Medical economics has been a major sociopolitical issue in the United States for the past 20 years, with concerns focused on increasing medical spending. These costs are projected to continue to rise, from 15.3% of gross domestic product in 2002 to 19.6% in 2017.¹

Multiple steps have been taken to help reduce the cost of health care, many of which center on physician reimbursement. The Balanced Budget Act of 1997 worked to control Medicare spending by increasing reimbursement for clinic visits by setting reductions for procedural reimbursements. This specifically affects orthopedic surgeons, who between 1991 and 2002 experienced a 28% reduction in reimbursement, after inflation, for commonly performed orthopedic procedures, including hip and knee arthroplasty.² Unfortunately, this system does not take into account the value of services as perceived by patients.

Total hip and knee arthroplasty (THA, TKA) are well-established surgical treatments for advanced osteoarthritis of the hip and knee, respectively. Much research has been done on patient satisfaction with these procedures and on their long-term results and cost-effectiveness. These procedures rank among the highest in patient satisfaction, and improvements in technique and technology have steadily improved long-term results. THA and TKA have proved to be cost-effective in appropriately indicated patients.

The demand for THA and TKA is projected to increase by 174% and 673%, respectively, from 2005 to 2030.³ Legislators, payers, health care providers, and patients are understandably concerned about the rising cost of health care and the implications for access to elective surgical procedures. In a recent study by Foran and colleagues,⁴ surveyed postoperative patients indicated that Medicare reimbursement was “much lower” for arthroplasty than it should be. In addition, they overestimated (compared with national averages) what Medicare reimburses for hip and knee arthroplasty. Many raised concerns that orthopedic surgeons might drop Medicare entirely.⁴

These misconceptions about reimbursement may stem partly from the inaccessibility of health care cost information. Rosenthal and colleagues⁵ recently queried a random selection of US hospitals and demonstrated the difficulty in obtaining THA pricing information.

In a system in which consumers and payers are often not one and the same, it is unclear if consumers understand the cost of their health care. We conducted a study to assess patients’ perceptions of the cost of total joint arthroplasty (TJA) and gain insight into their understanding of health care costs and their sense of the value of this elective surgical procedure.

Materials and Methods

After obtaining institutional review board approval and informed consent for this study, we surveyed 284 consecutive patients who underwent THA or TKA at an academic medical center. Patients had either primary or revision surgery performed (by Dr. Hallstrom or Dr. Urquhart) and were surveyed during their first (2-week) postoperative visit, between March 1, 2012 and December 20, 2012.

Surveys were labeled with patient identifiers to facilitate abstraction of data from electronic medical records. Operative reports and discharge summaries were reviewed for data that included sex, age, diagnosis, procedure, surgeon, implant, admission date, and length of stay.

The survey asked for demographic information, including level of education, insurance coverage, and annual household income, and included a question to verify the surgical procedure and a question to determine if the patient had reviewed a hospital billing statement pertaining to the patient’s admission. The survey also included these questions about reimbursement and cost:

• How much do you feel your orthopedic surgeon was reimbursed for your surgery? (EXCLUDING payments to the hospital)

• How much do you think your surgeon gets reimbursed to see you IN THE HOSPITAL after surgery?

• How much do you think your surgeon gets reimbursed per visit to see you IN CLINIC for follow-up during the first 3 months after surgery?

• How much do you think the implant used in your surgery cost?

• How much do you think the hospital was reimbursed for your surgery and admission to the hospital after surgery? (EXCLUDING payments to the surgeon)

• How much do you think it cost the hospital to provide your surgery and admission to the hospital after surgery?

Responses were limited to numeric currency format using a response area as shown in Figure 1. Overall patient satisfaction was elicited with use of a 5-point scale ranging from 1 (very unsatisfied) to 5 (very satisfied). Regarding type of implant used, patients could select from 6 prominent vendors or indicate “other” or “don’t know.” They were also asked which of several factors should primarily determine surgeon reimbursement: overall patient satisfaction, technical difficulty, amount of risk/possible harm, duration/amount of time, and rate of complications. A free-response comments section was provided at the end of the survey.

Data from the survey and the electronic medical records were collected using Research Electronic Data Capture (REDCap; Vanderbilt University, Nashville, Tennessee). Statistical analysis was performed with SAS Version 9.3 (SAS Institute, Cary, North Carolina). Data were screened before further analysis. Patients who provided nonnumeric responses in numeric response fields were excluded from further analysis. Numeric ranges were applied in subsequent analysis using the mean of the range. Implausible responses resulted in the removal of the entire encounter from subsequent analysis.

Demographic data used to define categories for further subgroup analysis are presented as percentages of the group. Medians, means, and interquartile ranges were calculated for all responses regarding reimbursement and cost. Differences in perceptions of reimbursement and cost based on subgroups, including procedure type, diagnosis, education level, and satisfaction, were calculated. Independent-samples Student t tests were used to determine the statistical significance of the differences detected.

Results

Of the 400 eligible patients seen at the first postoperative follow-up, 284 (71%) were enrolled in the study. Mean (SD) age was 62.6 (12.6) years. Of the 284 patients enrolled, 154 (54%) were female. Of the participants who reported their education and income, 125 (44%) had a bachelor’s degree or higher degree, and 68 (23.9%) reported income of more than $100,000 per year. The largest payers reported by patients were private insurance (80%) and Medicare (46%). Additional demographic details are listed in Table 1.

Of the 284 patients enrolled in the study, 159 (56%) had THA, and 88 (31%) had TKA (Table 2). Thirty-seven patients (13%) underwent revision procedures. Only 5 patients (2%) indicated they had reviewed their hospital billing statement from their most recent admission. Two hundred forty-two patients (85%) were satisfied or very satisfied with their procedure.

Regarding the implant used in their surgery, 216 patients (76%) indicated they did not know which company manufactured it. Of the 68 patients (24%) who named a manufacturer, 53 (78%) were correct in their selection (intraoperative records were checked). Patients indicated they thought the implant used in their surgery cost $6447 on average (95% CI, $5581-$7312).

On average, patients thought their surgeon was reimbursed $12,014 (95% CI, $10,845-$13,183) for their procedure, and they estimated that the hospital was reimbursed $28,392 (95% CI, $25,271-$31,512) for their perioperative care and that it cost the hospital $24,389 (95% CI, $21,612-$27,165) to provide it. Means, confidence intervals, medians, and interquartile ranges for parameters of reimbursement and cost are listed in Table 3. Seventy-one patients (25%) thought on average that the hospital took a net loss for each TJA performed, and 146 patients (51%) thought on average that the hospital generated a net profit for each TJA.

On average, patients thought surgeons were reimbursed $11,872 for a THA and $12,263 for a TKA. Patients also estimated a higher hospital cost (THA, $22,981; TKA, $26,998) and reimbursement (THA, $27,366; TKA, $30,230) after TKA than THA. These differences in perceptions of cost and reimbursement for THA and TKA appear in Table 4 and Figure 2.

Statistically significant differences were also found in perceptions of cost and reimbursement based on level of education and overall patient satisfaction. Patients with a bachelor’s degree or higher estimated physician reimbursement at $11,006, whereas patients with a lower level of education estimated reimbursement at $12,890. In addition, patients with a lower level of education gave estimates of hospital cost and reimbursement that were $7698 and $10,799 higher, respectively, than the estimates given by patients with a higher level of education (Table 5, Figure 3). Patients who were satisfied or very satisfied with their overall TJA experience estimated surgeon reimbursement at $11,673. Patients who indicated they were unsatisfied, very unsatisfied, or neutral regarding their overall experience gave a higher estimate of surgeon reimbursement: $14,317 (Table 6, Figure 4).

Because of the small number of enrolled patients who had revision surgery and the high variability in patient responses, there were no meaningful or statistically significant differences in perceptions of cost and reimbursement based on revision or primary surgery.

Patients also estimated substantial additional reimbursements to physicians for services included at no additional charge with the global surgical package. Median estimates were $300 for reimbursement to a physician making rounds in the hospital and $250 for reimbursement for an outpatient follow-up. Only 47 patients (17%) and 35 patients (12%) correctly indicated there is no additional payment for making rounds and outpatient follow-up, respectively. Estimates of these reimbursements varied by education level, procedure, and overall satisfaction (Tables 4–6).

Discussion

The sustainable growth rate (SGR) formula, part of the Balanced Budget Act of 1997, was constructed to manage health care costs in the context of overall economic growth. By 2001, Medicare health care expenditures had begun to outpace economic growth, and the SGR formula dictated a reduction in reimbursement to physicians. Each year over the past decade, Congress has passed legislation providing a temporary reprieve, staving off a drastic reduction of as much as 25% in 2010.⁶ Despite these adjustments, reimbursement continues to decrease because of overall inflation.

More worrisome is that “more than half of the nearly trillion dollar price tag for expanding coverage under the Affordable Care Act (ACA) will be paid by decreasing spending for the more than 46.3 million individuals covered by Medicare.”⁷ ACA provisions will also create an Independent Payment Advisory Board (IPAB) to oversee health care costs and reduce Medicare spending when it is expected to exceed target levels.⁸ As IPAB cannot recommend increasing revenues or changing benefits, and because it is initially prohibited from recommending decreasing payments to hospitals, the decreases will likely have the greatest impact on physician reimbursement.^7-9

Health care policy has been a major campaign issue during recent US elections. The public and popular media remain engaged in this important discussion. Although patients, policymakers, and physicians are understandably concerned about cost and access to health care, it is unclear if patients understand the distribution of health care cost and reimbursement.

Other authors have studied patients’ perceptions of physician reimbursement for TJA. Hayden and colleagues¹⁰ surveyed 1000 residents of a Texas city. The 121 who responded to the survey thought that fair compensation for performing a TKA was $5080, on average.¹⁰ Although this was significantly higher than the actual Medicare reimbursement at the time, a later study, by Foran and colleagues,⁴ found patients’ estimates of both fair reimbursement and Medicare reimbursement for TJA to be even higher. Foran and colleagues⁴ surveyed 1120 patients who thought surgeons deserved to be paid $14,358 for THA and $13,322 for TKA, on average. These reimbursement values are nearly an order of magnitude higher than actual reimbursements. For Medicare payments, patients lowered their estimates to $8212 for THA and $7196 for TKA.⁴

To our knowledge, the present study is the first to use a “postconsumer” survey to assess patients’ perceptions of THA and TKA costs. Our results confirmed that patients substantially overestimated reimbursement for THA and TKA at $11,872 and $12,263, respectively, relative to the average Medicare reimbursements of $1467 and $1530, respectively.¹¹ We also found that patients overestimated both hospital cost and reimbursement for THA at $22,981 and $27,366, respectively, relative to recently published hospital economic analyses showing THA cost and reimbursement to be $11,688 and $15,789, respectively.¹² Few patients enrolled in our study demonstrated an understanding of the services included in the global surgical package. Only about 12% of patients correctly indicated there was no additional payment to the physician for initial follow-up appointments. However, patients were fairly accurate in their estimates of implant cost. On average, patients who underwent THA priced their implant at $6823, which is only about 9% higher than the reported median cost of $6072 to $6400.^13,14

We also found significant differences in perceptions of cost based on level of education, joint replaced, and overall level of satisfaction. On average, patients with a bachelor’s degree or higher gave estimates of cost and reimbursement that were lower than those given by patients with a lower level of education. Estimates of physician reimbursement and hospital reimbursement and cost were higher from patients who had TKA than from patients who had THA.

Comparing perceptions of reimbursement for appendectomy and coronary artery bypass with perceptions for TJA, Foran and colleagues⁴ found that patients understood the relative complexity of each procedure, as evidenced by their estimates of fair reimbursement for each. However, in comparing patient estimates for the different components of cost and reimbursement for TJA, we found great variability in understanding. Patients in our study overestimated payments to the hospital by 73% but overestimated the cost of the THA implant by only 9%. However, the same patients overestimated physician reimbursement for THA by about 800%. If these patients’ estimates of reimbursement are considered surrogates for relative value, then physicians, based on actual payments, are grossly undervalued relative to implant manufacturers.

Our study had several limitations. First, the enrolled patients were all seen at one medical center, in Ann Arbor, Michigan, and our results may not be generalizable outside the region. Second, the survey respondents were postoperative patients who had an established relationship with the study’s principal investigators—a relationship that may have been a source of bias in the consideration of reimbursement as a function of value. Third, despite our efforts to carefully design a survey with open-ended responses, the order in which the survey questions were presented may have influenced patient responses. Fourth, the open-ended question design may have had an impact on responses where the correct answer would have required entering 0.00.

Despite these limitations, our study results demonstrated general public misconceptions about cost and reimbursement for common orthopedic procedures. Although more transparency in health care cost information may not immediately result in a more well-informed population,¹⁵ our patients, given the opportunity to develop an understanding of the economics of their own medical treatment, may become better prepared to make informed choices regarding changes in health care policy.

Medical economics has been a major sociopolitical issue in the United States for the past 20 years, with concerns focused on increasing medical spending. These costs are projected to continue to rise, from 15.3% of gross domestic product in 2002 to 19.6% in 2017.¹

Multiple steps have been taken to help reduce the cost of health care, many of which center on physician reimbursement. The Balanced Budget Act of 1997 worked to control Medicare spending by increasing reimbursement for clinic visits by setting reductions for procedural reimbursements. This specifically affects orthopedic surgeons, who between 1991 and 2002 experienced a 28% reduction in reimbursement, after inflation, for commonly performed orthopedic procedures, including hip and knee arthroplasty.² Unfortunately, this system does not take into account the value of services as perceived by patients.

Total hip and knee arthroplasty (THA, TKA) are well-established surgical treatments for advanced osteoarthritis of the hip and knee, respectively. Much research has been done on patient satisfaction with these procedures and on their long-term results and cost-effectiveness. These procedures rank among the highest in patient satisfaction, and improvements in technique and technology have steadily improved long-term results. THA and TKA have proved to be cost-effective in appropriately indicated patients.

The demand for THA and TKA is projected to increase by 174% and 673%, respectively, from 2005 to 2030.³ Legislators, payers, health care providers, and patients are understandably concerned about the rising cost of health care and the implications for access to elective surgical procedures. In a recent study by Foran and colleagues,⁴ surveyed postoperative patients indicated that Medicare reimbursement was “much lower” for arthroplasty than it should be. In addition, they overestimated (compared with national averages) what Medicare reimburses for hip and knee arthroplasty. Many raised concerns that orthopedic surgeons might drop Medicare entirely.⁴

These misconceptions about reimbursement may stem partly from the inaccessibility of health care cost information. Rosenthal and colleagues⁵ recently queried a random selection of US hospitals and demonstrated the difficulty in obtaining THA pricing information.

In a system in which consumers and payers are often not one and the same, it is unclear if consumers understand the cost of their health care. We conducted a study to assess patients’ perceptions of the cost of total joint arthroplasty (TJA) and gain insight into their understanding of health care costs and their sense of the value of this elective surgical procedure.

Materials and Methods

After obtaining institutional review board approval and informed consent for this study, we surveyed 284 consecutive patients who underwent THA or TKA at an academic medical center. Patients had either primary or revision surgery performed (by Dr. Hallstrom or Dr. Urquhart) and were surveyed during their first (2-week) postoperative visit, between March 1, 2012 and December 20, 2012.

Surveys were labeled with patient identifiers to facilitate abstraction of data from electronic medical records. Operative reports and discharge summaries were reviewed for data that included sex, age, diagnosis, procedure, surgeon, implant, admission date, and length of stay.

The survey asked for demographic information, including level of education, insurance coverage, and annual household income, and included a question to verify the surgical procedure and a question to determine if the patient had reviewed a hospital billing statement pertaining to the patient’s admission. The survey also included these questions about reimbursement and cost:

• How much do you feel your orthopedic surgeon was reimbursed for your surgery? (EXCLUDING payments to the hospital)

• How much do you think your surgeon gets reimbursed to see you IN THE HOSPITAL after surgery?

• How much do you think your surgeon gets reimbursed per visit to see you IN CLINIC for follow-up during the first 3 months after surgery?

• How much do you think the implant used in your surgery cost?

• How much do you think the hospital was reimbursed for your surgery and admission to the hospital after surgery? (EXCLUDING payments to the surgeon)

• How much do you think it cost the hospital to provide your surgery and admission to the hospital after surgery?

Responses were limited to numeric currency format using a response area as shown in Figure 1. Overall patient satisfaction was elicited with use of a 5-point scale ranging from 1 (very unsatisfied) to 5 (very satisfied). Regarding type of implant used, patients could select from 6 prominent vendors or indicate “other” or “don’t know.” They were also asked which of several factors should primarily determine surgeon reimbursement: overall patient satisfaction, technical difficulty, amount of risk/possible harm, duration/amount of time, and rate of complications. A free-response comments section was provided at the end of the survey.

Data from the survey and the electronic medical records were collected using Research Electronic Data Capture (REDCap; Vanderbilt University, Nashville, Tennessee). Statistical analysis was performed with SAS Version 9.3 (SAS Institute, Cary, North Carolina). Data were screened before further analysis. Patients who provided nonnumeric responses in numeric response fields were excluded from further analysis. Numeric ranges were applied in subsequent analysis using the mean of the range. Implausible responses resulted in the removal of the entire encounter from subsequent analysis.

Demographic data used to define categories for further subgroup analysis are presented as percentages of the group. Medians, means, and interquartile ranges were calculated for all responses regarding reimbursement and cost. Differences in perceptions of reimbursement and cost based on subgroups, including procedure type, diagnosis, education level, and satisfaction, were calculated. Independent-samples Student t tests were used to determine the statistical significance of the differences detected.

Results

Of the 400 eligible patients seen at the first postoperative follow-up, 284 (71%) were enrolled in the study. Mean (SD) age was 62.6 (12.6) years. Of the 284 patients enrolled, 154 (54%) were female. Of the participants who reported their education and income, 125 (44%) had a bachelor’s degree or higher degree, and 68 (23.9%) reported income of more than $100,000 per year. The largest payers reported by patients were private insurance (80%) and Medicare (46%). Additional demographic details are listed in Table 1.

