Tourniquets are often used in total knee arthroplasty (TKA) to improve visualization of structures, shorten operative time, reduce intraoperative bleeding, and improve cementing technique. Despite these advantages, controversy remains regarding the safety of tourniquet use. Tourniquets have been associated with nerve palsies, vascular injury, and muscle damage.^1-5 Some have hypothesized they may cause venous stasis or direct endothelial damage that may develop into deep vein thrombosis (DVT). Abdel-Salam and Eyres⁶ found an increased incidence of postoperative wound complications and DVTs associated with tourniquet use.

Moreover, investigators have analyzed the role of tourniquets in populations at high risk for wound complications. DeLaurentis and colleagues⁷ performed a prospective and retrospective analysis of 1182 TKA patients, 24 (2%) of whom had preexisting peripheral vascular disease (PVD), defined as a history of arterial insufficiency, absent dorsalis pedis and/or absent posterior tibial pulsations, and arterial calcifications. A tourniquet was used in each case. Arterial complications occurred in 6 of the 24 patients with PVD. As expected, the authors found that a history of intermittent claudication, pain at rest, and arterial ulcers resulted in a high risk for vascular complications. Further studies have supported this finding and expanded the list of predisposing factors to include previous vascular surgery and absent and asymmetric pedal pulsations.^7-11 Of particular concern to total joint arthroplasty surgeons was the finding by DeLaurentis and colleagues⁷ that patients with radiographic evidence of calcification of the distal superficial femoral artery and/or popliteal artery were at risk for arterial complications. This finding is also supported by other studies.^8,11 In TKA, damage to arterial structures proximal to the surgical field could manifest as impaired postoperative wound healing or an ischemic limb. Wound healing depends on adequate blood flow to the healing tissue, and any damage to arterial or venous structures can theoretically compromise this process.

Added to vascular/wound complications as concerning complications in orthopedic surgery is venous thromboembolism (VTE). The role of tourniquets in the formation of VTEs is controversial. A tourniquet has the potential to increase the risk for DVT because of the stasis of venous blood in the lower limb or possible damage to calcified blood vessels. Callam and colleagues¹² studied the connection between artery disease and chronic leg ulcers and found that half the patients diagnosed with peripheral artery disease also had stigmata of chronic venous insufficiency. Therefore, the entities can occur in tandem, and surgeons should keep this in mind.

Here we report on a study we conducted to determine whether tourniquet use in TKA in patients with preexisting radiographic evidence of vascular disease increases the risk for wound complications or VTE.

Patients and Methods

We retrospectively reviewed 461 consecutive primary TKAs (373 patients) performed between January 2007 and June 2012 by 2 attending orthopedic surgeons specializing in adult reconstruction. Medical records and operative reports of 583 patients were examined after receiving institutional review board approval. Of these patients, 373 (64%) had a minimum of 12-month follow-up data available. Twelve months was deemed long enough to discover wound complications or DVTs secondary to the index procedure. Most of these outcomes manifest within the first 3 months after surgery and certainly by 12 months. Follow-up longer than 12 months may become a confounder, as wound complications outside the acute to subacute postoperative window could be related to patients’ underlying PVD and not directly to tourniquet use during surgery. Patient demographics and comorbidities were recorded. Comorbidities were obtained from preoperative medical evaluations and surgeons’ preoperative evaluations. All patients had preoperative palpable dorsalis pedis and posterior tibialis arterial pulses. No patient required preoperative vascular studies based on preoperative examination or comorbidities. No patient had prior vascular bypass surgery or stenting.

TKA was performed in a nonlaminar flow, positive-pressure, high-efficiency particulate air-filtered room with sterile toga/surgical helmet systems. For all patients, a pneumatic thigh tourniquet was applied, and the patient was prepared and draped. After limb exsanguination using a rubber bandage, the limb was elevated and the tourniquet inflated to a pressure of 250 to 300 mm Hg. The tourniquet was released either just before closure or immediately after closure in all cases; it was always let down before placement of final bandages.

Prophylactic chemical anticoagulation consisting of warfarin, aspirin, or enoxaparin was used in all patients and continued for 4 to 6 weeks after surgery. All patients received mechanical DVT prophylaxis with sequential compression devices, and all were mobilized out of bed beginning either the day of surgery or the next day. All patients received perioperative intravenous antibiotics, with the preoperative dose given before tourniquet inflation and the last postoperative dose stopped within 24 hours of surgery.

All patients who had primary TKA underwent preoperative medical evaluation and optimization. The patient’s hospital course was monitored closely, and complications noted by the orthopedic team were documented. Follow-up documentation was retrospectively reviewed for evidence of wound complications or VTE. Wound complications were defined as cellulitis, delayed wound healing, wound dehiscence, and/or periprosthetic joint infection. In the case of VTE, physical examination findings were not sufficient for inclusion. Venous duplex ultrasonography demonstrating the clot was reviewed before inclusion.

Preoperative radiographs were examined for arterial calcification (Figure). We refer to calcification seen above the knee joint as proximal calcification and to calcification observed below the joint as distal calcification. Patients exhibited calcification proximally only, distally only, or both proximally and distally. The 373 patients were placed into 2 groups based on whether they had preoperative arterial calcification on plain radiography of the knee. One group (285 patients with no radiographic evidence of preoperative knee arterial calcification) underwent 365 TKAs, and the other group (88 patients with radiographic evidence of preoperative knee arterial calcification) underwent 96 TKAs.

A sample size calculation was performed to determine how many patients were needed in each group with 80% power and an α of 0.05. With an estimated difference in VTE/wound complication rate between the calcification and no-calcification groups of 12%, we needed to review 316 TKAs total. This 12% difference was based on study findings of a 25% complication rate in PVD patients who underwent tourniquet-assisted TKA, and the rate of VTE/wound complication after TKA in patients overall, which can be up to 12%.^7,13,14 We exceeded minimal enrollment and had 461 TKAs. Descriptive statistics were reported, with means and ranges provided where appropriate. Independent t test was used to evaluate the differences in continuous data (age) between the groups. Univariate analysis (using Pearson χ² and Fisher exact tests) and multivariate logistic regression analysis were used to evaluate the effects of categorical variables (sex, comorbidity, calcification [presence, absence], and location of calcification [proximal only, distal only, both]) on wound complication and VTE rates. All tests were 2-tailed and performed with a type I error rate of 0.05. Data analysis was performed with SPSS Version 19.0 (SPSS).

Results

Patient characteristics are summarized in Table 1. Of the 373 patients, 285 lacked calcification, and 88 had calcification. Mean age was 67.73 years (range, 24-92 years) for all patients, 65.99 years (range, 24-89 years) for the no-calcification group, and 74.32 years (range, 54-92 years) for the calcification group; the calcification group demonstrated a trend toward older age, but the difference was not significantly different (P = .07). Of the 373 patients, 156 (41.82%) were male: 110 in the no-calcification group (38.60%) and 46 in the calcification group (52.27%); sex was significantly (P = .002) different between groups, with more males in the calcification group.

Data on total preoperative comorbidities are summarized in Table 2. Hypertension, hyperlipidemia, diabetes, and coronary artery disease (CAD) were the most common comorbidities, and they were all significantly (P ≤ .05) increased in the calcification group.

No patients had reported arterial complications, such as arterial bleeding, aneurysm, intimal tears, or loss of distal pulses. Wound complication after TKA was detected in 3.04% of all cases (Table 3). Rate of DVT after TKA was 2.60% of all cases, and rate of pulmonary embolism after TKA was 2.17% of all cases. Of the 96 TKAs with preoperative radiographic evidence of calcification, 47 (48.96%) had proximal calcification only, 11 (11.46%) had distal calcification only, and 38 (39.58%) had both proximal and distal calcification (Table 4). There was no significant difference between the rate of wound complication or VTE based on location of vascular calcification.

Univariate analysis demonstrated that presence of arterial knee calcification did not increase the risk for postoperative wound complication (odds ratio [OR], 1.04; 95% confidence interval [CI], 0.28-3.80; P > .05) (Table 5). Location of arterial knee calcification also did not increase the risk for postoperative wound complication. In addition, univariate analysis demonstrated that presence of arterial knee calcification did not increase the risk for postoperative VTE (OR, 1.20; 95% CI, 0.43-3.36; P > .05 (Table 6).

Of the 14 wound complications, the most common infections were cellulitis (5/14 cases; 35.71%) and infected hardware that required component revision (5/14 cases; 35.71%). Mean time from TKA to infection was 137.93 days (range, 5-783 days). The most common organism grown in culture from the wound was Staphylococcus (5/14 cases; 35.71%).

Additional univariate statistical analysis revealed that presence of diabetes, hypertension, prior VTE, CAD, and male sex was linked to higher incidence of wound complication (P < .05) (Table 5). When multivariate analysis was performed, hypertension, prior VTE, and male sex remained significant (P < .05) (Table 5).

Discussion

TKA is a safe and effective procedure used to treat osteoarthritis of the knee and improve patients’ quality of life.¹⁵ About 700,000 TKAs are performed annually in the United States.¹⁶ Because of improvements in preventive medicine and medical technology, life expectancy is increasing, and TKAs are now being performed in higher numbers and in an older patient population. Over the next few decades, these developments will lead to more postoperative complications. It is projected that, by 2030, the need for TKAs in the United States will increase by 673% to 3.48 million.¹⁷ Postoperative complications are rare but unfortunately often lead to poor outcomes or even mortality.¹⁸ To help minimize the number of postoperative complications, we must understand the safety of tourniquet use in TKA. Other investigators have concluded that tourniquet use is unsafe in patients with preoperative vascular calcifications on plain radiographs.^7,8,11 The present study, designed to elucidate whether preoperative evidence of knee arterial calcification may predispose TKA patients to postoperative wound complication or VTE, had some important findings.

In our study, wound complication and VTE occurred in a considerable number of patients after TKA. Despite exceeding the number of patients calculated by the power analysis, our population may have been inadequate to fully detect statistical significance. Thus, our conclusion of failing to reject the null hypothesis may have been because of sample size, a type II error. We found that, after primary TKA, 3.04% of patients developed wound complications and 4.77% VTE. According to the literature, the incidence of infection after primary TKA is between 0.5% and 12%, and that of VTE reported within 3 months after TKA is 1.3% to 10%.^13,14 Although we had 100% VTE prophylaxis, meeting the standard of care, VTE after TKA remains a postoperative complication.¹⁹ This study also found that a considerable percentage of primary TKA patients (23.59%) had preoperative calcification of the knee arteries. To our knowledge, this study was the first to quantify the incidence of knee arterial calcification in patients who underwent TKA.

Preoperative calcification of the knee arteries in patients who underwent TKA did not increase the risk for wound complication, VTE, or arterial damage. These calcifications, however, do pose an increased systemic vascular risk.²⁰ Calcification of the vascular wall predicts increased cardiovascular risk, independent of classical cardiovascular risk factors.^3,18,21-24 Clinically, patients who have both diabetes and calcifications are at significant excess risk for total mortality, stroke mortality, and cardiovascular mortality, compared with patients with diabetes but without such calcifications. They also had a significantly higher incidence of coronary heart disease events, stroke events, and lower extremity amputations.^25,26

All our patients underwent tourniquet-assisted TKA. Although previous studies have indicated that tourniquet use may increase arterial complications and wound complications or even limb loss in patients with calcified arteries, we did not find this link.^7,27 Our population had no reported arterial complications related to tourniquet use. Other, smaller studies have had similar findings. Vandenbussche and colleagues²⁸ prospectively studied 80 TKA cases randomized to tourniquet use or no tourniquet use and found no postoperative nerve palsies, wound infections, wound healing problems, or hematomas. Our study is also in accord with studies that have reported tourniquet use did not increase risk for DVT.²⁹ Therefore, unlike earlier data, our data demonstrated that tourniquet use in patients with knee arterial calcification was safe.^7,27,30,31

Patients with calcification were more likely to have the medical comorbidities of hypertension, diabetes, hyperlipidemia, and CAD. All these comorbidities are linked to the development of arterial calcification, or atherosclerotic occlusive disease.^32,33 As life expectancy and the need for TKA increase, it is likely that a larger percentage of TKA patients will have preoperative radiographic evidence of knee arterial calcification. Although current dogma is that tourniquet-assisted TKA is contraindicated for patients with preoperative radiographic evidence of femoral-popliteal calcification, our study results showed that this calcification should not affect preoperative TKA planning for these patients.

We divided our patients into 3 categories: those with proximal calcification (above the joint line), those with distal calcification (below the joint line), and those with both proximal and distal calcification. Location of arterial calcification did not have an effect on their rates of postoperative wound complication or VTE. We hypothesized that patients with proximal calcification would be at increased risk for direct arterial injury and subsequent wound complication because the tourniquet is placed proximally. Previous research has indicated that arterial occlusion and subsequent wound complication can occur because of low blood flow stemming from tourniquet use.⁷ Further, intraoperative manipulation (flexing) of a knee with calcified vessels causes arterial complications after TKA because these vessels are less elastic than nonatheromatous vessels.³¹ However, we found no such effect. At the same time, having arterial calcification might also be an indication of venous disease in this location,¹² which may be especially important for proximal calcifications. Proximal DVT more likely is a precursor to pulmonary embolic events than distal DVT is.^31,34 However, we found no difference in VTE rates among the 3 arterial location groups, which is supported by studies that have found that tourniquet use does not increase DVT incidence.^29,35-40

Risk for wound complications was higher in male patients and in patients with diabetes, prior VTE, hypertension, or CAD. This finding is important because, with the increasing age of patients who undergo TKA, those with serious medical comorbidities will continue to need and have this surgery.¹⁷ Diabetes may increase the rate of wound complication because patients with diabetes have poor microcirculation, poor collagen synthesis, and reduced wound strength.⁴¹ Malinzak and colleagues⁴² demonstrated that, compared with patients without diabetes, those with diabetes had a significantly higher risk for infection after TKA. Prior VTE, specifically DVT, may increase the rate of wound complication because after DVT the deep veins may be damaged and exhibit valvular dysfunction. Labropoulos and colleagues⁴³ showed that DVT history was strongly associated with ulcer nonhealing. Perhaps hypertension has been overlooked as a risk factor for wound complication in TKA. No previous studies have assessed the link between hypertension and wound complications after TKA. However, a study of wound healing after total hip arthroplasty found that, compared with normotensive patients, hypertensive patients had delayed wound healing, putting them at higher risk for infection.⁴⁴ In addition, we found that patients with CAD were at increased risk for wound complications—an unexpected finding, as CAD traditionally is not a risk factor for infection or poor wound healing. Recently, however, CAD was identified as an independent risk factor for surgical site infections in posterior lumbar–instrumented arthrodesis.⁴⁵ The etiology of this association is unknown. Also, male patients were at increased risk for wound complication. Male sex has been implicated as an independent risk factor for development of surgical site infections and has been established as an important predisposing factor for periprosthetic joint infections.⁴⁶

It is possible that patients who present with diabetes, VTE, hypertension, or CAD before TKA should have a consultation with a vascular surgeon or should have TKA performed without a tourniquet, but this conclusion cannot be considered definitive without a large prospective randomized trial or possibly registry data. Our data indicate that patients with these comorbidities have higher rates of wound complications irrespective of preoperative radiographic calcifications. On the basis of our study results, however, we certainly recommend that patients with these risk factors have preoperative medical optimization. Orthopedic surgeons should take a thorough history and perform a meticulous physical examination on these patients to look for evidence of PVD. We recommend that, if vascular claudication is elicited in the history, or if there is evidence of peripheral arterial disease—such as hair loss, skin discoloration, dystrophic nail changes, or absent or unequal peripheral pulses—the ankle-brachial index test should be performed. If the index value is less than 0.9, then a preoperative vascular surgery consultation should be obtained.

This study had some weaknesses. First, it was retrospective, so it is possible that some wound or VTE complications were not reported and thus not found in the paper charts or electronic medical records. Some patients may have had VTE diagnostic scans at other hospitals, and their results may not have been recorded across databases. Moreover, some patients may have seen wound specialists for wound infections or wound healing problems, and these may not have been reported to the orthopedic surgeons. Second, though our patient population was not small, it may not have been of adequate size to fully detect statistical significance. We met our enrollment numbers based on our sample size calculations from an a priori power analysis; however, we still draw conclusions with the possibility of committing a type II error in mind by failing to reject the null hypothesis when in reality a statistically significant difference does exist. Third, none of our consecutive patients carried the preoperative diagnosis of PVD, and none had preoperative vascular surgery. Therefore, though calcifications were noted on radiographs, clinically our patients were asymptomatic with respect to vascular health. Last, the 2 groups were not randomized. All patients underwent tourniquet-assisted TKA.           

Conclusion

To our knowledge, this is the largest study to examine the effect of preoperative knee arterial calcification on wound complication and VTE after tourniquet-assisted TKA. Contrary to previously published recommendations, we conclude that TKA can be safely performed with a tourniquet in the presence of preoperative radiographic evidence of such calcification. However, we recommend that patients with diabetes, hypertension, CAD, or prior VTE undergo an appropriate physical examination to elicit any signs or symptoms of vascular disease. If before surgery there is any question of vascular competence, a vascular surgeon should be consulted.

Tourniquets are often used in total knee arthroplasty (TKA) to improve visualization of structures, shorten operative time, reduce intraoperative bleeding, and improve cementing technique. Despite these advantages, controversy remains regarding the safety of tourniquet use. Tourniquets have been associated with nerve palsies, vascular injury, and muscle damage.^1-5 Some have hypothesized they may cause venous stasis or direct endothelial damage that may develop into deep vein thrombosis (DVT). Abdel-Salam and Eyres⁶ found an increased incidence of postoperative wound complications and DVTs associated with tourniquet use.

Moreover, investigators have analyzed the role of tourniquets in populations at high risk for wound complications. DeLaurentis and colleagues⁷ performed a prospective and retrospective analysis of 1182 TKA patients, 24 (2%) of whom had preexisting peripheral vascular disease (PVD), defined as a history of arterial insufficiency, absent dorsalis pedis and/or absent posterior tibial pulsations, and arterial calcifications. A tourniquet was used in each case. Arterial complications occurred in 6 of the 24 patients with PVD. As expected, the authors found that a history of intermittent claudication, pain at rest, and arterial ulcers resulted in a high risk for vascular complications. Further studies have supported this finding and expanded the list of predisposing factors to include previous vascular surgery and absent and asymmetric pedal pulsations.^7-11 Of particular concern to total joint arthroplasty surgeons was the finding by DeLaurentis and colleagues⁷ that patients with radiographic evidence of calcification of the distal superficial femoral artery and/or popliteal artery were at risk for arterial complications. This finding is also supported by other studies.^8,11 In TKA, damage to arterial structures proximal to the surgical field could manifest as impaired postoperative wound healing or an ischemic limb. Wound healing depends on adequate blood flow to the healing tissue, and any damage to arterial or venous structures can theoretically compromise this process.

Added to vascular/wound complications as concerning complications in orthopedic surgery is venous thromboembolism (VTE). The role of tourniquets in the formation of VTEs is controversial. A tourniquet has the potential to increase the risk for DVT because of the stasis of venous blood in the lower limb or possible damage to calcified blood vessels. Callam and colleagues¹² studied the connection between artery disease and chronic leg ulcers and found that half the patients diagnosed with peripheral artery disease also had stigmata of chronic venous insufficiency. Therefore, the entities can occur in tandem, and surgeons should keep this in mind.

Here we report on a study we conducted to determine whether tourniquet use in TKA in patients with preexisting radiographic evidence of vascular disease increases the risk for wound complications or VTE.

Patients and Methods

We retrospectively reviewed 461 consecutive primary TKAs (373 patients) performed between January 2007 and June 2012 by 2 attending orthopedic surgeons specializing in adult reconstruction. Medical records and operative reports of 583 patients were examined after receiving institutional review board approval. Of these patients, 373 (64%) had a minimum of 12-month follow-up data available. Twelve months was deemed long enough to discover wound complications or DVTs secondary to the index procedure. Most of these outcomes manifest within the first 3 months after surgery and certainly by 12 months. Follow-up longer than 12 months may become a confounder, as wound complications outside the acute to subacute postoperative window could be related to patients’ underlying PVD and not directly to tourniquet use during surgery. Patient demographics and comorbidities were recorded. Comorbidities were obtained from preoperative medical evaluations and surgeons’ preoperative evaluations. All patients had preoperative palpable dorsalis pedis and posterior tibialis arterial pulses. No patient required preoperative vascular studies based on preoperative examination or comorbidities. No patient had prior vascular bypass surgery or stenting.

TKA was performed in a nonlaminar flow, positive-pressure, high-efficiency particulate air-filtered room with sterile toga/surgical helmet systems. For all patients, a pneumatic thigh tourniquet was applied, and the patient was prepared and draped. After limb exsanguination using a rubber bandage, the limb was elevated and the tourniquet inflated to a pressure of 250 to 300 mm Hg. The tourniquet was released either just before closure or immediately after closure in all cases; it was always let down before placement of final bandages.

Prophylactic chemical anticoagulation consisting of warfarin, aspirin, or enoxaparin was used in all patients and continued for 4 to 6 weeks after surgery. All patients received mechanical DVT prophylaxis with sequential compression devices, and all were mobilized out of bed beginning either the day of surgery or the next day. All patients received perioperative intravenous antibiotics, with the preoperative dose given before tourniquet inflation and the last postoperative dose stopped within 24 hours of surgery.

All patients who had primary TKA underwent preoperative medical evaluation and optimization. The patient’s hospital course was monitored closely, and complications noted by the orthopedic team were documented. Follow-up documentation was retrospectively reviewed for evidence of wound complications or VTE. Wound complications were defined as cellulitis, delayed wound healing, wound dehiscence, and/or periprosthetic joint infection. In the case of VTE, physical examination findings were not sufficient for inclusion. Venous duplex ultrasonography demonstrating the clot was reviewed before inclusion.

Preoperative radiographs were examined for arterial calcification (Figure). We refer to calcification seen above the knee joint as proximal calcification and to calcification observed below the joint as distal calcification. Patients exhibited calcification proximally only, distally only, or both proximally and distally. The 373 patients were placed into 2 groups based on whether they had preoperative arterial calcification on plain radiography of the knee. One group (285 patients with no radiographic evidence of preoperative knee arterial calcification) underwent 365 TKAs, and the other group (88 patients with radiographic evidence of preoperative knee arterial calcification) underwent 96 TKAs.

A sample size calculation was performed to determine how many patients were needed in each group with 80% power and an α of 0.05. With an estimated difference in VTE/wound complication rate between the calcification and no-calcification groups of 12%, we needed to review 316 TKAs total. This 12% difference was based on study findings of a 25% complication rate in PVD patients who underwent tourniquet-assisted TKA, and the rate of VTE/wound complication after TKA in patients overall, which can be up to 12%.^7,13,14 We exceeded minimal enrollment and had 461 TKAs. Descriptive statistics were reported, with means and ranges provided where appropriate. Independent t test was used to evaluate the differences in continuous data (age) between the groups. Univariate analysis (using Pearson χ² and Fisher exact tests) and multivariate logistic regression analysis were used to evaluate the effects of categorical variables (sex, comorbidity, calcification [presence, absence], and location of calcification [proximal only, distal only, both]) on wound complication and VTE rates. All tests were 2-tailed and performed with a type I error rate of 0.05. Data analysis was performed with SPSS Version 19.0 (SPSS).

Results

Patient characteristics are summarized in Table 1. Of the 373 patients, 285 lacked calcification, and 88 had calcification. Mean age was 67.73 years (range, 24-92 years) for all patients, 65.99 years (range, 24-89 years) for the no-calcification group, and 74.32 years (range, 54-92 years) for the calcification group; the calcification group demonstrated a trend toward older age, but the difference was not significantly different (P = .07). Of the 373 patients, 156 (41.82%) were male: 110 in the no-calcification group (38.60%) and 46 in the calcification group (52.27%); sex was significantly (P = .002) different between groups, with more males in the calcification group.

Data on total preoperative comorbidities are summarized in Table 2. Hypertension, hyperlipidemia, diabetes, and coronary artery disease (CAD) were the most common comorbidities, and they were all significantly (P ≤ .05) increased in the calcification group.

No patients had reported arterial complications, such as arterial bleeding, aneurysm, intimal tears, or loss of distal pulses. Wound complication after TKA was detected in 3.04% of all cases (Table 3). Rate of DVT after TKA was 2.60% of all cases, and rate of pulmonary embolism after TKA was 2.17% of all cases. Of the 96 TKAs with preoperative radiographic evidence of calcification, 47 (48.96%) had proximal calcification only, 11 (11.46%) had distal calcification only, and 38 (39.58%) had both proximal and distal calcification (Table 4). There was no significant difference between the rate of wound complication or VTE based on location of vascular calcification.

Univariate analysis demonstrated that presence of arterial knee calcification did not increase the risk for postoperative wound complication (odds ratio [OR], 1.04; 95% confidence interval [CI], 0.28-3.80; P > .05) (Table 5). Location of arterial knee calcification also did not increase the risk for postoperative wound complication. In addition, univariate analysis demonstrated that presence of arterial knee calcification did not increase the risk for postoperative VTE (OR, 1.20; 95% CI, 0.43-3.36; P > .05 (Table 6).

Of the 14 wound complications, the most common infections were cellulitis (5/14 cases; 35.71%) and infected hardware that required component revision (5/14 cases; 35.71%). Mean time from TKA to infection was 137.93 days (range, 5-783 days). The most common organism grown in culture from the wound was Staphylococcus (5/14 cases; 35.71%).

Additional univariate statistical analysis revealed that presence of diabetes, hypertension, prior VTE, CAD, and male sex was linked to higher incidence of wound complication (P < .05) (Table 5). When multivariate analysis was performed, hypertension, prior VTE, and male sex remained significant (P < .05) (Table 5).

