In the Clinic

Venous Leg
Ulcers

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
Why do patients with chronic venous
insufficiency develop VLU?

 CVI most common cause of VLU

 VLU patients have venous hypertension, or abnormally
sustained elevation of venous pressure on walking
 Caused by vein valve reflux, outflow problems or both

 Venous outflow issues

 Venous obstruction
 Poor function of calf muscle pump impairs venous
system's ability to return venous blood to heart
 Ankle movement limitations contribute to calf muscle
pump failure

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
What are the risk factors for VLU?

 Age older than 55 years

 Family history of CVI
 Ulcer history, parental history of ankle ulcers
 Higher body mass index
 History of pulmonary embolism
 Venous reflux in deep veins, history of superficial/DVT
 Lower extremities skeletal or joint disease
 Number of pregnancies
 Physical inactivity
 Severe lipodermatosclerosis

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
Are there measures that can prevent VLU
or their recurrence?

 Aggressive management of reversible risk factors

 Control of relevant comorbid conditions (CHF, PVD)
 Healthy diet, appropriate exercise, weight control
 Management of a hypercoagulable state

 Stockings that achieve at least 20-30 mm Hg pressure

 Patients should use highest level of compression tolerable

 Surgical venous ablation

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
CLINICAL BOTTOM LINE: Prevention...

 CVI is the leading cause of VLU

 Venous hypertension with calf muscle pump dysfunction
 Manage comorbid risk factors
 CVI, obesity, hypercoagulable states
 Skeletal and joint disease of the lower extremities
 Compression stockings
 For primary and secondary prevention
 Venous intervention
 For secondary prevention

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
What symptoms and physical findings are
suggestive of CVI?

 Swelling and aching of legs, worse at end of day and

improved by leg elevation
 History of ulcer recurrence, particularly at same location
 Dependent edema, telangiectasias, varicose veins,
reddish-brown pigmentation and purpura, and
subsequent hemosiderin deposition
 Eczematous changes with redness, scaling, pruritus
 Smooth, ivory-white, stellate atrophic plaques of
sclerosis with telangiectases (atrophie blanche)
 Chronic lipodermatosclerosis (LDS) and acute LDS

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
Chronic venous insufficiency

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
Atrophie blanche

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
What symptoms and physical findings
suggest that VLU are due to CVI?

 VLU may be painful—dull, aching, or burning pain

 Location over medial lower third of the legs
 Usually 1 ulcer w/ irregular, flat, or only slightly steep borders
 Ulcer bed shallow, with granulation tissue or fibrinous material
 Wound surface rarely shows necrosis, exposed tendons, bone
 Venous dermatitis, LDS, or atrophie blanche around ankle
 Assessment: Test for neuropathy
 Severity of CVI correlates with decreased range of motion at ankle
and is associated with peripheral neuropathy
 VLU pain neuropathic in origin in some patient

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
Venous leg ulcer

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
What other conditions should be
considered during evaluation of a patient
with possible VLU?
 Common causes of lower extremity ulcers
 CVI
 Arterial insufficiency
 Diabetic neuropathy
 Prolonged pressure

 Less common causes

 Trauma
 Inflammatory or metabolic conditions
 Cancer
 Infections
© Copyright Annals of Internal Medicine, 2016
Ann Int Med. 165 (2): ITC2-1.
What is the role of laboratory testing?

 No single laboratory test is diagnostic

 Testing may be indicated depending on specific patient
history, comorbidities, and family history
 In patients with history of recurrent ulceration or
thrombosis, evaluate for hypercoagulable states

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
What is the role of noninvasive tests, such
as ankle-brachial index and duplex
ultrasonography?
 Ankle-brachial index should be performed
 For PAD screening: concomitant arterial disease in ~20%
 Compression therapy could worsen an arterial ulcer

 Color duplex ultrasonography

 For accurate diagnosis and to provide prognostic info

 Photo and air plethysmography

 Whole-limb venous hemodynamics at rest and after exercise

 CT exam
 Intractable edema associated with pain despite compression

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
What is the role of routine testing for
infection?

 Swab culture testing unwarranted w/o signs of infection

 If atypical infection suspected: send tissue from wound
biopsy for microscopic examination and culture
 Use antibiotic therapy only for clinically infected ulcers
 Evidence supports topical cadexomer iodine for healing
 No evidence supports use of systemic antibiotics

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
When should clinicians consider obtaining a
biopsy or referring the patient to a surgical
or nonsurgical specialist for diagnosis?

 To rule out other causes of VLU, especially cancer

 When ulcers are atypical-appearing ulcers
 When ulcers have not healed after 4 weeks of active
treatment

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
CLINICAL BOTTOM LINE: Diagnosis...
 Typically based on clinical history and physical examination
 Presence of CVI
 Single, painful ulcer with irregular, flat borders and
granulating or fibrinous bed on medial lower third of legs
 Color duplex ultrasonography to characterize venous disease
in all patients
 Ankle-brachial index to exclude concurrent PAD
 If VLU do not improve within 4 weeks of active therapy:
consider referral to specialist or biopsy

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
What is the overall approach to treatment?

