Review article

Venous Ulcer

Irene Dorthy Santoso, Hanny Nilasari, Shannaz Nadia Yusharyahya

Department of Dermatology & Venereology, Faculty of Medicine Universitas Indonesia,

Dr. Cipto Mangunkusumo National Hospital,
Jakarta, Indonesia

E-mail: irene.dorthy@yahoo.co.id

Abstract

Leg ulcers are common problems in the adult and geriatric population with approximately 1-2% prevalence.
Sedentary lifestyle and obesity increase the incidence of leg ulcers. Deterioriation of quality of life in patients with
venous ulcers happens due to slow healing and high rate of occurrence. Diagnosis, latest treatments, and
preventive measures are essential to discuss.

Keywords: venous ulcer, geriatric, diagnosis, management, prevention

Background prevalence of venous ulcers vary between 0.6-2%8,

Indonesia is the fourth most populous country in the
world with 237 million people.1 In the next 25 years,
this number is expected to continually rising. The
number of people aged above 65 years old will also
increase from 5% to 10.6% with the improvement of
life expectancy, which increased from 67.89 years in
2010 to 68.87 years in 2014. This number is also
predicted to rise to 72.9 years in 2035. 3 This aging
population will come with various health problems.4
Ulcers of the lower extremities is a common problem,
found in 1-2% of the adult and geriatric population.
Sedentary lifestyle including long hours sitting, lack
of physical activity, and obesity, contributes to the
growing number of patients with leg ulcers.5
Leg ulcers are defined as ulcers located in the lower
extremities that are difficult to heal within 4-6 weeks.6
The most common form of leg ulcers is venous
ulcers, which account for 45-85% of all leg ulcers.7-9
Venous ulcers are leg ulcers (located between the
lower knee until above the medial ankle) caused by
venous insufficiency. Venous ulcers can be classified
as acute and chronic, with a cut-off of 6 weeks.6,10,11
Chronic venous insufficiency causes high venous
pressure in the lower extremities.12 The global
and happens more in females than males. 9
The decline in quality of life is generally caused by
sleep disturbance due to pain,13 limited limb
movement,14 psychiatric problems such as
depression and social evasion (happens in 91.66%
of patients),15 disturbances in the workplace, and the
high cost of treatment.11,16,17 Slow healing rate,
varying around 4-72 weeks (with an average of 24
weeks), and the level of recurrence happening in 26-
72% of patients within the first year further contribute
to the patients’ low quality of life. 18 Therefore,
appropriate diagnosis, latest treatments, and
preventive measures are fundamental to discuss.
Risk Factors
The main risk factors found in most of the available
literature are old age and the female sex. Venous
ulcers are mostly found in people aged 60-80 years
old, and the number of cases increases with age.19
Around 72% of patients present with their first ulcer
at age 60, 22% of patients were in their 40s, and 13%
were younger than 30 years old.8,20 The influencing
factors include the increasing venous rigidity causing
hypertension followed by the decreasing endothelial
relaxation which contributes to vascular problems.

