Erratum to "Intratumoral Heterogeneity of MAGE-C1/CT7 and MAGE-C2/CT10 Expression in Mucosal Melanoma".

[This corrects the article DOI: 10.1155/2015/432479.].

Physician-patient communication and patient-reported outcomes in the actinic keratosis treatment adherence initiative (AK-TRAIN): a multicenter, prospective, real-life study of treatment satisfaction, quality of life and adherence to topical field-directed therapy for the treatment of actinic keratosis in Italy.

BACKGROUND: Patients with multiple actinic keratoses (AKs) should be treated with field-directed therapy. Such treatments challenge patients' adherence due to out-of-pocket costs, length of treatment and severity of local skin reactions (LSRs). Effective physician-patient communication (PPC) may buffer therapy-related distress, thus improving quality of life, treatment satisfaction and adherence. OBJECTIVES: We evaluated the interplay between PPC, LSR intensity (safety) and lesion clearance rates (effectiveness) on treatment satisfaction, quality of life and treatment adherence among patients with multiple AKs receiving topical field-directed therapies. METHODS: In this observational, multicentre, longitudinal, cohort study, we included 1136 adult patients with discrete, clinically detectable, visible, multiple (three or more lesions in a 25 cm2 area), Grade I/II AKs, for whom the attending dermatologist has prescribed treatment with a topical field-directed therapy. We matched self-reported data and medical information recorded by dermatologists in standard clinical forms. Patients were followed up at two time points (T1: 8 days; T2: 25-30 days) RESULTS: Most patients were elderly, married, men with poor socio-economic status and multiple lesions of the scalp or face. The majority (n = 961) had a prescription of ingenol mebutate (IMB) and 175 received either diclofenac 3% in hyaluronic acid (DHA) or imiquimod 5% (IMQ). Clearance rate at 1 month was 84%. Most patients felt very supported (n = 819, 73%) and rated dermatologist's explanations very clear (n = 608, 54%). Treatment satisfaction (effectiveness and convenience scales) increased along the follow-up, especially for those on IMB (Δpre-post  = -4.00; other: Δpre-post  = -0.25; interaction P < 0.001). Communication clarity was associated with higher treatment satisfaction scores (ß = 0.4-0.6, P < 0.01) and lower risk of non-adherence among IMB patients (risk difference: 16%, P < 0.01). CONCLUSION: Communication clarity was associated with patient-reported outcomes and adherence beyond AK-related clinical parameters. Our study questions the current episodic approach to AK management and provides the rationale to develop chronic care models fostering patients' engagement and treatment alliance.

Omalizumab therapy in a patient with cronic spontaneous urticaria, ulcerative colitis, hypereosinophilia and prurigo Besnier: a case report.

The case of a woman who suffered from CSU and prurigo Besnier, with a history of chronic hyper-eosinophilia, ulcerative colitis and thyroiditis, unresponsive to anti-histamines and steroids is reported. The patient received omalizumab treatment, and obtained resolution of urticaria along with improvement of cutaneous symptoms of prurigo.

Topical cetirizine and oral vitamin D: a valid treatment for hypotrichosis caused by ectodermal dysplasia.

BACKGROUND: Ectodermal dysplasia is a clinically and genetically heterogeneous group of inherited disorders characterized by abnormal development of two or more of the following ectodermal-derived structures: hair, teeth, nails and sweat glands. The hair is the most frequently affected structure. Hair shaft abnormalities are of great concern to these patients, but no effective treatments are available. METHODS: We describe three girls with congenital hypotrichosis (9, 5 and 6 years old) caused by ectodermal dysplasia treated with topical cetirizine solution (2 mL. once daily) and oral vitamin D supplementation (1000 IU daily). RESULTS: After 6 months of treatment, the density of hair on the scalp increased in all patients. The vellus hair was replaced by terminal hair. Hair regrowth was evaluated both from the clinical and trichoscopic point of view. CONCLUSION: We propose a combination of topical cetirizine and oral vitamin D as a rational treatment of choice in congenital hypotrichosis caused by ectodermal dysplasia.

Peripheral blood regulatory T cell measurements correlate with serum vitamin D level in patients with psoriasis.

