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BACKGROUND: In the era of precision medicine, identification of possible predictive factors of clinical response to treatment is fundamental. This need is particularly strong for anogenital warts (AGW), because there are several treatment modalities with different clearance and recurrence rates. However, data regarding the effect of mental health parameters on response to treatment in patients with AGW are lacking. OBJECTIVES: The purpose of the present study was to evaluate the association between patients' mental health parameters and AGW treatment outcomes. METHODS: This was a single-centre, prospective study that included newly diagnosed male patients with AGW. At their initial visit, all patients completed the State-Trait Anxiety Inventory (STAI), the Symptom Checklist-90-Revised (SCL-90-R) and the Eysenck Personality Questionnaire (EPQ) questionnaires, which evaluate anxiety, psychopathological manifestations and personality traits, respectively. All patients received cryotherapy until clearance of lesions and were followed up for 18 months for detection of recurrences. RESULTS: The study included 167 male patients. The mean number of days for AGW clearance was 89 ± 65. During the 18-month follow-up, 28% of participants showed a recurrence, after a mean number of 150 ± 132 days. No statistically significant association was detected between questionnaires scores and (a) time needed for AGW clearance, (b) time until 1st recurrence and (c) number of recurrences. CONCLUSION: If confirmed, our findings indicate that we may not need to modify our AGW treatment plan according to a patient's mental health profile.

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BACKGROUND: Few studies have investigated the long-term outcomes of secukinumab in real-life psoriasis treatment where diverse patient profiles require a personalized approach. OBJECTIVES: To determine long-term performance of secukinumab in moderate-to-severe plaque psoriasis, and identify potential clinical factors predictive of sustained optimal response under real-world conditions. METHODS: In this 78-week, single-centre, retrospective study, effectiveness, safety and drug survival of secukinumab were evaluated. Effectiveness data are reported as observed. Co-primary endpoints were absolute Psoriasis Area and Severity Index (PASI) ≤3 at week 4, 16, 52, 78, and clinical predictors of PASI ≤3 and PASI100 responses at week 52 and 78. RESULTS: A total of 85 patients (75.3% male; mean age 48.6 years) were included. Absolute PASI ≤3 was achieved in 73% and 83% of patients at week 52 and 78, respectively. PASI 75/90/100 responses at week 52 (71.6%, 50.8%, and 40.3%, respectively) were sustained at week 78 (73.6%, 64.2%, and 45.3%, respectively). Median absolute PASI remained low at week 52/78 (0.9/0.6, respectively), while mean absolute PGA also sustained low (0-1) values after 16-78 weeks. Investigator's Global Assessment 0/1 response rate was maintained by week 52/78 (72/83%, respectively). The drug survival rate of secukinumab at week 78 was 79.1%. Treatment was discontinued in 17.9% of patients after an average of 41.7 weeks, mainly due to loss of effectiveness (10.4%). A total of 27% experienced adverse events, without critical safety concerns. Based on multivariate analysis, advanced body mass index (BMI) and presence of ≥3 comorbidities decreased the chance of achieving PASI ≤3 at week 78 [OR (95% CI) 0.78 (0.64-0.97); P = 0.024, and OR (95% CI) 0.045 (0.002-0.83); P = 0.037, respectively]. CONCLUSIONS: Secukinumab showed consistently high effectiveness in this real-life cohort, with an acceptable safety profile. Over time, persistence of PASI ≤3 response appears to be lower in patients with high BMI or multiple comorbidities.

