Leg ulcers are debilitating and painful, greatly reducing patient's quality of life.
These ulcers are often difficult to treat and the successful treatment of leg ulcers
depends upon the accurate diagnosis and treatment of the underlying cause. According
to most of the Western and European studies, the most common type of leg ulcer is
venous ulcer the others being neuropathic ulcer and arterial ulcers. These three kinds
of ulcers account for almost 90% of cases of lower leg ulceration. In tropical
countries like India, there is a paucity of epidemiological studies regarding prevalence
and etiology of leg ulcers. A study from one center in India suggests leprosy (40%),
diabetes (23%), venous disease (11%), and trauma (13%) causes of lower extremity wounds.
The following evidence-based recommendations are in general to lower leg ulcers without
referring to any specific cause of ulcerations and adherence to these will lead to
speedy healing of lower leg ulcerations.
Clinical history and examination of leg and ulcer (Level B)
Clinical assessment includes full clinical history and physical examination of the
patient of leg ulcer presenting either first time or with recurrent leg ulcer. In
history, the duration/recurrence of an ulcer, pain, trauma, comorbid factors, and
associated medical causes should be considered. The comorbid factors such as old age,
malnutrition, poor hygiene, intravenous drug abuse, obesity, varicose veins, deep
vein thrombosis, and coexisting medical causes such as diabetes mellitus, peripheral
arterial diseases, rheumatoid arthritis, systemic vasculitis adversely affect both
prognosis, and outcome of the treatment.
Examination of both legs should be done, which includes palpation of peripheral pulses,
edema if present whether it is pitting or nonpitting type, signs of venous hypertension
such as varicose veins, hemosiderin pigmentation, varicose eczema, atrophie blanche,
and lipodermatosclerosis should be noted. The range of hip, knee, and ankle movement
should be determined, and sensation should be tested to exclude peripheral neuropathy
(evidence Level B).[1
Clinical assessment of ulcer includes the assessment of site, size, depth, edge, margins,
floor, base, and condition of the surrounding skin. The site of the ulcer medial,
lateral, anterior, posterior, or combination should be noticed, this give clue to
the underlying etiology of the ulcer. The size and surface area of the ulcer is determined
by measuring the two maximum perpendicular axis, tracing the margins, and clinical
photography. The surface area of the ulcer should be serially measured over time (evidence
8] A study compared the accuracy of ulcer measurement from digital images with contact
tracing, and it was found that the two methods were equally accurate and reproducible,
but that the digital image measurement was significantly quicker and offered a number
advantages (evidence Level C).
In patients with lower extremity ulcers, the accurate assessment of the arterial and
venous systems is necessary to establish the diagnosis and essential for adequate
treatment selection (Level B).[10
Doppler measurement of ankle/brachial pressure index
All patients presenting with an ulcer should be screened for arterial disease by Doppler
measurement of ankle/brachial pressure index (ABPI) (evidence Level B).[10
Ankle/brachial pressure index: Is an objective evidence to substantiate the presence
or absence of significant peripheral arterial disease (except in heavily calcified
vessels) is the ratio of the ankle to brachial systolic pressure and can be measured
using a sphygmomanometer and hand held Doppler device. The significance of its assessment
is highlighted by the fact that compression therapy can be safely applied to patients
with ABPI >0.8 (evidence Level C).[10
12] Compression applied to legs with arterial insufficiency could result in pressure
damage, limb ischemia, and even amputation. Doppler ultrasound to measure ABPI should
also be conducted when the ulcer is deteriorating, ulcer not healed fully by 12 weeks,
sudden increase in size of ulcer, sudden increase in pain, foot color or temperature
change, or there is recurrence of ulcer (evidence Level B).[13
Role of color flow Doppler imaging in arterial disease
Color flow Doppler imaging is advantageous over ABPI measurements in cases in which
wounds and ulcers prevent the use of a cuff for measuring ABPI (evidence Level D).
Color flow Doppler imaging quantifies any proximal arterial disease (aortoiliac) and
the degree of involvement of distal vessels. And in addition, may detect nonflow limiting
lesions to nonaxial arteries such as the deep femoral artery or lesions limited to
a single tibial artery.
Role of venous color flow Doppler imaging
It is a gold standard investigation for the assessment of the venous system of lower
limb (evidence Level B).[15
This noninvasive modality has revolutionized the diagnostic approach to venous disorders.
It assesses the superficial, deep or perforating veins separately for the presence
of obstruction and reflux. Absence of flow is considered as obstruction and reflux
is defined as the retrograde flow lasting more than 0.5 s, which is the time required
for valve closure. It is highly recommended in the setting of venous ulcers.
