The vasculopathy of Raynaud's phenomenon and scleroderma☆
Section snippets
Vasospasm and cold-induced vasoconstrictiond
Patients who have SSc initially present with evidence of vasospastic arterial disease; approximately 95% display Raynaud's phenomenon [1], [2]. Raynaud's phenomenon is an abnormal vasoconstrictor response to cold (or emotional stress) that causes spasm or closure of cutaneous arteries resulting in sharply demarcated cutaneous pallor and cyanosis [3]. Although the digital arteries of the fingers and toes are most commonly affected, the disease can also strike the tongue, nose, ears, and nipples.
Vascular remodeling in SSc
In contrast to primary Raynaud's disease, the SSc disease process progresses to a structural vasculopathy in the microcirculation [5], [47], [48]. Small arteries and arterioles (50–500 μ in diameter) develop a fibrous, concentric intimal lesion [5], [47], [48]. The microvascular lesion is often associated with intravascular thrombi which can cause complete lumen occlusion. Platelet activity seems to be increased, whereas the fibrinolytic process seems to be impaired in SSc [5], [47], [48].
Multi-functional signaling in a multi-dysfunctional disease
SSc is a multi-dysfunctional disease that is characterized by immune activation, vascular dysfunction, and generation of intravascular and extravascular fibrosis. Effective proposals to integrate the diverse pathologies of the disease, must, therefore, consider interaction or interdependence of these regulatory systems. Dysfunction in ubiquitous signaling systems (eg, ROS, matrix proteins, endothelin, α2C-ARs) could clearly impact multiple aspects of SSc pathogenesis. Current models of the
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2014, Autoimmunity ReviewsCitation Excerpt :Ongoing experiments are being performed to define whether ACA can effectively react with recombinant VIP to support, at molecular levels, the previously demonstrated reactivity of VIP with autoantibodies [98]. Finally, the high association between the presence of vascular remodeling and that of anti-Sm/RNP autoantibodies in MCTD- and SLE-RP [58] and the ability of anti-Scl-70 antibodies [149] to induce endothelial apoptosis [150], and release chemokines and/or cytokines [151], provide indirect evidence that autoantibodies can also contribute to vessel structural alterations up to vascular remodeling in SSc-RP. The aim of medical therapy in RP is to counteract vasoconstriction in order to prevent or cure all possible arrays of clinical manifestations and their complications.
Acute retinal artery occlusion in systemic sclerosis: A rare manifestation of systemic sclerosis fibroproliferative vasculopathy
2013, Seminars in Arthritis and RheumatismCitation Excerpt :Systemic sclerosis (SSc) is a systemic connective tissue disorder characterized by severe and often progressive cutaneous and visceral fibrosis [1–4]. One of the critical abnormalities in SSc is a diffuse fibroproliferative vasculopathy most commonly involving the microvasculature system [5–11]. Although patients with SSc can present a variety of ophthalmologic abnormalities [12–16], retinal artery occlusion is an unusual complication that has been described in only a few reports [17–20].
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NAF gratefully acknowledges support from the Scleroderma Research Foundation and the NIH (AR46126).