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

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BACKGROUND: Epidemiological data on primary syphilis in Greece are limited. OBJECTIVE: The purpose of the present study was to investigate the trends of the disease in Greece during the last few years and whether they are in accordance with the trends in other European countries and the United States of America. METHODS: We conducted a retrospective analysis based on records of patients who visited the Sexually Transmitted Infections Unit of 'A. Sygros' Hospital in Athens, Greece, during the period 2005-2012. Our hospital is a tertiary referral centre for sexually transmitted infections covering an area of more than four million people, which is almost half the population of Greece. We documented the total annual number of patients, the male to female ratio, sexual orientation, patients' ethnic origin and education level. RESULTS: We reviewed the records of 1185 patients with a confirmed diagnosis of primary syphilis. The total number of patients with primary syphilis has risen from 111 in 2005 to 158 in 2012, an increase of 42.3%. The mean annual number is 148. The mean male to female ratio is 4.76 : 1, with a peak value of 8.50 : 1 in 2011. The majority of patients are of Greek origin, ranging from 67.4% to 87.2%. Within the male patients group, it seems that the percentage of men having sex with men has risen steadily from 2005 (20.7%) up to 2010 (59.1%) with a decline in 2012 (46.0%). The mean value over 8 years is 45.0%. CONCLUSION: Primary syphilis in Greece is on the rise. Τhe majority of our patients are Greek, despite immigrant influx. Men clearly outnumber women, representing more than 80% of the total number of patients. Furthermore, there seems to be a trend towards predominance of men having sex with men as the core group among male patients.

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Vitiligo is a disorder of depigmentation, for which the pathogenesis is as yet unclear. Interleukin (IL)-8 (CXCL8) is a key inflammatory chemokine. We investigated the regulation of IL-8 production in human melanocytes, and the IL-8 serum levels and skin gene expression in patients with vitiligo and in controls. Cultured melanocytes were stimulated for 24 h with tumour necrosis factor (TNF) 100 ng/mL and IL-1ß 10 ng/mL, with or without pretreatment with luteolin 50 µmol/L for 30 min, and IL-8 release was measured by ELISA. Serum cytokines were measured by a microbead array. Skin biopsies were taken from healthy subjects (n = 14) as well as from marginal lesional and nonlesional skin from patients with vitiligo (n = 15). IL-8 gene expression was evaluated by quantitative real time PCR. Both TNF and IL-1ß stimulated significant IL-8 release (P < 0.01) from melanocytes, whereas pretreatment with luteolin significantly inhibited this effect (P < 0.01). IL-8 gene expression was significantly increased in vitiligo compared with control skin (P < 0.05). IL-8 may be involved in vitiligo inflammation. Inhibition by luteolin of IL-8 release could be useful for vitiligo therapy.

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Giant condyloma acuminatum (GCA), or Buschke-Löwenstein tumour (BLT), is a rare large tumour of the anogenital area. It is caused by human papillomavirus genotypes 6 and 11, and it is characterized by aggressive local invasion and frequent recurrences after treatment. Treatment of choice is radical excision, although chemotherapy and radiation are also used in special cases. We report a case of a young man with anogenital GCA, presenting with a large perianal mass and pain during defaecation. The patient was treated by surgical removal of almost the entirety of the mass, using radiofrequency surgical dissection. The concurrent use of oral acitretin for the treatment of erythrodermic psoriasis led to elimination of the remaining disease. The patient remains free of disease 26 months after the end of treatment.

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Vitiligo is a cutaneous disorder of depigmentation, clinically characterized by well-demarcated, white macules of varying size and distribution. It can affect up to 2 percent of the population, especially younger ages. In spite of recent findings implicating genetic, immune and oxidative stress factors, the exact pathogenesis of vitiligo remains obscure. Here, we briefly discuss the prevailing theories, and offer new suggestions that could explain in part the damage of melanocyte in the vitiliginous lesions. Our emerging hypothesis is that neuropeptides released from peripheral nerve endings could synergize with new cytokines to adversely affect melanocyte function and viability. These may include corticotropin- releasing hormone (CRH) and neurotensin (NT), as well as interleukin 33 (IL-33) and thymic stromal lymphopoietin (TSLP). Such interactions could serve the basis for further research, possibly leading to new treatments.

