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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 1, January/February 2018
44
AFRICA
lumen. Table 1 shows the patients’ characteristics. All stents were
made of 316L stainless steel.
Exclusion criteria included insertion of drug-eluting stents,
immunosuppressive therapy, pregnancy, and marked cutaneous
inflammation, especially at the patch testing site. Neither the
study nor the control group included HIV-infected patients.
Three patients in the study group and five in the control group
had a prior history of metal allergies. All patients were tested
with the metals listed in Table 2. They were patch tested using
allergens from Chemotechnique Diagnostics
®
(Malmö, Sweden).
Patches were applied onto the patient’s upper back using Finn
Chambers
®
on Scanpor
®
(Epitest OY, Tuusula, Finland). All
patients were tested for reactions, which were read at D2/3 and
D4/5 using ICDRG criteria.
6
We used the chi-squared test in order to determine differences
between the groups. Statistical significance was determined at a
value of
p
≤
0.05.
Results
The two study groups did not display any significant differences
in terms of age, gender, diabetes, hypertension, lipid profiles and
smoking status (Table 1). The data from the patch test reactions
are provided in Table 3. Of the 99 patients included in the study,
28 (28.3%) had at least one reaction to the tested metals.
There were a total of 40 positive reactions in both groups.
The most common reactions were to nickel, followed by
chromate and cobalt. Four of the patients had reactions to
both nickel and cobalt. Table 4 shows the distribution of the
positive reactions to metals among the two study groups.
Metal sensitivity rate between the two groups did not differ
significantly (
p
=
0.921).
Discussion
Grade 316 is the standard molybdenum-bearing grade, second
in overall volume production to grade 304 among the austenitic
stainless steels. The molybdenum gives grade 316 better overall
corrosion-resistant properties than grade 304, particularly
higher resistance to pitting and crevice corrosion in chloride
environments. Grade 316L, the low-carbon version of 316, has
high resistance to sensitisation.
7
Over a decade has passed since Koster suggested metal
allergy may play a role in the pathogenesis of ISR. Follow up
on studies
4,5,8,9
of ISR in patients who had received stainless steel
stents did not confirm Koster’s initial observations.
A recent report from Turkey showed a correlation between
nickel allergy and ISR among patients who were treated with
cobalt chromium stents, which have a three times higher
concentration of nickel than 316L stainless steel stents.
10
It
has been speculated that nickel ions may influence expression
of the adhesion molecule ICAM-1 in endothelial cells,
11
which
in turn may trigger local inflammation and lead to ISR. By
contrast, Thyssen
et al.
12
studied a large cohort of patients with
pre-existing nickel allergy and found that these individuals did
not appear to have a higher risk for ISR.
In comparison with the above studies, both our study and
control groups had higher positive reaction rates to nickel and
chromate. This comes as no surprise as metal allergy is more
common in Israel,
13,14
compared to Europe andNorthAmerica.
15,16
Legislative and market-related factors result in higher metal
sensitisation rates in Israel. There were no significant differences,
however, between our study and control groups.
Our results are in line with most earlier studies and do not
support a role for nickel, cobalt, chromate or molybdenum
allergy in ISR. Conversely, recent convincing data demonstrate
that gold allergy is a contributing factor to ISR. It is possible that
gold, which is a more potent sensitiser than nickel,
17
may induce
a stronger immunological reaction, resulting in endothelial
proliferation.
The weaknesses of our study, as of previously published
reports, are its relatively small size and its retrospective design.
We suggest the need for larger, prospective, confirmatory cohort
studies of patients with ISR.
Table 1. Characteristics of the study and control group individuals
p-
value
Control group (
n
=
70)
Study group (
n
=
29)
Characteristic
0.6003
62.9 ± 5.8
64.7 ± 7.2
Age
0.827
27 (39)
11 (38)
Diabetes
0.713
31 (44)
14 (48)
Hypertension
0.557
34 (49)
16 (55)
Smoking
0.689
17 (24)
8 (28)
Female
0.778
36 (51)
14 (48)
Hyperlipidaemia
Table 2. Patch-tested metals in the study
Vehicle
Concentration (%)
Material
petrolatum
5
Nickel sulphate
petrolatum
0.5
Potassium dichromate
petrolatum
0.25
Molybdenum chloride
petrolatum
0.5
Molybdenum chloride
petrolatum
10
Manganese oxide
petrolatum
1
Cobalt chloride
as is
–
316L stainless steel
Table 3. Distribution of positive reactions
% of study and
control groups
% of total positive
reactions
No of positive
reactions
Metal
15.1
37.5
15
Nickel
8
20
8
Chromate
5
12.5
5
Cobalt
2
5
2
Manganese
4
10
4
Molybdenum 0.25%
5
12.5
5
Molybdenum 0.5%
1
2.5
1
Stainless steel
40.1
100
40
Total positive reactions
Table 4. Distribution of metal sensitivity in both study groups
p
-value
Control group
(
n
=
70)
Study group
(
n
=
29)
Metal
0.641
10
5
Nickel
0.383
6
2
Chromate
0.491
3
2
Cobalt
0.553
2
0
Manganese
0.935
3
1
Molybdenum 0.25%
0.491
3
2
Molybdenum 0.5%
0.172
0
1
Stainless steel
0.556
27
13
Total positive reactions