Of the 284 patients enrolled in the study, 159 (56%) had THA, and 88 (31%) had TKA (Table 2). Thirty-seven patients (13%) underwent revision procedures. Only 5 patients (2%) indicated they had reviewed their hospital billing statement from their most recent admission. Two hundred forty-two patients (85%) were satisfied or very satisfied with their procedure.

Regarding the implant used in their surgery, 216 patients (76%) indicated they did not know which company manufactured it. Of the 68 patients (24%) who named a manufacturer, 53 (78%) were correct in their selection (intraoperative records were checked). Patients indicated they thought the implant used in their surgery cost $6447 on average (95% CI, $5581-$7312).

On average, patients thought their surgeon was reimbursed $12,014 (95% CI, $10,845-$13,183) for their procedure, and they estimated that the hospital was reimbursed $28,392 (95% CI, $25,271-$31,512) for their perioperative care and that it cost the hospital $24,389 (95% CI, $21,612-$27,165) to provide it. Means, confidence intervals, medians, and interquartile ranges for parameters of reimbursement and cost are listed in Table 3. Seventy-one patients (25%) thought on average that the hospital took a net loss for each TJA performed, and 146 patients (51%) thought on average that the hospital generated a net profit for each TJA.

On average, patients thought surgeons were reimbursed $11,872 for a THA and $12,263 for a TKA. Patients also estimated a higher hospital cost (THA, $22,981; TKA, $26,998) and reimbursement (THA, $27,366; TKA, $30,230) after TKA than THA. These differences in perceptions of cost and reimbursement for THA and TKA appear in Table 4 and Figure 2.

Statistically significant differences were also found in perceptions of cost and reimbursement based on level of education and overall patient satisfaction. Patients with a bachelor’s degree or higher estimated physician reimbursement at $11,006, whereas patients with a lower level of education estimated reimbursement at $12,890. In addition, patients with a lower level of education gave estimates of hospital cost and reimbursement that were $7698 and $10,799 higher, respectively, than the estimates given by patients with a higher level of education (Table 5, Figure 3). Patients who were satisfied or very satisfied with their overall TJA experience estimated surgeon reimbursement at $11,673. Patients who indicated they were unsatisfied, very unsatisfied, or neutral regarding their overall experience gave a higher estimate of surgeon reimbursement: $14,317 (Table 6, Figure 4).

Because of the small number of enrolled patients who had revision surgery and the high variability in patient responses, there were no meaningful or statistically significant differences in perceptions of cost and reimbursement based on revision or primary surgery.

Patients also estimated substantial additional reimbursements to physicians for services included at no additional charge with the global surgical package. Median estimates were $300 for reimbursement to a physician making rounds in the hospital and $250 for reimbursement for an outpatient follow-up. Only 47 patients (17%) and 35 patients (12%) correctly indicated there is no additional payment for making rounds and outpatient follow-up, respectively. Estimates of these reimbursements varied by education level, procedure, and overall satisfaction (Tables 4–6).

Discussion

The sustainable growth rate (SGR) formula, part of the Balanced Budget Act of 1997, was constructed to manage health care costs in the context of overall economic growth. By 2001, Medicare health care expenditures had begun to outpace economic growth, and the SGR formula dictated a reduction in reimbursement to physicians. Each year over the past decade, Congress has passed legislation providing a temporary reprieve, staving off a drastic reduction of as much as 25% in 2010.⁶ Despite these adjustments, reimbursement continues to decrease because of overall inflation.

More worrisome is that “more than half of the nearly trillion dollar price tag for expanding coverage under the Affordable Care Act (ACA) will be paid by decreasing spending for the more than 46.3 million individuals covered by Medicare.”⁷ ACA provisions will also create an Independent Payment Advisory Board (IPAB) to oversee health care costs and reduce Medicare spending when it is expected to exceed target levels.⁸ As IPAB cannot recommend increasing revenues or changing benefits, and because it is initially prohibited from recommending decreasing payments to hospitals, the decreases will likely have the greatest impact on physician reimbursement.^7-9

Health care policy has been a major campaign issue during recent US elections. The public and popular media remain engaged in this important discussion. Although patients, policymakers, and physicians are understandably concerned about cost and access to health care, it is unclear if patients understand the distribution of health care cost and reimbursement.

Other authors have studied patients’ perceptions of physician reimbursement for TJA. Hayden and colleagues¹⁰ surveyed 1000 residents of a Texas city. The 121 who responded to the survey thought that fair compensation for performing a TKA was $5080, on average.¹⁰ Although this was significantly higher than the actual Medicare reimbursement at the time, a later study, by Foran and colleagues,⁴ found patients’ estimates of both fair reimbursement and Medicare reimbursement for TJA to be even higher. Foran and colleagues⁴ surveyed 1120 patients who thought surgeons deserved to be paid $14,358 for THA and $13,322 for TKA, on average. These reimbursement values are nearly an order of magnitude higher than actual reimbursements. For Medicare payments, patients lowered their estimates to $8212 for THA and $7196 for TKA.⁴

To our knowledge, the present study is the first to use a “postconsumer” survey to assess patients’ perceptions of THA and TKA costs. Our results confirmed that patients substantially overestimated reimbursement for THA and TKA at $11,872 and $12,263, respectively, relative to the average Medicare reimbursements of $1467 and $1530, respectively.¹¹ We also found that patients overestimated both hospital cost and reimbursement for THA at $22,981 and $27,366, respectively, relative to recently published hospital economic analyses showing THA cost and reimbursement to be $11,688 and $15,789, respectively.¹² Few patients enrolled in our study demonstrated an understanding of the services included in the global surgical package. Only about 12% of patients correctly indicated there was no additional payment to the physician for initial follow-up appointments. However, patients were fairly accurate in their estimates of implant cost. On average, patients who underwent THA priced their implant at $6823, which is only about 9% higher than the reported median cost of $6072 to $6400.^13,14

We also found significant differences in perceptions of cost based on level of education, joint replaced, and overall level of satisfaction. On average, patients with a bachelor’s degree or higher gave estimates of cost and reimbursement that were lower than those given by patients with a lower level of education. Estimates of physician reimbursement and hospital reimbursement and cost were higher from patients who had TKA than from patients who had THA.

Comparing perceptions of reimbursement for appendectomy and coronary artery bypass with perceptions for TJA, Foran and colleagues⁴ found that patients understood the relative complexity of each procedure, as evidenced by their estimates of fair reimbursement for each. However, in comparing patient estimates for the different components of cost and reimbursement for TJA, we found great variability in understanding. Patients in our study overestimated payments to the hospital by 73% but overestimated the cost of the THA implant by only 9%. However, the same patients overestimated physician reimbursement for THA by about 800%. If these patients’ estimates of reimbursement are considered surrogates for relative value, then physicians, based on actual payments, are grossly undervalued relative to implant manufacturers.

Our study had several limitations. First, the enrolled patients were all seen at one medical center, in Ann Arbor, Michigan, and our results may not be generalizable outside the region. Second, the survey respondents were postoperative patients who had an established relationship with the study’s principal investigators—a relationship that may have been a source of bias in the consideration of reimbursement as a function of value. Third, despite our efforts to carefully design a survey with open-ended responses, the order in which the survey questions were presented may have influenced patient responses. Fourth, the open-ended question design may have had an impact on responses where the correct answer would have required entering 0.00.

Despite these limitations, our study results demonstrated general public misconceptions about cost and reimbursement for common orthopedic procedures. Although more transparency in health care cost information may not immediately result in a more well-informed population,¹⁵ our patients, given the opportunity to develop an understanding of the economics of their own medical treatment, may become better prepared to make informed choices regarding changes in health care policy.

Medical economics has been a major sociopolitical issue in the United States for the past 20 years, with concerns focused on increasing medical spending. These costs are projected to continue to rise, from 15.3% of gross domestic product in 2002 to 19.6% in 2017.¹

Multiple steps have been taken to help reduce the cost of health care, many of which center on physician reimbursement. The Balanced Budget Act of 1997 worked to control Medicare spending by increasing reimbursement for clinic visits by setting reductions for procedural reimbursements. This specifically affects orthopedic surgeons, who between 1991 and 2002 experienced a 28% reduction in reimbursement, after inflation, for commonly performed orthopedic procedures, including hip and knee arthroplasty.² Unfortunately, this system does not take into account the value of services as perceived by patients.

Total hip and knee arthroplasty (THA, TKA) are well-established surgical treatments for advanced osteoarthritis of the hip and knee, respectively. Much research has been done on patient satisfaction with these procedures and on their long-term results and cost-effectiveness. These procedures rank among the highest in patient satisfaction, and improvements in technique and technology have steadily improved long-term results. THA and TKA have proved to be cost-effective in appropriately indicated patients.

The demand for THA and TKA is projected to increase by 174% and 673%, respectively, from 2005 to 2030.³ Legislators, payers, health care providers, and patients are understandably concerned about the rising cost of health care and the implications for access to elective surgical procedures. In a recent study by Foran and colleagues,⁴ surveyed postoperative patients indicated that Medicare reimbursement was “much lower” for arthroplasty than it should be. In addition, they overestimated (compared with national averages) what Medicare reimburses for hip and knee arthroplasty. Many raised concerns that orthopedic surgeons might drop Medicare entirely.⁴

These misconceptions about reimbursement may stem partly from the inaccessibility of health care cost information. Rosenthal and colleagues⁵ recently queried a random selection of US hospitals and demonstrated the difficulty in obtaining THA pricing information.

In a system in which consumers and payers are often not one and the same, it is unclear if consumers understand the cost of their health care. We conducted a study to assess patients’ perceptions of the cost of total joint arthroplasty (TJA) and gain insight into their understanding of health care costs and their sense of the value of this elective surgical procedure.

Materials and Methods

After obtaining institutional review board approval and informed consent for this study, we surveyed 284 consecutive patients who underwent THA or TKA at an academic medical center. Patients had either primary or revision surgery performed (by Dr. Hallstrom or Dr. Urquhart) and were surveyed during their first (2-week) postoperative visit, between March 1, 2012 and December 20, 2012.

Surveys were labeled with patient identifiers to facilitate abstraction of data from electronic medical records. Operative reports and discharge summaries were reviewed for data that included sex, age, diagnosis, procedure, surgeon, implant, admission date, and length of stay.

The survey asked for demographic information, including level of education, insurance coverage, and annual household income, and included a question to verify the surgical procedure and a question to determine if the patient had reviewed a hospital billing statement pertaining to the patient’s admission. The survey also included these questions about reimbursement and cost:

• How much do you feel your orthopedic surgeon was reimbursed for your surgery? (EXCLUDING payments to the hospital)

• How much do you think your surgeon gets reimbursed to see you IN THE HOSPITAL after surgery?

• How much do you think your surgeon gets reimbursed per visit to see you IN CLINIC for follow-up during the first 3 months after surgery?

• How much do you think the implant used in your surgery cost?

• How much do you think the hospital was reimbursed for your surgery and admission to the hospital after surgery? (EXCLUDING payments to the surgeon)

• How much do you think it cost the hospital to provide your surgery and admission to the hospital after surgery?

Responses were limited to numeric currency format using a response area as shown in Figure 1. Overall patient satisfaction was elicited with use of a 5-point scale ranging from 1 (very unsatisfied) to 5 (very satisfied). Regarding type of implant used, patients could select from 6 prominent vendors or indicate “other” or “don’t know.” They were also asked which of several factors should primarily determine surgeon reimbursement: overall patient satisfaction, technical difficulty, amount of risk/possible harm, duration/amount of time, and rate of complications. A free-response comments section was provided at the end of the survey.

Data from the survey and the electronic medical records were collected using Research Electronic Data Capture (REDCap; Vanderbilt University, Nashville, Tennessee). Statistical analysis was performed with SAS Version 9.3 (SAS Institute, Cary, North Carolina). Data were screened before further analysis. Patients who provided nonnumeric responses in numeric response fields were excluded from further analysis. Numeric ranges were applied in subsequent analysis using the mean of the range. Implausible responses resulted in the removal of the entire encounter from subsequent analysis.

Demographic data used to define categories for further subgroup analysis are presented as percentages of the group. Medians, means, and interquartile ranges were calculated for all responses regarding reimbursement and cost. Differences in perceptions of reimbursement and cost based on subgroups, including procedure type, diagnosis, education level, and satisfaction, were calculated. Independent-samples Student t tests were used to determine the statistical significance of the differences detected.

Results

Of the 400 eligible patients seen at the first postoperative follow-up, 284 (71%) were enrolled in the study. Mean (SD) age was 62.6 (12.6) years. Of the 284 patients enrolled, 154 (54%) were female. Of the participants who reported their education and income, 125 (44%) had a bachelor’s degree or higher degree, and 68 (23.9%) reported income of more than $100,000 per year. The largest payers reported by patients were private insurance (80%) and Medicare (46%). Additional demographic details are listed in Table 1.

Of the 284 patients enrolled in the study, 159 (56%) had THA, and 88 (31%) had TKA (Table 2). Thirty-seven patients (13%) underwent revision procedures. Only 5 patients (2%) indicated they had reviewed their hospital billing statement from their most recent admission. Two hundred forty-two patients (85%) were satisfied or very satisfied with their procedure.

Regarding the implant used in their surgery, 216 patients (76%) indicated they did not know which company manufactured it. Of the 68 patients (24%) who named a manufacturer, 53 (78%) were correct in their selection (intraoperative records were checked). Patients indicated they thought the implant used in their surgery cost $6447 on average (95% CI, $5581-$7312).

On average, patients thought their surgeon was reimbursed $12,014 (95% CI, $10,845-$13,183) for their procedure, and they estimated that the hospital was reimbursed $28,392 (95% CI, $25,271-$31,512) for their perioperative care and that it cost the hospital $24,389 (95% CI, $21,612-$27,165) to provide it. Means, confidence intervals, medians, and interquartile ranges for parameters of reimbursement and cost are listed in Table 3. Seventy-one patients (25%) thought on average that the hospital took a net loss for each TJA performed, and 146 patients (51%) thought on average that the hospital generated a net profit for each TJA.

On average, patients thought surgeons were reimbursed $11,872 for a THA and $12,263 for a TKA. Patients also estimated a higher hospital cost (THA, $22,981; TKA, $26,998) and reimbursement (THA, $27,366; TKA, $30,230) after TKA than THA. These differences in perceptions of cost and reimbursement for THA and TKA appear in Table 4 and Figure 2.

Statistically significant differences were also found in perceptions of cost and reimbursement based on level of education and overall patient satisfaction. Patients with a bachelor’s degree or higher estimated physician reimbursement at $11,006, whereas patients with a lower level of education estimated reimbursement at $12,890. In addition, patients with a lower level of education gave estimates of hospital cost and reimbursement that were $7698 and $10,799 higher, respectively, than the estimates given by patients with a higher level of education (Table 5, Figure 3). Patients who were satisfied or very satisfied with their overall TJA experience estimated surgeon reimbursement at $11,673. Patients who indicated they were unsatisfied, very unsatisfied, or neutral regarding their overall experience gave a higher estimate of surgeon reimbursement: $14,317 (Table 6, Figure 4).

Because of the small number of enrolled patients who had revision surgery and the high variability in patient responses, there were no meaningful or statistically significant differences in perceptions of cost and reimbursement based on revision or primary surgery.

Patients also estimated substantial additional reimbursements to physicians for services included at no additional charge with the global surgical package. Median estimates were $300 for reimbursement to a physician making rounds in the hospital and $250 for reimbursement for an outpatient follow-up. Only 47 patients (17%) and 35 patients (12%) correctly indicated there is no additional payment for making rounds and outpatient follow-up, respectively. Estimates of these reimbursements varied by education level, procedure, and overall satisfaction (Tables 4–6).

Discussion

The sustainable growth rate (SGR) formula, part of the Balanced Budget Act of 1997, was constructed to manage health care costs in the context of overall economic growth. By 2001, Medicare health care expenditures had begun to outpace economic growth, and the SGR formula dictated a reduction in reimbursement to physicians. Each year over the past decade, Congress has passed legislation providing a temporary reprieve, staving off a drastic reduction of as much as 25% in 2010.⁶ Despite these adjustments, reimbursement continues to decrease because of overall inflation.

More worrisome is that “more than half of the nearly trillion dollar price tag for expanding coverage under the Affordable Care Act (ACA) will be paid by decreasing spending for the more than 46.3 million individuals covered by Medicare.”⁷ ACA provisions will also create an Independent Payment Advisory Board (IPAB) to oversee health care costs and reduce Medicare spending when it is expected to exceed target levels.⁸ As IPAB cannot recommend increasing revenues or changing benefits, and because it is initially prohibited from recommending decreasing payments to hospitals, the decreases will likely have the greatest impact on physician reimbursement.^7-9

Health care policy has been a major campaign issue during recent US elections. The public and popular media remain engaged in this important discussion. Although patients, policymakers, and physicians are understandably concerned about cost and access to health care, it is unclear if patients understand the distribution of health care cost and reimbursement.

Other authors have studied patients’ perceptions of physician reimbursement for TJA. Hayden and colleagues¹⁰ surveyed 1000 residents of a Texas city. The 121 who responded to the survey thought that fair compensation for performing a TKA was $5080, on average.¹⁰ Although this was significantly higher than the actual Medicare reimbursement at the time, a later study, by Foran and colleagues,⁴ found patients’ estimates of both fair reimbursement and Medicare reimbursement for TJA to be even higher. Foran and colleagues⁴ surveyed 1120 patients who thought surgeons deserved to be paid $14,358 for THA and $13,322 for TKA, on average. These reimbursement values are nearly an order of magnitude higher than actual reimbursements. For Medicare payments, patients lowered their estimates to $8212 for THA and $7196 for TKA.⁴

To our knowledge, the present study is the first to use a “postconsumer” survey to assess patients’ perceptions of THA and TKA costs. Our results confirmed that patients substantially overestimated reimbursement for THA and TKA at $11,872 and $12,263, respectively, relative to the average Medicare reimbursements of $1467 and $1530, respectively.¹¹ We also found that patients overestimated both hospital cost and reimbursement for THA at $22,981 and $27,366, respectively, relative to recently published hospital economic analyses showing THA cost and reimbursement to be $11,688 and $15,789, respectively.¹² Few patients enrolled in our study demonstrated an understanding of the services included in the global surgical package. Only about 12% of patients correctly indicated there was no additional payment to the physician for initial follow-up appointments. However, patients were fairly accurate in their estimates of implant cost. On average, patients who underwent THA priced their implant at $6823, which is only about 9% higher than the reported median cost of $6072 to $6400.^13,14

We also found significant differences in perceptions of cost based on level of education, joint replaced, and overall level of satisfaction. On average, patients with a bachelor’s degree or higher gave estimates of cost and reimbursement that were lower than those given by patients with a lower level of education. Estimates of physician reimbursement and hospital reimbursement and cost were higher from patients who had TKA than from patients who had THA.

