Angiogenesis in Psoriatic Skin and its Modifications after Administration of Etanercept: Videocapillaroscopic, Histological and Immunohistochemical Evaluation

Abstract

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.

Combined Clinical, Capillaroscopic and Ultrasound Evaluation during Treatment of Plaque Psoriasis with Oral Cyclosporine

“…Although a few studies have monitored response to treatment by YO (or videocapillaroscopy) in patients with plaque psoriasis (8,(15)(16)(17), to our knowledge, only one previous study has used this technique to monitor improvement in plaque psoriasis following Cs treatment (5). In that study, Cs was administered to patients for 3 months and although there was an approximately 70% resolution oflesions, none ofthe lesions returned to normal capillaroscopic pattern, as assessed by videocapillaroscopy.…”

“…However, this sample was sufficient to permit us to closely monitor the temporal improvement in patients treated with two different doses of Cs, which would not have been possible if variability was a problem. Other studies have successfully diagnosed and monitored disease progression using these imaging techniques with similar sample sizes (5,(7)(8)(12)(13)(14)(15)(16)(17)(18)(19)(20). Ideally, a larger sample size would have permitted multivariate analysis to examine in greater detail characteristics contributing to improvement rate.…”

The Role of Angiogenesis in the Pathogenesis of Psoriasis: Mechanisms and Clinical Implications

“…Moreover, immunohistochemical staining revealed lower presence of Ang2, VEGF, Tie2 and TNF-α within scales after 12 weeks of treatment. Similar studies regarding the impact of etanercept on microcirculation of psoriatic were also conducted [54,55]. It was found to decrease angiogenesis and promote the regression of already altered networks.…”

Anti-Angiogenic Effects of Anti–Tumor Necrosis Factor α Agents in the Treatment of Behçet Disease

“…23 Immunohistochemical investigations confirmed a reduction in VEGF levels in patients with PSA after etanercept treatment. 16,23 The efficacy of adalimumab has been established in neovascular age-related macular degeneration refractory to anti-VEGF therapy. 24 Infliximab and adalimumab have shown antiangiogenic activity in Crohn disease and psoriasis.…”