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Background: Certolizumab is an Fc-free PEGylated tumor necrosis factor-alpha (TNFα) inhibitor recently approved for the treatment of moderate-to-severe plaque psoriasis, although there is limited real-world evidence on the effectiveness and safety in patients with plaque psoriasis treated with certolizumab. The objective of this article is to determine the effectiveness, drug survival, and safety, including pregnancy, childbirth, and lactation, of certolizumab in moderate-to-severe plaque psoriasis under real-world conditions., Methods: This is a retrospective, multicenter, observational study performed in 15 hospitals in Spain. It evaluates the effectiveness and safety of certolizumab in plaque psoriasis in the clinical practice setting., Results: A total of 67 patients (73% female) were evaluated with a mean baseline Psoriasis Area Severity Index (PASI) of 8.9. At Week 12, the mean PASI was 2.3 (n = 67), 1.3 (n = 57) at Week 24 and 1.3 at Week 52 (n = 34). Absolute PASI < 3 was achieved in 69, 86, and 92% of patients at Weeks 12, 24, and 52, respectively, as observed. For its part, using the under-response imputation analysis, PASI < 3 at Weeks 12, 24, and 52 were achieved by 69, 73, and 49% of the patients, respectively. A total of 35 patients (52%) had concomitant psoriatic arthritis, and, in 24 of them, Disease Activity in Psoriatic Arthritis Score (DAPSA) was recorded at baseline, with a mean value of 17.9 which decreased to 8.2 at Week 12 (n = 22) and to 3.6 at Week 24 (n = 18). Certolizumab treatment was discontinued in 14 out of 67 patients (21%), due to lack/loss of cutaneous or articular effectiveness (n = 11) or patient decision (n = 2) or adverse event in only one patient who developed active tuberculosis. A lower baseline PASI [hazard ratio (HR): 1.12 (1.02-1.23); P = 0.023] and a more significant reduction in PASI at Week 12 [HR: 1.16 (1.07-1.27); P < 0.001] and Week 52 [HR: 1.47 (1.11-1.96); P = 0.007] was shown to be significantly related with better survival for the entire follow-up period. Fourteen patients were treated during pregnancy and/or lactation without reporting adverse events in either the patient or the newborn., Conclusions: Certolizumab consistently showed high effectiveness and drug survival rates in this real-life cohort. The safety demonstrated in clinical trials during pregnancy and lactation seems to be confirmed in clinical practice., (© 2024 the International Society of Dermatology.)

Competing Interests: Conflict of interest The authors declare no conflicts of interest.