Comparing perceptions of reimbursement for appendectomy and coronary artery bypass with perceptions for TJA, Foran and colleagues⁴ found that patients understood the relative complexity of each procedure, as evidenced by their estimates of fair reimbursement for each. However, in comparing patient estimates for the different components of cost and reimbursement for TJA, we found great variability in understanding. Patients in our study overestimated payments to the hospital by 73% but overestimated the cost of the THA implant by only 9%. However, the same patients overestimated physician reimbursement for THA by about 800%. If these patients’ estimates of reimbursement are considered surrogates for relative value, then physicians, based on actual payments, are grossly undervalued relative to implant manufacturers.

Our study had several limitations. First, the enrolled patients were all seen at one medical center, in Ann Arbor, Michigan, and our results may not be generalizable outside the region. Second, the survey respondents were postoperative patients who had an established relationship with the study’s principal investigators—a relationship that may have been a source of bias in the consideration of reimbursement as a function of value. Third, despite our efforts to carefully design a survey with open-ended responses, the order in which the survey questions were presented may have influenced patient responses. Fourth, the open-ended question design may have had an impact on responses where the correct answer would have required entering 0.00.

Despite these limitations, our study results demonstrated general public misconceptions about cost and reimbursement for common orthopedic procedures. Although more transparency in health care cost information may not immediately result in a more well-informed population,¹⁵ our patients, given the opportunity to develop an understanding of the economics of their own medical treatment, may become better prepared to make informed choices regarding changes in health care policy.

Polydactyly is the presence of extra digits. Its incidence is likely underestimated because many practitioners treat simple “nubbins” without referring them to orthopedic specialists.^1-3 Polydactyly can be detected by ultrasound as early as 14 weeks’ gestational age, with partial autoamputation seen in most isolated polydactylies.⁴ The thumb, responsible for 40% of hand function, must be able to oppose the other digits with a stable pinch.⁵ Polydactyly encumbers this motion when the duplicated digits deviate from normal alignment. Ezaki⁶ noted that the anatomy is better described as “split” than “duplicated.” There are many dichotomous ways to classify polydactyly: preaxial (radial) versus postaxial (ulnar), thumb versus triphalangeal, simple versus complex (Figure 1). Mixed polydactyly is defined as the presence of preaxial and postaxial polydactyly.⁷ Surgical management seeks to allow normal hand function and to restore cosmesis.

Epidemiology

Sun and colleagues⁸ reported the overall polydactyly incidence as 2 per 1000 live births in China from 1998 to 2009, with a slight male predominance; polydactyly was also 3 times more common than syndactyly in this population. Ivy,⁹ in a 5-year audit of Pennsylvania Department of Health records, found polydactyly to be the fourth most common congenital anomaly after clubfoot, cleft lip/palate, and spina bifida. Thumb duplication occurs in 0.08 to 1.4 per 1000 live births and is more common in American Indians and Asians than in other races.^5,10 It occurs in a male-to-female ratio of 2.5 to 1 and is most often unilateral.⁵ Postaxial polydactyly is predominant in black infants; it is most often inherited in an autosomal dominant fashion, if isolated, or in an autosomal recessive pattern, if syndromic.¹ A prospective San Diego study of 11,161 newborns found postaxial type B polydactyly in 1 per 531 live births (1 per 143 black infants, 1 per 1339 white infants); 76% of cases were bilateral, and 86% had a positive family history.³ In patients of non-African descent, it is associated with anomalies in other organs. Central duplication is rare and often autosomal dominant.^5,10

Genetics and Development

As early as 1896, the heritability of polydactyly was noted.¹¹ As of 2010, polydactyly has been associated with 310 diseases.¹² Ninety-nine genes, most involved in regulation of anterior-posterior formation of the limb bud, have been implicated.^12,13

The upper limb begins to form at day 26 in utero.¹⁴ Apoptosis in the interdigital necrotic zones results in the formation of individual digits. It is presumed that, in polydactyly, the involved tissue is hypoplastic because of an abnormal interaction between mesoderm and ectoderm.⁵ Presence of an apical ectodermal ridge determines the formation of a limb bud, and on it the zone of polarizing activity (ZPA) dictates preaxial and postaxial alignment.^14,15 The ZPA is located on the posterior zone of the developing limb bud. The levels of GLI3, a zinc finger-containing DNA-binding protein, are highest in the anterior area, and HAND2, a basic helix-loop-helix DNA-binding protein, is found in the ZPA. This polarity promotes sonic hedgehog (Shh) gene expression in the posterior region, which in turn prevents GLI3 cleavage into its repressed form. GLI3R (repressed) and GLI3A (active) concentrations are highest, therefore, in the anterior and posterior portions of the bud, respectively. The GLI3A:GLI3R ratio is responsible for the identity and number of digits in the hand (ie, the thumb develops in regions of high GLI3R). GLI and Shh mutations lead to polydactylous hands with absent thumbs (Figure 2).¹⁶

Ciliopathies have also been shown to cause postaxial polydactyly, possibly because of the role that nonmotile cilia play in hedgehog signaling.¹⁷ Mutations in Shh genomic regulators cause preaxial polydactyly.¹⁸ HoxD activates Shh in the ZPA; HoxD13 mutations are associated with synpolydactyly.^16,19 In each of these mutations, Shh production is altered, and some form of polydactyly results.

Associations

Many syndromes have been associated with polydactyly. Not all polydactyly is associated with other disorders, but the more complex the polydactyly, the more likely that other anomalies are present. Every patient who presents with polydactyly should have a full history taken and a physical examination performed (Figure 3). Any patient with syndromic findings or atypical presentations (eg, triphalangism, postaxial polydactyly in a patient of non-African descent, central and index polydactyly) should be referred to a geneticist.

Classifications

The Wassel²⁰ classification describes the anatomical presentation of thumb duplication on the basis of 70 cases in Iowa (Figures 4, 5; Table 1). Because some duplications fall outside the Wassel classification, many researchers have proposed modifications (Figure 6).^21-25

The Temtamy and McKusick¹⁰ classification, which is the product of geneticists, classifies duplications by grouping genetically related presentations (Table 2). It provides the most commonly used postaxial classification, with type A being a fully developed digit and type B a rudimentary and pedunculated digit, informally referred to as a nubbin. Type B is more common than type A. Given inheritance patterns, it is assumed that type A is likely multifactorial and type B autosomal dominant.¹⁰ Thumb polydactyly inheritance is still unclear. The other types of preaxial polydactyly and high degrees of polydactyly are rare but seem to be passed on in an autosomal dominant fashion on pedigree analysis.¹⁰

The Stelling and Turek classification presents the duplication from a tissue perspective: Type I duplication is a rudimentary mass devoid of other tissue elements; type II is a subtotal duplication with some normal structures; and type III is a duplication of the entire “osteoarticular column,” including the metacarpal.¹ It is interesting to note that histology of type I duplications shows neuroma-like tissue.^26-28 Again, normal is a relative term because, in polydactyly, the duplications are hypoplastic and deviated, with anomalous anatomy.

The Rayan classification describes ulnar polydactyly and was derived from a case study series of 148 patients in Oklahoma (Table 3).²⁹

There are also some complex polydactylies that are not easily classified: ulnar dimelia, cleft hand, pentadactyly, and hyperphalangism. Ulnar dimelia, also known as “mirror hand,” is typically 7 digits with no thumb, but other variations are seen. The radius is often absent, and the elbow is abnormal. There is some debate about whether it is a fusion of 2 hands. Pentadactyly, or the 5-fingered hand, appears as 5 triphalangeal digits with no thumb (Figure 7).

Isolated thumb triphalangism might appear similar to pentadactyly. Miura^30,31 pointed out that the radial digit in the pentadactylous hand may be opposable (thumb-like) or nonopposable; in his studies, the patients with the opposable thumb had a metacarpal with a proximal epiphysis (Figure 8). Consequently, the triphalangeal thumb metacarpal with a distal epiphysis is true pentadactyly, whereas that with a proximal epiphysis is hyperphalangism (Figure 9). Treatment of these complex polydactylies involves the same underlying principles as for preaxial and postaxial polydactyly, albeit with additional proximal upper extremity considerations.

When to Operate (Timing)

Ezaki⁶ recommended surgical intervention at age 6 to 9 months, before fine motor skills have developed with the abnormal anatomy. Cortical learning occurs as the child begins prehensile activities before 6 months, but the risks of anesthesia outweigh functional benefits until the child is older. Waiting until 1 year of age is not uncommon, though surgery at an earlier age may be beneficial if the polydactyly affects hand function.³² It is not uncommon to wait with the more balanced thumb polydactylies to assess thumb function. Hypoplasia might also delay surgical intervention until there is enough tissue inventory for reconstruction. Wassel²⁰ noted that surgical intervention ideally occurs before the supernumerary elements displace the normal elements, as tends to happen with growth. Suture ligation is an option in the neonatal unit for some pedunculated digits.³³ Studies have shown satisfactory results in adults treated for polydactyly, if the patient presents later than expected.³⁴

Surgical Considerations

Knavel recommended simple excision, stating that “ablation requires no ingenuity and creates no problems.”⁵ This belief, though true for some duplications, will not lead to the best outcome for more complex polydactylies. The goal of surgery is a stable and well-aligned thumb for pinch and prehensile activity, as well as a cosmetically pleasing hand. Incisions should not be made linearly along the axis of the digit, as the scar will cause deviation with growth.²⁴

Wassel type I polydactyly might appear incidentally as a broad thumb, in which case it requires no intervention (Figure 10). However, in Wassel types I and II polydactyly with deformity, the Bilhaut-Cloquet procedure is useful for both bifid and duplicated phalanges (Figure 11).^5,6,30,32,35 Collateral ligaments may need to be released in type II because of difficulty in opposing the tissue. Cosmetic results with Bilhaut-Cloquet are unpredictable. The original technique required symmetrically sized digits; results today have been improved with microtechniques and preservation of an entire nail.³⁶ Another option is ablation of the more hypoplastic osseous element and soft-tissue augmentation of the residual digit. The theme of ablation and augmentation is seen throughout the literature for the surgical treatment of polydactyly (Figure 12).¹

For type III polydactyly, the bifid proximal phalanx is narrowed by resection and realigned with osteotomy of the remaining diaphysis. Type IV polydactyly, the most common thumb duplication, often requires advancement of the abductor pollicis brevis to the base of the proximal phalanx to aid in metacarpophalangeal (MCP) stabilization, abduction, and opposition. The metacarpal head, if broad and with 2 facets, can be shaped to form a single articulating surface. The metacarpal, occasionally with the proximal phalanx, often requires realignment by closing wedge osteotomy. Last, tendons on the resected bony elements should be rebalanced on the remaining digit, and anomalous slips must be released. For instance, given a radial insertion of the long flexor tendon on the distal phalanx, the tendon should be moved centrally. A strong flexor or extensor tendon on the amputated digit should be transferred to the remaining digit.²⁴

Types V and VI are treated similarly to type IV, with the addition of a first web space Z-plasty or web widening if there is thenar eminence contracture. Acral transposition has also been described, with transposition of the tip of the ablated digit in place of the tip of the kept digit; this technique is ideal if one digit has a more normal proximal part while the other has a more normal distal part (Figure 13).³⁵

Type VII thumb polydactyly, the type most likely inherited and associated with other disorders, should be treated like type VI. The nail should be preserved; amputation of the distal phalanx is not advised. Resection of the delta phalanx or 1 interphalangeal (IP) joint is an option. Articular surfaces will remodel if done before the age of 1 year. If the thenar eminence is hypoplastic, then Huber transfer of the abductor digiti minimi should be considered.³⁷ Resection of the triphalangeal thumb is also advised, even if the biphalangeal thumb is more hypoplastic, with transfer of the ligaments and tendons, as described earlier.^{5,6,24,30,32,35}

Thumb triphalangism, if isolated, and hyperphalangism in the other digits, can be treated with resection of the delta phalanx or one of the IP joints if it is affecting function or cosmesis.^1,6 Wood and Flatt²³ recommended early resection of a thumb delta phalanx because of the likelihood of deviation that impedes thumb function. For children, they recommended delta phalanx resection and Kirschner wire fixation for 6 weeks; for adults, they recommended resection or fusion of the joint, with osteotomy as needed for deviation.^23,24 For thumb triphalangism, multiple surgeries are the norm, as Wood²⁴ reported in his study of 21 patients who underwent 78 operations in total.

Index polydactyly may present as a simple pedunculated skin tag, which can be simply excised, or as a more complex musculoskeletal duplication. More complex presentations can be treated with procedures similar to those used for the thumb. Typically, the additional digit is radially deviated and angulated, eventually leading to impingement of thumb pinch and the first web space. Ray amputation is also an option if no reconstructive surgery will produce the stable, sensate radial pinch that is essential to hand function.³²

Ring-finger polydactyly and long-finger polydactyly are often complicated by some element of syndactyly, resulting in a relative paucity of skin (Figure 14). There is failure of both formation (hypoplasia) and differentiation (syndactyly). The hypoplasia particularly affects the function of these digits by tethering them; multiple surgeries to restore proper hand function are the norm.¹ Reconstructive surgery for these digits requires preoperative tissue inventory followed by resection and augmentation; as in syndactyly, skin for coverage is at a premium. Creation of a 3-fingered hand is an option.²³

Temtamy and McKusick¹⁰ type A little-finger polydactyly is treated similarly to the thumb, with the caveat that hypothenar and intrinsic muscles that insert on the resected little finger are transferred to the remaining digit. In contrast to thumb polydactyly, the extrinsic musculature tends to be in good position. Suture ligation of type B polydactyly, as described by Flatt, is likely more common than orthopedists appreciate, as pediatricians and neonatal unit practitioners commonly perform this procedure in the nursery.^1-3 It has been described with 2-0 Vicryl³ (Ethicon, Somerville, New Jersey) and 4-0 silk sutures,³² with the goal of necrosis and autoamputation. Parents should be told the finger generally falls off about 10 days (range, 4-21 days) after ligation.³ Multiple authors have cited a report of exsanguination from suture ligation, but we could not locate the primary source. It is advisable to wait until a patient is 6 months of age if planning to resect the nubbin in the operating room, given the anesthesia risk and the lack of functional impairment. Katz and Linder³³ indicated they remove type B polydactyly in the nursery suite used for circumcisions; they use anesthetizing cream on the skin, and sharp excision with a scalpel, followed by direct pressure and Steri-Strip (3M, St. Paul, Minnesota) application. Suture ligation is recommended only if there is a narrow, thin (<2 mm) soft-tissue stalk; any broad or bony stalk necessitates surgical removal to avoid neuroma formation and failure of autonecrosis (Figure 15).²⁷ Other options are a single swipe of a scalpel and elliptical excision; sharp transaction of the digital nerve with subsequent retraction is advised to avoid neuroma formation.²

Barton described ulnar dimelia operations as “spare parts surgery.”¹ Extra digits are ablated and a thumb created (Figure 16). The hand might have a digit in relatively good rotational position for thumbplasty, or the principles of pollicization may need to be used. If the patient is already using the hand, the surgeon should note which finger the patient uses as a thumb.²⁴ Any accompanying wrist flexion contracture must be corrected with careful attention to musculotendinous balancing. Because the forearm and elbow, and occasionally even the more proximal limb, will be abnormal in this disorder, multiple surgeries are again the norm.¹

Pentadactyly is treated like thumb hypoplasia, with first web space creation.¹

Complications

In polydactyly, a reoperation rate of up to 25% has been reported, with most reoperations performed because of residual or subsequent deformity.^5,30,31,38 Risk factors for reoperation are type IV thumb duplication, preoperative “zigzag” deformity, and radially deviated thumb elements at presentation.⁵ The delta phalanx may not show on radiographs until the patient is 18 months old, but functional deformity will worsen as long as it is present. Zigzag deformity may be due to the delta phalanx or to musculotendinous imbalance, such as a radially inserted flexor pollicis longus (FPL) or lack of stable MCP abduction. Miura³¹ found that careful reconstruction of the joint capsule and thenar muscles from the ablated digit to the remnant digit is the key to a successful initial surgery. Lee and colleagues³⁹ defined zigzag deformity as more than 20° MCP and IP angulation; for cases present before surgery, they recommended FPL relocation by the pullout technique in addition to osteotomies to prevent further interphalangeal deviation (Figures 17, 18).

Abnormal physeal growth, joint instability, and stiffness can all occur. Stiffness is particularly difficult to treat but seldom presents a functional problem. Joint enlargement, which is not uncommon, results from either broad articular surfaces or retained cartilage from the perichondral ring after resection that later ossifies.^5,38 Nubbin-type duplications may not fall off after suture ligation, necessitating further excision, and a cosmetic bump is seen after 40% of suture ligations.³ Patillo and Rayan²⁸ and Rayan and Frey²⁹ warned against suture ligation unless the nubbin has a small stalk because of the possibility of infection and gangrene. The excised nubbin tissue is histologically nervous, and there have been reports of painful neuromas in the remaining scar of a ligated nubbin that respond well to excision.^26,27,40 It is thought that these painful lesions form because the ligature prevents the digital nerves to the vestigial digit from retracting.²⁷ Nail deformity and IP joint stiffness are seen with the Bilhaut-Cloquet procedure, though often finger function remains satisfactory.

Conclusion

Polydactyly is a common congenital hand abnormality. Its true incidence is unknown because of inconsistent documentation. Surgeons must strive for a functional, cosmetic hand, given a diverse set of possible anomalies. Hypoplasia is the rule; tissue should be ablated and augmented as necessary. Musculotendinous insertions may need to be centralized. Patients’ family members should always be counseled that more surgery may be needed in the future, as further deformity can occur with growth. Surgically corrected thumb duplications will be stiffer, shorter, and thinner than their normal counterparts. Nail ridges are common. However, it should be noted that 88% of these patients are satisfied with their results.⁴¹ Some amount of contracture and abnormal function should be expected with index-, long-, and ring-finger duplications. The only remnant of type B postaxial duplications may be a slight discoloration or bump, though stiffness and deformity can happen with a type A deformity. A “duplicated” digit that requires surgical correction will never be completely normal, but acceptable function is routinely achievable.

