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Human papillomavirus (HPV) is a well-established carcinogenic agent. This study aimed to assess prevalence and persistence rate of genital HPV infection in sexually transmitted infections (STIs) patients and healthy subjects. The risk factors influencing the persistence of genital HPV infection were also investigated. The samples were collected with the ThinPrep liquid-based cytology system. Among the HPV-positive patients, those consenting were retested after 12 months. Overall, 145/292 subjects proved HPV positive with a higher prevalence (51%) in STI than in healthy population (43%). The persistence of genital HPV infection was statistically associated with female gender, HR-HPV infection, smoking, and Ureaplasma parvum infection.

After the incidental observation of an almost complete resolution of maculopapular eruption in a patient having simultaneously secondary syphilis and trichomonas vaginalis infection, we extended the treatment with tinidazole (500 mg 4 times daily for 7 days) to 10 other early syphilis patients before the start of the conventional penicillin treatment. All patients showed marked improvement of their lesions in a few days. After the introduction of the conventional penicillin regimen, the lesions further improved and VDRL titers declined at least 4-fold within 6 months in all patients. Tinidazole is a 5-nitroimidazole derivative as well as metronidazole but with a longer plasma half-life. It is activated intracellularly by bacterial/parasitic enzymes to a redox cytotoxic intermediate that damages large protein molecules and inhibits repair and transcription of DNA affecting also the cell wall. With this action, tinidazole might also have a synergic action with penicillin and doxycycline, facilitating the entry of such drugs. It is possible that tinidazole has the same bactericidal action on spirochetes other than Borrelia, such as Treponema pallidum, explaining its rapid therapeutic action on the lesions of early syphilis. Whether this action could be confirmed by studies on larger series of patients, tinidazole might be considered in case of allergy to penicillin or other antibiotics usually prescribed in syphilis.

Epstein-Barr virus (EBV) is a human herpesvirus spread in childhood by contact with saliva. In all populations, the great majority of people are infected by middle age. EBV can cause asymptomatic infection, nonspecific symptoms or, especially in adolescents and young adults, the infectious mononucleosis (IM), characterized by pharyngitis, lymphadenopathy, fatigue, and fever. Two main types of skin rashes, accounted as atypical exanthems, occur in patients with acute IM: a faint erythematous maculopapular eruption of 24-48 hours duration (5-15% of the patients) or a pruritic maculopapular rash in almost all patients receiving ampicillin or amoxicillin. Moreover EBV acute infection has been related to other cutaneous manifestations, such as Gianotti-Crosti syndrome, unilateral laterothoracic exanthem (especially in children), and others. In this study, we reported a case of atypical exanthem with an erythematous-papulovesicular pattern in a 22-year-old female patient with IM and performed a review of the literature of the cutaneous and mucosal eruptions occurring during EBV acute infections.

Different therapeutic modalities for ano-genital warts (AGWs) are available but data on the efficacy of 5-fluorouracil 0.5%/salicylic acid 10% solution (5FU/SAsol) in the treatment of AGWs are scarse. We enrolled 17 patients with AGWs (14 males, 3 females with a mean age of 34.2 years) who gave written informed consent to the off-label use of topical 5FU/Sasol. Response to treatment was assessed based on the AGWs number: complete if there was complete clearance of the lesions; partial if there was50% decrease in the lesion number and none if there was50% decrease in the lesion number. Considering together partial and complete treatment response, 88% of the patients at 3 months and 94% at 6 months benefited from the 5FU/SAsol treatment. 5FU/SAsol was well tolerated by all the patients except one who experienced a burning sensation immediately after the application. The clearance rate that we found for 5-FU/SAsol after 3 months of treatment is comparable with that of the other commonly used therapeutic modalities (liquid nitrogen cryotherapy, imiquimod 5% cream). However, several patients on imiquimod and almost who underwent cryotherapy reported pain as adverse event while a mild pain was rarely reported with 5-FU/Sasol. In conclusion, although nowadays in Italy 5-FU/SAsol is marketed only for the treatment of actinic keratosis, our study described its effectiveness and tolerability also in the treatment of AGWs. Our data suggest that 5-FU/SAsol should be considered not only in case of resistant/recurrent AGWs but also as the first therapeutic option, especially when the number of lesions is small.

