Prevalence and Characterization of Pruritus in Epidermolysis Bullosa

Qualitative data suggest that pruritus is a burdensome symptom in patients with epidermolysis bullosa (EB), but the prevalence of pruritus in children and adults with EB and factors that contribute to pruritus are unknown. The objective of the current study was to quantitatively identify and to characterize pruritus that EB patients experience using a comprehensive online questionnaire. A questionnaire was developed to evaluate pruritus in all ages and all types of EB. Questions that characterize pruritus were included and factors that aggravate symptoms were investigated. Patients from seven North American EB centers were invited to participate. One hundred forty‐six of 216 questionnaires were completed (response rate 68%; 73 male, 73 female; median age 20.0 years). Using a 5‐point Likert scale (1 = never, 2 = rarely, 3 = sometimes, 4 = often, 5 = always), itchiness was the most bothersome EB complication (mean 3.3). The average daily frequency of pruritus increased with self‐reported EB severity. Pruritus was most frequent at bedtime (mean 3.8) and interfered with sleep. Factors that aggravated pruritus included healing wounds, dry skin, infected wounds, stress, heat, dryness, and humidity. Pruritus is common in individuals with EB and can be bothersome. Future studies will need to investigate the most effective treatments given to individuals with EB for pruritus.     

Increased expression of fibroblast activation protein-alpha in keloid fibroblasts: implications for development of a novel treatment option

Keloid scars are common benign fibroproliferative reticular dermal lesions with unknown etiology and ill-defined management with high rate of recurrence post surgery. The progression of keloids is characterized by increased deposition of extracellular matrix proteins, invasion into the surrounding healthy skin and inflammation. Fibroblasts are considered to be the key cellular mediators of fibrogenesis in keloid scars. Fibroblast activation protein alpha (FAP-α) and dipeptidyl peptidase IV (DPPIV) are proteases located at the plasma membrane promoting cell invasiveness and tumor growth and have been previously associated with keloid scars. Therefore, in this study we analyzed in further detail the expression of FAP-α in keloid fibroblasts compared to control skin fibroblasts. Dermal fibroblasts were obtained from punch-biopsies from the active margin of four keloids and four control skin samples. Flow cytometry was used to analyze FAP-α expression and the CytoSelect^® 24-Well Collagen I Cell Invasion Assay was applied to study fibroblast invasion. Secretion of extracellular matrix (ECM) proteins was investigated by multiplexed particle-based flow cytometric assay and enzyme-linked immunosorbent assay. We found an increased expression of FAP-α in keloid fibroblasts compared to control skin fibroblasts (p < 0.001). Inhibition of FAP-α/DPPIV activity using the irreversible inhibitor H₂N-Gly-Pro diphenylphosphonate reduced the increased invasiveness of keloid fibroblasts (p < 0.001) indicating that keloid invasion may be partly FAP-α/DPPIV mediated. FAP-α/DPPIV inhibition had no effect, (a) on the synthesis of the ECM proteins procollagen type I C-terminal peptide and fibronectin, (b) on the production of fibroblast growth factor or vascular endothelial growth factor, (c) on the expression of the proinflammatory cytokines interleukin-6 (IL-6), interleukin 8 (IL-8) or monocyte chemotactic protein-1. These results suggest a potential role for FAP-α and DPPIV in the invasive behavior of keloids. FAP-α and DPPIV may increase the invasive capacity of keloid fibroblasts rather than by modulating inflammation or ECM production. Since FAP-α expression is restricted to reactive fibroblasts in wound healing and normal adult tissues are generally FAP-α negative, inhibiting FAP-α/DPPIV activity may be a novel treatment option to prevent keloid progression.     

Nicotinamide and skin cancer chemoprevention: The jury is still out

Following the publication of the results of a Phase III trial, the administration of oral nicotinamide has been widely advocated as effective in non‐melanoma skin cancer chemoprevention in high‐risk individuals. However, I performed a Bayesian analysis of the reported findings and show there is insufficient evidence to demonstrate its efficacy, highlighting the significant probability that the positive conclusions drawn will not be reproducible. Given the potential widespread use of oral nicotinamide, future position statements regarding its efficacy are likely to require higher standards of evidence.     

A support vector machine for decision support in melanoma recognition

Please cite this paper as: A support vector machine for decision support in melanoma recognition. Experimental Dermatology 2010; 19 : 830–835. Abstract: The early diagnosis of melanoma is critical to achieving reduced mortality and increased survival. Although clinical examination is currently the method of choice for melanocytic lesion assessment, difficulties may arise in the diagnosis of atypical lesions. From both the naked eye and dermoscopic perspective, dysplastic naevi often exhibit a prominent heterogeneity of structure that renders their clinical distinction from melanoma difficult. To address these problems in diagnosis, there exists a heightened interest among researchers regarding the utility of machine learning techniques in computerised image analysis. Here we report on the utility, for dermatologists, of support vector machine (SVM) technology in melanoma diagnosis, using an archive of 199 digital dermoscopic images of excised atypical melanocytic lesions. Our best validation models achieved an average sensitivity and specificity for melanoma diagnosis of 0.86 and 0.72, respectively. Applying the best model to our test set yielded a sensitivity of 0.89, a diagnostic odds ratio of 14.09 and an area under the receiver operated characteristic curve (AUC) of 0.76. Advantages of the procedure implemented are the simplicity of feature extraction and the computationally cheap and efficient nature of SVMs. The derived model generalises well with outcomes that compare favourably with competing algorithms and expert assessment. In line with the concept of the utility of decision support systems in clinical practice, we propose that to reduce the risk of missed melanomas, both the dermatologists’ assessment and the SVM diagnosis be incorporated into the clinical decision‐making process.     

Deletion of 8p: a report of a child with normal intelligence

The case is presented of a female infant with a distal deletion of 8p (8p23.1-->pter) whose development was monitored over a 5-year period from 12 months of age. Although previous literature has suggested that 8p deletion is associated with mild to moderate intellectual disability, the child reported here has normal intelligence. Despite initial delays in gross motor and language skills, cognitive development (assessed with the Bayley Scales of Infant Development) and intellectual ability (measured on the Stanford-Binet Intelligence Scale) were within average range. It is argued that the small number of previous case reports may have created a misleading impression of intellectual development in individuals with distal deletions of 8p.