Clinical experience of imiquimod 3.75% for actinic keratosis: results from a case series.

BACKGROUND: In clinical studies, imiquimod 3.75% was shown to detect and treat actinic keratosis (AK) lesions across an entire sun-exposed field such as the full face or balding scalp. The aim of this study was to evaluate imiquimod 3.75% in a real-life clinical setting. METHODS: Ten AK patients applied imiquimod 3.75% to the full face or scalp once-daily in two 2-week treatment cycles separated by a two-week treatment-free interval and were followed-up eight weeks later. Seven patients rated imiquimod 3.75% versus prior treatments (cryotherapy, photodynamic therapy, diclofenac sodium 3%, imiquimod 5%, ingenol mebutate). RESULTS: The median clinical lesion count at baseline was 12.5. This increased to a median Lmax (maximum lesion count during treatment) of 22.5 as imiquimod 3.75% unmasked previously invisible subclinical lesions. At final follow-up, the median lesion count was 0. Local skin reactions such as erythema, scabbing and erosion occurred during each treatment cycle and were easy to manage. All patients considered imiquimod 3.75% easier to apply than prior treatments and 5 reported fewer or similar side effects. CONCLUSIONS: In this cohort, imiquimod 3.75% effectively cleared clinical and subclinical lesions across the entire affected field and was well tolerated.

Cutaneous manifestations of hepatitis C in the era of new antiviral agents.

The association of chronic hepatitis C virus (HCV) infection with a wide spectrum of cutaneous manifestations has been widely reported in the literature, with varying strength of epidemiological association. Skin diseases which are certainly related with chronic HCV infection due to a strong epidemiological and pathogenetic association are mixed cryoglobulinemia, lichen planus and porphyria cutanea tarda. Chronic pruritus and necrolytic acral erythema are conditions that may share a possible association with HCV infection, while several immune-mediated inflammatory skin conditions, such as psoriasis, chronic urticaria and vitiligo, have been only anecdotally reported in the setting of chronic HCV infection. Traditional interferon-based treatment regimens for HCV infection are associated with substantial toxicity and a high-risk of immune-related adverse events, while the advent of new direct-acting antivirals with sustained virological response and improved tolerability will open the door for all-oral, interferon-free regimens. In the new era of these direct acting antivirals there will be hopefully a renewed interest in extra-hepatic manifestations of HCV infection. The aim of the present paper is to review the main cutaneous HCV-related disorders - mixed cryoglobulinemia, lichen planus, porphyria cutanea tarda and chronic pruritus - and to discuss the potential impact of new antiviral treatments on the course of these extra-hepatic manifestations of chronic HCV infection.

Giant neglected squamous cell carcinoma of the skin.

Nonmelanoma skin cancers (NMSCs) are the most common type of skin tumor, representing about one-third of all malignancies diagnosed worldwide each year. Cutaneous squamous cell carcinoma (cSCC) is the second most common form of NMSCs and the risk of cSCC invasiveness should be assessed on the basis of tumor size, anatomical location, and histological subtype. Although most cSCCs are early diagnosed and successfully treated, in a small percentage of patients with giant cSCC (maximum diameter >5 cm), metastases may occur; treatment options are limited and not really effective. We report the case of a giant metastatic cSCC that had been neglected for more than 20 years. Radiotherapy or surgery were not feasible and polichemotherapy (cisplatin, 5-fluorouracil and paclitaxel) was not effective. Therefore, the patient was treated with palliative electrochemotherapy (ECT) achieving a partial reduction of cutaneous metastasis and pain relief but unfortunately the patient died 3 months after the second ECT treatment.

The first skin cancer screening day at the Italian parliament: a Euromelanoma initiative.

BACKGROUND: The effort to decrease incidence/mortality of skin cancer should target not only the general public but also politicians and decision makers, to create a proper health policy. We report the results of the first Skin Cancer Screening Day at the Italian Parliament, organized to draw politicians' attention on skin cancer. METHODS: A questionnaire was used to collect data on participants' characteristics and suspected skin cancers. RESULTS: We screened 70 members of parliament (61.4% males, median age 54 years). Overall skin cancer suspicion rate was 14.5%. Suspicion rate, detection rate, and positive predictive values for melanoma were respectively 1.6, 1.6, and 100%, and for basal cell carcinoma 6.5, 1.6, and 25%. Highly educated, <54-year-old females reported sun-seeking behaviors. CONCLUSIONS: The considerable suspicion rate produced by this screening is justified by the particular demographics of the study population. Italian members of parliament display sun-seeking behaviors similar to those previously described in the general public. Increasing politicians' attention on skin cancer is vital for sufficient resources to be allocated to prevention strategies. Expert medical groups and politicians should cooperate to create a proper, integrated policy on skin cancer.

