Arthroplasty/Joint Replacement

In shoulder arthroplasty, it is not uncommon for patients to receive postoperative blood transfusions; rates range from 7% to 43%.^1-6 Allogeneic blood transfusions (ABTs) are costly and not entirely free of risks.⁷ The risk for infection has decreased because of improved screening and risk reduction strategies, but there are still significant risks associated with ABTs, such as clerical errors, acute and delayed hemolytic reactions, graft-versus-host reactions, transfusion-related acute lung injury, and anaphylaxis.^8-10 As use of shoulder arthroplasty continues to increase, the importance of minimizing unnecessary transfusions is growing as well.⁷

Predictive factors for ABT have been explored in other orthopedic settings, yet little has been done in shoulder arthroplasty.^1-6,11-15 Previous shoulder arthroplasty studies have shown that low preoperative hemoglobin (Hb) levels are independent risk factors for postoperative blood transfusion. However, there is debate over the significance of other variables, such as procedure type, age, sex, and medical comorbidities. Further, prior studies were limited by relatively small samples from single institutions; the largest series included fewer than 600 patients.^1-6

We conducted a study to determine predictors of ABT in a large cohort of patients admitted to US hospitals for shoulder arthroplasty. We also wanted to evaluate the effect of ABT on postoperative outcomes, including inpatient mortality, adverse events, prolonged hospital stay, and nonroutine discharge. According to the null hypothesis, in shoulder arthroplasty there will be no difference in risk factors between patients who require ABT and those who did not, after accounting for confounding variables.

Materials and Methods

This study was exempt from institutional review board approval, as all data were appropriately deidentified before use in this project. We used the Nationwide Inpatient Sample (NIS) to retrospectively study the period 2002–2011, from which all demographic, clinical, and resource use data were derived.¹⁶ NIS, an annual survey conducted by the Agency for Healthcare Research and Quality (AHRQ) since 1988, has generated a huge amount of data, forming the largest all-payer inpatient care database in the United States. Yearly samples contain discharge data from about 8 million hospital stays at more than 1000 hospitals across 46 states, approximating a 20% random sample of all hospital discharges at participating institutions.¹⁷ These data are then weighted to generate statistically valid national estimates.

The NIS database uses International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) codes to identify 15 medical diagnoses up to the year 2008 and a maximum of 25 medical diagnoses and 15 procedures thereafter. In addition, the database includes information on patient and hospital characteristics as well as inpatient outcomes such as length of stay, total hospitalization charges, and discharge disposition.^18,19 Given its large sample size and data volume, NIS is a powerful tool in the analysis of data associated with a multitude of medical diagnoses and procedures.²⁰

We used the NIS database to study a population of 422,371 patients (age, >18 years) who underwent total shoulder arthroplasty (TSA) or hemiarthroplasty (HSA) between 2002 and 2011. ICD-9-CM procedure codes for TSA (81.80, 81.88) and HSA (81.81) were used to identify this population. We also analyzed data for reverse TSA for the year 2011. Then we divided our target population into 2 different cohorts: patients who did not receive any blood transfusion products and patients who received a transfusion of allogeneic packed cells (ICD-9-CM code 99.04 was used to identify the latter cohort).

In this study, normal distribution of the dataset was assumed, given the large sample size. The 2 cohorts were evaluated through bivariate analysis using the Pearson χ² test for categorical data and the independent-samples t test for continuous data. The extent to which diagnosis, age, race, sex, and medical comorbidities were predictive of blood transfusion after TSA or HSA was evaluated through multivariate binary logistic regression analysis. Statistical significance was set at P < .05. All statistical analyses and data modeling were performed with SPSS Version 22.0.

Results

Using the NIS database, we stratified an estimated 422,371 patients who presented for shoulder arthroplasty between January 1, 2002, and December 31, 2011, into a TSA cohort (59.3%) and an HSA cohort (40.7%). Eight percent (33,889) of all patients received an ABT; the proportion of patients who received ABT was higher (P < .001) for the HSA cohort (55.6%) than the TSA cohort (39.4%). Further, the rate of ABT after shoulder arthroplasty showed an upward inclination (Figure).

Demographically, patients who received ABT tended (P < .001) to be older (74±11 years vs 68±11 years) and of a minority race (black or Hispanic) and to fall in either the lowest range of median household income (21.5% vs 20.7%; ≤$38,999) or the highest (27.3% vs 25.4%; ≥$63,000). Shoulder arthroplasty with ABT occurred more often (P < .001) at hospitals that were urban (13.3% vs 11.3%), medium in size (27.3% vs 23.4%), and nonteaching (56.2% vs 54.3%). In addition, ABT was used more often (P < .001) in patients with a primary diagnosis of fracture (43.1% vs 14.3%) or fracture nonunion (4.4% vs 2.1%). These groups also had a longer (P < .001) hospital stay (5.0±4.3 days vs 2.5±2.2 days). Table 1 summarizes these findings.

The 2 cohorts were then analyzed for presence of medical comorbidities (Table 2). Patients who required ABT during shoulder arthroplasty had a significantly (P < .001) higher prevalence of congestive heart failure, chronic lung disease, hypertension, uncomplicated and complicated diabetes mellitus, liver disease, renal failure, fluid and electrolyte disorders, pulmonary circulatory disease, weight loss, coagulopathy, and deficiency anemia.

In multivariate regression modeling (Table 3), demographic predictors of ABT (P < .001) included increasing age (odds ratio [OR], 1.03 per year; 95% confidence interval [95% CI], 1.03-1.03), female sex (OR, 1.55; 95% CI, 1.51-1.60), and minority race (black or Hispanic). Odds of requiring ABT were higher for patients with Medicare (OR, 1.25; 95% CI, 1.20-1.30) and patients with Medicaid (OR, 1.63; 95% CI, 1.51-1.77) than for patients with private insurance.

ABT was more likely to be required (P < .001) in patients with a primary diagnosis of fracture (OR, 4.49; 95% CI, 4.34-4.65), avascular necrosis (OR, 2.06; 95% CI, 1.91-2.22), rheumatoid arthritis (OR, 1.91; 95% CI, 1.72-2.12), fracture nonunion (OR, 3.55; 95% CI, 3.33-3.79), or rotator cuff arthropathy (OR, 1.47; 95% CI, 1.41-1.54) than for patients with osteoarthritis. Moreover, compared with patients having HSA, patients having TSA were more likely to require ABT (OR, 1.20; 95% CI, 1.17-1.24). According to the analysis restricted to the year 2011, compared with patients having anatomical TSAs, patients having reverse TSAs were 1.6 times more likely (P < .001) to require ABT (OR, 1.63; 95% CI, 1.50-1.79).

With the exception of obesity, all comorbidities were significant (P < .001) independent predictors of ABT after shoulder arthroplasty: deficiency anemia (OR, 3.42; 95% CI, 3.32-3.52), coagulopathy (OR, 2.54; 95% CI, 2.36-2.73), fluid and electrolyte disorders (OR, 1.91; 95% CI, 1.84-1.97), and weight loss (OR, 1.78; 95% CI, 1.58-2.00).

Patients who received ABT were more likely to experience adverse events (OR, 1.74; 95% CI, 1.68-1.81), prolonged hospital stay (OR, 3.21; 95% CI, 3.12-3.30), and nonroutine discharge (OR, 1.77; 95% CI, 1.72-1.82) (Table 4). There was no difference in mortality between the 2 cohorts.

Discussion

There is an abundance of literature on blood transfusions in hip and knee arthroplasty, but there are few articles on ABT in shoulder arthroplasty, and they all report data from single institutions with relatively low caseloads.^{1,2,11-13,15,21} In the present study, we investigated ABT in shoulder arthroplasty from the perspective of a multi-institutional database with a caseload of more than 400,000. Given the rapidly increasing rates of shoulder arthroplasty, it is important to further examine this issue to minimize unnecessary blood transfusion and its associated risks and costs.⁷

We found that 8% of patients who had shoulder arthroplasty received ABT, which is consistent with previously reported transfusion rates (range, 7%-43%).^1-6 Rates of ABT after shoulder arthroplasty have continued to rise. The exception, a decrease during the year 2010, can be explained by increased efforts to more rigidly follow transfusion indication guidelines to reduce the number of potentially unnecessary ABTs.^21-24 Our study also identified numerous significant independent predictors of ABT in shoulder arthroplasty: age, sex, race, insurance status, procedure type, primary diagnoses, and multiple medical comorbidities.

Demographics

According to our analysis, more than 80% of patients who received ABT were over age 65 years, which aligns with what several other studies have demonstrated: Increasing age is a predictor of ABT, despite higher rates of comorbidities and lower preoperative Hb levels in this population.^{1,2,4,5,25-27} Consistent with previous work, female sex was predictive of ABT.^2,5 It has been suggested that females are more likely predisposed to ABT because of lower preoperative Hb and smaller blood mass.^2,5,28 Interestingly, our study showed a higher likelihood of ABT in both black and Hispanic populations. Further, patients with Medicare or Medicaid were more likely to receive ABT.

Primary Diagnosis

Although patients with a primary diagnosis of osteoarthritis constitute the majority of patients who undergo shoulder arthroplasty, our analysis showed that patients with a diagnosis of proximal humerus fracture were more likely to receive ABT. This finding is reasonable given studies showing the high prevalence of proximal humerus fractures in elderly women.^29,30 Similarly, patients with a humerus fracture nonunion were more likely to receive a blood transfusion, which is unsurprising given the increased complexity associated with arthroplasty in this predominately elderly population.³¹ Interestingly, compared with patients with osteoarthritis, patients with any one of the other primary diagnoses were more likely to require a transfusion—proximal humerus fracture being the most significant, followed by humerus fracture nonunion, avascular necrosis, rheumatoid arthritis, and rotator cuff arthropathy.

Type of Arthroplasty

Bivariate analysis revealed that 55.6% of the patients who received ABT underwent HSA; the other 44.4% underwent TSA. The effect of primary diagnosis on procedure choice likely played a role in this finding. HSA indications include humerus fracture, which has been associated with increased ABT, whereas patients with osteoarthritis requiring TSA are significantly less likely to require ABT, as reflected in this analysis.^7,32-34 Previous studies have failed to show a difference in blood transfusion rates between TSA and HSA.^2,4-6,35 Conversely, with confounding factors controlled for, multivariate logistic regression analysis showed that TSA was 1.2 times more likely than HSA to require ABT, which could be explained by the increased operative time, case complexity, and blood loss that may be associated with the glenoid exposure.^36,37 With analysis restricted to the year 2011, patients with reverse TSAs were 1.6 times more likely than patients with anatomical TSAs to receive a blood transfusion (OR, 1.63; 95% CI, 1.50-1.79). Although this finding differs from what was previously reported, it fits given that patients having reverse TSAs are often older and may present with a more significant comorbidity profile.³ In addition, there are the increased technical surgical aspects associated with “salvage surgery” for challenging indications such as cuff arthropathy and failed previous arthroplasty.^38-41

Medical Comorbidities

Patients who received ABT were more likely to present with numerous medical comorbidities. Previous studies have indicated that the presence of multiple medical comorbidities significantly increased blood transfusion rates, possibly by working synergistically.⁴² All studies of blood transfusion in shoulder arthroplasty concluded that lower preoperative Hb was an independent predictor.^1-6 Schumer and colleagues⁴ reported a 4-fold increase in likelihood of blood transfusion in patients with a preoperative Hb level less than 12.5 g/dL. In addition, Millett and colleagues⁶ showed a 20-fold increase in likelihood of transfusion in patients with a preoperative Hb level less than 11.0 g/dL compared with patients with a level higher than 13.0 g/dL. Patients with a Hb level between 11.0 and 13.0 g/dL showed a 5-fold increase in likelihood of transfusion.⁶ We should note that correction of preoperative anemia through various pharmacologic methods (eg, erythropoietin, intravenous iron supplementation) has been shown to decrease postoperative transfusion rates.^43,44 Although we could not include preoperative Hb levels in the present study, given inherent limitations in using NIS, our multivariate analysis showed that preoperative deficiency anemia and coagulopathy were the most significant predictors of ABT.

In addition, the multivariate logistic regression model showed that both cardiac disease and diabetes were independent predictors of ABT, confirming data reported by Ahmadi and colleagues.¹ Although not as well characterized in other studies, in the current analysis multiple other medical comorbidities, including fluid and electrolyte abnormalities, weight loss, liver disease, renal failure, and chronic lung disease, had significant predictive value. Contrarily, obesity significantly decreased the odds of ABT, likely because of higher baseline blood volume in obese patients.

Patient Outcomes

Patients who undergo shoulder arthroplasty with ABT are more likely to experience adverse events or a prolonged hospital stay and are more often discharged to a nursing home or an extended-care facility. In this population, however, deaths did not occur at a significantly higher rate—similar to what was found for patients who underwent hip or knee arthroplasty with blood transfusions.⁴⁵

Little has been done to investigate the effect of pharmacologic agents on the need for perioperative ABT for orthopedic shoulder procedures. Aprotinin, tranexamic acid, epoetin-α, and aminocaproic acid have all been effective in limiting ABT during the perioperative period in various orthopedic hip, knee, and spine procedures.^9,46-53 Given the increased morbidity associated with ABT, it may be beneficial to use similar methods to limit blood loss in high-risk patients undergoing shoulder arthroplasty.

Study Limitations

NIS has intrinsic limitations. Given its massive volume, it is subject to errors in both data entry and clinical coding. Moreover, the database lacks data that would have been useful in our study: preoperative Hb levels, intraoperative course, number of units transfused, total blood loss, use of blood conservation techniques, transfusion protocols, and severity of comorbidities. Reverse TSA was given a unique ICD-9-CM code in October 2010, so 2011 was the only year we were able to examine the relationship between reverse TSA and transfusions. Further, our analysis was unable to identify any medications, including chronic anticoagulants or postoperative prophylaxis, that have been shown to significantly affect blood transfusion rates.⁵⁴ Yet, there are obvious advantages to using the NIS database, as previously outlined across the medical landscape.

Conclusion

Our results confirmed previous findings and identified new predictors of ABT in shoulder arthroplasty in a large cohort. We examined demographics and perioperative complications while identifying predictors of ABT use. Patients who received ABT were older, female, and nonwhite and were covered by Medicare or Medicaid insurance, and many had a primary diagnosis of proximal humerus fracture. The ABT cohort had numerous medical comorbidities, including deficiency anemia and coagulopathy. Identifying this patient population is a prerequisite to educating patients while minimizing unnecessary risks and costs.

Using NIS data on a population of 422,371 patients who underwent shoulder arthroplasty, we identified the 5 likeliest predictors of ABT: fracture, fracture nonunion, deficiency anemia, coagulopathy, and avascular necrosis. Of the identified variables associated with ABT, deficiency anemia may be the most amenable to treatment; therefore, there may be benefit in delaying elective shoulder arthroplasty in this cohort. Given these findings, it is important to identify at-risk patients before surgery, with the intent to provide education and minimize risk.

In shoulder arthroplasty, it is not uncommon for patients to receive postoperative blood transfusions; rates range from 7% to 43%.^1-6 Allogeneic blood transfusions (ABTs) are costly and not entirely free of risks.⁷ The risk for infection has decreased because of improved screening and risk reduction strategies, but there are still significant risks associated with ABTs, such as clerical errors, acute and delayed hemolytic reactions, graft-versus-host reactions, transfusion-related acute lung injury, and anaphylaxis.^8-10 As use of shoulder arthroplasty continues to increase, the importance of minimizing unnecessary transfusions is growing as well.⁷

Predictive factors for ABT have been explored in other orthopedic settings, yet little has been done in shoulder arthroplasty.^1-6,11-15 Previous shoulder arthroplasty studies have shown that low preoperative hemoglobin (Hb) levels are independent risk factors for postoperative blood transfusion. However, there is debate over the significance of other variables, such as procedure type, age, sex, and medical comorbidities. Further, prior studies were limited by relatively small samples from single institutions; the largest series included fewer than 600 patients.^1-6

We conducted a study to determine predictors of ABT in a large cohort of patients admitted to US hospitals for shoulder arthroplasty. We also wanted to evaluate the effect of ABT on postoperative outcomes, including inpatient mortality, adverse events, prolonged hospital stay, and nonroutine discharge. According to the null hypothesis, in shoulder arthroplasty there will be no difference in risk factors between patients who require ABT and those who did not, after accounting for confounding variables.

Materials and Methods

This study was exempt from institutional review board approval, as all data were appropriately deidentified before use in this project. We used the Nationwide Inpatient Sample (NIS) to retrospectively study the period 2002–2011, from which all demographic, clinical, and resource use data were derived.¹⁶ NIS, an annual survey conducted by the Agency for Healthcare Research and Quality (AHRQ) since 1988, has generated a huge amount of data, forming the largest all-payer inpatient care database in the United States. Yearly samples contain discharge data from about 8 million hospital stays at more than 1000 hospitals across 46 states, approximating a 20% random sample of all hospital discharges at participating institutions.¹⁷ These data are then weighted to generate statistically valid national estimates.

The NIS database uses International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) codes to identify 15 medical diagnoses up to the year 2008 and a maximum of 25 medical diagnoses and 15 procedures thereafter. In addition, the database includes information on patient and hospital characteristics as well as inpatient outcomes such as length of stay, total hospitalization charges, and discharge disposition.^18,19 Given its large sample size and data volume, NIS is a powerful tool in the analysis of data associated with a multitude of medical diagnoses and procedures.²⁰

We used the NIS database to study a population of 422,371 patients (age, >18 years) who underwent total shoulder arthroplasty (TSA) or hemiarthroplasty (HSA) between 2002 and 2011. ICD-9-CM procedure codes for TSA (81.80, 81.88) and HSA (81.81) were used to identify this population. We also analyzed data for reverse TSA for the year 2011. Then we divided our target population into 2 different cohorts: patients who did not receive any blood transfusion products and patients who received a transfusion of allogeneic packed cells (ICD-9-CM code 99.04 was used to identify the latter cohort).

