Critical appraisal of the oxidative stress pathway in vitiligo: a systematic review and meta-analysis.

BACKGROUND: The pathogenesis of vitiligo remains a topic of extensive debate. This is partly due to the moderate efficacy of current treatments. The role of the oxidative stress pathway in vitiligo is a popular although controversial research topic. OBJECTIVE: To clarify the role of the oxidative stress pathway in vitiligo compared to other inflammatory skin disorders and to assess the therapeutic role of antioxidants. METHODS: We conducted a systematic search of the existing literature on the aberrancies of the oxidative stress pathway in vitiligo. Subsequently, the efficacy of both topical and oral antioxidants in clinical trials was investigated. RESULTS: A deregulated oxidative pathway is clearly evident with elevated superoxide dismutase, decreased catalase and increased lipid peroxidation. However, similar results have been obtained in other inflammatory skin diseases such as psoriasis, atopic dermatitis, lichen planus and urticaria. This questions the unique role of oxidative stress in the development of vitiligo. Some isolated successes have been reported with oral ginkgo biloba, polypodium leucotomos and vitamin C and E preparations, while other clinical trials have failed to show reproducible results. The use of topical antioxidants delivers in general no beneficial results. CONCLUSION: The oxidative pathway is affected in vitiligo, but its unique initiating or contributory role in the pathogenesis is less evident. Interesting data support the added value of oral antioxidants in vitiligo although confirmatory studies are missing.

The intriguing role of soluble urokinase receptor in inflammatory diseases.

Inflammation is a key player in the development of an increasing amount of diseases. The soluble urokinase plasminogen activator receptor (suPAR) is a highly flexible molecule with intrinsic chemotactic properties. This glycoprotein has been evaluated as a biomarker of inflammation, immune activation, organ damage and clinical outcome in several pathologies, including cardiovascular disease, hepatitis, renal disorders and rheumatic pathologies. The use of this early warning inflammatory biomarker could potentially improve the prediction of the severity of these diseases and mortality. In the present paper, we describe the general characteristics of suPAR and its intriguing role as a biomarker in different inflammatory diseases.

Secukinumab: IL-17A inhibition to treat psoriatic arthritis.

Interleukin-17A is an important cytokine in the pathogenesis of psoriatic arthritis. Secukinumab is a recombinant, high-affinity, fully human immunoglobulin G1kappa monoclonal antibody with a selective binding and neutralization of interleukin-17A. By providing an alternative mechanism of action to current treatments, secukinumab has shown efficacy in the key clinical domains of psoriatic arthritis. In the present paper, we discuss the role of interleukin-17A as a clinically relevant target in the treatment of psoriatic arthritis, based on preclinical findings, dose-ranging and regimen-finding, randomized, placebo-controlled clinical trials.

Detecting doping use: more than an analytical problem.

The recent Armstrong case, where more than 250 negative doping tests are confronted with the athlete's confession of erythropoietin use, blood doping, steroid, and growth hormone abuse, illustrates the limitations of current laboratory tests in detecting doping in sport. Despite numerous doping controls and simultaneous indications of common doping abuse among professional athletes in the last two decades, the number of positive urine tests for recombinant human erythropoietin (rHuEPO) remains remarkably low. Athletes are using various masking strategies, among them protease inhibitors, intravenous injections of rHuEPO and alternative erythropoiesis stimulating agents. As one of the countermeasures, the Athlete's Biological Passport has been introduced. The sensitivity of the Athlete's Biological Passport is limited if the effect of a low-dose doping remains within the intra-individual reference range. A possible solution could be the use of a novel Epo test (MAIIA Diagnostics). Another performance-enhancing strategy is the return to 'old' doping techniques, such as autologous blood transfusions. Several indirect methods to detect autologous blood transfusions have been proposed with the majority relying on changes in erythropoiesis-sensitive blood markers. Currently, an algorithm based on the haemoglobin (Hb) level concentration and the percentage of reticulocytes (OFF-hr model; Hb(g/l)-60·âˆš%ret) is approved by the World Anti-Doping Agency. Genetic factors have been identified which may interfere with test interpretation. A large inter- and intra-ethnic variation in testosterone glucuronidation and excretion has been described. Consideration of genetic variation should improve performance of the testosterone doping test. Taking into account the pre-analytical care and better tailoring of the threshold values could increase test sensitivity. Anti-doping laboratories should routinely adjust for multiple testing as failure of doping control to detect cheaters could lead to more frequent controls. Finally, despite the huge technological progress, there is a need for increased collaboration between physiologists, analytical chemists, biostatisticians, and ethicists to reduce doping in sport.

The haptoglobin phenotype influences the risk of cutaneous squamous cell carcinoma in kidney transplant patients.

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) is the most frequent skin cancer after organ transplantation. Currently, the pre-identification of transplant patients at increased risk for non-melanoma skin cancer remains difficult. OBJECTIVE: To investigate the Hp polymorphism as a marker for the identification of a subset of patients with an increased susceptibility to develop SCC/Bowen's disease. METHODS: Haptoglobin phenotyping was performed with haemoglobin-supplemented starch gel electrophoresis in 300 kidney transplant patients. High-performance gel permeation chromatography was used in case of low serum haptoglobin concentration. RESULTS: Cox regression analysis (adjusted for age, gender and Mediterranean origin) showed a significant association of the Hp 1-1 phenotype with a higher risk of SCC/Bowen's disease (P = 0.035) and multiple primary SCCs (P = 0.002). No significant difference between the Hp phenotypes was found for the development of Bowen's disease and SCCs in the first 10 years following renal transplantation. However, after a follow-up of >10 years, a significant association between the Hp 1-1 phenotype and the occurrence of Bowen's disease and SCC was reported (P = 0.002 and P = 0.001 respectively). CONCLUSIONS: This study shows an increased risk for the development of (multiple) SCCs in kidney transplant patients with the Hp 1-1 phenotype. This finding points to the role of Hp 1-1 phenotype as an important predictor in identifying a subset of patients with an increased need for preventive measures and is in agreement with the decreased anti-inflammatory capacity of this phenotype.

Immune reactions in benign and malignant melanocytic lesions: lessons for immunotherapy.

Spontaneous regression of benign and malignant melanocytic lesions can be a visible sign of immunosurveillance. In this review, we discuss different immune reactions against melanocytic lesions: halo nevus, Meyerson's nevus, regression in melanoma and melanoma-associated depigmentation. These entities present with particular clinical aspects, histology and evolution. In all entities, a melanocyte-specific T-cell reaction has been assumed but a different degree of melanocyte destruction is present. A focus on the immune responses in melanocytic lesions reveals several aspects of an adequate skin immunity and may help to identify the key points in the immune destruction of melanocytes. These insights can add to the knowledge of how to optimize immunotherapeutic strategies in melanoma.

Pelger-Huët anomaly: a critical review of the literature.

Pelger-Huët anomaly (PHA), an autosomal dominant haematological trait is characterised by neutrophil nuclear hypolobulation and modified chromatin distribution. Mutations in the lamin B receptor gene, a member of the sterol reductase family have been identified as the underlying cause. Due to its asymptomatic nature or lack of observer familiarity, PHA is often overlooked. In this review, we give an overview of the main pathophysiological, clinical, morphological and functional aspects of PHA. Furthermore, we highlight the importance of a comprehensive approach to the assessment of this laminopathy.