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., Competing Interests: Conflicts of interest J.M.C. has participated as a speaker and/or advisor and/or principal investigator/senior investigator in clinical trials sponsored by for Celgene, Janssen, Lilly, Leo Pharma, Novartis, Pfizer, MSD, Biogen, Mylan, Amgen, AbbVie and Sandoz. A.G.-Q. acted as consultant and/or speaker for and/or participated in clinical trials as principal investigator and subinvestiator for AbbVie, Almirall, Amgen, Boehringer, Janssen, Leo Pharma, Lilly, Novartis, MSD, Pfizer-Wyeth and UCB. R.R.-D. acted as consultant and/or speaker for and/or participated in clinical trials as principal investigator for AbbVie, Almirall, Amgen, Boehringer, Janssen, Leo Pharma, Lilly, Novartis, MSD, Pfizer-Wyeth and UCB. A.S.-T. has served as a consultant and/or paid speaker for and/or participated in clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis, including AbbVie, Celgene, Janssen-Cilag, LEO Pharma, Lilly, Novartis and Pfizer. M.L.-V. acted as a consultant and speaker and participated in clinical trials for Janssen-Cilag, AbbVie, Boehringer, Celgene, Pfizer, Novartis, Lilly, Almirall, UCB, Kyowa Kirin and Leo Pharma. E.H.-A. has served as consultant and/or speaker with Leo Pharma, Novartis, Janssen, Lilly, Celgene and AbbVie. P.d.l.C. acted as a consultant and/or speaker for Janssen-Cilag, AbbVie, MSD, Pfizer, Novartis, Lilly, Almirall, UCB, Biogen, Celgene, Amgen, Sandoz, Sanofi and Leo Pharma. O.B.-R. acted as a consultant and/or speaker for Janssen-Cilag, AbbVie, Pfizer, Novartis, Lilly, Celgene, Leo Pharma, Amgen, Boehringer, UCB and Almirall. L.L.-E. participated as advisory board member and received educational grants from Janssen, AbbVie, MSD, Lilly, Novartis, LeoPharma and Pfizer. I.B. acted as a consultant and/or speaker for and/or participated in clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis, including Janssen Pharmaceuticals Inc., Almirall SA, Lilly, AbbVie, Novartis, Celgene, Biogen Amgen, Leo Pharma, UCB, Pfizer-Wyeth and MSD. M.F. has participated as speaker and/or advisor for Janssen, Lilly, Novartis, Pfizer, MSD, AbbVie Celgene and Almirall. A.M. acted as consultant and/or speaker for AbbVie, Almirall, Celgene, Janssen, Leo Pharma, Lilly, Novartis. L.R. acted as a consultant and speaker for Janssen-Cilag, AbbVie, MSD, Pfizer, Novartis, Lilly, Almirall, Celgene and Leo Pharma. J.R.-M. acted as a consultant and/or speaker for and/or participated in clinical trials sponsored by AbbVie, Almirall, Janssen, Leo Pharma, Novartis, UCB, Pfizer, Lilly, Amgen and Boehringer Ingelheim. G.C. has been reimbursed by Janssen, AbbVie, Novartis, Pfizer, MSD and Celgene for advisory service and conference attendance. C.G.-D. participated as advisory board member for AbbVie, Almirall and speaker for Janssen, Lilly and Celgene. C.P.-M. acted as a consultant and/or speaker for Janssen-Cilag, AbbVie, MSD, Pfizer, Novartis, Lilly, Almirall, UCB, Celgene and Leo Pharma. E.D.A. has participated as a speaker and/or and/or PI/SI clinical trials sponsored by Amgen, Almirall, Janssen, Lilly, Leo Pharma, Novartis, UCB and AbbVie. J.A.S.-P. has served as consultant and/or speaker with Leo Pharma, Novartis, Janssen, Lilly, Celgene, AbbVie, Amgen, Sanofi, Almirall and Pfizer. D.P.R.-G. has been reimbursed by Pfizer, Janssen, Celgene, AbbVie, Novartis and LeoPharma for advisory services and conference attendance. I.G.D. received travel grants for congresses from AbbVie, MSD, Pfizer and Sanofi., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.

Summary: Background: Promoter methylation of tumour suppressor genes (TSGs) has recently been implicated in the pathogenesis of several types of cancer. Regarding melanoma, over 100 genes that contribute to its pathogenesis have been identified to be aberrantly hypermethylated. Objectives: This is a retrospective observational study that aims to analyse the prevalence of CpG island methylation in a series of primary melanomas, to identify the associations with the main clinicopathological features, and to explore the prognostic significance of methylation in melanoma survival. Materials and methods: DNA methylation was analysed using methylation‐specific multiplex ligation‐dependent probe amplification in a series of 170 melanoma formalin‐fixed paraffin‐embedded tumour samples. The relationship between the methylation status, known somatic mutations and clinicopathological features was evaluated. Disease‐free survival (DFS) and overall survival (OS) were displayed by the Kaplan–Meier method. Results: In the entire cohort, one or more genes were detected to be methylated in 55% of the patients. The most prevalent methylated genes were RARB 31%, PTEN 24%, APC 16%, CDH13 16%, ESR1 14%, CDKN2A 6% and RASSF1 5%. An association between aberrant methylation and aggressive clinicopathological features was observed (older age, increased Breslow thickness, presence of mitosis and ulceration, fast‐growing melanomas, advancing stage and TERT mutations). Furthermore, Kaplan–Meier survival analysis showed a correlation of methylation and poorer DFS and OS. Conclusions: Aberrant methylation of TSGs is a frequent event in melanoma. It is associated with aggressive clinicopathological features and poorer survival. Epigenetic alterations may represent a significant prognostic marker with utility in routine practice. [ABSTRACT FROM AUTHOR]