J Gen Proced Dermatol Venereol Indones. 2017;2(2):64-76 64

Most of the collagen and smooth muscles are
accumulated in the subendothelial layer, causing the
skin to appear thinner, increasing susceptibility to
ulceration and disturbed tissue perfusion.12 Venous
ulcers are found to be 1.42% more prevalent in
females than males (0.76%).5,12 Hormonal factors
and esthetics cause women to seek treatment three
times more often than men.21
Other influencing factors for venous ulcers include
obesity, non-Hispanic racial background, history of
physical trauma and family history of ulcers. History
of deep vein thrombosis, chronic edema of the lower
extremities or presence of congestive heart disease
also increase the risk of developing venous ulcer.
Sedentary lifestyle, number of pregnancies, and
patients who works in a standing position for long
hours also have higher risk in developing venous
ulcer.5,11
Anatomy and Physiology
The lower extremity venous system consists of the
superficial veins, the deep veins, and the perforating
veins. The main superficial veins are the great
saphenous vein (v. saphena magna) and the short
saphenous vein (v. saphena parva). When calf
muscles contract, blood will flow from the superficial
vein to the deep veins, towards the heart. The normal
calf muscle pumps will pump 85-90% of the venous
blood in the legs, and the superficial component will
carry 10-15% of the blood. During relaxation, The
deep veins will dilate, causing negative pressure,
which will pull blood from the superficial venous
system to the deep veins through the perforating
veins. In venous insufficiency, blood flows back to the
superficial veins from the deep veins. In healthy
people, optimum function of the perforating veins’
valves prevent this from happening.8
Patophysiology
Venous ulcers occur due to failure of the calf muscle
pump, which causes an increase in venous pressure
(venous hypertension).19,20 Several theories try to
explain the pathophysiology of venous ulcers, such
as the pericapillary fibrin cuff theory, the fibrinolytic
abnormalities theory, the growth factor trap
hypothesis, and the white cell trapping hypothesis. 8
The pericapillary fibrin cuffs and fibrinolytic
abnormalities theory was first postulated in 1982 by
Browse and Burnand based on histological
examination of lipodermatosclerosis. Venous
hypertension will affect capillary circulation, causing
J Gen Proced Dermatol Venereol Indones. 2017;2(2):64-76
capillary wall dilatation, and macromolecule leakage
of fibrinogens from the capillaries to the dermis and
subcutaneous tissue. The fibrinogen will form
pericapillary cuffs that obstruct oxygen and nutrition
diffusion, causing tissue necrosis and ulceration.
Fibrin and fibrinogen also have direct effects on type
1 procollagen synthesis by fibroblasts, which will
impede the healing process.11,22
Falanga and Eaglstein proposed a theory on how the
leakage of fibrinogen, α2-macroglobulin and other
macromolecules into the dermis is caused by venous
hypertension or capillary damage, and will cause
failure in the maintenance of tissue integrity and
wound repair, causing ulceration.8
Arterial and venous pressure differences in venous
hypertension causes erythrocyte aggregation and
leukocyte plugging in the capillaries, causing local
tissue ischemia. The release of mediators such as
collagenase, elastase, cytokines, free radicals, and
chemotactic factors will lead to fibrinogen release to
the pericapillary tissue. These acute changes are
reversible when the leg is elevated.20 But none of the
hypotheses has been able to precisely explain
venous ulcers’ pathophysiology.23
Diagnosis
Risk factors for venous ulcers are important to
investigate during history-taking, including lower
extremity swelling which worsens at night and
improves with leg elevation; legs that felt heavy,
itchy, tender; pins and needles sensation; history of
previous thromboembolism; and usage of oral
contraception.24,25
Physical Examination
Venous ulcers are usually found in the gaiter area
(Figure 2), which is the area from the mid-calf to the
ankle, and are generally located around the medial
malleolus compared to the lateral malleolus or other
more proximal areas (Figure 3). Ulcers located
above the mid-calf or on the foot are rarely of venous
origin. Venous ulcers can present as single or
multiple ulcers, can be of various sizes, with irregular
shape. They are usually shallow, rarely extending to
the muscles, fascia, or bone. The ulcer bed may
contain granulation tissue or yellow fibrinous
exudates, while black necrotic tissue is rarely seen.
The region around the ulcer is surrounded by
hyperpigmentation due to hemosiderin deposits. 11
65
Patients with venous disorders can present with
various degrees of skin manifestations, ranging from
edema, lipodermatosclerosis, to venous ulcers.
Lipodermatosclerosis is a chronic process of dermal
and subcutaneous fibrosis caused by venous
insufficiency, where the skin seems hardened and
indurated (Figure 4). In acute lipodermatosclerosis,
the skin is indurated, erythematous, and tender. In
the chronic stages, the skin is hardened and the legs
have an upside-down bottle appearance, where the
proximal leg is swollen while the distal leg is
constricted due to fibrosis and loss of subcutaneous
tissue.5
Physical examination is fundamental in diagnosing
venous ulcers, and in 1994 the American Venous
Forum published a classification for chronic venous
diseases, the CEAP (Clinical, Etiology, Anatomy,
and Physiology) classification.24 CEAP is
recommended in many of the current literature over
other less used classification systems, including the
Venous Clinical Severity Score (VCSS), Venous
Segmental Disease Score (VSDS), and Venous
Disability Score (VDS).24-26 The CEAP classification
utilizes the description of objective clinical findings
(C), etiology (E), anatomy (A) in the form of reflux or
obstruction distribution in the superficial, deep, or
perforating veins, and the underlying
pathophysiology (P) (reflux or obstruction). 27 (Table
1)
In identifying the ulcer, description includes the
ulcer’s location and its size (length, width, and
depth). Taking a photograph of the ulcer with a ruler
will assist ulcer measurement.28,29 The ulcer’s
characteristics, the amount and type of exudate,
appearance of the ulcer bed, signs of infection, smell,
and tenderness should be documented in each
visit.25
Moreover, there are several factors that can impair
venous ulcers healing, which are the ulcers’ size,
duration, ABPI (Ankle Brachial Pressure Index) <0.8,
history of venous surgery, history of hip or knee
replacement surgery, and >50% fibrin content in
ulcers.11
Workup
After taking the patient’s history and a
comprehensive physical examination, further workup
can be performed to make the diagnosis and
determine treatment approach. Examination of the
J Gen Proced Dermatol Venereol Indones. 2017;2(2):64-76
arterial system is also needed to rule out the
presence of concomitant arterial and venous
disorder; almost 25% of patients with venous ulcers
also have arterial disorders.5 Generally, the workup
can be divided into non-invasive and invasive
procedures. The types of ancillary examinations for
detection of chronic venous insufficiency that
underlie venous ulcers include:
1. ABPI (Ankle Brachial Pressure Index) and
TBPI (Toe Brachial Pressure Index)
ABPI is a non-invasive procedure that can be
performed for screening purposes, with a
sensitivity of 85% and specificity of 97% in
detecting arterial occlusion. The ABPI value is
obtained from dividing the doppler pressure of
the ankles with the highest value of brachial
pressure. The normal value for ABPI is 0.9 to 1.3.
Toe Brachial Pressure Index (TBPI) is a non-
invasive procedure to measure the arterial
perfusion of the thumb and soles. The device is
put on the hallux, and the result is divided by the
highest value of brachial systolic pressure. TBPI
is able to identify arterial calcification in patients
with diabetes mellitus and kidney diseases.5,28
2. Handheld continuous wave doppler (CW
doppler)
CW doppler is a non-invasive procedure using
ultrasound technology to measure venous flow.
The reliability of CW doppler is considered low in
detecting obstruction or reflux in the deep veins.
This device is not capable of providing
