Psoriasis: What Is New in Markers of Disease Severity?

Introduction. Psoriasis is a chronic inflammatory skin disease and is the result of the interaction between numerous external and internal factors. Psoriasis presents a wide range of skin manifestations encompassing individual lesions varying from pinpoint to large plaques that can evolve into generalised forms. The lesions mirror the pathophysiological mechanisms involved in psoriasis pathogenesis, such as inflammation, dysregulation of immune response, uncontrolled proliferation of keratinocytes and angiogenesis. In this article, we present the latest advances achieved regarding markers that correlate with psoriasis severity. Material and method. We have performed a narrative review on markers of psoriasis severity, including articles published between March 2018-March 2023. Results. We have identified four categories of markers: inflammation markers, oxidative stress markers, hormonal markers and cancer-related markers. The main focus was on inflammation biomarkers, including immunomodulatory molecules, haematological parameters, inflammatory cells and costimulatory molecules. Conclusions. The analysed data indicate that markers associated with inflammation, oxidative stress and hormones, and cancer-related markers could be useful in assessing the severity of psoriasis. Nevertheless, additional research is required to ascertain the practical importance of these biomarkers in clinical settings.

Ischemia-Modified Albumin-A Potential New Marker of Oxidative Stress in Dermatological Diseases.

There is growing evidence that oxidative stress is involved in the pathogenesis of numerous conditions, including dermatological diseases. Various markers are available to assess oxidative stress, but none of these can be considered the ideal marker. Recent studies have shown that ischemia-modified albumin (IMA) is not only an indicator of ischemia, but also a marker of oxidative stress. We have conducted a narrative review to evaluate the role of IMA in dermatological diseases. We have identified 24 original articles that evaluated IMA in skin disorders (psoriasis, acne vulgaris, hidradenitis suppurativa, urticaria, vitiligo and Behcet's disease) and hair disorders (alopecia areata, androgenetic alopecia and telogen effluvium). The results of the studies analyzed reveal that IMA may be considered a new marker of oxidative stress in dermatological diseases and offer new insights into the pathogenesis of these disorders and the theoretical basis for the development of new, effective, targeted therapies. To the best of our knowledge, this is the first review that gathers up data on the role of IMA in dermatological diseases.

Viral Infections Confined to Tattoos-A Narrative Review.

Since ancient times, people have tattooed their skin for various reasons. In the past, tattoos were associated with low social status; nowadays, tattoos are very popular and are considered a form of art. However, tattoos are associated with various clinical problems, including immune reactions, inflammatory disorders, infections, and even skin cancer. Epidemiological and clinical data of infections on tattoos are scarce. Tattoo-related infections are mostly bacterial; only a few localized viral infections have been reported so far and are caused by molluscum contagiosum virus (MCV), human papillomavirus (HPV), and herpes simplex virus (HSV). In most cases, the lesions were strictly confined to the area of the tattoo. In this review, we have analysed reported cases of viral infections localized on tattoos and discussed the possible mechanisms involved in the occurrence of these infections.

Tumour Microenvironment in Skin Carcinogenesis.

Tumour microenvironment is a complex system comprising cells and molecules that will provide the necessary conditions for tumour development and progression. Cells residing in the tumour microenvironment gain specific phenotypes and specific functions that are pro-tumorigenic. Tumour progression is in fact a combination between tumour cell characteristics and its interplay with tumour microenvironment. This dynamic network will allow tumour cells to grow, migrate and invade tissues. In the present chapter, we are highlighting some traits that characterise tumour microenvironment in basal cell carcinoma, squamous cell carcinoma and cutaneous melanoma. In skin cancers, there are some common tumour microenvironment characteristics such as the presence of tumour-associated macrophages and regulatory T lymphocytes that are non-tumour cells promoting tumorigenesis. There are also skin cancer type differences in terms of tumour microenvironment characteristics. Thus, markers such as macrophage migration inhibitory factor in melanoma or the extraordinary diverse genetic make-up in the cancer-associated fibroblasts associated to squamous cell carcinoma are just a few of specific traits in skin cancer types. New technological advances for evaluation of tumour environment are presented. Thus, non-invasive skin imaging techniques such as reflectance confocal microscopy can evaluate skin tumour inflammatory infiltrates for density and cellular populations. Analysing tumour micromedium in depth may offer new insights into cancer therapy and identify new therapy targets.

Advances in Understanding the Immunological Pathways in Psoriasis.

Psoriasis vulgaris is a chronic, immune-mediated, inflammatory, polygenic skin disorder affecting approximately 2% of the population. It has a great impact on quality of life; patients often experience depression, anxiety, stigma as well as suicidal behavior. Even though psoriasis is one of the most studied dermatological conditions, the pathogenesis of the disease is still not completely elucidated. The complex interactions between keratinocytes, dendritic cells, T-lymphocytes, neutrophils and mast cells are responsible for the histopathological changes seen in psoriasis. The pathogenic model leading to the formation of psoriatic plaques has however evolved a lot over the years. There is now enough evidence to support the role of interleukin (IL) -23, IL-17, IL-22, T helper (Th) -17 cells, Th-22 cells, T regulatory cells, transforming growth factor (TGF)-ß1 and IL-10 in the pathogenesis of the disease. Moreover, several inflammatory and anti-inflammatory molecules are currently being investigated, some of them showing promising results. The aim of this paper is to look over the most recent advances in the immunological pathways involved in the pathogenesis of psoriasis vulgaris.

The Relationship between the Soluble Receptor for Advanced Glycation End Products and Oxidative Stress in Patients with Palmoplantar Warts.

BACKGROUND AND OBJECTIVES: Warts are the most common lesions caused by human papillomavirus (HPV). Recent research suggests that oxidative stress and inflammation are involved in the pathogenesis of HPV-related lesions. It has been shown that the soluble receptor for advanced glycation end products (sRAGE) may act as a protective factor against the deleterious effects of inflammation and oxidative stress, two interconnected processes. However, in HPV infection, the role of sRAGE, constitutively expressed in the skin, has not been investigated in previous studies. MATERIALS AND METHODS: In order to analyze the role of sRAGE in warts, we investigated the link between sRAGE and the inflammatory response on one hand, and the relationship between sRAGE and the total oxidant/antioxidant status (TOS/TAS) on the other hand, in both patients with palmoplantar warts (n = 24) and healthy subjects as controls (n = 28). RESULTS: Compared to the control group, our results showed that patients with warts had lower levels of sRAGE (1036.50 ± 207.60 pg/mL vs. 1215.32 ± 266.12 pg/mL, p < 0.05), higher serum levels of TOS (3.17 ± 0.27 vs. 2.93 ± 0.22 µmol H2O2 Eq/L, p < 0.01), lower serum levels of TAS (1.85 ± 0.12 vs. 2.03 ± 0.14 µmol Trolox Eq/L, p < 0.01) and minor variations of the inflammation parameters (high sensitivity-CRP, interleukin-6, fibrinogen, and erythrocyte sedimentation rate). Moreover, in patients with warts, sRAGE positively correlated with TAS (r = 0.43, p < 0.05), negatively correlated with TOS (r = -0.90, p < 0.01), and there was no significant correlation with inflammation parameters. There were no significant differences regarding the studied parameters between groups when we stratified the patients according to the number of the lesions and disease duration. CONCLUSIONS: Our results suggest that sRAGE acts as a negative regulator of oxidative stress and could represent a mediator involved in the development of warts. However, we consider that the level of sRAGE cannot be used as a biomarker for the severity of warts. To the best of our knowledge, this is the first study to demonstrate that sRAGE could be involved in HPV pathogenesis and represent a marker of oxidative stress in patients with warts.

Ascorbic acid deficiency in patients with lichen planus.

OBJECTIVES: Recent studies have highlighted the role of oxidative stress in the pathogenesis of lichen planus (LP). In the present study, the interest of the authors is focused on the investigation of ascorbic acid status in patients with LP and identification of parameters that might influence the level of this vitamin. MATERIAL AND METHOD: We analyzed the level of urinary ascorbic acid (reflectometric method) in 77 patients with LP (cutaneous LP (CLP)-49 cases; oral LP (OLP)-28 cases) and 50 control subjects. The evaluation of all participants included clinical examination and laboratory and imaging tests. RESULTS: Compared to the control group (19.82 mg/dl) the level of ascorbic acid was significantly lower both in patients with CLP (8.47 mg/dl, p = 0.001) and in those with OLP (8.04 mg/dl, p = 0.001). In patients with LP it was found that the deficiency of ascorbic acid increases with age (r = -0.318, p = 0.032). The urinary concentrations of ascorbic acid were significantly lower in patients with LP associated with infections compared to patients with LP without infections. CONCLUSIONS: The urinary ascorbic acid level may be a useful parameter in identifying patients with LP who are at risk of developing viral or bacterial infections.