In this study, normal distribution of the dataset was assumed, given the large sample size. The 2 cohorts were evaluated through bivariate analysis using the Pearson χ² test for categorical data and the independent-samples t test for continuous data. The extent to which diagnosis, age, race, sex, and medical comorbidities were predictive of blood transfusion after TSA or HSA was evaluated through multivariate binary logistic regression analysis. Statistical significance was set at P < .05. All statistical analyses and data modeling were performed with SPSS Version 22.0.

Results

Using the NIS database, we stratified an estimated 422,371 patients who presented for shoulder arthroplasty between January 1, 2002, and December 31, 2011, into a TSA cohort (59.3%) and an HSA cohort (40.7%). Eight percent (33,889) of all patients received an ABT; the proportion of patients who received ABT was higher (P < .001) for the HSA cohort (55.6%) than the TSA cohort (39.4%). Further, the rate of ABT after shoulder arthroplasty showed an upward inclination (Figure).

Demographically, patients who received ABT tended (P < .001) to be older (74±11 years vs 68±11 years) and of a minority race (black or Hispanic) and to fall in either the lowest range of median household income (21.5% vs 20.7%; ≤$38,999) or the highest (27.3% vs 25.4%; ≥$63,000). Shoulder arthroplasty with ABT occurred more often (P < .001) at hospitals that were urban (13.3% vs 11.3%), medium in size (27.3% vs 23.4%), and nonteaching (56.2% vs 54.3%). In addition, ABT was used more often (P < .001) in patients with a primary diagnosis of fracture (43.1% vs 14.3%) or fracture nonunion (4.4% vs 2.1%). These groups also had a longer (P < .001) hospital stay (5.0±4.3 days vs 2.5±2.2 days). Table 1 summarizes these findings.

The 2 cohorts were then analyzed for presence of medical comorbidities (Table 2). Patients who required ABT during shoulder arthroplasty had a significantly (P < .001) higher prevalence of congestive heart failure, chronic lung disease, hypertension, uncomplicated and complicated diabetes mellitus, liver disease, renal failure, fluid and electrolyte disorders, pulmonary circulatory disease, weight loss, coagulopathy, and deficiency anemia.

In multivariate regression modeling (Table 3), demographic predictors of ABT (P < .001) included increasing age (odds ratio [OR], 1.03 per year; 95% confidence interval [95% CI], 1.03-1.03), female sex (OR, 1.55; 95% CI, 1.51-1.60), and minority race (black or Hispanic). Odds of requiring ABT were higher for patients with Medicare (OR, 1.25; 95% CI, 1.20-1.30) and patients with Medicaid (OR, 1.63; 95% CI, 1.51-1.77) than for patients with private insurance.

ABT was more likely to be required (P < .001) in patients with a primary diagnosis of fracture (OR, 4.49; 95% CI, 4.34-4.65), avascular necrosis (OR, 2.06; 95% CI, 1.91-2.22), rheumatoid arthritis (OR, 1.91; 95% CI, 1.72-2.12), fracture nonunion (OR, 3.55; 95% CI, 3.33-3.79), or rotator cuff arthropathy (OR, 1.47; 95% CI, 1.41-1.54) than for patients with osteoarthritis. Moreover, compared with patients having HSA, patients having TSA were more likely to require ABT (OR, 1.20; 95% CI, 1.17-1.24). According to the analysis restricted to the year 2011, compared with patients having anatomical TSAs, patients having reverse TSAs were 1.6 times more likely (P < .001) to require ABT (OR, 1.63; 95% CI, 1.50-1.79).

With the exception of obesity, all comorbidities were significant (P < .001) independent predictors of ABT after shoulder arthroplasty: deficiency anemia (OR, 3.42; 95% CI, 3.32-3.52), coagulopathy (OR, 2.54; 95% CI, 2.36-2.73), fluid and electrolyte disorders (OR, 1.91; 95% CI, 1.84-1.97), and weight loss (OR, 1.78; 95% CI, 1.58-2.00).

Patients who received ABT were more likely to experience adverse events (OR, 1.74; 95% CI, 1.68-1.81), prolonged hospital stay (OR, 3.21; 95% CI, 3.12-3.30), and nonroutine discharge (OR, 1.77; 95% CI, 1.72-1.82) (Table 4). There was no difference in mortality between the 2 cohorts.

Discussion

There is an abundance of literature on blood transfusions in hip and knee arthroplasty, but there are few articles on ABT in shoulder arthroplasty, and they all report data from single institutions with relatively low caseloads.^{1,2,11-13,15,21} In the present study, we investigated ABT in shoulder arthroplasty from the perspective of a multi-institutional database with a caseload of more than 400,000. Given the rapidly increasing rates of shoulder arthroplasty, it is important to further examine this issue to minimize unnecessary blood transfusion and its associated risks and costs.⁷

We found that 8% of patients who had shoulder arthroplasty received ABT, which is consistent with previously reported transfusion rates (range, 7%-43%).^1-6 Rates of ABT after shoulder arthroplasty have continued to rise. The exception, a decrease during the year 2010, can be explained by increased efforts to more rigidly follow transfusion indication guidelines to reduce the number of potentially unnecessary ABTs.^21-24 Our study also identified numerous significant independent predictors of ABT in shoulder arthroplasty: age, sex, race, insurance status, procedure type, primary diagnoses, and multiple medical comorbidities.

Demographics

According to our analysis, more than 80% of patients who received ABT were over age 65 years, which aligns with what several other studies have demonstrated: Increasing age is a predictor of ABT, despite higher rates of comorbidities and lower preoperative Hb levels in this population.^{1,2,4,5,25-27} Consistent with previous work, female sex was predictive of ABT.^2,5 It has been suggested that females are more likely predisposed to ABT because of lower preoperative Hb and smaller blood mass.^2,5,28 Interestingly, our study showed a higher likelihood of ABT in both black and Hispanic populations. Further, patients with Medicare or Medicaid were more likely to receive ABT.

Primary Diagnosis

Although patients with a primary diagnosis of osteoarthritis constitute the majority of patients who undergo shoulder arthroplasty, our analysis showed that patients with a diagnosis of proximal humerus fracture were more likely to receive ABT. This finding is reasonable given studies showing the high prevalence of proximal humerus fractures in elderly women.^29,30 Similarly, patients with a humerus fracture nonunion were more likely to receive a blood transfusion, which is unsurprising given the increased complexity associated with arthroplasty in this predominately elderly population.³¹ Interestingly, compared with patients with osteoarthritis, patients with any one of the other primary diagnoses were more likely to require a transfusion—proximal humerus fracture being the most significant, followed by humerus fracture nonunion, avascular necrosis, rheumatoid arthritis, and rotator cuff arthropathy.

Type of Arthroplasty

Bivariate analysis revealed that 55.6% of the patients who received ABT underwent HSA; the other 44.4% underwent TSA. The effect of primary diagnosis on procedure choice likely played a role in this finding. HSA indications include humerus fracture, which has been associated with increased ABT, whereas patients with osteoarthritis requiring TSA are significantly less likely to require ABT, as reflected in this analysis.^7,32-34 Previous studies have failed to show a difference in blood transfusion rates between TSA and HSA.^2,4-6,35 Conversely, with confounding factors controlled for, multivariate logistic regression analysis showed that TSA was 1.2 times more likely than HSA to require ABT, which could be explained by the increased operative time, case complexity, and blood loss that may be associated with the glenoid exposure.^36,37 With analysis restricted to the year 2011, patients with reverse TSAs were 1.6 times more likely than patients with anatomical TSAs to receive a blood transfusion (OR, 1.63; 95% CI, 1.50-1.79). Although this finding differs from what was previously reported, it fits given that patients having reverse TSAs are often older and may present with a more significant comorbidity profile.³ In addition, there are the increased technical surgical aspects associated with “salvage surgery” for challenging indications such as cuff arthropathy and failed previous arthroplasty.^38-41

Medical Comorbidities

Patients who received ABT were more likely to present with numerous medical comorbidities. Previous studies have indicated that the presence of multiple medical comorbidities significantly increased blood transfusion rates, possibly by working synergistically.⁴² All studies of blood transfusion in shoulder arthroplasty concluded that lower preoperative Hb was an independent predictor.^1-6 Schumer and colleagues⁴ reported a 4-fold increase in likelihood of blood transfusion in patients with a preoperative Hb level less than 12.5 g/dL. In addition, Millett and colleagues⁶ showed a 20-fold increase in likelihood of transfusion in patients with a preoperative Hb level less than 11.0 g/dL compared with patients with a level higher than 13.0 g/dL. Patients with a Hb level between 11.0 and 13.0 g/dL showed a 5-fold increase in likelihood of transfusion.⁶ We should note that correction of preoperative anemia through various pharmacologic methods (eg, erythropoietin, intravenous iron supplementation) has been shown to decrease postoperative transfusion rates.^43,44 Although we could not include preoperative Hb levels in the present study, given inherent limitations in using NIS, our multivariate analysis showed that preoperative deficiency anemia and coagulopathy were the most significant predictors of ABT.

In addition, the multivariate logistic regression model showed that both cardiac disease and diabetes were independent predictors of ABT, confirming data reported by Ahmadi and colleagues.¹ Although not as well characterized in other studies, in the current analysis multiple other medical comorbidities, including fluid and electrolyte abnormalities, weight loss, liver disease, renal failure, and chronic lung disease, had significant predictive value. Contrarily, obesity significantly decreased the odds of ABT, likely because of higher baseline blood volume in obese patients.

Patient Outcomes

Patients who undergo shoulder arthroplasty with ABT are more likely to experience adverse events or a prolonged hospital stay and are more often discharged to a nursing home or an extended-care facility. In this population, however, deaths did not occur at a significantly higher rate—similar to what was found for patients who underwent hip or knee arthroplasty with blood transfusions.⁴⁵

Little has been done to investigate the effect of pharmacologic agents on the need for perioperative ABT for orthopedic shoulder procedures. Aprotinin, tranexamic acid, epoetin-α, and aminocaproic acid have all been effective in limiting ABT during the perioperative period in various orthopedic hip, knee, and spine procedures.^9,46-53 Given the increased morbidity associated with ABT, it may be beneficial to use similar methods to limit blood loss in high-risk patients undergoing shoulder arthroplasty.

Study Limitations

NIS has intrinsic limitations. Given its massive volume, it is subject to errors in both data entry and clinical coding. Moreover, the database lacks data that would have been useful in our study: preoperative Hb levels, intraoperative course, number of units transfused, total blood loss, use of blood conservation techniques, transfusion protocols, and severity of comorbidities. Reverse TSA was given a unique ICD-9-CM code in October 2010, so 2011 was the only year we were able to examine the relationship between reverse TSA and transfusions. Further, our analysis was unable to identify any medications, including chronic anticoagulants or postoperative prophylaxis, that have been shown to significantly affect blood transfusion rates.⁵⁴ Yet, there are obvious advantages to using the NIS database, as previously outlined across the medical landscape.

Conclusion

Our results confirmed previous findings and identified new predictors of ABT in shoulder arthroplasty in a large cohort. We examined demographics and perioperative complications while identifying predictors of ABT use. Patients who received ABT were older, female, and nonwhite and were covered by Medicare or Medicaid insurance, and many had a primary diagnosis of proximal humerus fracture. The ABT cohort had numerous medical comorbidities, including deficiency anemia and coagulopathy. Identifying this patient population is a prerequisite to educating patients while minimizing unnecessary risks and costs.

Using NIS data on a population of 422,371 patients who underwent shoulder arthroplasty, we identified the 5 likeliest predictors of ABT: fracture, fracture nonunion, deficiency anemia, coagulopathy, and avascular necrosis. Of the identified variables associated with ABT, deficiency anemia may be the most amenable to treatment; therefore, there may be benefit in delaying elective shoulder arthroplasty in this cohort. Given these findings, it is important to identify at-risk patients before surgery, with the intent to provide education and minimize risk.

In shoulder arthroplasty, it is not uncommon for patients to receive postoperative blood transfusions; rates range from 7% to 43%.^1-6 Allogeneic blood transfusions (ABTs) are costly and not entirely free of risks.⁷ The risk for infection has decreased because of improved screening and risk reduction strategies, but there are still significant risks associated with ABTs, such as clerical errors, acute and delayed hemolytic reactions, graft-versus-host reactions, transfusion-related acute lung injury, and anaphylaxis.^8-10 As use of shoulder arthroplasty continues to increase, the importance of minimizing unnecessary transfusions is growing as well.⁷

Predictive factors for ABT have been explored in other orthopedic settings, yet little has been done in shoulder arthroplasty.^1-6,11-15 Previous shoulder arthroplasty studies have shown that low preoperative hemoglobin (Hb) levels are independent risk factors for postoperative blood transfusion. However, there is debate over the significance of other variables, such as procedure type, age, sex, and medical comorbidities. Further, prior studies were limited by relatively small samples from single institutions; the largest series included fewer than 600 patients.^1-6

We conducted a study to determine predictors of ABT in a large cohort of patients admitted to US hospitals for shoulder arthroplasty. We also wanted to evaluate the effect of ABT on postoperative outcomes, including inpatient mortality, adverse events, prolonged hospital stay, and nonroutine discharge. According to the null hypothesis, in shoulder arthroplasty there will be no difference in risk factors between patients who require ABT and those who did not, after accounting for confounding variables.

Materials and Methods

This study was exempt from institutional review board approval, as all data were appropriately deidentified before use in this project. We used the Nationwide Inpatient Sample (NIS) to retrospectively study the period 2002–2011, from which all demographic, clinical, and resource use data were derived.¹⁶ NIS, an annual survey conducted by the Agency for Healthcare Research and Quality (AHRQ) since 1988, has generated a huge amount of data, forming the largest all-payer inpatient care database in the United States. Yearly samples contain discharge data from about 8 million hospital stays at more than 1000 hospitals across 46 states, approximating a 20% random sample of all hospital discharges at participating institutions.¹⁷ These data are then weighted to generate statistically valid national estimates.

The NIS database uses International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) codes to identify 15 medical diagnoses up to the year 2008 and a maximum of 25 medical diagnoses and 15 procedures thereafter. In addition, the database includes information on patient and hospital characteristics as well as inpatient outcomes such as length of stay, total hospitalization charges, and discharge disposition.^18,19 Given its large sample size and data volume, NIS is a powerful tool in the analysis of data associated with a multitude of medical diagnoses and procedures.²⁰

We used the NIS database to study a population of 422,371 patients (age, >18 years) who underwent total shoulder arthroplasty (TSA) or hemiarthroplasty (HSA) between 2002 and 2011. ICD-9-CM procedure codes for TSA (81.80, 81.88) and HSA (81.81) were used to identify this population. We also analyzed data for reverse TSA for the year 2011. Then we divided our target population into 2 different cohorts: patients who did not receive any blood transfusion products and patients who received a transfusion of allogeneic packed cells (ICD-9-CM code 99.04 was used to identify the latter cohort).

In this study, normal distribution of the dataset was assumed, given the large sample size. The 2 cohorts were evaluated through bivariate analysis using the Pearson χ² test for categorical data and the independent-samples t test for continuous data. The extent to which diagnosis, age, race, sex, and medical comorbidities were predictive of blood transfusion after TSA or HSA was evaluated through multivariate binary logistic regression analysis. Statistical significance was set at P < .05. All statistical analyses and data modeling were performed with SPSS Version 22.0.

Results

Using the NIS database, we stratified an estimated 422,371 patients who presented for shoulder arthroplasty between January 1, 2002, and December 31, 2011, into a TSA cohort (59.3%) and an HSA cohort (40.7%). Eight percent (33,889) of all patients received an ABT; the proportion of patients who received ABT was higher (P < .001) for the HSA cohort (55.6%) than the TSA cohort (39.4%). Further, the rate of ABT after shoulder arthroplasty showed an upward inclination (Figure).

Demographically, patients who received ABT tended (P < .001) to be older (74±11 years vs 68±11 years) and of a minority race (black or Hispanic) and to fall in either the lowest range of median household income (21.5% vs 20.7%; ≤$38,999) or the highest (27.3% vs 25.4%; ≥$63,000). Shoulder arthroplasty with ABT occurred more often (P < .001) at hospitals that were urban (13.3% vs 11.3%), medium in size (27.3% vs 23.4%), and nonteaching (56.2% vs 54.3%). In addition, ABT was used more often (P < .001) in patients with a primary diagnosis of fracture (43.1% vs 14.3%) or fracture nonunion (4.4% vs 2.1%). These groups also had a longer (P < .001) hospital stay (5.0±4.3 days vs 2.5±2.2 days). Table 1 summarizes these findings.

The 2 cohorts were then analyzed for presence of medical comorbidities (Table 2). Patients who required ABT during shoulder arthroplasty had a significantly (P < .001) higher prevalence of congestive heart failure, chronic lung disease, hypertension, uncomplicated and complicated diabetes mellitus, liver disease, renal failure, fluid and electrolyte disorders, pulmonary circulatory disease, weight loss, coagulopathy, and deficiency anemia.

In multivariate regression modeling (Table 3), demographic predictors of ABT (P < .001) included increasing age (odds ratio [OR], 1.03 per year; 95% confidence interval [95% CI], 1.03-1.03), female sex (OR, 1.55; 95% CI, 1.51-1.60), and minority race (black or Hispanic). Odds of requiring ABT were higher for patients with Medicare (OR, 1.25; 95% CI, 1.20-1.30) and patients with Medicaid (OR, 1.63; 95% CI, 1.51-1.77) than for patients with private insurance.

