Molecular Mechanisms of Neurogenic Inflammation of the Skin.

The skin, including the hypodermis, is the largest body organ and is in constant contact with the environment. Neurogenic inflammation is the result of the activity of nerve endings and mediators (neuropeptides secreted by nerve endings in the development of the inflammatory reaction in the skin), as well as interactions with other cells such as keratinocytes, Langerhans cells, endothelial cells and mast cells. The activation of TRPV-ion channels results in an increase in calcitonin gene-related peptide (CGRP) and substance P, induces the release of other pro-inflammatory mediators and contributes to the maintenance of cutaneous neurogenic inflammation (CNI) in diseases such as psoriasis, atopic dermatitis, prurigo and rosacea. Immune cells present in the skin (mononuclear cells, dendritic cells and mast cells) also express TRPV1, and their activation directly affects their function. The activation of TRPV1 channels mediates communication between sensory nerve endings and skin immune cells, increasing the release of inflammatory mediators (cytokines and neuropeptides). Understanding the molecular mechanisms underlying the generation, activation and modulation of neuropeptide and neurotransmitter receptors in cutaneous cells can aid in the development of effective treatments for inflammatory skin disorders.

High-frequency ultrasound in the diagnosis and treatment of skin neoplasms.

High-frequency ultrasonography (HFUS) is a non-invasive and highly repetitive medical imaging method with a great and still rising value in the diagnostic process of skin tumours. It accompanies the physician's examination, dermoscopy, and biopsy; facilitates real-time assessment of locoregional staging and planning of surgical excision; and provides postoperative inspection of treatment results. The aim of this review article is to discuss HFUS application in common cutaneous malignant tumours while depicting the use of both the grayscale and colour Doppler methods.

Bowel-associated dermatosis-arthritis syndrome (BADAS): a narrative review.

Bowel-associated dermatosis-arthritis syndrome is a neutrophilic dermatosis presenting with flu-like symptoms, arthritis and skin lesions. The type of skin presentation varies although typically consists of red patches progressing into papulopustular-type lesions. Initially, the pathogenesis of the disease was linked exclusively to bariatric surgery, but more recent reports indicate the role of gastrointestinal diseases resulting in bacterial overgrowth and consequent translocation of bacteria into the bloodstream. The disease may resolve spontaneously, however sometimes requires a treatment aimed at managing inflammation and excessive bacterial overgrowth, and therefore antibiotic therapy, immunosuppressive drugs, biological treatment and sometimes intestinal surgeries are applied.

Incidence of different types of cancer in the follow-up period after primary diagnosis and treatment of melanoma. Single-centre 4-year follow-up on a population of 709 patients.

Introduction: Follow-up plays a key role in melanoma management, especially in the first years after diagnosis. During this period it is crucial to assess possible recurrence, progression of the disease or treatment complications. An important aspect is also the possibility of formation of new primary foci or other skin cancers. Aim: To assess the coincidence of skin lesions and cancers among the melanoma patients. Material and methods: Patients treated in the Comprehensive Cancer Centre between 2019 and 2022 were retrospectively analysed for occurrence of skin lesions diagnosed during the follow-up, and confirmed by biopsy. The lesions considered included skin cancers, dysplastic nevus and actinic keratosis. Results: In 100 (14%) out of 709 enrolled patients, 184 lesions were diagnosed. In 7 patients it was melanoma, in 49 BCC, and in 16 SCC. Dysplastic nevus and actinic keratosis were excised in 28 and 14 patients, respectively. More than one site of the skin lesion was observed in 39 patients, and more than one type of the lesion in 13 patients. Patients with lesions were on average 8.6 years older (p < 0.001), had less advanced tumours (p = 0.010), and primary melanoma was more often located on the head and neck (p = 0.056). Conclusions: Among melanoma patients, particular attention must be paid to, apart from early detection of melanoma recurrence and progression, the occurrence of new primary foci or independent skin cancers.

The Brain-Skin Axis in Psoriasis-Psychological, Psychiatric, Hormonal, and Dermatological Aspects.