Resistance pattern of multi-drug resistant strains of Mycobacterium tuberculosis and characteristics of patients with multi-drug resistant tuberculosis.

Introduction: Multi-drug resistant tuberculosis (MDR-TB) is a major concern in the medical community. Knowledge about the drug resistance pattern of Mycobacterium tuberculosis strains plays an essential role in the management of the disease. Material and methods: We conducted a retrospective, 3-year study (2009-2011), in an urban area. We collected data on the drug resistance for 497 M. tuberculosis strains, isolated from patients with pulmonary TB. Among the 497 strains, we identified 158 MDR strains. Eighty medical recorders of patients infected with MDR strains were available and we included those patients in the study group. Results: Of the 497 analysed strains, 8% were resistant to a single anti-TB drug. We identified 5.2% polyresistant drug strains, the most frequent combination being INH+EMB (1.4%). Of the 158 MDR strains identified (31.8%), over 60% were resistant to all first line anti-TB drugs tested. Most of them presented resistance to STM (86.1%) and EMB (67.7%). With respect to second line anti-TB drugs resistance to KM (23.4%) was the most common, followed by OFX (8.2%). With respect to the patients with MDR-TB, a percentage of 61.2% of them had a history of anti-TB treatment. Regarding lifestyle habits, 61.2% of the patients were smokers and 18.8% were abusing alcohol. Out of 51 patients, for whom information was available regarding their occupation, only 33.3 % were employees. Conclusion: MDR strains of Mycobacterium tuberculosis display an increased resistance to first line anti-TB drugs. Extension of resistance to second line anti-TB drugs narrows the therapeutic options. Knowledge of MDR-TB risk factors is imperative for the correct and rapid initiation of the treatment.

The Interplay between Nitrosative Stress, Inflammation, and Antioxidant Defense in Patients with Lichen Planus.

BACKGROUND: Lichen planus (LP) is a chronic inflammatory skin disease of unelucidated etiology. LP immunopathogenesis is mainly governed by cytotoxic T lymphocytes that mediate an immune response in basal keratinocytes, which may transform into a reservoir of antigens able to initiate an autoimmune reaction. However, other pathogenic pathways complement these mechanisms. Recent studies highlight the involvement of nitrosative stress in the pathogenesis of chronic inflammatory skin diseases. Current data on its role in the pathogenesis of LP are scarce. METHODS: In this article, we investigated nitrosative stress in 40 cutaneous LP (CLP) patients compared to 40 healthy subjects using serum markers including nitrosative stress markers-direct nitrite, total nitrite, nitrate and symmetric dimethylarginine (SDMA), total antioxidant status (TAS), and hsCRP, a marker of inflammation, and analyzed the relationship between nitrosative stress, antioxidant defense, and inflammation to offer new insights into the role of the NO pathway in LP pathogenesis. RESULTS: We identified significantly higher serum levels of direct nitrite, total nitrite, nitrate, SDMA and hsCRP, and significantly lower levels of TAS in CLP patients versus controls. There were significant negative correlations between the serum levels of TAS and significantl positive correlations between the serum levels of hsCRP and the analyzed nitrosative stress markers in patients with CLP. CONCLUSION: Our results indicate an increased level of nitrosative stress in LP patients that correlates with a pro-inflammatory status and altered antioxidant defense.

A New Horizon for Atopic Dermatitis Treatments: JAK Inhibitors.

The article entitled "Application of Janus Kinase Inhibitors in Atopic Dermatitis: An Updated Systematic Review and Meta-Analysis of Clinical Trials" that belongs to the Special Issue, " Personalized medicine in the field of inflammatory skin diseases", a collection of articles addressing the current critical issues in the pathogenesis and management of chronic inflammatory skin disorders, represents a valuable work that has contributed to elucidating the role of Janus kinase (JAK) inhibitors as a treatment option for atopic dermatitis (AD), as well as their safety profiles [...].

