Dark pigmented lesions: Diagnostic accuracy of dermoscopy and reflectance confocal microscopy in a tertiary referral center for skin cancer diagnosis.

BACKGROUND: There is lack of studies on the diagnostic accuracy of dermoscopy and reflectance confocal microscopy (RCM) for dark pigmented lesions. OBJECTIVE: To assess the diagnostic accuracy of dermoscopy plus confocal microscopy for melanoma diagnosis of dark pigmented lesions in real life. METHODS: Prospective analysis of difficult dark lesions with clinical/dermoscopic suspicion of melanoma referred for RCM for further analysis. The outcome could be excision or dermoscopic digital follow-up. RESULTS: We included 370 clinically dark lesions from 350 patients (median age, 45 y). Because of the clinical/dermoscopic/RCM approach, we saved 129 of 213 unnecessary biopsies (specificity of 60.6%), with a sensitivity of 98.1% (154/157). The number needed to excise with the addition of RCM was 1.5 for melanoma diagnosis. LIMITATIONS: Single institution based; Italian population only. CONCLUSIONS: This study showed that RCM coupled with dermoscopy increases the specificity for diagnosing melanoma, and it helps correctly identify benign lesions. Our findings provide the basis for subsequent prospective studies on melanocytic neoplasms belonging to patients in different countries.

Cutaneous mastocytosis: A dermatological perspective.

Mastocytosis is a rare disease characterised by expansion and collection of clonal mast cells in various organs including the skin, bone marrow, spleen, lymph nodes and gastrointestinal tract. The prevalence of mastocytosis has been estimated to be one in 10 000, while the estimated incidence is one per 100 000 people per year. Cutaneous mastocytosis is classified into (i) maculopapular cutaneous mastocytosis, also known as urticaria pigmentosa; (ii) diffuse cutaneous mastocytosis; and (iii) mastocytoma of the skin. In adults, cutaneous lesions are usually associated with indolent systemic mastocytosis and have a chronic evolution. Paediatric patients, on the contrary, have often cutaneous manifestations without systemic involvement and usually experience a spontaneous regression. Diagnosis of cutaneous mastocytosis may be challenging due to the rarity of the disease and the overlap of cutaneous manifestations. This short review describes pathogenesis and clinical aspects of cutaneous mastocytosis with a focus on diagnosis and currently available therapies.

Efficacy of Vismodegib in pigmented basal cell carcinoma: Appearances are deceiving.

Basal cell carcinoma (BCC) is the most common skin cancer in humans. Pigmented basal cell carcinoma (pBCC) is a rare variant of BCC. Vismodegib, was the first drug to be approved for the treatment of locally advanced (laBCCs) or metastatic basal cell carcinoma. The aim of this study was to evaluate the efficacy of Vismodegib in patients with pBCCs. We retrospectively analyzed patients receiving Vismodegib as treatment for laBCCs presenting also various pBCCs. After 6 months of treatment, we performed excisional biopsies of pBCCs, that apparently at clinical and dermoscopic assessment did not respond to therapy. A total of nine patients were assessed. After 6 months of treatment, locally advanced target BCCs showed complete remission in four out of nine patients (44.4%), four patients (44.4%) were considered in partial remission and one patient (11%) showed no response to treatment. On the contrary, all the pBCCs showed both clinically and dermoscopically resistance to treatment. Therefore, clinically persistent pBCCs were surgically removed in three patients. Histology showed a complete elimination of the neoplastic cells together with features of previous regression. Our findings indicate that the efficacy of Vismodegib is higher than that documented by clinical or even dermatoscopic observation alone.

Clinical efficacy and safety of certolizumab pegol in cutaneous symptoms on psoriasis in patients with psoriatic arthritis: A retrospective analysis in real life.

We present the results on retrospective analysis about the efficacy of Certolizumab pegol (CZP), an antitumor necrosis factor-alpha agent, as monotherapy on skin psoriasis (PsO) in patients affect both by psoriatic arthritis (PsA) and mild-severe PsO. To date, the CZP is authorized for the treatment of PsA, PsO beyond that rheumatoid arthritis, axial spondyloarthritis/ankylosing spondylitis, and Crohn's. Assessments included an evaluation of the Psoriasis Area and Severity Index (PASI). Twelve patients (9M and 3F mean age 57.8 ± 8 years) were enrolled in our study. Nine patients had been previously treated with others biologic agents, three patients were naïve. Clinical and laboratory evaluations including PASI, erythrosedimentation rate, and C-reactive protein were performed at baseline (BL), at Week 12 (W12), Week 24 (W24), and Week 52 (W52) of treatment. Although the combination between methotrexate and CZP is allowed, we included, in our study, patients treated only with CZP. In such a way as to be as specific as possible, topical corticosteroids, vitamin D derivatives, retinoid creams, anthralin derivatives as well as p-UVA or UV-B have been forbidden to enrolled patients. With the same purpose, all the patients used the identical moisturizing cream two times a day. Mean PASI score decreased from 18 (BL) to 0 (W52) as follows: 18 at BL, 4 at W12, 0 at W24, and 0 at W52. Severe adverse events were not reported. Safety evaluations were performed every 3 months: liver and renal functions were monitored in all patients during the treatment, and no patient presented abnormal values. To the best of our knowledge, this is the first report that highlights the efficacy of CZP as monotherapy in psoriasis with mild to severe cutaneous involvement. Although to date the drug is authorized only for PsA, our results demonstrate that CZP is safe and effective on both cutaneous and joint components representing, therefore, an effective option in the treatment of cutaneous symptoms of PsO. Limitations of our study are presented by the relatively short observation time (W52) and by numeric small study group. Long-term data with a larger number of enrolled patients are necessary in order to confirm our preliminary observations.