information on venous morphology, thus it is not
appropriate for investigating anatomical
abnormalities of the vein.25
3. Duplex ultrasound examination (DUS)
DUS is a combination of ultrasound and pulsed
wave Doppler used to investigate the anatomy
and hemodynamics of the venous system. DUS
can show blood flow with color to improve
accuracy. With the availability of DUS, invasive
procedures such as phlebography is rarely
performed. DUS can be considered to be a gold
standard to diagnose chronic venous diseases,
and it can also be used for therapy
evaluation.25,29
4. Plethysmography
Plethysmography provides information on
venous reflux, obstruction, and functions of the
calf muscle pump. The use of plethysmography
is limited due to the scarcity of the device. This
66
 procedure includes strain gauge
plethysmography, photoplethysmograph, air
plethysmography (APG).25,29
5. Phlebography
Radiological examination with contrast can be
classified into ascending phlebography and
descending central phlebography. The use of
phlebography have decreased significantly since
the availability of DUS, due to its similar reliability
to phlebography. Phlebography can provide
additional information on the thrombus’ age,
valve damage, and further information on the
venous system for surgery preparation.5 In cases
of obstruction of pelvic vein insufficiency and
vascular malformation, and the problem of
device availability, phlebography is a preferable
solution.26
6. Other imaging methods
Several other imaging methods include CTV
(Computed Tomography Venography) and MRV
(Magnetic Resonance Venography), which can
provide detailed three-dimensional images of the
venous vessels. This method can be used in
cases of post-thrombotic obstruction and venous
compression or stenosis.25
7. Ulcer biopsy
Biopsy must be obtained from several sides,
including the border and the center of the wound.
26
8. Ulcer microbiology examination
Contamination or colonization of bacteria and
fungi is found in the majority of leg ulcers, but 10-
15% is negative upon examination. The
microorganisms often found in cultures are
Staphylococcus, Streptococci (excluding group
A beta-hemolytic), and Pseudomonas
aeruginosa. Anaerobic bacteria are found in 30%
of cultures, and Candida albicans and other
fungal species are found in 15-30% of
specimens.30 Several studies recommend
against routine microbial culture unless an
indication is present. Indications include signs of
infection such as erysipelas, increasing pain,
increasing ulcer size, redness around the ulcer,
and purulent exudate.31
9. Blood workup
Blood workup commonly performed are blood
glucose to rule out diabetes mellitus, hemoglobin
level to rule out hematological disorders, albumin
J Gen Proced Dermatol Venereol Indones. 2017;2(2):64-76
and transferrin to rule out nutritional deficiency,
and reactive C protein. Reactive C protein can
be detected in 25% of patients with venous
ulcers and in 50% of patients with recurrent
venous thrombosis. Patients with chronic and
recurrent venous ulcers can often be associated
with thrombophilia.29
10. Ultrasonography (USG) to detect cutaneous
changes in chronic venous diseases
USG is not only used to determine the location
and form of venous disorders, but also to identify
acute and chronic disturbances that are not
clearly visible. Cutaneous USG can contribute to
the determination of venous disorders’ degree of
severity. The disadvantage of this examination is
that it is operator-dependent.32
Differential Diagnosis
Several differential diagnosis that can be considered
when a patient presents with leg ulcers include: 7
1. Arterial ulcers (Figure 5)
Arterial insufficiency is caused by
atherosclerosis and is worsened by smoking and
hypertension, which can cause tissue necrosis.
Arterial ulcers are mainly found on the hallux and
heel. On examination, whitish or blueish, shiny
punched out lesions are observed. Patients
usually complain of pain at night when lying on
the bed or at rest and when the legs are elevated.
The pain decreases when the patients’ feet steps
on the ground, due to increasing blood flow.
2. Diabetic ulcers (Figure 6)
Diabetic ulcers are found in diabetic patients with
uncontrolled blood glucose levels, due to a
combination of arterial disorders, neural
damage, commonly found on pressure points
such as the halux and heels. Early lesions can
present as callous as a response to repeated
trauma, which will progress to ulceration. The
characteristic form is a punched-out lesion,
similar to arterial ulcers. Charcot joints, which are
swollen joints due to repeated trauma in areas
with neuropathy, are often found at the same
time as diabetic ulcers.
3. Neuropathic ulcers (Figure 7)
Neuropathic ulcers that are unrelated to diabetes
can happen due to infections of the nervous
system such as leprosy and Bechet disease. If a
non-diabetic patient presents with ulcers similar
67
 to diabetic ulcers in appearance, the underlying
process must be investigated.
4. Pyoderma gangrenosum (PG) (Figure 12)
PG is rare, with an incidence of 1:100,000. The
patient’s chief complaint is chronic, painful
wound. There are four clinical variants:
ulcerative, bullous, pustular, and superficial
granulomatous. The cause of PG is generally
unknown, but 45-75% of the cases are related to
systemic diseases including bowel diseases,
myeloproliferative disorders, and rheumatoid
arthritis. PG ulcers usually have purulent ulcer
beds, centrifugal with irregular border, dark blue
to greyish brown in color. The healed ulcer
usually leaves a cribriform, atrophic, and
pigmented scar. Ulceration in PG can happen
after cutaneous trauma or damage, and this
phenomenon is known as pathergy.
Other differential diagnoses include vasculitis,
panniculitis with ulceration, calciphylaxis, marjolin
Table 1. CEAP (Clinical, Etiology, Anatomy, and Physiology) classification in chronic venous disease 5
Clinical classification (C) Etiologic
classification (E)
C0: No visible or palpable Ec: Congenital
signs of venous disease
C1: Teleangiectasis or reticular Ep: Primary
veins
C2: Varicose veins Es: Secondary
C3: Edema En: No venous cause
identified
C4a: Pigmentation or eczema
C4b: Lipodermatosclerosis or atrophie blanche
C5: Healed venous ulcer
C6: Active venous ulcer
S: Symptomatic, including ache, pain, tightness, skin irritation, heaviness, and muscle cramps, and other
complaints attributable to venous dysfunction.
A: Asymptomatic
2. Wound dressing
There are no single dressing that can be used in all
stages of the ulcer, because each dressing has its
own specification for different stages of wound
healing.34 Novel dressings have different mode of
action from traditional ones. They provide wound
protection, whilst traditional dressings maintain
wound dryness.35 Novel dressings for venous ulcers
J Gen Proced Dermatol Venereol Indones. 2017;2(2):64-76
ulcer, bacterial infections, martorell ulcers, or
Hypertensive Ischemic Leg Ulcer (HYIL), and
malignant wound (Figure 8-11).33 In ulcers with slow
healing rate, allergic contact dermatitis should be
considered.26
Treatment
1. Wound cleansing
Ulcer treatment is initiated with wound cleansing. 19
Wound cleansing has three components, which are
technique, solution, and equipment. Cleansing
techniques consist of swabbing, irrigation, and
bathing. Swabbing is rubbing with wet gauze to
discard dead tissue and contaminants. Irrigation
includes spraying the wound with 0.9% normal saline
using 18 or 19G needle with a 30-35 ml syringe or a
spraying device, with 4-15 psi pressure. Bathing is
bathing the wounded leg, included in hydrotherapy.
Other than normal saline, water and antiseptic
solutions can be used as cleansing solutions.16
Anatomic Pathophysiology (P)
classification (A)
As: Superficial Pr: Reflux
veins
Ap: Perforating Po: Obstruction
veins
Ad: Deep veins Pr, o: Reflux and obstruction
An: No venous Pn: No venous
location pathophysiology identified
identified
do not only ensure a moist wound environment, but
also avoid maceration, because excessive moisture
will facilitate production of toxic mediators.
Traditional dressings using gauze dampened with
normal saline or ringer solution usually cause
problems when the gauze has dried up, because the
gauze will stick to the wound.36
68
 Table 2. Recommendation and clinical evaluation of venous ulcer work-up24