OBJECTIVE: Vitamin D is the precursor of a hormone (1,25-dihydroxyvitamin D3), which has many biological effects in the skin. The immune modulator properties of vitamin D are mediated in part through effects on regulatory T cells (T-reg). Currently, in psoriasis, the relationship between vitamin D and T-reg has not well elucidated. We assess whether vitamin D status is correlated with circulating T-reg in patients affected by psoriasis and if there is a correlation with the severity of the disease evaluated with Psoriasis Area Severity Index (PASI) score. PATIENTS AND METHODS: For each patient we have analyzed, PASI-score, serum levels vitamin D and regulatory T cell percentages. Spearmen's coefficient was used between serum vitamin D levels and the predictors. Subsequently, the independent predictive factors were assessed by Multiple Regression. RESULTS: A total of 26 patients were included in our analysis. Using no parametric Spearman's Coefficient test between serum levels of vitamin D and the single variables, we found an association with T-reg population (p < 0.001) and with PASI-score (p = 0.04). CONCLUSIONS: While vitamin D treatment induces a cytokine profile known to favor the differentiation of T cells with suppressive activity, at the same time, several studies showed how vitamin D can prime for tolerogenic dendritic cells able to favor the differentiation of Treg from T naïve cells. Low levels of vitamin-D may decrease the number of circulatory T-reg, disrupting the immunological homeostasis in psoriatic patients and encouraging the inflammatory activity.

Is the prognosis and course of acral melanoma related to site-specific clinicopathological features?

OBJECTIVE: Acral melanoma is an uncommon type of melanoma in Caucasian patients. However, acral melanoma is the most common type of melanoma in African and Asian patients. Comparison analyses between hand-acral melanoma and foot-acral melanoma have been rarely reported in the literature. Acral melanoma is an uncommon melanocytic tumor characterized by an intrinsic aggressiveness, with specific histological and clinicopathological features. Acral melanoma involves the palms, soles and sub-ungueal sites. PATIENTS AND METHODS: A total of 244 patients with acral melanoma were included in our analysis. The current study was performed in three different medical centers: Sapienza University of Rome, San Gallicano Institute of Rome and University of Magna Graecia (Italy). The Kaplan-Meier product was used to estimate survival curves for disease-free survival and overall survival. The log-rank test was used to evaluate differences between the survival curves. Assuming that the effects of the predictor variables are constant over time, the independent predictive factors were assessed by Spearman's test and subsequently data were analyzed performing Cox proportional-hazard regression. RESULTS: In both univariate and multivariate analyses Breslow thickness (p < 0.0001) and ulceration (p = 0.003) remained the main predictors. General BRAF mutation was detected in 13.8% of cases. We found that median Breslow value and the percentage of recurrences were similar in hand-acral melanoma and foot-acral melanoma, as well as there were no differences in both short and long-term. CONCLUSIONS: The absence of differences in survival between hand-acral melanoma and foot-acral melanoma shows that the aggressiveness of the disease is related to distinct mutational rate, as well as to anatomical site-specific features, rather than to the visibility of the primary lesion.

Chiari type 1 malformation in Neurofibromatosis type 1: experience of a center and review of the literature.

OBJECTIVE: To evaluate the possible correlation and the true incidence between Neurofibromatosis type 1 and Arnold-Chiari malformation type I. MATERIALS AND METHODS: We reviewed all clinical charts, neurological consultations and MRI scans of 428 NF1 patients followed by 1994 to 2014 in our Department. NF1 patients in our clinic are seen usually every year by both the dermatologist and the neurologist. All patients also undergo a brain and spinal cord with the same 1.5 Tesla MRI scan. RESULTS: We found a diagnosis of Arnold Chiari malformation type I in 9 of the 428 NF1 cases (2%). CONCLUSION: This frequency is higher than that expected on the basis of a chance association. Therefore we underline the importance of serial MRI studies in patients with NF1 to assess the presence of cranio-cervical anomalies. Future studies should try to better understand what are the pathogenetic mechanisms underlying this close association.

Daylight-Photodynamic Therapy for the Treatment of Actinic Keratosis in Different Seasons.

