*3.6.1 Cutaneous leukocytoclastic angiitis*

Cutaneous leukocytoclastic angiitis is an inflammation of small vessels, characterized by an inflammatory infiltrate associated with leukocytoclasia by neutrophil fragmentation and fibrinoid necrosis in small vessel postcapillary venules. It is the most common histological type of cutaneous vasculitis and usually is idiopathic, although antibiotics are also linked [24]. It is often clinically manifested by a palpable purpura, which is found anywhere on the body, but usually affects more lower limbs and can cause arthralgia [24, 25].

Several symptomatic treatments may be proposed to patients: analgesics, nonsteroidal anti-inflammatory drugs and antihistamines. For chronic or persistent vasculitis, dapsone and/or colchicine may be effective. The use of colchicine in the treatment is beneficial through its effect on reducing neutrophil chemotaxis, blocking leukocyte adhesion and stabilizing lysosomal membranes. Colchicine at a dose of 0.6–1.8 mg/day induces resolution within 1–2 weeks, according to several authors [18].

The best indication for colchicine is in moderate severity vasculitis. It is an effective and inexpensive treatment that can be used alone or in combination. However, its prescription is sometimes limited because of its gastrointestinal side effects [18].

In cases of severe skin necrosis and/or systemic manifestations, systemic corticotherapy (prednisolone or prednisone 20–60 mg/d) with progressive weaning may control the situation in some cases. For patients with systemic manifestations, initial therapy should include high doses of corticosteroids and/or cyclophosphamide. Intravenous immunoglobulins may be useful in the treatment of severe and refractory disease in patients who have a contraindication to traditional immunosuppressive therapy [26].

Other drug-associated vasculitis, autoimmune diseases or even infectious diseases require treatment of the underlying disease. In some cases, systemic corticosteroid therapy is necessary, and corticosteroid-sparing immunosuppressive drugs and even intravenous immunoglobulin may be required [26].

## **4. Cutaneous vasculopathies**

Vasculopathies are diseases that present a hyperactivity of blood vessels in the skin with systemic repercussions, but of unknown etiology. They are usually classified as diseases with circulatory disorders such as acrocyanosis, livedo reticularis, Raynaud's phenomenon, erythromelalgia, vessel occlusion leading to necrosis such as atherosclerosis obliterans, Buerger's disease, lymphocyte-mediated inflammatory changes such as livedoid vasculitis, malignant atrophic papulosis and neutrophilmediated inflammatory changes such as pyoderma gangrenosum. Below, the most common representatives will be discussed [27].

#### **4.1 Antiphospholipid antibodies syndrome (APS)**

Antiphospholipid antibodies syndrome or Hughes syndrome is a systemic, autoimmune disease in which there are repeat thrombotic events, repeated fetal losses and positive autoantibodies such as anticardiolipin and lupus anticoagulant. As skin manifestations, ulcerations and livedo reticularis are the most common signs [27, 28]. Some authors relate Sneddon's syndrome, which is a disease with strokes and livedo reticularis, as a spectrum of APS [29]. Libman-Sacks endocarditis in systemic lupus erythematosus patients also has an accumulation of antiphospholipid antibodies in the subendothelial layer of the heart valves. However, the correlation with APS is not well established [30].

For patients with a diagnosis of APS, treatment as well as prophylaxis is required. However, there are patients who have met the diagnostic criteria but with no thrombotic events. In these patients, behavioral changes such as smoking and alcohol cessation, lipid control, diabetes management and nonuse of exogenous estrogens are the most important measures [27].

Avoiding prolonged immobilizations and other behaviors that predispose to thrombotic events is also recommended. Some authors advocate the use of aspirin without scientific consensus [28].