Polydactyly is the presence of extra digits. Its incidence is likely underestimated because many practitioners treat simple “nubbins” without referring them to orthopedic specialists.^1-3 Polydactyly can be detected by ultrasound as early as 14 weeks’ gestational age, with partial autoamputation seen in most isolated polydactylies.⁴ The thumb, responsible for 40% of hand function, must be able to oppose the other digits with a stable pinch.⁵ Polydactyly encumbers this motion when the duplicated digits deviate from normal alignment. Ezaki⁶ noted that the anatomy is better described as “split” than “duplicated.” There are many dichotomous ways to classify polydactyly: preaxial (radial) versus postaxial (ulnar), thumb versus triphalangeal, simple versus complex (Figure 1). Mixed polydactyly is defined as the presence of preaxial and postaxial polydactyly.⁷ Surgical management seeks to allow normal hand function and to restore cosmesis.

Epidemiology

Sun and colleagues⁸ reported the overall polydactyly incidence as 2 per 1000 live births in China from 1998 to 2009, with a slight male predominance; polydactyly was also 3 times more common than syndactyly in this population. Ivy,⁹ in a 5-year audit of Pennsylvania Department of Health records, found polydactyly to be the fourth most common congenital anomaly after clubfoot, cleft lip/palate, and spina bifida. Thumb duplication occurs in 0.08 to 1.4 per 1000 live births and is more common in American Indians and Asians than in other races.^5,10 It occurs in a male-to-female ratio of 2.5 to 1 and is most often unilateral.⁵ Postaxial polydactyly is predominant in black infants; it is most often inherited in an autosomal dominant fashion, if isolated, or in an autosomal recessive pattern, if syndromic.¹ A prospective San Diego study of 11,161 newborns found postaxial type B polydactyly in 1 per 531 live births (1 per 143 black infants, 1 per 1339 white infants); 76% of cases were bilateral, and 86% had a positive family history.³ In patients of non-African descent, it is associated with anomalies in other organs. Central duplication is rare and often autosomal dominant.^5,10

Genetics and Development

As early as 1896, the heritability of polydactyly was noted.¹¹ As of 2010, polydactyly has been associated with 310 diseases.¹² Ninety-nine genes, most involved in regulation of anterior-posterior formation of the limb bud, have been implicated.^12,13

The upper limb begins to form at day 26 in utero.¹⁴ Apoptosis in the interdigital necrotic zones results in the formation of individual digits. It is presumed that, in polydactyly, the involved tissue is hypoplastic because of an abnormal interaction between mesoderm and ectoderm.⁵ Presence of an apical ectodermal ridge determines the formation of a limb bud, and on it the zone of polarizing activity (ZPA) dictates preaxial and postaxial alignment.^14,15 The ZPA is located on the posterior zone of the developing limb bud. The levels of GLI3, a zinc finger-containing DNA-binding protein, are highest in the anterior area, and HAND2, a basic helix-loop-helix DNA-binding protein, is found in the ZPA. This polarity promotes sonic hedgehog (Shh) gene expression in the posterior region, which in turn prevents GLI3 cleavage into its repressed form. GLI3R (repressed) and GLI3A (active) concentrations are highest, therefore, in the anterior and posterior portions of the bud, respectively. The GLI3A:GLI3R ratio is responsible for the identity and number of digits in the hand (ie, the thumb develops in regions of high GLI3R). GLI and Shh mutations lead to polydactylous hands with absent thumbs (Figure 2).¹⁶

Ciliopathies have also been shown to cause postaxial polydactyly, possibly because of the role that nonmotile cilia play in hedgehog signaling.¹⁷ Mutations in Shh genomic regulators cause preaxial polydactyly.¹⁸ HoxD activates Shh in the ZPA; HoxD13 mutations are associated with synpolydactyly.^16,19 In each of these mutations, Shh production is altered, and some form of polydactyly results.

Associations

Many syndromes have been associated with polydactyly. Not all polydactyly is associated with other disorders, but the more complex the polydactyly, the more likely that other anomalies are present. Every patient who presents with polydactyly should have a full history taken and a physical examination performed (Figure 3). Any patient with syndromic findings or atypical presentations (eg, triphalangism, postaxial polydactyly in a patient of non-African descent, central and index polydactyly) should be referred to a geneticist.

Classifications

The Wassel²⁰ classification describes the anatomical presentation of thumb duplication on the basis of 70 cases in Iowa (Figures 4, 5; Table 1). Because some duplications fall outside the Wassel classification, many researchers have proposed modifications (Figure 6).^21-25

The Temtamy and McKusick¹⁰ classification, which is the product of geneticists, classifies duplications by grouping genetically related presentations (Table 2). It provides the most commonly used postaxial classification, with type A being a fully developed digit and type B a rudimentary and pedunculated digit, informally referred to as a nubbin. Type B is more common than type A. Given inheritance patterns, it is assumed that type A is likely multifactorial and type B autosomal dominant.¹⁰ Thumb polydactyly inheritance is still unclear. The other types of preaxial polydactyly and high degrees of polydactyly are rare but seem to be passed on in an autosomal dominant fashion on pedigree analysis.¹⁰

The Stelling and Turek classification presents the duplication from a tissue perspective: Type I duplication is a rudimentary mass devoid of other tissue elements; type II is a subtotal duplication with some normal structures; and type III is a duplication of the entire “osteoarticular column,” including the metacarpal.¹ It is interesting to note that histology of type I duplications shows neuroma-like tissue.^26-28 Again, normal is a relative term because, in polydactyly, the duplications are hypoplastic and deviated, with anomalous anatomy.

The Rayan classification describes ulnar polydactyly and was derived from a case study series of 148 patients in Oklahoma (Table 3).²⁹

There are also some complex polydactylies that are not easily classified: ulnar dimelia, cleft hand, pentadactyly, and hyperphalangism. Ulnar dimelia, also known as “mirror hand,” is typically 7 digits with no thumb, but other variations are seen. The radius is often absent, and the elbow is abnormal. There is some debate about whether it is a fusion of 2 hands. Pentadactyly, or the 5-fingered hand, appears as 5 triphalangeal digits with no thumb (Figure 7).

Isolated thumb triphalangism might appear similar to pentadactyly. Miura^30,31 pointed out that the radial digit in the pentadactylous hand may be opposable (thumb-like) or nonopposable; in his studies, the patients with the opposable thumb had a metacarpal with a proximal epiphysis (Figure 8). Consequently, the triphalangeal thumb metacarpal with a distal epiphysis is true pentadactyly, whereas that with a proximal epiphysis is hyperphalangism (Figure 9). Treatment of these complex polydactylies involves the same underlying principles as for preaxial and postaxial polydactyly, albeit with additional proximal upper extremity considerations.

When to Operate (Timing)

Ezaki⁶ recommended surgical intervention at age 6 to 9 months, before fine motor skills have developed with the abnormal anatomy. Cortical learning occurs as the child begins prehensile activities before 6 months, but the risks of anesthesia outweigh functional benefits until the child is older. Waiting until 1 year of age is not uncommon, though surgery at an earlier age may be beneficial if the polydactyly affects hand function.³² It is not uncommon to wait with the more balanced thumb polydactylies to assess thumb function. Hypoplasia might also delay surgical intervention until there is enough tissue inventory for reconstruction. Wassel²⁰ noted that surgical intervention ideally occurs before the supernumerary elements displace the normal elements, as tends to happen with growth. Suture ligation is an option in the neonatal unit for some pedunculated digits.³³ Studies have shown satisfactory results in adults treated for polydactyly, if the patient presents later than expected.³⁴

Surgical Considerations

Knavel recommended simple excision, stating that “ablation requires no ingenuity and creates no problems.”⁵ This belief, though true for some duplications, will not lead to the best outcome for more complex polydactylies. The goal of surgery is a stable and well-aligned thumb for pinch and prehensile activity, as well as a cosmetically pleasing hand. Incisions should not be made linearly along the axis of the digit, as the scar will cause deviation with growth.²⁴

Wassel type I polydactyly might appear incidentally as a broad thumb, in which case it requires no intervention (Figure 10). However, in Wassel types I and II polydactyly with deformity, the Bilhaut-Cloquet procedure is useful for both bifid and duplicated phalanges (Figure 11).^5,6,30,32,35 Collateral ligaments may need to be released in type II because of difficulty in opposing the tissue. Cosmetic results with Bilhaut-Cloquet are unpredictable. The original technique required symmetrically sized digits; results today have been improved with microtechniques and preservation of an entire nail.³⁶ Another option is ablation of the more hypoplastic osseous element and soft-tissue augmentation of the residual digit. The theme of ablation and augmentation is seen throughout the literature for the surgical treatment of polydactyly (Figure 12).¹

For type III polydactyly, the bifid proximal phalanx is narrowed by resection and realigned with osteotomy of the remaining diaphysis. Type IV polydactyly, the most common thumb duplication, often requires advancement of the abductor pollicis brevis to the base of the proximal phalanx to aid in metacarpophalangeal (MCP) stabilization, abduction, and opposition. The metacarpal head, if broad and with 2 facets, can be shaped to form a single articulating surface. The metacarpal, occasionally with the proximal phalanx, often requires realignment by closing wedge osteotomy. Last, tendons on the resected bony elements should be rebalanced on the remaining digit, and anomalous slips must be released. For instance, given a radial insertion of the long flexor tendon on the distal phalanx, the tendon should be moved centrally. A strong flexor or extensor tendon on the amputated digit should be transferred to the remaining digit.²⁴

Types V and VI are treated similarly to type IV, with the addition of a first web space Z-plasty or web widening if there is thenar eminence contracture. Acral transposition has also been described, with transposition of the tip of the ablated digit in place of the tip of the kept digit; this technique is ideal if one digit has a more normal proximal part while the other has a more normal distal part (Figure 13).³⁵

Type VII thumb polydactyly, the type most likely inherited and associated with other disorders, should be treated like type VI. The nail should be preserved; amputation of the distal phalanx is not advised. Resection of the delta phalanx or 1 interphalangeal (IP) joint is an option. Articular surfaces will remodel if done before the age of 1 year. If the thenar eminence is hypoplastic, then Huber transfer of the abductor digiti minimi should be considered.³⁷ Resection of the triphalangeal thumb is also advised, even if the biphalangeal thumb is more hypoplastic, with transfer of the ligaments and tendons, as described earlier.^{5,6,24,30,32,35}

Thumb triphalangism, if isolated, and hyperphalangism in the other digits, can be treated with resection of the delta phalanx or one of the IP joints if it is affecting function or cosmesis.^1,6 Wood and Flatt²³ recommended early resection of a thumb delta phalanx because of the likelihood of deviation that impedes thumb function. For children, they recommended delta phalanx resection and Kirschner wire fixation for 6 weeks; for adults, they recommended resection or fusion of the joint, with osteotomy as needed for deviation.^23,24 For thumb triphalangism, multiple surgeries are the norm, as Wood²⁴ reported in his study of 21 patients who underwent 78 operations in total.

Index polydactyly may present as a simple pedunculated skin tag, which can be simply excised, or as a more complex musculoskeletal duplication. More complex presentations can be treated with procedures similar to those used for the thumb. Typically, the additional digit is radially deviated and angulated, eventually leading to impingement of thumb pinch and the first web space. Ray amputation is also an option if no reconstructive surgery will produce the stable, sensate radial pinch that is essential to hand function.³²

Ring-finger polydactyly and long-finger polydactyly are often complicated by some element of syndactyly, resulting in a relative paucity of skin (Figure 14). There is failure of both formation (hypoplasia) and differentiation (syndactyly). The hypoplasia particularly affects the function of these digits by tethering them; multiple surgeries to restore proper hand function are the norm.¹ Reconstructive surgery for these digits requires preoperative tissue inventory followed by resection and augmentation; as in syndactyly, skin for coverage is at a premium. Creation of a 3-fingered hand is an option.²³

Temtamy and McKusick¹⁰ type A little-finger polydactyly is treated similarly to the thumb, with the caveat that hypothenar and intrinsic muscles that insert on the resected little finger are transferred to the remaining digit. In contrast to thumb polydactyly, the extrinsic musculature tends to be in good position. Suture ligation of type B polydactyly, as described by Flatt, is likely more common than orthopedists appreciate, as pediatricians and neonatal unit practitioners commonly perform this procedure in the nursery.^1-3 It has been described with 2-0 Vicryl³ (Ethicon, Somerville, New Jersey) and 4-0 silk sutures,³² with the goal of necrosis and autoamputation. Parents should be told the finger generally falls off about 10 days (range, 4-21 days) after ligation.³ Multiple authors have cited a report of exsanguination from suture ligation, but we could not locate the primary source. It is advisable to wait until a patient is 6 months of age if planning to resect the nubbin in the operating room, given the anesthesia risk and the lack of functional impairment. Katz and Linder³³ indicated they remove type B polydactyly in the nursery suite used for circumcisions; they use anesthetizing cream on the skin, and sharp excision with a scalpel, followed by direct pressure and Steri-Strip (3M, St. Paul, Minnesota) application. Suture ligation is recommended only if there is a narrow, thin (<2 mm) soft-tissue stalk; any broad or bony stalk necessitates surgical removal to avoid neuroma formation and failure of autonecrosis (Figure 15).²⁷ Other options are a single swipe of a scalpel and elliptical excision; sharp transaction of the digital nerve with subsequent retraction is advised to avoid neuroma formation.²

Barton described ulnar dimelia operations as “spare parts surgery.”¹ Extra digits are ablated and a thumb created (Figure 16). The hand might have a digit in relatively good rotational position for thumbplasty, or the principles of pollicization may need to be used. If the patient is already using the hand, the surgeon should note which finger the patient uses as a thumb.²⁴ Any accompanying wrist flexion contracture must be corrected with careful attention to musculotendinous balancing. Because the forearm and elbow, and occasionally even the more proximal limb, will be abnormal in this disorder, multiple surgeries are again the norm.¹

Pentadactyly is treated like thumb hypoplasia, with first web space creation.¹

Complications

In polydactyly, a reoperation rate of up to 25% has been reported, with most reoperations performed because of residual or subsequent deformity.^5,30,31,38 Risk factors for reoperation are type IV thumb duplication, preoperative “zigzag” deformity, and radially deviated thumb elements at presentation.⁵ The delta phalanx may not show on radiographs until the patient is 18 months old, but functional deformity will worsen as long as it is present. Zigzag deformity may be due to the delta phalanx or to musculotendinous imbalance, such as a radially inserted flexor pollicis longus (FPL) or lack of stable MCP abduction. Miura³¹ found that careful reconstruction of the joint capsule and thenar muscles from the ablated digit to the remnant digit is the key to a successful initial surgery. Lee and colleagues³⁹ defined zigzag deformity as more than 20° MCP and IP angulation; for cases present before surgery, they recommended FPL relocation by the pullout technique in addition to osteotomies to prevent further interphalangeal deviation (Figures 17, 18).

Abnormal physeal growth, joint instability, and stiffness can all occur. Stiffness is particularly difficult to treat but seldom presents a functional problem. Joint enlargement, which is not uncommon, results from either broad articular surfaces or retained cartilage from the perichondral ring after resection that later ossifies.^5,38 Nubbin-type duplications may not fall off after suture ligation, necessitating further excision, and a cosmetic bump is seen after 40% of suture ligations.³ Patillo and Rayan²⁸ and Rayan and Frey²⁹ warned against suture ligation unless the nubbin has a small stalk because of the possibility of infection and gangrene. The excised nubbin tissue is histologically nervous, and there have been reports of painful neuromas in the remaining scar of a ligated nubbin that respond well to excision.^26,27,40 It is thought that these painful lesions form because the ligature prevents the digital nerves to the vestigial digit from retracting.²⁷ Nail deformity and IP joint stiffness are seen with the Bilhaut-Cloquet procedure, though often finger function remains satisfactory.

Conclusion

Polydactyly is a common congenital hand abnormality. Its true incidence is unknown because of inconsistent documentation. Surgeons must strive for a functional, cosmetic hand, given a diverse set of possible anomalies. Hypoplasia is the rule; tissue should be ablated and augmented as necessary. Musculotendinous insertions may need to be centralized. Patients’ family members should always be counseled that more surgery may be needed in the future, as further deformity can occur with growth. Surgically corrected thumb duplications will be stiffer, shorter, and thinner than their normal counterparts. Nail ridges are common. However, it should be noted that 88% of these patients are satisfied with their results.⁴¹ Some amount of contracture and abnormal function should be expected with index-, long-, and ring-finger duplications. The only remnant of type B postaxial duplications may be a slight discoloration or bump, though stiffness and deformity can happen with a type A deformity. A “duplicated” digit that requires surgical correction will never be completely normal, but acceptable function is routinely achievable.

Polydactyly is the presence of extra digits. Its incidence is likely underestimated because many practitioners treat simple “nubbins” without referring them to orthopedic specialists.^1-3 Polydactyly can be detected by ultrasound as early as 14 weeks’ gestational age, with partial autoamputation seen in most isolated polydactylies.⁴ The thumb, responsible for 40% of hand function, must be able to oppose the other digits with a stable pinch.⁵ Polydactyly encumbers this motion when the duplicated digits deviate from normal alignment. Ezaki⁶ noted that the anatomy is better described as “split” than “duplicated.” There are many dichotomous ways to classify polydactyly: preaxial (radial) versus postaxial (ulnar), thumb versus triphalangeal, simple versus complex (Figure 1). Mixed polydactyly is defined as the presence of preaxial and postaxial polydactyly.⁷ Surgical management seeks to allow normal hand function and to restore cosmesis.

Epidemiology

Sun and colleagues⁸ reported the overall polydactyly incidence as 2 per 1000 live births in China from 1998 to 2009, with a slight male predominance; polydactyly was also 3 times more common than syndactyly in this population. Ivy,⁹ in a 5-year audit of Pennsylvania Department of Health records, found polydactyly to be the fourth most common congenital anomaly after clubfoot, cleft lip/palate, and spina bifida. Thumb duplication occurs in 0.08 to 1.4 per 1000 live births and is more common in American Indians and Asians than in other races.^5,10 It occurs in a male-to-female ratio of 2.5 to 1 and is most often unilateral.⁵ Postaxial polydactyly is predominant in black infants; it is most often inherited in an autosomal dominant fashion, if isolated, or in an autosomal recessive pattern, if syndromic.¹ A prospective San Diego study of 11,161 newborns found postaxial type B polydactyly in 1 per 531 live births (1 per 143 black infants, 1 per 1339 white infants); 76% of cases were bilateral, and 86% had a positive family history.³ In patients of non-African descent, it is associated with anomalies in other organs. Central duplication is rare and often autosomal dominant.^5,10

Genetics and Development

As early as 1896, the heritability of polydactyly was noted.¹¹ As of 2010, polydactyly has been associated with 310 diseases.¹² Ninety-nine genes, most involved in regulation of anterior-posterior formation of the limb bud, have been implicated.^12,13

The upper limb begins to form at day 26 in utero.¹⁴ Apoptosis in the interdigital necrotic zones results in the formation of individual digits. It is presumed that, in polydactyly, the involved tissue is hypoplastic because of an abnormal interaction between mesoderm and ectoderm.⁵ Presence of an apical ectodermal ridge determines the formation of a limb bud, and on it the zone of polarizing activity (ZPA) dictates preaxial and postaxial alignment.^14,15 The ZPA is located on the posterior zone of the developing limb bud. The levels of GLI3, a zinc finger-containing DNA-binding protein, are highest in the anterior area, and HAND2, a basic helix-loop-helix DNA-binding protein, is found in the ZPA. This polarity promotes sonic hedgehog (Shh) gene expression in the posterior region, which in turn prevents GLI3 cleavage into its repressed form. GLI3R (repressed) and GLI3A (active) concentrations are highest, therefore, in the anterior and posterior portions of the bud, respectively. The GLI3A:GLI3R ratio is responsible for the identity and number of digits in the hand (ie, the thumb develops in regions of high GLI3R). GLI and Shh mutations lead to polydactylous hands with absent thumbs (Figure 2).¹⁶

Ciliopathies have also been shown to cause postaxial polydactyly, possibly because of the role that nonmotile cilia play in hedgehog signaling.¹⁷ Mutations in Shh genomic regulators cause preaxial polydactyly.¹⁸ HoxD activates Shh in the ZPA; HoxD13 mutations are associated with synpolydactyly.^16,19 In each of these mutations, Shh production is altered, and some form of polydactyly results.

Associations

Many syndromes have been associated with polydactyly. Not all polydactyly is associated with other disorders, but the more complex the polydactyly, the more likely that other anomalies are present. Every patient who presents with polydactyly should have a full history taken and a physical examination performed (Figure 3). Any patient with syndromic findings or atypical presentations (eg, triphalangism, postaxial polydactyly in a patient of non-African descent, central and index polydactyly) should be referred to a geneticist.

Classifications

The Wassel²⁰ classification describes the anatomical presentation of thumb duplication on the basis of 70 cases in Iowa (Figures 4, 5; Table 1). Because some duplications fall outside the Wassel classification, many researchers have proposed modifications (Figure 6).^21-25

The Temtamy and McKusick¹⁰ classification, which is the product of geneticists, classifies duplications by grouping genetically related presentations (Table 2). It provides the most commonly used postaxial classification, with type A being a fully developed digit and type B a rudimentary and pedunculated digit, informally referred to as a nubbin. Type B is more common than type A. Given inheritance patterns, it is assumed that type A is likely multifactorial and type B autosomal dominant.¹⁰ Thumb polydactyly inheritance is still unclear. The other types of preaxial polydactyly and high degrees of polydactyly are rare but seem to be passed on in an autosomal dominant fashion on pedigree analysis.¹⁰

The Stelling and Turek classification presents the duplication from a tissue perspective: Type I duplication is a rudimentary mass devoid of other tissue elements; type II is a subtotal duplication with some normal structures; and type III is a duplication of the entire “osteoarticular column,” including the metacarpal.¹ It is interesting to note that histology of type I duplications shows neuroma-like tissue.^26-28 Again, normal is a relative term because, in polydactyly, the duplications are hypoplastic and deviated, with anomalous anatomy.

The Rayan classification describes ulnar polydactyly and was derived from a case study series of 148 patients in Oklahoma (Table 3).²⁹

There are also some complex polydactylies that are not easily classified: ulnar dimelia, cleft hand, pentadactyly, and hyperphalangism. Ulnar dimelia, also known as “mirror hand,” is typically 7 digits with no thumb, but other variations are seen. The radius is often absent, and the elbow is abnormal. There is some debate about whether it is a fusion of 2 hands. Pentadactyly, or the 5-fingered hand, appears as 5 triphalangeal digits with no thumb (Figure 7).

Isolated thumb triphalangism might appear similar to pentadactyly. Miura^30,31 pointed out that the radial digit in the pentadactylous hand may be opposable (thumb-like) or nonopposable; in his studies, the patients with the opposable thumb had a metacarpal with a proximal epiphysis (Figure 8). Consequently, the triphalangeal thumb metacarpal with a distal epiphysis is true pentadactyly, whereas that with a proximal epiphysis is hyperphalangism (Figure 9). Treatment of these complex polydactylies involves the same underlying principles as for preaxial and postaxial polydactyly, albeit with additional proximal upper extremity considerations.

When to Operate (Timing)

Ezaki⁶ recommended surgical intervention at age 6 to 9 months, before fine motor skills have developed with the abnormal anatomy. Cortical learning occurs as the child begins prehensile activities before 6 months, but the risks of anesthesia outweigh functional benefits until the child is older. Waiting until 1 year of age is not uncommon, though surgery at an earlier age may be beneficial if the polydactyly affects hand function.³² It is not uncommon to wait with the more balanced thumb polydactylies to assess thumb function. Hypoplasia might also delay surgical intervention until there is enough tissue inventory for reconstruction. Wassel²⁰ noted that surgical intervention ideally occurs before the supernumerary elements displace the normal elements, as tends to happen with growth. Suture ligation is an option in the neonatal unit for some pedunculated digits.³³ Studies have shown satisfactory results in adults treated for polydactyly, if the patient presents later than expected.³⁴

Surgical Considerations

Knavel recommended simple excision, stating that “ablation requires no ingenuity and creates no problems.”⁵ This belief, though true for some duplications, will not lead to the best outcome for more complex polydactylies. The goal of surgery is a stable and well-aligned thumb for pinch and prehensile activity, as well as a cosmetically pleasing hand. Incisions should not be made linearly along the axis of the digit, as the scar will cause deviation with growth.²⁴

Wassel type I polydactyly might appear incidentally as a broad thumb, in which case it requires no intervention (Figure 10). However, in Wassel types I and II polydactyly with deformity, the Bilhaut-Cloquet procedure is useful for both bifid and duplicated phalanges (Figure 11).^5,6,30,32,35 Collateral ligaments may need to be released in type II because of difficulty in opposing the tissue. Cosmetic results with Bilhaut-Cloquet are unpredictable. The original technique required symmetrically sized digits; results today have been improved with microtechniques and preservation of an entire nail.³⁶ Another option is ablation of the more hypoplastic osseous element and soft-tissue augmentation of the residual digit. The theme of ablation and augmentation is seen throughout the literature for the surgical treatment of polydactyly (Figure 12).¹

For type III polydactyly, the bifid proximal phalanx is narrowed by resection and realigned with osteotomy of the remaining diaphysis. Type IV polydactyly, the most common thumb duplication, often requires advancement of the abductor pollicis brevis to the base of the proximal phalanx to aid in metacarpophalangeal (MCP) stabilization, abduction, and opposition. The metacarpal head, if broad and with 2 facets, can be shaped to form a single articulating surface. The metacarpal, occasionally with the proximal phalanx, often requires realignment by closing wedge osteotomy. Last, tendons on the resected bony elements should be rebalanced on the remaining digit, and anomalous slips must be released. For instance, given a radial insertion of the long flexor tendon on the distal phalanx, the tendon should be moved centrally. A strong flexor or extensor tendon on the amputated digit should be transferred to the remaining digit.²⁴

Types V and VI are treated similarly to type IV, with the addition of a first web space Z-plasty or web widening if there is thenar eminence contracture. Acral transposition has also been described, with transposition of the tip of the ablated digit in place of the tip of the kept digit; this technique is ideal if one digit has a more normal proximal part while the other has a more normal distal part (Figure 13).³⁵

Type VII thumb polydactyly, the type most likely inherited and associated with other disorders, should be treated like type VI. The nail should be preserved; amputation of the distal phalanx is not advised. Resection of the delta phalanx or 1 interphalangeal (IP) joint is an option. Articular surfaces will remodel if done before the age of 1 year. If the thenar eminence is hypoplastic, then Huber transfer of the abductor digiti minimi should be considered.³⁷ Resection of the triphalangeal thumb is also advised, even if the biphalangeal thumb is more hypoplastic, with transfer of the ligaments and tendons, as described earlier.^{5,6,24,30,32,35}

Thumb triphalangism, if isolated, and hyperphalangism in the other digits, can be treated with resection of the delta phalanx or one of the IP joints if it is affecting function or cosmesis.^1,6 Wood and Flatt²³ recommended early resection of a thumb delta phalanx because of the likelihood of deviation that impedes thumb function. For children, they recommended delta phalanx resection and Kirschner wire fixation for 6 weeks; for adults, they recommended resection or fusion of the joint, with osteotomy as needed for deviation.^23,24 For thumb triphalangism, multiple surgeries are the norm, as Wood²⁴ reported in his study of 21 patients who underwent 78 operations in total.

Index polydactyly may present as a simple pedunculated skin tag, which can be simply excised, or as a more complex musculoskeletal duplication. More complex presentations can be treated with procedures similar to those used for the thumb. Typically, the additional digit is radially deviated and angulated, eventually leading to impingement of thumb pinch and the first web space. Ray amputation is also an option if no reconstructive surgery will produce the stable, sensate radial pinch that is essential to hand function.³²

Ring-finger polydactyly and long-finger polydactyly are often complicated by some element of syndactyly, resulting in a relative paucity of skin (Figure 14). There is failure of both formation (hypoplasia) and differentiation (syndactyly). The hypoplasia particularly affects the function of these digits by tethering them; multiple surgeries to restore proper hand function are the norm.¹ Reconstructive surgery for these digits requires preoperative tissue inventory followed by resection and augmentation; as in syndactyly, skin for coverage is at a premium. Creation of a 3-fingered hand is an option.²³

Temtamy and McKusick¹⁰ type A little-finger polydactyly is treated similarly to the thumb, with the caveat that hypothenar and intrinsic muscles that insert on the resected little finger are transferred to the remaining digit. In contrast to thumb polydactyly, the extrinsic musculature tends to be in good position. Suture ligation of type B polydactyly, as described by Flatt, is likely more common than orthopedists appreciate, as pediatricians and neonatal unit practitioners commonly perform this procedure in the nursery.^1-3 It has been described with 2-0 Vicryl³ (Ethicon, Somerville, New Jersey) and 4-0 silk sutures,³² with the goal of necrosis and autoamputation. Parents should be told the finger generally falls off about 10 days (range, 4-21 days) after ligation.³ Multiple authors have cited a report of exsanguination from suture ligation, but we could not locate the primary source. It is advisable to wait until a patient is 6 months of age if planning to resect the nubbin in the operating room, given the anesthesia risk and the lack of functional impairment. Katz and Linder³³ indicated they remove type B polydactyly in the nursery suite used for circumcisions; they use anesthetizing cream on the skin, and sharp excision with a scalpel, followed by direct pressure and Steri-Strip (3M, St. Paul, Minnesota) application. Suture ligation is recommended only if there is a narrow, thin (<2 mm) soft-tissue stalk; any broad or bony stalk necessitates surgical removal to avoid neuroma formation and failure of autonecrosis (Figure 15).²⁷ Other options are a single swipe of a scalpel and elliptical excision; sharp transaction of the digital nerve with subsequent retraction is advised to avoid neuroma formation.²

Barton described ulnar dimelia operations as “spare parts surgery.”¹ Extra digits are ablated and a thumb created (Figure 16). The hand might have a digit in relatively good rotational position for thumbplasty, or the principles of pollicization may need to be used. If the patient is already using the hand, the surgeon should note which finger the patient uses as a thumb.²⁴ Any accompanying wrist flexion contracture must be corrected with careful attention to musculotendinous balancing. Because the forearm and elbow, and occasionally even the more proximal limb, will be abnormal in this disorder, multiple surgeries are again the norm.¹

Pentadactyly is treated like thumb hypoplasia, with first web space creation.¹

Complications

In polydactyly, a reoperation rate of up to 25% has been reported, with most reoperations performed because of residual or subsequent deformity.^5,30,31,38 Risk factors for reoperation are type IV thumb duplication, preoperative “zigzag” deformity, and radially deviated thumb elements at presentation.⁵ The delta phalanx may not show on radiographs until the patient is 18 months old, but functional deformity will worsen as long as it is present. Zigzag deformity may be due to the delta phalanx or to musculotendinous imbalance, such as a radially inserted flexor pollicis longus (FPL) or lack of stable MCP abduction. Miura³¹ found that careful reconstruction of the joint capsule and thenar muscles from the ablated digit to the remnant digit is the key to a successful initial surgery. Lee and colleagues³⁹ defined zigzag deformity as more than 20° MCP and IP angulation; for cases present before surgery, they recommended FPL relocation by the pullout technique in addition to osteotomies to prevent further interphalangeal deviation (Figures 17, 18).

Abnormal physeal growth, joint instability, and stiffness can all occur. Stiffness is particularly difficult to treat but seldom presents a functional problem. Joint enlargement, which is not uncommon, results from either broad articular surfaces or retained cartilage from the perichondral ring after resection that later ossifies.^5,38 Nubbin-type duplications may not fall off after suture ligation, necessitating further excision, and a cosmetic bump is seen after 40% of suture ligations.³ Patillo and Rayan²⁸ and Rayan and Frey²⁹ warned against suture ligation unless the nubbin has a small stalk because of the possibility of infection and gangrene. The excised nubbin tissue is histologically nervous, and there have been reports of painful neuromas in the remaining scar of a ligated nubbin that respond well to excision.^26,27,40 It is thought that these painful lesions form because the ligature prevents the digital nerves to the vestigial digit from retracting.²⁷ Nail deformity and IP joint stiffness are seen with the Bilhaut-Cloquet procedure, though often finger function remains satisfactory.

Conclusion

Polydactyly is a common congenital hand abnormality. Its true incidence is unknown because of inconsistent documentation. Surgeons must strive for a functional, cosmetic hand, given a diverse set of possible anomalies. Hypoplasia is the rule; tissue should be ablated and augmented as necessary. Musculotendinous insertions may need to be centralized. Patients’ family members should always be counseled that more surgery may be needed in the future, as further deformity can occur with growth. Surgically corrected thumb duplications will be stiffer, shorter, and thinner than their normal counterparts. Nail ridges are common. However, it should be noted that 88% of these patients are satisfied with their results.⁴¹ Some amount of contracture and abnormal function should be expected with index-, long-, and ring-finger duplications. The only remnant of type B postaxial duplications may be a slight discoloration or bump, though stiffness and deformity can happen with a type A deformity. A “duplicated” digit that requires surgical correction will never be completely normal, but acceptable function is routinely achievable.

Clinicians should avoid routinely screening venous thromboembolism patients for thrombophilias, and should instead weigh the risks of recurrent thrombosis against the chances of bleeding with prolonged anticoagulation, according to a review article published in the April issue of the Journal of Vascular Surgery: Venous and Lymphatic Disorders.

“These laboratory tests are costly, and surprisingly, there is little evidence showing that testing leads to improved clinical outcomes,” said Dr. Elna Masuda at Straub Clinic and Hospital, Honolulu, and her associates. “Until data from well-designed, controlled trials are available comparing different durations of anticoagulation with specific thrombophilic states, treatment should be based on clinical risk factors and less on laboratory abnormalities.”

More than half of patients with an initial venous thromboembolism (VTE) episode had a positive thrombophilia screen in one study (Ann. Intern. Med. 2001;135:367-73), the reviewers noted. Testing, however, usually does not affect clinical management or prevent VTE recurrence, and it can cost more than $3,000 per patient, they said.

For these reasons, the American Society of Hematology, the National Institute for Health Care and Excellence, and the Society for Vascular Medicine discourage screening after an initial VTE episode if patients have a known cause or transient risk factor for thrombosis.

Testing also is unlikely to benefit patients with first-time unprovoked (or idiopathic) VTE, patients with a permanent risk factor for thrombosis such as cancer, or patients with arterial thrombosis or thrombosis of the retina or upper arm veins, Dr. Masuda and her associates said. And because recurrent VTE generally merits long-term anticoagulation, affected patients only should be screened if they are considering stopping treatment and test results could inform that decision, they added (J. Vasc. Surg. Venous Lymphat. Disord. 2015;3:228-35).

Some subgroups of patients, however, could benefit from targeted thrombophilia testing. The reviewers recommended antiphospholipid antibody testing if patients have a history of several unexplained pregnancy losses or another reason to suspect antiphospholipid syndrome. Patients with heparin resistance should be tested for antithrombin deficiency, and patients with warfarin necrosis or neonatal purpura fulminans should be tested for protein C and S deficiencies, they added.

Clinicians also should consider screening women with a personal or family history of VTE if they are pregnant and are considering anticoagulation or are considering oral contraceptives or hormone replacement therapy, Dr. Masuda and her associates said.

Screening such patients remains controversial, but it could help guide anticoagulation therapy before and after delivery or might help patients decide whether or not to take exogenous hormones. “In the subgroup of those pregnant or planning pregnancy, history of prior VTE and strong family history of thrombosis are two factors that appear to play a clinically important role in identifying those who may benefit from screening,” they concluded.

Patients who want to pursue testing need to understand that management is mainly based on clinical risk and that test results usually will not change treatment recommendations, the reviewers also emphasized. “If testing will change management, it may be appropriate to proceed,” they added. “If long-term anticoagulation is preferred on the basis of positive test results, the risk of bleeding should be considered.”

