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Background: Percutaneous absorption of topically applied 0.05% clobetasol propionate (CLO) can be assessed indirectly by measuring cortisol levels. A direct way is to measure systemic levels of topically applied CLO., Methods: Serum concentrations of CLO were measured by liquid chromatography-tandem mass spectrometry (LC/MS/MS), and were related to serum cortisol levels in 25 patients with an exacerbation of atopic dermatitis (AD) before and after the first day of treatment with 0.05% CLO in hospital. The body surface area (BSA) affected by AD was measured., Results: Before the start of 0.05% CLO treatment, normal cortisol levels were measured (0.47 ± 0.18 μmol/l) and CLO concentrations could not be detected. After the first day of treatment, cortisol levels decreased to 0.04 ± 0.05 μmol/l. Serum concentrations of CLO could be detected in all patients (0.112-4.504 ng/ml). Levels did not differ between patients who had received two applications versus one application of 0.05% CLO. There was no correlation between the affected BSA and serum concentrations of CLO., Conclusion: Serum levels of CLO can be measured by LC/MS/MS. When prescribing 0.05% CLO, one must bear in mind that, even after an application of 20-30 g, CLO is systemically available and potent enough to induce adrenal gland suppression.

Background: Studies assessing the relationship between disease activity and quality of life (QoL) in adults with atopic dermatitis (AD), before and after therapy are lacking. The relation between disease activity and QoL in AD patients was evaluated before (t = 0) and after 6 weeks (t = 6) of treatment with cyclosporin 5 mg/kg., Methods: In 54 patients with severe AD, disease activity was assessed using objective Scoring Atopic Dermatitis index (SCORAD), Six Area Six Sign Atopic Dermatitis (SASSAD), 'rule of nines' extent score and serum levels of thymus and activation-regulated chemokine (TARC). Patients filled out the Dermatology Life Quality Index (DLQI). To study the relation between disease activity and QoL, correlations were calculated and regression analysis was performed., Results: At t = 0 there was a small, non-significant correlation between the DLQI and the objective SCORAD, 'rule of nines' or serum TARC levels. At t = 6 the objective SCORAD, serum TARC and the 'rule of nines' score showed moderate and significant correlations with the DLQI (r = 0.34, P = 0.02; r = 0.31, P = 0.03; r = 0.49, P < 0.001). An individual's improvement in disease activity (objective SCORAD, SASSAD and 'rule of nines') with 10 points was associated with an improvement of 1.3, 1.5 and 1.1 points respectively in DLQI., Conclusions: Disease activity correlated better with QoL when disease activity was less severe and disease extent ('rule of nines') correlated better with QoL than disease severity. An individual's improvement of 10 points in disease activity was accompanied by only a small improvement in QoL. Other factors than disease activity may influence QoL in patients with AD., (© 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.)

UV-mediated DNA damage and repair are important mechanisms in research on UV-induced carcinogenesis. UV-induced DNA-damage and repair can be determined by immunohistochemical staining of photoproduct positive nuclei of keratinocytes in the epidermis. We developed a new method of analysing and quantifying thymine dimer (TT-CPD) positive cells in the epidermis. Normal skin of healthy controls was exposed to UVB ex vivo and in vivo. Skin samples were immunohistochemically stained for TT-CPDs. Digital images of the epidermis were quantified for TT-CPDs both visually and digitally. There was a UVB-dose dependent induction of TT-CPDs present in the ex vivo UVB-irradiated skin samples. The linear measurement range of the digital quantification was increased compared to the manual counting. The average 24-hour repair rate of the initiated TT-CPDs elicited by the UVB irradiation at T=0 of the 8 HCs showed a 34% decrease of TT-CPD photoproducts by the manual counting method and a 51% decrease determined by digital counting. The digital quantification method improves immunohistochemical quantification of DNA photo damage. It is more sensitive in measuring the extent of DNA-damage per nucleus., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Low bone mineral density (BMD) has been reported in 30.4% of adult patients with atopic dermatitis (AD)., Objective: The aim of this study was to determine the prevalence of low BMD in children with moderate to severe AD and to investigate the relation between BMD and corticosteroid and cyclosporine therapy., Methods: Lumbar spine BMD was measured by dual-energy X-ray absorptiometry in 60 children (age 5-16 years) with moderate to severe AD. BMD (in g/cm(2)) was expressed in Z-scores, the number of SD above or below the mean value of an age- and sex-matched reference population. In children, low BMD was defined as a Z-score less than -2. Information on lifestyle parameters and bone fractures were collected by use of a standardized questionnaire. The cumulative dose of corticosteroids and cyclosporine therapy was calculated for the previous 5-year period., Results: Three patients (5%) had low BMD; one patient (1.7%) had osteoporosis. The observed prevalence of low BMD in this study (6.7%; 95% confidence interval 1.8%-16.2%) does not differ from the expected prevalence of low BMD in the general population (P = .06). Overall, use of topical corticosteroids in the previous 5 years was not associated with a decrease in BMD (Z-score). When children received additional systemic treatment (oral corticosteroids and/or cyclosporine) in the previous 5 years, BMD decreased, although the decrease was not statistically significant. Correction for lifestyle parameters did not change these associations., Limitations: The number of patients studied was limited. The cumulative dose of corticosteroids and cyclosporine therapy was only registered for the previous 5 years, and relatively low amounts of topical corticosteroids were used. The definition of low BMD differs between adults (Z-score < -1) and children (Z-score < -2). Because there is no Dutch BMD reference population for children, normative BMD references were obtained from a different population (US children)., Conclusions: Low BMD did not occur more frequently in this population of children with moderate to severe AD compared with the general population. Use of topical corticosteroids in the previous 5 years was not associated with a decrease in BMD., (Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

