**1. Introduction**

Systemic vasculitides are a heterogenous group of disorders characterized by destructive inflammation and fibrinoid necrosis of the blood vessel wall, blood vessel occlusion and ischemia of surrounding tissue. Typical clinical manifestations vary depending on the size of the affected blood vessels, and include fever, weight loss, malaise, arthralgias and arthritis. Vasculitides can be idiopathic, primary, secondary to another disease such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Artritis (RA), or associated with infections, such as infective endocarditis, pharmaceutical drug use, such as propylthiouracil and hydralazine, or other chemical exposures [1]. Vasculitis can be isolated to one organ or vessel and be relatively insignificant clinically or can present as a systemic life-treatening illness involving several organs and vessels [2].

ANCA- associated Systemic Vasculitis (AASV) is the most common primary systemic smallvessel vasculitis that occurs in adults. AASV is a small-vessel vasculitis affecting arterioles, venules, capillaries, and occasionally medium-sized arteries that commonly involves multiple organ systems. Although infrequent, the incidence of AASV is increasing. AASV is also called pauci-immune vasculitis, because no immunoglobulins or complement components are detected in the vasculitic lesions.

AASV is associated with significant morbidity and mortality, with almost all patients requiring aggressive immunosuppression. Without treatment, the mortality approaches 100% in 5 years [3]. Based upon the clinical presentation and the predominant organ involvement, AASV cases are classified as Wegener's granulomatosis (WG), microscopic polyangiitis (MPA), Churg-Strauss syndrome (CSS) and Renal Limited Vasculitis (RLV). ANCA are predominantly IgG

© 2013 Abdgawad; 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.

antibodies that were first described in the 1980s by Davies et al. in patients with necrotizing glomerulonephritis [4]. These antibodies are directed against antigenic components of neutrophilic granules or lysosomes. Indirect immunofluorescence (IIF) of ethanol-fixed neutrophils reveals cytoplasmic (cANCA) or perinuclear (pANCA) staining. cANCA staining correlates with proteinase-3 (PR3) reactivity, while pANCA staining correlates with reactivity towards myeloperoxidase (MPO) or other antigens.

systemic vasculitis [12]. In 1936, Friedrich Wegener, a German pathologist, described three patients with necrotizing granuloma and later interpreted the pathological and clinical findings to represent a distinctive disease entity in 1939 [13]. Goodman and Churg in 1954 wrote a detailed description of the disease known as "Wegener´s granulomatosis" (WG) presenting definite criteria: necrotizing granulomata of the respiratory tract, generalized vasculitis and necrotizing glomerulonephritis [14]. DeRemee and colleages in 1976 proposed the ELK classification (E= upper respiratory tract including paranasal sinuses; L= lung; K= kidney), allowing them to understand and manage cases that did not fit the strict criteria of Goodman and Churg [15]. In the early 1970s, Fauci and Wolff introduced treatment with cyclophosphamide and corticosteroids for WG, which resulted in a nearly complete and longlasting remission of the disease [16]. In addition, DeRemee published in 1985 a report on the benefits of using cotrimoxazole (trimethoprim/ sulfamethoxazole) in WG with local disease [17]. In the same year, a major breakthrough was made by Van der Woude et al who reported autoantibodies sensitive and specific for the disease. These autoantibodies reacted with the cytoplasm of ethanol-fixed neutrophils, and monocytes and were called Anti-neutrophil

History, Classification and Pathophysiology of Small Vessel Vasculitis

http://dx.doi.org/10.5772/55238

3

There are 20 recognized primary forms of vasculitis, which are classified according to the size of the affected blood vessels. The large vessel vasculitides, giant cell (temporal) arteritis and Takayasu arteritis, are caused by a granulomatous inflammation of the aorta and its major branches. In the case of giant cell arteritis, there is a particular predeliction for the extracranial branches of the carotid artery, often with involvement of the temporal artery and frequent association with polymyalgia rheumatica. The age of the patient is helpful in distinguishing between the two conditions, because giant cell arteritis is rare in patients under the age of 50

Classical polyarteritis nodosa affects medium-sized vessels and therefore should not involve glomerulonephritis or vasculitis in arterioles, capillaries or venules. Kawasaki's disease is a medium-sized vessel vasculitis that frequently involves the coronary arteries, is associated

Small vessel vasculitides include the immune-complex associated vasculitis of Henoch-Shoenlein pupura and essential cryoglobulinemic vasculitis. Henoch-Schönlein pupura has predominantly IgA immune complex deposition and involves the skin, gut and glomeruli with arthritis and arthralgia, while essential cryoglobulinemic vasculitis is caused by the deposition of cryoglobulins predominantly in the small vessels of the skin and glomeruli and is frequently associated with Hepatitis C infection. Another small vessel vasculitis category is cutaneous leucocytoclastic vasculitis, which is confined only to the skin, has no systemic involvement

with the mucocutaneous lymph node syndrome and is most common in children [2].

and has a better prognosis than vasculitides with systemic involvement [2].

Examples of different types of vasculitis are depicted in Table 1.

and Takayasu's disease is more common in younger patients [19].

Cytoplasmic Autoantibodies (ANCA) [18].

**3. Classification**

PR3-ANCAs are mainly detected in patients with WG, whereas MPO-ANCAs are predomi‐ nantly detected in patients with MPA and CSS. These diseases exhibit similar pathological focal necrotizing lesions, though WG and CSS also have granulomatous lesions [5].

Henoch-Schönlein purpura (HSP) is the most common systemic small-vessel vasculitis in children [6]. HSP is a systemic vasculitis affecting small vessels and capillaries. HSP is characterized by palpable purpura, edema, abdominal pain, joint pain and renal symptoms [7]. The prognosis is good as long as the patients have no renal symptoms. Renal symptoms vary from intermittent hematuria and proteinuria to rapidly progressive glomerulonephritis.

In this chapter, we shall discuss the pathophysiology of the most common primary small vessel vasculitis in adults, AASV, as well as the most common small vessel vasculitis in children, HSP.