Pityriasis rosea (PR), PR-like eruptions (PR-LE), and herpes zoster have been frequently reported during the COVID-19 pandemic and following COVID-19 vaccination. PR is a self-limiting exanthematous disease and herpes zoster is a treatable condition; therefore, their occurrence does not require discontinuation of the vaccination schedule. PR-LE is a hypersensitivity reaction and is, therefore, less predictable in its course. In the case of a booster dose, the clinical manifestation may not recur, may be different from PR-LE, or may present with systemic symptoms; however, in the case of PR-LE, the possibility of mild and predominantly cutaneous adverse events should not discourage all eligible candidates from receiving and completing the COVID-19 vaccination program, as such adverse reactions represent a small risk considering the possible severe and fatal outcome of COVID-19. We emphasize the relevance of looking for any viral reactivation in patients infected with SARS-CoV-2 who have skin eruptions. The search for viral reactivations could be useful not only for distinguishing between PR and PR-LE but also because viral reactivations may contribute to a patient's systemic inflammation and influence the course of the disease.

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 summary Each 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.

In response to the Covid-19 outbreak, among other previous ``non-pharmaceutical interventions99, on March 22, 2020 the Italian Government imposed an economic lockdown and ordered the closing of all non-essential economic activities. This paper estimates the causal effect of this measure on mortality by Covid-19 and on mobility patterns. The identification of the causal effect exploits the variation in the number of active workers across municipalities induced by the economic lockdown. The difference-in-difference empirical design compares outcomes in municipalities above and below the median variation in the share of active population before and after the lockdown within a province, also controlling for municipality-specific dynamics, daily-shocks at the provincial level and municipal unobserved characteristics. Our results show that the intensity of the economic lockdown is associated to a statistically significant reduction in mortality by Covid-19 and, in particular, for age groups between 40-64 and older. Back of the envelope calculations indicate that 4,793 deaths were avoided, in the 26 days between April 5 to April 30, in the 3,518 municipalities which experienced a more intense lockdown. Assuming linearity, a 1 percentage point reduction in the share of active population caused a 1.32 percentage points reduction in mortality by Covid-19. We also find that the economic lockdown, as expected, led to a reduction in human mobility. Several robustness checks corroborate our empirical findings.

Highlights • An enanthem is a mucosal eruption that precede, follow or occur simultaneously with an exanthem. • Enanthems may be triggered by an underlying infection or a drug received by the patient or both. • Patterns are: vesicular, macular, maculo-papular, maculo-papular-petechial, and petechial. • Erythemato-vesicular and petechial patterns are the most frequent in adults. • Some enanthems are pathognomonic for a disease as Koplik's spots for measles., Globalization entails several medical problems, along with economic and social complications. Migrations from the other continents, increasing numbers of tourists world-wide, importation of foreign parasites, Aedes albopictus for example, have made diseases so far unknown in Europe a reality. The rapid spread of the COVID-19 pandemic throughout the world is a warning that other epidemics are still possible. Most, if not all of these diseases, transmitted by viruses or bacteria, present with cutaneous symptoms and signs that are highly important for a speedy diagnosis, a fundamental concept for arresting the diseases and saving lives. Dermatologists play a significant role in delineating cutaneous and mucosal lesions that are often lumped together as a rash. We provide a review of many of these cutaneous and mucosal lesions that sometimes are forgotten or even ignored.

Sexually transmitted infections (STIs) may impact on the patient's physical, psychological and sexual health and negatively influence their Quality of Life (QOL). Studies on this topic are scarce. This study aimed to assess the impact of STIs different from HIV on QOL, mood and sexual functioning in the patients attending our STIs center in comparison with patients affected by chronic inflammatory bowel diseases (IBD).An anonymous questionnaire was provided. It included 3 validated questionnaires: the European Quality of Life 5 dimensions 5 levels; the Beck Depression Inventory-II for depressive symptoms; the Changes in Sexual Functioning Questionnaire (CSFQ) for sexual functioning.Seventy-three STIs patients and 51 IBD patients participated in the study. The mean EQ-5D-5L questionnaire scores were 86.72 in STIs and 89.21 in IBD patients, without statistically significant difference between the two groups. Symptoms of depression were more common and severe in STIs patients compared to IBD patients. Sexual functioning was slightly worse in STIs patients than in IBD patients.This is one the very few studies focused on the impact of STIs on patient's physical, psychological and sexual health. Physicians dealing with STIs should consider the possible psychological consequences of the disease.