Primary prophylaxis with low-dose aspirin prophylaxis is usually prescribed to prevent thrombosis in women with recurrent miscarriages, but it does not prevent deep vein thrombosis in men with APS. In systemic lupus and secondary APS, hydroxychloroquine has been proven to have a protective effect against thrombosis, as well as a reduction in cholesterol and glycemia. Patients who undergo surgery and require prolonged immobilization require prophylactic heparinization, and in APS,

**147**

*Vasculitis and Vasculopathies*

**4.2 Blue finger syndrome**

**4.3 Acrocyanosis**

**4.4 Erythromelalgia**

toward this focus.

be controlled [27].

ment of secondary infections are essential [32].

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

weight heparin is used. Warfarin may also be used [28].

plasmapheresis, immunoglobulin and dapsone, among others [27].

sometimes doses should be higher than usual due to resistance to anticoagulant effects. For treatment, as initial therapy, unfractionated heparin or low molecular

Because patients with APS and thrombosis are at high risk for recurrent thromboembolism episodes, prolonged oral anticoagulant therapy is the best option for attempting to prevent further episodes. The most used oral anticoagulant is warfarin with a therapeutic goal of maintaining INR greater than or equal to 3 [31]. In cases of APS secondary to the underlying systemic disease, it should not open the treatment with systemic oral corticoid. Other agents that can be used are

In refractory and catastrophic cases that there is multiple organ infarction, anticoagulation combinations, steroids, plasmapheresis, intravenous immunoglobulin and fish oil derivatives can be used. Fibrinolytic agents have no proven benefit [28]. In case of pregnancy, the best alternative during this period is heparin associated with low doses of aspirin. Combined treatment is more effective to prevent miscarriages than just aspirin alone. Unfractionated heparin, low molecular weight heparin (enoxaparin 40 mg/day) and dalteparin 5000 UI/day can be used during this period. Warfarin should not be used in pregnant women. Accidental discovery of antiphospholipid antibodies during pregnancy, with no clinical history of problems such as thromboembolic events or systemic lupus erythematosus, does not require treatment [28].

It is a sudden cutaneous manifestation in which the fingers, especially the toe, develop cyanotic and painful character. The priority etiology is embolic, but there may be other causes such as rheumatologic and neoplastic, among others. Treatment for this condition depends on the treatment of the underlying disease. However, general and local care such as limb warm-up, physical protection, treat-

Acrocyanosis is a disease resulting from chronic vasospasm that causes reflex vasodilation in the affected extremities, usually by medication or central nervous system disorders. It may be painful, cold, discolored, hyperhidrosis, paresthesia and even tingling. Like for blue finger syndrome, treatment is only supportive [27].

Erythromelalgia is characterized by vasodilation of the extremities, especially in male children, and is usually associated with limb warm-up, pain and burning. It is believed that there is some change in calcium channels, so therapy is directed

In the case of primary erythromelalgia, anesthetics, antiarrhythmics, anticonvulsants and even oral magnesium may be used. In the case of secondary erythromelalgia, besides the treatment already discussed, the underlying disease needs to

Its treatment includes topical drugs like 5% lidocaine and 0.075% capsaicin. For oral medications, we have amitriptyline 10 mg/day, gabapentin 900–1800 mg/ day, pregabalin 75 mg/day, flecainide 200 mg/day and buflomedil 200–330 mg/day. Tricyclic antidepressants, selective serotonin reuptake inhibitors and, in selected cases, acetylsalicylic acid, beta blockers and calcium channel antagonists may be excellent associations. In refractory cases, we may use epidural infusions of opioids,

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

*Vascular Biology - Selection of Mechanisms and Clinical Applications*

effects [18].

suppressive therapy [26].

**4. Cutaneous vasculopathies**

common representatives will be discussed [27].

with APS is not well established [30].

without scientific consensus [28].

estrogens are the most important measures [27].

