Immune-Mediated Skin Diseases: From Pathophysiology to Novel Therapeutic Approaches 2.0

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 31717

Special Issue Editors

Dermatological Unit, Department of Clinical and Molecular Sciences, Polytechnic University of the Marche Region, Ancona, Italy
Interests: skin immune-mediated skin diseases; psoriasis; suppurative hidradenitis; chronic urticaria; atopic dermatitis; adnexal diseases; melanoma and non-melanoma skin cancer; scleroderma
Special Issues, Collections and Topics in MDPI journals
Dermatological Unit, Department of Clinical and Molecular Sciences, Polytechnic University of the Marche Region, Ancona, Italy
Interests: skin immune-mediated skin diseases; psoriasis; suppurative hidradenitis; chronic urticaria; atopic dermatitis; adnexal diseases; auto-inflammatory dermatoses; acne; contact dermatitis; scleroderma
Special Issues, Collections and Topics in MDPI journals
Dermatological Unit, Department of Clinical and Molecular Sciences, Polytechnic University of the Marche Region, Ancona, Italy
Interests: skin immune-mediated skin diseases; psoriasis; suppurative hidradenitis; chronic urticaria; atopic dermatitis; adnexal diseases; melanoma and non-melanoma skin cancer; scleroderma
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Growing interest in the pathogenesis of immune-mediated skin diseases (skin IMIDs) has led to the identification of several inflammatory pathways crucial for their development and maintenance.

Morbidity associated with cutaneous IMIDs has been extensively reconsidered following knowledge acquired regarding the repercussions of these diseases on the general health of patients, all skin IMIDs having large impacts on quality of life and most being associated with an increased risk of developing atherosclerosis, metabolic syndrome, psychological/psychiatric disorders, generalized atopic status, infections, neoplastic risk, and other systemic IMIDs (e.g., diabetes, Crohn's disease, ulceration, colitis, polycystic ovary syndrome, uveitis, and asthma).

Dermatologists can be considered sentinel clinicians in the development of the systemic involvement related to skin IMIDs, and so can play a significant role in modifying their natural history through early recognition, a correct patient assessment, and specific therapeutic interventions.

Fortunately, in recent years, research has led to highly effective new treatment options, with others expected in the near future. However, the following questions remain: What are the main pathological drivers of skin IMIDs? What is the role of the skin’s microenvironment? What are the mechanisms underlying systemic involvement in skin IMIDs? Are there predictive biomarkers for systemic targeted treatments? Can an early therapeutic intervention really change the natural history of skin IMIDs and their systemic repercussions?

This Special Issue intends to provide plausible answers to these and other questions by presenting the latest research on skin IMIDs, as well as highlighting research gaps that should be addressed in future studies.

Prof. Dr. Anna Campanati
Dr. Emanuela Martina
Prof. Dr. Annamaria Offidani
Guest Editors

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Keywords

  • skin immune-mediated skin diseases
  • psoriasis
  • suppurative hidradenitis
  • atopic dermatitis
  • acne
  • lichen sclerosus
  • skin bullous diseases
  • chronic urticaria
  • neutrophilic dermatoses
  • scleroderma

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Published Papers (11 papers)

