Todd P. Pierce, M.D. 
, David P. Martin, M.D., and Melvyn A. Harrington, M.D.
Department of Orthopedics, Baylor College of Medicine, Houston, Texas, USA
Correspondence to: toddpierce47@gmail.com
Additional information
- Ethical approval: exempt from IRB approval
- Consent: N/a
- Funding: No industry funding
- Conflicts of interest: N/a
- Author contribution: Todd P. Pierce – Manuscript composition, study design, data tabulation. David P. Martin – Study design, manuscript preparation . Melvyn A. Harrington – Study design; manuscript preparation
- Guarantor: Todd P. Pierce
- Provenance and peer-review:
Commissioned and externally peer-reviewed - Data availability statement: N/a
Keywords: inpatient complications, systemic lupus erythematosus, total knee arthroplasty.
Peer Review
Received: 5 August 2024
Revised: 23 September 2024
Accepted: 23 September 2024
Published: 3 October 2024
Abstract
Introduction: An increasing number of people diagnosed with systemic lupus erythematosus (SLE) will undergo total knee arthroplasty (TKA) for end-stage knee osteoarthritis. The purpose of this systematic review was to assess the cumulative inpatient complications of those with SLE who underwent TKA in comparison to those without this diagnosis.
Methods: A thorough review of 3 databases was performed to evaluate all potential complications of those who underwent TKA with and without a diagnosis of SLE. Following the completion of our search and review of manuscripts, we found 4 studies that were included in this systematic review consisting of 55,381 arthroplasties in patients with a diagnosis of SLE with 12,835,627 arthroplasties in the comparison cohort.
Results: The SLE cohort had an overall higher complication rate (25% versus 22%; p = 0.001). This cohort had a higher chance of postoperative anemia (11.7 versus 10.6%; p = 0.001) and a subsequent need for transfusion (11.1 versus 10.1%; p = 0.001), prosthetic joint infection (0.17 versus 0.11%; p = 0.001), wound infection (0.13 versus 0.09%; p = 0.001), pneumonia (0.5 versus 0.34%; p = 0.001), and cerebrovascular accident (0.03 versus 0.01%; p = 0.001). Mortality risk was lower within the SLE cohort ((0.04 versus 0.06%; p = 0.047). There was no difference in the risk of acute kidney injury (p = 0.15), venous thromboembolic disease (p = 0.33), periprosthetic fracture (p = 0.23), prosthetic dislocation (p = 0.53), and myocardial infarction (p = 0.11).
Discussion: Our results show that a diagnosis of SLE confers a higher risk of overall complications and multiple specific complications. However, SLE patients had a lower rate of mortality. Furthermore, there were multiple complications that those with SLE were not found to have a higher risk of suffering. Future studies should focus on how to optimize the safety and efficacy of TKA in the short- and long-term outcomes of patients with a diagnosis of SLE.
Introduction
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multiple clinical manifestations and an unpredictable clinical course that most commonly affects African American women of childbearing age.1–3 It has been shown that the cost can be approximately $30,000 over a 2-year period per patient.4 However, these patients have reported 10-year survival rates of greater than 90%.2,5,6 Given these survival rates and the multisystem nature of this disease, these patients require medical professionals in multiple subspecialties to ensure their appropriate treatment. Despite the fact that this disease involves multiple body systems, the most common presenting complaint is related to musculoskeletal symptoms, with more than 90% having a diagnosis of arthritis of major joints such as the knee.7 When knee arthritis progresses to a late-stage refractory to conservative treatment modalities, the definitive treatment is considered to be a total knee arthroplasty (TKA). A diagnosis of SLE confers approximately double the incidence of undergoing a TKA when compared to those without SLE.8,9 However, even with this increased need, there is some concern among practitioners that this cohort of patients has an increased risk of postoperative morbidity and mortality.10,11
There have been several small and large studies regarding the safety and efficacy of TKA in patients with SLE. However, to the best of our knowledge, there is a need for a systematic review of the literature to further elucidate inpatient outcomes. Therefore, the purpose of this systematic review was to assess the cumulative inpatient complications of those with SLE who underwent TKA in comparison to those without this diagnosis.
