Publications by authors named "Angelika Hofer"

27 Publications

  • Page 1 of 1

Effectiveness and clinical predictors of drug survival in psoriasis patients receiving apremilast: A registry analysis.

JAAD Int 2021 Mar 26;2:62-75. Epub 2020 Dec 26.

Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria.

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,  = .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.
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http://dx.doi.org/10.1016/j.jdin.2020.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362309PMC
March 2021

Long-Term Course of Polymorphic Light Eruption: A Registry Analysis.

Front Med (Lausanne) 2021 16;8:694281. Epub 2021 Jul 16.

Research Unit for Photodermatology, Department of Dermatology, Medical University of Graz, Graz, Austria.

Little is known about the long-term course of polymorphic light eruption (PLE). To predict disease course, a questionnaire was sent to patients whose PLE had been diagnosed between March 1990 and December 2018 and documented in the Austrian Cooperative Registry for Photodermatoses. In January 2019, 205 PLE patients were contacted by mail and asked to complete a questionnaire on their disease course, including whether the skin's sun sensitivity had normalized (i.e., PLE symptoms had disappeared), improved, stayed the same, or worsened over time. Patients who reported normalization of sun sensitivity were asked to report when it had occurred. Ninety-seven patients (79 females, 18 males) returned a completed questionnaire. The mean (range) duration of follow-up from PLE onset was 29.6 (17-54) years for females and 29.4 (16-47) years for males. The disease disappeared in 32 (41%) females after 17.4 (2-41) years and in 4 (24%) males after 11.8 (5-26) years. Twenty-nine (37%) females and 6 (35%) males reported improvement of symptoms over time; 15 females (19%) and 7 males (41%) reported no change; and 3 females (4%) and no males reported worsening of symptoms. Kaplan-Meier analysis revealed that after 20 years 74% (95%CI, 64-82%) of patients still suffered from PLE. PLE lesion persistence (>1 week) tended to predict a prolonged course of PLE. PLE usually takes a long-term course over many years though in most patients its symptoms improve or disappear over time. How improvement relates to the pathophysiology of the disease remains to be determined.
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http://dx.doi.org/10.3389/fmed.2021.694281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323194PMC
July 2021

Quality of Life, Anxiety, and Depression in Patients With Early-Stage Mycosis Fungoides and the Effect of Oral Psoralen Plus UV-A (PUVA) Photochemotherapy on it.

Front Med (Lausanne) 2020 5;7:330. Epub 2020 Aug 5.

Research Unit for Photodermatology, Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria.

Little is known about psychological discomfort and quality of life (QoL) in early stage mycosis fungoides (MF) and the effect of psoralen plus UV-A (PUVA) on it. To evaluate QoL, anxiety, and depression with validated instruments in early stage MF patients and whether PUVA treatment improves it. Patients with stage IA to IIA MF were treated with PUVA twice weekly for 12-24 weeks, followed by maintenance treatment or not, in a prospective randomized clinical trial. Patients completed a questionnaire on DLQI as well as the Hospital Anxiety and Depression Scale (HADS) prior to therapy, after their last PUVA exposure, and after the PUVA maintenance or observance phase. For 24 patients with early stage MF, completed questionnaires were available and analyzed. Prior to treatment, 17% reported strong (DLQI > 10) and 29% moderate impairment (DLQI 6-10) in QoL; 33% of patients reported HADS scores indicating anxiety, and 21% reported scores indicating depression. PUVA significantly improved overall QoL by reducing mean DLQI scores by 58.6% ( = 0.003), HADS-A by 30% ( = 0.045), and HADS-D by 44% ( = 0.002). Improvements in QoL and psychological well-being seemed to be sustained, irrespective of maintenance treatment or not. Small sample size. PUVA sustainably improves QoL and psychological well-being in patients with early stage MF. ClinicalTrials.gov identifier: NCT01686594.
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http://dx.doi.org/10.3389/fmed.2020.00330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419471PMC
August 2020

Evaluation of Low-Dose, Low-Frequency Oral Psoralen-UV-A Treatment With or Without Maintenance on Early-Stage Mycosis Fungoides: A Randomized Clinical Trial.

JAMA Dermatol 2019 05;155(5):538-547

Research Unit for Photodermatology, Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria.

Importance: Psoralen-UV-A (PUVA) photochemotherapy is standard first-line treatment for skin-limited, early-stage mycosis fungoides capable of producing high initial complete response (CR) rates. However, much remains unknown about PUVA's therapeutic mechanisms, optimal duration and frequency of treatment, dose escalation, or use as maintenance therapy.

Objectives: To evaluate low-dose, low-frequency PUVA, and whether maintenance treatment extends disease-free remission in patients with mycosis fungoides.

Design, Setting, And Participants: This prospective randomized clinical trial with defined PUVA dosing regimen was carried out in 5 centers (Graz, Vienna, Hietzing, Innsbruck, and Salzburg) across Austria. Patients with stage IA to IIA mycosis fungoides (n = 27) were enrolled in the study beginning March 13, 2013, with the last patient enrolled March 21, 2016. These patients were treated with oral 8-methoxypsoralen followed by UV-A exposure 2 times per week for 12 to 24 weeks until CR. Patients with CR were randomized to PUVA maintenance for 9 months (14 total exposures) or no maintenance. The study was conducted from April 27, 2012, to July 27, 2018. Data analysis of the primary end point was of the intention-to-treat population, and the secondary end point analysis was of the evaluable population.

