**4.1. Clinical presentation**

In general, the venous ulcer is an irregularly, well‐defined border and typically non‐painful [4, 8]. Nevertheless, deep ulcers or small venous ulcers surrounded by atrophie blanche are highly painful [28]. The size and site of ulcers are variable, but they usually located over the medial malleolus (**Figure 1**).

**Figure 1.** Typical venous ulcer over the medial malleolus.

There may be yellow fibrinous exudates on the ulcer bed. Varicose veins and ankle edema are common. The surrounding skin is erythematous or hyperpigmented with variable degrees of induration. Eczematous changes associated with venous dermatitis are commonly present. Long‐standing venous disease can lead to loss of the subcutaneous fat and fibrotic changes in the skin called lipodermatosclerosis, giving the characteristic "inverted champagne‐bottle" appearance of the leg [29]. The main complications of chronic venous ulcers are osteomyelitis and neoplastic transformation [4, 30]. Long‐term ulcers may require biopsy at regular intervals for malignant change. If osteomyelitis is suspected, radiography, bone scanning, and bone biopsy should be considered.

### **4.2. Diagnostic testing**

The diagnosis of venous ulcers is mainly based on patient history and clinical examination; however, there are diagnostic tests to evaluate venous anatomy and aid the diagnosis.

### *4.2.1. Venous duplex ultrasound*

transforming growth factor β (TGF‐β). Trapping of growth factors can impair activation of the

In general, the venous ulcer is an irregularly, well‐defined border and typically non‐painful [4, 8]. Nevertheless, deep ulcers or small venous ulcers surrounded by atrophie blanche are highly painful [28]. The size and site of ulcers are variable, but they usually located over the medial

There may be yellow fibrinous exudates on the ulcer bed. Varicose veins and ankle edema are common. The surrounding skin is erythematous or hyperpigmented with variable degrees of induration. Eczematous changes associated with venous dermatitis are commonly present. Long‐standing venous disease can lead to loss of the subcutaneous fat and fibrotic changes in the skin called lipodermatosclerosis, giving the characteristic "inverted champagne‐bottle" appearance of the leg [29]. The main complications of chronic venous ulcers are osteomyelitis and neoplastic transformation [4, 30]. Long‐term ulcers may require biopsy at regular intervals for malignant change. If osteomyelitis is suspected, radiography, bone scanning, and bone

The diagnosis of venous ulcers is mainly based on patient history and clinical examination; however, there are diagnostic tests to evaluate venous anatomy and aid the diagnosis.

cells that are needed for healing process [27].

282 Wound Healing - New insights into Ancient Challenges

**Figure 1.** Typical venous ulcer over the medial malleolus.

biopsy should be considered.

**4.2. Diagnostic testing**

**4. Diagnosis**

**4.1. Clinical presentation**

malleolus (**Figure 1**).

Duplex ultrasound is the first‐line diagnostic test to evaluate the insufficiency in venous ulcers [31]. Continuous‐wave Doppler provides information about superficial venous incompetence or obstruction; nonetheless, it can be difficult to differentiate deep from superficial venous incompetence [32, 33].

### *4.2.2. Venous plethysmography*

Photoplethysmography and air plethysmography measure the degree of venous reflux and the calf muscle pump efficiency [8, 34, 35].

### *4.2.3. Venous imaging*

In case of suspected venous obstruction, additional contrast imaging with computed tomog‐ raphy venography or magnetic resonance venography should be done; whereupon diagnosis should be confirmed by contrast venography and intravascular ultrasound [31].

### *4.2.4. Laboratory testing*

Patients who have a history of venous thrombosis and thrombophilia should undergo a workup for inherited hypercoagulable factors including protein C and S, factor V Leiden, antiphospholipid antibodies, prothrombin gene mutation, homocysteine, cryoglobulins, and cryoagglutinins [8, 31].

### *4.2.5. Arterial testing—Ankle Brachial Pressure Index (ABI)*

Patients with venous leg ulcers may have concomitant peripheral arterial disease component. Therefore, arterial pulse examination, Doppler ultrasound and ABI should be evaluated for the elimination of coexistent arterial disease. ABI is the ratio of the systolic blood pressure at the ankle compared with the systolic blood pressure in the arm. An ABI in the range of 0.9– 1.1 is considered normal and 0.5–0.8 indicates moderate peripheral vascular disease and claudication, while less than 0.5 indicates more severe disease [4, 8, 36].