High-Risk Recurrence Basal Cell Carcinoma: Focus on Hedgehog Pathway Inhibitors and Review of the Literature.

Basal cell carcinoma is the most common skin tumour, with the majority of the cases occurring on the head and neck district, where cosmetic and functional results are crucial. It can be locally destructive if not diagnosed early and treated appropriately. Surgery is the treatment of choice for most lesions, but aggressive, recurrent, or unresectable tumours can be challenging to manage. Advanced basal cell carcinoma includes high recurrence risk subtypes, in which standard therapies demonstrate lack of efficacy. This led to a need for investigating more deeply the pathogenesis of the disease and to the discovery of the implication of the hedgehog pathway. The development of systemic inhibitors of this pathway provides new treatment options for patients with advanced disease, resulting in survival improvement. Food and Drug Administration, before, and European Medicines Agency later approved 2 Hedgehog pathway inhibitors for the treatment of advanced basal cell carcinomas, vismodegib and sonidegib. Here, we present a review of the current English language literature trying to analyze differences in the 2 drugs as a head-to-head comparison between them has not already been documented in a randomized controlled clinical trial. Although vismodegib and sonidegib showed similar efficacy and safety profiles, in an indirect comparison scenario, sonidegib has shown slightly better outcomes in locally advanced basal cell carcinoma than vismodegib. They present different molecular structures, as they bind different residues on their targets and develop resistance for different mutations. In a future scenario, clinical trials comparing the 2 drugs are needed, as well as expanding data on discontinuation of therapy and/or consequential administration of them, with the aim to improve our clinical practise.

Syringotropic Lichen Planus: A Potential Histopathologic Mimicker of Syringotropic Mycosis Fungoides.

Perieccrine inflammation may be observed in several different dermatoses, but true permeation of the secretory coil by lymphocytes (lymphocytic syringotropism) is a rather uncommon finding, usually observed in mycosis fungoides (MF-syringotropic MF). Rare cases of syringotropic lichen striatus and lymphocytic autoimmune hidradenitis showing a similar pattern have been described as well. We describe an exceptional case of lichen planus (LP) characterized by marked lymphocytic syringotropism with focal hyperplasia of the eccrine epithelium. Histopathology was characterized by the combination of features of conventional LP, prominent permeation of the secretory portion of the eccrine glands by reactive lymphocytes, and focal involvement of a hair follicle. Syringotropic LP may be regarded as a histologic mimicker of syringotropic MF, thus representing a potential diagnostic pitfall.

Investigational drugs currently in phase II clinical trials for actinic keratosis.

INTRODUCTION: Actinic keratoses (AKs) are limited areas of irregular epidermal growth on a background of excessive solar exposure. The entire sun-damaged skin is considered a field of cancerization with multiple visible and subclinical lesions. AK management requires field-directed therapies to block lesion relapse and prevent squamous cell carcinoma (SCC). AREAS COVERED: In this review, we focused on phase II clinical trials for AKs, involving well-known agents and newer molecules such as proapoptotic drugs (VDA-1102, SR-T100, oleogel-S10, ICVT, eflornithine), immunomodulants (isotretinoin, tretinoin) and chemopreventive agents (nicotinamide, perillyl alcohol, liposomal T4N5). We used the website 'ClinicalTrials.Gov' as main reference. We selected and discussed completed and ongoing trials and analysed chemical structure and mechanism of action of the investigated molecules. EXPERT OPINION: AK therapy should be tailored on the patient's profile considering first of all the age and site of the AKs, which are relevant parameters for local immune response. The new molecules could be combined to obtain a synergic effect blocking the different steps of skin tumorigenesis. Phase II trials highlight a new therapeutic opportunity to block selectively cell proliferation regulators and work both on the field of cancerization and on the AKs currently present.