Syphilis continues to be a significant public health issue in both low- and high-income countries, including the United States where the rate of syphilis infection has increased over the past 5 years. Treponema pallidum subsp. pallidum, the causative agent of syphilis, carries the outer membrane protein TprK that undergoes segmental gene conversion to constantly create new sequences. We performed full-length deep sequencing of TprK to examine TprK diversity in clinical T. pallidum subsp. pallidum strains. We then combined our results with data from all samples for which TprK deep sequencing results were available. We found almost no overlap in TprK sequences between different patients. Moreover, our data allowed us to estimate the total number of TprK variants that T. pallidum subsp. pallidum can potentially generate. Our results support how the T. pallidum subsp. pallidum TprK antigenic variation system is an equal adversary of the human immune system leading to pathogen persistence in the host., Immune evasion and disease progression of Treponema pallidum subsp. pallidum are associated with sequence diversity in the hypervariable 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 seven variable regions, or were conducted on isolates passed through rabbits. As a consequence, a complete profile of tprK during infection in the human host is still lacking. Furthermore, prior studies examining how T. pallidum subsp. pallidum uses its repertoire of genomic donor sites to generate diversity within the variable regions of the tprK have 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 subsp. pallidum collected from early lesions of patients attending two sexually transmitted infection clinics in Italy. We demonstrate that strains collected from cases of secondary syphilis contain significantly more unique variable region sequences and full-length TprK sequences than those from cases of primary syphilis. Our data, combined with recent data available on Chinese T. pallidum subsp. pallidum specimens, show the near-complete absence of overlap in TprK sequences among the 41 specimens profiled to date. We further estimate that the potential antigenic variability carried by TprK rivals that of current estimates of the human adaptive immune system. These data underscore the immunoevasive ability of TprK that allows T. pallidum subsp. pallidum to establish lifelong infection.

Pityriasis rosea (PR) is an exanthematous disease whose etiology is related to reactivation of herpes human herpesviruses 6 (HHV-6) and 7 (HHV-7). We observed two cases of PR arising during omalizumab therapy for chronic spontaneous urticaria (CSU). Here we report for the first time PR occurring during omalizumab treatment. After PR diagnosis, viral serology was performed. Data in literature about omalizumab mechanism of action, PR and HHV-6/7 infection were analyzed in order to identify possible correlations. In both our cases IgM against HHV-6 and HHV-7 were negative. The first patient presented altered IgG titers for both viruses (1:160 and 1:80, respectively) while only HHV-6 IgG (1:320) were detected in the second patient. From data in literature, we consider it presumable that apoptotic immune cells due to omalizumab immunomodulation could release viral proteins produced from integrated DNA. This could elicit cutaneous cross-reactivity and PR onset. In conclusion, we think there is a link between omalizumab therapy and PR occurring in patients with CSU. Our case history is too small to draw firm conclusions. Data collection of similar cases could be helpful to improve our knowledge.

We describe a patient presenting with annular-arciform symmetric lesions of the palms as the unique manifestation of secondary syphilis. The polymorphism of skin lesions in secondary syphilis depends entirely on the degree of inflammatory infiltrate, the level of vascular involvement and the resulting ischemia of the skin. Besides the transient and diffuse maculo-papules (roseola syphilitica), secondary syphilis skin lesions may have different morphology and shape. It has already been reported that in cases of reinfections by Treponema pallidum the skin lesions may be arciform, as in our patient, and asymmetric. Indeed, previous syphilis may attenuate the clinical and laboratory manifestations of a new infection with T.pallidum, that occurs with less severe skin manifestations or presents as latent syphilis. However, to our knowledge, annular-arciform lesions of the palms as unique manifestations of secondary syphilis have never been described. Clinicians should be well trained to recognize the atypical presentations of syphilis, especially in patients who have already received a syphilis diagnosis, since its incidence is steadily increasing in Europe, especially in men having sex with men.