BACKGROUND: non-melanoma skin cancer (NMSC) is the most common malignancy, whose public health significance is often unrecognized. Its incidence continues to grow at an alarming rate, becoming an occupational disease. Available treatments alternative to surgery include: photodynamic therapy, electrochemiotherapy, cryotherapy, ablative lasers, 5-fluorouracil, imiquimod, ingenol mebutate, and diclofenac. Each of these options has its advantages and disadvantages. Photodynamic therapy (PDT), using topically applied photosensitizer precursors such as methylaminolaevulinate (MAL), is a useful nonsurgical treatment, well accepted by patients, but the main limitation is pain. Recently, in order to overcome this limit, visible light irradiation photherapy was considered. AIM: we report our experience comparing conventional PDT (406 patients) with daylight-mediated PDT (D-PDT) 240 patients with multiple actinic keratoses (AK), afferent to our photodynamic outpatients clinic from September 2013 to June 2014. MATERIALS AND METHODS: to establish predictors for the clinical response to conventional PDT and daylight PDT (DPDT), a retrospective study on 646 patients was performed. The following parameters have been evaluated: sex, age, anatomic site of the primary tumor and local skin reactions. We used the Spearmen's coefficient between the clinical response and the predictors analyzed; while Odds Ratio (OR) was performed to evaluate general clinical response and local skin reaction between PDT and D-PDT patients. Subsequently, we performed a sub-analysis, focusing to the anatomical sites, and we subdivided anatomical sites in face and scalp, nose, trunk, and extremities. RESULTS: a total of 406 patients treated with PDT and 240 patients treated with D-PDT, were enrolled in the current report. The median age was 71 years in PDT and 73 years in D-PDT. The mean clinical response in PDT was of 74.4% and 95% in D-PDT. Performing OR between PDT and D-PDT, according to the clinical response, we found a better behavior in patients treated with D-PDT (P < 0.03); the same significance was maintained according to the presence or absence of local skin reaction (P < 0.0002). Using no parametric Spearman's Coefficient test among predictive factors and the therapeutical response we found that D-PDT showed a better clinical response in patients with AK size ≥ 0.6 mm (P < 0.03), while this evidence was not present in PDT. The nose remained in both PDT and DPDT the main anatomical site with a better clinical response to the treatment. CONCLUSION: Since efficacy of D-PDT is comparable or superior to conventional type, but is simpler and better appreciated by patients, in our opinion it may be used routinely to treat sun exposed multiple AKs especially in sun damaged skin also for aesthetic purposes.

Intratumoral Heterogeneity of MAGE-C1/CT7 and MAGE-C2/CT10 Expression in Mucosal Melanoma.

Mucosal melanoma is a rare disease, which differs from its cutaneous counterpart genetically and for its clinical behaviour. Moreover this is a heterogeneous disease based on the tissue of origin. As CT7 and CT10 are highly expressed in cutaneous melanoma and are immunogenic in this disease, we analysed their expression throughout the different subtypes of mucosal melanoma and tumor development. We detected a frequent expression of CT7 in primaries and corresponding metastases (55%) as well as for CT10 (30%). This expression resulted to be heterogeneous in the same tumor specimen and moreover influenced by the tissue of origin. Our results support the role of these antigens in immunotherapy for mucosal melanoma.

Improvement of survival in patients with melanoma and non-melanoma skin cancers compared to patients without double cutaneous malignancies.

OBJECTIVE: The worldwide incidence of cutaneous malignant melanoma (MM) has been rising steadily over the past 30 years. At the same time non-melanoma skin cancers (NMSC) are the most prevalent type of cancer in United States and Europe. Up to date, no paper has explored the influence on the general survival in patients with MM and NMSC. We decided to perform a study with the aim to evaluate the different survival in patients with MM-NMSC compared to control patients (MM-CTRL). PATIENTS AND METHODS: To evaluate prognosis in both groups, we analyzed disease-free survival (DFS) and overall survival (OS).Kaplan-Meier product was performed for the survival analysis. Median DFS was 73 months in group and 72 months in MM-CTRL patients (p = 0.4); while, median OS was 74.2 months in MM-NMSC patients and 63.1 in MM-CTRL (p < 0.001). Also at Odds-Ratio (OR), the statistical significance was maintained (p < 0.007) with a better prognostic value for MM-NMSC. RESULTS: Among group patients, the ones with a basal cell carcinoma showed a batter behavior, than the ones with squamous cell carcinoma (p = 0.01). CONCLUSIONS: Patients with MM-NMSC showed a better survival than MM-CTRL patients (p < 0.001). The causes of this improved survival are still unknown; probably the endogenous immune response can play a pivotal role in this class of patients. However, further studies are necessary to better understand this phenomenon, not yet explored in literature.