Background: Secukinumab is a first-in-class interleukin 17A monoclonal antibody that has demonstrated an excellent safety and efficacy profile in phase 3 studies., Objective: To evaluate the effectiveness of secukinumab in daily clinical practice and to understand the clinical and epidemiologic characteristics of patients treated with secukinumab in clinical settings., Methods: In this multicenter prospective observational study, we recruited adult patients with moderate-to-severe plaque psoriasis from 12 hospitals in Spain during January-December 2016. These patients were treated with secukinumab and prospectively followed at 12-week intervals for 52 weeks., Results: In total, 158 patients were recruited to the study. A Psoriasis Area and Severity Index (PASI) score improvement ≥75% over baseline (PASI-75) was achieved by 57%, 83.5%, 89%, and 78.5% of patients at weeks 4, 12, 24, and 52, respectively. PASI-90 was achieved in 27.8%, 62%, 64.6%, and 63.2% of patients at weeks 4, 12, 24, and 52, respectively; PASI-75 and PASI-90 responders were significantly more common among patients with a body mass index <30 kg/cm 2 and patients without previous biologic therapy failures., Limitations: Observational study. Time from onset of psoriasis was not evaluated., Conclusion: Secukinumab is a safe treatment with effectiveness rates similar to those found in its phase 3 studies. These rates endure up to a year from start of treatment., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background/Objectives: Secukinumab was shown to be effective in treating moderate-to-severe plaque psoriasis in adults and pediatric patients ≥6 years. Methods: A literature review was conducted to identify studies published in the preceding 5 years assessing the effectiveness and/or survival (safety in the second instance) associated with secukinumab treatment for moderate-to-severe plaque psoriasis with/without psoriatic arthritis (PsA) in real-world clinical practice in Spain. Results: 11 references were included, corresponding to seven studies (six retrospective and one prospective) (n = 1050). Baseline characteristics were mean age 46.5–53.0 years; 28.7–55.0% women; 30.0–53.1% patients with PsA; 27.9–47.4% naïve to biologic treatments; mean Psoriasis Area and Severity Index (PASI) score 12.5 (standard deviation [SD]: 6.9)–18.1 (SD: 10.3). PASI 90 response rates were 54–65% at Week 24 and 46–63% at Week 52; 43–47% of patients showed PASI ≤ 1 at Week 12 and 47–56% at Week 52. Treatment persistence at Week 52 was 72–89%, being 74.5% in the larger cohort series (n = 384) at 2 years. Adverse-event-related treatment discontinuation was rare. Conclusions: Secukinumab demonstrated long-term safety and efficacy in treating adult patients with moderate-to-severe plaque psoriasis in actual clinical practice, with survival rates of up to two years and consistent efficacy in Spain. [ABSTRACT FROM AUTHOR]

Phosphodiesterase-4 (PDE4) is involved in the synthesis of inflammatory cytokines that mediate several chronic inflammatory disorders, including psoriasis and atopic dermatitis. In recent years, the therapeutic armamentarium in dermatology has expanded with the introduction of PDE4 inhibitors, both in oral and topical formulations. PDE4 inhibitors have gained increasing interest due to their remarkable safety record and ease of prescription, as evidenced by the recent influx of literature detailing its off-label uses. Apremilast was the first PDE4 inhibitor approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for psoriasis, psoriatic arthritis, and oral ulcers of Behcet's disease. Off-label use has been reported in diverse dermatological conditions, including aphthous stomatitis, chronic actinic dermatitis, atopic dermatitis, cutaneous sarcoidosis, hidradenitis suppurativa, lichen planus, and discoid lupus erythematosus. Roflumilast is a PDE4 inhibitor that was approved by the FDA and the EMA as an oral treatment of chronic obstructive pulmonary disease. Since patent expiration, several generic formulations of oral roflumilast have become available, and various studies have documented its off-label use in psoriasis and other dermatological conditions such as hidradenitis suppurativa, recurrent oral aphthosis, nummular eczema, lichen planus, and Behçet's disease. Topical roflumilast has received FDA approval for treatment of plaque psoriasis and seborrheic dermatitis. The favorable safety profile encourages its long-term use as an alternative to corticosteroids, addressing the chronic nature of many dermatological conditions. New oral PDE4 inhibitors are being developed, such as orismilast (LEO-32731), mufemilast (Hemay005), difamilast (OPA-15406) or lotamilast (E6005/RVT-501), among others. This narrative review provides a comprehensive synthesis of the pharmacology, clinical efficacy, safety profile, and practical considerations regarding the oral and topical use of PDE4 inhibitors in dermatology. [ABSTRACT FROM AUTHOR]