Discussion

TKA is a safe and effective procedure used to treat osteoarthritis of the knee and improve patients’ quality of life.¹⁵ About 700,000 TKAs are performed annually in the United States.¹⁶ Because of improvements in preventive medicine and medical technology, life expectancy is increasing, and TKAs are now being performed in higher numbers and in an older patient population. Over the next few decades, these developments will lead to more postoperative complications. It is projected that, by 2030, the need for TKAs in the United States will increase by 673% to 3.48 million.¹⁷ Postoperative complications are rare but unfortunately often lead to poor outcomes or even mortality.¹⁸ To help minimize the number of postoperative complications, we must understand the safety of tourniquet use in TKA. Other investigators have concluded that tourniquet use is unsafe in patients with preoperative vascular calcifications on plain radiographs.^7,8,11 The present study, designed to elucidate whether preoperative evidence of knee arterial calcification may predispose TKA patients to postoperative wound complication or VTE, had some important findings.

In our study, wound complication and VTE occurred in a considerable number of patients after TKA. Despite exceeding the number of patients calculated by the power analysis, our population may have been inadequate to fully detect statistical significance. Thus, our conclusion of failing to reject the null hypothesis may have been because of sample size, a type II error. We found that, after primary TKA, 3.04% of patients developed wound complications and 4.77% VTE. According to the literature, the incidence of infection after primary TKA is between 0.5% and 12%, and that of VTE reported within 3 months after TKA is 1.3% to 10%.^13,14 Although we had 100% VTE prophylaxis, meeting the standard of care, VTE after TKA remains a postoperative complication.¹⁹ This study also found that a considerable percentage of primary TKA patients (23.59%) had preoperative calcification of the knee arteries. To our knowledge, this study was the first to quantify the incidence of knee arterial calcification in patients who underwent TKA.

Preoperative calcification of the knee arteries in patients who underwent TKA did not increase the risk for wound complication, VTE, or arterial damage. These calcifications, however, do pose an increased systemic vascular risk.²⁰ Calcification of the vascular wall predicts increased cardiovascular risk, independent of classical cardiovascular risk factors.^3,18,21-24 Clinically, patients who have both diabetes and calcifications are at significant excess risk for total mortality, stroke mortality, and cardiovascular mortality, compared with patients with diabetes but without such calcifications. They also had a significantly higher incidence of coronary heart disease events, stroke events, and lower extremity amputations.^25,26

All our patients underwent tourniquet-assisted TKA. Although previous studies have indicated that tourniquet use may increase arterial complications and wound complications or even limb loss in patients with calcified arteries, we did not find this link.^7,27 Our population had no reported arterial complications related to tourniquet use. Other, smaller studies have had similar findings. Vandenbussche and colleagues²⁸ prospectively studied 80 TKA cases randomized to tourniquet use or no tourniquet use and found no postoperative nerve palsies, wound infections, wound healing problems, or hematomas. Our study is also in accord with studies that have reported tourniquet use did not increase risk for DVT.²⁹ Therefore, unlike earlier data, our data demonstrated that tourniquet use in patients with knee arterial calcification was safe.^7,27,30,31

Patients with calcification were more likely to have the medical comorbidities of hypertension, diabetes, hyperlipidemia, and CAD. All these comorbidities are linked to the development of arterial calcification, or atherosclerotic occlusive disease.^32,33 As life expectancy and the need for TKA increase, it is likely that a larger percentage of TKA patients will have preoperative radiographic evidence of knee arterial calcification. Although current dogma is that tourniquet-assisted TKA is contraindicated for patients with preoperative radiographic evidence of femoral-popliteal calcification, our study results showed that this calcification should not affect preoperative TKA planning for these patients.

We divided our patients into 3 categories: those with proximal calcification (above the joint line), those with distal calcification (below the joint line), and those with both proximal and distal calcification. Location of arterial calcification did not have an effect on their rates of postoperative wound complication or VTE. We hypothesized that patients with proximal calcification would be at increased risk for direct arterial injury and subsequent wound complication because the tourniquet is placed proximally. Previous research has indicated that arterial occlusion and subsequent wound complication can occur because of low blood flow stemming from tourniquet use.⁷ Further, intraoperative manipulation (flexing) of a knee with calcified vessels causes arterial complications after TKA because these vessels are less elastic than nonatheromatous vessels.³¹ However, we found no such effect. At the same time, having arterial calcification might also be an indication of venous disease in this location,¹² which may be especially important for proximal calcifications. Proximal DVT more likely is a precursor to pulmonary embolic events than distal DVT is.^31,34 However, we found no difference in VTE rates among the 3 arterial location groups, which is supported by studies that have found that tourniquet use does not increase DVT incidence.^29,35-40

Risk for wound complications was higher in male patients and in patients with diabetes, prior VTE, hypertension, or CAD. This finding is important because, with the increasing age of patients who undergo TKA, those with serious medical comorbidities will continue to need and have this surgery.¹⁷ Diabetes may increase the rate of wound complication because patients with diabetes have poor microcirculation, poor collagen synthesis, and reduced wound strength.⁴¹ Malinzak and colleagues⁴² demonstrated that, compared with patients without diabetes, those with diabetes had a significantly higher risk for infection after TKA. Prior VTE, specifically DVT, may increase the rate of wound complication because after DVT the deep veins may be damaged and exhibit valvular dysfunction. Labropoulos and colleagues⁴³ showed that DVT history was strongly associated with ulcer nonhealing. Perhaps hypertension has been overlooked as a risk factor for wound complication in TKA. No previous studies have assessed the link between hypertension and wound complications after TKA. However, a study of wound healing after total hip arthroplasty found that, compared with normotensive patients, hypertensive patients had delayed wound healing, putting them at higher risk for infection.⁴⁴ In addition, we found that patients with CAD were at increased risk for wound complications—an unexpected finding, as CAD traditionally is not a risk factor for infection or poor wound healing. Recently, however, CAD was identified as an independent risk factor for surgical site infections in posterior lumbar–instrumented arthrodesis.⁴⁵ The etiology of this association is unknown. Also, male patients were at increased risk for wound complication. Male sex has been implicated as an independent risk factor for development of surgical site infections and has been established as an important predisposing factor for periprosthetic joint infections.⁴⁶

It is possible that patients who present with diabetes, VTE, hypertension, or CAD before TKA should have a consultation with a vascular surgeon or should have TKA performed without a tourniquet, but this conclusion cannot be considered definitive without a large prospective randomized trial or possibly registry data. Our data indicate that patients with these comorbidities have higher rates of wound complications irrespective of preoperative radiographic calcifications. On the basis of our study results, however, we certainly recommend that patients with these risk factors have preoperative medical optimization. Orthopedic surgeons should take a thorough history and perform a meticulous physical examination on these patients to look for evidence of PVD. We recommend that, if vascular claudication is elicited in the history, or if there is evidence of peripheral arterial disease—such as hair loss, skin discoloration, dystrophic nail changes, or absent or unequal peripheral pulses—the ankle-brachial index test should be performed. If the index value is less than 0.9, then a preoperative vascular surgery consultation should be obtained.

This study had some weaknesses. First, it was retrospective, so it is possible that some wound or VTE complications were not reported and thus not found in the paper charts or electronic medical records. Some patients may have had VTE diagnostic scans at other hospitals, and their results may not have been recorded across databases. Moreover, some patients may have seen wound specialists for wound infections or wound healing problems, and these may not have been reported to the orthopedic surgeons. Second, though our patient population was not small, it may not have been of adequate size to fully detect statistical significance. We met our enrollment numbers based on our sample size calculations from an a priori power analysis; however, we still draw conclusions with the possibility of committing a type II error in mind by failing to reject the null hypothesis when in reality a statistically significant difference does exist. Third, none of our consecutive patients carried the preoperative diagnosis of PVD, and none had preoperative vascular surgery. Therefore, though calcifications were noted on radiographs, clinically our patients were asymptomatic with respect to vascular health. Last, the 2 groups were not randomized. All patients underwent tourniquet-assisted TKA.           

Conclusion

To our knowledge, this is the largest study to examine the effect of preoperative knee arterial calcification on wound complication and VTE after tourniquet-assisted TKA. Contrary to previously published recommendations, we conclude that TKA can be safely performed with a tourniquet in the presence of preoperative radiographic evidence of such calcification. However, we recommend that patients with diabetes, hypertension, CAD, or prior VTE undergo an appropriate physical examination to elicit any signs or symptoms of vascular disease. If before surgery there is any question of vascular competence, a vascular surgeon should be consulted.

Tourniquets are often used in total knee arthroplasty (TKA) to improve visualization of structures, shorten operative time, reduce intraoperative bleeding, and improve cementing technique. Despite these advantages, controversy remains regarding the safety of tourniquet use. Tourniquets have been associated with nerve palsies, vascular injury, and muscle damage.^1-5 Some have hypothesized they may cause venous stasis or direct endothelial damage that may develop into deep vein thrombosis (DVT). Abdel-Salam and Eyres⁶ found an increased incidence of postoperative wound complications and DVTs associated with tourniquet use.

Moreover, investigators have analyzed the role of tourniquets in populations at high risk for wound complications. DeLaurentis and colleagues⁷ performed a prospective and retrospective analysis of 1182 TKA patients, 24 (2%) of whom had preexisting peripheral vascular disease (PVD), defined as a history of arterial insufficiency, absent dorsalis pedis and/or absent posterior tibial pulsations, and arterial calcifications. A tourniquet was used in each case. Arterial complications occurred in 6 of the 24 patients with PVD. As expected, the authors found that a history of intermittent claudication, pain at rest, and arterial ulcers resulted in a high risk for vascular complications. Further studies have supported this finding and expanded the list of predisposing factors to include previous vascular surgery and absent and asymmetric pedal pulsations.^7-11 Of particular concern to total joint arthroplasty surgeons was the finding by DeLaurentis and colleagues⁷ that patients with radiographic evidence of calcification of the distal superficial femoral artery and/or popliteal artery were at risk for arterial complications. This finding is also supported by other studies.^8,11 In TKA, damage to arterial structures proximal to the surgical field could manifest as impaired postoperative wound healing or an ischemic limb. Wound healing depends on adequate blood flow to the healing tissue, and any damage to arterial or venous structures can theoretically compromise this process.

Added to vascular/wound complications as concerning complications in orthopedic surgery is venous thromboembolism (VTE). The role of tourniquets in the formation of VTEs is controversial. A tourniquet has the potential to increase the risk for DVT because of the stasis of venous blood in the lower limb or possible damage to calcified blood vessels. Callam and colleagues¹² studied the connection between artery disease and chronic leg ulcers and found that half the patients diagnosed with peripheral artery disease also had stigmata of chronic venous insufficiency. Therefore, the entities can occur in tandem, and surgeons should keep this in mind.

Here we report on a study we conducted to determine whether tourniquet use in TKA in patients with preexisting radiographic evidence of vascular disease increases the risk for wound complications or VTE.

Patients and Methods

We retrospectively reviewed 461 consecutive primary TKAs (373 patients) performed between January 2007 and June 2012 by 2 attending orthopedic surgeons specializing in adult reconstruction. Medical records and operative reports of 583 patients were examined after receiving institutional review board approval. Of these patients, 373 (64%) had a minimum of 12-month follow-up data available. Twelve months was deemed long enough to discover wound complications or DVTs secondary to the index procedure. Most of these outcomes manifest within the first 3 months after surgery and certainly by 12 months. Follow-up longer than 12 months may become a confounder, as wound complications outside the acute to subacute postoperative window could be related to patients’ underlying PVD and not directly to tourniquet use during surgery. Patient demographics and comorbidities were recorded. Comorbidities were obtained from preoperative medical evaluations and surgeons’ preoperative evaluations. All patients had preoperative palpable dorsalis pedis and posterior tibialis arterial pulses. No patient required preoperative vascular studies based on preoperative examination or comorbidities. No patient had prior vascular bypass surgery or stenting.

TKA was performed in a nonlaminar flow, positive-pressure, high-efficiency particulate air-filtered room with sterile toga/surgical helmet systems. For all patients, a pneumatic thigh tourniquet was applied, and the patient was prepared and draped. After limb exsanguination using a rubber bandage, the limb was elevated and the tourniquet inflated to a pressure of 250 to 300 mm Hg. The tourniquet was released either just before closure or immediately after closure in all cases; it was always let down before placement of final bandages.

Prophylactic chemical anticoagulation consisting of warfarin, aspirin, or enoxaparin was used in all patients and continued for 4 to 6 weeks after surgery. All patients received mechanical DVT prophylaxis with sequential compression devices, and all were mobilized out of bed beginning either the day of surgery or the next day. All patients received perioperative intravenous antibiotics, with the preoperative dose given before tourniquet inflation and the last postoperative dose stopped within 24 hours of surgery.

All patients who had primary TKA underwent preoperative medical evaluation and optimization. The patient’s hospital course was monitored closely, and complications noted by the orthopedic team were documented. Follow-up documentation was retrospectively reviewed for evidence of wound complications or VTE. Wound complications were defined as cellulitis, delayed wound healing, wound dehiscence, and/or periprosthetic joint infection. In the case of VTE, physical examination findings were not sufficient for inclusion. Venous duplex ultrasonography demonstrating the clot was reviewed before inclusion.

Preoperative radiographs were examined for arterial calcification (Figure). We refer to calcification seen above the knee joint as proximal calcification and to calcification observed below the joint as distal calcification. Patients exhibited calcification proximally only, distally only, or both proximally and distally. The 373 patients were placed into 2 groups based on whether they had preoperative arterial calcification on plain radiography of the knee. One group (285 patients with no radiographic evidence of preoperative knee arterial calcification) underwent 365 TKAs, and the other group (88 patients with radiographic evidence of preoperative knee arterial calcification) underwent 96 TKAs.

A sample size calculation was performed to determine how many patients were needed in each group with 80% power and an α of 0.05. With an estimated difference in VTE/wound complication rate between the calcification and no-calcification groups of 12%, we needed to review 316 TKAs total. This 12% difference was based on study findings of a 25% complication rate in PVD patients who underwent tourniquet-assisted TKA, and the rate of VTE/wound complication after TKA in patients overall, which can be up to 12%.^7,13,14 We exceeded minimal enrollment and had 461 TKAs. Descriptive statistics were reported, with means and ranges provided where appropriate. Independent t test was used to evaluate the differences in continuous data (age) between the groups. Univariate analysis (using Pearson χ² and Fisher exact tests) and multivariate logistic regression analysis were used to evaluate the effects of categorical variables (sex, comorbidity, calcification [presence, absence], and location of calcification [proximal only, distal only, both]) on wound complication and VTE rates. All tests were 2-tailed and performed with a type I error rate of 0.05. Data analysis was performed with SPSS Version 19.0 (SPSS).

Results

Patient characteristics are summarized in Table 1. Of the 373 patients, 285 lacked calcification, and 88 had calcification. Mean age was 67.73 years (range, 24-92 years) for all patients, 65.99 years (range, 24-89 years) for the no-calcification group, and 74.32 years (range, 54-92 years) for the calcification group; the calcification group demonstrated a trend toward older age, but the difference was not significantly different (P = .07). Of the 373 patients, 156 (41.82%) were male: 110 in the no-calcification group (38.60%) and 46 in the calcification group (52.27%); sex was significantly (P = .002) different between groups, with more males in the calcification group.

Data on total preoperative comorbidities are summarized in Table 2. Hypertension, hyperlipidemia, diabetes, and coronary artery disease (CAD) were the most common comorbidities, and they were all significantly (P ≤ .05) increased in the calcification group.

No patients had reported arterial complications, such as arterial bleeding, aneurysm, intimal tears, or loss of distal pulses. Wound complication after TKA was detected in 3.04% of all cases (Table 3). Rate of DVT after TKA was 2.60% of all cases, and rate of pulmonary embolism after TKA was 2.17% of all cases. Of the 96 TKAs with preoperative radiographic evidence of calcification, 47 (48.96%) had proximal calcification only, 11 (11.46%) had distal calcification only, and 38 (39.58%) had both proximal and distal calcification (Table 4). There was no significant difference between the rate of wound complication or VTE based on location of vascular calcification.

Univariate analysis demonstrated that presence of arterial knee calcification did not increase the risk for postoperative wound complication (odds ratio [OR], 1.04; 95% confidence interval [CI], 0.28-3.80; P > .05) (Table 5). Location of arterial knee calcification also did not increase the risk for postoperative wound complication. In addition, univariate analysis demonstrated that presence of arterial knee calcification did not increase the risk for postoperative VTE (OR, 1.20; 95% CI, 0.43-3.36; P > .05 (Table 6).

Of the 14 wound complications, the most common infections were cellulitis (5/14 cases; 35.71%) and infected hardware that required component revision (5/14 cases; 35.71%). Mean time from TKA to infection was 137.93 days (range, 5-783 days). The most common organism grown in culture from the wound was Staphylococcus (5/14 cases; 35.71%).

Additional univariate statistical analysis revealed that presence of diabetes, hypertension, prior VTE, CAD, and male sex was linked to higher incidence of wound complication (P < .05) (Table 5). When multivariate analysis was performed, hypertension, prior VTE, and male sex remained significant (P < .05) (Table 5).

Discussion

TKA is a safe and effective procedure used to treat osteoarthritis of the knee and improve patients’ quality of life.¹⁵ About 700,000 TKAs are performed annually in the United States.¹⁶ Because of improvements in preventive medicine and medical technology, life expectancy is increasing, and TKAs are now being performed in higher numbers and in an older patient population. Over the next few decades, these developments will lead to more postoperative complications. It is projected that, by 2030, the need for TKAs in the United States will increase by 673% to 3.48 million.¹⁷ Postoperative complications are rare but unfortunately often lead to poor outcomes or even mortality.¹⁸ To help minimize the number of postoperative complications, we must understand the safety of tourniquet use in TKA. Other investigators have concluded that tourniquet use is unsafe in patients with preoperative vascular calcifications on plain radiographs.^7,8,11 The present study, designed to elucidate whether preoperative evidence of knee arterial calcification may predispose TKA patients to postoperative wound complication or VTE, had some important findings.

In our study, wound complication and VTE occurred in a considerable number of patients after TKA. Despite exceeding the number of patients calculated by the power analysis, our population may have been inadequate to fully detect statistical significance. Thus, our conclusion of failing to reject the null hypothesis may have been because of sample size, a type II error. We found that, after primary TKA, 3.04% of patients developed wound complications and 4.77% VTE. According to the literature, the incidence of infection after primary TKA is between 0.5% and 12%, and that of VTE reported within 3 months after TKA is 1.3% to 10%.^13,14 Although we had 100% VTE prophylaxis, meeting the standard of care, VTE after TKA remains a postoperative complication.¹⁹ This study also found that a considerable percentage of primary TKA patients (23.59%) had preoperative calcification of the knee arteries. To our knowledge, this study was the first to quantify the incidence of knee arterial calcification in patients who underwent TKA.

Preoperative calcification of the knee arteries in patients who underwent TKA did not increase the risk for wound complication, VTE, or arterial damage. These calcifications, however, do pose an increased systemic vascular risk.²⁰ Calcification of the vascular wall predicts increased cardiovascular risk, independent of classical cardiovascular risk factors.^3,18,21-24 Clinically, patients who have both diabetes and calcifications are at significant excess risk for total mortality, stroke mortality, and cardiovascular mortality, compared with patients with diabetes but without such calcifications. They also had a significantly higher incidence of coronary heart disease events, stroke events, and lower extremity amputations.^25,26

All our patients underwent tourniquet-assisted TKA. Although previous studies have indicated that tourniquet use may increase arterial complications and wound complications or even limb loss in patients with calcified arteries, we did not find this link.^7,27 Our population had no reported arterial complications related to tourniquet use. Other, smaller studies have had similar findings. Vandenbussche and colleagues²⁸ prospectively studied 80 TKA cases randomized to tourniquet use or no tourniquet use and found no postoperative nerve palsies, wound infections, wound healing problems, or hematomas. Our study is also in accord with studies that have reported tourniquet use did not increase risk for DVT.²⁹ Therefore, unlike earlier data, our data demonstrated that tourniquet use in patients with knee arterial calcification was safe.^7,27,30,31

Patients with calcification were more likely to have the medical comorbidities of hypertension, diabetes, hyperlipidemia, and CAD. All these comorbidities are linked to the development of arterial calcification, or atherosclerotic occlusive disease.^32,33 As life expectancy and the need for TKA increase, it is likely that a larger percentage of TKA patients will have preoperative radiographic evidence of knee arterial calcification. Although current dogma is that tourniquet-assisted TKA is contraindicated for patients with preoperative radiographic evidence of femoral-popliteal calcification, our study results showed that this calcification should not affect preoperative TKA planning for these patients.

We divided our patients into 3 categories: those with proximal calcification (above the joint line), those with distal calcification (below the joint line), and those with both proximal and distal calcification. Location of arterial calcification did not have an effect on their rates of postoperative wound complication or VTE. We hypothesized that patients with proximal calcification would be at increased risk for direct arterial injury and subsequent wound complication because the tourniquet is placed proximally. Previous research has indicated that arterial occlusion and subsequent wound complication can occur because of low blood flow stemming from tourniquet use.⁷ Further, intraoperative manipulation (flexing) of a knee with calcified vessels causes arterial complications after TKA because these vessels are less elastic than nonatheromatous vessels.³¹ However, we found no such effect. At the same time, having arterial calcification might also be an indication of venous disease in this location,¹² which may be especially important for proximal calcifications. Proximal DVT more likely is a precursor to pulmonary embolic events than distal DVT is.^31,34 However, we found no difference in VTE rates among the 3 arterial location groups, which is supported by studies that have found that tourniquet use does not increase DVT incidence.^29,35-40

Risk for wound complications was higher in male patients and in patients with diabetes, prior VTE, hypertension, or CAD. This finding is important because, with the increasing age of patients who undergo TKA, those with serious medical comorbidities will continue to need and have this surgery.¹⁷ Diabetes may increase the rate of wound complication because patients with diabetes have poor microcirculation, poor collagen synthesis, and reduced wound strength.⁴¹ Malinzak and colleagues⁴² demonstrated that, compared with patients without diabetes, those with diabetes had a significantly higher risk for infection after TKA. Prior VTE, specifically DVT, may increase the rate of wound complication because after DVT the deep veins may be damaged and exhibit valvular dysfunction. Labropoulos and colleagues⁴³ showed that DVT history was strongly associated with ulcer nonhealing. Perhaps hypertension has been overlooked as a risk factor for wound complication in TKA. No previous studies have assessed the link between hypertension and wound complications after TKA. However, a study of wound healing after total hip arthroplasty found that, compared with normotensive patients, hypertensive patients had delayed wound healing, putting them at higher risk for infection.⁴⁴ In addition, we found that patients with CAD were at increased risk for wound complications—an unexpected finding, as CAD traditionally is not a risk factor for infection or poor wound healing. Recently, however, CAD was identified as an independent risk factor for surgical site infections in posterior lumbar–instrumented arthrodesis.⁴⁵ The etiology of this association is unknown. Also, male patients were at increased risk for wound complication. Male sex has been implicated as an independent risk factor for development of surgical site infections and has been established as an important predisposing factor for periprosthetic joint infections.⁴⁶

It is possible that patients who present with diabetes, VTE, hypertension, or CAD before TKA should have a consultation with a vascular surgeon or should have TKA performed without a tourniquet, but this conclusion cannot be considered definitive without a large prospective randomized trial or possibly registry data. Our data indicate that patients with these comorbidities have higher rates of wound complications irrespective of preoperative radiographic calcifications. On the basis of our study results, however, we certainly recommend that patients with these risk factors have preoperative medical optimization. Orthopedic surgeons should take a thorough history and perform a meticulous physical examination on these patients to look for evidence of PVD. We recommend that, if vascular claudication is elicited in the history, or if there is evidence of peripheral arterial disease—such as hair loss, skin discoloration, dystrophic nail changes, or absent or unequal peripheral pulses—the ankle-brachial index test should be performed. If the index value is less than 0.9, then a preoperative vascular surgery consultation should be obtained.

This study had some weaknesses. First, it was retrospective, so it is possible that some wound or VTE complications were not reported and thus not found in the paper charts or electronic medical records. Some patients may have had VTE diagnostic scans at other hospitals, and their results may not have been recorded across databases. Moreover, some patients may have seen wound specialists for wound infections or wound healing problems, and these may not have been reported to the orthopedic surgeons. Second, though our patient population was not small, it may not have been of adequate size to fully detect statistical significance. We met our enrollment numbers based on our sample size calculations from an a priori power analysis; however, we still draw conclusions with the possibility of committing a type II error in mind by failing to reject the null hypothesis when in reality a statistically significant difference does exist. Third, none of our consecutive patients carried the preoperative diagnosis of PVD, and none had preoperative vascular surgery. Therefore, though calcifications were noted on radiographs, clinically our patients were asymptomatic with respect to vascular health. Last, the 2 groups were not randomized. All patients underwent tourniquet-assisted TKA.           

Conclusion

To our knowledge, this is the largest study to examine the effect of preoperative knee arterial calcification on wound complication and VTE after tourniquet-assisted TKA. Contrary to previously published recommendations, we conclude that TKA can be safely performed with a tourniquet in the presence of preoperative radiographic evidence of such calcification. However, we recommend that patients with diabetes, hypertension, CAD, or prior VTE undergo an appropriate physical examination to elicit any signs or symptoms of vascular disease. If before surgery there is any question of vascular competence, a vascular surgeon should be consulted.

Perhaps more than any other medical specialty, psychiatry enjoys a longstanding and, at times, complicated relationship with cinema. Recent award-winning films, such as Still Alice, Silver Linings Playbook, and Birdman: Or (The Unexpected Virtue of Ignorance) continue traditions rooted in One Flew Over the Cuckoo’s Nest, Martha Marcy May Marlene, Spellbound, and dozens of other films. Through these films, psychiatry is afforded exposure unavailable to most medical specialties. This exposure has proven to be a double-edged sword, however.

Exposure vs accurate portrayal
Relative benefits and disadvantages of psychiatry’s position in film and popular media are difficult to calculate. A film such as Still Alice can provide a vivid, concrete personal narrative of a patient with Alzheimer’s disease, equipping millions of viewers with knowledge that might otherwise remain esoteric and inaccessible. Martha Marcy May Marlene offers a similar stage for posttraumatic stress disorder (PTSD), as does Spellbound for dissociative amnesia.

Such exposure comes at a cost, inevitably, because information about psychiatry is incorporated into a dramatic storyline assembled by filmmakers who are not medical professionals and who are bound by conflicting pressures. At times, those pressures outweigh the desire to accurately portray psychiatric illness.