Main Outcomes And Measures: Efficacy of the PUVA regimen was determined by the rate of CR as defined by a modified severity-weighted assessment tool (mSWAT) score reduction to 0. Levels of proinflammatory molecules in serum and histologic features and percentage of clonal T cells in skin were assessed to search for biomarkers of clinical response.

Results: In 27 patients with mycosis fungoides, 19 (70%) were male with mean (range) age 61 (30-80) years. At baseline, patients with CR had a mean (range) mSWAT score of 18.6 (1-66) compared with 16.8 (3-46) in patients with partial response. The 12- to 24-week PUVA induction regimen reduced the mSWAT score in all patients and led to CR in 19 (70%) of 27 patients and a low mean cumulative UV-A dose of 78.5 J/cm2. The subsequent standardized 9-month PUVA maintenance phase prolonged median (range) disease-free remission from 4 (1-20) months to 15 (1-54) months (P = .02). High density of histologic infiltrate and high percentage of clonal TCR sequences in skin biopsy specimens at baseline were inversely associated with therapeutic response. No severe adverse effects were seen during the PUVA induction or maintenance phase.

Conclusions And Relevance: This proof-of-concept study identifies potential biomarkers for therapeutic response to PUVA in mycosis fungoides; it also demonstrates that low-dose, low-frequency PUVA appears to be highly effective, and maintenance treatment may extend disease-free remission.

Trial Registration: ClinicalTrials.gov identifier: NCT01686594.
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http://dx.doi.org/10.1001/jamadermatol.2018.5905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506892PMC
May 2019

Frequency of occurrence of polymorphic light eruption in patients treated with photohardening and patients treated with phototherapy for other diseases.

Photodermatol Photoimmunol Photomed 2019 Mar 13;35(2):100-105. Epub 2018 Nov 13.

Research Unit for Photodermatology, Department of Dermatology, Medical University of Graz, Graz, Austria.

Background: Medical phototherapy can lead to the manifestation of polymorphic light eruption (PLE), though little is known about the frequency of such events.

Aims: The aim of this Austrian single center study was to retrospectively investigate over a 4-year time period the frequency of PLE in patients prone to the condition and patients with other diseases under phototherapy (mainly narrow-band and broad-band UVB).

Materials And Methods: The data for analysis were obtained from the electronic health and patient record database and patient files of the Photodermatology Unit, Department of Dermatology, Medical University of Graz, Austria.

Results: PLE occurred in 24.3% (18/74) of PLE patients but only 0.7% (3/421) of psoriasis patients under phototherapy (chi-square; P < 0.0001). PLE also occurred in 1.2% (3/257) of patients with atopic eczema, 0.8% (1/118) with prurigo, 3.5% (4/115, P = 0.0206) with parapsoriasis en plaques/mycosis fungoides, 7.4% (2/27, P = 0.0013) with granuloma anulare, 14.3% (1/7, P = 0.0002) with scleroderma, and 16.7% (1/6, P < 0.0001 vs. psoriasis) with pityriasis lichenoides chronica or pityriasis lichenoides eruptiva et varioliformis acuta.

Discussion And Conclusion: These results are helpful for treatment allocation and risk estimation of PLE occurrence with regard to obtaining informed consent not only from PLE-prone patients but also from patients with other skin disorders commonly treated by phototherapy.
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http://dx.doi.org/10.1111/phpp.12429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379702PMC
March 2019

Estimation of local and external contributions of biomass burning to PM in an industrial zone included in a large urban settlement.

Environ Sci Pollut Res Int 2017 Jan 3;24(2):2100-2115. Epub 2016 Nov 3.

Dipartimento di Scienze Ambientali, Informatica e Statistica, Università Ca' Foscari, Via Torino 155, 30172, Venezia Mestre, Italy.

A total of 85 PM samples were collected at a site located in a large industrial zone (Porto Marghera, Venice, Italy) during a 1-year-long sampling campaign. Samples were analyzed to determine water-soluble inorganic ions, elemental and organic carbon, and levoglucosan, and results were processed to investigate the seasonal patterns, the relationship between the analyzed species, and the most probable sources by using a set of tools, including (i) conditional probability function (CPF), (ii) conditional bivariate probability function (CBPF), (iii) concentration weighted trajectory (CWT), and (iv) potential source contribution function (PSCF) analyses. Furthermore, the importance of biomass combustions to PM was also estimated. Average PM concentrations ranged between 54 and 16 μg m in the cold and warm period, respectively. The mean value of total ions was 11 μg m (range 1-46 μg m): The most abundant ion was nitrate with a share of 44 % followed by sulfate (29 %), ammonium (14 %), potassium (4 %), and chloride (4 %). Levoglucosan accounted for 1.2 % of the PM mass, and its concentration ranged from few ng m in warm periods to 2.66 μg m during winter. Average concentrations of levoglucosan during the cold period were higher than those found in other European urban sites. This result may indicate a great influence of biomass combustions on particulate matter pollution. Elemental and organic carbon (EC, OC) showed similar behavior, with the highest contributions during cold periods and lower during summer. The ratios between biomass burning indicators (K, Cl, NO, SO, levoglucosan, EC, and OC) were used as proxy for the biomass burning estimation, and the contribution to the OC and PM was also calculated by using the levoglucosan (LG)/OC and LG/PM ratios and was estimated to be 29 and 18 %, respectively.
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http://dx.doi.org/10.1007/s11356-016-7987-0DOI Listing
January 2017

Differences Between Psoriasis Patients and Skin-healthy Controls Concerning Appraisal of Touching, Shame and Disgust.

