Chronic venous disease

Chronic venous disease (also referred to as chronic venous disorders) is an umbrella term for a variety of clinical manifestations caused by chronically increased venous pressure in the lower extremities. Depending on the severity of hemodynamic dysfunction, manifestations can include superficial dilated veins (including varicose veins), peripheral edema, skin changes (e.g., stasis dermatitis), and venous ulcers. Diagnosis is based on clinical features and duplex ultrasonography, which shows vascular reflux and/or obstruction. Advanced diagnostic studies, such as magnetic resonance venography (MRV), may be indicated for certain patients. Treatment is aimed at reducing underlying venous hypertension. Lifestyle changes and localized vascular compression therapy are indicated for all patients. Surgical intervention is additionally recommended for patients with advanced or refractory disease. Surgical procedures are typically minimally invasive (e.g., endovenous ablation), although vein removal or valvuloplasty may be required. Phlebotonic supplements, most of which are available as nutritional supplements in the US, may help relieve symptoms such as pain and the sensation of heaviness.

• Venous insufficiency: disturbance in venous outflow; may be congenital (e.g., congenital absence of valves, Klippel-Trenaunay syndrome) or acquired (e.g., valvular injury secondary to deep vein thrombosis) ^[1]
• Chronic venous disease/disorders (CVD): a spectrum of disorders caused by venous dysfunction; ranges from telangiectasia to venous ulceration
  • Chronic venous insufficiency (CVI): advanced CVD including edema, skin changes, and venous ulceration
  • Varicose veins: a type of CVD characterized by cylindrical dilation; (diameter > 3 mm) and tortuosity of superficial veins

The terms CVD and CVI are sometimes used interchangeably in literature because the pathophysiology is similar. However, most guideline definitions limit the term CVI to more advanced disease. ^[2][3][4]

• Prevalence
  • CVI affects 2–6% of women and ∼ 2% of men. ^[5]
  • Varicose veins affect approx. 23% of individuals in the US. ^[6]
• Sex: ♀ > ♂ (∼ 2:1)

Epidemiological data refers to the US, unless otherwise specified.

Risk factors for CVD include the following: : ^[4]

• Increasing age and female sex
• Family history of venous disease
• Ligamentous laxity
• Sedentary lifestyle and prolonged standing
• Obesity
• Pregnancy
• Smoking
• Prior deep vein thrombosis (DVT) causing postthrombotic syndrome
• Prior extremity trauma
• Congenital abnormalities

In healthy individuals, blood from the superficial veins of the leg passes through the perforating veins into the deep veins.

• Pathophysiology of varicose veins: elevated venous pressure (see “Risk factors” above) → incompetence of venous valves (superficial or deep veins) → reflux of blood into superficial veins and back into the extremity → further elevation of venous pressure → formation of varicose veins
• Pathophysiology of CVI: varicose veins → extravasation of protein and leukocytes → release of free radicals → damage to capillary basement membrane → leakage of plasma proteins → edema formation → ↓ oxygen supply → tissue hypoperfusion and hypoxia → inflammation and atrophy → possibly ulcer formation

The following are all features of venous hypertension:

• Generalized or localized pain, lower extremity discomfort/cramping, and limb swelling
  • Worsened by heat
  • Worse while standing, relieved by walking and raising of legs
• Pruritus, tingling, and numbness
• Edema (may be unilateral) that starts in the ankle and may involve the calf later in the disease course (in about half of affected individuals)
• Telangiectasias
• Yellow-brown or red-brown skin pigmentation of the medial ankle; later of the foot and possibly lower leg
  • RBC breakdown leads to hemosiderin release → accumulation in the dermis → skin pigmentation
  • May lead to stasis dermatitis; a scaly, pruritic rash
• Paraplantar varicose veins
• Lipodermatosclerosis: Localized chronic inflammation and fibrosis of skin and subcutaneous tissues of lower leg ^[7]
  • Painful, indurated, and hardened skin
  • Atrophie blanche: white, coin- to palm-sized atrophic plaques due to absent capillaries in the fibrotic tissue

