Chronic Venous Insufficiency

Overview

Definition

Chronic venous disease is a spectrum of disorders characterized by venous dilation and/or abnormal vein function in the lower extremities resulting from venous hypertension.

Epidemiology

• Females > males
• Lifetime incidence of chronic venous disease: up to 50% of individuals
• Lifetime incidence of chronic venous insufficiency:
  • Up to 40% of women 
  • Up to 17% of men 
  • Incidence ↑ with age

Etiology

• Chronic venous hypertension
• Causes of venous hypertension:
  • Obstruction: usually deep vein thrombosis (DVT)
  • Reflux (retrograde venous blood flow):
    • Usually due to valve incompetence
    • Valve incompetence may develop after obstruction.
• Primary disease: symptomatic presentation without a precipitating event (70%)
• Secondary disease: develops after obstruction due to DVT (30%)
• Risk factors for chronic venous insufficiency:
  • ↑ Age
  • ↑ BMI
  • Family history of venous disease
  • Laxity of ligaments (hernias, flat feet)
  • Prolonged standing
  • Smoking
  • Prior DVT
  • Klippel–Trenaunay syndrome
  • ↑ Estrogen states, including pregnancy

Pathophysiology

Venous hypertension

• DVT (obstruction) and/or primary valve incompetence (reflux) can cause: 
  • ↑ venous pressure in deep veins 
  • ↑ pressure in perforating veins 
  • ↑ pressure in superficial veins 
• Endothelial dysfunction of vein walls ensues from DVT.
• Chronic inflammation of vein walls leads to eventual remodeling of those vein walls:
  • ↑ Type 1 collagen
  • ↓ Type 3 collagen
  • ↓ Smooth muscle cells 
  • Degradation of the extracellular matrix
  • ↑ Proteinases lead to increased permeability.
• Severe wall dysfunction increases the risk of DVT due to: 
  • Inability to properly move blood forward (stagnation)
  • Chronic inflammation/endothelial damage

Skin and soft tissue changes

• The increase in venous hypertension is combined with increased vessel permeability.
• This leads to efflux of blood components into the subcutaneous space:
  • Fluid → edema → ↑ pressure in the extremity, which may lead to:
    • Necrosis
    • Impaired lymph drainage → further fluid accumulation and impaired waste removal
  • RBCs (which break down) → hemosiderin deposits → skin pigmentation
  • Proteinases → cutaneous ulcers
  • WBCs → cytokine release → subcutaneous fibrosis (lipodermatosclerosis) → ↓ capillaries in these areas:
    • White plaques (atrophie blanche) 
    • ↓ Blood flow → poor healing and ischemia/necrosis

Clinical Presentation

Spectrum of chronic venous disease

• Asymptomatic venous dilation
• Mild disease:
  • Telangiectasias
  • Reticular veins
  • Varicose veins
  • Mild dependent ankle edema
• Severe disease (chronic venous insufficiency):
  • Significant edema
  • Skin changes 
  • Ulcers

Presenting symptoms

• Dependent pitting edema 
• Lower extremity pain or discomfort: 
  • Often described as “heavy legs,” throbbing, aching, or cramping
  • Worse with standing
  • In contrast to peripheral artery disease (PAD), pain improves with:
    • Leg elevation
    • Walking
• Numbness or tingling
• Pruritus
• Visible tortuous veins:
  • Telangiectasias: dilated intradermal venules < 1 mm
  • Reticular veins: dilated subdermal veins, 1–3 mm in diameter 
  • Varicose veins: dilated subcutaneous veins > 3 mm in diameter
• Skin changes:
  • Brown or blue-gray discoloration of the skin from hemosiderin deposits
  • Stasis dermatitis (eczematous rash) characterized by:
    • Erythema
    • Scaling
    • Weeping
    • Erosions
    • Crusting
  • Lipodermatosclerosis: 
    • Firm, indurated areas
    • Skin is tacked down to the subcutaneous tissue (subcutaneous fibrosis).
    • Most common at the medial ankle
    • May form a constrictive band around the extremity
  • Atrophie blanche: 
    • Atrophic white plaques with red punctate dots or telangiectasias
    • Circular or stellate
    • Surrounded by hyperpigmentation
  • Ulcers: commonly over the medial malleolus

Diagnosis and Classification

Physical exam

Lower extremity appearance:

• Edema 
• Visible or palpable tortuous superficial veins
• Characteristic skin changes
• +/– Ulcers

Venous refilling time:

• Observe the time it takes for visible veins to distend after patient stands from a seated position.
• Refilling time of 20–40 or < 20 seconds is abnormal.

Ankle–brachial index:

• Ankle–brachial index = ratio of blood pressure of the ankle to blood pressure of the arm 
• Ankle–brachial index ≤ 0.9 → PAD
• Important: Compression therapy (standard in venous insufficiency) is contraindicated in PAD.

