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Venous Insufficiency Ulcers
Barbara J. Provo, MSN, RN, FNP-BC, CWON
Shahriar Alizadegan, MD
image BASICS
  • Venous insufficiency disorders include simple spider veins, varicose veins, and leg edema.
  • In the United States, 23% of adults have varicose veins, an estimated 22 million women and 11 million men.
  • Venous leg ulcers are the most serious consequence of venous insufficiency.
  • Venous leg ulcers are a type of chronic wound affecting up to 1% of adults in developed countries at some point during their lives.
  • 500,000 people in the United States have chronic venous ulcers, with an estimated treatment cost of >$3 billion per year.
DESCRIPTION
  • Full-thickness skin defect with surrounding pigmentation and dermatitis
  • Most frequently located in ankle region of lower leg (“gaiter region”)
  • Present for >30 days and fails to heal spontaneously
  • May only have mild pain unless infected
  • Other signs of chronic venous insufficiency include edema/brawny edema and chronic skin changes (i.e., hyperpigmentation and/or fibrosis).
EPIDEMIOLOGY
Up to 80% of leg ulcers are caused by venous disease; arterial disease accounts for 10-25%, which may coexist with venous disease.
Incidence
  • Overall incidence of venous ulcers is 18/100,000 persons.
  • Prevalent sex: women > men (20.4 vs. 14.6 per 100,000 for venous ulcer); increased with age for both sexes
Prevalence
  • Seen in ˜1% of adult population in industrialized countries, increased to 5% in patients ≥80 years old
  • Prevalence studies only available for Western countries
  • Point prevalence underestimates the extent of the disease because ulcers often recur.
  • 70% of ulcers recur within 5 years of closure.
ETIOLOGY AND PATHOPHYSIOLOGY
  • In a diseased venous system, venous pressure in the deep system fails to fall with ambulation, causing venous hypertension.
  • Venous hypertension comes from the following:
    • Venous obstruction
    • Incompetent venous valves in the deep or superficial system
    • Inadequate muscle contraction (e.g., arthritis, myopathies, neuropathies) so that the calf pump is ineffective
  • Venous pressure transmitted to capillaries leading to venous hypertensive microangiopathy and extravasation of RBCs and proteins (especially fibrinogen)
  • Increased RBC aggregation leads to reduced oxygen transport, slowed arteriolar circulation, and ischemia at the skin level, contributing to ulcers.
  • Leukocytes aggregate to hypoxic areas and increase local inflammation.
  • Factors promoting persistence of venous ulcers
    • Prolonged chronic inflammation
    • Bacterial infection, critical colonization
RISK FACTORS
  • History of leg injury
  • Obesity
  • Congestive heart failure (CHF)
  • History of deep venous thrombosis (DVT)
  • Failure of calf muscle pump (e.g., ankle fusion, inactivity) is a strong independent predictor of poorly healing wounds.
  • Previous varicose vein surgery
  • Family history
GENERAL PREVENTION
  • Primary prevention after symptomatic DVT: Prescribe compression hose to be used as soon as feasible for at least 2 years (≥20 to 30 mm Hg compression).
  • Secondary prevention of recurrent ulceration includes compression, correction of the underlying problem, and surveillance. Circumstantial evidence from two RCTs showed those who stopped wearing compression hose were more likely to recur.
  • Compression hose reduces rates of recurrence compared with no compression.
  • Because most ulcers develop following some type of trauma, avoiding lower leg trauma may help to prevent ulceration.
COMMONLY ASSOCIATED CONDITIONS
Up to 50% of patients have allergic reactions to topical agents commonly used for treatment.
  • Contact sensitivity was more common in patients with stasis dermatitis (62% vs. 38%).
  • Avoid neomycin sulfate in particular (including triple antibiotic ointment) (1)[A].
image DIAGNOSIS
A diagnosis of venous reflux or obstruction must be established by an objective test beyond the routine clinical examination of the extremity.
PHYSICAL EXAM
  • Look for evidence of venous insufficiency:
    • Pitting edema
    • Hemosiderin staining (red and brown spotty or diffuse pigment changes)
    • Stasis dermatitis
    • White skin lesions (atrophie blanche)
    • Lipodermatosclerosis (“bottle neck” narrowing in the lower leg from fibrosis and scarring)
  • Look for evidence of significant lymphedema (i.e., dorsal foot or toe edema, edema that does not resolve overnight or with elevation). This may require referral for special comprehensive lymph therapy.
  • Examine for palpable pulses.
DIFFERENTIAL DIAGNOSIS
  • Arterial insufficiency ulcer
  • Neuropathic ulcer
  • Malignancy
  • Sickle cell ulcer
  • Vasculitic ulcer
  • Calciphylaxis
  • Cryoglobulinemia
  • Pyoderma gangrenosum
  • Collagen vascular disease
  • Leishmaniasis
  • Cutaneous tuberculosis
DIAGNOSTIC TESTS & INTERPRETATION
  • Consider prothrombin time (PT)/international normalization ratio (INR) and partial thromboplastin time (PTT) if patient is anticoagulated.
