Diane Roseeuw

Randomized trial comparing cryopreserved cultured epidermal allografts with hydrocolloid dressings in healing chronic venous ulcers

BACKGROUND Cultured epidermal allografts have been successfully used to treat a variety of wounds. Their postulated mechanism of action is through release of cytokines that stimulate epithelialization. On the basis of previous experience we expected ulcers treated with cryopreserved cultured allografts (CCAs) to be healed by 6 weeks. Hydrocolloid dressings (HCDs) have also been reported to be effective in the treatment of venous ulcers. OBJECTIVE Our purpose was to compare the effectiveness of CCAs with HCDs in healing chronic venous ulcers. METHODS Forty-three patients with 47 ulcers were enrolled in a randomized controlled trial. Ulcers not healed by 6 weeks were changed to the other treatment. RESULTS No difference in the number of healed ulcers between the two groups was observed at 6 weeks. Healing rate, percent reduction of initial ulcer size, and radial progression toward wound closure were significantly greater for CCAs than for HCDs. Pain relief was not significantly different. CONCLUSION CCAs achieve more rapid healing and greater reduction in ulcer size than HCDs.

Is combined oral and topical therapy better than oral therapy alone in patients with moderate to moderately severe acne vulgaris? A comparison of the efficacy and safety of lymecycline plus adapalene gel 0.1%, versus lymecycline plus gel vehicle.

This multicenter, randomized, investigator-blinded study compared the efficacy and tolerability of a combination of lymecycline 300 mg/day orally and adapalene topical gel 0.1% (n = 118) to lymecycline 300 mg/day orally plus vehicle gel (n = 124) in patients with moderate to moderately severe acne vulgaris with both inflammatory and noninflammatory lesions. The primary efficacy end point, total lesion count at end point (last observation carried forward), showed a statistically significant difference in favor of the lymecycline plus adapalene group (P =.0011). The mean decrease in total, inflammatory and noninflammatory lesion counts was significantly greater at end point in the lymecycline plus adapalene group than in the lymecycline plus vehicle group (P <.01). In addition, a significant difference for inflammatory and total acne lesions was seen sooner in the adapalene plus lymecycline group. In total, 75.5% of patients in the lymecycline plus adapalene group were markedly improved, almost clear or clear of their lesions at week 12, compared with 51.8% of those in the lymecycline plus vehicle group (P <.001). Local cutaneous tolerance was generally good in both groups, although more patients receiving the lymecycline plus adapalene combination experienced cutaneous reactions than those receiving lymecycline plus vehicle. There are relatively few studies comparing the efficacy of combined oral and topical therapy with either individual therapy alone. This study clearly demonstrates that lymecycline plus adapalene combination treatment resulted in a significantly greater mean decrease in the number of inflammatory, noninflammatory and total lesions than lymecycline plus vehicle and was well tolerated.

New approaches to the treatment of onychomycosis

The purpose of this article is to review the pharmacologic properties of two newer agents, itraconazole and terbinafine, and to assess their clinical efficacy in onychomycosis. Both drugs are effective in treating infections caused by dermatophytes. Itraconazole appears to be more efficacious in infections caused by Candida species. The improved effectiveness of these agents is probably related to their rapid penetration into the nails and prolonged bioavailability at the site of infection.

Genotypic and Gene Expression Studies in Congenital Melanocytic Nevi: Insight into Initial Steps of Melanotumorigenesis

Large congenital melanocytic nevi (CMNs) are said to have a higher propensity to malignant transformation compared with acquired nevi. Thus, they represent a good model for studying initial steps of melanotumorigenesis. We have performed genotypic (karyotype, fluorescence in situ hybridization, and mutational analyses) and differential expression studies on a large cohort of medium (n=3) and large (n=24) CMN. Chromosomal abnormalities were rare and single, a feature probably reflecting the benignity of these lesions. Mutational screening showed a high frequency of NRAS mutations in our series (19/27 cases, 70%), whereas BRAF mutations were less common (4/27 cases, 15%). Differential did not show significant alterations of cellular processes such as cell proliferation, cell migration/invasion, angiogenesis, apoptosis, and immune/inflammatory responses. However, significant downregulation of genes involved in pigmentation and upregulation of genes playing a role in DNA protection were observed. Lastly, our microarrays displayed upregulation of genes mediating chemoresistance in cancer. As alteration of pigmentation mechanisms can trigger oxidative damage, increased expression of genes involved in maintenance of DNA integrity might reflect the ability of nevocytic cells to self-protect against cellular stress. Furthermore, the observed alterations linked to chemoresistance might partially account for the well-known inefficacy of chemotherapy in malignant melanoma.

Increased history of childhood and lifetime traumatic events among adults with alopecia areata

BACKGROUND Whether adult alopecia areata (AA) is associated with childhood or total lifetime traumatic events is not known. Previous studies have investigated only the relationship with recent stressful events. OBJECTIVE We sought to determine whether patients with AA experience more childhood or total lifetime traumatic events, as measured by the Traumatic Experiences Checklist. METHODS Using a case-control study, data on 90 patients with AA and 91 control subjects were analyzed. RESULTS Significantly more patients with AA experienced total lifetime and early childhood traumatic events, with an odds ratio of 2.46 (95% confidence interval 1.15-5.28; P = .017) and 2.16 (1.15-4.06; P = .016), respectively. In patients with AA, the global impact score related to their traumatic experiences was significantly higher than in control subjects (P < .001). In addition, patients with AA experienced significantly more emotionally and physically traumatic events. LIMITATION This case-control study is susceptible to recall bias and to confounding factors associated with stress caused by AA outbreaks or by a traumatic childhood history. CONCLUSION Our study documents an increased history of childhood trauma in patients with AA compared with control subjects.

