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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.

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.

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.

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.

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.

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.

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.

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.

Background Recently, Herpes simplex virus (HSV)-1 seroprevalence declined among adolescents, rendering young people lacking HSV-1 antibodies more susceptible to genital HSV-1 acquisition, if sexually exposed. The aim of the present study was to identify the possible risk factors for the development of HSV-1 related Herpes genitalis (HG). Methods From January 2012 to December 2015, patients with HG attending three Sexually Transmitted Infections Units in Northern Italy were recruited. A genital swab on the lesions for the search of HSV-1/2 DNA through real time polymerase chain reaction (PCR) and a serum sample for HSV-1/2 specific serology were performed. Moreover, patients were asked whether they had personal history of herpes labialis (HL). Patients with PCR proved HSV-1 HG were included as cases; asymptomatic subjects attending STI Units for a blood check were recruited as controls and were checked for HSV-1/2 serology. Results The study included 141 cases and 70 controls. Specific HSV-1 antibodies were found in 34.7% of the cases and 67% of the controls. History of recurrent herpes labialis (RHL) was found in 4% of the cases and 31% of the controls. The occurrence of RHL in HSV-1 seropositive patients resulted lower in the case group compared to the control group. Conclusions We can speculate about a protective role for RHL against the clinical appearance of HSV-1 HG. The clinical usefulness of our study involved especially the counselling in serodiscordant couples. The presence of HSV-1 antibodies in asymptomatic sexual partners does appear protective for HG manifestation only in presence of RHL history.

Tularemia is an infectious zoonosis caused by Francisella tularensis, an aerobic, noncapsulated, Gram-negative coccobacillus. It is more common in the northern hemisphere, and there are sporadic reports in non-endemic areas. The bacterium is usually transmitted by the bite or feces of a tick or other arthropods such as mosquitoes and horseflies. We report a case of an Italian patient with tularemia after a horsefly bite.

Background Pityriasis rosea (PR) is an exanthematous disease associated with the endogenous systemic reactivation of human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7). Oropharyngeal lesions may be associated with the exanthema, but anecdotal evidence suggests that few dermatologists are aware of their occurrence. Objective Classifying oropharyngeal lesions in PR, establishing their prevalence, and assessing their possible association with different PR forms. Methods The records of all PR cases diagnosed in the Dermatology Clinic of Genoa University between 2003 and 2016 were retrospectively reviewed to examine sex and age of the patients, PR type, presence of enanthema, systemic symptoms, specific anti–HHV-6 and or HHV-7 serology, and HHV-6 and/or HHV-7 DNA loads. Results The oropharyngeal mucosa was carefully examined in 527 patients with PR. Painless oropharyngeal lesions were observed in 149 patients with PR (28%) and classified as erythematomacular, macular and papular, erythematovesicular, and petechial lesions. The petechial and macular and papular patterns were those most frequently observed. There was no statistically significant difference in the levels of HHV-6 and HHV-7 viremia in the plasma of patients with enanthema and those without. Limitations Because this was a retrospective study, biopsies on mucosal lesions were not performed. Conclusion Our findings showed that enanthemas are frequently associated with forms of PR different from the classic form.

BACKGROUND Dermatitis herpetiformis (DH) is characterized by the presence of antitissue transglutaminase (tTG) IgA antibodies in patient sera. In 2002, antiepidermal transglutaminase (eTG) antibodies have been identified in DH patients. Nowadays, their role is still controversial. The aim of this study was to evaluate any association between presence/absence of anti-eTG antibodies and cutaneous manifestations during the follow-up. METHODS Anti-eTG and anti-tTG antibodies from 13 patients on gluten-free diet (GFD) were studied during follow-up on ELISA. Cutaneous manifestations baseline differences among age, gender, anti-eTG IgA, anti-tTG IgA, and treatment groups were tested by the Wilcoxon Rank Sum and Fisher's Exact Test. In order to investigate the associations of cutaneous manifestations with age, gender, anti-eTG IgA, anti-tTG IgA, and treatment groups the mixed-effects (ME) model was performed. To test whether the cutaneous manifestations in treatment groups were different according to the anti-eTG levels, an exploratory interaction analysis was carried out using the ME Model. RESULTS Seven patients (53.85%) had an anti-eTG value greater than 22 AU/mL, while six (46.15%) were classified as anti-eTG value

A high-risk population, formed by 79 consecutive male attendees of our sexually transmissible infections clinic, and who did not have any overt signs of human papillomavirus (HPV) infection, were examined. Oral HPV prevalence (37%) was much higher than previously reported. Periurethral HPV-DNA was found in 49% of the patients and anal HPV-DNA was found in 43% of the patients. Considering the high prevalence of oral HPV obtained in the current study, it is important to further investigate the burden of oral HPV, not only in men who have sex with men, but also in heterosexual men and in women.

