Painful Neuropathy and Foot Ulceration in Diabetic Patients

Abstract

To examine the prevalence of painful symptoms in neuropathic patients with or without foot ulceration. It has been suggested that there are two clinical presentations of sensory diabetic neuropathy with little overlap: painful (acute or chronic) and painless with recurrent foot ulceration.
We examined three groups of diabetic patients matched for age and duration of diabetes--24 without neuropathy on clinical grounds (mean age 56.1 yr [range 38-76 yr], diabetes duration 12.6 yr [0.4-40 yr]), 30 with neuropathy (mean age 55.3 yr [range 21-73 yr], diabetes duration 17.3 yr [range 0.2-61 yr]), and 40 with neuropathic foot ulceration (mean age 58.1 yr [range 41-72 yr], diabetes duration 18.5 yr [range 1-46 yr])--and compared them with 20 healthy subjects (mean age 50 yr [range 37-69 yr]). For evaluation of neuropathy, the neuropathy symptom score, neuropathy disability score, and vibration perception threshold were measured.
No difference existed between the neuropathic and foot ulcer groups in the neuropathy symptom score (4.2 +/- 3.9 [mean +/- SD] vs. 2.5 +/- 2.1, NS) and neuropathy disability score (15.1 +/- 5.7 vs. 16.8 +/- 6.1, NS), but the vibration perception threshold was lower in the neuropathic group (30.1 +/- 13.4 vs. 40.5 +/- 13.8 V, P < 0.001). Painful symptoms (neuropathy symptom score > 3), either in the past or during the time the study was conducted, had been experienced by none of the control subjects, 7 (29%) of the nonneuropathic group, 18 (60%) of the neuropathic group, and 17 (43%) of the foot ulcer group (NS for the last two groups), and were present at the time of examination in 13 (43%) of the neuropathic group and in 13 (33%) of the foot ulcer group (NS in all groups). Duration of symptoms was < 12 mo in 12 (40%) neuropathic and 15 (38%) foot ulcer patients (NS).
We conclude that painful symptoms are frequent in diabetic neuropathy, irrespective of the presence or absence of foot ulceration and that these symptoms can occur at any stage of the disease. These results suggest that there is a spectrum of neuropathic syndromes from the painful to the patients with foot ulceration, and that much overlap exists.

Full text

SHORT
REPORT
Painful Neuropathy and Foot
Ulceration in Diabetic Patients
ARISTIDIS VEVES, MD
CHRISTOS MANES, MD
HEATHER J. MURRAY, DPM
MATTHEW J. YOUNG, MD
ANDREW J. M. BOULTON, MD
OBJECTIVE— To examine the prevalence of painful symptoms in neuropathic
patients with or without foot ulceration. It has been suggested that there are two
clinical presentations of sensory diabetic neuropathy with little overlap: painful
(acute or chronic) and painless with recurrent foot ulceration.
RESEARCH DESIGN AND METHODS— We examined three groups of dia-
betic patients matched for age and duration of diabetes—24 without neuropathy on
clinical grounds (mean age 56.1 yr [range 38-76 yr], diabetes duration 12.6 yr
[0.4-40 yr]), 30 with neuropathy (mean age 55.3 yr [range 21-73 yr], diabetes
duration 17.3 yr [range 0.2-61 yr]), and 40 with neuropathic foot ulceration (mean
age 58.1 yr [range 41-72 yr], diabetes duration 18.5 yr [range 1-46 yr])—and
compared them with 20 healthy subjects (mean age 50 yr [range 37-69 yr]). For
evaluation of neuropathy, the neuropathy sympton score, neuropathy disability
score, and vibration perception threshold were measured.
RESULTS — No difference existed between the neuropathic and foot ulcer groups
in the neuropathy symptom score (4.2 ± 3.9 [mean ± SD] vs. 2.5 ±2.1, NS) and
neuropathy disability score (15.1 ± 5.7 vs. 16.8 ± 6.1, NS), but the vibration per-
ception threshold was lower in the neuropathic group (30.1 ± 13.4 vs. 40.5 ± 13.8
V, P < 0.001). Painful symptoms (neuropathy symptom score > 3), either in the
past or during the time the study was conducted, had been experienced by none of
the control subjects, 7 (29%) of the nonneuropathic group, 18 (60%) of the neuro-
pathic group, and 17 (43%) of the foot ulcer group (NS for the last two groups), and
were present at the time of examination in 13 (43%) of the neuropathic group and
in 13 (33%) of the foot ulcer group (NS in all groups). Duration of symptoms was
<
12
mo in 12 (40%) neuropathic and 15 (38%) foot ulcer patients (NS).
CONCLUSIONS— We conclude that painful symptoms are frequent in diabetic
neuropathy, irrespective of the presence or absence of foot ulceration and that these
symptoms can occur at any stage of the disease. These results suggest that there is a
spectrum of neuropathic syndromes from the painful to the patients with foot
ulceration, and that much overlap exists.
FROM THE DIABETES CENTRE, UNIVERSITY DEPARTMENT OF MEDICINE, MANCHESTER ROYAL INFIRMARY,
MANCHESTER, UNITED KINGDOM.
ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO ARISTIDIS VEVES, MD, UNIVERSITY DEPARTMENT
OF MEDICINE, MANCHESTER ROYAL INFIRMARY, OXFORD ROAD, MANCHESTER M13 9WL, UK.
RECEIVED FOR PUBLICATION 19 NOVEMBER 1992 AND ACCEPTED IN REVISED
FORM
15 APRIL 1993.
NSS, NEUROPATHY SYMPTOM SCORE; NDS, NEUROPATHY DISABILITY SCORE; VPT, VIBRATION PERCEPTION
THRESHOLD; TYPE I DIABETES, INSULIN-DEPENDENT DIABETES MELLITUS; TYPE II DIABETES, NON-INSULIN-
DEPENDENT
DIABETES
MELLITUS;
API, ANKLE PRESSURE
INDEX.
P
ainful symptoms such as paresthe-
siae,
lancinating or aching pain,
and/or burning sensation in the feet
with a typical nocturnal exacerbation are
common in diabetic neuropathy (1).
Etiopathogenesis and natural history of
painful diabetic neuropathy are not well
established (2). It has been suggested
that painful and painless diabetic neu-
ropathy are two separate clinical condi-
tions with little overlap (3,4). According
to this suggestion, patients with painful
neuropathy do not usually develop foot
ulcers, whereas in patients with recur-
rent foot ulceration painful symptoms
are rare. The aim of this study is to ex-
amine the prevalence of painful symp-
toms,
either past or present, in diabetic
patients with and without foot ulcer-
ation.
RESEARCH DESIGN AND
METHODS — We studied three groups
of patients with type I or type II diabetes
and one group of healthy subjects. All
diabetic groups were matched for age
and known duration of diabetes. The
first group included 24 diabetic patients
(15 men, 6 type I) without neuropathy,
according to the criteria described. Mean
age was 56.1 yr (range 38-76 yr), and
mean duration of diabetes was 12.6 yr
(range 0.4-40 yr). The second group
included 30 neuropathic diabetic pa-
tients (23 men, 13 type I). Mean age was
55.3 yr (range 21-73 yr), and mean du-
ration of diabetes was 17.3 yr (range
0.2-61 yr). The third group included 40
patients with neuropathic foot ulceration
(30 men, 14 type I). Mean age was 58.1
yr (range 41—72 yr), and mean duration
of diabetes was 18.5 yr (range 1-46 yr).
The nonneuropathic and neuropathic
patients were randomly selected from the
diabetes outpatient clinic, whereas the
foot ulcer patients were randomly se-
lected from the diabetic foot clinic where
patients with active foot ulcers receive
treatment. Two patients from the neuro-
pathic group and one with a foot ulcer
were treated with tricyclic antidepres-
DIABETES CARE, VOLUME 16, NUMBER 8, AUGUST 1993
1187

Painful
neuropathy and foot ulceration
Table 1—Clinical characteristics of studied groups
Study groups
Control Nonneuropathic Neuropathic Foot ulcer
n
Age (yr)
Diabetes duration (yr)
API
20
50.0 (37-69)*
1.4 ± 1.1*
24
56.1 (38-76)
12.6 (0.4-40)
0.9 ± 0.4*
30
55.3 (21-73)*
17.3 (0.2-61)
1.1 ±0.3
40
58.1 (41-72)t
18.5 (1-46)
1.1 ±0.3
Data are means ± SD (range) and means ± SD for API.
*P<0.05.
tP<0.01
sants for painful neuropathy. The control
group included 20 healthy nondiabetic
subjects (16 men), with a mean age of
50.0 yr (range 37-69 yr). Clinical details
of the groups studied are shown in Table
1.