No. Recommendation Clinical

evaluation
1. ABPI (Ankle Brachial Pressure Index) dan TBPI (Toe Brachial Pressure Index)
Arterial examination and ABPI measurement are recommended to be performed on all 1B
venous ulcers patients
2. Duplex ultrasound examination (DUS)
Comprehensive DUS examination of the lower extremity is recommended for all patients 1B
with suspected venous leg ulcers.
3. Plethysmography
Selective use of venous plethysmography is suggested in the evaluation of patients with 2B
suspected venous leg ulcer if venous DUS does not provide definitive diagnostic
information.
4. Other venous imaging
Other types of venous imaging can be suggested for operative planning before open or 2C
endovenous interventions such as computed tomography venography, magnetic
resonance venography, contrast venography and intravascular ultrasound
5. Ulcer biopsy
Ulcer biopsy is recommended for leg ulcers that do not improve with standard therapy and 1C
post-therapeutic compression for 4-6 weeks, and atypical ulcers
6. Ulcer microbiology work-up
Routine venous ulcer culture is not recommended. Culture is only performed after clinical 2C
evidence of infection.
7. Blood work-up
Perform blood laboratory work-up investigating thrombophilia in patients with history of 2C
recurrent venous thrombosis and chronic venous ulcers

The factors considered in choosing the 3. Compression therapy

appropriate dressing include wound depth,
amount of exudate, wound characteristics, cost,
dressing change frequency, and the need for
secondary dressing. The ideal dressing is a
dressing that can maintain moisture, discard
excessive exudate, facilitate debridement,
enable gas exchange, minimize scar formation,
impermeable to bacteria, non-toxic, and
comfortable for the patient.37
The types of dressing available on the markets
are semi-permeable film, foams, alginates,
hydrocolloids, hydrogels, and hydroactive. Semi-
permeable film is used for ulcers with
epithelialization, foams are used for exudative
wounds, alginates are used for bleeding wounds,
hydrocolloids are used for wounds with
hypogranulation, hydrogels are used for necrotic
wounds, and hydroactive functions similarly to
foams for exudative wounds. Hydrophobic
dressings can be used for trapping bacteria in
infectious wounds.38-42
Compression therapy is a preferred therapeutic
approach in venous ulcers, which aims to
accelerate venous ulcer healing by improving
blood flow and reducing edema and distension. 43
Types of compression can be divided into static
and dynamic compression.26 Compression
techniques include bandage, stocking or socks,
and using intermittent compression devices.
Bandages can be classified as elastic (long
stretch) and inelastic (short stretch). The elastic
bandage can be stretched out to 100-200% of its
original size, while the inelastic type can only be
stretched 40-99%. Elastic bandages can
conform to the leg’s size and shape, while
inelastic bandage is more rigid and can hold the
expansion of calf muscles during contraction, but
does not press down on the calf when the limbs
are in supine position.44 The Unna boot is a type
of bandage with a zinc oxide lining, a type of
inelastic bandage.45 Inelastic bandages are
recommended for ulcers of mixed arterial-
venous origins.44

