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2.
Dermatol Ther (Heidelb) ; 14(5): 1079-1091, 2024 May.
Article in English | MEDLINE | ID: mdl-38700645

ABSTRACT

Hidradenitis suppurativa (HS) is a debilitating chronic skin disorder characterized by painful inflammatory nodules, abscesses and sinus tracts involving intertriginous areas and has an adverse impact on patient quality of life. Over the past decade, the therapeutic options of HS have increased significantly to comprise multiple modalities, including topical medication, systemic therapies (mainly antibiotics, retinoids, and biologics), surgical approaches, and lifestyle modifications. Biologics alone or in combination with surgery remain the treatment of choice for moderate to severe disease. However, non-biologic therapies (including retinoids) may be used as monotherapy for mild disease and in combination with biologics and surgical treatment in moderate to severe disease. Retinoids, specifically isotretinoin, acitretin, and alitretinoin, are historically used in the management of HS, supported by anecdotal evidence and with variable treatment response. Although the current American and European guidelines offer different recommendations on the use of retinoids in HS, retinoids remain a valuable ally in HS management. This review provides a comprehensive analysis of the current scientific literature on retinoid therapy (topical and systemic) in HS, highlighting disparities in mechanisms of action, efficacy, and safety to clarify their role in HS treatment.

3.
Br J Dermatol ; 190(6): 836-845, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38470171

ABSTRACT

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with a substantial disease burden. Secukinumab has previously been reported to have sustained efficacy with a favourable safety profile in patients with moderate-to-severe HS. It is unknown whether prior biologic exposure affects the efficacy and safety of secukinumab. OBJECTIVES: To investigate the efficacy and safety of secukinumab in patients with moderate-to-severe HS based on prior exposure to -biologics. METHODS: This was an analysis of the SUNSHINE and SUNRISE phase III trials of secukinumab in patients with moderate-to-severe HS. Patients were randomized at baseline to receive secukinumab every 2 (SECQ2W) or 4 weeks (SECQ4W), or placebo for 16 weeks. After week 16, patients on the SECQ2W and SECQ4W schedules remained on the same treatment regimen, while patients randomized to placebo were switched to either SECQ2W or SECQ4W up to week 52. Assessments based on prior exposure to biologics included Hidradenitis Suppurativa Clinical Response (HiSCR), abscess and inflammatory nodule (AN) count, flare rates, HS-related pain [numerical rating scale 30 (NRS30)], 55% reduction in the International Hidradenitis Suppurativa Severity Score System (IHS4-55), Dermatology Life Quality Index, EuroQol-5D and safety. RESULTS: Overall, 1084 patients were randomized in the SUNSHINE and SUNRISE trials and included in this analysis; 255 (23.5%) were biologic-experienced [SECQ2W (n = 80); SECQ4W (n = 81); placebo (n = 94)] and 829 (76.5%) were biologic-naïve [SECQ2W (n = 281); SECQ4W (n = 279); placebo (n = 269)]. At week 16, responses were more efficacious for secukinumab than for placebo with regard to HiSCR in patients who were biologic-experienced {SECQ2W 37.0% [odds ratio (OR) 1.60, 95% confidence interval (CI) 0.83-3.08]; SECQ4W 38.8% [OR 1.67, 95% CI 0.86-3.22]; placebo 27.3%} and biologic-naïve [SECQ2W 45.6% (OR 1.64, 95% CI 1.15-2.33); SECQ4W 45.4% (OR 1.61, 95% CI 1.13-2.29); placebo 34.2%]. Similar results were observed for AN count, NRS30 and IHS4-55. The higher response seen at week 16 with secukinumab was sustained, with a trend toward improvement over time, through to week 52 in both subgroups. Additional efficacy was observed for quality-of-life assessments, and no differences in safety between subgroups were observed. CONCLUSIONS: Regardless of prior biologic exposure, secukinumab was efficacious in improving the signs and symptoms of HS. This finding positions secukinumab as the first option in patients who are biologic-naïve, as well as in patients who have previously been treated with other biologic therapy, based on individual patient needs.


