Jacques Choucair

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130 Updates in the Diagnosis and Treatment of Vasculitis

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/55189

**1. Introduction**

#### **1.1. Infectious vasculitis**

The vasculitides are a heterogeneous group of clinicopathological entities that share the common feature of vascular inflammation and injury. There is no universally acceptable classification of this group of disorders. While a number of underlying causes can be identified in some disorders, the aetiology is unknown in many. The pathogenetic mechanisms involved are mainly immunological, immune complex mediated tissue injury being the most commonly incriminated factor.

In 1952, Zeek [1] became the first author to incorporate a clinicopathological assessment based on the size of the vessels involved in the inflammatory process in her classification of necrot‐ izing vasculitis. A number of alternative classification systems were proposed later and a major break was made in the 1990s with the 1990 American College of Rheumatology criteria (ACR 1990 criteria); and the elaboration of a uniform terminology for naming, defining, classifying and diagnosing vasculitic disorders at the Chapel

Hill Conference 1992 (1992 CHC definitions). The 1990 ACR criteria were reviewed in 1996 by Hunder [2]. The 1992 CHC definitions now include immunodiagnostically significant markers [e.g. ANCA in Wegener's granulomatosis (WG) and immunohistological findings (e.g. IgA‐ dominant immune deposits in Henoch–Schönlein purpura) which are specific for certain diseases and were described by Jennette *et al.* [3]

The major problem with previous classification schemes was the lack of standardized diag‐ nostic terms and definitions. As a consequence, different names had been applied to the same disease and the same name to different diseases. Therefore, the CHC committee—comprised of internists, rheumatologists, nephrologists, immunologists and pathologists who have in common extensive experience with diagnosing vasculitides—proposed the names and definitions given in Table 3.

© 2013 Choucair; 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.

#### 132 Updates in the Diagnosis and Treatment of Vasculitis


By contrast, immune complex deposits *in situ* are the hallmark of immune complex vasculitis, which is frequently associated with low complement levels. Granulomatous arteritis is characterized by an inflammatory infiltrate induced by Th1 cells. The predominant immune phenomena in systemic vasculitides associated with the major hypersensitivity reaction type

Infectious Causes of Vasculitis http://dx.doi.org/10.5772/55189 133

While some forms of vasculitides may be ascribed to underlying factors like infections, malignancy, drug reactions or connective tissue disorders, the cause may remain undeter‐ mined in many vasculitic syndromes. Immunologic damage by immune-complex deposition

**1. Deposition of circulating antigen-antibody complex** or in -situ formation of immune complex within the vessel wall. This leads to complement activation and chemotactic attraction of neutrophils by complement components. Subsequent phagocytosis of such complexes with liberation of neutrophil granular products leads to vascular damage. **2. Cell-mediated hypersensitivity**: Antigenic exposure may attract lymphocytes which liberate cytokines causing tissue damage and further activation of macrophages and

**3.** Failure to clear the antigen may lead to persistent inflammation and eventual formation of epithelioid cells and giant cells, giving rise to a **granulomatous tissue reaction**.

Whatever the underlying mechanism, vascular inflammation and necrosis ensues which is often accompanied by thrombosis. These pathologic changes result in tissue ischaemia,

or cell-mediated hypersensitivity is responsible in the majority of cases.

The possible immunopathologic mechanism in the causation of vasculitis are:

are given in Fig. 1.

**Figure 1.** Pease add caption

lymphocytes.

a Large vessel refers to the aorta and the largest branches directed towards major body regions (e.g. to the extremities and the head and neck); medium-sized vessel refers to the main visceral arteries (e.g. renal, hepatic, coronary, and mesenteric arteries); small veseel refers to venules, capillaries, arterioles, and the intraparenchymal distal arterial radicals that connect with arterioles. Some small and large vessel vasculitides may involve medium-sized arteries,but large- and medium- sized vessel vasculitides do not involve vessels smaller than arteries. Essential components are represented by normal type; italicized type represent usual, but not essential components.

bPreffered term.

c Strongly associated with ANCA.

Reproduced from [4] with permission.

**Table 1.** Names and definitions of vasculitides adopted by the Chapel Hill Concensus Conference on the Nomenclature of Systemic Vasculitis

#### **2. Immunopathogenesis**

Most of the vasculitic syndromes are mediated by immunopathogenic mechanisms ('immune vasculitides') and most 'immune vasculitides' are idiopathic (= 'primary' vasculitis).

