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.

Management of Stable Vitiligo-A Review of the Surgical Approach.

At present, vitiligo is the most common depigmenting skin disorder, characterized by clearly demarcated discolored patches of various shapes and sizes. Depigmentation results from the initial dysfunction and subsequent destruction of melanin-producing cells, called melanocytes, which are located in the basal layer of the epidermis and in hair follicles. This review concludes that the extent of repigmentation, regardless of the treatment method, is greatest in stable localized vitiligo patients. The aim of this review is to provide an overview of the clinical evidence for which the vitiligo treatment method (cellular or tissue) is more effective. The treatment relies on multiple factors, ranging from patient skin predisposition for repigmentation to the experience of the facility performing the procedure. Vitiligo is a significant problem in modern society. Although it is a typically asymptomatic and not life-threatening disease, it may have significant psychological and emotional impacts. Standard treatment relies on pharmacotherapy and phototherapy; however, the treatment of patients with stable vitiligo varies. The stability of vitiligo more than often implies the exhaustion of the potential for skin self-repigmentation. Thus, the surgical methods that distribute normal melanocytes into the skin are crucial elements of these patients' therapy. The most commonly used methods are described in the literature, with an indication of their recent progress and changes. In addition, information on the efficiency of the individual methods at specific locations is compiled in this study, and the prognostic factors indicating repigmentation are presented. Cellular methods are the best therapeutic option for large-sized lesions; although they are more exorbitant than tissue methods, they benefit from more rapid healing times and presenting fewer side effects. Dermoscopy is a valuable tool used to assess the further course of repigmentation, where it is of great value to evaluate the patient prior to and following an operation.

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.

Retracted: Affective temperament, depressive symptoms and interleukins in patients with psoriasis.

[This retracts the article DOI: 10.5114/ada.2021.104289.].

The Impact of Pruritus on the Quality of Life and Sleep Disturbances in Patients Suffering from Different Clinical Variants of Psoriasis.

BACKGROUND: Quality of life (QoL) and sleep, which are essential for well-being in the mental, physical, and socioeconomic domains, are impaired in psoriatic patients. However, the exact role of the clinical subtype of psoriasis in this aspect remains poorly studied. OBJECTIVES: The aim of this study was to investigate differences in QoL impairment and sleeping problems in patients suffering from various clinical subtypes of psoriasis and to evaluate the effects of pruritus on QoL. METHODS: This cross-sectional, multicenter study included 295 eligible subjects with diagnosed psoriasis. Each patient was examined with the use of the same questionnaire. Measures included predominant subtype of psoriasis, disease severity, pruritus scores, patients' health-related QoL and the incidence of sleep disturbance. RESULTS: The QoL of most patients was decreased irrespectively of clinical psoriasis subtype, however, the most impaired QoL was in patients with erythrodermic psoriasis. The majority of patients reported sleep disturbances caused by pruritus, albeit there was no relevant differences between analyzed subgroups in this aspect of patients' well-being. Pruritus was an important factor determining QoL and sleeping problems in the studied population. CONCLUSIONS: Identifying the most disturbing area of life and recognizing the most bothersome subjective symptoms of psoriasis are pivotal to focusing on the most relevant treatment goal and achieving therapeutic success.

Cognitive Functions Associated with Brain Imaging Markers in Patients with Psoriasis.

Psoriasis is a severe inflammatory disease associated with a higher comorbidity of depression, cognitive dysfunction and brain atrophy. The association between psoriasis, magnetic resonance imaging (MRI) markers and cognitive impairment has rarely been investigated, and the existing results are conflicting. METHODS: This study included 89 subjects (53 patients with psoriasis and 36 healthy controls). The severity of psoriasis was evaluated using the Psoriasis Area and Severity Index (PASI) score; for depression, the Hospital Anxiety and Depression Scale (HADS) scale was used. Neuropsychological tests were also applied, including a Trail Making Test (TMT) as well as Digit Span, Stroop, Verbal Fluency and Rey Auditory Verbal Learning tests. MRI scans were performed using a 1.5 T scanner. Brain volumetry, white matter lesions, grey matter and white matter were evaluated. The extent of these changes was assessed on the Fazekas scale. The differences between groups were evaluated using a Student's t-test and a Mann-Whitney U test, and a Pearson correlation analysis was also performed. RESULTS: Patients with psoriasis presented worse achievements on all the neuropsychological tests and showed more intense changes on MRI compared to healthy controls. The severity of psoriasis as determined by PASI scores was associated with depression, and a greater psychomotor slowness severity of changes in the brain was associated with poorer results on the neurological tests. CONCLUSIONS: Our results indicate the possibility of progressive brain atrophy related to cognitive decline in psoriasis.

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.

Concurrent subcutaneous and ocular infections with Dirofilaria repens in a Polish patient: a case report in the light of epidemiological data.

Dirofilariasis is an emerging zoonosis caused by nematodes of the genus Dirofilaria, most often D. repens and D. immitis. The main final hosts and reservoirs of pathogens are dogs. The intermediate hosts and vectors of infection are female mosquitoes (Culicidae). Human is an accidental host in which the parasite does not usually mature. Over the past 20 years, the range of Dirofilaria spp. in Europe has expanded. We present an unusual case of multifocal dirofilariasis of mixed subcutaneous-ocular course caused by D. repens in a 52-year-old Polish patient who was probably infected in Spain or Croatia, where she stayed one year before the onset of symptoms. Surgical removal of the nematodes followed by treatment with Ivermectin in a single dose of 1200 µg and Doxycycline 200 mg daily for 7 days resulted in complete recovery. We believe that all cases of human dirofilariasis, especially in countries where the disease is not frequent at present, should be registered for epidemiological purposes. Moreover, due to the widening of the range of D. repens and D. immitis occurrence and the possibility of atypical courses of infection with both nematodes, diagnostics should include the species identification of the parasite.