Conditions simulating androgenetic alopecia.

Androgenetic alopecia is a common form of hair loss, characterized by a progressive hair follicular miniaturization, caused by androgen hormones on a genetically susceptible hair follicle, in androgenic-dependent areas. Characteristic phenotype of androgenetic alopecia is also observed in many other hair disorders. These disorders are androgenetic-like diseases that cause many differential diagnosis or therapeutic error problems. The objective of this review was to systematically analyse the greatest number of conditions that mimic the AGA pattern and explain their disease pathogenesis.

Evaluation of Ingenol mebutate efficacy for the treatment of actinic keratosis with Antera 3D camera.

OBJECTIVE: Cumulative exposure of the skin to ultraviolet radiation promotes mutation in keratinocytes and their abnormal growth led to the formation of scaly lesions, called actinic keratoses (AKs). Its incidence is growing at an emerging rate, becoming a worldwide problem especially for occupational ultraviolet (UV) rays exposure. Detectable lesions are often associated with field changes, where the surrounding skin is altered and subclinical lesions may be present. Thus, a field-directed therapy, such as topical treatment, should be preferred for the prevention of invasive cancer development. A retrospective analysis was made, evaluating the efficacy of ingenol-mebutate gel, using a novel device the 3D in vivo optical skin Imaging (Antera 3D, Miravex, Ireland). PATIENTS AND METHODS: We included all patients with multiple non-hypertrophic Aks, to whom it was prescribed ingenol-mebutate gel, applied at the dosages of 0.015 for lesions in the scalp/face (for 3 consecutive days) and at the dosage of 0.05% for lesions in the trunk and/or extremities (for 2 consecutive days). RESULTS: A reduction of the lesions and of median hemoglobin levels, after a follow-up of 60 days, was observed in 100% of patients. CONCLUSIONS: Ingenol mebutate gel, the last topical molecule appeared in the Italian market showed its efficacy using Antera 3D also in terms of hemoglobin reduction. Therefore, this camera could be considered an useful tool for the identification of the area to be treated and for therapeutic follow-up.

Immunohistochemical expression of VDR is associated with reduced integrity of tight junction complex in psoriatic skin.

BACKGROUND: Cell junctions are crucial for the formation and maintenance of the paracellular barrier and for cell polarity in simple epithelia and endothelia. Altered localization and formation of tissue junction proteins in the epidermis have been described in plaque-type psoriasis. Vitamin D receptor (VDR) is a nuclear hormone involved in anti-proliferative and pro-differentiation pathways in keratinocytes. However, still to date, vitamin D/VDR signalling involved in tissue barrier related to psoriasis remains largely unknown. OBJECTIVE: To study the expression of VDR and tight junctions (TJ) proteins (claudin 1, ZO-1 and occludin) in psoriatic skin, and to correlate the expression of VDR with that of the junctional proteins claudin- 1, occludin and ZO- 1. METHODS: A total of 20 psoriatic tissue samples were included in the analysis. Immunohistochemical studies for VDR, claudin-1, occludin and ZO-1 were performed. RESULTS: We observed a reduction of VDR, claudin-1 and ZO-1 expression in psoriatic skin if compared to normal skin, and the statistical analysis showed a significant correlation between a downgrading of VDR expression and that of claudin-1 (P < 0.005) and ZO-1(P < 0.005). CONCLUSIONS: Our results suggest a new role of VDR in the maintenance of the homeostasis skin barrier. Although the exiguity of our cohort, VDR status appears to be associated with the expression level and functions of TJ proteins, suggesting multiple and different cellular functions of the VDR.

Association between autoimmune disease and cutaneous melanoma with regard to melanoma prognosis.