Psoriasis is a chronic inflammatory skin disease with systemic manifestation, in which psychological factors play an important role. The etiology of psoriasis is complex and multifactorial, including genetic background and environmental factors such as emotional or physical stress. Psychological stress may also play a role in exacerbation of psoriasis, by dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic-adrenal-medullary axis, peripheral nervous system, and immune system. Skin cells also express various neuropeptides and hormones in response to stress, including the fully functional analog of the HPA axis. The deterioration of psoriatic lesions is accompanied by increased production of inflammatory mediators, which could contribute to the imbalance of neurotransmitters and the development of symptoms of depression and anxiety. Therefore, deregulation of the crosstalk between endocrine, paracrine, and autocrine stress signaling pathways contributes to clinical manifestations of psoriasis, which requires multidisciplinary approaches.

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.

Resveratrol in the treatment of asthma based on an animal model.

Resveratrol is a natural polyphenol found, for example, in red wine, grapes or nuts. One of the resveratrol's health properties is a cardioprotective activity - it is believed that resveratrol is responsible for the French paradox and anticancer activity. Moreover, the effectiveness of resveratrol in the treatment of asthma is confirmed by multiple research. Resveratrol displays a multiway impact on the reduction of the symptoms of the disease which contributes to the alleviation of inflammation i.a. by: inhibition of cellular infiltration, suppression of oxidative stress, reduction in the volume of mucus, relaxation of smooth muscle, stalling of the fibrosis affecting the respiratory tract or counteracting bronchial hyperresponsiveness. Resveratrol reduces the concentration of eosinophils, pro-inflammatory interleukins and interferes with many signal transduction pathways. In case of concomitance of obesity, resveratrol alleviates the course of asthma. The review juxtaposes the mechanisms of resveratrol activity and presents the results of the published research conducted on rodents.

The report and analysis concerning the usefulness of basic telemedicine tools in the skin cancer diagnostic screening process during COVID-19 pandemics.

Introduction: A rapid spread of the emerging COVID-19 pandemic limited the availability of professional medical advice. As a result, a significant increase in the number of undiagnosed and chronically ill patients without medical care was noticed. In reaction to the urgent need, the telemedical consultation, instead of the classical form, may be introduced as a vulnerable tool in preclinical evaluation of patients with potentially malignant skin lesions. Aim: In this study the results of the implementation of telemedical consultation programme with the intention to early detect the skin cancers in patients who, due to the COVID-19 pandemic, could not undergo the standard consultation was presented. Material and methods: The programme of remote dermatological consultation, which was introduced on 1 June 2020, covered all patients who had no possibility or will to visit the standard healthcare units. In case of suspicion of life-threatening skin lesions patients were invited for additional diagnostics or surgery. Obtained data, including demography, age, surgery description and pathomorphological examination were descriptively analysed. Results: In total, 80 consecutive patients were enrolled during the screening programme. In total, 31 lesions in 25 patients were excised. In this group there were 10 serious diagnoses including 5 cases of basal cell carcinoma, melanoma in situ and dysplastic nevi. Moreover, another 10 patients were referred to other specialists or specific recommendations were advised. Conclusions: An alternative track using teledermatology for patients with skin diseases was successfully introduced under the specific conditions of epidemiologic danger. Despite its disadvantages teledermatology enabled the diagnosis and treatment in a significant number of serious cases.

Atherosclerosis attacks in patients with psoriasis vulgaris but without a relationship with the severity and course of the disease.