Acta Derm Venereol 2016 Aug;96(217):78-82

University Clinic of Psychiatry, Medical University of Graz, Auenbruggerplatz 31, AT-8036 Graz, Austria.

Psoriasis is a chronic skin disease associated with high levels of psychological distress and considerable life impact. Feelings of shame and stigmatization can lead to avoidance of social activity and intimacy. In this study, the questionnaire TSD-Q was used to evaluate pleasure in touching oneself and in a partnership, parental touching during childhood and (skin-related) shame and disgust. Skin-related disgust and shame were significantly higher in psoriatic patients than in healthy controls. Moreover, psoriasis-patients scored significantly lower than skin-healthy controls concerning appraisal of self-touching and parental touching. In contrast, psoriasis-patients scored higher concerning appraisal of touching in a partnership. Due to the fact that low self-esteem might enhance the negative evaluation of touch and the feelings of shame and disgust, psychological interventions should be integrated in the treatment of psoriasis.
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http://dx.doi.org/10.2340/00015555-2373DOI Listing
August 2016

Survival and Effectiveness of Tumour Necrosis Factor-alpha Inhibitors in the Treatment of Plaque Psoriasis under Daily Life Conditions: Report from the Psoriasis Registry Austria.

Acta Derm Venereol 2016 Feb;96(2):207-12

Department of Dermatology, Medical University of Graz, Auenbruggerplatz 8, AT-8036 Graz, Austria.

This retrospective multicentre analysis from the Psoriasis Registry Austria (PsoRA) was conducted to determine drug effectiveness and survival of anti-tumour necrosis factor alpha (anti-TNF-α) agents in patients with moderate-to-severe chronic plaque psoriasis over a 9-year period. Data on 1,019 treatment cycles with adalimumab (n = 460), etanercept (n = 501), and/or infliximab (n = 58) administered to 827 patients (272 women, 555 men) were available for analysis. Compared with etanercept, adalimumab and infliximab showed superior short-term effectiveness. Intention-to-treat-calculated median drug survivals for adalimumab (1,264 days) and etanercept (1,438 days) were similar to each other (p = 0.74), but significantly superior to that of infliximab (477 days) (p = 7.0e-07 vs. adalimumab and p=2.2e-07 vs. etanercept, respectively). Their drug survival rates at 36 months were 51.6%, 56.0%, and 22.6%, respectively. Survival rates correlated significantly with effectiveness for adalimumab and etanercept, but not for infliximab.
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http://dx.doi.org/10.2340/00015555-2214DOI Listing
February 2016

Microbial community composition shapes enzyme patterns in topsoil and subsoil horizons along a latitudinal transect in Western Siberia.

Soil Biol Biochem 2015 Apr;83:106-115

University of Vienna, Department of Microbiology and Ecosystem Science, Division of Terrestrial Ecosystem Research, Vienna, Austria ; Austrian Polar Research Institute, Vienna, Austria.

Soil horizons below 30 cm depth contain about 60% of the organic carbon stored in soils. Although insight into the physical and chemical stabilization of soil organic matter (SOM) and into microbial community composition in these horizons is being gained, information on microbial functions of subsoil microbial communities and on associated microbially-mediated processes remains sparse. To identify possible controls on enzyme patterns, we correlated enzyme patterns with biotic and abiotic soil parameters, as well as with microbial community composition, estimated using phospholipid fatty acid profiles. Enzyme patterns (i.e. distance-matrixes calculated from these enzyme activities) were calculated from the activities of six extracellular enzymes (cellobiohydrolase, leucine-amino-peptidase, N-acetylglucosaminidase, chitotriosidase, phosphatase and phenoloxidase), which had been measured in soil samples from organic topsoil horizons, mineral topsoil horizons, and mineral subsoil horizons from seven ecosystems along a 1500 km latitudinal transect in Western Siberia. We found that hydrolytic enzyme activities decreased rapidly with depth, whereas oxidative enzyme activities in mineral horizons were as high as, or higher than in organic topsoil horizons. Enzyme patterns varied more strongly between ecosystems in mineral subsoil horizons than in organic topsoils. The enzyme patterns in topsoil horizons were correlated with SOM content (i.e., C and N content) and microbial community composition. In contrast, the enzyme patterns in mineral subsoil horizons were related to water content, soil pH and microbial community composition. The lack of correlation between enzyme patterns and SOM quantity in the mineral subsoils suggests that SOM chemistry, spatial separation or physical stabilization of SOM rather than SOM content might determine substrate availability for enzymatic breakdown. The correlation of microbial community composition and enzyme patterns in all horizons, suggests that microbial community composition shapes enzyme patterns and might act as a modifier for the usual dependency of decomposition rates on SOM content or C/N ratios.
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http://dx.doi.org/10.1016/j.soilbio.2015.01.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381299PMC
April 2015

Autonomic nervous tone in vitiligo patients--a case-control study.

Acta Derm Venereol 2015 Feb;95(2):169-72

Department of Psychiatry, Medical University of Graz, Auenbruggerplatz 31/1, AT-8036 Graz , Austria.

