In his August editorial, Dr. Hickner noted that an article in the issue prompted him to “wonder whether ultrasound might become the stethoscope of the future” (J Fam Pract. 2016;65:516). To that I say that we need to avoid conflating the stethoscope with point-of-care ultrasound (POCUS).

It is well documented that auscultation skills rapidly deteriorate (specifically in the cardiology realm) in clinical practice.¹ This may occur because many physicians already think ultrasound can replace actually listening to their patients’ hearts. The motto has become, “I’ll just order an echo.”

POCUS is an imaging modality. Period. It can be used to auscultate, but Doppler ultrasound is not as precise as the stethoscope when used by a practiced listener for identifying the source and subtle characteristics of murmurs.² The stethoscope remains an outstanding, inexpensive, and convenient screening tool and its use needs to be emphasized.

I strongly believe in training all medical students in POCUS—but as a complementary and adjunctive tool—not as something to replace a perfectly functional piece of equipment used around the world to provide good care.

Todd Fredricks, DO
Athens, Ohio

In his August editorial, Dr. Hickner noted that an article in the issue prompted him to “wonder whether ultrasound might become the stethoscope of the future” (J Fam Pract. 2016;65:516). To that I say that we need to avoid conflating the stethoscope with point-of-care ultrasound (POCUS).

It is well documented that auscultation skills rapidly deteriorate (specifically in the cardiology realm) in clinical practice.¹ This may occur because many physicians already think ultrasound can replace actually listening to their patients’ hearts. The motto has become, “I’ll just order an echo.”

POCUS is an imaging modality. Period. It can be used to auscultate, but Doppler ultrasound is not as precise as the stethoscope when used by a practiced listener for identifying the source and subtle characteristics of murmurs.² The stethoscope remains an outstanding, inexpensive, and convenient screening tool and its use needs to be emphasized.

I strongly believe in training all medical students in POCUS—but as a complementary and adjunctive tool—not as something to replace a perfectly functional piece of equipment used around the world to provide good care.

Todd Fredricks, DO
Athens, Ohio

In his August editorial, Dr. Hickner noted that an article in the issue prompted him to “wonder whether ultrasound might become the stethoscope of the future” (J Fam Pract. 2016;65:516). To that I say that we need to avoid conflating the stethoscope with point-of-care ultrasound (POCUS).

It is well documented that auscultation skills rapidly deteriorate (specifically in the cardiology realm) in clinical practice.¹ This may occur because many physicians already think ultrasound can replace actually listening to their patients’ hearts. The motto has become, “I’ll just order an echo.”

POCUS is an imaging modality. Period. It can be used to auscultate, but Doppler ultrasound is not as precise as the stethoscope when used by a practiced listener for identifying the source and subtle characteristics of murmurs.² The stethoscope remains an outstanding, inexpensive, and convenient screening tool and its use needs to be emphasized.

I strongly believe in training all medical students in POCUS—but as a complementary and adjunctive tool—not as something to replace a perfectly functional piece of equipment used around the world to provide good care.

Todd Fredricks, DO
Athens, Ohio

The article, “Diabetes update: Your guide to the latest ADA standards,” by Shubrook, et al (J Fam Pract. 2016;65:310-318) is a precise review of current recommendations for diabetes. We would like to draw attention, however, to comorbid diabetes and mental illness.

Diabetes and serious mental illness often coincide, making the treatment of both conditions difficult and leading to higher rates of complications.¹

The American Diabetes Association (ADA)’s “Standards of Medical Care in Diabetes” recognizes that hemoglobin A1C targets for patients should be individualized.² We consider it important to discuss challenges and limitations with each patient.

For example, a more lenient A1C goal may be appropriate when:

• the assessment of the patient shows that he or she is struggling with active symptoms of mental illness
• new medications with undesirable metabolic effects are prescribed or titrated
• social support is poor
• patients have limited confidence in their ability to accomplish tasks and goals
• patients have cognitive limitations
• patients abuse substances.

We suggest that when factors are favorable (eg, younger patient, well-controlled serious mental illness, adequate support, good cognitive skills, no hazardous use of substances, good level of confidence in the ability to control diabetes), the A1C target can be set lower. When the factors are less favorable (eg, older patient, poorly controlled mental illness, abusing substances, cognitive impairment), the target should be set higher and incrementally reduced as care engagement, circumstances, and symptom control improve.

There is a need for further research to investigate the factors that can impact diabetes self-management in patients with comorbid mental illness.

Corinna Falck-Ytter, MD
Stephanie W. Kanuch, MEd
Richard McCormick, PhD
Michael Purdum, PhD
Neal V. Dawson, MD
Shari D. Bolen, MD, MPH
Martha Sajatovic, MD
Cleveland, Ohio

The article, “Diabetes update: Your guide to the latest ADA standards,” by Shubrook, et al (J Fam Pract. 2016;65:310-318) is a precise review of current recommendations for diabetes. We would like to draw attention, however, to comorbid diabetes and mental illness.

Diabetes and serious mental illness often coincide, making the treatment of both conditions difficult and leading to higher rates of complications.¹

The American Diabetes Association (ADA)’s “Standards of Medical Care in Diabetes” recognizes that hemoglobin A1C targets for patients should be individualized.² We consider it important to discuss challenges and limitations with each patient.

For example, a more lenient A1C goal may be appropriate when:

• the assessment of the patient shows that he or she is struggling with active symptoms of mental illness
• new medications with undesirable metabolic effects are prescribed or titrated
• social support is poor
• patients have limited confidence in their ability to accomplish tasks and goals
• patients have cognitive limitations
• patients abuse substances.

We suggest that when factors are favorable (eg, younger patient, well-controlled serious mental illness, adequate support, good cognitive skills, no hazardous use of substances, good level of confidence in the ability to control diabetes), the A1C target can be set lower. When the factors are less favorable (eg, older patient, poorly controlled mental illness, abusing substances, cognitive impairment), the target should be set higher and incrementally reduced as care engagement, circumstances, and symptom control improve.

There is a need for further research to investigate the factors that can impact diabetes self-management in patients with comorbid mental illness.

Corinna Falck-Ytter, MD
Stephanie W. Kanuch, MEd
Richard McCormick, PhD
Michael Purdum, PhD
Neal V. Dawson, MD
Shari D. Bolen, MD, MPH
Martha Sajatovic, MD
Cleveland, Ohio

The article, “Diabetes update: Your guide to the latest ADA standards,” by Shubrook, et al (J Fam Pract. 2016;65:310-318) is a precise review of current recommendations for diabetes. We would like to draw attention, however, to comorbid diabetes and mental illness.

Diabetes and serious mental illness often coincide, making the treatment of both conditions difficult and leading to higher rates of complications.¹

The American Diabetes Association (ADA)’s “Standards of Medical Care in Diabetes” recognizes that hemoglobin A1C targets for patients should be individualized.² We consider it important to discuss challenges and limitations with each patient.

For example, a more lenient A1C goal may be appropriate when:

• the assessment of the patient shows that he or she is struggling with active symptoms of mental illness
• new medications with undesirable metabolic effects are prescribed or titrated
• social support is poor
• patients have limited confidence in their ability to accomplish tasks and goals
• patients have cognitive limitations
• patients abuse substances.

We suggest that when factors are favorable (eg, younger patient, well-controlled serious mental illness, adequate support, good cognitive skills, no hazardous use of substances, good level of confidence in the ability to control diabetes), the A1C target can be set lower. When the factors are less favorable (eg, older patient, poorly controlled mental illness, abusing substances, cognitive impairment), the target should be set higher and incrementally reduced as care engagement, circumstances, and symptom control improve.

There is a need for further research to investigate the factors that can impact diabetes self-management in patients with comorbid mental illness.

Corinna Falck-Ytter, MD
Stephanie W. Kanuch, MEd
Richard McCormick, PhD
Michael Purdum, PhD
Neal V. Dawson, MD
Shari D. Bolen, MD, MPH
Martha Sajatovic, MD
Cleveland, Ohio

An 88-year-old woman presented to our primary care clinic with recurrent right upper quadrant abdominal pain. Her history was negative for nausea, fever, vomiting, chest pain, heartburn, back pain, or changes in bowel movement patterns. There was no association between the pain and her eating patterns. She described the pain as dull, and rated it as a 4 to 5 out of 10. A physical examination was unremarkable except for a minimally tender mass in the right upper quadrant that was detected during palpation of the abdomen. A Murphy’s test was negative. A comprehensive metabolic panel, complete blood count, lipase test, amylase test, abdominal ultrasound, and abdominal x-ray (FIGURE) were ordered.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

Diagnosis: Porcelain gallbladder

We diagnosed this patient with porcelain gallbladder based on her history, physical exam, and x-ray, which revealed a well-defined air gas bubble encased in a calcified pouch. (The patient’s lab work was unremarkable and the ultrasound revealed the same findings as seen on the x-ray.)

Porcelain gallbladder is a rare condition.¹ It is characterized by intramural calcifications of the gallbladder wall, which is rarely seen with chronic cholecystitis.²

One theory suggests that porcelain gallbladder is due to the obstruction of cystic ducts, which leads to bile stasis in the gallbladder, followed by the accumulation of calcium carbonate salts.

There are a few theories behind the etiology of porcelain gallbladder. One theory is that gallstones can irritate the gallbladder wall, leading to inflammation and then calcification. Others believe that porcelain gallbladder is due to the obstruction of cystic ducts, which leads to bile stasis in the gallbladder, followed by the accumulation of calcium carbonate salts.³

Patients may present with biliary pain or a firm palpable mass in the right upper quadrant. However, patients are often asymptomatic.⁴

Cancer risk. There is about a 2% to 3% risk of gallbladder cancer in patients with porcelain gallbladder.⁵ The nature of the calcification has been linked to the probability that a patient will develop gallbladder cancer. Specifically, there is a higher probability of gallbladder cancer if discontinuous calcification is noted, or if only some portion of the gallbladder wall has calcified.⁶ About 80% of all gallbladder cancers are adenocarcinomas.⁶

Differential diagnosis includes GERD, cholecystitis

Right upper quadrant pain is associated with acute hepatitis, acute cholecystitis, acute pancreatitis, gastroesophageal reflex disease (GERD), ulcers, and umbilical hernias. In this patient’s case, her history and physical examination made a number of diagnoses less likely, including acute cholecystitis, GERD, ulcers, and an umbilical hernia. In addition, normal values on the patient’s lipase and amylase tests ruled out pancreatitis.

Imaging brought things into focus. The most significant finding in this case was the abdominal x-ray, which showed a well-defined air gas bubble encased in a calcified pouch.

In addition to an x-ray or an ultrasound, a computed tomography scan can confirm the diagnosis of porcelain gallbladder.

For most patients, cholecystectomy is recommended

Treatment and management is based on the pattern of calcification and the patient’s current health status. If there is incomplete calcification, cholecystectomy is warranted. Cholecystectomy may also be warranted when a patient is symptomatic and has complete calcification of the gallbladder. Regardless of the pattern of calcification, imaging surveillance of the patient is necessary. Moreover, cholecystectomy is preferred regardless of the status of the calcification if the patient is a good surgical candidate.⁷

It is important to send the gallbladder for histopathological examination after it is removed to determine the likelihood of malignancy.⁷ If cancer is ruled out, then no further work-up is necessary. If cancer is detected, then further evaluation, including additional surgery, may be necessary.

Our patient was a good surgical candidate, so we recommended cholecystectomy. The patient underwent surgery and the pathology report was negative for cancer.

CORRESPONDENCE
Pradeepa Vimalachandran, MD, MPH, 601 North 30th Street, Suite 6720, Omaha, NE 68131; PradeepaVimalachandran@creighton.edu.

An 88-year-old woman presented to our primary care clinic with recurrent right upper quadrant abdominal pain. Her history was negative for nausea, fever, vomiting, chest pain, heartburn, back pain, or changes in bowel movement patterns. There was no association between the pain and her eating patterns. She described the pain as dull, and rated it as a 4 to 5 out of 10. A physical examination was unremarkable except for a minimally tender mass in the right upper quadrant that was detected during palpation of the abdomen. A Murphy’s test was negative. A comprehensive metabolic panel, complete blood count, lipase test, amylase test, abdominal ultrasound, and abdominal x-ray (FIGURE) were ordered.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

Diagnosis: Porcelain gallbladder

We diagnosed this patient with porcelain gallbladder based on her history, physical exam, and x-ray, which revealed a well-defined air gas bubble encased in a calcified pouch. (The patient’s lab work was unremarkable and the ultrasound revealed the same findings as seen on the x-ray.)

Porcelain gallbladder is a rare condition.¹ It is characterized by intramural calcifications of the gallbladder wall, which is rarely seen with chronic cholecystitis.²

One theory suggests that porcelain gallbladder is due to the obstruction of cystic ducts, which leads to bile stasis in the gallbladder, followed by the accumulation of calcium carbonate salts.

There are a few theories behind the etiology of porcelain gallbladder. One theory is that gallstones can irritate the gallbladder wall, leading to inflammation and then calcification. Others believe that porcelain gallbladder is due to the obstruction of cystic ducts, which leads to bile stasis in the gallbladder, followed by the accumulation of calcium carbonate salts.³

Patients may present with biliary pain or a firm palpable mass in the right upper quadrant. However, patients are often asymptomatic.⁴

Cancer risk. There is about a 2% to 3% risk of gallbladder cancer in patients with porcelain gallbladder.⁵ The nature of the calcification has been linked to the probability that a patient will develop gallbladder cancer. Specifically, there is a higher probability of gallbladder cancer if discontinuous calcification is noted, or if only some portion of the gallbladder wall has calcified.⁶ About 80% of all gallbladder cancers are adenocarcinomas.⁶

Differential diagnosis includes GERD, cholecystitis

Right upper quadrant pain is associated with acute hepatitis, acute cholecystitis, acute pancreatitis, gastroesophageal reflex disease (GERD), ulcers, and umbilical hernias. In this patient’s case, her history and physical examination made a number of diagnoses less likely, including acute cholecystitis, GERD, ulcers, and an umbilical hernia. In addition, normal values on the patient’s lipase and amylase tests ruled out pancreatitis.

Imaging brought things into focus. The most significant finding in this case was the abdominal x-ray, which showed a well-defined air gas bubble encased in a calcified pouch.

In addition to an x-ray or an ultrasound, a computed tomography scan can confirm the diagnosis of porcelain gallbladder.

For most patients, cholecystectomy is recommended

Treatment and management is based on the pattern of calcification and the patient’s current health status. If there is incomplete calcification, cholecystectomy is warranted. Cholecystectomy may also be warranted when a patient is symptomatic and has complete calcification of the gallbladder. Regardless of the pattern of calcification, imaging surveillance of the patient is necessary. Moreover, cholecystectomy is preferred regardless of the status of the calcification if the patient is a good surgical candidate.⁷

It is important to send the gallbladder for histopathological examination after it is removed to determine the likelihood of malignancy.⁷ If cancer is ruled out, then no further work-up is necessary. If cancer is detected, then further evaluation, including additional surgery, may be necessary.

Our patient was a good surgical candidate, so we recommended cholecystectomy. The patient underwent surgery and the pathology report was negative for cancer.

CORRESPONDENCE
Pradeepa Vimalachandran, MD, MPH, 601 North 30th Street, Suite 6720, Omaha, NE 68131; PradeepaVimalachandran@creighton.edu.

An 88-year-old woman presented to our primary care clinic with recurrent right upper quadrant abdominal pain. Her history was negative for nausea, fever, vomiting, chest pain, heartburn, back pain, or changes in bowel movement patterns. There was no association between the pain and her eating patterns. She described the pain as dull, and rated it as a 4 to 5 out of 10. A physical examination was unremarkable except for a minimally tender mass in the right upper quadrant that was detected during palpation of the abdomen. A Murphy’s test was negative. A comprehensive metabolic panel, complete blood count, lipase test, amylase test, abdominal ultrasound, and abdominal x-ray (FIGURE) were ordered.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

Diagnosis: Porcelain gallbladder

We diagnosed this patient with porcelain gallbladder based on her history, physical exam, and x-ray, which revealed a well-defined air gas bubble encased in a calcified pouch. (The patient’s lab work was unremarkable and the ultrasound revealed the same findings as seen on the x-ray.)

Porcelain gallbladder is a rare condition.¹ It is characterized by intramural calcifications of the gallbladder wall, which is rarely seen with chronic cholecystitis.²

One theory suggests that porcelain gallbladder is due to the obstruction of cystic ducts, which leads to bile stasis in the gallbladder, followed by the accumulation of calcium carbonate salts.

There are a few theories behind the etiology of porcelain gallbladder. One theory is that gallstones can irritate the gallbladder wall, leading to inflammation and then calcification. Others believe that porcelain gallbladder is due to the obstruction of cystic ducts, which leads to bile stasis in the gallbladder, followed by the accumulation of calcium carbonate salts.³

Patients may present with biliary pain or a firm palpable mass in the right upper quadrant. However, patients are often asymptomatic.⁴

Cancer risk. There is about a 2% to 3% risk of gallbladder cancer in patients with porcelain gallbladder.⁵ The nature of the calcification has been linked to the probability that a patient will develop gallbladder cancer. Specifically, there is a higher probability of gallbladder cancer if discontinuous calcification is noted, or if only some portion of the gallbladder wall has calcified.⁶ About 80% of all gallbladder cancers are adenocarcinomas.⁶

Differential diagnosis includes GERD, cholecystitis

Right upper quadrant pain is associated with acute hepatitis, acute cholecystitis, acute pancreatitis, gastroesophageal reflex disease (GERD), ulcers, and umbilical hernias. In this patient’s case, her history and physical examination made a number of diagnoses less likely, including acute cholecystitis, GERD, ulcers, and an umbilical hernia. In addition, normal values on the patient’s lipase and amylase tests ruled out pancreatitis.

Imaging brought things into focus. The most significant finding in this case was the abdominal x-ray, which showed a well-defined air gas bubble encased in a calcified pouch.

In addition to an x-ray or an ultrasound, a computed tomography scan can confirm the diagnosis of porcelain gallbladder.

For most patients, cholecystectomy is recommended

Treatment and management is based on the pattern of calcification and the patient’s current health status. If there is incomplete calcification, cholecystectomy is warranted. Cholecystectomy may also be warranted when a patient is symptomatic and has complete calcification of the gallbladder. Regardless of the pattern of calcification, imaging surveillance of the patient is necessary. Moreover, cholecystectomy is preferred regardless of the status of the calcification if the patient is a good surgical candidate.⁷

It is important to send the gallbladder for histopathological examination after it is removed to determine the likelihood of malignancy.⁷ If cancer is ruled out, then no further work-up is necessary. If cancer is detected, then further evaluation, including additional surgery, may be necessary.

Our patient was a good surgical candidate, so we recommended cholecystectomy. The patient underwent surgery and the pathology report was negative for cancer.

CORRESPONDENCE
Pradeepa Vimalachandran, MD, MPH, 601 North 30th Street, Suite 6720, Omaha, NE 68131; PradeepaVimalachandran@creighton.edu.

Evidence summary

A cross-sectional study found no correlation between knuckle popping and osteoarthritis (OA) of the hand.¹ Investigators recruited 300 consecutive patients (ages 45 years and older, mean age 63 years) and evaluated them for a history of habitual knuckle popping (74 of 300 patients, mean duration 35 years) and hand arthritis or dysfunction. Investigators excluded patients with neuromuscular, inflammatory, or malignant diseases.

Investigators found OA equally in both patients who did and didn’t pop their knuckles (12 of 74 vs 36 of 226, respectively; P nonsignificant); joint swelling was more common in participants with a history of knuckle popping (84% vs 6%; P<.01). Investigators didn’t describe how OA was diagnosed or specify which joints were affected.

Another cross-sectional study also found no correlation between habitual knuckle popping of the metacarpal phalangeal joint and the prevalence of OA in that joint.² Investigators recruited 28 patients (mean age 78.5 years; 23 women and 5 men) from a Jewish home for the aged and asked them whether they had habitually cracked their knuckles during their lifetime. They then performed clinical and radiographic hand examinations (excluding patients with a history of ­traumatic injury, rheumatoid arthritis, gout, chondrocalcinosis, and hemochromatosis).

Knuckle popping didn’t correlate with OA of the metacarpal phalanges (1 of 15 knuckle popping patients vs 5 of 13 patients who didn’t pop their knuckles; P=.06). All 6 patients with radiographic evidence of OA showed involvement at the metacarpal phalangeal and distal interphalangeal joints, whether or not they popped their knuckles.

A case control study found no correlation between OA in the hands and habitual knuckle popping.³ Investigators recruited 215 patients 50 to 89 years old who had received a radiograph of their right hand during the previous 5 years and divided them into cases with OA (135 patients), and controls without OA (80 patients). Patients completed questionnaires assessing the prevalence (20%), frequency (1 to 20 times per day), and duration (26 to 36 years) of knuckle popping.

Patients most commonly popped proximal interphalangeal joints (15.9%) followed by metacarpal phalangeal joints (13.5%), distal interphalangeal joints (6.1%), and first carpal metacarpal joints (2.3%). OA most often affected the distal interphalangeal joint (68.4%), followed by the first carpal metacarpal (57.1%), proximal interphalangeal (54.1%), and metacarpal phalangeal joints (28.6%). Investigators found no difference in the prevalence of knuckle popping between cases and controls (18% in cases vs 23.2% in controls; P=.361).

When investigators evaluated total knuckle popping exposure in “crack years” (number of times per day multiplied by years) in the distal interphalangeal or metacarpal phalangeal joints, they found no significant association between crack years and OA (distal interphalangeal joint, mean 108 crack years; metacarpal phalangeal joint, mean 75 crack years).

50 years of knuckle popping without ill effects

An n-of-1 case control study found similar results.⁴ The researcher, a physician, popped only the knuckles of his left hand, twice a day, for 50 years. He compared his hands at the end of the trial and found no arthritis in either hand and no visible differences.

But knuckle popping does have a downside

A paper described 2 case reports of acute injuries sustained during attempted knuckle popping—a partial tear of the ulnar collateral ligament of the thumb and subluxation of the extensor tendon of the fifth digit.⁵ Both injuries were associated with forceful manipulation of the digits, and both resolved with conservative management within 4 weeks.

Evidence summary

A cross-sectional study found no correlation between knuckle popping and osteoarthritis (OA) of the hand.¹ Investigators recruited 300 consecutive patients (ages 45 years and older, mean age 63 years) and evaluated them for a history of habitual knuckle popping (74 of 300 patients, mean duration 35 years) and hand arthritis or dysfunction. Investigators excluded patients with neuromuscular, inflammatory, or malignant diseases.

