Hans Alkemade

Constitutive and inducible expression of SKALP/elafin provides anti-elastase defense in human epithelia.

Skin-derived antileukoproteinase (SKALP), also known as elafin, is a serine proteinase inhibitor first discovered in keratinocytes from hyperproliferative human epidermis. In addition to the proteinase inhibiting domain which is directed against polymorphonuclear leukocyte (PMN) derived enzymes such as elastase and proteinase 3, SKALP contains multiple transglutaminase (TGase) substrate domains which enable crosslinking to extracellular and cell envelope proteins. Here we show that SKALP is constitutively expressed in several epithelia that are continuously subjected to inflammatory stimuli, such as the oral cavity and the vagina where it co-localizes with type 1 TGase. All epithelia from sterile body cavities are negative for SKALP. In general, stratified squamous epithelia are positive, whereas pseudostratified epithelia, simple/glandular epithelia and normal epidermis are negative. SKALP was found in fetal tissues of the oral cavity from 17 wk gestation onwards where it continued to be expressed up to adult life. Remarkably, in fetal epidermis SKALP was found from week 28 onwards, but was downregulated to undetectable levels in neonatal skin within three months, suggesting a role during pregnancy in feto-maternal interactions or in the early maturation phase of the epidermis. Immunoelectron microscopy revealed the presence of SKALP in secretory vesicles including the lamellar granules. In culture models for epidermal keratinocytes we found that expression of the endogenous SKALP gene provided protection against cell detachment caused by purified elastase or activated PMNs. Addition of exogenous recombinant SKALP fully protected the keratinocytes against PMN-dependent detachment whereas superoxide dismutase and catalase were only marginally effective. These findings strongly suggest that the constitutive expression of SKALP in squamous epithelia, and the inducible expression in epidermis participate in the control of epithelial integrity, by inhibiting PMN derived proteinases.

No increased risk of cancer after coal tar treatment in patients with psoriasis or eczema.

Coal tar is an effective treatment for psoriasis and eczema, but it contains several carcinogenic compounds. Occupational and animal studies have shown an increased risk of cancer after exposure to coal tar. Many dermatologists have abandoned this treatment for safety reasons, although the risk of cancer after coal tar in dermatological practice is unclear. This large cohort study included 13,200 patients with psoriasis and eczema. Information on skin disease and treatment, risk factors, and cancer occurrence was retrieved from medical files, questionnaires, and medical registries. Proportional hazards regression was used to evaluate differences in cancer risk by treatment modality. Patients treated with coal tar were compared with a reference category of patients treated with dermatocorticosteroids (assumed to carry no increased cancer risk). The median exposure to coal tar ointments was 6 months (range 1-300 months). Coal tar did not increase the risk of non-skin malignancies (hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.78-1.09), or the risk of skin cancer (HR 1.09; 95% CI 0.69-1.72). This study has sufficient power to show that coal tar treatment is not associated with an increased risk of cancer. These results indicate that coal tar can be maintained as a safe treatment in dermatological practice.

Current and future treatment options for acne.

Acne is a frequent skin disease with abnormalities in the process of keratinization, sebaceous gland functioning and inflammation. In this review, our understanding of the pathogenesis of acne has been updated. An overview of efficacy and side effects of available anti‐acne treatments is presented. Based on the present overview a recommendation for the treatment of various manifestations of acne is provided, also reconciling beneficial combinations of treatments. It is attractive to speculate that the increased insight into the pathogenesis of acne will create new treatment options. Challenging new options comprise blue light, photodynamic therapy, retinoic acid metabolism blocking agents and inhibitors of Th‐1 cytokines.

A simple tool with which to study the course of chronic hand eczema in clinical practice: a reduced-item score

Physicians need a simple, disease‐specific tool with which to assess disease severity and the effect of therapeutic intervention in patients with chronic hand eczema. The currently available clinical scoring systems include numerous items, which makes them laborious to complete and limit their use in daily practice.

Diagnosis of Basal Cell Carcinoma by Reflectance Confocal Microscopy: Study Design and Protocol of a Randomized Controlled Multicenter Trial

Background Skin cancer, including basal cell carcinoma (BCC), has become a major health care problem. The limitations of a punch biopsy (at present the gold standard) as diagnostic method together with the increasing incidence of skin cancer point out the need for more accurate, cost-effective, and patient friendly diagnostic tools. In vivo reflectance confocal microscopy (RCM) is a noninvasive imaging technique that has great potential for skin cancer diagnosis. Objective To investigate whether in vivo RCM can correctly identify the subtype of BCC and to determine the cost-effectiveness of RCM compared with punch biopsy (usual care). Study design: Randomized controlled multicenter trial. Methods On the basis of 80% power and an alpha of 0.05, 329 patients with lesions clinically suspicious for BCC will be included in this study. Patients will be randomized for RCM or for a punch biopsy (usual care). When a BCC is diagnosed, surgical excision will follow and a follow-up visit will be planned 3 months later. Several questionnaires will be filled in (EQ-5D, EQ-5D VAS, iMTA PCQ, and TSQM-9). We will perform statistical analysis, cost-effectiveness, and patient outcome analysis after data collection. Results This research started in January 2016 and is ethically approved. We expect to finish this study at the end of 2018. Conclusions In this study, we will investigate whether RCM is at least as good in identifying BCC subtypes as conventional pathological investigation of skin biopsies. Anticipating that RCM is found to be a cost-effective alternative, it saves on direct medical consumption like labor of the pathologist and other medical personnel as well as materials related to treatment failure with at least equal effectiveness. Trial Registration Clinicaltrials.gov NCT02623101; https://clinicaltrials.gov/ct2/show/NCT02623101 (Archived by WebCite at http://www.webcitation.org/6id54WQa2)

Real-life Data on Patient Characteristics, Cost and Effectiveness of Field-directed Treatment for Actinic Keratoses: An Observational Study

Actinic keratoses (AK) occur frequently; however, real-life clinical data on personalized treatment choice and costs are scarce. This multicentre one-year observational study investigated patient-characteristics, cost and effectiveness of methylaminolaevulinate photodynamic therapy (MAL-PDT), imiquimod (IMI) and 5-fluorour-acil (5-FU) in patients with AKs on the face/scalp. A total of 104 patients preferred MAL-PDT, 106 preferred IMI and 110 preferred 5-FU. At baseline, significant differences between treatment groups were found; most patients were severely affected (mean 32.5 AK in PDT-group, 20.2 in IMI-group, 22.8 in 5-FU-group). A mean reduction in lesions of 81% after MAL-PDT, 82% after IMI and 88% after 5-FU was found after one year. Annual costs were €1,950 for MAL-PDT, €877 for IMI and €738 for 5-FU. These results show that, compared with clinical trials, in the real-life clinical setting AK patients are usually more severely affected and treatment costs are much higher. Furthermore, patient characteristics are important factors in treatment choice.