*3.1.1 Takayasu arteritis*

It is a large vessel vasculitis whose etiologic agent is unknown. It is more frequently found in young Asiatic women, in the proportion from 5 to 12 W:1 M, and usually affects the aorta and its main branches. It is not a rare disease but is not as usual as arteritis of giant cells. The diagnosis is usually late because these patients develop many collateral arteries, they have nonspecific symptoms and the development of these affections is very slow. Pregnancy in patients affected by Takayasu arteritis is a troubling problem because it affects women of childbearing age, and it will cause risks to the mother and the child. The arteritis could be associated with Crohn's and rectocolitis disease [6].

**137**

between 3 and 21% [6].

*3.1.2 Giant cell arteritis (GCA)*

*Vasculitis and Vasculopathies*

3 Small vessel vasculitis

4 Small vessel vasculitis Immune complex

*DOI: http://dx.doi.org/10.5772/intechopen.92778*

ANCA-associated vasculitis

7 Vasculitis associated with systemic

8 Vasculitis associated with probable

disease

cause

**Table 1.**

**Classification Diseases** 1 Large vessel vasculitis Takayasu arteritis

2 Medium vessel Polyarteritis nodosa

5 Variable vessel vasculitis Behçet's syndrome

6 Single-organ vasculitis Cutaneous leukocytoclastic angiitis

Giant cell arteritis

Kawasaki disease

(Churg-Strauss)

Cogan's syndrome

Cutaneous arteritis

Lupus vasculitis Rheumatoid vasculitis Sarcoid vasculitis Others

vasculitis)

Microscopic polyangiitis

Granulomatosis with polyangiitis (Wegener's) Eosinophilic granulomatosis with polyangiitis

Antiglomerular basement membrane disease Cryoglobulinemic vasculitis (CV)

IgA vasculitis (Henoch-Schönlein)

Primary central nervous system vasculitis

Drug-associated immune complex vasculitis Drug-associated ANCA-associated vasculitis

Hepatitis C virus-associated CV Hepatitis B virus-associated vasculitis Syphilis-associated aortitis

Cancer-associated vasculitis

Hypocomplementemic urticarial vasculitis (anti-C1q

The more effective treatments are oral corticosteroids, but there are many relapses when corticosteroids taper. High doses of corticosteroids (40–60 mg/day of prednisone or equivalent) should be initiated immediately after the diagnosis to induce remission. During disease remission, it is necessary sparing the drug until 15-20mg/day for two or three months, and after a year decrease the doses to 10mg/ day or less. The immunosuppressive agents are used as corticoid sparing agents such as methotrexate, azathioprine, leflunomide, mycophenolate mofetil and cyclophosphamide [6]. There are evidences that biological agents such as anti-TNF-alpha, tocilizumab and rituximab could be effective in refractory cases, but more trials are necessary to evaluate the effectiveness of these drugs [8]. In addition, patients with ischemic problems need endovascular interventions. The mortality range is

*2012 International Chapel Hill Consensus Conference Nomenclature of Vasculitides [3].*

Others

It is a systemic vasculitis of large vessels, with tropism to the aorta and its branches, mainly external carotid. It is a most common vasculitis in above 50-yearolds and affects more women than men (3 W:2 M). The corticosteroids are the most common therapeutic used in these cases. In the beginning, we need high doses of corticosteroids to control the inflammation, and then it could be used sparingly

### *Vasculitis and Vasculopathies DOI: http://dx.doi.org/10.5772/intechopen.92778*

*Vascular Biology - Selection of Mechanisms and Clinical Applications*

Phospholipid Antibody Syndrome, Blue Finger Syndrome, Acrocyanosis and others. The final objective was summing up the dermatology vasculitis and vasculopathies and

*Purpuric macules and papules coalescing into patches (A) in small vessel vasculitis and fixed livedo reticularis* 

Cutaneous vasculitis may affect vessels of different calibers, especially small and medium in the skin and the subcutaneous tissue, resulting in just a small cutaneous lesion until serious systemic commitment. Nevertheless, the classification is not a consensus. In general, they are classified using clinical criteria, size of the vessels, histopathological exams, laboratorial findings and etiologic agents [3, 4]. In 2012, the *Chapel Hill Consensus Conference (CHCC)* proposed a new classification from the most used since 1994, removing many eponymous. The classification is a strategic pillar to help choose the right path to lead these patients through the right

It is a large vessel vasculitis whose etiologic agent is unknown. It is more frequently found in young Asiatic women, in the proportion from 5 to 12 W:1 M, and usually affects the aorta and its main branches. It is not a rare disease but is not as usual as arteritis of giant cells. The diagnosis is usually late because these patients develop many collateral arteries, they have nonspecific symptoms and the development of these affections is very slow. Pregnancy in patients affected by Takayasu arteritis is a troubling problem because it affects women of childbearing age, and it will cause risks to the mother and the child. The arteritis could be associated with

helping physicians in early diagnosis and treatment.