Investigators found OA equally in both patients who did and didn’t pop their knuckles (12 of 74 vs 36 of 226, respectively; P nonsignificant); joint swelling was more common in participants with a history of knuckle popping (84% vs 6%; P<.01). Investigators didn’t describe how OA was diagnosed or specify which joints were affected.

Another cross-sectional study also found no correlation between habitual knuckle popping of the metacarpal phalangeal joint and the prevalence of OA in that joint.² Investigators recruited 28 patients (mean age 78.5 years; 23 women and 5 men) from a Jewish home for the aged and asked them whether they had habitually cracked their knuckles during their lifetime. They then performed clinical and radiographic hand examinations (excluding patients with a history of ­traumatic injury, rheumatoid arthritis, gout, chondrocalcinosis, and hemochromatosis).

Knuckle popping didn’t correlate with OA of the metacarpal phalanges (1 of 15 knuckle popping patients vs 5 of 13 patients who didn’t pop their knuckles; P=.06). All 6 patients with radiographic evidence of OA showed involvement at the metacarpal phalangeal and distal interphalangeal joints, whether or not they popped their knuckles.

A case control study found no correlation between OA in the hands and habitual knuckle popping.³ Investigators recruited 215 patients 50 to 89 years old who had received a radiograph of their right hand during the previous 5 years and divided them into cases with OA (135 patients), and controls without OA (80 patients). Patients completed questionnaires assessing the prevalence (20%), frequency (1 to 20 times per day), and duration (26 to 36 years) of knuckle popping.

Patients most commonly popped proximal interphalangeal joints (15.9%) followed by metacarpal phalangeal joints (13.5%), distal interphalangeal joints (6.1%), and first carpal metacarpal joints (2.3%). OA most often affected the distal interphalangeal joint (68.4%), followed by the first carpal metacarpal (57.1%), proximal interphalangeal (54.1%), and metacarpal phalangeal joints (28.6%). Investigators found no difference in the prevalence of knuckle popping between cases and controls (18% in cases vs 23.2% in controls; P=.361).

When investigators evaluated total knuckle popping exposure in “crack years” (number of times per day multiplied by years) in the distal interphalangeal or metacarpal phalangeal joints, they found no significant association between crack years and OA (distal interphalangeal joint, mean 108 crack years; metacarpal phalangeal joint, mean 75 crack years).

50 years of knuckle popping without ill effects

An n-of-1 case control study found similar results.⁴ The researcher, a physician, popped only the knuckles of his left hand, twice a day, for 50 years. He compared his hands at the end of the trial and found no arthritis in either hand and no visible differences.

But knuckle popping does have a downside

A paper described 2 case reports of acute injuries sustained during attempted knuckle popping—a partial tear of the ulnar collateral ligament of the thumb and subluxation of the extensor tendon of the fifth digit.⁵ Both injuries were associated with forceful manipulation of the digits, and both resolved with conservative management within 4 weeks.

Evidence summary

A cross-sectional study found no correlation between knuckle popping and osteoarthritis (OA) of the hand.¹ Investigators recruited 300 consecutive patients (ages 45 years and older, mean age 63 years) and evaluated them for a history of habitual knuckle popping (74 of 300 patients, mean duration 35 years) and hand arthritis or dysfunction. Investigators excluded patients with neuromuscular, inflammatory, or malignant diseases.

Investigators found OA equally in both patients who did and didn’t pop their knuckles (12 of 74 vs 36 of 226, respectively; P nonsignificant); joint swelling was more common in participants with a history of knuckle popping (84% vs 6%; P<.01). Investigators didn’t describe how OA was diagnosed or specify which joints were affected.

Another cross-sectional study also found no correlation between habitual knuckle popping of the metacarpal phalangeal joint and the prevalence of OA in that joint.² Investigators recruited 28 patients (mean age 78.5 years; 23 women and 5 men) from a Jewish home for the aged and asked them whether they had habitually cracked their knuckles during their lifetime. They then performed clinical and radiographic hand examinations (excluding patients with a history of ­traumatic injury, rheumatoid arthritis, gout, chondrocalcinosis, and hemochromatosis).

Knuckle popping didn’t correlate with OA of the metacarpal phalanges (1 of 15 knuckle popping patients vs 5 of 13 patients who didn’t pop their knuckles; P=.06). All 6 patients with radiographic evidence of OA showed involvement at the metacarpal phalangeal and distal interphalangeal joints, whether or not they popped their knuckles.

A case control study found no correlation between OA in the hands and habitual knuckle popping.³ Investigators recruited 215 patients 50 to 89 years old who had received a radiograph of their right hand during the previous 5 years and divided them into cases with OA (135 patients), and controls without OA (80 patients). Patients completed questionnaires assessing the prevalence (20%), frequency (1 to 20 times per day), and duration (26 to 36 years) of knuckle popping.

Patients most commonly popped proximal interphalangeal joints (15.9%) followed by metacarpal phalangeal joints (13.5%), distal interphalangeal joints (6.1%), and first carpal metacarpal joints (2.3%). OA most often affected the distal interphalangeal joint (68.4%), followed by the first carpal metacarpal (57.1%), proximal interphalangeal (54.1%), and metacarpal phalangeal joints (28.6%). Investigators found no difference in the prevalence of knuckle popping between cases and controls (18% in cases vs 23.2% in controls; P=.361).

When investigators evaluated total knuckle popping exposure in “crack years” (number of times per day multiplied by years) in the distal interphalangeal or metacarpal phalangeal joints, they found no significant association between crack years and OA (distal interphalangeal joint, mean 108 crack years; metacarpal phalangeal joint, mean 75 crack years).

50 years of knuckle popping without ill effects

An n-of-1 case control study found similar results.⁴ The researcher, a physician, popped only the knuckles of his left hand, twice a day, for 50 years. He compared his hands at the end of the trial and found no arthritis in either hand and no visible differences.

But knuckle popping does have a downside

A paper described 2 case reports of acute injuries sustained during attempted knuckle popping—a partial tear of the ulnar collateral ligament of the thumb and subluxation of the extensor tendon of the fifth digit.⁵ Both injuries were associated with forceful manipulation of the digits, and both resolved with conservative management within 4 weeks.

THE CASE

A 49-year-old woman visited our family medicine clinic because she’d had 3 episodes of epistaxis during the previous month. She’d already visited the emergency department, and the doctor there had treated her symptomatically and referred her to our clinic.

On physical examination, we noted a whitish mass in the patient’s right nostril that was attached to the nasal septum. The patient’s vital signs were within normal limits. She had a history of hypertension, depression, anxiety, gastroesophageal reflux disease, and post-traumatic stress disorder. Her medications included amlodipine-benazepril, atenolol-chlorthalidone, citalopram, clonazepam, prazosin, and omeprazole. The patient lived alone and denied using tobacco or illicit drugs, but she drank one to 2 glasses of brandy every day. She denied any past medical or family history of similar complaints, autoimmune disorders, or skin rashes.

A complete blood count, international normalized ratio, sedimentation rate, anti-nuclear antibody test, and an anti-neutrophil cytoplasmic antibody panel were normal.

THE DIAGNOSIS

We referred the patient to an ear, nose, and throat doctor for a nasal endoscopy and a biopsy, which showed granulation tissue. A maxillofacial computed tomography (CT) scan revealed a 1.44 cm x 0.8 cm polypoid soft tissue mass in the right nasal cavity adherent to the nasal septum with no posterior extension (FIGURE 1).

Pyogenic granuloma (PG) is a benign vascular tumor of the skin and mucous membranes that is not associated with an infection. Rather, it is a hyperplastic, neovascular, inflammatory response to an angiogenic stimulus. Several enhancers and inhibitors of angiogenesis have been shown to play a role in PG, including hormones, medications, and local injury. In fact, a local injury or hormonal factor is identified as a stimulus in more than half of PG patients.¹

The hormone connection. Estrogen promotes production of nerve growth factor, granulocyte-macrophage colony-stimulating factor, basic fibroblast growth factor, vascular endothelial growth factor, and transforming growth factor beta 1. Progesterone enhances inflammatory mediators as well. Although there are no direct receptors for estrogen and progesterone in the oral and nasal mucosa, some of these pro-inflammatory effects create an environment conducive to the development of PG. This is supported by several studies documenting an increased incidence of PGs with oral contraceptive use and regression of PGs after childbirth.^2-4

In more than half of patients with pyogenic granuloma, a local injury or hormonal factor is at work.

Medication may play a role. Drug-induced PG has also been described in several studies.^5,6 Offending medications include systemic and topical retinoids, capecitabine, etoposide, 5-fluorouracil, cyclosporine, docetaxel, and human immunodeficiency virus protease inhibitors.

Local injury may also be a culprit. Nasal PGs are commonly attached to the anterior septum and typically result from nasal packing, habitual picking, or nose boring.⁷ In this particular case, however, we were unable to identify the irritant.

The classic presentation

PG classically presents as a painless mass that spontaneously develops over days to weeks. The mass can be sessile or pedunculated, and is frequently hemorrhagic. Intranasal PG usually presents with epiphora.⁷ While the prevalence of intraoral PG was found to be one in 25,000 individuals³, data for nasal lesions is scarce. Most cases of PG are seen in the second and third decades of life.^1,3 In children, PG is slightly more predominant in males.^1,3 Mucosal lesions, however, have a higher incidence in females.^1,3 Granuloma gravidarum, the term used to describe mucosal PG in pregnant females, was found in 0.2% to 5% of pregnancies.^2,3,8

Differential Dx includes warts, squamous cell carcinoma

The differential diagnosis of PG includes Spitz nevus, glomus tumors, common warts, amelanotic melanoma, squamous cell carcinoma, basal cell carcinoma, Kaposi’s sarcoma, bacillary angiomatosis, infantile hemangioma, and angiolymphoid hyperplasia, among others.^3,5 Foreign bodies, nasal polyps, angiofibroma, meningocele, Wegener’s granulomatosis, and sarcoidosis should also be considered.

Radiologic evaluation may be beneficial—especially with nasal lesions—when looking for findings suggestive of malignancy. Both CT and magnetic resonance imaging with contrast identify PG as a soft tissue mass with lobulated contours,^9,10 but histopathologic analysis is required to confirm the diagnosis. The histopathologic appearance of PG is characterized by a polypoid lesion with circumscribed anastomosing networks of capillaries arranged in one or more lobules at the base in an edematous and fibroblastic stroma.

Alternatives to surgery include electrocautery, cryotherapy, laser therapy, and intralesional and topical agents, but the recurrence rate with these is often higher.

Treatment is determined by the location and size of the lesion

The most suitable treatment is determined by considering the location of the lesion, the characteristics of the lesion (morphology/size), its amenability to surgery, risk of scar formation, and the presence or absence of a causative irritant. Excision is often preferred because it yields a specimen for pathologic analysis. Alternative treatments include electrocautery, cryotherapy, laser therapy, and intralesional and topical agents,^3,6,7 but the recurrence rate is higher (up to 15%) with some of these modalities, when compared with excision (3.6%).³

Our patient underwent excision of the mass and was seen for an annual follow-up appointment. All of her symptoms resolved and no recurrence was noted.

THE TAKEAWAY

Although PG is a common and benign condition, it is rarely seen in the nasal cavity without an obvious history of a possible irritant. PG should be considered as a diagnosis for rapidly growing cutaneous or mucosal hemorrhagic lesions. Appropriate tissue pathology is essential to rule out malignancy and other serious conditions, such as bacillary angiomatosis and Wegener’s granulomatosis.

Treatment is usually required to avoid the frequent complications of ulceration and bleeding. Surgical treatments are preferred. The location of the lesion largely determines whether referral to a specialist is necessary.

THE CASE

A 49-year-old woman visited our family medicine clinic because she’d had 3 episodes of epistaxis during the previous month. She’d already visited the emergency department, and the doctor there had treated her symptomatically and referred her to our clinic.

On physical examination, we noted a whitish mass in the patient’s right nostril that was attached to the nasal septum. The patient’s vital signs were within normal limits. She had a history of hypertension, depression, anxiety, gastroesophageal reflux disease, and post-traumatic stress disorder. Her medications included amlodipine-benazepril, atenolol-chlorthalidone, citalopram, clonazepam, prazosin, and omeprazole. The patient lived alone and denied using tobacco or illicit drugs, but she drank one to 2 glasses of brandy every day. She denied any past medical or family history of similar complaints, autoimmune disorders, or skin rashes.

A complete blood count, international normalized ratio, sedimentation rate, anti-nuclear antibody test, and an anti-neutrophil cytoplasmic antibody panel were normal.

THE DIAGNOSIS

We referred the patient to an ear, nose, and throat doctor for a nasal endoscopy and a biopsy, which showed granulation tissue. A maxillofacial computed tomography (CT) scan revealed a 1.44 cm x 0.8 cm polypoid soft tissue mass in the right nasal cavity adherent to the nasal septum with no posterior extension (FIGURE 1).

Pyogenic granuloma (PG) is a benign vascular tumor of the skin and mucous membranes that is not associated with an infection. Rather, it is a hyperplastic, neovascular, inflammatory response to an angiogenic stimulus. Several enhancers and inhibitors of angiogenesis have been shown to play a role in PG, including hormones, medications, and local injury. In fact, a local injury or hormonal factor is identified as a stimulus in more than half of PG patients.¹

The hormone connection. Estrogen promotes production of nerve growth factor, granulocyte-macrophage colony-stimulating factor, basic fibroblast growth factor, vascular endothelial growth factor, and transforming growth factor beta 1. Progesterone enhances inflammatory mediators as well. Although there are no direct receptors for estrogen and progesterone in the oral and nasal mucosa, some of these pro-inflammatory effects create an environment conducive to the development of PG. This is supported by several studies documenting an increased incidence of PGs with oral contraceptive use and regression of PGs after childbirth.^2-4

In more than half of patients with pyogenic granuloma, a local injury or hormonal factor is at work.

Medication may play a role. Drug-induced PG has also been described in several studies.^5,6 Offending medications include systemic and topical retinoids, capecitabine, etoposide, 5-fluorouracil, cyclosporine, docetaxel, and human immunodeficiency virus protease inhibitors.

Local injury may also be a culprit. Nasal PGs are commonly attached to the anterior septum and typically result from nasal packing, habitual picking, or nose boring.⁷ In this particular case, however, we were unable to identify the irritant.

The classic presentation

PG classically presents as a painless mass that spontaneously develops over days to weeks. The mass can be sessile or pedunculated, and is frequently hemorrhagic. Intranasal PG usually presents with epiphora.⁷ While the prevalence of intraoral PG was found to be one in 25,000 individuals³, data for nasal lesions is scarce. Most cases of PG are seen in the second and third decades of life.^1,3 In children, PG is slightly more predominant in males.^1,3 Mucosal lesions, however, have a higher incidence in females.^1,3 Granuloma gravidarum, the term used to describe mucosal PG in pregnant females, was found in 0.2% to 5% of pregnancies.^2,3,8

Differential Dx includes warts, squamous cell carcinoma

The differential diagnosis of PG includes Spitz nevus, glomus tumors, common warts, amelanotic melanoma, squamous cell carcinoma, basal cell carcinoma, Kaposi’s sarcoma, bacillary angiomatosis, infantile hemangioma, and angiolymphoid hyperplasia, among others.^3,5 Foreign bodies, nasal polyps, angiofibroma, meningocele, Wegener’s granulomatosis, and sarcoidosis should also be considered.

Radiologic evaluation may be beneficial—especially with nasal lesions—when looking for findings suggestive of malignancy. Both CT and magnetic resonance imaging with contrast identify PG as a soft tissue mass with lobulated contours,^9,10 but histopathologic analysis is required to confirm the diagnosis. The histopathologic appearance of PG is characterized by a polypoid lesion with circumscribed anastomosing networks of capillaries arranged in one or more lobules at the base in an edematous and fibroblastic stroma.

Alternatives to surgery include electrocautery, cryotherapy, laser therapy, and intralesional and topical agents, but the recurrence rate with these is often higher.

Treatment is determined by the location and size of the lesion

The most suitable treatment is determined by considering the location of the lesion, the characteristics of the lesion (morphology/size), its amenability to surgery, risk of scar formation, and the presence or absence of a causative irritant. Excision is often preferred because it yields a specimen for pathologic analysis. Alternative treatments include electrocautery, cryotherapy, laser therapy, and intralesional and topical agents,^3,6,7 but the recurrence rate is higher (up to 15%) with some of these modalities, when compared with excision (3.6%).³

Our patient underwent excision of the mass and was seen for an annual follow-up appointment. All of her symptoms resolved and no recurrence was noted.

THE TAKEAWAY

Although PG is a common and benign condition, it is rarely seen in the nasal cavity without an obvious history of a possible irritant. PG should be considered as a diagnosis for rapidly growing cutaneous or mucosal hemorrhagic lesions. Appropriate tissue pathology is essential to rule out malignancy and other serious conditions, such as bacillary angiomatosis and Wegener’s granulomatosis.

Treatment is usually required to avoid the frequent complications of ulceration and bleeding. Surgical treatments are preferred. The location of the lesion largely determines whether referral to a specialist is necessary.

THE CASE

A 49-year-old woman visited our family medicine clinic because she’d had 3 episodes of epistaxis during the previous month. She’d already visited the emergency department, and the doctor there had treated her symptomatically and referred her to our clinic.

On physical examination, we noted a whitish mass in the patient’s right nostril that was attached to the nasal septum. The patient’s vital signs were within normal limits. She had a history of hypertension, depression, anxiety, gastroesophageal reflux disease, and post-traumatic stress disorder. Her medications included amlodipine-benazepril, atenolol-chlorthalidone, citalopram, clonazepam, prazosin, and omeprazole. The patient lived alone and denied using tobacco or illicit drugs, but she drank one to 2 glasses of brandy every day. She denied any past medical or family history of similar complaints, autoimmune disorders, or skin rashes.

A complete blood count, international normalized ratio, sedimentation rate, anti-nuclear antibody test, and an anti-neutrophil cytoplasmic antibody panel were normal.

THE DIAGNOSIS

We referred the patient to an ear, nose, and throat doctor for a nasal endoscopy and a biopsy, which showed granulation tissue. A maxillofacial computed tomography (CT) scan revealed a 1.44 cm x 0.8 cm polypoid soft tissue mass in the right nasal cavity adherent to the nasal septum with no posterior extension (FIGURE 1).

Pyogenic granuloma (PG) is a benign vascular tumor of the skin and mucous membranes that is not associated with an infection. Rather, it is a hyperplastic, neovascular, inflammatory response to an angiogenic stimulus. Several enhancers and inhibitors of angiogenesis have been shown to play a role in PG, including hormones, medications, and local injury. In fact, a local injury or hormonal factor is identified as a stimulus in more than half of PG patients.¹

The hormone connection. Estrogen promotes production of nerve growth factor, granulocyte-macrophage colony-stimulating factor, basic fibroblast growth factor, vascular endothelial growth factor, and transforming growth factor beta 1. Progesterone enhances inflammatory mediators as well. Although there are no direct receptors for estrogen and progesterone in the oral and nasal mucosa, some of these pro-inflammatory effects create an environment conducive to the development of PG. This is supported by several studies documenting an increased incidence of PGs with oral contraceptive use and regression of PGs after childbirth.^2-4

In more than half of patients with pyogenic granuloma, a local injury or hormonal factor is at work.

Medication may play a role. Drug-induced PG has also been described in several studies.^5,6 Offending medications include systemic and topical retinoids, capecitabine, etoposide, 5-fluorouracil, cyclosporine, docetaxel, and human immunodeficiency virus protease inhibitors.

Local injury may also be a culprit. Nasal PGs are commonly attached to the anterior septum and typically result from nasal packing, habitual picking, or nose boring.⁷ In this particular case, however, we were unable to identify the irritant.

The classic presentation

PG classically presents as a painless mass that spontaneously develops over days to weeks. The mass can be sessile or pedunculated, and is frequently hemorrhagic. Intranasal PG usually presents with epiphora.⁷ While the prevalence of intraoral PG was found to be one in 25,000 individuals³, data for nasal lesions is scarce. Most cases of PG are seen in the second and third decades of life.^1,3 In children, PG is slightly more predominant in males.^1,3 Mucosal lesions, however, have a higher incidence in females.^1,3 Granuloma gravidarum, the term used to describe mucosal PG in pregnant females, was found in 0.2% to 5% of pregnancies.^2,3,8

Differential Dx includes warts, squamous cell carcinoma

The differential diagnosis of PG includes Spitz nevus, glomus tumors, common warts, amelanotic melanoma, squamous cell carcinoma, basal cell carcinoma, Kaposi’s sarcoma, bacillary angiomatosis, infantile hemangioma, and angiolymphoid hyperplasia, among others.^3,5 Foreign bodies, nasal polyps, angiofibroma, meningocele, Wegener’s granulomatosis, and sarcoidosis should also be considered.

Radiologic evaluation may be beneficial—especially with nasal lesions—when looking for findings suggestive of malignancy. Both CT and magnetic resonance imaging with contrast identify PG as a soft tissue mass with lobulated contours,^9,10 but histopathologic analysis is required to confirm the diagnosis. The histopathologic appearance of PG is characterized by a polypoid lesion with circumscribed anastomosing networks of capillaries arranged in one or more lobules at the base in an edematous and fibroblastic stroma.

Alternatives to surgery include electrocautery, cryotherapy, laser therapy, and intralesional and topical agents, but the recurrence rate with these is often higher.

Treatment is determined by the location and size of the lesion

The most suitable treatment is determined by considering the location of the lesion, the characteristics of the lesion (morphology/size), its amenability to surgery, risk of scar formation, and the presence or absence of a causative irritant. Excision is often preferred because it yields a specimen for pathologic analysis. Alternative treatments include electrocautery, cryotherapy, laser therapy, and intralesional and topical agents,^3,6,7 but the recurrence rate is higher (up to 15%) with some of these modalities, when compared with excision (3.6%).³

Our patient underwent excision of the mass and was seen for an annual follow-up appointment. All of her symptoms resolved and no recurrence was noted.

THE TAKEAWAY

Although PG is a common and benign condition, it is rarely seen in the nasal cavity without an obvious history of a possible irritant. PG should be considered as a diagnosis for rapidly growing cutaneous or mucosal hemorrhagic lesions. Appropriate tissue pathology is essential to rule out malignancy and other serious conditions, such as bacillary angiomatosis and Wegener’s granulomatosis.