In this cross-sectional, exploratory case-control study the vegetative arousal in vitiligo patients compared to an age and gender matched healthy control group was assessed. Forty-eight participants (24 outpatients with generalised vitiligo and 24 healthy controls) completed a test procedure consisting of an initial period of rest (R1), a defined mental stress task (the d2 test of attention), a second period of rest (R2) followed by an individually, age adapted physical stress task (bicycle ergometry) and a final period of rest (R3). Based on a continuously recorded electrocardiogram, heart rate variability, in particular high frequency (HF) and low frequency (LF) components were determined. Within the 3 periods of rest, vitiligo patients showed a higher vegetative arousal than controls, represented by the ratio of LF/HF which mirrors the sympatho-vagal balance (R1: p = 0.027; R2: p = 0.003; R3: p = 0.029). No differences between the 2 groups were found during the mental (p = 0.187) and the physical stress task (p = 0.773). The results suggest a higher vegetative arousal in vitiligo patients.
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http://dx.doi.org/10.2340/00015555-1896DOI Listing
February 2015

Effects of soil organic matter properties and microbial community composition on enzyme activities in cryoturbated arctic soils.

PLoS One 2014 4;9(4):e94076. Epub 2014 Apr 4.

University of Vienna, Department of Microbiology and Ecosystem Science, Division of Terrestrial Ecosystem Research, Vienna, Austria; Austrian Polar Research Institute, Vienna, Austria.

Enzyme-mediated decomposition of soil organic matter (SOM) is controlled, amongst other factors, by organic matter properties and by the microbial decomposer community present. Since microbial community composition and SOM properties are often interrelated and both change with soil depth, the drivers of enzymatic decomposition are hard to dissect. We investigated soils from three regions in the Siberian Arctic, where carbon rich topsoil material has been incorporated into the subsoil (cryoturbation). We took advantage of this subduction to test if SOM properties shape microbial community composition, and to identify controls of both on enzyme activities. We found that microbial community composition (estimated by phospholipid fatty acid analysis), was similar in cryoturbated material and in surrounding subsoil, although carbon and nitrogen contents were similar in cryoturbated material and topsoils. This suggests that the microbial community in cryoturbated material was not well adapted to SOM properties. We also measured three potential enzyme activities (cellobiohydrolase, leucine-amino-peptidase and phenoloxidase) and used structural equation models (SEMs) to identify direct and indirect drivers of the three enzyme activities. The models included microbial community composition, carbon and nitrogen contents, clay content, water content, and pH. Models for regular horizons, excluding cryoturbated material, showed that all enzyme activities were mainly controlled by carbon or nitrogen. Microbial community composition had no effect. In contrast, models for cryoturbated material showed that enzyme activities were also related to microbial community composition. The additional control of microbial community composition could have restrained enzyme activities and furthermore decomposition in general. The functional decoupling of SOM properties and microbial community composition might thus be one of the reasons for low decomposition rates and the persistence of 400 Gt carbon stored in cryoturbated material.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0094076PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976392PMC
December 2014

GC-MS analyses and chemometric processing to discriminate the local and long-distance sources of PAHs associated to atmospheric PM2.5.

Environ Sci Pollut Res Int 2012 Sep 8;19(8):3142-51. Epub 2012 Aug 8.

Dipartimento di Scienze Ambientali, Informatica e Statistica, Università Ca' Foscari, Dorsoduro 2137, 30123 Venezia, Italy.

Purpose: This study presents a procedure to differentiate the local and remote sources of particulate-bound polycyclic aromatic hydrocarbons (PAHs).

Methods: Data were collected during an extended PM(2.5) sampling campaign (2009-2010) carried out for 1 year in Venice-Mestre, Italy, at three stations with different emissive scenarios: urban, industrial, and semirural background. Diagnostic ratios and factor analysis were initially applied to point out the most probable sources. In a second step, the areal distribution of the identified sources was studied by applying the discriminant analysis on factor scores. Third, samples collected in days with similar atmospheric circulation patterns were grouped using a cluster analysis on wind data. Local contributions to PM(2.5) and PAHs were then assessed by interpreting cluster results with chemical data.

Results: Results evidenced that significantly lower levels of PM(2.5) and PAHs were found when faster winds changed air masses, whereas in presence of scarce ventilation, locally emitted pollutants were trapped and concentrations increased. This way, an estimation of pollutant loads due to local sources can be derived from data collected in days with similar wind patterns. Long-range contributions were detected by a cluster analysis on the air mass back-trajectories. Results revealed that PM(2.5) concentrations were relatively high when air masses had passed over the Po Valley. However, external sources do not significantly contribute to the PAHs load.

Conclusions: The proposed procedure can be applied to other environments with minor modifications, and the obtained information can be useful to design local and national air pollution control strategies.
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http://dx.doi.org/10.1007/s11356-012-0858-4DOI Listing
September 2012

Retrospective long-term follow-up in patients with chronic palmoplantar dermatoses after good response to bath PUVA therapy.

J Dtsch Dermatol Ges 2012 Nov 28;10(11):814-8. Epub 2012 Jun 28.

Research Unit for Photodermatology, Department of Dermatology and Venereology, Medical University of Graz, Austria.

Background: Numerous studies have confirmed the short-term effectiveness of 8-methoxypsoralen bath PUVA therapy in patients with chronic palmoplantar dermatoses; however, little is known about long-term results.