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Research

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13 pages, 2694 KiB  
Article
Immunohistological Analysis of Lichen Sclerosus of the Foreskin in Pediatric Age: Could It Be Considered a Premalignant Lesion?
by Salvatore Arena, Antonio Ieni, Monica Currò, Mario Vaccaro, Donatella Di Fabrizio, Fabiola Cassaro, Roberta Bonfiglio, Angela Simona Montalto, Giovanni Tuccari, Angela Alibrandi, Pietro Impellizzeri and Carmelo Romeo
Biomedicines 2023, 11(7), 1986; https://doi.org/10.3390/biomedicines11071986 - 13 Jul 2023
Viewed by 1332
Abstract
Background: A major worry of juvenile penile LS is potential malignant degeneration to spinocellular carcinoma (SCC) in adulthood. LS is characterized by increased CD8+ and CD57+ cells, dermal sclerosis, epidermal atrophy, and hyperkeratosis. p53 and Ki67 are reliable premalignant markers. Our aim was [...] Read more.
Background: A major worry of juvenile penile LS is potential malignant degeneration to spinocellular carcinoma (SCC) in adulthood. LS is characterized by increased CD8+ and CD57+ cells, dermal sclerosis, epidermal atrophy, and hyperkeratosis. p53 and Ki67 are reliable premalignant markers. Our aim was to define the LS immunohistochemical profile of foreskin in children, focusing on tissue immune response and cell proliferation. Methods: Thirty specimens of foreskins removed from pediatric patients during circumcision were included: six from ritual operation (A), twelve from phimosis (B), and twelve from phimosis with LS (C). Formalin-fixed paraffin-embedded sections were stained for histomorphology and immunohistochemistry. A quantitative evaluation for CD8, CD57, p53, and Ki-67 and a statistical analysis were performed. Results: As compared to groups A and B, the samples from group C patients showed an acanthotic epidermis, a dermal band of lymphoid infiltrate with a significant enhancement of CD8+ CD57+ lymphocytes, and a keratinocytic hyperplasia with an overexpression of Ki67+ and p53+ cells. Conclusions: Immunohistological findings confirmed an immune reaction and proliferative behavior in juvenile LS of foreskin. We believe that radical circumcision should be the first treatment of choice in pediatric patients with clinical suspicious of LS for the potential risk of transformation to SCC in adulthood. Full article
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13 pages, 1553 KiB  
Article
Expression of CCR8 and CCX-CKR on Basophils in Chronic Urticaria Is Amplified by IgE-Mediated Activation
by Ewa A. Bartko, Lars H. Blom, Jesper Elberling, Lars K. Poulsen and Bettina M. Jensen
Biomedicines 2023, 11(6), 1537; https://doi.org/10.3390/biomedicines11061537 - 25 May 2023
Viewed by 949
Abstract
Recruitment to the local tissue and alerted phenotype are the hallmarks of basophils in chronic urticaria (CU). Chemokine receptors such as chemokine (C-C motif) receptor 4 (CCR4) or CCR8 have been studied in skin diseases, e.g., atopic dermatitis, but not in CU. In [...] Read more.
Recruitment to the local tissue and alerted phenotype are the hallmarks of basophils in chronic urticaria (CU). Chemokine receptors such as chemokine (C-C motif) receptor 4 (CCR4) or CCR8 have been studied in skin diseases, e.g., atopic dermatitis, but not in CU. In this study, we aimed to define CU’s basophil homing potential and receptor profile and the effect of Omalizumab treatment on these. Unstimulated and activated (anti-IgE, fMLP, C5a, and Substance P) whole blood basophils from 11 Omalizumab-treated CU patients and 10 healthy subjects were investigated with flow cytometry. Unstimulated basophils in CU showed higher expression of the skin-associated (CCR8) and scavenger (CCX-CKR) receptors and lower expression of the lung-associated (CCR3) receptor in contrast to healthy ones. IgE-mediated activation increased the percentage of CCR8 and CCX-CKR in CU compared to healthy group and elevated the expression of the lung-associated chemokine receptor, XCR1, in all groups. A trend of augmented expression of the coagulation cascade (CD87) and fMLP (FPR1) receptors was seen on basophils in CU, while a tendency of reduced expression was seen for itch (IL-31RA) and immunotolerance (CD109) receptors. fMLP and C5a increased the expression of CCR4, CCR8, CCX-CKR, and CD87 and decreased CCR2 and CCR3, though no changes between the groups were found. In conclusion, CU basophils exhibit skin-homing potential amplified by IgE-mediated stimulation. Full article
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19 pages, 8086 KiB  
Article
Facial Skin Microbiome: Aging-Related Changes and Exploratory Functional Associations with Host Genetic Factors, a Pilot Study
by Edda Russo, Leandro Di Gloria, Matteo Cerboneschi, Serena Smeazzetto, Gian Paolo Baruzzi, Francesca Romano, Matteo Ramazzotti and Amedeo Amedei
Biomedicines 2023, 11(3), 684; https://doi.org/10.3390/biomedicines11030684 - 23 Feb 2023
Cited by 3 | Viewed by 1988
Abstract
In this exploratory study, we investigate the variation in the facial skin microbiome architecture through aging and their functional association with host genetic factors in a cohort of healthy women, living in the same area and without cutaneous diseases. Notably, facial skin microbiota [...] Read more.