Data on the prevalence of sexually transmitted infections (STIs) and risk factors among incarcerated people are few and data about STIs awareness among inmates are even lacking. This study aimed to assess prevalence of STIs, risky behaviours and STIs level of knowledge in male inmates of the Casa Circondariale-Genova Marassi, the main penitentiary in Genoa, Italy. Between January and June 2019, 662 inmate medical records were retrospectively examined to obtain clinical and laboratory data about STIs. To investigate the inmate level of knowledge of STIs and their risky behaviours, 111consenting participants answered, anonymously, a written questionnaire. One hundred and twenty-two patients had at least one infectious disease when entered the prison: HIV (1.8%), HBV (2.7%), HCV (12.5%) and syphilis (1.3%). When asked to select from a list of diseases which ones they thought to be sexually transmitted, only 12% of the inmates answered correctly; most of them ignored which body fluids are at risk for HIV transmission, which STIs can induce tumors and if any vaccination exists to prevent STIs. Substance abuse was common among inmates that frequently exchanged needles for injecting drugs. To reduce the STIs incidence, it is necessary to target high-risk populations: everyone entering a prison should be offered a systematic screening of all STIs, including those currently neglected. Since STIs knowledge among inmates is poor and risky behaviours are diffuse, informative interventions in prison may provide an opportunity to educate such a high-risk population.

Human papillomavirus (HPV) infection is the most common sexually transmitted infection (STI) worldwide. In women with genital infection, the virus can be transmitted by sex to the oral cavity of their partners and then to their own oral cavity. The aim of the present study was to establish the prevalence of cervical/anal/oral HPV infection in women attending the Dermatology Unit of the Policlinico San Martino of Genoa, the regional reference hospital in Liguria, Italy.Between January 2016 and December 2018, the female patients attending the STI center (cases) and those requiring a full body skin examination for skin cancer screening ("supposed" healthy population: controls) were recruited. Cervical/anal/oral samples were collected with ThinPrep liquid based cytology preparation system: polymerase chain reaction for HPV and cytological evaluation were performed. Overall, 85 cases and 31 controls were recruited.Cervical HPV infection was detected in 60% of the cases and 48% of the controls; anal HPV infection in 44% of the cases and 26% of the controls. Cervical and anal HPV infection resulted associated, especially in the control group. Moreover, 32% of the cases and 29% of the controls proved HPV positive in the oral cavity. In the cases of our series, prevalence of cervical, anal and oral HPV infection was higher compared with the controls.The high prevalence of anal-oral infections and the frequent association between anal and cervical infections, provide reason to suggest HPV screening also in the anal and oral regions, which may represent HPV reservoirs and grounds for cancer development.

A new type of coronavirus family (SARS-CoV-2), which can be found in humans and animals, with many varieties and clinical symptoms, was first seen in Wuhan, China in late 2019, under the name novel Coronavirus Disease 2019 (COVID-19). In the literature, cutaneous symptoms related to the disease are generally emphasized. However, it is not yet known whether this new SARS-CoV-2 virus, which has entered our lives, plays a role in the etiopathogenesis of dermatological diseases. The patients who were admitted to the dermatology outpatient clinic between 1 April and 15 May 2019, and on 1 April and 15 May 2020 were retrospectively analyzed by searching the hospital automation system and patient files. The reason for the same months to be included in the study was to exclude seasonal effects on the diseases. After pandemic, the number of patients with Pityriasis rosea and Kawasaki disease increased significantly in patients who applied to the dermatology outpatient clinic. Our study is the first study showing Pityriasis rosea increase during the pandemic period. We think that this increase is related to HHV-6 reactivation. Herein, we wanted to draw attention to two diseases in which Human Herpes 6 (HHV-6) was accused in etiopathogenesis: Kawasaki disease and Pityriasis rosea.

Herpes zoster (HZ) is typically characterized by pain involving the area of vesicular eruption. Several patients, however, complain of unilateral radicular pain without rash (zoster sine herpete [ZSH]). To evaluate whether the severity and duration of pain and the use of analgesics are greater in ZSH patients than in typical HZ with rash, 16 consecutive patients with acute unilateral pain, without vesicular eruption (ZSH), were compared with 16 controls suffering from typical HZ eruption. Only patients with laboratory evidence of varicella-zoster virus (VZV) reactivation were selected. Serum samples were obtained from all patients at their initial visit and 1 and 2 months later. Monthly, the administered therapies and the average pain score (visual analog scale [VAS] score) were recorded. VZV DNA persisted statistically higher in ZSH sera than HZ sera 1 month after onset (P = 0.0007). ZSH patients averaged greater pain than HZ patients, scoring VAS 76.88 and 66.88 ( P = 0.0012), respectively. ZSH patients used significantly more opioid therapy than HZ patients ( P = 0.0449; OR, 9.00). This is the first study comparing pain in ZSH and HZ patients: greater severity and duration of pain and more opioid use was detected in patients with ZSH.