Treatment is usually required to avoid the frequent complications of ulceration and bleeding. Surgical treatments are preferred. The location of the lesion largely determines whether referral to a specialist is necessary.

CASE 1

A 13-month-old boy who was recently adopted from Ethiopia presented to a primary care physician with a 3-week history of bloody diarrhea accompanied by flatulence and bloating. Stool cultures were positive for Campylobacter and Shigella. He was prescribed azithromycin but saw only moderate improvement. He was then referred to the Infectious Diseases Department. Neonatal, pregnancy, and immunization histories were unknown and a review of systems was unremarkable. On exam, the child looked well; he weighed 9.6 kg (15th percentile), was 69.5 cm long (<3rd percentile), and his head circumference was 45 cm (10th percentile). Head and neck, cardiorespiratory, and abdominal examinations were unremarkable.

A complete blood count (CBC) showed an elevated white blood cell (WBC) count of 26 x 10⁹/L (normal: 4-10 x 10⁹/L) with predominant eosinophilia (10.4 x 10⁹/L or 40.1% of WBCs; normal: <0.45 x 10⁹/L or 0%-8%). Hemoglobin and platelets were within normal limits. Stool testing for ova and parasites showed Strongyloides stercoralis larvae. Strongyloides serology was negative and Filaria serology was equivocal.

CASE 2

A 15-year-old boy was assessed for a 3-week history of fever and eosinophilia. He had enlarged cervical lymph nodes, a new rash, and had lost 4 pounds. He denied gastrointestinal symptoms, dyspnea, headaches, or chest pain. His past medical and family histories were unremarkable and he reported no drug use or allergies. He had traveled to Cuba with his family for 15 days 3 months prior to presentation. He recalled diarrhea while traveling, which resolved spontaneously. He and his family had traveled “off the beaten track,” eating foods prepared at local establishments and swimming in local rivers. He received pre-travel immunizations.

On examination, he appeared unwell, though his vital signs were normal. He had diffuse lymphadenopathy and a petechial rash on his chest, back, upper buttocks, legs, and feet. Cardiorespiratory and abdominal examinations were unremarkable. A CBC revealed an elevated WBC count of 76.9 x 10⁹/L with predominant eosinophilia (71.5 x 10⁹/L or 92% of WBCs). Hemoglobin, platelets, electrolytes, and liver function tests were normal. The patient was referred to a tertiary care center and was admitted to the hospital. Stool testing for ova and parasites, as well as serology for parasitic infections, was negative. A bone marrow aspiration and biopsy were performed and revealed the diagnosis of acute lymphoblastic leukemia (ALL).

These 2 cases highlight how the presentation of eosinophilia can vary and how important it is to maintain a broad differential diagnosis (TABLE 1^1-4). Causes of eosinophilia are numerous and can be divided into 3 categories: primary, secondary, and idiopathic.^1,5 Hematologic malignancy, where eosinophilia is clonal, is an example of a primary etiology. Causes of secondary eosinophilia include infectious diseases, drugs (TABLE 2⁵), autoimmune disorders, and allergic conditions. Prolonged eosinophilia that is >3 x 10⁹/L is associated with end-organ damage. Dermatologic, pulmonary, gastro­intestinal, and cardiac involvement is most common.²

Eosinophilia associated with parasitic infection

In returning travelers and international adoptees, multicellular helminthic parasites are the most common causes of eosinophilia, with eosinophilia occurring during tissue migration or penetration.^1,3

Schistosomiasis is a chronic parasitic infection of the human vascular system. It is transmitted by contact with contaminated fresh water, where cercariae penetrate the skin. High prevalence areas include Africa and Southeast Asia. Acute infection can result in Katayama fever—a febrile illness with prominent eosinophilia that occurs 4 to 7 weeks after exposure.⁴ Diagnosis is primarily clinical with appropriate epidemiology, as serology may be negative early in infection. Praziquantel is the treatment of choice, though dosing varies by species, so expert consultation should be considered.

Soil-transmitted helminths, such as Ascaris (Ascaris lumbricoides), whipworm (Trichuris trichiura), and hookworm (Ancyclostoma duodenale and Necator americanus), can also cause eosinophilia during larval tissue migration. Following infection by ingestion or skin penetration, an acute respiratory illness, termed Löffler’s syndrome, can develop with associated eosinophilia.¹ Once the helminths reach the adult stage, eosinophilia subsides. Patients are most commonly treated with albendazole 400 mg orally for 3 days.⁴

Prolonged eosinophilia that is >3 x 10⁹/L is associated with end-organ damage.Fascioliasis is common in sheep-rearing areas. Humans are infected through ingestion of aquatic plants (eg, watercress). Parasitic migration through the duodenal wall and liver parenchyma can lead to fever, right upper quadrant pain, and eosinophilia. The incubation period is 6 to 12 weeks. Diagnosis during acute infection is by serology.⁴

Filarial infections, eg lymphatic filariasis, loiasis, and onchocerciasis, can also cause eosinophilia. The rise in eosinophils can be triggered by either the adult worms or circulating microfilariae.⁴ Treatment of fascioliasis and filarial infections varies and expert consultation is recommended.

Eosinophilia associated with primary hematologic malignancy

Eosinophilia is a rare presentation of hematologic malignancy. Acute myeloid leukemia, acute lymphoblastic leukemia (ALL), chronic myeloid leukemia, and myeloproliferative disorders have all been associated with eosinophilia. Hepatosplenomegaly, generalized lymphadenopathy, and cytopenias in other cell lines are often noted. Also, the degree of eosinophilia is often more pronounced (>5 x 10⁹/L). Patients with suspected hematologic malignancy should be urgently referred for expert consultation.⁵

Consider the following approach in the assessment of patients with eosinophilia seen in the ambulatory care setting. Inpatients or patients being seen in developing areas may require a modified approach.

History. All patients with eosinophilia should have a thorough history taken, with particular attention paid to travel history. A travel history should make note of dates, duration and location of travel, and any relevant exposures, such as arthropod bites or swimming in freshwater. Dietary habits, such as ingestion of seafood, game, or undercooked meat can also be helpful in making a diagnosis.^3,4

Causes of secondary eosinophilia include infectious diseases, drugs, autoimmune disorders, and allergic conditions.

Physical exam. In addition to a general physical examination, the following features may be helpful in determining the etiology of eosinophilia. Wheeze is characteristic of parasites in a lung migration phase (eg, strongyloidiasis and ascariasis) or asthma. Hepatomegaly can be seen with liver flukes, visceral larva migrans, or schistosomiasis. Periorbital edema can be observed with Trichinella infection. Loa loa, a type of filarial infection, produces a transient, migratory angioedema, often localized to the wrists and large joints (termed Calabar swelling). Dermatitis of varying intensity may suggest filarial infection, schistosomiasis, or atopy. Perianal dermatitis is observed with strongyloidiasis. Cutaneous larva migrans is characterized by a linear, serpiginous rash.^3,4

Laboratory investigations. Investigation will vary depending on the patient’s history, exposures, exam findings, and degree of eosinophilia. Any patient who is unwell or has significant eosinophilia (≥3 x 10⁹/L) may warrant more urgent referral to infectious disease, travel medicine, or hematology. Basic laboratory investigations should include a CBC with differential, routine serum chemistries, and liver enzymes. In the setting of significant eosinophilia, an electrocardiogram, cardiac enzyme levels, and a chest x-ray should be obtained to screen for end-organ damage related to eosinophilia.^3-5

In patients in whom you suspect hematologic malignancy, bone marrow aspiration and biopsy are often needed to make the diagnosis.⁵

In returning travelers and international adoptees, multicellular helminthic parasites are the most common causes of eosinophilia.

Parasitic infections are most often diagnosed on stool examination for ova and parasites or by serology. Stool should be collected on 3 separate days to increase diagnostic yield. Certain species of Schistosoma can also be diagnosed on direct microscopy of urine specimens. Serologic assays are available for schistosomiasis, strongyloidiasis, Toxocara, fascioliasis, filariasis, and Trichinella. Further investigations for filiariasis, including blood films, eye exam, and skin snips will vary with filarial species, so expert consultation should be considered.^3,4

Our patients. The first patient with strongyloidiasis was treated with ivermectin 200 µg/kg/day orally for 2 days and experienced symptomatic improvement and resolution of eosinophilia. The second patient with ALL was admitted and referred to hematology and received induction chemotherapy. Treatment was well tolerated and the patient was discharged one week later, with appropriate follow-up.

THE TAKEAWAY

Eosinophilia is commonly encountered in primary care. The approach to eosinophilia and the differential diagnosis can be challenging. The correct diagnosis was reached in both cases by maintaining a broad differential diagnosis. Obtaining a travel and exposure history is fundamental, although noninfectious causes, including allergy, malignancy, and drug reaction, must always be considered.

CASE 1

A 13-month-old boy who was recently adopted from Ethiopia presented to a primary care physician with a 3-week history of bloody diarrhea accompanied by flatulence and bloating. Stool cultures were positive for Campylobacter and Shigella. He was prescribed azithromycin but saw only moderate improvement. He was then referred to the Infectious Diseases Department. Neonatal, pregnancy, and immunization histories were unknown and a review of systems was unremarkable. On exam, the child looked well; he weighed 9.6 kg (15th percentile), was 69.5 cm long (<3rd percentile), and his head circumference was 45 cm (10th percentile). Head and neck, cardiorespiratory, and abdominal examinations were unremarkable.

A complete blood count (CBC) showed an elevated white blood cell (WBC) count of 26 x 10⁹/L (normal: 4-10 x 10⁹/L) with predominant eosinophilia (10.4 x 10⁹/L or 40.1% of WBCs; normal: <0.45 x 10⁹/L or 0%-8%). Hemoglobin and platelets were within normal limits. Stool testing for ova and parasites showed Strongyloides stercoralis larvae. Strongyloides serology was negative and Filaria serology was equivocal.

CASE 2

A 15-year-old boy was assessed for a 3-week history of fever and eosinophilia. He had enlarged cervical lymph nodes, a new rash, and had lost 4 pounds. He denied gastrointestinal symptoms, dyspnea, headaches, or chest pain. His past medical and family histories were unremarkable and he reported no drug use or allergies. He had traveled to Cuba with his family for 15 days 3 months prior to presentation. He recalled diarrhea while traveling, which resolved spontaneously. He and his family had traveled “off the beaten track,” eating foods prepared at local establishments and swimming in local rivers. He received pre-travel immunizations.

On examination, he appeared unwell, though his vital signs were normal. He had diffuse lymphadenopathy and a petechial rash on his chest, back, upper buttocks, legs, and feet. Cardiorespiratory and abdominal examinations were unremarkable. A CBC revealed an elevated WBC count of 76.9 x 10⁹/L with predominant eosinophilia (71.5 x 10⁹/L or 92% of WBCs). Hemoglobin, platelets, electrolytes, and liver function tests were normal. The patient was referred to a tertiary care center and was admitted to the hospital. Stool testing for ova and parasites, as well as serology for parasitic infections, was negative. A bone marrow aspiration and biopsy were performed and revealed the diagnosis of acute lymphoblastic leukemia (ALL).

These 2 cases highlight how the presentation of eosinophilia can vary and how important it is to maintain a broad differential diagnosis (TABLE 1^1-4). Causes of eosinophilia are numerous and can be divided into 3 categories: primary, secondary, and idiopathic.^1,5 Hematologic malignancy, where eosinophilia is clonal, is an example of a primary etiology. Causes of secondary eosinophilia include infectious diseases, drugs (TABLE 2⁵), autoimmune disorders, and allergic conditions. Prolonged eosinophilia that is >3 x 10⁹/L is associated with end-organ damage. Dermatologic, pulmonary, gastro­intestinal, and cardiac involvement is most common.²

Eosinophilia associated with parasitic infection

In returning travelers and international adoptees, multicellular helminthic parasites are the most common causes of eosinophilia, with eosinophilia occurring during tissue migration or penetration.^1,3

Schistosomiasis is a chronic parasitic infection of the human vascular system. It is transmitted by contact with contaminated fresh water, where cercariae penetrate the skin. High prevalence areas include Africa and Southeast Asia. Acute infection can result in Katayama fever—a febrile illness with prominent eosinophilia that occurs 4 to 7 weeks after exposure.⁴ Diagnosis is primarily clinical with appropriate epidemiology, as serology may be negative early in infection. Praziquantel is the treatment of choice, though dosing varies by species, so expert consultation should be considered.

Soil-transmitted helminths, such as Ascaris (Ascaris lumbricoides), whipworm (Trichuris trichiura), and hookworm (Ancyclostoma duodenale and Necator americanus), can also cause eosinophilia during larval tissue migration. Following infection by ingestion or skin penetration, an acute respiratory illness, termed Löffler’s syndrome, can develop with associated eosinophilia.¹ Once the helminths reach the adult stage, eosinophilia subsides. Patients are most commonly treated with albendazole 400 mg orally for 3 days.⁴

Prolonged eosinophilia that is >3 x 10⁹/L is associated with end-organ damage.Fascioliasis is common in sheep-rearing areas. Humans are infected through ingestion of aquatic plants (eg, watercress). Parasitic migration through the duodenal wall and liver parenchyma can lead to fever, right upper quadrant pain, and eosinophilia. The incubation period is 6 to 12 weeks. Diagnosis during acute infection is by serology.⁴

Filarial infections, eg lymphatic filariasis, loiasis, and onchocerciasis, can also cause eosinophilia. The rise in eosinophils can be triggered by either the adult worms or circulating microfilariae.⁴ Treatment of fascioliasis and filarial infections varies and expert consultation is recommended.

Eosinophilia associated with primary hematologic malignancy

Eosinophilia is a rare presentation of hematologic malignancy. Acute myeloid leukemia, acute lymphoblastic leukemia (ALL), chronic myeloid leukemia, and myeloproliferative disorders have all been associated with eosinophilia. Hepatosplenomegaly, generalized lymphadenopathy, and cytopenias in other cell lines are often noted. Also, the degree of eosinophilia is often more pronounced (>5 x 10⁹/L). Patients with suspected hematologic malignancy should be urgently referred for expert consultation.⁵

Consider the following approach in the assessment of patients with eosinophilia seen in the ambulatory care setting. Inpatients or patients being seen in developing areas may require a modified approach.

History. All patients with eosinophilia should have a thorough history taken, with particular attention paid to travel history. A travel history should make note of dates, duration and location of travel, and any relevant exposures, such as arthropod bites or swimming in freshwater. Dietary habits, such as ingestion of seafood, game, or undercooked meat can also be helpful in making a diagnosis.^3,4

Causes of secondary eosinophilia include infectious diseases, drugs, autoimmune disorders, and allergic conditions.

Physical exam. In addition to a general physical examination, the following features may be helpful in determining the etiology of eosinophilia. Wheeze is characteristic of parasites in a lung migration phase (eg, strongyloidiasis and ascariasis) or asthma. Hepatomegaly can be seen with liver flukes, visceral larva migrans, or schistosomiasis. Periorbital edema can be observed with Trichinella infection. Loa loa, a type of filarial infection, produces a transient, migratory angioedema, often localized to the wrists and large joints (termed Calabar swelling). Dermatitis of varying intensity may suggest filarial infection, schistosomiasis, or atopy. Perianal dermatitis is observed with strongyloidiasis. Cutaneous larva migrans is characterized by a linear, serpiginous rash.^3,4

Laboratory investigations. Investigation will vary depending on the patient’s history, exposures, exam findings, and degree of eosinophilia. Any patient who is unwell or has significant eosinophilia (≥3 x 10⁹/L) may warrant more urgent referral to infectious disease, travel medicine, or hematology. Basic laboratory investigations should include a CBC with differential, routine serum chemistries, and liver enzymes. In the setting of significant eosinophilia, an electrocardiogram, cardiac enzyme levels, and a chest x-ray should be obtained to screen for end-organ damage related to eosinophilia.^3-5

In patients in whom you suspect hematologic malignancy, bone marrow aspiration and biopsy are often needed to make the diagnosis.⁵

In returning travelers and international adoptees, multicellular helminthic parasites are the most common causes of eosinophilia.

Parasitic infections are most often diagnosed on stool examination for ova and parasites or by serology. Stool should be collected on 3 separate days to increase diagnostic yield. Certain species of Schistosoma can also be diagnosed on direct microscopy of urine specimens. Serologic assays are available for schistosomiasis, strongyloidiasis, Toxocara, fascioliasis, filariasis, and Trichinella. Further investigations for filiariasis, including blood films, eye exam, and skin snips will vary with filarial species, so expert consultation should be considered.^3,4

Our patients. The first patient with strongyloidiasis was treated with ivermectin 200 µg/kg/day orally for 2 days and experienced symptomatic improvement and resolution of eosinophilia. The second patient with ALL was admitted and referred to hematology and received induction chemotherapy. Treatment was well tolerated and the patient was discharged one week later, with appropriate follow-up.

THE TAKEAWAY

Eosinophilia is commonly encountered in primary care. The approach to eosinophilia and the differential diagnosis can be challenging. The correct diagnosis was reached in both cases by maintaining a broad differential diagnosis. Obtaining a travel and exposure history is fundamental, although noninfectious causes, including allergy, malignancy, and drug reaction, must always be considered.

CASE 1

A 13-month-old boy who was recently adopted from Ethiopia presented to a primary care physician with a 3-week history of bloody diarrhea accompanied by flatulence and bloating. Stool cultures were positive for Campylobacter and Shigella. He was prescribed azithromycin but saw only moderate improvement. He was then referred to the Infectious Diseases Department. Neonatal, pregnancy, and immunization histories were unknown and a review of systems was unremarkable. On exam, the child looked well; he weighed 9.6 kg (15th percentile), was 69.5 cm long (<3rd percentile), and his head circumference was 45 cm (10th percentile). Head and neck, cardiorespiratory, and abdominal examinations were unremarkable.

A complete blood count (CBC) showed an elevated white blood cell (WBC) count of 26 x 10⁹/L (normal: 4-10 x 10⁹/L) with predominant eosinophilia (10.4 x 10⁹/L or 40.1% of WBCs; normal: <0.45 x 10⁹/L or 0%-8%). Hemoglobin and platelets were within normal limits. Stool testing for ova and parasites showed Strongyloides stercoralis larvae. Strongyloides serology was negative and Filaria serology was equivocal.

CASE 2

A 15-year-old boy was assessed for a 3-week history of fever and eosinophilia. He had enlarged cervical lymph nodes, a new rash, and had lost 4 pounds. He denied gastrointestinal symptoms, dyspnea, headaches, or chest pain. His past medical and family histories were unremarkable and he reported no drug use or allergies. He had traveled to Cuba with his family for 15 days 3 months prior to presentation. He recalled diarrhea while traveling, which resolved spontaneously. He and his family had traveled “off the beaten track,” eating foods prepared at local establishments and swimming in local rivers. He received pre-travel immunizations.

On examination, he appeared unwell, though his vital signs were normal. He had diffuse lymphadenopathy and a petechial rash on his chest, back, upper buttocks, legs, and feet. Cardiorespiratory and abdominal examinations were unremarkable. A CBC revealed an elevated WBC count of 76.9 x 10⁹/L with predominant eosinophilia (71.5 x 10⁹/L or 92% of WBCs). Hemoglobin, platelets, electrolytes, and liver function tests were normal. The patient was referred to a tertiary care center and was admitted to the hospital. Stool testing for ova and parasites, as well as serology for parasitic infections, was negative. A bone marrow aspiration and biopsy were performed and revealed the diagnosis of acute lymphoblastic leukemia (ALL).

These 2 cases highlight how the presentation of eosinophilia can vary and how important it is to maintain a broad differential diagnosis (TABLE 1^1-4). Causes of eosinophilia are numerous and can be divided into 3 categories: primary, secondary, and idiopathic.^1,5 Hematologic malignancy, where eosinophilia is clonal, is an example of a primary etiology. Causes of secondary eosinophilia include infectious diseases, drugs (TABLE 2⁵), autoimmune disorders, and allergic conditions. Prolonged eosinophilia that is >3 x 10⁹/L is associated with end-organ damage. Dermatologic, pulmonary, gastro­intestinal, and cardiac involvement is most common.²

Eosinophilia associated with parasitic infection

In returning travelers and international adoptees, multicellular helminthic parasites are the most common causes of eosinophilia, with eosinophilia occurring during tissue migration or penetration.^1,3

Schistosomiasis is a chronic parasitic infection of the human vascular system. It is transmitted by contact with contaminated fresh water, where cercariae penetrate the skin. High prevalence areas include Africa and Southeast Asia. Acute infection can result in Katayama fever—a febrile illness with prominent eosinophilia that occurs 4 to 7 weeks after exposure.⁴ Diagnosis is primarily clinical with appropriate epidemiology, as serology may be negative early in infection. Praziquantel is the treatment of choice, though dosing varies by species, so expert consultation should be considered.

Soil-transmitted helminths, such as Ascaris (Ascaris lumbricoides), whipworm (Trichuris trichiura), and hookworm (Ancyclostoma duodenale and Necator americanus), can also cause eosinophilia during larval tissue migration. Following infection by ingestion or skin penetration, an acute respiratory illness, termed Löffler’s syndrome, can develop with associated eosinophilia.¹ Once the helminths reach the adult stage, eosinophilia subsides. Patients are most commonly treated with albendazole 400 mg orally for 3 days.⁴

Prolonged eosinophilia that is >3 x 10⁹/L is associated with end-organ damage.Fascioliasis is common in sheep-rearing areas. Humans are infected through ingestion of aquatic plants (eg, watercress). Parasitic migration through the duodenal wall and liver parenchyma can lead to fever, right upper quadrant pain, and eosinophilia. The incubation period is 6 to 12 weeks. Diagnosis during acute infection is by serology.⁴

Filarial infections, eg lymphatic filariasis, loiasis, and onchocerciasis, can also cause eosinophilia. The rise in eosinophils can be triggered by either the adult worms or circulating microfilariae.⁴ Treatment of fascioliasis and filarial infections varies and expert consultation is recommended.

Eosinophilia associated with primary hematologic malignancy

Eosinophilia is a rare presentation of hematologic malignancy. Acute myeloid leukemia, acute lymphoblastic leukemia (ALL), chronic myeloid leukemia, and myeloproliferative disorders have all been associated with eosinophilia. Hepatosplenomegaly, generalized lymphadenopathy, and cytopenias in other cell lines are often noted. Also, the degree of eosinophilia is often more pronounced (>5 x 10⁹/L). Patients with suspected hematologic malignancy should be urgently referred for expert consultation.⁵

Consider the following approach in the assessment of patients with eosinophilia seen in the ambulatory care setting. Inpatients or patients being seen in developing areas may require a modified approach.