INTRODUCTION: In recent years numerous research studies have indicated that chronic inflammation in psoriasis can be associated with an increased risk of developing atherosclerosis. AIM: The presented study was aimed at demonstrating whether patients suffering from psoriasis vulgaris are at a greater risk of developing atherosclerosis depending on the presence of selected cardiovascular risk factors and the course and severity of the disease. MATERIAL AND METHODS: Sixty-two patients with diagnosed psoriasis vulgaris and 42 healthy volunteers were included in the study. All the patients underwent carotid ultrasound with the assessment of the common carotid artery intima-media thickness (IMT) and the computed tomography with determination of coronary artery calcification (CAC). RESULTS: The IMT was significantly higher in the study group (1.030 ±0.303 mm vs. 0.838 ±0.151 mm, p < 0.0001). We also found a significantly increased severity of Calcium Score (CS) in Agatston units (168.20 ±309.63 vs. 24.52 ±43.21, p = 0.0207) of CAC in patients with psoriasis. There was no significant correlation between the degree of atherosclerosis and psoriasis severity determined in the PASI (Psoriasis Area and Severity Index) scale, duration of the disease, number of exacerbations per year or C-reactive protein values. CONCLUSIONS: The study showed an increased risk of developing atherosclerosis in patients diagnosed with psoriasis vulgaris, but no correlation was found between the degree of atherosclerosis and the severity of the disease.

Acne - therapeutic challenges to the cooperation between a dermatologist and a cosmetologist.

Acne vulgaris is one of the most common skin diseases in adolescence, causing a significant negative impact on the quality of life of young people who - in a large percentage of cases - do not accept their appearance. The complex pathogenesis of this disease requires appropriate preventive and curative treatment from both a dermatologist and a cosmetologist. The aim of the study was to discuss the methods currently used by dermatologists in local therapy for mild and intermediate forms of acne vulgaris, and to provide an overview of possible preventive and caring activities in the cosmetologist's office. Possible directions of cooperation between the dermatologist and the cosmetologist in the prevention of acne relapse and treatment of possible acne complications were also discussed.

The microbiome of the human skin and its variability in psoriasis and atopic dermatitis.

The human organism is inhabited by very diverse microorganisms, which constitute the so-called human microbiome and are necessary for the proper functioning of the macroorganism. The correct microbiome ensures homeostasis of the body. A disturbance in its homeostasis leads to dysbiosis. Such deviations may also be related to the development of inflammatory skin diseases, including atopic dermatitis and psoriasis. This review aims to analyse the most current published data on the microbiome of the human skin and examine its role in cutaneous skin diseases, such as atopic dermatitis and psoriasis. This review was compiled by collaborating dermatologists specializing in atopic dermatitis and psoriasis. A comprehensive review of current literature was done using PubMed and limited to relevant case reports and original papers on the skin microbiome in atopic dermatitis and/or psoriasis. It has not been yet established whether changes in the microbiome are the cause or consequence of disease (atopic dermatitis/psoriasis). However, it was found that in the cases where pathological microflora predominated, an intensification of lesion severity is observed, while with clinical improvement, commensal microflora is restored. Modification of the composition of the microflora may lead to changes in the activation of the immune system and eventually to the development of inflammatory diseases. Adverse effects on the microbiome may include antibiotics, poor diet, stress and adverse environmental conditions. However, more research is needed to identify exact details and mechanisms.

The use of complementary and alternative medicine by patients suffering from psoriasis and psoriatic arthritis.

INTRODUCTION: Psoriasis is a chronic inflammatory disease, affecting 1-3% of the general population. In recent years there has been an increase in the use of complementary and alternative medicine (CAM) by psoriasis patients. AIM: To assess the frequency of use of CAM by psoriasis patients, depending on selected demographic and clinical factors, and to examine such aspects as sources of knowledge about CAM therapies provided by patients, reasons for their use, and subjective patient satisfaction. MATERIAL AND METHODS: The study involved 117 psoriatic patients (female = 44, male = 73), hospitalised in the Dermatology Department of the Heliodor Swiecicki Clinical Hospital in Poznan. The research tool was the author's questionnaire, consisting of single- and multiple-choice questions about the use of CAM. RESULTS: 57.26% of the respondents declared that they used or had used CAM for psoriasis. The analysis showed that the patients with psoriasis diagnosed in childhood statistically significantly more often used CAM compared to other patients (p = 0.017). The most frequent CAM therapies used by the responders were the use of topical agents (73.13%) and dietary supplements (71.64%). The main reason why psoriasis patients decided to use CAM was curiosity (34.33%), and the most commonly reported source of knowledge about CAM was the Internet (49.25%). The majority of responders monthly expenditure on CAM averaged less than PLN 100 (58.2%), and they were very dissatisfied with the effects of CAM (56.7%). CONCLUSIONS: Psoriasis patients use complementary and alternative medicine quite frequently. Dermatologists should keep this fact in mind and should ask about the use of CAM in interviews.

