Extrafacial lentigo maligna: A progression model and enhanced diagnostic techniques using dermatoscopy and reflectance confocal microscopy.

Lentigo maligna (LM) is a subtype of lentiginous melanoma confined to the epidermis, which is associated with chronic sun exposure. Its clinical, dermatoscopic, and histopathological diagnosis can be challenging, particularly in the early and advanced stages, requiring appropriate clinicopathological correlation. This article reviews the clinical presentation, diagnosis through noninvasive methods (dermoscopy and confocal microscopy), and provides insights for diagnosis of extrafacial LM through the presentation of four representative clinical cases from different phases of a theoretical-practical progression model. Recognizing these lesions is crucial, as once they invade the dermis, they can behave like any other type of melanoma.

Safety of biologic therapy in combination with methotrexate in moderate to severe psoriasis: a cohort study from the BIOBADADERM registry.

BACKGROUND: Safety is an important consideration in decisions on treatment for patients with moderate-to-severe psoriasis and the study of drug safety is the main purpose of the BIOBADADERM registry. The combination of a biologic agent and a conventional systemic drug [generally methotrexate (MTX)] is a common treatment in clinical practice. However, there is a paucity of evidence from real-world practice on the safety of such combination regimens in the treatment of psoriasis. OBJECTIVES: The primary objective of this study was to ascertain whether the use of regimens combining biologic drugs with MTX in the management of moderate-to-severe psoriasis increases the risk of adverse events (AEs) or serious AEs (SAEs). We compared monotherapy using tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors with the use of the same drugs in combination with MTX. METHODS: Using data from the BIOBADADERM registry, we compared biologic monotherapies with therapies that were combined with MTX. We estimated adjusted incidence rate ratios (aIRR) using a random effects Poisson regression with 95% confidence intervals for all AEs, SAEs, infections and serious infections and other AEs by system organ class. RESULTS: We analysed data from 2829 patients and 5441 treatment cycles, a total of 12 853 patient-years. The combination of a biologic with MTX was not associated with statistically significant increases in overall risk of AEs or SAEs in any treatment group. No increase in the total number of infections or serious infections in patients receiving combined therapy was observed for any group. However, treatment with a TNF inhibitor combined with MTX was associated with an increase in the incidence of gastrointestinal AEs (aIRR 2.50, 95% CI 1.57-3.98; P < 0.002). CONCLUSIONS: The risk of AEs and SAEs was not significantly increased in patients with moderate-to-severe psoriasis receiving different classes of biologic drugs combined with MTX compared with those on biologic monotherapy.

Dermoscopic changes in 22 extrafacial in situ and invasive lentiginous melanomas

Background: Diagnosis of non-facial melanomas on sun-damaged skin or extrafacial lentigo maligna is challenging. Objectives: To identify the evolutionary dermoscopic signs, characteristic of this type of non-facial melanoma on sun-damaged skin. Materials & Methods: This retrospective descriptive observational study included 90 dermoscopic follow-up images of 22 non-facial melanomas on sun-damaged skin from 17 high-risk melanoma patients, followed with digital dermoscopy and diagnosed between January 2016 and October 2020. We recorded dermoscopic changes by comparing each dermoscopic image with the previous one (mean dermoscopic follow-up of the excised lesions was 3.6 years). Confocal microscopy images were taken at diagnosis. Results: In total, 51.5% (95% CI: 39-64) showed an appearance or increase in featureless areas with surrounding small round or triangular dark brown-blue structures, 23% (95% CI: 23-46) showed an increase in other geometric structures (angulated lines, zig-zag lines and polycyclic structures), 5.9% (95% CI: 2-14) showed an appearance or increase in bright white lines and atypical vascularization, 26.5% (95% CI: 17-39) showed an appearance or increase in follicular pigmentation structures or follicular radial lines, and 39.7% (95% CI: 28-52) showed focal islands of pigmentation in these areas. Of the changes, 54% occurred at the last and diagnostic visit. There was an increase in size in only 20.6% (95% CI: 12-32). Also, 81.8% showed pagetoid cells in the epidermis, 95.5% atypical cells at the dermoepidermal junction by reflectance confocal microscopy, and 95.5% showed non-edged or edged and non-edged papillae. Conclusion: This study identifies the dermoscopic evolutionary changes associated with extrafacial lentigo maligna.

Monkeypox: a new differential diagnosis when addressing genital ulcer disease.

We describe a case of genital ulcer and inguinal adenopathies that were attributable to monkeypox virus infection. We suggest clinicians adopt a low threshold for suspicion, particularly when evaluating genital ulcer disease.