Background & Aims: To better understand the role of small intestinal bacterial overgrowth (SIBO) in rosacea, we aimed to assess the presence of SIBO in patients with rosacea and the clinical effectiveness of its eradication. Methods: We enrolled 113 consecutive rosacea ambulatory patients (31 M/82 F; mean age, 52 15 years) and 60 healthy controls who were sex- and age-matched. Patients and controls underwent lactulose and glucose breath tests (BTs) to assess the presence of SIBO. Patients positive for SIBO were randomized to receive rifaximin therapy (1200 mg/day for 10 days) or placebo. A group of patients with negative BTs were also treated with rifaximin. Eradication was assessed 1 month after the end of therapy. Two dermatologists, unblinded on therapy, evaluated rosacea patients before and after treatment on the basis of an objective scale. Results: The prevalence of SIBO was higher in patients than controls (52/113 vs 3/60, P < .001). After eradication, cutaneous lesions cleared in 20 of 28 and greatly improved in 6 of 28 patients, whereas patients treated with placebo remained unchanged (18/20) or worsened (2/20) (P < .001). Placebo patients were subsequently switched to rifaximin therapy, and SIBO was eradicated in 17 of 20 cases. Fifteen had a complete resolution of rosacea. After antibiotic therapy, 13 of 16 patients with negative BTs for SIBO remained unchanged, and this result differed from SIBO-positive cases (P < .001). Conclusions: This study demonstrated that rosacea patients have a significantly higher SIBO prevalence than controls. Moreover, eradication of SIBO induced an almost complete regression of their cutaneous lesions and maintained this excellent result for at least 9 months.

Background In clinical trichology, reference values are often arbitrary. The difficulty in setting them up depends mostly on the presence of the androgenetic alopecia (AGA) genotype in subjects with clinically unapparent forms. Prepubertal children, who lack 5α-reductase (a real indicator of the AGA phenotype), might provide reference values independent from AGA. We verified whether the vertex/occiput ratios (V/O) of hair density and the V/O of hair diameter are suitable parameters. Methods In sixty 4–10-year-old Caucasian children, we measured the ratio between the hair density at the vertex and the occiput. The same was done for the diameter. Results The V/O of density averaged 1.07 ± 0.17 and the V/O of diameter 1.02 ± 0.11. Conclusions Taking the mean ± 2SD as normal values, our “normal” V/O of density ranged between 0.73 and 1.41 and our “normal” V/0 of diameter between 0.8 and 1.24. People with lower ratios would have, therefore, AGA with 95% of probability. Moreover, we found that hair shedding using the hair pull test and the modified wash test come to 1-2 hairs/day.

The objective of this study was to evaluate the efficacy of an enhanced treatment regimen for syphilis with the addition of doxycycline and ceftriaxone to the conventional benzathine penicillin G (BPG) treatment. Sixty-nine syphilis patients were recruited and were randomly assigned to two groups: group 1 (38 patients) received standard therapy and group 2 (31 patients) received the enhanced therapy. All patients were followed-up for at least 12 months. Patients underwent physical examination and serology every 6 months as well as echocardiography and neurological examination every year. A three- to four-fold decline in the initial Venereal Disease Research Laboratory (VDRL) titre within 6 months after therapy was considered as serological cure. At 12 months, 68% of patients in group 1 and 100% in group 2 were serologically cured (P = 0.002). During follow-up, no patients in group 2 experienced complications related to syphilis. In contrast, one patient in group 1 developed neurosyphilis. In conclusion, the enhanced treatment is more effective than standard treatment and results in a higher and faster cure rate. Moreover, it provides treponemicidal antibiotic levels in the cerebrospinal fluid, thereby preventing possible late complications.

We report the first case of drug rash with eosinophilia and systemic symptoms (DRESS) following strontium ranelate (SR) treatment associated with systemic human HHV-7 reactivation. DRESS syndrome is a severe adverse drug-induced reaction presenting as a diffuse maculopapular skin rash with fever, hematological abnormalities (leukocytosis, eosinophilia, and/or atypical lymphocytosis), and multiorgan involvement. In our patient, diagnosis of DRESS was confirmed by the presence of six of the seven diagnostic criteria established in 2006 by the Japanese Research Committee on Severe Cutaneous Adverse Drug Reaction: maculopapular skin rash developing at least 3 weeks after starting therapy with a limited number of drugs, prolonged clinical symptoms after discontinuation of the causative drug, lymphadenopathy, fever, leukocyte abnormalities, and liver abnormalities. The diagnostic criteria of human herpesvirus (HHV)-6 reactivation have not been fulfilled in our patient, but a HHV-7 active infection was demonstrated by the presence of HHV-7 DNA and IgM in the patient's serum. In fact, in some DRESS instances, reactivation of HHVs other than HHV-6 may be detected, including HHV-7, Epstein-Barr virus (EBV), and cytomegalovirus (CMV). Our case underlines that not only HHV-6 but also HHV-7 systemic reactivation may be associated with a more severe and even fatal course of this syndrome.

Sweet’s syndrome (SS) is an inflammatory disease characterized by fever, leucocytosis and distinctive skin lesions that histologically consist of a dermal infiltrate of neutrophils with nuclear fragmentation. Aseptic neutrophilic inflammation may occur also in other organs. Central nervous system involvement in SS, Neuro-Sweet’s syndrome (NSS), is rare and reported especially among Asian patients. A systematic review of the literature has been performed to find articles reporting cases of SS with neurological involvement. The search terms: “Sweet’s syndrome/disease with neurological involvement, Neuro Sweet Syndrome/Disease” were used in the Pubmed Database. Sixty-nine NSS patients including 46 males and 23 females, more Asian than Caucasian, have been described from 1983 to date. The average age was 48.7 year-old. The most representative neurologic symptom was the altered state of consciousness, followed by headache and memory disorders. Differently from SS with skin or other district involvement, NSS appears to be more common in Asian patients than in Caucasian ones and affects mainly the male sex in the third or fourth decade of life. A very wide range of symptoms and signs can occur, depending on which part of the nervous system is affected. Initial presentation is usually with the SS typical skin lesions followed by neurological involvement. However, also an opposite presentation or a simultaneous skin and nervous involvement may happen. Awareness of the possible neurological complications in SS is important to avoid unnecessary therapies for other forms of meningoencephalitis and lead to successful treatment with systemic corticosteroids.

Gianotti-Crosti syndrome (GCS) is a self-limiting exanthem of acute onset with a characteristic acral distribution, usually occurring in children. It is characterized by symmetric pink to red-brown papular or papulovesicular lesions that are a few millimetres in diameter, distributed on the face, buttocks and limbs. It may be accompanied by low-grade fever, hepato-splenomegaly and lymphadenopathy. GCS is considered a unique cutaneous response to viral infection, mostly associated with hepatitis B virus and Epstein-Barr virus (EBV), but other viruses, bacterial infections and recent immunizations may be inciting factors. We report a case of a 3-year-old girl presenting generalized, pruritic, papulovesicular eruption on the face and extremities for one month. In our case, GCS was related to cytomegalovirus (CMV) primary infection and may be considered the presenting sign of the infection.

Sarcoidosis is a chronic multisystem disease that usually has a good prognosis but in some cases, especially when cardiac involvement occurs, the outcome is fatal. Cardiac sarcoidosis is insidious to diagnose because it is usually asymptomatic and when clinically apparent, it may have a wide variety of manifestations. The aim of this study was to investigate the possible cardiac involvement in cutaneous sarcoidosis patients. Diagnosis of cutaneous sarcoidosis was confirmed by skin biopsy, laboratory tests and radiological findings in 13 Caucasian patients. To evaluate cardiac damage, electrocardiography, echocardiography, and contrast-enhanced cardiac magnetic resonance were performed. Magnetic resonance identified cardiac sarcoidosis only in one of the cutaneous sarcoidosis patients. We suggest investigating cardiac involvement in patients with cutaneous sarcoidosis, albeit asymptomatic, since cardiac lesions are frequently associated with a poorer prognosis.