J Gen Proced Dermatol Venereol Indones. 2017;2(2):64-76 69

 Table 3. Stocking classification44
Ankle
Class pressure Indication
(mmHg)
I 20-30 Mild edema, varicose
veins, and venous ulcers
II 30-40 Moderate edema,
moderate venous
disorders, varicose veins,
and venous ulcers
III 40-50 Severe edema, severe
venous disorders, venous
ulcers, and lymphedema
IV 50-60 Lymphedema
Based on the number of bandage layers,
bandage usage can be divided into 1 layer, 2
layers, 3 layers, and 4 layers, then simplified into
simple component and multi component; the 4-
layers bandage is known as 4LB.27 4LB provides
consistent pressure of 40 mmHg even at rest.43
4LB is proven to be safe and effective in ulcer
recovery with minimal complications, while also
reducing symptoms and accelerating healing, so
the patient can go back to their daily activities. 46
Compression is proven to significantly increase
healing rate and improve psychosocial
complaints, compared to no compression. 47
Stocking or socks, also including leggings, are
also part of compression therapy. Stocking is
mostly used as maintenance therapy after the
venous ulcers have healed. Stocking use
improves QALys (Quality Adjusted Life-years)
because some patients choose stockings due to
more affordable cost and better comfort
compared to bandages. Stockings consist of
knee-high stockings, calf-high stockings, and
waist-high stockings; knee-high stockings are
most commonly used due to the comfort.27
Incorrect compression can cause disorders such
as distal gangrenes and predominant arterial
diseases.44 Adequate movement of the ankles
must be preserved. Patients need to be informed
to monitor signs of poor perfusion such as
numbness, pins and needles, changes in skin
color, worsening pain, or paresthesia.33
Intermittent Pneumatic Compression (IPC)
produces sequential pressure to the limbs, so it
can be used simultaneously with bandages and
J Gen Proced Dermatol Venereol Indones. 2017;2(2):64-76
stockings. IPC is usually used for immobilized
patients to prevent edema of the lower
extremities.44 IPC is proven to speed up the
healing process compared to no compression.48
4. Medications
a. Pentoxifylline improves healing of venous
ulcers, especially ulcers older than one year
old. Pentoxifylline is a methylxanthin
derivate with good oral absorption rate,
metabolized in the liver before being
excreted through the urine.45 Pentoxifylline is
an inhibitor of prostaglandin E, and can
reduce elastase levels.33 The recommended
dose is 400 mg three times a day, with dose
adjustments for patients with kidney failure.
Several studies reported 800 mg three times
a day is more effective compared to 400 mg.
The maximum effect can be observed after
2-4 months. A few of pentoxifylline’s
mechanisms of action include increasing
erythrocite deformability and inhibition of
neutophil adhesion and activation. Side
effects of pentoxifylline are nausea,
abdominal discomfort, dizziness, and
prolonged bleeding time.44 Pentoxifylline is
an effective adjuvant ineiodinfor
compression therapy in venous ulcers.50
b. Sulodexide is an antithrombotic and
fibrinolytic agent, used for vascular disorders
including venous ulcers. Sulodexide acts as
a vascular protective and anti-inflammatory
agent, making it appropriate as an adjuvant
therapy for venous ulcers44, although the
body of evidence supporting this is still weak
and further studies are needed.51
c. Simvastatin, aside from being used to
reduce cholesterol levels, have pleiotropic
effects which can assist wound healing. A 40
mg dose once a day is proven to significantly
accelerate wound healing.52
d. Aspirin is used to reduce pain, fever, and
inflammatory processes, and preventing
blood clot formation. Aspirin cuts wound
healing duration and lower the recurrence
rate of venous ulcers.53 A once daily dose of
300 mg aspirin combined with compression
therapy show clinical improvement and
reduction of ulcer size. Aspirin therapy is
administered if no contraindications are
present.45
e. Flavonoid can be synthesized and is found
in cocoa, tea, and red grape plants. 33
Flavonoids accelerate venous ulcers healing
70
 by reducing edema thus improving venous
pressure, assisting lymphatic drainage, and
protecting microcirculation. But, flavonoid
therapy’s efficacy needs further
investigation.54 Inflammation response and
symptoms of chronic venous disorders will
be diminished after consumption of 500 mg
of flavonoid taken twice a day for 6 months.44
f. Systemic antibiotic is not given routinely in
patients with venous ulcers.55 Antibiotics are
administered if there are signs of infection in
clinical or laboratory examinations.
Antibiotics are given if >106 bacteria per
gram of tissue are found, because the toxin
from the bacteria can cause tissue damage
and impede wound healing in superficial
wounds. Several topical antimicrobial
alternatives are available, such as ionized
silversulfadiazine (SSD) and cadexomer
iodine.44 Evidence of SSD use in venous
ulcers is limited.56 Cadexomer iodine is a
topical antiseptic with anti-microbial
properties, which is safe and effective for
wound debridement and for stimulating
granulation tissue.8,55 Iodine is proven to be
as effective as other antiseptics and does not
disturb the wound healing process.57
g. Honey has been used for years to speed up
the wound healing process.58 Honey has
antimicrobial effects and it stimulates cell
growth. Studies report that honey can
decrease wound size, pain, and foul smell
after 12 weeks of use.59 In venous ulcer
management, the use of honey is still
controversial, due to the wide variety of
honey used in studies.58
5. Surgical therapy
a. Debridement
Debridement is recommended to be
performed during the initial assessment to
discard of necrotic tissue. Most of the
patients receiving debridement procedure
experience improvement in wound healing
compared to patients who were not
debrided.24 The evidence is not conclusive
on whether the frequency of debridement
J Gen Proced Dermatol Venereol Indones. 2017;2(2):64-76
significantly affects wound healing.60 Local,
usually topical, anesthesia can be
administered to reduce discomfort during the
debridement process. Use of EMLA 5%
cream (lidocaine-prilocaine) is proven to
significantly reduce pain score compared to
no topical anesthetic agents.61 Infiltrative
anesthesia, regional block, or general
anesthesia should be used for extensive
debridement. Several types of debridement
can be used, such as sharp debridement,
enzimatic debridement, mechanical
debridement, biological debridement, and
autolytic debridement.62
b. Skin grafting
Skin grafting is a procedure of taking skin of
various thickness to be relocated, in order to
induce new blood circulation in the new
location.63 Skin grafting is proven to reduce
pain intensity compared to conservative
therapy.64 Skin grafting can be classified as
punch graft and split thickness graft, and
both are proven effective for treating venous
ulcers.44 Skin grafts can be divided into
autograft or allograft, according to the donor.
Based on the type of the synthesized skin, it
can be divided into single layer or bilayer. 19
When used with compression therapy,
bilayer artificial skin is more effective than
single layer.63
c. Surgery for venous insufficiency
Invasive procedures such as venous
stripping have been replaced by less
invasive percutaneous surgery procedures,
such as ultrasound guided foam
sclerotherapy, endovascular laser ablation
(EVA), and radiofrequency therapy.
Recalcitrant venous ulcers can be managed
through compression of the iliac vein or the
vena cava.44 Venous stripping is a procedure
done under local or general anesthesia to
remove the whole length of the vein. 65 EVA
is a minimally-invasive procedure, with
similar efficacy and safety to venous
stripping.44
71
 24
Table 4. Treatment recommendation and clinical evaluation

No. Recommendation Clinical

evaluation
1. Wound cleaning
Venous ulcers are recommended to be cleansed initially and at each dressing change with a 2C
neutral, nonirritating, nontoxic solution, with minimal chemical or mechanical trauma.
2. Wound dressing
 The recommended dressings are dressings that will manage exudate and maintain 2C
moisture.
 Topical antimicrobial-containing dressings are not recommended for treating non-infected 2A
venous leg ulcers.
3. Compression therapy
 Compression therapy is recommended to increase the healing rate of venous leg ulcers. 1A
 Multicomponent compression bandage is recommended over single component bandages 2B
for the treatment of venous leg ulcers.
 In venous leg ulcers with underlying arterial disease, compression therapy is not 2C
recommended if the ABPI is 0.5 or less, or if the absolute ankle pressure is less than 60
mmHg.
 Intermittent pneumatic compression is recommended if other compression therapy is 2C
unavailable, cannot be used, or have failed in treating venous ulcers after prolonged
compression therapy.
4. Mechanical therapy – negative pressure
Negative pressure therapy is not recommended for routine treatment of venous ulcers. 2C
5. Debridement
 Debridement is recommended during initial evaluation to remove necrotic tissue, 1B
excessive bacterial burden, and cellular burden of dead and senescent cells.
 Additional debridement can be performed to maintain optimal skin condition for healing. 2C
 Enzymatic debridement is preferred if no trained clinician is available to perform surgical
debridement. 2C
Skin grafting
 Split-thickness skin grafting is not recommended as a main therapy for venous ulcers.
 Split-thickness skin grafting with compression is recommended for extensive venous 2B
ulcers that do not improve after 4-6 weeks of standard therapy. 2B
7. Larval therapy
Larval therapy can be performed as an alternative to surgical debridement. 2B
8. Physiotherapy and extremity elevation
 Electrical stimulation therapy is not recommended in venous ulcers. 2C
 Active exercise under supervision is recommended to improve muscle pump function and 2B
to reduce pain and edema in patients with venous leg ulcers.
9. Nutrition management Best
Nutririon management is recommended for malnourished patients with venous ulcers. practice
10. Prevention
 Compression therapy is recommended to prevent recurrency of venous ulcers. 2B
 Patients with clinical CEAP (Clinical, Etiology, Anatomy, and Physiology) C3-4 disease
due to primary valvular reflux are recommended to receive 20-30 mmHg knee or thigh 2C
high compression.

J Gen Proced Dermatol Venereol Indones. 2017;2(2):64-76 72

6. Larval therapy
With the rise of microbial resistance, MDT
(Maggot Debridement Therapy) is starting to be
considered as an alternative therapy for chronic
wounds and ulcers. MDT is indicated for open
wounds and ulcerations with or without signs of
infection. MDT usually utilizes live and sterile
larvae, such as the green bottle fly (Phaenicia
(Lucilia) sericata).66 Meta-analysis have reported
MDT to be more effective and efficient for wound
healing, granulation tissue formation, and
chronic ulcers debridement compared to
conventional therapy.67 MDT works through
induction and enhancement of IL-6,
carboxypeptidase, leucine aminopeptidase,
collagenase, serine protease, and epidermal
growth factors.68-69 Optimal duration for MDT is
2-3 larvae cycles or 3-5 days, and there is no
benefits of prolonging therapy for more than a
week.70 Severao reported complications of MDT
include pain, mild fecer, and larvaes getting
loose from the dressing.71
7. Physiotherapy and limb elevation
Physiotherapy aims to reduce venous pressure
and edema, resulting in venous ulcers
improvement.72-73 Symptoms experienced by
patients with venous ulcers include limited range
of motion (ROM) of the ankles, and reduction of
walking speed and endurance, mobility, and
activity level.74 Vascular physiotherapy for
chronic venous disorders is called vascular
kinesiotherapy, consisting of three phases: warm
up, training, and relaxation. This exercise is
performed three times a week for one hour.
Evaluation of wound diameter, venous functions,
and gait is performed in various periods, ranging
from 6 weeks to 6 months.21 In addition to
physical therapy, other techniques are available
such as HVS (High Voltage Stimulation), LLLT
(Low Level Laser Therapy) and ultrasound
therapy.7 HVS and ultrasound can be used as an
adjuvant therapy for small venous ulcers, but are
not effective for recurrent cases.75-76 LLLT is not
efficient for venous ulcer management. 77
Limb elevation is performed by raising the limb
above the heart, to reduce swelling, improve
microcirculation and oxygen distribution, and
accelerate ulcer healing.27 Elevation should be
done 3-4 times a day for 30 minutes or 1-2 hours
twice a day.45 Limb elevation is not beneficial in
severe venous disorders.27
J Gen Proced Dermatol Venereol Indones. 2017;2(2):64-76
8. Nutritional management
Patients with venous ulcers have higher
metabolism rate due to the systemic
inflammation and increased cellular activity on
the wound, thus needing larger nutritional intake
to assist wound healing. Vitamin C, zinc, protein,
and amino acids are important nutrients for
wound healing. Vitamin C is important for
synthesizing connective tissue; inadequate
vitamin C intake causes weakness of the fibrous
tissue and increases risk of wound dehiscence.
Zinc plays a role in tissue regeneration and
collagen formation, because zinc facilitates
synthesis of DNA and RNA. Amino acids are
important for tissue regeneration and systemic
immunity. Polyunsaturated Fatty Acids (PUFA)
manipulation through diet is an effective method
to reduce inflammation and accelerate healing of
venous ulcers.78
9. Prevention
Venous ulcer prevention can be done by using
stockings, superficial or perforating vein surgery,
sclerotherapy, aside from exercise, limb
elevation, and lifestyle changes.79 High
compression hosiery is more effective in
reducing recurrence compared to no
compression.80 Stocking is recommended to be
worn throughout the day, everyday, for maximum
efficacy. The use of moisturizers, diet,
supplements, smoking cessation, weight loss are
important in patients with a history of venous
ulcers.79 Furthermore, the patient and their family
members need to be informed on the disease,
recurrence rate, factors that help and disrupt
wound healing, and the efficacy and side effects
of the current treatment choice. Education can
be given through various media, such as leaflets,
TV, computer, or person-to-person education.81
Conclusion
Several therapeutic choices are available for patients
with venous ulcers. Choice of therapy can depend on
various factors, such as the patients’ unique clinical
conditions, socioeconomic factors, family support,
and patients’ choices. Collaboration between the
physician and the patient is an important key to
therapeutic success and long-term recurrency
prevention.
73
References
1. Survei Demografi dan Kesehatan Indonesia
2012. Badan Pusat Statistik. [cited September
2017 ] Available from: http://chnrl.org/pelatihan-
demografi/SDKI-2012.pdf.
2. Data BPS angka harapan hidup 2010-2014.
Badan Pusat Statistik. [cited September 2017 ]
Available from:
https://www.bps.go.id/linkTableDinamis/view/id/
1114.
3. Proyeksi penduduk Indonesia 2010-2035.
Badan Perencanaan Pembangunan Nasional.
[cited September 2017] Available from:
http://www.bappenas.go.id/files/5413/9148/410
9/Proyeksi_Penduduk_Indonesia_2010-
2035.pdf.
4. Margolis DJ, Bilker W, Santanna J, Baumgarten
M. Venous leg ulcer: Incidence and prevalence
in the elderly. J Am Acad Dermatol.
2002;46(3):381-5.
5. Alavi A, et al. What’s new: Management of
venous leg ulcers Approach to venous leg ulcers.
J Am Acad Dermatol. 2016;74:627-40.
6. Sularsito SA. Ulkus kruris. In: Ilmu Penyakit Kulit
dan Kelamin Edisi 7, cetakan pertama. Badan
Penerbit Fakultas Kedokteran Universitas
Indonesia. 2015;2:279-87.