The researchers reported no funding sources. Dr. Masuda reported having served on the speakers bureau for Janssen Pharmaceuticals.

Clinicians should avoid routinely screening venous thromboembolism patients for thrombophilias, and should instead weigh the risks of recurrent thrombosis against the chances of bleeding with prolonged anticoagulation, according to a review article published in the April issue of the Journal of Vascular Surgery: Venous and Lymphatic Disorders.

“These laboratory tests are costly, and surprisingly, there is little evidence showing that testing leads to improved clinical outcomes,” said Dr. Elna Masuda at Straub Clinic and Hospital, Honolulu, and her associates. “Until data from well-designed, controlled trials are available comparing different durations of anticoagulation with specific thrombophilic states, treatment should be based on clinical risk factors and less on laboratory abnormalities.”

More than half of patients with an initial venous thromboembolism (VTE) episode had a positive thrombophilia screen in one study (Ann. Intern. Med. 2001;135:367-73), the reviewers noted. Testing, however, usually does not affect clinical management or prevent VTE recurrence, and it can cost more than $3,000 per patient, they said.

For these reasons, the American Society of Hematology, the National Institute for Health Care and Excellence, and the Society for Vascular Medicine discourage screening after an initial VTE episode if patients have a known cause or transient risk factor for thrombosis.

Testing also is unlikely to benefit patients with first-time unprovoked (or idiopathic) VTE, patients with a permanent risk factor for thrombosis such as cancer, or patients with arterial thrombosis or thrombosis of the retina or upper arm veins, Dr. Masuda and her associates said. And because recurrent VTE generally merits long-term anticoagulation, affected patients only should be screened if they are considering stopping treatment and test results could inform that decision, they added (J. Vasc. Surg. Venous Lymphat. Disord. 2015;3:228-35).

Some subgroups of patients, however, could benefit from targeted thrombophilia testing. The reviewers recommended antiphospholipid antibody testing if patients have a history of several unexplained pregnancy losses or another reason to suspect antiphospholipid syndrome. Patients with heparin resistance should be tested for antithrombin deficiency, and patients with warfarin necrosis or neonatal purpura fulminans should be tested for protein C and S deficiencies, they added.

Clinicians also should consider screening women with a personal or family history of VTE if they are pregnant and are considering anticoagulation or are considering oral contraceptives or hormone replacement therapy, Dr. Masuda and her associates said.

Screening such patients remains controversial, but it could help guide anticoagulation therapy before and after delivery or might help patients decide whether or not to take exogenous hormones. “In the subgroup of those pregnant or planning pregnancy, history of prior VTE and strong family history of thrombosis are two factors that appear to play a clinically important role in identifying those who may benefit from screening,” they concluded.

Patients who want to pursue testing need to understand that management is mainly based on clinical risk and that test results usually will not change treatment recommendations, the reviewers also emphasized. “If testing will change management, it may be appropriate to proceed,” they added. “If long-term anticoagulation is preferred on the basis of positive test results, the risk of bleeding should be considered.”

The researchers reported no funding sources. Dr. Masuda reported having served on the speakers bureau for Janssen Pharmaceuticals.

Clinicians should avoid routinely screening venous thromboembolism patients for thrombophilias, and should instead weigh the risks of recurrent thrombosis against the chances of bleeding with prolonged anticoagulation, according to a review article published in the April issue of the Journal of Vascular Surgery: Venous and Lymphatic Disorders.

“These laboratory tests are costly, and surprisingly, there is little evidence showing that testing leads to improved clinical outcomes,” said Dr. Elna Masuda at Straub Clinic and Hospital, Honolulu, and her associates. “Until data from well-designed, controlled trials are available comparing different durations of anticoagulation with specific thrombophilic states, treatment should be based on clinical risk factors and less on laboratory abnormalities.”

More than half of patients with an initial venous thromboembolism (VTE) episode had a positive thrombophilia screen in one study (Ann. Intern. Med. 2001;135:367-73), the reviewers noted. Testing, however, usually does not affect clinical management or prevent VTE recurrence, and it can cost more than $3,000 per patient, they said.

For these reasons, the American Society of Hematology, the National Institute for Health Care and Excellence, and the Society for Vascular Medicine discourage screening after an initial VTE episode if patients have a known cause or transient risk factor for thrombosis.

Testing also is unlikely to benefit patients with first-time unprovoked (or idiopathic) VTE, patients with a permanent risk factor for thrombosis such as cancer, or patients with arterial thrombosis or thrombosis of the retina or upper arm veins, Dr. Masuda and her associates said. And because recurrent VTE generally merits long-term anticoagulation, affected patients only should be screened if they are considering stopping treatment and test results could inform that decision, they added (J. Vasc. Surg. Venous Lymphat. Disord. 2015;3:228-35).

Some subgroups of patients, however, could benefit from targeted thrombophilia testing. The reviewers recommended antiphospholipid antibody testing if patients have a history of several unexplained pregnancy losses or another reason to suspect antiphospholipid syndrome. Patients with heparin resistance should be tested for antithrombin deficiency, and patients with warfarin necrosis or neonatal purpura fulminans should be tested for protein C and S deficiencies, they added.

Clinicians also should consider screening women with a personal or family history of VTE if they are pregnant and are considering anticoagulation or are considering oral contraceptives or hormone replacement therapy, Dr. Masuda and her associates said.

Screening such patients remains controversial, but it could help guide anticoagulation therapy before and after delivery or might help patients decide whether or not to take exogenous hormones. “In the subgroup of those pregnant or planning pregnancy, history of prior VTE and strong family history of thrombosis are two factors that appear to play a clinically important role in identifying those who may benefit from screening,” they concluded.

Patients who want to pursue testing need to understand that management is mainly based on clinical risk and that test results usually will not change treatment recommendations, the reviewers also emphasized. “If testing will change management, it may be appropriate to proceed,” they added. “If long-term anticoagulation is preferred on the basis of positive test results, the risk of bleeding should be considered.”

The researchers reported no funding sources. Dr. Masuda reported having served on the speakers bureau for Janssen Pharmaceuticals.

To the Editor:

The shiitake mushroom (Lentinula edodes) is a popular Asian food and represents the second most consumed mushroom in the world. It is known for having a range of strong health benefits including antihypertensive, anti-inflammatory, and immunomodulatory effects. Especially in Asia, this mushroom has been used in patients with cancers of the gastrointestinal tract and also may be helpful in the treatment of human immunodeficiency virus.^1,2 The source of these effects is lentinan, a polysaccharide in the mushroom. However, lentinan also can cause a toxic reaction of the skin when the mushrooms are eaten raw or undercooked. These reactions are mainly reported in Asia, but more cases have been published in the last decade in Europe and the United States, evidence that the incidence of this adverse effect has increased in the Western world.

A 65-year-old woman with no notable medical history presented to our outpatient practice with sudden onset of a pruritic, erythematous, papular eruption on the neck. The eruption began that morning. The diagnosis of eczematous dermatitis was made and hydrocortisone cream 2.5% was started. Three days later, she returned with spread of the rash to the trunk, arms, and legs despite the topical treatment. She denied fevers, chills, or constitutional symptoms. The patient also denied recent travel or bug bites. However, she reported that she recently had started using raw shiitake mushrooms in her salad; the first time was 3 days before the symptoms appeared. Physical examination revealed erythematous skin with long flagellate streaks composed of petechiae, papules, and vesicles involving the trunk, arms, and legs (Figure). Oral and nasal mucosae were uninvolved. Dermatographism was negative. The diagnosis of flagellate dermatitis from shiitake mushrooms was made given the patient’s history and the unique clinical findings of the skin. Blood work and a biopsy were not performed. Instead, the patient was advised to avoid shiitake mushrooms and use clobetasol propionate cream 0.05% twice daily for 2 weeks on the affected areas. The symptoms resolved within 10 days.

Erythematous flagellate streaks composed of petechiae, papules, and vesicles localized on the patient’s back (A) and right upper arm (B) associated with shiitake mushroom consumption.

The first known case of toxicoderma to shiitake mushrooms was reported in Japan by Nakamura³ in 1977. Since this seminal report, numerous cases have followed. This disorder is mainly seen in Asia.

Patients usually present with linear groups of pruritic, papular, petechial, and vesicular lesions in a flagellate pattern, most commonly localized on the trunk, arms, and legs. Oral and nasal mucosae usually are not involved, and fever and malaise may be associated. All symptoms typically occur 1 to 2 days after ingestion of the mushrooms. The patient’s history and typical clinical findings lead to a diagnosis; however, blood tests may show inflammation with leukocytosis and elevated C-reactive protein levels. Biopsy of the skin shows lymphocytic dermal infiltrates with spongiosis and necrotic cells within the epidermis.⁴

Differential diagnoses include flagellate dermatitis associated with bleomycin, a glycopeptide antibiotic produced by the bacterium Streptomyces verticillus. Because it causes breaks in the DNA, bleomycin is commonly used as a chemotherapeutic agent in treating Hodgkin lymphoma and other malignancies. It presents with linear postinflammatory hyperpigmentation of the skin. However, unlike shiitake dermatitis, there is a lack of papules. Another differential diagnosis includes herpes zoster virus, which should be ruled out clinically.

All symptoms in shiitake dermatitis usually resolve within 1 to 8 weeks of avoidance of the culprit food. Topical steroids and antihistamines can be given.

The underlying pathology is a toxic reaction to the polysaccharide lentinan in the mushrooms, which is known as a thermolabile agent.⁵ Therefore, it may only cause a toxic reaction when the mushrooms are consumed raw or undercooked. Prick testing is usually negative in these patients, which suggests a toxic and not an immunologic reaction of the human body.⁶ Other forms of reaction to shiitake mushrooms include contact dermatitis after skin contact and allergic alveolitis after occupational exposure to mushroom spores, mainly in individuals cultivating shiitake mushrooms (mushroom worker’s lung). In these forms of the disease, prick testing may be positive.^7,8

Flagellate dermatitis caused by shiitake mushrooms is still an uncommon dermatologic phenomenon in the Western world. Future studies and cases should be reported to increase the awareness of this disorder. Although the patients present with typical clinical findings, the diagnosis can be missed if history is not carefully considered.

To the Editor:

The shiitake mushroom (Lentinula edodes) is a popular Asian food and represents the second most consumed mushroom in the world. It is known for having a range of strong health benefits including antihypertensive, anti-inflammatory, and immunomodulatory effects. Especially in Asia, this mushroom has been used in patients with cancers of the gastrointestinal tract and also may be helpful in the treatment of human immunodeficiency virus.^1,2 The source of these effects is lentinan, a polysaccharide in the mushroom. However, lentinan also can cause a toxic reaction of the skin when the mushrooms are eaten raw or undercooked. These reactions are mainly reported in Asia, but more cases have been published in the last decade in Europe and the United States, evidence that the incidence of this adverse effect has increased in the Western world.

A 65-year-old woman with no notable medical history presented to our outpatient practice with sudden onset of a pruritic, erythematous, papular eruption on the neck. The eruption began that morning. The diagnosis of eczematous dermatitis was made and hydrocortisone cream 2.5% was started. Three days later, she returned with spread of the rash to the trunk, arms, and legs despite the topical treatment. She denied fevers, chills, or constitutional symptoms. The patient also denied recent travel or bug bites. However, she reported that she recently had started using raw shiitake mushrooms in her salad; the first time was 3 days before the symptoms appeared. Physical examination revealed erythematous skin with long flagellate streaks composed of petechiae, papules, and vesicles involving the trunk, arms, and legs (Figure). Oral and nasal mucosae were uninvolved. Dermatographism was negative. The diagnosis of flagellate dermatitis from shiitake mushrooms was made given the patient’s history and the unique clinical findings of the skin. Blood work and a biopsy were not performed. Instead, the patient was advised to avoid shiitake mushrooms and use clobetasol propionate cream 0.05% twice daily for 2 weeks on the affected areas. The symptoms resolved within 10 days.

Erythematous flagellate streaks composed of petechiae, papules, and vesicles localized on the patient’s back (A) and right upper arm (B) associated with shiitake mushroom consumption.

The first known case of toxicoderma to shiitake mushrooms was reported in Japan by Nakamura³ in 1977. Since this seminal report, numerous cases have followed. This disorder is mainly seen in Asia.

Patients usually present with linear groups of pruritic, papular, petechial, and vesicular lesions in a flagellate pattern, most commonly localized on the trunk, arms, and legs. Oral and nasal mucosae usually are not involved, and fever and malaise may be associated. All symptoms typically occur 1 to 2 days after ingestion of the mushrooms. The patient’s history and typical clinical findings lead to a diagnosis; however, blood tests may show inflammation with leukocytosis and elevated C-reactive protein levels. Biopsy of the skin shows lymphocytic dermal infiltrates with spongiosis and necrotic cells within the epidermis.⁴

Differential diagnoses include flagellate dermatitis associated with bleomycin, a glycopeptide antibiotic produced by the bacterium Streptomyces verticillus. Because it causes breaks in the DNA, bleomycin is commonly used as a chemotherapeutic agent in treating Hodgkin lymphoma and other malignancies. It presents with linear postinflammatory hyperpigmentation of the skin. However, unlike shiitake dermatitis, there is a lack of papules. Another differential diagnosis includes herpes zoster virus, which should be ruled out clinically.

All symptoms in shiitake dermatitis usually resolve within 1 to 8 weeks of avoidance of the culprit food. Topical steroids and antihistamines can be given.

The underlying pathology is a toxic reaction to the polysaccharide lentinan in the mushrooms, which is known as a thermolabile agent.⁵ Therefore, it may only cause a toxic reaction when the mushrooms are consumed raw or undercooked. Prick testing is usually negative in these patients, which suggests a toxic and not an immunologic reaction of the human body.⁶ Other forms of reaction to shiitake mushrooms include contact dermatitis after skin contact and allergic alveolitis after occupational exposure to mushroom spores, mainly in individuals cultivating shiitake mushrooms (mushroom worker’s lung). In these forms of the disease, prick testing may be positive.^7,8

Flagellate dermatitis caused by shiitake mushrooms is still an uncommon dermatologic phenomenon in the Western world. Future studies and cases should be reported to increase the awareness of this disorder. Although the patients present with typical clinical findings, the diagnosis can be missed if history is not carefully considered.

To the Editor:

The shiitake mushroom (Lentinula edodes) is a popular Asian food and represents the second most consumed mushroom in the world. It is known for having a range of strong health benefits including antihypertensive, anti-inflammatory, and immunomodulatory effects. Especially in Asia, this mushroom has been used in patients with cancers of the gastrointestinal tract and also may be helpful in the treatment of human immunodeficiency virus.^1,2 The source of these effects is lentinan, a polysaccharide in the mushroom. However, lentinan also can cause a toxic reaction of the skin when the mushrooms are eaten raw or undercooked. These reactions are mainly reported in Asia, but more cases have been published in the last decade in Europe and the United States, evidence that the incidence of this adverse effect has increased in the Western world.

A 65-year-old woman with no notable medical history presented to our outpatient practice with sudden onset of a pruritic, erythematous, papular eruption on the neck. The eruption began that morning. The diagnosis of eczematous dermatitis was made and hydrocortisone cream 2.5% was started. Three days later, she returned with spread of the rash to the trunk, arms, and legs despite the topical treatment. She denied fevers, chills, or constitutional symptoms. The patient also denied recent travel or bug bites. However, she reported that she recently had started using raw shiitake mushrooms in her salad; the first time was 3 days before the symptoms appeared. Physical examination revealed erythematous skin with long flagellate streaks composed of petechiae, papules, and vesicles involving the trunk, arms, and legs (Figure). Oral and nasal mucosae were uninvolved. Dermatographism was negative. The diagnosis of flagellate dermatitis from shiitake mushrooms was made given the patient’s history and the unique clinical findings of the skin. Blood work and a biopsy were not performed. Instead, the patient was advised to avoid shiitake mushrooms and use clobetasol propionate cream 0.05% twice daily for 2 weeks on the affected areas. The symptoms resolved within 10 days.

Erythematous flagellate streaks composed of petechiae, papules, and vesicles localized on the patient’s back (A) and right upper arm (B) associated with shiitake mushroom consumption.

The first known case of toxicoderma to shiitake mushrooms was reported in Japan by Nakamura³ in 1977. Since this seminal report, numerous cases have followed. This disorder is mainly seen in Asia.

Patients usually present with linear groups of pruritic, papular, petechial, and vesicular lesions in a flagellate pattern, most commonly localized on the trunk, arms, and legs. Oral and nasal mucosae usually are not involved, and fever and malaise may be associated. All symptoms typically occur 1 to 2 days after ingestion of the mushrooms. The patient’s history and typical clinical findings lead to a diagnosis; however, blood tests may show inflammation with leukocytosis and elevated C-reactive protein levels. Biopsy of the skin shows lymphocytic dermal infiltrates with spongiosis and necrotic cells within the epidermis.⁴

Differential diagnoses include flagellate dermatitis associated with bleomycin, a glycopeptide antibiotic produced by the bacterium Streptomyces verticillus. Because it causes breaks in the DNA, bleomycin is commonly used as a chemotherapeutic agent in treating Hodgkin lymphoma and other malignancies. It presents with linear postinflammatory hyperpigmentation of the skin. However, unlike shiitake dermatitis, there is a lack of papules. Another differential diagnosis includes herpes zoster virus, which should be ruled out clinically.

All symptoms in shiitake dermatitis usually resolve within 1 to 8 weeks of avoidance of the culprit food. Topical steroids and antihistamines can be given.

The underlying pathology is a toxic reaction to the polysaccharide lentinan in the mushrooms, which is known as a thermolabile agent.⁵ Therefore, it may only cause a toxic reaction when the mushrooms are consumed raw or undercooked. Prick testing is usually negative in these patients, which suggests a toxic and not an immunologic reaction of the human body.⁶ Other forms of reaction to shiitake mushrooms include contact dermatitis after skin contact and allergic alveolitis after occupational exposure to mushroom spores, mainly in individuals cultivating shiitake mushrooms (mushroom worker’s lung). In these forms of the disease, prick testing may be positive.^7,8

Flagellate dermatitis caused by shiitake mushrooms is still an uncommon dermatologic phenomenon in the Western world. Future studies and cases should be reported to increase the awareness of this disorder. Although the patients present with typical clinical findings, the diagnosis can be missed if history is not carefully considered.

