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Background Little is known about the effectiveness and drug survival associated with apremilast under real-world conditions. Objective To investigate the influence of patient and disease characteristics on drug survival associated with apremilast and to elucidate clinical effectiveness with regard to the psoriasis area and severity index (PASI) reduction. Methods This was an observational, retrospective, multicenter analysis from the Austrian Psoriasis Registry. Results Data from 367 patients were eligible for analysis. The 12-month drug survival rate associated with apremilast (ie, the proportion of patients on the drug) was 57.3% and decreased significantly in patients younger than 40 years (relative hazard ratio = 1.49, P = .007918). Sex; concomitant arthritis; previous biologic therapy; obesity; and palmoplantar, scalp, nail, and intertriginous involvement did not significantly affect drug survival. At 12 months, the response rates in patients receiving apremilast per protocol with a PASI of 50, 75, 90, and 100 were 80.0%, 56.4%, 38.2%, and 22.7%, respectively. Limitations Inclusion of a substantial number of patients with no record of absolute PASI at study entry and lack of PASI reduction follow-up data of 103 patients (28.1%) after starting apremilast treatment. Conclusion Apremilast is a robust antipsoriatic drug for which the drug survival is not strongly influenced by most patient- or disease-related factors except age. Drug survival is significantly shorter in patients younger than 40 years.

We assessed the efficacy, safety, and tolerability of ponesimod, an oral, selective, reversible modulator of sphingosine 1-phosphate receptor 1, in patients with moderate to severe chronic plaque psoriasis.Between Sept 22, 2010, and Oct 24, 2012, patients with psoriasis area and severity index (PASI) scores higher than 10 were enrolled into this multicentre double-blind, phase 2 study. They received 20 mg or 40 mg ponesimod or placebo once daily for 16 weeks. Those with at least 50% reduction in PASI score at 16 weeks and who were receiving ponesimod were rerandomised to receive maintenance ponesimod therapy or placebo until week 28. The primary endpoint was reduction in PASI score from baseline of at least 75% (PASI75) at week 16. This study is registered with ClinicalTrials.gov, number NCT01208090.Of 326 patients initially randomised (20 mg ponesimod n=126, 40 mg ponesimod n=133, and placebo n=67) PASI75 was achieved at week 16 in 58 (46·0%), 64 (48·1%), and nine (13·4%), respectively. The treatment effect was significant for the two ponesimod doses (both p0·0001). Of 219 patients who entered the maintenance period, PASI75 was achieved by week 28 in 35 (71·4%) of 49 who continued on 20 mg ponesimod and 41 (77·4%) of 53 on 40 mg ponesimod, and in 19 (42·2%) of 45 who swapped from 20 mg to placebo and 19 (40·4%) of 47 from 40 mg to placebo. Ponesimod was associated with dyspnoea, raised liver enzyme concentrations, and dizziness.Significant clinical benefit was seen at week 16 that increased with maintenance therapy.Actelion Pharmaceuticals.

There is mounting evidence that menopause affects some functions of the skin. Hormone replacement therapy (HRT) appears to limit some of the climacteric aspects of cutaneous aging.In the light of a growing interest in the endocrinological influence of skin, we performed a study evaluating the effects of HRT on skin aging in postmenopausal women.Forty non-hysterectomized, postmenopausal women were included in this prospective, randomized, double-blind, placebo-controlled study on the influence of oral sequential treatment with a combination of 2 mg 17beta-estradiol/10 mg dydrogesterone (Femoston) for seven 28-day cycles. Skin elasticity, skin surface lipids, skin hydration and skin thickness were measured by non-invasive methods, and both adverse-event profile and clinical-dermatological status were evaluated.After 7 months of HRT, skin elasticity increased significantly at the right ramus of the mandible, while skin hydration tended to improve significantly at the right upper arm (inner side); skin thickness improved significantly but skin surface lipids did not. Absolute effects did not differ significantly between HRT and placebo patients. A dermatological evaluation was largely consistent with measurement results. Safety and tolerability of HRT were positive.The results showed improvements in the parameters involved in skin aging in the HRT group as compared to baseline. While skin aging is no indication for systemic hormone supplementation, a positive effect on aging skin can be observed.

