Disparate effects of adalimumab and fumaric acid esters on cardiovascular risk factors in psoriasis patients: results from a prospective, randomized, observer-blinded head-to-head trial.

BACKGROUND: The effect of adalimumab and fumaric acid esters (FAE) on the cardiovascular risk associated with psoriasis has only been investigated scarcely in randomized controlled studies. OBJECTIVE: The aim of this prospective, randomized controlled head-to-head trial was to compare the influence of adalimumab and FAE on cardiovascular disease markers in psoriasis patients. METHODS: Sixty-five patients with moderate to severe plaque psoriasis were randomly assigned to adalimumab or FAE treatment for 6 months. Cardiovascular haemodynamic parameters [flow-mediated dilation (FMD), nitro-glycerine mediated dilation (NMD) and carotid intima-media thickness (CIMT), blood pressure] were assessed at baseline (v0) and after 6 months (v6). Cutaneous disease severity, inflammatory and lipid cardiovascular risk markers were analysed at baseline(v0), after 3 (v3) and 6 months (v6). RESULTS: After 6 months of treatment FMD in the adalimumab group increased significantly [v0 5.9% (6.4% SD), v6 8.0% (4.8% SD), P = 0.048) but not in the FAE group. (v0 7.0% (4.1% SD), v6 8.4% (6.1% SD), P = 0.753]. This was paralleled by a significant decrease of high sensitive C-reactive protein (hsCRP) in the adalimumab group in comparison to the FAE group (v0: 0.39 mg/dL (0.38 SD), v6: 0.39 mg/dL (0.48 SD), P = 0.043). No significant changes were observed in any other haemodynamic parameters. FAE, however, additionally decreased total cholesterol (P = 0.046) and apolipoprotein B (P = 0.041) levels compared to adalimumab. Mean Psoriasis Area and Severity Index (psoriasis area severity score) reduction was greater but not significant (P = 0.116) under adalimumab treatment compared to FAE treatment [-71.1% (29.9 SD) vs. -54.6% (45.7%)]. CONCLUSION: In our study, both treatments were documented to exert effects on the cardiovascular system. While adalimumab showed anti-inflammatory effects and improved FMD, FAE interacted favourably with the cholesterol metabolism.

5-Aminolevulinic acid patch (Alacare) photodynamic therapy for actinic cheilitis: data from a prospective 12-month follow-up study on 21 patients.

BACKGROUND: Actinic cheilitis (AC) is a variant of actinic keratosis (AK) affecting the lips and caused by chronic ultraviolet exposure. OBJECTIVE: Alacare is a self-adhesive, skin-coloured 5-aminolaevulinic acid patch that has been developed for use in photodynamic therapy (PDT) of mild-to-moderate AK. Based on promising preliminary results in the treatment of AC with Alacare patch PDT, we decided to extend our previous investigation to gain more data on the efficacy, tolerability, safety and cosmetic outcome of Alacare patch PDT for AC. METHODS: Twenty-one patients with a clinical diagnosis of mild-to-moderate AC were included in the study and subjected to one single session of PDT. After occlusion with the Alacare patch for 4 h, the AC lesions were illuminated for 10 min with red light at a dose of 37 J/cm2 . All patients received local anaesthesia prior to illumination. Additionally, all lesions were cooled during PDT with a cold air blower. PDT-induced pain and skin phototoxicity were monitored during and up to 7 days after PDT. Clinical assessment of efficacy, cosmetic outcome and global patient satisfaction was performed at 3, 6 and 12 months after treatment. RESULTS: Nineteen patients completed the study. Three months after PDT, 17 patients (89.5%) had achieved complete remission. Of these, one patient presented with recurrence of AC at the 6-month follow-up, whereas all other patients remained in remission until the end of the observation period. The complete clinical cure rate at 1 year after a single Alacare patch PDT thus was 84.2%. Pain during illumination and the phototoxic skin reaction were in general mild to moderate. The cosmetic outcome was excellent. CONCLUSION: The present prospective study on Alacare patch PDT for AC confirms its high clinical efficacy, good tolerability and favourable cosmetic effects. Alacare patch PDT should be considered as a valid treatment option for patients with AC.

Serum levels of folate, 25-hydroxyvitamin D3 and cobalamin during UVB phototherapy: findings in a large prospective trial.

BACKGROUND: Narrowband UVB phototherapy (NB-UVB) is a mainstay in the treatment of numerous inflammatory dermatoses. Whereas, a wealth of studies has shown that NB-UVB treatment increases 25-hydroxyvitamin D3 (25(OH)D) levels, only sparse and controversial data exist on its effect on serum folate and cobalamin. OBJECTIVES: To determine whether exposure to NB-UVB alters serum folate or cobalamin levels. METHODS: A single-centre, prospective, open observational study on 101 patients subjected to NB-UVB phototherapy between late fall and early spring. Serum folate, 25(OH)D and cobalamin levels were measured after 0, 12, 24 and 36 NB-UVB exposures. RESULTS: After 12 NB-UVB exposures a significant decrease of mean serum folate (-1.0 nmol/L; P = 0.03) and cobalamin (-14.5 pmol/L, P = 0.03) levels was observed whereas serum levels of 25(OH)D showed a significant increase (35.4 nmol/L, P < 0.0001). CONCLUSIONS: A standard course of NB-UVB induces a small but significant decrease of serum folate and cobalamin levels.

Quality of life and comorbidities in palmoplantar pustulosis - a cross-sectional study on 102 patients.