 Treatment goals
 Reduce edema and pain
 Heal ulcers
 Prevent recurrence

 Systematic approach needed

 Assess frequently and escalate treatment if unresponsive

 Simplest treatment: bed rest with leg elevation

 Elevate legs above heart 30 minutes, 3 to 4x/d + at night
 Reduces swelling, improves venous microcirculation
 Most patients struggle to follow this recommendation

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
What is the role of compression therapy?

 Cornerstone of therapy
 Because sustained leg elevation often difficult to achieve
 Gold standard: multiple elastic layers for graduated
compression

 Increases interstitial hydrostatic pressure

 Improves venous return
 Reduces venous hypertension and edema
 Improves ulcer healing rates

 Use cautiously with CHF and with arterial insufficiency

 Don’t use with severe arterial insufficiency

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
How long should clinicians prescribe
compression therapy?

 Continue until the ulcer heals

 Continue indefinitely after healing to prevent recurrence
 To enhance adherence, instruct how to put on stockings
 Ensure proper measurement and fit
 Assistive devices may help arthritic, obese, elderly patients
 Replace at least every 6 months

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
What is the role of medication?

 To improve healing in combination with compression

 Aspirin (300 mg daily)
 Pentoxifylline (400-800 mg 3x/d)

 To reduce LDS inflammation, pain, induration

 Stanozolol
 Oxandrolone
 Horse chestnut seed extract (active ingredient: aescin)

 To reduce pain (based on neuropathic origin)

 Amitriptyline, gabapentin, pregabalin

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
What is the role of growth factors?

 Granulocyte macrophage colony-stimulating factor

 Topical and perilesional injection increases ulcer healing
 Promotes wound healing through many mechanisms
(homeostasis, inflammation, proliferation, maturation)
 Increases vascularization
 FDA-approved for neutropenia but not wound healing
 Phase 3 trials stopped due to bone pain associated with
perilesional injections

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
What is the role of physical therapy or
exercise?

 Aim: to improve range of ankle movement and calf

muscle pump function
 Might enhance ulcer healing
 But evidence conflicting and RCTs lacking
 RCT underway: comparing compression therapy with
compression therapy + 12 weeks of supervised exercise

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
What is the role of hyperbaric oxygen
therapy?

 Adjunct to standard wound care

 Controversial because evidence for treating VLU extremely
limited
 100% oxygen at 2-2.5 atmosphere absolute for 60- to 120-
minute periods over 15-30 sessions

 Goal: increase partial pressure of oxygen at the wound

 Role in pathogenesis and treatment unclear
 Fibrin cuff theory: fibrin cuffs formed around precapillary
vessels may result in wound hypoxia, so increased oxygen
might aid healing

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
What is the role of surgical debridement or
skin grafting?

 Debridement
 Removes nonviable tissue to achieve an appropriate
wound bed with granulation tissue
 Standard care despite lack of controlled data on healing

 Skin grafting
 Enhances healing for large or slow-healing ulcers
 May rapidly decrease pain and aid functional status
 Pinch grafts, split-thickness skin grafts, and micro-skin
grafts used successfully but RCTs lacking

 Skin equivalents (cellular, acellular) may aid healing

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
What is the role of venous surgery in
treatment and prevention?
 Venous surgery
 Doesn’t improve healing but reduces recurrence
 Open surgery has significant potential morbidity
 Cochrane review found no evidence for benefit or harm

 Subfascial endoscopic perforator surgery

 Safer, possible improved healing, decreased recurrence

 Minimally invasive procedures

 Treat CVI and recurrence
 Endovenous thermal ablation (laser, radiofrequency, steam)
 US-guided foam sclerotherapy; cyanoacrylate embolization

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
When should clinicians consider referring
the patient to a surgical or nonsurgical
specialist for treatment?
 Prognostic factors associated with slower healing
 Larger wound area (>5 cm2) and long duration (>6 months)
 LDS and ulcer history, BMI >33 kg/m, physical inactivity
 Prolonged venous filling time, deep venous insufficiency
 Ulcer depth >2 cm, atypical ulcer location (posterior calf)

 Refer to wound specialist when wounds fail to decrease

in size during first month of treatment
 Expertise may be found in a variety of specialties
 Vascular medicine and surgery, podiatry, dermatology

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
How should clinicians educate patients?

 Encourage patients to adhere to compression therapy

 Provide educational materials on pathophysiology,
management, and prevention
 Consider video-based educational interventions to teach
patients about the disease
 Consider patient support groups for education on self-
management

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.
CLINICAL BOTTOM LINE: Treatment...
 Goals: reduce edema, improve pain and LDS, heal ulcer,
prevent recurrence
 Maintenance:
 Moist wound bed and regular sharp debridement
 Infection control
 Compression with elastic multilayer bandages
 If no improvement in 4 weeks: consider referral to wound
expert and adjuvant therapies
 Prevent recurrence: indefinite use of compression stockings
and vascular intervention

© Copyright Annals of Internal Medicine, 2016

Ann Int Med. 165 (2): ITC2-1.