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Psoriasis (PsO) and Psoriatic Arthritis (PsA)

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 63553

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Special Issue Editors

Prof. Dr. Aleksandra Lesiak

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Department of Dermatology, Paediatric Dermatology and Oncology, Medical University of Lodz, Lodz, Poland
Interests: atopic dermatitis; urticaria; non-melanoma skin cancers; photocancerogenesis; psoriasis
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Joanna Narbutt

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Department of Dermatology, Pediatric Dermatology and Dermatological Oncology, Medical University of Lodz, 91-347 Lodz, Poland
Interests: autoinflammatory and autoimmune skin diseases; photobiology and phototherapy
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Adam Reich

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Department of Dermatology, Institute of Medical Sciences, Medical College of Rzeszow University, 35-959 Rzeszow, Poland
Interests: itch; psychodermatology; psoriasis; autoimmune connective tissue disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Psoriasis is a chronic and recurrent disease with the prevalence of approximately 2-3% in the general population. Despite the scientific achievements over the last few decades, we still do not fully understand this disease. Significant improvements in psoriasis treatment are connected with the introduction of biological therapies that have changed patients’ lives, however many questions still remain on how to enhance effectiveness of treatment based on molecular findings. The Special Issue “Psoriasis and Psoriatic Arthritis” will present the current knowledge on psoriasis and psoriatic arthritis with a special emphasis on pathogenesis and treatment. Articles on genetics of psoriasis, biological markers (from skin to blood), biological treatment – especially in relation to the outcomes of treatment are welcome. The differential diagnosis of psoriatic arthritis can be a difficult one – we would like to invite papers on this topic, as it can be a significant problem, especially in relation to osteoarthritis.

The Special Issue would like to follow the psoriatic patient’s journey into how the basic science may influence the treatment, using the translational medicine concept to give readers a deeper understanding of this complex disease.

Prof. Dr. Aleksandra Lesiak
Guest Editor

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

psoriasis
psoriatic arthritis
genetics
therapy
immunology
microbiota
blood

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Published Papers (11 papers)

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Research

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13 pages, 2296 KiB

Open AccessArticle

Interplay between Humoral and CLA⁺ T Cell Response against Candida albicans in Psoriasis

by Carmen de Jesús-Gil, Lídia Sans-de San Nicolàs, Ester Ruiz-Romeu, Marta Ferran, Laura Soria-Martínez, Irene García-Jiménez, Anca Chiriac, Josep Manel Casanova-Seuma, Josep Manel Fernández-Armenteros, Sherry Owens, Antonio Celada, Michael D. Howell, Ramòn María Pujol and Luis Francisco Santamaria-Babí

Int. J. Mol. Sci. 2021, 22(4), 1519; https://doi.org/10.3390/ijms22041519 - 3 Feb 2021

Cited by 13 | Viewed by 3182

Abstract

Candida albicans (CA) infections have been associated with psoriasis onset or disease flares. However, the integrated immune response against this fungus is still poorly characterized in psoriasis. We studied specific immunoglobulins in plasma and the CA response in cocultures of circulating memory CD45RA⁻ cutaneous lymphocyte antigen (CLA)^+/− T cell with autologous epidermal cells from plaque and guttate psoriasis patients (cohort 1, n = 52), and also healthy individuals (n = 17). A complete proteomic profile was also evaluated in plaque psoriasis patients (cohort 2, n = 114) regarding their anti-CA IgA levels. Increased anti-CA IgA and IgG levels are present in the plasma from plaque but not guttate psoriasis compared to healthy controls. CA cellular response is confined to CLA⁺ T cells and is primarily Th17. The levels of anti-CA IgA are directly associated with CLA⁺ Th17 response in plaque psoriasis. Proteomic analysis revealed distinct profiles in psoriasis patients with high anti-CA IgA. C-C motif chemokine ligand 18, chitinase-3-like protein 1 and azurocidin were significantly elevated in the plasma from plaque psoriasis patients with high anti-CA levels and severe disease. Our results indicate a mechanism by which Candida albicans exposure can trigger a clinically relevant IL-17 response in psoriasis. Assessing anti-CA IgA levels may be useful in order to evaluate chronic psoriasis patients. Full article

