practice

Understanding the underlying

causes of chronic leg ulceration
Leg ulcers are debilitating and have a significant negative impact on patients’

quality of life. It is particularly important to understand the underlying causes of

leg ulcers that are described as ‘slow to heal’ to ensure they are managed effectively
leg ulcers; venous incompetence; arterial insufficiency; diabetes

L
eg ulcers affect 1–2% of the adult popula- urements. The latter identify and quantify the pres- M. Clarke Moloney,
RN, HDip (Specialist
tion of the UK and Ireland.1-3 Prevalence is ence and severity of arterial disease,13 which must be
Nursing),Vascular
greater in women aged over 70 years3 as ruled out before applying compression bandaging.14 Research Assistant;
increasing age is associated with delayed Compression on a leg with a compromised arterial P. Grace, MCh, FRCS(1),
cellular migration, proliferation, meta- blood supply caused by arterial disease will further Consultant Vascular
Surgeon and Professor of
bolic response and matrix biosynthetic response.4,5 reduce arterial blood supply to the limb, which can Surgical Science,
A chronic ulcer can be defined as an open wound lead to severe tissue necrosis.14 University of Limerick;
of full-thickness depth that has no source of An ABPI greater than 1.0 usually indicates the both at Department of
Vascular Surgery, Mid-
re-epithelialisation left in the centre and is slow to absence of arterial disease. It is normally consid- Western Regional
heal.6 A wound described as ‘slow to heal’ has ered safe to apply compression bandaging on Hospital, Dooradoyle,
usually been present for more than four weeks.6,7 patients with an ABPI of ≥0.8 without compromis- Ireland.
The main causes of lower leg ulceration are: ing their arterial blood supply.15,16 However, a value Email:mclarkemoloney@
mwhb.ie
● Venous incompetence less than 0.92 indicates some degree of arterial dis-
● Arterial insufficiency ease. If a patient finds high compression intolera-
● Diabetes ble, their arterial disease may be greater than
● A combination of the above.3,8 indicated by the ABPI.13 References
Successful treatment of leg ulcers depends on an 1 Callam, M.J., Harper, D.R.,
Dale, J.J., Ruckley, C.V.
accurate diagnosis of the underlying cause. Most Arterial insufficiency Chronic ulcer of the leg:
ulcers are secondary to venous or arterial disease, Arterial ulcers account for almost 10% of ulcers clinical history. Br Med J
but other causes should be considered when the (Fig 2).3,8 Medical history, clinical presentation and 1987; 294: 1389-1391.
2 Baker, S.R., Stacey, M.C.,
ulcer does not fit into these categories or fails to predisposing factors are considered when making a Jopp-McKay, A.G. et al.
respond to treatment.9 diagnosis. Patients with arterial ulceration may Epidemiology of chronic
describe a history of leg pain during exercise. This venous ulcers. Br J Surg
1991; 78: 864-867.
Venous disease is due to arterial occlusion secondary to peripheral 3 O’Brien, J.F., Grace, P.A.,
Approximately 80% of leg ulcers result from venous vascular disease. Burke, P.E. Prevalence and
hypertension,3,8 secondary to failure of the calf mus- Clinical signs and symptoms are listed in Box 2. aetiology of leg ulcers in
Ireland. Ir J Med Sci 2000;
cle to effectively empty the veins in the lower limb Investigations include ABPI measurement and 169: 110-112.
(Fig 1). This may be due to valvular incompetence, angiography, which identifies the degree of stenosis 4 Gerstein, A.D., Philips, T.J.,
venous obstruction, calf-muscle impairment or a in the larger vessels. Patients with intermittent clau- Rogers, G.S., Gilchrest, B.A.
Wound healing and aging.
combination of these factors.10,11 Incompetence of dication usually have ABPI values of 0.5–0.9.13 Dermatol Clin 1993; 11: 4,
either the deep or superficial veins increases pres- Patients who have leg pain at rest, signifying critical 749-757.
sure in the veins at the ankle, leading to swelling ischaemia, usually have ABPI values under 0.5.13 5 Eaglstein, W.H. Wound
healing and ageing.
of the tissue, sequestration of red blood cells, iron Treatment for arterial ulcers aims to restore blood Dermatol Clin 1986; 4: 3,
deposition, lipodermatosclerosis and ulceration.6,12 supply to the limb. The treatment options for 481-484.
Venous ulcers are generally found in the distal
medial third of the lower leg just above the ankle.11
Patients with superficial vein incompetence present
with varicose veins. Those with incompetent
perforating or deep veins may not have obvious
varicosities but will present with varying degrees of
skin changes (Box 1).
Diagnosis is based on medical history, clinical
examination and non-invasive investigations, pri-
▲

marily ankle brachial pressure index (ABPI) meas- Fig 1.Venous ulcer Fig 2. Arterial ulcer

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 practice
6 Grace, P. (ed). Guidelines
for the Management of Leg
Ulcers in Ireland. Smith and
Nephew, 2002.
7 Callam, M.J. Leg ulcer and
chronic venous
insufficiency in the
community. In: Ruckley,
C.V., Fowkes, F.G.R.,
Bradbury, A.W. (eds).
Venous Disease,
Epidemiology, Management
and Delivery of Care.
Springer-Verlag, 1999.
8 Callam, M.J., Ruckley, C.V.,
Harper, D.R., Dale, J.J.
Chronic ulceration of the
leg: extent of the problem
and provision of care. Br
Med J 1985; 290: 1855-1856.
9 Bull, R. Common causes
of leg ulceration. Hosp Med
1998, 59: 11, 845-849.
10 Browse, N.L., Burnand,
K.G., Irvine, A.T., Wilson,
N.M. Physiology and
functional anatomy. In:
Browse, N.L., Burnand, K.G.,
Irvine, A.T., Wilson, N.M.
(eds). Diseases of the Veins,
(2nd edn). Arnold, 1999.
11 Grace, P., Hornick, K.,
Taylor, K., Bouchier-Hayes,
D. Cardiovascular
disorders. In: Cuschieri, A.,
Hennessy, T.P., Greenhalgh,
R.M. et al. (eds). Clinical
Surgery. Blackwell Science,
1996.
12 London, N.J., Donnelly,
R. ABC of arterial and
venous disease: ulcerated
lower limb. Br Med J 2000;
320: 1589-1591.
13 Colgan, M.P. Assessment
of patients with leg ulcers.
In: Grace, P.A.(ed.).
Guidelines for the
Management of Leg Ulcers
in Ireland. Smith and
Nephew, 2002.
14 Leaper, D., Harding, K.
Factors affecting wound
healing. In: An introduction
to Wounds. Emap
Healthcare, 2000.
15 European Wound
Management Association.
Understanding
Compression Therapy.
Medical Education
Partnership, 2003.
16 Moffatt, C. Issues in the
assessment of leg
ulceration. J Wound Care
1998; 7: 9, 467-473.
17 Davis, M. Critical leg
ischaemia, ulcers and
gangrene. In: Baker, D. (ed.).
Primary Care of Vascular
Disease. Medical Education
Network, 2000.
18 Hiatt, W.R.
Pharmacologic therapy for
peripheral arterial disease
and claudication. J Vasc Surg
2002; 36: 6, 1283-1291.
216
Box 1. Signs of venous disease
Oedema — due to increased venous pressure and
failure to pump excessive tissue fluid along the
lymphatics. Often generalised and may worsen by day
when the patient is active
Varicose eczema (dermatitis) — caused by
extravasation of proteolytic enzymes and other
metabolic waste products due to the increased
pressure in the limb
Pigmentation — brown staining is characteristic of
venous ulceration, resulting from deep venous
incompetence due to leakage of red blood cells into the
interstitial spaces and the deposition of haemosiderin
Ankle flare — small dilated vessels above the
malleolus extending to the sole of the foot, associated
with perforator vein incompetence
Lipodermatosclerosis — leg may take the shape of an
inverted champagne bottle, wide at the knee and
narrow at the ankle, and areas of the skin appear as
woody scar tissue. Results from progressive fibrosis of
the skin and subcutaneous tissues induced by prolonged
inflammatory processes and venous hypertension
Atrophe blanche — white areas of extremely thin
fragile skin dotted with tiny tortuous blood vessels
Box 2. Signs of arterial disease
Cold shiny, hairless skin and thickened nails
Leg pain brought on by exercise
Pain in limb relieved by positioning leg in a dependent
position
Ulcer has a punched-out appearance
Poor capillary refilling time
Absent pedal pulses
patients with ulceration due to critical ischaemia
are revascularisation by endovascular means
(angiopasty, stenting) or bypass surgery.17 Patients
should also be given advice on smoking cessation,
diet and exercise.17-19
Diabetes
Diabetic ulcers are most common on the feet, and
may be the result of ischaemia or neuropathy
(Fig 3). Ischaemic ulcers are caused by arterial insuf-
ficiency in people with or without diabetes, but
arteriosclerosis is more severe in people with dia-
betes due to hypertension and high serum choles-
terol and triglyceride.6 Arteriosclerosis decreases the
delivery of oxygen and nutrients to the tissues, pre-
disposing patients to ulceration and delaying
wound healing.6,20
Patients with diabetes also develop microvascular
disease, further reducing blood flow to the tissues,
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predisposing them to ulceration.6
Neuropathic ulcers develop as a result of peri-
pheral nerve dysfunction and leave patients with
diabetes vulnerable to trauma and pressure to the
feet, which can result in ulceration.
Venous disease affects patients with diabetes, as
it does the general population, so ulceration due to
venous incompetence should not be excluded.
Diagnosis of a diabetic ulcer will primarily
depend on clinical presentation and medical his-
tory, including history of diabetes. Blood glucose
levels and ABPI should be checked. ABPI measure-
ments should be interpreted with caution as there
may be calcification of the arteries. High measure-
ments can sometimes be deceptive and may not be
a true representation of the degree of arterial disease
as it can be difficult to identify whether the arteries
are occluded due to calcification.13
Treatment will depend on the underlying aetiol-
ogy. In ulcers related to neuropathy or peripheral
vascular disease, treatment focuses on relieving
external pressure at the wound site, surgical debride-
ment of devitalised tissue, infection control,
maintaining control of glucose levels and arterial
reconstruction if necessary.
Malignant ulcers
Certain types of tumour can appear as skin
ulcers. Those on the leg are usually squamous cell
carcinoma, basal cell carcinoma or malignant
melanoma.6
Squamous cell carcinoma can develop secondar-
ily in chronic long standing leg ulcers, commonly
indicated by a raised or thickened edge (Marjolin’s
ulcer).11 It is estimated that up to 2% of chronic leg
ulcers are malignant, but diagnosis is often missed.21
Diagnosis is by histological examination of a
biopsy specimen from the ulcer margin and base.
Treatment is by wide excision.
Pressure ulcers
Pressure ulcers result from prolonged external
pressure on a bony prominence leading to tissue
anoxia and cell death. In leg ulceration the bony
prominences most often affected are the malleolus
(ankle) and the heel.
Treatment primarily involves removing the
source of external pressure with pressure-relieving
devices. The wound should then be treated
with appropriate dressings to remove debris and
promote granulation. Any necrotic tissue may be
surgically debrided.22,23
Rare causes of ulceration
Rheumatoid arthritis
Leg ulceration in patients with rheumatoid arthritis
is thought to result from local vasculitis, poor venous
return due to immobility of the ankle joint and the
J O U R N A L O F WO U N D C A R E VO L 1 3 , N O 6 , J U N E 2 0 0 4
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19 Earnshaw, J.J., Murie, J.A.