Referral to a specialist unit for biopsy should be considered if the appearance of
the ulcer is atypical or if there is deterioration or failure to progress after 12
weeks of active treatment (evidence Level C).[18
Bacteriological swabbing is unnecessary unless there is evidence of clinical infections
such as inflammation, redness, cellulitis, increased pain, purulent exudates, rapid
deterioration of the ulcer, pyrexia, and foul odor (evidence Level B).[21
Bacteriological swabs have certain limitations the swab cultures typically show the
presence of numerous organisms, which have little or no clinical relevance, there
is no standard technique for obtaining a swab culture, which shows reproducible results,
inappropriate technique for taking swabs like from necrotic or nonviable tissue and
they lack the ability to differentiate between bacteria resting on the wound surface
versus infecting organisms. There are no reports in the literature that validate the
use of swab cultures in chronic wounds.
However, a quantitative tissue biopsy should be obtained if there is no progression
of the wound after 2 weeks of standard treatment (evidence Level B).[22
The gold standard for the treatment of infection is >105 colony-forming units of bacteria
per gram of tissue on quantitative biopsy. The exception to this rule is β-hemolytic
streptococcus, which is harmful at any level in the wound tissue.
Leg ulcer patients with dermatitis/eczema should be considered for patch-testing (evidence
The incidence of contact allergy increases with the duration of ulceration. Two
studies in which patients with venous leg ulcer were patch-tested for a range of allergens
contained in current ulcer dressings found that in one, 46% and in the other 61% of
reactions were to these additional allergens.[27
28] Several large patch-test studies have demonstrated that the principal sensitizers
are ingredients of applications, dressings, and bandages, with common sensitizers
being lanolin, antibiotics, antiseptics, preservatives, emulsifiers, resins, and latex.[26
Cleaning of an ulcer is recommended using simple irrigation with either normal saline
compresses or plain tap water (evidence Level E).[30
Dressing technique should be clean and aimed at preventing cross-infection (evidence
Wounds and skin are colonized by bacteria and currently there is a lack of evidence
that the presence of colonizing bacteria impedes wound healing. In a systematic review
of the effects of antimicrobials including topical antiseptics on chronic wounds identified
no randomized controlled trials (RCT's) to support the cleansing by antiseptic solutions.
In another systematic review that looked for effects of using tap water in comparison
to distilled water or boiled water or normal saline for cleansing of wound found no
difference in infection or healing rates while using any of them.
When slough and wound debris obscure the base of the ulcer, debridement becomes essential.
Removal of necrotic and devitalized tissue can be achieved through mechanical, autolytic,
chemical, or enzymatic debridement. Mechanical debridement should be undertaken by
the expert with the surgical skills (evidence Level C).[32
37] Necrotic tissue left in the ulcer contributes to reduced host resistance to infection
because it acts like a foreign body. In this area, there is usually a high concentration
of harmful proteases and bacteria that can inhibit wound healing. Skin debridement
consists of removing nonviable, nonbleeding skin. A chronic wound has to be converted
by debridement to an acute wound, so that it can proceed through the normal healing
33] However, debridement is contraindicated in ulcers when healing is complicated
by severe arterial insufficiency. There are several methods of wound debridement
available to the clinician. These include autolytic, chemical, mechanical, surgical
and biological modalities. In general, autolytic debridement (i.e. breakdown and removal
of dead tissues by body's own cells and enzymes) is recommended for wounds with minimal
debris and without clinical signs of infection. This is facilitated through the maintenance
of the moist wound environment by simple nonadherent wound dressing. Surgical debridement
is most appropriate in wounds with large amounts of necrosis and eschar, but must
be undertaken by specialist.
Chronic ulcer management requires the use of the wound dressings that provide the
optimal “moist” environment. Dressing should be simple, low or nonadherent, low cost
and acceptable to the patient (evidence Level A).[32
No single dressing material is favored (evidence Level C).[32
In the two systematic reviews, many RCT's are identified comparing various dressings
and topical agents in patients of venous ulcers, but no single consensus can be drawn
in favor of any particular dressing material.[32
38] The different types of wound dressings available are occlusive plastic films,
hydrocolloid dressing, absorbent dressings, calcium alginate, hydrogels, and biological
dressings. In a recent in vitro study of effects of different dressing on keratinocyte
cell viability and proliferation has highlighted few important points, which can be
used as a guide to decide the dressing material. The study results showed that silver-based
dressings are cytotoxic and should not be used in the absence of infection. Alginate
dressings with high calcium content affect keratinocyte proliferation probably by
triggering terminal differentiation of keratinocytes. Such dressings should be used
with caution in cases in which keratinocyte proliferation is essential. All dressings
should be tested in vitro before clinical application.
