Venous Disease: Ulcers and So Much More

As wound care practitioners, we commonly encounter patients who are referred for evaluation and management of venous ulcers due to venous hypertension. These ulcers are the most common lesions of the lower extremities, affecting 1%-3% of the US population.¹ Patient may have coexisting medical comorbidities such as cardiac failure and advanced arterial disease, which may impact the usage of compression therapy. The longstanding venous disease may be associated with additional morbidities such as pain, disability, and malignant transformation. Effective clinical outcomes require patient adherence with recommendations that involve a lifelong commitment to management. This article will serve as a generalized overview of this burdensome disease.

To better understand a venous ulcer requires an appreciation of what lies beneath as its physical manifestation is due to a perturbation within the underlying and associated micro- and macrocirculation. The former involves dysfunction of the capillaries and lymphatics secondary to microthrombi resulting in leakage of plasma proteins, accumulation of hemosiderin, neutrophil activation, and fibrin formation.^2,3 These changes contribute to the stagnation of capillary blood flow, endothelial damage due to white cell trapping,⁴ and decreased oxygen pressure near the ulcers resulting from the diffusion barrier of the fibrin cuff.⁵ Dysfunction within the venous macrocirculation may manifest because of valvular incompetency and failure of the calf muscle pump. Under normal circumstances, the valves function to prevent retrograde venous flow, and the calf muscles exert a squeeze to propel venous return to the heart. Failure of either entity may contribute to venous hypertension with abnormally elevated pressures within the superficial and deep veins. While insufficiency may involve any venous structure of the limb, more than 85% of patients with chronic venous insufficiency have disease within their superficial venous system, of which 70%-80% involve the great saphenous veins.⁶ Isolated deep vein incompetence is uncommon; however, when combined with reflux involving the perforator veins, it is associated with a higher rate of ulcer recurrence and prolonged healing.⁷

The evaluation of a patient with a leg ulcer requires a complete history. On physical examination, the clinical stigmata may include—but not limited to—pigmentary changes from hemosiderin deposition, varicosities, venous stasis dermatitis, pain, and swelling. Due to possible concomitant mixed arterial and venous pathology, patients should have a vascular assessment prior to surgical ulcer debridement and the application of multilayered compression therapy. An ankle-brachial index can be easily obtained with a handheld Doppler device within the traditional outpatient wound care setting. Referrals can perform advanced arterial and venous studies such as duplex and plethysmography to vascular interventionists. A tissue biopsy may be warranted for patients with longstanding ulcers of more than three months to rule out underlying malignancy.

The clinical management of venous ulcers involves utilizing standard wound care to treat problematic wounds directly. This can include maintaining a moist wound bed environment, addressing bioburden with surgical or nonsurgical debridement, controlling exudate, applying advanced topical therapies, and managing associated pain. The mainstay for the management and prevention of venous ulcers is compression therapy. Additionally, venoactive drugs such as micronized purified flavonoid fraction have been used to strengthen the venous walls, improve lymphatic drainage, and normalize capillary permeability.⁸ Dietary modifications, smoking cessation, weight reduction, and psychological support may enhance outcomes and improve the patient’s quality of life.⁹ Surgical interventions may be used to ablate or remove varicosities. Operative intervention for venous ulcers has shown an 88% healing rate with only a 13% recurrence rate over ten months; however, there is no evidence for the superiority of surgical intervention over medical management.¹⁰

Unfortunately, ulcer recurrences are common, and patients are best prepared to realize that their disease will be managed and not “cured.”

1. Anatomy

• Deep venous system: located within lower extremity muscles
• Anterior tibial, posterior tibial, peroneal, popliteal, profunda femoral, common femoral
• Superficial venous system: located in subcutaneous tissue
• Great saphenous vein, short saphenous vein
• Perforator/communicator veins

2. Pathophysiology

2A. Macrovascular Venous System

• Venous reflux due to incompetent valves
• Calf muscle pump failure
• Obstruction

• Superficial thrombophlebitis
• Deep venous thrombosis
• Proximal outflow obstruction (ie, May-Thurner syndrome)

2B. Microvascular Venous System

• Dermal capillary leakage
• Lymphatic dysfunction

3. Predisposing Risk Factors

• Age >55 years
• Family history
• Obesity
• Pregnancy
• Prolonged standing
• Hypercoagulable disorders
• Previous deep vein thrombosis
• Postthrombotic syndrome
• Calf muscle pump failure

4. Clinical Features

• Itching
• Stasis dermatitis
• Pain
• Disability
• Depression
• Drainage
• Wound infection
• Chronic leg edema
• Lipodermatosclerosis
• Atrophy blanche

5. Diagnostic Evaluation

• Ankle-brachial index
• Venous duplex
• Venous plethysmography
• Arterial duplex

6. Recommended Therapies 

• Standard wound care
• Debridement, exudate management, bioburden control, use of advanced cellular therapies, skin graft
• Compression therapy
• Calf muscle pump exercises
• Leg elevation
• Weight loss
• Psychological support
• Surgical intervention
• Ablative therapy
• Phlebectomy

Clinical Case

The patient is a 62-year-old male with diabetes and a history of polycythemia vera, atrial fibrillation, and a chronic, draining wound involving the left lower leg. 