Mast Cell Activation Syndrome Update-A Dermatological Perspective.

Mast cells (MCs) are infamous for their role in potentially fatal anaphylaxis reactions. In the last two decades, a more complex picture has emerged, as it has become obvious that MCs are much more than just IgE effectors of anaphylaxis. MCs are defenders against a host of infectious and toxic aggressions (their interactions with other components of the immune system are not yet fully understood) and after the insult has ended, MCs continue to play a role in inflammation regulation and tissue repair. Unfortunately, MC involvement in pathology is also significant. Apart from their role in allergies, MCs can proliferate clonally to produce systemic mastocytosis. They have also been implicated in excessive fibrosis, keloid scaring, graft rejection and chronic inflammation, especially at the level of the skin and gut. In recent years, the term MC activation syndrome (MCAS) was proposed to account for symptoms caused by MC activation, and clear diagnostic criteria have been defined. However, not all authors agree with these criteria, as some find them too restrictive, potentially leaving much of the MC-related pathology unaccounted for. Here, we review the current knowledge on the physiological and pathological roles of MCs, with a dermatological emphasis, and discuss the MCAS classification.

Markers of Oxidative Stress in Patients with Acne: A Literature Review.

Acne vulgaris is a chronic inflammatory skin disease of the pilosebaceous unit. Its pathogenesis is multifactorial and involves the overlap between four main processes: alteration of the keratinization, increased sebum production, colonization with Cutibacterium acnes, and inflammation. The role of oxidative stress (OS) has been intensively studied in inflammatory skin conditions such as psoriasis, vitiligo, or atopic dermatitis. However, the involvement of OS in the pathogenesis of acne is less known. The evidence accumulated over the last decade suggests that in the case of acne patients, there is an imbalance between oxidants and antioxidants. In this review, we analyzed studies that evaluated markers of OS in patients with acne, published in the last ten years, with the aim of providing new insights into the pathogenesis of acne.

A Meta-Analysis on the Effectiveness of Sertaconazole 2% Cream Compared with Other Topical Therapies for Seborrheic Dermatitis.

Seborrheic dermatitis (SD) is a relapsing inflammatory skin disorder that affects the seborrheic areas of the body. Its etiology is not completely elucidated; however, the link between disease exacerbations and the proliferation of Malassezia spp., along with the good response to antifungal agents, indicate the role of fungi in its pathophysiology. Sertaconazole nitrate is a relatively new imidazole antifungal agent with a particular structure, consisting in a benzothiophene ring similar to the indole ring of tryptophan, and it acts mainly through the inhibition of ergosterol synthesis and the formation of pores in the fungal cell membrane. The aim of our study was to evaluate the efficiency of sertaconazole 2% cream compared with other topical treatments in patients with SD. We performed an extensive literature search by browsing the PubMed database with the keyword combination "sertaconazole AND seborrheic dermatitis AND clinical trial", which retrieved eight controlled clinical trials evaluating the effects of sertaconazole in SD. All of the clinical trials included a standard scoring index (SI). At 28 days since the beginning of the treatment, the sertaconazole regimen was associated with a significantly higher percentage of patients with mild SI and a lower percentage of patients with moderate or severe SI (odds ratio 0.51) than the other investigated treatments-hydrocortisone, ketoconazole, clotrimazole, metronidazole, pimecrolimus, and tacrolimus (odds ratio 1.95). In conclusion, treatment with sertaconazole 2% cream may represent an efficient alternative therapy for patients with SD.

Thiol-Disulfide Homeostasis in Skin Diseases.

Oxidative stress represents the imbalance between oxidants and antioxidants and has been associated with a wide range of diseases. Thiols are the most important compounds in antioxidant defense. There is an equilibrium between thiols and their oxidized forms, disulfides, known as dynamic thiol-disulfide homeostasis (TDH). In 2014, Erel and Neselioglu developed a novel automated assay to measure thiol and disulfide levels. Subsequently, many researchers have used this simple, inexpensive and fast method for evaluating TDH in various disorders. We have reviewed the literature on the role of TDH in skin diseases. We identified 26 studies that evaluated TDH in inflammatory diseases (psoriasis, seborrheic dermatitis, atopic dermatitis, vitiligo, acne vulgaris and rosacea), allergic diseases (acute and chronic urticaria) and infectious diseases (warts, pityriasis rosea and tinea versicolor). The results are heterogeneous, but in most cases indicate changes in TDH that shifted toward disulfides or toward thiols, depending on the extent of oxidative damage.