7. Scheinfeld NS. Skin disorders in older adults:
Cutaneous ulcers, Part 1. Consultant. 2011;565-
72.
8. Valencia IC, Falabella A, Kirsner RS, Eaglstein
WH. Chronic venous insufficiency and venous
leg ulceration. J Am Acad Dermatol.
2001;44(3):401-17.
9. Davis MDP. Leg Ulcerations. In: Dermatological
Signs of Internal Disease Edisi 4. Elsevier.
2009;40:381-400.
10. Omar MH. Common skin disorders in the elderly.
SA Fam Pract. 2006;48(5):29-34.
11. Etufugh CN, Phillips TJ. Venous ulcers. Clin
Dermatol. 2007; 25:121-30.
12. Theodosatos A. Common Vascular Disorders in
the Elderly. In: Norman RA. Diagnosis of Aging
Skin Disease. 18th ed. 2008.p.225-31.
13. Domingues EAR, et al. Pain prevalence, socio-
demographic and clinical features in patients
with ulcers. J Tissue Viability. 2016;25(3):180-4.
14. Green J, Jester R, McKinley R, Pooler A. The
impact of chronic venous leg ulcers: a systematic
review. J Wound Care. 2014;23(12):601-12.
15. Salome GM, Blanes L, Ferreira LM. Evaluation
of depressive symptoms in patients with venous
ulcers. Rev Bras Cir Plast. 2012;27(1):124-9.
J Gen Proced Dermatol Venereol Indones. 2017;2(2):64-76
16. McLain NEM, Moore ZEH. Wound cleansing for
treating venous leg ulcers. Cochrane Database of
Syst Rev. 2015;4:1-11.
17. Lal BK. Venous ulcers of the lower extremity:
Definition, epidemiology and economic and
social burdens. Semin Vasc Surg. 2015;28:3-5.
18. Herber OR, Schnepp W, Rieger MA. A
systematic review on the impact of leg ulceration
on patients’ quality of life. Health and Qual Life
Outcomes. 2007;5:44:1-12.
19. Scottish Intercollegiate Guidelines Network.
Management of chronic venous leg ulcers. A
National clinical guideline. SIGN; 2010.
20. Gonsalves CF. Venous leg ulcer. Tech Vasc
Interv Radiol. 2003;6(3):132-6.
21. Leal FJ, Couto RC, da Silva TP, Tenorio VO.
Vascular physiotherapy in treatment of chronic
venous disease. J Vasc Bras. 2015;14(3):22430.
22. Agale SV. Chronic Leg Ulcers: Epidemiology,
Aetiopathogenesis, and Management. Ulcers.
2013.
23. Liu YC, Margolis DJ, Isseroff RR. Does
Inflammation Have a Role in the Pathogenesis of
Venous Ulcers? A Critical Review of the
Evidence. J Invest Dermatol. 2011;131:818-27.
24. O’Donnell TF Jr, et al. Management of venous
leg ulcers: Clinical practice guidelines of the
Society for Vascular Surgery® and the American
Venous Forum. J Vasc Surg. 2014;60:2S-47S.
25. Wittens C, et al. Editor’s choice – Management
of Chronic Venous Disease. Eur J Vasc
Endovasc Surg. 2015;9:678-737.
26. Neumann M, et al. Evidence based (S3)
Guidelines for diagnostics and treatment of
venous leg ulcers. European Dermatology
Forum. 2014.
27. Kelechi, Teresa J, et al. Chronic venous disease
and venous leg ulcers: An evidence-based
update. J Vasc Nurs. 2015;33(2):36-46.
28. Vasudevan B. Venous leg ulcers:
Pathophysiology and Classification. Indian
Dermatol Online J. 2014;5(3):366-70.
29. Sreedharan S. Management of venous leg ulcers
in general practice – a practical guideline.
Australian Family Physician. 2014; 43(9):1-5.
30. Pugliese DJ. Infection in Venous Leg Ulcers:
Considerations for Optimal Management in the
Elderly. Drugs Aging. 2016;33:87-96.
31. McNulty C. Venous leg ulcers: infection
diagnosis and microbiological investigation.
Public Health England. 2016. p. 1-16.
74
32. Caggiati A. Ultrasonography of Skin Changes in
Legs with Chronic Venous Disease. Eur J Vasc
Endovasc Surg. 2016;52:534-42.
33. Woo KY, Alavi A, Evans R, Despatis M, Allen J.
New Advances in Compression Therapy for
Venous Leg Ulcers. Surg Technol Int.
2013;23:61-8.
34. Weller C, Sussman G. Wound Dressings
Update. J Pharm Pract Res. 2006;36:318-24.
35. O’Donnell TF, Lau J. A systematic review of
randomized controlled trials of wound dressing
for chronic venous ulcer. J Vasc Surg.
2006;44:1118-25.
36. Hartmann P. Phase-specific wound
management of venous leg ulcer. Hartmann
Medical Edition. 2008.
37. Vowden K, Vowden P. Wound dressing:
principles and practice. Surgery.
2017;35(9):489-94.
38. Rucigaj TP. How to choose the proper dressing
in venous leg ulcers care. Reviews in Vascular
Medicine. 2014;2:58-61.
39. Ribeiro CTD, Dias FAL, Fregonezi GAF. Hydrogel
dressings for venous leg ulcers. Cochrane
Database of Syst Rev. 2013;9:1-15.
40. Ribeiro CTD, Fregonezi GAF, Resqueti VR,
Dornelas de Andrade A, Dias FAL. Hydrocolloid
dressings for healing venous leg ulcers. Cochrane
Database of Syst Rev. 2014;1:1-14.
41. O'Meara S, Martyn-St James M, Adderley UJ.
Alginate dressings for venous leg ulcers. Cochrane
Database of Syst Rev. 2015;8:1-75.
42. O'Meara S, Martyn-St James M. Foam dressings
for venous leg ulcers. Cochrane Database of Syst
Rev. 2013;5:1-113.
43. Kramer SA. Compression wraps for venous ulcer
healing: A review. J Vasc Nurs. 1999;17(4):89-
97.
44. Alavi A, et al. What’s new: Management of
venous leg ulcers Treating venous leg ulcers. J
Am Acad Dermatol 2016;74:643-64.
45. Collins L, Seraj S. Diagnosis and Treatment of
Venous Ulcers. Am Fam Physician.
2010;81(8):989-96,1003.
46. Kota AA, Selvaraj AD, Premkumar P, Ponraj S,
Agarwal S. Four layer dressing in the
management of chronic venous ulcers in the
outpatient setting of a tertiary hospital in India.
Wound Medicine. 2014;5:21-4.
47. So WKW et al. Effect of compression bandaging
on wound healing and psychosocial outcomes in
older people with venous ulcers: a randomized
controlled trial. Hong Kong Med J. 2014;20:S40-
