Background Chronic spontaneous urticaria (CSU) is defined as spontaneous occurrence of wheals and/or angioedema for ≥6 weeks. Omalizumab is a monoclonal anti-IgE antibody effective in refractory CSU, but its mechanism of action and markers predictive of response remain not completely defined.Objectives To correlate baseline levels of two proposed biomarkers, total IgE (bIgE) and D-dimer (bD-dimer), and clinical parameters to omalizumab response and to relapses after drug withdrawal.Methods In this retrospective Italian multicentre study, clinical data were collected in 470 CSU patients, and bIgE and bDdimer were measured in 340 and 342 patients, respectively. Disease activity was determined by Urticaria Activity Score 7 (UAS7) at week 1 and 12 after omalizumab starting. Relapses were evaluated during a 2-and 3-month interval after a first and a second course of treatment, respectively.Results bIgE correlated to a good response to omalizumab since levels were significantly higher in responders than nonresponders (P = 0.0002). Conversely, bD-dimer did not correlate to response. There was no correlation between both bIgE and D-dimer and either first or second relapse. Disease duration was significantly longer in patients who experienced either first or second relapse (P < 0.0001 and P = 0.0105, respectively), while baseline UAS7 correlated only to first relapse (P = 0.0023).Conclusions Our study confirms bIgE as a reliable biomarker predicting response to omalizumab in CSU, while it does not support the usefulness of bD-dimer unlike previous findings. CSU duration before omalizumab and baseline UAS7 may be clinical markers of relapse risk. JEADV 2019, 33, 918-924 Predictors of response to omalizumab and relapse in CSU Positivity for antithyroglobulin or antithyroperoxidase autoantibodies §, n (%) 106 (26.7) 15 (36.6) 0.1995 †IgE values missing for 130 patients. ‡D-dimer values missing for 128 patients. §Data missing for 32 patients. IQR: interquartile range; SD: standard deviation.

Psoriasis is a chronic skin disease, characterized by epidermal hyperplasia, inflammation, angiogenesis and vascular remodelling. An immunohistochemical study on fifteen cryosections of psoriatic skin was performed using antibodies against VEGF, HIFl-a, CD34, Factor VIII, MMP-2, MMP-9, TIMP-l and TIMP-2. Psoriatic skin showed a diffuse VEGF positive staining (13.15± 6.6), while no expression was observed in normal epidermis. No or faint HIF-la immunostaining was detected in healthy skin, while in psoriatic skin HIF-la was diffusely expressed. A positive correlation between HIF-la and VEGF was reported in psoriatic skin (r= 0.644; p=0.010). In psoriatic sections CD34 expression was significantly higher in respect to control skin (19.15 ± 12.61 vs 3.0 ± 0.23; p= 0.04), factor VIII immunostaining also demonstrated a significant increased development of the microvasculature in comparison with healthy skin (18.39 ± 8.16 vs 7.4 ± 0.20; p= 0.033). Total MMP-2 expression of healthy skin (30± 2.26) was significantly lower in respect to the MMP-2 psoriatic skin (71.5±4.13; p= 0.0001) an4-a-positive correlation was observed between VEGF and MMP-2 in psoriatic patients (r= 0.688; p= 0.046). In psoriatic skin MMP-9 expression was significantly increased in comparison to control skin (31±3.3 vs 8±6.1; p=0.007). All cases of psoriatic skin tissue showed that TIMP-2 and TIMP-l expression statistically decreased in psoriatic skin (respectively 11±1.2 and 12±1.5) in comparison with healthy skin (respectively 15±3.2 and 53±3.8; p=O.OOOI). In conclusion, we observed that VEGF overexpression correlated with HIF-la and MMP-2 expression, underlining the role of VEGF in psoriasis as a key factor in the link between inflammation and angiogenesis.Psoriasis is a chronic skin disease, characterized by epidermal hyperplasia, inflammation, angiogenesis and vascular remodelling (1-2). Microvascular changes within lesional skin include pronounced dilatation, tortuosity, increased permeability and endothelial cell proliferation within the venous limb of capillaries in the dermal papillae (3). Morphometric analysis of the vascular changes in psoriasis has shown that there is an increase in the capillary mass, compared with normal skin (4). Other studies have demonstrated that increased blood flow and tortuosity of the dermal capillary loops occur early in the progression of a lesion, before epidermal hyperplasia can be