History. All patients with eosinophilia should have a thorough history taken, with particular attention paid to travel history. A travel history should make note of dates, duration and location of travel, and any relevant exposures, such as arthropod bites or swimming in freshwater. Dietary habits, such as ingestion of seafood, game, or undercooked meat can also be helpful in making a diagnosis.^3,4

Causes of secondary eosinophilia include infectious diseases, drugs, autoimmune disorders, and allergic conditions.

Physical exam. In addition to a general physical examination, the following features may be helpful in determining the etiology of eosinophilia. Wheeze is characteristic of parasites in a lung migration phase (eg, strongyloidiasis and ascariasis) or asthma. Hepatomegaly can be seen with liver flukes, visceral larva migrans, or schistosomiasis. Periorbital edema can be observed with Trichinella infection. Loa loa, a type of filarial infection, produces a transient, migratory angioedema, often localized to the wrists and large joints (termed Calabar swelling). Dermatitis of varying intensity may suggest filarial infection, schistosomiasis, or atopy. Perianal dermatitis is observed with strongyloidiasis. Cutaneous larva migrans is characterized by a linear, serpiginous rash.^3,4

Laboratory investigations. Investigation will vary depending on the patient’s history, exposures, exam findings, and degree of eosinophilia. Any patient who is unwell or has significant eosinophilia (≥3 x 10⁹/L) may warrant more urgent referral to infectious disease, travel medicine, or hematology. Basic laboratory investigations should include a CBC with differential, routine serum chemistries, and liver enzymes. In the setting of significant eosinophilia, an electrocardiogram, cardiac enzyme levels, and a chest x-ray should be obtained to screen for end-organ damage related to eosinophilia.^3-5

In patients in whom you suspect hematologic malignancy, bone marrow aspiration and biopsy are often needed to make the diagnosis.⁵

In returning travelers and international adoptees, multicellular helminthic parasites are the most common causes of eosinophilia.

Parasitic infections are most often diagnosed on stool examination for ova and parasites or by serology. Stool should be collected on 3 separate days to increase diagnostic yield. Certain species of Schistosoma can also be diagnosed on direct microscopy of urine specimens. Serologic assays are available for schistosomiasis, strongyloidiasis, Toxocara, fascioliasis, filariasis, and Trichinella. Further investigations for filiariasis, including blood films, eye exam, and skin snips will vary with filarial species, so expert consultation should be considered.^3,4

Our patients. The first patient with strongyloidiasis was treated with ivermectin 200 µg/kg/day orally for 2 days and experienced symptomatic improvement and resolution of eosinophilia. The second patient with ALL was admitted and referred to hematology and received induction chemotherapy. Treatment was well tolerated and the patient was discharged one week later, with appropriate follow-up.

THE TAKEAWAY

Eosinophilia is commonly encountered in primary care. The approach to eosinophilia and the differential diagnosis can be challenging. The correct diagnosis was reached in both cases by maintaining a broad differential diagnosis. Obtaining a travel and exposure history is fundamental, although noninfectious causes, including allergy, malignancy, and drug reaction, must always be considered.

ILLUSTRATIVE CASE

A 64-year-old woman presents to your office for a follow-up visit for her hypertension. She is currently managed on lisinopril 20 mg/d and hydrochlorothiazide 25 mg/d without any problems. The patient’s blood pressure (BP) in the office today is 148/84 mm Hg, but her home blood pressure (HBP) readings are much lower (see TABLE). Should you increase her lisinopril dose today?

Hypertension has been diagnosed on the basis of office readings of BP for almost a century, but the readings can be so inaccurate that they are not useful.² The US Preventive Services Task Force recommends the use of ambulatory blood pressure monitoring (ABPM) to accurately diagnose hypertension in all patients, while The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends ABPM for patients suspected of having white-coat hypertension and any patient with resistant hypertension,^3,4 but ABPM is not always acceptable to patients.⁵

Guidelines recommend HBP monitoring for long-term follow-up of hypertension

The European Society of Hypertension practice guideline on HBP monitoring suggests that HBP values <130/80 mm Hg may be considered normal, while a mean HBP ≥135/85 mm Hg is considered elevated.⁹ The guideline recommends HBP monitoring for 3 to 7 days prior to a patient’s follow-up appointment with 2 readings taken one to 2 minutes apart in the morning and evening.⁹ In a busy clinic, averaging all of these home values can be time-consuming.

So how can primary care physicians accurately and efficiently streamline the process? This study sought to answer that question.

STUDY SUMMARY

When 3 of 10 readings are elevated, it’s predictive

This multicenter trial compared HBP monitoring to 24-hour ABPM in 286 patients with uncomplicated essential hypertension to determine the optimal percentage of HBP readings needed to diagnose uncontrolled BP (HBP ≥135/85 mm Hg). Patients were included if they were diagnosed with uncomplicated hypertension, not pregnant, ≥18 years of age, and taking ≤3 antihypertensive medications. Medication compliance was verified by a study nurse at a clinic visit. Patients were excluded if they had a significant abnormal left ventricular mass index (women >59 g/m²; men >64 g/m²), coronary artery or renal disease, secondary hypertension, serum creatinine exceeding 1.6 mg/dL, aortic valve stenosis, upper limb obstructive atherosclerosis, or BP >180/100 mm Hg.

The researchers found that if at least 3 of the last 10 home BP readings were elevated, the patient was likely to have hypertension on 24-hour ambulatory monitoring.

Approximately half of the participants were women (53%), average body mass index was 29.4 kg/m², and the average number of hypertension medications being taken was 2.4. The patients were instructed to take 2 BP readings (one minute apart) at home 3 times daily, in the morning (between 6 am and 10 am), at noon, and in the evening (between 6 pm and 10 pm), and to record only the second reading for 7 days. Only the morning and evening readings were used for analysis in the study. The 24-hour ABP was measured every 30 minutes during the daytime hours and every 60 minutes overnight. The primary outcome was to determine the optimal number of systolic HBP readings above goal (135 mm Hg), from the last 10 recordings, that would best predict elevated 24-hour ABP. Secondary outcomes were various cardiovascular markers of target end-organ damage.

The researchers found that if at least 3 of the last 10 HBP readings were elevated (≥135 mm Hg systolic), the patient was likely to have hypertension on 24-hour ABPM (≥130 mm Hg). When patients had <3 HBP elevations out of 10 readings, their mean (±standard deviation [SD]) 24-hour ambulatory daytime systolic BP was 132.7 (±11.1) mm Hg and their mean systolic HBP value was 120.4 (±9.8) mm Hg. When patients had ≥3 HBP elevations, their mean 24-hour ambulatory daytime systolic BP was 143.4 (±11.2) mm Hg and their mean systolic HBP value was 147.4 (±10.5) mm Hg.

The positive and negative predictive values of ≥3 HBP elevations were 0.85 (95% confidence interval [CI], 0.78-0.91) and 0.56 (95% CI, 0.48-0.64), respectively, for a 24-hour systolic ABP of ≥130 mm Hg. Three elevations or more in HBP, out of the last 10 readings, was also an indicator for target organ disease assessed by aortic stiffness and increased left ventricular mass and decreased function.

The sensitivity and specificity of ≥3 elevations for mean 24-hour ABP systolic readings ≥130 mm Hg were 62% and 80%, respectively, and for 24-hour ABP daytime systolic readings ≥135 mm Hg were 65% and 77%, respectively.

WHAT’S NEW

Monitoring home BP can be simplified

The researchers found that HBP monitoring correlates well with ABPM and that their method provides clinicians with a simple way (3 of the past 10 measurements ≥135 mm Hg systolic) to use HBP readings to make clinical decisions regarding BP management.

CAVEATS

Ideal BP goals are hazy, and a lot of patient education is required

Conflicting information and opinions remain regarding the ideal intensive and standard BP goals in different populations.^10,11 Systolic BP goals in this study (≥130 mm Hg for overall 24-hour ABP and ≥135 mm Hg for 24-hour ABP daytime readings) are recommended by some experts, but are not commonly recognized goals in the United States. This study found good correlation between HBP and ABPM at these goals, and it seems likely that this correlation could be extrapolated for similar BP goals.

Patients using home blood pressure monitors should be counseled on how to determine the appropriate cuff size so that measurements are accurate.

Other limitations are that: 1) The study focused only on systolic BP goals; 2) Patients in the study adhered to precise instructions on BP monitoring. HBP monitoring requires significant patient education on the proper use of the equipment and the monitoring schedule; and 3) While end-organ complication outcomes showed numerical decreases in function, the clinical significance of these reductions for patients is unclear.

CHALLENGES TO IMPLEMENTATION

Cost of device and improper cuff sizes could be barriers

The cost of HBP monitors ($40-$60) has decreased significantly over time, but the devices are not always covered by insurance and may be unobtainable for some people. Additionally, patients should be counseled on how to determine the appropriate cuff size to ensure the accuracy of the measurements.

The British Hypertensive Society maintains a list of validated BP devices on their Web site: http://bhsoc.org/bp-monitors/bp-monitors.¹²

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 64-year-old woman presents to your office for a follow-up visit for her hypertension. She is currently managed on lisinopril 20 mg/d and hydrochlorothiazide 25 mg/d without any problems. The patient’s blood pressure (BP) in the office today is 148/84 mm Hg, but her home blood pressure (HBP) readings are much lower (see TABLE). Should you increase her lisinopril dose today?

Hypertension has been diagnosed on the basis of office readings of BP for almost a century, but the readings can be so inaccurate that they are not useful.² The US Preventive Services Task Force recommends the use of ambulatory blood pressure monitoring (ABPM) to accurately diagnose hypertension in all patients, while The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends ABPM for patients suspected of having white-coat hypertension and any patient with resistant hypertension,^3,4 but ABPM is not always acceptable to patients.⁵

Guidelines recommend HBP monitoring for long-term follow-up of hypertension

The European Society of Hypertension practice guideline on HBP monitoring suggests that HBP values <130/80 mm Hg may be considered normal, while a mean HBP ≥135/85 mm Hg is considered elevated.⁹ The guideline recommends HBP monitoring for 3 to 7 days prior to a patient’s follow-up appointment with 2 readings taken one to 2 minutes apart in the morning and evening.⁹ In a busy clinic, averaging all of these home values can be time-consuming.

So how can primary care physicians accurately and efficiently streamline the process? This study sought to answer that question.

STUDY SUMMARY

When 3 of 10 readings are elevated, it’s predictive

This multicenter trial compared HBP monitoring to 24-hour ABPM in 286 patients with uncomplicated essential hypertension to determine the optimal percentage of HBP readings needed to diagnose uncontrolled BP (HBP ≥135/85 mm Hg). Patients were included if they were diagnosed with uncomplicated hypertension, not pregnant, ≥18 years of age, and taking ≤3 antihypertensive medications. Medication compliance was verified by a study nurse at a clinic visit. Patients were excluded if they had a significant abnormal left ventricular mass index (women >59 g/m²; men >64 g/m²), coronary artery or renal disease, secondary hypertension, serum creatinine exceeding 1.6 mg/dL, aortic valve stenosis, upper limb obstructive atherosclerosis, or BP >180/100 mm Hg.

The researchers found that if at least 3 of the last 10 home BP readings were elevated, the patient was likely to have hypertension on 24-hour ambulatory monitoring.

Approximately half of the participants were women (53%), average body mass index was 29.4 kg/m², and the average number of hypertension medications being taken was 2.4. The patients were instructed to take 2 BP readings (one minute apart) at home 3 times daily, in the morning (between 6 am and 10 am), at noon, and in the evening (between 6 pm and 10 pm), and to record only the second reading for 7 days. Only the morning and evening readings were used for analysis in the study. The 24-hour ABP was measured every 30 minutes during the daytime hours and every 60 minutes overnight. The primary outcome was to determine the optimal number of systolic HBP readings above goal (135 mm Hg), from the last 10 recordings, that would best predict elevated 24-hour ABP. Secondary outcomes were various cardiovascular markers of target end-organ damage.

The researchers found that if at least 3 of the last 10 HBP readings were elevated (≥135 mm Hg systolic), the patient was likely to have hypertension on 24-hour ABPM (≥130 mm Hg). When patients had <3 HBP elevations out of 10 readings, their mean (±standard deviation [SD]) 24-hour ambulatory daytime systolic BP was 132.7 (±11.1) mm Hg and their mean systolic HBP value was 120.4 (±9.8) mm Hg. When patients had ≥3 HBP elevations, their mean 24-hour ambulatory daytime systolic BP was 143.4 (±11.2) mm Hg and their mean systolic HBP value was 147.4 (±10.5) mm Hg.

The positive and negative predictive values of ≥3 HBP elevations were 0.85 (95% confidence interval [CI], 0.78-0.91) and 0.56 (95% CI, 0.48-0.64), respectively, for a 24-hour systolic ABP of ≥130 mm Hg. Three elevations or more in HBP, out of the last 10 readings, was also an indicator for target organ disease assessed by aortic stiffness and increased left ventricular mass and decreased function.

The sensitivity and specificity of ≥3 elevations for mean 24-hour ABP systolic readings ≥130 mm Hg were 62% and 80%, respectively, and for 24-hour ABP daytime systolic readings ≥135 mm Hg were 65% and 77%, respectively.

WHAT’S NEW

Monitoring home BP can be simplified

The researchers found that HBP monitoring correlates well with ABPM and that their method provides clinicians with a simple way (3 of the past 10 measurements ≥135 mm Hg systolic) to use HBP readings to make clinical decisions regarding BP management.

CAVEATS

Ideal BP goals are hazy, and a lot of patient education is required

Conflicting information and opinions remain regarding the ideal intensive and standard BP goals in different populations.^10,11 Systolic BP goals in this study (≥130 mm Hg for overall 24-hour ABP and ≥135 mm Hg for 24-hour ABP daytime readings) are recommended by some experts, but are not commonly recognized goals in the United States. This study found good correlation between HBP and ABPM at these goals, and it seems likely that this correlation could be extrapolated for similar BP goals.

Patients using home blood pressure monitors should be counseled on how to determine the appropriate cuff size so that measurements are accurate.

Other limitations are that: 1) The study focused only on systolic BP goals; 2) Patients in the study adhered to precise instructions on BP monitoring. HBP monitoring requires significant patient education on the proper use of the equipment and the monitoring schedule; and 3) While end-organ complication outcomes showed numerical decreases in function, the clinical significance of these reductions for patients is unclear.

CHALLENGES TO IMPLEMENTATION

Cost of device and improper cuff sizes could be barriers

The cost of HBP monitors ($40-$60) has decreased significantly over time, but the devices are not always covered by insurance and may be unobtainable for some people. Additionally, patients should be counseled on how to determine the appropriate cuff size to ensure the accuracy of the measurements.

The British Hypertensive Society maintains a list of validated BP devices on their Web site: http://bhsoc.org/bp-monitors/bp-monitors.¹²

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 64-year-old woman presents to your office for a follow-up visit for her hypertension. She is currently managed on lisinopril 20 mg/d and hydrochlorothiazide 25 mg/d without any problems. The patient’s blood pressure (BP) in the office today is 148/84 mm Hg, but her home blood pressure (HBP) readings are much lower (see TABLE). Should you increase her lisinopril dose today?

Hypertension has been diagnosed on the basis of office readings of BP for almost a century, but the readings can be so inaccurate that they are not useful.² The US Preventive Services Task Force recommends the use of ambulatory blood pressure monitoring (ABPM) to accurately diagnose hypertension in all patients, while The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends ABPM for patients suspected of having white-coat hypertension and any patient with resistant hypertension,^3,4 but ABPM is not always acceptable to patients.⁵

Guidelines recommend HBP monitoring for long-term follow-up of hypertension

The European Society of Hypertension practice guideline on HBP monitoring suggests that HBP values <130/80 mm Hg may be considered normal, while a mean HBP ≥135/85 mm Hg is considered elevated.⁹ The guideline recommends HBP monitoring for 3 to 7 days prior to a patient’s follow-up appointment with 2 readings taken one to 2 minutes apart in the morning and evening.⁹ In a busy clinic, averaging all of these home values can be time-consuming.

So how can primary care physicians accurately and efficiently streamline the process? This study sought to answer that question.

STUDY SUMMARY

When 3 of 10 readings are elevated, it’s predictive

This multicenter trial compared HBP monitoring to 24-hour ABPM in 286 patients with uncomplicated essential hypertension to determine the optimal percentage of HBP readings needed to diagnose uncontrolled BP (HBP ≥135/85 mm Hg). Patients were included if they were diagnosed with uncomplicated hypertension, not pregnant, ≥18 years of age, and taking ≤3 antihypertensive medications. Medication compliance was verified by a study nurse at a clinic visit. Patients were excluded if they had a significant abnormal left ventricular mass index (women >59 g/m²; men >64 g/m²), coronary artery or renal disease, secondary hypertension, serum creatinine exceeding 1.6 mg/dL, aortic valve stenosis, upper limb obstructive atherosclerosis, or BP >180/100 mm Hg.

The researchers found that if at least 3 of the last 10 home BP readings were elevated, the patient was likely to have hypertension on 24-hour ambulatory monitoring.

Approximately half of the participants were women (53%), average body mass index was 29.4 kg/m², and the average number of hypertension medications being taken was 2.4. The patients were instructed to take 2 BP readings (one minute apart) at home 3 times daily, in the morning (between 6 am and 10 am), at noon, and in the evening (between 6 pm and 10 pm), and to record only the second reading for 7 days. Only the morning and evening readings were used for analysis in the study. The 24-hour ABP was measured every 30 minutes during the daytime hours and every 60 minutes overnight. The primary outcome was to determine the optimal number of systolic HBP readings above goal (135 mm Hg), from the last 10 recordings, that would best predict elevated 24-hour ABP. Secondary outcomes were various cardiovascular markers of target end-organ damage.

The researchers found that if at least 3 of the last 10 HBP readings were elevated (≥135 mm Hg systolic), the patient was likely to have hypertension on 24-hour ABPM (≥130 mm Hg). When patients had <3 HBP elevations out of 10 readings, their mean (±standard deviation [SD]) 24-hour ambulatory daytime systolic BP was 132.7 (±11.1) mm Hg and their mean systolic HBP value was 120.4 (±9.8) mm Hg. When patients had ≥3 HBP elevations, their mean 24-hour ambulatory daytime systolic BP was 143.4 (±11.2) mm Hg and their mean systolic HBP value was 147.4 (±10.5) mm Hg.

The positive and negative predictive values of ≥3 HBP elevations were 0.85 (95% confidence interval [CI], 0.78-0.91) and 0.56 (95% CI, 0.48-0.64), respectively, for a 24-hour systolic ABP of ≥130 mm Hg. Three elevations or more in HBP, out of the last 10 readings, was also an indicator for target organ disease assessed by aortic stiffness and increased left ventricular mass and decreased function.

The sensitivity and specificity of ≥3 elevations for mean 24-hour ABP systolic readings ≥130 mm Hg were 62% and 80%, respectively, and for 24-hour ABP daytime systolic readings ≥135 mm Hg were 65% and 77%, respectively.

WHAT’S NEW

Monitoring home BP can be simplified

The researchers found that HBP monitoring correlates well with ABPM and that their method provides clinicians with a simple way (3 of the past 10 measurements ≥135 mm Hg systolic) to use HBP readings to make clinical decisions regarding BP management.

CAVEATS

Ideal BP goals are hazy, and a lot of patient education is required

Conflicting information and opinions remain regarding the ideal intensive and standard BP goals in different populations.^10,11 Systolic BP goals in this study (≥130 mm Hg for overall 24-hour ABP and ≥135 mm Hg for 24-hour ABP daytime readings) are recommended by some experts, but are not commonly recognized goals in the United States. This study found good correlation between HBP and ABPM at these goals, and it seems likely that this correlation could be extrapolated for similar BP goals.

Patients using home blood pressure monitors should be counseled on how to determine the appropriate cuff size so that measurements are accurate.

Other limitations are that: 1) The study focused only on systolic BP goals; 2) Patients in the study adhered to precise instructions on BP monitoring. HBP monitoring requires significant patient education on the proper use of the equipment and the monitoring schedule; and 3) While end-organ complication outcomes showed numerical decreases in function, the clinical significance of these reductions for patients is unclear.

CHALLENGES TO IMPLEMENTATION

Cost of device and improper cuff sizes could be barriers

The cost of HBP monitors ($40-$60) has decreased significantly over time, but the devices are not always covered by insurance and may be unobtainable for some people. Additionally, patients should be counseled on how to determine the appropriate cuff size to ensure the accuracy of the measurements.

The British Hypertensive Society maintains a list of validated BP devices on their Web site: http://bhsoc.org/bp-monitors/bp-monitors.¹²

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Most family physicians are accustomed to treating active patients with shin splints and stress fractures. But many are less familiar with, and slower to recognize, other sources of exertional leg pain (ELP), defined as exercise-related pain that localizes in the lower extremity distal to the knee and proximal to the talocrural joint.¹

ELP has a broad differential diagnosis that includes other musculoskeletal conditions—most notably chronic exertional compartment syndrome (CECS), which has been found to affect 33% of athletes with chronic ELP¹—as well as a number of vascular and neurologic causes.^2-4 In addition, etiologies may overlap. Greater awareness of the many causes of ELP can help you to avoid the unnecessary use of expensive diagnostic tests as well as delayed diagnosis and treatment.

A thorough medical and activity history, symptom review, and physical examination are your most important tools when patients present with ELP. When the cause is not obvious or the patient fails to respond to conservative measures, x-rays, magnetic resonance imaging (MRI), vascular studies, electromyography and nerve conduction studies, and/or intracompartmental pressure testing may be needed to find the source of the symptoms. In the text that follows, we review both common and relatively uncommon sources of ELP, using a stepwise diagnostic approach. You’ll find a diagnostic challenge, in which you can test your skills and a more comprehensive differential diagnosis in the TABLE.^1-3,5-9

Musculoskeletal injuries: Shin splints and beyond

Medial tibial stress syndrome (MTSS), commonly known as shin splints, is characterized by pain and tenderness over the posteromedial aspect of the distal tibia.³ It typically results in diffuse pain that occurs with exercise, but may persist at rest in severe cases.^3-6 Less often, localized swelling may also be present.²

MTSS accounts for between 6% and 16% of all running injuries.^2,10 It is associated with a spectrum of tibial stress injuries, including periostitis, tendinopathy, and stress reaction, with dysfunction of the tibialis posterior, tibialis anterior, and soleus muscles thought to be contributing factors.^2,11 Intrinsic factors include high body mass index (BMI), female sex, excessive internal and external hip rotation, hyperpronation, and hyper plantar flexion.^2,10,12

X-rays of the leg are typically normal in patients with MTSS and should be considered only if the clinical presentation suggests the possibility of an alternative diagnosis, such as a stress fracture or tumor.^2-4,13 Advanced imaging such as MRI or triple phase bone scans (TPBS) are useful when the diagnosis is in question and will reveal an abnormally high signal along the posterior medial tibial surface or the classic train-track appearance of nucleotide uptake in patients with MTSS.² MRI readily shows periosteal reaction and bony edema and has a sensitivity of 78% to 89% and a specificity of 33% to 100% for the diagnosis of MTSS.^14,15

While ice, NSAIDs, proper conditioning, physical therapy, and activity modification are all appropriate treatment for shin splints, none of these interventions are more effective than rest alone.

