C l ini c a l and labo r a t o r y st u dy Prediction in leg ulcer healing 
K E Y 
WORD S 
clinical test, 
out-come, 
predictive 
value, 
quality 
assurance, 
leg ulcer 
Prediction of healiTZg in patients with 
venous leg ulcers 
G. B. E. Jemec, T. Karlsmark, T. Brink-Kjrer and H. C. Wulf 
----------------- ------~ ABSTR AC T 
Background. The treatment of venous leg ulcers is often prolonged. This is perceived as unsatisfactory 
by patients who desire more precise information about the prognosis. There is a need for predictive 
information about the most likely expected outcome of treatment. This information may not only aid the 
counseling of patients but also the allocation of resources. A predictive score system based on clinical 
aspects of leg ulcers has been suggested, but not independently tested. 
Methods. This study was conducted as a prospective study of patients referred to a hospital to assess 
the pred ictive value and accuracy of a previously proposed predictive test (scores O - 1 O). A score of 5 or 
less in the proposed predictive index was associated with complete or partial healing (P= 0.04). 
Results. No significant correlation was found between any of the general biochemical factors at first 
presentation and ultimate wound healing. lnitial wound size correlated significantly with final wound size 
and rate of healing. The study confirmed that ulcer area and duration as well as patients age can be 
combined in a predictive score tor the rate of wound healing. The variation of outcomes tora given score 
was, however, widely suggesting that the proposed test might be of a rather limited use as a guide to the 
prognosis of individual patients. Routine examination of general biochemical factors in patients with 
venous leg ulcers does not appear to have a significant predictive value with regard to the outcome of 
ulcer t reatment. 
Introduction 
Biophysical and clin ica l investigations in to the 
pathogenesis of leg ulcers give va luable predictive 
information and make a clinically useful classification 
possible (1, 2, 3, 4, 5) . A number of new treatments 
have become available but conservative therapy most 
often remains a lengthy process. Patients frequently wish 
to have an info rmation about the prognosis . Such 
information is rarely published and may vary greatly 
be tw een institutio ns , making historlcai o r bib lio -
graphical references less useful in the actual counseling 
of the patient. There is therefore a practical need for 
methods, which can give this information. 
In addition to accuracy, it is important that a pre-
dictive test functions in a routine clinical setting, i.e . 
acta dermatovenerologica A.P.A. Vol 8, 99, No 1 19 
Prediction in leg ulcer healing Clinical and laboratory study 
Table l. The results of routine biochemical testing in patients with venous leg ulcers. 
Hemoglobin 
(mmol/1) 
White Blood celi count 
(*109/1) 
Sodium 
(mol/1) 
Potassium 
(mmol/1) 
Creatinine 
(mmol/1) 
Glucose 
(mmol/1) 
Albumin 
(mmol/1) 
ASAT 
(U/1) 
Alkaline phosphatase 
(U/1) 
while subject to the unpredictable variations in therapy 
and to various external factors such as e.g. infection. A 
predictive test has limited value if it only works in a 
strictly controlled environment - it must be rugged to 
be of any use. 
A prognostic index to predict tirne of healing has 
been suggested based on ulcer area, ulcer duration, 
patient's age and possible deep vein involvement as 
measured by photoplethysmography (6). The test has, 
however, not been independently validated. It was 
therefore decided to study the predictive value of this 
test to a group of patients undergoing routine treat-
ment. 
o 
3-9 3 
(10) 
136 - 146 o 
3.5 - 5.0 o 
0.040 - 0.110 10 
(0.183) 
4.0 - 8.4 2 
(17.3) 
600 - 830 o 
(257) 
1 O - 14 15 
(37) 
80 - 275 6 
(400) 
In contrast to physical measurements of e.g. blood 
pressure, the significance of biochemical investigation 
was not similarly investigated ancl therefore remains 
unclear at present. Anecdotal reports ancl clinical 
impression suggest those biochemical investigations of 
e.g. albumen or hemoglobin may, occasionally, be 
useful in practical management of patients with leg 
ulcers. 
We have therefore assessed the usefulness of the 
proposecl prognostic inclex in routine treatment ancl 
undertaken a simple evaluation of the predictive value 
of general biochemical factors in the routine mana-
gement of venous leg ulcers. 
Table II. The outcome of routine treatment of venous leg ulcers compared with pre-treatment 
assessment according to Skene et al. 6• Lower scores are re/ated to a better average rate of 
healing (P= 0.04). Ulcers in the high score group increased at an average rate of 2 cm2 per month. 
20 
4 
(26) 
4 
(26) 
24 
(-10 - 58) 
-2 
(-16 - 12) 
acta dermatovenero/ogica A.P.A. Vol 8, 99, No 1 
! 
Clinical and laboratory study 
Materials and methods 
This study was conducted as a part of the quality 
assurance project at the department of dermatology of 
a tertiary referral center. A total of 79 consecutive new 
patients referred to the Department of dermatology at 
Rigshospitalet 1992-95 for the treatment of leg ulcers 
were studied. All patients had their ankle/brachial blood 
pressure ratio or the distal blood pressure (toe) 
measured. Blood samples were drawn for routine 
analysis of the factors listed in Table I, and the outline 
of the ulcers was traced for calculation of wound area. 