Background: Pityriasis rosea (PR) is a self-limiting exanthematous disease associated with human herpesvirus (HHV)-6 and/or HHV-7 reactivation. In pregnant women, PR may be associated with pregnancy complications. Objective: To determine relevant risk factors in the development of negative pregnancy outcome in PR. Methods: Between 2005 and 2017 at the Department of Dermatology, University of Genoa, we recruited 76 women who developed PR during pregnancy. In 60 patients without known risk factors for intrauterine fetal death (30 with pregnancy complications and 30 without) we analyzed the pregnancy week of PR onset, presence of enanthem and of constitutional symptoms, PR body surface area involvement, age, and in 50 patients (20 with pregnancy complications and 30 without), the viral load of HHV-6 and HHV-7 (copies/mL). Results: In logistic regression analysis, early onset of PR (p = 0.0017) and enanthem (p = 0.0392) proved to be significantly associated with pregnancy complications. HHV-6 viral load (copies/mL) (p < 0.0001), constitutional symptoms (p < 0.001), and PR body surface area involvement (p < 0.004) were also significantly associated with pregnancy complications. Conclusion: The onset of PR before week 15 and enanthem may be considered major risk factors that should alarm the dermatologist. Constitutional symptoms and involvement of > 50% of the body area may be considered minor risk factors.

Nicotinamide is the precursor of nicotinamide adenine dinucleotide (NAD+), an essential cofactor for adenosine triphosphate (ATP) production. It has recently been reported to be effective in reducing the rates of new non-melanoma skin cancers (NMSCs) and actinic keratosis (AKs). We studied the efficacy of oral nicotinamide as treatment for AKs in transplant recipients. We recruited 38 transplant (eight liver and 30 kidney) patients with single or multiple AKs. Nineteen patients were randomly assigned to Group 1 and took nicotinamide 500 mg/daily (cases); the other 19 patients were randomly assigned to Group 2 without nicotinamide (controls). At base-line, AKs were identified, measured, and photographed for follow-up. Five patients underwent an AK biopsy for histopathology. Statistical analyses were performed using the Student t test. At baseline, no statistically significant differences were observed regarding AK size between the two groups. After six months, among the cases, AKs had significantly decreased in size in 18/19 patients (88%). Among these 18 patients, seven patients (42%) had shown complete clinical regression and no patient developed new AKs. Conversely, among the controls, 91% showed an increase in AK size and/or developed new AKs. Seven pre-existing AKs progressed to squamous-cell carcinoma. Nicotinamide appears to be effective in preventing and treating AKs, although the mechanisms are still unclear. Further studies with a larger sample of organ transplant recipients and a longer follow-up period are needed to further support our conclusions.

Human papillomavirus (HPV) is a carcinogenic agent responsible for tumor development in many sexually involved tissues. We present a survey on the prevalence of HPV infection in a risk population for sexually transmitted infections (STIs). The studied population was formed by 125 STI clinic attendees, who took part in a screening program on STIs. To be included in the study, the patients had to show no overt clinical signs of HPV infection. Genital (cervical in women, urethral in men), anal, and oral samples were collected with ThinPrep liquid based cytology preparation system. Overall, of the screened population, 56% proved positive for genital HPV, 37% for oral HPV, and 42% for anal HPV infection. Our data indicate that in STI patients, HPV infection is more prevalent, than previously estimated. Further studies are needed to better understand the epidemiological burden of HPV in sexually involved tissues, especially in the oral mucosa.

Chronic wounds include arterial, venous, diabetic and pressure ulcers. The term "chronic wound" defines wounds that have not healed within three months. The possible causes that transform a simple wound into a chronic one are the object of study, and research has focused on infection as one of the crucial factors in producing and maintaining chronic wounds. In fact, 60% of chronic wounds are colonized by bacteria living in a biofilm. A biofilm is a complex aggregation of microorganisms characterized by the secretion of an adhesive and protective matrix. The two most common biofilm generators are Staphylococcus aureus and Pseudomonas aeruginosa. Several conditions constitute risk factors for the formation of biofilms, such as diabetes mellitus, venous insufficiency, malnutrition, cancer, oedema, and repetitive trauma. There are no standard diagnostic tests to determine the presence of biofilms, but there are several clinical indications which can help, and performing a tissue biopsy is better than a swab. Wound bed preparation is a crucial part of biofilm treatment and surgical or conservative sharp wound debridement are the preferred treatments that are effective in removing or reducing biofilms. We report three cases of complex wounds and their treatment.

