**Author details**

Mislav Radić<sup>1</sup> and Josipa Radić<sup>2</sup>

1 Division of Rheumatology and Clinical Immunology, University Hospital Centre Split, University of Split School of Medicine, Split, Croatia

2 Division of Nephrology, University Hospital Centre Split, University of Split School of Medicine, Split, Croatia

### **References**

[1] Medsger, T. A. Jr. Natural history of systemic sclerosis and the assessment of disease activity, severity, functional status, and psychologic well-being. Rheumatic diseases clinics of North America. (2003). , 29(2), 255-73.

[2] LeRoy ECSystemic sclerosis. A vascular perspective. Rheumatic diseases clinics of North America. (1996). , 22(4), 675-94.

of the syndrome, and might be defined as rheumatoid vasculopathy. Several disease-related mechanisms may be involved in the development of premature vascular damage in RA. Increased synthesis of proinflammatory mediators, autoantibodies against endothelial cell components, perturbations in T-cell subsets, genetic polymorphisms, hyperhomocysteinemia, oxidative stress and abnormal vascular repair are associated with atherosclerosis in RA.

Vascular involvement in SLE may be of inflammatory or thrombotic origin. Both mechanisms involve the immune system. The activation and consequent endothelial lesions play a very important role in the disease pathogenesis. The common hypothesis for vasculopathy in SLE concerns the endothelial deposition of circulating immune complexes. There are many various autoantibodies in SLE as circulating immune complexes which directly or indirectly affect endothelial cells, causing chronic vessel wall damage. Furthermore, vasculitis in SLE is proatherogenic condition and is characterized by leucocytes activation and production of

Although SSc is considered a fibrosing disease, vascular involvement plays a major role in pathogenesis and organ dysfunction. SSc vascular disease involves vasculopathy with luminal occlusion, thrombosis and vasospasm. The vascular pathology in SSc is not necessarily an inflammatory process and would be better be characterised as a vasculopathy in the absence of vasculitis. In the current pathogenic model of SSc, a vascular injury of unknown cause leads to endothelial apoptosis and initiates the process of SSc vasculopathy. Histopathology of SSc vasculopathy reflects the underlying pathogenesis, with myofibroblast proliferation and matrix deposit in the subendothelial layer leading to obliterative thickening of vessel walls. Inflammatory infiltrates are absent, and the internal elastic lamina remains intact. In contrast to vasculopathy, concurrent vasculitis in SSc shows histopathological evidence of inflamma‐

tion with presence of mononuclear infiltrates and destruction of the vascular wall.

1 Division of Rheumatology and Clinical Immunology, University Hospital Centre Split,

2 Division of Nephrology, University Hospital Centre Split, University of Split School of

[1] Medsger, T. A. Jr. Natural history of systemic sclerosis and the assessment of disease activity, severity, functional status, and psychologic well-being. Rheumatic diseases

cytokine and other inflammatory mediators.

176 Updates in the Diagnosis and Treatment of Vasculitis

and Josipa Radić<sup>2</sup>

University of Split School of Medicine, Split, Croatia

clinics of North America. (2003). , 29(2), 255-73.

**Author details**

Medicine, Split, Croatia

Mislav Radić<sup>1</sup>

**References**


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**Chapter 8**

**Treatment of ANCA-Associated Vasculitis in Adults**

Vasculitis is the general term used to describe diseases associated with inflammation of the blood vessels. This inflammation results in end-organ ischemia and damage with lifethreatening consequences. Treatment is tailored to the type of vasculitis the patient has, prognostic features and disease severity. Two main treatment phases are recognized: induction of remission, and maintenance of remission. In this chapter we will focus on the treatment of ANCA-associated vasculitis (AAV), namely: Granulomatosis with polyangiitis (GPA), formerly Wegener's Granulomatosis; Eosinophilic granulomatosis with polyangiitis (EGPA), formerly Churg-Strauss Syndrome, and Microscopic Polyangiitis (MPA). Patients with Polyarteritis nodosa (PAN) were included in the initial therapeutic trials of these diseases,

We introduce first the historical use of glucocorticoids, which are uniformly incorporated in the treatment protocols of therapeutic trials. Cyclophosphamide is recommended for the induction of remission in AAV, and in particular for generalized and severe disease. CY‐ CLOPS, a trial of oral versus intravenous cyclophosphamide, demonstrated that intravenous dosing was as effective in inducing remission with a reduced cumulative dose, and with fewer episodes of leucopenia, but in long-term follow-up relapse was more common in the intrave‐ nous treatment group. NORAM compared the use of methotrexate compared to oral cyclo‐ phosphamide for induction of remission in patients with limited GPA, and concluded that methotrexate was nearly as effective as cyclosphosphamide in achieving remission, but in long-term follow-up more corticosteroids and further immunosuppressive agents were required. More recently, rituximab use for the induction of remission was studied in the RAVE and RITUXVAS clinical trials. Rituximab was proven to be effective as cyclophosphamide, but without a reduction in the rate of infection as had been expected. Plasma exchange in combi‐ nation with oral cyclophosphamide for patients with severe renal involvement significantly decreases the risk of end-stage renal disease compared to intravenous steroids and oral

> © 2013 Fifi-Mah and Barnabe; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

> © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

and reproduction in any medium, provided the original work is properly cited.

therefore some of the studies results have been applied to that population as well.

cyclophosphamide, but without a significant difference in patient survival.

Aurore Fifi-Mah and Cheryl Barnabe

http://dx.doi.org/10.5772/54290

**1. Introduction**

Additional information is available at the end of the chapter