Methods
This work was exempt from institutional review board approval. This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines as well as A Measurement Tool to Assess Systematic Reviews version 2 (AMSTAR 2) guidelines (Appendix A and B).12,13 This study was registered with the research registry unique identifying number “reviewregistry1889”
(https://researchregistry.knack.com/researchregistry#registryofsystematicreviewsmetaanalyses/registryofsystematicreviewsmetaanalysesdetails/66f17fa92928ae02de9dcaa4/). A thorough review of the databases PubMed, EBSCOhost, and Scopus was performed to identify all studies addressing TKA in patients with a diagnosis of SLE. All articles published from January 2005 to July 2023 were identified using the following Boolean search string: total [title] AND knee [title] AND arthroplast*[title] AND lupus [title]. Given the evolution of surgical techniques over time, we chose to limit the potential of this confounder by narrowing our search between 2010 and 2023. These searches yielded a total of 54 reports.
The following reports were excluded: (1) non-English manuscripts; (2) isolated case reports; (3) studies with less than 5 subjects; (4) animal studies; and (5) review papers. Excluded were 24 reports, leaving 30 reports relevant for this review. Of these, 25 reports lacked the data needed for this study. Cross-referencing yielded no further additional sources for a total of 5 reports. After analyzing each report for raw data, 1 study was excluded for a lack of raw data, leaving a total of 4 studies that met inclusion criteria.14–17 These 4 studies consisted of 55,381 arthroplasties in patients with a diagnosis of SLE with 12,835,627 arthroplasties in the comparison cohort (Figure 1).
From this, we were able to specifically assess overall complication rate, mortality, acute kidney injury (AKI), postoperative anemia, need for transfusion, prosthetic joint infection (PJI), wound infection, deep venous thrombosis (DVT), pulmonary embolism (PE), periprosthetic fracture, prosthetic dislocation, pneumonia, cerebrovascular accident (CVA), and myocardial infarction (MI). All outcomes were tabulated into an Excel spreadsheet (Excel, Microsoft Corporation, Redmond, Washington) for statistical analysis. The statistical software GraphPad Prism version 5.01 (GraphPad Software Inc., La Jolla, California) was used for all statistical calculations. Statistical comparisons of proportions between cohorts were performed using a two-tailed Z-test to determine if there was a statistically significant difference. A p-value of less than 0.05 was considered significant.
Results
The final outcomes showed an overall higher complication rate in the SLE cohort as opposed to its comparison counterparts (25 versus 22%; p = 0.001). More specifically, those with SLE had a higher chance of postoperative anemia (11.7 versus 10.6%; p = 0.001) and a subsequent need for transfusion (11.1 versus 10.1%; p = 0.001), PJI (0.17 versus 0.11%; p = 0.001), wound infection (0.13 versus 0.09%; p = 0.001), pneumonia (0.5 versus 0.34%; p = 0.001), and CVA (0.03 versus 0.01%; p = 0.001). However, the mortality risk was decreased in those with a diagnosis of SLE (0.04 versus 0.06%; p = 0.047). There was no difference in the rates of AKI (p = 0.15), DVT/PE (p = 0.33), periprosthetic fracture (p = 0.23), prosthetic dislocation (p = 0.53), and MI (p = 0.11) (Table 1).
Table 1: Outcomes of Studies.
| p-value | Complications Rate | Mortality | AKI | Post-op anemia | Transfusion rate | PJI | Wound infection | DVT/PE | Perirposthetic Fx | Prosthetic dx | Pneumonia | CVA | MI |
| SLE | 24.7% | 0.04% | 0.61% | 11.71% | 11.10% | 0.17% | 0.13% | 0.29% | 0.03% | 0.04% | 0.50% | 0.03% | 0.03% |
| Control | 22.3% | 0.06% | 0.57% | 10.65% | 10.06% | 0.11% | 0.09% | 0.27% | 0.02% | 0.03% | 0.34% | 0.01% | 0.02% |
| p-value | 0.001 | 0.047 | 0.147 | 0.001 | 0.001 | 0.001 | 0.001 | 0.330 | 0.226 | 0.529 | 0.001 | 0.001 | 0.110 |
Discussion
SLE is a chronic autoimmune disorder that affects multiple organ systems and requires multidisciplinary care. Many of these patients have arthritis in major joints such as the knee, and may ultimately require a TKA for definitive pain management. Our systematic review aimed to determine if the inpatient outcomes of these patients were inferior to their counterparts. Our study showed that overall, SLE patients have a higher risk of complications. Specifically, these patients have a higher risk of complications such as postoperative anemia, PJI, wound complications, CVA, and pneumonia. However, these patients had a lower mortality rate compared to the control cohort. Unique to other studies, this provides a cumulative systematic review of outcomes following TKA in patients with a diagnosis of SLE.