‘Magical realism’
Two of last year’s celebrated films, Birdman and Still Alice, have continued the longstanding tradition of portraying mental illness in film. Medicine often is touted as art and science; film likewise sits at this intersection. However, filmmakers are artists, primarily, and the nature of storytelling is to emphasize art over scientific accuracy.

The main character in Birdman, for example, manifests psychosis, but many of his presenting signs and symptoms are incongruent with any diagnosable form of psychosis. To tell its story, the film employs magical realism, a celebrated literary and film technique. Although magical realism might detract from the accuracy of the condition portrayed, it adds cinematic appeal to the film, likely creates more entertainment value, and, in turn, garners appreciation from a broader audience.

Expansion of medical information, accurate and otherwise
As in the 1970’s, we are, today, in the midst of rapidly evolving societal norms. One of the most rapid changes is in how the public acquires information. We are in the midst of the “Googlification” of medical knowledge and the expansion of online medical resources. These resources can, simultaneously, inform and mislead the public.

Popular films behave in much the same way. There is no motion picture-guild requirement that mentally ill characters in films such as Birdman meet any set of psychiatric criteria, from DSM-5 or elsewhere. Similarly, the fact that psychiatrists do not control the information in films that portray mental illness comes as no surprise.

‘One flew East, one flew West…’
The tension between engaging storytelling and medical accuracy certainly is not a new phenomenon, extending not only to representations of disease but to representations of treatment. Consider director Miloš Forman’s seminal 1975 film, One Flew Over the Cuckoo’s Nest, whose chief importance for psychiatry rests not in its individualized representations of patients but in a portrayal of the environment in which they are treated. Louise Fletcher’s Academy Award-winning portrayal of cruel Nurse Ratched has lingered in the public consciousness, remaining a prominent image for many Americans when they think of a psychiatric institution.

When Cuckoo’s Nest was released, it was considered by critics to be an “exploration of society’s enforcement of conformism” that “almost willfully overlooked the realities of mental illness”¹ so that it could vivify its protagonist’s struggle against tyrannical Nurse Ratched. The film’s primary intent might not have been to make a statement about the injustices of the time, but it has certainly had a lasting effect on the public’s perception of psychiatric illness and treatment.

Films offer an opportunity for discussion
Films on the theme of psychiatry and mental illness have long held a distinctive position in the canon of Western cinema. In this vein, films from the past year have made timely contributions to the genre. Although Still Alice and Birdman might prove to be ground-breaking in changing societal views over time, we must not expect them to do so.

Nevertheless, psychiatry ought to take advantage of popular films’ wide exposure and ability to destigmatize mental illness—rather than lament medical inaccuracies in these films.

Cinema is, first and foremost, an art. Although patients and the public might pick up misconceptions about psychosis, Alzheimer’s disease, or PTSD because popular films take artistic liberty about mental illness, psychiatrists are available to set the record straight. After all, psychiatry has long been about managing perceptions, and patient education is at the core of our specialty.

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Perhaps more than any other medical specialty, psychiatry enjoys a longstanding and, at times, complicated relationship with cinema. Recent award-winning films, such as Still Alice, Silver Linings Playbook, and Birdman: Or (The Unexpected Virtue of Ignorance) continue traditions rooted in One Flew Over the Cuckoo’s Nest, Martha Marcy May Marlene, Spellbound, and dozens of other films. Through these films, psychiatry is afforded exposure unavailable to most medical specialties. This exposure has proven to be a double-edged sword, however.

Exposure vs accurate portrayal
Relative benefits and disadvantages of psychiatry’s position in film and popular media are difficult to calculate. A film such as Still Alice can provide a vivid, concrete personal narrative of a patient with Alzheimer’s disease, equipping millions of viewers with knowledge that might otherwise remain esoteric and inaccessible. Martha Marcy May Marlene offers a similar stage for posttraumatic stress disorder (PTSD), as does Spellbound for dissociative amnesia.

Such exposure comes at a cost, inevitably, because information about psychiatry is incorporated into a dramatic storyline assembled by filmmakers who are not medical professionals and who are bound by conflicting pressures. At times, those pressures outweigh the desire to accurately portray psychiatric illness.

‘Magical realism’
Two of last year’s celebrated films, Birdman and Still Alice, have continued the longstanding tradition of portraying mental illness in film. Medicine often is touted as art and science; film likewise sits at this intersection. However, filmmakers are artists, primarily, and the nature of storytelling is to emphasize art over scientific accuracy.

The main character in Birdman, for example, manifests psychosis, but many of his presenting signs and symptoms are incongruent with any diagnosable form of psychosis. To tell its story, the film employs magical realism, a celebrated literary and film technique. Although magical realism might detract from the accuracy of the condition portrayed, it adds cinematic appeal to the film, likely creates more entertainment value, and, in turn, garners appreciation from a broader audience.

Expansion of medical information, accurate and otherwise
As in the 1970’s, we are, today, in the midst of rapidly evolving societal norms. One of the most rapid changes is in how the public acquires information. We are in the midst of the “Googlification” of medical knowledge and the expansion of online medical resources. These resources can, simultaneously, inform and mislead the public.

Popular films behave in much the same way. There is no motion picture-guild requirement that mentally ill characters in films such as Birdman meet any set of psychiatric criteria, from DSM-5 or elsewhere. Similarly, the fact that psychiatrists do not control the information in films that portray mental illness comes as no surprise.

‘One flew East, one flew West…’
The tension between engaging storytelling and medical accuracy certainly is not a new phenomenon, extending not only to representations of disease but to representations of treatment. Consider director Miloš Forman’s seminal 1975 film, One Flew Over the Cuckoo’s Nest, whose chief importance for psychiatry rests not in its individualized representations of patients but in a portrayal of the environment in which they are treated. Louise Fletcher’s Academy Award-winning portrayal of cruel Nurse Ratched has lingered in the public consciousness, remaining a prominent image for many Americans when they think of a psychiatric institution.

When Cuckoo’s Nest was released, it was considered by critics to be an “exploration of society’s enforcement of conformism” that “almost willfully overlooked the realities of mental illness”¹ so that it could vivify its protagonist’s struggle against tyrannical Nurse Ratched. The film’s primary intent might not have been to make a statement about the injustices of the time, but it has certainly had a lasting effect on the public’s perception of psychiatric illness and treatment.

Films offer an opportunity for discussion
Films on the theme of psychiatry and mental illness have long held a distinctive position in the canon of Western cinema. In this vein, films from the past year have made timely contributions to the genre. Although Still Alice and Birdman might prove to be ground-breaking in changing societal views over time, we must not expect them to do so.

Nevertheless, psychiatry ought to take advantage of popular films’ wide exposure and ability to destigmatize mental illness—rather than lament medical inaccuracies in these films.

Cinema is, first and foremost, an art. Although patients and the public might pick up misconceptions about psychosis, Alzheimer’s disease, or PTSD because popular films take artistic liberty about mental illness, psychiatrists are available to set the record straight. After all, psychiatry has long been about managing perceptions, and patient education is at the core of our specialty.

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Perhaps more than any other medical specialty, psychiatry enjoys a longstanding and, at times, complicated relationship with cinema. Recent award-winning films, such as Still Alice, Silver Linings Playbook, and Birdman: Or (The Unexpected Virtue of Ignorance) continue traditions rooted in One Flew Over the Cuckoo’s Nest, Martha Marcy May Marlene, Spellbound, and dozens of other films. Through these films, psychiatry is afforded exposure unavailable to most medical specialties. This exposure has proven to be a double-edged sword, however.

Exposure vs accurate portrayal
Relative benefits and disadvantages of psychiatry’s position in film and popular media are difficult to calculate. A film such as Still Alice can provide a vivid, concrete personal narrative of a patient with Alzheimer’s disease, equipping millions of viewers with knowledge that might otherwise remain esoteric and inaccessible. Martha Marcy May Marlene offers a similar stage for posttraumatic stress disorder (PTSD), as does Spellbound for dissociative amnesia.

Such exposure comes at a cost, inevitably, because information about psychiatry is incorporated into a dramatic storyline assembled by filmmakers who are not medical professionals and who are bound by conflicting pressures. At times, those pressures outweigh the desire to accurately portray psychiatric illness.

‘Magical realism’
Two of last year’s celebrated films, Birdman and Still Alice, have continued the longstanding tradition of portraying mental illness in film. Medicine often is touted as art and science; film likewise sits at this intersection. However, filmmakers are artists, primarily, and the nature of storytelling is to emphasize art over scientific accuracy.

The main character in Birdman, for example, manifests psychosis, but many of his presenting signs and symptoms are incongruent with any diagnosable form of psychosis. To tell its story, the film employs magical realism, a celebrated literary and film technique. Although magical realism might detract from the accuracy of the condition portrayed, it adds cinematic appeal to the film, likely creates more entertainment value, and, in turn, garners appreciation from a broader audience.

Expansion of medical information, accurate and otherwise
As in the 1970’s, we are, today, in the midst of rapidly evolving societal norms. One of the most rapid changes is in how the public acquires information. We are in the midst of the “Googlification” of medical knowledge and the expansion of online medical resources. These resources can, simultaneously, inform and mislead the public.

Popular films behave in much the same way. There is no motion picture-guild requirement that mentally ill characters in films such as Birdman meet any set of psychiatric criteria, from DSM-5 or elsewhere. Similarly, the fact that psychiatrists do not control the information in films that portray mental illness comes as no surprise.

‘One flew East, one flew West…’
The tension between engaging storytelling and medical accuracy certainly is not a new phenomenon, extending not only to representations of disease but to representations of treatment. Consider director Miloš Forman’s seminal 1975 film, One Flew Over the Cuckoo’s Nest, whose chief importance for psychiatry rests not in its individualized representations of patients but in a portrayal of the environment in which they are treated. Louise Fletcher’s Academy Award-winning portrayal of cruel Nurse Ratched has lingered in the public consciousness, remaining a prominent image for many Americans when they think of a psychiatric institution.

When Cuckoo’s Nest was released, it was considered by critics to be an “exploration of society’s enforcement of conformism” that “almost willfully overlooked the realities of mental illness”¹ so that it could vivify its protagonist’s struggle against tyrannical Nurse Ratched. The film’s primary intent might not have been to make a statement about the injustices of the time, but it has certainly had a lasting effect on the public’s perception of psychiatric illness and treatment.

Films offer an opportunity for discussion
Films on the theme of psychiatry and mental illness have long held a distinctive position in the canon of Western cinema. In this vein, films from the past year have made timely contributions to the genre. Although Still Alice and Birdman might prove to be ground-breaking in changing societal views over time, we must not expect them to do so.

Nevertheless, psychiatry ought to take advantage of popular films’ wide exposure and ability to destigmatize mental illness—rather than lament medical inaccuracies in these films.

Cinema is, first and foremost, an art. Although patients and the public might pick up misconceptions about psychosis, Alzheimer’s disease, or PTSD because popular films take artistic liberty about mental illness, psychiatrists are available to set the record straight. After all, psychiatry has long been about managing perceptions, and patient education is at the core of our specialty.

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

THE CASE

A 25-year-old G2P2 woman came to our family practice clinic because she had multiple positive home pregnancy test results despite having undergone a sterilization procedure 4 years earlier. She said that 9 months ago, she had begun to experience hot flashes and night sweats that were getting progressively worse. Her menstrual cycles had been regular until 6 months earlier, when her bleeding became very light and irregular (2- to 6-week cycles with only one day of menstruation). Then 3 months ago, she stopped menstruating.

She’d had 2 uncomplicated pregnancies with normal vaginal deliveries 3 and 4 years ago, and had undergone a transcervical sterilization procedure after delivering her second child. Her medical history included hypothyroidism diagnosed at age 15, moderate persistent asthma, and seasonal allergies. She was taking levothyroxine 250 mcg/d, inhaled fluticasone/salmeterol, albuterol, and intranasal mometasone.

Transvaginal ultrasound failed to identify an intrauterine or ectopic pregnancy, and the patient’s ovaries were not visualized (uterine anatomy was normal with an endometrial stripe of 5.7 mm). The result of a serum human chorionic gonadotropin (hCG) test was 6.73 mIU/ mL. (In a nonpregnant, premenopausal woman, hCG is typically undetectable.) Subsequent serial hCG measurements remained low (6.72-7.09 mIU/mL), but persistent. Given these low hCG levels, it was imperative to rule out an intrauterine or ectopic pregnancy. A urine hCG was negative.

THE DIAGNOSIS

Because of our patient’s vasomotor symptoms, we ordered additional laboratory studies, which revealed an elevated follicle-stimulating hormone (FSH) level (66.08 mIU/mL and 42.2 mIU/mL taken one year apart; normal, 1.98-9.58 mIU/mL in a premenopausal female), an elevated luteinizing hormone (LH) level (46.1 mIU/mL; normal, 2.58-15.5 mIU/mL in a premenopausal female), a low thyroid-stimulating hormone (TSH) level (0.445 mIU/mL; normal, 0.465-4.65 mIU/mL), and a normal prolactin level (12.5 mIU/mL). Based on these results, we diagnosed primary ovarian insufficiency (POI).

DISCUSSION

POI, formerly known as premature ovarian failure, is defined as 4 to 6 months of amenorrhea or oligomenorrhea in a woman younger than 40 with an elevated FSH on 2 occasions, at least 4 weeks apart.^1-3

The etiology of POI is broad. It can be caused by a failure of the pituitary gland or hypothalamus to secrete regulating hormones to stimulate the ovaries. Possible genetic causes include Turner’s syndrome, fragile X permutation, and other autosomal disorders that cause follicle dysfunction or destruction.¹ Infections such as mumps, varicella, and tuberculosis are known to affect ovary function, as well.^1,4 In addition, women who are exposed to chemotherapy or radiation are at higher risk for developing POI.¹

Because POI and autoimmune disorders tend to occur together, consider screening any patient with POI for disorders such as hypothyroidism and Addison’s disease. A serum analysis to evaluate for autoantibodies against steroid-producing cells may be a potential marker for POI in patients with an autoimmune disease that affects the adrenal glands or thyroid. However, patients with isolated Addison’s disease, autoimmune hypothyroidism, or diabetes mellitus in the absence of POI do not appear to have steroid-specific antibodies.² In our patient’s case, her hypothyroidism may have placed her at higher risk of having a second organ system adversely affected by her immune system.

What causes a false-positive pregnancy test? This case is unique because our patient reported multiple positive home pregnancy test results and had persistently low serum hCG levels. While she had symptoms that suggested menopause (hot flashes, oligomenorrhea that progressed to amenorrhea), she believed these symptoms were related to pregnancy. In addition to pregnancy, an elevated serum hCG measurement can be due to various malignancies, molar pregnancy, pituitary production of hCG, elevated LH, cross-reactivity with multiple animal exposures (due to the production of human anti-animal antibodies that react with testing), and recent mononucleosis infection.⁵

Other potential causes for false-positive urine pregnancy test results include tuboovarian abscess,⁶ adenomyosis,⁷ and cancers that produce hCG, such as colon, pancreatic, lung, liver, and urothelial bladder carcinoma.^8,9 Urine with significant proteinuria can also cause a positive pregnancy test result.¹⁰

Our patient likely had a false-positive hCG due to elevated LH, secondary to POI, that demonstrated cross-reactivity on the hCG assay. The similarity in the chemical structure of the beta subunits of hCG and LH have been reported as false-positive tests in the absence of pregnancy.⁵

Hormone therapy and supplemental calcium and vitamin D are recommended for women with primary ovarian insufficiency to help prevent loss of bone density and other negative effects of low estrogen.

Because home pregnancy tests are designed to detect pregnancy as early as possible, they typically feature a high sensitivity by detecting very low levels of hCG, which leads to more frequent false-positive results. It is possible that different assay methods could account for the discrepancy between our patient’s positive home pregnancy tests and our negative laboratory urine pregnancy test.

Our patient and her husband were both counseled regarding her POI diagnosis. We conducted further studies to establish a possible etiology. She was found to have a normal karyotype of 46, XX, which ruled out Turner’s syndrome. Testing for permutations of the FMR1 gene was negative for fragile X syndrome, and antibody testing for thyroid and adrenal glands was negative for autoimmune disease.

Hormone therapy and supplemental calcium and vitamin D are recommended for women with POI to help prevent bone loss and other negative effects of low estrogen.¹¹ We did not take this tack with our patient, however, because she decided she wanted to pursue a tubal ligation reversal in order to get pregnant. So instead, we decreased her dose of levothyroxine to 150 mcg (since her TSH was low) and we referred her to the Reproductive Endocrinology Department.

THE TAKEAWAY

Although many cases of POI have no discernible etiology, it is important to rule out malignancies, failure of pituitary production, genetic causes, infections, and other possible causes. Hormone therapy and prophylactic doses of calcium and vitamin D are recommended for patients diagnosed with POI.

THE CASE

A 25-year-old G2P2 woman came to our family practice clinic because she had multiple positive home pregnancy test results despite having undergone a sterilization procedure 4 years earlier. She said that 9 months ago, she had begun to experience hot flashes and night sweats that were getting progressively worse. Her menstrual cycles had been regular until 6 months earlier, when her bleeding became very light and irregular (2- to 6-week cycles with only one day of menstruation). Then 3 months ago, she stopped menstruating.

She’d had 2 uncomplicated pregnancies with normal vaginal deliveries 3 and 4 years ago, and had undergone a transcervical sterilization procedure after delivering her second child. Her medical history included hypothyroidism diagnosed at age 15, moderate persistent asthma, and seasonal allergies. She was taking levothyroxine 250 mcg/d, inhaled fluticasone/salmeterol, albuterol, and intranasal mometasone.

Transvaginal ultrasound failed to identify an intrauterine or ectopic pregnancy, and the patient’s ovaries were not visualized (uterine anatomy was normal with an endometrial stripe of 5.7 mm). The result of a serum human chorionic gonadotropin (hCG) test was 6.73 mIU/ mL. (In a nonpregnant, premenopausal woman, hCG is typically undetectable.) Subsequent serial hCG measurements remained low (6.72-7.09 mIU/mL), but persistent. Given these low hCG levels, it was imperative to rule out an intrauterine or ectopic pregnancy. A urine hCG was negative.

THE DIAGNOSIS

Because of our patient’s vasomotor symptoms, we ordered additional laboratory studies, which revealed an elevated follicle-stimulating hormone (FSH) level (66.08 mIU/mL and 42.2 mIU/mL taken one year apart; normal, 1.98-9.58 mIU/mL in a premenopausal female), an elevated luteinizing hormone (LH) level (46.1 mIU/mL; normal, 2.58-15.5 mIU/mL in a premenopausal female), a low thyroid-stimulating hormone (TSH) level (0.445 mIU/mL; normal, 0.465-4.65 mIU/mL), and a normal prolactin level (12.5 mIU/mL). Based on these results, we diagnosed primary ovarian insufficiency (POI).

DISCUSSION

POI, formerly known as premature ovarian failure, is defined as 4 to 6 months of amenorrhea or oligomenorrhea in a woman younger than 40 with an elevated FSH on 2 occasions, at least 4 weeks apart.^1-3

The etiology of POI is broad. It can be caused by a failure of the pituitary gland or hypothalamus to secrete regulating hormones to stimulate the ovaries. Possible genetic causes include Turner’s syndrome, fragile X permutation, and other autosomal disorders that cause follicle dysfunction or destruction.¹ Infections such as mumps, varicella, and tuberculosis are known to affect ovary function, as well.^1,4 In addition, women who are exposed to chemotherapy or radiation are at higher risk for developing POI.¹

Because POI and autoimmune disorders tend to occur together, consider screening any patient with POI for disorders such as hypothyroidism and Addison’s disease. A serum analysis to evaluate for autoantibodies against steroid-producing cells may be a potential marker for POI in patients with an autoimmune disease that affects the adrenal glands or thyroid. However, patients with isolated Addison’s disease, autoimmune hypothyroidism, or diabetes mellitus in the absence of POI do not appear to have steroid-specific antibodies.² In our patient’s case, her hypothyroidism may have placed her at higher risk of having a second organ system adversely affected by her immune system.

What causes a false-positive pregnancy test? This case is unique because our patient reported multiple positive home pregnancy test results and had persistently low serum hCG levels. While she had symptoms that suggested menopause (hot flashes, oligomenorrhea that progressed to amenorrhea), she believed these symptoms were related to pregnancy. In addition to pregnancy, an elevated serum hCG measurement can be due to various malignancies, molar pregnancy, pituitary production of hCG, elevated LH, cross-reactivity with multiple animal exposures (due to the production of human anti-animal antibodies that react with testing), and recent mononucleosis infection.⁵

Other potential causes for false-positive urine pregnancy test results include tuboovarian abscess,⁶ adenomyosis,⁷ and cancers that produce hCG, such as colon, pancreatic, lung, liver, and urothelial bladder carcinoma.^8,9 Urine with significant proteinuria can also cause a positive pregnancy test result.¹⁰

Our patient likely had a false-positive hCG due to elevated LH, secondary to POI, that demonstrated cross-reactivity on the hCG assay. The similarity in the chemical structure of the beta subunits of hCG and LH have been reported as false-positive tests in the absence of pregnancy.⁵

Hormone therapy and supplemental calcium and vitamin D are recommended for women with primary ovarian insufficiency to help prevent loss of bone density and other negative effects of low estrogen.

Because home pregnancy tests are designed to detect pregnancy as early as possible, they typically feature a high sensitivity by detecting very low levels of hCG, which leads to more frequent false-positive results. It is possible that different assay methods could account for the discrepancy between our patient’s positive home pregnancy tests and our negative laboratory urine pregnancy test.

Our patient and her husband were both counseled regarding her POI diagnosis. We conducted further studies to establish a possible etiology. She was found to have a normal karyotype of 46, XX, which ruled out Turner’s syndrome. Testing for permutations of the FMR1 gene was negative for fragile X syndrome, and antibody testing for thyroid and adrenal glands was negative for autoimmune disease.

Hormone therapy and supplemental calcium and vitamin D are recommended for women with POI to help prevent bone loss and other negative effects of low estrogen.¹¹ We did not take this tack with our patient, however, because she decided she wanted to pursue a tubal ligation reversal in order to get pregnant. So instead, we decreased her dose of levothyroxine to 150 mcg (since her TSH was low) and we referred her to the Reproductive Endocrinology Department.

THE TAKEAWAY

Although many cases of POI have no discernible etiology, it is important to rule out malignancies, failure of pituitary production, genetic causes, infections, and other possible causes. Hormone therapy and prophylactic doses of calcium and vitamin D are recommended for patients diagnosed with POI.

THE CASE

A 25-year-old G2P2 woman came to our family practice clinic because she had multiple positive home pregnancy test results despite having undergone a sterilization procedure 4 years earlier. She said that 9 months ago, she had begun to experience hot flashes and night sweats that were getting progressively worse. Her menstrual cycles had been regular until 6 months earlier, when her bleeding became very light and irregular (2- to 6-week cycles with only one day of menstruation). Then 3 months ago, she stopped menstruating.

She’d had 2 uncomplicated pregnancies with normal vaginal deliveries 3 and 4 years ago, and had undergone a transcervical sterilization procedure after delivering her second child. Her medical history included hypothyroidism diagnosed at age 15, moderate persistent asthma, and seasonal allergies. She was taking levothyroxine 250 mcg/d, inhaled fluticasone/salmeterol, albuterol, and intranasal mometasone.

Transvaginal ultrasound failed to identify an intrauterine or ectopic pregnancy, and the patient’s ovaries were not visualized (uterine anatomy was normal with an endometrial stripe of 5.7 mm). The result of a serum human chorionic gonadotropin (hCG) test was 6.73 mIU/ mL. (In a nonpregnant, premenopausal woman, hCG is typically undetectable.) Subsequent serial hCG measurements remained low (6.72-7.09 mIU/mL), but persistent. Given these low hCG levels, it was imperative to rule out an intrauterine or ectopic pregnancy. A urine hCG was negative.

THE DIAGNOSIS

Because of our patient’s vasomotor symptoms, we ordered additional laboratory studies, which revealed an elevated follicle-stimulating hormone (FSH) level (66.08 mIU/mL and 42.2 mIU/mL taken one year apart; normal, 1.98-9.58 mIU/mL in a premenopausal female), an elevated luteinizing hormone (LH) level (46.1 mIU/mL; normal, 2.58-15.5 mIU/mL in a premenopausal female), a low thyroid-stimulating hormone (TSH) level (0.445 mIU/mL; normal, 0.465-4.65 mIU/mL), and a normal prolactin level (12.5 mIU/mL). Based on these results, we diagnosed primary ovarian insufficiency (POI).

DISCUSSION

POI, formerly known as premature ovarian failure, is defined as 4 to 6 months of amenorrhea or oligomenorrhea in a woman younger than 40 with an elevated FSH on 2 occasions, at least 4 weeks apart.^1-3

The etiology of POI is broad. It can be caused by a failure of the pituitary gland or hypothalamus to secrete regulating hormones to stimulate the ovaries. Possible genetic causes include Turner’s syndrome, fragile X permutation, and other autosomal disorders that cause follicle dysfunction or destruction.¹ Infections such as mumps, varicella, and tuberculosis are known to affect ovary function, as well.^1,4 In addition, women who are exposed to chemotherapy or radiation are at higher risk for developing POI.¹

Because POI and autoimmune disorders tend to occur together, consider screening any patient with POI for disorders such as hypothyroidism and Addison’s disease. A serum analysis to evaluate for autoantibodies against steroid-producing cells may be a potential marker for POI in patients with an autoimmune disease that affects the adrenal glands or thyroid. However, patients with isolated Addison’s disease, autoimmune hypothyroidism, or diabetes mellitus in the absence of POI do not appear to have steroid-specific antibodies.² In our patient’s case, her hypothyroidism may have placed her at higher risk of having a second organ system adversely affected by her immune system.

