The role of smoking in psoriasis.

Psoriasis has a clear and strong connection with smoking in both its pathogenesis and clinical course. Smoking can cause a serious worsening of both the disease itself and the systemic complications such as cardiovascular events, psoriatic arthritis (PsA), cancer and depression. Smoking also seems to alter the gut microbiota and thus promote psoriasis itself. The aim of our article is to review all the most interesting discoveries on its role and thus provide a good picture of the current state of knowledge. Furthermore, we provide some alternative and healthier coping mechanisms for stress and depression related to the disease such as exercise, meditation, balneotherapy and acupuncture.

Characteristics of pruritus in various clinical variants of psoriasis: Final report of the binational, multicentre, cross-sectional study.

BACKGROUND: Pruritus, which is the most frequent subjective symptom of psoriasis, may cause significant discomfort, embarrassment and even interfere with patients normal daily activities. However, the perception of itch in various psoriasis subtypes remains unknown. OBJECTIVES: The aim of this study was to investigate and to characterize pruritus in different clinical variants of psoriasis. METHODS: This cross-sectional, binational, multicentre study included 295 subjects suffering from nine different clinical subtypes of psoriasis: large-plaque psoriasis (n = 45), nummular psoriasis (n = 32), guttate psoriasis (n = 31), scalp psoriasis (n = 32), inverse psoriasis (n = 23), erythrodermic psoriasis (n = 33), palmoplantar psoriasis vulgaris (n = 33), palmoplantar pustular psoriasis (n = 42) and generalized pustular psoriasis (n = 23). Measures included sociodemographic and anthropometric data, detailed pruritus characteristics including but not limited to pruritus intensity, frequency and extend, as well as psoriasis severity. RESULTS: The lifetime prevalence of pruritus in each clinical variant of psoriasis was similar and quite high, reaching up to 100% in some disease subtypes (i.e., nummular psoriasis, scalp psoriasis and generalized pustular psoriasis). Psoriasis severity correlated with pruritus intensity in scalp psoriasis, palmoplantar pustular psoriasis and generalized pustular psoriasis. The age, duration of psoriasis and BMI did not interfere with the intensity of itch. CONCLUSIONS: Pruritus is highly prevalent in each clinical variant of psoriasis. However, the sensation of itch is very individual, difficult to universally describe even in the same subtype.

The Role of Mast Cells in the Induction and Maintenance of Inflammation in Selected Skin Diseases.

Under physiological conditions, skin mast cells play an important role as guardians that quickly react to stimuli that disturb homeostasis. These cells efficiently support, fight infection, and heal the injured tissue. The substances secreted by mast cells allow for communication inside the body, including the immune, nervous, and blood systems. Pathologically non-cancerous mast cells participate in allergic processes but also may promote the development of autoinflammatory or neoplastic disease. In this article, we review the current literature regarding the role of mast cells in autoinflammatory, allergic, neoplastic skin disease, as well as the importance of these cells in systemic diseases with a pronounced course with skin symptoms.

mRNA expression of caspase 14 in skin epithelial malignancies.

Introduction: The skin is the largest organ in the human body and it is also a complex organ. Its protective function is properly maintained due to its continuous renewal. Malignancies develop when the balance between proliferation and cell death is dysregulated in skin cells. Skin epithelial cancers are the most common neoplasms in humans. Although caspases are proteins which regulate the cell cycle and cell death, caspase 14 is a unique representative of the caspase family which does not participate in apoptosis. The detailed role of caspase 14 in skin epithelial malignancies has not been elucidated. Material and methods: We performed a prospective study aimed at the analysis of the mRNA expression of caspase 14 in groups of skin epithelial malignancies. We enrolled 56 patients (control group n = 21, study group n = 35). The mRNA expression of caspase 14 was lower in the non-lesional skin of patients with basal cell cancer or squamous cell cancer compared to a combined group of non-lesional samples from actinic keratosis patients and the control group. Results: The prognostic potential of caspase 14 mRNA is suggested when trying to identify patients predisposed to skin cancer. Moreover, the expression level was lower in combined groups of non-lesional skin obtained from patients with basal cell cancer (BCC)/squamous cell cancer (SCC) in comparison with lesional samples obtained from patients with BCC/SCC. Conclusions: We present primary results of a pilot study and define further goals for research continuation.

