**4. Classification**

Vasculitis is a taxonomist's nightmare. Diseases with diverse causes and pathology may share the same symptomatology. On the other hand, a disease may show different histopathologic features at different periods in its evolution. Many diseases have overlapping features and it is impossible to formulate a classification scheme that unifies clinicopathological, etiological and immunological features of different diseases.

#### **4.1. Immunopathologic classification**

	- **•** Polyarteritis nodosa
	- **•** Microscopic polyangiitis
	- **•** Hypersensitivity vasculitis
	- **•** (Leukocytoclastic vasculitis)
	- **•** Henoch-Schonlein purpura
	- **•** Giant cell arteritis
	- **•** Takayasu's arteritis
	- **•** Churg-Strauss disease (allergic granulomatosis)
	- **•** Wegener's granulomatosis
	- **•** Isolated CNS vasculitis

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

**i.** Large vessel vasculitis:

necrosis and infarction, leading to a variety of clinical manifestations depending on the

Perivascular cellular infiltration is a common histological finding in many disease entities, but for a definitive diagnosis of vasculitis, the presence of vascular damage, particularly in the

Vasculitis may involve blood vessels of varying calibers and this feature forms the basis of a useful pathological classification of vasculitis. An infiltrate, composed of a variety of cell types, like neutrophils, lymphocytes, and histiocytes may invade the vessel wall and the surrounding tissue. Extravasation of red cells is a prominent feature in many vasculitides. Granulomatous

Vasculitis is a taxonomist's nightmare. Diseases with diverse causes and pathology may share the same symptomatology. On the other hand, a disease may show different histopathologic features at different periods in its evolution. Many diseases have overlapping features and it is impossible to formulate a classification scheme that unifies clinicopathological, etiological

inflammation with giant cell formation is a characteristic finding in some types.

**ii.** Vasculitis due to cellular hypersensitivity (Granulomatous vasculitis)

**•** Churg-Strauss disease (allergic granulomatosis)

anatomic structures involved

134 Updates in the Diagnosis and Treatment of Vasculitis

form of fibrinoid degeneration, is necessary.

and immunological features of different diseases.

**i.** Immune- complex mediated vasculitis:

**4.1. Immunopathologic classification**

**•** Polyarteritis nodosa

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

**•** Wegener's granulomatosis

**•** Isolated CNS vasculitis

**•** Microscopic polyangiitis **•** Hypersensitivity vasculitis **•** (Leukocytoclastic vasculitis) **•** Henoch-Schonlein purpura

**3. Pathology**

**4. Classification**

	- **•** Polyarteritis nodosa
	- **•** Kawasaki disease
	- **•** Microscopic polyangiitis
	- **•** Leukocytoclastic vasculitis
	- **•** Wegener's granulomatosis
	- **•** Churg-Strauss disease

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

	- **•** Polyarteritis nodosa
	- **•** Henoch-Schonlein purpura
	- **•** Vasculitis due to drugs, infections, and connective tissue diseases
	- **•** Erythema elevatum diutinum
	- **•** Granuloma faciale etc.
	- **•** Lupus erythematosus
	- **•** Lymphoma
	- **•** Pityriasis lichenoides
	- **•** Churg-Strauss vasculitis
	- **•** Wegener's granulomatosis and Churg-Strauss
	- **•** Temporal arteritis

**•** Takayasu's arteritis

#### **4.4. Clinical classification**

	- **•** Polyarteritis nodosa
		- **◦** Classical
		- **◦** Microscopic polyangiitis
		- **◦** Allergic granulomatosis
		- **◦** Polyangiitis overlap
	- **•** Temporal arteritis
	- **•** Takayasu's disease
	- **a.** Idiopathic
	- **b.** Secondary:
		- **Infection**: ( Streptococcus, Staph, TB, Leprosy, Hep.B and C, HIV, Subacute bacterial endocarditis, EBV, parvovirus, Rickettsia)