Effectiveness of Platelet-Rich Plasma Therapy in Androgenic Alopecia-A Meta-Analysis.

Platelet-rich plasma (PRP) represents a novel therapy tested and is used more and more frequently in dermatology and cosmetic surgery for a variety of conditions, including androgenic alopecia (AGA), a common condition with a complex pathogenesis involving genetic factors, hormonal status and inflammation. We performed an extensive literature search which retrieved 15 clinical trials concerning the use in AGA of PRP therapy, alone or in combination, in male, female or mixed patient groups. A quantitative statistical meta-analysis of n = 17 trial groups proved significant increases in hair density from 141.9 ± 108.2 to 177.5 ± 129.7 hairs/cm2 (mean ± SD) following PRP (p = 0.0004). To the best of our knowledge, this is the first meta-analysis that proved a statistically significant correlation between the number of PRP treatments per month and the percentage change in hair density (r = 0.5, p = 0.03), as well as a negative correlation between the mean age of treatment group and the percentage change in hair density (r = -0.56, p = 0.016). Other factors considered for analysis were the PRP preparation method, amount used per treatment, hair diameter, terminal hairs and pull test. We conclude that PRP represents a valuable and effective therapy for AGA in both males and females if patients are rigorously selected.

Apprising Diagnostic and Prognostic Biomarkers in Cutaneous Melanoma-Persistent Updating.

The incidence of melanoma, a very aggressive skin cancer, has increased over the past few decades. Although there are well-established clinical, dermoscopic and histopathological criteria, the diagnosis is often performed late, which has important implications on the patient's clinical outcome. Unfortunately, melanoma is one of the most challenging tumors to diagnose because it is a heterogeneous neoplasm at the clinical, histopathological, and molecular level. The use of reliable biomarkers for the diagnosis and monitoring of disease progression is becoming a standard of care in modern medicine. In this review, we discuss the latest studies, which highlight findings from the genomics, epitranscriptomics, proteomics and metabolomics areas, pointing out different genes, molecules and cells as potential diagnostic and prognostic biomarkers in cutaneous melanoma.

Serum Sialylation Changes in Actinic Keratosis and Cutaneous Squamous Cell Carcinoma Patients.

Cutaneous squamous cell carcinoma (cSCC), a malignant proliferation of the cutaneous epithelium, is the second most common skin cancer after basal cell carcinoma (BCC). Unlike BCC, cSCC exhibits a greater aggressiveness and the ability to metastasize to any organ in the body. Chronic inflammation and immunosuppression are important processes linked to the development of cSCC. The tumor can occur de novo or from the histological transformation of preexisting actinic keratoses (AK). Malignant cells exhibit a higher amount of sialic acid in their membranes than normal cells, and changes in the amount, type, or linkage of sialic acid in malignant cell glycoconjugates are related to tumor progression and metastasis. The aim of our study was to investigate the sialyation in patients with cSCC and patients with AK. We have determined the serum levels of total sialic acid (TSA), lipid-bound sialic acid (LSA), beta-galactoside 2,6-sialyltransferase I (ST6GalI), and neuraminidase 3 (NEU3) in 40 patients with cSCC, 28 patients with AK, and 40 healthy subjects. Data analysis indicated a significant increase in serum levels of TSA (p < 0.001), LSA (p < 0.001), ST6GalI (p < 0.001), and NEU3 (p < 0.001) in the cSCC group compared to the control group, whereas in patients with AK only the serum level of TSA was significantly higher compared to the control group (p < 0.001). When the cSCC and AK groups were compared, significant differences between the serum levels of TSA (p < 0.001), LSA (p < 0.001), ST6GalI (p < 0.001) and NEU3 (p < 0.001) were found. The rate of synthesis of sialoglycoconjugates and their rate of enzymatic degradation, expressed by the ST6GalI/NEU3 ratio, is 1.64 times lower in the cSCC group compared to the control group (p < 0.01) and 1.53 times lower compared to the AK group (p < 0.01). The tumor diameter, depth of invasion, and Ki67 were associated with higher levels of TSA and LSA. These results indicate an aberrant sialylation in cSCC that correlates with tumor aggressiveness.