Adverse skin reactions during treatment with cetuximab plus radiotherapy: Multidisciplinary approach to minimize radio-chemotherapy interruption.

BACKGROUND: Antibodies against the epidermal growth factor receptor (EGFR), such as cetuximab, are effective in loco-regional advanced squamous cell carcinoma of the head and neck (SCCHN) in association with radiotherapy. Cutaneous reactions are well known as adverse events during treatment with EGFR inhibitors. OBJECTIVE: To identify a multidisciplinary approach for mucous-cutaneous toxicity during cetuximab-radiotherapy treatment in order to reduce the risk of an early radio-chemotherapy interruption. METHODS: The data of 38 patients with SCCHN receiving cetuximab and radiotherapy were retrospectively analyzed. The control group (n = 15) received the standardized treatments according to the severity of skin reactions with dermatologic visits only for high degrees of toxicity. The experimental group (n = 23) was monitored and daily treated by dermatologists since grade 1 of cutaneous toxicity. The primary end-point of our study was the mean days of antitumor therapy interruption. RESULTS: The mean number of days of antitumor therapy suspension was 12.6 (7.6) in the standard treatment group and 5.0 (6.6) in the experimental group (p = 0.002). This difference was observed for each grade of toxicity. CONCLUSION: The early interruption of radio-chemotherapy has a negative impact on survival in patients with SCCHN. In our study, a closer dermatological examination and treatment for all degrees of toxicity reduced early interruptions of chemo-radiotherapy.

The Italian Euromelanoma Day: evaluation of results and implications for future prevention campaigns.

BACKGROUND: Melanoma incidence/mortality is increasing worldwide. "Euromelanoma Day" is a pan-European campaign for skin cancer prevention. Results of the 2010 Euromelanoma Day in Italy are reported herein. MATERIALS AND METHODS: A questionnaire was used to collect data on participants' characteristics and suspected skin cancers. RESULT: A total of 1085 participants was screened (64.1% females, median age 44 years). Suspicion rate, detection rate, and positive predictive values for melanoma were 1.3, 0.28 and 21.4%, respectively. Poorly educated, ≥35 years old, pale-skinned males were at higher risk for skin cancer than highly educated, <35 years old, darker-skinned females, although the latter groups reported sun-seeking behaviors. Full skin examination and dermoscopy were performed in 85.5 and 79.2% of participants. CONCLUSIONS: The 2010 Italian Euromelanoma Day produced good results in terms of melanoma detection/suspicion rates, likely due to the extensive use of full clinical and dermoscopic examinations. The campaign failed to attract many high-risk individuals. Targeted communication strategies are needed to this regard.

Quality of life in patients with anogenital warts.

BACKGROUND: Anogenital warts (GW) are among the most common sexually transmitted diseases. Few studies have investigated the quality of life (QoL) of GW patients. OBJECTIVE: We undertook an exhaustive description of the health status of GW patients and assessed disease impact on QoL. METHODS: GW patients enrolled at the Sexually Transmitted Diseases service of Rome Catholic University were administered the SF-36 questionnaire to assess health status, the Skindex-29 to evaluate the impact of dermatological aspects and the GHQ-12 questionnaire to identify patients with probable minor psychiatric non-psychotic conditions. Clinical severity was assessed with the Physician Global Assessment (PGA) and through quantitative measures. RESULTS: There was a significant association between greater disease severity and lower SF-36 values (reflecting a worse QoL). The severity parameters showed no significant differences in any of the Skindex-29 scales except for Emotions, which showed higher values (reflecting a worse QoL) in patients with severe disease assessed by PGA. The GHQ-positive patients (23.7%) consistently showed worse QoL scores on all the SF-36 scales and on all the Skindex-29 scales compared to GHQ-negative patients. CONCLUSIONS: To the best of our knowledge, this is the first study of the impact of GW on QoL to use a range of validated tools, both generic and dermatology-specific. We observed a strong influence of GW on the mental and physical components of QoL in terms of general health status (SF-36). The effects in terms of specific dermatological aspects (Skindex-29) were less significant, but still reflected an impact on patients' emotional state.