ABT was more likely to be required (P < .001) in patients with a primary diagnosis of fracture (OR, 4.49; 95% CI, 4.34-4.65), avascular necrosis (OR, 2.06; 95% CI, 1.91-2.22), rheumatoid arthritis (OR, 1.91; 95% CI, 1.72-2.12), fracture nonunion (OR, 3.55; 95% CI, 3.33-3.79), or rotator cuff arthropathy (OR, 1.47; 95% CI, 1.41-1.54) than for patients with osteoarthritis. Moreover, compared with patients having HSA, patients having TSA were more likely to require ABT (OR, 1.20; 95% CI, 1.17-1.24). According to the analysis restricted to the year 2011, compared with patients having anatomical TSAs, patients having reverse TSAs were 1.6 times more likely (P < .001) to require ABT (OR, 1.63; 95% CI, 1.50-1.79).

With the exception of obesity, all comorbidities were significant (P < .001) independent predictors of ABT after shoulder arthroplasty: deficiency anemia (OR, 3.42; 95% CI, 3.32-3.52), coagulopathy (OR, 2.54; 95% CI, 2.36-2.73), fluid and electrolyte disorders (OR, 1.91; 95% CI, 1.84-1.97), and weight loss (OR, 1.78; 95% CI, 1.58-2.00).

Patients who received ABT were more likely to experience adverse events (OR, 1.74; 95% CI, 1.68-1.81), prolonged hospital stay (OR, 3.21; 95% CI, 3.12-3.30), and nonroutine discharge (OR, 1.77; 95% CI, 1.72-1.82) (Table 4). There was no difference in mortality between the 2 cohorts.

Discussion

There is an abundance of literature on blood transfusions in hip and knee arthroplasty, but there are few articles on ABT in shoulder arthroplasty, and they all report data from single institutions with relatively low caseloads.^{1,2,11-13,15,21} In the present study, we investigated ABT in shoulder arthroplasty from the perspective of a multi-institutional database with a caseload of more than 400,000. Given the rapidly increasing rates of shoulder arthroplasty, it is important to further examine this issue to minimize unnecessary blood transfusion and its associated risks and costs.⁷

We found that 8% of patients who had shoulder arthroplasty received ABT, which is consistent with previously reported transfusion rates (range, 7%-43%).^1-6 Rates of ABT after shoulder arthroplasty have continued to rise. The exception, a decrease during the year 2010, can be explained by increased efforts to more rigidly follow transfusion indication guidelines to reduce the number of potentially unnecessary ABTs.^21-24 Our study also identified numerous significant independent predictors of ABT in shoulder arthroplasty: age, sex, race, insurance status, procedure type, primary diagnoses, and multiple medical comorbidities.

Demographics

According to our analysis, more than 80% of patients who received ABT were over age 65 years, which aligns with what several other studies have demonstrated: Increasing age is a predictor of ABT, despite higher rates of comorbidities and lower preoperative Hb levels in this population.^{1,2,4,5,25-27} Consistent with previous work, female sex was predictive of ABT.^2,5 It has been suggested that females are more likely predisposed to ABT because of lower preoperative Hb and smaller blood mass.^2,5,28 Interestingly, our study showed a higher likelihood of ABT in both black and Hispanic populations. Further, patients with Medicare or Medicaid were more likely to receive ABT.

Primary Diagnosis

Although patients with a primary diagnosis of osteoarthritis constitute the majority of patients who undergo shoulder arthroplasty, our analysis showed that patients with a diagnosis of proximal humerus fracture were more likely to receive ABT. This finding is reasonable given studies showing the high prevalence of proximal humerus fractures in elderly women.^29,30 Similarly, patients with a humerus fracture nonunion were more likely to receive a blood transfusion, which is unsurprising given the increased complexity associated with arthroplasty in this predominately elderly population.³¹ Interestingly, compared with patients with osteoarthritis, patients with any one of the other primary diagnoses were more likely to require a transfusion—proximal humerus fracture being the most significant, followed by humerus fracture nonunion, avascular necrosis, rheumatoid arthritis, and rotator cuff arthropathy.

Type of Arthroplasty

Bivariate analysis revealed that 55.6% of the patients who received ABT underwent HSA; the other 44.4% underwent TSA. The effect of primary diagnosis on procedure choice likely played a role in this finding. HSA indications include humerus fracture, which has been associated with increased ABT, whereas patients with osteoarthritis requiring TSA are significantly less likely to require ABT, as reflected in this analysis.^7,32-34 Previous studies have failed to show a difference in blood transfusion rates between TSA and HSA.^2,4-6,35 Conversely, with confounding factors controlled for, multivariate logistic regression analysis showed that TSA was 1.2 times more likely than HSA to require ABT, which could be explained by the increased operative time, case complexity, and blood loss that may be associated with the glenoid exposure.^36,37 With analysis restricted to the year 2011, patients with reverse TSAs were 1.6 times more likely than patients with anatomical TSAs to receive a blood transfusion (OR, 1.63; 95% CI, 1.50-1.79). Although this finding differs from what was previously reported, it fits given that patients having reverse TSAs are often older and may present with a more significant comorbidity profile.³ In addition, there are the increased technical surgical aspects associated with “salvage surgery” for challenging indications such as cuff arthropathy and failed previous arthroplasty.^38-41

Medical Comorbidities

Patients who received ABT were more likely to present with numerous medical comorbidities. Previous studies have indicated that the presence of multiple medical comorbidities significantly increased blood transfusion rates, possibly by working synergistically.⁴² All studies of blood transfusion in shoulder arthroplasty concluded that lower preoperative Hb was an independent predictor.^1-6 Schumer and colleagues⁴ reported a 4-fold increase in likelihood of blood transfusion in patients with a preoperative Hb level less than 12.5 g/dL. In addition, Millett and colleagues⁶ showed a 20-fold increase in likelihood of transfusion in patients with a preoperative Hb level less than 11.0 g/dL compared with patients with a level higher than 13.0 g/dL. Patients with a Hb level between 11.0 and 13.0 g/dL showed a 5-fold increase in likelihood of transfusion.⁶ We should note that correction of preoperative anemia through various pharmacologic methods (eg, erythropoietin, intravenous iron supplementation) has been shown to decrease postoperative transfusion rates.^43,44 Although we could not include preoperative Hb levels in the present study, given inherent limitations in using NIS, our multivariate analysis showed that preoperative deficiency anemia and coagulopathy were the most significant predictors of ABT.

In addition, the multivariate logistic regression model showed that both cardiac disease and diabetes were independent predictors of ABT, confirming data reported by Ahmadi and colleagues.¹ Although not as well characterized in other studies, in the current analysis multiple other medical comorbidities, including fluid and electrolyte abnormalities, weight loss, liver disease, renal failure, and chronic lung disease, had significant predictive value. Contrarily, obesity significantly decreased the odds of ABT, likely because of higher baseline blood volume in obese patients.

Patient Outcomes

Patients who undergo shoulder arthroplasty with ABT are more likely to experience adverse events or a prolonged hospital stay and are more often discharged to a nursing home or an extended-care facility. In this population, however, deaths did not occur at a significantly higher rate—similar to what was found for patients who underwent hip or knee arthroplasty with blood transfusions.⁴⁵

Little has been done to investigate the effect of pharmacologic agents on the need for perioperative ABT for orthopedic shoulder procedures. Aprotinin, tranexamic acid, epoetin-α, and aminocaproic acid have all been effective in limiting ABT during the perioperative period in various orthopedic hip, knee, and spine procedures.^9,46-53 Given the increased morbidity associated with ABT, it may be beneficial to use similar methods to limit blood loss in high-risk patients undergoing shoulder arthroplasty.

Study Limitations

NIS has intrinsic limitations. Given its massive volume, it is subject to errors in both data entry and clinical coding. Moreover, the database lacks data that would have been useful in our study: preoperative Hb levels, intraoperative course, number of units transfused, total blood loss, use of blood conservation techniques, transfusion protocols, and severity of comorbidities. Reverse TSA was given a unique ICD-9-CM code in October 2010, so 2011 was the only year we were able to examine the relationship between reverse TSA and transfusions. Further, our analysis was unable to identify any medications, including chronic anticoagulants or postoperative prophylaxis, that have been shown to significantly affect blood transfusion rates.⁵⁴ Yet, there are obvious advantages to using the NIS database, as previously outlined across the medical landscape.

Conclusion

Our results confirmed previous findings and identified new predictors of ABT in shoulder arthroplasty in a large cohort. We examined demographics and perioperative complications while identifying predictors of ABT use. Patients who received ABT were older, female, and nonwhite and were covered by Medicare or Medicaid insurance, and many had a primary diagnosis of proximal humerus fracture. The ABT cohort had numerous medical comorbidities, including deficiency anemia and coagulopathy. Identifying this patient population is a prerequisite to educating patients while minimizing unnecessary risks and costs.

Using NIS data on a population of 422,371 patients who underwent shoulder arthroplasty, we identified the 5 likeliest predictors of ABT: fracture, fracture nonunion, deficiency anemia, coagulopathy, and avascular necrosis. Of the identified variables associated with ABT, deficiency anemia may be the most amenable to treatment; therefore, there may be benefit in delaying elective shoulder arthroplasty in this cohort. Given these findings, it is important to identify at-risk patients before surgery, with the intent to provide education and minimize risk.

National Hockey League (NHL), Major League Soccer (MLS), and US Olympic/World Cup Ski/Snowboard (Olympic) athletes receive orthopedic care from a select group of surgeons. There are 30 NHL teams, 19 MLS teams, 1 Olympic ski team, and 1 Olympic snowboard team, for a total of 51 teams and a rough total of 2229 athletes (1500 NHL, 570 MLS, 159 Olympic).¹

Studies have shown that MLS athletes and X-Game skiers and snowboarders have performed well on return to sport (RTS) after anterior cruciate ligament (ACL) reconstruction.^2,3 However, the techniques, graft choices, and rehabilitation protocols used to return these elite athletes to their preinjury level of performance have not been elucidated. It is unclear if the treatment given to these elite athletes differs from that given to recreational athletes and nonathletes. Bradley and colleagues⁴ examined how 32 NFL team orthopedists treated ACL tears, and Erickson and colleagues⁵ recently surveyed NFL and National Collegiate Athletic Association (NCAA) team physicians to determine practice patterns (eg, surgical techniques, graft choices, postoperative protocols) in treating ACL tears. Until now, however, no one has examined NHL, MLS, or Olympic team orthopedic surgeons’ practice patterns as they relate to ACL reconstruction.

We conducted an online survey of NHL, MLS, and Olympic team orthopedic surgeons to determine practice patterns relating to ACL reconstruction in elite athletes. Given the practice patterns of surgeons in our practice, we hypothesized that the surveyed surgeons treating these elite athletes would most commonly use bone–patellar tendon–bone (BPTB) autograft with a single-bundle technique. We also hypothesized that they would permit RTS without a brace at a minimum of 6 months after surgery, with a normal physical examination, and after successful completion of a structured battery of RTS tests.

Materials and Methods

On the SurveyMonkey website (http://www.surveymonkey.com), we created a 7-question base survey, with other questions added for the NHL and MLS surveys (Figure 1). We sent this survey to 94 team orthopedic surgeons (41 NHL, 26 MLS, 27 Olympic) identified through Internet searches and direct contact with team public relations departments. The survey was approved by MLS and NHL research committees. In 2013, each survey was sent out 5 times. The response rates for each round are shown in Figure 2. All responses remained confidential; we did not learn surgeons’ identities. Data were collected and analyzed through the SurveyMonkey website. Each surgeon was instructed to respond to all relevant questions in the survey. The survey was designed such that the participant could not submit the survey without answering all the questions. Descriptive statistics were calculated for each study and parameter analyzed. Continuous variable data are reported as means and standard deviations (weighted means where applicable). Categorical data are reported as frequencies with percentages.

Results

Of the 94 team orthopedic surgeons surveyed, 47 (50%) responded (NHL, 49%; MLS, 50%; Olympic, 52%). Mean (SD) experience as a team physician was 7.73 (5.33) years (range, 2-20 years) for NHL, 6.77 (6.64) years (range, 2-20 years) for MLS, and 1.14 (0.36) years (range, 1-10 years) for Olympic. Mean (SD) number of ACL reconstructions performed in 2012 was 101 (51) for NHL (range, 50-200), 78 (38) for MLS (range, 20-150), and 110 (105) for Olympic (range, 25-175) (Table 1). Of the 47 surgeons, 42 (89.4%) used autograft in the treatment of elite athletes, and 5 (10.6%) used allograft. Autograft choices were BPTB (n = 33; 70.2%), 4-strand semitendinosus (n = 7; 14.9%), and quadriceps (n = 2; 4.3%); allograft choices were 4-strand semitendinosus (n = 4; 8.5%) and BPTB (n = 1; 2.1%) (Table 2).

Of the 40 surgeons (85.1%) who indicated they would use autograft in 25-year-old recreational athletes, 25 (53.2%) would use BPTB, 13 (27.7%) would use 4-strand semitendinosus, and 2 (4.3%) would use quadriceps; of the 7 who indicated they would use allograft, 4 (8.5%) would use 4-strand semitendinosus, and 3 (6.4%) would use BPTB. In the NHL and MLS surveys, 19 surgeons (57.6%) indicated they would use autograft (6 would use BPTB, 13 would use 4-strand semitendinosus), and 14 (42.4%) would use allograft (7 would use BPTB, 5 would use Achilles, and 2 would use tibialis anterior) in 35-year-old recreational athletes.

Twenty-one surgeons (44.7%) were drilling the femoral tunnel through a transtibial portal, 36.2% through an anteromedial portal, and 12.8% using a 2-incision technique. All surgeons indicated they were using a single-bundle technique in ACL reconstruction. Thirty-three surgeons (70.2%) did not recommend a brace for their elite athletes on RTS. Olympic team surgeons had the highest rate of brace wear in RTS (50%, both skiers and snowboarders); NHL and MLS surgeons had significantly lower rates (25% and 15.4%, respectively) (Table 3).

Twenty (60.6%) of the NHL and MLS surgeons recommended waiting at least 6 months before RTS; 2 (6.1%) recommended waiting at least 9 months; no surgeon recommended waiting at least 12 months; and the others did not have a specific time frame for RTS. Twenty-seven surgeons (81.8%) recommended RTS after an athlete passed a series of RTS tests (eg, Vail, single-leg hop). Nineteen surgeons (57.6%) recommended waiting until the athlete had full range of motion, no pain, full strength, and subjective stability in the knee. Physicians could choose more than one answer for the previous question, allowing for a total percentage higher than 100%.

Discussion

The goal of this study was to determine how NHL, MLS, and Olympic team orthopedic surgeons manage ACL tears in elite and recreational athletes. Our study hypotheses were confirmed, as 70.2% of those surveyed used BPTB autograft for elite athletes, 100% used the single-bundle technique, 70.2% did not require a brace on RTS, 81.8% recommended RTS after the athlete passed a series of RTS tests (eg, Vail, single-leg hop), and 60.6% waited at least 6 months after surgery.

As soccer and skiing are the top 2 sports in which participants sustain ACL tears, it is necessary to report how surgeons obtain successful results in these patient populations.⁶ Using the US and Norwegian ACL reconstruction registries, Granan and colleagues⁶ found that, over a 7-year period, 5760 ACL tears occurred during soccer, and 2030 occurred during skiing. The scope of ACL injuries is broad, and treatment patterns must be elucidated. Although most surgeons do not treat elite athletes, many high school and college athletes compete at very high levels. Therefore, replicating the methods of the surgeons who treat elite athletes may be warranted.

In our survey, autograft (89.4%), particularly BPTB autograft (70.2%), was the most common graft choice for elite athletes. The rate of allograft use (42.4%) was higher for 35-year-old recreational athletes. As BPTB autograft produces reliable long-term results, this graft type is a reasonable choice.⁷ However, only 18% of our surveyed orthopedic surgeons indicated they would use BPTB autograft in older, recreational athletes. This stark difference is likely related to the more than 40% long-term side effects of anterior knee pain and graft harvest site morbidity with BPTB autograft as opposed to allograft and other types of autograft.^8,9 Younger patients may be more willing to accept some anterior knee pain to ensure bone-to-bone healing with BPTB autograft. This shift in graft choice may also reflect the desire to minimize skin incisions and their resulting scars, especially in female recreational athletes.

In a meta-analysis of more than 5000 patients, Kraeutler and colleagues⁷ found that BPTB autograft outperformed allograft according to several knee scores, including Lysholm and Tegner, and had a lower re-rupture rate (4.3% vs 12.7%). However, despite the superior performance of BPTB autograft, graft choice cannot overcome surgeon error in graft placement.¹⁰ BPTB autograft appears to remain the gold standard for ACL reconstruction for many reasons, including low failure rates and decreased costs.¹¹ Recently, investigators have tried to challenge the superiority of BPTB autograft. In a retrospective case–control study, Mascarenhas and colleagues¹² found that hamstring autograft afforded patients better extension and higher subjective outcome scores. Bourke and colleagues¹³ found a higher rate of contralateral ACL rupture in patients treated with BPTB autograft compared with hamstring autograft.

According to this survey, 44.7% of surgeons indicated they drilled the femoral tunnel through a transtibial portal, 36.2% used an anteromedial portal, and 12.8% used the 2-incision technique. These methods were recently evaluated to determine if any is superior to the others, but the study results were not definitive.¹⁴ Franceschi and colleagues¹⁵ found improved rotational and anterior stability of the knee with use of an anteromedial approach, but their findings were not clinically or functionally significant. Wang and colleagues¹⁶ found an extension loss in the late-stance phase of gait with the anteromedial approach; the transtibial approach was correlated with inferior anterior-posterior stability during the stance phase of gait. Therefore, our results parallel those in the current literature in that the surveyed population is split on which technique to use and likely bases its practice on comfort level and residency/fellowship training.