Patients And Methods: In this retrospective study we examined the long-term results in 79 patients (mean age: 48 years) with chronic palmoplantar dermatoses who were treated with bath PUVA three times a week over an 8-year period. A good clinical response (a reduction of more than 50% of the skin lesions) occurred after a mean of 23 treatments and a mean cumulative UVA dose of 39 J/cm(2) in 51 patients (65%). In 2007 a questionnaire was sent to these 51 patients to assess the long-term outcome.

Results: With bath PUVA treatment, the best results were found in patients with hyperkeratotic eczema (17/22; 77% good clinical response) followed by patients with palmoplantar psoriasis (26/41; 63%) and patients with dyshidrotic eczema (8/16; 50%). Thirty-four patients (67%) answered the questionnaire after a mean follow-up interval of 4.3 years (10-87 months). Among these patients, 36% reported an improved course of disease after PUVA therapy with reduced frequency and/or intensity of the skin rash, and 29% of patients reported continued complete clearance. 79% of our patients reported a long-term reduction in the use of topical corticosteroids during the follow-up period (mean: 4.3 years). In addition, 67% of patients reported a lasting improvement in quality of life.

Conclusions: These data show that bath PUVA may have a long-term, beneficial influence on the course of disease in a majority of patients with recalcitrant chronic palmoplantar dermatoses.
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http://dx.doi.org/10.1111/j.1610-0387.2012.07975.xDOI Listing
November 2012

311 nm ultraviolet B-accelerated response of psoriatic lesions in adalimumab-treated patients.

Photodermatol Photoimmunol Photomed 2011 Aug;27(4):186-9

Research Unit for Photodermatology, Department of Dermatology, Medical University of Graz, Graz, Austria.

Background: Treatment with the tumor necrosis factor-alpha antibody adalimumab for 12-16 weeks produces a satisfactory response [i.e., 75% reduction in psoriasis area and severity index (PASI)] in a majority (70-80%) of patients with psoriasis. We asked whether 311 nm ultraviolet B (UVB) can improve therapeutic response of psoriatic lesions to adalimumab.

Methods: Four patients (age range, 49-67 years) with moderate to severe plaque-type psoriasis were treated with standard dosage of adalimumab. During adalimumab therapy, a randomly selected body half (left or right, excluding the head) was irradiated with 311 nm UVB three times weekly for 6 weeks. Treatment response was monitored weekly in terms of half-body PASI.

Results: 311 nm UVB significantly accelerated the therapeutic response during adalimumab treatment. At the start of 311 nm UVB therapy, the mean PASI was 14.8. After 6 weeks of 311 nm UVB therapy, the mean PASI was 2.0 on UV-irradiated body halves and 6.9 on non-irradiated body halves (difference, 4.9; 95% confidence interval, 0.4-9.4; P=0.041; 2-tailed paired t-test). This corresponded to an overall mean PASI reduction from baseline (i.e., adalimumab start) of 86% on UV-irradiated body halves vs. 53% on non-irradiated body halves.

Conclusion: 311 nm UVB may accelerate and improve the clearance of psoriatic lesions in adalimumab-treated patients.
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http://dx.doi.org/10.1111/j.1600-0781.2011.00594.xDOI Listing
August 2011

Topical liposomal DNA-repair enzymes in polymorphic light eruption.

Photochem Photobiol Sci 2011 Jul 24;10(7):1118-28. Epub 2011 Mar 24.

Research Unit for Photodermatology, Department of Dermatology, Medical University of Graz, Auenbrugger Platz 8, A-8036, Graz, Austria.

Polymorphic light eruption (PLE) is a very frequent photodermatosis in Europe whose pathogenesis may involve resistance to UV-induced immune suppression and simultaneous immune reactions against skin photoneoantigens. We performed a randomized, double-blind, placebo-controlled intra-individual half-body trial to investigate the protective effect of an after-sun (AS) lotion containing DNA-repair enzymes (photolyase from Anacystis nidulans and Micrococcus luteus extract with endonuclease activity). Fourteen PLE patients were exposed to suberythemal doses of solar-simulated UV radiation on 4 consecutive days at 4 symmetrically located PLE-prone test fields per patient. The test fields were treated with (i) active AS lotion or (ii) a placebo lotion immediately after each UV exposure, or (iii) an SPF30 sunscreen before UV exposure or left untreated. All test fields were exposed to photoactivating blue light 1 h after each UV exposure. As shown by a newly established specific PLE test score (AA + SI + 0.4P [range, 0-12], where AA is affected area score [range, 0-4], SI is skin infiltration score [range, 0-4], and P is pruritus score on a visual analogue scale [range, 0-10]), PLE symptoms were significantly fewer on test sites treated with active AS lotion than on untreated (P = 0.00049) or placebo-treated test sites (P = 0.024). At 144 h after first UV exposure (the time point of maximal PLE symptoms), the mean test scores for untreated, active AS lotion-treated, and placebo-treated test fields were 4.39, 1.73 (61% reduction; 95% confidence interval (CI), 36% to 85%), and 3.20 (27% reduction; 95% CI, 3% to 51%), respectively. Pretreatment with SPF30 sunscreen completely prevented PLE symptoms in all patients. The present results indicate that DNA damage may trigger PLE and that the application of topical liposomes containing DNA repair enzymes to increase DNA repair may effectively prevent PLE.
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http://dx.doi.org/10.1039/c1pp05009eDOI Listing
July 2011

Photohardening restores the impaired neutrophil responsiveness to chemoattractants leukotriene B4 and formyl-methionyl-leucyl-phenylalanin in patients with polymorphic light eruption.