(eds). The Evidence for
Vascular Surgery. Frontier,
1999.
20 Shipperley, T. The
importance of assessing
patients with leg ulceration.
Br J Nurs 1997; 6: 2, 71-80.
21 Yang, D., Morrison, B.D.,
Vandogen,Y.K. et al.
Fig 3. Diabetic ulcer Fig 4. Sclerodermal ulcer Fig 5. Pyoderma gangraenosum Malignancy in chronic leg
ulcers. Med J Aust 1996;
164: 718-720.
effect of long-term steroid therapy on the skin. In caused by a number of conditions, most commonly 22 European Pressure
addition, the long-term use of steroids can delay scleroderma, which can affect the fingers and toes.31 Ulcer Advisory Panel.
Pressure Ulcer Prevention
healing.24 Associated ulceration on the fingers or toes can be Guidelines. EPUAP, 2003.
very painful. 23 Royal College of
Vasculitis Scleroderma is an autoimmune connective tissue Nursing. Pressure Ulcer
Risk Assessment and
This is the acute or chronic inflammation of small, disease commonly associated with Raynaud’s Prevention. Clinical Practice
medium and large veins or arteries, resulting in syndrome (Fig 4).30 Vasodilating drugs such as the Guidelines. RCN, 2000.
fibrosis and thrombi formation. It may present as calcium channel blocker nifedipine (Adalat) or 24 Min, D.I., Monaco, A.P.
Complications associated
purpura, erythema urticaria, nodules, bullae or skin intravenous prostacyclin may be prescribed.32 with immunosuppressive
infarction, leading to ulceration.25 Biopsy confirms therapy and their
diagnosis. Treatment is with steroids and cytotoxic Other causes of ulceration management.
Pharmacotherapy 1991; 11:
or immunosuppressive agents. Pyoderma gangraenosum 5, 119S-125S.
This is thought to be an immunological disorder, 25 Joyce, J.W. Uncommon
Infectious diseases although its pathenogenesis is not clear (Fig 5). It is arteriopathies. In:
Rutherford, R.B.
Tissue necrosis and ulceration can be caused by often associated with systemic diseases such as (ed.).Vascular Surgery (4th
micro-organisms such as β-haemolytic Streptococcus rheumatoid arthritis, chronic inflammatory bowel edn). Saunders, 1995.
pyogenes.26 Symptoms range from erysipelas, disease, Crohn’s disease, ulcerative colitis, mono- 26 Shanson, D.C.
Microbiology in Clinical
ecthyma, deep cellulitis to necrotising fasciitis, sep- clonal gammopathy and, rarely, leukaemia.33 How- Practice (2nd edn). Wright,
sis and multi-organ failure. Treatment is immediate ever, it may also occur without any reported 1989.
administration of high-dose antibiotics. underlying disease. 27 Martorell, F.
Hypertensive ulcer of the
Ulcers may also be associated with tuberculosis, These ulcers can appear quite suddenly, often at leg. J Cardiovasc Surg 1978;
syphilis, human immunodeficiency virus (HIV) and the site of a minor injury, and may occur singly or 19: 599-600.
various tropical diseases. in groups. They might start as a small pustule, red 28 Davidson, S., Lee, E.,
Newtown, E.D. Martorell’s
bump or blood-blister, after which the skin breaks
ulcer revisited. Wounds
Microcirculatory disorders down, resulting in an ulcer. The ulcer can deepen 2003;15: 6, 208-212.
Martorell (hypertensive) ulcer and widen rapidly. Characteristically, the edge of 29 Choucair, M.M.,
Patients with severe, prolonged, poorly controlled the ulcer is purple and undermined as it enlarges, Fivenson, D.P. Leg ulcer
diagnosis and management.
hypertension can develop a Martorell ulcer, which and there are peripheral red borders. It is usually Dermatologic Clin 2001;
is a result of tissue ischaemia caused by increased very painful.34,35 19: 659-678.
vascular resistance.27 Histological examination of Pyoderma gangrenosum is diagnosed by its clini- 30 Porter, J.M., Edwards,
J.M. Occlusive and
hypertensive ulcers has shown a thickened tunica cal and histological appearance. Treatment is with vasospastic diseases
media without atheroma and calcification.28 These high-dose systemic steroids.34,35 involving distal upper
extremity arteries –
ulcers, which are extremely painful, are normally
Raynaud’s syndrome. In:
located above the malloelus and contain black Haematological disorders Rutherford, R.B.
necrotic tissue. Haematological conditions that are most com- (ed.).Vascular Surgery (4th
edn). Saunders, 1995.
Diagnosis is made after excluding other causes monly linked to leg ulceration are sickle cell
31 Beynon, H. Raynaud’s
and undertaking a histological examination.29 Treat- anaemia, thrombocythaemia, thalassaemia and phenomenon. In: Baker, D.
ment consists of lowering hypertension and local polycythaemia rubra vera.12 (ed). Primary Care of
Vascular Disease. Medical
ulcer care.28 In sickle cell anaemia there is an increased num- Education Network, 2000.
ber of activated endothelial cells. It is thought that 32 Scorza, R., Caronni, M.,
Raynaud’s phenomenon interaction between the sickle cells and endothelial Mascagni, B. et al. Effects of
long-term cyclic iloprost
Raynaud’s phenomenon affects the distal extremities cells promotes the formation of thrombus, leading therapy in systemic
as a result of exaggerated vasospasm caused by the to vaso-occlusion, which can result in ulceration. sclerosis with Raynaud’s
closure of arteries and arterioles in response to cold The pathogenesis of ulceration in other haemato- phenomenon: a
randomised, controlled
or emotional stress.30 Primary Raynaud’s predomi- logical disorders is also linked to poor arterial blood study. Clin Exp Rheumatol
nantly affects the hands. Secondary Raynaud’s is flow, again through thrombus formation.36,37 2001; 19: 503-508.