Initial management of MTSS is conservative, with the mainstay of treatment consisting of rest, ice, and nonsteroidal anti-inflammatory drugs (NSAIDs).^3,13,16 While ice, NSAIDs, proper conditioning, physical therapy to stretch and strengthen the calf musculature, rigid orthotics to correct foot hyperpronation, and activity modification are all appropriate treatments, randomized controlled trials have shown none of these interventions to be more effective than rest alone.² Non-operative treatment is usually successful, but surgery may be required for severe or refractory cases. Procedures include posteromedial fasciotomy, release of the medial soleus fascial bridge, deep compartment fasciotomy, or removal of a section of the distal tibia periosteum.^3,4

Lower extremity stress fracture. Stress fractures are caused by repetitive loading that results in microtrauma, including bony microfractures. The vast majority of cases—80% to 95% of stress fractures—affect the lower extremities, and most involve the tibia.^2-4,6,13,17 The most common presentation is an insidious onset of pain over a specific bony area with a normal appearance, although localized swelling or erythema may occasionally be present.^3,14,17,18 The pain may be reproduced or worsened by weight-bearing activities and relieved by rest.^14,18

Consider the female athlete triad. In evaluating a patient with a stress fracture, pay close attention to dietary history, BMI, and, in female athletes, take a detailed menstrual history. Such patients are at risk for amenorrhea, low bone mineral density, and nutritional deficits—the “female athlete triad,” which carries an increased risk of stress fractures.^3,14,17-19

Stress fractures can often be diagnosed with a thorough medical history and physical, with imaging used for confirmation.^6,14,17,18 Historical features of a stress fracture that may differentiate it from MTSS include pain that is unilateral and absent at rest and occurs with more prolonged activity, as well as post-exercise and/or nocturnal pain. Notable physical exam features include pain that is reproduced in a focal area with a single leg hop or percussion with a tuning fork or ultrasound.^5,11,17

Initially, sensitivity for a plain radiograph is as low as 10%.^2,11 Abnormalities on x-ray are usually seen after 2 to 8 weeks of symptoms^2,7,11 and may include a faint periosteal reaction, a fluffy area of callus, or a cortical lucency sometimes referred to as the “dreaded black line.”^3,6,17 If a radiographic exam shows evidence of a stress fracture, further imaging is typically unnecessary. MRI or TPBS is suggested, however, when x-rays appear normal but suspicion of a stress fracture remains.^3,17,18 MRI may show edema within 3 days of symptom onset and is more sensitive and specific than computed tomography (CT) or TPBS for diagnosing stress fractures of the tibia.^2,16

Treatment of tibial stress fractures is typically non-operative and consists of alterations in activity (eg, non weight-bearing), correction of nutritional deficits, such as inadequate caloric intake or too little calcium or iron, and addressing problems with footwear, training regimen, and/or running surface.^3,14,18 Fibular and posteromedial tibial stress fractures are considered low risk and heal with weight-bearing restrictions and rest, initially for a minimum of 2 to 4 weeks.³

Posteromedial tibia injuries tend to heal well because they are on the compression side of the bone. Anterior tibia stress fractures, which are located on the tension side of the bone^2,7 and account for approximately 5% of all tibia stress fractures, are more prone to non-union or progression to a complete fracture.^7,20 Thus, anterior tibia stress injuries warrant a more aggressive approach, with treatment options including non-weight bearing status that may last longer than 8 weeks, pneumatic brace casting, and/or orthopedic referral to evaluate for surgical intervention.^7,20-22 Time for radiographic evidence of healing may exceed 8 months, so early surgical intervention should be considered, especially for high-level athletes.^7,20,21

When to suspect chronic exertional compartment syndrome

Leg pain in CECS results from increased pressure within the lower extremity fascial compartments temporally related to exercise.^2,23,24 Its incidence in the general population is unknown, but CECS has been found to range from 14% to 27% in patients with previously undiagnosed leg pain^1,14,25 and to affect about a third of athletes with chronic ELP. In addition, CECS has been found in 90% of patients who have both diabetes and ELP with normal findings on vascular studies.^1,3,4,26

Pain associated with a stress fracture can typically be reproduced in a focal area with a single leg hop or percussion with a tuning fork.

The anterior compartment is most commonly affected, followed by the lateral, deep posterior, and superficial posterior compartments.^3,13,23,27 Symptoms are bilateral 60% to 95% of the time.^2,13,14,25 Factors contributing to CECS include fixed muscular compartment constraints, muscle swelling, thickened fascia, muscle hypertrophy related to resistance training, dynamic muscular contraction patterns, and low muscle capillary supply. Stretching of fascial pain receptors and pressure fibers and inadequate myocyte response to increased metabolism may play a role, as well.^14,28

The initial clinical presentation is usually predictable leg pain—ie, pain that begins at about the same time, distance, or intensity of a workout and resolves with rest; numbness and weakness may occur as the workout progresses. In time, leg pain associated with CECS may be present with everyday activity or at rest. The physical exam may be normal or reveal swelling, tenderness over the involved compartments, pain with passive digit or ankle motion, and palpable muscle herniation.¹⁴

Measurement of intracompartmental pressure before and after exercise is the gold standard for diagnosis of CECS.^2,14,27 Pre-exercise values ≥15 mm Hg and post-exercise values ≥30 mm Hg at one minute or ≥20 mm Hg at 5 minutes are all considered diagnostic of CECS,¹¹ although these widely accepted criteria for bilateral testing of all compartments yields a false-positive rate of 5%.²⁷ CECS is almost always bilateral,²⁹ and some clinicians advocate limiting the number of needle insertions by taking only post-exercise measurements and testing only symptomatic compartments in one limb.

Imaging has limited value, as both x-rays and MRIs are usually normal.¹⁴ How­ever, post-exertional T2-weighted MRI findings of muscular edema correspond to increased intracompartmental pressures, with a sensitivity of 87% and a specificity of 62%.^14,24,30,31 Infrared spectroscopy, which measures levels of oxygenated and deoxygenated blood, is sensitive for CECS when the post-exercise ratio of deoxygenated to oxygenated blood remains elevated.^14,24 Neither of these screening modalities is routinely obtained or considered diagnostic, however. Their chief role is to exclude an alternative diagnosis.¹⁴

Treatment and symptom relief. Discontinuing or modifying the aggravating activity typically brings relief of CECS. But this is not a long-term solution, as symptoms are likely to recur when the patient returns to the activity in question.¹ The definitive treatment is compartment release via fasciotomy. Success rates for anterior and lateral compartment releases are >80%.^1,28 The success of fasciotomy of posterior compartments, however, is <50%—a finding attributed to more complex anatomy, difficult visualization, and the presence of additional compartments.^1,32

When the cause is vascular

Arterial endofibrosis—the fibrotic thickening of the intima of an artery—is thought to be caused by repetitive hip flexion.⁸ This results in hyperplasia, wall thickening, and eventual stenosis of the vessel, with 90% of cases affecting the external iliac artery.^8,33 The condition is most common in activities such as cycling, but is also seen in such activities as running, skiing, soccer, and rugby. Symptoms are typically unilateral, but an estimated 15% of patients experience bilateral symptoms.^8,33

Loss of power in the affected leg, with intermittent claudication and pain due to presumed ischemia from the vascular defect, is the usual presentation, although some patients develop cramping of the buttocks and/or paresthesia of the affected leg and foot during uphill running or cycling.^8,33 The physical exam is often normal, but there may be a post-exercise arterial bruit over the femoral artery when the hip is flexed.^8,34

Consider spinal stenosis in patients who report bilateral lower extremity numbness and tingling that radiates down the legs.

Pre-exercise ankle-brachial index (ABI) <0.5 and post-exercise ABI <0.66 at one minute is suggestive of moderate arterial endofibrosis, with 90% sensitivity and 87% specificity.^8,33,34 Arterial ultrasound and color Doppler may also be used for diagnosis, but are often operator dependent. Magnetic resonance angiography (MRA), while more expensive, can detect excessive kinking or compression of the vessel and is not operator dependent.^8,33 Angioplastic balloon catheter dilation and stenting, bypass surgery, vascular reconstruction and endarterectomy with vein patch are the options for treatment. The success rates of the various interventions are unknown due to a lack of head-to-head studies and long-term follow-up.^8,33

Popliteal artery entrapment syndrome (PAES) is a constellation of symptoms caused by vascular impingement in the popliteal fossa of the knee.^8,34 The typical presenting symptoms are lower limb ischemia and pain caused by intense exercise that resolves quickly afterwards. Symptoms correlate more with the intensity than the duration of exercise.^3,8

PAES is usually caused by a variant of the gastrocnemius muscle in which a medial head passes behind the popliteal artery in males younger than 30 years.^8,33-35 Less commonly, it is the result of an overuse or acute orthopedic injury that irritates structures surrounding the popliteal fossa.^8,34 PAES affects football, basketball, and soccer players, as well as runners because of excessive dorsiflexion and plantar flexion of the ankle.^3,4

The physical exam for a patient with PAES is typically normal, but a post-exercise popliteal bruit with weak peripheral pulses may be elicited.^8,33 An ABI in the neutral, forced dorsiflexion and forced plantar flexion positions can serve as a useful screening tool. An ABI <0.9 is abnormal, with a sensitivity and specificity of 90% and 98%, respectively, for stenosis >50%.^2,36

An ankle-brachial index in the neutral, forced dorsiflexion and forced plantar flexion positions is a useful screening tool for popliteal artery entrapment syndrome.

Arteriography is the gold standard for diagnosis of PAES. Contrast arteriography is most commonly used because of its availability and cost. But MRA better differentiates functional from anatomic entrapment—a differentiation that less invasive tests, such as duplex ultrasound studies, lack the specificity to reveal.^8,34 Treatment requires either surgical removal of the offending musculotendinous structures or arterial bypass and grafting of the chronically impinged area, as conservative therapies lack efficacy.^2,8,34

Cystic adventitial disease (CAD) is the narrowing of an artery by mucoid cysts in the arterial wall or adventitia.^8,9 It is a rare condition, accounting for just 0.1% of all vascular diseases, most commonly occurring in men in their mid-40s.^8,33 CAD is thought to be the result of mucin-producing cells being haphazardly incorporated into the adventitia during arterial development. About 85% of patients whose popliteal artery is affected in this way will experience intermittent claudication with activity.^8,9

On exam, such patients often have diminished ankle-brachial pressure indices, and duplex ultrasound often reveals stenosis in the affected artery, as well as a collection of mucoid cysts in the adventitia.^8,9

Diagnosis can be confirmed by MRA.^8,37 Evidence for the treatment of CAD is largely anecdotal.⁹ Cysts may be aspirated but tend to recur, and stenting does not correct the cystic-induced narrowing of the vessel. Surgical removal of the cysts is the only successful treatment.^8,9

Neurologic causes to consider

Spinal stenosis is caused by central canal narrowing secondary to congenital abnormalities, trauma, or, most commonly, degenerative changes in the lumbar spine. Spinal stenosis is generally seen in men or women ages 50 to 70 years.³⁸ Patients experience unilateral or bilateral claudication that improves with sitting or flexion of the spine⁵ and may develop bilateral lower extremity numbness and tingling from the buttocks that radiates down the legs. Diagnosis is typically made with a combination of a lumbar x-ray and an MRI, which will show nerve compression and bony overgrowth.³⁸ CT myelogram, another imaging option, isless sensitive in the acute phase, but can be used to monitor the disease course.

Initial treatment includes physical therapy and NSAIDs.⁵ If conservative therapy fails, epidural or nerve root corticosteroid injections and surgical decompression or laminectomy are options.³⁸

Nerve entrapment is a less common source of lower extremity pain in which the superficial peroneal nerve is most often affected.^4,12,17,39 Trauma is the usual cause of nerve entrapment, but it may also be associated with overuse, most notably related to dance, soccer, or tennis.^2,14,40,41 The most likely anatomic site is where the nerve exits the deep fascia within the lateral compartment in the lower third of the leg.^39,40 Less frequently, the common peroneal nerve at the fibular neck, the saphenous nerve as it passes through Hunter’s canal, the posterior tibial nerve at the tarsal tunnel, and the sural nerve in the posterior calf may be affected.^{3,4,12,17,20,40,41} Entrapment of the peroneal nerve may be associated with activities involving repetitive inversion and eversion, such as running and cycling. Injury of the saphenous nerve is seen in sports involving repetitive knee flexion like rowing and cycling. Sural nerve entrapment is a result of crural fascia compression of the nerve during activities like running and track.^{3,14,40,42,43}

Patients typically experience burning, tingling, and radiation of pain with activity. Symptoms worsen with continued exercise. The physical exam is often normal, especially early in the disease process, but may reveal sensory loss, motor weakness, and a loss of reflexes.^2,40 Patients with superficial peroneal nerve involvement may have distal lateral leg pain that radiates into the dorsum of the foot, often exacerbated by lower leg percussion and resulting in diminished sensation.¹ Common peroneal nerve involvement may alter sensation of the lateral leg, as well, but may also cause foot drop.² The saphenous nerve can cause medial knee or leg symptoms, while the sural nerve can yield pain in the lateral ankle and foot.²

To diagnose nerve entrapment, electromyography and nerve conduction velocities at the level of the lesion may yield positive results 3 to 4 weeks after symptom onset.^2,13,40 There are wide ranges of sensitivity and specificity for these studies, but they are nonetheless considered the tests of choice for nerve entrapment.^1,44 Conservative treatment with activity modification, physical therapy, massage, and NSAIDs is often sufficient,² with surgical management warranted only for refractory cases.^2,14,40,41

CORRESPONDENCE
Jonathan A. Becker, MD, CAQSM, University of Louisville Department of Family and Geriatric Medicine, 201 Abraham Flexner Way, Suite 690, Louisville, KY 40202; jon.becker@louisville@edu.

Most family physicians are accustomed to treating active patients with shin splints and stress fractures. But many are less familiar with, and slower to recognize, other sources of exertional leg pain (ELP), defined as exercise-related pain that localizes in the lower extremity distal to the knee and proximal to the talocrural joint.¹

ELP has a broad differential diagnosis that includes other musculoskeletal conditions—most notably chronic exertional compartment syndrome (CECS), which has been found to affect 33% of athletes with chronic ELP¹—as well as a number of vascular and neurologic causes.^2-4 In addition, etiologies may overlap. Greater awareness of the many causes of ELP can help you to avoid the unnecessary use of expensive diagnostic tests as well as delayed diagnosis and treatment.

A thorough medical and activity history, symptom review, and physical examination are your most important tools when patients present with ELP. When the cause is not obvious or the patient fails to respond to conservative measures, x-rays, magnetic resonance imaging (MRI), vascular studies, electromyography and nerve conduction studies, and/or intracompartmental pressure testing may be needed to find the source of the symptoms. In the text that follows, we review both common and relatively uncommon sources of ELP, using a stepwise diagnostic approach. You’ll find a diagnostic challenge, in which you can test your skills and a more comprehensive differential diagnosis in the TABLE.^1-3,5-9

Musculoskeletal injuries: Shin splints and beyond

Medial tibial stress syndrome (MTSS), commonly known as shin splints, is characterized by pain and tenderness over the posteromedial aspect of the distal tibia.³ It typically results in diffuse pain that occurs with exercise, but may persist at rest in severe cases.^3-6 Less often, localized swelling may also be present.²

MTSS accounts for between 6% and 16% of all running injuries.^2,10 It is associated with a spectrum of tibial stress injuries, including periostitis, tendinopathy, and stress reaction, with dysfunction of the tibialis posterior, tibialis anterior, and soleus muscles thought to be contributing factors.^2,11 Intrinsic factors include high body mass index (BMI), female sex, excessive internal and external hip rotation, hyperpronation, and hyper plantar flexion.^2,10,12

X-rays of the leg are typically normal in patients with MTSS and should be considered only if the clinical presentation suggests the possibility of an alternative diagnosis, such as a stress fracture or tumor.^2-4,13 Advanced imaging such as MRI or triple phase bone scans (TPBS) are useful when the diagnosis is in question and will reveal an abnormally high signal along the posterior medial tibial surface or the classic train-track appearance of nucleotide uptake in patients with MTSS.² MRI readily shows periosteal reaction and bony edema and has a sensitivity of 78% to 89% and a specificity of 33% to 100% for the diagnosis of MTSS.^14,15

While ice, NSAIDs, proper conditioning, physical therapy, and activity modification are all appropriate treatment for shin splints, none of these interventions are more effective than rest alone.

Initial management of MTSS is conservative, with the mainstay of treatment consisting of rest, ice, and nonsteroidal anti-inflammatory drugs (NSAIDs).^3,13,16 While ice, NSAIDs, proper conditioning, physical therapy to stretch and strengthen the calf musculature, rigid orthotics to correct foot hyperpronation, and activity modification are all appropriate treatments, randomized controlled trials have shown none of these interventions to be more effective than rest alone.² Non-operative treatment is usually successful, but surgery may be required for severe or refractory cases. Procedures include posteromedial fasciotomy, release of the medial soleus fascial bridge, deep compartment fasciotomy, or removal of a section of the distal tibia periosteum.^3,4

Lower extremity stress fracture. Stress fractures are caused by repetitive loading that results in microtrauma, including bony microfractures. The vast majority of cases—80% to 95% of stress fractures—affect the lower extremities, and most involve the tibia.^2-4,6,13,17 The most common presentation is an insidious onset of pain over a specific bony area with a normal appearance, although localized swelling or erythema may occasionally be present.^3,14,17,18 The pain may be reproduced or worsened by weight-bearing activities and relieved by rest.^14,18

Consider the female athlete triad. In evaluating a patient with a stress fracture, pay close attention to dietary history, BMI, and, in female athletes, take a detailed menstrual history. Such patients are at risk for amenorrhea, low bone mineral density, and nutritional deficits—the “female athlete triad,” which carries an increased risk of stress fractures.^3,14,17-19

Stress fractures can often be diagnosed with a thorough medical history and physical, with imaging used for confirmation.^6,14,17,18 Historical features of a stress fracture that may differentiate it from MTSS include pain that is unilateral and absent at rest and occurs with more prolonged activity, as well as post-exercise and/or nocturnal pain. Notable physical exam features include pain that is reproduced in a focal area with a single leg hop or percussion with a tuning fork or ultrasound.^5,11,17

Initially, sensitivity for a plain radiograph is as low as 10%.^2,11 Abnormalities on x-ray are usually seen after 2 to 8 weeks of symptoms^2,7,11 and may include a faint periosteal reaction, a fluffy area of callus, or a cortical lucency sometimes referred to as the “dreaded black line.”^3,6,17 If a radiographic exam shows evidence of a stress fracture, further imaging is typically unnecessary. MRI or TPBS is suggested, however, when x-rays appear normal but suspicion of a stress fracture remains.^3,17,18 MRI may show edema within 3 days of symptom onset and is more sensitive and specific than computed tomography (CT) or TPBS for diagnosing stress fractures of the tibia.^2,16

Treatment of tibial stress fractures is typically non-operative and consists of alterations in activity (eg, non weight-bearing), correction of nutritional deficits, such as inadequate caloric intake or too little calcium or iron, and addressing problems with footwear, training regimen, and/or running surface.^3,14,18 Fibular and posteromedial tibial stress fractures are considered low risk and heal with weight-bearing restrictions and rest, initially for a minimum of 2 to 4 weeks.³

Posteromedial tibia injuries tend to heal well because they are on the compression side of the bone. Anterior tibia stress fractures, which are located on the tension side of the bone^2,7 and account for approximately 5% of all tibia stress fractures, are more prone to non-union or progression to a complete fracture.^7,20 Thus, anterior tibia stress injuries warrant a more aggressive approach, with treatment options including non-weight bearing status that may last longer than 8 weeks, pneumatic brace casting, and/or orthopedic referral to evaluate for surgical intervention.^7,20-22 Time for radiographic evidence of healing may exceed 8 months, so early surgical intervention should be considered, especially for high-level athletes.^7,20,21

When to suspect chronic exertional compartment syndrome

Leg pain in CECS results from increased pressure within the lower extremity fascial compartments temporally related to exercise.^2,23,24 Its incidence in the general population is unknown, but CECS has been found to range from 14% to 27% in patients with previously undiagnosed leg pain^1,14,25 and to affect about a third of athletes with chronic ELP. In addition, CECS has been found in 90% of patients who have both diabetes and ELP with normal findings on vascular studies.^1,3,4,26

Pain associated with a stress fracture can typically be reproduced in a focal area with a single leg hop or percussion with a tuning fork.

The anterior compartment is most commonly affected, followed by the lateral, deep posterior, and superficial posterior compartments.^3,13,23,27 Symptoms are bilateral 60% to 95% of the time.^2,13,14,25 Factors contributing to CECS include fixed muscular compartment constraints, muscle swelling, thickened fascia, muscle hypertrophy related to resistance training, dynamic muscular contraction patterns, and low muscle capillary supply. Stretching of fascial pain receptors and pressure fibers and inadequate myocyte response to increased metabolism may play a role, as well.^14,28

The initial clinical presentation is usually predictable leg pain—ie, pain that begins at about the same time, distance, or intensity of a workout and resolves with rest; numbness and weakness may occur as the workout progresses. In time, leg pain associated with CECS may be present with everyday activity or at rest. The physical exam may be normal or reveal swelling, tenderness over the involved compartments, pain with passive digit or ankle motion, and palpable muscle herniation.¹⁴

Measurement of intracompartmental pressure before and after exercise is the gold standard for diagnosis of CECS.^2,14,27 Pre-exercise values ≥15 mm Hg and post-exercise values ≥30 mm Hg at one minute or ≥20 mm Hg at 5 minutes are all considered diagnostic of CECS,¹¹ although these widely accepted criteria for bilateral testing of all compartments yields a false-positive rate of 5%.²⁷ CECS is almost always bilateral,²⁹ and some clinicians advocate limiting the number of needle insertions by taking only post-exercise measurements and testing only symptomatic compartments in one limb.