Variations of Thiol-Disulfide Homeostasis Parameters after Treatment with H1-Antihistamines in Patients with Chronic Spontaneous Urticaria.

BACKGROUND: The pathogenesis of chronic spontaneous urticaria involves metabolic, immunological, and psychological factors. The thiol-disulfide exchange reactions could be a mechanism to counteract oxidative stress in patients with chronic spontaneous urticaria. OBJECTIVE: The assessment of thiol-disulfide homeostasis parameters (TDHPs) according to disease severity and the influence of H1-antihistamine therapy in patients with chronic spontaneous urticaria. MATERIAL AND METHOD: We have included 30 patients with chronic spontaneous urticaria in the study and we have determined the levels of native thiol, total thiol, disulfides as well as the disulfide/native thiol ratio, disulfide/total thiol ratio and the native thiol/total thiol ratio, before and after therapy with H1-antihistamines. RESULTS: The results of the study showed altered levels of TDHPs and their normalization after treatment with H1-antihistamines in patients with chronic spontaneous urticaria. We determined a statistically significant increase in the serum levels of total thiol, native thiol, and native thiol/total thiol ratio and a significant reduction in the levels of disulfides, disulfide/native thiol ratio and disulfide/total thiol ratio after treatment with H1-antihistamines. The normalization of the serum levels of TDHPs has been associated with the relief of symptoms and reduction or resolution of pruritus and urticarial plaques. CONCLUSION: These results suggest the involvement of thiol-disulfide homeostasis in the defense against the harmful effects of reactive oxygen species in patients with chronic spontaneous urticaria and the potential role of TDHPs in monitoring H1-antihistamine therapy. To the best of our knowledge, this is the first study investigating TDHPs in patients with chronic spontaneous urticaria before and after treatment.

Oxidative Stress in Cutaneous Lichen Planus-A Narrative Review.

Lichen planus (LP) is a chronic, immune-mediated inflammatory skin condition that mainly affects the skin (cutaneous LP, CLP) and oral mucosa (oral LP, OLP). However, the mechanisms involved in the pathogenesis of the disease are not fully elucidated. Over time, several theories that could explain the appearance of LP lesions have been postulated. The key players in LP pathogenesis are the inflammatory infiltrate consisting of T cells and the proinflammatory cytokines. The cytokines stimulate the production of reactive oxygen species that induce cell apoptosis, a defining element encountered in LP. The lead inquiry triggered by this revolves around the role of oxidative stress in LP development. There are currently numerous studies showing the involvement of oxidative stress in OLP, but in terms of CLP, data are scarce. In this review, we analyze for the first time the currently existing studies on oxidative stress in CLP and summarize the results in order to assess the role of oxidative stress in skin lesions offering a fresher updated perspective.

Cellular Response against Oxidative Stress, a Novel Insight into Lupus Nephritis Pathogenesis.

The interaction of reactive oxygen species (ROS) with lipids, proteins, nucleic acids and hydrocarbonates promotes acute and chronic tissue damage, mediates immunomodulation and triggers autoimmunity in systemic lupus erythematous (SLE) patients. The aim of the study was to determine the pathophysiological mechanisms of the oxidative stress-related damage and molecular mechanisms to counteract oxidative stimuli in lupus nephritis. Our study included 38 SLE patients with lupus nephritis (LN group), 44 SLE patients without renal impairment (non-LN group) and 40 healthy volunteers as control group. In the present paper, we evaluated serum lipid peroxidation, DNA oxidation, oxidized proteins, carbohydrate oxidation, and endogenous protective systems. We detected defective DNA repair mechanisms via 8-oxoguanine-DNA-glycosylase (OGG1), the reduced regulatory effect of soluble receptor for advanced glycation end products (sRAGE) in the activation of AGE-RAGE axis, low levels of thiols, disulphide bonds formation and high nitrotyrosination in lupus nephritis. All these data help us to identify more molecular mechanisms to counteract oxidative stress in LN that could permit a more precise assessment of disease prognosis, as well as developing new therapeutic targets.