What causes a false-positive pregnancy test? This case is unique because our patient reported multiple positive home pregnancy test results and had persistently low serum hCG levels. While she had symptoms that suggested menopause (hot flashes, oligomenorrhea that progressed to amenorrhea), she believed these symptoms were related to pregnancy. In addition to pregnancy, an elevated serum hCG measurement can be due to various malignancies, molar pregnancy, pituitary production of hCG, elevated LH, cross-reactivity with multiple animal exposures (due to the production of human anti-animal antibodies that react with testing), and recent mononucleosis infection.⁵

Other potential causes for false-positive urine pregnancy test results include tuboovarian abscess,⁶ adenomyosis,⁷ and cancers that produce hCG, such as colon, pancreatic, lung, liver, and urothelial bladder carcinoma.^8,9 Urine with significant proteinuria can also cause a positive pregnancy test result.¹⁰

Our patient likely had a false-positive hCG due to elevated LH, secondary to POI, that demonstrated cross-reactivity on the hCG assay. The similarity in the chemical structure of the beta subunits of hCG and LH have been reported as false-positive tests in the absence of pregnancy.⁵

Hormone therapy and supplemental calcium and vitamin D are recommended for women with primary ovarian insufficiency to help prevent loss of bone density and other negative effects of low estrogen.

Because home pregnancy tests are designed to detect pregnancy as early as possible, they typically feature a high sensitivity by detecting very low levels of hCG, which leads to more frequent false-positive results. It is possible that different assay methods could account for the discrepancy between our patient’s positive home pregnancy tests and our negative laboratory urine pregnancy test.

Our patient and her husband were both counseled regarding her POI diagnosis. We conducted further studies to establish a possible etiology. She was found to have a normal karyotype of 46, XX, which ruled out Turner’s syndrome. Testing for permutations of the FMR1 gene was negative for fragile X syndrome, and antibody testing for thyroid and adrenal glands was negative for autoimmune disease.

Hormone therapy and supplemental calcium and vitamin D are recommended for women with POI to help prevent bone loss and other negative effects of low estrogen.¹¹ We did not take this tack with our patient, however, because she decided she wanted to pursue a tubal ligation reversal in order to get pregnant. So instead, we decreased her dose of levothyroxine to 150 mcg (since her TSH was low) and we referred her to the Reproductive Endocrinology Department.

THE TAKEAWAY

Although many cases of POI have no discernible etiology, it is important to rule out malignancies, failure of pituitary production, genetic causes, infections, and other possible causes. Hormone therapy and prophylactic doses of calcium and vitamin D are recommended for patients diagnosed with POI.

In my struggle to keep abreast of all things pediatric, I sample a variety of sources.

Of course each month I scan almost all of the abstracts in the journal Pediatrics. But to get a sense of what the nonmedical community is reading, I begin each morning with a cruise through the electronic versions of the New York Times and the Portland (Maine) Press Herald.

By lunch time I usually have hopscotched my way through the Wall Street Journal. And during our evening adult beverage quiet time, I amuse myself with our local daily. If a news story includes a link to an original article, I usually bore down deep enough to at least read the abstract. Keep in mind that this whole process of keeping current takes little more than a half an hour, 45 minutes tops.

It seems that psychology-related topics dominate the science and medicine stories that I encounter. This shouldn’t surprise you because most of us want to know more about why humans behave the way we do. We also wonder if animal behavior may provide some clues.

It may be because I was trained by careful and skeptical “hard” scientists that I have always read psychosocial and behavioral studies with several grains of salt. Despite my skepticism, I am not beneath embracing the odd study that seems to support one of my biases. The studies that don’t sync with my world view I quickly cast on the rubbish heap because the “sample group was too small,” or the “variables were not adequately controlled for,” or simply because I thought the study was poorly done.

It turns out that my skepticism has not only been well founded, but should have been broader in scope. In a recent study published in the journal Science, three young psychologists undertook a heroic and courageous effort to reproduce 100 studies from three leading psychology journals (Science 2015 Aug 28. doi:10.1126/science.aac4716). Chosen from a larger group, these studies were thought to reflect the core knowledge from which psychologists develop their understanding of such basics as learning, memory, and relationships.

The investigators found that in more than half the studies, they were unable to reproduce the results reported in the original studies despite the fact that in many cases, they were assisted by the original investigators in their attempts to replicate the conditions of the initial studies.

The authors quickly assert that their findings do not suggest that the original investigators were attempting to deceive. Nor does the failure to reproduce results necessarily mean that other future studies might confirm the original findings. Their primary point is that evaluating reproducibility is difficult.

However, this new study is troubling for two reasons. First, it casts even more doubt on the decision to expand the MCAT (Medical College Admission Test) by adding several hours of questions based on psychosocial topics in hopes of creating physicians who are more in tune with the emotional needs and social challenges of their future patients. If the results of more than half of the studies that might be considered the underpinnings of modern psychology can’t be reproduced, are we just asking aspiring medical students to learn a larger collection of half truths? And thus have medical students spend less time learning basic science and developing better critical thinking skills? There are better ways to sort for more empathetic and sensitive physicians than by building an unevenly weighted exam.

Second, although this study highlights the core of what makes science such a powerful and effective tool for discovering the truth, the anti-science folks will point to it as just another example of how we shouldn’t trust anything science tells us.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.” Email him at [email protected].

In my struggle to keep abreast of all things pediatric, I sample a variety of sources.

Of course each month I scan almost all of the abstracts in the journal Pediatrics. But to get a sense of what the nonmedical community is reading, I begin each morning with a cruise through the electronic versions of the New York Times and the Portland (Maine) Press Herald.

By lunch time I usually have hopscotched my way through the Wall Street Journal. And during our evening adult beverage quiet time, I amuse myself with our local daily. If a news story includes a link to an original article, I usually bore down deep enough to at least read the abstract. Keep in mind that this whole process of keeping current takes little more than a half an hour, 45 minutes tops.

It seems that psychology-related topics dominate the science and medicine stories that I encounter. This shouldn’t surprise you because most of us want to know more about why humans behave the way we do. We also wonder if animal behavior may provide some clues.

It may be because I was trained by careful and skeptical “hard” scientists that I have always read psychosocial and behavioral studies with several grains of salt. Despite my skepticism, I am not beneath embracing the odd study that seems to support one of my biases. The studies that don’t sync with my world view I quickly cast on the rubbish heap because the “sample group was too small,” or the “variables were not adequately controlled for,” or simply because I thought the study was poorly done.

It turns out that my skepticism has not only been well founded, but should have been broader in scope. In a recent study published in the journal Science, three young psychologists undertook a heroic and courageous effort to reproduce 100 studies from three leading psychology journals (Science 2015 Aug 28. doi:10.1126/science.aac4716). Chosen from a larger group, these studies were thought to reflect the core knowledge from which psychologists develop their understanding of such basics as learning, memory, and relationships.

The investigators found that in more than half the studies, they were unable to reproduce the results reported in the original studies despite the fact that in many cases, they were assisted by the original investigators in their attempts to replicate the conditions of the initial studies.

The authors quickly assert that their findings do not suggest that the original investigators were attempting to deceive. Nor does the failure to reproduce results necessarily mean that other future studies might confirm the original findings. Their primary point is that evaluating reproducibility is difficult.

However, this new study is troubling for two reasons. First, it casts even more doubt on the decision to expand the MCAT (Medical College Admission Test) by adding several hours of questions based on psychosocial topics in hopes of creating physicians who are more in tune with the emotional needs and social challenges of their future patients. If the results of more than half of the studies that might be considered the underpinnings of modern psychology can’t be reproduced, are we just asking aspiring medical students to learn a larger collection of half truths? And thus have medical students spend less time learning basic science and developing better critical thinking skills? There are better ways to sort for more empathetic and sensitive physicians than by building an unevenly weighted exam.

Second, although this study highlights the core of what makes science such a powerful and effective tool for discovering the truth, the anti-science folks will point to it as just another example of how we shouldn’t trust anything science tells us.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.” Email him at [email protected].

In my struggle to keep abreast of all things pediatric, I sample a variety of sources.

Of course each month I scan almost all of the abstracts in the journal Pediatrics. But to get a sense of what the nonmedical community is reading, I begin each morning with a cruise through the electronic versions of the New York Times and the Portland (Maine) Press Herald.

By lunch time I usually have hopscotched my way through the Wall Street Journal. And during our evening adult beverage quiet time, I amuse myself with our local daily. If a news story includes a link to an original article, I usually bore down deep enough to at least read the abstract. Keep in mind that this whole process of keeping current takes little more than a half an hour, 45 minutes tops.

It seems that psychology-related topics dominate the science and medicine stories that I encounter. This shouldn’t surprise you because most of us want to know more about why humans behave the way we do. We also wonder if animal behavior may provide some clues.

It may be because I was trained by careful and skeptical “hard” scientists that I have always read psychosocial and behavioral studies with several grains of salt. Despite my skepticism, I am not beneath embracing the odd study that seems to support one of my biases. The studies that don’t sync with my world view I quickly cast on the rubbish heap because the “sample group was too small,” or the “variables were not adequately controlled for,” or simply because I thought the study was poorly done.

It turns out that my skepticism has not only been well founded, but should have been broader in scope. In a recent study published in the journal Science, three young psychologists undertook a heroic and courageous effort to reproduce 100 studies from three leading psychology journals (Science 2015 Aug 28. doi:10.1126/science.aac4716). Chosen from a larger group, these studies were thought to reflect the core knowledge from which psychologists develop their understanding of such basics as learning, memory, and relationships.

The investigators found that in more than half the studies, they were unable to reproduce the results reported in the original studies despite the fact that in many cases, they were assisted by the original investigators in their attempts to replicate the conditions of the initial studies.

The authors quickly assert that their findings do not suggest that the original investigators were attempting to deceive. Nor does the failure to reproduce results necessarily mean that other future studies might confirm the original findings. Their primary point is that evaluating reproducibility is difficult.

However, this new study is troubling for two reasons. First, it casts even more doubt on the decision to expand the MCAT (Medical College Admission Test) by adding several hours of questions based on psychosocial topics in hopes of creating physicians who are more in tune with the emotional needs and social challenges of their future patients. If the results of more than half of the studies that might be considered the underpinnings of modern psychology can’t be reproduced, are we just asking aspiring medical students to learn a larger collection of half truths? And thus have medical students spend less time learning basic science and developing better critical thinking skills? There are better ways to sort for more empathetic and sensitive physicians than by building an unevenly weighted exam.

Second, although this study highlights the core of what makes science such a powerful and effective tool for discovering the truth, the anti-science folks will point to it as just another example of how we shouldn’t trust anything science tells us.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.” Email him at [email protected].

Fracture of the distal radius is the wrist injury most often encountered by orthopedic and hand surgeons.¹ The number of fractures of the distal radius in the United States was estimated to be 640,000 in 2001, and the incidence is increasing.^2,3 Recent evidence has shown a substantial increase in treating these fractures with internal rather than closed fixation, even in the elderly.⁴

Treatment of complex intra-articular fractures of the distal radius requires an accurate diagnosis of the fracture pattern and a thoughtful approach to fixation. Although a majority of the fractures that meet the operative criteria are now treated with various anterior locked-plating techniques with good results, a subset requires more technically demanding fixation approaches, including fragment-specific approaches, dorsal and palmar plating, and combined internal and external fixation.

The sustentaculum lunatum, as we have named the palmar lunate facet, deserves specific attention because of its importance in load transmission across the radiocarpal joint and its key role in restoring the anatomy of the palmar distal radial metaphysis during internal fixation. This fragment in comminuted fractures was first ascribed special importance by Melone⁵ in his description of common fracture patterns. In the present article, we describe the anatomical characteristics of the sustentaculum lunatum and the clinical relevance of this fragment to management of fractures of the distal radius.

Classification

A variety of classification systems have been proposed to characterize and guide treatment of fractures of the distal radius. The earliest descriptions of fracture patterns were presented by Castaing⁶ and Frykman⁷ in the 1960s. The Frykman classification historically has been popular but is limited in accuracy in its characterization of fragments and their displacement and is limited in its ability to guide treatment. The classification system proposed by Melone and colleagues^5,8-10 was the first to truly describe fracture of the distal radius fragments in a relevant manner, including their characteristic “4 parts” (Figure 1). The authors emphasized the importance of the “medial complex” as the cornerstone of the radiocarpal and radioulnar joints.

The classification system developed by Müller and colleagues,¹¹ which was adopted by the AO (Arbeitsgemeinschaft für Osteosynthesefragen), might be the most descriptive and informative system, and it is widely used to conduct research and direct treatment. This system classifies fractures into A (extra-articular), B (partial articular), and C (complete articular) types and subclassifies them according to fracture location and comminution. These classifications, along with a conceptualization of the distal forearm as a 3-column structure involving the radial, ulnar, and intermediate columns (including the lunate facet), as proposed by Peine and colleagues,¹² gave us a framework for approaching fixation of fractures of the distal radius.

Etymology and Definition

Sustentaculum, from the Latin sustinere, “to support, check, or put off,” and taculum, “receptacle or holding space,” is a fitting description of the most distal portion of the palmar lunate facet, as it supports and holds the carpus, and specifically the lunate, on the radial articular surface. This portion is analogous to the sustentaculum tali, the named portion of the calcaneus that supports and articulates with the middle calcaneal articular surface of the talus¹³ and provides a reliable fragment for internal fixation of the calcaneus.

Anatomical and Biomechanical Considerations

The distal radial articular surface is composed of distinct scaphoid and lunate facets that articulate with their respective carpal bones. Several studies have characterized the anatomy of the distal radius.^14-17 Linscheid¹⁴ found that the lunate and scaphoid facets account for 46% and 43% of the contact area across the radiocarpal joint, respectively; this has been corroborated by others.¹⁵ A biomechanical study by Genda and Horii¹⁸ showed that the majority of stress across the wrist joint was concentrated at the palmar side of the distal radius in the neutral position. Although it is recognized that the scaphoid facet bears most of the load across the wrist in the neutral wrist position, most activities of daily living place the wrist in a slightly extended and ulnarly deviated position. This position results in a shift of the majority of load to the radiolunar articulation, constituting 53% of total force transmission.¹⁸ Subchondral bone density analyses have supported this lunate-predominant loading pattern across the radiocarpal articulation in most people.¹⁹ This loading pattern is also supported by the observation that failure of fixation and carpal subluxation generally occurs at the radiolunate articulation.

The palmar lip of the distal radius traditionally has been depicted and conceptualized as a flat extension of the metaphysis, leading to the development of implants that are not ideally designed for capturing this area in the fracture setting. A 3-dimensional (3-D) computed tomography (CT) study of the distal radii of healthy volunteers, conducted by Andermahr and colleagues,²⁰ showed that the contour of the palmar lunate facet projects from the palmar cortex of the radius by 3 mm on average and is about 19 mm in width (radial to ulnar dimension) (Figures 2A-2C). In the axial plane, the anterior cortex of the distal radius slopes in a palmar direction, from radial to ulnar. This presents a challenge in attempts to support the entire surface (scaphoid and lunate facets) with a single palmar implant.^20-25

A study conducted by Harness and colleagues²⁴ showed that the majority of palmar shear fractures are composed of multiple fragments of the lunar articular facet. Anatomical studies of the distal radiocarpal articulation have also described the ligamentous attachments to the sustentaculum lunatum.²⁶ The short radiolunate ligament, which originates from this fragment and inserts onto the lunate, provides stability to the carpus and, if not adequately fixed, leads to an incompetent restraint to palmar carpal translation. Isolated injuries of the short radiolunate ligament or fractures of the palmar lunate facet have been shown to result in palmar carpal translation.^27,28 In addition, attachments of the palmar radioulnar ligament and other more ulnar radiocarpal ligaments act as deforming forces on the palmar lunate facet.^24,26

Fracture Pattern Recognition

Although the AO type B palmar shear fracture pattern, also known as the Barton fracture, has classically been recognized as the fracture involving the palmar lunate facet and requiring special attention, many complete articular fractures feature involvement and fragmentation of this portion of the distal radius (Figures 3A-3F).²⁹ In highly comminuted complete articular and palmar shear fracture patterns, the morphology of the sustentaculum lunatum should be appreciated, and its adequate fixation to the radial metaphysis ensured, to prevent loss of reduction.

Visualization of the palmar lunate facet as a distinct fragment might be difficult in cases of highly comminuted fracture patterns. Standard CT or more recently described 3-D CT techniques with subtraction of the carpus might facilitate appreciation of this fragment for preoperative planning of approach and fixation.^29,30 Our institutional protocol involves obtaining preoperative traction radiographs of every fracture of the distal radius. These radiographs have reduced the need for CT in understanding the fracture pattern and aid in decision making.³¹

Besides appreciating the existence of the sustentaculum lunatum fragment, we should recognize that some injury patterns that split the lunate facet into unstable dorsal and palmar fragments might necessitate a separate dorsal approach to reduce and fix the dorsal lunate fragment. Traction radiographs can be especially useful in recognizing these patterns (a V sign is present) (Figures 4A, 4B).

Open Fractures

Highly comminuted fractures of the distal radius presenting with displaced lunate facet fragments can have high-energy mechanisms of injury. Although open fractures of the distal radius are associated with lower risk for infection (compared with open fractures of other long bones), they deserve special attention because of associated tendon and neurovascular injuries. Few studies have specifically assessed open fractures of the distal radius.^32-35 Only the study by Rozental and Blazar³⁴ listed associated injuries at the wrist level. The authors identified 4 patients (out of 18) with concomitant flexor tendon or neurovascular injuries that included radial or ulnar artery injury. In our experience, many open fractures of the distal radius are caused by an inside-out mechanism and present with an open wound either over the ulnar styloid or in the area of the ulnar side of the palmar radial metaphysis corresponding to the metaphyseal spike that mates with the sustentaculum lunatum (Figures 5A, 5B). Given these findings, we approach this intermediate column with particular care in cases of open fracture, paying attention to important structures (flexors, neurovascular) and looking for contamination from the environment into the fracture.

Fixation Techniques

The approach to fixation of partial articular palmar shear fractures is fairly straightforward. Buttress plate fixation has been well described and has had reliably good results.³⁶ However, in very distal fracture patterns and in cases in which the palmar lunate facet is fragmented as part of a complete articular fracture, a fragment-specific approach to fixation with or without spanning external fixation often is necessary.³⁷ The unrecognized sustentaculum lunatum fragment in comminuted complete articular fractures can lead to inadequate fixation constructs, resulting in loss of reduction and carpal subluxation in a palmar direction.^24,34,38

Our surgical approach uses the standard anterior interval between the radial artery and the flexor carpi radialis, as described by Henry.³⁹ The flexor pollicis longus is retracted ulnarly, revealing the pronator quadratus. We then reflect the pronator quadratus from the distal radial metaphysis until the most proximal and ulnar extent of the fracture is easily visualized. The palmar ulnar metaphyseal cortex that mates with the displaced sustentaculum lunatum is, in our experience, often the least comminuted portion of the metaphysis, thus providing a cortical key for restoration of height and alignment (Figures 5A, 5B). At our institution, fixation typically is achieved by contouring miniplates (1.3 or 1.5 mm) to capture and buttress the sustentaculum lunatum (Figures 6A, 6B). In our experience, the screw lengths in the most distal fixed-angle constructs at the palmar lip are limited to 6 mm or less to avoid penetration of the articular surface, though this has not been previously reported in the literature. After restoring the length and tilt of this intermediate column of the distal radius, we proceed with “rebuilding” the remainder of the fragments to our stabilized initial construct.

Various authors^40-43 have described alternative fixation methods for the palmar lunate facet fragment. Jupiter and Marent-Huber⁴² described 2.4-mm locked-plate fixation with either a standard palmar plate or T- or L-plates for cases in which the palmar lip fragment is very distal and small. In fact, some newer anatomical distal radius implants include features designed to target these fragments (Figures 7A, 7B). An alternative fixation method involves use of a 26-gauge stainless steel wire passed through drill holes in the metaphysis 1 cm proximal to the fracture and then passed through the palmar capsule just distal to the fragment and secured in figure-8 fashion while the fragment is manually held reduced.⁴¹ Still others have recommended limited internal fixation of the sustentaculum lunatum through an ulna-sided palmar approach to the distal radius (between the ulnar neurovascular bundle and the flexor tendons) combined with external fixation to restore length and palmar tilt in highly comminuted fractures.^40,43

A method involving arthroscopically assisted reduction and fixation of the lunate facet has also been described, though this procedure is technically demanding and has limited indications.⁴⁴ It uses a Freer elevator passed through the standard 3-4 portal after initial visualization and evacuation of hematoma. The Freer elevator is used to disimpact the sustentaculum lunatum and to elevate it from its depressed position. With the dorsal lunate facet left displaced to facilitate access to the palmar fragment, a nerve hook retractor is used to reduce the palmar facet to the radial styloid, and Kirschner wires are used to achieve interfragmentary fixation. The dorsal lunate fragment is then pieced back to the articular segment, and the entire construct is fixed to the radial metaphysis with additional Kirschner wires.

Discussion

Given the increasing incidence of fractures of the distal radius, internal fixation of these injuries will continue to be relevant. American Academy of Orthopaedic Surgeons guidelines recommend operative fixation for fractures with postreduction radial shortening of more than 3 mm, dorsal tilt of more than 10°, or intra-articular displacement or step-off of more than 2 mm.⁴⁵ Dr. Eglseder and Dr. Pensy indicate operative treatment of any incongruity of more than 2 mm in a young, active adult with a fracture of the distal radius. For the multifragmentary distal radius being treated operatively, attempts are made to achieve reduction more accurate than this, but formal dorsal exposure or direct visualization of the joint surface via dorsal capsulotomy is carefully chosen based on age, activity level, and bone quality. Recent high-level evidence⁴⁶ showed that closed treatment of unstable fractures of the distal radius results in good outcomes in the elderly. However, it is important to note that fractures displaced in a palmar direction and palmar shear patterns were excluded from that work. It is widely accepted that palmar carpal translation should be addressed with internal fixation, and specific attention must therefore be paid to the lunate facet as the cornerstone of the distal radius. Furthermore, high-energy comminuted fractures in young patients still necessitate internal fixation of fragments to restore alignment and articular congruity.

Conclusion

The importance of the palmar lunate facet in providing support and restraint to palmar carpal translation and the key role of this facet in restoring the anatomy of the distal radius have been known. This fragment deserves special attention because failure to adequately stabilize it results in loss of fixation and carpal subluxation. Various approaches and fixation techniques have been recommended, including the method we prefer and have described here. Our newly proposed term, sustentaculum lunatum, our review of its structure and function, and our descriptions of fixation techniques are intended to promote awareness of this fragment in the treatment of fractures of the distal radius.

Fracture of the distal radius is the wrist injury most often encountered by orthopedic and hand surgeons.¹ The number of fractures of the distal radius in the United States was estimated to be 640,000 in 2001, and the incidence is increasing.^2,3 Recent evidence has shown a substantial increase in treating these fractures with internal rather than closed fixation, even in the elderly.⁴

Treatment of complex intra-articular fractures of the distal radius requires an accurate diagnosis of the fracture pattern and a thoughtful approach to fixation. Although a majority of the fractures that meet the operative criteria are now treated with various anterior locked-plating techniques with good results, a subset requires more technically demanding fixation approaches, including fragment-specific approaches, dorsal and palmar plating, and combined internal and external fixation.

The sustentaculum lunatum, as we have named the palmar lunate facet, deserves specific attention because of its importance in load transmission across the radiocarpal joint and its key role in restoring the anatomy of the palmar distal radial metaphysis during internal fixation. This fragment in comminuted fractures was first ascribed special importance by Melone⁵ in his description of common fracture patterns. In the present article, we describe the anatomical characteristics of the sustentaculum lunatum and the clinical relevance of this fragment to management of fractures of the distal radius.

Classification

A variety of classification systems have been proposed to characterize and guide treatment of fractures of the distal radius. The earliest descriptions of fracture patterns were presented by Castaing⁶ and Frykman⁷ in the 1960s. The Frykman classification historically has been popular but is limited in accuracy in its characterization of fragments and their displacement and is limited in its ability to guide treatment. The classification system proposed by Melone and colleagues^5,8-10 was the first to truly describe fracture of the distal radius fragments in a relevant manner, including their characteristic “4 parts” (Figure 1). The authors emphasized the importance of the “medial complex” as the cornerstone of the radiocarpal and radioulnar joints.

The classification system developed by Müller and colleagues,¹¹ which was adopted by the AO (Arbeitsgemeinschaft für Osteosynthesefragen), might be the most descriptive and informative system, and it is widely used to conduct research and direct treatment. This system classifies fractures into A (extra-articular), B (partial articular), and C (complete articular) types and subclassifies them according to fracture location and comminution. These classifications, along with a conceptualization of the distal forearm as a 3-column structure involving the radial, ulnar, and intermediate columns (including the lunate facet), as proposed by Peine and colleagues,¹² gave us a framework for approaching fixation of fractures of the distal radius.

Etymology and Definition

Sustentaculum, from the Latin sustinere, “to support, check, or put off,” and taculum, “receptacle or holding space,” is a fitting description of the most distal portion of the palmar lunate facet, as it supports and holds the carpus, and specifically the lunate, on the radial articular surface. This portion is analogous to the sustentaculum tali, the named portion of the calcaneus that supports and articulates with the middle calcaneal articular surface of the talus¹³ and provides a reliable fragment for internal fixation of the calcaneus.

Anatomical and Biomechanical Considerations

The distal radial articular surface is composed of distinct scaphoid and lunate facets that articulate with their respective carpal bones. Several studies have characterized the anatomy of the distal radius.^14-17 Linscheid¹⁴ found that the lunate and scaphoid facets account for 46% and 43% of the contact area across the radiocarpal joint, respectively; this has been corroborated by others.¹⁵ A biomechanical study by Genda and Horii¹⁸ showed that the majority of stress across the wrist joint was concentrated at the palmar side of the distal radius in the neutral position. Although it is recognized that the scaphoid facet bears most of the load across the wrist in the neutral wrist position, most activities of daily living place the wrist in a slightly extended and ulnarly deviated position. This position results in a shift of the majority of load to the radiolunar articulation, constituting 53% of total force transmission.¹⁸ Subchondral bone density analyses have supported this lunate-predominant loading pattern across the radiocarpal articulation in most people.¹⁹ This loading pattern is also supported by the observation that failure of fixation and carpal subluxation generally occurs at the radiolunate articulation.