Biological wound dressings are effective when used along with compression therapy
in venous ulcers as compared with compression therapy alone (evidence Level A).
Regarding the role of biological wound dressings containing cultured, allogenic, bilayered
human skin equivalents a randomized multicentered prospective study of 275 patients
of venous ulcer, have shown it more effective than compression therapy alone. The
researchers found that treatment with human skin equivalent was more effective than
compression therapy alone in the percentage of patients healed at 6 months (63% vs.
49%). Furthermore, the median time to complete wound closure was 61 days for the human
skin equivalent group compared to 181 days for those receiving compression therapy
alone. Both results were considered statistically significant. Although, this dressing
is expensive, but human skin equivalent may provide an alternative treatment for nonhealing
Topical antimicrobials and antiseptics
Antibiotics are indicated in cases of overt wound infection where the classical signs
of infection are evident (evidence Level C).[41
In chronic wounds, reduction of certain microbial species, such as anaerobic bacteria
in order to limit undesirable odors or perhaps mixed communities of four or more bacterial
species that impede healing use of topical antibiotics may be justified (evidence
Various studies on dressings incorporating antibiotics and antiseptics are reviewed,
but no single consensus for any particular topical agent could be made. This is partly
due to the different mechanism and spectrum of action of the antimicrobials. The most
frequently used topical antimicrobials in wound care practice are chlorhexidine, iodine,
silver containing products, and mupriocin, fucidic acid. In the past acetic acid,
honey, hydrogen peroxide, sodium hypochlorite, potassium permanganate, and proflavine
have been used.
Effective in reducing vascular and epidural catheter bacterial colonization (evidence
Use is associated with fewer adverse effects on wound healing (evidence Level C).
In a systematic review, which assessed the effect of chlorhexidine-impregnated dressing
on the risk of vascular and epidural catheter bacterial colonization and infection,
around eight randomized controlled clinical trials comparing chlorhexidine-impregnated
dressing with placebo or povidine-iodine dressing were identified. It concluded that
chlorhexidine-impregnated dressing is effective in reducing vascular and epidural
catheter bacterial colonization and is also associated with a trend toward reduction
in the catheter-related bloodstream or central nervous system infections. In a
recent evaluation of human studies has demonstrated that it is associated with few
adverse effects on healing. Despite reports of decreased bacterial counts, increased
healing rates, and lack of toxicity, it is concluded that at present, there is insufficient
data to assess safety and efficacy, and that further clinical trials are required
before the use of chlorhexidine on open wounds is either recommended or condemned.
Iodine: Available as povidine-iodine and second generation dextranomer and cadexomer
Reduces bacterial load, decreases infection rates and promotes healing (evidence Level
In one study, healing rates of chronic venous leg ulcers, each treated with one of
three topical agents were compared to untreated control ulcers in each respective
patient. All agents were seen to reduce bacterial load, silver sulfadiazine, and chlorhexidine
digluconate caused slight improvements in healing rates and times, but povidine-iodine
yielded statistically significant increases. Furthermore, histological assessment
indicated a lack of cytotoxicity because povidine-iodine induced less change in microvessels
and dendrocytes. In addition, a report of the ability of iodine released from
a dressing to modulate the secretion of cytokines by human macrophages in vitro has
provided another justification of its role in promoting healing.
Cadexomer iodine: Leads to reduction of methicillin resistant Staphylococcus aureus
and Pseudomonas aeruginosa with evidence from clinical reports of efficacy in stimulating
healing (evidence Level C).[44
48] Its lack of toxicity for human fibroblasts in vitro suggests a lack of toxicity
for chronic wounds in vivo (evidence Level D).
Silver (evidence Level C)
At present, human studies with silver containing dressings are rather limited, yet
many trials provide encouraging results.[50
53] In an uncontrolled, prospective study of a series of chronic wounds treated with
an ionized nanocrystalline silver dressing demonstrated improved clinical parameters
together with decreased surface wound bioburden, but unchanged deep tissue loads.
The implication was that surface flora contributed more significantly to delayed healing
than deeper flora (evidence Level D).
A systematic review identified one small RCT (n = 30) of patients with leg ulcer,
which compared topical mupirocin with placebo, in addition to standard compression
for all. There was no significant difference between groups in rates of complete healing,
or eradication of Gram-positive bacteria. There is insufficient evidence on which
to base a recommendation for mupirocin.