Imaging has limited value, as both x-rays and MRIs are usually normal.¹⁴ How­ever, post-exertional T2-weighted MRI findings of muscular edema correspond to increased intracompartmental pressures, with a sensitivity of 87% and a specificity of 62%.^14,24,30,31 Infrared spectroscopy, which measures levels of oxygenated and deoxygenated blood, is sensitive for CECS when the post-exercise ratio of deoxygenated to oxygenated blood remains elevated.^14,24 Neither of these screening modalities is routinely obtained or considered diagnostic, however. Their chief role is to exclude an alternative diagnosis.¹⁴

Treatment and symptom relief. Discontinuing or modifying the aggravating activity typically brings relief of CECS. But this is not a long-term solution, as symptoms are likely to recur when the patient returns to the activity in question.¹ The definitive treatment is compartment release via fasciotomy. Success rates for anterior and lateral compartment releases are >80%.^1,28 The success of fasciotomy of posterior compartments, however, is <50%—a finding attributed to more complex anatomy, difficult visualization, and the presence of additional compartments.^1,32

When the cause is vascular

Arterial endofibrosis—the fibrotic thickening of the intima of an artery—is thought to be caused by repetitive hip flexion.⁸ This results in hyperplasia, wall thickening, and eventual stenosis of the vessel, with 90% of cases affecting the external iliac artery.^8,33 The condition is most common in activities such as cycling, but is also seen in such activities as running, skiing, soccer, and rugby. Symptoms are typically unilateral, but an estimated 15% of patients experience bilateral symptoms.^8,33

Loss of power in the affected leg, with intermittent claudication and pain due to presumed ischemia from the vascular defect, is the usual presentation, although some patients develop cramping of the buttocks and/or paresthesia of the affected leg and foot during uphill running or cycling.^8,33 The physical exam is often normal, but there may be a post-exercise arterial bruit over the femoral artery when the hip is flexed.^8,34

Consider spinal stenosis in patients who report bilateral lower extremity numbness and tingling that radiates down the legs.

Pre-exercise ankle-brachial index (ABI) <0.5 and post-exercise ABI <0.66 at one minute is suggestive of moderate arterial endofibrosis, with 90% sensitivity and 87% specificity.^8,33,34 Arterial ultrasound and color Doppler may also be used for diagnosis, but are often operator dependent. Magnetic resonance angiography (MRA), while more expensive, can detect excessive kinking or compression of the vessel and is not operator dependent.^8,33 Angioplastic balloon catheter dilation and stenting, bypass surgery, vascular reconstruction and endarterectomy with vein patch are the options for treatment. The success rates of the various interventions are unknown due to a lack of head-to-head studies and long-term follow-up.^8,33

Popliteal artery entrapment syndrome (PAES) is a constellation of symptoms caused by vascular impingement in the popliteal fossa of the knee.^8,34 The typical presenting symptoms are lower limb ischemia and pain caused by intense exercise that resolves quickly afterwards. Symptoms correlate more with the intensity than the duration of exercise.^3,8

PAES is usually caused by a variant of the gastrocnemius muscle in which a medial head passes behind the popliteal artery in males younger than 30 years.^8,33-35 Less commonly, it is the result of an overuse or acute orthopedic injury that irritates structures surrounding the popliteal fossa.^8,34 PAES affects football, basketball, and soccer players, as well as runners because of excessive dorsiflexion and plantar flexion of the ankle.^3,4

The physical exam for a patient with PAES is typically normal, but a post-exercise popliteal bruit with weak peripheral pulses may be elicited.^8,33 An ABI in the neutral, forced dorsiflexion and forced plantar flexion positions can serve as a useful screening tool. An ABI <0.9 is abnormal, with a sensitivity and specificity of 90% and 98%, respectively, for stenosis >50%.^2,36

An ankle-brachial index in the neutral, forced dorsiflexion and forced plantar flexion positions is a useful screening tool for popliteal artery entrapment syndrome.

Arteriography is the gold standard for diagnosis of PAES. Contrast arteriography is most commonly used because of its availability and cost. But MRA better differentiates functional from anatomic entrapment—a differentiation that less invasive tests, such as duplex ultrasound studies, lack the specificity to reveal.^8,34 Treatment requires either surgical removal of the offending musculotendinous structures or arterial bypass and grafting of the chronically impinged area, as conservative therapies lack efficacy.^2,8,34

Cystic adventitial disease (CAD) is the narrowing of an artery by mucoid cysts in the arterial wall or adventitia.^8,9 It is a rare condition, accounting for just 0.1% of all vascular diseases, most commonly occurring in men in their mid-40s.^8,33 CAD is thought to be the result of mucin-producing cells being haphazardly incorporated into the adventitia during arterial development. About 85% of patients whose popliteal artery is affected in this way will experience intermittent claudication with activity.^8,9

On exam, such patients often have diminished ankle-brachial pressure indices, and duplex ultrasound often reveals stenosis in the affected artery, as well as a collection of mucoid cysts in the adventitia.^8,9

Diagnosis can be confirmed by MRA.^8,37 Evidence for the treatment of CAD is largely anecdotal.⁹ Cysts may be aspirated but tend to recur, and stenting does not correct the cystic-induced narrowing of the vessel. Surgical removal of the cysts is the only successful treatment.^8,9

Neurologic causes to consider

Spinal stenosis is caused by central canal narrowing secondary to congenital abnormalities, trauma, or, most commonly, degenerative changes in the lumbar spine. Spinal stenosis is generally seen in men or women ages 50 to 70 years.³⁸ Patients experience unilateral or bilateral claudication that improves with sitting or flexion of the spine⁵ and may develop bilateral lower extremity numbness and tingling from the buttocks that radiates down the legs. Diagnosis is typically made with a combination of a lumbar x-ray and an MRI, which will show nerve compression and bony overgrowth.³⁸ CT myelogram, another imaging option, isless sensitive in the acute phase, but can be used to monitor the disease course.

Initial treatment includes physical therapy and NSAIDs.⁵ If conservative therapy fails, epidural or nerve root corticosteroid injections and surgical decompression or laminectomy are options.³⁸

Nerve entrapment is a less common source of lower extremity pain in which the superficial peroneal nerve is most often affected.^4,12,17,39 Trauma is the usual cause of nerve entrapment, but it may also be associated with overuse, most notably related to dance, soccer, or tennis.^2,14,40,41 The most likely anatomic site is where the nerve exits the deep fascia within the lateral compartment in the lower third of the leg.^39,40 Less frequently, the common peroneal nerve at the fibular neck, the saphenous nerve as it passes through Hunter’s canal, the posterior tibial nerve at the tarsal tunnel, and the sural nerve in the posterior calf may be affected.^{3,4,12,17,20,40,41} Entrapment of the peroneal nerve may be associated with activities involving repetitive inversion and eversion, such as running and cycling. Injury of the saphenous nerve is seen in sports involving repetitive knee flexion like rowing and cycling. Sural nerve entrapment is a result of crural fascia compression of the nerve during activities like running and track.^{3,14,40,42,43}

Patients typically experience burning, tingling, and radiation of pain with activity. Symptoms worsen with continued exercise. The physical exam is often normal, especially early in the disease process, but may reveal sensory loss, motor weakness, and a loss of reflexes.^2,40 Patients with superficial peroneal nerve involvement may have distal lateral leg pain that radiates into the dorsum of the foot, often exacerbated by lower leg percussion and resulting in diminished sensation.¹ Common peroneal nerve involvement may alter sensation of the lateral leg, as well, but may also cause foot drop.² The saphenous nerve can cause medial knee or leg symptoms, while the sural nerve can yield pain in the lateral ankle and foot.²

To diagnose nerve entrapment, electromyography and nerve conduction velocities at the level of the lesion may yield positive results 3 to 4 weeks after symptom onset.^2,13,40 There are wide ranges of sensitivity and specificity for these studies, but they are nonetheless considered the tests of choice for nerve entrapment.^1,44 Conservative treatment with activity modification, physical therapy, massage, and NSAIDs is often sufficient,² with surgical management warranted only for refractory cases.^2,14,40,41

CORRESPONDENCE
Jonathan A. Becker, MD, CAQSM, University of Louisville Department of Family and Geriatric Medicine, 201 Abraham Flexner Way, Suite 690, Louisville, KY 40202; jon.becker@louisville@edu.

Most family physicians are accustomed to treating active patients with shin splints and stress fractures. But many are less familiar with, and slower to recognize, other sources of exertional leg pain (ELP), defined as exercise-related pain that localizes in the lower extremity distal to the knee and proximal to the talocrural joint.¹

ELP has a broad differential diagnosis that includes other musculoskeletal conditions—most notably chronic exertional compartment syndrome (CECS), which has been found to affect 33% of athletes with chronic ELP¹—as well as a number of vascular and neurologic causes.^2-4 In addition, etiologies may overlap. Greater awareness of the many causes of ELP can help you to avoid the unnecessary use of expensive diagnostic tests as well as delayed diagnosis and treatment.

A thorough medical and activity history, symptom review, and physical examination are your most important tools when patients present with ELP. When the cause is not obvious or the patient fails to respond to conservative measures, x-rays, magnetic resonance imaging (MRI), vascular studies, electromyography and nerve conduction studies, and/or intracompartmental pressure testing may be needed to find the source of the symptoms. In the text that follows, we review both common and relatively uncommon sources of ELP, using a stepwise diagnostic approach. You’ll find a diagnostic challenge, in which you can test your skills and a more comprehensive differential diagnosis in the TABLE.^1-3,5-9

Musculoskeletal injuries: Shin splints and beyond

Medial tibial stress syndrome (MTSS), commonly known as shin splints, is characterized by pain and tenderness over the posteromedial aspect of the distal tibia.³ It typically results in diffuse pain that occurs with exercise, but may persist at rest in severe cases.^3-6 Less often, localized swelling may also be present.²

MTSS accounts for between 6% and 16% of all running injuries.^2,10 It is associated with a spectrum of tibial stress injuries, including periostitis, tendinopathy, and stress reaction, with dysfunction of the tibialis posterior, tibialis anterior, and soleus muscles thought to be contributing factors.^2,11 Intrinsic factors include high body mass index (BMI), female sex, excessive internal and external hip rotation, hyperpronation, and hyper plantar flexion.^2,10,12

X-rays of the leg are typically normal in patients with MTSS and should be considered only if the clinical presentation suggests the possibility of an alternative diagnosis, such as a stress fracture or tumor.^2-4,13 Advanced imaging such as MRI or triple phase bone scans (TPBS) are useful when the diagnosis is in question and will reveal an abnormally high signal along the posterior medial tibial surface or the classic train-track appearance of nucleotide uptake in patients with MTSS.² MRI readily shows periosteal reaction and bony edema and has a sensitivity of 78% to 89% and a specificity of 33% to 100% for the diagnosis of MTSS.^14,15

While ice, NSAIDs, proper conditioning, physical therapy, and activity modification are all appropriate treatment for shin splints, none of these interventions are more effective than rest alone.

Initial management of MTSS is conservative, with the mainstay of treatment consisting of rest, ice, and nonsteroidal anti-inflammatory drugs (NSAIDs).^3,13,16 While ice, NSAIDs, proper conditioning, physical therapy to stretch and strengthen the calf musculature, rigid orthotics to correct foot hyperpronation, and activity modification are all appropriate treatments, randomized controlled trials have shown none of these interventions to be more effective than rest alone.² Non-operative treatment is usually successful, but surgery may be required for severe or refractory cases. Procedures include posteromedial fasciotomy, release of the medial soleus fascial bridge, deep compartment fasciotomy, or removal of a section of the distal tibia periosteum.^3,4

Lower extremity stress fracture. Stress fractures are caused by repetitive loading that results in microtrauma, including bony microfractures. The vast majority of cases—80% to 95% of stress fractures—affect the lower extremities, and most involve the tibia.^2-4,6,13,17 The most common presentation is an insidious onset of pain over a specific bony area with a normal appearance, although localized swelling or erythema may occasionally be present.^3,14,17,18 The pain may be reproduced or worsened by weight-bearing activities and relieved by rest.^14,18

Consider the female athlete triad. In evaluating a patient with a stress fracture, pay close attention to dietary history, BMI, and, in female athletes, take a detailed menstrual history. Such patients are at risk for amenorrhea, low bone mineral density, and nutritional deficits—the “female athlete triad,” which carries an increased risk of stress fractures.^3,14,17-19

Stress fractures can often be diagnosed with a thorough medical history and physical, with imaging used for confirmation.^6,14,17,18 Historical features of a stress fracture that may differentiate it from MTSS include pain that is unilateral and absent at rest and occurs with more prolonged activity, as well as post-exercise and/or nocturnal pain. Notable physical exam features include pain that is reproduced in a focal area with a single leg hop or percussion with a tuning fork or ultrasound.^5,11,17

Initially, sensitivity for a plain radiograph is as low as 10%.^2,11 Abnormalities on x-ray are usually seen after 2 to 8 weeks of symptoms^2,7,11 and may include a faint periosteal reaction, a fluffy area of callus, or a cortical lucency sometimes referred to as the “dreaded black line.”^3,6,17 If a radiographic exam shows evidence of a stress fracture, further imaging is typically unnecessary. MRI or TPBS is suggested, however, when x-rays appear normal but suspicion of a stress fracture remains.^3,17,18 MRI may show edema within 3 days of symptom onset and is more sensitive and specific than computed tomography (CT) or TPBS for diagnosing stress fractures of the tibia.^2,16

Treatment of tibial stress fractures is typically non-operative and consists of alterations in activity (eg, non weight-bearing), correction of nutritional deficits, such as inadequate caloric intake or too little calcium or iron, and addressing problems with footwear, training regimen, and/or running surface.^3,14,18 Fibular and posteromedial tibial stress fractures are considered low risk and heal with weight-bearing restrictions and rest, initially for a minimum of 2 to 4 weeks.³

Posteromedial tibia injuries tend to heal well because they are on the compression side of the bone. Anterior tibia stress fractures, which are located on the tension side of the bone^2,7 and account for approximately 5% of all tibia stress fractures, are more prone to non-union or progression to a complete fracture.^7,20 Thus, anterior tibia stress injuries warrant a more aggressive approach, with treatment options including non-weight bearing status that may last longer than 8 weeks, pneumatic brace casting, and/or orthopedic referral to evaluate for surgical intervention.^7,20-22 Time for radiographic evidence of healing may exceed 8 months, so early surgical intervention should be considered, especially for high-level athletes.^7,20,21

When to suspect chronic exertional compartment syndrome

Leg pain in CECS results from increased pressure within the lower extremity fascial compartments temporally related to exercise.^2,23,24 Its incidence in the general population is unknown, but CECS has been found to range from 14% to 27% in patients with previously undiagnosed leg pain^1,14,25 and to affect about a third of athletes with chronic ELP. In addition, CECS has been found in 90% of patients who have both diabetes and ELP with normal findings on vascular studies.^1,3,4,26

Pain associated with a stress fracture can typically be reproduced in a focal area with a single leg hop or percussion with a tuning fork.

The anterior compartment is most commonly affected, followed by the lateral, deep posterior, and superficial posterior compartments.^3,13,23,27 Symptoms are bilateral 60% to 95% of the time.^2,13,14,25 Factors contributing to CECS include fixed muscular compartment constraints, muscle swelling, thickened fascia, muscle hypertrophy related to resistance training, dynamic muscular contraction patterns, and low muscle capillary supply. Stretching of fascial pain receptors and pressure fibers and inadequate myocyte response to increased metabolism may play a role, as well.^14,28

The initial clinical presentation is usually predictable leg pain—ie, pain that begins at about the same time, distance, or intensity of a workout and resolves with rest; numbness and weakness may occur as the workout progresses. In time, leg pain associated with CECS may be present with everyday activity or at rest. The physical exam may be normal or reveal swelling, tenderness over the involved compartments, pain with passive digit or ankle motion, and palpable muscle herniation.¹⁴

Measurement of intracompartmental pressure before and after exercise is the gold standard for diagnosis of CECS.^2,14,27 Pre-exercise values ≥15 mm Hg and post-exercise values ≥30 mm Hg at one minute or ≥20 mm Hg at 5 minutes are all considered diagnostic of CECS,¹¹ although these widely accepted criteria for bilateral testing of all compartments yields a false-positive rate of 5%.²⁷ CECS is almost always bilateral,²⁹ and some clinicians advocate limiting the number of needle insertions by taking only post-exercise measurements and testing only symptomatic compartments in one limb.

Imaging has limited value, as both x-rays and MRIs are usually normal.¹⁴ How­ever, post-exertional T2-weighted MRI findings of muscular edema correspond to increased intracompartmental pressures, with a sensitivity of 87% and a specificity of 62%.^14,24,30,31 Infrared spectroscopy, which measures levels of oxygenated and deoxygenated blood, is sensitive for CECS when the post-exercise ratio of deoxygenated to oxygenated blood remains elevated.^14,24 Neither of these screening modalities is routinely obtained or considered diagnostic, however. Their chief role is to exclude an alternative diagnosis.¹⁴

Treatment and symptom relief. Discontinuing or modifying the aggravating activity typically brings relief of CECS. But this is not a long-term solution, as symptoms are likely to recur when the patient returns to the activity in question.¹ The definitive treatment is compartment release via fasciotomy. Success rates for anterior and lateral compartment releases are >80%.^1,28 The success of fasciotomy of posterior compartments, however, is <50%—a finding attributed to more complex anatomy, difficult visualization, and the presence of additional compartments.^1,32

When the cause is vascular

Arterial endofibrosis—the fibrotic thickening of the intima of an artery—is thought to be caused by repetitive hip flexion.⁸ This results in hyperplasia, wall thickening, and eventual stenosis of the vessel, with 90% of cases affecting the external iliac artery.^8,33 The condition is most common in activities such as cycling, but is also seen in such activities as running, skiing, soccer, and rugby. Symptoms are typically unilateral, but an estimated 15% of patients experience bilateral symptoms.^8,33

Loss of power in the affected leg, with intermittent claudication and pain due to presumed ischemia from the vascular defect, is the usual presentation, although some patients develop cramping of the buttocks and/or paresthesia of the affected leg and foot during uphill running or cycling.^8,33 The physical exam is often normal, but there may be a post-exercise arterial bruit over the femoral artery when the hip is flexed.^8,34

Consider spinal stenosis in patients who report bilateral lower extremity numbness and tingling that radiates down the legs.

Pre-exercise ankle-brachial index (ABI) <0.5 and post-exercise ABI <0.66 at one minute is suggestive of moderate arterial endofibrosis, with 90% sensitivity and 87% specificity.^8,33,34 Arterial ultrasound and color Doppler may also be used for diagnosis, but are often operator dependent. Magnetic resonance angiography (MRA), while more expensive, can detect excessive kinking or compression of the vessel and is not operator dependent.^8,33 Angioplastic balloon catheter dilation and stenting, bypass surgery, vascular reconstruction and endarterectomy with vein patch are the options for treatment. The success rates of the various interventions are unknown due to a lack of head-to-head studies and long-term follow-up.^8,33

Popliteal artery entrapment syndrome (PAES) is a constellation of symptoms caused by vascular impingement in the popliteal fossa of the knee.^8,34 The typical presenting symptoms are lower limb ischemia and pain caused by intense exercise that resolves quickly afterwards. Symptoms correlate more with the intensity than the duration of exercise.^3,8

PAES is usually caused by a variant of the gastrocnemius muscle in which a medial head passes behind the popliteal artery in males younger than 30 years.^8,33-35 Less commonly, it is the result of an overuse or acute orthopedic injury that irritates structures surrounding the popliteal fossa.^8,34 PAES affects football, basketball, and soccer players, as well as runners because of excessive dorsiflexion and plantar flexion of the ankle.^3,4

The physical exam for a patient with PAES is typically normal, but a post-exercise popliteal bruit with weak peripheral pulses may be elicited.^8,33 An ABI in the neutral, forced dorsiflexion and forced plantar flexion positions can serve as a useful screening tool. An ABI <0.9 is abnormal, with a sensitivity and specificity of 90% and 98%, respectively, for stenosis >50%.^2,36

An ankle-brachial index in the neutral, forced dorsiflexion and forced plantar flexion positions is a useful screening tool for popliteal artery entrapment syndrome.

Arteriography is the gold standard for diagnosis of PAES. Contrast arteriography is most commonly used because of its availability and cost. But MRA better differentiates functional from anatomic entrapment—a differentiation that less invasive tests, such as duplex ultrasound studies, lack the specificity to reveal.^8,34 Treatment requires either surgical removal of the offending musculotendinous structures or arterial bypass and grafting of the chronically impinged area, as conservative therapies lack efficacy.^2,8,34

Cystic adventitial disease (CAD) is the narrowing of an artery by mucoid cysts in the arterial wall or adventitia.^8,9 It is a rare condition, accounting for just 0.1% of all vascular diseases, most commonly occurring in men in their mid-40s.^8,33 CAD is thought to be the result of mucin-producing cells being haphazardly incorporated into the adventitia during arterial development. About 85% of patients whose popliteal artery is affected in this way will experience intermittent claudication with activity.^8,9

On exam, such patients often have diminished ankle-brachial pressure indices, and duplex ultrasound often reveals stenosis in the affected artery, as well as a collection of mucoid cysts in the adventitia.^8,9

Diagnosis can be confirmed by MRA.^8,37 Evidence for the treatment of CAD is largely anecdotal.⁹ Cysts may be aspirated but tend to recur, and stenting does not correct the cystic-induced narrowing of the vessel. Surgical removal of the cysts is the only successful treatment.^8,9

Neurologic causes to consider

Spinal stenosis is caused by central canal narrowing secondary to congenital abnormalities, trauma, or, most commonly, degenerative changes in the lumbar spine. Spinal stenosis is generally seen in men or women ages 50 to 70 years.³⁸ Patients experience unilateral or bilateral claudication that improves with sitting or flexion of the spine⁵ and may develop bilateral lower extremity numbness and tingling from the buttocks that radiates down the legs. Diagnosis is typically made with a combination of a lumbar x-ray and an MRI, which will show nerve compression and bony overgrowth.³⁸ CT myelogram, another imaging option, isless sensitive in the acute phase, but can be used to monitor the disease course.

