Host response - Orthopaedic Biomaterials in Research and Practice - page 356

The majority of these studies depend on a simple epicutaneous test
for sensitivity. These tests are notorious for lack of sensitivity and, in
particular, may produce false negatives if the test subject is already
responding to a challenge agent. A more recent study using skin patch
testing of patients with well-functioning implants found positive reac-
tions to metal ions at about twice that of the general population (25%).
In patients with a failed or poorly functioning implant, this number
increases to 60%. This sensitivity still has room for improvement. Using
a much more sensitive in vitro test of leukocyte chemotactic ability (the
leucocyte migration inhibition or LIF test), one study suggests that a
high proportion, perhaps as high as 75%, of patients having cobalt-base
implants removed may have developed a sensitivity to metal and that as
many as 50% of these may show signs of active response, suggesting a
continuing challenge above the sensitivity threshold. The results of these
studies are shown schematically in Figure 14.4. Although common, skin
testing is not considered an accurate preoperative predictor of the poten-
tial for metallic implant hypersensitivity and is still not routine part of
the patient selection process. There are currently no known definitive
tests to confirm metal hypersensitivity, although considerable progress
has occurred (Hallab and Jacobs 2009).
A parallel study by Merritt and Brown provided a rare opportunity
to examine 32 patients presenting for internal fixation of fractures and
then to retest them at removal (both tests were LIF). The results are
shown in Figure 14.5. Despite the unusually high level of sensitivity
seen preoperatively (59%), the same pattern emerges. Patients who have

Pre-implantation
(629)

At removal

(283)

Stainless
steel
(187)

Cobalt
base
(55)

Not
sensitive
(122)
43%

Not
sensitive
(472)
75%

43% 26%

Sensitive
(82)
29%

57% 74%

Sensitive
non-
migrators
(79) 28%

Co +2
Cr +6
Ni +2

15%
3.5%
18%

Sensitive
(157)
25%

FIGUre 14.4 Preimplantation and postremoval hypersensitivity to
metallic implants. (adapted from merritt, K., brown, s.a., biological
effects of corrosion products from metals. in fraker, a.C., Griffin, C.d.
(eds): Corrosion and Degradation of Implant Materials . astm stP 859.
american society for testing and materials, Philadelphia, pp. 195-206,
1985.)