Limitations

This study had several limitations. First, it provided level V evidence of team physicians in 3 major sports. Although some of these physicians were also treating athletes in other sports, our survey targeted NHL, MLS, and Olympic athletes. It did not address all ages and both sexes—which is significant, given the higher rate of ACL tears in females. All NHL and MLS players are male, and there was a high rate of BPTB graft use in these sports. However, recreational athletes include both males and females, and the fact that some surgeons would choose a hamstring graft for a female for cosmetic reasons must not be overlooked. Conversely, that there was no difference in the number of BPTB autografts chosen between NHL and MLS surgeons versus Olympic surgeons, where females are included (all chose about 60% BPTB autografts for their elite athletes), disputes this limitation. Our survey response rate was 50%. Other studies have had similar rates in relation to ACL practices,¹⁷ especially elite team physicians’ practices,⁵ and recent literature has confirmed that lower response rates in surveys did not alter results and may in fact have improved results.^18,19 This percentage could be falsely low if some of our email addresses were incorrect. This rate also raises the possibility of selection bias, as surgeons who routinely used allograft in their athlete population may not have wanted to admit this. It is possible that some NHL, MLS, and Olympic athletes were treated by surgeons not included in this survey (in some cases, a non–team surgeon may have performed the athlete’s surgery). This survey did not address concomitant knee pathology or cover all possible technique variables.

Conclusion

Most of the NHL, MLS, and Olympic team orthopedic surgeons who were surveyed perform their ACL reconstructions using BPTB autograft, using a single-bundle technique, through a transtibial portal, and do not require bracing for their athletes returning to sport. Most required their athletes to complete a series of RTS tests before resuming competitive play.

National Hockey League (NHL), Major League Soccer (MLS), and US Olympic/World Cup Ski/Snowboard (Olympic) athletes receive orthopedic care from a select group of surgeons. There are 30 NHL teams, 19 MLS teams, 1 Olympic ski team, and 1 Olympic snowboard team, for a total of 51 teams and a rough total of 2229 athletes (1500 NHL, 570 MLS, 159 Olympic).¹

Studies have shown that MLS athletes and X-Game skiers and snowboarders have performed well on return to sport (RTS) after anterior cruciate ligament (ACL) reconstruction.^2,3 However, the techniques, graft choices, and rehabilitation protocols used to return these elite athletes to their preinjury level of performance have not been elucidated. It is unclear if the treatment given to these elite athletes differs from that given to recreational athletes and nonathletes. Bradley and colleagues⁴ examined how 32 NFL team orthopedists treated ACL tears, and Erickson and colleagues⁵ recently surveyed NFL and National Collegiate Athletic Association (NCAA) team physicians to determine practice patterns (eg, surgical techniques, graft choices, postoperative protocols) in treating ACL tears. Until now, however, no one has examined NHL, MLS, or Olympic team orthopedic surgeons’ practice patterns as they relate to ACL reconstruction.

We conducted an online survey of NHL, MLS, and Olympic team orthopedic surgeons to determine practice patterns relating to ACL reconstruction in elite athletes. Given the practice patterns of surgeons in our practice, we hypothesized that the surveyed surgeons treating these elite athletes would most commonly use bone–patellar tendon–bone (BPTB) autograft with a single-bundle technique. We also hypothesized that they would permit RTS without a brace at a minimum of 6 months after surgery, with a normal physical examination, and after successful completion of a structured battery of RTS tests.

Materials and Methods

On the SurveyMonkey website (http://www.surveymonkey.com), we created a 7-question base survey, with other questions added for the NHL and MLS surveys (Figure 1). We sent this survey to 94 team orthopedic surgeons (41 NHL, 26 MLS, 27 Olympic) identified through Internet searches and direct contact with team public relations departments. The survey was approved by MLS and NHL research committees. In 2013, each survey was sent out 5 times. The response rates for each round are shown in Figure 2. All responses remained confidential; we did not learn surgeons’ identities. Data were collected and analyzed through the SurveyMonkey website. Each surgeon was instructed to respond to all relevant questions in the survey. The survey was designed such that the participant could not submit the survey without answering all the questions. Descriptive statistics were calculated for each study and parameter analyzed. Continuous variable data are reported as means and standard deviations (weighted means where applicable). Categorical data are reported as frequencies with percentages.

Results

Of the 94 team orthopedic surgeons surveyed, 47 (50%) responded (NHL, 49%; MLS, 50%; Olympic, 52%). Mean (SD) experience as a team physician was 7.73 (5.33) years (range, 2-20 years) for NHL, 6.77 (6.64) years (range, 2-20 years) for MLS, and 1.14 (0.36) years (range, 1-10 years) for Olympic. Mean (SD) number of ACL reconstructions performed in 2012 was 101 (51) for NHL (range, 50-200), 78 (38) for MLS (range, 20-150), and 110 (105) for Olympic (range, 25-175) (Table 1). Of the 47 surgeons, 42 (89.4%) used autograft in the treatment of elite athletes, and 5 (10.6%) used allograft. Autograft choices were BPTB (n = 33; 70.2%), 4-strand semitendinosus (n = 7; 14.9%), and quadriceps (n = 2; 4.3%); allograft choices were 4-strand semitendinosus (n = 4; 8.5%) and BPTB (n = 1; 2.1%) (Table 2).

Of the 40 surgeons (85.1%) who indicated they would use autograft in 25-year-old recreational athletes, 25 (53.2%) would use BPTB, 13 (27.7%) would use 4-strand semitendinosus, and 2 (4.3%) would use quadriceps; of the 7 who indicated they would use allograft, 4 (8.5%) would use 4-strand semitendinosus, and 3 (6.4%) would use BPTB. In the NHL and MLS surveys, 19 surgeons (57.6%) indicated they would use autograft (6 would use BPTB, 13 would use 4-strand semitendinosus), and 14 (42.4%) would use allograft (7 would use BPTB, 5 would use Achilles, and 2 would use tibialis anterior) in 35-year-old recreational athletes.

Twenty-one surgeons (44.7%) were drilling the femoral tunnel through a transtibial portal, 36.2% through an anteromedial portal, and 12.8% using a 2-incision technique. All surgeons indicated they were using a single-bundle technique in ACL reconstruction. Thirty-three surgeons (70.2%) did not recommend a brace for their elite athletes on RTS. Olympic team surgeons had the highest rate of brace wear in RTS (50%, both skiers and snowboarders); NHL and MLS surgeons had significantly lower rates (25% and 15.4%, respectively) (Table 3).

Twenty (60.6%) of the NHL and MLS surgeons recommended waiting at least 6 months before RTS; 2 (6.1%) recommended waiting at least 9 months; no surgeon recommended waiting at least 12 months; and the others did not have a specific time frame for RTS. Twenty-seven surgeons (81.8%) recommended RTS after an athlete passed a series of RTS tests (eg, Vail, single-leg hop). Nineteen surgeons (57.6%) recommended waiting until the athlete had full range of motion, no pain, full strength, and subjective stability in the knee. Physicians could choose more than one answer for the previous question, allowing for a total percentage higher than 100%.

Discussion

The goal of this study was to determine how NHL, MLS, and Olympic team orthopedic surgeons manage ACL tears in elite and recreational athletes. Our study hypotheses were confirmed, as 70.2% of those surveyed used BPTB autograft for elite athletes, 100% used the single-bundle technique, 70.2% did not require a brace on RTS, 81.8% recommended RTS after the athlete passed a series of RTS tests (eg, Vail, single-leg hop), and 60.6% waited at least 6 months after surgery.

As soccer and skiing are the top 2 sports in which participants sustain ACL tears, it is necessary to report how surgeons obtain successful results in these patient populations.⁶ Using the US and Norwegian ACL reconstruction registries, Granan and colleagues⁶ found that, over a 7-year period, 5760 ACL tears occurred during soccer, and 2030 occurred during skiing. The scope of ACL injuries is broad, and treatment patterns must be elucidated. Although most surgeons do not treat elite athletes, many high school and college athletes compete at very high levels. Therefore, replicating the methods of the surgeons who treat elite athletes may be warranted.

In our survey, autograft (89.4%), particularly BPTB autograft (70.2%), was the most common graft choice for elite athletes. The rate of allograft use (42.4%) was higher for 35-year-old recreational athletes. As BPTB autograft produces reliable long-term results, this graft type is a reasonable choice.⁷ However, only 18% of our surveyed orthopedic surgeons indicated they would use BPTB autograft in older, recreational athletes. This stark difference is likely related to the more than 40% long-term side effects of anterior knee pain and graft harvest site morbidity with BPTB autograft as opposed to allograft and other types of autograft.^8,9 Younger patients may be more willing to accept some anterior knee pain to ensure bone-to-bone healing with BPTB autograft. This shift in graft choice may also reflect the desire to minimize skin incisions and their resulting scars, especially in female recreational athletes.

In a meta-analysis of more than 5000 patients, Kraeutler and colleagues⁷ found that BPTB autograft outperformed allograft according to several knee scores, including Lysholm and Tegner, and had a lower re-rupture rate (4.3% vs 12.7%). However, despite the superior performance of BPTB autograft, graft choice cannot overcome surgeon error in graft placement.¹⁰ BPTB autograft appears to remain the gold standard for ACL reconstruction for many reasons, including low failure rates and decreased costs.¹¹ Recently, investigators have tried to challenge the superiority of BPTB autograft. In a retrospective case–control study, Mascarenhas and colleagues¹² found that hamstring autograft afforded patients better extension and higher subjective outcome scores. Bourke and colleagues¹³ found a higher rate of contralateral ACL rupture in patients treated with BPTB autograft compared with hamstring autograft.

According to this survey, 44.7% of surgeons indicated they drilled the femoral tunnel through a transtibial portal, 36.2% used an anteromedial portal, and 12.8% used the 2-incision technique. These methods were recently evaluated to determine if any is superior to the others, but the study results were not definitive.¹⁴ Franceschi and colleagues¹⁵ found improved rotational and anterior stability of the knee with use of an anteromedial approach, but their findings were not clinically or functionally significant. Wang and colleagues¹⁶ found an extension loss in the late-stance phase of gait with the anteromedial approach; the transtibial approach was correlated with inferior anterior-posterior stability during the stance phase of gait. Therefore, our results parallel those in the current literature in that the surveyed population is split on which technique to use and likely bases its practice on comfort level and residency/fellowship training.

Limitations

This study had several limitations. First, it provided level V evidence of team physicians in 3 major sports. Although some of these physicians were also treating athletes in other sports, our survey targeted NHL, MLS, and Olympic athletes. It did not address all ages and both sexes—which is significant, given the higher rate of ACL tears in females. All NHL and MLS players are male, and there was a high rate of BPTB graft use in these sports. However, recreational athletes include both males and females, and the fact that some surgeons would choose a hamstring graft for a female for cosmetic reasons must not be overlooked. Conversely, that there was no difference in the number of BPTB autografts chosen between NHL and MLS surgeons versus Olympic surgeons, where females are included (all chose about 60% BPTB autografts for their elite athletes), disputes this limitation. Our survey response rate was 50%. Other studies have had similar rates in relation to ACL practices,¹⁷ especially elite team physicians’ practices,⁵ and recent literature has confirmed that lower response rates in surveys did not alter results and may in fact have improved results.^18,19 This percentage could be falsely low if some of our email addresses were incorrect. This rate also raises the possibility of selection bias, as surgeons who routinely used allograft in their athlete population may not have wanted to admit this. It is possible that some NHL, MLS, and Olympic athletes were treated by surgeons not included in this survey (in some cases, a non–team surgeon may have performed the athlete’s surgery). This survey did not address concomitant knee pathology or cover all possible technique variables.

Conclusion

Most of the NHL, MLS, and Olympic team orthopedic surgeons who were surveyed perform their ACL reconstructions using BPTB autograft, using a single-bundle technique, through a transtibial portal, and do not require bracing for their athletes returning to sport. Most required their athletes to complete a series of RTS tests before resuming competitive play.

National Hockey League (NHL), Major League Soccer (MLS), and US Olympic/World Cup Ski/Snowboard (Olympic) athletes receive orthopedic care from a select group of surgeons. There are 30 NHL teams, 19 MLS teams, 1 Olympic ski team, and 1 Olympic snowboard team, for a total of 51 teams and a rough total of 2229 athletes (1500 NHL, 570 MLS, 159 Olympic).¹

Studies have shown that MLS athletes and X-Game skiers and snowboarders have performed well on return to sport (RTS) after anterior cruciate ligament (ACL) reconstruction.^2,3 However, the techniques, graft choices, and rehabilitation protocols used to return these elite athletes to their preinjury level of performance have not been elucidated. It is unclear if the treatment given to these elite athletes differs from that given to recreational athletes and nonathletes. Bradley and colleagues⁴ examined how 32 NFL team orthopedists treated ACL tears, and Erickson and colleagues⁵ recently surveyed NFL and National Collegiate Athletic Association (NCAA) team physicians to determine practice patterns (eg, surgical techniques, graft choices, postoperative protocols) in treating ACL tears. Until now, however, no one has examined NHL, MLS, or Olympic team orthopedic surgeons’ practice patterns as they relate to ACL reconstruction.

We conducted an online survey of NHL, MLS, and Olympic team orthopedic surgeons to determine practice patterns relating to ACL reconstruction in elite athletes. Given the practice patterns of surgeons in our practice, we hypothesized that the surveyed surgeons treating these elite athletes would most commonly use bone–patellar tendon–bone (BPTB) autograft with a single-bundle technique. We also hypothesized that they would permit RTS without a brace at a minimum of 6 months after surgery, with a normal physical examination, and after successful completion of a structured battery of RTS tests.

Materials and Methods

On the SurveyMonkey website (http://www.surveymonkey.com), we created a 7-question base survey, with other questions added for the NHL and MLS surveys (Figure 1). We sent this survey to 94 team orthopedic surgeons (41 NHL, 26 MLS, 27 Olympic) identified through Internet searches and direct contact with team public relations departments. The survey was approved by MLS and NHL research committees. In 2013, each survey was sent out 5 times. The response rates for each round are shown in Figure 2. All responses remained confidential; we did not learn surgeons’ identities. Data were collected and analyzed through the SurveyMonkey website. Each surgeon was instructed to respond to all relevant questions in the survey. The survey was designed such that the participant could not submit the survey without answering all the questions. Descriptive statistics were calculated for each study and parameter analyzed. Continuous variable data are reported as means and standard deviations (weighted means where applicable). Categorical data are reported as frequencies with percentages.

Results

Of the 94 team orthopedic surgeons surveyed, 47 (50%) responded (NHL, 49%; MLS, 50%; Olympic, 52%). Mean (SD) experience as a team physician was 7.73 (5.33) years (range, 2-20 years) for NHL, 6.77 (6.64) years (range, 2-20 years) for MLS, and 1.14 (0.36) years (range, 1-10 years) for Olympic. Mean (SD) number of ACL reconstructions performed in 2012 was 101 (51) for NHL (range, 50-200), 78 (38) for MLS (range, 20-150), and 110 (105) for Olympic (range, 25-175) (Table 1). Of the 47 surgeons, 42 (89.4%) used autograft in the treatment of elite athletes, and 5 (10.6%) used allograft. Autograft choices were BPTB (n = 33; 70.2%), 4-strand semitendinosus (n = 7; 14.9%), and quadriceps (n = 2; 4.3%); allograft choices were 4-strand semitendinosus (n = 4; 8.5%) and BPTB (n = 1; 2.1%) (Table 2).

Of the 40 surgeons (85.1%) who indicated they would use autograft in 25-year-old recreational athletes, 25 (53.2%) would use BPTB, 13 (27.7%) would use 4-strand semitendinosus, and 2 (4.3%) would use quadriceps; of the 7 who indicated they would use allograft, 4 (8.5%) would use 4-strand semitendinosus, and 3 (6.4%) would use BPTB. In the NHL and MLS surveys, 19 surgeons (57.6%) indicated they would use autograft (6 would use BPTB, 13 would use 4-strand semitendinosus), and 14 (42.4%) would use allograft (7 would use BPTB, 5 would use Achilles, and 2 would use tibialis anterior) in 35-year-old recreational athletes.

Twenty-one surgeons (44.7%) were drilling the femoral tunnel through a transtibial portal, 36.2% through an anteromedial portal, and 12.8% using a 2-incision technique. All surgeons indicated they were using a single-bundle technique in ACL reconstruction. Thirty-three surgeons (70.2%) did not recommend a brace for their elite athletes on RTS. Olympic team surgeons had the highest rate of brace wear in RTS (50%, both skiers and snowboarders); NHL and MLS surgeons had significantly lower rates (25% and 15.4%, respectively) (Table 3).

Twenty (60.6%) of the NHL and MLS surgeons recommended waiting at least 6 months before RTS; 2 (6.1%) recommended waiting at least 9 months; no surgeon recommended waiting at least 12 months; and the others did not have a specific time frame for RTS. Twenty-seven surgeons (81.8%) recommended RTS after an athlete passed a series of RTS tests (eg, Vail, single-leg hop). Nineteen surgeons (57.6%) recommended waiting until the athlete had full range of motion, no pain, full strength, and subjective stability in the knee. Physicians could choose more than one answer for the previous question, allowing for a total percentage higher than 100%.

Discussion

The goal of this study was to determine how NHL, MLS, and Olympic team orthopedic surgeons manage ACL tears in elite and recreational athletes. Our study hypotheses were confirmed, as 70.2% of those surveyed used BPTB autograft for elite athletes, 100% used the single-bundle technique, 70.2% did not require a brace on RTS, 81.8% recommended RTS after the athlete passed a series of RTS tests (eg, Vail, single-leg hop), and 60.6% waited at least 6 months after surgery.