The patient reported that the wound began in the summer of 2018. Initially, the patient was evaluated by a vascular team at an outside facility and underwent balloon venoplasty due to diffuse narrowing of the left iliac vein. Venous ablation of the left and right great saphenous veins occurred three months later. There was no previous history of deep vein thrombosis.

Ten months following the aforementioned initial interventions, the patient presented to the wound care center for evaluation. He had been wearing compression wraps and attempted to manage the wound drainage with multiple absorptive dressings. His medications included apixaban (ELIQUIS; Bristol Myers Squibb) due to a history of atrial fibrillation.

On physical examination, no open wounds involving the right lower extremity were found. There was sizeable venous ulceration of the left anterolateral lower leg with copious serous drainage, macerated periwound, and heavy fibrinous debris within the wound bed. The measured total area of involvement was 187.5 cm2 (Figure 1). The ankle-brachial indices were elevated at 1.37 on the right and 1.45 on the left.

The patient was managed with standard wound care, including wound cleansing with Vashe Wound Solution (URGO Medical), serial surgical selective debridement, and full-length left leg compression wraps. Venous studies were repeated to evaluate the left limb and proximal system. Results demonstrated a widely patent inferior vena cava and bilateral common iliac veins. No deep vein thrombosis was detected. The patient was found to have symptomatic varicosities of the left calf with a reflux of 5.3 seconds. In the mid to distal calf, perforator veins were identified with a reflux of 6.3 seconds.

While awaiting his scheduled procedure for ablation of the venous perforators, the patient was referred to the lymphedema clinic for manual lymphatic drainage therapy. Two months after his ablative procedure, the wound area had decreased to 104 cm2 but then stalled in its healing trajectory. Cellular- and/or tissue-based products were applied, but the patient continued to have moderate drainage. He then underwent the application of a split-thickness skin graft facilitated by negative pressure wound therapy for ten days (Figure 2).

Postoperatively, multilayer compression therapy was utilized in the wound care center and was transitioned to the continued home use of Farrow wraps. Within three months, the patient’s wound was completely reepithelialized (Figure 3).

References

1. Bonkemeyer Millan S, Gan R, Townsend PE. Venous ulcers: diagnosis and treatment. Am Fam Physician. 2019;100(5):298-305.
2. Comerota A,Lurie F. Pathogenesis of venous ulcer. Seminars in Vascular Surgery 28(2015):6-14
3. Jünger M, Steins A, Hahn M, Häfner HM. Microcirculatory dysfunction in chronic venous insufficiency (CVI). Microcirculation. 2000;7(6 Pt 2):S3-S12.
4. Falanga V, Eaglstein WH. The “trap” hypothesis of venous ulceration. Lancet. 1993;341(8851):1006-1008. doi:10.1016/0140-6736(93)91085-z
5. Van de Scheur M, Falanga V. Pericapillary fibrin cuffs in venous disease. A reappraisal. Dermatol Surg. 1997;23(10):955-959. doi:10.1111/j.1524-4725.1997.tb00759.x
6. Shami SK, Sarin S, Cheatle TR, Scurr JH, Smith PD. Venous ulcers and the superficial venous system. J Vasc Surg. 1993;17(3):487-490.
7. Burnand K, Thomas MI, O'Donell T, et al. Relation between postphlebitic changes in the deep veins and results of surgical treatment of venous ulcers. Lancet. 1976;1(7966):936-938.
8. Jindal R, Dekiwadia DB, Krishna PR, et al. Evidence-based clinical practice points for the management of venous ulcers. Indian J Surg. 2018;80(2):171-182. doi:10.1007/s12262-018-1726-3
9. Sinha S, Sreedharan S. Management of venous leg ulcers in general practice - a practical guideline. Aust Fam Physician. 2014;43(9):594-598.
10. Collins L, Seraj S. Diagnosis and treatment of venous ulcers. Am Fam Physician. 2010;81(8):989-996.