Anti-Inflammatory Action of Keratinocyte-Derived Vaspin: Relevance for the Pathogenesis of Psoriasis.

Impaired cross talk between keratinocytes (KCs) and immune cells is believed to contribute to the pathogenesis of chronic inflammatory skin diseases, such as psoriasis. We have previously identified KCs as a rich source of the serpin protease inhibitor vaspin (serpinA12), originally described as an adipokine in adipose tissue. Herein, we studied whether dysregulated vaspin expression in KCs contributes to the pathogenesis of psoriasis. We found vaspin expression to be closely associated to epidermal differentiation, with low levels in proliferating KCs and high levels in differentiated cells. Consistently, in human psoriasis and in a mouse model of a psoriasis-like skin inflammation, epidermal vaspin expression was significantly down-regulated. Down-regulation of vaspin in KCs resulted in decreased expression of differentiation-associated genes and up-regulation of interferon-inducible and inflammation-associated psoriasis signature genes. Vaspin was also shown to modulate the communication between KCs and inflammatory cells under co-culture conditions. A decrease in vaspin expression in KCs stimulated the secretion of tumor necrosis factor-α, IL-1ß, IL-6, IL-8, and monocyte chemoattractant protein-1 by co-cultured dendritic cells, macrophages, monocytes, and neutrophils. Consequently, the application of vaspin inhibited myeloid cell infiltration in a mouse model of a psoriasis-like skin inflammation. In conclusion, vaspin expression by maturing KCs modulates cutaneous immune responses and may be involved in the pathogenesis of psoriasis.

How to perform extracorporeal photopheresis via port catheter.

BACKGROUND: Extracorporeal photopheresis (ECP) is commonly performed via peripheral venous access catheter. If this is not possible, a tunneled central venous catheter may be considered. However, this access mode may be associated with high complication rates. Port catheters and permanent arteriovenous fistulas in principle could serve as alternative options; however, treatment opinions are limited. STUDY DESIGN AND METHODS: We report on four adult patients with poor peripheral vein conditions in whom we performed ECP via port catheter. RESULTS: In three of four patients, problems arising from temporarily impaired blood aspiration or reinfusion were solved by repositioning the patient, intermittent flushing of the port catheter, and, in one patient, by instillation of 2500 units of heparin into the port prior to the first ECP of the 2-day cycle. One female patient sustained extensive central venous thrombosis. CONCLUSION: A port catheter may, in certain circumstances, constitute a patient-friendly alternative for venous ECP access when patients' peripheral veins are unsuitable. However, a prolonged ECP procedure duration must be taken into account for decision making.

High-Fat Diet Exacerbates Early Psoriatic Skin Inflammation Independent of Obesity: Saturated Fatty Acids as Key Players.

In obesity, hypertrophic adipocytes secrete high amounts of adipocytokines, resulting in low-grade inflammation amplified by infiltrating proinflammatory macrophages, oxidative stress, hypoxia, and lipolysis. These chronic proinflammatory conditions support the development of type II diabetes and cardiovascular diseases, but the mechanisms of obesity-related exacerbation of inflammatory skin disorders like psoriasis are unclear. In this study, we uncovered dietary saturated fatty acids (SFAs) as major risk factors for the amplification of skin inflammation, independent of obesity-related parameters such as fat mass extension, adipocytokine levels, and glucose homeostasis. Correlation analyses in a cohort of psoriasis vulgaris patients showed that free fatty acid serum level was the only obesity-associated parameter affecting disease severity. Studies in mice with high-fat diet-induced obesity with psoriasiform inflammation confirmed this critical role of free fatty acids. An increase of free fatty acids in healthy, lean mice alone was sufficient to induce an exacerbation of psoriasiform inflammation. In particular, saturated fatty acids sensitize myeloid cells to an increased inflammatory response in answer to proinflammatory stimuli, which in turn augments the activation of keratinocytes. Consequently, reduction of nutritional saturated fatty acids alone diminished the psoriatic phenotype in obese mice. Thus, our findings may open new perspectives for adjuvant dietary measures accompanying anti-inflammatory psoriasis therapies in lean and obese patients.

Updated results of 100 patients on clinical features and therapeutic options in necrobiosis lipoidica in a retrospective multicentre study.

BACKGROUND: Necrobiosis lipoidica (NL) is a rare granulomatous disorder of unknown aetiology which can manifest in ulcerative skin lesions and is widely recognised in association with diabetes. We evaluated in total 100 patients to improve knowledge about the epidemiology and clinical course of NL. Additionally we focused on treatment options according to evidence level and expert opinion. OBJECTIVE: To examine the clinical features of patients with necrobiosis lipoidica and to give recommendations for topical and systemic treatment. MATERIALS & METHODS: This multicentre retrospective study covers data from 100 patients with the diagnosis of NL of the lower leg, treated during the period between 01/2006 and 06/2014. Data from 5 German dermatological centres with 23 men and 77 women with a median age of 52 years were evaluated. We also asked 15 dermatological experts for their opinions about ulceration, associated diseases and their preferences for treatment modalities of NL. RESULTS: Patients' ages ranged from 15 to 95 years (median age 52 years, mean age 49.8 years). NL was significantly more common in women (77%). Ulceration of the NL was observed in 33% of cases, in particular in male patients and in patients with concomitant diabetes mellitus. Thyroidal disorders were found in 15% of all cases. CONCLUSION: Our data confirm that female sex, middle age and endocrine disorders like diabetes mellitus or thyroid dysfunction are characteristics of patients suffering from NL. Existing therapeutic options were very variable and - according to the opinion of our experts - only a few highly effective.

Update on clinical and laboratory features in necrobiosis lipoidica: a retrospective multicentre study of 52 patients.

Necrobiosis lipoidica (NL) is a rare granulomatous disorder of unknown etiology which can manifest in ulcerative skin lesions and is widely recognised in association with diabetes mellitus. Our aim was to improve knowledge about the epidemiology and clinical course of NL and evaluate treatment approaches. This multicentre retrospective study covered data from 52 patients with NL of the lower leg, treated between 2006 and 2011. Data from three German dermatological centres were analysed. Twelve men and 40 women, aged 15 to 87 years, were evaluated with regard to epidemiological data, ulcerations, co-morbidities, laboratory values and treatment options. NL was significantly more frequent in women (76.9%). Ulceration of NL was observed in 25% of all patients and in 37.5% with concomitant diabetes mellitus. 88% received topical treatment with corticosteroids, 56% compression therapy of the lower legs, 42% UV-phototherapy and 29% topical calcineurininhibitors. Systemic therapies were also used occasionally. Our data indicate that female sex, middle age and endocrine disorders like diabetes mellitus are characteristics of NL patients. As new aspects, we found an accumulation of thyroidal dysfunction (13%) and that ulcerations are predominantly in males (58%). Associations with co-morbidities may become clearer in prospective studies of larger cohorts. Topical steroids, calcineurin inhibitors, compression therapy and phototherapy seem to be the basis therapies although our evaluation showed that standardized guidelines are missing. More experimental therapeutic options, like biologicals, photodynamic therapy or the use of fumaric acid esters, should be assessed for efficacy and safety by large, randomized, controlled trials.