As soccer and skiing are the top 2 sports in which participants sustain ACL tears, it is necessary to report how surgeons obtain successful results in these patient populations.⁶ Using the US and Norwegian ACL reconstruction registries, Granan and colleagues⁶ found that, over a 7-year period, 5760 ACL tears occurred during soccer, and 2030 occurred during skiing. The scope of ACL injuries is broad, and treatment patterns must be elucidated. Although most surgeons do not treat elite athletes, many high school and college athletes compete at very high levels. Therefore, replicating the methods of the surgeons who treat elite athletes may be warranted.

In our survey, autograft (89.4%), particularly BPTB autograft (70.2%), was the most common graft choice for elite athletes. The rate of allograft use (42.4%) was higher for 35-year-old recreational athletes. As BPTB autograft produces reliable long-term results, this graft type is a reasonable choice.⁷ However, only 18% of our surveyed orthopedic surgeons indicated they would use BPTB autograft in older, recreational athletes. This stark difference is likely related to the more than 40% long-term side effects of anterior knee pain and graft harvest site morbidity with BPTB autograft as opposed to allograft and other types of autograft.^8,9 Younger patients may be more willing to accept some anterior knee pain to ensure bone-to-bone healing with BPTB autograft. This shift in graft choice may also reflect the desire to minimize skin incisions and their resulting scars, especially in female recreational athletes.

In a meta-analysis of more than 5000 patients, Kraeutler and colleagues⁷ found that BPTB autograft outperformed allograft according to several knee scores, including Lysholm and Tegner, and had a lower re-rupture rate (4.3% vs 12.7%). However, despite the superior performance of BPTB autograft, graft choice cannot overcome surgeon error in graft placement.¹⁰ BPTB autograft appears to remain the gold standard for ACL reconstruction for many reasons, including low failure rates and decreased costs.¹¹ Recently, investigators have tried to challenge the superiority of BPTB autograft. In a retrospective case–control study, Mascarenhas and colleagues¹² found that hamstring autograft afforded patients better extension and higher subjective outcome scores. Bourke and colleagues¹³ found a higher rate of contralateral ACL rupture in patients treated with BPTB autograft compared with hamstring autograft.

According to this survey, 44.7% of surgeons indicated they drilled the femoral tunnel through a transtibial portal, 36.2% used an anteromedial portal, and 12.8% used the 2-incision technique. These methods were recently evaluated to determine if any is superior to the others, but the study results were not definitive.¹⁴ Franceschi and colleagues¹⁵ found improved rotational and anterior stability of the knee with use of an anteromedial approach, but their findings were not clinically or functionally significant. Wang and colleagues¹⁶ found an extension loss in the late-stance phase of gait with the anteromedial approach; the transtibial approach was correlated with inferior anterior-posterior stability during the stance phase of gait. Therefore, our results parallel those in the current literature in that the surveyed population is split on which technique to use and likely bases its practice on comfort level and residency/fellowship training.

Limitations

This study had several limitations. First, it provided level V evidence of team physicians in 3 major sports. Although some of these physicians were also treating athletes in other sports, our survey targeted NHL, MLS, and Olympic athletes. It did not address all ages and both sexes—which is significant, given the higher rate of ACL tears in females. All NHL and MLS players are male, and there was a high rate of BPTB graft use in these sports. However, recreational athletes include both males and females, and the fact that some surgeons would choose a hamstring graft for a female for cosmetic reasons must not be overlooked. Conversely, that there was no difference in the number of BPTB autografts chosen between NHL and MLS surgeons versus Olympic surgeons, where females are included (all chose about 60% BPTB autografts for their elite athletes), disputes this limitation. Our survey response rate was 50%. Other studies have had similar rates in relation to ACL practices,¹⁷ especially elite team physicians’ practices,⁵ and recent literature has confirmed that lower response rates in surveys did not alter results and may in fact have improved results.^18,19 This percentage could be falsely low if some of our email addresses were incorrect. This rate also raises the possibility of selection bias, as surgeons who routinely used allograft in their athlete population may not have wanted to admit this. It is possible that some NHL, MLS, and Olympic athletes were treated by surgeons not included in this survey (in some cases, a non–team surgeon may have performed the athlete’s surgery). This survey did not address concomitant knee pathology or cover all possible technique variables.

Conclusion

Most of the NHL, MLS, and Olympic team orthopedic surgeons who were surveyed perform their ACL reconstructions using BPTB autograft, using a single-bundle technique, through a transtibial portal, and do not require bracing for their athletes returning to sport. Most required their athletes to complete a series of RTS tests before resuming competitive play.

Magnetic resonance imaging (MRI) is the preferred modality in the evaluation of complications of anterior cruciate ligament reconstruction (ACL-R).^1-3 ACL-R complications may be broadly characterized as those resulting in decreased range of motion (ROM), eg, arthrofibrosis and impingement, and those resulting in increased laxity, ie, graft disruption.⁴ Short tau inversion recovery (STIR) sequences best minimize artifact related to field inhomogeneity in the presence of metal-containing fixation devices. Patients with contraindications to MRI may undergo high-resolution computed tomographic arthrography of the knee for evaluation of postoperative graft abnormalities.¹

Arthrofibrosis refers to focal or diffuse synovial scar tissue, which may limit ROM. Preoperative irritation, preoperative limited ROM, and reconstruction within 4 weeks of trauma may all play a role in the development of arthrofibrosis.^5,6 The focal form, cyclops lesion, named for its arthroscopic appearance, has been reported in 1% to 10% of patients with ACL-R.¹ On MRI, focal arthrofibrosis may be seen as a focal or diffuse intermediate signal lesion in the anterior intercondylar notch extending linearly along the intercondylar roof¹ (Figure 1).

MRI can be used to accurately determine the position of the femoral and tibial tunnels. Correct femoral tunnel position results in isometry of the graft during full ROM of the knee. Graft impingement can occur when the tibial tunnel is placed too far anteriorly such that the graft contacts the roof of the intercondylar notch before the knee is able to fully extend.⁷ A tibial tunnel placed anterior to the intersection of the Blumensaat line and the tibia is at higher risk for impingement.^1,4 Impingement may be accompanied by signal change in the graft on intermediate-weighted and fluid-sensitive sequences. The signal abnormality is usually focal and persists longer than the expected signal changes related to revascularization of immature grafts within the first year (Figure 2). If left untreated, impingement may progress to graft rupture.⁴

Complete graft rupture is diagnosed on the basis of discontinuity of the graft fibers. MRI findings include fluid-filled defect or absence of intact graft fibers. Other reliable signs include large joint effusion, anterior tibial translation, pivot-shift–type marrow edema pattern, and horizontal orientation, laxity, or resorption of the graft fibers.^1,8,9 The diagnosis of partial graft rupture may be challenging, as there are several other causes of increased graft signal, including revascularization (within 12 months after procedure), signal heterogeneity between individual bundles of hamstring grafts, and focal signal changes related to impingment (Figures 3, 4).

Fluid within the tunnels is a normal finding after surgery and typically resolves within the first 18 months.¹ Cyst formation within the tibial tunnel is an uncommon complication of ACL-R and may be incidental to or present with clinical symptoms caused by extension into the pretibial soft tissues or expansion of the tunnel (Figure 5). Communication of cyst with joint space is important, as a noncommunicating cyst requires simple excision without need for bone grafting.⁷

Hardware-related complications (eg, loosening of fixation devices) are uncommon but may require revision surgery (Figure 6). Septic arthritis after ACL-R has a cumulative incidence of 0.1% to 0.9% and may be difficult to diagnose clinically because of the lack of classic symptoms of a septic joint.¹ Diagnosis requires joint aspiration.

MRI is reliably and accurately used to assess ACL-R complications. The clinical history helps in stratifying complications that result in decreased ROM or increased laxity.

Magnetic resonance imaging (MRI) is the preferred modality in the evaluation of complications of anterior cruciate ligament reconstruction (ACL-R).^1-3 ACL-R complications may be broadly characterized as those resulting in decreased range of motion (ROM), eg, arthrofibrosis and impingement, and those resulting in increased laxity, ie, graft disruption.⁴ Short tau inversion recovery (STIR) sequences best minimize artifact related to field inhomogeneity in the presence of metal-containing fixation devices. Patients with contraindications to MRI may undergo high-resolution computed tomographic arthrography of the knee for evaluation of postoperative graft abnormalities.¹

Arthrofibrosis refers to focal or diffuse synovial scar tissue, which may limit ROM. Preoperative irritation, preoperative limited ROM, and reconstruction within 4 weeks of trauma may all play a role in the development of arthrofibrosis.^5,6 The focal form, cyclops lesion, named for its arthroscopic appearance, has been reported in 1% to 10% of patients with ACL-R.¹ On MRI, focal arthrofibrosis may be seen as a focal or diffuse intermediate signal lesion in the anterior intercondylar notch extending linearly along the intercondylar roof¹ (Figure 1).

MRI can be used to accurately determine the position of the femoral and tibial tunnels. Correct femoral tunnel position results in isometry of the graft during full ROM of the knee. Graft impingement can occur when the tibial tunnel is placed too far anteriorly such that the graft contacts the roof of the intercondylar notch before the knee is able to fully extend.⁷ A tibial tunnel placed anterior to the intersection of the Blumensaat line and the tibia is at higher risk for impingement.^1,4 Impingement may be accompanied by signal change in the graft on intermediate-weighted and fluid-sensitive sequences. The signal abnormality is usually focal and persists longer than the expected signal changes related to revascularization of immature grafts within the first year (Figure 2). If left untreated, impingement may progress to graft rupture.⁴

Complete graft rupture is diagnosed on the basis of discontinuity of the graft fibers. MRI findings include fluid-filled defect or absence of intact graft fibers. Other reliable signs include large joint effusion, anterior tibial translation, pivot-shift–type marrow edema pattern, and horizontal orientation, laxity, or resorption of the graft fibers.^1,8,9 The diagnosis of partial graft rupture may be challenging, as there are several other causes of increased graft signal, including revascularization (within 12 months after procedure), signal heterogeneity between individual bundles of hamstring grafts, and focal signal changes related to impingment (Figures 3, 4).

Fluid within the tunnels is a normal finding after surgery and typically resolves within the first 18 months.¹ Cyst formation within the tibial tunnel is an uncommon complication of ACL-R and may be incidental to or present with clinical symptoms caused by extension into the pretibial soft tissues or expansion of the tunnel (Figure 5). Communication of cyst with joint space is important, as a noncommunicating cyst requires simple excision without need for bone grafting.⁷

Hardware-related complications (eg, loosening of fixation devices) are uncommon but may require revision surgery (Figure 6). Septic arthritis after ACL-R has a cumulative incidence of 0.1% to 0.9% and may be difficult to diagnose clinically because of the lack of classic symptoms of a septic joint.¹ Diagnosis requires joint aspiration.

MRI is reliably and accurately used to assess ACL-R complications. The clinical history helps in stratifying complications that result in decreased ROM or increased laxity.

Magnetic resonance imaging (MRI) is the preferred modality in the evaluation of complications of anterior cruciate ligament reconstruction (ACL-R).^1-3 ACL-R complications may be broadly characterized as those resulting in decreased range of motion (ROM), eg, arthrofibrosis and impingement, and those resulting in increased laxity, ie, graft disruption.⁴ Short tau inversion recovery (STIR) sequences best minimize artifact related to field inhomogeneity in the presence of metal-containing fixation devices. Patients with contraindications to MRI may undergo high-resolution computed tomographic arthrography of the knee for evaluation of postoperative graft abnormalities.¹

Arthrofibrosis refers to focal or diffuse synovial scar tissue, which may limit ROM. Preoperative irritation, preoperative limited ROM, and reconstruction within 4 weeks of trauma may all play a role in the development of arthrofibrosis.^5,6 The focal form, cyclops lesion, named for its arthroscopic appearance, has been reported in 1% to 10% of patients with ACL-R.¹ On MRI, focal arthrofibrosis may be seen as a focal or diffuse intermediate signal lesion in the anterior intercondylar notch extending linearly along the intercondylar roof¹ (Figure 1).

MRI can be used to accurately determine the position of the femoral and tibial tunnels. Correct femoral tunnel position results in isometry of the graft during full ROM of the knee. Graft impingement can occur when the tibial tunnel is placed too far anteriorly such that the graft contacts the roof of the intercondylar notch before the knee is able to fully extend.⁷ A tibial tunnel placed anterior to the intersection of the Blumensaat line and the tibia is at higher risk for impingement.^1,4 Impingement may be accompanied by signal change in the graft on intermediate-weighted and fluid-sensitive sequences. The signal abnormality is usually focal and persists longer than the expected signal changes related to revascularization of immature grafts within the first year (Figure 2). If left untreated, impingement may progress to graft rupture.⁴

Complete graft rupture is diagnosed on the basis of discontinuity of the graft fibers. MRI findings include fluid-filled defect or absence of intact graft fibers. Other reliable signs include large joint effusion, anterior tibial translation, pivot-shift–type marrow edema pattern, and horizontal orientation, laxity, or resorption of the graft fibers.^1,8,9 The diagnosis of partial graft rupture may be challenging, as there are several other causes of increased graft signal, including revascularization (within 12 months after procedure), signal heterogeneity between individual bundles of hamstring grafts, and focal signal changes related to impingment (Figures 3, 4).

Fluid within the tunnels is a normal finding after surgery and typically resolves within the first 18 months.¹ Cyst formation within the tibial tunnel is an uncommon complication of ACL-R and may be incidental to or present with clinical symptoms caused by extension into the pretibial soft tissues or expansion of the tunnel (Figure 5). Communication of cyst with joint space is important, as a noncommunicating cyst requires simple excision without need for bone grafting.⁷

Hardware-related complications (eg, loosening of fixation devices) are uncommon but may require revision surgery (Figure 6). Septic arthritis after ACL-R has a cumulative incidence of 0.1% to 0.9% and may be difficult to diagnose clinically because of the lack of classic symptoms of a septic joint.¹ Diagnosis requires joint aspiration.

MRI is reliably and accurately used to assess ACL-R complications. The clinical history helps in stratifying complications that result in decreased ROM or increased laxity.

Gorham-Stout disease (GSD) is a rare condition characterized by spontaneous idiopathic resorption of bone with lymphovascular proliferation and an absence of malignant features. It was originally described by Jackson¹ in an 1838 report of a 36-year-old man whose “arm bone, between the shoulder and elbow” had completely vanished after 2 fractures. The disease was defined and its pathology characterized by Gorham and Stout² in 1955 in a series of 24 patients. Despite about 200 reported cases in the literature,³ its etiology remains unclear. Any bone in the skeleton may be affected by GSD, although there is a predilection for the skull, humerus, clavicle, ribs, pelvis, and femur.^4-6 It commonly manifests within the first 3 decades of life, but case reports range from as early as 2 months of age to the eighth decade.^5,7

Gorham-Stout disease is a diagnosis of exclusion that requires careful consideration of the clinical context, radiographic findings, and histopathology. Typical histopathologic findings include benign lymphatic or vascular proliferation, involution of adipose tissue within the bone marrow, and thinning of bony trabeculae.⁶ Fibrous tissue may replace vascular tissue after the initial vasoproliferative, osteolytic phase.⁶ Some authors describe the disease as having 2 phases, the first with massive osteolysis followed by relative dormancy and the second without progression or re-ossification.^8,9 Treatment remains controversial and is guided by management of the disease’s complications. Options range from careful observation and supportive management to aggressive surgical resection and reconstruction, with positive outcomes reported using many different modalities.¹⁰ Most treatment successes, however, hinge on halting bony resorption using medical and radiation therapy. Surgery is usually reserved as a salvage option for patients who have failed medical modalities and have residual symptoms or functional limitations.⁶

This case report describes the successful surgical management of a patient with pelvic GSD who had progressive pain and functional limitation despite exhaustive medical and radiation therapy. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A healthy 27-year-old man sought medical attention after a fall while mowing his lawn that resulted in difficulty ambulating. Radiographic studies showed discontinuous lytic lesions in the right periacetabular region and the right sacroiliac (SI) joint. Biopsy at an outside institution revealed an infiltration of thin-walled branching vascular channels involving intertrabecular marrow spaces and periosteal connective tissue. The vessels were devoid of a muscular coat and lined by flattened epithelium; these features were seen as consistent with GSD.

The patient was managed medically at the outside institution for approximately 2 years, with regimens consisting of zoledronate, denosumab, sorafenib, vincristine, sirolimus, and bevacizumab. Because there is no standard chemotherapy protocol for GSD, this broad regimen was likely an attempt by treating physicians to control disease progression before considering radiation or surgery. Zoledronate, a bisphosphonate, and denosumab, a monoclonal antibody against the receptor activator of nuclear factor κβ ligand (RANKL), both inhibit bone resorption, making them logical choices in treating an osteolytic disease. Sorafenib, vincristine, sirolimus, and bevacizumab may be of clinical benefit in GSD via inhibition of vascular proliferation, which is a key histologic feature in GSD. Sorafenib inhibits the vascular endothelial growth factor (VEGF) receptor, vincristine and sirolimus inhibit VEGF production, and bevacizumab is a monoclonal antibody targeting VEGF.

The patient’s disease continued to involve more of his right hemipelvis despite this extensive regimen of chemotherapy, and he experienced significant functional decline about 2 years after initial presentation, when he was no longer able to ambulate unassisted. Radiation therapy to the pelvis was attempted at the outside institution (6/15 MV photons, 5040 cGy, 28 fractions) without improvement. Three years after his initial injury, he presented to our clinic.

