HOT CLINICAL STUDY Systemic therapy of plaque-type psoriasis ameliorates endothelial cell function: results of a prospective longitudinal pilot trial Sandra Boehncke • Stephan Fichtlscherer • Rebekka Salgo • Jurate Garbaraviciene • Heike Beschmann • Sandra Diehl • Katja Hardt • Diamant Thac ¸i • Wolf-Henning Boehncke Received: 31 August 2010 / Revised: 22 November 2010 / Accepted: 1 December 2010 / Published online: 18 December 2010 Ó Springer-Verlag 2010 Abstract Severe psoriasis is associated with significant cardiovascular mortality. We therefore investigated the effects of systemic therapy on the cardiovascular risk of psoriasis patients. Thirteen consecutive patients receiving fumaric acid esters were included and followed for 24 weeks both clinically and by means of laboratory monitoring, 10 completed the study. Eight of ten patients showed a PASI-50 response. Two of three patients with clinical insulin resistance (Homeostasis Model Assessment of insulin resistance [ 2.5) showed normal insulin respon- siveness at the end of the study. Clinical improvement was paralleled by a reduction of high-sensitive CRP serum levels (median -25%). There was a trend toward reduced serum levels for the vascular endothelial growth factor (median -10%) and resistin (median -4%), while the potentially cardio-protective adiponectin showed a trend toward increased serum levels under therapy (median ?19%). Systemic endothelial function assessed by venous occlusion plethysmography revealed an improvement of endothelial vasodilator function after 24 weeks of treat- ment (p \ 0.02). This is the first prospective study docu- menting an amelioration of endothelial cell function in patients with moderate-to-severe plaque-type psoriasis under effective continuous systemic therapy. Future studies need to compare the cardioprotective effects of different treatment modalities, based on hard end points such as the rate of myocardial infarction. Keywords Psoriasis Á Comorbidities Á Myocardial infarction Á Insulin resistance Á Endothelial cell dysfunction Á Adipokines Introduction Psoriasis is a common, chronic inflammatory skin disease that typically presents with sharply demarked, red scaly plaques on the skin [27]. There is increasing awareness that psoriasis is more than ‘‘skin deep’’ and that it has important systemic manifestations that are shared with other chronic inflammatory diseases, such as Crohn’s disease and rheu- matoid arthritis [26]. Of emerging significance is the relationship between severe psoriasis and cardiovascular diseases [2]: A recent population-based study identified severe psoriasis as an independent risk factor for myocar- dial infarction [11], and a case–control study showed substantially elevated levels of coronary artery calcification as an early indicator for coronary artery disease [21]. These observations explain the increased mortality of psoriasis patients with severe psoriasis [12]. Other studies, however, failed to identify psoriasis as an independent cardiovascu- lar risk factor [31]. The systemic nature of the psoriatic inflammation is reflected, among others, by elevated levels of pro-inflam- matory cytokines as well as by increased C-reactive protein (CRP) levels [4, 5] and platelet activation [10, 22]. These features of the psoriatic inflammation provide the patho- physiological link to cardiovascular disease, as they play a S. Boehncke and S. Fichtlscherer contributed equally to this project. S. Boehncke Á S. Fichtlscherer Department of Internal Medicine, Clinic of the Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany R. Salgo Á J. Garbaraviciene Á H. Beschmann Á S. Diehl Á K. Hardt Á D. Thac ¸i Á W.-H. Boehncke (&) Department of Dermatology, Clinic of the Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany e-mail: Boehncke@em.uni-frankfurt.de 123 Arch Dermatol Res (2011) 303:381–388 DOI 10.1007/s00403-010-1108-6