-lactamase production was detected using nitrocefin test. Among PPNG isolates, four blaTEM alleles were identified as follows: blaTEM-1, blaTEM-228, blaTEMP14S, and blaTEM-135. The African plasmid possessed the blaTEM-1, blaTEM-228, and blaTEMP14S, whereas blaTEM-135 was identified in Toronto/Rio and Asian plasmids. The percentage of isolates with the blaTEM-1-carrying African plasmid increa...

Anogenital warts (AGWs) are an important issue for public health centers dealing with Sexually Transmitted Infections. They are epidemiologically relevant, with significant morbidity and an established effective treatment is lacking. In this article, we examine the epidemiological, diagnostic, and therapeutic aspect of the problem in order to give an up to date picture of the situation and a practical clue for the management of AGWs.