Photographs from Hospital Medicine 2015, which took place March 29-April 1 at the Gaylord National Hotel and Conference Center in National Harbor, Md.

Photos by Manuel Noguera

[gallery ids="9476,9477,9479,9480,9481,9482,9483,9484,9485,9486,9487,9488,9489,9490,9491,9492,9493,9494,9495,9496,9497,9498,9499,9500,9501,9502,9503,9504,9505,9506,9507,9508,9509,9510,9511,9512,9516,9518,9519,9520,9521,9522,9523,9524,9525,9526,9528,9529,9530,9531,9532,9533,9534,9535,9536,9538,9540,9541,9542,9543,9545,9546,9548,9549,9551"]

Photographs from Hospital Medicine 2015, which took place March 29-April 1 at the Gaylord National Hotel and Conference Center in National Harbor, Md.

Photos by Manuel Noguera

[gallery ids="9476,9477,9479,9480,9481,9482,9483,9484,9485,9486,9487,9488,9489,9490,9491,9492,9493,9494,9495,9496,9497,9498,9499,9500,9501,9502,9503,9504,9505,9506,9507,9508,9509,9510,9511,9512,9516,9518,9519,9520,9521,9522,9523,9524,9525,9526,9528,9529,9530,9531,9532,9533,9534,9535,9536,9538,9540,9541,9542,9543,9545,9546,9548,9549,9551"]

Photographs from Hospital Medicine 2015, which took place March 29-April 1 at the Gaylord National Hotel and Conference Center in National Harbor, Md.

Photos by Manuel Noguera

[gallery ids="9476,9477,9479,9480,9481,9482,9483,9484,9485,9486,9487,9488,9489,9490,9491,9492,9493,9494,9495,9496,9497,9498,9499,9500,9501,9502,9503,9504,9505,9506,9507,9508,9509,9510,9511,9512,9516,9518,9519,9520,9521,9522,9523,9524,9525,9526,9528,9529,9530,9531,9532,9533,9534,9535,9536,9538,9540,9541,9542,9543,9545,9546,9548,9549,9551"]

In an audiocast summarizing his Sunday Lunch Talk at the Annual Clinical Meeting of the American College of Obstetricians and Gynecologists (ACOG) on May 3, 2015, Dr. Michael L. Krychman discusses new treatment options for vulvar and vaginal atrophy (VVA), including over-the-counter and prescription products and procedures. He emphasizes that a better understanding of the physical and anatomic changes in menopause has led to these improved options.

Dr. Krychman also recommends the use of "genitourinary syndrome of menopause" (GSM), new terminology for VVA suggested by the International Society for the Study of Women's Sexual Health and the North American Menopause Society.¹

Among the products Dr. Krychman details are neogyn^® Feminine Soothing Cream (neogyn, inc., Switzerland); RepHresh™ Vaginal Gel (Church & Dwight Co., Inc., Princeton, New Jersey); Replens™ Long-Lasting Vaginal Moisturizer (Church & Dwight); silicone- and water-based lubricants (Replens™ Silky Smooth Lubricant [Church & Dwight]; JuvaGyn^® Feminine Moisturizer [neogyn, inc.]); and ospemifene (Osphena^®, Shionogi Inc., Florham Park, New Jersey).

Dr. Krychman is interested in a new laser procedure for VVA/GSM, but comments that more study is needed before he can recommend its general use. He also talks about other exciting alternatives in the pipeline.

In an audiocast summarizing his Sunday Lunch Talk at the Annual Clinical Meeting of the American College of Obstetricians and Gynecologists (ACOG) on May 3, 2015, Dr. Michael L. Krychman discusses new treatment options for vulvar and vaginal atrophy (VVA), including over-the-counter and prescription products and procedures. He emphasizes that a better understanding of the physical and anatomic changes in menopause has led to these improved options.

Dr. Krychman also recommends the use of "genitourinary syndrome of menopause" (GSM), new terminology for VVA suggested by the International Society for the Study of Women's Sexual Health and the North American Menopause Society.¹

Among the products Dr. Krychman details are neogyn^® Feminine Soothing Cream (neogyn, inc., Switzerland); RepHresh™ Vaginal Gel (Church & Dwight Co., Inc., Princeton, New Jersey); Replens™ Long-Lasting Vaginal Moisturizer (Church & Dwight); silicone- and water-based lubricants (Replens™ Silky Smooth Lubricant [Church & Dwight]; JuvaGyn^® Feminine Moisturizer [neogyn, inc.]); and ospemifene (Osphena^®, Shionogi Inc., Florham Park, New Jersey).

Dr. Krychman is interested in a new laser procedure for VVA/GSM, but comments that more study is needed before he can recommend its general use. He also talks about other exciting alternatives in the pipeline.

In an audiocast summarizing his Sunday Lunch Talk at the Annual Clinical Meeting of the American College of Obstetricians and Gynecologists (ACOG) on May 3, 2015, Dr. Michael L. Krychman discusses new treatment options for vulvar and vaginal atrophy (VVA), including over-the-counter and prescription products and procedures. He emphasizes that a better understanding of the physical and anatomic changes in menopause has led to these improved options.

Dr. Krychman also recommends the use of "genitourinary syndrome of menopause" (GSM), new terminology for VVA suggested by the International Society for the Study of Women's Sexual Health and the North American Menopause Society.¹

Among the products Dr. Krychman details are neogyn^® Feminine Soothing Cream (neogyn, inc., Switzerland); RepHresh™ Vaginal Gel (Church & Dwight Co., Inc., Princeton, New Jersey); Replens™ Long-Lasting Vaginal Moisturizer (Church & Dwight); silicone- and water-based lubricants (Replens™ Silky Smooth Lubricant [Church & Dwight]; JuvaGyn^® Feminine Moisturizer [neogyn, inc.]); and ospemifene (Osphena^®, Shionogi Inc., Florham Park, New Jersey).

Dr. Krychman is interested in a new laser procedure for VVA/GSM, but comments that more study is needed before he can recommend its general use. He also talks about other exciting alternatives in the pipeline.

Photographs from Hospital Medicine 2015, which took place March 29-April 1 at the Gaylord National Hotel and Conference Center in National Harbor, Md.

Photos by Manuel Noguera

[gallery ids="9426,9427,9428,9429,9430,9431,9432,9433,9434,9435,9436,9437,9439,9440,9441,9442,9444,9445,9447,9449,9450,9451,9452,9453,9454,9455,9457,9458,9459,9460,9461,9462,9463,9464,9465,9467,9468,9469,9471,9472,9474"]

tk

Photographs from Hospital Medicine 2015, which took place March 29-April 1 at the Gaylord National Hotel and Conference Center in National Harbor, Md.

Photos by Manuel Noguera

[gallery ids="9426,9427,9428,9429,9430,9431,9432,9433,9434,9435,9436,9437,9439,9440,9441,9442,9444,9445,9447,9449,9450,9451,9452,9453,9454,9455,9457,9458,9459,9460,9461,9462,9463,9464,9465,9467,9468,9469,9471,9472,9474"]

tk

Photographs from Hospital Medicine 2015, which took place March 29-April 1 at the Gaylord National Hotel and Conference Center in National Harbor, Md.

Photos by Manuel Noguera

[gallery ids="9426,9427,9428,9429,9430,9431,9432,9433,9434,9435,9436,9437,9439,9440,9441,9442,9444,9445,9447,9449,9450,9451,9452,9453,9454,9455,9457,9458,9459,9460,9461,9462,9463,9464,9465,9467,9468,9469,9471,9472,9474"]

tk

WASHINGTON – An implantable device that stimulates the sphenopalatine ganglion nerve bundle either reduced or eliminated pain in 68% of more than 5,000 cluster headaches, a 3-year study has determined.

The device, which is approved in Europe, was more effective in attacks of moderate severity, with a 78% rate of pain reduction or elimination, Dr. Jose Miguel Lainez reported at the annual meeting of the American Academy of Neurology.

Courtesy Autonomic Technologies Inc.

The Pulsante System, manufactured by Autonomic Technologiesof Redwood City, Calif., consists of a neurostimulator about the size of an almond, and a lead with six electrodes. It’s inserted under local anesthetic via a small incision in the upper gum on the side in which the patient experiences symptoms. The electrodes are positioned along the sphenopalatine ganglion (SPG) nerve and the neurostimulator is affixed to the zygomatic process.

A hand-held remote controller placed against the cheek activates the device and controls the intensity of stimulation, which is thought to work by blocking signals to the postganglionic parasympathetic fibers. Those fibers innervate facial structures and the cerebral and meningeal blood vessels and are implicated in the pain and accompanying autonomic symptoms of a cluster headache attack.

Dr. Lainez, professor of neurology at Catholic University of Valencia (Spain), presented 3-year follow-up data from Pathway CH-1, a randomized, sham-controlled trial of 43 patients with cluster headache. Of these, 33 completed the 3-year follow-up period. Of the remaining 10, 1 was lost from observation, 5 violated protocol, 1 had the device implanted incorrectly, and 3 had the device explanted because of incorrect placement or lead migration.

Most of the patients were male. Mean age was 41 years. They had a mean disease duration of 10 years and averaged 17 cluster headaches per week but ranged from 4 to 70 attacks per week. Over the 3 years, 5,130 attacks were treated; the mean stimulation duration for these was 14 minutes with a mean response time of 11 minutes. Therapy was considered effective in 65% (3,354) of these attacks based on a clinically meaningful reduction in pain or pain elimination.

Dr. Lainez did not parse these results. However, in the initial 28-week phase of the Pathway CH-1 study, pain was reduced in 68% of attacks treated with the device and 7% of those treated with the sham control. Pain freedom by 15 minutes was achieved in 34% of attacks with full stimulation, compared with 1.5% of those treated with sham.

In the follow-up study, the device seemed most effective in attacks of moderate severity (78% response rate of pain reduction or elimination). The response rate was 59% in mild attacks and 51% in severe attacks. Most attacks treated with the device (77%) did not involve the use of abortive therapy.

Dr. Lainez did not mention adverse events related to the device. However, in the 28-week study, there were 92, including parasthesias and numbness; facial and tooth pain; and swelling. Others were considered mild and included dry eye, nose bleed, and facial asymmetry.

The device is currently being investigated in a U.S. study. The open-label Pathway-CH2 study aims to recruit 120 patients. For information on Pathway CH-2, contact Anthony Caparso.

The trial was sponsored by Autonomic Technologies Inc. Dr. Lainez had no financial ties with the company.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

WASHINGTON – An implantable device that stimulates the sphenopalatine ganglion nerve bundle either reduced or eliminated pain in 68% of more than 5,000 cluster headaches, a 3-year study has determined.

The device, which is approved in Europe, was more effective in attacks of moderate severity, with a 78% rate of pain reduction or elimination, Dr. Jose Miguel Lainez reported at the annual meeting of the American Academy of Neurology.

Courtesy Autonomic Technologies Inc.

The Pulsante System, manufactured by Autonomic Technologiesof Redwood City, Calif., consists of a neurostimulator about the size of an almond, and a lead with six electrodes. It’s inserted under local anesthetic via a small incision in the upper gum on the side in which the patient experiences symptoms. The electrodes are positioned along the sphenopalatine ganglion (SPG) nerve and the neurostimulator is affixed to the zygomatic process.

A hand-held remote controller placed against the cheek activates the device and controls the intensity of stimulation, which is thought to work by blocking signals to the postganglionic parasympathetic fibers. Those fibers innervate facial structures and the cerebral and meningeal blood vessels and are implicated in the pain and accompanying autonomic symptoms of a cluster headache attack.

Dr. Lainez, professor of neurology at Catholic University of Valencia (Spain), presented 3-year follow-up data from Pathway CH-1, a randomized, sham-controlled trial of 43 patients with cluster headache. Of these, 33 completed the 3-year follow-up period. Of the remaining 10, 1 was lost from observation, 5 violated protocol, 1 had the device implanted incorrectly, and 3 had the device explanted because of incorrect placement or lead migration.

Most of the patients were male. Mean age was 41 years. They had a mean disease duration of 10 years and averaged 17 cluster headaches per week but ranged from 4 to 70 attacks per week. Over the 3 years, 5,130 attacks were treated; the mean stimulation duration for these was 14 minutes with a mean response time of 11 minutes. Therapy was considered effective in 65% (3,354) of these attacks based on a clinically meaningful reduction in pain or pain elimination.

Dr. Lainez did not parse these results. However, in the initial 28-week phase of the Pathway CH-1 study, pain was reduced in 68% of attacks treated with the device and 7% of those treated with the sham control. Pain freedom by 15 minutes was achieved in 34% of attacks with full stimulation, compared with 1.5% of those treated with sham.

In the follow-up study, the device seemed most effective in attacks of moderate severity (78% response rate of pain reduction or elimination). The response rate was 59% in mild attacks and 51% in severe attacks. Most attacks treated with the device (77%) did not involve the use of abortive therapy.

Dr. Lainez did not mention adverse events related to the device. However, in the 28-week study, there were 92, including parasthesias and numbness; facial and tooth pain; and swelling. Others were considered mild and included dry eye, nose bleed, and facial asymmetry.

The device is currently being investigated in a U.S. study. The open-label Pathway-CH2 study aims to recruit 120 patients. For information on Pathway CH-2, contact Anthony Caparso.

The trial was sponsored by Autonomic Technologies Inc. Dr. Lainez had no financial ties with the company.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

WASHINGTON – An implantable device that stimulates the sphenopalatine ganglion nerve bundle either reduced or eliminated pain in 68% of more than 5,000 cluster headaches, a 3-year study has determined.

The device, which is approved in Europe, was more effective in attacks of moderate severity, with a 78% rate of pain reduction or elimination, Dr. Jose Miguel Lainez reported at the annual meeting of the American Academy of Neurology.

Courtesy Autonomic Technologies Inc.

The Pulsante System, manufactured by Autonomic Technologiesof Redwood City, Calif., consists of a neurostimulator about the size of an almond, and a lead with six electrodes. It’s inserted under local anesthetic via a small incision in the upper gum on the side in which the patient experiences symptoms. The electrodes are positioned along the sphenopalatine ganglion (SPG) nerve and the neurostimulator is affixed to the zygomatic process.

A hand-held remote controller placed against the cheek activates the device and controls the intensity of stimulation, which is thought to work by blocking signals to the postganglionic parasympathetic fibers. Those fibers innervate facial structures and the cerebral and meningeal blood vessels and are implicated in the pain and accompanying autonomic symptoms of a cluster headache attack.

Dr. Lainez, professor of neurology at Catholic University of Valencia (Spain), presented 3-year follow-up data from Pathway CH-1, a randomized, sham-controlled trial of 43 patients with cluster headache. Of these, 33 completed the 3-year follow-up period. Of the remaining 10, 1 was lost from observation, 5 violated protocol, 1 had the device implanted incorrectly, and 3 had the device explanted because of incorrect placement or lead migration.

Most of the patients were male. Mean age was 41 years. They had a mean disease duration of 10 years and averaged 17 cluster headaches per week but ranged from 4 to 70 attacks per week. Over the 3 years, 5,130 attacks were treated; the mean stimulation duration for these was 14 minutes with a mean response time of 11 minutes. Therapy was considered effective in 65% (3,354) of these attacks based on a clinically meaningful reduction in pain or pain elimination.

Dr. Lainez did not parse these results. However, in the initial 28-week phase of the Pathway CH-1 study, pain was reduced in 68% of attacks treated with the device and 7% of those treated with the sham control. Pain freedom by 15 minutes was achieved in 34% of attacks with full stimulation, compared with 1.5% of those treated with sham.

In the follow-up study, the device seemed most effective in attacks of moderate severity (78% response rate of pain reduction or elimination). The response rate was 59% in mild attacks and 51% in severe attacks. Most attacks treated with the device (77%) did not involve the use of abortive therapy.

Dr. Lainez did not mention adverse events related to the device. However, in the 28-week study, there were 92, including parasthesias and numbness; facial and tooth pain; and swelling. Others were considered mild and included dry eye, nose bleed, and facial asymmetry.

The device is currently being investigated in a U.S. study. The open-label Pathway-CH2 study aims to recruit 120 patients. For information on Pathway CH-2, contact Anthony Caparso.

The trial was sponsored by Autonomic Technologies Inc. Dr. Lainez had no financial ties with the company.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

Micrograph showing MDS

WASHINGTON, DC—An investigational drug can increase hemoglobin levels and eliminate transfusion dependence in patients with lower-risk myelodysplastic syndromes (MDS), results of a phase 2 trial suggest.

The drug, luspatercept, is a modified activin receptor type IIB fusion protein that acts as a ligand trap for members in the TGF-β superfamily involved in the late stages of erythropoiesis.

Luspatercept regulates late-stage erythrocyte precursor differentiation and maturation.

Uwe Platzbecker, MD, of the University Hospital in Dresden, Germany, presented results from an ongoing phase 2 study of luspatercept at the 13th International Symposium on Myelodysplastic Syndromes (abstract 53).

The trial is supported by Acceleron Pharma Inc. and Celgene Corporation, the companies developing luspatercept.

“We are excited by the results in lower-risk MDS patients, which confirm and extend our previous findings,” Dr Platzbecker said. “Luspatercept may be useful early in the treatment of lower-risk MDS patients, either as the initial treatment for anemia or in patients who do not respond or become refractory to treatment with erythropoiesis-stimulating agents.”

Patient and dosing details

The researchers enrolled 58 patients in this study. Twenty-seven have completed treatment as part of the dose-escalation cohort. These patients received luspatercept at 7 doses ranging from 0.125 mg/kg to 1.75 mg/kg.

Thirty-one patients are still receiving treatment in the expansion cohort. The starting dose in this cohort is 1.0 mg/kg, and patients are receiving individual dose titration up to 1.75 mg/kg. Seventeen patients from this cohort received at least 4 cycles of treatment or discontinued early and were included in the analysis presented at the meeting.