In this exploratory study, we investigate the variation in the facial skin microbiome architecture through aging and their functional association with host genetic factors in a cohort of healthy women, living in the same area and without cutaneous diseases. Notably, facial skin microbiota (SM) samples were collected from a cohort of 15 healthy Caucasian females, firstly divided into three age groups (younger women aged 20–35 years old; middle aged women of 36–52 years old; and older women aged 53–68 years old). Then, the recruited cohort was divided into two groups based on their facial hydration level (dry and normal skin). The facial SM revealed a different composition in the three analyzed aging groups and between normal and dry skins. The middle-aged women also revealed functional variations associated with collagen biosynthesis and oxidative stress damage repair. Otherwise, the association between selected host SNPs (single nucleotide polymorphisms) and the facial SM profile showed significant associations, suggesting a negative correlation with collagen metabolism and ROS damage protection. Finally, the composition and functionality of the facial SM seemed to affect the aging process through the two aging-correlated pathways of host ROS damage repair and collagen metabolism. Our exploratory data could be useful for future studies characterizing the structure, function, and dynamics of the SM in the aging process to design personalized therapeutic agents focusing on potential genomic targets, microbes, and their metabolites. Full article
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10 pages, 1194 KiB  
Article
Evaluation of the Role of Faecal Calprotectin in the Management of Psoriatic Patients under Treatment with Biologic Drugs
by Eugenia Veronica Di Brizzi, Annachiara Rocco, Graziella Babino, Dario Buononato, Giuseppe Argenziano and Anna Balato
Biomedicines 2022, 10(11), 2968; https://doi.org/10.3390/biomedicines10112968 - 18 Nov 2022
Cited by 1 | Viewed by 1431
Abstract
Background: Fecal calprotectin has emerged as a significant, validated, and non-invasive biomarker allowing for the evaluation of inflammatory bowel disease. Our study assessed the reliability of the use of faecal calprotectin as a valuable tool in the management of psoriatic patients on biological [...] Read more.
Background: Fecal calprotectin has emerged as a significant, validated, and non-invasive biomarker allowing for the evaluation of inflammatory bowel disease. Our study assessed the reliability of the use of faecal calprotectin as a valuable tool in the management of psoriatic patients on biological therapy. Methods: This was a single-centre prospective study including adult patients affected by moderate-to-severe psoriasis starting biological therapy. Faecal calprotectin levels were evaluated at baseline and at week 24 (W24) of treatment in all enrolled patients. Results: Overall, 129 patients were enrolled. The mean baseline faecal calprotectin levels were 74.7 μg/g and a significant reduction was detected at W24 of biological therapy (57.5 μg/g). An analysis of faecal CP values stratified by therapy type was performed. No significant reduction was assessed at W24 for any of the anti-IL17 drugs, whereas a significant reduction was detected for all IL23 inhibitors. Conclusions: Our study showed the potential use of faecal CP levels as a valuable tool for exploring intestinal inflammation in the management of psoriatic patients undergoing treatment with biologic drugs. Full article
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9 pages, 1194 KiB  
Article
Adalimumab Originator vs. Biosimilar in Hidradenitis Suppurativa: A Multicentric Retrospective Study
by Martina Burlando, Gabriella Fabbrocini, Claudio Marasca, Paolo Dapavo, Andrea Chiricozzi, Dalma Malvaso, Valentina Dini, Anna Campanati, Annamaria Offidani, Annunziata Dattola, Raffaele Dante Caposiena Caro, Luca Bianchi, Marina Venturini, Paolo Gisondi, Claudio Guarneri, Giovanna Malara, Caterina Trifirò, Piergiorigio Malagoli, Maria Concetta Fargnoli, Stefano Piaserico, Luca Carmisciano, Riccardo Castelli and Aurora Parodiadd Show full author list remove Hide full author list
Biomedicines 2022, 10(10), 2522; https://doi.org/10.3390/biomedicines10102522 - 09 Oct 2022
Cited by 6 | Viewed by 2420
Abstract
This study aimed to compare adalimumab originator vs. biosimilar in HS patients, and to evaluate the effect of a switch to a biosimilar, or a switch back to the originator, in terms of treatment ineffectiveness. Patients with a diagnosis of HS were enrolled [...] Read more.
This study aimed to compare adalimumab originator vs. biosimilar in HS patients, and to evaluate the effect of a switch to a biosimilar, or a switch back to the originator, in terms of treatment ineffectiveness. Patients with a diagnosis of HS were enrolled from 14 Italian sites. Treatment ineffectiveness was measured using Hurley score. The major analyses were 1) comparison between the two treatment groups (non-switcher analysis), and 2) the cross-over trend of Hurley score between treatment switchers (switcher analysis). Cox and Poisson regression models were used to compare the treatment ineffectiveness between groups. A total of 326 patients were divided into four groups: 171 (52.5%) taking originator; 61 (18.7%) patients taking biosimilar; 66 (20.2%) switchers; 28 (8.6%) switchers from originator to biosimilar and switched. A greater loss of efficacy was observed in the group allocated to the biosimilar than the originator group. The switcher analysis showed an effectiveness loss in the biosimilar compared to the originator. These results seem to indicate that a switch from one drug to the other may lead to a greater risk of inefficacy. A return to the previous treatment also does not ensure efficaciousness. Full article
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Review

