Vitiligo Treated with Combined Piperine-Based Topical Treatment and Narrowband Ultraviolet B Therapy: Follow-Up with Reflectance Confocal Microscopy.

BACKGROUND: Reflectance confocal microscopy (RCM) has a defined in vivo morphology of vitiligo and re-pigmentation. Combination therapies seem more effective than monotherapies. OBJECTIVE: We aim to describe the clinical and RCM features of re-pigmentation with combined narrowband ultraviolet B (NB-UVB) and piperine-based topical treatment in localized vitiligo. METHODS: Eight patients enrolled at a single center received combined treatment: topical treatment was applied twice daily + NB-UVB twice weekly for 2 × 2-month periods. Clinical changes were analyzed by the Vitiligo Noticeability Scale (VNS) and percentage of re-pigmentation. The evaluator agreement was assessed. Predefined RCM features had the presence/absence of (i) blood vessels, (ii) dendritic cells, and the quantity of (i) an irregular honeycombed pattern and (ii) non-pigmented papillae. Clinical and RCM monitoring was performed at the baseline, 2, 3, 5, and 7 months. RESULTS: Macules were "slightly less noticeable" with 25-50% re-pigmentation. Irregular honeycomb patterns and non-pigmented papillae were significantly less frequently observed, and in less extended areas (T1 vs. T2, p = 0.039; T0 vs. T1, p = 0.005 and T2 vs. T4, p = 0.033). Dendritic cells and blood vessels improved, with significant changes in blood vessels (T1 vs. T2, p = 0.005 and T3 vs. T4, p = 0.008). CONCLUSIONS: RCM confirms the morphological changes induced by combined treatment for localized vitiligo.

Acral perineurioma: A case report of a rare neoplasm successfully treated with autologous skin graft reconstructive surgery.

Soft tissues perineurioma is a rare nerve sheath tumor that affects most of all the subcutaneous tissue. Even if it could present as a large mass, it is a benign neoplasm for which a complete surgical excision represents the gold standard treatment. Considering that it usually affects acral sites of young people, it can be challenging to perform a reconstructive surgery that allows a full functional recovery. We report the case of a woman in her 20s presenting a perineurioma of the sole of the right foot, a nodule of about 2 cm of diameter that compromised the support of the foot on the ground. We performed a radical surgical excision with no recurrence after 3 years of follow up and we obtained a full functional recovery thanks to an autologous full-thickness skin graft.

Use of Apremilast® in the psoriasis treatment: a real-life multicenter Italian experience.

BACKGROUND: Apremilast® (Amgen, Thousand Oaks, CA, USA) is the first small molecule approved for the treatment of moderate-to-severe psoriasis in adult patients; however, real-life data are still limited. We investigated the effectiveness and safety of this drug in a multicenter real-world setting. METHODS: We retrospectively reviewed data from all psoriatic patients who received at least one dose of Apremilast® (Amgen) and collected demographic data and medical history at baseline and periodically for 36 months. RESULTS: A total of 111 patients entered in the study. The mean drug survival duration was 21.8±10.6 months; however, it was significantly shorter when comorbidities were ≥3 and if biologic drugs were previously administered. ΔPASI90 was achieved in 29% of patients and ΔPASI50 in 68% at T4; the rate of ΔPASI improvement increased progressively at T12, T24, T36 in patients who continued to receive Apremilast® (Amgen). At the end of the study 50 patients discontinued the treatment because of adverse events (19.8%), primary failure (19%) or secondary failure (6.3%). CONCLUSIONS: Apremilast® (Amgen) proved to be an effective, safe, and manageable drug, showing effectiveness also in difficult-to-treat patients with psoriasis, with a favorable tolerability profile and a potentially valid weight loss effect. We believe that treating patients with few comorbidities who are naive to biological therapy may result in higher response rates and longer mean drug survival.

Comparative study of imiquimod 3.75% vs. photodynamic therapy for actinic keratosis of the scalp.