**•** Hyperimmunoglobulinemia D

**•** Familial Mediterranean fever.

**•** Behcet's disease Buerger's disease

**iv.** Other vasculitic syndromes:

**•** Kawasaki's disease

**•** Cogan's syndrome

**5. Immunodiagnostic approach**

**•** Isolated CNS vasculitis

**•** Acute hemorrhagic edema of children

Primary systemic vasculitides were reclassified based on ANCA serology, the presence of immune deposits *in situ*, and the size of the vessels involved. WG, MPA and CSS were subsumed in the group of ANCA‐associated vasculitides, which are characterized clinically by a WG, CSS or non‐granulomatous MPA inflammation commonly involving the respiratory tract and ear–nose–throat (ENT) region and by a necrotizing pauci‐immune (= no or minimal

Infectious Causes of Vasculitis http://dx.doi.org/10.5772/55189 137

ANCA are a heterogeneous group of autoantibodies that can be subdivided by indirect immunofluorescence tests (IFTs) and by enzyme‐linked immunosorbent assays (ELISAs). IFTs can distinguish two major fluorescence patterns on ethanol‐fixed human granulocytes: one of these patterns, classic cANCA, is highly specific for WG, while the other, perinuclear pANCA, is commonly seen in MPA (rarely in WG), but may be detected in a wide variety of other autoimmune conditions (e.g. systemic lupus erythematosus, rheumatoid arthritis, Felty's

The clinical utility of cANCA as a diagnostic marker for WG was recently confirmed in a large prospective European study undertaken with sera from vasculitis patients (sensitivity 60%, specificity 95%) [6]. However, when employed as a routine screening method for WG (defined according to ACR criteria) in patients with suspected vasculitis, the sensitivity of cANCA in a recent prospective single‐centre study on 346 consecutive patients was only 28% (specificity for WG: 98%). The sensitivity rose to 83% if only biopsy‐proven WG was considered [7]. A meta‐analysis of 15 studies comprising 13 652 patients (including 736 cases of WG) yielded a pooled sensitivity of 66% and a specificity of 98% [8]. Taken together, these data show that the value of cANCA testing is limited by a rather low sensitivity; the greatest utility of cANCA testing may be in patients with suspected, but not yet proven, WG. This view is supported by a recent analysis of ANCA results in a large routine laboratory (Regional Immunology Laboratory, Belfast, UK). The overall positive predictive value for primary systemic vasculi‐ tides was 38% for all cANCA and only 20% for all pANCA. Specificity improved when only antinuclear antibody (ANA)‐negative samples with a high ANCA titre were considered

immune deposits) vasculitis typically affecting small‐ to medium‐sized vessels.

syndrome and chronic inflammatory bowel diseases with associated disorders).

	- **•** Henoch-Schonlein purpura
	- **•** Urticarial vasculitis
	- **•** Serum sickness
	- **•** Erythema elevatum diutinum
	- **•** Granuloma faciale

**•** Takayasu's arteritis

136 Updates in the Diagnosis and Treatment of Vasculitis

**i.** Systemic necrotizing vasculitis : **•** Polyarteritis nodosa

> **◦** Microscopic polyangiitis **◦** Allergic granulomatosis

**iii.** Predominantly Cutaneous small vessel vasculitis :

Dermatomyositis )

**•** Henoch-Schonlein purpura

**•** Erythema elevatum diutinum

**•** Urticarial vasculitis

**•** Granuloma faciale

**•** Serum sickness

**• Infection**: ( Streptococcus, Staph, TB, Leprosy, Hep.B and C, HIV, Subacute

**• Drugs**: Penicillin, sulpha, phenytoin, allopurinol, gold, thiazide, NSAIDs,

**• Connective tissue disease** (SLE, Sjogren's syndrome, RA, Scleroderma,

**• Other diseases**: Cryoglobulinemia, complement deficiency, alpha1 antitryp‐ sin deficiency Inflammatory bowel disease, Chronic active hepatitis, intestinal

bypass surgery, primary biliary cirrhosis,Relapsing polychondritis

bacterial endocarditis, EBV, parvovirus, Rickettsia)

**• Malignancy** (Lymphoma, leukemia, solid organ tumors )

Frusemide, quinidine, thiouracils, mefloquine

**c.** Clinical syndromes with leukocytoclastic vasculitis:

**◦** Polyangiitis overlap

**•** Temporal arteritis **•** Takayasu's disease

**a.** Idiopathic **b.** Secondary:

**◦** Classical

**•** Wegener's granulomatosis **ii.** Giant cell vasculitis

**4.4. Clinical classification**

