Publications by authors named "Franz J Legat"

24 Publications

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Chronic Nodular Prurigo: A European Cross-sectional Study of Patient Perspectives on Therapeutic Goals and Satisfaction.

Acta Derm Venereol 2021 Feb 17;101(2):adv00403. Epub 2021 Feb 17.

Department of Dermatology and Center for Chronic Pruritus, University Hospital Münster, Von- Esmarch-Str. 58, DE-48149 Münster, Germany. E-mail:

Chronic nodular prurigo is characterized by recalcitrant itch. Patient perspectives on therapeutic goals, satisfaction with therapy and efficacy of therapeutic regimens for this condition are unknown. This questionnaire study examined these issues in 406 patients with chronic nodular prurigo from 15 European dermatological centres. Improvements in itch, skin lesions and sleep were the most important goals. Emollients, topical corticosteroids and antihistamines were the most frequently used treatments, while a minority of patients were prescribed potent medications, such as systemic immunosuppressants and gabapentinoids. Most patients were not satisfied with their previous therapy (56.8%), while 9.8% did not receive any therapy despite having active disease. A substantial number of respondents (28.7%) considered none of the therapeutic options effective. Although chronic nodular prurigo is a severe disease, most patients were not treated with potent systemic drugs, which may contribute to the high levels of dissatisfaction and disbelief in available therapies. Specific guidelines for chronic nodular prurigo and the development of novel therapies are necessary to improve care.
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http://dx.doi.org/10.2340/00015555-3726DOI Listing
February 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

Trial of Nemolizumab in Moderate-to-Severe Prurigo Nodularis.

N Engl J Med 2020 02;382(8):706-716

From the Department of Dermatology and Center for Chronic Pruritus, University Hospital Münster, Münster (S.S.), the Department of Dermatology and Allergy, Christine Kühne Center for Allergy Research and Education, University Hospital, Bonn (T.B.), and the Department of Dermatology and Allergy, Ludwig Maximilian University of Munich, Munich (A.W.) - all in Germany; the Itch Center, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Hospital, Miami (G.Y.); the Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria (F.J.L.); the Department of Dermatology, University Hospital of Nice, Nice (J.-P.L.), the Department of Dermatology, University of Toulouse, Toulouse (C. Paul), and the Department of Dermatology, University Hospital of Brest, Brest (L.M.) - all in France; the Department of Dermatology, Medical University of Lodz, Lodz (J.N.), and the Department of Dermatology, University of Rzeszow, Rzeszow (A.R.) - both in Poland; Galderma, Fort Worth, TX (F.A.); and Galderma, Lausanne, Switzerland (C. Piketty).

Background: Prurigo nodularis is a chronic pruritic skin disease with multiple nodular skin lesions. Nemolizumab is a monoclonal antibody targeting the interleukin-31 receptor, which is involved in the pathogenesis of prurigo nodularis.

Methods: We conducted a 12-week, randomized, double-blind, phase 2 trial of nemolizumab (at a dose of 0.5 mg per kilogram of body weight) administered subcutaneously at baseline, week 4, and week 8, as compared with placebo, in patients with moderate-to-severe prurigo nodularis and severe pruritus. Moderate-to-severe prurigo nodularis was defined as 20 or more nodules, and severe pruritus was defined as a mean score of at least 7 for the worst daily intensity of pruritus on the numerical rating scale (scores range from 0 [no itch] to 10 [worst itch imaginable]). The primary outcome was the percent change from baseline in the mean peak score for pruritus on the numerical rating scale at week 4. Secondary outcomes included additional measures of itching and disease severity. Safety assessments were performed through week 18.

Results: A total of 70 patients were randomly assigned in a 1:1 ratio to receive nemolizumab (34 patients) or placebo (36). The initial pruritus score on the numerical rating scale was 8.4 in each group. At week 4, the peak pruritus score on the numerical rating scale was reduced from baseline by 4.5 points (change, -53.0%) in the nemolizumab group, as compared with a reduction of 1.7 points (change, -20.2%) in the placebo group (difference, -32.8 percentage points; 95% confidence interval, -46.8 to -18.8; P<0.001). Results for secondary outcomes were in the same direction as for the primary outcome. Nemolizumab was associated with gastrointestinal symptoms (abdominal pain and diarrhea) and musculoskeletal symptoms.