Calcipotriene/betamethasone dipropionate foam: primary evidence supporting its use in patients with psoriasis vulgaris. A narrative review.

Psoriasis vulgaris is a chronic, immune-mediated disorder, which has a substantial impact on all aspects of patients' quality of life. In most patients, the disease is mild to moderate and is successfully treated with topical agents. The most common therapy involves a vitamin D3 analogue (calcipotriene) in combination with a synthetic corticosteroid (betamethasone dipropionate). The aerosol vehicle (foam) with softening properties is another formulation of this combination drug, apart from ointment and gel, expanding the therapeutic options available to patients with psoriasis. The article describes the pharmacokinetic and pharmacodynamic properties of calcipotriene/betamethasone dipropionate foam. The results of the key randomised clinical studies investigating the efficacy, including patients' quality of life and safety of the foam versus ointment, gel and either active ingredient in foam vehicle are presented. In addition, the results of a study on maintenance treatment with calcipotriene/betamethasone dipropionate foam as well as reports on real-world use of this medicine in patients with psoriasis, are discussed.

Does HSP90 play an important role in psoriasis?

Introduction: Psoriasis is a chronic, inflammatory skin disease. Environmental, genetic, autoinflammatory and autoimmune factors play a role in the pathogenesis of disease. It is believed that heat shock protein 90 (HSP90) is an interleukin-17 (IL-17) receptor, which plays an essential role in the psoriasis pathogenesis. Aim: To evaluate the expression of the gene encoding HSP90 protein in keratinocytes of patients with psoriasis depending on its duration, recurrences, exacerbating factors, therapy form, and the coexistence of metabolic disorders and cardiovascular diseases. Material and methods: Skin samples from 40 psoriatic patients were investigated in this study. Control skin biopsies were collected from 20 healthy volunteers. HSP90 expression level was measured by qRT-PCR reaction. Results: This study has shown an increased mRNA expression of HSP90 in psoriatic patients as compared to healthy volunteers. A positive correlation of HSP90 expression and the frequency of exacerbations was found. A negative correlation between the HSP90 activity and the age of patients was demonstrated in the coexistence of psoriasis with hyperlipidaemia or diabetes. Among the factors exacerbating psoriasis, acute infections induced HSP90 expression most significantly. Conclusions: HSP90 plays a role in the pathogenesis of psoriasis. The expression of HSP90 increases with the frequency of exacerbations of psoriasis throughout the year. Hyperlipidaemia or diabetes associated with psoriasis in young adults, and acute infections and emotional stress increase the expression of HSP90. The expression of HSP90 in psoriatic patients is not dependent on the type of psoriasis, comorbidity of cardiovascular diseases, smoking and alcohol addiction.

The effects of baths and wet wraps with a sweet whey solution on the level of hydration and barrier function of the epidermis.

INTRODUCTION: Sweet whey is known for its various pharmacological uses as an anti-inflammatory and antioxidant agent. This is because whey proteins accelerate the release of bioactive peptides, increase the level of intracellular glutathione and the production of interleukin IL-8. However, the potential skin care effects of whey, especially in its unprocessed state, are still not clear. AIM: To evaluate in vivo the cosmetic features of sweet whey baths and wet wraps on human skin. MATERIAL AND METHODS: Thirteen healthy Caucasian adult females with no dermatological diseases were examined. We used the Courage-Khazaka MPA-9 device to evaluate the effects of sweet whey baths/wet wraps on skin hydration, transepidermal water loss (TEWL) and melanin and erythema index and pH level in human skin. RESULTS: It appeared that bathing in the sweet whey solution significantly improved the barrier function of the skin in comparison with tap water treated control area on the face cheek as well as on the forearm by decreasing the value of transepidermal water loss with statistical significance. Skin hydration was enhanced only on the facial skin. No significant differences concerning other parameters were observed. CONCLUSIONS: We showed that sweet whey may have decreased the TEWL level and fixed the barrier function of epidermis in this way. It seems that a bath solution with sweet whey is well tolerated and may promote local blood circulation without affecting the pH value of the skin.

Variability of the rs333 in Polish patients with lupus erythematosus.

INTRODUCTION: Lupus erythematosus (LE) is an autoimmune disease with a strong influence of genetic and environmental factors. C-C motif chemokine receptor 5 (CCR5) gene expression may affect the development and intensity of LE. AIM: To evaluate the possible association between the 32bp deletion in rs333 locus located within the CCR5 gene and the development of LE or the occurrence of various clinical symptoms in the course of the disease. MATERIAL AND METHODS: One hundred and twenty patients with LE (77 with systemic lupus erythematosus (SLE) and 43 with discoid lupus erythematosus (DLE)) and 100 healthy controls from the Polish population were genotyped for deletion in rs333. RESULTS: 32 bp deletion in the rs333 was significantly more frequent among healthy individuals than DLE patients. Moreover, heterozygotes and homozygotes with deletion in rs333 were significantly more frequent within the control group than the group of patients with discoid lupus erythematosus. In contrast, any statistically significant differences in allele or genotype frequencies between healthy persons and SLE patients were observed. Furthermore, nucleotide sequence variability of rs333 was not associated with certain clinical symptoms of LE patients. CONCLUSIONS: Deletion in the rs333 might be a protective factor for DLE, but not SLE in the Polish population. Nevertheless further studies performed on larger populations are needed to confirm these observations.

Metal allergy after the Nuss procedure for pectus excavatum: a review.

Minimally invasive repair of pectus excavatum (MIRPE) technique (the Nuss procedure) is a minimally-invasive method that is commonly used in the treatment of pectus excavatum. An allergic reaction to the metal alloy bar that is implanted in the thorax during the procedure is a reported complication. We briefly review current literature concerning epidemiology, mechanisms and research results of allergic reactions after Nuss bar implantation. This allergic reaction occurs in approximately 2.7% of patients and is caused by metals used in the medical implant. The most common symptoms include fever and skin lesions such as allergic dermatitis. Elevated levels of C-reactive protein is a frequent finding in laboratory tests. In order to minimize the risk of such complications, taking a detailed allergy-based medical history and conducting allergy tests, i.e. patch test are required. Allergic reactions can be managed with conservative treatment such as general or topical glucocorticosteroid therapy and antihistamine agents. Severe allergic reactions can be addressed by implant revision, replacement of the steel bar with a titanium substitute or removal of the stabilization at all. Although the risk of an allergic reaction to titanium is smaller it still exists, the titanium substitute is not routinely used due to its higher cost and lesser plasticity which has a negative impact on matching a stabilizing bar during the surgery. Surgeons treating pectus excavatum should remember about the possible allergic reactions after implantation of the metal bar and be familiar with methods of diagnosis and treatment of those complications.

Treatment of haemangiomas using propranolol in paediatric patients: a retrospective cohort study.

INTRODUCTION: Haemangioma, one of the most common benign neoplasms of early childhood, is a significant clinical problem due to cosmetic reasons but also because of possible health complications. AIM: Presentation of the method and results of treatment of infantile haemangiomas (IHs) using propranolol in a maximum dose of 3 mg/kg/day. MATERIAL AND METHODS: In 2013 to 2018 there were 108 patients with IHs multidisciplinary diagnosed and treated. 77 of them were girls and 31 were boys; all were between the ages of 2 and 21 months (mean: 6.87 months). Lesions were most often located in the head region (n = 73). The main imaging study assessing the arteriovenous flow was USG, which was used to assess the size of haemangioma and its regression or progression. Also, coagulation parameters were analysed using laboratory tests. RESULTS: Reduction of lesions occurred in 103 of 108 patients, which results in a percentage score above 95. In 19 patients, after completion of treatment, there were abnormalities of coagulation in laboratory tests whereas before the treatment, these abnormalities occurred in 82 patients. The average duration of treatment was longer than 12 months and the maximum dose of propranolol of 3 mg/kg/day was achieved after 3 to 5 months of treatment. Side effects occurred totally in 19 patients, with night anxiety and nightmares being the most common. CONCLUSIONS: After achieving the maximum dose of the drug later than recommended in the Recommendation of the Polish Haemangioma and Vascular Malformations Group criteria, there was no need for longer therapy, while the effectiveness of the treatment remained unchanged. Side effects that occurred were not life-threatening or detrimental to the health of patients.

