Date of Award

January 2012

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Carrie Swigart

Second Advisor

Lisa A. Mandl

Subject Area(s)

Medicine, Biomechanics, Immunology

Abstract

Anant Vasudevan, Edward F. DiCarlo, Timothy Wright, Dan Chen, Mark. P Figgie, Steven R. Goldring, Lisa A. Mandl. Department of Rheumatology, Hospital for Special Surgery, Weill Cornell Medical College, New York, NY. (Sponsored by Carrie Swigart, Department of Orthopaedics and Rehabilitation, Yale University School of Medicine).

In the setting of inflammatory arthritis, the histopathologic reaction to foreign body wear debris generated from a failing arthroplasty has not been definitively characterized. This study examined whether patients with rheumatoid arthritis (RA) demonstrate different patterns of prosthetic wear or cellular responses to implant wear debris compared to patients without inflammatory joint disease. Thirty-eight patients who had a primary revision of a total elbow arthroplasty (TEA) for aseptic loosening between 1996 and 2008 were identified. Twenty-five had RA and 13 had no inflammatory arthritis. Clinical data, gross wear patterns of the removed prostheses, and histopathological analyses of peri-implant tissue were compared between RA and non-RA patients. Evaluation of the retrieved prostheses showed that conformational change of the humeral polyethylene bushing was associated with the generation of polyethylene and metal particles. The amount and type of wear debris in peri-prosthetic tissues was similar in RA and non-RA patients. RA patients not on anti-tumor necrosis factor (TNF) therapy exhibited a histologic pattern of interstitial and sheet-like lymphocytic infiltrates associated with a high plasma cell composition, which was different from the predominantly perivascular infiltrates with few plasma cells seen in non-RA patients (p-value = 0.04). RA patients on anti-TNF therapy showed a mixed perivascular and interstitial pattern of infiltrates with variable plasma cell composition. Based on this data, we propose that RA patients exhibit a distinct cellular response to implant wear debris compared with non-RA patients. This reaction was unrelated to differences in the type or amount of wear debris and was mitigated by anti-TNF therapy. These results suggest an intrinsic alteration in immunoregulation in RA and have implications for potential immunologic treatment of osteolysis in these patients.

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This is an Open Access Thesis.

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