(This article belongs to the Special Issue Psoriasis (PsO) and Psoriatic Arthritis (PsA))

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Review

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23 pages, 1415 KiB

Open AccessReview

Conundrum for Psoriasis and Thyroid Involvement

by Cristina-Ilinca Cira, Mara Carsote, Claudiu Nistor, Aida Petca, Razvan-Cosmin Petca and Florica Sandru

Int. J. Mol. Sci. 2023, 24(5), 4894; https://doi.org/10.3390/ijms24054894 - 3 Mar 2023

Cited by 6 | Viewed by 4544

Abstract

Strategies concerning thyroid anomalies in patients confirmed with psoriasis, either on clinical level or molecular levels, and their genetic findings remain an open issue. Identification of the exact subgroup of individuals that are candidates to endocrine assessments is also controversial. Our purpose in this work was to overview clinical and pathogenic data concerning psoriasis and thyroid comorbidities from a dual perspective (dermatologic and endocrine). This was a narrative review of English literature between January 2016 and January 2023. We included clinically relevant, original articles with different levels of statistical evidence published on PubMed. We followed four clusters of conditions: thyroid dysfunction, autoimmunity, thyroid cancer, and subacute thyroiditis. A new piece of information in this field was the fact that psoriasis and autoimmune thyroid diseases (ATD) have been shown to be related to the immune-based side effects of modern anticancer drugs—namely, immune checkpoint inhibitors (ICP). Overall, we identified 16 confirmatory studies, but with heterogeneous data. Psoriatic arthritis had a higher risk of positive antithyroperoxidase antibodies (TPOAb) (25%) compared to cutaneous psoriasis or control. There was an increased risk of thyroid dysfunction versus control, and hypothyroidism was the most frequent type of dysfunction (subclinical rather than clinical), among thyroid anomalies correlated with >2-year disease duration, peripheral > axial and polyarticular involvement. With a few exceptions, there was a female predominance. Hormonal imbalance included, most frequently, low thyroxine (T4) and/or triiodothyronine (T3) with normal thyroid stimulating hormone (TSH), followed by high TSH (only one study had higher total T3). The highest ratio of thyroid involvement concerning dermatologic subtypes was 59% for erythrodermic psoriasis. Most studies found no correlation between thyroid anomalies and psoriasis severity. Statistically significant odds ratios were as follows: hypothyroidism: 1.34–1.38; hyperthyroidism: 1.17–1.32 (fewer studies than hypo); ATD: 1.42–2.05; Hashimoto’s thyroiditis (HT): 1.47–2.09; Graves’ disease: 1.26–1.38 (fewer studies than HT). A total of 8 studies had inconsistent or no correlations, while the lowest rate of thyroid involvement was 8% (uncontrolled studies). Other data included 3 studies on patients with ATD looking for psoriasis, as well as 1 study on psoriasis and thyroid cancer. ICP was shown to potentially exacerbate prior ATD and psoriasis or to induce them both de novo (5 studies). At the case report level, data showed subacute thyroiditis due to biological medication (ustekinumab, adalimumab, infliximab). Thyroid involvement in patients with psoriasis thus remained puzzling. We observed significant data that confirmed a higher risk of identifying positive antibodies and/or thyroid dysfunction, especially hypothyroidism, in these subjects. Awareness will be necessary to improve overall outcomes. The exact profile of individuals diagnosed with psoriasis who should be screened by the endocrinology team is still a matter of debate, in terms of dermatological subtype, disease duration, activity, and other synchronous (especially autoimmune) conditions. Full article

(This article belongs to the Special Issue Psoriasis (PsO) and Psoriatic Arthritis (PsA))

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12 pages, 920 KiB

Open AccessReview

Psychological Stress, Mast Cells, and Psoriasis—Is There Any Relationship?

by Ewelina Woźniak, Agnieszka Owczarczyk-Saczonek and Waldemar Placek

Int. J. Mol. Sci. 2021, 22(24), 13252; https://doi.org/10.3390/ijms222413252 - 9 Dec 2021