Background The association of human herpesvirus 6 (HHV-6) and HHV-7 with pityriasis rosea suggests that systemic drugs directed against HHV may hasten recovery of patients with pityriasis rosea. Objective The purpose of this study was to verify the efficacy of oral acyclovir in the treatment of pityriasis rosea. Methods Eighty-seven consecutive patients were treated for 1 week with either oral acyclovir (800 mg 5 times daily) or placebo. In all patients, the time of lesion clearing and the number of new lesions appearing during treatment were recorded. Results On the 14th day of treatment, 79% of treated patients fully regressed compared with 4% of the placebo group. The lesions cleared in 18.5 days in treated patients and in 37.9 days in the placebo group. Clearance was achieved in 17.2 days in patients treated in the first week from onset and in 19.7 days in the patients treated later. On the 7th day, there were significantly fewer new lesions in patients treated in the first week than in those treated later. Limitations This trial was neither randomized nor double blind. Objectivity was achieved by counting the lesions. Conclusion Acyclovir may be effective in the treatment of pityriasis rosea, especially in patients treated in the first week from onset, when replicative viral activity of HHV is probably very high.

Lipomas are the most common benign soft-tissue tumors found in the body. They tend to occur in areas of abundant adipose tissue, which explains why they are rarely found in the sole. Very few published cases of lipomas in the sole exist. When lipomas cannot be excised for histologic confirmation, ultrasonography has been shown to be a valuable assessment tool with high diagnostic capabilities. We present the case of 100-year-old patient with a long-standing plantar mass with late-stage clinical and sonographic features of a calcified lipoma.

Letter to the EditorA Case of Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) In-duced by Telaprevir Associated with HHV-6 Active InfectionFrancesco Broccolo, Giulia Ciccarese, Antonino Picciotto, Francesco DragoPII: S0168-8278(14)00668-0DOI: http://dx.doi.org/10.1016/j.jhep.2014.09.014Reference: JHEPAT 5348To appear in

Introduction. Pityriasis rosea (PR) is an exanthematous disease related to human herpesvirus- (HHV-) 6/7 reactivation. The network of mediators involved in recruiting the infiltrating inflammatory cells has never been studied.Object. To investigate the levels of serum cytokines, growth factors, and chemokines in PR and healthy controls in order to elucidate the PR pathogenesis.Materials and Methods. Interleukin- (IL-) 1, IL-6, IL-17, interferon- (IFN-)γ, tumor necrosis factor- (TNF-)α, vascular endothelial growth factor (VEGF), granulocyte colony stimulating factor (G-CSF), and chemokines, CXCL8 (IL-8) and CXCL10 (IP-10), were measured simultaneously by a multiplex assay in early acute PR patients’ sera and healthy controls. Subsequently, sera from PR patients were analysed at 3 different times (0, 15, and 30 days).Results and discussion. Serum levels of IL-17, IFN-γ, VEGF, and IP-10 resulted to be upregulated in PR patients compared to controls. IL-17 has a key role in host defense against pathogens stimulating the release of proinflammatory cytokines/chemokines. IFN-γhas a direct antiviral activity promoting NK cells and virus specific T cells cytotoxicity. VEGF stimulates vasculogenesis and angiogenesis. IP-10 can induce chemotaxis, apoptosis, cell growth, and angiogenesis.Conclusions. Our findings suggest that these inflammatory mediators may modulate PR pathogenesis in synergistic manner.