Our study has several limitations. Our study only evaluates inpatient complications; hence, we cannot comment on any complications that may have occurred after discharge. Additionally, since this is a systematic review, we cannot account for the various nuances in perioperative care at different institutions. Furthermore, this study is unable to comment on the medical management of SLE patients and how well their symptoms were controlled up to the time of surgery. Moreover, the National Inpatient Sample (NIS) database does not record incidence numbers of 10 or fewer; hence, this may have had some impact on our findings. Despite these limitations, we believe that our study provides important insight into the potential perioperative outcomes of those with SLE following TKA when compared to the general population.
There are many studies that support the findings of this systematic review, particularly as it relates to anemia and the need for transfusions. Recently, Viswanathan et al. evaluated the inpatient outcomes of patients with SLE in comparison to those without that diagnosis using the NIS database from 2016 to 2019 (n = 2,094 SLE arthroplasties; 556,267 non-SLE arthroplasties).14 They found that those in the SLE cohort had substantially higher rates of postoperative anemia (OR = 1.3; 95% CI, 0.76 to 1.0; p = 0.001) and the need for subsequent transfusion (OR = 1.9; 95% CI, 0.53 to 1.0; p = 0.001). Similarly, Singh and Cleveland assessed these outcomes in SLE patients (n = 30,912 arthroplasties) when compared to a control cohort (n = 8,127,282 arthroplasties) using the NIS database from 1998 to 2014.12 They found a higher risk of transfusion in the SLE cohort (OR = 1.34; 95% CI, 1.25 to 1.42).
Additionally, this study found an increased risk of infectious complications. Similarly, in the aforementioned study by Viswanathan et al., they found that those with SLE had a substantially increased risk of periprosthetic joint infection (OR = 1.86; 95% CI, 0.54 to 1.0; p <0.001).14 Conversely, some smaller studies that did not meet inclusion criteria for this systematic review have failed to show an association between infectious complications and a diagnosis of SLE. Gholson et al. evaluated the inpatient outcomes using the NIS database from 2009 to 2011 of patients with SLE (n = 2,284 arthroplasties) who underwent TKA in relation to a matched cohort who underwent the same procedure without an SLE diagnosis (n = 6,852 arthroplasties).10 They found no association with either PJI (OR = 1; 95% CI, 0.14 to 7.15; p = 1) or wound infection (OR = 0.85; 95% CI, 0.35 to 2.05; p = 0.72). In addition, Fein et al. assessed short-term outcomes of 52 SLE patients with a 1:2 matched comparison cohort.18
They found no difference in the risk of PJI (p = 1) or wound infection (p = 0.11). However, these results should be interpreted cautiously, given that they are smaller studies and so may lack statistical power. Among medical complications, this study found pneumonia and CVA following TKA to be associated with SLE. The literature shows varied results regarding medical complications. Aziz et al. assessed the surgical and medical complications of those with SLE (n = 2,094) and those without SLE (n = 556,267) who underwent TKA using the NIS database from 2016 to 2019 [16]. They found an association between postoperative pneumonia and SLE following TKA (OR = 1.4, 95% CI, 1.1 to 1.9). However, this study did not find a similar association with CVA (OR = 0.9; 95% CI, 0.3 to 3.3). Similarly, the aforementioned matched study published by Fein et al. showed no difference in the rates of pneumonia (p = 0.99) or CVA (p = 1) among those with SLE and the control cohort.
One of the notable findings of this study was the fact that those with SLE had lower inpatient mortality rates. However, previous studies appear to show no difference. The study performed by Viswanathan et al. showed no association with mortality following TKA and SLE (p = 0.14).14 Additionally, the NIS database study published by Singh and Cleveland showed similar mortality rates between those with and without a diagnosis of SLE following TKA (OR 0.83, 95% CI, 0.34 to 2.0).15 Furthermore, there are multiple small studies showing no inpatient deaths following TKA in either the SLE or non-SLE cohorts.10 17,18 Additionally, it is important to note that many of these NIS database studies do not record numbers of 10 or fewer. Given that mortality is a low-prevalence event following TKA, it may be difficult to make determinations regarding an association between SLE and mortality following TKA.
Conclusion
In conclusion, this systematic review found an increase in certain peri-operative medical and surgical complications in the inpatient period of patients with SLE following a TKA. Specifically, there is an increased risk of postoperative anemia requiring transfusion, infectious complications, and CVA. However, there are multiple complications that showed no difference with this diagnosis. Hence, TKA for these patients can still be considered an effective treatment for knee arthritis refractory to conservative treatment modalities. Future studies should focus on how to optimize the safety and efficacy of TKA in the short- and long-term outcomes of patients with a diagnosis of SLE.
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