According to recommendations systemic antibiotic should only be used in cases of clinical
infection and not for bacterial colonization (evidence Level C).[55
A systematic review included five small RCTs of variable quality examining healing
rates of ulcers with a range of systemic antibiotics given for a variable period of
time (10 days to 20 weeks). Studies did not differentiate between infected and colonized
ulcers. There was insufficient evidence to support the routine use of antibiotics.
One randomized, controlled trial compared the use of elastic support bandages to the
same treatment plus systemic antibiotics. No significant differences were noted in
terms of healing rates or changes in bacterial flora. The routine use of systemic
antibiotics is ineffective, costly, and will only facilitate the emergence of yet
more drug-resistant bacteria.
Recommendations are for graduated, multi-layered high compression system with adequate
padding should be the first line of treatment for uncomplicated venous leg ulcers
with ABPI ≥0.8 in all settings (evidence Level A).[57
Three systematic reviews of the literature identifying many randomised controlled
60] concluded that compression systems improve the healing of venous leg ulcers and
should be used routinely in uncomplicated venous ulcers.
Compression systems may be classified into three groups: Short-stretch bandages (SSB),
long-stretch bandages, and stockings. If the limb affected by the ulcer is edematous,
most experts recommend using an SSB system (evidence Level C).[61
63] Compression pressures of at least 30-40 mm Hg at the ankle should be utilized
in the management of venous leg ulcers. All compression bandage systems must create
a pressure gradient from ankle to knee.
Regular monitoring of patients for pain associated with leg ulcers is required. It
is important to formulate individual management plan, which may consist of simple
physical methods such as leg elevation and exercise, compression therapy, and analgesia
(evidence Level C).[64
The assessment of pain should include the severity, type, timing of pain and establishing
the exacerbating and relieving factors. Simple physical methods considered such as
raising the foot end of the bed in venous ulceration or lowering the foot end of the
bed in arterial disease. Leg elevation is important in venous ulcers since it aids
venous return and reduces swelling and pain in leg. Opioids like morphine are extremely
useful for very severe pain uncontrolled by weaker agents and particularly for severe
exacerbations. For neuropathic pain, antidepressants (e.g. amitryptiline) or anticonvulsants
(e.g. gabapentin) are alternative agents of proven efficacy (evidence Level D).
Compression therapy counteracts the harmful effects of venous hypertension and may
relieve pain (evidence Level B).
Role of eutectic mixture of local anesthetic (EMLA) is highlighted by a systematic
review which identified six RCTs comparing EMLA with placebo in pain during debridement.
The meta-analysis showed that EMLA cream was associated with pain reduction (evidence
Other supportive treatment
Systematic review identifying nine RCT's recommend the use of pentoxifylline (1200-2400
mg) along with compression therapy, enhances healing of venous ulcer (evidence Level
Use of granulocyte macrophage colony-stimulating factor
The topical and peri-lesional injections of granulocyte macrophage colony-stimulating
factor (GM-CSF) promotes healing of leg ulcers and is safe (evidence Level B).[68
The GM-CSF promotes wound healing through many mechanisms, affecting one or all of
the wound healing phases, such as homeostasis, inflammation, proliferation, and maturation.
Several case series and pilot studies have demonstrated that topical and peri-lesional
injection of GM-CSF promotes healing of leg ulcer wounds.[68
72] Two randomized, double-blind, placebo-controlled studies showed increased healing
of chronic leg ulcers treated with GM-CSF compared with controls.[68
69] In first RCT authors found that half of the patients treated with a single intradermal,
peri-lesional injection of 400 μg of GM-CSF led to complete healing of the ulcers
at 8 weeks as compared with 11% of patients in the placebo group. The second randomized
trial aimed at dose-finding, it was a double-blind trial of weekly dosages of either
200 μg or 400 μg of GM-CSF given peri-lesional in patients with chronic venous leg
ulcers. The two conclusions drawn out of the study were higher rate of healing in
patients receiving peri-lesional injected GM-CSF as compared with the placebo group
and 57% versus 61% patients showed healing of leg ulcers at week 13 of study in 200
μg and 400 μg groups respectively. Case reports and case series have shown that
GM-CSF is useful for treating leg ulcers due to various other causes as well.[70
72] Because of the pain associated with injections of GM-CSF, use of topical GM-CSF
in a series of 52 venous ulcers was studied and about 90% of ulcers healed, with an
average healing time of 19 weeks.
Though the use of GM-CSF in chronic leg ulcer is shown beneficial for healing in all
above mentioned studies, but further studies are necessary to confirm the efficacy
of this agent in healing venous ulcers and to define the optimal dose and dosing schedule.