The risk of hepatic adverse events of systemic medications for psoriasis: a prospective cohort study using the BIOBADADERM registry.

BACKGROUND: Limited information is available regarding the risk of incident liver disease in patients with psoriasis receiving systemic therapies. OBJECTIVES: To describe the liver safety findings of conventional and modern systemic therapies for moderate-to-severe psoriasis, and to compare the relative incidence rates of hepatic adverse events (AEs) for each drug. METHODS: All the patients on the BIOBADADERM registry were included. Crude and adjusted incidence rate ratios (cIRR and aIRR, respectively) of hepatic AEs, using anti-TNF drugs as reference, were determined. Outcomes of interest were hypertransaminasemia, nonalcoholic fatty liver disease (NADFLD) and a group of other, less represented, hepatic AEs. RESULTS: Our study included 3,171 patients exposed to systemic drugs (6279 treatment cycles). Incident hypertransaminasemia was the most frequent hepatic AE (incidence rate of 21 per 1000 patients-years [CI 95% 18-23]), followed by NAFLD (8 cases per 1000 patients-years [95% CI 6-10]). Methotrexate (aIRR 3.06 [2.31-4.4]; p = 0.000) and cyclosporine (aIRR 2.37 [1.05-5.35]; p = .0378) were associated with an increased risk for hypertransaminasemia when compared to anti-TNF-α agents. No differences were observed between different groups of biologics. Conventional therapies were not associated with new incident NAFLD. CONCLUSIONS: Comparative information of the incidence of hepatic AEs could facilitate drug selection in moderate-to-severe psoriasis.

Dermocosmetics: beneficial adjuncts in the treatment of acne vulgaris.

Introduction: Dermocosmetics are increasingly being recognized as an integral part of acne management. Dermocosmetics may minimize the side effects of acne medications, provide synergistic effects by improving the efficacy of other treatments, and limit exposure to environmental factors such as ultraviolet radiation. We aimed to provide an overview of the active ingredients and different types of preparations used in dermocosmetics for acne, and highlight supporting evidence for their use in clinical practice.Methods: A literature search for selected key words was performed using PubMed. Additional papers were identified based on author expertize.Results and discussion: The different types of active ingredients in dermocosmetics for acne can be classified as: sebum-controlling, antimicrobial, anti-inflammatory, anti-oxidant and/or keratolytic. Such agents may modulate the pathogenic pathways in acne. Dermocosmetics can be formulated as emulsions/creams, cleansers or camouflaging make-up. Dermocosmetics are useful treatment adjuncts for acne and have been shown to improve the clinical signs of acne, reduce transepidermal water loss and modify sebum production. Dermocosmetics have also been associated with reducing side effects of pharmacological treatments, high levels of patient satisfaction and increased adherence to treatment regimens. Together this evidence supports the use of dermocosmetics in clinical practice.

Management Pearls on the Treatment of Actinic Keratoses and Field Cancerization.

Field cancerization (FC) is a chronic disease involving multiple clinical and subclinical actinic keratoses (AK) on large photo-exposed surfaces with multifocal areas of dysplasia and precancerous changes. Patients and treatment must be properly monitored and managed to avoid aggravation and progression of the disease. Management of actinic keratoses includes lesion-directed treatments, such as cryotherapy and field-directed therapies. Field-directed therapies may have the potential to address subclinical damage, reduce AK recurrence rates and potentially reduce the risk of squamous cell carcinoma development. Multiple studies have demonstrated the efficacy of field-directed treatments, including 5-fluorouracil, photodynamic therapy, imiquimod, chemical exfoliation with trichloroacetic acid and diclofenac gel, for multiple AK and FC. The choice of therapy should be based on multiple factors, such as efficacy, tolerability, patient risk profile, costs and cosmetic results. Management of AK includes not only treatment but also prevention. Medical devices, such as sunscreens containing liposome-encapsulated DNA repair enzymes, can repair DNA damage associated with chronic UV radiation and reduce the number of new AK lesions. Here we provide therapeutic pearls and expert opinions on the treatment of AK and FC (as monotherapy or in combination) with the overall aim to achieve better, faster, and well-tolerated clinical responses.

Delphi-based recommendations for the management of cardiovascular comorbidities in patients with psoriatic arthritis and moderate-to-severe psoriasis.

The aim of this study was to generate practical recommendations to assist rheumatologists and dermatologists in the management of cardiovascular (CV) comorbidities in patients with moderate-to-severe psoriasis (MS-PSO) and psoriatic arthritis (PsA). A two-round Delphi study was conducted. A panel of experts rated their agreement with a set of statements (n = 52) on a nine-point Likert scale (1 = totally disagree; 9 = totally agree). Statements were classified as inappropriate (median 1-3), irrelevant (median 4-6) or appropriate (median 7-9). Consensus was established when at least two-thirds of the panel responded with a score within any one range. A total of 25 experts, 60% rheumatologists and 40% dermatologists, participated in two consultation rounds. There was overall unanimity on the appropriateness of an initial assessment for CV risk factors in all patients with MS-PSO and PsA. Most panelists (88.0%) also supported the evaluation of patients' psychological and physical status. Additionally, most panelists (72.2%) agreed on a novel sequential approach for the management of CV comorbidities. This sequence starts with the assessment of hypertension, diabetes and dyslipidemia along with the identification of depression and anxiety disorders. Once these factors are under control, smoking cessation programs might be initiated. Finally, if patients have not met weight loss goals with lifestyle modifications, they should receive specialized treatment for obesity. This study has drawn up a set of practical recommendations that will facilitate the management of CV comorbidities in patients with MS-PSO and PsA.

Nevus-associated melanoma: An observational retrospective study of 22 patients evaluated with dermoscopy and reflectance confocal microscopy.

BACKGROUND: The frequency of nevus-associated melanoma (NAM) has been estimated to be 29% of diagnosed melanomas. MATERIALS AND METHODS: This is an observational retrospective study of 22 cases of NAM diagnosed in the Universitary Hospital Alcorcón between September 2011 and 2018. The main objective was to analyze dermoscopic and RCM features of NAM. We also studied if there was an association between any dermoscopic or RCM parameter and Breslow depth. RESULTS: The most frequent dermoscopic characteristics were multicomponent pattern (50%), multifocal pigmentation (45.5%), atypical network (59.1%), and blue-gray regression structures (77.3%). RCM evidenced pagetoid cells in 95.5% melanomas (abundant in 59.1%), non-edged dermal papillae in 86.4%, atypical cells at the dermal-epidermal junction in 90.9%, and atypical junctional nesting in 81.8%. Deeper Breslow index was associated with red color (mean Breslow 0.65 vs 0.37 in melanomas without red, P = 0.035), shiny white streaks (0.85 vs 0.38, P = 0.041), abundant pagetoid cells (0.68 vs 0.26, P = 0.017), and non-edged papillae (0.59 vs 0.00, P = 0.014). CONCLUSION: RCM is a valuable tool for diagnosing NAM. Even it is very difficult to differentiate NAM from DNM both with dermoscopy and RCM, RCM can help us to detect remnants of a preexisting nevus and estimate Breslow depth.

Key dermoscopic signs in the diagnosis and progression of extrafacial lentigo maligna: Evaluation of a series of 41 cases.

BACKGROUND/OBJECTIVES: Lentigo maligna is usually located on the face. Extrafacial lentigo maligna is less common, and diagnosis of early forms is very difficult. Confocal microscopy of facial and extrafacial lentigo maligna shares the same features (abundant dendritic cells and generalised atypical junctional thickenings) and helps us to identify the dermoscopic features of extrafacial lentigo maligna. METHODS: We analysed dermoscopic and clinical features of 41 lesions diagnosed by confocal microscopy of extrafacial lentigo maligna confirmed on histology to identify dermoscopic signs of early lesions. RESULTS: Erased areas on dermoscopy were the clue to diagnose early lesions. At the borders of these areas, very small, round or triangular structures were found. At the lesion periphery, dermoscopy revealed a fine reticular pattern that helped to identify them as a melanocytic lesion. A progressive increase of the number and size of erased areas was accompanied by the appearance of various angulated structures around them (angulated lines, zig-zag structures or polygonal structures). Analysis of invasive lesions revealed very large erased areas containing white lines and atypical vascularisation. CONCLUSIONS: We have identified the dermoscopic early features and signs of progression by examining the dermoscopic and reflectance confocal microscopy findings of early and invasive extrafacial lentigo maligna.

Laser therapy for hair removal on grafts and flaps.

The diversity and utility of laser procedures have increased over the recent years and nowadays, applications for medical and cosmetic reasons have increased considerably. Problematic intraoral and cutaneous hirsutisms have been described as a consequence of complex reconstruction usually after oncology surgery. We present three patients in whom hair removal laser was performed on grafts and flaps in different compromised anatomical areas: oral cavity, penis, and auricular pavilion. All three patients were men; in two of them the hairy graft was a consequence after oncologic surgery reconstruction whereas the third patient presented hair in his auricular pavilion after cochlear implant due to a congenital ear malformation. In all the patients, neodymium:yttrium, aluminum, garnet laser (Nd:YAG) (1,064 nm) laser was performed with excellent aesthetic and functional outcomes with only three sessions. Hair removal laser is a well-accepted and effective method of achieving permanent decrease in hair density. Several lasers have been used successfully, including the long-pulse Alexandrite (755 nm), the long-pulse diode (810 nm), and the Nd:YAG laser (1,064 nm). There is currently no standard protocol for laser use on hairy grafts or flaps and there is limited published data regarding skin graft revision to enhance aesthetics and function.

