INTRODUCTION
Definition, rationale and scope
Venous leg ulcers (VLUs) are defined as open lesions between the knee and ankle joint
that occur in the presence of venous disease.[1] They are the most common cause of
leg ulcers, accounting for 60-80% of them.[2] The prevalence of VLUs is between 0.18%
and 1%.[3] Over the age of 65, the prevalence increases to 4%.[4] On an average 33-60%
of these ulcers persist for more than 6 weeks and are therefore referred to as chronic
VLUs.[5] These ulcers represent the most advanced form of chronic venous disorders
like varicose veins and lipodermatosclerosis.[6]
Risk factors for development of VLUs include older age, female sex, obesity, trauma,
immobility, congenital absence of veins, deep vein thrombosis (DVT), phlebitis, and
factor V Leiden mutation.[7
8
9]
Poor prognostic factors[10
11]
Duration of more than 1 year - recurrence rate in these ulcers is more than 70%
Larger wounds
Fibrin in >50% of wound surface
Ankle-brachial pressure index (ABPI) <0.8
History of venous stripping/ligation.[10
11]
Chronic venous leg ulcer results in reduced mobility, significant financial implications,
and poor quality of life. There are no uniform guidelines for assessment and management
of this group of conditions, which is reaching epidemic proportions in the prevalence.
There is a wide variation in healing and recurrence rates of these ulcers in the Indian
population due to differing nutritional status, availability of medical facilities
and trained medical staff to diagnose and manage such conditions. These guidelines
are devised based on current available evidence to help all concerned in accurately
assessing, correctly investigating and also providing appropriate treatment for this
condition.
Pathophysiology
Venous hypertension
Deep vein thrombosis, perforator insufficiency, superficial and deep vein insufficiencies,
arteriovenous fistulas and calf muscle pump insufficiencies lead to increased pressure
in the distal veins of the leg and finally venous hypertension.
Fibrin cuff theory
Fibrin gets excessively deposited around capillary beds leading to elevated intravascular
pressure. This causes enlargement of endothelial pores resulting in further increased
fibrinogen deposition in the interstitium. The “fibrin cuff” which surrounds the capillaries
in the dermis decreases oxygen permeability 20-fold. This permeability barrier inhibits
diffusion of oxygen and other nutrients, leading to tissue hypoxia causing impaired
wound healing.[12]
Inflammatory trap theory
Various growth factors and inflammatory cells, which get trapped in the fibrin cuff
promote severe uncontrolled inflammation in surrounding tissue preventing proper regeneration
of wounds.[13] Leukocytes get trapped in capillaries, releasing proteolytic enzymes
and reactive oxygen metabolites, which cause endothelial damage. These injured capillaries
become increasingly permeable to various macromolecules, accentuating fibrin deposition.
Occlusion by leukocytes also causes local ischemia thereby increasing tissue hypoxia
and reperfusion damage.
Dysregulation of various cytokines
Dysregulation of various pro-inflammatory cytokines and growth factors like tumor
necrosis factor-α (TNF-α), TGF-β and matrix metalloproteinases lead to chronicity
of the ulcers.[14
15]
Miscellaneous
Thrombophilic conditions like factor V Leiden mutation, prothrombin mutations, deficiency
of antithrombin, presence of antiphospholipid antibodies, protein C and S deficiencies
and hyperhomocysteinemia are also implicated.[16]
CLASSIFICATION OF CHRONIC VENOUS INSUFFICIENCY
The classification and staging of chronic venous insufficiency (clinical severity)
can be measured by a scoring system called clinical manifestations, etiological factors,
anatomical distribution, and pathophysiological conditions[17
18] (evidence Level D) [Table 1].
Table 1
Classification of venous ulcers
Assessment and stepwise approach to diagnosis of VLU.
CLINICAL ASSESSMENT
1. Rule out arterial disease, which are indicated by:[19]
History of intermittent claudication, cardiovascular disease and stroke
Absence of pedal pulses
Abnormal blood pressure (BP): It gives clues to the presence of any cardiovascular
disease.