A 48-year-old woman presented us with multiple annular erythematous-squamous plaques over trunk and limbs appeared 3 weeks before. There was no mucosal involvement. Her medical history included systemic lupus erythematosus (LES), diagnosed 3 years before and currently no longer treated, and gastroesophageal reflux for which she was in therapy with lansoprazole (30mg/daily) from 2months.Microscopy in 10 % potassium hydroxide and culture for mycoses was negative. Routine laboratory investigations were normal, antinuclear antibodies (ANA) negative, and anti-Ro/SSA antibodies positive (titer 1/80). Histology of an annular lesion showed atrophy of the epidermis, hydropic degeneration of the basal layer, edema in the upper dermis, and perivascular and periadnexial lymphohistiocytic infiltrate, consistent with subacute cutaneous lupus erythematosus (SCLE). A direct immunofluorescence test was negative. The patient received oral methylprednisolone (0.5 mg/kg/daily), topical steroids, and continued lansoprazolewith improvement but without complete resolution of the lesions. Therefore, lansoprazole was suspected to be responsible of the eruption and replaced by alginate and bicarbonate sodium with complete remission in a few days. Hence, diagnosis of drug-induced SCLE (DI-SCLE) was made. SCLE is a subtype of cutaneous lupus erythematosus that usually manifests as annular, psoriasiform lesions with limited systemic involvement and typically associated with positive ANA, anti-Ro/SSA, and anti-La/SSB antibodies. It may also be induced or exacerbated by drugs, including thiazide diuretics, calcium channel blockers, and also proton pump inhibitors (PPI) [1]. DI-SCLE does not differ clinically, histopathologically, or immunologically from idiopathic SCLE even though some authors have emphasized that DI-SCLE presented more disseminated cutaneous manifestations (as in our patient) and more frequent occurrence of malar rash and bullous, targetoid, and vasculitic lesions [1]. Patients with autoimmune diseases are more prone to druginduced or exacerbated SCLE [1], but the pathogenesis of DISCLE is not completely understood. However, it may be correlated to antimicrobial peptides (AMPs), small effector molecules of the innate immune system with well-known antimicrobial activity [2, 3]. In fact, several AMPs are increased in CLE at both gene and protein levels. In particular, AMPs were found to be significantly more highly induced in subacute CLE as compared with discoid LE and LE tumidus [2]. This might also explain the low prevalence of skin infections in CLE [2]. The selectivity of AMPs to bacterial cells relies on their cationic structures that are crucial for the interaction with negatively charged bacterial membranes [3]. Cathelicidins are a family of evolutionarily conserved AMPs, and hCAP-18 is the only cathelicidin in humans. Proteolytic cleavage of this preprotein releases a 37-residue known as LL-37 that is secreted by bone marrow cells, circulating leukocytes, and numerous types of epithelial tissues, such as skin. LL-37 could mediate innate immunity through regulating chemotaxis of leukocytes and production of cytokines at sites of infection/ inflammation as well as promoting re-epithelization during wound healing. LL-37 orients near the surface of phospholipid bilayers and forms oligomeric structures possessing the ability to disrupt cell membrane [3]. Depending on cellular context, autophagy may serve as a pro-death either pro-survival mechanism through p53 activation [3]. Human LL-37 and its derivatives may contribute to the control of immune-mediated inflammatory diseases through the regulation of proand antiinflammatory cytokines [4]. * Sanja Javor javor.med@gmail.com

Parvovirus B19 (B19V) infection may differently manifest in various age groups. Erythema infectiosum ('fifth disease') is the most common B19V manifestations in children. Arthralgias and arthritis, with or without rash, are common manifestations of B19V infection in adults. Pruritus is usually present in adults and children. However, other cutaneous manifestations and atypical exanthems have been occasionally reported during B19V infection. To investigate the putative role of B19V infection in atypical exanthems, a total of 390 consecutive patients with atypical exanthems were analysed for B19V infection by determining B19V IgG and IgM antibodies titres in acute and convalescent phase as well as B19V DNA detection in serum by polymerase chain reaction (PCR). Atypical exanthems resulted related to B19V infection in 6 of the 120 pediatric (5%) and 14 of the 270 adult patients (5.2%). In conclusion this study reveals that atypical exanthems related to B19V infection are possible both in children and in adults, with a similar prevalence.

Background Adverse cutaneous drug reactions (ACDR) are unexpected cutaneous changes occurring at drug dosages that are normally used for disease prophylaxis, diagnosis or treatment. Objective The aim of the study was to determine the clinical types of ACDR, the causative agents, the latency time between drug intake and onset of ACDR and the recovery time in an outpatient population.Method Ninety-five patients diagnosed with ACDR at the Department of Dermatology of the University of Genoa between 2003 and 2012 were retrospectively studied. Results Antimicrobials, especially cephalosporins, were the most responsible for ACDR, followed by non-steroidal anti-inflammatory drugs and antihypertensives. The most common clinical manifestations were exanthema (42.1 %), erythema multiforme (10.53 %) and vasculitis (9.53 %). Patients with peripheral eosinophilia showed a more severe clinical manifestation, they were treated with systemic therapies and their recovery time was longer. Conclusion It is important to have an appropriate clinical approach according to the ACDR severity degree. We think that eosinophilia may characterise severe cutaneous eruptions and that it should always be investigated when ACDR is suspected in order to manage the patient with the appropriate treatment.