Erythema nodosum induced by kerion celsi of the scalp in a child: a case report and mini-review of literature.

A 9-year-old girl, presented with a 4-week history of an inflammatory suppurative plaque, 8 cm in diameter, localised in the occipital area of the scalp. Mycological direct examination showed ectoendothrix invasion of the hair and Trichophyton mentagrophytes was isolated. Oral therapy with griseofulvin 25 mg kg(-1) day(-1) was prescribed, but after 2 weeks of treatment appeared multiple erythematous subcutaneous nodules localised in the legs. Erythema nodosum (EN) was confirmed by histological examination of a nodule and then we combined therapy with 1 mg Kg(-1) day(-1) of prednisone. At the remission of the panniculitis, which occurred in about 10 days, the steroid therapy was suspended, while the orally administered griseofulvin continued for 6 weeks until full recovery. EN is the most frequent clinical form of acute nodular panniculitis and it is considered an epiphenomenon relative to various infectious and non-infectious stimuli. The association of EN with dermatophytosis of the scalp is infrequent, with only 15 cases reported in the Literature.

Polymorphisms in base excision DNA repair genes and association with melanoma risk in a pilot study on Central-South Italian population.

Base excision repair plays a key role in the removing of DNA damage from exposure to endogenous and exogenous carcinogens. The BER pathway removes alterations of a single oxidized, reduced or methylated base. Recently some studies have explored the association between risk for cutaneous melanoma and non-synonymous single-nucleotide polymorphisms (nsSNPs) in DNA-repair genes, although with contradictory results. We hypothesized that common nsSNPs of BER genes, specifically ADPRT rs1136410, XRCC1 rs25487, rs25489, rs1799782, APEX1 rs1130409, OGG1 rs1052133, LIG3 rs3136025 and MUTYH rs3219466, may contribute to risk of melanoma. The aim of this study is to investigate whether or not a correlation between these nsSNPs and melanoma risk and/or aggressiveness is present. 167 melanoma patients and 186 healthy control subjects were analysed. By multivariate statistical analysis no association was found between nsSNP and melanoma aggressiveness, while only the two XRCC1 (rs25487 and rs25489) nsSNPs showed a strong correlation (p<0.001) with melanoma risk. To our knowledge this is the first study reporting an association between BER nsSNPs and melanoma risk in Central-South Italian individuals. Our findings, if confirmed in larger population studies, will allow the inclusion of these XRCC1 nsSNPs in a screening panel for those individuals at higher risk for melanoma.

A suspected squamous cell carcinoma in a renal transplant recipient revealing a rare cutaneous phaeohyphomycosis by Alternaria infectoria.

BACKGROUND: Squamous cell carcinoma of the skin is the most common neoplasm after organ transplantation. In addition, fungal infections are increasingly described in immunocompromised patients, such as kidney recipients. METHOD AND RESULTS: We report a case of a 64-year-old woman with a renal transplant presenting with 6-month-old skin lesions. In other centers, she had undergone previous biopsies, the results of which were suggestive of squamous cell carcinoma and aspecific inflammation. Therefore, she came to our center for surgical excision. Only our clinical experience and a detailed clinical history allowed us to doubt previous diagnoses and perform further examinations. Our investigation revealed an extremely rare fungus infection: phaeohyphomycosis by Alternaria infectoria. It was successfully treated with oral terbinafine until a complete regression of the lesions was achieved. At a 16-month follow-up visit, no recurrence of the skin lesion was observed. CONCLUSION: Despite a difficult diagnosis and rare occurrence, physicians and surgeons should be aware of infection with this emerging fungus in immunocompromised patients.

Human Papillomaviruses, p16INK4a and Akt expression in basal cell carcinoma.