BACKGROUND/PURPOSE: To assess efficacy, tolerability, adverse effects, recurrence, and aesthetic results of imiquimod 3.75% vs. photodynamic therapy with 5-aminolaevulinic acid (MAL-PDT) for actinic keratosis (AK). METHODS: A small randomized, intraindividual right-left pilot study for AK treatment of multiple scalp lesions was performed. Patients were treated with imiquimod and subsequently MAL-PDT (on opposite sides of the scalp) 14 days apart. Study end points were evaluated with clinical and dermoscopic examinations at 1, 3, 6, and 12 months. RESULTS: Nine male bald patients were enrolled. Imiquimod achieved a slightly higher overall clearance rate than MAP-PDT (68.1% vs 56.5%). According to AK degree of severity, clearance rates were greater for degree I and III with imiquimod (68.8%, 64.5% and 75% with imiquimod vs. 48%, 69.8%, and 66.7% for MAL-PDT, respectively). At 12 months, a slightly higher total recurrence rate was noted for imiquimod compared with MAL-PDT (9.9% vs. 8.6%); new lesions were 2 degree I for imiquimod and 4 degree I for MAL-PDT. For both treatments, pain was moderate/strong (even if MAL-PDT seems to be less tolerable) adverse effects are common and transient; aesthetic results excellent. CONCLUSION: Both imiquimod and MAL-PDT were effective in the reduction in the number of AK. In the long-term, both present a good effectiveness maintained over time with excellent aesthetic results. A combination or sequential therapy could optimize the management of the cancerization field.

Claimed Effects, Outcome Variables and Methods of Measurement for Health Claims Proposed Under European Community Regulation 1924/2006 in the Framework of Maintenance of Skin Function.

Evidence suggests a protective role for several nutrients and foods in the maintenance of skin function. Nevertheless, all the requests for authorization to use health claims under Article 13(5) in the framework of maintenance of skin function presented to the European Food Safety Authority (EFSA) have received a negative opinion. Reasons for such failures are mainly due to an insufficient substantiation of the claimed effects, including the choice of inappropriate outcome variables (OVs) and methods of measurement (MMs). The present paper reports the results of an investigation aimed at collecting, collating and critically analyzing the information with relation to claimed effects (CEs), OVs and MMs related to skin health compliance with Regulation 1924/2006. CEs, OVs and MMs were collected from both the EFSA Guidance document and from the authorization requests of health claims under Article 13(5). The critical analysis of OVs and MMs was based on a literature review, and was aimed at defining their appropriateness (alone or in combination with others) in the context of a specific CE. The results highlight the importance of an adequate choice of OVs and MMs for an effective substantiation of the claims.

Are Anti-TNF-α Agents Safe for Treating Psoriasis in Hepatitis C Virus Patients with Advanced Liver Disease? Case Reports and Review of the Literature.

Tumor necrosis factor-alpha (TNF-α) inhibitors represent an effective treatment for severe psoriasis in hepatitis C virus (HCV) patients. The literature reports mainly on short-term treatment in patients with chronic hepatitis with minimum-to-moderate activity with an acceptable safety profile. We report the first 2 cases of hepatocellular carcinoma (HCC) arising in HCV psoriatic patients with advanced liver disease during long-term treatment with etanercept. Our first patient, known to have had HCV infection for 41 years, developed an HCC after 21 months of therapy with etanercept (50 mg/week). The second patient, HCV+ for 20 years, was treated for 58 months with the same therapy, and despite no signs of liver function impairment was diagnosed with HCC. Both of them presented with cirrhosis, which was diagnosed 9 and 5 years earlier, respectively. It remains to be clarified whether there is any connection between psoriasis treatment with anti-TNF-α agents and the development of HCC in HCV-infected patients. Further long-term, follow-up studies and registries of HCV patients with mild/moderate activity may contribute to clarify this issue.

Recessive bullous dermolysis of the newborn in preterm siblings with a missense mutation in type VII collagen.

Bullous dermolysis of the newborn is a dominant or recessive inherited subtype of dystrophic epidermolysis bullosa characterized by the tendency to spontaneously stop blistering within the first months of life. Here we report two siblings with bullous dermolysis of the newborn who were born prematurely and have a novel recessive mutation, p.Pro2259Leu, in the triple helix domain of type VII collagen. We discuss the possible relationship between genotype and prematurity and clinical manifestations in these patients.

Comparative study of trichloroacetic acid vs. photodynamic therapy with topical 5-aminolevulinic acid for actinic keratosis of the scalp.