Does molecular scarring in psoriasis exist? A review of the literature.

Plaque psoriasis is a chronic inflammatory dermatosis characterized by a tendency to recur in the same locations after discontinuation of treatment. The implementation of therapy with drugs targeting cytokines like interleukin (IL) 17A (IL-17A) and IL-23 has revolutionized the treatment of psoriasis and enabled the achievement of skin without lesions. However, despite the clinical resolution of psoriatic eruptions, cells that maintain the local memory of the disease remain in the dermis and epidermis, constituting a kind of molecular scar. The cells responsible for maintaining memory in the skin of patients and influencing the rapid relapse of the disease after the triggering factor are primarily tissue resident memory T cells (TRM), but it seems that regulatory T lymphocytes (Treg), dendritic cells (DC), and Langerhans cells (LC) may also play an important role in this process. We reviewed the literature to explain the concept of molecular scarring in psoriasis, and to assess the effect of various therapies on immune memory.

Atypical presentation of Sweet syndrome with nodular erythema and oral ulcerations provoked by Ad26.COV2.S SARS-CoV-2 vaccination and review of literature.

The aim of this article is to present the case of acute febrile neutrophilic dermatosis (Sweet syndrome-SS) after Ad26.COV2.S vaccination against SARS-CoV-2. To the best of our knowledge, this is the second case of SS provoked by this specific vaccine. What is more, the mildly symptomatic beginning of the disease, later followed by typical SS manifestation with a variety of symptoms including nodular erythema of the feet and oral ulcerations, made it very challenging to establish the diagnosis. The article focuses on the current literature on the acute febrile neutrophilic dermatosis, along with the coexistence with other neutrophilic dermatoses and anti-SARS-CoV-2 vaccinations as provoking factors. It emphasizes the necessity for sharing the knowledge and experience on the subject of SS's clinical manifestations and underlying causes to facilitate prompt diagnosis and introduction of appropriate treatment.

Cyclosporine-induced gingival overgrowth-Review.

Drug-induced gingival overgrowth (DIGO) is an undesirable effect resulting from the therapy of one of the three groups of drugs: phenytoin, calcium channel blockers, and cyclosporine A (CsA). It is caused by a fibrous overgrowth leading to gingivitis, periodontitis, and even tooth loss. Possible consequences include tooth decay worsening, pain and difficulty in eating, bleeding gums, and bad breath. The pathomechanism of the hypertrophy is unknown, but there is a correlation between insufficient oral hygiene and the severity of this phenomenon. The gender and age predilection of gingival hyperplasia as a result of CsA therapy is also noticeable. It is most common in children and adolescents of the male sex. The beneficial effect of the removal of tartar and local irritants in reducing the above symptoms has been demonstrated. One of the treatments for DIGO is conventional gingivectomy. The paper is a review article about cyclosporine-induced gingival hyperplasia.

The Role of the Neutrophilic Network in the Pathogenesis of Psoriasis.

One role of neutrophils, the most abundant innate immune sentinels, is neutrophil extracellular trap (NET) formation, which plays a significant role in immune surveillance. However, NET operation is bidirectional. Recent studies report that NETs may contribute to the development of autoimmune diseases such as psoriasis. The participation of neutrophils in the pathogenesis of that disease is dependent on an autoinflammatory feedback loop between neutrophils, lymphocytes, dendritic cells and keratinocytes. Our aim was to clarify the field of NET research in psoriasis and highlight the main factors required for NET generation, which may be a target of new therapies. This article presents a comphrehensive review concerning studies addressing the participation of neutrophils in the pathogenesis of psoriasis. Based on the available English-language literature, we discuss original papers presenting significant research findings which may help to understand and interpret the NET formation process in psoriasis, as well as the newest systematic reviews on PubMed. Next, the comparison, synthesis and summary of reported results were performed to clearly indicate the specific component of the NET which participates in the development of psoriasis.

New Insights into Psoriasis.

Psoriasis is a chronic inflammatory skin disease with many comorbidities resulting from not only local but also systemic inflammation [...].

The Analysis of a Genome-Wide Association Study (GWAS) of Overweight and Obesity in Psoriasis.