BACKGROUND: Association of palmoplantar pustulosis (PPP) with metabolic and autoimmune diseases has been reported in mostly small case series or anecdotal cases. OBJECTIVE: To assess health-related quality of life and prevalence of comorbidities in a large cohort of PPP patients. METHODS: We conducted a cross-sectional study on patients with either active or past PPP. Disease severity was measured by the Palmoplantar Pustulosis Area and Severity Index (ppPASI). Quality of life was assessed by the Dermatology Life Quality Index (DLQI). Comorbidities were evaluated by medical history, blood examination, stool testing for Helicobacter pylori antigen and screening tools for depression and psoriatic arthritis. RESULTS: A total of 102 patients (87 women, 15 men) with a mean age of 52.6 ± 14.1 years were evaluated. The mean DLQI was 7 ± 6. Comorbidities were frequent and consisted of hypercholesterolaemia (38%), hypertension (32%), obesity (27%), metabolic syndrome (26%), depression (24%), diabetes (19%), autoimmune thyroiditis (16%) and psoriatic arthritis (16%). CONCLUSION: Patients with PPP have an impaired quality of life and a broad range of comorbidities. Contrary to other reports, our investigation failed to show an association between PPP and coeliac disease or H. pylori infection.

Randomized controlled trial comparing 35% trichloroacetic acid peel and 5-aminolaevulinic acid photodynamic therapy for treating multiple actinic keratosis.

BACKGROUND: Photodynamic therapy (PDT) and chemical peels with trichloroacetic acid (TCA) can be applied to large skin areas and thus are suitable treatment options for patients with multiple actinic keratosis (AK). However, despite its long use, TCA has been investigated only rarely in this indication. OBJECTIVES: This randomized, observer-blinded, intrapatient comparative study sought to investigate the efficacy and safety of 35% TCA vs. aminolaevulinic acid 20% (ALA) PDT in patients with extensive field cancerization and multiple AKs in the face or on the scalp. METHODS: Twenty-eight patients with at least five AKs in two comparable anatomical areas on the head were treated with 35% TCA and ALA PDT randomly assigned to each area. Their therapeutic efficacy, adverse events and cosmetic outcome were assessed by a blinded investigator at 1, 3, 6 and 12 months after treatment. RESULTS: After 12-months' follow-up TCA and ALA PDT reduced the total lesion count, the primary outcome, by 31% and 58%, respectively (P = 0·006). Complete clearance of pre-existing AKs were 49% for TCA and 74% for ALA PDT (P = 0·011). Treatment failure (number of AKs greater than 50% of the baseline count) was observed in seven patients (25%) after TCA and in two patients (7%) after PDT treatment. Treatment-related pain was significantly higher for ALA PDT (visual analogue scale 7·5 ± 2·3 vs. TCA: 5·1 ± 2·6; P = 0·04), whereas scarring (n = 6, 21%) was seen only in TCA treated patients. CONCLUSIONS: ALA PDT provided better clinical results than TCA in the treatment of patients with extensive field cancerization and multiple AKs.

Response of vitiligo to once- vs. twice-daily topical tacrolimus: a controlled prospective, randomized, observer-blinded trial.

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.

A prospective, randomized, double-blind, placebo-controlled study on the influence of a hormone replacement therapy on skin aging in postmenopausal women.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Changes in concentrations of sera proteins in war wound].

UNLABELLED: During the general reaction to trauma, substantional changes in protein composition of sera occure. The aim of the prospective study was to investigate net change in total protein and albumin concentrations, as well as albumin/globulin ratio in sera of war casualties during the first 14 posttraumatic days, and to establish the correlation between these changes and severity of trauma. Subjects were 79 war casualties. CONTROLS: 33 blood donors. METHODS: Injury severity was determined according to ISS and blood samples were collected 12 hours after trauma, then on the 1st, 2nd, 5th and 14th posttraumatic day. In war casualties values of total protein and albumin concentrations and albumin/globulin ratio were significantly decreased. Minimal concentrations were measured on 2nd posttraumatic day (589.04 g/l for total proteins, p; 36.66.21 g/l for albumins, p) or on 5th day (0.860.2 for albumin/globulin ratio, p). CONCLUSIONS: During the acute-phase response to trauma, significant changes in concentration of total proteins, albumins and albumin/globulin ratio occure in sera of war casualties. These changes are the most promminent during the first 5 days, with tendency for normalization after that. Intensity of these changes depends of the severity of trauma.

[C-reactive protein as an indicator of the severity of war injuries]. / C-reaktivni protein kao pokazatelj tezine ratne povrede.

UNLABELLED: During the general reaction to trauma, acute phase proteins are synthetized. The aim of the prospective study was to determine CRP concentrations in sera of war casualties during the first 14 posttraumatic days, and to establish the correlation between these changes and severity of trauma. Subjects were 79 war casualties. CONTROLS: 33 blood donors. METHODS: Injury severity was determined according to ISS and CRP concentrations with immunonephelometric analysis. Blood samples were collected 12 hours after trauma, then on the 1st, 2nd, 5th and 14th posttraumatic day. In war casualties CRP values were significantly increased (56.257.53 mg/dl after 12 hrs, 107.0976.08 on 1st, 144.3570.23 on 2nd, 71.42558.66 on 5th and 37.656.14 on 14th posttraumatic day; p). Significant differences were observed between groups with ISS and ISS12 (p) in first two days and later between group with ISS24 (144.1766.94 mg/dl on 5th and 111.588.5 on 14th posttraumatic day) and others (p). CONCLUSIONS: During the acute-phase response to trauma, significant changes in concentration of CRP occur in sera of war casualties. These changes are the most prominent during the first 48 hours, with tendency for normalization after the 5th day. Intensity of these changes depend on the severity of trauma. CRP is valid marker of war wound severity.