Tourniquet tests for varicose veins

Bedside tourniquet tests may help determine the site of venous insufficiency, but imaging is required for diagnostic confirmation. ^[2][4]

• Trendelenburg test: evaluates the function of superficial and perforating venous valves ^[6]
• Perthes test: assesses deep venous patency ^[6][8]

• CVD is classified using the CEAP classification system. ^[9]
  • C: clinical signs, ranked in severity from C0–C6
  • E: etiology; may be congenital (E_c), primary (E_p), or secondary (E_s) , or ranked as unidentified (E_n)
  • A: anatomy; involves the superficial veins (A_s), perforators (A_p), or deep veins (A_d), or is ranked as unidentified (A_n)
  • P: pathophysiology; caused by reflux (P_r), obstruction (P_o), or both (P_r,o), or is ranked as unidentified (P_n)
• The clinical component of CEAP is often used alone in primary care as it does not require venous studies. ^[10]

Approach

• Assess patients according to CEAP classification.
  • Perform a thorough history and clinical examination.
  • Obtain venous duplex ultrasound (US).
• Consider additional studies in consultation with vascular surgery if there is:
  • Complicated disease
  • Suspected suprainguinal venous obstruction ^[3]
  • Diagnostic uncertainty
  • Planned intervention
• Evaluate for concurrent peripheral arterial disease (PAD).
  • All patients: Check for pedal pulses. ^[2]
  • Patients with venous ulcers ^[11]
    • Measure ankle-brachial index.
    • If ≤ 0.9, refer to a vascular specialist for diagnostics for PAD. ^[11]

Venous duplex ultrasound ^[2][4]

• Indications: all patients with varicose veins or suspected CVI ^[2][3][4]
• Characteristic findings
  • Evidence of venous reflux ^[2][3]
  • Ultrasound features of DVT (acute or chronic) ^[11]

Additional studies ^[2][3]

Not routinely required; consider in complications, diagnostic uncertainty, or planned interventions

Laboratory studies

• CBC and BMP: patients with venous ulcers ^[2]
• Thrombophilia panel: patients with recurrent DVT, thrombosis at a young age, or thrombosis in an atypical site (see also “DVT diagnostics”) ^[2]
• Microbiology : patients with venous ulceration and signs of active infection (see “Complications of CVI”)

Venous plethysmography (venous function test)

• A noninvasive test used to assess venous blood flow and detect reflux and/or obstruction
• Indications include quantification of reflux or obstruction if duplex US findings are unclear. ^[2][3][12]

Further imaging

• Abdominal/pelvic US: Consider as initial study for suspected suprainguinal venous obstruction. ^[3]
• CT or MR venography: Consider if duplex US is inconclusive and before planned intervention for suprainguinal venous obstruction. ^[2][3]
• Invasive imaging (e.g., contrast venography, intravascular ultrasound): Consider if CT/MRV is inconclusive or inadequate. ^[3]

• Telangiectasia
  • Autoimmune disease, e.g., CREST syndrome
  • Genetic causes, e.g., hereditary hemorrhagic telangiectasia
  • Spider telangiectasia in chronic liver disease or pregnancy
• Edema: See “Differential diagnoses of peripheral edema.”
• Skin changes ^[13]
  • Cellulitis
  • Allergic contact dermatitis
  • Pigmented purpuric dermatosis
  • Exercise-induced vasculitis
• Ulceration ^[11]
  • Arterial ulcer
  • Diabetic foot wounds (malum perforans)
  • Pyoderma gangrenosum
  • Ulcerated skin tumors (e.g., basal cell carcinoma)
  • Pressure ulcer
  • Vasculitis
  • Iliocaval venous obstruction ^[14][15]

The differential diagnoses listed here are not exhaustive.

Approach ^[2][4][10]

• All patients
  • Identify and treat concomitant disease (e.g., DVT, PAD).
  • Recommend lifestyle measures to improve venous return and prevent progression of CVD.
  • Use the revised venous clinical severity score to assess treatment response.
• Symptomatic patients
  • Initiate compression therapy.
  • Consider phlebotonic supplements.
  • Symptomatic varicose veins and/or edema (CEAP C2/CEAP C3): Consider interventional therapies.
  • Skin changes or ulceration (CEAP C4–C6): Refer to vascular surgery for interventional therapies. ^[3]
  • See also “Complications of CVI” for further information on the management of venous ulcers and stasis dermatitis.

