Finasteride and androgenic alopecia; from therapeutic options to medical implications.

Androgenic alopecia (AGA) is an esthetic condition with varying psycho-social implications, easily accepted by some patients and tolerated only with difficulty by others. Modern therapeutic options such as 5α-reductase inhibitors have significant outcomes, but also exert significant side effects in a subset of patients. The literature describes three distinct situations regarding finasteride administration, a compound largely used for AGA. Some studies show finasteride to be very safe with minimal or no side effects. Other studies take a more cautious approach, recognizing such side effects but, at the same time, considering the putative relationship between finasteride and adverse effects to be disputable, given that placebo administration in AGA is associated with relatively similar or even more severe side effects. Finally, some authors/studies are concerned that, when compared to placebo, finasteride administration may result in side effects with greater frequency and severity, and sometimes that persist even after treatment cessation in the form of post-finasteride syndrome. Several factors presented in this paper appear to explain finasteride inconsistency regarding its therapeutic and side effects. Such factors should be further investigated and used to categorize subjects into distinct subgroups, either predisposed to adverse reactions or more tolerant of the finasteride administration.

Reactive Carbonyl Species as Potential Pro-Oxidant Factors Involved in Lichen Planus Pathogenesis.

The constant generation of reactive carbonyl species (RCSs) by lipid peroxidation during aerobic metabolism denotes their involvement in cell homeostasis. Skin represents the largest organ of the body that is exposed to lipid peroxidation. Previous studies have suggested the involvement of oxidative stress in the development of lichen planus (LP), a chronic inflammatory skin condition with a complex pathogenesis. The aim of our study is to investigate a panel of pro-oxidants (4-hydroxy-nonenal (4-HNE), thiobarbituric acid reactive substances (TBARS), and malondialdehyde (MDA)), the total antioxidant status (TAS), and thiol-disulfide homeostasis parameters (TDHP), including total thiol (TT), native thiol (NT), disulfides (DS), DS/NT ratio, DS/TT ratio, and NT/TT ratio. The comparative determinations of serum levels of 4-HNE, TBARS, and MDA in patients with LP (n = 31) and controls (n = 26) show significant differences between the two groups (4-HNE: 7.81 ± 1.96 µg/mL vs. 6.15 ± 1.17 µg/mL, p < 0.05, TBARS: 4.23 ± 0.59 µmol/L vs. 1.99 ± 0.23 µmol/L, p < 0.05, MDA: 32.3 ± 6.26 ng/mL vs. 21.26 ± 2.36 ng/mL). The serum levels of TAS are lower in LP patients compared to the control group (269.83 ± 42.63 µmol/L vs. 316.46 ± 28.76 µmol/L, p < 0.05). The serum levels of TDHP are altered in LP patients compared to controls (NT: 388.10 ± 11.32 µmol/L vs. 406.85 ± 9.32., TT: 430.23 ± 9.93 µmol/L vs. 445.88 ± 9.01 µmol/L, DS: 21.06 ± 1.76 µmol/L vs. 19.52 ± 0.77µmol/L). Furthermore, a negative association between pro-oxidants and TAS is identified (4-HNE - rho = -0.83, p < 0.01, TBARS - rho = -0.63, p < 0.01, and MDA - rho = -0.69, p < 0.01). Understanding the mechanisms by which bioactive aldehydes exert their biological effects on the skin could help define effective therapeutical strategies to counteract the cytotoxic effects of these reactive metabolic intermediates.

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.

Photodynamic therapy: A hot topic in dermato-oncology.

Photodynamic therapy (PDT) is a modern, non-invasive therapeutic method used for the destruction of various cells and tissues. It requires the simultaneous presence of three components: a photosensitizer (PS), a light source and oxygen. Precancerous skin lesions are conditions associated with a high likelihood of malignant transformation to squamous cell carcinoma. Data available so far indicate that PDT is a promising treatment method which can be successfully employed in several medical fields including dermatology, urology, ophthalmology, pneumology, cardiology, dentistry and immunology. Numerous authors therefore have studied this technique in order to improve its efficacy. As a result, significant advancement has been achieved with regard to PSs and drug delivery systems. Substantial progress was also obtained with respect to PDT for the treatment of precancerous skin lesions, several authors focusing their efforts on the study of daylight-PDT and on identifying methods of decreasing technique-related pain. This review reports on the most recent findings in PDT, with emphasis on cutaneous precancerous lesions.

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.

Correlations between related-purine derivatives and renal disorders in patients with psoriasis vulgaris.