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15 pages, 681 KiB  
Review
Novel Therapeutic Targets for the Treatment of Atopic Dermatitis
by Gaku Tsuji, Kazuhiko Yamamura, Koji Kawamura, Makiko Kido-Nakahara, Takamichi Ito and Takeshi Nakahara
Biomedicines 2023, 11(5), 1303; https://doi.org/10.3390/biomedicines11051303 - 27 Apr 2023
Cited by 4 | Viewed by 3017
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease that significantly impacts quality of life. The pathogenesis of AD is a complex combination of skin barrier dysfunction, type II immune response, and pruritus. Progress in the understanding of the immunological mechanisms of AD [...] Read more.
Atopic dermatitis (AD) is a chronic inflammatory skin disease that significantly impacts quality of life. The pathogenesis of AD is a complex combination of skin barrier dysfunction, type II immune response, and pruritus. Progress in the understanding of the immunological mechanisms of AD has led to the recognition of multiple novel therapeutic targets. For systemic therapy, new biologic agents that target IL-13, IL-22, IL-33, the IL-23/IL-17 axis, and OX40-OX40L are being developed. Binding of type II cytokines to their receptors activates Janus kinase (JAK) and its downstream signal, namely signal transduction and activator of transcription (STAT). JAK inhibitors block the activation of the JAK-STAT pathway, thereby blocking the signaling pathways mediated by type II cytokines. In addition to oral JAK inhibitors, histamine H4 receptor antagonists are under investigation as small-molecule compounds. For topical therapy, JAK inhibitors, aryl hydrocarbon receptor modulators, and phosphodiesterase-4 inhibitors are being approved. Microbiome modulation is also being examined for the treatment of AD. This review outlines current and future directions for novel therapies of AD that are currently being investigated in clinical trials, focusing on their mechanisms of action and efficacy. This supports the accumulation of data on advanced treatments for AD in the new era of precision medicine. Full article
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10 pages, 275 KiB  
Review
New Indications of Biological Drugs in Allergic and Immunological Disorders: Beyond Asthma, Urticaria, and Atopic Dermatitis
by Daniele Russo, Paola Di Filippo, Sabrina Di Pillo, Francesco Chiarelli and Marina Attanasi
Biomedicines 2023, 11(2), 236; https://doi.org/10.3390/biomedicines11020236 - 17 Jan 2023
Cited by 2 | Viewed by 2389
Abstract
Asthma, chronic urticaria, and atopic dermatitis are some of the most numerous allergic diseases affecting children. Recent advances in the understanding of their specific intracellular molecular pathways have led to the approval of monoclonal antibodies targeting definite inflammatory molecules in order to control [...] Read more.
Asthma, chronic urticaria, and atopic dermatitis are some of the most numerous allergic diseases affecting children. Recent advances in the understanding of their specific intracellular molecular pathways have led to the approval of monoclonal antibodies targeting definite inflammatory molecules in order to control symptoms and improve quality of life. Less is known about other allergic and immunologic disorders such as rhinosinusitis with nasal polyps, eosinophilic esophagitis, anaphylaxis, and food allergy undergoing allergen immunotherapy. The increasing evidence of the molecular mechanisms underlying their pathogeneses made it possible to find in children new indications for known biological drugs, such as omalizumab and dupilumab, and to develop other ones even more specific. Promising results were recently obtained, although few are currently approved in the pediatric population. In this review, we aim to provide the latest evidence about the role, safety, and efficacy of biologic agents to treat allergic and immunologic diseases in children. Full article
22 pages, 567 KiB  
Review
Bullous Pemphygoid and Novel Therapeutic Approaches
by Giovanni Marco D’Agostino, Giulio Rizzetto, Andrea Marani, Samuele Marasca, Matteo Candelora, Daisy Gambini, Helena Gioacchini, Edoardo De Simoni, Andrea Maurizi, Anna Campanati and Annamaria Offidani
Biomedicines 2022, 10(11), 2844; https://doi.org/10.3390/biomedicines10112844 - 08 Nov 2022
Cited by 6 | Viewed by 1744
Abstract
Bullous pemphigoid is a subepidermal blistering disease associated with autoantibodies (auto-ab) to BP180 and BP230 which affects elderly patients, predominately. Although it is a rare disease, bullous pemphigoid is the most common among the autoimmune bullous skin diseases. Systemic corticosteroids and immunosuppressants represent [...] Read more.
Bullous pemphigoid is a subepidermal blistering disease associated with autoantibodies (auto-ab) to BP180 and BP230 which affects elderly patients, predominately. Although it is a rare disease, bullous pemphigoid is the most common among the autoimmune bullous skin diseases. Systemic corticosteroids and immunosuppressants represent milestones in the treatment of patients suffering from bullous pemphigoid; however, therapeutic management of patients still represents a clinical challenge, owing to the chronic nature of the disease and to potential adverse effects related to the long-term use of systemic treatments. Recent discoveries on the pathogenesis of bullous pemphigoid have allowed investigation of new target therapies against selective pro-inflammatory mediators. These therapies appear to yield satisfactory results with fewer side effects in cases of refractory disease. The review discusses current evidence on these new therapeutic targets and specific drugs under investigation. Full article
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11 pages, 590 KiB  
Review
Hidradenitis Suppurativa in Patients with HIV: A Scoping Review
by Laura Macca, Vittoria Moscatt, Manuela Ceccarelli, Ylenia Ingrasciotta, Giuseppe Nunnari and Claudio Guarneri
Biomedicines 2022, 10(11), 2761; https://doi.org/10.3390/biomedicines10112761 - 31 Oct 2022
Cited by 3 | Viewed by 1906
Abstract
Hidradenitis suppurativa (HS) is a chronic, debilitating skin disease of the apocrine glands. Bibliographic search revealed few studies concerning the association between HS and human immunodeficiency virus (HIV). To assess this link, we performed a systematic review of the current knowledge through a [...] Read more.
Hidradenitis suppurativa (HS) is a chronic, debilitating skin disease of the apocrine glands. Bibliographic search revealed few studies concerning the association between HS and human immunodeficiency virus (HIV). To assess this link, we performed a systematic review of the current knowledge through a careful analysis of the relevant and authoritative medical literature in the field. Results showed that people with HIV are particularly susceptible to developing HS with the characteristic involvement of atypical sites, such as face or thighs, due to HIV-related immunosuppression. Based on the pathogenesis of both conditions and according to our review, we suggest that HIV screening should be routinely performed in suspected cases while monitoring and integrated approach in management are mandatory in the management of HIV-positive patients with HS. Full article
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21 pages, 1684 KiB  
Review
Gut–Skin Axis: Unravelling the Connection between the Gut Microbiome and Psoriasis
by Angel Yun-Kuan Thye, Yi-Rou Bah, Jodi Woan-Fei Law, Loh Teng-Hern Tan, Ya-Wen He, Sunny-Hei Wong, Sivakumar Thurairajasingam, Kok-Gan Chan, Learn-Han Lee and Vengadesh Letchumanan
Biomedicines 2022, 10(5), 1037; https://doi.org/10.3390/biomedicines10051037 - 30 Apr 2022
Cited by 36 | Viewed by 10625
Abstract
Evidence has shown that gut microbiome plays a role in modulating the development of diseases beyond the gastrointestinal tract, including skin disorders such as psoriasis. The gut–skin axis refers to the bidirectional relationship between the gut microbiome and skin health. This is regulated [...] Read more.
Evidence has shown that gut microbiome plays a role in modulating the development of diseases beyond the gastrointestinal tract, including skin disorders such as psoriasis. The gut–skin axis refers to the bidirectional relationship between the gut microbiome and skin health. This is regulated through several mechanisms such as inflammatory mediators and the immune system. Dysregulation of microbiota has been seen in numerous inflammatory skin conditions such as atopic dermatitis, rosacea, and psoriasis. Understanding how gut microbiome are involved in regulating skin health may lead to development of novel therapies for these skin disorders through microbiome modulation, in particularly psoriasis. In this review, we will compare the microbiota between psoriasis patients and healthy control, explain the concept of gut–skin axis and the effects of gut dysbiosis on skin physiology. We will also review the current evidence on modulating gut microbiome using probiotics in psoriasis. Full article
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Other

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15 pages, 824 KiB  
Systematic Review
The Impact of Treatment with IL-17/IL-23 Inhibitors on Subclinical Atherosclerosis in Patients with Plaque Psoriasis and/or Psoriatic Arthritis: A Systematic Review
by Aikaterini Tsiogka, Stamatios Gregoriou, Alexander Stratigos, Stergios Soulaidopoulos, Natalia Rompoti, Pantelis Panagakis, Marina Papoutsaki, Panagiotis Kostakis, George Kontochristopoulos, Konstantinos Tsioufis, Anna Campanati, Annamaria Offidani, Charalambos Vlachopoulos and Dimitrios Rigopoulos
Biomedicines 2023, 11(2), 318; https://doi.org/10.3390/biomedicines11020318 - 23 Jan 2023
Cited by 3 | Viewed by 2923
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 [...] Read more.
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. Full article
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