  • Consider biopsy of leg ulcers that fail to heal or have atypical features.
  • Consider factor V Leiden mutation; strongly associated with venous ulcers.
  • Test for diabetes as necessary with fasting glucose.
  • Use duplex imaging to diagnose anatomic and hemodynamic abnormalities with venous insufficiency. It will also identify any DVT present.
Diagnostic Procedures/Other
  • Check ABI for evidence of arterial disease.
  • An ABI <0.8 is a relative contraindication to compression therapy.
  • Duplex imaging for evaluation of superficial and deep venous reflux and incompetent perforator veins
  • With concomitant severe arterial insufficiency, refer to a vascular surgeon for revascularization.
Test Interpretation
Strongly consider biopsy on wounds with atypical locations, failure to heal, or any suspicion of malignancy.
image TREATMENT
GENERAL MEASURES
Dressings: All wounds need some kind of a dressing underneath the compression system.
  • Wound dressings: No single type of dressing proved superior (2)[B].
  • Maintain semimoist wound environment: not excessively wet or dry.
  • Wounds are often exudative until edema is decreased: Use absorptive dressings (calcium alginate or absorptive pads). Both superabsorbent diapers and female protection pads are cost-effective alternatives.
  • Consider using barrier ointment/cream to prevent maceration of surrounding skin.
  • If wound tends to be dry, use a hydrogel.
  • A hydrocolloid dressing may be used with minimal exudate, if skin adhesive is tolerated.
MEDICATION
  • Effective compression management is the cornerstone of therapy.
  • P.1111

  • Diuretics may help to reduce edema, but compression is the mainstay.
  • Routine use of antibiotics for all venous ulcers is not recommended (1)[A],(3).
  • Levamisole, not widely available, was the only systemic antibiotic with some evidence of benefit in terms of ulcer healing, versus treatment of infection (2)[B],(3).
  • Evidence is insufficient for use of silver-based preparations and honey for healing wounds.
  • Pentoxifylline 400 mg PO TID, in addition to local care and compression, improves cure rates. There is some response even without compression. GI side effects are common (4)[A].
  • Aspirin 300 mg PO daily; effective when used with compression therapy
ISSUES FOR REFERRAL
  • With prominent toe or foot edema, consider lymphedema. Refer to a certified lymphedema therapist (CLT).
  • Refer to a wound clinic for complex or poorly healing ulcers.
  • Refer to a vein clinic or vascular specialist for recurrent ulcers.
  • Use home health nurses to help with immobile patients needing frequent wrapping/dressing changes.
ADDITIONAL THERAPIES
  • Edema management: Reduce venous hypertension and improve venous return to reduce inflammation, pain, and improve healing (5)[A].
    • Compression therapy for edema management is the cornerstone of treatment for venous insufficiency with or without ulcers.
    • Short-stretch multilayer bandages are ideal for acute phase, until edema is stable, and the patient can be fitted for compression hose.
    • Long-term compression hose (fit once edema is reduced). Aim for a minimum pressure 20 to 30 mm Hg, preferably 30 to 40 mm Hg.
    • Elevation of legs to heart level for 30 minutes 3 to 4 times per day.
    • Exercise to strengthen calf muscle pump is also effective.
  • Infection control
    • Débride necrotic tissue.
    • Treat cellulitis (usually gram-positive bacteria) with bactericidal systemic antibiotics. Suspect local infection when there is pain or no improvement in the wound after 2 weeks of compression. Consider deep quantitative swab, after thorough cleansing, or tissue biopsy for culture.
    • Treat critical colonization with topical antimicrobials, such as cadexomer iodine (silver dressings and honey are widely used, but definitive data are lacking) (3)[B].
  • For venous ulcers resistant to healing with wound care and compression, consider adding an intermittent compression pump 1 to 4 hr/day.
  • Encourage exercise (e.g., activation of calf muscle pump with ankle flexion and extension) in conjunction with leg compression and elevation.
  • Vacuum-assisted closure (VAC) dressings may be beneficial, but no clear benefit over optimal traditional wound care.
SURGERY/OTHER PROCEDURES
  • Necrotic tissue impedes healing.
    • Consider sharp débridement.
    • Other methods include enzymatic ointments (collagenase), low-frequency ultrasound, and wet-to-dry dressings.
    • Avoid using collagenase with silver dressings because silver inactivates the enzyme.
  • Allografts made of synthetic skin bilayered with living keratinocytes and fibroblasts improve healing at 6 months; insufficient evidence to support use of autografts.
  • In patients with ulcers refractory to conservative therapy, a variety of endovenous and surgical options exist. Consultation with a vascular surgeon is recommended.