AIM: The aim of this study was to show the influence of three different hormone replacement therapy regimes (HRT) by comparing the changes in skin thickness. METHOD: Skin thickness was measured using a high-frequency ultrasound system on the inner side of the left upper arm of perimenopausal women with a low oestradiol level (< 45 pg/ml). The patients were allocated to different groups: Group1 (n = 6) received oestradiol merely transdermally; Group 2 (n = 7) was given transdermal oestradiol as well as progesterone vaginally; Group 3 (n = 8) took oral oestradiol and vaginal progesterone; Group 4 (n = 3) served as the control group without therapy. RESULTS: The median value of skin thickness in all HRT-groups increased highly significantly (0.15 mm) after six months (0.91 mm before therapy versus 1.06 mm after six months of HRT), but there was no significant change in the control group. CONCLUSIONS: The study shows that HRT leads to an increase of skin thickness which can be demonstrated by a high-frequency ultrasound.

Background A few studies on the treatment of vitiligo with topical tacrolimus have been published and showed promising results. However, most of these trials were uncontrolled. Objective This study aims to assess the response of vitiligo to once- or twice-daily treatment with 0.1% tacrolimus in a controlled, randomized, observer-blinded study. Methods Seventeen patients with generalized vitiligo were enrolled in this study. In each patient, two lesions were selected and randomized to treatment with either once- or twice-daily application of 0.1% tacrolimus for a total period of 6 months. In 10 patients, a third patch was left untreated to serve as a control. Results Fifteen patients with 40 target lesions completed the study. Twice-daily treatment induced excellent (> 75%) repigmentation in two lesions, moderate (> 25–50%) and poor (1–25%) repigmentation in four lesions each, and no response in five lesions. Once-daily treatment resulted in moderate repigmentation in two lesions and poor repigmentation in five lesions, whereas no effect was observed in the remaining eight lesions. One out of 10 control lesions developed moderate spontaneous repigmentation, the other nine remained unchanged. Besides the frequency of tacrolimus application, the treatment outcome was determined by the localization of the affected areas with the facial region showing the best response. Conclusions Tacrolimus ointment appears to be an effective treatment option for facial vitiligo. A guarded prognosis is advisable for vitiliginous lesions on other localizations. Treatment must be applied twice daily for optimum response. Conflict of Interest None declared.

Acrokeratosis paraneoplastica (Bazex's syndrome) is a rare obligate paraneoplastic dermatosis characterized by erythematosquamous lesions localized symmetrically at the acral sites. The condition almost exclusively affects Caucasian men older than 40 years. It is usually associated with primary malignant neoplasms of the upper aerodigestive tract. In most cases, the skin changes precede the clinical manifestation of the underlying neoplasm. The dermatosis can be cured only by removal of the underlying carcinoma. We describe a case of acrokeratosis paraneoplastica associated with a retroperitoneal liposarcoma in a 71-year-old Caucasian man. The liposarcoma was surgically removed but recurred several times, with acrokeratosis paraneoplastica showing a parallel development. We, therefore, add liposarcoma to the growing list of malignant neoplasms associated with acrokeratosis paraneoplastica.

Maximilian C. Aichelburg, MD; Robert Loewe, MD; Nikolaus Schicher, MD; Paul-Gunther Sator, MD; Franz M. Karlhofer, MD; Georg Stingl, MD; Ahmad Jalili, MD, PhD; Divisions of Immunology, Allergy, and Infectious Diseases (Drs Aichelburg, Karlhofer, Stingl, and Jalili) and General Dermatology (Drs Loewe and Schicher), Department of Dermatology, Medical University of Vienna, and Department of Dermatology, Hietzing Municipal Hospital (Dr Sator), Vienna, Austria