The palmar lip of the distal radius traditionally has been depicted and conceptualized as a flat extension of the metaphysis, leading to the development of implants that are not ideally designed for capturing this area in the fracture setting. A 3-dimensional (3-D) computed tomography (CT) study of the distal radii of healthy volunteers, conducted by Andermahr and colleagues,²⁰ showed that the contour of the palmar lunate facet projects from the palmar cortex of the radius by 3 mm on average and is about 19 mm in width (radial to ulnar dimension) (Figures 2A-2C). In the axial plane, the anterior cortex of the distal radius slopes in a palmar direction, from radial to ulnar. This presents a challenge in attempts to support the entire surface (scaphoid and lunate facets) with a single palmar implant.^20-25

A study conducted by Harness and colleagues²⁴ showed that the majority of palmar shear fractures are composed of multiple fragments of the lunar articular facet. Anatomical studies of the distal radiocarpal articulation have also described the ligamentous attachments to the sustentaculum lunatum.²⁶ The short radiolunate ligament, which originates from this fragment and inserts onto the lunate, provides stability to the carpus and, if not adequately fixed, leads to an incompetent restraint to palmar carpal translation. Isolated injuries of the short radiolunate ligament or fractures of the palmar lunate facet have been shown to result in palmar carpal translation.^27,28 In addition, attachments of the palmar radioulnar ligament and other more ulnar radiocarpal ligaments act as deforming forces on the palmar lunate facet.^24,26

Fracture Pattern Recognition

Although the AO type B palmar shear fracture pattern, also known as the Barton fracture, has classically been recognized as the fracture involving the palmar lunate facet and requiring special attention, many complete articular fractures feature involvement and fragmentation of this portion of the distal radius (Figures 3A-3F).²⁹ In highly comminuted complete articular and palmar shear fracture patterns, the morphology of the sustentaculum lunatum should be appreciated, and its adequate fixation to the radial metaphysis ensured, to prevent loss of reduction.

Visualization of the palmar lunate facet as a distinct fragment might be difficult in cases of highly comminuted fracture patterns. Standard CT or more recently described 3-D CT techniques with subtraction of the carpus might facilitate appreciation of this fragment for preoperative planning of approach and fixation.^29,30 Our institutional protocol involves obtaining preoperative traction radiographs of every fracture of the distal radius. These radiographs have reduced the need for CT in understanding the fracture pattern and aid in decision making.³¹

Besides appreciating the existence of the sustentaculum lunatum fragment, we should recognize that some injury patterns that split the lunate facet into unstable dorsal and palmar fragments might necessitate a separate dorsal approach to reduce and fix the dorsal lunate fragment. Traction radiographs can be especially useful in recognizing these patterns (a V sign is present) (Figures 4A, 4B).

Open Fractures

Highly comminuted fractures of the distal radius presenting with displaced lunate facet fragments can have high-energy mechanisms of injury. Although open fractures of the distal radius are associated with lower risk for infection (compared with open fractures of other long bones), they deserve special attention because of associated tendon and neurovascular injuries. Few studies have specifically assessed open fractures of the distal radius.^32-35 Only the study by Rozental and Blazar³⁴ listed associated injuries at the wrist level. The authors identified 4 patients (out of 18) with concomitant flexor tendon or neurovascular injuries that included radial or ulnar artery injury. In our experience, many open fractures of the distal radius are caused by an inside-out mechanism and present with an open wound either over the ulnar styloid or in the area of the ulnar side of the palmar radial metaphysis corresponding to the metaphyseal spike that mates with the sustentaculum lunatum (Figures 5A, 5B). Given these findings, we approach this intermediate column with particular care in cases of open fracture, paying attention to important structures (flexors, neurovascular) and looking for contamination from the environment into the fracture.

Fixation Techniques

The approach to fixation of partial articular palmar shear fractures is fairly straightforward. Buttress plate fixation has been well described and has had reliably good results.³⁶ However, in very distal fracture patterns and in cases in which the palmar lunate facet is fragmented as part of a complete articular fracture, a fragment-specific approach to fixation with or without spanning external fixation often is necessary.³⁷ The unrecognized sustentaculum lunatum fragment in comminuted complete articular fractures can lead to inadequate fixation constructs, resulting in loss of reduction and carpal subluxation in a palmar direction.^24,34,38

Our surgical approach uses the standard anterior interval between the radial artery and the flexor carpi radialis, as described by Henry.³⁹ The flexor pollicis longus is retracted ulnarly, revealing the pronator quadratus. We then reflect the pronator quadratus from the distal radial metaphysis until the most proximal and ulnar extent of the fracture is easily visualized. The palmar ulnar metaphyseal cortex that mates with the displaced sustentaculum lunatum is, in our experience, often the least comminuted portion of the metaphysis, thus providing a cortical key for restoration of height and alignment (Figures 5A, 5B). At our institution, fixation typically is achieved by contouring miniplates (1.3 or 1.5 mm) to capture and buttress the sustentaculum lunatum (Figures 6A, 6B). In our experience, the screw lengths in the most distal fixed-angle constructs at the palmar lip are limited to 6 mm or less to avoid penetration of the articular surface, though this has not been previously reported in the literature. After restoring the length and tilt of this intermediate column of the distal radius, we proceed with “rebuilding” the remainder of the fragments to our stabilized initial construct.

Various authors^40-43 have described alternative fixation methods for the palmar lunate facet fragment. Jupiter and Marent-Huber⁴² described 2.4-mm locked-plate fixation with either a standard palmar plate or T- or L-plates for cases in which the palmar lip fragment is very distal and small. In fact, some newer anatomical distal radius implants include features designed to target these fragments (Figures 7A, 7B). An alternative fixation method involves use of a 26-gauge stainless steel wire passed through drill holes in the metaphysis 1 cm proximal to the fracture and then passed through the palmar capsule just distal to the fragment and secured in figure-8 fashion while the fragment is manually held reduced.⁴¹ Still others have recommended limited internal fixation of the sustentaculum lunatum through an ulna-sided palmar approach to the distal radius (between the ulnar neurovascular bundle and the flexor tendons) combined with external fixation to restore length and palmar tilt in highly comminuted fractures.^40,43

A method involving arthroscopically assisted reduction and fixation of the lunate facet has also been described, though this procedure is technically demanding and has limited indications.⁴⁴ It uses a Freer elevator passed through the standard 3-4 portal after initial visualization and evacuation of hematoma. The Freer elevator is used to disimpact the sustentaculum lunatum and to elevate it from its depressed position. With the dorsal lunate facet left displaced to facilitate access to the palmar fragment, a nerve hook retractor is used to reduce the palmar facet to the radial styloid, and Kirschner wires are used to achieve interfragmentary fixation. The dorsal lunate fragment is then pieced back to the articular segment, and the entire construct is fixed to the radial metaphysis with additional Kirschner wires.

Discussion

Given the increasing incidence of fractures of the distal radius, internal fixation of these injuries will continue to be relevant. American Academy of Orthopaedic Surgeons guidelines recommend operative fixation for fractures with postreduction radial shortening of more than 3 mm, dorsal tilt of more than 10°, or intra-articular displacement or step-off of more than 2 mm.⁴⁵ Dr. Eglseder and Dr. Pensy indicate operative treatment of any incongruity of more than 2 mm in a young, active adult with a fracture of the distal radius. For the multifragmentary distal radius being treated operatively, attempts are made to achieve reduction more accurate than this, but formal dorsal exposure or direct visualization of the joint surface via dorsal capsulotomy is carefully chosen based on age, activity level, and bone quality. Recent high-level evidence⁴⁶ showed that closed treatment of unstable fractures of the distal radius results in good outcomes in the elderly. However, it is important to note that fractures displaced in a palmar direction and palmar shear patterns were excluded from that work. It is widely accepted that palmar carpal translation should be addressed with internal fixation, and specific attention must therefore be paid to the lunate facet as the cornerstone of the distal radius. Furthermore, high-energy comminuted fractures in young patients still necessitate internal fixation of fragments to restore alignment and articular congruity.

Conclusion

The importance of the palmar lunate facet in providing support and restraint to palmar carpal translation and the key role of this facet in restoring the anatomy of the distal radius have been known. This fragment deserves special attention because failure to adequately stabilize it results in loss of fixation and carpal subluxation. Various approaches and fixation techniques have been recommended, including the method we prefer and have described here. Our newly proposed term, sustentaculum lunatum, our review of its structure and function, and our descriptions of fixation techniques are intended to promote awareness of this fragment in the treatment of fractures of the distal radius.

Fracture of the distal radius is the wrist injury most often encountered by orthopedic and hand surgeons.¹ The number of fractures of the distal radius in the United States was estimated to be 640,000 in 2001, and the incidence is increasing.^2,3 Recent evidence has shown a substantial increase in treating these fractures with internal rather than closed fixation, even in the elderly.⁴

Treatment of complex intra-articular fractures of the distal radius requires an accurate diagnosis of the fracture pattern and a thoughtful approach to fixation. Although a majority of the fractures that meet the operative criteria are now treated with various anterior locked-plating techniques with good results, a subset requires more technically demanding fixation approaches, including fragment-specific approaches, dorsal and palmar plating, and combined internal and external fixation.

The sustentaculum lunatum, as we have named the palmar lunate facet, deserves specific attention because of its importance in load transmission across the radiocarpal joint and its key role in restoring the anatomy of the palmar distal radial metaphysis during internal fixation. This fragment in comminuted fractures was first ascribed special importance by Melone⁵ in his description of common fracture patterns. In the present article, we describe the anatomical characteristics of the sustentaculum lunatum and the clinical relevance of this fragment to management of fractures of the distal radius.

Classification

A variety of classification systems have been proposed to characterize and guide treatment of fractures of the distal radius. The earliest descriptions of fracture patterns were presented by Castaing⁶ and Frykman⁷ in the 1960s. The Frykman classification historically has been popular but is limited in accuracy in its characterization of fragments and their displacement and is limited in its ability to guide treatment. The classification system proposed by Melone and colleagues^5,8-10 was the first to truly describe fracture of the distal radius fragments in a relevant manner, including their characteristic “4 parts” (Figure 1). The authors emphasized the importance of the “medial complex” as the cornerstone of the radiocarpal and radioulnar joints.

The classification system developed by Müller and colleagues,¹¹ which was adopted by the AO (Arbeitsgemeinschaft für Osteosynthesefragen), might be the most descriptive and informative system, and it is widely used to conduct research and direct treatment. This system classifies fractures into A (extra-articular), B (partial articular), and C (complete articular) types and subclassifies them according to fracture location and comminution. These classifications, along with a conceptualization of the distal forearm as a 3-column structure involving the radial, ulnar, and intermediate columns (including the lunate facet), as proposed by Peine and colleagues,¹² gave us a framework for approaching fixation of fractures of the distal radius.

Etymology and Definition

Sustentaculum, from the Latin sustinere, “to support, check, or put off,” and taculum, “receptacle or holding space,” is a fitting description of the most distal portion of the palmar lunate facet, as it supports and holds the carpus, and specifically the lunate, on the radial articular surface. This portion is analogous to the sustentaculum tali, the named portion of the calcaneus that supports and articulates with the middle calcaneal articular surface of the talus¹³ and provides a reliable fragment for internal fixation of the calcaneus.

Anatomical and Biomechanical Considerations

The distal radial articular surface is composed of distinct scaphoid and lunate facets that articulate with their respective carpal bones. Several studies have characterized the anatomy of the distal radius.^14-17 Linscheid¹⁴ found that the lunate and scaphoid facets account for 46% and 43% of the contact area across the radiocarpal joint, respectively; this has been corroborated by others.¹⁵ A biomechanical study by Genda and Horii¹⁸ showed that the majority of stress across the wrist joint was concentrated at the palmar side of the distal radius in the neutral position. Although it is recognized that the scaphoid facet bears most of the load across the wrist in the neutral wrist position, most activities of daily living place the wrist in a slightly extended and ulnarly deviated position. This position results in a shift of the majority of load to the radiolunar articulation, constituting 53% of total force transmission.¹⁸ Subchondral bone density analyses have supported this lunate-predominant loading pattern across the radiocarpal articulation in most people.¹⁹ This loading pattern is also supported by the observation that failure of fixation and carpal subluxation generally occurs at the radiolunate articulation.

The palmar lip of the distal radius traditionally has been depicted and conceptualized as a flat extension of the metaphysis, leading to the development of implants that are not ideally designed for capturing this area in the fracture setting. A 3-dimensional (3-D) computed tomography (CT) study of the distal radii of healthy volunteers, conducted by Andermahr and colleagues,²⁰ showed that the contour of the palmar lunate facet projects from the palmar cortex of the radius by 3 mm on average and is about 19 mm in width (radial to ulnar dimension) (Figures 2A-2C). In the axial plane, the anterior cortex of the distal radius slopes in a palmar direction, from radial to ulnar. This presents a challenge in attempts to support the entire surface (scaphoid and lunate facets) with a single palmar implant.^20-25

A study conducted by Harness and colleagues²⁴ showed that the majority of palmar shear fractures are composed of multiple fragments of the lunar articular facet. Anatomical studies of the distal radiocarpal articulation have also described the ligamentous attachments to the sustentaculum lunatum.²⁶ The short radiolunate ligament, which originates from this fragment and inserts onto the lunate, provides stability to the carpus and, if not adequately fixed, leads to an incompetent restraint to palmar carpal translation. Isolated injuries of the short radiolunate ligament or fractures of the palmar lunate facet have been shown to result in palmar carpal translation.^27,28 In addition, attachments of the palmar radioulnar ligament and other more ulnar radiocarpal ligaments act as deforming forces on the palmar lunate facet.^24,26

Fracture Pattern Recognition

Although the AO type B palmar shear fracture pattern, also known as the Barton fracture, has classically been recognized as the fracture involving the palmar lunate facet and requiring special attention, many complete articular fractures feature involvement and fragmentation of this portion of the distal radius (Figures 3A-3F).²⁹ In highly comminuted complete articular and palmar shear fracture patterns, the morphology of the sustentaculum lunatum should be appreciated, and its adequate fixation to the radial metaphysis ensured, to prevent loss of reduction.

Visualization of the palmar lunate facet as a distinct fragment might be difficult in cases of highly comminuted fracture patterns. Standard CT or more recently described 3-D CT techniques with subtraction of the carpus might facilitate appreciation of this fragment for preoperative planning of approach and fixation.^29,30 Our institutional protocol involves obtaining preoperative traction radiographs of every fracture of the distal radius. These radiographs have reduced the need for CT in understanding the fracture pattern and aid in decision making.³¹

Besides appreciating the existence of the sustentaculum lunatum fragment, we should recognize that some injury patterns that split the lunate facet into unstable dorsal and palmar fragments might necessitate a separate dorsal approach to reduce and fix the dorsal lunate fragment. Traction radiographs can be especially useful in recognizing these patterns (a V sign is present) (Figures 4A, 4B).

Open Fractures

Highly comminuted fractures of the distal radius presenting with displaced lunate facet fragments can have high-energy mechanisms of injury. Although open fractures of the distal radius are associated with lower risk for infection (compared with open fractures of other long bones), they deserve special attention because of associated tendon and neurovascular injuries. Few studies have specifically assessed open fractures of the distal radius.^32-35 Only the study by Rozental and Blazar³⁴ listed associated injuries at the wrist level. The authors identified 4 patients (out of 18) with concomitant flexor tendon or neurovascular injuries that included radial or ulnar artery injury. In our experience, many open fractures of the distal radius are caused by an inside-out mechanism and present with an open wound either over the ulnar styloid or in the area of the ulnar side of the palmar radial metaphysis corresponding to the metaphyseal spike that mates with the sustentaculum lunatum (Figures 5A, 5B). Given these findings, we approach this intermediate column with particular care in cases of open fracture, paying attention to important structures (flexors, neurovascular) and looking for contamination from the environment into the fracture.

Fixation Techniques

The approach to fixation of partial articular palmar shear fractures is fairly straightforward. Buttress plate fixation has been well described and has had reliably good results.³⁶ However, in very distal fracture patterns and in cases in which the palmar lunate facet is fragmented as part of a complete articular fracture, a fragment-specific approach to fixation with or without spanning external fixation often is necessary.³⁷ The unrecognized sustentaculum lunatum fragment in comminuted complete articular fractures can lead to inadequate fixation constructs, resulting in loss of reduction and carpal subluxation in a palmar direction.^24,34,38

Our surgical approach uses the standard anterior interval between the radial artery and the flexor carpi radialis, as described by Henry.³⁹ The flexor pollicis longus is retracted ulnarly, revealing the pronator quadratus. We then reflect the pronator quadratus from the distal radial metaphysis until the most proximal and ulnar extent of the fracture is easily visualized. The palmar ulnar metaphyseal cortex that mates with the displaced sustentaculum lunatum is, in our experience, often the least comminuted portion of the metaphysis, thus providing a cortical key for restoration of height and alignment (Figures 5A, 5B). At our institution, fixation typically is achieved by contouring miniplates (1.3 or 1.5 mm) to capture and buttress the sustentaculum lunatum (Figures 6A, 6B). In our experience, the screw lengths in the most distal fixed-angle constructs at the palmar lip are limited to 6 mm or less to avoid penetration of the articular surface, though this has not been previously reported in the literature. After restoring the length and tilt of this intermediate column of the distal radius, we proceed with “rebuilding” the remainder of the fragments to our stabilized initial construct.

Various authors^40-43 have described alternative fixation methods for the palmar lunate facet fragment. Jupiter and Marent-Huber⁴² described 2.4-mm locked-plate fixation with either a standard palmar plate or T- or L-plates for cases in which the palmar lip fragment is very distal and small. In fact, some newer anatomical distal radius implants include features designed to target these fragments (Figures 7A, 7B). An alternative fixation method involves use of a 26-gauge stainless steel wire passed through drill holes in the metaphysis 1 cm proximal to the fracture and then passed through the palmar capsule just distal to the fragment and secured in figure-8 fashion while the fragment is manually held reduced.⁴¹ Still others have recommended limited internal fixation of the sustentaculum lunatum through an ulna-sided palmar approach to the distal radius (between the ulnar neurovascular bundle and the flexor tendons) combined with external fixation to restore length and palmar tilt in highly comminuted fractures.^40,43

A method involving arthroscopically assisted reduction and fixation of the lunate facet has also been described, though this procedure is technically demanding and has limited indications.⁴⁴ It uses a Freer elevator passed through the standard 3-4 portal after initial visualization and evacuation of hematoma. The Freer elevator is used to disimpact the sustentaculum lunatum and to elevate it from its depressed position. With the dorsal lunate facet left displaced to facilitate access to the palmar fragment, a nerve hook retractor is used to reduce the palmar facet to the radial styloid, and Kirschner wires are used to achieve interfragmentary fixation. The dorsal lunate fragment is then pieced back to the articular segment, and the entire construct is fixed to the radial metaphysis with additional Kirschner wires.

Discussion

Given the increasing incidence of fractures of the distal radius, internal fixation of these injuries will continue to be relevant. American Academy of Orthopaedic Surgeons guidelines recommend operative fixation for fractures with postreduction radial shortening of more than 3 mm, dorsal tilt of more than 10°, or intra-articular displacement or step-off of more than 2 mm.⁴⁵ Dr. Eglseder and Dr. Pensy indicate operative treatment of any incongruity of more than 2 mm in a young, active adult with a fracture of the distal radius. For the multifragmentary distal radius being treated operatively, attempts are made to achieve reduction more accurate than this, but formal dorsal exposure or direct visualization of the joint surface via dorsal capsulotomy is carefully chosen based on age, activity level, and bone quality. Recent high-level evidence⁴⁶ showed that closed treatment of unstable fractures of the distal radius results in good outcomes in the elderly. However, it is important to note that fractures displaced in a palmar direction and palmar shear patterns were excluded from that work. It is widely accepted that palmar carpal translation should be addressed with internal fixation, and specific attention must therefore be paid to the lunate facet as the cornerstone of the distal radius. Furthermore, high-energy comminuted fractures in young patients still necessitate internal fixation of fragments to restore alignment and articular congruity.

Conclusion

The importance of the palmar lunate facet in providing support and restraint to palmar carpal translation and the key role of this facet in restoring the anatomy of the distal radius have been known. This fragment deserves special attention because failure to adequately stabilize it results in loss of fixation and carpal subluxation. Various approaches and fixation techniques have been recommended, including the method we prefer and have described here. Our newly proposed term, sustentaculum lunatum, our review of its structure and function, and our descriptions of fixation techniques are intended to promote awareness of this fragment in the treatment of fractures of the distal radius.

“I have acute appendicitis,” I told my wife. “I need to go to the radiologist.”

A computed tomography (CT) scan of my abdomen confirmed my suspicion. After learning that I also had leukocytosis, we headed to the emergency department. The ED doctor was pleasantly surprised that someone had come to his facility completely evaluated. All he had to do was call the surgeon. But first he introduced me to a 4th-year medical student who was participating in a surgical rotation.

Prioritizing the EMR over the patient

The student wheeled his large computer to the side of my gurney and began to question me about my abdominal pain. Within 5 minutes, this unsupervised student had somehow acquired all the information he needed for my admission. He thanked me for my time and told me that he would see me in the operating room.

Unfortunately for him, I was not about to let him leave my cubicle without a redirect. I told him I have type 1 diabetes and several comorbidities. I wear an insulin pump and continuous glucose sensor that alerts me to impending hypoglycemia. I take 11 medications to successfully manage my metabolic disorders.

The student wheeled his machine back to the side of my gurney.

With his eyes fixed squarely on his computer and his finger on a mouse, he asked me to list all of my medications. He had never heard of a rapid-acting insulin analogue, nor was he familiar with my GLP-1 receptor agonist or SGLT2 inhibitor. And the pump and sensor? There were no check boxes for these devices in his electronic medical record (EMR).

He—like several of the doctors I met during my subsequent stay—suggested that I remove the pump and meter so that they could manage my diabetes.

Still in considerable pain, I suggested to the student and anyone else who would listen that my pump and sensor were off limits. As long as I was conscious, I would self-manage my diabetes.

I also told him that his history and physical exam were deficient. Although he did listen to my bowel sounds (or lack thereof) through a blanket and hospital gown, he overlooked examining my heart, lungs, eyes, mouth, and feet.

It frightens me to think what might have happened during my hospital stay if I hadn’t provided information that wasn’t required by the EMR.

“You failed to ask me about my medical history or my diabetes," I said. The student searched his EMR for the appropriate questions to ask, but to no avail. Stunned, he appeared to be at a loss of words. I suggested that he ask about the type of diabetes I had, the duration of the disease, how well my glucose levels were controlled, my most recent HbA1c, and if I had developed any long-term microvascular or macrovascular complications. He politely thanked me, moved the mouse around on his computer stand, and began to wheel his computer away.

“Wait!” I thought. “Don’t you think you should examine my eyes, mouth, and feet?” I reminded myself that this student hadn’t evaluated me for peritoneal signs. So why should I insist that he look at non-critical parts of my body?

My physical pain was increasing and I was becoming increasingly distressed. The student was more interested in inputting data into the EMR than learning about acute abdomens and type 1 diabetes.

Postop: From bad to worse

My postoperative course was dreadful. I nearly died from complications that included acute renal failure, dehydration, hypokalemia, and a postoperative ileus that persisted for 8 days. My blood glucose levels, however, were perfect. Still, the Attendings and the students blamed my complications on diabetes.

“Yeah, I see this all the time,” said the hospitalist who was caring for me. “Diabetes causes gastroparesis. What we should do is have you take off that pump and sensor device. We’ll have the pharmacist help you manage your diabetes.” The hospitalist who suggested this course of action was immediately relieved of his duties by my wife as I drifted in and out of consciousness in the intensive care unit (ICU).

Despite the state of my health, I began to provide professional guidance for my own care. I demanded that the nurse give me a 250 cc rider of normal saline and increase my IV flow rate from 50 cc to 150 cc. The nasogastric tube was removed and I began using IV erythromycin, which increases gastric motility. I received oral and IV potassium.

I suggested that the medical students needed to unplug their smart phones, computers, and iPads and spend a day or 2 with one of us “old-time docs.”

While in the ICU, I was questioned by physicians and medical students, but never examined. I am convinced that had I not been an experienced family physician, I would have suffered a fatal postoperative event. The medical students assigned to my care would not have known that I died, unless they received a notification via Twitter.

Providing care in a digital age

My experience as a patient was in stark contrast to the way I practice medicine.

I use an EMR only to e-prescribe, and have chosen not to participate in submitting meaningful use data to the government. Rather than spending 2 hours a day making eye contact with an EMR, I prefer to use that time to listen to my patients’ concerns about their health. I know how to conduct a review of systems and I touch my patients at each visit. I look at their feet, skin, and eyes, listen to their heart and lungs, and palpate their abdomen. I perform a rectal exam on every patient who presents with abdominal pain.

I have learned to communicate my suspicions and thoughts (both positive and negative) to all of my patients. I take notes on scratch paper, not on a computer, just as my grandfather and father used to do when they were practicing medicine. I only order tests to confirm a suspected diagnosis, not as a primary means of evaluating patients.

Could my hospital experience lead to change?

Upon my discharge from the hospital, I reached out to the director of clinical studies at the local medical school and explained the deficiencies I’d encountered. I explained that the 4th-year medical students were ill-equipped to perform an adequate history or physical exam. They lacked knowledge of basic pharmacology. And they failed to appropriately follow a patient during the perioperative period.

The director appreciated my concern and provided me with the details of a corrective action plan that she had been working on.

“We need to implement our patient simulation computer program designed to teach our students how to appropriately interact with their distressed patients,” she said.

Really?

I suggested that the medical students needed to unplug their smartphones, computers, and iPads. Let them spend a day or 2 with one of us “old-time docs” who still work with our hands—hands that are skilled at evaluating patients, rather than texting and data entry. We’ll show these students how to become caring, intelligent, and dedicated clinicians.

“I have acute appendicitis,” I told my wife. “I need to go to the radiologist.”

A computed tomography (CT) scan of my abdomen confirmed my suspicion. After learning that I also had leukocytosis, we headed to the emergency department. The ED doctor was pleasantly surprised that someone had come to his facility completely evaluated. All he had to do was call the surgeon. But first he introduced me to a 4th-year medical student who was participating in a surgical rotation.

Prioritizing the EMR over the patient

The student wheeled his large computer to the side of my gurney and began to question me about my abdominal pain. Within 5 minutes, this unsupervised student had somehow acquired all the information he needed for my admission. He thanked me for my time and told me that he would see me in the operating room.

Unfortunately for him, I was not about to let him leave my cubicle without a redirect. I told him I have type 1 diabetes and several comorbidities. I wear an insulin pump and continuous glucose sensor that alerts me to impending hypoglycemia. I take 11 medications to successfully manage my metabolic disorders.

The student wheeled his machine back to the side of my gurney.

With his eyes fixed squarely on his computer and his finger on a mouse, he asked me to list all of my medications. He had never heard of a rapid-acting insulin analogue, nor was he familiar with my GLP-1 receptor agonist or SGLT2 inhibitor. And the pump and sensor? There were no check boxes for these devices in his electronic medical record (EMR).

He—like several of the doctors I met during my subsequent stay—suggested that I remove the pump and meter so that they could manage my diabetes.

Still in considerable pain, I suggested to the student and anyone else who would listen that my pump and sensor were off limits. As long as I was conscious, I would self-manage my diabetes.

I also told him that his history and physical exam were deficient. Although he did listen to my bowel sounds (or lack thereof) through a blanket and hospital gown, he overlooked examining my heart, lungs, eyes, mouth, and feet.

It frightens me to think what might have happened during my hospital stay if I hadn’t provided information that wasn’t required by the EMR.

“You failed to ask me about my medical history or my diabetes," I said. The student searched his EMR for the appropriate questions to ask, but to no avail. Stunned, he appeared to be at a loss of words. I suggested that he ask about the type of diabetes I had, the duration of the disease, how well my glucose levels were controlled, my most recent HbA1c, and if I had developed any long-term microvascular or macrovascular complications. He politely thanked me, moved the mouse around on his computer stand, and began to wheel his computer away.

“Wait!” I thought. “Don’t you think you should examine my eyes, mouth, and feet?” I reminded myself that this student hadn’t evaluated me for peritoneal signs. So why should I insist that he look at non-critical parts of my body?

My physical pain was increasing and I was becoming increasingly distressed. The student was more interested in inputting data into the EMR than learning about acute abdomens and type 1 diabetes.

Postop: From bad to worse

My postoperative course was dreadful. I nearly died from complications that included acute renal failure, dehydration, hypokalemia, and a postoperative ileus that persisted for 8 days. My blood glucose levels, however, were perfect. Still, the Attendings and the students blamed my complications on diabetes.

“Yeah, I see this all the time,” said the hospitalist who was caring for me. “Diabetes causes gastroparesis. What we should do is have you take off that pump and sensor device. We’ll have the pharmacist help you manage your diabetes.” The hospitalist who suggested this course of action was immediately relieved of his duties by my wife as I drifted in and out of consciousness in the intensive care unit (ICU).

Despite the state of my health, I began to provide professional guidance for my own care. I demanded that the nurse give me a 250 cc rider of normal saline and increase my IV flow rate from 50 cc to 150 cc. The nasogastric tube was removed and I began using IV erythromycin, which increases gastric motility. I received oral and IV potassium.

I suggested that the medical students needed to unplug their smart phones, computers, and iPads and spend a day or 2 with one of us “old-time docs.”

While in the ICU, I was questioned by physicians and medical students, but never examined. I am convinced that had I not been an experienced family physician, I would have suffered a fatal postoperative event. The medical students assigned to my care would not have known that I died, unless they received a notification via Twitter.

Providing care in a digital age

My experience as a patient was in stark contrast to the way I practice medicine.

I use an EMR only to e-prescribe, and have chosen not to participate in submitting meaningful use data to the government. Rather than spending 2 hours a day making eye contact with an EMR, I prefer to use that time to listen to my patients’ concerns about their health. I know how to conduct a review of systems and I touch my patients at each visit. I look at their feet, skin, and eyes, listen to their heart and lungs, and palpate their abdomen. I perform a rectal exam on every patient who presents with abdominal pain.

I have learned to communicate my suspicions and thoughts (both positive and negative) to all of my patients. I take notes on scratch paper, not on a computer, just as my grandfather and father used to do when they were practicing medicine. I only order tests to confirm a suspected diagnosis, not as a primary means of evaluating patients.

Could my hospital experience lead to change?

Upon my discharge from the hospital, I reached out to the director of clinical studies at the local medical school and explained the deficiencies I’d encountered. I explained that the 4th-year medical students were ill-equipped to perform an adequate history or physical exam. They lacked knowledge of basic pharmacology. And they failed to appropriately follow a patient during the perioperative period.

The director appreciated my concern and provided me with the details of a corrective action plan that she had been working on.

“We need to implement our patient simulation computer program designed to teach our students how to appropriately interact with their distressed patients,” she said.

Really?

I suggested that the medical students needed to unplug their smartphones, computers, and iPads. Let them spend a day or 2 with one of us “old-time docs” who still work with our hands—hands that are skilled at evaluating patients, rather than texting and data entry. We’ll show these students how to become caring, intelligent, and dedicated clinicians.

“I have acute appendicitis,” I told my wife. “I need to go to the radiologist.”

A computed tomography (CT) scan of my abdomen confirmed my suspicion. After learning that I also had leukocytosis, we headed to the emergency department. The ED doctor was pleasantly surprised that someone had come to his facility completely evaluated. All he had to do was call the surgeon. But first he introduced me to a 4th-year medical student who was participating in a surgical rotation.

Prioritizing the EMR over the patient

The student wheeled his large computer to the side of my gurney and began to question me about my abdominal pain. Within 5 minutes, this unsupervised student had somehow acquired all the information he needed for my admission. He thanked me for my time and told me that he would see me in the operating room.

Unfortunately for him, I was not about to let him leave my cubicle without a redirect. I told him I have type 1 diabetes and several comorbidities. I wear an insulin pump and continuous glucose sensor that alerts me to impending hypoglycemia. I take 11 medications to successfully manage my metabolic disorders.

The student wheeled his machine back to the side of my gurney.

With his eyes fixed squarely on his computer and his finger on a mouse, he asked me to list all of my medications. He had never heard of a rapid-acting insulin analogue, nor was he familiar with my GLP-1 receptor agonist or SGLT2 inhibitor. And the pump and sensor? There were no check boxes for these devices in his electronic medical record (EMR).

He—like several of the doctors I met during my subsequent stay—suggested that I remove the pump and meter so that they could manage my diabetes.

Still in considerable pain, I suggested to the student and anyone else who would listen that my pump and sensor were off limits. As long as I was conscious, I would self-manage my diabetes.

I also told him that his history and physical exam were deficient. Although he did listen to my bowel sounds (or lack thereof) through a blanket and hospital gown, he overlooked examining my heart, lungs, eyes, mouth, and feet.

It frightens me to think what might have happened during my hospital stay if I hadn’t provided information that wasn’t required by the EMR.

“You failed to ask me about my medical history or my diabetes," I said. The student searched his EMR for the appropriate questions to ask, but to no avail. Stunned, he appeared to be at a loss of words. I suggested that he ask about the type of diabetes I had, the duration of the disease, how well my glucose levels were controlled, my most recent HbA1c, and if I had developed any long-term microvascular or macrovascular complications. He politely thanked me, moved the mouse around on his computer stand, and began to wheel his computer away.

“Wait!” I thought. “Don’t you think you should examine my eyes, mouth, and feet?” I reminded myself that this student hadn’t evaluated me for peritoneal signs. So why should I insist that he look at non-critical parts of my body?

My physical pain was increasing and I was becoming increasingly distressed. The student was more interested in inputting data into the EMR than learning about acute abdomens and type 1 diabetes.

Postop: From bad to worse

My postoperative course was dreadful. I nearly died from complications that included acute renal failure, dehydration, hypokalemia, and a postoperative ileus that persisted for 8 days. My blood glucose levels, however, were perfect. Still, the Attendings and the students blamed my complications on diabetes.

“Yeah, I see this all the time,” said the hospitalist who was caring for me. “Diabetes causes gastroparesis. What we should do is have you take off that pump and sensor device. We’ll have the pharmacist help you manage your diabetes.” The hospitalist who suggested this course of action was immediately relieved of his duties by my wife as I drifted in and out of consciousness in the intensive care unit (ICU).

Despite the state of my health, I began to provide professional guidance for my own care. I demanded that the nurse give me a 250 cc rider of normal saline and increase my IV flow rate from 50 cc to 150 cc. The nasogastric tube was removed and I began using IV erythromycin, which increases gastric motility. I received oral and IV potassium.

I suggested that the medical students needed to unplug their smart phones, computers, and iPads and spend a day or 2 with one of us “old-time docs.”

While in the ICU, I was questioned by physicians and medical students, but never examined. I am convinced that had I not been an experienced family physician, I would have suffered a fatal postoperative event. The medical students assigned to my care would not have known that I died, unless they received a notification via Twitter.

Providing care in a digital age

My experience as a patient was in stark contrast to the way I practice medicine.

I use an EMR only to e-prescribe, and have chosen not to participate in submitting meaningful use data to the government. Rather than spending 2 hours a day making eye contact with an EMR, I prefer to use that time to listen to my patients’ concerns about their health. I know how to conduct a review of systems and I touch my patients at each visit. I look at their feet, skin, and eyes, listen to their heart and lungs, and palpate their abdomen. I perform a rectal exam on every patient who presents with abdominal pain.

I have learned to communicate my suspicions and thoughts (both positive and negative) to all of my patients. I take notes on scratch paper, not on a computer, just as my grandfather and father used to do when they were practicing medicine. I only order tests to confirm a suspected diagnosis, not as a primary means of evaluating patients.

Could my hospital experience lead to change?

Upon my discharge from the hospital, I reached out to the director of clinical studies at the local medical school and explained the deficiencies I’d encountered. I explained that the 4th-year medical students were ill-equipped to perform an adequate history or physical exam. They lacked knowledge of basic pharmacology. And they failed to appropriately follow a patient during the perioperative period.

The director appreciated my concern and provided me with the details of a corrective action plan that she had been working on.

“We need to implement our patient simulation computer program designed to teach our students how to appropriately interact with their distressed patients,” she said.

Really?

I suggested that the medical students needed to unplug their smartphones, computers, and iPads. Let them spend a day or 2 with one of us “old-time docs” who still work with our hands—hands that are skilled at evaluating patients, rather than texting and data entry. We’ll show these students how to become caring, intelligent, and dedicated clinicians.

Perilunate injuries typically stem from a high-energy insult to the carpus. Because of their relative infrequency and often subtle radiographic and physical examination findings, these injuries are often undetected in the emergency department setting.¹ Early anatomic reduction of any carpal malalignment is essential. Even with optimal treatment, complications such as generalized wrist stiffness, diminished grip strength, and posttraumatic arthritis, commonly develop; however, recent studies suggest these issues are often well tolerated.^1-5 In this article, the diagnosis, treatment, and outcomes after perilunate injuries are examined. 

History and Physical Examination

Perilunate injuries result from high-energy trauma to the carpus. Patients with these injuries often present with vague wrist pain and loss of wrist motion. Their fingers are frequently held in slight flexion. The patient may complain of numbness and tingling in the median nerve distribution. An acute carpal tunnel syndrome can rapidly develop. The general belief is that acute carpal tunnel syndrome occurs more commonly in pure volar lunate dislocations than in dorsal perilunate dislocations. However, no studies compare the incidence of acute carpal tunnel syndrome in lunate versus perilunate dislocations.

Radiographic Evaluation

Standard radiographic evaluation of a potential perilunate injury includes posteroanterior (PA), lateral, and oblique views of the wrist (Figure 1). A scaphoid view (ie, PA view with the wrist in ulnar deviation) may also be helpful. The PA view is particularly helpful because it enables assessment of Gilula lines, which are imaginary lines drawn across the proximal and distal aspects of the proximal carpal row and the proximal aspect of the distal carpal row. These lines should appear as 3 smooth arcs running nearly parallel to each other.⁶ Any disruption in these lines suggests carpal incongruity. It may be possible to note a triangular-shaped lunate on the PA view, which is a sign of lunate dislocation.⁷ 

While the PA view is certainly useful, the lateral view is the most important in diagnosing a perilunate injury. The lateral view allows assessment of the collinearity of radius, lunate, and capitate. Any disruption in this collinearity strongly suggests a perilunate dislocation.^7,8 

Classification

Mayfield and colleagues^9,10 described 4 stages of perilunate instability proceeding from a radial to an ulnar direction around the lunate. Stage I involves disruption of the scapholunate joint, while stage II involves both the scapholunate and capitolunate joints. In stage III, the scapholunate, capitolunate, and lunotriquetral ligaments are disrupted, and the result is a perilunate dislocation, usually dorsal. Finally, in stage IV, all the ligaments surrounding the lunate are disrupted and the lunate dislocates, most often volarly.

Lastly, perilunate injuries can be classified as greater-arc injuries if concomitant fracture of the carpus occurs, lesser-arc injuries if the injury is purely ligamentous, or inferior-arc injuries if there is an associated fracture of the volar rim of the distal radius.⁸

Treatment

Closed Reduction

All acute perilunate dislocations should be managed initially with an attempted closed reduction.¹¹ If the injury is older than 72 hours, such an attempt may be futile. For any closed reduction performed in the emergency department setting, intravenous sedation is generally advised for muscle relaxation. Gentle traction with finger traps can also be used prior to the reduction attempt. For a dorsal perilunate dislocation, longitudinal traction followed by volar flexion of the wrist with volar pressure on the lunate and dorsal pressure on the capitate (ie, Tavernier’s maneuver) is required. Once reduction is complete, PA and lateral views of the wrist should be obtained to assess carpal alignment. If closed reduction is unsuccessful, an open reduction is required, although the timing of said procedure is an area of debate, which we will discuss later.^1,3 Restoration of anatomic carpal alignment is essential to optimizing outcome, although it does not guarantee a good overall result.

Open Reduction

If successful closed reduction is achieved, the patient can be immobilized temporarily in a short-arm plaster splint. However, open reduction and either pinning or internal fixation will be required to maintain this alignment. The exact timing of open reduction and fixation is debatable and often dictated by the absence or presence of median nerve symptoms.^1,3 If a patient with no median nerve symptoms undergoes a successful closed reduction, he or she may be stabilized surgically within 3 to 5 days (or longer) with either pins or headless screws. If closed reduction is unsuccessful, an open reduction should be done within 2 to 3 days. However, if the patient has progressive numbness in the median nerve distribution upon presentation that fails to improve or worsens despite a successful closed reduction, an urgent open reduction (within 24 hours) and carpal tunnel release should be performed to prevent permanent damage to the median nerve.

Once open reduction is undertaken, a dorsal, volar, and combined approach can be used.^2-4 In most cases the dorsal approach is selected first. A longitudinal incision is made over the dorsum of the wrist, centered on the Lister tubercle. Dissection occurs between the third and fourth dorsal compartments. After the capsule is exposed, reduction of the lunate to the capitate is confirmed. If any fractures are present in the carpus (eg, scaphoid), they are internally fixed. The scapholunate articulation is then addressed. In general, the scapholunate ligament is not disrupted with a transscaphoid perilunate dislocation. However, if the scapholunate ligament is disrupted, the joint should be reduced and pinned. Repair or reconstruction of the scapholunate ligament is performed. Finally, the lunotriquetral articulation is reduced and stabilized with pins. There are no studies that specifically suggest direct repair of the lunotriquetral ligament versus pinning of the lunotriquetral articulation, but the lunotriquetral ligament could be repaired in similar fashion to the scapholunate ligament at the surgeon’s discretion.

As an alternative to percutaneous pinning, intercarpal screw fixation can be used to stabilize the carpus. A 2007 study by Souer and colleagues¹² showed no substantial difference in outcome between the 2 methods of fixation. However, a second procedure is required to remove the screws.

The volar approach, if selected, is typically done second and performed via an extended carpal tunnel incision. It allows decompression of the carpal tunnel and enables repair of volar capsular ligaments (ie, long and short radiolunate ligaments, volar scapholunate ligament, and volar lunotriquetral ligament), which increases overall carpal stability. Currently, many surgeons favor a combined dorsal-volar approach for its efficacy.^2,3 Some use a dorsal approach in all patients and perform a volar procedure only if the patient has median nerve symptoms.⁴ However, Başar and colleagues¹³ report use of only the volar approach for treatment of perilunate injuries. The authors repaired the long and short radiolunate ligaments, volar scapholunate ligament, and volar lunotriquetral ligament. They reported reasonably good outcomes, which are equivalent to those reported in similar studies using dorsal or combined dorsal-volar approaches. However, no studies in the literature directly compare any of the different approaches with each other.

Postoperatively, patients are placed in a long-arm thumb-spica cast for 4 weeks, and then in a short-arm cast for 4 to 8 weeks (Figure 2). If present, pins are removed in 3 to 12 weeks, with most authors recommending removal at 8 weeks.^2,14

Lastly, carpal tunnel symptoms can develop late and even after a successful reduction and surgical stabilization. One theory is that a significant perilunate injury can create slightly higher baseline carpal tunnel pressures, which can compromise the blood flow to the median nerve and cause carpal tunnel symptoms. Additionally, it is possible that direct median nerve contusion and/or traction injury via a displaced lunate can also cause these symptoms. Whatever the inciting cause of median-nerve irritation, a delayed carpal tunnel release is sometimes required.

Conclusion

Outcomes after either perilunate or lunate dislocation are fair to good at best but can be optimized with prompt, appropriate treatment. Closed reduction and casting as definitive treatment has been abandoned because of frequent loss of reduction.¹² Early open reduction (ie, less than 3 days after injury) has been shown to be beneficial.^1,2 However, even those treated early and with anatomic restoration of carpal alignment can expect a loss of grip strength and a range of motion of approximately 70% compared with the contralateral side.^2-5 A recent study has suggested that lesser-arc injures generally have a poorer overall outcome than their greater-arc counterparts.¹⁵

More than half of all patients with perilunate injuries will develop radiographic signs of osteoarthritis, and some will require additional salvage procedures.3-5 Kremer and colleagues4 showed that overall results after perilunate injuries deteriorate with time. However, according to a paper by Forli and colleagues5 in which patients were followed a minimum of 10 years after their injuries, the authors found that, despite radiographic progression of arthritis, most patients maintained reasonable hand function.

Perilunate injuries typically stem from a high-energy insult to the carpus. Because of their relative infrequency and often subtle radiographic and physical examination findings, these injuries are often undetected in the emergency department setting.¹ Early anatomic reduction of any carpal malalignment is essential. Even with optimal treatment, complications such as generalized wrist stiffness, diminished grip strength, and posttraumatic arthritis, commonly develop; however, recent studies suggest these issues are often well tolerated.^1-5 In this article, the diagnosis, treatment, and outcomes after perilunate injuries are examined. 

History and Physical Examination

Perilunate injuries result from high-energy trauma to the carpus. Patients with these injuries often present with vague wrist pain and loss of wrist motion. Their fingers are frequently held in slight flexion. The patient may complain of numbness and tingling in the median nerve distribution. An acute carpal tunnel syndrome can rapidly develop. The general belief is that acute carpal tunnel syndrome occurs more commonly in pure volar lunate dislocations than in dorsal perilunate dislocations. However, no studies compare the incidence of acute carpal tunnel syndrome in lunate versus perilunate dislocations.

Radiographic Evaluation

Standard radiographic evaluation of a potential perilunate injury includes posteroanterior (PA), lateral, and oblique views of the wrist (Figure 1). A scaphoid view (ie, PA view with the wrist in ulnar deviation) may also be helpful. The PA view is particularly helpful because it enables assessment of Gilula lines, which are imaginary lines drawn across the proximal and distal aspects of the proximal carpal row and the proximal aspect of the distal carpal row. These lines should appear as 3 smooth arcs running nearly parallel to each other.⁶ Any disruption in these lines suggests carpal incongruity. It may be possible to note a triangular-shaped lunate on the PA view, which is a sign of lunate dislocation.⁷ 

While the PA view is certainly useful, the lateral view is the most important in diagnosing a perilunate injury. The lateral view allows assessment of the collinearity of radius, lunate, and capitate. Any disruption in this collinearity strongly suggests a perilunate dislocation.^7,8 

Classification

Mayfield and colleagues^9,10 described 4 stages of perilunate instability proceeding from a radial to an ulnar direction around the lunate. Stage I involves disruption of the scapholunate joint, while stage II involves both the scapholunate and capitolunate joints. In stage III, the scapholunate, capitolunate, and lunotriquetral ligaments are disrupted, and the result is a perilunate dislocation, usually dorsal. Finally, in stage IV, all the ligaments surrounding the lunate are disrupted and the lunate dislocates, most often volarly.

Lastly, perilunate injuries can be classified as greater-arc injuries if concomitant fracture of the carpus occurs, lesser-arc injuries if the injury is purely ligamentous, or inferior-arc injuries if there is an associated fracture of the volar rim of the distal radius.⁸

Treatment

Closed Reduction

All acute perilunate dislocations should be managed initially with an attempted closed reduction.¹¹ If the injury is older than 72 hours, such an attempt may be futile. For any closed reduction performed in the emergency department setting, intravenous sedation is generally advised for muscle relaxation. Gentle traction with finger traps can also be used prior to the reduction attempt. For a dorsal perilunate dislocation, longitudinal traction followed by volar flexion of the wrist with volar pressure on the lunate and dorsal pressure on the capitate (ie, Tavernier’s maneuver) is required. Once reduction is complete, PA and lateral views of the wrist should be obtained to assess carpal alignment. If closed reduction is unsuccessful, an open reduction is required, although the timing of said procedure is an area of debate, which we will discuss later.^1,3 Restoration of anatomic carpal alignment is essential to optimizing outcome, although it does not guarantee a good overall result.

Open Reduction

If successful closed reduction is achieved, the patient can be immobilized temporarily in a short-arm plaster splint. However, open reduction and either pinning or internal fixation will be required to maintain this alignment. The exact timing of open reduction and fixation is debatable and often dictated by the absence or presence of median nerve symptoms.^1,3 If a patient with no median nerve symptoms undergoes a successful closed reduction, he or she may be stabilized surgically within 3 to 5 days (or longer) with either pins or headless screws. If closed reduction is unsuccessful, an open reduction should be done within 2 to 3 days. However, if the patient has progressive numbness in the median nerve distribution upon presentation that fails to improve or worsens despite a successful closed reduction, an urgent open reduction (within 24 hours) and carpal tunnel release should be performed to prevent permanent damage to the median nerve.

Once open reduction is undertaken, a dorsal, volar, and combined approach can be used.^2-4 In most cases the dorsal approach is selected first. A longitudinal incision is made over the dorsum of the wrist, centered on the Lister tubercle. Dissection occurs between the third and fourth dorsal compartments. After the capsule is exposed, reduction of the lunate to the capitate is confirmed. If any fractures are present in the carpus (eg, scaphoid), they are internally fixed. The scapholunate articulation is then addressed. In general, the scapholunate ligament is not disrupted with a transscaphoid perilunate dislocation. However, if the scapholunate ligament is disrupted, the joint should be reduced and pinned. Repair or reconstruction of the scapholunate ligament is performed. Finally, the lunotriquetral articulation is reduced and stabilized with pins. There are no studies that specifically suggest direct repair of the lunotriquetral ligament versus pinning of the lunotriquetral articulation, but the lunotriquetral ligament could be repaired in similar fashion to the scapholunate ligament at the surgeon’s discretion.

As an alternative to percutaneous pinning, intercarpal screw fixation can be used to stabilize the carpus. A 2007 study by Souer and colleagues¹² showed no substantial difference in outcome between the 2 methods of fixation. However, a second procedure is required to remove the screws.

The volar approach, if selected, is typically done second and performed via an extended carpal tunnel incision. It allows decompression of the carpal tunnel and enables repair of volar capsular ligaments (ie, long and short radiolunate ligaments, volar scapholunate ligament, and volar lunotriquetral ligament), which increases overall carpal stability. Currently, many surgeons favor a combined dorsal-volar approach for its efficacy.^2,3 Some use a dorsal approach in all patients and perform a volar procedure only if the patient has median nerve symptoms.⁴ However, Başar and colleagues¹³ report use of only the volar approach for treatment of perilunate injuries. The authors repaired the long and short radiolunate ligaments, volar scapholunate ligament, and volar lunotriquetral ligament. They reported reasonably good outcomes, which are equivalent to those reported in similar studies using dorsal or combined dorsal-volar approaches. However, no studies in the literature directly compare any of the different approaches with each other.

Postoperatively, patients are placed in a long-arm thumb-spica cast for 4 weeks, and then in a short-arm cast for 4 to 8 weeks (Figure 2). If present, pins are removed in 3 to 12 weeks, with most authors recommending removal at 8 weeks.^2,14

Lastly, carpal tunnel symptoms can develop late and even after a successful reduction and surgical stabilization. One theory is that a significant perilunate injury can create slightly higher baseline carpal tunnel pressures, which can compromise the blood flow to the median nerve and cause carpal tunnel symptoms. Additionally, it is possible that direct median nerve contusion and/or traction injury via a displaced lunate can also cause these symptoms. Whatever the inciting cause of median-nerve irritation, a delayed carpal tunnel release is sometimes required.

Conclusion

Outcomes after either perilunate or lunate dislocation are fair to good at best but can be optimized with prompt, appropriate treatment. Closed reduction and casting as definitive treatment has been abandoned because of frequent loss of reduction.¹² Early open reduction (ie, less than 3 days after injury) has been shown to be beneficial.^1,2 However, even those treated early and with anatomic restoration of carpal alignment can expect a loss of grip strength and a range of motion of approximately 70% compared with the contralateral side.^2-5 A recent study has suggested that lesser-arc injures generally have a poorer overall outcome than their greater-arc counterparts.¹⁵

More than half of all patients with perilunate injuries will develop radiographic signs of osteoarthritis, and some will require additional salvage procedures.3-5 Kremer and colleagues4 showed that overall results after perilunate injuries deteriorate with time. However, according to a paper by Forli and colleagues5 in which patients were followed a minimum of 10 years after their injuries, the authors found that, despite radiographic progression of arthritis, most patients maintained reasonable hand function.

Perilunate injuries typically stem from a high-energy insult to the carpus. Because of their relative infrequency and often subtle radiographic and physical examination findings, these injuries are often undetected in the emergency department setting.¹ Early anatomic reduction of any carpal malalignment is essential. Even with optimal treatment, complications such as generalized wrist stiffness, diminished grip strength, and posttraumatic arthritis, commonly develop; however, recent studies suggest these issues are often well tolerated.^1-5 In this article, the diagnosis, treatment, and outcomes after perilunate injuries are examined. 

