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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.

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.

An exanthem is any eruptive skin rash that may be associated with lesions of the mucous membranes, fever or systemic symptoms. It may be the manifestation of an infectious disease or an adverse reaction to drugs. Six exanthems have been classified as classic; others with different morphology have been defined “atypical exanthems”.

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.

BACKGROUND 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). METHODS 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. RESULTS Seventy-three STIs patients and 51 IBD patients partecipated 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. CONCLUSIONS 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 take into account the possible psychological consequences of the disease.

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.

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.

Treponema pallidum subsp. pallidum DNA and RNA were detected in a semen specimen of a syphilis patient with no genital or anal sores and no clinically evident orchitis. No nucleic acids were found in a urine sample of the same patient collected immediately before the semen sample. Exposure to the syphilis agent through semen could account for transmission episodes in the absence of direct contact with a syphilitic sore.

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.

Dear Editor, We agree with Shiva et al 1 about the relevance of assessing Treponema pallidum particle agglutination (TPPA) titres in the cerebrospinal fluid (CSF) samples of patients with suspected neurosyphilis. For many years, we have been using T. pallidum haemagglutination test (TPHA) both in diagnosing neurosyphilis and in the follow-up of our patients after treatment. It would have been interesting to know the trend of CSF-TPPA titres over time in Shiva’s …

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.

Aim To identify the prevalence of onychomycosis and epidemiological features in older adults (>65%) with toenail onychodystrophy. In particular, the aim of the study was to analyze risk factors/protective factors, clinical manifestations, comorbidities and etiological agents. Methods A prospective study was carried out from February 2012 to May 2012 at San Martino-IST of Genoa, Italy. The inclusion criteria for enrolment were the presence of onychodystrophy of one or more toenails and age >65 years. The exclusion criteria were systemic/topical antifungal treatments in the previous 6 months, drilling of the nail plate in the previous 6 months and a specialist's diagnosis or suspicion of onychomycosis. A database was created for the patients' anamnesis, the clinics and testing results. Several statistical analyses were carried out. Results A total of 100 patients fulfilled the inclusion criteria. A total of 35 cases had positive results, and the etiological agent was isolable in 14 cases. The most represented was Trichophyton mentagrophytes followed by Trichophyton rubrum and others. Multivariate logistic regression analysis showed the significant roles of sex and diabetes as risk factors, and the use of statins as a protective factor. Conclusions Onychomycosis has a high prevalence in older adults with onychodystrophy. It is important not to overlook onychodystrophy, and to carry out laboratory testing to exclude a fungal infection. In fact, as older patients often cannot undergo systemic antifungal therapies, it is fundamental to treat them early and avoid the spread of infection. Geriatr Gerontol Int 2015; ●●: ●●–●●.

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.