SERENA is an ongoing European noninterventional longitudinal study evaluating retention, effectiveness, safety, and quality of life (QoL) in secukinumab‐treated patients with active moderate‐to‐severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. Herein, 3‐year interim results among patients with psoriasis enrolled in Greece are presented. Consented adults receiving secukinumab according to the approved label for ≥16 weeks were included. Of 292 patients enrolled, 290 eligible patients (mean age 48.4 years, 71.7% male) were analyzed. At treatment initiation, 65.9% of patients were biologic‐naïve and mean total Psoriasis Area Severity Index (PASI) score was 29.0. At enrolment, mean treatment duration was approximately 1.0 year. The treatment retention rate at 1/2/3 years after enrolment was 94.4/87.3/85.9%; main reasons for discontinuation were lack of effectiveness and adverse events (AEs) (43.6% and 28.2% of discontinuations, respectively). At enrolment, the mean PASI score was 4.0, 61.3% of patients had PASI ≤ 3, 71.7% had Physician's Global Assessment (PGA) score 0/1, 59.5% had Dermatology Life Quality Index (DLQI) score 0/1, while the mean EuroQoL Visual Analogue Scale (EQ‐VAS) score was 82.0. At 1/2/3 years postenrolment, the mean PASI score was 1.9/1.6/1.0, 86.6/89.4/90.0% had PASI ≤ 3, 89.5/94.8/97.5% had PGA 0/1, 71.1/75.9/81.8% had DLQI 0/1, and mean EQ‐VAS score was 85.7/90.0/92.0. Of enrolled patients, 7.2% experienced secukinumab‐related AEs, while special interest AEs (candida infections, malignancy, and major adverse cardiovascular events) were reported in ≤2 patients, each. These results demonstrate high secukinumab persistence in the Greek population up to three years after study enrolment, accompanied by sustained improvements in both clinical and QoL parameters and a favorable safety profile. [ABSTRACT FROM AUTHOR]

Simple Summary: Angiogenesis is a crucial process in the progression and metastasis of melanoma. Recent research has highlighted the significant role of epigenetic modifications in regulating angiogenesis. This review comprehensively examines the current understanding of how epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs, influence angiogenic pathways in melanoma, with some important therapeutic approaches. Angiogenesis, the formation of new blood vessels from pre-existing ones, is a crucial process in the progression and metastasis of melanoma. Recent research has highlighted the significant role of epigenetic modifications in regulating angiogenesis. This review comprehensively examines the current understanding of how epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs, influence angiogenic pathways in melanoma. DNA methylation, a key epigenetic modification, can silence angiogenesis inhibitors such as thrombospondin-1 and TIMP3 while promoting pro-angiogenic factors like vascular endothelial growth factor (VEGF). Histone modifications, including methylation and acetylation, also play a pivotal role in regulating the expression of angiogenesis-related genes. For instance, the acetylation of histones H3 and H4 is associated with the upregulation of pro-angiogenic genes, whereas histone methylation patterns can either enhance or repress angiogenic signals, depending on the specific histone mark and context. Non-coding RNAs, particularly microRNAs (miRNAs) further modulate angiogenesis. miRNAs, such as miR-210, have been identified as key regulators, with miR-9 promoting angiogenesis by targeting E-cadherin and enhancing the expression of VEGF. This review also discusses the therapeutic potential of targeting epigenetic modifications to inhibit angiogenesis in melanoma. Epigenetic drugs, such as DNA methyltransferase inhibitors (e.g., 5-azacytidine) and histone deacetylase inhibitors (e.g., Vorinostat), have shown promise in preclinical models by reactivating angiogenesis inhibitors and downregulating pro-angiogenic factors. Moreover, the modulation of miRNAs and lncRNAs presents a novel approach for anti-angiogenic therapy. [ABSTRACT FROM AUTHOR]

Background: New oncologic therapies, including immune checkpoint inhibitors (ICIs), have revolutionized the survival and prognosis of cancer patients. However, these therapies are often complicated by immune-related adverse effects (irAEs) that may impact quality of life and potentially limit their use. Among these adverse events are psoriasis and psoriatic arthritis that may develop de novo or flare under treatment with ICIs. Given the exceptional immune status of patients receiving ICIs, managing these conditions without interfering with the effect of the oncologic treatment may prove very challenging. Aim: To review the literature data on ICI-induced psoriasis exacerbation or development, to present our own experience, and to discuss the pathogenic mechanisms underlying this association and the optimal therapeutic approach for these patients. Case Reports: We report three cases of ICI-induced de novo psoriasis and two cases of ICI-induced psoriasis exacerbation that required systemic treatment. Oral acitretin treatment successfully controlled psoriasis lesions in three cases and allowed for the continuation of immunotherapy. Literature Review: We performed a medical literature search across several databases (PubMed, Medline, Google Scholar) using the search terms "immune checkpoint inhibitor-induced psoriasis/psoriasiform dermatitis/psoriasis arthritis". We identified and revised 80 relevant publications that reported 1102 patients with psoriasis and/or psoriasis arthritis induced or exacerbated by ICIs. We assessed the type of cancer, the therapeutic agent involved, the clinical form of psoriasis, the presence or absence of psoriatic arthritis, the personal and family history of psoriasis, the age, the gender, the time until onset or exacerbation of skin lesions, the specific treatment recommended, the need for ICI discontinuation, and the patient's outcome. Conclusions: As ICIs represent a fairly novel therapy, the association with several adverse effects is only now unraveling. Psoriasis exacerbation or onset following the initiation of immunotherapy is one such example, as more and more reports and case series are being published. Awareness of the relationship between psoriasis and treatment with ICIs, prompt recognition, and initiation of adequate skin-directed therapies are essential for the avoidance of skin lesions worsening, the need for systemic treatments that may interfere with ICIs' effects, or the discontinuation of the latter. In the absence of generally accepted guidelines, it is advisable to treat patients with severe, widespread psoriasis with drugs that do not impair the effects of immunotherapy and thus do not alter the patient's prognosis. [ABSTRACT FROM AUTHOR]

The prognosis of patients with malignant melanoma has been improved in recent decades due to advancements in immunotherapy. However, a considerable proportion of patients are refractory to treatment, particularly at advanced stages. This underscores the necessity of developing a new strategy to improve it. Alternative polyadenylation (APA), as a marker of crucial posttranscriptional regulation, has emerged as a major new type of epigenetic marker involved in tumorigenesis. However, the potential roles of APA in shaping the tumor microenvironment (TME) are largely unexplored. Herein, we collected two cohorts comprising melanoma patients who received immune checkpoint inhibitor (ICI) immunotherapy to quantify transcriptome-wide discrepancies in APA. We observed a global change in 3′-UTRs between responders and non-responders, which might involve DNA damage response, angiogenesis, PI3K-AKT signaling pathways, etc. Ten putative master APA regulatory factors for those APA events were detected via a network analysis. Notably, we established an immune response-related APA scoring system (IRAPAss), which exhibited a great performance of predicting immunotherapy response in multiple cohorts. Furthermore, we examined the correlation of APA with TME at the single-cell level using four single-cell immune profiles of tumor-infiltrating lymphocytes (TILs), which revealed an overall discrepancy in 3′-UTR length across diverse T cell populations, probably contributing to immunoregulation in melanoma. In conclusion, our study provides a transcriptional landscape of APA implicated in immunoregulation, which might lay the foundation for developing a new strategy for improving immunotherapy response for melanoma patients by targeting APA. [ABSTRACT FROM AUTHOR]

We present a 45 years old male with dermatomyositis refractory to eight months of standard treatment who responded to plasma exchange. The efficacy of the procedure is estimated from clinical follow-up (increase in strength) and serum creatine-kinase activity (decrease from 3,380 to 44 u/ml.) after five sessions of plasma exchange. The therapeutic indications for PE are reviewed in dermatological diseases with emphasis on cases where the response to steroids or cytotoxic drugs is inadequate.