Imaging

Duplex ultrasonography:

• 1st-line test to:
  • Confirm the diagnosis (if in question)
  • Determine the etiology
  • Rule out a DVT
  • Assess the severity of deep vein disease
  • Localize affected anatomy
• Combines: 
  • B-mode imaging of deep and superficial veins
  • Doppler assessment of blood flow
• Obstruction shows: 
  • Absence of blood flow
  • Noncompressible veins
• Reflux shows: 
  • Reversal of blood flow
  • > 0.5 second in the superficial and perforator veins
  • > 1 second in deep veins

Cross-sectional venography with CT or MRI:

• Used to evaluate the deep venous system poorly accessible by ultrasound (e.g., infrainguinal area)
• Consider in patients with normal or equivocal ultrasound

Catheter-based (invasive) venography:

• Gold standard test
• Rarely needed to make diagnosis
• Used prior to more invasive intervention

Clinical, etiologic, anatomic, and pathophysiologic (CEAP) classification of chronic venous disease

• Clinical signs: 
  • C0: no visible or palpable disease
  • C1: telangiectasias and reticular veins
  • C2: varicose veins
  • C3: edema
  • C4: skin changes 
    • C4_a: pigmentation or stasis dermatitis (eczematous rash)
    • C4_b: lipodermatosclerosis
  • C5: healed ulcer
  • C6: active ulcer
  • C6_R: recurrent active ulcer
• Etiologic signs:
  • Ep: primary causes, usually degeneration of valves leading to reflux
  • Es: secondary causes, usually DVT or trauma
  • Ec: congenital causes
• Anatomic signs:
  • As: superficial veins (within the subcutaneous tissue)
  • Ad: deep veins (within the muscle compartments bound by fascia)
  • Ap: perforating veins (veins that connect superficial to deep veins by traversing the muscular fascia)
• Pathophysiologic signs:
  • Pr: venous reflux (retrograde flow)
  • Po: venous obstruction (thrombosis)
  • Pr,o: both reflux and obstruction

Management

Goals

• Reduce edema.
• Reduce discomfort.
• Prevent and treat skin manifestations.
• Heal ulcers.
• Improve modifiable risk factors.

Conservative (nonsurgical) management

• Frequent leg elevation (30 minutes, 3–4 times daily)  → improve venous drainage
• Exercise → improve calf muscle pump
• Weight loss → ↓ pressure
• Skin care:
  • Cleansing
  • Emollients:
    • To maintain skin barrier
    • Prevent dryness and fissuring
    • ↓ Scratching (which can lead to ulcers)
• Compression therapy (hosiery):
  • Primary initial management technique
  • Contraindicated with coexisting PAD
  • Long-term adherence required
• Venoactive substances to ↑ venous tone:
  • Used in patients with:
    • Resistant edema in spite of compression therapy
    • Contraindications to compression therapy
  • Beneficial for treating edema, but not for ulcer healing
  • Options available in the United States:
    • Escin (horse chestnut seed extract)
    • Micronized purified flavonoid fraction

Ulcer care

• Debridement: 
  • Removes surrounding necrotic tissue
  • Promotes healthy granulation tissue
  • Enhances reepithelialization
  • ↓ Risk for infection
  • May be done using surgical, enzymatic, or biologic methods
• Topical agents (most do not improve healing rates):
  • Cadexomer iodine
  • Silver sulfadiazine
  • Avoid topical antiseptics.
• Systemic antibiotics: only in patients with acute cellulitis or clinically infected ulcer
• Dressings
• Medical options for treating resistant ulcers:
  • Stanozolol: an anabolic steroid that stimulates fibrinolysis
  • Pentoxifylline: ↑ microcirculation and tissue oxygenation

Surgical management

Goals:

• Occlude (or remove) the damaged vessels and restore proper blood flow 
• Decrease venous hypertension to reduce edema and skin effects

Options include:

• Superficial venous ablation (thermal destruction)
• Sclerotherapy (injection of toxic substances causing fibrosis and occlusion)
• Phlebectomy (vein excision)
• Angioplasty and stenting (relieve obstructions in the deep veins)
• Valve repair (deep veins)

Complications

• Bleeding from varicose veins
• DVT
• Superficial thrombophlebitis:
  • Inflammation within the vein walls → thrombosis
  • Treatment:
    • NSAIDs
    • Compression therapy
• Cellulitis or infected ulcers:
  • Require treatment with systemic antibiotics and debridement
  • May lead to amputation

Differential Diagnosis

• Heart failure: clinical syndrome resulting from dysfunction of the cardiac pump that leads to low tissue perfusion and congestion in the venous system: Heart failure can be distinguished from chronic venous insufficiency by the presence of dyspnea, jugular venous distention, and an S3 heart sound. Diagnosis is made from a combination of clinical, laboratory, and imaging findings, and management is directed toward medical optimization.
• Cirrhosis: progressive fibrosis and failure of the liver, which leads to portal hypertension: Portal hypertension can cause venous congestion distally, resulting in ascites, gastric and esophageal varices, and peripheral edema. Telangiectasias are also possible. Symptoms also include jaundice, GI bleeding, neurologic symptoms, and coagulation disorders. Management is mostly supportive, with the goal of reducing complications.
• Nephrotic syndrome: Damaged renal podocytes lead to massive proteinuria, which ultimately can result in significant peripheral edema similar to chronic venous disease. It is also associated with a hypercoagulable state due to urinary loss of antithrombin III, so DVTs may develop. Renal biopsy will yield a definitive diagnosis. Management is largely supportive and directed at the underlying cause.
• PAD: atherosclerosis leading to decreased blood flow in the peripheral arteries, commonly in the lower extremities: The atherosclerosis results in claudication (pain that is induced by exercise and relieved with rest). The decreased arterial blood flow in PAD may also lead to ulcers secondary to ischemia. Diagnosis is established clinically and supported by vascular imaging. Treatment involves medications and surgical revascularization.
• Squamous cell carcinoma (SCC): a malignant tumor arising from the epidermal keratinocytes, usually in sun-exposed areas: SCCs can form well-demarcated, scaling, pink plaques that can resemble inflammatory skin changes. Diagnosis is established with a biopsy. SCC can also arise in chronic venous ulcers. The mainstay of treatment is surgical excision.