Affective temperament, depressive symptoms and interleukins in patients with psoriasis.

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease, in which psychological factors play an important role. In the studies of common markers of psoriasis and depression, the abnormal function of the stress axis in both diseases is highlighted, whereas interleukin-6 (IL-6) and interleukin-1 are indicated as particularly important. AIM: To evaluate the relationship between the affective temperament traits and the intensity of depressive symptoms in patients with psoriasis in the context of immunoenzymatic markers. MATERIAL AND METHODS: The study included 208 subjects. Severity of psoriasis was assessed by PASI. TEMPS-A was applied for the evaluation of affective temperament and BDI was used for the assessment of the intensity of depressive symptoms. The level of cytokines was determined by means of the immunoenzymatic method. RESULTS: Patients presented a specific profile of affective temperament, with higher scores on depressive, anxious and irritable dimensions. The severity of depressive symptoms correlated positively with the severity of psoriasis. A significant correlation was found between IL-6 and the severity of psoriasis in patients with depressive disorders and psoriasis. No similar correlation was found in patients without depressive disorder. CONCLUSIONS: Results of the present study show common mechanisms for psoriasis and depression. Specific traits of affective temperament may play an important role in the clinical picture of both diseases. Higher levels of IL-6 in patients with psoriasis predispose to more frequent occurrence of depressive disorders and the depressive dimension of affective temperament.

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.

Allergic phenotypes in adult patients with atopic dermatitis, determined with the ISAC test (ImmunoCAP ISAC).

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory dermatosis, often with a concomitant allergy. The ImmunoCAP ISAC (Immuno Solid-Phase Allergen Chip) test is a novel method to determine the allergenic phenotype in a given patient. AIM: In this study, we used the ImmunoCAP ISAC test to analyze allergic phenotypes in adult patients with AD. MATERIAL AND METHODS: The study included 19 adult patients with AD. The severity of AD was assessed using SCORAD index. Serum concentrations of total IgE were determined by means fluoro-enzyme immunoassay (FEIA). The levels of asIgE were measured with the ImmunoCAP ISAC kits. RESULTS: Positive results of the ISAC test were documented in 84.2% of the study subjects. All patients synthesized asIgE against species-specific respiratory allergens; major components of animal allergens (57.87%), tree pollen allergens (47.3%), grass pollen allergens (42.1%), dust mite allergens (26.3%) and major allergen of mugwort (26.3%). 47.3% of the subjects were sensitive to cross-reactive allergenic components, most often proteins of the lipocalin family (57.8%), followed by PR-10 (26.3%), PR-14 (21%) and PR-5 proteins (21%). asIgE against species-specific allergens were found in 10.5% of the study subjects. No statistically significant relationships were observed between the severity or duration of AD and the prevalence and levels of asIgE against the allergens included in the ISAC panel. However, duration of AD correlated significantly with the serum concentration of total IgE. CONCLUSIONS: The ISAC test is suitable for determination of the allergenic phenotype in a given patient, and as such has an unquestioned diagnostic and therapeutic value.

Cognitive impairment in patients with severe psoriasis.

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease, in which an important role is played by psychological factors. AIM: To evaluate the frontal cognitive functions in patients with psoriasis. MATERIAL AND METHODS: The study included 188 subjects (97 patients with psoriasis and 91 healthy controls). To assess the dorsolateral prefrontal cortex functions, the Trail Making Test and the Stroop test were applied. Severity of psoriasis was assessed by means of the PASI index. RESULTS: Compared to healthy subjects, psoriatics scored lower in neuropsychological tests assessing memory and executive functions. CONCLUSIONS: Cognitive dysfunction disclosed by neuropsychological assessment of frontal functions was evident in patients with psoriasis.

The incidence and management of cutaneous adverse events of the epidermal growth factor receptor inhibitors.

Overexpression of the epidermal growth factor receptor (EGFR) is found in many cancers, including those of the head and neck area, non-small-cell lung cancer, and colorectal, cervical, prostate, breast, ovary, stomach, and pancreatic cancer. The EGFR inhibitors are used at present in the treatment of such cancers. Skin lesions that develop during and after cancer treatment may be due to specific cytostatics, molecular-targeted drugs, radiation therapy, complementary therapy, or the cancer itself, and hence knowledge is essential to distinguish between them. The mechanism through which skin toxicity arises during treatment with EGFR inhibitors is not well known, but seems to be due to the modification of the RAS/RAF/MEK/ERK signal path associated with its activation, which results in the similarity between the adverse effects of EGFR inhibitors and the treatment of melanoma with BRAF and MEK inhibitors. The most common side effects are pruritus, xerosis, papulopustular rash, hand-foot skin reaction, alopecia and dystrophy of the hair, and paronychia. This work presents options for prevention and suggestions for managing these adverse events, which are of importance in the care of patients undergoing oncological treatment.