Comparison of methods to estimate the affected body surface area and the dosage of topical treatments in psoriasis and atopic dermatitis: the advantage of a picture-based tool.

BACKGROUND: The accurate determination of the dosage of topical treatments is important given its repercussions on patient adherence and therapeutic efficacy. Up till now, the fingertip unit calculated by the rule of hands is considered the gold standard, although its use is associated with several drawbacks. OBJECTIVE: To compare different methods to estimate the affected body surface area (BSA) and dosage of topical treatments in atopic dermatitis and psoriasis and investigate its reliability, user-friendliness and timing. METHODS: In this study, we compared the reliability of three different methods: (i) the fingertip unit calculated by the 1% hand rule; (ii) a picture-based tool [termed Cutaneous Inflammatory Disease Extent Score (CIDES)]; and (iii) a digital drawing tool. Eleven observers scored 40 patients with psoriasis and eczema to assess the inter-rater and intrarater reliability. Timing was automatically recorded, and user-friendliness was investigated by a questionnaire. RESULTS: An excellent intraclass correlation (ICC) was found for both inter-rater agreement and intrarater agreement for the picture-based tool (ICC = 0.92 and ICC = 0.96, respectively). The ICCs for drawing the area of involvement on a silhouette were 0.89 and 0.93, respectively. Finally, the rule of hands was associated with an increased inter-rater variability although an excellent intrarater agreement was found (ICC = 0.79 and 0.95, respectively). Automated calculation of the amount of topical treatment improved reliability, and CIDES was associated with the least variation. CIDES was considered the preferred method by all observers and was fast to perform (median: 30 s). CONCLUSION: A picture-based method offered the most advantages (in terms of reliability, speed and user-friendliness) to estimate the affected BSA and calculate the dosage of topical treatments.

Infrared spectroscopy as a novel tool to diagnose onychomycosis.

BACKGROUND: The determination of causative organisms of onychomycosis is still not optimal. There remains a need for a cheap, fast and easy-to-perform diagnostic tool with a high capacity to distinguish between organisms. OBJECTIVES: To determine whether attenuated total-reflectance Fourier transform infrared (ATR-FTIR) spectroscopy can detect and differentiate causative agents in culture-based, ex vivo nail and in vivo nail models. METHODS: A methodological study was conducted. Both the ex vivo nail model and in vivo pilot study were carried out in an academic university hospital. RESULTS: Analysis of cultured fungi revealed spectral differences for dermatophytes (1692-1606 and 1044-1004 cm-1 ) and nondermatophytes and yeasts (973-937 cm-1 ), confirmed by dendrograms showing an excellent separation between samples from different genera or species. Exploration of dermatophytes, nondermatophytes and yeasts growing on ex vivo nails exposed prominent differences from 1200 to 900 cm-1 . Prediction models resulted in a 96·9% accurate classification of uninfected nails and nails infected with dermatophytes, nondermatophytes and yeasts. Overall correct classification rates of 91·0%, 97·7% and 98·6% were obtained for discrimination between dermatophyte, nondermatophyte and yeast genera or species, respectively. Spectra of in vivo infected and uninfected nails also revealed distinct spectral differences (3000-2811 cm-1 , 1043-950 cm-1 and 1676-1553 cm-1 ), illustrated by two main clusters (uninfected vs. infected) on a dendrogram. CONCLUSIONS: Our data suggest that ATR-FTIR spectroscopy may be a promising, fast and accurate method to determine onychomycosis, including identification of the causative organism, bypassing the need for lengthy fungal cultures.

Characteristics of high- and low-risk individuals in the PRIORITY study: urinary proteomics and mineralocorticoid receptor antagonism for prevention of diabetic nephropathy in Type 2 diabetes.