Genetic variation at the glycosaminoglycan metabolism pathway contributes to the risk of psoriatic arthritis but not psoriasis.

OBJECTIVE: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA. METHODS: We performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case-control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA. RESULTS: We identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDR<0.05). From these, the glycosaminoglycan (GAG) metabolism pathway was confirmed to be disease-specific after comparing the PsA cohort with the cohorts of patients with PsC and RA. Finally, we identified candidate drug targets in the GAG metabolism pathway as well as new PsA indications for approved drugs. CONCLUSION: These findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.

Reaccion acneiforme noduloquistica secundaria a vemurafenib con buena respuesta a isotretinoina oralSevere acneiform eruption associated with vemurafenib with response to isotretinoin.

Vemurafenib, a kinase inhibitor that targets tumors with the BRAF V600E mutation, is a promising option for unresectable or metastatic melanoma. Cutaneous side-effects have been reported including alopecia, photosensitivity, squamous cell carcinoma, keratoacanthomas, keratosis pilaris-like eruption, and palmoplantar hyperkeratosis. Acneiform eruptions have been reported in 3%-6% of the patients treated with BRAF inhibitors,and 5 cases are described in the literature. Although they responded well to topical therapies, oral antibiotics, or observation, one case required oral etretinate and the withdrawal of vemurafenib because the adverse event reached grade 3. We report one case of a severe acneiform eruption associated with vemurafenib with a good response to isotretinoin allowing continuation of the BRAF inhibitor.

Combined in vivo reflectance confocal microscopy and digital dermoscopy for follow up of patients at high risk of malignant melanoma: A prospective case series study.

Digital dermoscopy (DD) follow up is a useful strategy for monitoring patients at high risk of melanoma. Reflectance confocal microscopy (RCM) is a valuable second-level examination after dermoscopy for the evaluation of difficult to diagnose lesions. The aim of this study was to assess the value of RCM in routine DD monitoring of patients at high risk of melanoma. In this prospective study, performed over 22 months, changing melanocytic lesions were detected by DD and excised. RCM imaging was performed before surgical excision of all the lesions, and histopathology used as the gold standard diagnostic test. Eighty-seven lesions, including 11 thin melanomas, were studied. Dermoscopic evaluation at follow up revealed a significant association between melanoma and asymmetry in two axes (P = 0.035). Enlargement and other changes in structure or color did not significantly differ between nevi and melanomas. Widespread pagetoid cells, non-edged papillae, irregular and dishomogeneous junctional clusters, and sheet-like structures were significantly associated with malignancy (P < 0.001). RCM allowed accurate diagnosis of melanoma in 10 of 11 cases (90.9%). The remaining case was classified as a dysplastic nevus. Forty-six lesions (52.8%) in which RCM revealed no atypia were deemed unnecessarily removed. This study was limited by sample size. In conclusion, combined DD and RCM facilitates the recognition of thin malignant melanomas and reduces unnecessary excisions.

Human papilloma virus dermatosis in human immunodeficiency virus-positive patients: A 14-year retrospective study in 965 patients. / Dermatosis por virus de papiloma humano (VPH) en pacientes infectados por el virus de la inmunodeficiencia humana (VIH): estudio retrospectivo de 965 pacientes durante 14 años.

INTRODUCTION: The incidence of the human papilloma virus (HPV) has not dropped in HIV-positive patients despite the discovery of antiretroviral therapy (ART). Our goal is to assess the prevalence of HPV in HIV patients and its relationship with the epidemiological and virological characteristics of HIV patients. PATIENTS AND METHODS: Retrospective cohort of 965 patients diagnosed with HIV from 1998 to 2012. We analyzed patients' demographic factors and factors related to the HPV. RESULTS: Of the 965 patients examined, 333 consulted a dermatologist. Of these, 52 patients had genital warts (15.6%), 43 had common warts (12.9%) and 8% had both conditions. In total, 28.5% of patients had a skin lesion caused by HPV. DISCUSSION AND CONCLUSION: This is the first longitudinal observational study carried out on HIV-positive patients in the era of ART in which HPV infection is the most common skin pathology. We observed a similar trend in countries with access to ART. This study spreads awareness on the importance of preventing HPV and the difficulty of treating it in HIV-positive patients.