  • Endovenous ablation of incompetent superficial and perforator veins has shown to reduce the size and recurrence of ulcers in those who have failed conventional compression therapy (6)[A].
  • A subset of patients with nonhealing ulcers have stenosis and obstruction of the deep venous system. Venous angioplasty and stenting is emerging as an important adjunct to compression and other medical therapy (7)[A].
COMPLEMENTARY & ALTERNATIVE MEDICINE
  • Chestnut seed extract (50 mg BID) is effective for venous insufficiency but not ulceration.
  • Topical medicinal honey used on wounds shows no evidence of improved healing.
  • Oral zinc has not been shown to be beneficial
INPATIENT CONSIDERATIONS
For those with acute significant cellulitis
Admission Criteria/Initial Stabilization
Infected wounds requiring IV antibiotics, especially in diabetics
image ONGOING CARE
  • Venous insufficiency is a lifelong issue.
  • After resolution of an ulcer, edema management must be maintained lifelong.
FOLLOW-UP RECOMMENDATIONS
When ulcers are nearly healed and edema is controlled, switch from compression bandages to compression hose.
  • Insurance may not reimburse for compression hose unless an ulcer is present.
  • Referral for hose fitting must be done just prior to the ulcer being healed.
Patient Monitoring
Monitor the ulcer for healing by measuring its area. Expect at least 10% reduction every 2 weeks.
DIET
  • Obese patients may benefit from weight loss.
  • Low-salt diets help fluid retention.
PATIENT EDUCATION
Patient education for understanding of underlying mechanism is important for long-term management.
  • Develop long-term plan for edema management and instruction on compression therapy.
  • Instruct the patient on topical wound therapy.
  • Teach early recognition and treatment of new ulcers or cellulitis.
PROGNOSIS
  • Ulcers recur frequently. Early identification and immediate treatment are essential.
  • Ongoing diligence, with edema control, avoiding infections, and avoiding trauma are important.
REFERENCES
1. Machet L, Couché C, Perrinaud A, et al. A high prevalence of sensitization still persists in leg ulcer patients: a retrospective series of 106 patients tested between 2001 and 2002 and a meta-analysis of 1975-2003 data. Br J Dermatol. 2004;150(5):929-935.
2. Palfreyman SJ, Nelson EA, Lochiel R, et al. WITHDRAWN: dressings for healing venous leg ulcers. Cochrane Database Syst Rev. 2014;(5):CD001103.
3. O'Meara S, Al-Kurdi D, Ologun Y, et al. Antibiotics and antiseptics for venous leg ulcers. Cochrane Database Syst Rev. 2014;(1):CD003557.
4. Jull AB, Arroll B, Parag V, et al. Pentoxifylline for treating venous leg ulcers. Cochrane Database Syst Rev. 2012;(12):CD001733.
5. O'Meara S, Cullum NA, Nelson EA. Compression for venous leg ulcers. Cochrane Database Syst Rev. 2012;(11):CD000265.
6. Harlander-Locke M, Lawrence PF, Alktaifi A, et al. The impact of ablation of incompetent superficial and perforator veins on ulcer healing rates. J Vasc Surg. 2012;55(2):458-464.
7. Raju S, Darcey R, Neglén P. Unexpected major role for venous stenting in deep reflux disease. J Vasc Surg. 2010;51(2):401-408.
Additional Reading
&NA;
  • Hamdan A. Management of varicose veins and venous insufficiency. JAMA. 2012;308(24):2612-2621.
  • Kearon C, Kahn SR, Agnelli G, et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 Suppl):454S-545S.
  • Metcalf DG, Bowler PG. Biofilm delays wound healing: a review of the evidence. Burns Trauma. 2013;1(1);5-12.
  • O'Donnell TF Jr, Passman MA, Marston WA, et al. Management of venous leg ulcers: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum. J Vasc Surgery. 2014;60(2 Suppl):3S-59S.
  • Varatharajan L, Thapar A, Lane T, et al. Pharmacological adjuncts for chronic venous ulcer healing: a systematic review [published online ahead of print June 1, 2015]. Phlebology.
Codes
&NA;
ICD10
  • I87.2 Venous insufficiency (chronic) (peripheral)
  • I83.009 Varicose veins of unsp lower extremity w ulcer of unsp site
  • I89.0 Lymphedema, not elsewhere classified
Clinical Pearls
&NA;
  • Initial diagnostic workup should include venous duplex scan and arterial evaluation.
  • Refer patients with ABI <0.8 to vascular surgery specialist.
  • Refer patients with recurrent or poor healing venous ulcers to venous specialist or wound specialist.
  • Compression is essential for edema management with or without wounds.
  • Treat critical colonization with topical antimicrobials (avoid neomycin).
  • Make sure that the diagnosis is correct, and biopsy when in doubt.