Conclusions: Nemolizumab resulted in a greater reduction in pruritus and severity of skin lesions than placebo in patients with prurigo nodularis but was associated with adverse events. Larger and longer trials are needed to determine the durability and safety of nemolizumab for the treatment of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT03181503.).
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http://dx.doi.org/10.1056/NEJMoa1908316DOI Listing
February 2020

Is there still a role for UV therapy in itch treatment?

Authors:
Franz J Legat

Exp Dermatol 2019 12 19;28(12):1432-1438. Epub 2019 Aug 19.

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

Itching is a frequent and greatly distressing symptom related to many skin and systemic diseases. New insights into the pathophysiology of itchy skin and potentially involved mediators have increased the interest in and development of new treatments that specifically act on targets involved in the transmission and perception of itching. Phototherapy has long been known and used as an effective treatment for various kinds of chronic itching. However, despite its well-known beneficial effects, the mechanisms behind the antipruritic effect of phototherapy are less well-known. In addition, phototherapy requires the use of expensive equipment in dermatology offices, patients must undergo repeated treatments and no large, randomized, controlled trials have yet supported the antipruritic effect of UV. Therefore, phototherapy is rarely recommended as a treatment method for chronic pruritic diseases or only used as a last recourse. However, the wide range of pruritic conditions that can be successfully treated with phototherapy, together with its low acute side effects, extremely low frequency of interactions with other medications, possibilities to combine phototherapy with other treatment modalities and the fact that patients of almost all ages-from childhood to old age, including women during pregnancy or lactation-can be treated make UV therapy advantageous over other treatments of chronic pruritus. Thus, despite the development of new targeted therapies against pruritus, UV therapy is neither outdated nor the 'last recourse', but should be considered early on in the treatment of chronic pruritus.
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http://dx.doi.org/10.1111/exd.14011DOI Listing
December 2019

The Antipruritic Effect of Phototherapy.

Authors:
Franz J Legat

Front Med (Lausanne) 2018 30;5:333. Epub 2018 Nov 30.

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

Phototherapy is widely used to treat inflammatory skin diseases such as psoriasis and atopic dermatitis. Repeated suberythemogenic doses of UV-light reduce inflammation in these diseases and ultimately may lead to a complete disappearance of cutaneous symptoms for weeks or months. Chronic pruritus is an important and highly distressing symptom of many of these inflammatory skin diseases. Interestingly, pruritus is also reduced or completely abolished by UV-treatment of psoriasis and atopic dermatitis, and sometimes reduction of pruritus is the first indication for skin improvement by phototherapy. The cutaneous nervous system is an integral part of skin anatomy, and free nerve endings of sensory cutaneous nerve fibers reach up into the epidermis getting in close contact with epidermal cells and mediators from epidermal cells released into the intercellular space. Stimulation of "pruriceptors" within this group of sensory nerve fibers generates a neuronal signal eventually transmitted via the dorsal root and the spinal cord to the brain, where it is recognized as "itch". UV-light may directly affect cutaneous sensory nerve fibers or, via the release of mediators from cells within the skin, indirectly modulate their function as well as the transmission of itch to the central nervous system inducing the clinically recognized antipruritic effect of phototherapy.
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http://dx.doi.org/10.3389/fmed.2018.00333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287194PMC
November 2018

Humanistic burden of chronic pruritus in patients with inflammatory dermatoses: Results of the European Academy of Dermatology and Venereology Network on Assessment of Severity and Burden of Pruritus (PruNet) cross-sectional trial.

J Am Acad Dermatol 2018 Sep;79(3):457-463.e5

Center for Chronic Pruritus, Department of Dermatology, University Hospital of Münster, Münster, Germany.

Background: Chronic pruritus is a multifactorial, challenging symptom of global relevance.

Objective: The European Academy of Dermatology and Venereology Network on Assessment of Severity and Burden of Pruritus (PruNet) investigation aimed to analyze the severity and humanistic burden of chronic pruritus in patients suffering from inflammatory dermatoses across Europe.