### *4.2.6. Wound biopsy*

Most studies suggest wound biopsy for those that do not improve with standard wound and compression therapy after a period of 4–6 weeks of treatment. The biopsy specimen should be obtained from several sites, including the wound edge and central provisional matrix [31].

### **4.3. Classification**

### *4.3.1. CEAP*

Classification of venous ulcers, known as CEAP [clinical findings (C), etiology (E), anatomical distribution (A), and pathophysiology (P)] based on clinical findings was introduced in 1994 and revised in 2004 [37, 38] (**Table 1**).


**Table 1.** Basic revised clinical, etiologic, anatomic, and pathophysiologic (CEAP) classification system.

The clinical findings are divided into six categories, where C0indicates no visible or palpable signs of venous disease; C1, the presence of telangiectasies or reticular veins; C2, varicose veins; C3, edema; C4, changes in skin and subcutaneous tissue secondary to venous disease (C4a, pigmentation or eczema; C4b, lipodermatosclerosis or atrophie blanche); C5, skin changes with healed venous ulcer; C6, active venous ulcer. Each clinical class is further supplemented by (A) for asymptomatic and (S) for symptomatic presentation. Symptoms include aching, pain, skin irritation, tightness, heaviness, muscle cramps, and other complaints. The etiologic classification is separated into three categories; Ec, congenital; Ep, primary; Es, secondary (post‐traumatic or post‐thrombotic); and En, no venous cause identified. The anatomical classification is divided into four categories: As, superficial veins; Ap, perforator veins; Ad, deep veins; and An, no venous location identified. The pathophysiologic classification is divided into four categories; Pr, reflux; Po, obstruction; Pr,o, combination of reflux and obstruction; and Pn, no venous pathophysiology identifiable.

**CEAP Definition**

284 Wound Healing - New insights into Ancient Challenges

C2 Varicose veins C3 Edema

C0 No visible or palpable signs of venous disease

C4b Lipodermatosclerosis and/or atrophie blanche

CS Symptoms, including ache, pain, tightness, skin irritation, heaviness, muscle

cramps, as well as other complaints attributable to venous dysfunction

C1 Telangiectasies or reticular veins

C4a Pigmentation and/or eczema

Es Secondary (post‐thrombotic) En No venous etiology identified

An No venous location identified

Pr,o Reflux and obstruction

Pn No venous pathophysiology identifiable

**Table 1.** Basic revised clinical, etiologic, anatomic, and pathophysiologic (CEAP) classification system.

The clinical findings are divided into six categories, where C0indicates no visible or palpable signs of venous disease; C1, the presence of telangiectasies or reticular veins; C2, varicose veins; C3, edema; C4, changes in skin and subcutaneous tissue secondary to venous disease (C4a, pigmentation or eczema; C4b, lipodermatosclerosis or atrophie blanche); C5, skin changes with healed venous ulcer; C6, active venous ulcer. Each clinical class is further supplemented by (A) for asymptomatic and (S) for symptomatic presentation. Symptoms include aching, pain,

C5 Healed venous ulcer C6 Active venous ulcer

CA Asymptomatic

As Superficial veins Ap Perforator veins Ad Deep veins

Ec Congenital Ep Primary

Clinical classification

Etiologic classification

Anatomic classification

Pathophysiologic classification

Modified from Eklöf et al. [38].

Pr Reflux Po Obstruction

(basic)

The venous clinical severity score (VCSS) was developed because of subjective and inadequate definition of the categories in CEAP classification (**Table 2**).



Modified from Vasquez MA, Rabe E, McLafferty RB, Shortell CK, Marston WA, Gillespie D, et al. Revision of the venous clinical severity score: venous outcomes consensus statement: special communication of the American Venous Forum Ad Hoc Outcomes Working Group. J Vasc Surg 2010;52:1387–96.

**Table 2.** Revised venous clinical severity score (VCSS) system.

A VCSS may range from 0 to 30 [31, 33, 39]. A score of more than eight indicates the progression of venous problem. In addition, the VCSS has been shown to be useful to evaluate the response to treatment.