Now age 30 years, the patient ambulated only with crutches and endorsed minimal improvement in his pain over 3 years of treatment. Physical examination of the patient revealed that he was a tall, thin man in visible discomfort. Sensation was intact to light touch in the bilateral L1 to S1 nerve distributions. There was marked weakness of the right lower extremity, and his examination was limited by pain. He could not perform a straight leg raise on the right side. Right quadriceps strength was 4/5, and right hamstrings strength was 3/5. There was no weakness in the left leg. Reflexes were normal and symmetric bilaterally at the patellar and gastrocnemius soleus tendons. Distal circulatory status in both extremities was normal, and there were no deformities of the skin.

Figure 1 shows the patient’s computed tomography (CT) scan. Figures 1A and 1B reveal fragmentation of the posterior ilia and sacrum along both SI joints. Dislocation of the pubic symphysis is shown in Figures 1C and 1D, and discontinuous involvement of the ischium and posterior wall of the acetabulum is visible in Figure 1E.

Serum studies, including C-reactive protein, erythrocyte sedimentation rate, and a complete blood count, were within normal limits. A CT-guided core needle biopsy and aspiration of the right SI joint revealed no infection; pathology was nondiagnostic. Anesthetic injection of the hip joint resulted in no relief. As this man was severely functionally limited and had exhausted all medical and radiation treatment options, a collaborative decision was made to proceed with surgical management. Surgical options included spinopelvic fusion unilaterally or bilaterally, hip arthroplasty, or sacropelvic resection with or without reconstruction. The patient opted for intralesional surgery and spinopelvic fusion in place of more radical options.

Thirty-seven months after his initial presentation, he underwent posterior spinal fusion L5 to S1, SI fusion, and anterior locking plate fixation of the pubic symphysis, as seen in Figure 2. Pathology from surgical specimens, seen at original magnification ×20 and ×100 in Figures 3A and 3B, respectively, showed prominent vascular proliferation in the right ilium, with reactive bone changes in the left ilium and right sacrum. A lytic lesion showed fibrous tissue with an embedded fragment of necrotic bone.

Six weeks after surgery, the patient had substantial improvement in his pain and was partially weight-bearing. He was able to ambulate with crutches and returned to work. The patient’s overall clinical status continued to improve throughout the postoperative course. He developed low back pain 7 months after surgery and was found to have a sacrococcygeal abscess and coccygeal fracture anterior to the sacrum. He underwent irrigation and débridement of the abscess and distal coccygectomy and was treated with 6 weeks of intravenous cefazolin and long-term suppression with levofloxacin and rifampin for methicillin-sensitive Staphylococcus aureus hardware infection and osteomyelitis. The patient’s clinical course subsequently improved. At latest follow-up 16 months after the index operation, pain was reported as manageable and mostly an annoyance. He was prescribed up to 40 mg of oxycodone daily for pain. The patient returned to work, ambulates with a cane (no other assistive devices), and reports being able to get around without any difficulty.

Discussion

Gorham-Stout disease is an exceedingly rare condition resulting in spontaneous osteolysis. Approximately 200 cases have been reported with no apparent gender, race, or familial predilection or systemic symptoms differentiating it from other etiologies of idiopathic osteolysis.⁶ These patients often seek medical attention after sustaining a pathologic fracture,⁶ when a broad differential diagnosis narrows to GSD only after biopsy excludes other possibilities and demonstrates characteristic angiomatosis without malignant features.^2,4,6,8,10 Gorham-Stout disease appears more frequently at particular sites within the skeleton, and pelvic involvement is common—more than 20% of cases in 1 review.^5,10 Limitations in the patient’s ability to ambulate invariably result from osteolysis of the pelvis, which is concerning considering the young age at which GSD typically presents. A variety of treatment modalities have been described for pelvic GSD, but surgery has been undertaken in relatively few cases.⁵

The diagnosis is one of exclusion after considering the clinical context and radiologic and pathologic findings. In this case, a pathologic fracture was discovered with osteolytic lesions throughout the hemipelvis. Biopsy excluded malignancy and demonstrated the key hemangiomatous vascular proliferation with thin-walled vessels that is classic for GSD. While our patient initially appeared to have 2 sites of disease, the surgical specimen revealed a primary site of vascular proliferation in the right ilium from which 2 apparent foci had spread, consistent with the typical monocentric presentation of GSD.¹¹ A broad differential diagnosis must be considered at initial presentation, including osteomyelitis, metastatic disease, multiple myeloma, and primary bone sarcoma. Upon identifying a primary osteolytic process, several considerations besides GSD remain, such as Hajdu-Cheney syndrome, Winchester syndrome, multicentric osteolysis with nephropathy, familial osteolysis, Farber disease, and neurogenic osteolysis; most of these etiologies involve familial predispositions and/or systemic symptoms.

Treatment options for GSD include supportive care, medical therapy, radiation, and surgery. For pelvic GSD, numerous reports have demonstrated good outcomes with supportive management, since osteolysis often spontaneously arrests.^8,9,12 Others have had success with medical treatments in attempts to halt bone resorption.^6,13-15 Bisphosphonates are the cornerstone of medical therapy in GSD, as they appear to halt further osteoclastic bone breakdown. The levels of VEGF have been shown to be elevated in GSD,¹³ likely consistent with the vascular proliferation evident on pathology, and therapies such as bevacizumab and interferon α-2b have been used to target osteolysis via this pathway with good outcome.^13,14,16 External beam-radiation therapy has been shown to prevent local progression of osteolysis in up to 80% of cases.⁴ However, even with arrest of bone resorption, damage to affected bone may have progressed to the point of significant functional limitation. This may be especially true in the pelvis.

We present a case of a patient who continued to deteriorate after maximal medical and radiation therapy. Many reported cases of pelvic GSD have had good outcomes with some combination of conservative management, medical therapy, and radiation. However, in our patient, the pelvis and lumbosacral spine were unstable as a result of significant bone loss and fracture, and his clinical deterioration was dramatic. We considered reasonable surgical approaches, including local intralesional débridement and massive en bloc resection with structural allograft. We chose the less radical procedure given the patient’s age, minimal surgical history, and personal preference. Although structural pelvic allograft has been successful in a few cases, there remains a high risk of complications, such as fracture, resorption, or infection.¹⁷ We considered the addition of hip arthroplasty with either scenario, but we elected not to perform this component given his young age and lack of symptomatic improvement with diagnostic anesthetic hip injection. The key to this patient’s surgical reconstruction, aside from eliminating gross disease, was the stabilization of the spinopelvic junction and pelvic ring. His functional improvement as early as 6 weeks after surgery demonstrates that surgery can have an important role for patients with pelvic GSD who fail medical and radiation therapy.

Gorham-Stout disease (GSD) is a rare condition characterized by spontaneous idiopathic resorption of bone with lymphovascular proliferation and an absence of malignant features. It was originally described by Jackson¹ in an 1838 report of a 36-year-old man whose “arm bone, between the shoulder and elbow” had completely vanished after 2 fractures. The disease was defined and its pathology characterized by Gorham and Stout² in 1955 in a series of 24 patients. Despite about 200 reported cases in the literature,³ its etiology remains unclear. Any bone in the skeleton may be affected by GSD, although there is a predilection for the skull, humerus, clavicle, ribs, pelvis, and femur.^4-6 It commonly manifests within the first 3 decades of life, but case reports range from as early as 2 months of age to the eighth decade.^5,7

Gorham-Stout disease is a diagnosis of exclusion that requires careful consideration of the clinical context, radiographic findings, and histopathology. Typical histopathologic findings include benign lymphatic or vascular proliferation, involution of adipose tissue within the bone marrow, and thinning of bony trabeculae.⁶ Fibrous tissue may replace vascular tissue after the initial vasoproliferative, osteolytic phase.⁶ Some authors describe the disease as having 2 phases, the first with massive osteolysis followed by relative dormancy and the second without progression or re-ossification.^8,9 Treatment remains controversial and is guided by management of the disease’s complications. Options range from careful observation and supportive management to aggressive surgical resection and reconstruction, with positive outcomes reported using many different modalities.¹⁰ Most treatment successes, however, hinge on halting bony resorption using medical and radiation therapy. Surgery is usually reserved as a salvage option for patients who have failed medical modalities and have residual symptoms or functional limitations.⁶

This case report describes the successful surgical management of a patient with pelvic GSD who had progressive pain and functional limitation despite exhaustive medical and radiation therapy. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A healthy 27-year-old man sought medical attention after a fall while mowing his lawn that resulted in difficulty ambulating. Radiographic studies showed discontinuous lytic lesions in the right periacetabular region and the right sacroiliac (SI) joint. Biopsy at an outside institution revealed an infiltration of thin-walled branching vascular channels involving intertrabecular marrow spaces and periosteal connective tissue. The vessels were devoid of a muscular coat and lined by flattened epithelium; these features were seen as consistent with GSD.

The patient was managed medically at the outside institution for approximately 2 years, with regimens consisting of zoledronate, denosumab, sorafenib, vincristine, sirolimus, and bevacizumab. Because there is no standard chemotherapy protocol for GSD, this broad regimen was likely an attempt by treating physicians to control disease progression before considering radiation or surgery. Zoledronate, a bisphosphonate, and denosumab, a monoclonal antibody against the receptor activator of nuclear factor κβ ligand (RANKL), both inhibit bone resorption, making them logical choices in treating an osteolytic disease. Sorafenib, vincristine, sirolimus, and bevacizumab may be of clinical benefit in GSD via inhibition of vascular proliferation, which is a key histologic feature in GSD. Sorafenib inhibits the vascular endothelial growth factor (VEGF) receptor, vincristine and sirolimus inhibit VEGF production, and bevacizumab is a monoclonal antibody targeting VEGF.

The patient’s disease continued to involve more of his right hemipelvis despite this extensive regimen of chemotherapy, and he experienced significant functional decline about 2 years after initial presentation, when he was no longer able to ambulate unassisted. Radiation therapy to the pelvis was attempted at the outside institution (6/15 MV photons, 5040 cGy, 28 fractions) without improvement. Three years after his initial injury, he presented to our clinic.

Now age 30 years, the patient ambulated only with crutches and endorsed minimal improvement in his pain over 3 years of treatment. Physical examination of the patient revealed that he was a tall, thin man in visible discomfort. Sensation was intact to light touch in the bilateral L1 to S1 nerve distributions. There was marked weakness of the right lower extremity, and his examination was limited by pain. He could not perform a straight leg raise on the right side. Right quadriceps strength was 4/5, and right hamstrings strength was 3/5. There was no weakness in the left leg. Reflexes were normal and symmetric bilaterally at the patellar and gastrocnemius soleus tendons. Distal circulatory status in both extremities was normal, and there were no deformities of the skin.

Figure 1 shows the patient’s computed tomography (CT) scan. Figures 1A and 1B reveal fragmentation of the posterior ilia and sacrum along both SI joints. Dislocation of the pubic symphysis is shown in Figures 1C and 1D, and discontinuous involvement of the ischium and posterior wall of the acetabulum is visible in Figure 1E.

Serum studies, including C-reactive protein, erythrocyte sedimentation rate, and a complete blood count, were within normal limits. A CT-guided core needle biopsy and aspiration of the right SI joint revealed no infection; pathology was nondiagnostic. Anesthetic injection of the hip joint resulted in no relief. As this man was severely functionally limited and had exhausted all medical and radiation treatment options, a collaborative decision was made to proceed with surgical management. Surgical options included spinopelvic fusion unilaterally or bilaterally, hip arthroplasty, or sacropelvic resection with or without reconstruction. The patient opted for intralesional surgery and spinopelvic fusion in place of more radical options.

Thirty-seven months after his initial presentation, he underwent posterior spinal fusion L5 to S1, SI fusion, and anterior locking plate fixation of the pubic symphysis, as seen in Figure 2. Pathology from surgical specimens, seen at original magnification ×20 and ×100 in Figures 3A and 3B, respectively, showed prominent vascular proliferation in the right ilium, with reactive bone changes in the left ilium and right sacrum. A lytic lesion showed fibrous tissue with an embedded fragment of necrotic bone.

Six weeks after surgery, the patient had substantial improvement in his pain and was partially weight-bearing. He was able to ambulate with crutches and returned to work. The patient’s overall clinical status continued to improve throughout the postoperative course. He developed low back pain 7 months after surgery and was found to have a sacrococcygeal abscess and coccygeal fracture anterior to the sacrum. He underwent irrigation and débridement of the abscess and distal coccygectomy and was treated with 6 weeks of intravenous cefazolin and long-term suppression with levofloxacin and rifampin for methicillin-sensitive Staphylococcus aureus hardware infection and osteomyelitis. The patient’s clinical course subsequently improved. At latest follow-up 16 months after the index operation, pain was reported as manageable and mostly an annoyance. He was prescribed up to 40 mg of oxycodone daily for pain. The patient returned to work, ambulates with a cane (no other assistive devices), and reports being able to get around without any difficulty.

Discussion

Gorham-Stout disease is an exceedingly rare condition resulting in spontaneous osteolysis. Approximately 200 cases have been reported with no apparent gender, race, or familial predilection or systemic symptoms differentiating it from other etiologies of idiopathic osteolysis.⁶ These patients often seek medical attention after sustaining a pathologic fracture,⁶ when a broad differential diagnosis narrows to GSD only after biopsy excludes other possibilities and demonstrates characteristic angiomatosis without malignant features.^2,4,6,8,10 Gorham-Stout disease appears more frequently at particular sites within the skeleton, and pelvic involvement is common—more than 20% of cases in 1 review.^5,10 Limitations in the patient’s ability to ambulate invariably result from osteolysis of the pelvis, which is concerning considering the young age at which GSD typically presents. A variety of treatment modalities have been described for pelvic GSD, but surgery has been undertaken in relatively few cases.⁵

The diagnosis is one of exclusion after considering the clinical context and radiologic and pathologic findings. In this case, a pathologic fracture was discovered with osteolytic lesions throughout the hemipelvis. Biopsy excluded malignancy and demonstrated the key hemangiomatous vascular proliferation with thin-walled vessels that is classic for GSD. While our patient initially appeared to have 2 sites of disease, the surgical specimen revealed a primary site of vascular proliferation in the right ilium from which 2 apparent foci had spread, consistent with the typical monocentric presentation of GSD.¹¹ A broad differential diagnosis must be considered at initial presentation, including osteomyelitis, metastatic disease, multiple myeloma, and primary bone sarcoma. Upon identifying a primary osteolytic process, several considerations besides GSD remain, such as Hajdu-Cheney syndrome, Winchester syndrome, multicentric osteolysis with nephropathy, familial osteolysis, Farber disease, and neurogenic osteolysis; most of these etiologies involve familial predispositions and/or systemic symptoms.

Treatment options for GSD include supportive care, medical therapy, radiation, and surgery. For pelvic GSD, numerous reports have demonstrated good outcomes with supportive management, since osteolysis often spontaneously arrests.^8,9,12 Others have had success with medical treatments in attempts to halt bone resorption.^6,13-15 Bisphosphonates are the cornerstone of medical therapy in GSD, as they appear to halt further osteoclastic bone breakdown. The levels of VEGF have been shown to be elevated in GSD,¹³ likely consistent with the vascular proliferation evident on pathology, and therapies such as bevacizumab and interferon α-2b have been used to target osteolysis via this pathway with good outcome.^13,14,16 External beam-radiation therapy has been shown to prevent local progression of osteolysis in up to 80% of cases.⁴ However, even with arrest of bone resorption, damage to affected bone may have progressed to the point of significant functional limitation. This may be especially true in the pelvis.

We present a case of a patient who continued to deteriorate after maximal medical and radiation therapy. Many reported cases of pelvic GSD have had good outcomes with some combination of conservative management, medical therapy, and radiation. However, in our patient, the pelvis and lumbosacral spine were unstable as a result of significant bone loss and fracture, and his clinical deterioration was dramatic. We considered reasonable surgical approaches, including local intralesional débridement and massive en bloc resection with structural allograft. We chose the less radical procedure given the patient’s age, minimal surgical history, and personal preference. Although structural pelvic allograft has been successful in a few cases, there remains a high risk of complications, such as fracture, resorption, or infection.¹⁷ We considered the addition of hip arthroplasty with either scenario, but we elected not to perform this component given his young age and lack of symptomatic improvement with diagnostic anesthetic hip injection. The key to this patient’s surgical reconstruction, aside from eliminating gross disease, was the stabilization of the spinopelvic junction and pelvic ring. His functional improvement as early as 6 weeks after surgery demonstrates that surgery can have an important role for patients with pelvic GSD who fail medical and radiation therapy.

Gorham-Stout disease (GSD) is a rare condition characterized by spontaneous idiopathic resorption of bone with lymphovascular proliferation and an absence of malignant features. It was originally described by Jackson¹ in an 1838 report of a 36-year-old man whose “arm bone, between the shoulder and elbow” had completely vanished after 2 fractures. The disease was defined and its pathology characterized by Gorham and Stout² in 1955 in a series of 24 patients. Despite about 200 reported cases in the literature,³ its etiology remains unclear. Any bone in the skeleton may be affected by GSD, although there is a predilection for the skull, humerus, clavicle, ribs, pelvis, and femur.^4-6 It commonly manifests within the first 3 decades of life, but case reports range from as early as 2 months of age to the eighth decade.^5,7

Gorham-Stout disease is a diagnosis of exclusion that requires careful consideration of the clinical context, radiographic findings, and histopathology. Typical histopathologic findings include benign lymphatic or vascular proliferation, involution of adipose tissue within the bone marrow, and thinning of bony trabeculae.⁶ Fibrous tissue may replace vascular tissue after the initial vasoproliferative, osteolytic phase.⁶ Some authors describe the disease as having 2 phases, the first with massive osteolysis followed by relative dormancy and the second without progression or re-ossification.^8,9 Treatment remains controversial and is guided by management of the disease’s complications. Options range from careful observation and supportive management to aggressive surgical resection and reconstruction, with positive outcomes reported using many different modalities.¹⁰ Most treatment successes, however, hinge on halting bony resorption using medical and radiation therapy. Surgery is usually reserved as a salvage option for patients who have failed medical modalities and have residual symptoms or functional limitations.⁶

This case report describes the successful surgical management of a patient with pelvic GSD who had progressive pain and functional limitation despite exhaustive medical and radiation therapy. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A healthy 27-year-old man sought medical attention after a fall while mowing his lawn that resulted in difficulty ambulating. Radiographic studies showed discontinuous lytic lesions in the right periacetabular region and the right sacroiliac (SI) joint. Biopsy at an outside institution revealed an infiltration of thin-walled branching vascular channels involving intertrabecular marrow spaces and periosteal connective tissue. The vessels were devoid of a muscular coat and lined by flattened epithelium; these features were seen as consistent with GSD.