Cited by 16 | Viewed by 5708

Abstract

Psoriasis vulgaris is a common inflammatory skin disease with still unknown pathogenesis. In recent years, genetic and environmental factors have been mentioned as the main causes. Among environmental factors, many researchers are trying to investigate the role of mental health and its importance in the development of many diseases. In the pathophysiology of psoriasis, the role of the interaction between the nervous, endocrine, and immune systems are often emphasized. So far, no one has clearly indicated where the pathological process begins. One of the hypotheses is that chronic stress influences the formation of hormonal changes (lowering the systemic cortisol level), which favors the processes of autoimmunity. In inflammatory skin conditions, mast cells (MCs) are localized close to blood vessels and peripheral nerves, where they probably play an important role in the response to environmental stimuli and emotional stress. They are usually connected with a fast immune response, not only in allergies but also a protective response to microbial antigens. Among many cells of the immune system, MCs have receptors for the hormones of the hypothalamic–pituitary–adrenal (HPA) axis on their surface. In this review, we will try to take a closer look at the role of MCs in the pathophysiology of psoriasis. This knowledge may give the opportunity to search for therapeutic solutions. Full article

(This article belongs to the Special Issue Psoriasis (PsO) and Psoriatic Arthritis (PsA))

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16 pages, 543 KiB

Open AccessReview

Psoriasis and Atherosclerosis—Skin, Joints, and Cardiovascular Story of Two Plaques in Relation to the Treatment with Biologics

by Karina Wierzbowska-Drabik, Aleksandra Lesiak, Małgorzata Skibińska, Michał Niedźwiedź, Jarosław D. Kasprzak and Joanna Narbutt

Int. J. Mol. Sci. 2021, 22(19), 10402; https://doi.org/10.3390/ijms221910402 - 27 Sep 2021

Cited by 10 | Viewed by 3804

Abstract

It is known that both psoriasis (PSO) limited to the skin and psoriatic arthritis (PSA) increase the risk of cardiovascular complications and atherosclerosis progression by inducing systemic inflammatory response. In recent decades, the introduction of biological medications directed initially against TNF-α and, later, different targets in the inflammatory cascade brought a significant breakthrough in the efficacy of PSO/PSA treatment. In this review, we present and discuss the most recent findings related to the interplay between the genetics and immunology mechanisms involved in PSO and PSA, atherosclerosis and the development of cardiac dysfunction, as well as the current PSO/PSA treatment in view of cardiovascular safety and prognosis. Full article

(This article belongs to the Special Issue Psoriasis (PsO) and Psoriatic Arthritis (PsA))

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16 pages, 1160 KiB

Open AccessReview

Purinergic Signaling and Inflammasome Activation in Psoriasis Pathogenesis

by Davide Ferrari, Fabio Casciano, Paola Secchiero and Eva Reali

Int. J. Mol. Sci. 2021, 22(17), 9449; https://doi.org/10.3390/ijms22179449 - 31 Aug 2021

Cited by 19 | Viewed by 4195

Abstract

Psoriasis is a chronic inflammatory disease of the skin associated with systemic and joint manifestations and accompanied by comorbidities, such as metabolic syndrome and increased risk of cardiovascular disease. Psoriasis has a strong genetic basis, but exacerbation requires additional signals that are still largely unknown. The clinical manifestations involve the interplay between dendritic and T cells in the dermis to generate a self-sustaining inflammatory loop around the TNFα/IL-23/IL-17 axis that forms the psoriatic plaque. In addition, in recent years, a critical role of keratinocytes in establishing the interplay that leads to psoriatic plaques’ formation has re-emerged. In this review, we analyze the most recent evidence of the role of keratinocytes and danger associates molecular patterns, such as extracellular ATP in the generation of psoriatic skin lesions. Particular attention will be given to purinergic signaling in inflammasome activation and in the initiation of psoriasis. In this phase, keratinocytes’ inflammasome may trigger early inflammatory pathways involving IL-1β production, to elicit the subsequent cascade of events that leads to dendritic and T cell activation. Since psoriasis is likely triggered by skin-damaging events and trauma, we can envisage that intracellular ATP, released by damaged cells, may play a role in triggering the inflammatory response underlying the pathogenesis of the disease by activating the inflammasome. Therefore, purinergic signaling in the skin could represent a new and early step of psoriasis; thus, opening the possibility to target single molecular actors of the purinome to develop new psoriasis treatments. Full article

(This article belongs to the Special Issue Psoriasis (PsO) and Psoriatic Arthritis (PsA))

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19 pages, 1222 KiB

Open AccessReview

Generalized Pustular Psoriasis: Divergence of Innate and Adaptive Immunity

by Dominik Samotij, Justyna Szczęch and Adam Reich

Int. J. Mol. Sci. 2021, 22(16), 9048; https://doi.org/10.3390/ijms22169048 - 22 Aug 2021

Cited by 28 | Viewed by 8266

Abstract

Generalized pustular psoriasis (GPP) is a severe, relapsing, immune-mediated disease characterized by the presence of multiple sterile pustules all over the body. The exact pathomechanisms behind GPP remain elusive, although increased interest in the genetic basis and immunological disturbances have provided some revealing insights into the underlying signaling pathways and their mutual interaction. The genetic background of GPP has been thoroughly investigated over the past few years. The conducted studies have identified genetic variants that predispose to pustular forms of psoriasis. The loss-of-function mutation of the interleukin 36 receptor antagonist gene, along with rare gain-of-function mutations in the gene that encodes the keratinocyte signaling molecule (CARD14), are examples of the uncovered abnormalities. Interleukin 36 (IL-36), along with neutrophils, is now considered a central cytokine in GPP pathogenesis, with IL-36 signaling providing a link between innate and adaptive immune responses. More recently, a new concept of inflammation, caused by a predominantly genetically determined abnormal activation of innate immune response and leading to inflammatory keratinization, has arisen. GPP is currently considered a representative of this novel group of skin conditions, called autoinflammatory keratinization diseases. As no therapeutic agents have been approved for GPP to date in the United States and Europe, the novel anti-IL-36R antibodies are particularly promising and may revolutionize management of the disease. Full article

(This article belongs to the Special Issue Psoriasis (PsO) and Psoriatic Arthritis (PsA))

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11 pages, 970 KiB

Open AccessReview

The Role of NLRP1, NLRP3, and AIM2 Inflammasomes in Psoriasis: Review

by Magdalena Ciążyńska, Irmina Olejniczak-Staruch, Dorota Sobolewska-Sztychny, Joanna Narbutt, Małgorzata Skibińska and Aleksandra Lesiak

Int. J. Mol. Sci. 2021, 22(11), 5898; https://doi.org/10.3390/ijms22115898 - 31 May 2021

Cited by 59 | Viewed by 5911

Abstract

Inflammasomes are high-molecular-weight protein complexes that may cleave the two main proinflammatory cytokines, pro-interleukin-1β and pro-interleukin-18, into active forms, and contribute to psoriasis. Despite recent advances made in the pathogenesis of psoriasis, mainly studied as an autoimmune condition, activation of immune response triggers of psoriasis is still not completely understood. Recently, focus was placed on the role of inflammasomes in the pathogenesis of psoriasis. Multiple types of inhibitors and activators of various inflammasomes, inflammasome-related genes, and genetic susceptibility loci were recognized in psoriasis. In this systemic review, we collect recent and comprehensive evidence from the inflammasomes, NLRP1, NLRP3, and AIM2, in pathogenesis of psoriasis. Full article

(This article belongs to the Special Issue Psoriasis (PsO) and Psoriatic Arthritis (PsA))

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14 pages, 1048 KiB

Open AccessReview

Alcohol in Psoriasis—From Bench to Bedside

by Zita Szentkereszty-Kovács, Krisztián Gáspár, Andrea Szegedi, Lajos Kemény, Dóra Kovács and Dániel Törőcsik

Int. J. Mol. Sci. 2021, 22(9), 4987; https://doi.org/10.3390/ijms22094987 - 7 May 2021

Cited by 16 | Viewed by 4883

Abstract

Alcohol affects the symptoms, compliance and comorbidities as well as the safety and efficacy of treatments in psoriatic patients. In this review, we aim to summarize and link clinical observations with a molecular background, such as signaling pathways at the cellular level and genetic variations, and to provide an overview of how this knowledge could influence our treatment selection and patient management. Full article