AIM: To compare clinical baseline data in individuals with Type 2 diabetes and normoalbuminuria, who are at high or low risk of diabetic kidney disease based on the urinary proteomics classifier CKD273. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled international multicentre clinical trial and observational study in participants with Type 2 diabetes and normoalbuminuria, stratified into high- or low-risk groups based on CKD273 score. Clinical baseline data for the whole cohort and stratified by risk groups are reported. The associations between CKD273 and traditional risk factors for diabetic kidney disease were evaluated using univariate and logistic regression analysis. RESULTS: A total of 1777 participants from 15 centres were included, with 12.3% of these having a high-risk proteomic pattern. Participants in the high-risk group (n=218), were more likely to be men, were older, had longer diabetes duration, a lower estimated GFR and a higher urinary albumin:creatinine ratio than those in the low-risk group (n=1559, P<0.02). Numerical differences were small and univariate regression analyses showed weak associations (R2 < 0.04) of CKD273 with each baseline variable. In a logistic regression model including clinical variables known to be associated with diabetic kidney disease, estimated GFR, gender, log urinary albumin:creatinine ratio and use of renin-angiotensin system-blocking agents remained significant determinants of the CKD273 high-risk group: area under the curve 0.72 (95% CI 0.68-0.75; P<0.01). CONCLUSIONS: In this population of individuals with Type 2 diabetes and normoalbuminuria, traditional diabetic kidney disease risk factors differed slightly between participants at high risk and those at low risk of diabetic kidney disease, based on CKD273. These data suggest that CKD273 may provide additional prognostic information over and above the variables routinely available in the clinic. Testing the added value will be subject to our ongoing study. (European Union Clinical Trials Register: EudraCT 2012-000452-34 and Clinicaltrials.gov: NCT02040441).

Can increased vigilance for chronic kidney disease in hospitalised patients decrease late referral and improve dialysis-free survival?

BACKGROUND: Insufficient vigilance for renal insufficiency is associated with late referral, increased morbidity and mortality. The present study examines whether increased vigilance for chronic kidney disease (CKD) leads to quicker referral to and better follow-up by a nephrologist, and whether it is associated with an improved outcome. METHODS: Patients with an eGFR < 45 ml/min/1.73 m2 during hospitalisation at the Ghent University Hospital were enrolled during a period of 100 days. The patients were interviewed about their awareness of CKD. Both the patients and their general practitioner were subsequently informed about CKD. The primary endpoint was the number of patients referred for nephrological follow-up within three months. The secondary endpoint was need for dialysis and mortality from any cause one year after inclusion. RESULTS: Of the 72 included patients, 54 had proven CKD, with eGFR consistently < 45 ml/min/1.73 m2 during at least three months before inclusion. Merely 65% was aware of having CKD and only 41% was in regular nephrological follow-up. After intervention, the percentage of patients with CKD in follow-up increased from 41% to 71% (p = 0.002). The proportion reaching the secondary endpoint was significant lower in the patients who were referred quickly than in those who were not (p = 0.015). Similarly, the proportion was significant lower in the patients who received nephrological follow-up than in those who did not (p = 0.006). CONCLUSION: Vigilance for CKD is poor. Simple interventions to augment the vigilance for CKD, as presented in this study, lead to a quicker referral to and follow-up by a nephrologist, which may result in better outcome.

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.

Biomarkers of disease activity in vitiligo: A systematic review.

The pathophysiology of vitiligo is complex although recent research has discovered several markers which are linked to vitiligo and associated with disease activity. Besides providing insights into the driving mechanisms of vitiligo, these findings could reveal potential biomarkers. Activity markers can be used to monitor disease activity in clinical trials and may also be useful in daily practice. The aim of this systematic review was to document which factors have been associated with vitiligo activity in skin and blood. A second goal was to determine how well these factors are validated in terms of sensitivity and specificity as biomarkers to determine vitiligo activity. Both in skin (n=43) as in blood (n=66) an adequate number of studies fulfilled the predefined inclusion criteria. These studies used diverse methods and investigated a broad range of plausible biomarkers. Unfortunately, sensitivity and specificity analyses were scarce. In skin, simple histopathology with or without supplemental CD4 and CD8 stainings can still be considered as the gold standard, although more recently chemokine (C-X-C motif) ligand (CXCL) 9 and NLRP1 have demonstrated a good and possibly even better association with progressive disease. Regarding circulating biomarkers, cytokines (IL-1ß, IL-17, IFN-γ, TGF-ß), autoantibodies, oxidative stress markers, immune cells (Tregs), soluble CDs (sCD25, sCD27) and chemokines (CXCL9, CXCL10) are still competing. However, the two latter may be preferable as both chemokines and soluble CDs are easy to measure and the available studies display promising results. A large multicenter study could make more definitive statements regarding their sensitivity and specificity.