*and subcutaneous nodules (B) in medium vessel vasculitis (polyarteritis nodosa) [2].*

**3. Cutaneous vasculitis**

**Figure 1.**

treatment [4, 5] (**Table 1**).

**3.1 Large vessel vasculitis**

Crohn's and rectocolitis disease [6].

*3.1.1 Takayasu arteritis*

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#### **Table 1.**

*2012 International Chapel Hill Consensus Conference Nomenclature of Vasculitides [3].*

The more effective treatments are oral corticosteroids, but there are many relapses when corticosteroids taper. High doses of corticosteroids (40–60 mg/day of prednisone or equivalent) should be initiated immediately after the diagnosis to induce remission. During disease remission, it is necessary sparing the drug until 15-20mg/day for two or three months, and after a year decrease the doses to 10mg/ day or less. The immunosuppressive agents are used as corticoid sparing agents such as methotrexate, azathioprine, leflunomide, mycophenolate mofetil and cyclophosphamide [6]. There are evidences that biological agents such as anti-TNF-alpha, tocilizumab and rituximab could be effective in refractory cases, but more trials are necessary to evaluate the effectiveness of these drugs [8]. In addition, patients with ischemic problems need endovascular interventions. The mortality range is between 3 and 21% [6].

#### *3.1.2 Giant cell arteritis (GCA)*

It is a systemic vasculitis of large vessels, with tropism to the aorta and its branches, mainly external carotid. It is a most common vasculitis in above 50-yearolds and affects more women than men (3 W:2 M). The corticosteroids are the most common therapeutic used in these cases. In the beginning, we need high doses of corticosteroids to control the inflammation, and then it could be used sparingly

until controlled in the patient. These strategies are valid for simple and complicated forms of the disease [7].

Simple form is defined by cephalic isolated symptoms with visual disturbance or changes in central nervous system. Nowadays, the gold standard treatment is oral prednisone or equivalent 40–60 mg/day, and methylprednisolone is not used anymore. The initial dose recommended is 0.7 mg/kg day of prednisone and the maximum dose is 80 mg/day [7].

The complicated form is defined when there is an ophthalmologic or a central nervous or extracephalic complication, mainly aorta and its branches. In these cases, methylprednisolone in pulses of 500 mg<sup>−</sup><sup>1</sup> g a day shall be used for 1 to 5 consecutive days. During maintenance, some authors believe in doses less than 5 mg/day. The American Society of Ophthalmology recommends pulses of intravenous methylprednisolone, when patients have ophthalmologic symptoms, but the Rheumatology Society prefers oral corticosteroid [7].

It is strategic to introduce corticosteroid-sparing drugs when the disease course is lasting long. Methotrexate is the most used treatment and with more evidence levels. There are four trials with methotrexate as a sparing drug, but the doses and the management are variable from 7.5–15 mg/week [7].

Cyclophosphamide has demonstrated effectiveness in patients dependent on corticosteroids or resistant to treatment. It is necessary to give more than 20 mg/day for 6 months or 10 mg/day for 1 year or more. The dose from 500 mg/m<sup>2</sup> or 500 mg/ injection in 6 courses is standard from 5 months on average. It is highly important to warn patients of several side effects such as bone marrow suppression [7].

Azathioprine therapy has less controlled studies. Some studies showed a modest improvement. Hydroxychloroquine, an antimalarial synthetic drug, was tested also. One French study divided patients into two groups: one took prednisone 0.7 mg/ kg/day in the beginning associated with hydroxychloroquine (400 mg/day) and the control group just received prednisone and placebo. The group that had hydroxychloroquine and corticoid had usually stopped later the prednisone and they had more relapses [7].