(This article belongs to the Special Issue Psoriasis (PsO) and Psoriatic Arthritis (PsA))

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10 pages, 1013 KiB

Open AccessReview

Exploring the Role of IL-36 Cytokines as a New Target in Psoriatic Disease

by Helena Iznardo and Lluís Puig

Int. J. Mol. Sci. 2021, 22(9), 4344; https://doi.org/10.3390/ijms22094344 - 21 Apr 2021

Cited by 53 | Viewed by 5950

Abstract

Unmet needs in the treatment of psoriasis call for novel therapeutic strategies. Pustular psoriasis and psoriatic arthritis often represent a therapeutic challenge. Focus on IL-36 cytokines offers an interesting approach, as the IL-36 axis has been appointed a critical driver of the autoinflammatory responses involved in pustular psoriasis. Two IL-36R blocking antibodies, imsidolimab and spesolimab, are currently undergoing phase II and III clinical trials, with promising results. Full article

(This article belongs to the Special Issue Psoriasis (PsO) and Psoriatic Arthritis (PsA))

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19 pages, 920 KiB

Open AccessReview

Alterations of the Skin and Gut Microbiome in Psoriasis and Psoriatic Arthritis

by Irmina Olejniczak-Staruch, Magdalena Ciążyńska, Dorota Sobolewska-Sztychny, Joanna Narbutt, Małgorzata Skibińska and Aleksandra Lesiak

Int. J. Mol. Sci. 2021, 22(8), 3998; https://doi.org/10.3390/ijms22083998 - 13 Apr 2021

Cited by 93 | Viewed by 12226

Abstract

Numerous scientific studies in recent years have shown significant skin and gut dysbiosis among patients with psoriasis. A significant decrease in microbiome alpha-diversity (abundance of different bacterial taxa measured in one sample) as well as beta-diversity (microbial diversity in different samples) was noted in psoriasis skin. It has been proven that the representation of Cutibacterium, Burkholderia spp., and Lactobacilli is decreased and Corynebacterium kroppenstedii, Corynebacterium simulans, Neisseria spp., and Finegoldia spp. increased in the psoriasis skin in comparison to healthy skin. Alterations in the gut microbiome in psoriasis are similar to those observed in patients with inflammatory bowel disease. In those two diseases, the F. prausnitzii, Bifidobacterium spp., Lactobacillus spp., Parabacteroides and Coprobacillus were underrepresented, while the abundance of Salmonella sp., Campylobacter sp., Helicobacter sp., Escherichia coli, Alcaligenes sp., and Mycobacterium sp. was increased. Several research studies provided evidence for the significant influence of psoriasis treatments on the skin and gut microbiome and a positive influence of orally administered probiotics on the course of this dermatosis. Further research is needed to determine the influence of the microbiome on the development of inflammatory skin diseases. The changes in microbiome under psoriasis treatment can serve as a potential biomarker of positive response to the administered therapy. Full article

(This article belongs to the Special Issue Psoriasis (PsO) and Psoriatic Arthritis (PsA))

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11 pages, 261 KiB

Open AccessReview

Molecular Aspects of Pruritus Pathogenesis in Psoriasis

by Kamila Jaworecka, Joanna Muda-Urban, Marian Rzepko and Adam Reich

Int. J. Mol. Sci. 2021, 22(2), 858; https://doi.org/10.3390/ijms22020858 - 16 Jan 2021

Cited by 15 | Viewed by 3210

Abstract

Psoriasis is a chronic, systemic inflammatory disease with a genetic background that involves almost 3% of the general population worldwide. Approximately, 70–90% of patients with psoriasis suffer from pruritus, an unpleasant sensation that provokes a desire to scratch. Despite the enormous progress in understanding the mechanisms that cause psoriasis, the pathogenesis of psoriasis-related pruritus still remains unclear. In order to improve patients’ quality of life, development of more effective and safer antipruritic therapies is necessary. In turn to make it possible, better understanding of complexed and multifactorial pathogenesis of this symptom is needed. In this article we have systematized the current knowledge about pruritus origin in psoriasis. Full article

(This article belongs to the Special Issue Psoriasis (PsO) and Psoriatic Arthritis (PsA))

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