Exp Dermatol 2011 Jun 16;20(6):473-6. Epub 2011 Mar 16.

Research Unit for Photodermatology, Department of Dermatology, Medical University of Graz, Graz, Austria.

A failure to induce immune suppression after UV exposure has been implicated in the pathogenesis of polymorphic light eruption (PLE). This immunological resistance has been linked to an impaired neutrophil infiltration into the skin following UV exposure. Therapeutic photohardening can restore this abnormal neutrophil infiltration in PLE skin and is thought to be responsible for the prophylactic efficacy. The aim of this study was to elucidate the pathogenic mechanism of the described neutrophil deficiency in PLE. Peripheral blood neutrophil responses to the chemoattractants leukotriene B4 (LTB(4)) and formyl-methionyl-leucyl-phenylalanin (fMLP) were investigated in vitro. Samples from 10 patients with PLE before and after 6 weeks of photohardening therapy were assessed. Flow cytometry was used to measure the changes associated with neutrophil activation. We found a significantly reduced neutrophil responsiveness to LTB(4) and fMLP in PLE patients, which was restored to normal levels after phototherapy. Indeed, PLE neutrophil responsiveness to these two chemoattractants after (but not before) phototherapy was similar to that of age- and sex-matched healthy control subjects. This indicates that an abnormal chemotactic potential to neutrophils is a crucial factor in the pathogenesis of PLE. Normalization following photohardening may therefore account for the therapeutic efficacy by restoring UV-induced neutrophil skin infiltration. Our results reveal a completely novel pathogenic mechanism involved in PLE and offer unique targets for therapy.
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http://dx.doi.org/10.1111/j.1600-0625.2011.01264.xDOI Listing
June 2011

A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.

Nat Genet 2010 Nov 17;42(11):985-90. Epub 2010 Oct 17.

Wellcome Trust Centre for Human Genetics, Oxford, UK.

To identify new susceptibility loci for psoriasis, we undertook a genome-wide association study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified associations at eight previously unreported genomic loci. Seven loci harbored genes with recognized immune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These associations were replicated in 9,079 European samples (six loci with a combined P < 5 × 10⁻⁸ and two loci with a combined P < 5 × 10⁻⁷). We also report compelling evidence for an interaction between the HLA-C and ERAP1 loci (combined P = 6.95 × 10⁻⁶). ERAP1 plays an important role in MHC class I peptide processing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk allele. Our findings implicate pathways that integrate epidermal barrier dysfunction with innate and adaptive immune dysregulation in psoriasis pathogenesis.
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http://dx.doi.org/10.1038/ng.694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749730PMC
November 2010

Common polymorphisms in the interleukin-22 gene are not associated with chronic plaque psoriasis.

Exp Dermatol 2009 Sep 27;18(9):796-8. Epub 2009 Mar 27.

Background: Psoriasis is a chronic inflammatory skin disease. Among other cytokines, interleukin 22 (IL-22) has been implicated in the pathogenesis of chronic plaque psoriasis. The purpose of this study was to investigate a hypothesized association between common IL-22 gene polymorphisms and chronic plaque psoriasis.

Methods: Genotypes of 10 common polymorphisms of the IL-22 gene were determined by fluorogenic 5' exonuclease assays (TaqMan) in 475 patients with chronic plaque psoriasis and 252 controls.

Results: Two blocks of high linkage disequilibrium, formed by eight polymorphisms upstream of exon 5 (rs2227485, rs2227491, rs2046068, rs1179251, rs1012356, rs2227501, rs2227503, rs976748) and two polymorphisms in the 3' near gene region (rs1182844, rs1179246), were observed within the IL-22 gene. Neither single polymorphisms nor haplotypes were significantly associated with the presence or clinical features of chronic plaque psoriasis (P > 0.05).

Conclusions: Our data suggest that the investigated IL-22 gene polymorphisms are unlikely major risk factors for chronic plaque psoriasis.
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http://dx.doi.org/10.1111/j.1600-0625.2009.00840.xDOI Listing
September 2009

The methylenetetrahydrofolate reductase 677C>T gene polymorphism is not associated with chronic plaque psoriasis.

Exp Dermatol 2008 Sep 18;17(9):748-51. Epub 2008 Mar 18.

Department of Dermatology, Medical University of Graz, Austria.

Background: Methylenetetrahydrofolate reductase (MTHFR) is involved in the formation of methyl donors, which contribute to DNA methylation. DNA methylation is an essential epigenetic feature playing a critical role in gene regulation and cellular differentiation. In addition, MTHFR activity affects plasma homocysteine levels. A functional polymorphism in the MTHFR gene (677C>T, rs1801133) leading to reduced enzyme activity has been associated with chronic plaque psoriasis in a Chinese population. This finding, however, has not yet been either confirmed or refuted in other populations. The purpose of the present study was to investigate a hypothesized association between the MTHFR 677C>T polymorphism and the presence of chronic plaque psoriasis in a Caucasian population.

Methods: Genotypes for the MTHFR 677C>T polymorphism were determined in 310 patients and 247 control subjects. In a subgroup of 33 patients and 33 sex- and age-matched control subjects, fasting plasma homocysteine concentrations were determined by high-performance liquid chromatography and immunological assays were used for the measurement of folate and vitamin B(12).