Recent data suggest that severe psoriasis is an independent risk factor for chronic renal disease. In the present study, we investigated the role of related-purine derivatives as predictors of renal dysfunctions in patients with psoriasis. A prospective study was conducted on a group of 45 patients with psoriasis vulgaris and 45 control cases, monitored over a 5-year period. Alterations of renal function, albumin/creatinine ratio (ACR, mg/g) and UA/creatinine ratio (UACR, mg/mg) were determined in spontaneous urine samples. The status of related-purine derivatives was evaluated by quantification of uric acid (UA, mg/dl), adenosine deaminase (ADA, UI/mg protein), xanthine oxidase (XO, UI/mg protein) and 8-hydroxy-deoxy-guanosine levels (8-OHdG, ng/ml) in serum samples. Compared to the controls, in patients with psoriasis there was an increase in related-purine derivatives levels, which was demonstrated by the elevated serum levels of UA (5.1±0.4 vs. 5.4±1.0, P=0.066), ADA (0.14±0.08 vs. 0.29±0.12, P=0.052), XO (0.22±0.11 vs. 0.42±0.21, P=0.011) and 8-OHdG (3.1±0.05 vs. 8.3±4.7, P=0.002). The serum levels of related-purine derivatives were associated with the severity of psoriasis. In addition, there was a link between the serum levels of related-purine derivatives and markers of renal impairment. There were positive correlations between 8-OHdG and ACR (r=0.452, P=0.028) and between ADA, XO, UA, 8-OHdG and UACR (r=0.297 and P=0.032, r=0.301 and P=0.002, r=0.431 and P=0.027, r=0.508 and P=0.002) and negative correlations between UA, 8-OHdG and the estimated glomerular filtration rate (r=-0.301 and P=0.036, r=-0.384 and P=0.002). Thus, severe psoriasis is a risk factor for the development of renal disease.

Potential pathogenic mechanisms involved in the association between lichen planus and hepatitis C virus infection.

Lichen planus (LP) is an immune-mediated inflammatory disease that particularly affects the skin and mucous membranes. Its etiology remains elusive, however some trigger factors, including viral or bacterial antigens, drugs and metals, have been postulated. There is a higher prevalence of hepatitis C virus (HCV) infection among patients with LP, with some geographical variations. HCV is an enveloped RNA virus that belongs to the Flaviviridae family and in most instances causes chronic liver infections. It has been hypothesized that HCV may contribute to LP development, but the link between the two disorders is not fully understood. It is still debatable whether HCV leads to the occurrence of LP lesions directly by replication inside the infected cells or indirectly by activating immunological pathways. Molecular studies have revealed HCV RNA in specimens collected from patients with LP. The autoimmune theory was also suggested given that several studies have revealed viral replication and immune response activation associated with autoantibody synthesis. The aim of this review is to summarize the main potential mechanisms involved in the association between LP and HCV infection. Understanding the link between the two disorders may shed some light on the pathogenesis of LP, which is a challenging issue.

Mediators of Inflammation - A Potential Source of Biomarkers in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common tumour of the oral cavity, associated with significant morbidity and mortality. It is a multifactorial condition, both genetic and environmental factors being involved in its development and progression. Its pathogenesis is not fully elucidated, but a pivotal role has been attributed to inflammation, strong evidence supporting the association between chronic inflammation and carcinogenesis. Moreover, an increasing number of studies have investigated the role of different mediators of inflammation in the early detection of OSCC. In this review, we have summarized the main markers of inflammation that could be useful in diagnosis and shed some light in OSCC pathogenesis.

New Insights in the Pathogenesis of HPV Infection and the Associated Carcinogenic Processes: The Role of Chronic Inflammation and Oxidative Stress.

Human papillomavirus (HPV) is a small double-stranded DNA virus with tropism for epithelial cells. To this date, over 150 genotypes are known and are classified into two major groups, low-risk and high-risk strains, depending on the ability of the virus to induce malignant transformation. The host's immunity plays a central role in the course of the infection; therefore, it may not be clinically manifest or may produce various benign or malignant lesions. The pathogenic mechanisms are complex and incompletely elucidated. Recent research suggests the role of chronic inflammation and oxidative stress (OS) in the pathogenesis of HPV infection and the associated carcinogenic processes. Chronic inflammation induces OS, which in turn promotes the perpetuation of the inflammatory process resulting in the release of numerous molecules which cause cell damage. Reactive oxygen species exert a harmful effect on proteins, lipids, and nucleic acids. Viral oncogenes E5, E6, and E7 are involved in the development of chronic inflammation through various mechanisms. In addition, HPV may interfere with redox homeostasis of host cells, inducing OS which may be involved in the persistence of the infection and play a certain role in viral integration and promotion of carcinogenesis. Knowledge regarding the interplay between chronic inflammation and OS in the pathogenesis of HPV infection and HPV-induced carcinogenesis has important consequences on the development of new therapeutic strategies.

The Pathophysiological Mechanisms and the Quest for Biomarkers in Psoriasis, a Stress-Related Skin Disease.

Psoriasis is a physically, emotionally, and socially invalidating multifactorial disorder, with a significant impact on the patients' quality of life. Stress is one of the leading triggers for psoriasis and has been associated with disease onset and subsequent flare-ups, while the flare-ups by themselves often lead to psychological discomfort. The treatment of psoriasis is individualized, depending on the patients' measurable severity of illness, as well as the impact the skin condition has on patients' quality of life, as assessed by standardized questionnaires. The clinical scales used nowadays for measuring the severity of psoriasis are characterized by low reproducibility and high variability between examiners. Hence, there is a real need to identify objectively measurable biomarkers to standardize the assessment of the severity of psoriasis. We aim to review the pathophysiological mechanisms involved in psoriasis, focusing on the most critical advances in psoriasis biomarker discovery, pointing out those biomarkers which have also been studied in other stress-related conditions, thus emphasizing the relationship between psoriasis and stress.

Androgenetic alopecia; drug safety and therapeutic strategies.

INTRODUCTION: Androgenetic alopecia (AGA) is a benign condition with variable psychosocial impact, with some individuals adapting well while others needing therapeutic support. Although 5α-reductase inhibitors like finasteride and dutasteride have proven effective in ameliorating AGA, their use/selection is currently a subject of debate. AREAS COVERED: Treatment of AGA with 5α-reductase inhibitors lead to variable adverse effects and relatively unstable results (therapeutic efficacy ending with treatment cessation), so the choice of optimal therapy is not straightforward. This paper presents a general perspective regarding AGA based on studies listed in PubMed, to better understand/appreciate the opportunity for long term use of medication for a biological condition having non-life threatening implications. Studies focussed on adverse effects suggest that finasteride should be used with caution in AGA, due to considerable and persistent side effects induced in some men. In contrast, efficacy data indicate that dutasteride (a stronger inhibitor) presents superior therapeutic results compared to finasteride. EXPERT OPINION: This paper argues that finasteride should be preferred to dutasteride in the treatment of AGA. Thus, finasteride preserves important physiological roles of dihydrotestosterone (unrelated to AGA) and, in addition, its adverse effects seem to be (at least in part) predictable.

Biological therapies in psoriasis - revisited.

Psoriasis is a chronic, immune mediated disorder affecting approximately 2% of the population. Even in our days, patients with psoriasis are confronted with stigmatization and social rejection. As a result, their quality of life is significantly impaired. Biological therapies have revolutionized the treatment of moderate to severe psoriasis. The aim of this paper is to look over the most important biological therapies available for the management of plaque-type psoriasis.

Capsaicin: Friend or Foe in Skin Cancer and Other Related Malignancies?

Capsaicin is the main pungent in chili peppers, one of the most commonly used spices in the world; its analgesic and anti-inflammatory properties have been proven in various cultures for centuries. It is a lipophilic substance belonging to the class of vanilloids and an agonist of the transient receptor potential vanilloid 1 receptor. Taking into consideration the complex neuro-immune impact of capsaicin and the potential link between inflammation and carcinogenesis, the effect of capsaicin on muco-cutaneous cancer has aroused a growing interest. The aim of this review is to look over the most recent data regarding the connection between capsaicin and muco-cutaneous cancers, with emphasis on melanoma and muco-cutaneous squamous cell carcinoma.

Kyrle's Disease in a Patient with Delusions of Parasitosis.

Acquired perforating disorders are a group of uncommon skin conditions characterized by transepidermal extrusion of altered dermal material, most often associated with diabetes mellitus and chronic kidney failure. Delusional parasitosis is a primary psychiatric disorder in which affected patients have fixed, false beliefs that their skin is infested by parasites, in the absence of any evidence supporting their statements. A 69 year old malepatient addressed the Dermatology Department for a skin eruption consisting of multiple umbilicated keratotic papules with a generalized distribution. The patient believed that the lesions were produced by small parasites entering and exiting his skin. The histopathological examination confirmed the clinical diagnosis of Kyrle's disease. The psychiatric examination established the diagnosis of delusions of parasitosis. This is the first reported case of Kyrle's disease associated with delusions of parasitosis. There is no evidence supporting the hypothesis that delusions of parasitosis might be a predisposing factor for Kyrle's disease. However, we believe that the pruritic dermatosis might have triggered the delusions of parasitosis due to the associated pruritus. On the other hand the constant excoriations and traumatizing of a skin prone to develop idiopathic Kyrle's disease in the attempt to remove the parasites prevented the complete resolution of the lesions.