In all, Dr Platzbecker presented results in 44 patients. Their median age was 71 (range, 27-88), and 57% were male. The median time since diagnosis was 2.5 years (range, 0.2-13.6 years). Sixty-one percent of patients had received prior treatment with erythropoiesis-stimulating agents, and 21% had received lenalidomide.

Fifteen patients had a low transfusion burden (LTB), as they received less than 4 units of red blood cells (RBCs) over 8 weeks. For these patients, the median hemoglobin at baseline was 9.0 g/dL (range, 6.8-10.1), and the median number of RBCs transfused over 8 weeks was 2 (range, 2-2).

Twenty-nine patients had a high transfusion burden (HTB) and received 4 or more RBC units over 8 weeks. The median number of RBCs transfused in this group was 6 (range, 4-14).

Fifty percent of patients had low-risk MDS according to IPSS, 46% had intermediate-1-risk disease, and 4% had intermediate-2-risk MDS. Eighty-one percent of patients were positive for ring sideroblasts, and 58% had the SF3B1 splicing mutation.

Efficacy and safety

The study’s primary efficacy endpoint was an increase in hemoglobin and/or a reduction in transfusion use. For LTB patients, the endpoint was a hemoglobin increase of 1.5 g/dL or more for 2 weeks or longer. For HTB patients, it was decrease in transfusion of 4 or more RBC units or a 50% or greater reduction in transfusion over 8 weeks.

Among the 9 patients who received lower doses of luspatercept (0.125-0.5 mg/kg), 33% met the primary efficacy endpoint. And 63% of the 35 patients in the higher dose group (0.75-1.75 mg/kg) achieved the primary efficacy endpoint.

Twenty-two percent of patients in the lower dose group achieved the International Working Group (IWG) hematologic improvement-erythroid (HI-E) threshold of efficacy, as did 54% of patients in the higher dose group.

Fourteen percent of patients in the lower dose group achieved transfusion independence, as did 36% of patients in the higher dose group. In the higher dose group, this included 4 of 6 patients with LTB and 6 of 22 patients with HTB.

Among patients who were ring-sideroblast-positive and received higher doses of luspatercept, 39% achieved transfusion independence, and 63% achieved IWG HI-E.

The majority of adverse events (AEs) were mild to moderate (grade 1 or 2). AEs included nasopharyngitis (14%), diarrhea (14%), myalgia (11%), bone pain (9%), bronchitis (9%), headache (9%), and muscle spasms (9%).

There were 2 serious AEs—grade 3 muscle pain and grade 3 worsening of general condition—that were considered possibly related to treatment. One non-serious grade 3 AE of blast cell count increase was considered possibly treatment-related as well.

In closing, Dr Platzbecker said luspatercept was generally safe and well-tolerated, in addition to providing “robust hematologic improvement.” And these results support further study of the drug in patients with lower-risk MDS.

Micrograph showing MDS

WASHINGTON, DC—An investigational drug can increase hemoglobin levels and eliminate transfusion dependence in patients with lower-risk myelodysplastic syndromes (MDS), results of a phase 2 trial suggest.

The drug, luspatercept, is a modified activin receptor type IIB fusion protein that acts as a ligand trap for members in the TGF-β superfamily involved in the late stages of erythropoiesis.

Luspatercept regulates late-stage erythrocyte precursor differentiation and maturation.

Uwe Platzbecker, MD, of the University Hospital in Dresden, Germany, presented results from an ongoing phase 2 study of luspatercept at the 13th International Symposium on Myelodysplastic Syndromes (abstract 53).

The trial is supported by Acceleron Pharma Inc. and Celgene Corporation, the companies developing luspatercept.

“We are excited by the results in lower-risk MDS patients, which confirm and extend our previous findings,” Dr Platzbecker said. “Luspatercept may be useful early in the treatment of lower-risk MDS patients, either as the initial treatment for anemia or in patients who do not respond or become refractory to treatment with erythropoiesis-stimulating agents.”

Patient and dosing details

The researchers enrolled 58 patients in this study. Twenty-seven have completed treatment as part of the dose-escalation cohort. These patients received luspatercept at 7 doses ranging from 0.125 mg/kg to 1.75 mg/kg.

Thirty-one patients are still receiving treatment in the expansion cohort. The starting dose in this cohort is 1.0 mg/kg, and patients are receiving individual dose titration up to 1.75 mg/kg. Seventeen patients from this cohort received at least 4 cycles of treatment or discontinued early and were included in the analysis presented at the meeting.

In all, Dr Platzbecker presented results in 44 patients. Their median age was 71 (range, 27-88), and 57% were male. The median time since diagnosis was 2.5 years (range, 0.2-13.6 years). Sixty-one percent of patients had received prior treatment with erythropoiesis-stimulating agents, and 21% had received lenalidomide.

Fifteen patients had a low transfusion burden (LTB), as they received less than 4 units of red blood cells (RBCs) over 8 weeks. For these patients, the median hemoglobin at baseline was 9.0 g/dL (range, 6.8-10.1), and the median number of RBCs transfused over 8 weeks was 2 (range, 2-2).

Twenty-nine patients had a high transfusion burden (HTB) and received 4 or more RBC units over 8 weeks. The median number of RBCs transfused in this group was 6 (range, 4-14).

Fifty percent of patients had low-risk MDS according to IPSS, 46% had intermediate-1-risk disease, and 4% had intermediate-2-risk MDS. Eighty-one percent of patients were positive for ring sideroblasts, and 58% had the SF3B1 splicing mutation.

Efficacy and safety

The study’s primary efficacy endpoint was an increase in hemoglobin and/or a reduction in transfusion use. For LTB patients, the endpoint was a hemoglobin increase of 1.5 g/dL or more for 2 weeks or longer. For HTB patients, it was decrease in transfusion of 4 or more RBC units or a 50% or greater reduction in transfusion over 8 weeks.

Among the 9 patients who received lower doses of luspatercept (0.125-0.5 mg/kg), 33% met the primary efficacy endpoint. And 63% of the 35 patients in the higher dose group (0.75-1.75 mg/kg) achieved the primary efficacy endpoint.

Twenty-two percent of patients in the lower dose group achieved the International Working Group (IWG) hematologic improvement-erythroid (HI-E) threshold of efficacy, as did 54% of patients in the higher dose group.

Fourteen percent of patients in the lower dose group achieved transfusion independence, as did 36% of patients in the higher dose group. In the higher dose group, this included 4 of 6 patients with LTB and 6 of 22 patients with HTB.

Among patients who were ring-sideroblast-positive and received higher doses of luspatercept, 39% achieved transfusion independence, and 63% achieved IWG HI-E.

The majority of adverse events (AEs) were mild to moderate (grade 1 or 2). AEs included nasopharyngitis (14%), diarrhea (14%), myalgia (11%), bone pain (9%), bronchitis (9%), headache (9%), and muscle spasms (9%).

There were 2 serious AEs—grade 3 muscle pain and grade 3 worsening of general condition—that were considered possibly related to treatment. One non-serious grade 3 AE of blast cell count increase was considered possibly treatment-related as well.

In closing, Dr Platzbecker said luspatercept was generally safe and well-tolerated, in addition to providing “robust hematologic improvement.” And these results support further study of the drug in patients with lower-risk MDS.

Micrograph showing MDS

WASHINGTON, DC—An investigational drug can increase hemoglobin levels and eliminate transfusion dependence in patients with lower-risk myelodysplastic syndromes (MDS), results of a phase 2 trial suggest.

The drug, luspatercept, is a modified activin receptor type IIB fusion protein that acts as a ligand trap for members in the TGF-β superfamily involved in the late stages of erythropoiesis.

Luspatercept regulates late-stage erythrocyte precursor differentiation and maturation.

Uwe Platzbecker, MD, of the University Hospital in Dresden, Germany, presented results from an ongoing phase 2 study of luspatercept at the 13th International Symposium on Myelodysplastic Syndromes (abstract 53).

The trial is supported by Acceleron Pharma Inc. and Celgene Corporation, the companies developing luspatercept.

“We are excited by the results in lower-risk MDS patients, which confirm and extend our previous findings,” Dr Platzbecker said. “Luspatercept may be useful early in the treatment of lower-risk MDS patients, either as the initial treatment for anemia or in patients who do not respond or become refractory to treatment with erythropoiesis-stimulating agents.”

Patient and dosing details

The researchers enrolled 58 patients in this study. Twenty-seven have completed treatment as part of the dose-escalation cohort. These patients received luspatercept at 7 doses ranging from 0.125 mg/kg to 1.75 mg/kg.

Thirty-one patients are still receiving treatment in the expansion cohort. The starting dose in this cohort is 1.0 mg/kg, and patients are receiving individual dose titration up to 1.75 mg/kg. Seventeen patients from this cohort received at least 4 cycles of treatment or discontinued early and were included in the analysis presented at the meeting.

In all, Dr Platzbecker presented results in 44 patients. Their median age was 71 (range, 27-88), and 57% were male. The median time since diagnosis was 2.5 years (range, 0.2-13.6 years). Sixty-one percent of patients had received prior treatment with erythropoiesis-stimulating agents, and 21% had received lenalidomide.

Fifteen patients had a low transfusion burden (LTB), as they received less than 4 units of red blood cells (RBCs) over 8 weeks. For these patients, the median hemoglobin at baseline was 9.0 g/dL (range, 6.8-10.1), and the median number of RBCs transfused over 8 weeks was 2 (range, 2-2).

Twenty-nine patients had a high transfusion burden (HTB) and received 4 or more RBC units over 8 weeks. The median number of RBCs transfused in this group was 6 (range, 4-14).

Fifty percent of patients had low-risk MDS according to IPSS, 46% had intermediate-1-risk disease, and 4% had intermediate-2-risk MDS. Eighty-one percent of patients were positive for ring sideroblasts, and 58% had the SF3B1 splicing mutation.

Efficacy and safety

The study’s primary efficacy endpoint was an increase in hemoglobin and/or a reduction in transfusion use. For LTB patients, the endpoint was a hemoglobin increase of 1.5 g/dL or more for 2 weeks or longer. For HTB patients, it was decrease in transfusion of 4 or more RBC units or a 50% or greater reduction in transfusion over 8 weeks.

Among the 9 patients who received lower doses of luspatercept (0.125-0.5 mg/kg), 33% met the primary efficacy endpoint. And 63% of the 35 patients in the higher dose group (0.75-1.75 mg/kg) achieved the primary efficacy endpoint.

Twenty-two percent of patients in the lower dose group achieved the International Working Group (IWG) hematologic improvement-erythroid (HI-E) threshold of efficacy, as did 54% of patients in the higher dose group.

Fourteen percent of patients in the lower dose group achieved transfusion independence, as did 36% of patients in the higher dose group. In the higher dose group, this included 4 of 6 patients with LTB and 6 of 22 patients with HTB.

Among patients who were ring-sideroblast-positive and received higher doses of luspatercept, 39% achieved transfusion independence, and 63% achieved IWG HI-E.

The majority of adverse events (AEs) were mild to moderate (grade 1 or 2). AEs included nasopharyngitis (14%), diarrhea (14%), myalgia (11%), bone pain (9%), bronchitis (9%), headache (9%), and muscle spasms (9%).

There were 2 serious AEs—grade 3 muscle pain and grade 3 worsening of general condition—that were considered possibly related to treatment. One non-serious grade 3 AE of blast cell count increase was considered possibly treatment-related as well.

In closing, Dr Platzbecker said luspatercept was generally safe and well-tolerated, in addition to providing “robust hematologic improvement.” And these results support further study of the drug in patients with lower-risk MDS.

Fresh whole blood

Photo by Elise Amendola

Using fresh whole blood (FWB) from single donors for cardiac procedures in children younger than 2 years of age is better than using component blood from multiple donors, researchers say.

FWB reduces the risk of getting transfusion-related illnesses by reducing donor exposures.

“Currently, whole blood is not generally made available to hospitals for use in pediatric heart surgery,” said David R. Jobes, MD, of The Children’s Hospital of Philadelphia in Pennsylvania.

“Blood centers separate donated blood into component parts, which are then stored for use in medical transfusions as needed.”

At The Children’s Hospital of Philadelphia, the standard preoperative blood order for elective pediatric heart surgery with cariopulmonary bypass is 2 units of FWB and 2 units of packed red blood cells. The FWB is to be used during and immediately after surgery and the components thereafter, if necessary.

The researchers set out to examine the effectiveness of this protocol. They conducted a retrospective study of patient records over a period of 15 years from a surgical registry and blood bank, comparing the cohort of 4111 patients to published reports.

The team defined donor exposures as transfusion requirements for the day of operation and the next postoperative day. All blood products issued were presumed to have been tranfused, and all aliquots from a single donor were counted as a single donor exposure.

Patients were a median age of 94 days and weighed a median of 4.4 kg.

Most (3836) patients received FWB, and 252 received components exclusively when no FWB was available. Twenty-three patients did not receive any blood products. A median of 2 whole blood units was transfused, for a total of 2 donor exposures for the entire cohort.

The researchers found that the youngest patients having complex procedures were exposed to the highest number of donors, while older patients having simpler procedures were exposed to fewer donors.

For example, 72 patients who were a median of 5 days old and underwent truncus arteriosus repair had a median of 4 donor exposures (range, 1-14). And 136 older patients who were a median of 610 days old and underwent fontan completion had a median of 1 donor exposure (range, 0-8).

The researchers concluded that the protocol resulted in fewer donor exposures compared with component use reported in the literature.

Dr Jobes said the risk for disease transmission in pediatric patients is essentially the same as the risk for adults, but it may be more costly for pediatric patients in the long run because infants and young children may live longer with chronic illness stemming from transfusion.

He added, “We hope that our research helps to re-examine current blood storage practice and make whole blood more readily available for pediatric patients.”

He and his colleagues described this research in The Annals of Thoracic Surgery.

Fresh whole blood

Photo by Elise Amendola

Using fresh whole blood (FWB) from single donors for cardiac procedures in children younger than 2 years of age is better than using component blood from multiple donors, researchers say.

FWB reduces the risk of getting transfusion-related illnesses by reducing donor exposures.

“Currently, whole blood is not generally made available to hospitals for use in pediatric heart surgery,” said David R. Jobes, MD, of The Children’s Hospital of Philadelphia in Pennsylvania.

“Blood centers separate donated blood into component parts, which are then stored for use in medical transfusions as needed.”

At The Children’s Hospital of Philadelphia, the standard preoperative blood order for elective pediatric heart surgery with cariopulmonary bypass is 2 units of FWB and 2 units of packed red blood cells. The FWB is to be used during and immediately after surgery and the components thereafter, if necessary.

The researchers set out to examine the effectiveness of this protocol. They conducted a retrospective study of patient records over a period of 15 years from a surgical registry and blood bank, comparing the cohort of 4111 patients to published reports.

The team defined donor exposures as transfusion requirements for the day of operation and the next postoperative day. All blood products issued were presumed to have been tranfused, and all aliquots from a single donor were counted as a single donor exposure.

Patients were a median age of 94 days and weighed a median of 4.4 kg.

Most (3836) patients received FWB, and 252 received components exclusively when no FWB was available. Twenty-three patients did not receive any blood products. A median of 2 whole blood units was transfused, for a total of 2 donor exposures for the entire cohort.

The researchers found that the youngest patients having complex procedures were exposed to the highest number of donors, while older patients having simpler procedures were exposed to fewer donors.

For example, 72 patients who were a median of 5 days old and underwent truncus arteriosus repair had a median of 4 donor exposures (range, 1-14). And 136 older patients who were a median of 610 days old and underwent fontan completion had a median of 1 donor exposure (range, 0-8).

The researchers concluded that the protocol resulted in fewer donor exposures compared with component use reported in the literature.

Dr Jobes said the risk for disease transmission in pediatric patients is essentially the same as the risk for adults, but it may be more costly for pediatric patients in the long run because infants and young children may live longer with chronic illness stemming from transfusion.

He added, “We hope that our research helps to re-examine current blood storage practice and make whole blood more readily available for pediatric patients.”

He and his colleagues described this research in The Annals of Thoracic Surgery.

Fresh whole blood

Photo by Elise Amendola

Using fresh whole blood (FWB) from single donors for cardiac procedures in children younger than 2 years of age is better than using component blood from multiple donors, researchers say.

FWB reduces the risk of getting transfusion-related illnesses by reducing donor exposures.

“Currently, whole blood is not generally made available to hospitals for use in pediatric heart surgery,” said David R. Jobes, MD, of The Children’s Hospital of Philadelphia in Pennsylvania.

“Blood centers separate donated blood into component parts, which are then stored for use in medical transfusions as needed.”

At The Children’s Hospital of Philadelphia, the standard preoperative blood order for elective pediatric heart surgery with cariopulmonary bypass is 2 units of FWB and 2 units of packed red blood cells. The FWB is to be used during and immediately after surgery and the components thereafter, if necessary.

The researchers set out to examine the effectiveness of this protocol. They conducted a retrospective study of patient records over a period of 15 years from a surgical registry and blood bank, comparing the cohort of 4111 patients to published reports.

The team defined donor exposures as transfusion requirements for the day of operation and the next postoperative day. All blood products issued were presumed to have been tranfused, and all aliquots from a single donor were counted as a single donor exposure.

Patients were a median age of 94 days and weighed a median of 4.4 kg.

Most (3836) patients received FWB, and 252 received components exclusively when no FWB was available. Twenty-three patients did not receive any blood products. A median of 2 whole blood units was transfused, for a total of 2 donor exposures for the entire cohort.

The researchers found that the youngest patients having complex procedures were exposed to the highest number of donors, while older patients having simpler procedures were exposed to fewer donors.

For example, 72 patients who were a median of 5 days old and underwent truncus arteriosus repair had a median of 4 donor exposures (range, 1-14). And 136 older patients who were a median of 610 days old and underwent fontan completion had a median of 1 donor exposure (range, 0-8).

The researchers concluded that the protocol resulted in fewer donor exposures compared with component use reported in the literature.

Dr Jobes said the risk for disease transmission in pediatric patients is essentially the same as the risk for adults, but it may be more costly for pediatric patients in the long run because infants and young children may live longer with chronic illness stemming from transfusion.

He added, “We hope that our research helps to re-examine current blood storage practice and make whole blood more readily available for pediatric patients.”

He and his colleagues described this research in The Annals of Thoracic Surgery.