**4.1 Antiphospholipid antibodies syndrome (APS)**

The best indication for colchicine is in moderate severity vasculitis. It is an effective and inexpensive treatment that can be used alone or in combination. However, its prescription is sometimes limited because of its gastrointestinal side

In cases of severe skin necrosis and/or systemic manifestations, systemic corticotherapy (prednisolone or prednisone 20–60 mg/d) with progressive weaning may control the situation in some cases. For patients with systemic manifestations, initial therapy should include high doses of corticosteroids and/or cyclophosphamide. Intravenous immunoglobulins may be useful in the treatment of severe and refractory disease in patients who have a contraindication to traditional immuno-

Other drug-associated vasculitis, autoimmune diseases or even infectious diseases require treatment of the underlying disease. In some cases, systemic corticosteroid therapy is necessary, and corticosteroid-sparing immunosuppressive

Vasculopathies are diseases that present a hyperactivity of blood vessels in the skin with systemic repercussions, but of unknown etiology. They are usually classified as diseases with circulatory disorders such as acrocyanosis, livedo reticularis, Raynaud's phenomenon, erythromelalgia, vessel occlusion leading to necrosis such as atherosclerosis obliterans, Buerger's disease, lymphocyte-mediated inflammatory changes such as livedoid vasculitis, malignant atrophic papulosis and neutrophilmediated inflammatory changes such as pyoderma gangrenosum. Below, the most

Antiphospholipid antibodies syndrome or Hughes syndrome is a systemic, autoimmune disease in which there are repeat thrombotic events, repeated fetal losses and positive autoantibodies such as anticardiolipin and lupus anticoagulant. As skin manifestations, ulcerations and livedo reticularis are the most common signs [27, 28]. Some authors relate Sneddon's syndrome, which is a disease with strokes and livedo reticularis, as a spectrum of APS [29]. Libman-Sacks endocarditis in systemic lupus erythematosus patients also has an accumulation of antiphospholipid antibodies in the subendothelial layer of the heart valves. However, the correlation

For patients with a diagnosis of APS, treatment as well as prophylaxis is required. However, there are patients who have met the diagnostic criteria but with no thrombotic events. In these patients, behavioral changes such as smoking and alcohol cessation, lipid control, diabetes management and nonuse of exogenous

Avoiding prolonged immobilizations and other behaviors that predispose to thrombotic events is also recommended. Some authors advocate the use of aspirin

Primary prophylaxis with low-dose aspirin prophylaxis is usually prescribed to prevent thrombosis in women with recurrent miscarriages, but it does not prevent deep vein thrombosis in men with APS. In systemic lupus and secondary APS, hydroxychloroquine has been proven to have a protective effect against thrombosis, as well as a reduction in cholesterol and glycemia. Patients who undergo surgery and require prolonged immobilization require prophylactic heparinization, and in APS,

drugs and even intravenous immunoglobulin may be required [26].

**146**

sometimes doses should be higher than usual due to resistance to anticoagulant effects. For treatment, as initial therapy, unfractionated heparin or low molecular weight heparin is used. Warfarin may also be used [28].

Because patients with APS and thrombosis are at high risk for recurrent thromboembolism episodes, prolonged oral anticoagulant therapy is the best option for attempting to prevent further episodes. The most used oral anticoagulant is warfarin with a therapeutic goal of maintaining INR greater than or equal to 3 [31].

In cases of APS secondary to the underlying systemic disease, it should not open the treatment with systemic oral corticoid. Other agents that can be used are plasmapheresis, immunoglobulin and dapsone, among others [27].

In refractory and catastrophic cases that there is multiple organ infarction, anticoagulation combinations, steroids, plasmapheresis, intravenous immunoglobulin and fish oil derivatives can be used. Fibrinolytic agents have no proven benefit [28].

In case of pregnancy, the best alternative during this period is heparin associated with low doses of aspirin. Combined treatment is more effective to prevent miscarriages than just aspirin alone. Unfractionated heparin, low molecular weight heparin (enoxaparin 40 mg/day) and dalteparin 5000 UI/day can be used during this period. Warfarin should not be used in pregnant women. Accidental discovery of antiphospholipid antibodies during pregnancy, with no clinical history of problems such as thromboembolic events or systemic lupus erythematosus, does not require treatment [28].