Erythrodermic psoriasis (EP) is a severe and rare variant of psoriasis (less than 3% of cases), characterized by generalized scaling and erythema affecting more than 90% of body surface area. Several systemic symptoms can be present in patients with EP such as lymphadenopathy, arthralgia, fever, fatigue, dehydration, serum electrolyte disturbances, and tachycardia making this condition a possible life-threatening disease, particularly if appropriate treatments are not performed. In this scenario, effective and safe therapies are required. Unfortunately, the rarity of EP makes head-to-head Phase III trials challenging, leading to the lack of established guidelines for its management. Globally, conventional systemic drugs such as cyclosporine, methotrexate, and retinoids often have contraindications linked to patients' comorbidities and have not shown a high profile of efficacy and safety. Recently, the development of biologic drugs including anti-tumor necrosis factor-α and anti-interleukin 12– 23, 23, and 17 has revealed favorable results for the management of plaque psoriasis, making them also a possible therapeutic option for EP disease. However, their use in EP is still off-label. The aim of our study was to review current literature on the use of biologic drugs for the treatment of EPs in order to offer a wide perspective on their possible application in EP management. [ABSTRACT FROM AUTHOR]

We present the first case of coma bullae observed in a 67-year-old woman due to pressure and ischemia associated with brachioradial artery. A skin biopsy taken from the ulcer border revealed extensive loss of the epidermis, fibrosis of dermis, mild infiltration by lymphocytes and neutrophils, and necrosis of the focal eccrine ducts. CT angiography of the right upper limb showed a high origin of the radial artery, meanwhile both high originating radial artery and the anastomoses were tortuous and were of relatively small caliber. The diagnosis of coma bullae was made. After tissue debridement, the skin lesions gradually recovered, leaving atrophic scars. [ABSTRACT FROM AUTHOR]

Up to now, there is only limited information available on a possible relationship between clinical characteristics and the mineralization of metacarpal bones and finger joint space distance (JSD) in patients with psoriatic arthritis (PsA). Computerized digital imaging techniques like digital X-ray radiogrammetry (DXR) and computer-aided joint space analysis (CAJSA) have significantly improved the structural analysis of hand radiographs and facilitate the recognition of radiographic damage. The objective of this study was to evaluate clinical features which potentially influence periarticular mineralization of the metacarpal bones and finger JSD in PsA-patients. 201 patients with PsA underwent computerized measurements of the metacarpal bone mineral density (BMD) with DXR and JSD of all finger joints by CAJSA. DXR-BMD and JSD were compared with clinical features such as age and sex, disease duration, C-reactive protein (CRP) as well as treatment with prednisone and disease-modifying antirheumatic drugs (DMARDs). A longer disease duration and an elevated CRP value were associated with a significant reduction of DXR-BMD, whereas JSD-parameters were not affected by both parameters. DXR-BMD was significantly reduced in the prednisone group (–0.0383 g/cm²), but prednisone showed no impact on finger JSD. Patients under the treatment with bDMARDs presented significant lower DXR-BMD (–0.380 g/cm²), JSDMCP (–0.0179 cm), and JSDPIP (–0.0121 cm) values. Metacarpal BMD was influenced by inflammatory activity, prednisone use, and DMARDs. In contrast, finger JSD showed only a change compared to baseline therapy. Therefore, metacarpal BMD as well as finger JSD represent radiographic destruction under different aspects. [ABSTRACT FROM AUTHOR]