Manage CVD in pregnancy with conservative measures only and reassess for persistent disease at 3–6 months after delivery. ^[3]

Lifestyle modifications ^[3][10][16]

• Frequent elevation of the legs ^[11]
• Daily exercise ^[4][13]
• Change in footwear ^[17]
• Avoidance of:
  • Long periods of standing and sitting
  • Hot temperatures ^[18]
• Smoking cessation
• Management of obesity
• Emollients to prevent dry skin ^[19]

Consider referral to physical therapy to increase calf pump activity and help improve mobility. ^[3]

Venous compression therapy

Indications ^[2][3][20]

• Primary treatment modality for:
  • Most patients with symptomatic mild venous disease (CEAP C1 or CEAP C2) or edema
  • Pregnant patients with any stage of CVD
• Adjunct to interventional therapy: patients with skin changes or ulceration (CEAP C4–C6)

Contraindications ^[3]

• PAD with either:
  • ABI < 0.6 (absolute) or < 0.8 (relative) ^[3][11]
  • Absolute ankle pressure < 60 mm Hg ^[3][11]
• Prior peripheral arterial bypass grafting at the site of compression
• NYHA III and IV congestive heart failure
• Severe diabetic neuropathy or microangiopathy
• Allergy to compression bandage materials

Active ulceration is not a contraindication to compression bandages; consult wound care to help manage concurrent wounds with compression dressings.

Avoid compression therapy in significant PAD.

Types of compression ^[2][3]

• Graded compression stockings
  • Options include below-the-knee, thigh-high, or waist-high products ^[21]
  • Can be applied by patients themselves
  • Should be worn long-term all day, every day; adherence is often poor. ^[22]
  • Elasticity is lost over time; provide two pairs that should be alternated daily and replace after 6–9 months. ^[4]
• Elastic or inelastic bandages (e.g., Unna boots)
  • Application of bandages requires trained staff.
  • Multicomponent elastic bandages are the most effective form of compression therapy for venous ulcers. ^[11]
• Adjustable compression garments ^[3]
  • Inelastic material with straps that can be tightened to increase pressure
  • Used as an alternative to compression stockings or bandages
• Intermittent pneumatic compression device: for refractory edema or as a second-line option for venous ulcers ^[3][11]

Some individuals (e.g., with obesity or limited mobility) may have difficulty applying compression garments and thus require a donning device or assistance. ^[13]

Amount of pressure ^[4]

Interventional procedures

Indications ^[2][3][23]

• Symptomatic varicose veins (CEAP C2) with:
  • Known reflux in the superficial venous system ^[2]
  • A history of complications, e.g., bleeding, recurrent superficial thrombophlebitis ^[3][24]
  • Unsuccessful conservative management
• Edema (CEAP C3): if other causes of edema are excluded and conservative management has failed ^[3]
• Skin changes or ulceration (CEAP C4–6)

Modalities

Management of venous reflux ^[2][3][23]

• Vein ablation therapies: minimally invasive; typically preferred
  • First-line: endovenous thermal ablation (laser or radiofrequency) ^[3]
  • Alternative: chemical ablation (sclerotherapy)
• Surgery
  • Partial or complete removal of a vein
    • Ambulatory phlebectomy: removal of superficial varicose veins via small incisions
    • Ligation with vein stripping: ligation of the saphenofemoral or saphenopopliteal junction and removal of the great and/or small saphenous veins
  • Vein valvuloplasty: reconstruction of valves in the deep veins ^[11]

Before ablating or stripping superficial veins, confirm the deep veins are patent using duplex US.