It is very important to rule out arterial etiology as application of compression in
such cases can cause severe damage[20
21] (evidence Level D).
2. Obtain clues from history suggesting venous etiology[22] (evidence Level D)
History of previous or current DVT
Family history of leg ulcers
Varicose veins or its treatment
History of phlebitis
Surgery, trauma or fractures of the affected leg, which can damage the valves
Chest pain, hemoptysis or pulmonary embolism
Occupations of prolonged standing or sitting
Obesity
Multiple pregnancies
Aching pain in the lower limbs.
3. Clinical examination to confirm the diagnosis of venous ulcer
Examination of ulcer
Location: Anterior to medial malleolus, pretibial area, lower third of leg (gaiter
region)[23] (evidence Level C)
Measurement of size: Serial measurement of surface area of ulcer is a reliable index
of prognosis and healing. Measurements of length, width and depth of ulcer with two
maximum perpendicular axes are important. Disposable ruler, photography, acetate tracings
and computerized calculation (planimetry) following digital photography are the methods
which are used in measurement. Measuring the ulcers help in identifying patients not
responding to conventional therapy and those requiring alternative therapy[24] (evidence
Level C)
Characteristics of the ulcer: Shallow depth, irregular shaped edges with well-defined
margins
Amount and type of exudates: Yellow-white in color
Appearance of ulcer bed: Presence of ruddy viable granulation tissue. Thick slough
or eschar indicates arterial insufficiency
Signs of infection: Cellulitis, delayed healing despite appropriate compression therapy,
increase in local skin temperature, increase in ulcer pain or change in nature of
pain, newly formed ulcers within inflamed margins of preexisting ulcers, wound bed
extension within inflamed margins, discoloration (esp. dull, dark brick-red), friable
granulation tissue that bleeds easily, increase in exudate viscosity, increase in
exudate volume, malodor, new-onset dusky wound hue, sudden appearance or increase
in an amount of slough, sudden appearance of necrotic black spots and ulcer enlargement[25]
(evidence Level D). Take a swab only if these signs are present
Ulcer odor
Pain associated with ulcer: Pain may be absent, mild or extreme. Pain is more at the
end of the day and usually relieved by elevation of the leg.
Periulcer area
Capillary leaking causing edema leading to maceration, pruritus and scaling. Associated
warmth and pruritus.
Associated changes in the leg
Firm (“brawny”) edema
Hemosiderin deposit (reddish brown pigmentation)
Lipodermatosclerosis
Evidence of healed ulcers
Dilated and tortuous superficial veins
Limb may be warm
Atrophie blanche
Eczema
Altered shape – inverted “champagne bottle”
Ankle flare.
4. Regular documentation to compare results before and after treatment and progression
with time
5. Assess comorbidities like obesity, malnutrition, intravenous drug use and coexisting
medical conditions prior to surgery. Reduced calorie and protein intake hampers ulcer
healing[26] (evidence Level D)
6. Rule out complications including severe infections, osteomyelitis and malignant
changes[7] (evidence Level D).
7. If no improvement after 12 weeks or in case of recurrence or no response to treatment
after 6 weeks: Reassess
Risk factors for nonhealing - Increased wound size and duration, history of venous
stripping or ligation, history of hip or knee replacement, ankle-brachial index <
0.8, >50% of wound covered in fibrin and undermined wound margin
Accuracy of etiology
Rule out allergic contact dermatitis to medications and differentiate from venous
eczema. Do a patch test in all cases of venous ulcers with eczema. The common sensitizers
are lanolin, topical antibiotics (gentamycin, neomycin, bacitracin), antiseptics,
preservatives, emulsifiers, resins and latex.[27
28
29
30
31] (evidence level C). Positive patch tests in these ulcers range from 40% to 82.5%.[27
32
33
34] (evidence Level B)
Any new comorbidities?
