046 Epidemiology of lentigo maligna and lentigo maligna melanoma in the Netherlands, 1989-2013

S | Clinical Outcomes 043 Mechanism of action of propranolol in Infantile Hemangioma: New insights from a xenograft model F Moisan, J Nissen, P Kaulanjan-Checkmodine, S Prey, P Dufourcq, T Couffinhal, H Rezvani and A Taieb 1 Dermatology, Bordeaux University, Bordeaux, France and 2 Cardiology, INSERM U1034, Pessac, France 8 years after propranolol was found efficacious in infantile hemangioma (IH), therapeutic mechanisms remain elusive. It has been shown, in an ovarian cancer model, that ADRB2 signaling is key for chronic stress induced tumor growth. In this model, tumor promotion is abolished by propranolol or ADRB2 siRNA but not by ADRB1 siRNA. In IH patients, after oral administration of 3 mg/kg/day of propranolol, plasma Cmax is below 1 mM, whereas propranolol has been used in vitro at 100 mM and up to 50 mg/kg in mouse models. Thus, an animal model which recapitulates propranolol response at clinical doses is still needed. We have chosen to develop an in vivo human model of xenografted malignant tumor (glioblastoma) which is very angiogenic and selectively ADRB2 positive. In such a model tumor hypoxia can be induced by the anti-VEGF-A bevacizumab (Avastin). In our model, 2 mg/kg/ day of propranolol, or ADRB2 knockdown, induces a modest inhibition of tumor induction but has no effect on doubling time. The growth of the tumors is only delayed. Using propranolol doses ranging from 2 to 50 mg/kg we observed an inverse dose response which has been already shown for periodontal disease. Elevated HIF1a in IH suggested strongly that a hypoxic environment can explain the specific response of IH to propranolol. Indeed, in the context of relative hypoxia induced by Avastin, our tumor model responds with markers shared by IH such as HIF1 a, GLUT1 or MMP9. In that situation, ADRB2 knockdown as well as low doses of propranolol have a significant impact on tumor growth. Furthermore, we could show that both propranolol and ADRB2 knockdown mediate an attenuation of MMP9 expression. Interestingly CREB3L1, which is a cAMP dependent transcription factor known for binding MMP9 promoter, was also downregulated both by propranolol and ADRB2 knockdown. MMP9 appears thus as a potential generic marker of propranolol antitumoral response also involved in the specific therapeutic response first evidenced in IH. S168 Journal of Investigative Dermatology (2016), Volume 136 044 Cellular mechanism of action of IgE-specific immunoadsorption in treatment of patients with severe atopic eczema R Wang, K Eyerich, S Eyerich, A Zink, J Thomas, T Biedermann and C Schmidt-Weber 1 Helmholtz Center, ZAUM Center for Allergy and Environment, Munich, Germany and 2 Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany IgE-specific immunoadsorption (IA) is an effective treatment for severe forms of atopic eczema (AE). However, mechanisms behind this therapeutic approach and biomarkers predicting the therapeutic outcome are not yet known. This study is aimed at detecting the impact of IA on cellular level and clinical outcome. Six patients with severe AD (SCORAD>40) and highly elevated IgE levels (IgE>2.000IU/ml) were included in the study. Every patient received a total of ten IgE-specific IA sessions that were conducted in three intervals with a break of two weeks between each interval. A follow-up examination was performed four weeks after the last session. Frequencies of different immune cell populations and their Fc receptor expression profiles as well as changes in basophil activation were monitored by flow cytometry at the beginning and the end of the first interval to detect shortterm effects and at the end of the last interval, respectively, to evaluate mid-term effects. Finally, the follow-up analysis monitored potential long-term effects. As expected, IA decreased IgE levels, which tended to increase again overnight but showed a slight overall reduction by 11,4% at follow-up. Despite this marginal and short-term effect on serum IgE levels, IA was clinically effective with an average reduction of the SCORAD of 46,2%. At cellular level, the relative number of neutrophil granulocytes decreased over time by 34,4%, while the number of other immune cells was unaltered. Even though the frequency of FceRIa on basophil granulocytes remained unchanged, the MFI declined. Moreover, the expression of CD32 on B cells decreased. In conclusion, although reduction of IgE levels by IgE-specific IA is not persistent, the improvement of SCORAD and patient well-being is long-lasting. Even though the underlying mechanisms are not yet fully elucidated, effects of IA at the cellular level might contribute to the clinical efficiency. 