Background Typically, hand-foot-and-mouth disease (HFMD) is a mild childhood illness associated with coxsackievirus (CV)-A16, CV-A6, enterovirus (EV)-A71. Objectives To identify the viral agents associated with severe cases of atypical HFMD in Italy. Study design Epidemiologically unrelated cases of severe atypical HFMD admitted to the Emergency Room (ER) of IRCCS San Martino IST (Genoa, Italy) in 2014–2016 were investigated. Serologic screening for viral positivity was performed against exanthem-inducing agents. Ten cases with serology indicative of recent EV infection were selected. Molecular assays were used to detect viral genomes in blood [EVs, Parvovirus B19 (PVB19), herpesviruses (CMV; EBV, HHV-6, -7, -8)]. Results CV-A6 was detected in 10 cases of severe atypical HFMD. Two cases were also infected with PVB19. Herpesviruses were not detected. Phylogenetic analysis mapped the CV-A6 strains into a single cluster related to two recent isolates from a German and an Asian child. Fever, systemic symptoms, severe vasculitis-like rash, and enanthem were predominant at presentation. Spontaneous recovery occurred in 1–3 weeks. Conclusions CV-A6 is emerging as a frequent cause of severe atypical HFMD in Italian adults. This viral agent is disseminating worldwide. Dermatologists must identify the manifold alterations caused by EVs and understand the diagnostic power of current virology methods.

Any infectious illness presenting with an eruption in a pregnant patient may be associated with an increased risk of fetal loss. The viruses that can infect the placenta during maternal infection and can be transmitted to the fetus and cause congenital disease include the rubella virus, the measles virus, the varicella zoster virus, parvovirus B19, human cytomegalovirus, arboviruses, and hepatitis E virus type 1. In addition, some bacteria responsible for exanthematous diseases, like Treponema pallidum, can be transmitted during pregnancy from the mother to the fetus and cause fetal loss. All these infectious agents can cause typical and/or atypical exanthems whose etiologic diagnosis is sometimes difficult but important to determine, especially in pregnant women because of the potential risk to the fetus. In the last 20 years, we have extensively studied pityriasis rosea from the clinical and laboratory perspectives, demonstrating the pathogenic role of human herpesvirus (HHV)-6 and -7. We synthesize the available evidence that PR may be associated with active HHV-6/7 infection and therefore with complications during pregnancy and fetal loss. We have also summarized the emerging infectious illnesses of dermatologic interest that may represent life-threatening health conditions for the fetus: measles, rubella, arbovirus infection, and syphilis.

Background In Italy, the incidence of new cases of melanoma is roughly 10,000 cases per year, with an average rate of mortality of 5-6 per 100,000 population per year respectively. The objective of this retrospective study was to evaluate the epidemiological incidence of primitive melanoma, including the incidence of multiple melanomas occurring in the same patient. Furthermore, we studied all histological different types of melanoma focusing on the presence of an association nevus-melanoma. Methods A clinical epidemiologic retrospective study from January 2010 to March 2015 was recorded. For each lesion, mitotic rate, Breslow's index, ulceration, presence of regression, vascular and perineural invasion, lymphocytic infiltrate, microsatellitosis and presence of pre-existencing nevus were also studied. Results Five hundred eighty primitive cutaneous melanomas (CMs) were removed from 525 patients with an incidence of 18-20 new melanomas/100,000 habitants/year. Eighty percent of these were at stage T0-1. Among other melanomas, SSM was the predominant subtype (85% of cases). Only 18 cases had lymph node metastases and 13 (2%) lymph node and/or distant metastases (stage IV) at time of diagnosis. Mitotic figures were present in 25% of cases (143 cases out of 580) without significant gender differences. Conclusions The incidence of new melanomas founded is close to the CM's incidence in US population in 2016 with a high percentage of superficial melanomas highlighting the importance of prevention campaigns. The presence of melanoma on a preexisting nevus in only 16% of cases allow to conclude that this association is overestimated in literature. On the contrary the high incidence of a second melanoma in the 7% of cases in a relatively short period of survey leads to the conclusion that this data is underestimated.