BACKGROUND: The pathogenic role of beta-HPVs in non melanoma skin cancer (NMSC), is not still completely understood, and literature data indicate that they might be at least cofactors in the development of certain cutaneous squamous cell carcinomas. However, only few reports contain data on basal cell carcinoma (BCC). The HPVs interact with many cellular proteins altering their function or the expression levels, like the p16INK4a and Akt. Our study aimed to determine the presence of different beta -HPV types and the expression of p16INK4a and Akt in BCC, the commonest NMSC, in the normal appearing perilesional skin and in forehead swab of 37 immunocompetent patients. METHODS: The expression of p16INK4a and Akt, by immunohistochemistry, and the HPV DNA, by nested PCR, were investigated in each sample. RESULTS: No correspondence of HPV types between BCC and swab samples was found, whereas a correspondence between perilesional skin and BCC was ascertained in the 16,7% of the patients. In BCC, 16 different types of beta HPV were found and the most frequent types were HPV107 (15,4%), HPV100 (11,5%) and HPV15 (11,5%) all belonging to the beta HPV species 2. Immunohistochemistry detected significant p16INK4a expression in almost all tumor samples (94,3%) with the highest percentages (> 30%) of positive cells detected in 8 cases. A statistically significant (p = 0,012) increase of beta HPV presence was detected in p16INK4a strongly positive samples, in particular of species 2. pAkt expression was detected in all tumor samples with only 2 cases showing rare positive cells, whereas Akt2 expression was found in 14 out of 35 BCC (40%); in particular in HPV positive samples over-expressing p16INK4a. CONCLUSIONS: Our data show that p16INK4a and pAkt are over-expressed in BCC and that the high expression of p16INK4a and of Akt2 isoform is often associated with the presence of beta-HPV species 2 (i.e. HPV 15). The association of these viruses with the up-regulation of p16INK4a and Akt/PI3K pathway suggests that in a subtype of BCC these viruses may exert a role in the carcinogenesis or in other, still undefined, biological property of these tumors. If this particular type of BCC reflects a different biology it will remain undisclosed until further studies on a larger number of samples will be performed.

Combined treatment with etanercept 50 mg once weekly and narrow-band ultraviolet B phototherapy in chronic plaque psoriasis.

The combination of etanercept, a tumour necrosis factor α inhibitor, with narrow-band ultraviolet B (NB-UVB) phototherapy has recently been reported to be effective in moderate-to-severe plaque psoriasis, yielding better results than either monotherapy. To assess the efficacy and safety of this combined treatment using the lower approved etanercept dosage. In this single-arm open-label study patients received etanercept 50 mg once weekly combined with NB-UVB phototherapy three times weekly for 8 weeks, followed by etanercept alone until week 12. We evaluated the proportion of patients achieving 75%, 90% and 100% improvement of their initial PASI score (PASI75, PASI90, and PASI100, respectively). Patients were 19 men and 14 women, mean age 48.3 years ± 12.1 standard deviation (SD) and mean baseline Psoriasis Area and Severity Index (PASI) score 22.5 ± 7.5. On treatment weeks 4, 8, and 12, 24.2%, 66.7%, and 81.8% of patients achieved PASI75; 8.0%, 15.1%, and 57.6% reached PASI90, and 0%, 6.0%, and 24.2% attained PASI100, respectively. There were no severe side effects. Low-dosage etanercept combined with NB-UVB phototherapy is an effective, safe and economical approach to treat moderate-to-severe plaque psoriasis. Further studies are clearly required to assess its long-term efficacy and safety.

Common genetic variants of MUTYH are not associated with cutaneous malignant melanoma: application of molecular screening by means of high-resolution melting technique in a pilot case-control study.

MUTYH glycosylase recognizes the 8-oxoG:A mismatch and is able to excise the adenine base using proofreading mechanisms. Some papers have reported a strong association between cancer development or aggressiveness and MUTYH gene mutations. The aim of this study was to find a possible association between the most frequent MUTYH mutations and melanoma in the context of a case-control pilot study. One hundred ninety-five melanoma patients and 195 healthy controls were matched for sex and age. Clinical and laboratory data were collected in a specific database and all individuals were analyzed for MUTYH mutations by high-resolution melting and direct sequencing techniques. Men and women had significantly different distributions of tumor sites and phototypes. No significant associations were observed between the Y165C, G382D and V479F MUTYH mutations and risk of melanoma development or aggressiveness. Our preliminary findings therefore do not confirm a role for MUTYH gene mutations in the melanoma risk. Further studies are necessary for the assessment of MUTYH not only in melanoma but also other cancer types with the same embryonic origin, in the context of larger arrays studies of genes involved in DNA stability or integrity.