Methods: Prospectively collected routine data on 552 patients (with atopic dermatitis, contact dermatitis, prurigo nodularis, psoriasis vulgaris, lichen planus, or mycosis fungoides [pruritus numeric rating scale score ≥3]) from 9 European centers (in Austria, France, Germany, Italy, Poland, Russia, Spain, Switzerland, and Turkey) were analyzed by univariate and multivariate variance analyses of various itch characteristics and quality of life (as measured by the Dermatology Life Quality Index and the ItchyQoL).

Results: Duration, frequency, and intensity of pruritus (according to a numeric rating scale and visual analog scale) and related impairment of quality of life differed between European centers and dermatologic diagnoses (P < .05). The country in which the center was located had a greater impact on how patients evaluated pruritus intensity and quality of life than diagnosis did (P < .001).

Limitations: One center per country was included.

Conclusion: The humanistic burden of chronic pruritus in patients with inflammatory dermatoses is high. European cross-cultural factors may have a stronger influence than a specific dermatologic diagnosis on how patients rate intensity of pruritus and quality of life.
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http://dx.doi.org/10.1016/j.jaad.2018.04.044DOI Listing
September 2018

[Importance of phototherapy in the treatment of chronic pruritus].

Authors:
Franz J Legat

Hautarzt 2018 Aug;69(8):631-640

Universitätsklinik für Dermatologie und Venerologie, Medizinische Universität Graz, Auenbruggerpl. 8, 8036, Graz, Österreich.

Phototherapy and photochemotherapy (PUVA) are important treatment modalities in inflammatory skin diseases such as psoriasis and atopic dermatitis as well as in cutaneous T‑cell lymphoma (e.g., mycosis fungoides/Sezary syndrome). Many of these skin diseases are accompanied by distracting pruritus. In addition, patients may suffer from intense pruritus in systemic diseases of the kidney and liver as well as of the endocrine and hematopoietic system. UV-light during phototherapy is capable of not only improving the inflammatory skin lesions but also of reducing the pruritus in skin and systemic diseases. The significant antipruritic effect, the usually low rate of well-known side effects, as well as the possibility to treat adults of any age, pregnant and lactating women, and under certain circumstances also children, make phototherapy a valuable treatment option for pruritus of various origin. Thus, the use of phototherapy should be considered early in the course of antipruritic therapy, when topical treatment modalities are insufficient to significantly improve pruritus.
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http://dx.doi.org/10.1007/s00105-018-4229-zDOI Listing
August 2018

S2k Guidelines for the diagnosis and treatment of chronic pruritus - update - short version.

J Dtsch Dermatol Ges 2017 Aug;15(8):860-872

Department of Clinical Social Medicine, Occupational and Environmental Dermatology, University Medical Center, Heidelberg, Germany.

Associated with a host of different diseases, pruritus is a cardinal symptom that poses an interdisciplinary diagnostic and therapeutic challenge. Over time, that symptom may progress independently of the initial cause, thus losing its function as a warning sign and turning into a clinically relevant disease of its own. In Germany, approximately 13.5 % of the general population are affected by chronic pruritus, with an incidence of 7 %. All forms of chronic pruritus require targeted treatment consisting of (a) diagnosis and management of the underlying disease, (b) dermatological treatment of primary or secondary (for example, dry skin, scratch lesions) symptoms, (c) symptomatic antipruritic treatment, and (d) psychological/psychotherapeutic treatment in case of an underlying or associated psychological or psychosomatic condition. Medical care of patients with chronic pruritus should therefore include an interdisciplinary approach, in particular with respect to diagnosis and therapy of the underlying disease as well as in terms of the management of treatment and adverse events. The objective of the present interdisciplinary guidelines is to define and standardize diagnostic and therapeutic procedures in patients with chronic pruritus. This is a short version of the current S2 guidelines on chronic pruritus. The long version may be found at www.awmf.org.
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http://dx.doi.org/10.1111/ddg.13304DOI Listing
August 2017

Sun-induced pustular dermatosis of the scalp - a new variant of erosive pustular dermatosis of the scalp?

Acta Derm Venereol 2014 Jul;94(4):457-8

Department of Dermatology and Venerology, Medical University of Graz, AT-8036 Graz, Austria.

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http://dx.doi.org/10.2340/00015555-1723DOI Listing
July 2014

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

Dermal PK/PD of a lipophilic topical drug in psoriatic patients by continuous intradermal membrane-free sampling.