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Merkel cell carcinoma is a rare but aggressive neuroendocrine carcinoma of the skin with a rising incidence and a high mortality rate. It occurs primarily in sun-exposed skin of older individuals. It is characterized by a high rate of local recurrence, regional lymph node metastases and distant metastases, occurring even after prompt treatment. Many controversies exist regarding its pathogenesis and optimal management. The discovery of Merkel cell polyomavirus has been a major breakthrough in understanding the aetiology of the disease. A recently adopted new international consensus staging system in combination with new international diagnostic codes are expected to facilitate future clinical trials and improve the management of patients. According to recent (2010) guidelines, most patients should be managed with a combination of surgery and radiotherapy.

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BACKGROUND: Factors predicting an unfavourable course of genital warts to treatment have not been determined. MATERIALS AND METHODS: Behavioural and baseline disease characteristics were recorded from 246 males with anogenital warts. Urethral swabs were obtained and examined using the Hybrid Capture 2 Microplate assay. Patients were treated for their anogenital warts with cryotherapy, imiquimod cream 5% or podophyllotoxin. They were followed up every 3 months for 1 year. RESULTS: Patients with a negative or low-risk initial test tended to respond earlier to treatment than those with a high/intermediate-risk human papillomavirus (HPV) or with a dual infection (P = 0.028). The response rate was unrelated (P > 0.05) to the duration, number and anatomical location of the lesions and to the patient's age and sexual orientation, and only marginally to the initial extent of the lesion (P = 0.046). However, the type of treatment predicted a favourable response (P < or = 0.001), with patients who received both imiquimod and crotherapy responding worse. Considering all factors simultaneously in logistic regression, only the type of treatment and extent of the disease were found to influence the response rate. CONCLUSION: The type of treatment and extent of the disease were the only factors found critical for patients' response.

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Epidermolysis bullosa acquisita (EBA) is a rare autoimmune bullous disorder that is often difficult to treat. Few cases have been reported and therapy consists mainly of combinations of systemic steroids, immunosuppressants and, recently, administration of intravenous human immunoglobulin (IVIg). We describe a case of EBA in which our therapeutic choices were limited due to the patient's poor general condition, including extensive infection of the lesions and a history of pulmonary tuberculosis. The patient was treated with IVIg at a dose of 400 mg/kg per day for 5 consecutive days every 4 weeks. The treatment was well tolerated and the results were satisfactory. It seems that IVIg, due to its possible immunomodulatory mode of action, can be an efficacious therapeutic agent in this rare autoimmune disease.

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BACKGROUND: Antithrombin III (AT-III) is a physiological inhibitor of thrombin and other serine proteases, and has antiinflammatory properties. Thrombin is known to enhance T lymphocyte activation in vitro and serine proteases can act as costimulators for lymphocyte proliferation and cytokine production. We have previously shown that AT-III significantly inhibited allograft rejection in a highly histoincompatible model of rat lung transplantation and in vitro cell proliferation in ConA-stimulated rat spleen cells. In this study, we examined the involvement of cytokine gene expression in the above inhibitory effect of AT-III. We also examined the effect of AT-III on several in vitro immune reactions in human peripheral blood mononuclear cells (PBMCs). METHODS: mRNA expression of cytokines/cytokine receptor important in lymphocyte activation was examined. Rat spleen cells were stimulated with Con-A with/without AT-III and submitted for reverse transcriptase-polymerase chain reaction (RT-PCR). To assess the effect of AT-III on human PBMCs, we examined the effects of AT-III on cell proliferation of human PBMCs stimulated in mixed lymphocyte reaction (MLR) (allogeneic stimulation), with OKT3 (T cell receptor activation) and with PHA (mitogenic stimulation). The effect of AT-III on PWM-stimulated immunoglobulin (Ig) production by human PBMCs was also examined. All experiments for cell proliferation were performed in 10% serum and in serum-free (SF) media to determine whether AT-III exerted its effects through its interaction with thrombin in serum. RESULTS: mRNA expression of IL-2, gamma-IFN and IL-4 in ConA-stimulated rat spleen cells was nearly completely inhibited by AT-III at 15 IU/ml. mRNA levels for IL-6, IL-2R and TGF-beta1 were not significantly affected by AT-III. AT-III showed a dose-dependent inhibition of cell proliferation in human PBMCs. At 15 IU/ml, cell proliferation was inhibited by approximately 86%, approximately 81% and approximately 56% in the MLR-, OKT3- and PHA-stimulated PBMCs, respectively in both serum and SF media. AT-III inhibited PWM-stimulated Ig production in a dose-dependent manner. IgG, IgM and IgA production was reduced by approximately 60%, 80% and 70%, respectively in cultures incubated with 15 IU/ml AT-III. CONCLUSIONS: (1) Inhibition of IL-2, gamma-IFN and IL-4 mRNA expression might be responsible for inhibition of cell proliferation by AT-III in ConA-stimulated rat spleen cells, (2) AT-III inhibits cell proliferation in the MLR-, OKT3- and PHA-stimulated human PBMCs, and Ig production in PWM-stimulated human PBMCs, (3) The immune regulatory effects of AT-III are independent of its interaction with thrombin since similar levels of suppression were seen in SF media, and (4) These results suggest that AT-III has potent inhibitory effects on lymphocyte activation and cytokine production and may have potential applications as an immunomodulatory agent.

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BACKGROUND: The ability to express genes with potential immunoregulatory capacity could reduce the immunogenicity of allografts and result in long-term graft survival. In this study, we examine the feasibility of transferring viral interleukin-10 (vIL-10) gene into rat hearts using adenovirus by intracoronary administration. The subsequent effects of delivered vIL-10 alone or with subtherapeutic doses of cyclosporine A (CsA) on parameters of allograft rejection (AR) were also examined. METHODS: Recombinant adenovirus vectors containing vIL-10 (Ad-vIL-10) or beta-galactosidase (Ad-beta-gal) were derived from adenovirus type 5. vIL-10 expression in supernatants of transfected COS7 cell cultures and in transfected heart allografts were examined by enzyme immunoassay (EIA) and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. Rat heart transplants (LEWS->ACI) were performed in five groups [group 1: no treatment, group 2: Ad-beta-gal, group 3: AdvIL-10, group 4: CsA (10 mg/kg), and group 5: Ad-vIL10+CsA (10 mg/kg)]. Allograft survival was determined by palpating heartbeats. Allograft tissues were also submitted for histological study. RESULTS: vIL-10 expression was shown in both transfected COS7 cells and heart isografts. Animals transfected with vIL-10 showed prolongation of graft survival (19.6 vs. 12 days, P<0.001) when compared to beta-gal transfected controls. Animals treated with a single low dose injection of CsA showed no significant prolongation of graft survival compared to controls (11.7 vs. 10.5 days). Animals treated with both vIL-10 and CsA demonstrated a synergistic prolongation of allograft survival compared with controls and with animals treated with CsA or vIL-10 treatment alone (36.7 days vs. 11.7, P<0.001 or 36.7 vs.19.6, P<0.001, respectively). Histological study showed that allografts from untreated controls exhibited extensive AR with loss of graft architecture by day 7 posttransplant while those from the vIL-10 group showed less AR. The best pathological scores were seen in vIL-10 + CsA-treated animals. CONCLUSIONS: 1) Delivering Ad-vIL-10 into donor hearts by intracoronary perfusion results in overexpression of vIL-10 and significantly prolongs cardiac allograft survival in a highly histoincompatible rat model. 2) Subtherapeutic doses of CsA do not prolong allograft survival, but act synergistically with vIL-10 to significantly prolong graft survival beyond that achieved with either agent alone.

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Cutaneous larva migrans (CLM) is a characteristic eruption that is caused by penetration and migration in the skin of nematode larvae. Both animal and human hookworms have been implicated in the pathogenesis of the condition, with Ancylostoma braziliensis and A. caninum being the most common among them. CLM is quite common in tropical areas, but, due to travelling, several cases have also been described in Europe. We present a patient with CLM who presumably contacted the disease during a holiday in Singapore. The patient was treated successfully with oral thiabendazole.

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