Nowadays, one option is biologics medicines. Anti-TNF-alpha does not have enough studies that showed control of the disease with this class of medication [7]. Tocilizumab, a humanized antibody that blocked membranous and soluble receptors of IL-6 (IL-6R), is a current option since IL-Il-6 is implicated in the etiopathogenesis of this affection. Three main studies evaluated the efficacy of the drug, although the therapeutics was different between these studies [7, 8].

A randomized control trial with 30 patients had tested 20 patients receiving corticoids and tocilizumab (8 mg/kg every 4 week during a year), and 10 received corticoids and placebo. The survival without relapses during a year was highest in patients treated with tocilizumab. However, there are no data available after the medication was stopped [7, 8].

Another promising biotherapy is abatacept. This medication with corticoids could decrease the risk of relapses, although more data is necessary to corroborate this hypothesis.

Ustekinumab, a subunit against anti-p40 IL-12/23 targeting Th1 and Th17 responses, has been showing similar side effects as corticoids. Some patients, who had refractory disease, have been treated with anakinra and they achieved success. Anakinra is a biopharmaceutical drug that blocks IL-1. All patients who had taken the drug had shown improvement in inflammation biomarkers and/or in their symptoms, with the disappearance of arterial inflammation in PET/CT. More studies are necessary though [7].

Other pharmacological drugs can be used as adjuvant treatments such as antiplatelets and anticoagulants, but there is no official recommendation about these

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**Table 2.**

*Vasculitis and Vasculopathies*

**3.2 Medium vessel vasculitis**

*3.2.1 Polyarteritis nodosa (PAN)*

B-associated PAN [9].

refractory cases [8].

geal abscess [10].

3 Rash

*3.2.2 Kawasaki disease (DK)*

the 5 main clinical features [10] (**Table 2**).

2 Bilateral bulbar conjunctival injection without exudate

5 Cervical lymphadenopathy (≥1.5 cm in diameter), usually unilateral

**Clinical features**

subacute phase

*Clinical features in Kawasaki disease [10].*

erythema

*DOI: http://dx.doi.org/10.5772/intechopen.92778*

drugs in the treatment of GAC. The statins do not influence the evolution of the disease, but they are used to prevent cardiovascular risk. Furthermore, these drugs could have an anti-inflammatory role via the inhibition of TH17 pathway [7].

It is a rare necrotizing systemic vasculitis that affects small- and medium-sized vessels and is not usually associated with ANCA [8, 9], although there are reports in the literature of patients with PAN and positive ANCA. Several treatments are

Cutaneous involvement and peripheral nerves are the favorite sites of the disease, cutaneous and gastrointestinal vasculitis have specific histopathological characteristics, and until now, it has no development glomerulonephritis described. Gastrointestinal tract involvement is common and is one of the predictors of disease morbidity and mortality. There is cutaneous PAN without systemic involvement, and it very rarely progresses to the systemic form of the disease. According to the new classification, PAN is subdivided into idiopathic PAN and hepatitis

Treatment of PAN is usually based on the combination of systemic corticosteroids and immunosuppressants. The most commonly used medications are cyclo-

The use of biological medications is reserved for cases of refractory PAN without association with hepatitis B. The use of rituximab, an anti-CD20 monoclonal antibody, has not been formally indicated for patients with PAN, but its use is supported in patients with ANCA-associated vasculitis. There are case reports using anti-TNF-alpha, such as etanercept and infliximab, and tocilizumab, but only in

phosphamide, azathioprine, methotrexate or mycophenolate mofetil [9].

It is a systemic vasculitis, common in male child, with fever, rash, nonexudative bilateral conjunctivitis, oral and pharyngeal mucosal erythema, cervical lymphadenopathy, and it can affect the extremity. They may have fewer common symptoms such as pyuria, meningitis, shock and retropharyngeal or parapharyn-

The etiology of Kawasaki disease is unknown. The diagnosis of Kawasaki disease is based on the presence of fever for ≥5 days, along with the presence of at least 4 of

1 Erythema and cracking of the lips, strawberry tongue and/or pharyngeal and oral mucosa

4 Erythema and edema of the hands and feet in the acute phase and/or periungual scaling in the

suggested for this condition, and the control is still a challenge [9].

drugs in the treatment of GAC. The statins do not influence the evolution of the disease, but they are used to prevent cardiovascular risk. Furthermore, these drugs could have an anti-inflammatory role via the inhibition of TH17 pathway [7].