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.

Clinical profile of generalized vitiligo patients with associated autoimmune/autoinflammatory diseases.

BACKGROUND: The significance of associated autoimmune/autoinflammatory diseases in generalized vitiligo patients with respect to their clinical profile has not yet been completely established. OBJECTIVE: The objective of this study was to evaluate the clinical significance of associated autoimmune/autoinflammatory diseases in generalized vitiligo patients with respect to some general clinical variables, distribution pattern, disease activity and treatment response. METHODS: Seven hundred generalized vitiligo patients were included in this retrospective observational cohort study. RESULTS: Associated autoimmune/autoinflammatory diseases were present in 15.4% of the patient population and were more common in women compared with men, especially concerning thyroid disease. Only vitiligo patients with thyroid disease had clear different clinical characteristics. The percentage of total body surface area involvement was significantly (P = 0.005) higher in the presence of thyroid disease which was more pronounced in women compared with men. Patients with thyroid disease had a particular predisposition to acral and joint depigmentations. No clear differences in disease activity or response to therapy were observed in vitiligo patients with or without autoimmune/autoinflammatory disorders. CONCLUSION: The presence of associated autoimmune/autoinflammatory diseases seems to influence the clinical profile of generalized vitiligo patients. Our results support the hypothesis that in the presence of a thyroid disorder, the disease activity of vitiligo is more extensive, in particular on areas prone to friction.

The distribution pattern of segmental vitiligo: clues for somatic mosaicism.

BACKGROUND: Segmental vitiligo is characterized by a unilateral and localized distribution. So far, the underlying mechanism is still an enigma. OBJECTIVES: To get an insight into the aetiopathogenesis of segmental vitiligo by comparison with the distribution pattern of dermatoses with a possible mosaic or neurogenic background. METHODS: In this retrospective observational study the distribution pattern of 724 unilateral, linear or band-shaped control lesions was compared with 181 segmental vitiligo lesions. Clinical photographs were used to score similarities according to a defined grading system (scale ranging from 0 for no similarities to 4 for complete similarity). Control lesions were evaluated both individually and after grouping into different cell types. RESULTS: In general, only a minority of cases (36·9%), showed similarities (grade 1-4) between control lesions and segmental vitiligo. Grade 2-4 similarities were seen mainly in segmental lentiginosis (73·7%, P < 0·001). The best grade for correspondence (grade 3-4) was observed significantly more only in segmental lentiginosis (36·8% vs. 3·5%, P<0·001) and epidermal naevus verrucosus (12·5% vs. 3·7%, P=0·008) compared with the other control lesions. The distribution pattern of segmental vitiligo significantly overlapped those of other disorders originating from melanocytes. CONCLUSIONS: Our results demonstrate that the distribution pattern of segmental vitiligo is not entirely similar to any other skin disease, although some mosaic skin disorders have more overlap with segmental vitiligo than others. The remarkable clinical similarity with several cases of mosaic diseases involving melanocytes supports the hypothesis that cutaneous mosaicism may be involved in segmental vitiligo.

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.

The pre-analytical challenges of routine urinalysis.

An effective diagnostic strategy for urinalysis should be based on standard procedures for collection, transport, sample preparation and analysis. In view of a better reproducibility of the analyses, the pre-analytical requirements become stricter. Various sample methods can cause significant pre-analytical errors. It is a challenge for the laboratory to control the steps in the pre-analytical phase that contribute to pre-analytical variability. To reduce the variability, it is necessary to look at the pre-analytical process as a complete entity, from test ordering to the moment of specimen processing. Clinical laboratories are responsible for the clinical and financial outcome of this phase. In a culture of increasing productivity, lower costs and improving quality, the challenge is to use several tools designed to standardize and optimize urinalysis. Despite advances in the performance of analytic systems, the pre-analytical phase of modern urinalyses has not been studied very thoroughly. This review of the literature lights on different problems in current pre-analytical requirements for particle and test strip analysis of urine samples.

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.