Eur J Pharm Biopharm 2012 Aug 24;81(3):635-41. Epub 2012 Apr 24.

HEALTH - Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft m.b.H., Graz, Austria.

Background: Methodologies for continuous sampling of lipophilic drugs and high-molecular solutes in the dermis are currently lacking. We investigated the feasibility of sampling a lipophilic topical drug and the locally released biomarker in the dermis of non-lesional and lesional skin of psoriatic patients over 25h by means of membrane-free dermal open-flow microperfusion probes (dOFM) and novel wearable multi-channel pumps.

Methods: Nine psoriatic patients received a topical p-38 inhibitor (BCT194, 0.5% cream) on a lesional and a non-lesional application site once daily for 8 days. Multiple dOFM sampling was performed for 25 h from each site on day 1 and day 8. Patients were mobile as dOFM probes were operated by a novel light-weight push-pull pump. Ultrasound was used to verify intradermal probe placement, cap-LC-MS/MS for BCT194 and ELISA for TNFα analysis.

Results: dOFM was well tolerated and demonstrated significant drug concentrations in lesional as well as non-lesional skin after 8 days, but did not show significant differences between tissues. On day 8, TNFα release following probe insertion was significantly reduced compared to day 1.

Conclusions: Novel membrane-free probes and wearable multi-channel pumps allowed prolonged intradermal PK/PD profiling of a lipophilic topical drug in psoriatic patients. This initial study shows that dOFM overcomes limitations of microdialysis sampling methodology, and it demonstrates the potential for PK/PD studies of topical products and formulations in a clinical setting.
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http://dx.doi.org/10.1016/j.ejpb.2012.04.009DOI Listing
August 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

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

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

Photodamage to the cutaneous sensory nerves: role in photoaging and carcinogenesis of the skin?

Photochem Photobiol Sci 2006 Feb 3;5(2):170-6. Epub 2005 Nov 3.

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

Chronic exposure to ultraviolet radiation (UVR) plays a significant role in aging and carcinogenesis of the skin. Sensory nerve fibers densely innervate all layers of the skin and get in close anatomical as well as functional contact with cellular components of the epidermis and dermis. In this review, we address the impact of acute and chronic UVR exposure on the cutaneous sensory nervous system and its mediators. We suggest that skin cell-derived nerve growth factor (NGF) and skin nerve-derived neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP) may play a central role in intrinsic aging as well as extrinsic (photo-) aging of the skin. In addition, we discuss the possible role of these mediators in photocarcinogenesis.
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http://dx.doi.org/10.1039/b508856aDOI Listing
February 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

The role of calcitonin gene-related peptide in cutaneous immunosuppression induced by repeated subinflammatory ultraviolet irradiation exposure.

Exp Dermatol 2004 Apr;13(4):242-50

Department of Dermatology, Emory University, School of Medicine, Atlanta, GA, USA.

Ultraviolet (UV) light is an effective treatment for skin disorders like psoriasis in which the cutaneous neurosensory system may have a pathogenic role. In this study, we examined the possibility that UV modulation of the cutaneous neurosensory system and calcitonin gene-related peptide (CGRP) may contribute to local immunosuppression mediated by repeated subinflammatory UV irradiation. Our results indicated that exposure of hairless mice to subinflammatory UV three times weekly for 4 weeks significantly increased the number of epidermal nerve fibers (ENFs) immunoreactive for CGRP without altering the total number of ENFs. The skin content of CGRP as measured by enzyme-linked immunosorbent assay was also significantly increased after exposure to this dose of UV. These effects were most apparent 1 day after the last UV exposure and declined 1 week after UV. The role of CGRP in UV-induced immunosuppression of contact hypersensitivity was then examined. Our results indicated that UV suppression of epicutaneous 2,4-dinitro-1-fluorobenzene (DNFB) sensitization could be significantly inhibited by a systemically administered CGRP receptor antagonist. A broad-spectrum sunscreen applied before UV exposure inhibited increased cutaneous CGRP and blocked immunosuppression. These findings support a role for CGRP in the local immunosuppression caused by chronic, repeated subinflammatory UV exposure.
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http://dx.doi.org/10.1111/j.0906-6705.2004.00185.xDOI Listing
April 2004

The cutaneous neurosensory system in skin disease.