Ulcers were classified according to the following 
definitions (7, 8): 
Venous ulcer: Arm/ankle index > 0.8 or toe blood 
pressure > 60 mm Hg. In cases where patients objected 
to measurement of distal blood pressure or where the 
ulcers prevented measuring, the following clinical 
definition was used: Warm, clinically well-perfused feet 
were taken to indicate a predominantly venous cause 
of leg ulcers if the patient was not diabetic and did not 
suffer from connective tissue diseases. 
The following patients were excluded: 7 with 
arteriosclerotic ulcers, 4 with diabetic ulcers , 2 with 
unclassifiable ulcers, 7 due to skin grafting and 8 were 
!ost during follow-up. Only patients fulfilling the above 
mentioned criteria for venous ulceration were studied. 
All patients were treated according to the routine 
regimen used in the Department, consisting of a short-
stretch double-layer compression bandage (Com-
prilan®, Beiersdorf, Germany) applied daily, and 
ointment dressings (changed on alternate days) or 
hydrocolloid dressings changed as appropriate. Treatment 
was however not standardized and variations therefore 
occurred dependent on various factors , e.g. infection, or 
minor differences in the approach by different physicians. 
It was expected that a clinically usefol test would be 
accurate even under these conditions. 
After a period (mean: 18 months; 95% confidence 
interval 14- 21 months) oftreatmentthewound area was 
measured, and the rate of healing in cm2 per month 
calculated. 
The following correlations were studied: The ability 
of biochemical factors to explain wound size or wound 
dura ti on, and the predictive value of biochemical testing 
for assessment of wound size 18 months later. 
Three patients had concomitant diseases (1 blind 
patient, 2 patient with rheumatoid arthritis). Patients' 
ability to walk at the tirne of the first examination varied 
from normal (21 patients), to partial (necessitating 
support or cane, 11 patients) to wheel chair bound (7 
patients), while no specific information on mobility was 
available for the remaining 11 patients 
Six patients were !ost to follow-up, leaving a subgroup 
of 45 patients available for the study of the previously 
proposed prognostic index. The index was calculated for 
each ulcer at the start of the investigation, and these scores 
acta dermatovenerologica A.P.A. Vol 8, 99, No 1 
Prediction in leg ulcer healing 
were compared with actual outcome 18 months later. The 
original index was calculated by adding scores for ulcer 
size, ulcer duration, patient's age and deep vein 
involvement as measured by photoplethysmography. The 
scores ranged O - 5 for area, O - 2 for ulcer duration, O - 3 
for patient's age and O - O.S for deep vein involvement, 
giving a total range ofO to 10.5 in steps of0.5 points. We 
modified the score and performed the calculation without 
the photoplethysmography, which is not available in our 
department. Because of photoplethysmography 's 
contribution to the overall index is ve1y low, its omission 
was not considered to impair the resull~. The modified 
score bas a range of O - 10 in steps of 1 point. The inclex 
scores were grouped into two categories: < 6 based on 
the data suggested by Skene et al., ancl the rate of healing 
compared. The numbers of patienl~ showing complete 
healing, partial healing and no healing or actual worse-
ning were also compared. 
Non-parametric statistics (Mann Whitney and Krus-
kall-Wallis test), Chi-square tests as well as nrnltiple 
linear regression analysis were used. 
Results 
The 51 patients had a mean age ± standard deviation 
of74.1 ± 13.8 years and a sex ratio of 1 : 1.8 (18 men/32 
women). The mean size ± standard deviation of the 
ulcers was 25.9 ± 62,9 cm 2, and the mean ulcer duration 
± standard deviation was 55.8 ± 116.2 months. No 
significant correlation was found between the baseline 
biochemical studies and wound area or wound duration 
at the first consultation. A number of biochemical abnor-
malities were found, see Table I, but none correlated 
with wound healing or ultimate wound size. 
The proposecl predictive test showed significantly 
more patients with a score of <5 had complete healing 
of their ulcers (P = 0.04) as can be seen from Table II. 
General physical parameters showed a significant 
correlation with the outcome of treatment. Multiple 
linear regression analysis showed that patients' age, 
ulcer duration and wound size are significantly 
correlatecl to both fina! wound size (P < 0.001) and rate 
ofhealing (P = 0.002). Initial wouncl size was, however, 
the one physical component, which was most signi-
ficant, and correlated to both fina! wound size and rate 
of healing (P < 0.001). 
Discussion 
Conservative leg ulcer therapy is usually a long 
process and patients' expectation to know the prognosis 
is justified. Benchmarking, i.e. comparison with other 
centers is clifficult, as the outcome of routine treatment is 
rarely reported. This may be of lesser importance as the 
experience can vary considerably both between and 
within different institutions. Prognosis should therefore 
21 
Clinical and labora t ory study 
ideally be established for individual patients by the use 
of appropriate testing. Multiple linear regression analysis 
confirmed that patient's age, ulcer duration and ulcer size 
are significantly correlated to both fina! wound size and 
rate of healing. 