045 Psoriasis and addictions: a neglected challenge A Zink, M Herrmann, T Fischer, A Bohner, F Lauffer, N Garzorz-Stark, T Biedermann and K Eyerich Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany Psoriasis affects up to 4% of the general population with an enormous socio-economical impact. Within the last few years substantial achievements have been made in understanding the pathogenesis of psoriasis, which led to the approval of a number of highly effective drugs. However, only a proportion of psoriasis patients actually receive best medical treatment. To investigate the association of psoriasis and addictions and its possible negative impact on treatment compliance, we screened psoriasis patients for the most common addictions in Germany. 102 patients with psoriasis treated at the University Department of Dermatology at Technical University of Munich were included between October 2015 and February 2016 and asked to fill out a paper-based self-reported anonymous questionnaire with 92 questions of validated screening tests for addiction (alcohol, nicotine, drugs and illegal drugs, gambling, food). The results were then compared to the federal report on prevalence of addictions in Germany in 2015. Of 102 patients, 57 showed addictive behaviour measured with the used screening tools. Thereof, 41% were regular smokers, 24% high risk drinkers, 11% at risk for drug abuse, 4% at risk for food dependency and 19% compulsive gamblers. Compared to the general population addictions were significantly higher for alcohol abuse (p<0.005), nicotine (p<0.00005) and gambling (p<0.0001). In addition the body mass index was increased in the study population (p<0.0001). Screening measures for addictions have to be promoted for the assessment of psoriasis and can be recommended for all doctors treating patients with psoriasis. Addictions negatively affect treatment compliance and might contribute to the undertreatment of patients with psoriasis in general. Parallel to new drug approvals and even more detailed insights into pathomechanisms of psoriasis, public health strategies and interdisciplinary approaches are essential for the future of sustained psoriasis healthcare. 046 Epidemiology of lentigo maligna and lentigo maligna melanoma in the Netherlands, 1989 e 2013 K Greveling, M Wakkee, T Nijsten, RR van den Bos and L Hollestein Dermatology, Erasmus MC Cancer Institute, Rotterdam, Netherlands Lentigo maligna (LM) is considered a precursor to LM melanoma (LMM). We assessed trends in LM and LMM incidence rates between 1989 and 2013 in the Netherlands, and estimated the risk of a LMM after LM. Data on newly diagnosed LM and LMM were obtained from the Netherlands Cancer Registry and PALGA (Dutch Pathology Database). Age-standardized incidence rates (European standardized rate [ESR]), estimated annual percentage changes (EAPC), and the cumulative incidence of LMM after LM were calculated. Between 19892013, 10,545 patients were diagnosed with a primary LM and 2,898 with a primary LMM in the Netherlands. The ESR for LM increased from 0.72 to 3.84 per 100,000 person-years, and for LMM from 0.24 to 1.19 between 1989-2013. LM incidence increased from 2002-2013 with 6.8% annually, prior to the e even steeper e rise in LMM incidence from 2007-2013 (EAPC: 12.4%). The cumulative incidence of LMM after a primary LM after 25 years follow-up was 2.0% for males and 2.6% for females. The increased incidence of LM and LMM in the Netherlands seems, besides increased awareness, increased histological confirmation, diagnostic drift and changed market forces, to reflect a true increase. The absolute risk of a LMM (at any location) after a histologically confirmed LM was low (2.0 e 2.6%). 047 Validation of the Self-Assessment Vitiligo Extent Score (SA-VES) as a patient reported outcome N van Geel, J Lommerts, M Bekkenk, CA Prinsen, V Eleftheriadou, A Taieb, M Picardo, K Ezzedine, A Wolkerstorfer and R Speeckaert 1 Dermatology, Ghent University Hospital, Ghent, Belgium, 2 Dermatology, University of Amsterdam and Netherlands Institute for Pigment Disorders, Amsterdam, Netherlands, 3 Dermatology, EA EpiDermE, UPE-Universite Paris-Est, Paris, France, 4 Dermatology, San Gallicano Dermatology Institute, Rome, Italy, 5 Dermatology, University Hospital Center of Bordeaux, Bordeaux, France, 6 Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, Netherlands and 7 Centre of Evidence Based Dermatology, University of Nottingham, Nottingham, United