Management of scars: updated practical guidelines and use of silicones

Hypertrophic scars and keloids resulting from surgery, burns, trauma and infection can be associated with substantial physical and psychological distress. Various non-invasive and invasive options are currently available for the prevention and treatment of these scars. Recently, an international multidisciplinary group of 24 experts on scar management (dermatologists; plastic and reconstructive surgeons; general surgeons; physical medicine, rehabilitation and burns specialists; psychosocial and behavioural researchers; epidemiologists; beauticians) convened to update a set of practical guidelines for the prevention and treatment of hypertrophic and keloid scars on the basis of the latest published clinical evidence on existing scar management options. Silicone-based products such as sheets and gels are recommended as the gold standard, first-line, non-invasive option for both the prevention and treatment of scars. Other general scar preventative measures include avoiding sun exposure, compression therapy, taping and the use of moisturisers. Invasive treatment options include intralesional injections of corticosteroids and/or 5-fluorouracil, cryotherapy, radiotherapy, laser therapy and surgical excision. All of these options may be used alone or as part of combination therapy. Of utmost importance is the regular re-evaluation of patients every four to eight weeks to evaluate whether additional treatment is warranted. The amount of scar management measures that are applied to each wound depends on the patient’s risk of developing a scar and their level of concern about the scar’s appearance. The practical advice presented in the current guidelines should be combined with clinical judgement when deciding on the most appropriate scar management measures for an individual patient.

Feeder layer- and animal product-free culture of neonatal foreskin keratinocytes: improved performance, usability, quality and safety

Since 1987, keratinocytes have been cultured at the Queen Astrid Military Hospital. These keratinocytes have been used routinely as auto and allografts on more than 1,000 patients, primarily to accelerate the healing of burns and chronic wounds. Initially the method of Rheinwald and Green was used to prepare cultured epithelial autografts, starting from skin samples from burn patients and using animal-derived feeder layers and media containing animal-derived products. More recently we systematically optimised our production system to accommodate scientific advances and legal changes. An important step was the removal of the mouse fibroblast feeder layer from the cell culture system. Thereafter we introduced neonatal foreskin keratinocytes (NFK) as source of cultured epithelial allografts, which significantly increased the consistency and the reliability of our cell production. NFK master and working cell banks were established, which were extensively screened and characterised. An ISO 9001 certified Quality Management System (QMS) governs all aspects of testing, validation and traceability. Finally, as far as possible, animal components were systematically removed from the cell culture environment. Today, quality controlled allograft production batches are routine and, due to efficient cryopreservation, stocks are created for off-the-shelf use. These optimisations have significantly increased the performance, usability, quality and safety of our allografts. This paper describes, in detail, our current cryopreserved allograft production process.

Beneficial effects of a skin tolerance-tested moisturizing cream on the barrier function in experimentally-elicited irritant and allergic contact dermatitis

In experimentally‐induced irritant (ICD) and allergic (ACD) contact dermatitis, an oil‐in‐water (o/w) cream was applied to investigate its effects on a disturbed barrier function compared to untreated physiological barrier repair. Transepidermal water loss (TEWL) measurements were performed. Before the start of the experiments, the skin tolerance of the cream was examined, revealing the non‐irritating characteristics of the ingredients and the absence of any contact allergic patch test reaction. In the ICD study, sodium lauryl sulfate (SLS) patches were applied to the forearms of young female volunteers. Consequently, it was observed that repeated cream application (14 days, 2×/day) significantly improved the TEWL of SLS‐damaged skin, leading to a complete recovery on day 15. In the ACD study, disruption of skin barrier function was obtained by a nickel‐mediated contact allergy patch (CAP) test. The cream was then applied 2×/day for 4 consecutive days. Assessment of TEWL clearly showed that recovery of the disrupted skin significantly improved after cream application in comparison to untreated barrier repair.

Evaluation of biophysical and clinical parameters of skin barrier function among hospital workers

The goal of this study was to evaluate biophysically and clinically the hand skin of nurses working in the operating room in comparison with the hand skin of a control group of female administrative employees. 19 nurses and 14 employees were included in this trial. Transepidermal water loss (TEWL) and stratum corneum (SC) hydration were evaluated on 4 different test sites − dominant and non‐dominant pulse, and dominant and non‐dominant hand dorsum. The clinical score Dermatology Life Quality Index (DLQI) and subjective evaluation of skin sensitivity were also recorded. In comparison with the control group, TEWL values among nurses were significantly higher on all test sites, while SC hydration was significantly lower on 3 of the 4 test sites. In addition, clinical score showed the presence of irritant contact dermatitis (ICD). DLQI reported a higher level of disability among the nurses group, while the subjective evaluation of skin sensitivity was identical in both groups. The results suggest the presence of skin barrier alterations and clinical signs of chronic ICD on the hands of nurses working in operating room units.

Analysis of Epidermal Lipids of the Healthy Human Skin: Factors Affecting the Design of a Control Population

The intervariability of studies on the lipids of human epidermis and stratum corneum is high because of the different origin of the skin samples and the variety of extraction methods used. In the present work, a high-performance thin-layer chromatographic technique has been used to study the parameters age, sex, and anatomical site for their effects on the lipid profiles recovered from healthy epidermal skin biopsy specimens. It was found that sex-related differences were seen at the level of the total ceramide concentration. Observed decreases in lipid concentration, due to ageing, depended on the anatomical site. Therefore, these variables should be controlled in a reproducible and standardized way in order to be able to study the direct relationship between skin condition and barrier lipid composition. Only when this relation is established, results of topical treatment can be scientifically evaluated.