The predictive ability of the index was compared 
with the outcome of treatment. Three groups were 
identified: patients with completely healed ulcers, 
patients with partially healed ulcers, and patients with 
unchanged or increasing ulcer area. Statistically signi-
ficant differences were seen, suggesting that the test 
was able to predict the outcome of treatment in patients. 
A score of 5 or less was found to be predictive of a 
better average rate of healing but not of a higher 
likelihood of complete healing, as can be seen from 
Table II. The number of patients was insufficient for 
further stratification of scores, and the variation of 
outcomes for a given score was large (wide conficlence 
intervals of the mean healing rate). The proposed test 
may therefore only be of limited use as a guide to the 
prognosis of incliviclual patients. 
Biochemical factors, which could hypothetically 
either promote or slow clown the healing of ulcers were 
studied as possible predictive parameters. No correlation 
to . wound size or ulcer cluration was seen, and the 
predictive value of the chosen biochemical investiga-
tions was not significant. Few biochemical abnormalities 
were seen, ancl the majority of these were thought to 
be clinically insignificant, see Table I. Two cases of 
hyperglycemia were found by the screening. No other 
new diseases were discovered by routine testing, but 
Prediction in leg ulcer healing 
this may be clue to the setting in a tertia1y referral center 
where patients have usually been seen by severa! phy-
sicians prior to referral. Potentially initiating and poten-
tially predisposing factors were studied. Hypothetical 
initiators of healing, such as e.g. hemoglobin did not 
show any correlation to the rate of wound healing, nor 
did potential inhibitors, such as sodium, potassium or 
albumen which could predispose to ulceration by 
increasing e.g. edema. Abnormal tests clid not have a 
discernible negative influence on the wouncl healing. 
In contrast to the information obtained by biophysical 
investigation of the vessels, general biochemical investi-
gation cloes therefore not appear to have any significant 
value for the description or prospective assessment of 
treatment outcome ofvenous leg ulcers (9). 
The results suggest that in good accordance with 
clinical experience, the ulcer size at the initial evaluation 
may be the most important prognostic factor. The results 
do not support the inclusion of specific tests to the 
standard biochemical investigations except for gluco-
suria in patients with venous leg ulcers in a tertiary 
referral center. If general biochemical parameters have 
any influence on the treatment outcome of venous leg 
ulcers, it is speculatecl that this occurs only in conjunc-
tion witl1 other and clinically relevant factors. 
More accurate information about the prognosis of 
individual patients is an important aspect of quality 
assurance in dermatology (10). This study suggests that 
even in areas where the outcome is clearly defined 
(healing of ulcers) tl1e current metl1oclology be stili not 
sufficiently developed. 
l. Baker SR, Stacey MC, Jopp-McKay AG, Hoskin SE, Thompson PJ. Epidemiology of chronic venous 
ulcers. Br J Surg 1991; 78: 864 - 7. 
AUTHORS' 
ADDRESSES 
2. Cornwall JV, Lewis JD. Leg ulcers revisited. Br J Surg 1983; 70: 681. 
3. Callam MJ, Ruckley CV, Harper DR, Dale JJ. Chronic ulceration of the leg: extent of the problem and 
provision of care. Br Med] 1985; 290: 1855 - 6. 
4. Callam MJ, Harper DR, Dale JJ, Ruckley CV. Arterial disease in chronic leg ulceration: an underestimated 
hazard? Lothian and Forth Valley leg ulcer study. Br MedJ 1987; 294: 929 - 31. 
5. Ruckley CV, DaleJJ, Callam MJ, Harper DR. Causes of chronic leg ulcer. Lancet 1982; 2: 615 - 16. 
6. SkeneAl, SmithJM, Dore CJ, CharlettA, Lewis]D. Venous legulcers: a prognosticindex to predici tirne 
to healing. Br MedJ 1992; 305: 1119- 21. 
7. Impasato AM, Kirn GE, Davidson T, et al. Intermittent claudicatio: its natura! course. Surgeiy 1975; 119: 75 -8. 
8. Lowe G. Drugs in cerebral and peripheral arterial disease. Br Med J 1990; 300: 524 - 8. 
9. The Alexander House Group. Census paper on venous leg ulcers. Phlebology 1992; 7: 48 - 58. 
1 O. Jemec GBE, Wulf HC. Quality assurance in dermatology- development of a framework. Int J Dermatol 
1997; 36: 721 - 6. 
Gregor B.E. Jemec, MD, consultant dermatologist, Department of 
Dermatology, D92, Bispebjerg Hospital, University of Copenhagen, DK-2400 
Copenhagen NV, Denmark. 
Tony Karlsmark, MD, consultant dermatologist, same address 
Tove Brink-Kjaer, RN, research nurse, same address 
Hans Christian Wulf, MD, PhD, professor, same address 
acta dermatovenerologica A.P.A. Vol 8, 99, No 1 -------------------------------- 23