BACKGROUND: Photodynamic therapy with 5-methyl-aminolevulinate and photodynamic therapy with trichloroacetic acid 50% are the two techniques utilized in the management of actinic keratosis. This study was planned to compare the efficacy, adverse effects, recurrence and cosmetic outcome of these option therapies in patients with multiple actinic keratosis of the scalp. METHODS: Thirteen patients with multiple actinic keratosis were treated with one of the two treatments on half of the scalp at baseline, while the other treatment was performed on the other half 15 days apart, randomly. Efficacy, adverse effects, cosmetic outcome and recurrence were recorded at follow-up visit at 1, 3, 6 and 12 months. RESULTS: Photodynamic therapy with 5 methyl-aminolevulinate was more effective than trichloroacetic acid although less tolerated by patients as it was more painful. Early adverse effects were almost the same even if trichloroacetic acid leads also to crust formation and to a worse cosmetic outcome characterized by hypopigmentation. Recurrence was lower in the area treated with photodynamic therapy. CONCLUSION: Trichloroacetic acid 50% is less effective than photodynamic therapy with 5 methyl-aminolevulinate in the treatment of multiple actinic keratosis of the scalp although better tolerated by patients. As this technique is less painful and less expensive than photodynamic therapy, we hypothesize and suggest that more sequential treatments could lead to better results.

Pigmented epithelioid melanocytoma: report of a case with favourable outcome after a 4-year follow-up period.

BACKGROUND: Pigmented epitheliod melanocytoma (PEM) is a uncommon melanocytoma with unique histopathological features and possibly with a favourable prognosis, because, although sentinel lymph-node metastases may occur, in the great majority of cases described up to now there is no spread beyond regional lymph-nodes. The nature of PEM, its biologic behaviour and its relationships to naevi and melanoma, however, remain to be clearly established, and several Authors suggest that further cases of PEM with long follow-up should be published, in order to better assess the biologic/prognostic characteristics of PEM. METHODS AND RESULTS: We report a new case of PEM, dealing with an oval, regularly marginated, darkly pigmented, asymptomatic nodule. The dermoscopic pattern showed a homogeneous blue-black pigmentation, without any other dermoscopic sign. The histopathologic analysis showed both isolated and nested oval melanocytes at the junctional level, and a mixture of epitheliod and spindle melanocytes, heavily pigmented, together with numerous melanophages in the dermis, with tendency to periadnexal distribution; cellular atypia was pronounced, but only occasional mitoses were identified in the superficial dermis. After a 4-year follow-up period after excision, no persistent lesion or metastases occurred. CONCLUSIONS: The present case suggests that PEM has a distinct histopathologic/diagnostic identity among melanocytic tumours. Although the up-to-now favourable outcome, however, our patient needs a large period of observation, and further studies with long follow-up are needed to better define the biologic/prognostic identity of PEM.

The vast majority of lymphocytes infiltrating primary cutaneous melanoma express the CD27 costimulatory receptor: implications for melanoma progression.

Melanoma progression is favoured by prevalence, within the micro-environment of primary cutaneous melanoma, of suppressive forces, e.g. exerted by CD4(+) CD25(+) FOXP3(+) regulatory T lymphocytes, over anti-melanoma immunity, e.g. exerted by CD8(+) cytolytic T lymphocytes. The CD27 glycoprotein is crucial because it is able to identify regulatory T cells endowed with strong suppressive ability, whilst CD8(+) T cells endowed with actual cytolytic ability become CD27(-). The present in situ quantitative immunohistochemical study, including a series of double labelling experiments and morphometrical cell analyses, shows that the vast majority of lymphocytes infiltrating primary cutaneous melanoma express CD27. Specifically, virtually the entire CD4(+) CD25(+) FOXP3(+) T subset infiltrating primary cutaneous melanoma also co-expressed CD27; CD27 was, moreover, co-expressed even by the vast majority of the CD8(+) T cells, and, conversely, effector/cytotoxic CD8(+)CD27(-) cells were very scarcely represented. The overwhelming CD27 co-expression may confer on the CD4(+)CD25(+)FOXP3(+) T subset a consistent capacity to suppress anti-melanoma immunity, whereas the too low CD8(+) CD27(-) cell proportion may presumably be insufficient to confer on the CD8(+) T subset a satisfactory anti-melanoma cytotoxic activity. We therefore propose that these CD27-discriminated pathways may trigger a functional imbalance within the microenvironment of primary cutaneous melanoma, thus favouring melanoma progression.