Hidradenitis suppurativa (HS) is a chronic skin disease that causes painful boils. HS is common and affects about 0.4% of the world's population. Treating the condition is difficult, but drugs called 'biologics' can help to improve the symptoms. For example, secukinumab is a biologic drug that has been shown to be effective and well-tolerated for the treatment of HS. In this analysis, we investigated whether previous treatment with biologics could affect the effectiveness and tolerability of secukinumab. This analysis included data from two identical clinical trials (called SUNSHINE and SUNRISE) that recruited adult patients with HS who had moderate-to-severe disease. In these trials, patients took secukinumab 300 mg every 2 weeks or every 4 weeks for 1 year, or a placebo for 4 months and then switched to secukinumab until 1 year. At regular intervals, the effectiveness and tolerability of secukinumab were examined and the results were compared between patients who had previously used another biologic and patients who had never used a biologic before. After 16 weeks, patients who took secukinumab had better results than the patients who took a placebo, independent of previous biologic use. Secukinumab was still effective and had improved results over 1 year of treatment in both subgroups. Regardless of whether patients had previously been taking another biologic, secukinumab was just as tolerable as placebo and there were no new safety risks. Our analysis shows that secukinumab is effective and tolerable, regardless of whether patients have previously used another biologic drug.


Subject(s)
Antibodies, Monoclonal, Humanized , Dermatologic Agents , Hidradenitis Suppurativa , Humans , Hidradenitis Suppurativa/drug therapy , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/administration & dosage , Male , Female , Adult , Treatment Outcome , Middle Aged , Double-Blind Method , Dermatologic Agents/adverse effects , Dermatologic Agents/administration & dosage , Dermatologic Agents/therapeutic use , Drug Administration Schedule
4.
Hum Cell ; 37(3): 729-738, 2024 May.
Article in English | MEDLINE | ID: mdl-38504052

ABSTRACT

Merkel cell carcinoma (MCC) is an aggressive skin cancer, with a propensity for early metastasis. Therefore, early diagnosis and the identification of novel targets become fundamental. The enzyme nicotinamide N-methyltransferase (NNMT) catalyzes the reaction of N-methylation of nicotinamide and other analogous compounds. Although NNMT overexpression was reported in many malignancies, the significance of its dysregulation in cancer cell phenotype was partly clarified. Several works demonstrated that NNMT promotes cancer cell proliferation, migration, and chemoresistance. In this study, we investigated the possible involvement of this enzyme in MCC. Preliminary immunohistochemical analyses were performed to evaluate NNMT expression in MCC tissue specimens. To explore the enzyme function in tumor cell metabolism, MCC cell lines have been transfected with plasmids encoding for short hairpin RNAs (shRNAs) targeting NNMT mRNA. Preliminary immunohistochemical analyses showed elevated NNMT expression in MCC tissue specimens. The effect of enzyme downregulation on cell proliferation, migration, and chemosensitivity was then evaluated through MTT, trypan blue, and wound healing assays. Data obtained clearly demonstrated that NNMT knockdown is associated with a decrease of cell proliferation, viability, and migration, as well as with enhanced sensitivity to treatment with chemotherapeutic drugs. Taken together, these results suggest that NNMT could represent an interesting MCC biomarker and a promising target for targeted anti-cancer therapy.


Subject(s)
Carcinoma, Merkel Cell , Skin Neoplasms , Humans , Nicotinamide N-Methyltransferase/genetics , Nicotinamide N-Methyltransferase/metabolism , Carcinoma, Merkel Cell/genetics , Drug Resistance, Neoplasm/genetics , Cell Proliferation/genetics , Skin Neoplasms/drug therapy , Skin Neoplasms/genetics , RNA, Small Interfering/genetics
5.
Dermatol Pract Concept ; 14(2)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38416060