Think of biopsy (in case of atypical and nonhealing ulcers) - to rule out malignancy,
systemic disorders, collagen vascular disorders and vasculitis[35] (evidence Level
D)
Take bacterial, mycobacterial and fungal cultures
Is the treatment appropriate?
Is patient compliant with treatment?
INVESTIGATIONS
Noninvasive
ABPI: This is a noninvasive test using the handheld Doppler ultrasound which identifies
peripheral arterial disease in the leg. Systolic BP is measured at the brachial artery
and at the ankle level.
ABPI = highest systolic foot pressure (dorsalis pedis/posterior tibial artery)/highest
systolic brachial BP
ABPI: 0.8-1.2: Indicative of good arterial flow. Suggestive of venous etiology if
an ulcer is present
ABPI: <0.8 with the clinical picture of arterial disease-arterial insufficiency
ABPI: >1.2: Suggestive of possible arterial calcification[36
37
38
39
40
41] (evidence Level B).
Nylon monofilament can be used as a simple screening test to rule out sensory neuropathy[42]
(evidence Level C)
Duplex ultrasound: It is a noninvasive test which combines ultrasound with Doppler
ultrasonography. Blood flow through arteries and veins can be investigated to reveal
any obstructions. It allows direct visualization of veins, identifies flow through
valves and can map both superficial and deep veins[43] (evidence Level C)
Photoplethysmography: This is a noninvasive test which measures venous refill time.
A probe placed on the skin surface just above the ankle is used for the detection.
The patient is instructed to perform calf muscle pump exercises for brief periods
followed by the rest. The probe actually measures the reduction in skin blood flow
following exercise. This determines the efficiency of the calf muscle pump and the
presence of any abnormal venous reflux. Patients with problems in superficial or deep
veins usually have poor emptying of the veins and abnormally rapid refilling (<25
s)[44] (evidence Level C)
Pulse oximetry: This is another noninvasive test which measures the red and infrared
light absorption of oxygenated and deoxygenated hemoglobin in a digit. Oxygenated
hemoglobin absorbs more infrared light and allows more red light to pass through a
digit. Deoxygenated hemoglobin absorbs more red light and allows more infrared light
to pass through the digit. However, there is insufficient evidence to recommend this
investigation as a primary diagnostic tool[45
46] (evidence Level C)
Toe brachial pressure index (TBPI): Noninvasive test that measures arterial perfusion
in toes and feet. A toe cuff is applied to hallux and pressure is divided by the highest
brachial systolic pressure, which is the best estimate of central systolic BP. TBPI
identifies incompressible calcified arteries in diabetics and renal disease patients[47]
Transcutaneous oxygen: Measures amount of oxygen reaching the skin through blood circulation.
Presently, insufficient evidence to recommend as primary diagnostic test.
Invasive
Biochemical tests
Blood glucose - To rule out diabetes
Hemoglobin - To rule out hematological disorders
Urea and electrolytes
Serum albumin, transferrin - To rule out nutritional deficiencies
Lipids
Rheumatoid factor
Auto antibodies
White blood cell count
Erythrocyte sedimentation rate
C-reactive protein.
Liver function testsk
Activated protein C: Detected in 25% venous ulcers and 50% of recurrent venous thromboses
patients[48] (evidence level D)
Microbiology: Bacterial wound swab when ulcer shows clinical signs of infection like
cellulitis, pyrexia, increased pain, rapid extension of the area of ulceration, malodor
and increased exudates[49] (evidence Level C)
Histopathology: Wound biopsy only if malignancy or other etiology is suspected.
SUMMARY [EVIDENCE LEVEL C]
The prevalence of VLUs is on the increase with chronic venous insufficiency being
the main culprit. A detailed accurate assessment of leg ulcer in patients is essential
to ensure starting of timely and appropriate treatment. It should be an ongoing continuous
assessment as signs and symptoms can rapidly change thereby requiring progressive
evaluation. Good and accurate quality patient assessment will save time and cost by
an enforcement of appropriate treatment regimens.