There is evidence that the concomitance of psoriasis and obesity may originate from the interplay between multiple genetic pathways and involve gene−gene interactions. The aim of this study was to compare the genetic background related to obesity among psoriatic patients versus healthy controls by means of a Genome-Wide Association Study (GWAS). A total of 972 psoriatic patients and a total of 5878 healthy donors were enrolled in this study. DNA samples were genotyped for over 500,000 single nucleotide polymorphisms (SNPs) using Infinium CoreExome BeadChips (Illumina, San Diego, CA, USA). Statistical analysis identified eleven signals (p < 1 × 10−5) associated with BMI across the study groups and revealed a varying effect size in each sub-cohort. Seven of the alternative alleles (rs1558902 in the FTO gene, rs696574 in the CALCRL gene, as well as rs10968110, rs4551082, rs4609724, rs9320269, and rs2338833,) are associated with increased BMI among all psoriatic patients and four (rs1556519 in the ITLN2 gene, rs12972098 in the AC003006.7 gene, rs12676670 in the PAG1 gene, and rs1321529) are associated with lower BMI. The results of our study may lead to further insights into the understanding of the pathogenesis of obesity among psoriatic patients.

Aseptic Abscess Syndrome in Rheumatoid Arthritis Patient.

Aseptic abscess syndrome (AAS) is a rare, potentially life-threatening disorder, with numerous features of neutrophilic dermatoses. The main symptoms include aseptic abscess-like collections in internal organs (spleen, liver, lungs), lack of microbes (bacteria, viruses, or parasites) after an exhaustive search, ineffectiveness of antibiotics, and high sensitivity to corticosteroid therapy. AAS is characterized by the development of deep, inflammatory abscesses and systemic symptoms (weight loss, abdominal pain, fever, and leukocytosis). They may be associated with inflammatory bowel disease (IBD) and autoimmune diseases. The patient in this study is a 67-year-old man, suffering from rheumatoid arthritis (RA), with numerous purulent abscesses in the mediastinum, within the subcutaneous tissue above the extension surfaces of the joints, and on the dorsum of the hands. The lesions are accompanied by bone destruction. The patient was treated with prednisone 40 mg and adalimumab, which resulted in a quick reduction of inflammatory markers and clinical improvement, as well as the healing and absorption of abscesses. Despite COVID-19 infection, treatment with remdesivir, prednisone, and adalimumab was continued, with the complete resolution of the lesions. AAS is difficult to recognize, so practitioners have to be aware of this condition, especially in patients with RA.

The effect of therapy on TRM in psoriatic lesions.

Introduction: The course of psoriasis is associated with recurrence of the lesions at the same location despite effective treatment. It is due to the presence of TRM (tissue-resident memory cells) in the seemingly healthy skin, which may initiate an inflammatory cascade. Aim: The assessment of TRM in psoriatic lesions prior to and after 12 weeks of systemic therapy with methotrexate (MTX) or secukinumab (SEC) or ixekizumab (IXE) or adalimumab (ADA). Material and methods: TRM markers (CD4, CD8, CD103, CD69, CD49, CXCR6) and the tissue expression of cytokines (IL-17, IL-22) in the psoriatic lesions obtained from 13 patients compared to 10 healthy skin samples were evaluated with immunohistochemistry. Biopsy specimens were collected three times from the same psoriatic plaque before and after 4 and 12 weeks of therapy. Results: The expression of TRM markers in the lesions decreased at three time points (W0, W4, W12), revealing the diminished intensity of fluorescence over time with each therapy. The most rapid response was observed with anti-IL-17 therapy at W4 of treatment, while with MTX and ADA at W12. Conclusions: The decreased expression of TRM markers occurring predominantly in the lesional dermis and not in the epidermis over 12 weeks of observation may be due to the poorer penetration of systemic drugs to the epidermis, or the process of psoriatic lesion regression in the epidermis is secondary to the reduction of inflammation in the skin, or TRM in the epidermis may be more resistant to therapy.

Assessment of stem cell factor expression and its c-KIT receptor in patients with vitiligo.