The use of biological drugs in psoriasis patients prior to pregnancy, during pregnancy and lactation: a review of current clinical guidelines.

INTRODUCTION: Information on the possibility of using biological drugs in psoriasis patients planning to conceive, patients who are pregnant or during lactation is limited. AIM: Presenting recommendations published in clinical guidelines regarding the use of biological drugs - adalimumab, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab, and ustekinumab, by psoriasis patients in the period of planning pregnancy, during pregnancy or during lactation. MATERIAL AND METHODS: The paper was based on a comprehensive review of over 40 websites of HTA agencies, dermatological associations worldwide and medical databases (PubMed, Embase), the objective of which was to identify clinical guidelines relating to biological treatment of women of childbearing potential, published after 2018, which used GRADE - a system for rating the quality of a body of evidence. FINDINGS: Certolizumab pegol is recommended in women who are planning to conceive. Furthermore, guidelines indicate other TNF-α inhibitors as possible treatment. Certolizumab pegol is also recommended as first-line treatment in pregnant patients. Furthermore, for trimesters 2 and 3, guidelines allow using other TNF-α inhibitors. Treatment with secukinumab and ustekinumab should be discontinued when planning pregnancy or when pregnancy was diagnosed. Biological treatment during pregnancy and lactation (continuation or initiation of treatment) can be used only after an analysis of risks and benefits has been conducted. CONCLUSIONS: TNF-α inhibitors seem to be the safest and most researched biological drugs used in psoriasis treatment of patients planning to conceive, during pregnancy or lactation. Given its non-existent or minimal placental permeability, most likely the safest alternative is certolizumab pegol.

Biostimulative effect of laser on growth of mesenchymal stem/stromal cells in vitro.

INTRODUCTION: Human adipose tissue-derived mesenchymal stem/stromal cells (hAT-MSCs) are multipotent stromal cells with a high potential application in tissue engineering and regenerative medicine. Laser irradiation of the place where the cells were implanted can stimulate their proliferation, increase the secretion of growth factors and thus increase the therapeutic effect. AIM: To evaluate the influence of two lasers: Er:YAG and diode on the growth of hAT-MSCs in vitro. MATERIAL AND METHODS: hAT-MSCs were isolated from human subcutaneous adipose tissue. Immunophenotype of hAT-MSCs was confirmed by flow cytometry. Multipotency of hAT-MSCs was confirmed by differentiation into adipogenic, osteogenic and chondrogenic lineages. hAT-MSCs were irradiated with Er:YAG laser (wavelength 2940 nm, frequency 5, 10 Hz, doses: 0.1-1.2 J/cm2) for 2 s and 4 s and diode laser (wavelength 635 nm and doses: 1-8 J/cm2) for 5, 10, 20, 30 and 40 s. Cell viability was analysed 24 h after the exposure using MTT assay. RESULTS: Growth stimulation of hAT-MSCs after 5 Hz Er:YAG laser exposure, 0.1 J/cm2 dose for 4 s and 0.3 J/cm2 dose for 4 s was shown in comparison with the control group. Significant growth stimulation of hAT-MSCs after diode laser irradiation in doses of 1-4 J/cm2 was demonstrated compared to the control group. CONCLUSIONS: The presented results indicate that both lasers, Er:YAG and diode can be used to stimulate stem/stromal cell growth in vitro. The biostimulative effect of laser therapy on stromal cells may be used in the future in aesthetic dermatology in combined laser and cell therapy.