The patient was managed medically at the outside institution for approximately 2 years, with regimens consisting of zoledronate, denosumab, sorafenib, vincristine, sirolimus, and bevacizumab. Because there is no standard chemotherapy protocol for GSD, this broad regimen was likely an attempt by treating physicians to control disease progression before considering radiation or surgery. Zoledronate, a bisphosphonate, and denosumab, a monoclonal antibody against the receptor activator of nuclear factor κβ ligand (RANKL), both inhibit bone resorption, making them logical choices in treating an osteolytic disease. Sorafenib, vincristine, sirolimus, and bevacizumab may be of clinical benefit in GSD via inhibition of vascular proliferation, which is a key histologic feature in GSD. Sorafenib inhibits the vascular endothelial growth factor (VEGF) receptor, vincristine and sirolimus inhibit VEGF production, and bevacizumab is a monoclonal antibody targeting VEGF.

The patient’s disease continued to involve more of his right hemipelvis despite this extensive regimen of chemotherapy, and he experienced significant functional decline about 2 years after initial presentation, when he was no longer able to ambulate unassisted. Radiation therapy to the pelvis was attempted at the outside institution (6/15 MV photons, 5040 cGy, 28 fractions) without improvement. Three years after his initial injury, he presented to our clinic.

Now age 30 years, the patient ambulated only with crutches and endorsed minimal improvement in his pain over 3 years of treatment. Physical examination of the patient revealed that he was a tall, thin man in visible discomfort. Sensation was intact to light touch in the bilateral L1 to S1 nerve distributions. There was marked weakness of the right lower extremity, and his examination was limited by pain. He could not perform a straight leg raise on the right side. Right quadriceps strength was 4/5, and right hamstrings strength was 3/5. There was no weakness in the left leg. Reflexes were normal and symmetric bilaterally at the patellar and gastrocnemius soleus tendons. Distal circulatory status in both extremities was normal, and there were no deformities of the skin.

Figure 1 shows the patient’s computed tomography (CT) scan. Figures 1A and 1B reveal fragmentation of the posterior ilia and sacrum along both SI joints. Dislocation of the pubic symphysis is shown in Figures 1C and 1D, and discontinuous involvement of the ischium and posterior wall of the acetabulum is visible in Figure 1E.

Serum studies, including C-reactive protein, erythrocyte sedimentation rate, and a complete blood count, were within normal limits. A CT-guided core needle biopsy and aspiration of the right SI joint revealed no infection; pathology was nondiagnostic. Anesthetic injection of the hip joint resulted in no relief. As this man was severely functionally limited and had exhausted all medical and radiation treatment options, a collaborative decision was made to proceed with surgical management. Surgical options included spinopelvic fusion unilaterally or bilaterally, hip arthroplasty, or sacropelvic resection with or without reconstruction. The patient opted for intralesional surgery and spinopelvic fusion in place of more radical options.

Thirty-seven months after his initial presentation, he underwent posterior spinal fusion L5 to S1, SI fusion, and anterior locking plate fixation of the pubic symphysis, as seen in Figure 2. Pathology from surgical specimens, seen at original magnification ×20 and ×100 in Figures 3A and 3B, respectively, showed prominent vascular proliferation in the right ilium, with reactive bone changes in the left ilium and right sacrum. A lytic lesion showed fibrous tissue with an embedded fragment of necrotic bone.

Six weeks after surgery, the patient had substantial improvement in his pain and was partially weight-bearing. He was able to ambulate with crutches and returned to work. The patient’s overall clinical status continued to improve throughout the postoperative course. He developed low back pain 7 months after surgery and was found to have a sacrococcygeal abscess and coccygeal fracture anterior to the sacrum. He underwent irrigation and débridement of the abscess and distal coccygectomy and was treated with 6 weeks of intravenous cefazolin and long-term suppression with levofloxacin and rifampin for methicillin-sensitive Staphylococcus aureus hardware infection and osteomyelitis. The patient’s clinical course subsequently improved. At latest follow-up 16 months after the index operation, pain was reported as manageable and mostly an annoyance. He was prescribed up to 40 mg of oxycodone daily for pain. The patient returned to work, ambulates with a cane (no other assistive devices), and reports being able to get around without any difficulty.

Discussion

Gorham-Stout disease is an exceedingly rare condition resulting in spontaneous osteolysis. Approximately 200 cases have been reported with no apparent gender, race, or familial predilection or systemic symptoms differentiating it from other etiologies of idiopathic osteolysis.⁶ These patients often seek medical attention after sustaining a pathologic fracture,⁶ when a broad differential diagnosis narrows to GSD only after biopsy excludes other possibilities and demonstrates characteristic angiomatosis without malignant features.^2,4,6,8,10 Gorham-Stout disease appears more frequently at particular sites within the skeleton, and pelvic involvement is common—more than 20% of cases in 1 review.^5,10 Limitations in the patient’s ability to ambulate invariably result from osteolysis of the pelvis, which is concerning considering the young age at which GSD typically presents. A variety of treatment modalities have been described for pelvic GSD, but surgery has been undertaken in relatively few cases.⁵

The diagnosis is one of exclusion after considering the clinical context and radiologic and pathologic findings. In this case, a pathologic fracture was discovered with osteolytic lesions throughout the hemipelvis. Biopsy excluded malignancy and demonstrated the key hemangiomatous vascular proliferation with thin-walled vessels that is classic for GSD. While our patient initially appeared to have 2 sites of disease, the surgical specimen revealed a primary site of vascular proliferation in the right ilium from which 2 apparent foci had spread, consistent with the typical monocentric presentation of GSD.¹¹ A broad differential diagnosis must be considered at initial presentation, including osteomyelitis, metastatic disease, multiple myeloma, and primary bone sarcoma. Upon identifying a primary osteolytic process, several considerations besides GSD remain, such as Hajdu-Cheney syndrome, Winchester syndrome, multicentric osteolysis with nephropathy, familial osteolysis, Farber disease, and neurogenic osteolysis; most of these etiologies involve familial predispositions and/or systemic symptoms.

Treatment options for GSD include supportive care, medical therapy, radiation, and surgery. For pelvic GSD, numerous reports have demonstrated good outcomes with supportive management, since osteolysis often spontaneously arrests.^8,9,12 Others have had success with medical treatments in attempts to halt bone resorption.^6,13-15 Bisphosphonates are the cornerstone of medical therapy in GSD, as they appear to halt further osteoclastic bone breakdown. The levels of VEGF have been shown to be elevated in GSD,¹³ likely consistent with the vascular proliferation evident on pathology, and therapies such as bevacizumab and interferon α-2b have been used to target osteolysis via this pathway with good outcome.^13,14,16 External beam-radiation therapy has been shown to prevent local progression of osteolysis in up to 80% of cases.⁴ However, even with arrest of bone resorption, damage to affected bone may have progressed to the point of significant functional limitation. This may be especially true in the pelvis.

We present a case of a patient who continued to deteriorate after maximal medical and radiation therapy. Many reported cases of pelvic GSD have had good outcomes with some combination of conservative management, medical therapy, and radiation. However, in our patient, the pelvis and lumbosacral spine were unstable as a result of significant bone loss and fracture, and his clinical deterioration was dramatic. We considered reasonable surgical approaches, including local intralesional débridement and massive en bloc resection with structural allograft. We chose the less radical procedure given the patient’s age, minimal surgical history, and personal preference. Although structural pelvic allograft has been successful in a few cases, there remains a high risk of complications, such as fracture, resorption, or infection.¹⁷ We considered the addition of hip arthroplasty with either scenario, but we elected not to perform this component given his young age and lack of symptomatic improvement with diagnostic anesthetic hip injection. The key to this patient’s surgical reconstruction, aside from eliminating gross disease, was the stabilization of the spinopelvic junction and pelvic ring. His functional improvement as early as 6 weeks after surgery demonstrates that surgery can have an important role for patients with pelvic GSD who fail medical and radiation therapy.

The incidence of Dupuytren disease increases with advancing age,¹ as do the medical comorbidities of patients seeking treatment for disabling hand contractures. For patients with significant comorbidities, open surgical fasciectomy, the current standard of treatment for Dupuytren disease,^2,3 may be associated with increased perioperative risks.

Collagenase enzymatic fasciotomy has become an accepted nonsurgical treatment alternative to traditional fasciectomy or surgical fasciotomy for significant digital contractures caused by Dupuytren disease.^4-6 Clostridium histolyticum collagenase (CHC) is a foreign protein, made up of 2 collagenases isolated from the bacteria C histolyticum.⁷ The collagenases are zinc-dependent matrix metalloproteinases that cleave the triple helical structure of collagen molecules.⁸ Also known as Xiaflex (Auxilium Pharmaceuticals), CHC was approved by the US Food and Drug Administration (FDA) in February 2010 for use in patients with Dupuytren contractures.

 Enzymatic rupture is safe and efficacious at midterm follow-up and offers the theoretical advantage of avoiding palmar and digital fasciectomy and the associated risks of surgical-site infection and wound-healing complications.⁶ The risks of surgical wound complications are magnified in immunosuppressed patients, particularly those on chronic steroid therapy; wound-healing complication rates may be increased 2 to 5 times compared with controls.⁹ In a pooled literature review, wound-healing complications were reported after 22.9% of open primary fasciectomies, with infection occurring in 2.4%.¹⁰ A nonsurgical alternative is therefore particularly appealing for a patient cohort that may be at higher risk for a frequently described complication of surgery for Dupuytren contracture.

The exclusion criteria in the trials for FDA approval were extensive and included breast-feeding, pregnancy, bleeding disorder, recent stroke, use of tetracycline derivative within 14 days before start of study, use of anticoagulant within 7 days before start of study, allergy to collagenase, and chronic muscular, neurologic, or neuromuscular disorder affecting the hands.⁶ Safety and efficacy of collagenase in patients requiring chronic immunosuppressive therapy for medical comorbidities have not been previously documented. Furthermore, although skin tears were reported in 11% of patients after manual cord rupture in the CORD (Collagenase Option for the Reduction of Dupuytren’s) I trial,⁶ the likelihood of deep and superficial infection and delayed wound healing has not been quantitated.

In this article, we report on outcomes of 13 collagenase enzymatic fasciotomies performed in 8 patients who were on chronic immunosuppressive therapy.

Methods

Institutional review board approval was obtained at both academic hand surgery institutions. We retrospectively reviewed prospectively collected clinical data within our 2 centers’ databases of patients with Dupuytren disease. Eight patients on chronic immunosuppressive therapies treated with collagenase for metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint contractures between February 2010 and December 2011 were identified. Three of these patients received collagenase injections into 2 or more separate Dupuytren cords at different encounters, resulting in a total of 13 individual collagenase enzymatic fasciotomies.

Collagenase injections were administered following CORD I trial protocol,⁶ except we injected Dupuytren cords crossing the PIP joint using a lateral approach to minimize risk of flexor tendon rupture. Manipulation of the treated joint was performed between 24 and 48 hours after collagenase injection under local anesthesia with 3 mL of 1% mepivacaine or lidocaine without epinephrine. After manipulation and cord rupture, patients were placed in a hand-based extension splint to wear at night for up to 3 months. Patients were followed at 1 and 12 months.

Results

Patients’ baseline characteristics are summarized in Table 1. Four patients were maintained on chronic prednisone therapy, 3 on methotrexate, and 1 on azathioprine. Therapy duration, medication dose, and diagnoses requiring immunosuppressant therapy varied among patients.

Outcomes and adverse events are summarized in Table 2. Mean number of joint contractures per hand treated was 2.8 (MP, 1.4; PIP, 1.4). However, not all joints met the intervention criteria. Of the 13 joints treated, 7 were MP joints, and 6 were PIP joints. Mean preinjection contracture of the treated joints was 53.0° (range, 20°-90°). Twelve of the 13 joint contractures improved. At mean follow-up of 6.7 months (range, 1-22 months), mean magnitude of contracture improved to 12.9° (range, 0°-45°). Mean MP joint contracture improved from 42.0° to 4.2° (range, 0°-10°), and mean PIP joint contracture improved from 65.8° to 21.7° (range, 0°-45°).

All 13 collagenase injections were well tolerated, and there were no systemic reactions. Injection-site pain was common. Mild injection-site bruising and edema were reported in all cases. Enzymatic fasciotomy was performed in all patients, and immediate improvement in contracture after manipulation 24 to 48 hours after injection was recorded.

Three of the 13 injections were complicated by skin tears during manipulation and cord rupture. All 3 skin tears were treated with local wound care, which included use of povidone-iodine and wet-to-dry dressings. There was no evidence of subsequent superficial or deep, local or regional infection. In 2 cases, the wound healed within 1 week; in the third case, wound healing was present by 2 weeks. Once the wounds showed early re-epithelialization, hand-based extension splinting in a position of comfort was used at night for up to 3 months after injection. Two of the 13 injections were complicated by small blood blisters. These were treated with observation and resolved spontaneously.

Discussion

Collagenase enzymatic fasciotomy appeared to be a safe and efficacious alternative to surgical treatment of Dupuytren contractures in this cohort of patients maintained on chronic immunosuppressive agents. MP contractures responded more substantially than PIP contractures did, as expected.⁶ No previously undescribed adverse outcomes were noted in these 8 patients on chronic immunosuppressive therapy beyond those reported in the CORD I trial. Three (23%) of the 13 collagenase injections in our series were complicated by skin tears after manipulation. Skins tears were reported in 22 (11%) of 204 patients after manual cord rupture in the CORD I trial.⁶ Given the limited numbers in this series, it remains unclear if chronic immunosuppression truly increases the risk of skin tears in this subset of patients. Other common treatment-related adverse events seen in the CORD I trial—injection-site hemorrhage (37%), pruritis (11%) and lymphadenopathy (10%)—were not seen after the 13 injections in our case series. We are prospectively following all patients with Dupuytren disease, and this is an area of ongoing research at our centers.

The immunosuppressive actions of prednisone, azathioprine, and methotrexate are well documented. Prednisone is a glucocorticoid, converted in the liver to prednisolone, which suppresses inflammation and immune responses by regulation of gene expression. Its immunosuppressive actions are multifactorial, relating to inhibition of lymphocytes, neutrophils, and monocytes. These effects are dose- and time-dependent¹¹ and may become evident in patients receiving low doses over prolonged periods. Skin atrophy¹² and delayed wound healing⁹ are side effects of long-term prednisone use. Skin atrophy may make the prednisone-treated patient more susceptible to skin tears after collagenase injection and manipulation. Azathioprine inhibits purine synthesis, which is especially important in the proliferation of immune cells.¹³ It has been shown to inhibit both cellular immunity at low doses and humoral immunity at higher doses.¹⁴ Methotrexate inhibits lymphocyte folic acid metabolism. The immunosuppressive properties of low-dose methotrexate have been linked to the induction of apoptosis in activated T cells.¹⁵

A more complex process in immunosuppressed patients is the immunogenicity of injected collagenase. As CHC in current use is a mixture of 2 foreign proteins, an immunologic response is expected in the host after injection. It has been shown that, after 3 injections of CHC into Dupuytren cords, 100% of patients developed antibodies to both enzymes in their serum.⁶ More than 85% demonstrated anti-CHC antibodies after a single injection. However, no patients showed signs of anaphylaxis or allergic reaction, and there was no correlation between serum levels of anti-CHC and adverse events. It has been hypothesized that there is a potential for cross-reactivity of the anti-CHC antibodies with human matrix metalloproteinases, causing enzymatic dysfunction within the host.¹⁶ This has yet to be reported clinically, and Xiaflex is currently under postmarketing surveillance. Immunocompromised people, with suppressed humoral and cellular immune responses, may produce less of an antibody response to the foreign CHC proteins. Whether this conclusively leads to a change in the side effect profile of the medication in these individuals is beyond the scope of this article. However, we identified no new side effects in this small but higher risk cohort. The issue should be continually monitored as collagenase is used in wider clinical settings.

Collagenase enzymatic fasciotomy is a new nonsurgical therapeutic option for Dupuytren disease. Indications and guidelines for use continue to evolve. This case series highlights the use of collagenase in 8 patients who were on long-term immunosuppressive therapy. This study has the limitations inherent to retrospective analyses. It is difficult to generalize results across broader immunosuppressed populations. A larger cohort, with long-term follow-up assessing recurrence of contracture, is needed to make definitive conclusions about use of collagenase in this challenging subset of patients. Based on our observations in this limited cohort, it appears appropriate to pursue further studies on use of collagenase enzymatic fasciotomy. A randomized, prospective or case–control series comparing surgical fasciectomy with enzymatic fasciotomy would yield further meaningful data. As more patients seek nonsurgical treatment for Dupuytren disease, its safety and efficacy in select cohorts of patients should continue to be evaluated.