ABSTRACT

INTRODUCTION: Genital involvement is observed in approximately 60% of patients with psoriasis, presenting clinicians with formidable challenges in treatment. While new biologic drugs have emerged as safe and effective options for managing psoriasis, their efficacy in challenging-to-treat areas remains inadequately explored. Intriguingly, studies have shown that interleukin (IL)-17 inhibitors exhibit effectiveness in addressing genital psoriasis. OBJECTIVES: We aimed to determine the effectiveness profile of bimekizumab in patients affected by moderate-to-severe plaque psoriasis with involvement of genitalia. METHODS: Bimekizumab, a dual inhibitor of both IL-17A and IL-17F, was the focus of our 16-week study, demonstrating highly favorable outcomes for patients with genital psoriasis. The effectiveness of bimekizumab was evaluated in terms of improvement in Static Physician Global Assessment of Genitalia (sPGA-G) and Psoriasis Area and Severity Index. RESULTS: Sixty-five adult patients were enrolled. Remarkably, 98.4% of our participants achieved a clear sPGA-G score (s-PGA-g = 0) within 16 weeks. Moreover, consistent improvements were observed in Psoriasis Area and Severity Index scores, accompanied by a significant reduction in the mean Dermatology Life Quality Index, signifying enhanced quality of life. Notably, none of the patients reported a severe impairment in their quality of life after 16 weeks of treatment. In our cohort of 65 patients, subgroup analyses unveiled that the effectiveness of bimekizumab remained unaffected by prior exposure to other biologics or by obesity. CONCLUSIONS: Our initial findings suggest that bimekizumab may serve as a valuable treatment option for genital psoriasis. Nevertheless, further research with larger sample sizes and longer-term follow-up is imperative to conclusively validate these results.

6.
Int J Mol Sci ; 24(21)2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37958840

ABSTRACT

Human skin, as the body's largest organ, orchestrates a multifaceted interplay of cellular interactions that regulate essential physiological processes, including inflammation, immune responses, wound healing, and angiogenesis [...].


Subject(s)
Autoimmunity , Skin , Humans , Wound Healing/physiology , Immunity , Inflammation
7.
Infez Med ; 31(3): 306-322, 2023.
Article in English | MEDLINE | ID: mdl-37701381

ABSTRACT

Antibiotic resistance of Gram-positive and Gramnegative bacteria is becoming increasingly prevalent. For this reason, the search for new molecules that can overcome current resistance and also recover antibiotics that are no longer effective is becoming increasingly urgent. Our research group at the 'Polytechnic University of Marche' managed to study the effectiveness of certain antimicrobial peptides (AMPs). We decided to review our experience with AMPs by classifying them according to their origin and evaluating their effect on Gram-negative and Gram-positive bacteria. AMPs can derive from mammals, amphibians, microorganisms, and insects. In conclusion, our research experience shows that the richest source of AMPs are amphibians. However, the studies done are mainly in vitro or in animal models, requiring further human studies to assess the efficacy and safety of these molecules. AMPs may be a new therapeutic option for infections sustained by multi-resistant micro-organisms and for overcoming the mechanisms of resistance to antibiotics currently used. In particular, combining AMPs with antibiotics, including those with limited antimicrobial activity due to antimicrobial resistance, has often shown a synergistic effect, increasing or restoring their efficacy. The possibility of using manageable and relatively safe antibiotics again is crucial, considering the widespread increase in bacterial resistance in hospitals and the community. Despite a plethora of research on AMPs and their application as potential treatment on infectious diseases, this area needs further exploration. There is evidence that the characteristics of AMPs can seriously improve through structural chemical modifications and different delivery systems to become alternatives drugs to conventional antibiotics. The aim is to provide an overview of the possible sources from which AMPs are extracted, evaluating their action exclusively on Gram-positive and negative bacteria. This is to determine, based on our experience, which might be the most promising sources of AMPs for future research as well.

8.
Medicina (Kaunas) ; 59(9)2023 Sep 12.
Article in English | MEDLINE | ID: mdl-37763769

ABSTRACT

Background and Objectives: Recently published articles reported an association between psoriasis and interstitial lung diseases (ILDs). The aim of this study is to evaluate the differences in ILD computed tomography (CT) patterns between smoker and never smoker plaque psoriasis (PP) patients under topical treatment without psoriatic arthritis (PA), inflammatory bowel disease (IBD) or connective tissue diseases (CTDs). Matherials and Methods: Two radiologists evaluated chest CT examinations of 65 patients (33 smokers, 32 never smokers) with PP. Results: Usual interstitial pneumonia (UIP) pattern was diagnosed in 36 patients, nonspecific interstitial pneumonia pattern in 19, hypersensitivity pneumonitis in 7 and pleuropulmonary fibroelastosis (PPFE) in 3 patients. UIP pattern showed a statistically significant higher frequency in smoker patients (p = 0.0351). Respiratory symptoms were reported in 80% of patients. Conclusions: ILDs seems to represent a new comorbidity associated with psoriasis. Moreover, a statistically significant association between smokers and UIP pattern in PP patients is found. Respiratory symptoms should be evaluated in PP patients, in collaboration with a radiologist and a pneumologist. However, further studies are required to better understand the epidemiology of ILDs in PP patients.