Initial treatment includes physical therapy and NSAIDs.⁵ If conservative therapy fails, epidural or nerve root corticosteroid injections and surgical decompression or laminectomy are options.³⁸

Nerve entrapment is a less common source of lower extremity pain in which the superficial peroneal nerve is most often affected.^4,12,17,39 Trauma is the usual cause of nerve entrapment, but it may also be associated with overuse, most notably related to dance, soccer, or tennis.^2,14,40,41 The most likely anatomic site is where the nerve exits the deep fascia within the lateral compartment in the lower third of the leg.^39,40 Less frequently, the common peroneal nerve at the fibular neck, the saphenous nerve as it passes through Hunter’s canal, the posterior tibial nerve at the tarsal tunnel, and the sural nerve in the posterior calf may be affected.^{3,4,12,17,20,40,41} Entrapment of the peroneal nerve may be associated with activities involving repetitive inversion and eversion, such as running and cycling. Injury of the saphenous nerve is seen in sports involving repetitive knee flexion like rowing and cycling. Sural nerve entrapment is a result of crural fascia compression of the nerve during activities like running and track.^{3,14,40,42,43}

Patients typically experience burning, tingling, and radiation of pain with activity. Symptoms worsen with continued exercise. The physical exam is often normal, especially early in the disease process, but may reveal sensory loss, motor weakness, and a loss of reflexes.^2,40 Patients with superficial peroneal nerve involvement may have distal lateral leg pain that radiates into the dorsum of the foot, often exacerbated by lower leg percussion and resulting in diminished sensation.¹ Common peroneal nerve involvement may alter sensation of the lateral leg, as well, but may also cause foot drop.² The saphenous nerve can cause medial knee or leg symptoms, while the sural nerve can yield pain in the lateral ankle and foot.²

To diagnose nerve entrapment, electromyography and nerve conduction velocities at the level of the lesion may yield positive results 3 to 4 weeks after symptom onset.^2,13,40 There are wide ranges of sensitivity and specificity for these studies, but they are nonetheless considered the tests of choice for nerve entrapment.^1,44 Conservative treatment with activity modification, physical therapy, massage, and NSAIDs is often sufficient,² with surgical management warranted only for refractory cases.^2,14,40,41

CORRESPONDENCE
Jonathan A. Becker, MD, CAQSM, University of Louisville Department of Family and Geriatric Medicine, 201 Abraham Flexner Way, Suite 690, Louisville, KY 40202; jon.becker@louisville@edu.

About 27 million Americans undergo surgery every year¹ and before doing so, they turn to you—their primary care physician—or their cardiologist for a preoperative evaluation. Of course, the goal of this evaluation is to determine an individual patient’s risk and compare it to procedural averages in an effort to identify opportunities for risk mitigation. But the preoperative evaluation is also an opportunity to make recommendations regarding perioperative management of medications. And certainly we want to conduct these evaluations in a way that is both expeditious and in keeping with the latest guidelines.

Current guidelines for preoperative evaluations are less complicated than they used to be and focus on cardiac and pulmonary risk stratification. While a risk calculator remains your primary tool, elements such as smoking cessation and identifying sleep apnea are important parts of the preop equation. In the review that follows, we present a simple algorithm (FIGURE 1^2-6) that we developed that can be completed in a single visit.

Cardiac assessment: A risk calculator is the primary tool

Cardiac risk estimation is perhaps the most important element in determining a patient’s overall surgical risk. But before you begin, you'll need to determine whether the preoperative evaluation of the patient is best handled by you or a specialist. Current guidelines recommend preoperative evaluation by a specialist when a patient has certain conditions, such as moderate or greater valvular stenosis/regurgitation, a cardiac implantable electronic device, pulmonary hypertension, congenital heart disease, or severe systemic disease.²

If these conditions are not present (and an immediate referral is not required), you can turn your attention to the cardiac assessment. The first step is to determine which cardiac risk calculator you’d like to use. In its comprehensive guideline on perioperative cardiovascular evaluation, the American College of Cardiology/American Heart Association (ACC/AHA) recommends the use of one of the 2 calculators described below.²

Revised Cardiac Risk Index. The most well-known cardiac risk calculator is the 6-element Revised Cardiac Risk Index (RCRI) (TABLE 1).⁷ Published in 1999, the RCRI was derived from a cohort of 2800 patients, verified in 1400 patients, and has been validated in numerous studies.² Each element increases the odds of a cardiac complication by a factor of 2 to 3, and more than one positive response indicates the patient is at high risk for complications.⁷

While a risk calculator remains your primary tool, elements such as smoking cessation and identifying sleep apnea are important parts of the equation.

The ACS NSQIP risk calculator has been criticized because it has not been validated in a group separate from the initial patient population used in its development.² Another criticism is the inclusion of the American Society of Anesthesiologists' (ASA) classification of the overall health of the patient, a simple yet subjective and unreliable method of patient characterization.²

Choosing a calculator. The ACS NSQIP calculator may be more useful for primary care physicians because it provides individualized risks for numerous complications and is easy to use. The output page can be printed as documentation of the preoperative evaluation, and is useful for counseling patients about reconsideration of surgery or risk-reduction strategies. The RCRI is also simple to use, but considers only cardiac risk. Although the RCRI has been validated in numerous studies, the ACS NSQIP was derived from a more substantial 1.4 million patients.

The next step in the preoperative evaluation process is to calculate your patient’s risk score and determine whether it is low or high. If the risk is determined to be low—either an RCRI score <2 or an ACS NSQIP cardiac complication risk <1%—the patient can be referred to surgery without further evaluation.²

If the patient has a functional status of >4 METs, refer him or her for surgery without further evaluation.

If the calculator suggests higher risk, the patient’s functional status should be assessed. If the patient has a functional status of >4 metabolic equivalents (METs), then the patient can be recommended for surgery without further evaluation.² Examples of activities that are greater than 4 METs are yard work such as raking leaves, weeding, or pushing a power mower; sexual relations; climbing a flight of stairs; walking up a hill; and participating in moderate recreational activities like golf, bowling, dancing, doubles tennis, or throwing a baseball or football.⁹

Patient can’t perform >4 METs? If the patient does not have a functional capacity of >4 METs, further risk stratification should be considered if the results would change management.² Prior guidelines recommended either perioperative beta-blockers to mitigate risk or coronary interventions, but both are controversial due to lack of proven benefit.

Perioperative beta-blocker use. A recommendation to consider starting beta-blockers at least one day prior to surgery remains in the 2014 ACC/AHA guidelines for patients with 3 or more RCRI risk factors.² But a group of studies supporting beta-blocker use has been discredited due to serious flaws and fabricated data. At the same time, a large study arguing against perioperative beta-blockers has been criticized for starting high doses of beta-blockers on the day of surgery.^2,10,11 In the end, mortality benefit from perioperative beta-blockers is uncertain, and the suggested reduction in cardiac events is partially offset by an increased risk of stroke.²

Stress testing is of questionable value. A patient with high cardiac risk (as evaluated with a calculator) may need to forego the surgical procedure or undergo a modified procedure. Alternatively, he or she may need to be referred to a cardiologist for consultation and possible pharmacologic nuclear stress testing. Although a normal stress test has a high negative predictive value, an abnormal test often leads to percutaneous coronary intervention or bypass surgery, and neither has been shown to reduce cardiac surgical risk.² Percutaneous coronary interventions require a period of dual antiplatelet therapy, delaying surgery for unproven benefit.²

EKGs and echocardiograms are of limited use. An anesthesia group or surgical center will often require an electrocardiogram (EKG) as part of a preoperative evaluation, but preoperative evaluation by EKG or echocardiogram is controversial due to unproven benefits and potential risks. The 2014 ACC/AHA guidelines recommend against a 12-lead EKG for patients with low cardiac risk using the RCRI or ACS NSQIP or those who are having a low-risk procedure, such as endoscopy or cataract surgery.² The United States Preventive Health Services Task Force also recommends against screening low-risk patients and says that screening EKGs and stress testing in asymptomatic medium- to high-risk patients is of undetermined value.¹² They noted no evidence of benefit from resting or exercise EKG, with harm from a 1.7% complication rate of angiography, which is performed after up to 2.9% of exercise EKG testing.¹²

Mortality benefit from perioperative beta-blockers is uncertain, and the suggested reduction in cardiac events is partially offset by an increased risk of stroke.

There are no recommendations for preoperative echocardiogram in the asymptomatic patient. Only unexplained dyspnea or other clinical signs of heart failure require an echocardiogram. For patients with known heart failure that is clinically stable, the ACC/AHA guidelines suggest that an echocardiogram should be performed within the year prior to surgery, although this is based on expert opinion.²

Because of the controversy over both coronary interventions and perioperative beta-blocker therapy, consider cardiology referral for a patient with poor functional activity level who does not meet low-risk criteria. While stress testing is acceptable, it may not lead to improved patient outcomes.

Optimize preventive care

Begin by ensuring that blood pressure (BP) and cholesterol are managed according to ACC/AHA guidelines. Then consider whether to start preoperative medications. You'll also want to screen for sleep apnea and discuss smoking status and cessation, if appropriate.

Initiate medications preoperatively?

In addition to having value as long-term primary prevention, there is some evidence that statins help prevent cardiac events during surgery. A randomized trial of over 200 vascular surgery patients showed that starting statins an average of 30 days prior to surgery significantly reduced cardiac complications.¹³ Another systematic review demonstrated that preoperative statins significantly reduce acute kidney injury from surgery.¹⁴

Unlike statins, aspirin started prior to surgery does not confer benefit. Aspirin was shown to significantly increase bleeding risk without improving cardiac outcomes in a large trial.¹⁵

Screen for sleep apnea

Sleep apnea increases the rate of respiratory failure between 2 and 3 times and the rate of cardiac complications about 1.5 times.¹⁶ This is a potentially correctable risk factor. The European Society of Anaesthesiology recommends clinical screening for obstructive sleep apnea using the STOP-Bang screening tool⁵ (TABLE 2⁴). For its part, the ASA combines screening questions from the STOP-Bang screening questionnaire with a review of the medical record and physical exam, because the STOP-Bang questionnaire alone has an insufficient negative predictive value, ranging from 30% and 82%.⁶ Obstructive sleep apnea is not addressed on published pulmonary and cardiac risk tools.^2,3,7,8

Is the patient a smoker?

Smoking is a reversible risk factor for pulmonary, cardiac, and infectious complications, as well as overall mortality. Perioperative smoking cessation counseling has been complicated by concerns that stopping smoking within 8 weeks of surgery might worsen postoperative outcomes. A study that looked at intraoperative sputum retrieved via tracheal suction showed that patients who had stopped smoking for 2 months or more prior to surgery had the same amount of sputum as non-smokers, while those that quit smoking <2 months before surgery were more likely to have increased intraoperative sputum volume.¹⁸ This study did not demonstrate a difference in postoperative pulmonary complications, likely because it included patients receiving minor surgeries only. But based on this study, a cessation period of 2 months was often recommended.

A recent systematic review showed that smoking cessation shortly before surgery does not increase risk.¹⁹ In fact, although the review did not show a statistically significant reduction in postoperative complications among recent quitters as compared with continued smokers, there was a trend toward a reduction in overall complications with only a slight increase in pulmonary complications.¹⁹

Address potential pulmonary complications

In addition to screening for issues that could lead to cardiac complications, it’s important to address the potential for pulmonary complications. Postoperative pulmonary complications are at least as common as cardiac complications, and include all possible respiratory related outcomes of surgery, from pneumonia to respiratory failure.

During the preoperative evaluation, verify that BP and cholesterol are managed per ACC/AHA guidelines.

The seminal study on postoperative pulmonary complications is a systematic review published in 2006, which showed that the most important risk factors were surgery type, advanced age, ASA classification of overall health ≥II, and congestive heart failure.³ Chronic lung diseases and cigarette use were less predictive of pulmonary issues. All of these factors are included in the ACS NSQIP risk calculator.

One aspect of the preoperative evaluation that should not be overlooked is a thorough medication reconciliation. Primary care providers can support the operative team by recommending medication adjustments prior to surgery. Several classes of medications have specific perioperative recommendations, which are summarized here.

Hypertension medications

• Beta-blockers. A patient who regularly takes a beta-blocker should continue the medication on the day of surgery and restart after surgery.^2,20
• Calcium channel blockers. Calcium channel blockers can be continued through the day of surgery.^2,20
• Renin-angiotensin system antagonists. Given the increased risk of hypotension following anesthesia induction, have patients refrain from taking angiotensin-converting enzyme inhibitors and angiotensin receptor blocker medications for at least 10 hours prior to surgery.²⁰
• Diuretics. Diuretics can be given on the day of surgery, although they increase the risk of hypovolemia and electrolyte disturbances.²⁰

Diabetes medications

• Insulin. For patients with type I diabetes, recommend basal insulin of 0.2 to 0.3 units/kg/day of long-acting insulin.²¹ If the patient is using an insulin pump, basal rate should be continued. For patients with type 2 diabetes, the simplest method is to use one-half the normal long-acting insulin dose on the morning of surgery.²²
• Metformin. Discontinue metformin 24 hours prior to surgery because of the risk for lactic acidosis.^21,22 While the risk of lactic acidosis from metformin is low, mortality rates as high as 50% have been documented after lactic acidosis occurred with similar medications.²²
• Sulfonylureas. Sulfonylureas should be held on the day of surgery due to the risk of hypoglycemia and a possible increased risk of ischemia.^21,22
• Thiazolidinediones, dipeptidyl peptidase-4 inhibitors, and glucagon-like peptide-1 agonists. All should be held on the day of surgery.²¹

Anticoagulant medications

Whether patients quit smoking less than or more than 2 months before surgery is less important than that they quit.

• Vitamin K antagonists (warfarin). Discontinue warfarin 5 days prior to the procedure. The half-life is approximately 40 hours, requiring at least 5 days for the anticoagulant effect to be eliminated from the body.²³ Use of bridging therapy with regular- or low-molecular weight heparin remains controversial due to increased surgical bleeding risk without evidence of a decrease in cardiovascular events.²⁴ The patient’s risks of stroke and venous thromboembolism should be taken into account when deciding whether to use bridging therapy or not.
• Factor Xa inhibitor. Management of factor Xa inhibitors (rivaroxaban, apixaban) depends on the bleeding risk of the surgery and the patient’s renal function.^24,25 For instance, a patient undergoing cataract surgery (low risk) needs a shorter cessation time than a patient undergoing hip arthroplasty (high risk). Discontinuation times are listed in TABLE 3.²⁴
• Direct thrombin inhibitor. Management of direct thrombin inhibitors (dabigatran) is also dependent on surgical bleeding risk and renal function (TABLE 3).^23,24
• Aspirin, clopidogrel, ticlopidine, prasugrel. All should be stopped 7 to 10 days prior to surgery to allow new platelet growth. Low-dose aspirin for secondary prevention of cardiovascular disease or primary prevention in a high-risk patient can be continued through surgery.²³

Other

• Corticosteroids. Recent evidence suggests that stress-dose steroids are not needed to prevent adrenal insufficiency in patients taking corticosteroids chronically.²⁶ These patients should continue maintenance therapy at regular dosing.^26,27 Stress dosing of corticosteroids is only required when a patient has signs of adrenal insufficiency.²⁶
• Statins. Statin medications should be continued on the day of surgery.²
• Nonsteroidal anti-inflammatory drugs. NSAIDs should be stopped 5 days prior to surgery to reverse antiplatelet effects.²³

CORRESPONDENCE
CDR Michael J. Arnold, Naval Hospital, 2080 Child Street, Jacksonville, FL 32214; michael.j.arnold4.mil@mail.mil.

ACKNOWLEDGEMENT
The authors thank CDR Kristian Sanchack and LCDR Dustin Smith for their assistance with this manuscript.

About 27 million Americans undergo surgery every year¹ and before doing so, they turn to you—their primary care physician—or their cardiologist for a preoperative evaluation. Of course, the goal of this evaluation is to determine an individual patient’s risk and compare it to procedural averages in an effort to identify opportunities for risk mitigation. But the preoperative evaluation is also an opportunity to make recommendations regarding perioperative management of medications. And certainly we want to conduct these evaluations in a way that is both expeditious and in keeping with the latest guidelines.

Current guidelines for preoperative evaluations are less complicated than they used to be and focus on cardiac and pulmonary risk stratification. While a risk calculator remains your primary tool, elements such as smoking cessation and identifying sleep apnea are important parts of the preop equation. In the review that follows, we present a simple algorithm (FIGURE 1^2-6) that we developed that can be completed in a single visit.

Cardiac assessment: A risk calculator is the primary tool

Cardiac risk estimation is perhaps the most important element in determining a patient’s overall surgical risk. But before you begin, you'll need to determine whether the preoperative evaluation of the patient is best handled by you or a specialist. Current guidelines recommend preoperative evaluation by a specialist when a patient has certain conditions, such as moderate or greater valvular stenosis/regurgitation, a cardiac implantable electronic device, pulmonary hypertension, congenital heart disease, or severe systemic disease.²

If these conditions are not present (and an immediate referral is not required), you can turn your attention to the cardiac assessment. The first step is to determine which cardiac risk calculator you’d like to use. In its comprehensive guideline on perioperative cardiovascular evaluation, the American College of Cardiology/American Heart Association (ACC/AHA) recommends the use of one of the 2 calculators described below.²

Revised Cardiac Risk Index. The most well-known cardiac risk calculator is the 6-element Revised Cardiac Risk Index (RCRI) (TABLE 1).⁷ Published in 1999, the RCRI was derived from a cohort of 2800 patients, verified in 1400 patients, and has been validated in numerous studies.² Each element increases the odds of a cardiac complication by a factor of 2 to 3, and more than one positive response indicates the patient is at high risk for complications.⁷

While a risk calculator remains your primary tool, elements such as smoking cessation and identifying sleep apnea are important parts of the equation.

The ACS NSQIP risk calculator has been criticized because it has not been validated in a group separate from the initial patient population used in its development.² Another criticism is the inclusion of the American Society of Anesthesiologists' (ASA) classification of the overall health of the patient, a simple yet subjective and unreliable method of patient characterization.²

Choosing a calculator. The ACS NSQIP calculator may be more useful for primary care physicians because it provides individualized risks for numerous complications and is easy to use. The output page can be printed as documentation of the preoperative evaluation, and is useful for counseling patients about reconsideration of surgery or risk-reduction strategies. The RCRI is also simple to use, but considers only cardiac risk. Although the RCRI has been validated in numerous studies, the ACS NSQIP was derived from a more substantial 1.4 million patients.

The next step in the preoperative evaluation process is to calculate your patient’s risk score and determine whether it is low or high. If the risk is determined to be low—either an RCRI score <2 or an ACS NSQIP cardiac complication risk <1%—the patient can be referred to surgery without further evaluation.²

If the patient has a functional status of >4 METs, refer him or her for surgery without further evaluation.

If the calculator suggests higher risk, the patient’s functional status should be assessed. If the patient has a functional status of >4 metabolic equivalents (METs), then the patient can be recommended for surgery without further evaluation.² Examples of activities that are greater than 4 METs are yard work such as raking leaves, weeding, or pushing a power mower; sexual relations; climbing a flight of stairs; walking up a hill; and participating in moderate recreational activities like golf, bowling, dancing, doubles tennis, or throwing a baseball or football.⁹

Patient can’t perform >4 METs? If the patient does not have a functional capacity of >4 METs, further risk stratification should be considered if the results would change management.² Prior guidelines recommended either perioperative beta-blockers to mitigate risk or coronary interventions, but both are controversial due to lack of proven benefit.

Perioperative beta-blocker use. A recommendation to consider starting beta-blockers at least one day prior to surgery remains in the 2014 ACC/AHA guidelines for patients with 3 or more RCRI risk factors.² But a group of studies supporting beta-blocker use has been discredited due to serious flaws and fabricated data. At the same time, a large study arguing against perioperative beta-blockers has been criticized for starting high doses of beta-blockers on the day of surgery.^2,10,11 In the end, mortality benefit from perioperative beta-blockers is uncertain, and the suggested reduction in cardiac events is partially offset by an increased risk of stroke.²

Stress testing is of questionable value. A patient with high cardiac risk (as evaluated with a calculator) may need to forego the surgical procedure or undergo a modified procedure. Alternatively, he or she may need to be referred to a cardiologist for consultation and possible pharmacologic nuclear stress testing. Although a normal stress test has a high negative predictive value, an abnormal test often leads to percutaneous coronary intervention or bypass surgery, and neither has been shown to reduce cardiac surgical risk.² Percutaneous coronary interventions require a period of dual antiplatelet therapy, delaying surgery for unproven benefit.²

EKGs and echocardiograms are of limited use. An anesthesia group or surgical center will often require an electrocardiogram (EKG) as part of a preoperative evaluation, but preoperative evaluation by EKG or echocardiogram is controversial due to unproven benefits and potential risks. The 2014 ACC/AHA guidelines recommend against a 12-lead EKG for patients with low cardiac risk using the RCRI or ACS NSQIP or those who are having a low-risk procedure, such as endoscopy or cataract surgery.² The United States Preventive Health Services Task Force also recommends against screening low-risk patients and says that screening EKGs and stress testing in asymptomatic medium- to high-risk patients is of undetermined value.¹² They noted no evidence of benefit from resting or exercise EKG, with harm from a 1.7% complication rate of angiography, which is performed after up to 2.9% of exercise EKG testing.¹²

Mortality benefit from perioperative beta-blockers is uncertain, and the suggested reduction in cardiac events is partially offset by an increased risk of stroke.

There are no recommendations for preoperative echocardiogram in the asymptomatic patient. Only unexplained dyspnea or other clinical signs of heart failure require an echocardiogram. For patients with known heart failure that is clinically stable, the ACC/AHA guidelines suggest that an echocardiogram should be performed within the year prior to surgery, although this is based on expert opinion.²

Because of the controversy over both coronary interventions and perioperative beta-blocker therapy, consider cardiology referral for a patient with poor functional activity level who does not meet low-risk criteria. While stress testing is acceptable, it may not lead to improved patient outcomes.

Optimize preventive care

Begin by ensuring that blood pressure (BP) and cholesterol are managed according to ACC/AHA guidelines. Then consider whether to start preoperative medications. You'll also want to screen for sleep apnea and discuss smoking status and cessation, if appropriate.

Initiate medications preoperatively?

