Regarding diagnoses for revision hip arthroplasty, aseptic loosening was the most common, followed by infection and dislocation (Table 2). The highest proportions of hip revision cases associated with the presence of PVLI were found in infection (53%) and idiopathic pain (47%), followed by dislocation (25%), fracture (17%), and aseptic loosening (16%). However, when bearing surfaces were evaluated separately for aseptic loosening, PVLI was present more often (p < 0.001) in MoM hips (54%) than non-MoM hips (12%) and demonstrated more extensive involvement. In MoM hips, six of the seven cases of aseptic loosening with PVLI were rated greater than “few/+”; in non-MoM hips, all but one of the 15 cases were rated as “few/+”. For idiopathic pain, PVLI was present in 70% of the MoM hips, but none of the non-MoM hips.
Histologically, the extent of PVLI demonstrated no correlation to the extent of periprosthetic particle storage and tissue reaction in TKA, MoM, or non-MoM hip arthroplasty. On the other hand, the grade of PVLI was correlated to the grade of DLI in TKA (r = 0.46) and MoM hip (r = 0.61) revisions and weakly correlated in non-MoM hip revisions (r = 0.33).
Metallic debris is not benign. Highest during the initial running-in process and eventually reaching an asymptotic level after 6 months to 2 years, metallic abrasive wear particles are smaller, yet more numerous [17, 37] than PE wear particles . Ions can be generated from not only corrosion but also repassivation, modular components, delaminated metal coatings, impingement, and fixation screws [24, 30]. Although metal ions disseminate throughout the reticuloendothelial system at less than toxic levels [1, 8], metal particles can concentrate locally in the periprosthetic soft tissue  causing metallosis  and frank tissue necrosis . Histologic studies of MoM periprosthetic tissue have identified a characteristic pattern of DLI in the inner neocapsular layer and PVLI in the intermediate vascular layer [39, 40] suggestive of a DTH reaction. Although some authors have described these findings to be limited to MoM bearings [13, 29], careful review of the literature demonstrates prior descriptions of these chronic inflammatory cells in non-MoM implants [17, 26, 39]. The prevalence and role of this phenomenon in revision hip arthroplasty, both MoM and non-MoM, are not clear. It is thought metal-stimulated lymphocytes, as part of the adaptive immune response, can release osteolytic cytokines and contribute to aseptic loosening . Whether this process is related to the innate immune response and particle-stimulated macrophages [23, 39] or the local cytotoxicity and ulceration from metallic wear particles [13, 29] is unknown . We compared the incidence and severity of PVLI in failed hip metal-on-metal implants to non-metal-on-metal implants and TKA, PVLI in metal-on-metal and non-metal-on-metal hip arthroplasty based on reason for revision, and grade of PVLI to DLI and tissue reaction to metal particles.
There are several weaknesses in this study. First, it was not practical to include a control group of well-functioning implants to evaluate the presence of PVLI in surgical samples. Only autopsy samples could provide these data. Noninvasive tests for metal hypersensitivity such as dermal patch testing and lymphocyte transformation testing do not replicate the periprosthetic milieu , lack clinical validation , and are not widely accepted in the orthopaedic community [2, 21]. While the amount of metal released through corrosion by non-MoM implants would not likely change substantially based on implant integrity, well-positioned MoM implants are associated with lower wear rates and less metallosis [15, 16]. With fewer metallic particles, the prevalence of metal hypersensitivity reactions and PVLI may be reduced, but this correlation is not necessarily supported by this or other studies . Undoubtedly, a histologic study of healthy MoM and non-MoM implants would help determine whether ALVAL is a naturally occurring reaction to metal that only pathologically manifests itself in some patients or an indicator of problematic implants requiring revision. Second, only PVLI was the focus of this study. Although DLI, plasma cells, and macrophages with droplike inclusions similarly are components of ALVAL , PVLI was the prominent feature in first describing this phenomenon and associating it with a DTH reaction in contemporary literature . Third, histologic specimens were examined by a single pathologist only. While interobserver and intraobserver variability in histologic grading of ALVAL are known to exist (κ = 0.71, 0.68)  and could have potentially affected significance levels in this study, they are unlikely to alter the general trends found here.
In this study, PVLI occurred in 59% of MoM hip revisions, most extensively in cases of aseptic loosening and idiopathic pain. This supports the findings of previous authors [5, 31, 36]. In MoM failures, histologic findings of PVLI correlated strongly with the presence of DLI, another component of ALVAL, but did not correlate with periprosthetic particle storage and tissue reactions, indicators of metal particulate load. Several studies have similarly reported correlation between the extent of PVLI and DLI [5, 40] but not with local metallic particle burden [28, 36, 39, 40] or the extent of necrosis . Periprosthetic tissue from non-MoM bearings for a variety of reasons displayed an 18% rate of PVLI. Infectious diagnoses were associated with PVLI in 53% of all hip implants, and its prevalence may contribute to a higher rate of PVLI in TKA (40%) than hip arthroplasty (24%) as a whole. The association of PVLI and septic loosening is not new , but to the authors’ knowledge, the prevalence of PVLI in revision TKA has not been published.
Based on these findings, mild PVLI is present in a substantial proportion of failed total hip and knee prostheses, but higher levels of PVLI are most prominent in revised MoM bearings and TKA. Aseptic loosening and idiopathic pain in MoM hips are associated with PVLI, but metal particulate load is not. Additional studies are necessary to further elucidate the cause of PVLI in TKA and to prove whether these histologic characteristics suggestive of a DTH reaction in joint arthroplasty are primary instigators, secondary changes or merely incidental findings to adverse clinical processes.
We thank Sanita Bhatt, MD, for her assistance in pathologic interpretation of specimens, and Theodore Niemann, MD, for his assistance in photomicroscopy of specimens.
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