Care of surrounding skin
General care of the skin surrounding an ulcer is essential to maintain skin integrity
and minimize the risk of further ulceration. Gentle washing and emollients have been
shown to be effective in all forms of eczema/dermatitis. They help to restore the
barrier function and reduce the role of infective organisms as a cause of damage.
Washing for about 10 min twice a day is optimal. Water just above body temperature
is most desirable, and more natural the emollient soap, more supportive it is of the
epidermis (evidence Level E).
Calf muscle exercises are recommended (evidence Level B).
Role of supervised calf muscle exercises in increasing the calf muscle pump function
and improving the hemodynamics in venous leg ulcers had been highlighted in one prospective
study and another pilot RCT.[74
Patient of leg ulcer with suspected malnourishment should be assessed by a nutritionist
and dietician (evidence Level D).[76
Impaired/poor wound healing is associated with many factors one of which is malnutrition.
Studies have shown that changes in energy, carbohydrates, proteins, fats, vitamin,
and mineral metabolism affect the wound healing process. No significant benefit
on wound healing is seen with nutritional supplements such as vitamins C, A, E, and
zinc in a nondeficient individuals.[77
Large ulcers (>10 cm2) and long duration of ulcer leads to poorer health-related quality
of life (HRQoL) index (evidence Level D).
A cross-sectional study done to determine the association between clinical and social
variables and HRQoL in patients suffering from chronic leg ulcers showed that bodily
pain, emotional and social isolation was associated with patients of large ulceration
for longer duration. Such patients do well with adequate treatment in specialist units
and when provided with adequate psychological support along with.
Indications for surgery
Patient with chronic venous leg ulcer and superficial venous reflux should be considered
for surgery to promote ulcer healing and to prevent recurrence of the ulcer (evidence
Surgical ablation of incompetent superficial veins is done if an ulcer shows no sign
of healing after 3 months of best management of wound. Perforator incompetence and
disease of the superficial venous system can be managed using new surgical techniques
that are associated with only mild morbidity. After ulcer healing, if significant
superficial and/or perforator vein incompetence exists, surgical ablation/ligation
should be considered as part of overall preventive care to prevent ulcer recurrence.[32
Indications for sclerotherapy
Sclerotherapy is indicated for the superficial varicosities and incompetent perforators
surrounding the ulcer this also helps in fast healing of ulcers (evidence Level D).
Indications for laser therapy
No benefit of low-level laser therapy on leg ulcer healing (evidence Level A).
In the previous Cochrane systematic review, the four RCTs were identified studying
the local application of energy from low-level lasers to accelerate the healing of
venous leg ulcers. According to the review, there was no evidence of benefit associated
with low-level laser therapy on venous leg ulcer healing.
Endovascular laser therapy (EVLT) enhances leg ulcers healing (evidence Level C).[83
In recent studies on the effectiveness of EVLT have shown enhanced healing in venous
86] Data from a small RCT showed that 22 (81%) of patients in the EVLT group had healed
ulcers at 12 months compared with 6 (24%) in the control group - elastic or inelastic
compression therapy (P = 0.0001). The present data is minimal to support laser
therapy treatment. In conclusion, more studies are required to establish the role
of local laser therapies or EVLT in the treatment of leg ulcers.
Prevention of ulcer recurrence
Factors that are associated with ulcer nonhealing and recurrence: Overweight body
mass index, history of deep venous thrombosis, large ulcer area, noncompliance with
compression therapy, and triple-system venous disease involving superficial, perforating,
and deep veins (evidence Level D). The strategies to prevent the ulcer recurrence
should target these factors. These could be implemented as regular clinical evaluations,
patient education and life-long compression therapies. Patient's education should
be regarding skin care, elevation of the affected limb when immobile, compliance to
compression therapy, encourage mobility, and exercise. To encourage, early self-referral
at signs of possible skin breach.
Use of compression stockings reduces ulcer recurrence and is thus highly recommended
in patients of venous leg ulcers. Patients are encouraged to wear the strongest compression
they can tolerate for life-long, if not contraindicated otherwise (evidence Level
Indication for referral
The patients with chronic leg ulcer which are complicated by following conditions
requires specialist referral to medicine and surgery units (evidence Level E).[5
Patients with significant occlusive arterial disease require specialist assessment
of the severity
For treatment of underlying medical problems such as rheumatoid arthritis, peripheral
vascular disease, diabetes mellitus, etc.
Ulcers with mixed etiologies, diabetic ulcers
Suspected malignant ulcers
Nonhealing ulcers (a minimum of at least 6 months of compression and local wound care
followed by reassessment of venous function should be done before operative plastic
surgical intervention is considered)
Rapid deterioration of the ulcer
Reduced ABPI <0.8 or increased ABPI >1.0