Results: Prevalence of the homozygous MTHFR 677TT genotype did not significantly differ between patients and controls (15.2% vs 11.7%, P = 0.24). Mean plasma homocysteine concentrations were significantly higher in psoriasis patients than among control subjects (13.5 +/- 5.3 micromol/l vs 11.0 +/- 2.2 micromol/l, P = 0.026). No significant differences between either mean plasma folate or vitamin B(12) concentrations were observed between both groups.

Conclusion: Our data suggest that the MTHFR 677C>T gene polymorphism is not associated with chronic plaque psoriasis among Caucasians.
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http://dx.doi.org/10.1111/j.1600-0625.2008.00713.xDOI Listing
September 2008

The angiotensin-converting enzyme insertion/deletion and the endothelin -134 3A/4A gene polymorphisms in patients with chronic plaque psoriasis.

Exp Dermatol 2007 Dec;16(12):993-8

Department of Dermatology, Medical University of Graz, Austria.

Background: Psoriasis is a common chronic inflammatory skin disease. Vasoactive peptides such as endothelin-1 (ET-1) and bradykinin have previously been implicated in the pathogenesis of chronic plaque psoriasis. The angiotensin-converting enzyme (ACE) gene carries a 287-base pair insertion/deletion (I/D) gene polymorphism, which is associated with plasma concentrations of bradykinin-degrading ACE. A functional polymorphism (EDN1 -134 3A/4A) in the gene encoding ET-1 has been shown to affect ET-1 expression. The purpose of the present study was thus to investigate a hypothesized association between these gene polymorphisms and the presence of chronic plaque psoriasis.

Methods: The present case-control study comprised 207 patients with chronic plaque psoriasis (136 with early onset and 71 with late onset disease) and 182 control subjects. Genotypes of EDN1 and ACE were determined by a 5' exonuclease assay (Taqman).

Results: The prevalence of the homozygous ACE II genotype was significantly higher in patients with early-onset psoriasis than among control subjects (30.9% vs 19.2%, P = 0.016), yielding an odds ratio of 1.88 [95% confidence interval (CI): 1.12-3.15] for early-onset disease. For late-onset psoriasis, presence of the ACE II genotype was associated with a non-significant odds ratio 1.54 (95% CI: 0.81-2.92). As for the EDN1 -134 3A/4A gene polymorphism, no significant differences in genotype distributions were found between patients with either early- or late-onset psoriasis and control subjects (EDN1 -134 4A/4A: 9.6% in early-onset and 5.6% late-onset psoriasis vs 7.7% in controls; P > 0.05).

Conclusions: Our data suggest that homozygosity for the ACE I allele may affect susceptibility to early-onset psoriasis.
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http://dx.doi.org/10.1111/j.1600-0625.2007.00620.xDOI Listing
December 2007

Narrowband UV-B phototherapy, alefacept, and clearance of psoriasis.

Arch Dermatol 2007 Aug;143(8):1016-22

Research Unit for Photodermatology, Department of Dermatology, Medical University of Graz, Auenbruggerplatz 8, A-8036 Graz, Austria.

Objective: To determine whether the addition of 311-nm narrowband UV-B (NB UV-B) phototherapy accelerates and improves the therapeutic efficacy of alefacept, a biological antipsoriatic drug approved for the treatment of moderate to severe psoriasis.

Design: Randomized half-body comparison study.

Setting: Ambulatory section of a university hospital photodermatology unit.

Patients: Fourteen patients with moderate to severe psoriasis.

Interventions: All patients were treated with 7.5 mg of intravenous alefacept once weekly for 12 weeks. Three times each week, a randomly selected body half (left or right) was treated with NB UV-B light until complete remission, defined as a reduction in the Psoriasis Area Severity Index (PASI) to 3 or lower, was achieved on the irradiated body half.

Main Outcome Measures: Modified PASI, self-assessed visual analogue scale rating of skin lesions, and self-assessed therapeutic efficacy.

Results: After 12 weeks of treatment, the mean PASIs on UV-irradiated and nonirradiated body halves were significantly reduced by 81% and 62%, respectively (P < .001). From week 3 to week 12, the mean PASI was significantly lower on UV-irradiated body halves than on nonirradiated body halves (P < .001). At week 12, PASI reductions of greater than 75% had been achieved significantly more often on UV-irradiated body halves (86%, 12 of 14) than on nonirradiated body halves (43%, 6 of 14), and complete remission had been achieved significantly more often on UV-irradiated body halves (43%, 6 of 14) than on nonirradiated body halves (0 of 14) (McNemar test P = .03).

Conclusions: In this randomized half-side comparison of alefacept with and without phototherapy for psoriasis, alefacept with NB UV-B phototherapy accelerated and improved the clearance of psoriasis. This suggests a promising future for this combination as antipsoriatic therapy.
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http://dx.doi.org/10.1001/archderm.143.8.1016DOI Listing
August 2007

Macro-micro dermatology: erythematous papules and lentigo-like macules--a new entity?

J Dtsch Dermatol Ges 2007 Aug;5(8):645-6

Department of Dermatology, Medical University of Graz, Graz, Austria.

Galli-Galli disease is usually characterized by reticulate hyperpigmentation of the flexures. Rare patients may present without this finding, instead having only localized erythematous papules and brown, lentigo-like macules on the trunk and extremities. Histological changes consist of elongated and in part hyperpigmented rete ridges and areas of acantholysis.
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http://dx.doi.org/10.1111/j.1610-0387.2007.06451.xDOI Listing
August 2007

Psoralen plus UVA vs. UVB-311 nm for the treatment of lichen planus.