Subject(s)
Idiopathic Pulmonary Fibrosis , Lung Diseases, Interstitial , Psoriasis , Humans , Retrospective Studies , Lung Diseases, Interstitial/complications , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/epidemiology , Psoriasis/complications , Psoriasis/diagnostic imaging , Psoriasis/epidemiology , Tomography, X-Ray Computed
9.
Int J Mol Sci ; 24(15)2023 Aug 03.
Article in English | MEDLINE | ID: mdl-37569757

ABSTRACT

Pembrolizumab has been shown to increase survival in patients with metastatic melanoma. Considering the numerous oncoming studies, we decided to conduct a narrative review of the latest efficacy evidence regarding the use of pembrolizumab, alone or in combination, in patients with metastatic melanoma. A search was conducted in PubMed using "pembrolizumab," and "metastatic melanoma" as keywords, considering studies from 2022 onward. We reviewed pembrolizumab and associations, cost-effectiveness, virus, advanced acral melanoma, long-term outcomes, real-life data, biomarkers, obesity, and vaccines. In conclusion, pembrolizumab is a fundamental option in the therapy of metastatic melanoma. However, a certain group of patients do not respond and, therefore, new combination options need to be evaluated. In particular, the use of vaccines tailored to tumor epitopes could represent a breakthrough in the treatment of resistant forms. Further studies with larger sample numbers are needed to confirm the preliminary results.


Subject(s)
Melanoma , Neoplasms, Second Primary , Skin Neoplasms , Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Melanoma/pathology , Skin Neoplasms/drug therapy , Skin Neoplasms/chemically induced
10.
Front Med (Lausanne) ; 10: 1243843, 2023.
Article in English | MEDLINE | ID: mdl-37614958

ABSTRACT

Introduction: Bimekizumab is a monoclonal antibody that targets Interleukin-17 A and F, approved for the treatment of moderate-to-severe plaque psoriasis. While bimekizumab has been evaluated in several phase-III clinical trials, real-world evidence is still very limited. Method: This multicenter retrospective study included patients affected by plaque psoriasis treated with bimekizumab from May 1, 2022 to April 30, 2023, at 19 Italian referral hospitals. Patients affected by moderate-to-severe plaque psoriasis eligible for systemic treatments were included. The effectiveness of bimekizumab was evaluated in terms of reduction in psoriasis area and severity index (PASI) compared with baseline at weeks 4 and 16. The main outcomes were the percentages of patients achieving an improvement of at least 75% (PASI75), 90% (PASI90) and 100% (PASI100) in PASI score. Results: The study included 237 patients who received at least one injection of bimekizumab. One hundred and seventy-one patients and 114 reached four and 16 weeks of follow-up, respectively. Complete skin clearance was achieved by 43.3% and 75.4% of patients at weeks 4 and 16, respectively. At week 16, 86.8% of patients reported no impact on their quality of life. At week 16, there were no significant differences between bio-naïve and bio-experienced patients in terms of PASI75, PASI90 and PASI100. The most commonly reported adverse events (AEs) were oral candidiasis (10.1%). No severe AEs or AEs leading to discontinuation were observed throughout the study. Conclusion: Our experience supports the effectiveness and tolerability of bimekizumab in a real-world setting with similar results compared with phase-III clinical trials.

12.
Pigment Cell Melanoma Res ; 36(5): 423-430, 2023 09.
Article in English | MEDLINE | ID: mdl-37334675

ABSTRACT

In the last decades, the concept of adipose organ has emerged, giving adipose tissue an active endocrine and immunologic function through the secretion of multiple cytokines and chemokines that seem to be implicated in the development and progression of several cancer, including cutaneous melanoma. In this pilot experimental study, we analyzed the expression in the peritumor subcutaneous adipose tissue of the most significant adipokines involved in the processes of carcinogenesis and metastasis in a population of melanoma patients and in two control groups composed of melanocytic nevi and epidermoid cysts, respectively. We correlated the results obtained with the main disease prognostic factors observing a statistically significant increase in the expression of PAI1, LEP, CXCL1, NAMPT, and TNF-α at the level of the peritumor tissue of the melanoma samples compared to the control groups and a correlation of the same with the histopathological prognostic factor of melanoma. Our preliminary study shows that the overexpression of PAI1, LEP, CXCL1, NAMPT, and TNF-α may contribute to the growth and to the local aggressiveness of cutaneous melanoma. It opens the hypothesis of a direct oncogenic role of subcutaneous adipose tissue and adipokines in the tumorigenesis of melanoma.