Introduction: Melanocytes show antigen expressions characteristic for the immune response effector cells, and the immune reactions in the skin, especially those with inflammation background, significantly affect the function of melanocytes. Among the cytokines produced by keratinocytes, the stem cell factor (SCF) plays a leading role in stimulating melanogenesis. Aim: To compare the expression level of stem cell factor (mSCF, pSCF) and the c-Kit receptor in the centre of the vitiligo patch and in the area of healthy skin adjacent to the vitiligo patch. Material and methods: The research material consisted of skin samples from a vitiligo lesion and from non-lesional skin adjacent to the vitiligo patch. Real Time PCR analysis (Applied Biosystems 7900HT) was performed to determine the expression level of the studied genes. Results: The studies showed a statistically significant increase in the amount of mSCF within the vitiligo patch compared to both healthy skin of patients with vitiligo and controls. In patients with vitiligo, c-Kit receptor expression was significantly decreased in the area of the lesional skin compared to the healthy skin of the same patient and the skin of the control group. Conclusions: The membrane-bound form of the SCF is overexpressed within the vitiligo skin, which may indicate the participation of mSCF in the stimulation of melanogenesis in response to melanocyte damage. Decreased expression of C-Kit receptor by melanocytes in the vitiligo patch disrupts the ligand-receptor interaction and may therefore be related to melanocytes dysfunction and/or loss.

D-chiro-inositol as a treatment in plaque psoriasis: A randomized placebo-controlled clinical trial.

Cyclitols are widely available natural sugars which do not exert toxic effects. Their anti-inflammatory and antioxidant properties may be used in the treatment of psoriasis. The aim of this placebo-controlled, double-blind study was to evaluate the clinical effects of D-chiro-inositol (DCI) in mild plaque psoriasis (46 psoriatic patients and 10 healthy volunteers). Three stable psoriatic plaques were selected for evaluation in every patient. Different samples were applied on each lesion twice a day: vehiculum without an active agent, containing 1% DCI and 0.25% DCI. The lesions were assessed using the PSI, VAS scale, and the objective measurement of hydration, transepidermal water loss (TEWL), elasticity, and thickness (DermaLab Combo) at 0, 3, and 6 weeks. PSI and VAS were improved in all groups without significant statistical differences. 1% DCI sample presented the highest statistically significant increase in the hydration of 50%, but it was still significantly lower than in healthy controls. TEWL increased for 1% DCI, which was a statistically significant difference compared to 0.25% DCI and still higher than in controls. An improvement in elasticity was observed in all lesions-it was statistically significant for 1% DCI. The thickness of the lesion decreased for 1% DCI, but the change was not statistically significant. Subepidermal low-echogenic band showed a decreasing tendency in all groups, but it was not statistically significant. Favorable 1% DCI sample results indicate that it may be used as an adjuvant to the local treatment of psoriasis.

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

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.

Caspase-14-From Biomolecular Basics to Clinical Approach. A Review of Available Data.

Caspase-14 is a unique member of the caspase family-a family of molecules participating in apoptosis. However, it does not affect this process but regulates another form of programmed cell death-cornification, which is characteristic of the epidermis. Therefore, it plays a crucial role in the formation of the skin barrier. The cell death cycle has been a subject of interest for researchers for decades, so a lot of research has been done to expand the understanding of caspase-14, its role in cell homeostasis and processes affecting its expression and activation. Conversely, it is also an interesting target for clinical researchers searching for its role in the physiology of healthy individuals and its pathophysiology in particular diseases. A summary was done in 2008 by Denecker et al., concentrating mostly on the biotechnological aspects of the molecule and its physiological role. However, a lot of new data have been reported, and some more practical and clinical research has been conducted since then. The majority of studies tackled the issue of clinical data presenting the role of caspase in the etiopathology of many diseases such as retinal dysfunctions, multiple malignancies, and skin conditions. This review summarizes the available knowledge on the molecular and, more interestingly, the clinical aspects of caspase-14. It also presents how theoretical science may pave the way for medical research. Methods: The authors analyzed publications available on PubMed until 21 March 2021, using the search term "caspase 14".

The Role of Chemokines in Psoriasis-An Overview.