Correction to: Certolizumab Pegol in the Treatment of Psoriasis and Psoriatic Arthritis: Preliminary Real-Life Data.

In the original publication, part Fig. 3b and c were interchanged. The correct versions are given below.

Current developments in pharmacotherapy for actinic keratosis.

INTRODUCTION: Actinic keratosis (AK) is a superficial squamous cell carcinoma (SCC) where chronic sun exposure playing central role in its pathogenesis. UVB causes direct damage to DNA, producing pyrimidine dimers, and suppressing the protective role of p53. The stepwise progression of AK, with increased expression of anti-apoptotic Bcl-2, favors progression to SCC. Moreover, the dermal response characterized by inflammation and mediated by prostaglandins is a critical component of tumorigenesis that promotes tumor growth, tissue invasion, angiogenesis and metastasis. Other risk factors are represented by age, gender, phototype and drugs. AREAS COVERED: In this review, the authors document the recent developments of different therapies used to treat AK and provide their perspectives on current and future treatment strategies. EXPERT OPINION: The usefulness of long-term treatment with piroxicam and sun filters or diclofenac targeting the inflammation phases of skin tumorigenesis favors AK's healing and provides greater control of the cancerization field. Nonsteroidal anti-inflammatory drugs can be safely used in patients who use photosensitizing drugs and, therefore, are more at risk of developing skin tumors. Immunomodulatory therapies, which require shorter treatment, are characterized by more common local side effects, and need more attention by the dermatologist in the concern of patient education, resulting essential to improve adherence and outcomes.

Certolizumab Pegol in the Treatment of Psoriasis and Psoriatic Arthritis: Preliminary Real-Life Data.

INTRODUCTION: We present the results of real-life tests conducted in adults affected by psoriatic arthritis (PsA) with mild cutaneous involvement to evaluate the efficacy of certolizumab pegol (CZP), an anti-tumor necrosis factor-alpha agent approved in Europe for the treatment of rheumatoid arthritis and PsA. METHODS: Assessments included an evaluation of the Psoriasis Area and Severity Index (PASI) and the Disease Activity Score computed on 44 joints (DAS-44) correlated to the erythrocyte sedimentation rate (ESR) (DAS44-ESR). A total of 41 patients (16 men, 25 women; mean age 59.8 ± 8 years) completed the study. Of these, 36 patients were affected by both PsA and psoriasis, and five patients were affected only by PsA. A total of 32 patients (group A) completed 3 months of treatment (W12), and 12 patients completed 6 months of treatment (W24) (group B). RESULTS: The clinical efficacy of CZP was consistent on both the cutaneous and rheumatic components of the treatment. The mean PASI score decreased from 4.4 ± 4.7 at baseline (BL) to 2.3 ± 3.7 at W12 (group A), and from 5.1 ± 5.7 at BL to 0.8 ± 1.2 at W24 (group B). The DAS44-ESR decreased from 4.4 ± 0.6 at BL to a mean of 2.2 ± 0.9 at W12 (group A) and from 4.1 ± 0.6 at BL to a mean of 1.9 ± 0.5 at W24 (group B). No adverse events were reported. CONCLUSION: Our results demonstrate that CZP can be used safely and effectively to treat both the cutaneous and joint components of PsA. However, long-term data are needed to confirm our preliminary observations.

New insight into the pathogenesis of nail psoriasis and overview of treatment strategies.

Psoriasis is a chronic inflammatory disease affecting up to 3% of the general population. The prevalence of nail involvement in psoriasis patients varies between 15% and 79%. While the nails represent a small portion of the body surface area, psoriasis in these areas can have a disproportionate influence on a patient's physical and psychosocial activities. Differential diagnosis between an onychomycosis and a psoriatic nail could be challenging; nevertheless, coexistence of onychomycosis and nail psoriasis also occurs and both are common disorders in the general population. Nail psoriasis can be difficult to treat. Treatment of nail psoriasis should consider the body surface area of skin disease, psoriatic arthritis, severity of nail disease, and the impairment in the quality of life. All patients should be tested for onychomycosis before starting a therapy. This recommendation is underlined by the fact that nail psoriasis is mostly treated by immunosuppressive drugs, like steroids, methotrexate, or biologics, which may aggravate mycotic nail infections. Conventional systemic therapy, such as use of steroids, cyclosporine, methotrexate, and retinoid in the long term, can cause organ toxicities. Currently, use of apremilast and tofacitinib favors an early healing of nail psoriasis because they act directly on the pathogenic targets, distressing the inflammatory signals associated with the initiation and maintenance of the disease activity, and as with several conventional synthetic disease modifying antirheumatic drugs, they are characterized by the convenience of oral administration. The number of treatment options has increased considerably in recent years; however, given the heterogeneity of the disease, the therapy should be personalized to individual cases.