Photodermatol Photoimmunol Photomed 2007 Feb;23(1):15-9

Research Unit for Photodermatology, Medical University Graz, Graz, Austria.

Background: The purpose of this study was to evaluate and compare the short- and long-term therapeutic efficacy of psoralen plus UVA (PUVA) vs. UVB-311 nm in the treatment of patients with disseminated lichen planus.

Methods: A computerized data bank search and chart review revealed that data from a total of 28 patients, including 15 patients [11 women, four men; mean age 47 years (range, 16-65 years)] treated between 1998 and 2004 with PUVA and 13 patients [10 women, three men; mean age 51 years (range, 19-69 years)] treated with UVB-311 nm, were available at our institution for retrospective analysis.

Results: All 15 patients (100%) treated with oral PUVA had a complete [n=10 (67%)] or partial [n=5 (33%)] clinical response, whereas 10 of 13 patients (77%) treated with UVB-311 nm showed complete [n=4 (31%)] or partial [n=6 (46%)] clinical response. Statistical analysis revealed that the initial response to PUVA was superior to that of UVB-311 nm (P=0.0426; Wilcoxon's exact test). There were no statistically significant differences between the PUVA- and UVB-311 nm-treated patient groups with regard to mean therapy duration (10.5 vs. 8.2 weeks; P=0.1107; unpaired, two-tailed Student's t test) or mean number of treatment exposures (25.9 vs. 22.5; P=0.1775). After a mean follow-up period of 20.5 months (range, 2-49 months) and 35.7 months (range, 3-60 months), respectively, disease recurrence or deterioration was observed in seven of 15 PUVA-treated patients (47%) and three of 10 UVB-311 nm-treated patients (30%). Kaplan-Meier lifetime table analysis revealed no statistically significant difference between the 2 treatment groups in terms of sustained overall (i.e., partial and complete) clinical response rate (P=0.8593; log-rank test).

Conclusions: Even though oral PUVA produces a better initial clinical response rate, both oral PUVA and UVB-311 nm are effective treatments for lichen planus that produce similar long-term outcomes.
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http://dx.doi.org/10.1111/j.1600-0781.2007.00261.xDOI Listing
February 2007

Successful thalidomide therapy for actinic prurigo in a European woman.

J Dtsch Dermatol Ges 2006 Nov;4(11):961-4

Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria.

Actinic prurigo is a rare, often difficult-to-treat, idiopathic photodermatosis. Actinic prurigo is divided into a hereditary form appearing in the Native American population and a sporadic form occurring in non-Native Americans. We present a 28-year-old Caucasian woman who developed typical clinical signs and symptoms of actinic prurigo, just as had her mother and grandmother. The patient and her mother were HLA-A24 and HLA-DR 4 with the subtype HLA-DRB1*0408. Based on clinical symptoms and the HLA pattern, the diagnosis of actinic prurigo was made. Treatment with thalidomide led to resolution of the disease. This case report of a Caucasian woman suffering from a hereditary form of actinic prurigo questions the established classification of actinic prurigo into a hereditary Native American form and a sporadic form occurring in the non-Native American population.
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http://dx.doi.org/10.1111/j.1610-0387.2006.06125.xDOI Listing
November 2006

Reduction of treatment frequency and UVA dose does not substantially compromise the antipsoriatic effect of oral psoralen-UVA.

J Am Acad Dermatol 2004 Nov;51(5):746-54

Division of Photodermatology, Department of Dermatology, Medical University Graz Austria.

Background: The carcinogenic potential of 8-methoxypsoralen photochemotherapy (psoralen-UVA [PUVA]) is correlated with the total number of treatments and cumulative UVA dose applied during oral PUVA therapy.

Objective: We sought to determine whether reducing treatment frequency and UVA dose affects the therapeutic efficacy of oral PUVA for patients with chronic plaque psoriasis.

Methods: This was a prospective, randomized, half-side study performed in a photodermatology department in a dermatology hospital. Eighteen consecutive patients with chronic plaque psoriasis received paired PUVA regimens (0.5 minimal phototoxic dose [MPD] 4 times/wk vs 1 MPD twice/wk, 0.5 MPD twice/wk vs 1 MPD twice/wk, and 0.5 MPD twice/wk vs 0.75 MPD twice/wk). The PUVA regimens were assessed for reduction of Psoriasis Area and Severity Index (PASI) score and the number of treatments and cumulative UVA dose required to reduce PASI score to defined end points (ie, PASI reductions of 25%, 50%, and 75%) or to induce complete remission (PASI < 3).

Results: Reducing the number of treatments while maintaining the same UVA dose per week did not reduce overall therapeutic efficacy. Reducing the number of treatments to twice a week and reducing the UVA dose from 1 MPD to 0.75 or 0.5 MPD per treatment only slightly affected intermediate therapeutic efficacy (between the second and seventh weeks of therapy) but had no effect on final clearance rates. The time to complete clearance did not significantly differ between regimens. The mean cumulative UVA dose was significantly lower for the least intensive dose regimen (0.5 MPD twice/wk) than for the more intensive regimens.

Conclusions: Reducing treatment frequency and UVA dose does not substantially compromise the therapeutic efficacy of PUVA.
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http://dx.doi.org/10.1016/j.jaad.2004.04.029DOI Listing
November 2004
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