Subject(s)
Melanoma , Skin Neoplasms , Humans , Adipokines/metabolism , Melanoma/genetics , Melanoma/pathology , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Tumor Necrosis Factor-alpha , Obesity , Melanoma, Cutaneous Malignant
13.
Antibiotics (Basel) ; 12(6)2023 May 29.
Article in English | MEDLINE | ID: mdl-37370297

ABSTRACT

Hidradenitis suppurativa (HS) is a chronic, recurrent, and inflammatory skin disease characterized by painful, deep-seated, nodules, abscesses, and sinus tracts in sensitive areas of the body, including axillary, inguinal, and anogenital regions. Antibiotics represent the first-line pharmacological treatment of HS because of their anti-inflammatory properties and antimicrobial effects. This narrative review summarizes the most significant current issues on the role of systemic antibiotics in the management of HS, critically analyzing the main limits of their use (antibiotic resistance and toxicity). Although, in the last decades, several cytokines have been implicated in the pathomechanism of HS and the research on the use of novel biologic agents in HS has been intensified, antibiotics remain a valid therapeutic approach. Future challenges regarding antibiotic therapy in HS comprise their use in association with biologics in the management of acute flare or as a bridge therapy to surgery.

14.
Ital J Dermatol Venerol ; 158(2): 117-123, 2023 04.
Article in English | MEDLINE | ID: mdl-37153946

ABSTRACT

BACKGROUND: Since the COVID-19 pandemic started, great interest has been given to this disease, especially to its possible clinical presentations. Besides classical respiratory symptoms, dermatological manifestations occur quite often among infected and non-infected patients, particularly in children. A prominent IFN-I response, that is generally higher in children compared to adults, may not only cause chilblain lesions, but it could also prevent infection and viral replication, thus justifying the negative swab results, as well as the absence of relevant systemic symptoms in positive cases. Indeed, reports have emerged describing chilblain-like acral lesions in children and adolescents with either proven or suspected infection. METHODS: Patients aged from 1 to 18 years old were enrolled in this study from 23 Italian dermatological units and were observed for an overall period of 6 months. Clinical pictures were collected along with data on the location and duration of skin lesions, their association with concomitant local and systemic symptoms, presence of nail and/or mucosal involvement, as well as histological, laboratory and imaging findings. RESULTS: One hundred thirty-seven patients were included, of whom 56.9% were females. Mean age was 11.97±3.66 years. The most commonly affected sites were the feet (77 patients, 56.2%). Lesions (48.5%) featured cyanosis, chilblains, blisters, ecchymosis, bullae, erythema, edema, and papules. Concomitant skin manifestations included maculo-papular rashes (30%), unspecified rashes (25%), vesicular rashes (20%), erythema multiforme (10%), urticaria (10%) and erythema with desquamation (5%). Forty-one patients (29.9%) reported pruritus as the main symptom associated with chilblains, and 56 out of 137 patients also reported systemic symptoms such as respiratory symptoms (33.9%), fever (28%), intestinal (27%), headache (5.5%), asthenia (3.5%), and joint pain (2%). Associated comorbid conditions were observed in 9 patients presenting with skin lesions. Nasopharyngeal swabs turned out positive in 11 patients (8%), whereas the remainder were either negative (101, 73%) or unspecified (25, 18%). CONCLUSIONS: COVID-19 has been credited as the etiology of the recent increase in acro-ischemic lesions. The present study provides a description of pediatric cutaneous manifestations deemed to be potentially associated with COVID-19, revealing a possible association between acral cyanosis and nasopharyngeal swab positivity in children and teenagers. The identification and characterization of newly recognized patterns of skin involvement may aid physicians in diagnosing cases of asymptomatic or pauci-symptomatic COVID patients.