In addition to having value as long-term primary prevention, there is some evidence that statins help prevent cardiac events during surgery. A randomized trial of over 200 vascular surgery patients showed that starting statins an average of 30 days prior to surgery significantly reduced cardiac complications.¹³ Another systematic review demonstrated that preoperative statins significantly reduce acute kidney injury from surgery.¹⁴

Unlike statins, aspirin started prior to surgery does not confer benefit. Aspirin was shown to significantly increase bleeding risk without improving cardiac outcomes in a large trial.¹⁵

Screen for sleep apnea

Sleep apnea increases the rate of respiratory failure between 2 and 3 times and the rate of cardiac complications about 1.5 times.¹⁶ This is a potentially correctable risk factor. The European Society of Anaesthesiology recommends clinical screening for obstructive sleep apnea using the STOP-Bang screening tool⁵ (TABLE 2⁴). For its part, the ASA combines screening questions from the STOP-Bang screening questionnaire with a review of the medical record and physical exam, because the STOP-Bang questionnaire alone has an insufficient negative predictive value, ranging from 30% and 82%.⁶ Obstructive sleep apnea is not addressed on published pulmonary and cardiac risk tools.^2,3,7,8

Is the patient a smoker?

Smoking is a reversible risk factor for pulmonary, cardiac, and infectious complications, as well as overall mortality. Perioperative smoking cessation counseling has been complicated by concerns that stopping smoking within 8 weeks of surgery might worsen postoperative outcomes. A study that looked at intraoperative sputum retrieved via tracheal suction showed that patients who had stopped smoking for 2 months or more prior to surgery had the same amount of sputum as non-smokers, while those that quit smoking <2 months before surgery were more likely to have increased intraoperative sputum volume.¹⁸ This study did not demonstrate a difference in postoperative pulmonary complications, likely because it included patients receiving minor surgeries only. But based on this study, a cessation period of 2 months was often recommended.

A recent systematic review showed that smoking cessation shortly before surgery does not increase risk.¹⁹ In fact, although the review did not show a statistically significant reduction in postoperative complications among recent quitters as compared with continued smokers, there was a trend toward a reduction in overall complications with only a slight increase in pulmonary complications.¹⁹

Address potential pulmonary complications

In addition to screening for issues that could lead to cardiac complications, it’s important to address the potential for pulmonary complications. Postoperative pulmonary complications are at least as common as cardiac complications, and include all possible respiratory related outcomes of surgery, from pneumonia to respiratory failure.

During the preoperative evaluation, verify that BP and cholesterol are managed per ACC/AHA guidelines.

The seminal study on postoperative pulmonary complications is a systematic review published in 2006, which showed that the most important risk factors were surgery type, advanced age, ASA classification of overall health ≥II, and congestive heart failure.³ Chronic lung diseases and cigarette use were less predictive of pulmonary issues. All of these factors are included in the ACS NSQIP risk calculator.

One aspect of the preoperative evaluation that should not be overlooked is a thorough medication reconciliation. Primary care providers can support the operative team by recommending medication adjustments prior to surgery. Several classes of medications have specific perioperative recommendations, which are summarized here.

Hypertension medications

• Beta-blockers. A patient who regularly takes a beta-blocker should continue the medication on the day of surgery and restart after surgery.^2,20
• Calcium channel blockers. Calcium channel blockers can be continued through the day of surgery.^2,20
• Renin-angiotensin system antagonists. Given the increased risk of hypotension following anesthesia induction, have patients refrain from taking angiotensin-converting enzyme inhibitors and angiotensin receptor blocker medications for at least 10 hours prior to surgery.²⁰
• Diuretics. Diuretics can be given on the day of surgery, although they increase the risk of hypovolemia and electrolyte disturbances.²⁰

Diabetes medications

• Insulin. For patients with type I diabetes, recommend basal insulin of 0.2 to 0.3 units/kg/day of long-acting insulin.²¹ If the patient is using an insulin pump, basal rate should be continued. For patients with type 2 diabetes, the simplest method is to use one-half the normal long-acting insulin dose on the morning of surgery.²²
• Metformin. Discontinue metformin 24 hours prior to surgery because of the risk for lactic acidosis.^21,22 While the risk of lactic acidosis from metformin is low, mortality rates as high as 50% have been documented after lactic acidosis occurred with similar medications.²²
• Sulfonylureas. Sulfonylureas should be held on the day of surgery due to the risk of hypoglycemia and a possible increased risk of ischemia.^21,22
• Thiazolidinediones, dipeptidyl peptidase-4 inhibitors, and glucagon-like peptide-1 agonists. All should be held on the day of surgery.²¹

Anticoagulant medications

Whether patients quit smoking less than or more than 2 months before surgery is less important than that they quit.

• Vitamin K antagonists (warfarin). Discontinue warfarin 5 days prior to the procedure. The half-life is approximately 40 hours, requiring at least 5 days for the anticoagulant effect to be eliminated from the body.²³ Use of bridging therapy with regular- or low-molecular weight heparin remains controversial due to increased surgical bleeding risk without evidence of a decrease in cardiovascular events.²⁴ The patient’s risks of stroke and venous thromboembolism should be taken into account when deciding whether to use bridging therapy or not.
• Factor Xa inhibitor. Management of factor Xa inhibitors (rivaroxaban, apixaban) depends on the bleeding risk of the surgery and the patient’s renal function.^24,25 For instance, a patient undergoing cataract surgery (low risk) needs a shorter cessation time than a patient undergoing hip arthroplasty (high risk). Discontinuation times are listed in TABLE 3.²⁴
• Direct thrombin inhibitor. Management of direct thrombin inhibitors (dabigatran) is also dependent on surgical bleeding risk and renal function (TABLE 3).^23,24
• Aspirin, clopidogrel, ticlopidine, prasugrel. All should be stopped 7 to 10 days prior to surgery to allow new platelet growth. Low-dose aspirin for secondary prevention of cardiovascular disease or primary prevention in a high-risk patient can be continued through surgery.²³

Other

• Corticosteroids. Recent evidence suggests that stress-dose steroids are not needed to prevent adrenal insufficiency in patients taking corticosteroids chronically.²⁶ These patients should continue maintenance therapy at regular dosing.^26,27 Stress dosing of corticosteroids is only required when a patient has signs of adrenal insufficiency.²⁶
• Statins. Statin medications should be continued on the day of surgery.²
• Nonsteroidal anti-inflammatory drugs. NSAIDs should be stopped 5 days prior to surgery to reverse antiplatelet effects.²³

CORRESPONDENCE
CDR Michael J. Arnold, Naval Hospital, 2080 Child Street, Jacksonville, FL 32214; michael.j.arnold4.mil@mail.mil.

ACKNOWLEDGEMENT
The authors thank CDR Kristian Sanchack and LCDR Dustin Smith for their assistance with this manuscript.

About 27 million Americans undergo surgery every year¹ and before doing so, they turn to you—their primary care physician—or their cardiologist for a preoperative evaluation. Of course, the goal of this evaluation is to determine an individual patient’s risk and compare it to procedural averages in an effort to identify opportunities for risk mitigation. But the preoperative evaluation is also an opportunity to make recommendations regarding perioperative management of medications. And certainly we want to conduct these evaluations in a way that is both expeditious and in keeping with the latest guidelines.

Current guidelines for preoperative evaluations are less complicated than they used to be and focus on cardiac and pulmonary risk stratification. While a risk calculator remains your primary tool, elements such as smoking cessation and identifying sleep apnea are important parts of the preop equation. In the review that follows, we present a simple algorithm (FIGURE 1^2-6) that we developed that can be completed in a single visit.

Cardiac assessment: A risk calculator is the primary tool

Cardiac risk estimation is perhaps the most important element in determining a patient’s overall surgical risk. But before you begin, you'll need to determine whether the preoperative evaluation of the patient is best handled by you or a specialist. Current guidelines recommend preoperative evaluation by a specialist when a patient has certain conditions, such as moderate or greater valvular stenosis/regurgitation, a cardiac implantable electronic device, pulmonary hypertension, congenital heart disease, or severe systemic disease.²

If these conditions are not present (and an immediate referral is not required), you can turn your attention to the cardiac assessment. The first step is to determine which cardiac risk calculator you’d like to use. In its comprehensive guideline on perioperative cardiovascular evaluation, the American College of Cardiology/American Heart Association (ACC/AHA) recommends the use of one of the 2 calculators described below.²

Revised Cardiac Risk Index. The most well-known cardiac risk calculator is the 6-element Revised Cardiac Risk Index (RCRI) (TABLE 1).⁷ Published in 1999, the RCRI was derived from a cohort of 2800 patients, verified in 1400 patients, and has been validated in numerous studies.² Each element increases the odds of a cardiac complication by a factor of 2 to 3, and more than one positive response indicates the patient is at high risk for complications.⁷

While a risk calculator remains your primary tool, elements such as smoking cessation and identifying sleep apnea are important parts of the equation.

The ACS NSQIP risk calculator has been criticized because it has not been validated in a group separate from the initial patient population used in its development.² Another criticism is the inclusion of the American Society of Anesthesiologists' (ASA) classification of the overall health of the patient, a simple yet subjective and unreliable method of patient characterization.²

Choosing a calculator. The ACS NSQIP calculator may be more useful for primary care physicians because it provides individualized risks for numerous complications and is easy to use. The output page can be printed as documentation of the preoperative evaluation, and is useful for counseling patients about reconsideration of surgery or risk-reduction strategies. The RCRI is also simple to use, but considers only cardiac risk. Although the RCRI has been validated in numerous studies, the ACS NSQIP was derived from a more substantial 1.4 million patients.

The next step in the preoperative evaluation process is to calculate your patient’s risk score and determine whether it is low or high. If the risk is determined to be low—either an RCRI score <2 or an ACS NSQIP cardiac complication risk <1%—the patient can be referred to surgery without further evaluation.²

If the patient has a functional status of >4 METs, refer him or her for surgery without further evaluation.

If the calculator suggests higher risk, the patient’s functional status should be assessed. If the patient has a functional status of >4 metabolic equivalents (METs), then the patient can be recommended for surgery without further evaluation.² Examples of activities that are greater than 4 METs are yard work such as raking leaves, weeding, or pushing a power mower; sexual relations; climbing a flight of stairs; walking up a hill; and participating in moderate recreational activities like golf, bowling, dancing, doubles tennis, or throwing a baseball or football.⁹

Patient can’t perform >4 METs? If the patient does not have a functional capacity of >4 METs, further risk stratification should be considered if the results would change management.² Prior guidelines recommended either perioperative beta-blockers to mitigate risk or coronary interventions, but both are controversial due to lack of proven benefit.

Perioperative beta-blocker use. A recommendation to consider starting beta-blockers at least one day prior to surgery remains in the 2014 ACC/AHA guidelines for patients with 3 or more RCRI risk factors.² But a group of studies supporting beta-blocker use has been discredited due to serious flaws and fabricated data. At the same time, a large study arguing against perioperative beta-blockers has been criticized for starting high doses of beta-blockers on the day of surgery.^2,10,11 In the end, mortality benefit from perioperative beta-blockers is uncertain, and the suggested reduction in cardiac events is partially offset by an increased risk of stroke.²

Stress testing is of questionable value. A patient with high cardiac risk (as evaluated with a calculator) may need to forego the surgical procedure or undergo a modified procedure. Alternatively, he or she may need to be referred to a cardiologist for consultation and possible pharmacologic nuclear stress testing. Although a normal stress test has a high negative predictive value, an abnormal test often leads to percutaneous coronary intervention or bypass surgery, and neither has been shown to reduce cardiac surgical risk.² Percutaneous coronary interventions require a period of dual antiplatelet therapy, delaying surgery for unproven benefit.²

EKGs and echocardiograms are of limited use. An anesthesia group or surgical center will often require an electrocardiogram (EKG) as part of a preoperative evaluation, but preoperative evaluation by EKG or echocardiogram is controversial due to unproven benefits and potential risks. The 2014 ACC/AHA guidelines recommend against a 12-lead EKG for patients with low cardiac risk using the RCRI or ACS NSQIP or those who are having a low-risk procedure, such as endoscopy or cataract surgery.² The United States Preventive Health Services Task Force also recommends against screening low-risk patients and says that screening EKGs and stress testing in asymptomatic medium- to high-risk patients is of undetermined value.¹² They noted no evidence of benefit from resting or exercise EKG, with harm from a 1.7% complication rate of angiography, which is performed after up to 2.9% of exercise EKG testing.¹²

Mortality benefit from perioperative beta-blockers is uncertain, and the suggested reduction in cardiac events is partially offset by an increased risk of stroke.

There are no recommendations for preoperative echocardiogram in the asymptomatic patient. Only unexplained dyspnea or other clinical signs of heart failure require an echocardiogram. For patients with known heart failure that is clinically stable, the ACC/AHA guidelines suggest that an echocardiogram should be performed within the year prior to surgery, although this is based on expert opinion.²

Because of the controversy over both coronary interventions and perioperative beta-blocker therapy, consider cardiology referral for a patient with poor functional activity level who does not meet low-risk criteria. While stress testing is acceptable, it may not lead to improved patient outcomes.

Optimize preventive care

Begin by ensuring that blood pressure (BP) and cholesterol are managed according to ACC/AHA guidelines. Then consider whether to start preoperative medications. You'll also want to screen for sleep apnea and discuss smoking status and cessation, if appropriate.

Initiate medications preoperatively?

In addition to having value as long-term primary prevention, there is some evidence that statins help prevent cardiac events during surgery. A randomized trial of over 200 vascular surgery patients showed that starting statins an average of 30 days prior to surgery significantly reduced cardiac complications.¹³ Another systematic review demonstrated that preoperative statins significantly reduce acute kidney injury from surgery.¹⁴

Unlike statins, aspirin started prior to surgery does not confer benefit. Aspirin was shown to significantly increase bleeding risk without improving cardiac outcomes in a large trial.¹⁵

Screen for sleep apnea

Sleep apnea increases the rate of respiratory failure between 2 and 3 times and the rate of cardiac complications about 1.5 times.¹⁶ This is a potentially correctable risk factor. The European Society of Anaesthesiology recommends clinical screening for obstructive sleep apnea using the STOP-Bang screening tool⁵ (TABLE 2⁴). For its part, the ASA combines screening questions from the STOP-Bang screening questionnaire with a review of the medical record and physical exam, because the STOP-Bang questionnaire alone has an insufficient negative predictive value, ranging from 30% and 82%.⁶ Obstructive sleep apnea is not addressed on published pulmonary and cardiac risk tools.^2,3,7,8

Is the patient a smoker?

Smoking is a reversible risk factor for pulmonary, cardiac, and infectious complications, as well as overall mortality. Perioperative smoking cessation counseling has been complicated by concerns that stopping smoking within 8 weeks of surgery might worsen postoperative outcomes. A study that looked at intraoperative sputum retrieved via tracheal suction showed that patients who had stopped smoking for 2 months or more prior to surgery had the same amount of sputum as non-smokers, while those that quit smoking <2 months before surgery were more likely to have increased intraoperative sputum volume.¹⁸ This study did not demonstrate a difference in postoperative pulmonary complications, likely because it included patients receiving minor surgeries only. But based on this study, a cessation period of 2 months was often recommended.

A recent systematic review showed that smoking cessation shortly before surgery does not increase risk.¹⁹ In fact, although the review did not show a statistically significant reduction in postoperative complications among recent quitters as compared with continued smokers, there was a trend toward a reduction in overall complications with only a slight increase in pulmonary complications.¹⁹

Address potential pulmonary complications

In addition to screening for issues that could lead to cardiac complications, it’s important to address the potential for pulmonary complications. Postoperative pulmonary complications are at least as common as cardiac complications, and include all possible respiratory related outcomes of surgery, from pneumonia to respiratory failure.

During the preoperative evaluation, verify that BP and cholesterol are managed per ACC/AHA guidelines.

The seminal study on postoperative pulmonary complications is a systematic review published in 2006, which showed that the most important risk factors were surgery type, advanced age, ASA classification of overall health ≥II, and congestive heart failure.³ Chronic lung diseases and cigarette use were less predictive of pulmonary issues. All of these factors are included in the ACS NSQIP risk calculator.

One aspect of the preoperative evaluation that should not be overlooked is a thorough medication reconciliation. Primary care providers can support the operative team by recommending medication adjustments prior to surgery. Several classes of medications have specific perioperative recommendations, which are summarized here.

Hypertension medications

• Beta-blockers. A patient who regularly takes a beta-blocker should continue the medication on the day of surgery and restart after surgery.^2,20
• Calcium channel blockers. Calcium channel blockers can be continued through the day of surgery.^2,20
• Renin-angiotensin system antagonists. Given the increased risk of hypotension following anesthesia induction, have patients refrain from taking angiotensin-converting enzyme inhibitors and angiotensin receptor blocker medications for at least 10 hours prior to surgery.²⁰
• Diuretics. Diuretics can be given on the day of surgery, although they increase the risk of hypovolemia and electrolyte disturbances.²⁰

Diabetes medications

• Insulin. For patients with type I diabetes, recommend basal insulin of 0.2 to 0.3 units/kg/day of long-acting insulin.²¹ If the patient is using an insulin pump, basal rate should be continued. For patients with type 2 diabetes, the simplest method is to use one-half the normal long-acting insulin dose on the morning of surgery.²²
• Metformin. Discontinue metformin 24 hours prior to surgery because of the risk for lactic acidosis.^21,22 While the risk of lactic acidosis from metformin is low, mortality rates as high as 50% have been documented after lactic acidosis occurred with similar medications.²²
• Sulfonylureas. Sulfonylureas should be held on the day of surgery due to the risk of hypoglycemia and a possible increased risk of ischemia.^21,22
• Thiazolidinediones, dipeptidyl peptidase-4 inhibitors, and glucagon-like peptide-1 agonists. All should be held on the day of surgery.²¹

Anticoagulant medications

Whether patients quit smoking less than or more than 2 months before surgery is less important than that they quit.

• Vitamin K antagonists (warfarin). Discontinue warfarin 5 days prior to the procedure. The half-life is approximately 40 hours, requiring at least 5 days for the anticoagulant effect to be eliminated from the body.²³ Use of bridging therapy with regular- or low-molecular weight heparin remains controversial due to increased surgical bleeding risk without evidence of a decrease in cardiovascular events.²⁴ The patient’s risks of stroke and venous thromboembolism should be taken into account when deciding whether to use bridging therapy or not.
• Factor Xa inhibitor. Management of factor Xa inhibitors (rivaroxaban, apixaban) depends on the bleeding risk of the surgery and the patient’s renal function.^24,25 For instance, a patient undergoing cataract surgery (low risk) needs a shorter cessation time than a patient undergoing hip arthroplasty (high risk). Discontinuation times are listed in TABLE 3.²⁴
• Direct thrombin inhibitor. Management of direct thrombin inhibitors (dabigatran) is also dependent on surgical bleeding risk and renal function (TABLE 3).^23,24
• Aspirin, clopidogrel, ticlopidine, prasugrel. All should be stopped 7 to 10 days prior to surgery to allow new platelet growth. Low-dose aspirin for secondary prevention of cardiovascular disease or primary prevention in a high-risk patient can be continued through surgery.²³

Other

• Corticosteroids. Recent evidence suggests that stress-dose steroids are not needed to prevent adrenal insufficiency in patients taking corticosteroids chronically.²⁶ These patients should continue maintenance therapy at regular dosing.^26,27 Stress dosing of corticosteroids is only required when a patient has signs of adrenal insufficiency.²⁶
• Statins. Statin medications should be continued on the day of surgery.²
• Nonsteroidal anti-inflammatory drugs. NSAIDs should be stopped 5 days prior to surgery to reverse antiplatelet effects.²³

CORRESPONDENCE
CDR Michael J. Arnold, Naval Hospital, 2080 Child Street, Jacksonville, FL 32214; michael.j.arnold4.mil@mail.mil.

ACKNOWLEDGEMENT
The authors thank CDR Kristian Sanchack and LCDR Dustin Smith for their assistance with this manuscript.

Food and Drug Administration (FDA) Commissioner Robert Califf, MD, will deliver a keynote address on the opening morning of the NORD Rare Diseases and Orphan Products Breakthrough Summit to take place Oct. 17 and 18 in Arlington Virginia. Approximately one-third of the novel new drugs approved by FDA in recent years have been “orphan” drugs for rare diseases.

Dr. Califf will be joined on the program agenda by more than 25 additional FDA speakers, including Janet Woodcock, MD, Director of FDA’s Center for Drug Evaluation and Research, and Peter Marks, MD, PhD, Director of FDA’s Center for Biologics Evaluation and Research.

On Day Two of the conference, Kate Rawson, Senior Editor at Prevision Policy, will provide the morning keynote with a look ahead at possible implications of the national election for the rare disease community.  The NORD Summit attracts medical professionals, patient advocates, and others to examine issues related to rare disease research, diagnosis, treatment, and patient access to care. The conference is open to all. Click here to view the agenda.

Food and Drug Administration (FDA) Commissioner Robert Califf, MD, will deliver a keynote address on the opening morning of the NORD Rare Diseases and Orphan Products Breakthrough Summit to take place Oct. 17 and 18 in Arlington Virginia. Approximately one-third of the novel new drugs approved by FDA in recent years have been “orphan” drugs for rare diseases.

Dr. Califf will be joined on the program agenda by more than 25 additional FDA speakers, including Janet Woodcock, MD, Director of FDA’s Center for Drug Evaluation and Research, and Peter Marks, MD, PhD, Director of FDA’s Center for Biologics Evaluation and Research.

On Day Two of the conference, Kate Rawson, Senior Editor at Prevision Policy, will provide the morning keynote with a look ahead at possible implications of the national election for the rare disease community.  The NORD Summit attracts medical professionals, patient advocates, and others to examine issues related to rare disease research, diagnosis, treatment, and patient access to care. The conference is open to all. Click here to view the agenda.

Food and Drug Administration (FDA) Commissioner Robert Califf, MD, will deliver a keynote address on the opening morning of the NORD Rare Diseases and Orphan Products Breakthrough Summit to take place Oct. 17 and 18 in Arlington Virginia. Approximately one-third of the novel new drugs approved by FDA in recent years have been “orphan” drugs for rare diseases.

Dr. Califf will be joined on the program agenda by more than 25 additional FDA speakers, including Janet Woodcock, MD, Director of FDA’s Center for Drug Evaluation and Research, and Peter Marks, MD, PhD, Director of FDA’s Center for Biologics Evaluation and Research.

On Day Two of the conference, Kate Rawson, Senior Editor at Prevision Policy, will provide the morning keynote with a look ahead at possible implications of the national election for the rare disease community.  The NORD Summit attracts medical professionals, patient advocates, and others to examine issues related to rare disease research, diagnosis, treatment, and patient access to care. The conference is open to all. Click here to view the agenda.