By participating in both the recruitment and activation of T lymphocytes, macrophages and neutrophils at the site of psoriatic inflammation, chemokines play an important role in the pathogenesis of psoriasis and, crucially, may be one indicator of the response to the systemic treatment of the disease. As a result of their major involvement in both physiological and pathological processes, both chemokines and their receptors have been identified as possible therapeutic targets. Due to their presence in the inflammatory process, they play a role in the pathogenesis of diseases that often coexist with psoriasis, such as atherosclerosis and psoriatic arthritis. Chemokines, cytokines and adhesion molecules may be biological markers of disease severity in psoriasis. However, the mechanism of inflammation in psoriasis is too complex to select only one marker to monitor the disease process and improvement after treatment. The aim of this review was to summarize previous reports on the role of chemokines in the pathogenesis of psoriasis, its treatment and comorbidities.

Adalimumab and methotrexate affect the concentrations of regulatory cytokines (interleukin-10, transforming growth factor-ß1, and interleukin-35) in patients with plaque psoriasis.

Dysfunctional regulatory T lymphocytes are important for the pathogenesis of psoriasis and atherosclerosis. We analyzed the severity of atherosclerosis and the concentration of regulatory cytokines in patients with psoriasis who were administered methotrexate or adalimumab for 12 weeks. We included 34 patients with psoriasis (17 each, administered methotrexate or adalimumab) and eight healthy volunteers. BMI, psoriasis area and severity index (PASI), body surface area (BSA), and at least 75% and 90% improvements in PASI were observed. The 10-year risk of fatal cardiovascular disease was estimated using Systematic Coronary Risk Evaluation charts. The plasma interleukin (IL)-10, IL-35, and transforming growth factor ß1 (TGF-ß1) levels were determined using enzyme-linked immunosorbent assay before and after the 12-week treatment regimen. PASI (P = .0006) and BSA (P = .0001) were positively correlated with the BMI, IL-35 (-0.38), and IL-10 (0.48) levels. Baseline IL-35 concentrations were the highest in healthy volunteers; the IL-10 and TGF-ß1 level were the highest in the methotrexate group. IL-10 concentration decreased in both treatment groups (P = .02 for the methotrexate and P = .09 for adalimumab group), and IL-35 decreased in the adalimumab group (P = .019), consistent with skin lesion recovery. Thus, this study demonstrates the dysregulated secretion of regulatory cytokines in psoriatic patients under systemic treatment.

Pyoderma gangrenosum-like lesions provocated by botulinum injections.

Botulinum toxin (BoNT) is a valuable therapeutic tool with several medical indications and the most popular of all cosmetic procedures worldwide. This is the reason for the growing number of unregistered products that may be the reason for adverse reactions. We present a case of a 51-year-old woman, who developed a pyoderma gangrenosum-like reaction at injection sites after the administration of an unregistered BoNT product by a beautician. The clinical course, the morphology of the lesions, the result of histopathological biopsy, and the response to the treatment meets the criteria for diagnosis of pyoderma gangrenosum. The case presented by us is the first adverse reaction of this type after BoNT administration.

The Role of TRM Cells in the Pathogenesis of Vitiligo-A Review of the Current State-Of-The-Art.

Vitiligo is the most common hypopigmentation disease affecting both the skin and mucous membranes. The pathogenesis of this disorder is complex and involves the influence of genetic and environmental factors, oxidative stress, and autoimmune responses. Recent studies have indicated that skin lesions observed in vitiligo tend to recur in the same places where they were found before treatment. This phenomenon is explained by the presence of recently discovered tissue-resident memory T cells (TRM), whose primary function is to provide antiviral and antibacterial protection in non-lymphoid tissues. TRM cells show the presence of CD49a, CD69, and CD103 markers on their surface, although not all of them express these particles. Due to their ability to produce and secrete perforin, IFN-γ, and granzyme B, TRM cells demonstrate a cytotoxic effect on melanocytes, thus inducing depigmented lesions in the course of the vitiligo. It has been proved that the occurrence of TRM cells largely depends on IL-15, which promotes the TRM function ex vivo. The findings above, as well as their reference to the pathogenesis of autoimmune skin diseases will have a considerable influence on the development of new therapeutic strategies in the near future. This article presents an up-to-date review of information regarding the role of TRM cells in the development and progression of vitiligo.