Subject(s)
COVID-19 , Chilblains , Exanthema , Adult , Female , Humans , Adolescent , Child , Infant , Child, Preschool , Male , COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , Chilblains/diagnosis , Chilblains/etiology , Chilblains/epidemiology , Retrospective Studies , Pandemics , SARS-CoV-2 , Erythema/complications , Exanthema/complications , Italy/epidemiology , Blister/complications , Cyanosis/complications
15.
Int J Mol Sci ; 24(10)2023 May 09.
Article in English | MEDLINE | ID: mdl-37239847

ABSTRACT

Micro RNAs (miRNAs) are a type of non-coding RNA (ncRNA) and typically interact with specific target mRNAs through complementary base pairing, affecting their translation and/or stability. MiRNAs regulate nearly all cellular functions, including the cell fate of mesenchymal stromal cells (MSCs). It is now accepted that various pathologies arise at the stem level, and, in this scenario, the role played by miRNAs in the fate of MSCs becomes of primary concern. Here we have considered the existing literature in the field of miRNAs, MSCs and skin diseases, classified as inflammatory (such as psoriasis and atopic dermatitis-AD) and neoplastic (melanoma and non-melanoma-skin-cancer including squamous cell and basal cell carcinoma) diseases. In this scoping review article, the evidence recovered indicates that this topic has attracted attention, but it is still a matter of opinion. A protocol for this review was registered in PROSPERO with the registration number "CRD42023420245". According to the different skin disorders and to the specific cellular mechanisms considered (cancer stem cells, extracellular vesicles, inflammation), miRNAs may play a pro- or anti-inflammatory, as well as a tumor suppressive, or supporting, role, indicating a complex regulation of their function. It is evident that the mode of action of miRNAs is more than a switch on-off, and all the observed effects of their dysregulated expression must be checked in a detailed analysis of the targeted proteins. The involvement of miRNAs has been studied mainly for squamous cell carcinoma and melanoma, and much less in psoriasis and AD; different mechanisms have been considered, such as miRNAs included in extracellular vesicles derived both from MSCs or tumor cells, miRNAs involved in cancer stem cells formation, up to miRNAs as candidates to be new therapeutic tools.


Subject(s)
Mesenchymal Stem Cells , MicroRNAs , Neoplasms , Psoriasis , Skin Diseases , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Mesenchymal Stem Cells/metabolism , Cell Differentiation , Skin Diseases/genetics , Skin Diseases/metabolism , Neoplasms/genetics , Neoplasms/metabolism , Psoriasis/genetics , Psoriasis/metabolism
16.
Int J Mol Sci ; 24(9)2023 May 08.
Article in English | MEDLINE | ID: mdl-37176138

ABSTRACT

Hidradenitis suppurativa (HS) is an immune-mediated inflammatory disorder characterized by deep-seated nodules, abscesses, sinus tracts and scars localized in the intertriginous areas. It is accompanied by pain, malodourous secretion and a dramatically decreased quality of life. Although the pathogenesis has not been entirely elucidated, the primary event is follicular hyperkeratosis of the pilosebaceous apocrine unit. Since the registration of the tumor necrosis factor-alpha inhibitor Adalimumab in 2015, several cytokines have been implicated in the pathomechanism of HS and the research of novel therapeutic targets has been intensified. We provide an update on the inflammatory cytokines with a central role in HS pathogenesis and the most promising target molecules of future HS management.


Subject(s)
Hidradenitis Suppurativa , Humans , Hidradenitis Suppurativa/complications , Quality of Life , Adalimumab/therapeutic use , Skin , Cytokines/therapeutic use
17.
Dermatol Ther (Heidelb) ; 13(6): 1377-1387, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37198526

ABSTRACT

INTRODUCTION: The key role of microRNAs (miRNAs) in the pathogenesis of psoriasis has been extensively discussed in the literature. Increasing evidence suggests that the analysis of miRNA levels may constitute an innovative approach for exploring the clinical efficacy of anti-inflammatory therapies in patients with psoriasis. However, so far there have been no published studies evaluating the effects of modulating circulating miRNAs and the efficacy of anti-interleukin-23 (anti-IL-23) therapy. The main objective of the present was to evaluate the diagnostic/prognostic relevance of the levels of five circulating candidate miRNAs (miR-21, miR-146a, miR-155, miR-210, miR-378) in psoriatic patients treated with the anti-IL-23 drug risankizumab. METHODS: A total of eight psoriatic participants were recruited consecutively from January 2021 to July 2021 at the Dermatology Clinic of Università Politecnica delle Marche (UNIVPM) "Ospedali Riuniti" of Marche. Data on anamnestic, clinical and miRNA evaluations before the initiation of risankizumab therapy and after 1 year (January 2021-July 2022) of risankizumab therapy were available for all patients. RESULTS: A significant reduction in the signs and symptoms in patients treated with risankizumab was observed after 1 year of treatment, suggesting that the drug is effective for treating psoriasis in a context of real-life clinical evaluation. Plasma levels of the two prototypical inflammamiRs, miR-146a and miR-155, were significantly reduced after 1 year of risankizumab therapy. Also, in patients before treatment, a significant positive correlation was found between circulating levels of miR-210 and miR-378 and disease severity scores. CONCLUSIONS: Our results reinforce the notion that specific circulating miRNAs could have clinical relevance as diagnostic/prognostic biomarkers of psoriatic disease and suggest the potential relevance of these miRNAs as biomarkers of treatment response.