Introduction Aortitis is a well-recognized manifestation of the tertiary stage of syphilis. Evidence acquisition Although often regarded as an unexpected diagnosis, actually new cases of cardiovascular syphilis continue to be reported. Presumably, Treponema pallidum invades the aortic wall and the inflammatory response progresses towards obliterative endarteritis and necrosis of the muscular and elastic fibers in the aortic media. The consequent weakening of the aortic wall can lead to severe complications, represented by aortic aneurysm, aortic valvular insufficiency, aortic root dilation and coronary ostial stenosis. We perused the literature of the last 6 years to assess the prevalence and possible changes over time of syphilis cardiovascular manifestations. Evidence synthesis Forty four articles were collected, reporting on 66 patients. Many patients presented more than one complication. Aortic aneurysm was the most frequent involvement, detected in 71% of patients. Fusiform or saccular aneurysms often interested the thoracic aorta, primarily located on the ascending segment. The second most common complication was the aortic valvular insufficiency, found in 47% of patients. Coronary ostial stenosis and dilation of the aortic root were less frequent. Conclusions Comparing our study with the previous ones, the cardiovascular involvement appeared roughly constant over time. Although many articles fail to provide useful information, such as a detailed history and the presence of risk factors, we must note that most patients had no predisposing factors and denied a primary infection. Cardiovascular syphilis is still present nowadays and it is important not to forget the "great imitator" in the event of its characteristic symptoms.

PSOdisk is a 10-item visual instrument, aimed at assessing the burden of disease in patients with psoriasis. To compare PSOdisk with a scientifically validated questionnaire, the Dermatology Life Quality Index (DLQI), and asses both tools in relation to Psoriasis Severity Index (PASI) and patient acceptance. Fifty patients with cutaneous psoriasis and/or arthritic psoriasis were recruited. Correlation analysis between PSOdisk and DLQI was performed using Pearson’s product-moment correlation coefficient. A multivariate linear regression was carried out to investigate the effect of PASI on PSOdisk and DLQI scores. In addition, we evaluated completion times as well as patient satisfaction for both PSOdisk and DLQI. PSOdisk and DLQI mean scores were 22.04 ± 20.56 and 3.35 ± 4.52, respectively. The mean value for PASI was 5.98 ± 5.89 and for age was 55.88 ± 14.09 years. The mean value of Cronbach’s coefficient alpha was 0.88 for PSOdisk and 0.90 for DLQI, suggesting good reliability. A significant correlation was found between PSOdisk and PASI, and a statistically significant correlation between DLQI and PASI. Multivariate linear regression analysis demonstrated a statistically significant effect of PASI on both the DLQI score and PSOdisk score. PSOdisk demonstrates good correlation with DLQI and PASI, good patient satisfaction, and requires a short completion time.

An effective mechanism for introduction of phenotypic diversity within a bacterial population exploits changes in the length of repetitive DNA elements located within gene promoters. This phenomenon, known as phase variation, causes rapid activation or silencing of gene expression and fosters bacterial adaptation to new or changing environments. Phase variation often occurs in surface-exposed proteins, and in Treponema pallidum subsp. pallidum , the syphilis agent, it was reported to affect transcription of three putative outer membrane protein (OMP)-encoding genes. When the T. pallidum subsp. pallidum Nichols strain genome was initially annotated, the TP0126 open reading frame was predicted to include a poly(G) tract and did not appear to have a predicted signal sequence that might suggest the possibility of its being an OMP. Here we show that the initial annotation was incorrect, that this poly(G) is instead located within the TP0126 promoter, and that it varies in length in vivo during experimental syphilis. Additionally, we show that TP0126 transcription is affected by changes in the poly(G) length consistent with regulation by phase variation. In silico analysis of the TP0126 open reading frame based on the experimentally identified transcriptional start site shortens this hypothetical protein by 69 amino acids, reveals a predicted cleavable signal peptide, and suggests structural homology with the OmpW family of porins. Circular dichroism of recombinant TP0126 supports structural homology to OmpW. Together with the evidence that TP0126 is fully conserved among T. pallidum subspecies and strains, these data suggest an important role for TP0126 in T. pallidum biology and syphilis pathogenesis.