Several studies suggest that microangiopathy plays a crucial role in the pathogenesis of psoriasis. TNFalpha up-regulates the genetic transcription of VEGF, a pro-angiogenetic cytokine over-expressed in psoriatic skin, which promotes micrangiopathic modifications in psoriatic plaque. Etanercept is a chimeric protein used in the treatment of psoriasis and other immunomediated disorders, which blocks inflammatory response by interfering in the binding of TNF-alpha to its receptors. Starting from this data, we retain that etanercept can improve microangiopathy in psoriatic skin by reducing the synthesis of pro-angiogenetic chemokine VEGF. The aims of the study are: to verify the effect of etanercept on cutaneous en plaque capillaries in vivo using intra-vital videocapillaroscopy analysis, to evaluate the relation between the en plaque videocapillaroscopic pattern and the immunohistochemical cutaneous expression of VEGF in psoriasis, and finally to correlate all these in data with clinical disease activity. Eighteen patients (10 male and 8 female, mean age 51, range 21-60) suffering from stable, en plaque type psoriasis, involving at least 10 percent of body surface area (BSA), and not responsive to conventional therapy were included in the study. All the enrolled patients received etanercept 50mg/twice/week, subcutaneously, for 12 weeks, and were carefully followed up for clinical response with PASI score and DLQI index both before (T0) and after 12 weeks (T12) of treatment with etanercept. A well demarcated psoriatic plaque of the extensor surface of upper extremities was chosen to perform an intra-vital videocapillaroscopy analysis (IVCP), and a skin biopsy for immunohistochemical study both at T0 and T12 in all the included patients, in order to evaluate the presence of microangiopathy and its modification after therapy. All the patients experienced a clinical improvement of cutaneous disease with a significant decrease of PASI score (p<0.0001) and DLQI level (p<0.0001), throughout the twelve weeks of treatment. On IVCP analysis, microangiopathy dramatically decreased (p<0.0001), this modification being significantly related with PASI and DLQI decrease at T12. Immunohistochemical expression of VEGF decreased significantly from T0 to T12 (p<0.0001), and was related with a reduction of psoriatic microangiopathy at T12. The results of our videocapillaroscopic and immunohistochemical investigation confirm that the therapeutic potentiality of etanercept is based also on its capability to promote the regression of psoriatic microangiopathy. Moreover, according to these considerations, videocapillaroscopic evaluation of psoriatic plaque, both before and after treatment with etancercept, may be a useful tool to objectively demonstrate its effect on microcirculation.

Psoriatic arthritis (PsA) is a chronic inflammatory autoimmune arthritis, occurring in patients with psoriasis (Pso), that may affect the whole musculoskeletal system but also nails, eye, and gastrointestinal tract. Dermatologists and rheumatologists usually manage Pso and PsA separately, but early diagnosis and integrated management could achieve better outcomes of both skin and musculoskeletal manifestations, thus improving the health-related quality of life (HRQoL) of patients. In this work, we have described a model of integrated dermo-rheumatologic approach for the early diagnosis of PsA and to present the outcomes of the multidisciplinary management of PsA patients after 48 weeks of follow-up. Pso patients complaining musculoskeletal symptoms were enrolled in a DErmo-Rheumatologic Clinic (DERC) in order to screen, classify, and treat patients with PsA, employing an operative working procedure and a specific flowchart. The integrated dermatologic and rheumatologic management of PsA patients allowed a prompt establishment of the diagnosis and the best therapeutic approach in these patients, with a significant improvement of skin and articular diseases and, eventually, a consistent amelioration of HRQoL. Dermatologists and rheumatologists usually manage the "psoriatic disease" in separated outpatient clinics. In our study, we have demonstrated that a combined DERC, by means of a tight cooperation between the dermatologist and the rheumatologist, which use a specific working procedure and treatment flowchart, may achieve the optimal clinical management of these patients, with a consistent clinical remission of the disease and a significant amelioration of the HRQoL.

Introduction: Treat-to-target strategies are used in several chronic diseases to improve outcomes. Treatment goals have also been suggested for psoriasis, but there is currently no consensus on targets, and guidance is needed to implement this strategy in clinical practice. The project 'Treat to Target Italia' was launched by a scientific board (SB) of 10 psoriasis experts to generate expert consensus recommendations.