The incidence of Dupuytren disease increases with advancing age,¹ as do the medical comorbidities of patients seeking treatment for disabling hand contractures. For patients with significant comorbidities, open surgical fasciectomy, the current standard of treatment for Dupuytren disease,^2,3 may be associated with increased perioperative risks.

Collagenase enzymatic fasciotomy has become an accepted nonsurgical treatment alternative to traditional fasciectomy or surgical fasciotomy for significant digital contractures caused by Dupuytren disease.^4-6 Clostridium histolyticum collagenase (CHC) is a foreign protein, made up of 2 collagenases isolated from the bacteria C histolyticum.⁷ The collagenases are zinc-dependent matrix metalloproteinases that cleave the triple helical structure of collagen molecules.⁸ Also known as Xiaflex (Auxilium Pharmaceuticals), CHC was approved by the US Food and Drug Administration (FDA) in February 2010 for use in patients with Dupuytren contractures.

 Enzymatic rupture is safe and efficacious at midterm follow-up and offers the theoretical advantage of avoiding palmar and digital fasciectomy and the associated risks of surgical-site infection and wound-healing complications.⁶ The risks of surgical wound complications are magnified in immunosuppressed patients, particularly those on chronic steroid therapy; wound-healing complication rates may be increased 2 to 5 times compared with controls.⁹ In a pooled literature review, wound-healing complications were reported after 22.9% of open primary fasciectomies, with infection occurring in 2.4%.¹⁰ A nonsurgical alternative is therefore particularly appealing for a patient cohort that may be at higher risk for a frequently described complication of surgery for Dupuytren contracture.

The exclusion criteria in the trials for FDA approval were extensive and included breast-feeding, pregnancy, bleeding disorder, recent stroke, use of tetracycline derivative within 14 days before start of study, use of anticoagulant within 7 days before start of study, allergy to collagenase, and chronic muscular, neurologic, or neuromuscular disorder affecting the hands.⁶ Safety and efficacy of collagenase in patients requiring chronic immunosuppressive therapy for medical comorbidities have not been previously documented. Furthermore, although skin tears were reported in 11% of patients after manual cord rupture in the CORD (Collagenase Option for the Reduction of Dupuytren’s) I trial,⁶ the likelihood of deep and superficial infection and delayed wound healing has not been quantitated.

In this article, we report on outcomes of 13 collagenase enzymatic fasciotomies performed in 8 patients who were on chronic immunosuppressive therapy.

Methods

Institutional review board approval was obtained at both academic hand surgery institutions. We retrospectively reviewed prospectively collected clinical data within our 2 centers’ databases of patients with Dupuytren disease. Eight patients on chronic immunosuppressive therapies treated with collagenase for metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint contractures between February 2010 and December 2011 were identified. Three of these patients received collagenase injections into 2 or more separate Dupuytren cords at different encounters, resulting in a total of 13 individual collagenase enzymatic fasciotomies.

Collagenase injections were administered following CORD I trial protocol,⁶ except we injected Dupuytren cords crossing the PIP joint using a lateral approach to minimize risk of flexor tendon rupture. Manipulation of the treated joint was performed between 24 and 48 hours after collagenase injection under local anesthesia with 3 mL of 1% mepivacaine or lidocaine without epinephrine. After manipulation and cord rupture, patients were placed in a hand-based extension splint to wear at night for up to 3 months. Patients were followed at 1 and 12 months.

Results

Patients’ baseline characteristics are summarized in Table 1. Four patients were maintained on chronic prednisone therapy, 3 on methotrexate, and 1 on azathioprine. Therapy duration, medication dose, and diagnoses requiring immunosuppressant therapy varied among patients.

Outcomes and adverse events are summarized in Table 2. Mean number of joint contractures per hand treated was 2.8 (MP, 1.4; PIP, 1.4). However, not all joints met the intervention criteria. Of the 13 joints treated, 7 were MP joints, and 6 were PIP joints. Mean preinjection contracture of the treated joints was 53.0° (range, 20°-90°). Twelve of the 13 joint contractures improved. At mean follow-up of 6.7 months (range, 1-22 months), mean magnitude of contracture improved to 12.9° (range, 0°-45°). Mean MP joint contracture improved from 42.0° to 4.2° (range, 0°-10°), and mean PIP joint contracture improved from 65.8° to 21.7° (range, 0°-45°).

All 13 collagenase injections were well tolerated, and there were no systemic reactions. Injection-site pain was common. Mild injection-site bruising and edema were reported in all cases. Enzymatic fasciotomy was performed in all patients, and immediate improvement in contracture after manipulation 24 to 48 hours after injection was recorded.

Three of the 13 injections were complicated by skin tears during manipulation and cord rupture. All 3 skin tears were treated with local wound care, which included use of povidone-iodine and wet-to-dry dressings. There was no evidence of subsequent superficial or deep, local or regional infection. In 2 cases, the wound healed within 1 week; in the third case, wound healing was present by 2 weeks. Once the wounds showed early re-epithelialization, hand-based extension splinting in a position of comfort was used at night for up to 3 months after injection. Two of the 13 injections were complicated by small blood blisters. These were treated with observation and resolved spontaneously.

Discussion

Collagenase enzymatic fasciotomy appeared to be a safe and efficacious alternative to surgical treatment of Dupuytren contractures in this cohort of patients maintained on chronic immunosuppressive agents. MP contractures responded more substantially than PIP contractures did, as expected.⁶ No previously undescribed adverse outcomes were noted in these 8 patients on chronic immunosuppressive therapy beyond those reported in the CORD I trial. Three (23%) of the 13 collagenase injections in our series were complicated by skin tears after manipulation. Skins tears were reported in 22 (11%) of 204 patients after manual cord rupture in the CORD I trial.⁶ Given the limited numbers in this series, it remains unclear if chronic immunosuppression truly increases the risk of skin tears in this subset of patients. Other common treatment-related adverse events seen in the CORD I trial—injection-site hemorrhage (37%), pruritis (11%) and lymphadenopathy (10%)—were not seen after the 13 injections in our case series. We are prospectively following all patients with Dupuytren disease, and this is an area of ongoing research at our centers.

The immunosuppressive actions of prednisone, azathioprine, and methotrexate are well documented. Prednisone is a glucocorticoid, converted in the liver to prednisolone, which suppresses inflammation and immune responses by regulation of gene expression. Its immunosuppressive actions are multifactorial, relating to inhibition of lymphocytes, neutrophils, and monocytes. These effects are dose- and time-dependent¹¹ and may become evident in patients receiving low doses over prolonged periods. Skin atrophy¹² and delayed wound healing⁹ are side effects of long-term prednisone use. Skin atrophy may make the prednisone-treated patient more susceptible to skin tears after collagenase injection and manipulation. Azathioprine inhibits purine synthesis, which is especially important in the proliferation of immune cells.¹³ It has been shown to inhibit both cellular immunity at low doses and humoral immunity at higher doses.¹⁴ Methotrexate inhibits lymphocyte folic acid metabolism. The immunosuppressive properties of low-dose methotrexate have been linked to the induction of apoptosis in activated T cells.¹⁵

A more complex process in immunosuppressed patients is the immunogenicity of injected collagenase. As CHC in current use is a mixture of 2 foreign proteins, an immunologic response is expected in the host after injection. It has been shown that, after 3 injections of CHC into Dupuytren cords, 100% of patients developed antibodies to both enzymes in their serum.⁶ More than 85% demonstrated anti-CHC antibodies after a single injection. However, no patients showed signs of anaphylaxis or allergic reaction, and there was no correlation between serum levels of anti-CHC and adverse events. It has been hypothesized that there is a potential for cross-reactivity of the anti-CHC antibodies with human matrix metalloproteinases, causing enzymatic dysfunction within the host.¹⁶ This has yet to be reported clinically, and Xiaflex is currently under postmarketing surveillance. Immunocompromised people, with suppressed humoral and cellular immune responses, may produce less of an antibody response to the foreign CHC proteins. Whether this conclusively leads to a change in the side effect profile of the medication in these individuals is beyond the scope of this article. However, we identified no new side effects in this small but higher risk cohort. The issue should be continually monitored as collagenase is used in wider clinical settings.

Collagenase enzymatic fasciotomy is a new nonsurgical therapeutic option for Dupuytren disease. Indications and guidelines for use continue to evolve. This case series highlights the use of collagenase in 8 patients who were on long-term immunosuppressive therapy. This study has the limitations inherent to retrospective analyses. It is difficult to generalize results across broader immunosuppressed populations. A larger cohort, with long-term follow-up assessing recurrence of contracture, is needed to make definitive conclusions about use of collagenase in this challenging subset of patients. Based on our observations in this limited cohort, it appears appropriate to pursue further studies on use of collagenase enzymatic fasciotomy. A randomized, prospective or case–control series comparing surgical fasciectomy with enzymatic fasciotomy would yield further meaningful data. As more patients seek nonsurgical treatment for Dupuytren disease, its safety and efficacy in select cohorts of patients should continue to be evaluated.

The incidence of Dupuytren disease increases with advancing age,¹ as do the medical comorbidities of patients seeking treatment for disabling hand contractures. For patients with significant comorbidities, open surgical fasciectomy, the current standard of treatment for Dupuytren disease,^2,3 may be associated with increased perioperative risks.

Collagenase enzymatic fasciotomy has become an accepted nonsurgical treatment alternative to traditional fasciectomy or surgical fasciotomy for significant digital contractures caused by Dupuytren disease.^4-6 Clostridium histolyticum collagenase (CHC) is a foreign protein, made up of 2 collagenases isolated from the bacteria C histolyticum.⁷ The collagenases are zinc-dependent matrix metalloproteinases that cleave the triple helical structure of collagen molecules.⁸ Also known as Xiaflex (Auxilium Pharmaceuticals), CHC was approved by the US Food and Drug Administration (FDA) in February 2010 for use in patients with Dupuytren contractures.

 Enzymatic rupture is safe and efficacious at midterm follow-up and offers the theoretical advantage of avoiding palmar and digital fasciectomy and the associated risks of surgical-site infection and wound-healing complications.⁶ The risks of surgical wound complications are magnified in immunosuppressed patients, particularly those on chronic steroid therapy; wound-healing complication rates may be increased 2 to 5 times compared with controls.⁹ In a pooled literature review, wound-healing complications were reported after 22.9% of open primary fasciectomies, with infection occurring in 2.4%.¹⁰ A nonsurgical alternative is therefore particularly appealing for a patient cohort that may be at higher risk for a frequently described complication of surgery for Dupuytren contracture.

The exclusion criteria in the trials for FDA approval were extensive and included breast-feeding, pregnancy, bleeding disorder, recent stroke, use of tetracycline derivative within 14 days before start of study, use of anticoagulant within 7 days before start of study, allergy to collagenase, and chronic muscular, neurologic, or neuromuscular disorder affecting the hands.⁶ Safety and efficacy of collagenase in patients requiring chronic immunosuppressive therapy for medical comorbidities have not been previously documented. Furthermore, although skin tears were reported in 11% of patients after manual cord rupture in the CORD (Collagenase Option for the Reduction of Dupuytren’s) I trial,⁶ the likelihood of deep and superficial infection and delayed wound healing has not been quantitated.

In this article, we report on outcomes of 13 collagenase enzymatic fasciotomies performed in 8 patients who were on chronic immunosuppressive therapy.

Methods

Institutional review board approval was obtained at both academic hand surgery institutions. We retrospectively reviewed prospectively collected clinical data within our 2 centers’ databases of patients with Dupuytren disease. Eight patients on chronic immunosuppressive therapies treated with collagenase for metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint contractures between February 2010 and December 2011 were identified. Three of these patients received collagenase injections into 2 or more separate Dupuytren cords at different encounters, resulting in a total of 13 individual collagenase enzymatic fasciotomies.

Collagenase injections were administered following CORD I trial protocol,⁶ except we injected Dupuytren cords crossing the PIP joint using a lateral approach to minimize risk of flexor tendon rupture. Manipulation of the treated joint was performed between 24 and 48 hours after collagenase injection under local anesthesia with 3 mL of 1% mepivacaine or lidocaine without epinephrine. After manipulation and cord rupture, patients were placed in a hand-based extension splint to wear at night for up to 3 months. Patients were followed at 1 and 12 months.

Results

Patients’ baseline characteristics are summarized in Table 1. Four patients were maintained on chronic prednisone therapy, 3 on methotrexate, and 1 on azathioprine. Therapy duration, medication dose, and diagnoses requiring immunosuppressant therapy varied among patients.

Outcomes and adverse events are summarized in Table 2. Mean number of joint contractures per hand treated was 2.8 (MP, 1.4; PIP, 1.4). However, not all joints met the intervention criteria. Of the 13 joints treated, 7 were MP joints, and 6 were PIP joints. Mean preinjection contracture of the treated joints was 53.0° (range, 20°-90°). Twelve of the 13 joint contractures improved. At mean follow-up of 6.7 months (range, 1-22 months), mean magnitude of contracture improved to 12.9° (range, 0°-45°). Mean MP joint contracture improved from 42.0° to 4.2° (range, 0°-10°), and mean PIP joint contracture improved from 65.8° to 21.7° (range, 0°-45°).

All 13 collagenase injections were well tolerated, and there were no systemic reactions. Injection-site pain was common. Mild injection-site bruising and edema were reported in all cases. Enzymatic fasciotomy was performed in all patients, and immediate improvement in contracture after manipulation 24 to 48 hours after injection was recorded.

Three of the 13 injections were complicated by skin tears during manipulation and cord rupture. All 3 skin tears were treated with local wound care, which included use of povidone-iodine and wet-to-dry dressings. There was no evidence of subsequent superficial or deep, local or regional infection. In 2 cases, the wound healed within 1 week; in the third case, wound healing was present by 2 weeks. Once the wounds showed early re-epithelialization, hand-based extension splinting in a position of comfort was used at night for up to 3 months after injection. Two of the 13 injections were complicated by small blood blisters. These were treated with observation and resolved spontaneously.

Discussion

Collagenase enzymatic fasciotomy appeared to be a safe and efficacious alternative to surgical treatment of Dupuytren contractures in this cohort of patients maintained on chronic immunosuppressive agents. MP contractures responded more substantially than PIP contractures did, as expected.⁶ No previously undescribed adverse outcomes were noted in these 8 patients on chronic immunosuppressive therapy beyond those reported in the CORD I trial. Three (23%) of the 13 collagenase injections in our series were complicated by skin tears after manipulation. Skins tears were reported in 22 (11%) of 204 patients after manual cord rupture in the CORD I trial.⁶ Given the limited numbers in this series, it remains unclear if chronic immunosuppression truly increases the risk of skin tears in this subset of patients. Other common treatment-related adverse events seen in the CORD I trial—injection-site hemorrhage (37%), pruritis (11%) and lymphadenopathy (10%)—were not seen after the 13 injections in our case series. We are prospectively following all patients with Dupuytren disease, and this is an area of ongoing research at our centers.

The immunosuppressive actions of prednisone, azathioprine, and methotrexate are well documented. Prednisone is a glucocorticoid, converted in the liver to prednisolone, which suppresses inflammation and immune responses by regulation of gene expression. Its immunosuppressive actions are multifactorial, relating to inhibition of lymphocytes, neutrophils, and monocytes. These effects are dose- and time-dependent¹¹ and may become evident in patients receiving low doses over prolonged periods. Skin atrophy¹² and delayed wound healing⁹ are side effects of long-term prednisone use. Skin atrophy may make the prednisone-treated patient more susceptible to skin tears after collagenase injection and manipulation. Azathioprine inhibits purine synthesis, which is especially important in the proliferation of immune cells.¹³ It has been shown to inhibit both cellular immunity at low doses and humoral immunity at higher doses.¹⁴ Methotrexate inhibits lymphocyte folic acid metabolism. The immunosuppressive properties of low-dose methotrexate have been linked to the induction of apoptosis in activated T cells.¹⁵

A more complex process in immunosuppressed patients is the immunogenicity of injected collagenase. As CHC in current use is a mixture of 2 foreign proteins, an immunologic response is expected in the host after injection. It has been shown that, after 3 injections of CHC into Dupuytren cords, 100% of patients developed antibodies to both enzymes in their serum.⁶ More than 85% demonstrated anti-CHC antibodies after a single injection. However, no patients showed signs of anaphylaxis or allergic reaction, and there was no correlation between serum levels of anti-CHC and adverse events. It has been hypothesized that there is a potential for cross-reactivity of the anti-CHC antibodies with human matrix metalloproteinases, causing enzymatic dysfunction within the host.¹⁶ This has yet to be reported clinically, and Xiaflex is currently under postmarketing surveillance. Immunocompromised people, with suppressed humoral and cellular immune responses, may produce less of an antibody response to the foreign CHC proteins. Whether this conclusively leads to a change in the side effect profile of the medication in these individuals is beyond the scope of this article. However, we identified no new side effects in this small but higher risk cohort. The issue should be continually monitored as collagenase is used in wider clinical settings.

Collagenase enzymatic fasciotomy is a new nonsurgical therapeutic option for Dupuytren disease. Indications and guidelines for use continue to evolve. This case series highlights the use of collagenase in 8 patients who were on long-term immunosuppressive therapy. This study has the limitations inherent to retrospective analyses. It is difficult to generalize results across broader immunosuppressed populations. A larger cohort, with long-term follow-up assessing recurrence of contracture, is needed to make definitive conclusions about use of collagenase in this challenging subset of patients. Based on our observations in this limited cohort, it appears appropriate to pursue further studies on use of collagenase enzymatic fasciotomy. A randomized, prospective or case–control series comparing surgical fasciectomy with enzymatic fasciotomy would yield further meaningful data. As more patients seek nonsurgical treatment for Dupuytren disease, its safety and efficacy in select cohorts of patients should continue to be evaluated.