1.
J Gen Proced Dermatol Venereol Indones. 2017;2(2):64-76
48. Nelson E, Hillman A, Thomas K. Intermittent
pneumatic compression for treating venous leg
ulcers. Cochrane Database of Syst Rev. 2014;5:1-
39.
49. Dumville JC, Land L, Evans D, Peinemann F.
Negative pressure wound therapy for treating leg
ulcers. Cochrane Database of Syst
Rev. 2015;7:1-37.
50. Jull AB, Arroll B, Parag V, Waters
J. Pentoxifylline for treating venous leg
ulcers. Cochrane Database of Syst
Rev. 2012;12:CD001733.
51. Wu B, Lu J, Yang M, Xu T. Sulodexide for treating
venous leg ulcers. Cochrane Database of Syst Rev.
2016;6:1-36.
52. Evangelista MTP, Casintahan MFA, Villafuerte
LL. Simvastatin as a novel therapeutic agent for
venous ulcers: A randomized, double blind,
placebo-controlled trial. Br J Dermatol.
2014;170:1151-7.
53. de Oliveira Carvalho P, Magolbo NG, De Aquino
RF, Weller CD. Oral aspirin for treating venous leg
ulcers. Cochrane Database of Syst Rev. 2016;2:1-
29.
54. Scallon C, Bell-Syer SEM, Aziz Z. Flavonoids for
treating venous leg ulcers. Cochrane Database
of Syst Rev. 2013;5:1-38.
55. O'Meara S, Al-Kurdi D, Ologun Y, Ovington LG,
Martyn-St James M, Richardson R. Antibiotics and
antiseptics for venous leg ulcers. Cochrane
Database of Syst Rev. 2014;1:1-188.
56. Miller Ac, Rashid RM, Falzon L, Elamin EM,
Zethtabchi S. Silver sulfadiazine for the
treatment of partial-thickness burns and venous
stasis ulcers. J Am Acad Dermatol. 2012;66:
159-65.
57. Vermeulen H, Westerbos SJ, Ubbink DT. Benefit
and harm of iodine in wound care: a systematic
review. J Hosp Infect. 2010;76:191-9.
58. Jull AB, Cullum N, Dumville JC, Westby MJ,
Deshpande S, Walker N. Honey as a topical
treatment for wounds. Cochrane Database of Syst
Rev. 2015;3:1-126.
59. Holland LC, Norris JM. Medical grade honey in
the management of chronic venous leg ulcers.
Int J Surg. 2015;20:17-20.
60. Gethin G, Cowman S, Kolbach DN. Debridement
for venous leg ulcers. Cochrane Database of Syst
Rev. 2015;9:1-62.
61. Briggs M, Nelson EA, Martyn-St James M. Topical
agents or dressings for pain in venous leg ulcers.
Cochrane Database of Syst Rev.
2012;11:CD001177.
75
62. Angel D, et al. Australian and New Zealand
Clinical Practice Guideline for Prevention and
Management of Venous Leg Ulcers. Australian
Wound Management Association Inc. and the
New Zealand Wound Care Society Inc. 2011.
p.1-132.
63. Jones JE, Nelson EA, Al-Hity A. Skin grafting for
venous leg ulcers. Cochrane Database of Syst
Rev. 2013;1:CD001737.
64. Salome GM, de Almeida SA, Ferreira LM.
Evaluation of pain in patients with venous ulcers
after skin grafting. J Tissue Viability.
2014;23:115-20.
65. Franks, P., Barker, J., Collier, M. et al.
Management of patients with venous leg ulcer:
Challenges and current best practice. J Wound
Care. 2016;25:1–67.
66. Ruiz JC et al. Clinical Practice Guideline for the
Treatment of Acute and Chronic Wounds with
Maggot Therapy. Mexican Association for
Wound Care and Healing. 2010. p.1-43.
67. Mudge E, Price P, Neal W, Harding KG. A
randomized controlled trial of larval therapy for
the debridement of leg ulcers: Results of a
multicenter, randomized, controlled, open,
observer blind, parallel group study. Wound Rep
Reg. 2014;22:43-51.
68. Wilasrusmee C, et al. Maggot therapy for chronic
ulcer: A retrospective cohort and a meta-
analysis. Asian J Surg. 2014;37:138-47.
69. Linger, et al. Towards next generation maggot
debridement therapy: Transgenic Lucilia sericata
larvae that produce and secrete a human growth
factor. BMC Biotechnology. 2016;16:30.
70. Opletalova K, et al. Maggot Therapy for Wound
Debridement. Arch Dermatol. 2012;148(4):432-
8.
71. Sun X, et al. A systematic review of maggot
debridement therapy for chronically infected
wounds and ulcers. Int J Infect Dis. 2014;25:32-
7.
J Gen Proced Dermatol Venereol Indones. 2017;2(2):64-76
72. Yim E, et al. Effect of Physical Therapy on
Wound Healing and quality of Live in Patients
with Venous Leg Ulcers a Systematic Review.
JAMA Dermatol. 2015;151(3):320-7.
73. Roaldsen KS, Biguet G, Elfving B. Physical
activity in patients with venous leg ulcers -
between engagement and avoidance. A patient
perspective. Clin Rehabil. 2011;25:275–86.
74. O’Brien et al. Testing the effectiveness of a self-
efficacy based exercise intervention for adults
with venous leg ulcers: Protocol of a randomised
controlled trial. BMC Dermatology. 2014;14:16.
75. Taradaj J, et al. Early and long-term results of
physical methods in the treatment of venous leg
ulcers: Randomized controlled trial. Phlebology.
2011;26:237–45.
76. Ezzeldin N, Said D, Ashour MM, EL-leboudy M.
Efficiency of therapeutic ultrasound, low-level
laser and compression therapy for healing of
venous leg ulcers. Egypt Rheumatol Rehabil.
2015;42:27-33.
77. Taradaj J, et al. Physical Therapy in the
Treatment of Venous Leg Ulcers: Biophysical
Mechanisms. Wounds. 2012;24(5):138–45.
78. Kemmner K. Nutritional Intake Pattern of
Patients with Chronic Venous Leg Ulcers. Ohio
State University Collage of Nursing. 2014; 1-36.
79. Shenoy MM. Prevention of venous leg ulcer
recurrence. Indian Dermatol Online J.
2014;5(3):386-89.
80. Nelson EA, Bell-Syer SEM. Compression for
preventing recurrence of venous
ulcers. Cochrane Database of Syst Rev.
2012;8:1-27.
81. Shanley E, Moore ZEH. Patient education for
preventing venous leg ulceration. Cochrane
Database of Syst Rev. 2015;5:1-13.
76