Painful symptoms of neuropathy
were assessed using a modified NSS
based on the original one proposed by
Dyck (5). More specifically, the patients
were asked if they had experienced at
any time in the past or during the time
the study was conducted the following
symptoms: pins and needles, abnormal
cold or hot sensations in their feet, lan-
cinating or aching pain, burning pain of
the feet (causalgia), and/or irritation in
their feet and legs by the bedclothes at
night (paresthesiae). The patients were
also asked if the duration of symptoms
was > or <1 yr. Each symptom was
scored as the following: 1) unpleasant
but not affecting work or recreational
activities; 2) reducing ability for work or
recreational activities; 3) incapacitat-
ing—disabled for work or recreational
activities.
For the first five symptoms, 1 ex-
tra point was added if nocturnal exacer-
bation was present (maximum score of
23 points). The NSS was considered ab-
normal if it was >3 points. When equal
to 3 points, it was considered abnormal
only if more than one symptom was
present in this particular patient.
The NDS was used to quantify
the severity of diabetic neuropathy on
clinical examination as has been de-
scribed previously (6). In summary, the
sensations of pain, touch, cold, and vi-
bration were tested in both legs of all
patients and were scored according to
the level up to which the sensation was
impaired. An NDS >5 (maximum 28)
was considered abnormal.
The VPT was measured at the
great toe of the dominant side of each
patient using a biothesiometer (Bio-
medical Instruments, Newbury, OH).
The age-related upper normal limits
were derived from previously published
data (6). Peripheral neuropathy was di-
agnosed when at least two of the quan-
titative measurements (i.e., NSS, NDS,
and VPT) were abnormal.
API was calculated with the help
of a hand-held doppler apparatus. Pa-
tients had API measurements taken in
both legs. The lowest of the two mea-
surements was entered for the analysis.
The study was explained to all patients
and was approved by the Central
Manchester Health Authority Ethical
Committee. Nonparametric statistical
analysis with the Mann-Whitney U test
was performed using the Minitab statis-
tical software (Minitab, State College,
PA).
RESULTS— The mean NSS was simi-
lar in the neuropathic (4.2 ± 3.9) and
foot ulcer groups (2.5 ± 2.1), but was
higher in the neuropathic group when
compared with the nonneuropathic
group (1.8 ± 2.3, P < 0.05). No differ-
ence existed between the nonneuro-
pathic and the foot ulcer groups (Fig. 1).
None of the patients in the control group
NDS
VPT
Figure 1—Results of NSS, NDS, and VPT in
the diabetic groups. (M), Nonneuropathic group;
(W, neuropathic group; (M), foot ulcer group.
*P < 0.05.
complained of painful symptoms, either
in the present or in the past, and there-
fore the mean NSS was 0.
Painful symptoms (NSS >3), at
any time, either past or present, had been
experienced by 7 (29%) patients in the
nonneuropathic group, 18 (60%) in the
neuropathic group, and 17 (43%) in the
foot ulcer group (NS between the last
two groups). No statistical difference ex-
isted between the foot ulcer group and
the nonneuropathic and neuropathic
groups, but a significant difference ex-
isted between the last two groups
(P < 0.05, Fig. 2). Symptoms had been
present for >
12
mo in 4 (17%) nonneu-
ropathic, 12 (40%) neuropathic, and 15
(38%) foot ulcer patients (NS for all
groups). At the time of examination
painful symptoms were present in 5
(21%) patients in the nonneuropathic
group, 13 (43%) in the neuropathic
group, and 13 (33%) in the foot ulcer
group (NS for all groups). Two patients
with painful symptoms, one of recent
onset and one of long duration (> 10 yr),
also had Charcot arthropathy with gross
deformity of their feet.
The NDS was lower in the non-
neuropathic group (7.4 ± 6.4) when it
was compared with the neuropathic
(15.1 ± 5.7) and foot ulcer group
(16.8 ± 6.1), but no difference existed
between the last two groups. The VPT
1188
DIABETES CARE, VOLUME 16, NUMBER 8, AUGUST 1993

Veves and Associates
At any time
Figure 2—Prevalence of painful symptoms ei-
ther at any time or currently present in the
diabetic groups. No difference was found between
the neuropathic and foot ulcer groups. (•), Non-
neuropathic group; (W), neuropathic group;
(WO,
foot ulcer group. *P < 0.05.
was significantly higher in the foot
ulcer group (40.5 ± 13.8 V) compared
with the neuropathic (30.1 ±13.4, P <
0.001), nonneuropathic (18.5 ± 12.0,
P < 0.0001), and control (11.8 ± 8.2,
P < 0.0001) groups. The VPT in the
neuropathic group was also higher com-
pared with the nonneuropathic
(P < 0.002) and control (P < 0.0001)
groups, whereas it was higher in the non-
neuropathic group when compared with
the control group (P < 0.05).
No difference was found in the
API among the diabetic groups. API was
lower in the nonneuropathic group when
compared with the control group, but no
difference existed between the control,
neuropathic, and foot ulcer groups (Ta-
ble 1). API was >0.60 in all subjects
except in 2 patients with a foot ulcer,
both asymptomatic, in whom it was
0.40.
CONCLUSIONS— In this study we
have shown that painful symptoms can
be present in diabetic patients irrespec-
tive of the existence of foot ulceration. A
similar percentage of neuropathic pa-
tients with and without foot ulceration
complained of painful symptoms of com-
parable severity and duration. These re-
sults confirm our clinical experience that
painful symptoms can be present at any
stage of diabetic neuropathy, from sub-
clinical to very late neuropathy even with
severe Charcot arthropathy and foot ul-
ceration.
Recent studies that have exam-
ined the differences between painful neu-
ropathy and painless neuropathy with
recurrent foot ulceration have shown
that, in the former group, there is a sig-
nificant uniform dysfunction of small fi-
bers and a wide range of large fiber ab-
normalities, whereas in the latter group
the main characteristic is severe dysfunc-
tion of both large and small fibers (3,4).
These findings led to the hypothesis that
painful and painless neuropathy are two
distinct clinical syndromes with minimal
overlap. Our results cannot support this
hypothesis. Painful symptoms were sim-
ilarly present in patients with and with-
out foot ulceration, suggesting that pain-
less and painful neuropathy represent
extreme forms of the same syndrome.
Therefore, the presence or absence of
symptoms cannot predict foot ulcer-
ation, and the painful-painless foot at
risk of ulceration, as described by Ward
(7),
is often observed in diabetic neuro-
pathic patients. However, the VPT was
higher in the foot ulcer group and, as
recent studies have shown, it can predict
foot ulceration (8).
Peripheral vascular disease can
also cause pain in the lower limbs, but
the different clinical presentation, namely
pain induced by exercise and relieved by
resting the leg and the absence of pain,
makes the confusion with the neuro-
pathic pain unlikely. In this study the
API was similar in the neuropathic and
foot ulcer groups. No electrophysiologi-
cal measurements were used for the di-
agnosis and quantification of diabetic
neuropathy, but we believe that clinical
examination and quantitative sensory
testing are satisfactory in evaluating pain-
ful symptoms of diabetic neuropathy in
patients with or without foot ulceration.
Although a statistical difference was ob-
served in the age of the control group, we
do not think that this difference was of
any significant clinical importance. Fi-
nally, the fact that 3 patients were on
medication for the painful symptoms
does not seem to have influenced the
results of this study.
In summary, we have shown that
positive symptoms are frequent in dia-
betic neuropathy, irrespective of the
presence or absence of foot ulceration,
and these symptoms can occur at any
stage of the disease. Results suggest that
there is a spectrum of neuropathic syn-
dromes from the painful to the patients
with foot ulceration, and that much over-
lap exists.
References
1.
Boukon AJM, Ward
JD:
Diabetic neurop-
athies and pain. Clin Endocrinol Metab
15:917-31,
1986
2.
Boukon AJM: What causes neuropathic
pain?
J
Diab
Comp 6:58-63, 1992
3.
Young RJ, Zhou YQ, Rodriguez E, Pres-
cott RJ, Ewing DJ, Clarke BF: Variable
relationship between peripheral somatic
and autonomic neuropathy in patients
with different syndromes of diabetic
polyneuropathy. Diabetes 35:192-97,
1986
4.
Tsigos C, White A, Young RJ: Discrimi-
nation between painful and painless di-
abetic neuropathy based on testing of
large somatic nerve and sympathetic
nerve function.
Diabetic
Med 9:359-65,
1992
5.
Dyck
PJ:
Detection, characterization, and
staging of polyneuropathy: assessed in
diabetics. Muscle and Nerve 11:21-32,
1988
6. Wiles PG, Pearce SM, Rice PJS, Mitchell
JMO:
Vibration Perception Threshold:
influence of age, height, sex, and smok-
ing and calculation of accurate centile
values.
Diabetic
Med 8:157-61, 1991
7.
Ward JD: The diabetic leg.
Diabetologia
22:141-47, 1982
8. Young MJ, Manes C, Boukon AJM: Vi-
bration perception threshold predicts
foot ulceration: a prospective study (Ab-
stract).
Diabetic Med 9 (Suppl. 2):S42,
1992
DIABETES CARE, VOLUME 16, NUMBER 8, AUGUST 1993
1189