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 practice

Necrobiosis lipoidica ease, poor circulation, malnutrition or on certain

This is a rare ulcerative condition commonly associ- drug therapies.6 Cytotoxic drugs, corticosteroids and
ated with diabetes, although it can occur in its NSAIDs are associated with delayed healing.14,24
absence.38 Its aetiology is unknown but microangio- Treatment aims to address the underlying aetiology
pathic and neuropathic processes have been sug- and to provide local wound care.
gested, as well as collagen abnormality, altered
immune mechanisms and leucocyte functionality.39 Drugs
Lesions appear as well-circumscribed, erythematous In a small number of cases drug reactions result in
plaques, with a depressed, waxy telangiectatic centre. cutaneous ulceration. Causative drugs include,
A third may progress to ulcers if exposed to trauma.40 methotrexate,43 sulpiride44 and fluocinolone ace-
There is no reported standard treatment for these tonide-neomycin sulphate ointment.45 Treatment is
ulcers.40,41 Therapies commonly used include non- to remove the causative agent and provide local
steroidal anti-inflammatory drugs (NSAIDs) and wound care.
corticosteroids.41 Severe ulcerations often resist
medical and surgical treatment (deep excision and Conclusion
split-thickness skin grafting, skin flap or allografted Various studies have shown that leg ulceration has
cultured keratinocytes).42 a negative impact on quality of life46-48 but that
effective treatment can address this.46 This involves
Trauma identifying and treating the underlying aetiology of
Traumatic wounds resulting in tissue loss may the ulcer, as well as providing effective local wound
develop into a leg ulcer in patients with venous dis- management. ■
33 Callen, J.P., Case, J.D., lower-extremity ulcer. Is it lipoidica. J Eur Acad 42 Lowitt, M., Dover, J. fluocinolone acetonide.
Sager, D. Chlorambucil: an arterial, venous, Dermatol Venereol 2004; Necrobiosis lipoidica. J Am Arch Dermatol 1965; 92: 1,
effective corticosteroid neuropathic?.Wounds 1998; 18: 2, 199-200. Acad Dermatol 1991; 25: 52-53.
sparing therapy for pyoderma 10: 4, 125-131. 39 Paquette, D., Golomb, 5, 735-748. 46 Franks, P.J., Moffatt, C.J.,
gangrenosum. J Am Acad 37 Griesshammer, M., C. Ulcers caused by 43 McCoy, C.M. Connolly, M. et al.
Dermatol 1989; 21: 515-519. Klippel, S., Mohr, U. et al. inflammatory processes. In: Leflunomide-associated Community leg ulcer
34 Prystowsky, J.H., Sidney, PRV-1 mRNA expression Falanga,V. (ed.). Cutaneous skin ulceration. Ann clinics: effect on quality of
N.K., Lazarus, G.S. Present discriminates two types of Wound Healing. Martin Pharmacother 2002; 36: 6, life. Phlebology 1994; 9:
status of pyroderma essential thrombocythemia Dunitz, 2001. 1009-1011. 83-86.
gangrenosum. Arch and can predict transition 40 Onugha, N., Jones, A. 44 Srebrnik, A., Shachar, E., 47 Rich, A., McLachlan, L.
Dermatol 1989; 125: 57-64. to polycythemia vera. The management of hard- Brenner, S. Suspected How living with a leg ulcer
35 Mackowiak, P.A. Blood 2003; 102: 659a, to-heal necrobiosis with induction of a pyoderma affects people’s daily life? A
Necrotic ulceration of the Abstract 2440. Promogran. Brit J Nurs gangrenosum-like eruption nurse-led study. J Wound
skin and fascia. Clin Infect 38 Santos-Juanes, J., Tissue Viability Supplement due to sulpiride treatment. Care 2003; 12: 2, 51-54.
Dis 2003; 36: 7, 925-926. Galache, C., Curto, J.R. et 2003; 12: 15, S14-S20. Cutis 2001; 67: 3, 253-256. 48 Franks, P.J., Moffatt, C.J.
36 Goldstein, D.R., Mureebe, al. Squamous cell 41 Chakrabarty, A., Philips, 45 Bjornberg, A., Hellgren, Who suffers most from leg
L., Kerstein, M.D. Differential carcinoma arising in long- T.J. Necrobiosis lipoidica. L. Necrosis in leg ulcers: ulceration? J Wound Care
diagnosis: assessment of the standing necrobiosis Wounds 2003; 15: 2, 59-63. probable role of 1998; 7: 8, 383-385.

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