Adv Dermatol 2002 ;18:91-109

Department of Dermatology, Karl-Franzens University Graz, School of Medicine, Graz, Austria.

The cutaneous neurosensory system appears to be involved in a number of skin diseases. Ongoing studies continue to uncover potential new roles for the components of the neurosensory system in skin homeostasis and disease states. There is new evidence that neuropeptides may play a role in melanogenesis with effects on vitiligo. An increase of intraepidermal nerve fibers with a possible pathophysiologic role in photodamaged facial skin has been proposed. As our understanding of the interactions between the cutaneous neurosensory system and the various components of the skin and the immune system in times of health and disease increases, specific treatments modulating the neurocutaneous system will find their way into the armamentarium of daily dermatologic therapy.
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February 2003

Human corneal epithelial cells express functional PAR-1 and PAR-2.

Invest Ophthalmol Vis Sci 2003 Jan;44(1):99-105

Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia, USA.

Purpose: The objective of this study was to examine whether HCECs express functional proteinase-activated receptor (PAR)-1 and -2 and evaluate the effects of receptor activation on corneal epithelial cell proinflammatory cytokine production.

Methods: Expression of PAR-1 and -2 mRNAs was determined by RT-PCR in cultured primary human corneal epithelial cells (HCECs) and the human corneal epithelial cell line HCE-T. Localization of PAR-1 and -2 in whole normal human corneas was determined by immunofluorescence with PAR-1 and -2 antibodies. The functional competence of PAR-1 and -2 in corneal epithelial cells was assessed by measuring the rapid induction of intracellular [Ca(2+)] in response to thrombin, trypsin, and specific receptor-activating peptides derived from the tethered ligands of the PAR receptors. HCE-T expression of cytokines (IL-6, IL-8, and TNFalpha) in response to activation of PAR-1 and -2 was measured by quantitative RT-PCR and ELISA.

Results: Functional PAR-1 and -2 were expressed in both HCECs and HCE-T cells. Immunoreactivity for PAR-1 and -2 was detected in the outer epithelial layer of the cornea in whole human corneal sections. Activation of PAR-1 and -2 led to upregulation in HCE-T cells of both expression of mRNA and secretion of the proinflammatory cytokines IL-6, IL-8, and TNFalpha.

Conclusions: The results show for the first time that functional PAR-1 and -2 are present in human cornea. Activation of these receptors results in the production of various corneal epithelial cell proinflammatory cytokines. These observations indicate that PAR-1 and -2 may play an important role in modulating corneal inflammatory and wound-healing responses. These receptors may be useful therapeutic targets in several corneal disease processes.
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http://dx.doi.org/10.1167/iovs.02-0357DOI Listing
January 2003

Repeated subinflammatory ultraviolet B irradiation increases substance P and calcitonin gene-related peptide content and augments mustard oil-induced neurogenic inflammation in the skin of rats.

Neurosci Lett 2002 Sep;329(3):309-13

Department of Dermatology, Karl-Franzens-University Graz Medical School, Auenbruggerplatz 8, 8036 Graz, Austria.

The cutaneous neurosensory system is suggested to be involved in the pathophysiology of pruritus and skin diseases such as psoriasis. We investigated if repeated subinflammatory doses of ultraviolet B (UVB) irradiation similar to those used to treat pruritus or psoriasis would affect the cutaneous neurosensory system. Sprague-Dawley rats were irradiated thrice weekly for 2-4 weeks with subinflammatory doses of UVB. Three days after the last UVB exposure: (i), the skin contents of substance P (SP), calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF) were quantified; (ii), the skin nerve fiber density was observed; and (iii), the effect of UVB on mustard oil-induced neurogenic inflammation was determined. UV exposure significantly increased SP and CGRP content and mustard oil-induced neurogenic inflammation in UV-irradiated but not non-irradiated skin; however, it did not affect cutaneous NGF content or overall nerve fiber density. These data suggest that repeated subinflammatory UVB irradiation locally increases the content of cutaneous SP and CGRP by an increase of neuropeptide content of nerve fibers rather than by an increase of overall nerve fiber density.
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http://dx.doi.org/10.1016/s0304-3940(02)00428-7DOI Listing
September 2002