is missing (Correspondence)

We describe herein a woman who developed subcutaneous gummas in her trochanteric regions, bilaterally, although she had been treated for syphilis two decades earlier. Evidence of Treponema pallidum latent late infection was the presence of IgG antibodies against T. pallidum and the positive non-treponemal and treponemal tests. Moreover, immunohistochemical staining for T. pallidum detected some spirochetes close to the atrophic adipocytes allowing the diagnosis of lypo-atrophic panniculitis tertiary syphilis. This is the first case of tertiary syphilis presenting as panniculitis in an immunocompetent patient, demonstrating that subcutaneous fat may be another organ infected in tertiary 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.

Kawasaki disease (KD) is an acute systemic vasculitis that occurs primarily in children and rarely in adults, possibly after bacterial or viral infections in genetically susceptible hosts. KD may frequently be undiagnosed especially in adult patients without the presence of all the classical clinical criteria (incomplete or atypical KD). In addition, many differential diagnoses could be considered. Here, we report a case of KD in an adult patient with clinical features characteristic of the classical form. KD requires a long-term management in both paediatric and adult patients, in order to avoid complications that could follow both the acute and retrospective diagnoses of KD.

Pityriasis rosea (PR) is a common, self-limiting exanthematous disease associated with a systemic reactivation of human herpesvirus 6 (HHV-6) and/or HHV-7. It usually occurs in the second or third decade of life whereas it is uncommon in patients younger than 10 years. We studied the clinical features and virological parameters of 31 children with PR, comparing them with those in adults. Our findings indicate that PR presents different characteristics between children and adults, mainly consisting of time lapse between herald patch and generalized eruption, duration of the exanthem, oropharyngeal involvement and persistence of HHV-6 and HHV-7 plasma viremia. Overall, these results suggest that, following HHV-6 and/or HHV-7 systemic active infection, the pathogenetic mechanisms involved in PR may at least partly be different in children and adults.

Introduction During syphilis a compelling fight is engaged between the host's humoral and cellular immune responses that work to eliminate the infection and Treponema pallidum (T. pallidum) that manages to evade eradication and cause chronic infection. Different mechanisms are utilized by treponemes to overcome immunological response. Although penicillin (BPG) proved to be effective in quelling the early manifestations of the disease and consequently its contagiousness, questions remain about its ability to prevent the late complications and to provide a microbiological eradication in vivo. In fact, both serological and microbiological failures have been reported following conventional treatment. Evidence acquisition We reviewed some biologic properties of T. pallidum in order to establish a relationship with the persistence of the infection and the alleged treatment resistance. Evidence synthesis The host humoral response, sometimes, may not protect completely against T. pallidum and accounts for the persistent infection and tertiary damages. In fact, the cell mediated response during infection may be downregulate in response to pathogen-derived molecules, or indirectly by generating Treg cells. It is also possible that there are strain types of T. pallidum with higher ability of evasion determining neurosyphilis. In addition, apart the impressive results that BPG has made on the syphilis cutaneous lesions, concerns still remain on its efficacy in preventing late complications. Conclusions Understanding the biology of the T. pallidum may help researchers in this field to develop future target therapies in order to prevent persistent infection and progression of the disease.

Enteroviruses are the leading cause of exanthems in children, especially during summer and autumn. Enterovirus infections may occur in epidemics or small outbreaks. A 30-year-old woman presented with a three-day history of an erythematous maculopapular skin rash with petechiae localized exclusively under the nipple of the right breast. The skin eruption was associated with an erythematous-petechial enanthem. The patient complained of low-grade fever, headache, asthenia, sore throat and arthromyalgias. IgM (1:128) and IgG (1:640) antibodies against Coxsackievirus A4 were detected by the virus neutralization test. Reverse transcriptase real time polymerase chain reaction (PCR) assay detected enterovirus RNA in the patient's plasma and faeces. Diagnosis of an acute localized exanthem due to Coxsachievirus A4 was performed. Skin lesions improved in seven days and completely cleared in two weeks without any systemic or topical treatment. Physicians should be aware of the possibility that enteroviruses may determine localized skin eruptions in addition to hand-foot-mouth disease and atypical exanthems. Viral infections should be considered in the differential diagnosis of localized dermatitis especially when the skin eruption is associated with enanthems and with systemic symptoms.

is missing (Correspondence)