Background: Dickkopf-1 (Dkk-1) glycoprotein is an inhibitor of the canonical Wnt pathway. Recent studies have demonstrated elevated Dkk-1 serum levels in patients with diverse malignancies. In vitro studies with melanoma cell lines showed that loss of Dkk-1 expression may contribute to tumor progression. Objective: The present study is the first in vivo investigation of Dkk-1 serum levels in patients with cutaneous malignant melanoma. Methods: We analyzed serum levels of Dkk-1 protein in 82 patients with cutaneous melanoma. Results: Serum levels were significantly increased (mean 83.01 pmol/l) in comparison to healthy controls (mean 29.36 pmol/l). No statistical difference in Dkk-1 serum levels neither between patients without or with lymph node metastases (p = 0.719) nor between patients with or without visceral metastases (p = 0.929) was found. Patients before excision had moderately higher Dkk-1 serum levels than after excision or with florid metastases. Conclusion: Our data suggest that increased Dkk-1 expression is an early event in melanoma, decreasing in later tumor stages. It was shown previously that Dkk-1 activates cell death in melanoma cells. Our in vivo data indicate that a decrease in Dkk-1 could be a sign of loss of tumor control.

Background Recent studies suggest that ultraviolet (UV) A1 phototherapy is an effective treatment for localized scleroderma (LS); however, the optimum UVA1 dose remains to be determined. Objective We sought to compare the immediate and long-term efficacy of low- versus medium-dose UVA1 phototherapy for plaque-type LS. Methods Three comparable plaques in 16 patients were treated with 20 J/cm2 UVA1, 70 J/cm2 UVA1, or no irradiation. In total, 30 treatments were given. Skin thickness was determined by high-frequency ultrasound examination and clinical scoring. Assessments were done at baseline, immediately after treatment, and 3, 6, and 12 months thereafter. Results Ultrasound measurement showed a significantly greater reduction of skin thickness with 70 J/cm2 than with 20 J/cm2 at all time points of the study except immediately after UVA1 treatment. The clinical score of the irradiated plaques also decreased substantially but failed to detect a significant difference between the two dose regimens. Limitations Our results only pertain to plaque-type LS and are limited by a small sample size. Conclusion Medium-dose provides for better long-term results than low-dose UVA1 in LS as shown by ultrasound assessment. With clinical scoring, no significant difference between the two UVA1 dose regimens was detected, indicating that ultrasound measurement is a more sensitive method for quantifying treatment-induced skin changes in patients with LS.

Background: The water content of the stratum corneum and skin surface lipids are important factors in the appearance and function of the skin. A disruption of the balance between the two may lead to the clinical manifestation of dryness of skin in patients with atopic dermatitis. Objective: The aim of our study was to examine the so-called dry skin of patients with atopic dermatitis using objective parameters. We compared the epidermal hydration and the skin surface lipids, the so-called hydro-lipid film, of the clinically unaffected skin of patients suffering from atopic dermatitis with that of healthy subjects. Methods: A total of 48 patients of either gender were included in this retrospective case-control study. We used the Corneometer CM 820 (Courage+Khazaka Electronic GmbH, Cologne, Germany) and the Sebumeter SM 810 (Courage+Khazaka Electronic GmbH) as noninvasive measuring methods. Results: The results showed marked decreases in the atopic dermatitis group for both the Corneometer and Sebumeter measuring methods. Conclusion: Our results show that the dry skin of patients with atopic dermatitis, as previously shown, is due not only to a decrease in skin moisture but also to a reduction of skin lipids. This finding gives rise to a new understanding of the condition, and therefore one should always speak of a hydro-lipid film. (J Am Acad Dermatol 2003;48:352-8.)

Auteur(s) : Robert Feldmann1, Michael Schierl1, Helmut Rauschka2, Paul-Gunther Sator1, Friedrich Breier1, Andreas Steiner1 1Department of Dermatology and Venerology, Hospital Hietzing, Wolkersbergenstrasse 1, A-1130 Vienna, Austria 2Department of Neurology, Hospital Hietzing, Vienna Glatiramer acetate (GA) is a random mixture of synthetic polypeptides composed of L-glutamic acid, L-lysine, L-alanine and L-tyrosine. It is approved for the treatment of multiple sclerosis and administered [...]