History and Physical Examination

Perilunate injuries result from high-energy trauma to the carpus. Patients with these injuries often present with vague wrist pain and loss of wrist motion. Their fingers are frequently held in slight flexion. The patient may complain of numbness and tingling in the median nerve distribution. An acute carpal tunnel syndrome can rapidly develop. The general belief is that acute carpal tunnel syndrome occurs more commonly in pure volar lunate dislocations than in dorsal perilunate dislocations. However, no studies compare the incidence of acute carpal tunnel syndrome in lunate versus perilunate dislocations.

Radiographic Evaluation

Standard radiographic evaluation of a potential perilunate injury includes posteroanterior (PA), lateral, and oblique views of the wrist (Figure 1). A scaphoid view (ie, PA view with the wrist in ulnar deviation) may also be helpful. The PA view is particularly helpful because it enables assessment of Gilula lines, which are imaginary lines drawn across the proximal and distal aspects of the proximal carpal row and the proximal aspect of the distal carpal row. These lines should appear as 3 smooth arcs running nearly parallel to each other.⁶ Any disruption in these lines suggests carpal incongruity. It may be possible to note a triangular-shaped lunate on the PA view, which is a sign of lunate dislocation.⁷ 

While the PA view is certainly useful, the lateral view is the most important in diagnosing a perilunate injury. The lateral view allows assessment of the collinearity of radius, lunate, and capitate. Any disruption in this collinearity strongly suggests a perilunate dislocation.^7,8 

Classification

Mayfield and colleagues^9,10 described 4 stages of perilunate instability proceeding from a radial to an ulnar direction around the lunate. Stage I involves disruption of the scapholunate joint, while stage II involves both the scapholunate and capitolunate joints. In stage III, the scapholunate, capitolunate, and lunotriquetral ligaments are disrupted, and the result is a perilunate dislocation, usually dorsal. Finally, in stage IV, all the ligaments surrounding the lunate are disrupted and the lunate dislocates, most often volarly.

Lastly, perilunate injuries can be classified as greater-arc injuries if concomitant fracture of the carpus occurs, lesser-arc injuries if the injury is purely ligamentous, or inferior-arc injuries if there is an associated fracture of the volar rim of the distal radius.⁸

Treatment

Closed Reduction

All acute perilunate dislocations should be managed initially with an attempted closed reduction.¹¹ If the injury is older than 72 hours, such an attempt may be futile. For any closed reduction performed in the emergency department setting, intravenous sedation is generally advised for muscle relaxation. Gentle traction with finger traps can also be used prior to the reduction attempt. For a dorsal perilunate dislocation, longitudinal traction followed by volar flexion of the wrist with volar pressure on the lunate and dorsal pressure on the capitate (ie, Tavernier’s maneuver) is required. Once reduction is complete, PA and lateral views of the wrist should be obtained to assess carpal alignment. If closed reduction is unsuccessful, an open reduction is required, although the timing of said procedure is an area of debate, which we will discuss later.^1,3 Restoration of anatomic carpal alignment is essential to optimizing outcome, although it does not guarantee a good overall result.

Open Reduction

If successful closed reduction is achieved, the patient can be immobilized temporarily in a short-arm plaster splint. However, open reduction and either pinning or internal fixation will be required to maintain this alignment. The exact timing of open reduction and fixation is debatable and often dictated by the absence or presence of median nerve symptoms.^1,3 If a patient with no median nerve symptoms undergoes a successful closed reduction, he or she may be stabilized surgically within 3 to 5 days (or longer) with either pins or headless screws. If closed reduction is unsuccessful, an open reduction should be done within 2 to 3 days. However, if the patient has progressive numbness in the median nerve distribution upon presentation that fails to improve or worsens despite a successful closed reduction, an urgent open reduction (within 24 hours) and carpal tunnel release should be performed to prevent permanent damage to the median nerve.

Once open reduction is undertaken, a dorsal, volar, and combined approach can be used.^2-4 In most cases the dorsal approach is selected first. A longitudinal incision is made over the dorsum of the wrist, centered on the Lister tubercle. Dissection occurs between the third and fourth dorsal compartments. After the capsule is exposed, reduction of the lunate to the capitate is confirmed. If any fractures are present in the carpus (eg, scaphoid), they are internally fixed. The scapholunate articulation is then addressed. In general, the scapholunate ligament is not disrupted with a transscaphoid perilunate dislocation. However, if the scapholunate ligament is disrupted, the joint should be reduced and pinned. Repair or reconstruction of the scapholunate ligament is performed. Finally, the lunotriquetral articulation is reduced and stabilized with pins. There are no studies that specifically suggest direct repair of the lunotriquetral ligament versus pinning of the lunotriquetral articulation, but the lunotriquetral ligament could be repaired in similar fashion to the scapholunate ligament at the surgeon’s discretion.

As an alternative to percutaneous pinning, intercarpal screw fixation can be used to stabilize the carpus. A 2007 study by Souer and colleagues¹² showed no substantial difference in outcome between the 2 methods of fixation. However, a second procedure is required to remove the screws.

The volar approach, if selected, is typically done second and performed via an extended carpal tunnel incision. It allows decompression of the carpal tunnel and enables repair of volar capsular ligaments (ie, long and short radiolunate ligaments, volar scapholunate ligament, and volar lunotriquetral ligament), which increases overall carpal stability. Currently, many surgeons favor a combined dorsal-volar approach for its efficacy.^2,3 Some use a dorsal approach in all patients and perform a volar procedure only if the patient has median nerve symptoms.⁴ However, Başar and colleagues¹³ report use of only the volar approach for treatment of perilunate injuries. The authors repaired the long and short radiolunate ligaments, volar scapholunate ligament, and volar lunotriquetral ligament. They reported reasonably good outcomes, which are equivalent to those reported in similar studies using dorsal or combined dorsal-volar approaches. However, no studies in the literature directly compare any of the different approaches with each other.

Postoperatively, patients are placed in a long-arm thumb-spica cast for 4 weeks, and then in a short-arm cast for 4 to 8 weeks (Figure 2). If present, pins are removed in 3 to 12 weeks, with most authors recommending removal at 8 weeks.^2,14

Lastly, carpal tunnel symptoms can develop late and even after a successful reduction and surgical stabilization. One theory is that a significant perilunate injury can create slightly higher baseline carpal tunnel pressures, which can compromise the blood flow to the median nerve and cause carpal tunnel symptoms. Additionally, it is possible that direct median nerve contusion and/or traction injury via a displaced lunate can also cause these symptoms. Whatever the inciting cause of median-nerve irritation, a delayed carpal tunnel release is sometimes required.

Conclusion

Outcomes after either perilunate or lunate dislocation are fair to good at best but can be optimized with prompt, appropriate treatment. Closed reduction and casting as definitive treatment has been abandoned because of frequent loss of reduction.¹² Early open reduction (ie, less than 3 days after injury) has been shown to be beneficial.^1,2 However, even those treated early and with anatomic restoration of carpal alignment can expect a loss of grip strength and a range of motion of approximately 70% compared with the contralateral side.^2-5 A recent study has suggested that lesser-arc injures generally have a poorer overall outcome than their greater-arc counterparts.¹⁵

More than half of all patients with perilunate injuries will develop radiographic signs of osteoarthritis, and some will require additional salvage procedures.3-5 Kremer and colleagues4 showed that overall results after perilunate injuries deteriorate with time. However, according to a paper by Forli and colleagues5 in which patients were followed a minimum of 10 years after their injuries, the authors found that, despite radiographic progression of arthritis, most patients maintained reasonable hand function.

Family physicians are on the frontline for depression care, often being the first line of defense for diagnosis and management. This 1.25-hour, CME-certified activity will provide clinicians with a comprehensive review on the following:

• Clinical factors in the primary care setting that influence treatment outcomes in major depressive disorder
• Identification and management of residual symptoms
• Tools for effective monitoring of treatment outcomes
• Nonpharmacologic and pharmacologic therapies to treat patients to goal: remission and recovery
• Strategies to promote patient-focused, recovery-oriented care.

Click here to read the supplement.

After reading the supplement, click here to visit www.rapidcme.com/clinibriefs.aspx and complete the posttest and evaluation form for CME credit.

Family physicians are on the frontline for depression care, often being the first line of defense for diagnosis and management. This 1.25-hour, CME-certified activity will provide clinicians with a comprehensive review on the following:

• Clinical factors in the primary care setting that influence treatment outcomes in major depressive disorder
• Identification and management of residual symptoms
• Tools for effective monitoring of treatment outcomes
• Nonpharmacologic and pharmacologic therapies to treat patients to goal: remission and recovery
• Strategies to promote patient-focused, recovery-oriented care.

Click here to read the supplement.

After reading the supplement, click here to visit www.rapidcme.com/clinibriefs.aspx and complete the posttest and evaluation form for CME credit.

Family physicians are on the frontline for depression care, often being the first line of defense for diagnosis and management. This 1.25-hour, CME-certified activity will provide clinicians with a comprehensive review on the following:

• Clinical factors in the primary care setting that influence treatment outcomes in major depressive disorder
• Identification and management of residual symptoms
• Tools for effective monitoring of treatment outcomes
• Nonpharmacologic and pharmacologic therapies to treat patients to goal: remission and recovery
• Strategies to promote patient-focused, recovery-oriented care.

Click here to read the supplement.

After reading the supplement, click here to visit www.rapidcme.com/clinibriefs.aspx and complete the posttest and evaluation form for CME credit.

CASE 1 › Judy C is a newly employed 40-year-old health care worker who was born in China and received the bacille Calmette-Guérin (BCG) vaccination as a child. Her new employer requires her to undergo testing for tuberculosis (TB). Her initial tuberculin skin test (TST) is 0 mm, but on a second TST 2 weeks later, it is 8 mm. She is otherwise healthy, negative for human immunodeficiency virus (HIV), and has no constitutional symptoms. Does she have latent tuberculosis infection (LTBI)?

CASE 2 › A mom brings in her 3-year-old son, Patrick. She reports that a staff member at his day care center traveled outside the country for 3 months and was diagnosed with LTBI upon her return. She wants to know if her son should be tested.

More than 2 billion people—nearly one-third of the world’s population—are infected with Mycobacterium tuberculosis.¹ Most harbor the bacilli as LTBI, which means that while they have living TB bacilli within their bodies, these mycobacteria are kept dormant by an intact immune system. These individuals are not contagious, nor are they likely to become ill from active TB unless something adversely affects their immune system and increases the likelihood that LTBI will progress to active TB.

Two tests are available for diagnosing LTBI: the TST and the newer interferon gamma release assay (IGRA). Each test has advantages and disadvantages, and the best test to use depends on various patient-specific factors. This article describes whom you should test for LTBI, which test to use, and how to diagnose active TB.

Why test for LTBI?

LTBI is an asymptomatic infection; patients with LTBI have a 5% to 10% lifetime risk of developing active TB.² The risk of developing active TB is approximately 5% within the first 18 months of infection, and the remaining risk is spread out over the rest of the patient’s life.² Screening for LTBI is desirable because early diagnosis and treatment can reduce the activation risk to 1% to 2%,³ and treatment for LTBI is simpler, less costly, and less toxic than treatment for active TB.

Whom to test. Screening for LTBI should target patients for whom the benefits of treatment outweigh the cost and risks of treatment.⁴ A decision to screen for LTBI implies that the patient will be treated if he or she tests positive.³

The benefit of treatment increases in people who have a significant risk of progression to active TB—primarily those with recently acquired LTBI, or with co-existing conditions that increase their likelihood of progression (TABLE 1).⁵

Screening for latent TB infection is desirable because early diagnosis and treatment can reduce the activation risk to 1% to 2%.

All household contacts of patients with active TB and recent immigrants from countries with a high TB prevalence should be tested for LTBI.⁶ Those with a negative test and recent exposure should be retested in 8 to 12 weeks to allow for the delay in conversion to a positive test after recent infection.⁷ Health care workers and others who are potentially exposed to active TB on an ongoing basis should be tested at the time of employment, with repeat testing done periodically based on their risk of infection.^8,9

Individuals with coexisting conditions should be tested for LTBI as long as the benefit of treatment outweighs the risk of drug-induced hepatitis. Because the risk of drug-induced hepatitis increases with age, the decision to test/treat is affected by age as well as the individual’s risk of progression. Patients with the highest risk conditions would benefit from testing/treating regardless of age, while treatment may not be justified in those with lower-risk conditions. A reasonable strategy is as follows:¹⁰
• high-risk conditions: test regardless of age
• moderate-risk conditions: test those <65 years
• low-risk conditions: test those <50 years.

Children with LTBI are at particularly high risk of progression to active TB.⁵ The American Academy of Pediatrics (AAP) recommends assessing a child’s risk for TB at first contact with the child and once every 6 months for the first year of life. After one year, annual assessment is recommended, but specific TB testing is not required for children who don’t have risk factors.¹¹ The AAP suggests using a TB risk assessment questionnaire that consists of 4 screening questions with follow-up questions if any of the screening questions are positive (TABLE 2).¹¹

Use of TST is well established

To perform a TST, inject 5 tuberculin units (0.1 mL) of purified protein derivative (PPD) intradermally into the inner surface of the forearm using a 27- to 30-gauge needle. (In the United States, PPD is available as Aplisol or Tubersol.) Avoid the former practice of “control” or anergy testing with mumps or Candida antigens because this is rarely helpful in making TB treatment decisions, even in HIV-positive patients.¹²

To facilitate intradermal injection, gently stretch the skin taut during injection. Raising a wheal confirms correct placement. The test should be read 48 to 72 hours after it is administered by measuring the greatest diameter of induration at the administration site. (Erythema is irrelevant to how the test is interpreted.) Induration is best read by using a ballpoint pen held at a 45-degree angle pointing toward the injection site. Roll the point of the pen over the skin with gentle pressure toward the injection site until induration causes the pen to stop rolling freely (FIGURE). The induration should be measured with a rule that has millimeter measurements and interpreted as positive or negative based on the individual’s risk factors (TABLE 3).³

Watch for these 2 factors that can affect TST results

Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is (or has been) used as a routine childhood immunization in many parts of the world, although not in the United States.¹³ It is ordinarily given as a single dose shortly after birth, and has some utility in preventing serious childhood TB infection. The antigens in PPD and those in BCG are not identical, but they do overlap.

BCG administered after an individual’s first birthday resulted in false positive TSTs >10 mm in 21% of those tested more than 10 years after BCG was administered.¹⁴ However, a single BCG vaccine in infancy causes little if any change in the TST result in individuals who are older than age 10 years. When a TST is performed for appropriate reasons, a positive TST in people previously vaccinated with BCG is generally more likely to be the result of LTBI than of BCG.¹⁵ Current guidelines from the Centers for Disease Control and Prevention (CDC) recommend that previous BCG status not change the cutoffs used for interpreting TST results.¹⁶

Booster phenomenon. In many adults who have undiagnosed LTBI that they acquired in the distant past, or who received BCG vaccination as a child, immunity wanes after several decades. This can result in an initial TST being negative, but because the antigens in the PPD itself stimulate antigenic memory, the next time a TST is performed, it may be positive.

In people who will have annual TST screenings, such as health care workers or nursing home residents, a 2-step PPD can help discriminate this “booster” phenomenon from a new LTBI acquired during the first year of annual TST testing. A second TST is placed 1 to 2 weeks after the initial test, a time interval during which acquisition of LTBI would be unlikely. The result of the second test should be considered the person’s baseline for evaluation of subsequent TSTs. A subsequent TST would be considered positive if the induration is >10 mm and has increased by ≥6 mm since the previous baseline.¹⁷

IGRA offers certain benefits

IGRA uses antigens that are more specific for Mycobacterium tuberculosis than the TST, and as a result, this test is not influenced by previous BCG vaccination. It requires only one blood draw, and interpretation does not depend on the patient’s risk category or interpretation of skin induration. The primary disadvantage of IGRAs is high cost (currently $200 to $300 per test), and the need for a laboratory with adequate equipment and personnel trained in performing the test. IGRAs must be collected in special blood tubes, and the samples must be processed within 8 to 16 hours of collection, depending on the test used.⁵

Currently, 2 IGRAs are approved for use in the United States—the QuantiFERON-TB Gold In-Tube (QFT-GIT) and the T-SPOT.TB assay. Both tests may produce false positives in patients infected with Mycobacterium marinum or Mycobacterium kansasii, but otherwise are highly specific for Mycobacterium tuberculosis. IGRA results may be “boosted” by recent TST (ie, a TST given within the previous 3 months may cause a false positive IGRA result), and this effect may begin as early as 3 days after a TST is administered.¹⁸ Therefore, if an IGRA is needed to clarify a TST result, it should be drawn on the day the TST is read.¹⁹

CDC guidelines (2010) recommend that IGRAs may be used in place of—but not routinely in addition to—TSTs in all cases in which TST is otherwise indicated.²⁰ There are a few situations where one test may be preferred over the other.²¹

IGRA may be preferred over TST in individuals in one of 2 categories:
• those who have received BCG immunization. If a patient is unsure of their BCG status, the World Atlas of BCG Policies and Practices, available at www.bcgatlas.org,²² can aid clinicians in determining which patients likely received BCG as part of their routine childhood immunizations.
• those in groups that historically have poor rates of return for TST reading, such as individuals who are homeless or suffer from alcoholism or a substance use disorder.

Individuals in whom TST is preferred over IGRA include:
• children age <5 years, because data guiding use of IGRAs in this age group are limited.²³ Both TST and IGRA may be falsely negative in children under the age of 3 months.²⁴
• patients who require serial testing, because individuals with positive IGRAs have been shown to commonly test negative on subsequent tests, and there are limited data on interpretation and prognosis of positive IGRAs in people who require serial testing.²⁵

Individuals in whom performing both tests simultaneously could be helpful include:
• those with an initial negative test, but with a high risk for progression to active TB or a poor outcome if the first result is falsely negative (eg, patients with HIV infection or children ages <5 years who have been exposed to a person with active TB)
• those with an initial positive test who don’t believe the test result and are reluctant to be treated for LTBI.

TST and IGRA have comparable sensitivities—around 80% to 90%, respectively—for diagnosing LTBI. IGRAs have a specificity >95% for diagnosing LTBI. While TST specificity is approximately 97% in patients not vaccinated with BCG, it can be as low as 60% in people previously vaccinated with BCG.²⁶ IGRAs have been shown to have higher positive and negative predictive values than TSTs in high-risk patients.²⁷ A recent study suggested that the IGRAs might have a higher rate of false-positive results compared to TSTs in a low-risk population of health care workers.²⁸

Both the TST and IGRA have lag times of 3 to 8 weeks from the time of a new infection until the test becomes positive. It is therefore best to defer testing for LTBI infection until at least 8 weeks after a known TB exposure to decrease the likelihood of a false-negative test.³

Diagnose active TB based on symptoms, culture

The CDC reported 9412 new cases of active TB in the United States in 2014, for a rate of 3 new cases per 100,000 people.²⁹ This is the lowest rate reported since national reporting began in 1953, when the incidence in the United States was 53 cases per 100,000.

Who should you test for active TB? The risk factors for active TB are the same as those for LTBI: recent exposure to an individual with active TB, and other disease processes or medications that compromise the immune system. Consider active TB when a patient with one of these risk factors presents with:²
• persistent fever
• weight loss
• night sweats
• cough, especially if there is any blood.

Routine laboratory and radiographic studies that should prompt you to consider TB include:²
• upper lobe infiltrates on chest x-ray
• sterile pyuria on urinalysis with a negative culture for routine pathogens
• elevated levels of C-reactive protein or an elevated erythrocyte sedimentation rate without another obvious cause.

Active TB typically presents as pulmonary TB, but it can also affect nearly every other body system. Other common presentations include:³⁰
• vertebral destruction and collapse (“Pott's disease”)
• subacute meningitis
• peritonitis
• lymphadenopathy (especially in children).

IGRAs have been shown to have higher positive and negative predictive values than TSTs in high-risk patients.

Culture is the gold standard. Neither TST or IGRA should ever be relied upon to make or exclude the diagnosis of active TB, as these tests are neither sensitive nor specific for diagnosing active TB.^31,32 Instead, the gold standard for the diagnosis of active TB remains a positive culture from infected tissue—commonly sputum, pleura or pleural fluid, cerebrospinal fluid, urine, or peritoneal fluid. Cultures are crucial not only to confirm the diagnosis, but to guide therapy, because of the rapidly increasing resistance to firstline antibiotics used to treat TB.³³

Culture results and drug sensitivities are ordinarily not available until 2 to 6 weeks after the culture was obtained. A smear for acid-fast bacilli as well as newer rapid diagnostic tests such as nucleic acid amplification (NAA) tests are generally performed on the tissue sample submitted for culture, and these results, while less trustworthy, are generally available within 24 to 48 hours. The CDC recommends that an NAA test be performed in addition to microscopy and culture for specimens submitted for TB diagnosis.³⁴

A single BCG vaccine in infancy causes little if any change in the TST result in individuals who are older than 10 years of age.

Since 2011, the World Health Organization has endorsed the use of a new molecular diagnostic test called Xpert MTB/RIF in settings with high prevalence of HIV infection or multidrug-resistant TB (MDR-TB).³⁵ This test is able to detect M. tuberculosis as well as rifampin resistance, a surrogate for MDR-TB, within 2 hours, with sensitivity and specificity approaching that of culture.³⁶

“Culture-negative” TB? A small but not insignificant proportion of patients will present with risk factors for, and clinical signs and symptoms of, active TB; their cultures, however, will be negative. In such cases, consultation with an infectious disease or pulmonary specialist may be warranted. If no alternative diagnosis is found, such patients are said to have “culture-negative active TB” and should be continued on anti-TB drug therapy, although the course may be shortened.³⁷ This highlights the fact that while cultures are key to diagnosing and treating active TB, the condition is—practically speaking—a clinical diagnosis; treatment should not be withheld or stopped simply because of a negative culture or rapid diagnostic test.

CASE 1 › Based on her risk factors (being a health care worker, born in a country with a high prevalence of TB), Ms. C’s cutoff for a positive test is >10 mm, so her TST result is negative and she is not considered to have LTBI. The increase to 8 mm seen on the second TST probably represents either childhood BCG vaccination or previous infection with nontuberculous Mycobacterium.

CASE 2 › Strictly speaking, 3-year-old Patrick does not need testing, because he was exposed only to LTBI, which is not infectious. However, because children under age 5 are at particularly high risk for progressing to active TB and poor outcomes, it would be best to confirm the mother’s story with the day care center and/or health department. If it turns out that Patrick had, in fact, been exposed to active TB, much more aggressive management would be required.

CORRESPONDENCE
Jeff Hall, MD, Family Medicine Center, 3209 Colonial Drive Columbia, SC 29203; [email protected]

CASE 1 › Judy C is a newly employed 40-year-old health care worker who was born in China and received the bacille Calmette-Guérin (BCG) vaccination as a child. Her new employer requires her to undergo testing for tuberculosis (TB). Her initial tuberculin skin test (TST) is 0 mm, but on a second TST 2 weeks later, it is 8 mm. She is otherwise healthy, negative for human immunodeficiency virus (HIV), and has no constitutional symptoms. Does she have latent tuberculosis infection (LTBI)?

CASE 2 › A mom brings in her 3-year-old son, Patrick. She reports that a staff member at his day care center traveled outside the country for 3 months and was diagnosed with LTBI upon her return. She wants to know if her son should be tested.

More than 2 billion people—nearly one-third of the world’s population—are infected with Mycobacterium tuberculosis.¹ Most harbor the bacilli as LTBI, which means that while they have living TB bacilli within their bodies, these mycobacteria are kept dormant by an intact immune system. These individuals are not contagious, nor are they likely to become ill from active TB unless something adversely affects their immune system and increases the likelihood that LTBI will progress to active TB.

Two tests are available for diagnosing LTBI: the TST and the newer interferon gamma release assay (IGRA). Each test has advantages and disadvantages, and the best test to use depends on various patient-specific factors. This article describes whom you should test for LTBI, which test to use, and how to diagnose active TB.

Why test for LTBI?

LTBI is an asymptomatic infection; patients with LTBI have a 5% to 10% lifetime risk of developing active TB.² The risk of developing active TB is approximately 5% within the first 18 months of infection, and the remaining risk is spread out over the rest of the patient’s life.² Screening for LTBI is desirable because early diagnosis and treatment can reduce the activation risk to 1% to 2%,³ and treatment for LTBI is simpler, less costly, and less toxic than treatment for active TB.

Whom to test. Screening for LTBI should target patients for whom the benefits of treatment outweigh the cost and risks of treatment.⁴ A decision to screen for LTBI implies that the patient will be treated if he or she tests positive.³

The benefit of treatment increases in people who have a significant risk of progression to active TB—primarily those with recently acquired LTBI, or with co-existing conditions that increase their likelihood of progression (TABLE 1).⁵

Screening for latent TB infection is desirable because early diagnosis and treatment can reduce the activation risk to 1% to 2%.

All household contacts of patients with active TB and recent immigrants from countries with a high TB prevalence should be tested for LTBI.⁶ Those with a negative test and recent exposure should be retested in 8 to 12 weeks to allow for the delay in conversion to a positive test after recent infection.⁷ Health care workers and others who are potentially exposed to active TB on an ongoing basis should be tested at the time of employment, with repeat testing done periodically based on their risk of infection.^8,9

Individuals with coexisting conditions should be tested for LTBI as long as the benefit of treatment outweighs the risk of drug-induced hepatitis. Because the risk of drug-induced hepatitis increases with age, the decision to test/treat is affected by age as well as the individual’s risk of progression. Patients with the highest risk conditions would benefit from testing/treating regardless of age, while treatment may not be justified in those with lower-risk conditions. A reasonable strategy is as follows:¹⁰
• high-risk conditions: test regardless of age
• moderate-risk conditions: test those <65 years
• low-risk conditions: test those <50 years.