18.
Nutrients ; 15(7)2023 Mar 31.
Article in English | MEDLINE | ID: mdl-37049545

ABSTRACT

Psoriasis is an immune-mediated inflammatory systemic disease with skin tropism and chronic relapsing course; it is associated with an increased cardiovascular risk and with many metabolic comorbidities, emerging during childhood in 22-33% of cases. Diet influences the presentation and the clinical course of inflammatory diseases, including psoriasis; in particular, it was shown that a Mediterranean, gluten-free, or low-calorie diet may positively affect disease control in adult patients with psoriasis and adequate pharmacological therapy. These three dietary regimens may play a role also in children with psoriasis. It has been demonstrated that pediatric psoriasis is associated with psychological stress, celiac disease, and obesity, which may be positively influenced by these dietary regimens, respectively. Therefore, the expertise of multiple health figures (gastroenterologists, nutritionists, pediatricians, dermatologists) is required to plan a tailor-made dietary strategy, ensuring good growth, through an adequate intake of essential micro- and macronutrients and, at the same time, impacting the pro-inflammatory biochemical profile and on the associated cardiovascular risk of psoriasis disease.


Subject(s)
Psoriasis , Adult , Humans , Child , Obesity/complications , Comorbidity , Diet, Gluten-Free , Caloric Restriction
19.
Int J Mol Sci ; 24(5)2023 Mar 03.
Article in English | MEDLINE | ID: mdl-36902341

ABSTRACT

Vitiligo is an acquired hypopigmentation of the skin due to a progressive selective loss of melanocytes; it has a prevalence of 1-2% and appears as rounded, well-demarcated white macules. The etiopathology of the disease has not been well defined, but multiple factors contribute to melanocyte loss: metabolic abnormalities, oxidative stress, inflammation, and autoimmunity. Therefore, a convergence theory was proposed that combines all existing theories into a comprehensive one in which several mechanisms contribute to the reduction of melanocyte viability. In addition, increasingly in-depth knowledge about the disease's pathogenetic processes has enabled the development of increasingly targeted therapeutic strategies with high efficacy and fewer side effects. The aim of this paper is, by conducting a narrative review of the literature, to analyze the pathogenesis of vitiligo and the most recent treatments available for this condition.


Subject(s)
Hypopigmentation , Vitiligo , Humans , Vitiligo/etiology , Melanocytes/metabolism , Skin/metabolism , Oxidative Stress
20.
Biomedicines ; 11(2)2023 Jan 23.
Article in English | MEDLINE | ID: mdl-36830855

ABSTRACT

Accumulating evidence considers psoriasis a systemic inflammatory disorder that is associated with comorbidities such as psoriatic arthritis, cardiovascular disease, and metabolic syndrome. Although the precise pathogenetic links between psoriasis and atherosclerosis warrants further investigation, it is believed that chronic systemic inflammation along with the T helper (Th)-1 and Th17 polarization are associated with endothelial dysfunction and subsequent acceleration of atherosclerosis. Considering the above, several studies have evaluated if optimal control of the inflammation in psoriasis by inhibiting interleukins targeting the Interleukin (IL)-23/Th17 axis could subsequently reduce the atherosclerotic process during anti-psoriatic treatment by using a variety of surrogate markers of subclinical atherosclerosis. This systematic review summarizes current knowledge on the pathogenetic mechanisms and diagnostic evaluation of atherosclerosis in the context of psoriasis and provides a systematic review of the literature on the impact of treatment with biologics targeting the IL-23/Th17 axis on subclinical atherosclerosis in patients with plaque psoriasis and/or psoriatic arthritis.

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