BACKGROUND: An association between autoimmune disease and malignant melanoma (MM) has often been reported in the literature as a positive prognostic factor for MM. Consequently, we evaluated the influence of different autoimmune diseases on the prognosis of MM. AIM: To evaluate the prognosis of patients with MM who also had an autoimmune disorder, whether tumour-associated, paraneoplastic or drug-induced. METHODS: Autoimmune diseases were classified and analysed as tumour-associated, paraneoplastic or drug-induced. Patients were enrolled according to their clinicopathological features and matched with control groups. Kaplan-Meier analysis was used to estimate disease-free survival (DFS) and overall survival (OS), and log-rank test was used to evaluate differences between the survival curves. RESULTS: In total, 49 patients with MM and tumour-associated autoimmune disease were included in our analysis. No case of paraneoplastic autoimmune disease was detected. The survival analyses showed a range of results, from a worsening of DFS and OS to a lack of any difference. In a second analysis, we separately analysed patients who developed autoimmune disorders after starting adjuvant therapy with interferon-α; we did not find significant differences between these patients and the untreated patients. CONCLUSIONS: Autoimmune disease, whether tumour-associated or drug-induced, was not associated with better prognosis in patients with MM. The results suggest that the reported relationship between autoimmunity and MM may be a result of individual variation in sensitivity to the autoimmune disease, the tumour or the treatments.

Safety and prolonged efficacy of Botulin Toxin A in primary hyperhidrosis.

BACKGROUND: Hyperhidrosis is a condition characterized by generalized or localized hyperfunction of the eccrine sweat glands with a deep negative impact on patient's quality of life. OBJECTIVES: To evaluate the efficacy and the safety of Botulin Toxin A (BTX-A) intradermal injection in the treatment of primary axillary and palmar hyperhidrosis, investigating symptoms-free period, and the subjective improving of quality life. MATERIALS AND METHODS: 50 consecutive patients with primary hyperhidrosis were evaluated detecting age, gender, hyperhidrosis onset period, disease duration and years of treatment with BTX-A, Minor's iodine test, Hyperhidrosis Disease Severity Scale (HDSS), Dermatology Life Quality Index (DLQI). RESULTS: The treatment is significantly effective both for axillae and palms: the majority of the patients improved their HDSS and Minor's scores from a value of 4 in the two tests, to values of 1 (HDSS) and 0 (Minor test). Patients reported a duration of symptoms relief from 4 to 12 months, with a mean of 5.68 months; specifically, we have observed that the axillary group experienced a longer symptoms-free period (mean RFS 7.2 months) than the palmar group (mean: RFS 4.27 months). CONCLUSIONS: Authors suggest that BTX-A is a safe, easy, and fast procedure for the treatment of primary axillary and palmar hyperhidrosis.

Multiple painful papulo-nodular lesions: clinical pitfall.

A 43-year-old male presented with multiple (>10) painful, papulo-nodular lesions, associated with paresthesia, over the face, neck and trunk, appeared 15 years prior and increased with time. The patient's brother has cutaneous leiomyomas and testicle cancer, his mother underwent hysterectomy for symptomatic leiomyomas while his maternal grandfather died from aggressive renal cell carcinoma at age 57 years. The patient reported that he had removed a kidney cancer 5 years prior. Dermoscopy, histologic evaluation and genetical analysis were done and Hereditary leiomyomatosis and renal cell carcinoma was diagnosed.

Drug cutaneous side effect: focus on skin ulceration.

Skin ulcers are defined as tissue loss interesting the deeper layers of the dermis and hypodermis, with low tendency to spontaneous healing. They cause disability related to pain, risk of infection and amputation, chronic management, requiring working absence with notably economic burden. The major cause is often related to underlying vascular disease, infections, tumors, autoimmunity, trauma, even if literature occasionally reported several cases of drug inducing skin ulceration. Most of drugs involved are chemotherapy agents and more recently molecular target therapies. Evidences supporting these drugs as the major cause of skin ulcers include delay of onset after therapy initiation, improvement after withdrawal of the drug, recurrence after its reintroduction and, sometimes, simultaneous occurrence of other skin lesions that have previously been reported to be associated with these agents. Attention should be reserved to patients undergoing antineoplastic agents, especially if previously affected by predisposing comorbidities, considering such side effect as possible differential diagnosis for skin ulceration in neoplastic patients.