Children with LTBI are at particularly high risk of progression to active TB.⁵ The American Academy of Pediatrics (AAP) recommends assessing a child’s risk for TB at first contact with the child and once every 6 months for the first year of life. After one year, annual assessment is recommended, but specific TB testing is not required for children who don’t have risk factors.¹¹ The AAP suggests using a TB risk assessment questionnaire that consists of 4 screening questions with follow-up questions if any of the screening questions are positive (TABLE 2).¹¹

Use of TST is well established

To perform a TST, inject 5 tuberculin units (0.1 mL) of purified protein derivative (PPD) intradermally into the inner surface of the forearm using a 27- to 30-gauge needle. (In the United States, PPD is available as Aplisol or Tubersol.) Avoid the former practice of “control” or anergy testing with mumps or Candida antigens because this is rarely helpful in making TB treatment decisions, even in HIV-positive patients.¹²

To facilitate intradermal injection, gently stretch the skin taut during injection. Raising a wheal confirms correct placement. The test should be read 48 to 72 hours after it is administered by measuring the greatest diameter of induration at the administration site. (Erythema is irrelevant to how the test is interpreted.) Induration is best read by using a ballpoint pen held at a 45-degree angle pointing toward the injection site. Roll the point of the pen over the skin with gentle pressure toward the injection site until induration causes the pen to stop rolling freely (FIGURE). The induration should be measured with a rule that has millimeter measurements and interpreted as positive or negative based on the individual’s risk factors (TABLE 3).³

Watch for these 2 factors that can affect TST results

Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is (or has been) used as a routine childhood immunization in many parts of the world, although not in the United States.¹³ It is ordinarily given as a single dose shortly after birth, and has some utility in preventing serious childhood TB infection. The antigens in PPD and those in BCG are not identical, but they do overlap.

BCG administered after an individual’s first birthday resulted in false positive TSTs >10 mm in 21% of those tested more than 10 years after BCG was administered.¹⁴ However, a single BCG vaccine in infancy causes little if any change in the TST result in individuals who are older than age 10 years. When a TST is performed for appropriate reasons, a positive TST in people previously vaccinated with BCG is generally more likely to be the result of LTBI than of BCG.¹⁵ Current guidelines from the Centers for Disease Control and Prevention (CDC) recommend that previous BCG status not change the cutoffs used for interpreting TST results.¹⁶

Booster phenomenon. In many adults who have undiagnosed LTBI that they acquired in the distant past, or who received BCG vaccination as a child, immunity wanes after several decades. This can result in an initial TST being negative, but because the antigens in the PPD itself stimulate antigenic memory, the next time a TST is performed, it may be positive.

In people who will have annual TST screenings, such as health care workers or nursing home residents, a 2-step PPD can help discriminate this “booster” phenomenon from a new LTBI acquired during the first year of annual TST testing. A second TST is placed 1 to 2 weeks after the initial test, a time interval during which acquisition of LTBI would be unlikely. The result of the second test should be considered the person’s baseline for evaluation of subsequent TSTs. A subsequent TST would be considered positive if the induration is >10 mm and has increased by ≥6 mm since the previous baseline.¹⁷

IGRA offers certain benefits

IGRA uses antigens that are more specific for Mycobacterium tuberculosis than the TST, and as a result, this test is not influenced by previous BCG vaccination. It requires only one blood draw, and interpretation does not depend on the patient’s risk category or interpretation of skin induration. The primary disadvantage of IGRAs is high cost (currently $200 to $300 per test), and the need for a laboratory with adequate equipment and personnel trained in performing the test. IGRAs must be collected in special blood tubes, and the samples must be processed within 8 to 16 hours of collection, depending on the test used.⁵

Currently, 2 IGRAs are approved for use in the United States—the QuantiFERON-TB Gold In-Tube (QFT-GIT) and the T-SPOT.TB assay. Both tests may produce false positives in patients infected with Mycobacterium marinum or Mycobacterium kansasii, but otherwise are highly specific for Mycobacterium tuberculosis. IGRA results may be “boosted” by recent TST (ie, a TST given within the previous 3 months may cause a false positive IGRA result), and this effect may begin as early as 3 days after a TST is administered.¹⁸ Therefore, if an IGRA is needed to clarify a TST result, it should be drawn on the day the TST is read.¹⁹

CDC guidelines (2010) recommend that IGRAs may be used in place of—but not routinely in addition to—TSTs in all cases in which TST is otherwise indicated.²⁰ There are a few situations where one test may be preferred over the other.²¹

IGRA may be preferred over TST in individuals in one of 2 categories:
• those who have received BCG immunization. If a patient is unsure of their BCG status, the World Atlas of BCG Policies and Practices, available at www.bcgatlas.org,²² can aid clinicians in determining which patients likely received BCG as part of their routine childhood immunizations.
• those in groups that historically have poor rates of return for TST reading, such as individuals who are homeless or suffer from alcoholism or a substance use disorder.

Individuals in whom TST is preferred over IGRA include:
• children age <5 years, because data guiding use of IGRAs in this age group are limited.²³ Both TST and IGRA may be falsely negative in children under the age of 3 months.²⁴
• patients who require serial testing, because individuals with positive IGRAs have been shown to commonly test negative on subsequent tests, and there are limited data on interpretation and prognosis of positive IGRAs in people who require serial testing.²⁵

Individuals in whom performing both tests simultaneously could be helpful include:
• those with an initial negative test, but with a high risk for progression to active TB or a poor outcome if the first result is falsely negative (eg, patients with HIV infection or children ages <5 years who have been exposed to a person with active TB)
• those with an initial positive test who don’t believe the test result and are reluctant to be treated for LTBI.

TST and IGRA have comparable sensitivities—around 80% to 90%, respectively—for diagnosing LTBI. IGRAs have a specificity >95% for diagnosing LTBI. While TST specificity is approximately 97% in patients not vaccinated with BCG, it can be as low as 60% in people previously vaccinated with BCG.²⁶ IGRAs have been shown to have higher positive and negative predictive values than TSTs in high-risk patients.²⁷ A recent study suggested that the IGRAs might have a higher rate of false-positive results compared to TSTs in a low-risk population of health care workers.²⁸

Both the TST and IGRA have lag times of 3 to 8 weeks from the time of a new infection until the test becomes positive. It is therefore best to defer testing for LTBI infection until at least 8 weeks after a known TB exposure to decrease the likelihood of a false-negative test.³

Diagnose active TB based on symptoms, culture

The CDC reported 9412 new cases of active TB in the United States in 2014, for a rate of 3 new cases per 100,000 people.²⁹ This is the lowest rate reported since national reporting began in 1953, when the incidence in the United States was 53 cases per 100,000.

Who should you test for active TB? The risk factors for active TB are the same as those for LTBI: recent exposure to an individual with active TB, and other disease processes or medications that compromise the immune system. Consider active TB when a patient with one of these risk factors presents with:²
• persistent fever
• weight loss
• night sweats
• cough, especially if there is any blood.

Routine laboratory and radiographic studies that should prompt you to consider TB include:²
• upper lobe infiltrates on chest x-ray
• sterile pyuria on urinalysis with a negative culture for routine pathogens
• elevated levels of C-reactive protein or an elevated erythrocyte sedimentation rate without another obvious cause.

Active TB typically presents as pulmonary TB, but it can also affect nearly every other body system. Other common presentations include:³⁰
• vertebral destruction and collapse (“Pott's disease”)
• subacute meningitis
• peritonitis
• lymphadenopathy (especially in children).

IGRAs have been shown to have higher positive and negative predictive values than TSTs in high-risk patients.

Culture is the gold standard. Neither TST or IGRA should ever be relied upon to make or exclude the diagnosis of active TB, as these tests are neither sensitive nor specific for diagnosing active TB.^31,32 Instead, the gold standard for the diagnosis of active TB remains a positive culture from infected tissue—commonly sputum, pleura or pleural fluid, cerebrospinal fluid, urine, or peritoneal fluid. Cultures are crucial not only to confirm the diagnosis, but to guide therapy, because of the rapidly increasing resistance to firstline antibiotics used to treat TB.³³

Culture results and drug sensitivities are ordinarily not available until 2 to 6 weeks after the culture was obtained. A smear for acid-fast bacilli as well as newer rapid diagnostic tests such as nucleic acid amplification (NAA) tests are generally performed on the tissue sample submitted for culture, and these results, while less trustworthy, are generally available within 24 to 48 hours. The CDC recommends that an NAA test be performed in addition to microscopy and culture for specimens submitted for TB diagnosis.³⁴

A single BCG vaccine in infancy causes little if any change in the TST result in individuals who are older than 10 years of age.

Since 2011, the World Health Organization has endorsed the use of a new molecular diagnostic test called Xpert MTB/RIF in settings with high prevalence of HIV infection or multidrug-resistant TB (MDR-TB).³⁵ This test is able to detect M. tuberculosis as well as rifampin resistance, a surrogate for MDR-TB, within 2 hours, with sensitivity and specificity approaching that of culture.³⁶

“Culture-negative” TB? A small but not insignificant proportion of patients will present with risk factors for, and clinical signs and symptoms of, active TB; their cultures, however, will be negative. In such cases, consultation with an infectious disease or pulmonary specialist may be warranted. If no alternative diagnosis is found, such patients are said to have “culture-negative active TB” and should be continued on anti-TB drug therapy, although the course may be shortened.³⁷ This highlights the fact that while cultures are key to diagnosing and treating active TB, the condition is—practically speaking—a clinical diagnosis; treatment should not be withheld or stopped simply because of a negative culture or rapid diagnostic test.

CASE 1 › Based on her risk factors (being a health care worker, born in a country with a high prevalence of TB), Ms. C’s cutoff for a positive test is >10 mm, so her TST result is negative and she is not considered to have LTBI. The increase to 8 mm seen on the second TST probably represents either childhood BCG vaccination or previous infection with nontuberculous Mycobacterium.

CASE 2 › Strictly speaking, 3-year-old Patrick does not need testing, because he was exposed only to LTBI, which is not infectious. However, because children under age 5 are at particularly high risk for progressing to active TB and poor outcomes, it would be best to confirm the mother’s story with the day care center and/or health department. If it turns out that Patrick had, in fact, been exposed to active TB, much more aggressive management would be required.

CORRESPONDENCE
Jeff Hall, MD, Family Medicine Center, 3209 Colonial Drive Columbia, SC 29203; [email protected]

CASE 1 › Judy C is a newly employed 40-year-old health care worker who was born in China and received the bacille Calmette-Guérin (BCG) vaccination as a child. Her new employer requires her to undergo testing for tuberculosis (TB). Her initial tuberculin skin test (TST) is 0 mm, but on a second TST 2 weeks later, it is 8 mm. She is otherwise healthy, negative for human immunodeficiency virus (HIV), and has no constitutional symptoms. Does she have latent tuberculosis infection (LTBI)?

CASE 2 › A mom brings in her 3-year-old son, Patrick. She reports that a staff member at his day care center traveled outside the country for 3 months and was diagnosed with LTBI upon her return. She wants to know if her son should be tested.

More than 2 billion people—nearly one-third of the world’s population—are infected with Mycobacterium tuberculosis.¹ Most harbor the bacilli as LTBI, which means that while they have living TB bacilli within their bodies, these mycobacteria are kept dormant by an intact immune system. These individuals are not contagious, nor are they likely to become ill from active TB unless something adversely affects their immune system and increases the likelihood that LTBI will progress to active TB.

Two tests are available for diagnosing LTBI: the TST and the newer interferon gamma release assay (IGRA). Each test has advantages and disadvantages, and the best test to use depends on various patient-specific factors. This article describes whom you should test for LTBI, which test to use, and how to diagnose active TB.

Why test for LTBI?

LTBI is an asymptomatic infection; patients with LTBI have a 5% to 10% lifetime risk of developing active TB.² The risk of developing active TB is approximately 5% within the first 18 months of infection, and the remaining risk is spread out over the rest of the patient’s life.² Screening for LTBI is desirable because early diagnosis and treatment can reduce the activation risk to 1% to 2%,³ and treatment for LTBI is simpler, less costly, and less toxic than treatment for active TB.

Whom to test. Screening for LTBI should target patients for whom the benefits of treatment outweigh the cost and risks of treatment.⁴ A decision to screen for LTBI implies that the patient will be treated if he or she tests positive.³

The benefit of treatment increases in people who have a significant risk of progression to active TB—primarily those with recently acquired LTBI, or with co-existing conditions that increase their likelihood of progression (TABLE 1).⁵

Screening for latent TB infection is desirable because early diagnosis and treatment can reduce the activation risk to 1% to 2%.

All household contacts of patients with active TB and recent immigrants from countries with a high TB prevalence should be tested for LTBI.⁶ Those with a negative test and recent exposure should be retested in 8 to 12 weeks to allow for the delay in conversion to a positive test after recent infection.⁷ Health care workers and others who are potentially exposed to active TB on an ongoing basis should be tested at the time of employment, with repeat testing done periodically based on their risk of infection.^8,9

Individuals with coexisting conditions should be tested for LTBI as long as the benefit of treatment outweighs the risk of drug-induced hepatitis. Because the risk of drug-induced hepatitis increases with age, the decision to test/treat is affected by age as well as the individual’s risk of progression. Patients with the highest risk conditions would benefit from testing/treating regardless of age, while treatment may not be justified in those with lower-risk conditions. A reasonable strategy is as follows:¹⁰
• high-risk conditions: test regardless of age
• moderate-risk conditions: test those <65 years
• low-risk conditions: test those <50 years.

Children with LTBI are at particularly high risk of progression to active TB.⁵ The American Academy of Pediatrics (AAP) recommends assessing a child’s risk for TB at first contact with the child and once every 6 months for the first year of life. After one year, annual assessment is recommended, but specific TB testing is not required for children who don’t have risk factors.¹¹ The AAP suggests using a TB risk assessment questionnaire that consists of 4 screening questions with follow-up questions if any of the screening questions are positive (TABLE 2).¹¹

Use of TST is well established

To perform a TST, inject 5 tuberculin units (0.1 mL) of purified protein derivative (PPD) intradermally into the inner surface of the forearm using a 27- to 30-gauge needle. (In the United States, PPD is available as Aplisol or Tubersol.) Avoid the former practice of “control” or anergy testing with mumps or Candida antigens because this is rarely helpful in making TB treatment decisions, even in HIV-positive patients.¹²

To facilitate intradermal injection, gently stretch the skin taut during injection. Raising a wheal confirms correct placement. The test should be read 48 to 72 hours after it is administered by measuring the greatest diameter of induration at the administration site. (Erythema is irrelevant to how the test is interpreted.) Induration is best read by using a ballpoint pen held at a 45-degree angle pointing toward the injection site. Roll the point of the pen over the skin with gentle pressure toward the injection site until induration causes the pen to stop rolling freely (FIGURE). The induration should be measured with a rule that has millimeter measurements and interpreted as positive or negative based on the individual’s risk factors (TABLE 3).³

Watch for these 2 factors that can affect TST results

Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is (or has been) used as a routine childhood immunization in many parts of the world, although not in the United States.¹³ It is ordinarily given as a single dose shortly after birth, and has some utility in preventing serious childhood TB infection. The antigens in PPD and those in BCG are not identical, but they do overlap.

BCG administered after an individual’s first birthday resulted in false positive TSTs >10 mm in 21% of those tested more than 10 years after BCG was administered.¹⁴ However, a single BCG vaccine in infancy causes little if any change in the TST result in individuals who are older than age 10 years. When a TST is performed for appropriate reasons, a positive TST in people previously vaccinated with BCG is generally more likely to be the result of LTBI than of BCG.¹⁵ Current guidelines from the Centers for Disease Control and Prevention (CDC) recommend that previous BCG status not change the cutoffs used for interpreting TST results.¹⁶

Booster phenomenon. In many adults who have undiagnosed LTBI that they acquired in the distant past, or who received BCG vaccination as a child, immunity wanes after several decades. This can result in an initial TST being negative, but because the antigens in the PPD itself stimulate antigenic memory, the next time a TST is performed, it may be positive.

In people who will have annual TST screenings, such as health care workers or nursing home residents, a 2-step PPD can help discriminate this “booster” phenomenon from a new LTBI acquired during the first year of annual TST testing. A second TST is placed 1 to 2 weeks after the initial test, a time interval during which acquisition of LTBI would be unlikely. The result of the second test should be considered the person’s baseline for evaluation of subsequent TSTs. A subsequent TST would be considered positive if the induration is >10 mm and has increased by ≥6 mm since the previous baseline.¹⁷

IGRA offers certain benefits

IGRA uses antigens that are more specific for Mycobacterium tuberculosis than the TST, and as a result, this test is not influenced by previous BCG vaccination. It requires only one blood draw, and interpretation does not depend on the patient’s risk category or interpretation of skin induration. The primary disadvantage of IGRAs is high cost (currently $200 to $300 per test), and the need for a laboratory with adequate equipment and personnel trained in performing the test. IGRAs must be collected in special blood tubes, and the samples must be processed within 8 to 16 hours of collection, depending on the test used.⁵

Currently, 2 IGRAs are approved for use in the United States—the QuantiFERON-TB Gold In-Tube (QFT-GIT) and the T-SPOT.TB assay. Both tests may produce false positives in patients infected with Mycobacterium marinum or Mycobacterium kansasii, but otherwise are highly specific for Mycobacterium tuberculosis. IGRA results may be “boosted” by recent TST (ie, a TST given within the previous 3 months may cause a false positive IGRA result), and this effect may begin as early as 3 days after a TST is administered.¹⁸ Therefore, if an IGRA is needed to clarify a TST result, it should be drawn on the day the TST is read.¹⁹

CDC guidelines (2010) recommend that IGRAs may be used in place of—but not routinely in addition to—TSTs in all cases in which TST is otherwise indicated.²⁰ There are a few situations where one test may be preferred over the other.²¹

IGRA may be preferred over TST in individuals in one of 2 categories:
• those who have received BCG immunization. If a patient is unsure of their BCG status, the World Atlas of BCG Policies and Practices, available at www.bcgatlas.org,²² can aid clinicians in determining which patients likely received BCG as part of their routine childhood immunizations.
• those in groups that historically have poor rates of return for TST reading, such as individuals who are homeless or suffer from alcoholism or a substance use disorder.

Individuals in whom TST is preferred over IGRA include:
• children age <5 years, because data guiding use of IGRAs in this age group are limited.²³ Both TST and IGRA may be falsely negative in children under the age of 3 months.²⁴
• patients who require serial testing, because individuals with positive IGRAs have been shown to commonly test negative on subsequent tests, and there are limited data on interpretation and prognosis of positive IGRAs in people who require serial testing.²⁵

Individuals in whom performing both tests simultaneously could be helpful include:
• those with an initial negative test, but with a high risk for progression to active TB or a poor outcome if the first result is falsely negative (eg, patients with HIV infection or children ages <5 years who have been exposed to a person with active TB)
• those with an initial positive test who don’t believe the test result and are reluctant to be treated for LTBI.

TST and IGRA have comparable sensitivities—around 80% to 90%, respectively—for diagnosing LTBI. IGRAs have a specificity >95% for diagnosing LTBI. While TST specificity is approximately 97% in patients not vaccinated with BCG, it can be as low as 60% in people previously vaccinated with BCG.²⁶ IGRAs have been shown to have higher positive and negative predictive values than TSTs in high-risk patients.²⁷ A recent study suggested that the IGRAs might have a higher rate of false-positive results compared to TSTs in a low-risk population of health care workers.²⁸

Both the TST and IGRA have lag times of 3 to 8 weeks from the time of a new infection until the test becomes positive. It is therefore best to defer testing for LTBI infection until at least 8 weeks after a known TB exposure to decrease the likelihood of a false-negative test.³

Diagnose active TB based on symptoms, culture

The CDC reported 9412 new cases of active TB in the United States in 2014, for a rate of 3 new cases per 100,000 people.²⁹ This is the lowest rate reported since national reporting began in 1953, when the incidence in the United States was 53 cases per 100,000.

Who should you test for active TB? The risk factors for active TB are the same as those for LTBI: recent exposure to an individual with active TB, and other disease processes or medications that compromise the immune system. Consider active TB when a patient with one of these risk factors presents with:²
• persistent fever
• weight loss
• night sweats
• cough, especially if there is any blood.

Routine laboratory and radiographic studies that should prompt you to consider TB include:²
• upper lobe infiltrates on chest x-ray
• sterile pyuria on urinalysis with a negative culture for routine pathogens
• elevated levels of C-reactive protein or an elevated erythrocyte sedimentation rate without another obvious cause.

Active TB typically presents as pulmonary TB, but it can also affect nearly every other body system. Other common presentations include:³⁰
• vertebral destruction and collapse (“Pott's disease”)
• subacute meningitis
• peritonitis
• lymphadenopathy (especially in children).

IGRAs have been shown to have higher positive and negative predictive values than TSTs in high-risk patients.

Culture is the gold standard. Neither TST or IGRA should ever be relied upon to make or exclude the diagnosis of active TB, as these tests are neither sensitive nor specific for diagnosing active TB.^31,32 Instead, the gold standard for the diagnosis of active TB remains a positive culture from infected tissue—commonly sputum, pleura or pleural fluid, cerebrospinal fluid, urine, or peritoneal fluid. Cultures are crucial not only to confirm the diagnosis, but to guide therapy, because of the rapidly increasing resistance to firstline antibiotics used to treat TB.³³

Culture results and drug sensitivities are ordinarily not available until 2 to 6 weeks after the culture was obtained. A smear for acid-fast bacilli as well as newer rapid diagnostic tests such as nucleic acid amplification (NAA) tests are generally performed on the tissue sample submitted for culture, and these results, while less trustworthy, are generally available within 24 to 48 hours. The CDC recommends that an NAA test be performed in addition to microscopy and culture for specimens submitted for TB diagnosis.³⁴

A single BCG vaccine in infancy causes little if any change in the TST result in individuals who are older than 10 years of age.

Since 2011, the World Health Organization has endorsed the use of a new molecular diagnostic test called Xpert MTB/RIF in settings with high prevalence of HIV infection or multidrug-resistant TB (MDR-TB).³⁵ This test is able to detect M. tuberculosis as well as rifampin resistance, a surrogate for MDR-TB, within 2 hours, with sensitivity and specificity approaching that of culture.³⁶

“Culture-negative” TB? A small but not insignificant proportion of patients will present with risk factors for, and clinical signs and symptoms of, active TB; their cultures, however, will be negative. In such cases, consultation with an infectious disease or pulmonary specialist may be warranted. If no alternative diagnosis is found, such patients are said to have “culture-negative active TB” and should be continued on anti-TB drug therapy, although the course may be shortened.³⁷ This highlights the fact that while cultures are key to diagnosing and treating active TB, the condition is—practically speaking—a clinical diagnosis; treatment should not be withheld or stopped simply because of a negative culture or rapid diagnostic test.

CASE 1 › Based on her risk factors (being a health care worker, born in a country with a high prevalence of TB), Ms. C’s cutoff for a positive test is >10 mm, so her TST result is negative and she is not considered to have LTBI. The increase to 8 mm seen on the second TST probably represents either childhood BCG vaccination or previous infection with nontuberculous Mycobacterium.

CASE 2 › Strictly speaking, 3-year-old Patrick does not need testing, because he was exposed only to LTBI, which is not infectious. However, because children under age 5 are at particularly high risk for progressing to active TB and poor outcomes, it would be best to confirm the mother’s story with the day care center and/or health department. If it turns out that Patrick had, in fact, been exposed to active TB, much more aggressive management would be required.

CORRESPONDENCE
Jeff Hall, MD, Family Medicine Center, 3209 Colonial Drive Columbia, SC 29203; [email protected]

ANSWER
The correct interpretation includes normal sinus rhythm, right atrial enlargement, left ventricular hypertrophy, and a prolonged QT interval. Normal sinus rhythm is indicated by a P for every QRS and a QRS for every P, with a constant PR interval (see rhythm strip of lead I).

Right atrial enlargement is evidenced by the tall P waves in leads II, III, aVF, and V₁. Note that there is no biphasic P wave in lead V₁, so there is no evidence of accompanying left atrial enlargement.

High-voltage limb leads (sum of R in lead I and S in lead III ≥ 25 mm) or precordial leads (sum of S in V1 and R in V₅ or V₆ ≥ 35 mm) are indicative of left ventricular hypertrophy.

The QTc interval of 653 ms with a normal sinus rate is worrisome for prolonged QT syndrome. A review of the history shows the patient to be taking two drugs (lithium, azithromycin) known to prolong the QT interval. Although it is not known whether this patient has inherent QT prolongation, use of these types of agents should be avoided.  

ANSWER
The correct interpretation includes normal sinus rhythm, right atrial enlargement, left ventricular hypertrophy, and a prolonged QT interval. Normal sinus rhythm is indicated by a P for every QRS and a QRS for every P, with a constant PR interval (see rhythm strip of lead I).

Right atrial enlargement is evidenced by the tall P waves in leads II, III, aVF, and V₁. Note that there is no biphasic P wave in lead V₁, so there is no evidence of accompanying left atrial enlargement.

High-voltage limb leads (sum of R in lead I and S in lead III ≥ 25 mm) or precordial leads (sum of S in V1 and R in V₅ or V₆ ≥ 35 mm) are indicative of left ventricular hypertrophy.

The QTc interval of 653 ms with a normal sinus rate is worrisome for prolonged QT syndrome. A review of the history shows the patient to be taking two drugs (lithium, azithromycin) known to prolong the QT interval. Although it is not known whether this patient has inherent QT prolongation, use of these types of agents should be avoided.  

ANSWER
The correct interpretation includes normal sinus rhythm, right atrial enlargement, left ventricular hypertrophy, and a prolonged QT interval. Normal sinus rhythm is indicated by a P for every QRS and a QRS for every P, with a constant PR interval (see rhythm strip of lead I).

Right atrial enlargement is evidenced by the tall P waves in leads II, III, aVF, and V₁. Note that there is no biphasic P wave in lead V₁, so there is no evidence of accompanying left atrial enlargement.

High-voltage limb leads (sum of R in lead I and S in lead III ≥ 25 mm) or precordial leads (sum of S in V1 and R in V₅ or V₆ ≥ 35 mm) are indicative of left ventricular hypertrophy.

The QTc interval of 653 ms with a normal sinus rate is worrisome for prolonged QT syndrome. A review of the history shows the patient to be taking two drugs (lithium, azithromycin) known to prolong the QT interval. Although it is not known whether this patient has inherent QT prolongation, use of these types of agents should be avoided.