Introduction: There is limited evidence to guide clinicians on the treatment of psoriasis with biologics in patients with a history of malignancy who are often excluded from clinical trials investigating biologics. The aim of this work is to report a multicenter real-life experience of secukinumab treatment in patients with psoriasis and a personal history of cancer. Methods: This retrospective observational study included adult patients with moderate-to-severe plaque psoriasis treated with secukinumab for at least 24 weeks and a previous diagnosis of cancer at 15 Italian referral centers. The primary endpoint of the study was tumor recurrence or progression and new cancer diagnosis during treatment. Secondary outcome assessment of secukinumab effectiveness (reduction of Psoriasis Area and Severity Index [PASI] score, improvement of Dermatology Life Quality Index [DLQI], itch and pain). Results: Forty-two patients (27 male) were included. Malignancy was diagnosed in the previous 5 years in 21 (56.8%) and in the previous 10 years in 37 (88.1%). The mean interval between cancer diagnosis and the start of secukinumab treatment was 3.5 ± 3.3 years. No tumor recurrence nor progression occurred over a mean of 56 ± 31.7 weeks of treatment. Three patients developed a new malignancy not related to the previous cancer. At week 48, PASI 90 was reached by 64.7% of patients and PASI 100 by 38.2%. Mean DLQI, itch, and pain VAS scores significantly improved during treatment. Conclusions: Our multicenter real-life experience is the largest reported to date focusing on a specific biologic and adds evidence to the safety of secukinumab in psoriatic patients with a personal history of cancer. [ABSTRACT FROM AUTHOR]

Psoriasis is considered a multifactorial and heterogeneous systemic disease with many underlying pathologic mechanisms having been elucidated; however, the pathomechanism is far from entirely known. This opinion article will demonstrate the potential relevance of the somatosensory Piezo2 microinjury-induced quad-phasic non-contact injury model in psoriasis through a multidisciplinary approach. The primary injury is suggested to be on the Piezo2-containing somatosensory afferent terminals in the Merkel cell–neurite complex, with the concomitant impairment of glutamate vesicular release machinery in Merkel cells. Part of the theory is that the Merkel cell–neurite complex contributes to proprioception; hence, to the stretch of the skin. Piezo2 channelopathy could result in the imbalanced control of Piezo1 on keratinocytes in a clustered manner, leading to dysregulated keratinocyte proliferation and differentiation. Furthermore, the author proposes the role of mtHsp70 leakage from damaged mitochondria through somatosensory terminals in the initiation of autoimmune and autoinflammatory processes in psoriasis. The secondary phase is harsher epidermal tissue damage due to the primary impaired proprioception. The third injury phase refers to re-injury and sensitization with the derailment of healing to a state when part of the wound healing is permanently kept alive due to genetical predisposition and environmental risk factors. Finally, the quadric damage phase is associated with the aging process and associated inflammaging. In summary, this opinion piece postulates that the primary microinjury of our "sixth sense", or the Piezo2 channelopathy of the somatosensory terminals contributing to proprioception, could be the principal gateway to pathology due to the encroachment of our preprogrammed genetic encoding. [ABSTRACT FROM AUTHOR]

Melatonin is an important naturally occurring hormone in mammals. Melatonin-mediated biological effects include the regulation of circadian rhythms, which is important for optimal human health. Also, melatonin has a broad range of immunoenhancing actions. Moreover, its oncostatic properties, especially regarding breast cancer, involve a variety cancer-inhibitory processes and are well documented. Due to their promising effects on the prognosis of cancer patients, anti-cancer drugs with epigenetic actions have attracted a significant amount of attention in recent years. Epigenetic modifications of cancers are categorized into three major processes including non-coding RNAs, histone modification, and DNA methylation. Hence, the modification of the latter epigenetic event is currently considered an effective strategy for treatment of cancer patients. Thereby, this report summarizes the available evidence that investigated melatonin-induced effects in altering the status of DNA methylation in different cancer cells and models, e.g., malignant glioma and breast carcinoma. Also, we discuss the role of artificial light at night (ALAN)-mediated inhibitory effects on melatonin secretion and subsequent impact on global DNA methylation of cancer cells. [ABSTRACT FROM AUTHOR]