The Self-Administered Eczema Area and Severity Index (SA-EASI) is one of the few patient based atopic dermatitis (AD) disease activity scores and was found to be highly correlated with the EASI. Correlation with other frequently used scoring methods has not been investigated. The aim of this study was to evaluate the relation of the SA-EASI with two physician-based disease activity scores (objective SCORAD and SASSAD score) and with a serum marker for AD (Thymus and Activation-Regulated Cytokine [TARC]) in children with AD. Sixty children with moderate to severe AD were included. The SA-EASI was completed by caregivers, and the objective SCORAD and SASSAD scores were measured successively on the same day by a trained investigator. Blood for serum TARC measurement was drawn. The correlation between the SA-EASI and the objective SCORAD was high (ρ = 0.61, p = <0.001), mainly based on high correlation between the body surface area (BSA) measurements of both scores (ρ = 0.50, p = <0.001). The correlation with the SASSAD score (only severity measurement) was 0.43 (p = <0.001). The correlation with serum TARC levels was 0.46; p = <0.001, mainly based on the BSA score of the SA-EASI (ρ = 0.42, p = <0.001). Parents may have more difficulty in scoring severity of AD than scoring BSA involved. Educating parents in severity scoring of AD may improve agreement of the SA-EASI and the objective SCORAD, TARC, and SASSAD score. Additional use of the SA-EASI in routine clinical practice or in trials may then facilitate more frequent but still accurate assessment of AD., (© 2010 Wiley Periodicals, Inc.)

A bioanalytical assay for the topical corticosteroid clobetasol propionate was developed and validated. For the quantitative assay 0.5 ml human serum samples, supplemented with clobetasone butyrate as internal standard, were extracted with hexane-ether. Evaporated and reconstituted extracts were injected on a polar embedded octadecyl silica column with isocratic elution using formic acid in water-methanol as mobile phase. The eluate was led into the electrospray interface with positive ionization and the analyte was detected and quantified using the selective reaction monitoring mode of a triple quadrupole mass spectrometer. The assay was validated in the range 0.04-10 ng/ml, the lowest level of this range being the lower limit of quantification. Precisions were 5-10% and accuracies were between 102 and 109%. The drug was stable under all relevant conditions. Finally, the assay was successfully applied on patients suffering from severe atopic dermatitis treated topically with clobetasol propionate., (Copyright 2010 Elsevier B.V. All rights reserved.)

Background: Severe atopic dermatitis (AD) is often treated successfully with oral immunosuppressive drugs such as cyclosporin (CsA) or oral corticosteroids. However, some patients develop adverse effects or are unresponsive to these first-choice oral immunosuppressive drugs., Objectives: To evaluate whether enteric-coated mycophenolate sodium (EC-MPS) is an effective treatment in patients with severe, recalcitrant AD., Methods: Ten patients with severe, recalcitrant AD were treated with EC-MPS 720 mg twice daily for 6 months. All patients had to discontinue other oral immunosuppressive drugs due to adverse effects (n = 8) or nonresponsiveness (n = 2). Disease activity was monitored using the Severity Scoring of Atopic Dermatitis (modified SCORAD) index and the Leicester Sign Score (LSS). Additionally, the level of serum thymus and activation-regulated cytokine (TARC) was measured. During treatment, safety laboratory examination was performed. Total serum immunoglobulin E (IgE) was followed during treatment. Use of topical corticosteroids was recorded before and during treatment., Results: Compared with baseline, the mean scores for disease activity significantly decreased during treatment with EC-MPS [modified SCORAD (P = 0.04), LSS severity (P = 0.01), LSS extent (P = 0.01)]. In addition, serum TARC levels and total serum IgE levels significantly decreased after treatment compared with before (P = 0.03; P = 0.05). Disease activity decreased after approximately 2 months of treatment and stabilized during the 6-month treatment period. No differences in the amount of topical corticosteroids used in the 6 months prior to treatment compared with the 6-month treatment period were found (P = 0.4). None of the patients discontinued use of EC-MPS and only mild adverse effects were seen., Conclusions: In this study EC-MPS at a dose of 720 mg twice daily for 6 months has proven to be an effective and well-tolerated treatment for patients with severe, recalcitrant AD.

Background: Patients with severe atopic dermatitis (AD) often require treatment with oral immunosuppressive drugs. Everolimus is a rapamycin-derived macrolide with immunosuppressive and antiproliferative effects. Everolimus demonstrated efficacy not only in the prophylaxis of organ rejection in kidney transplant patients, but also in decreasing disease activity in psoriasis patients., Objective: To evaluate whether everolimus is an effective treatment in patients with severe AD., Methods: Two patients with severe AD were treated with everolimus in combination with low-dose cyclosporin A (CsA) or prednisone. During treatment, a disease activity and safety laboratory examination was performed., Results: Everolimus either in combination with prednisone or with CsA did not result in improvement of disease activity in two patients with severe AD., Conclusion: Everolimus does not seem to be an effective treatment in these two AD patients, either in combination with prednisone or with CsA.