Management of venous obstruction ^[3][23]

• First-line: endovascular recanalization and stenting
• Alternative: surgical reconstruction

Phlebotonic supplements ^[2][10][25]

• Venoactive drugs that increase tone and/or decrease capillary permeability
• Consider as an adjunct therapy for patients with pain or edema secondary to CVD. ^[2][3]
• Examples include horse chestnut seed extract and micronized purified flavonoid fraction (e.g., diosmiplex). ^[26]

Phlebotonics may improve some symptoms of CVI, but there is a paucity of evidence on the efficacy and safety of long-term use. ^[10]

Stasis dermatitis ^[13][27]

• Definition: eczematous dermatitis of the lower extremities caused by chronic venous hypertension and inflammation
• Clinical features
  • Poorly defined erythematous, eczematous, and sometimes scaly patches commonly involving the medial malleolus
  • Can involve pruritus; scratching may cause lichenification.
  • Acute stasis dermatitis can manifest with weeping, vesicles, and worsening erythema and edema.
• Diagnostics
  • Perform diagnostic studies for CVI, including duplex US.
  • Consider skin biopsy if there is diagnostic uncertainty. ^[13]
• Differential diagnosis: see “Differential diagnosis of CVI.”
• Treatment
  • Initiate treatment of CVI, including compression therapy and referral for interventional treatment.
  • Avoid harsh cleansers and regularly apply emollients (e.g., petroleum jelly).
  • Advise patients to avoid scratching. ^[28]
  • Identify and treat superimposed infections. ^[13]
  • Consider the following:
    • Cold and/or wet compresses ^[29]
    • Short-term use of topical steroids (e.g., triamcinolone acetonide 0.1% ) for acute presentations or pruritus ^[27]

Treatment of stasis dermatitis includes addressing the underlying CVI.

Consider antibiotic therapy for skin and soft tissue infections only if there is strong suspicion for cellulitis. ^[13][27][30]

Venous ulcers ^[11][14][31]

• Definition: an open skin lesion of the leg or foot in an area affected by venous hypertension ^[11]
• Etiology: usually caused by CVI with or without complications (e.g., untreated stasis dermatitis) ^[13]
• Clinical features ^[32]
  • Most frequently occurs just above the ankle (gaiter region)
  • Manifests as a shallow ulcer with irregular borders
  • Typically mild pain and pruritus
  • Additional clinical features of CVI are usually present; , e.g., edema, varicose veins.
• Diagnostics ^[14]
  • Perform diagnostic studies for CVI.
  • Perform ABI to rule out concurrent PAD.
  • Work up as needed for important differential diagnoses of leg ulcers (e.g., with diabetes screening).
  • Obtain aerobic and anaerobic wound cultures for suspected infections.
  • Tissue biopsy is indicated for ulcers with any of the following :
    • No signs of healing after being open continuously for 3 months or after 4–6 weeks of standard treatment
    • Worsening despite treatment (e.g., worsening pain, increase in size)
    • Atypical features
• Differential diagnosis: see “Differential diagnoses of CVI.” ^[11]
• Treatment ^[11][14][31]
  • Initiate treatment of CVI, including compression therapy and referral for interventional treatment.
  • Consider pentoxifylline to promote healing. ^[14][33]
  • Provide topical wound care.
    • Treat underlying stasis dermatitis. ^[11]
    • Consult wound care for debridement and dressing application.
    • Other topical agents (e.g., antiseptics, antibiotics) are not recommended. ^[11][31]
  • Start systemic antibiotics if there is evidence of infection (e.g., cellulitis, erysipelas)
  • Consider skin graft in large or refractory ulcers.
• Prognosis: Recurrence rate is as high as 70%. ^[14]

To prevent recurrence, compression therapy should be continued after a venous ulcer is healed. ^[11]

Other complications

• Complications of compression therapy
  • Incorrect fitting can lead to pain and skin breakdown. ^[2]
  • Contact dermatitis ^[11]
• Varicose vein hemorrhage
  • Elevate the leg and apply pressure to the bleeding site.
  • If bleeding is heavy, initiate management of hemorrhagic shock.
  • Intervention with ablation or vein ligation may be considered after bleeding is controlled. ^[3]
• Superficial thrombophlebitis ^[2]
• DVT ^[23]

We list the most important complications. The selection is not exhaustive.