The immunopathogenic mechanisms of vasculitides have been classified into the four types of hypersensitivity reaction described by Coombs and Gell [4]; this classification was reviewed recently [5]. Accordingly, clinicopathological and immunohistochemical studies have led to the terms allergic angiitis (I), antibody‐mediated angiitis, including the 'new' group of ANCA‐ associated vasculitides (II), immune complex vasculitis (III), and vasculitis associated with T‐ cell‐mediated hypersensitivity (IV). Eosinophilia and elevated IgE in the blood and tissues (*in situ*) are characteristically associated with allergic angiitis and granulomatosis ('Churg–Strauss syndrome'; CSS); in 'ANCA‐associated vasculitides' (AAV) few or no immune deposits are found *in situ* ('pauci‐immune vasculitis').

By contrast, immune complex deposits *in situ* are the hallmark of immune complex vasculitis, which is frequently associated with low complement levels. Granulomatous arteritis is characterized by an inflammatory infiltrate induced by Th1 cells. The predominant immune phenomena in systemic vasculitides associated with the major hypersensitivity reaction type are given in Fig. 1.

**Figure 1.** Pease add caption

**2. Immunopathogenesis**

Nomenclature of Systemic Vasculitis

a

c

bPreffered term.

Strongly associated with ANCA. Reproduced from [4] with permission.

132 Updates in the Diagnosis and Treatment of Vasculitis

found *in situ* ('pauci‐immune vasculitis').

Most of the vasculitic syndromes are mediated by immunopathogenic mechanisms ('immune

Large vessel refers to the aorta and the largest branches directed towards major body regions (e.g. to the extremities and the head and neck); medium-sized vessel refers to the main visceral arteries (e.g. renal, hepatic, coronary, and mesenteric arteries); small veseel refers to venules, capillaries, arterioles, and the intraparenchymal distal arterial radicals that connect with arterioles. Some small and large vessel vasculitides may involve medium-sized arteries,but large- and medium- sized vessel vasculitides do not involve vessels smaller than arteries. Essential components are represented by

normal type; italicized type represent usual, but not essential components.

The immunopathogenic mechanisms of vasculitides have been classified into the four types of hypersensitivity reaction described by Coombs and Gell [4]; this classification was reviewed recently [5]. Accordingly, clinicopathological and immunohistochemical studies have led to the terms allergic angiitis (I), antibody‐mediated angiitis, including the 'new' group of ANCA‐ associated vasculitides (II), immune complex vasculitis (III), and vasculitis associated with T‐ cell‐mediated hypersensitivity (IV). Eosinophilia and elevated IgE in the blood and tissues (*in situ*) are characteristically associated with allergic angiitis and granulomatosis ('Churg–Strauss syndrome'; CSS); in 'ANCA‐associated vasculitides' (AAV) few or no immune deposits are

vasculitides') and most 'immune vasculitides' are idiopathic (= 'primary' vasculitis).

**Table 1.** Names and definitions of vasculitides adopted by the Chapel Hill Concensus Conference on the

While some forms of vasculitides may be ascribed to underlying factors like infections, malignancy, drug reactions or connective tissue disorders, the cause may remain undeter‐ mined in many vasculitic syndromes. Immunologic damage by immune-complex deposition or cell-mediated hypersensitivity is responsible in the majority of cases.

The possible immunopathologic mechanism in the causation of vasculitis are:


Whatever the underlying mechanism, vascular inflammation and necrosis ensues which is often accompanied by thrombosis. These pathologic changes result in tissue ischaemia, necrosis and infarction, leading to a variety of clinical manifestations depending on the anatomic structures involved

**4.2. Classification based on caliber of blood vessel involved**

**i.** Large vessel vasculitis:

**•** Giant cell arteritis **•** Takayasu's arteritis

**•** Polyarteritis nodosa **•** Kawasaki disease

**•** Microscopic polyangiitis **•** Leukocytoclastic vasculitis **•** Wegener's granulomatosis

**•** Churg-Strauss disease

**•** Polyarteritis nodosa

**•** Henoch-Schonlein purpura

**•** Erythema elevatum diutinum

**•** Granuloma faciale etc.

**•** Lupus erythematosus

**•** Pityriasis lichenoides

**•** Churg-Strauss vasculitis

**•** Wegener's granulomatosis and Churg-Strauss

**ii.** Lymphocytic vasculitis:

**•** Lymphoma

**iii.** Eosinophilic vasculitis :

**iv.** Granulomatous vasculitis :

**•** Temporal arteritis

**v.** Giant cell arteritis:

**4.3. Classification based on cellular composition of the infiltrate**

**i.** *Leukocytoclastic vasculitis* (LCV): Neutrophils are predominant. Cellular fragments

Infectious Causes of Vasculitis http://dx.doi.org/10.5772/55189 135

and nuclear debris (leukocytoclasia) are found in the infiltrate.

**•** Vasculitis due to drugs, infections, and connective tissue diseases

**ii.** Medium vessel vasculitis:

**iii.** Small vessel vasculitis:
