The Journal of Family Practice

Your article, “Is an underlying cardiac condition causing your patient’s palpitations?” (J Fam Pract. 2021;70:60-68), listed a number of causes of palpitations in the table on page 62. However, 1 cause was noticeably missing: underlying genetic disorders, such as amyloidosis. Genetic disorders can affect the cardiac muscle and lead to increased rates of both cardiac arrhythmias and palpitations.

I recently treated a 43-year-old man who presented with shortness of breath and presyncopal episodes; his medical history included anxiety and gastritis. He previously had undergone a cervical spine fusion and was postoperatively given a diagnosis of bigeminy and frequent premature ventricular contractions (PVCs). An echocardiogram was ordered and came back negative, while a Holter monitor showed PVCs > 30%. Genetic testing was performed only after the family history offered some clues. The diagnosis was hereditary transthyretin (ATTR) amyloidosis. Now, he is awaiting cardiac magnetic resonance imaging to determine whether muscle or pericardium has been affected. 
 

Genetic disorders can affect the cardiac muscle and lead to increased rates of both cardiac arrhythmias and palpitations.

When I discussed the findings with the patient, he wisely stated, “Perhaps it is more common than studies show if patients are not normally tested until elderly or hospitalized.” This resonated with me when I considered that routine lab work done in an office would miss amyloidosis. This definitely reinforced my philosophy to always listen to the patient and take symptoms seriously, as sometimes we just haven’t figured out the true diagnosis yet. 

Your article, “Is an underlying cardiac condition causing your patient’s palpitations?” (J Fam Pract. 2021;70:60-68), listed a number of causes of palpitations in the table on page 62. However, 1 cause was noticeably missing: underlying genetic disorders, such as amyloidosis. Genetic disorders can affect the cardiac muscle and lead to increased rates of both cardiac arrhythmias and palpitations.

I recently treated a 43-year-old man who presented with shortness of breath and presyncopal episodes; his medical history included anxiety and gastritis. He previously had undergone a cervical spine fusion and was postoperatively given a diagnosis of bigeminy and frequent premature ventricular contractions (PVCs). An echocardiogram was ordered and came back negative, while a Holter monitor showed PVCs > 30%. Genetic testing was performed only after the family history offered some clues. The diagnosis was hereditary transthyretin (ATTR) amyloidosis. Now, he is awaiting cardiac magnetic resonance imaging to determine whether muscle or pericardium has been affected. 
 

Genetic disorders can affect the cardiac muscle and lead to increased rates of both cardiac arrhythmias and palpitations.

When I discussed the findings with the patient, he wisely stated, “Perhaps it is more common than studies show if patients are not normally tested until elderly or hospitalized.” This resonated with me when I considered that routine lab work done in an office would miss amyloidosis. This definitely reinforced my philosophy to always listen to the patient and take symptoms seriously, as sometimes we just haven’t figured out the true diagnosis yet. 

Your article, “Is an underlying cardiac condition causing your patient’s palpitations?” (J Fam Pract. 2021;70:60-68), listed a number of causes of palpitations in the table on page 62. However, 1 cause was noticeably missing: underlying genetic disorders, such as amyloidosis. Genetic disorders can affect the cardiac muscle and lead to increased rates of both cardiac arrhythmias and palpitations.

I recently treated a 43-year-old man who presented with shortness of breath and presyncopal episodes; his medical history included anxiety and gastritis. He previously had undergone a cervical spine fusion and was postoperatively given a diagnosis of bigeminy and frequent premature ventricular contractions (PVCs). An echocardiogram was ordered and came back negative, while a Holter monitor showed PVCs > 30%. Genetic testing was performed only after the family history offered some clues. The diagnosis was hereditary transthyretin (ATTR) amyloidosis. Now, he is awaiting cardiac magnetic resonance imaging to determine whether muscle or pericardium has been affected. 
 

Genetic disorders can affect the cardiac muscle and lead to increased rates of both cardiac arrhythmias and palpitations.

When I discussed the findings with the patient, he wisely stated, “Perhaps it is more common than studies show if patients are not normally tested until elderly or hospitalized.” This resonated with me when I considered that routine lab work done in an office would miss amyloidosis. This definitely reinforced my philosophy to always listen to the patient and take symptoms seriously, as sometimes we just haven’t figured out the true diagnosis yet. 

ILLUSTRATIVE CASE

A 55-year-old man with a history of chronic obstructive pulmonary disease (COPD) presents to you with increased sputum volume and increased dyspnea, but no fever. You diagnose a COPD exacerbation. Would point-of-care C-reactive protein (CRP) testing be a useful tool to guide antibiotic prescribing?

COPD is a common respiratory condition and one of the leading causes of death in the world.² COPD requires chronic therapy and frequent treatment for acute exacerbations.³ A systematic review found that exacerbations occur an average of 1.3 times per year for patients with known COPD.⁴ Antibiotics are often prescribed for COPD exacerbations, but which patients benefit most from antibiotic treatment is unclear and identification often is based on clinical features alone. Additionally, overprescribing of antibiotics can lead to unnecessary adverse effects, drive antibiotic resistance, and be a waste of resources.⁵

The European Respiratory Society/American Thoracic Society (ERS/ATS) provides a conditional recommendation to consider antibiotics in ambulatory patients with COPD exacerbation based on moderate-quality evidence.⁶ The 2020 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend antibiotics for moderately or severely ill patients with a COPD exacerbation who have increased cough and sputum purulence.⁷ While the ERS/ATS recommendations do not mention CRP, the GOLD guidelines discuss biomarkers as emerging tools in determining antibiotic utility.

Biomarkers such as procalcitonin and CRP are being examined as potential tools to distinguish which patients would benefit from antibiotic treatment in COPD exacerbations. In a 2013 study, CRP levels > 19.6 mg/L in the serum and > 15.2 mg/L in the sputum indicated a bacterial infection, but more research was needed to determine if CRP could help guide antibiotic prescribing.⁸ In a 2019 randomized trial of 101 patients with COPD exacerbations, researchers compared the GOLD strategy for antibiotic prescribing with a CRP-guided antibiotic strategy (CRP ≥ 50 mg/L) and found no difference in adverse events between study groups.⁹

This trial focused on point-of-care CRP-guided prescribing of antibiotics for patients with COPD exacerbations in the outpatient setting.

STUDY SUMMARY

Point-of-care CRP testing is noninferior to usual care

This open-label, multicenter, randomized controlled trial at 86 general medical practices in the United Kingdom examined whether the use of point-of-care CRP testing could reduce antibiotic use during acute exacerbations of COPD. Patients (N = 653; 650 needed to provide 81% to 90% power) were ages 40 years and older, had a diagnosis of COPD, and presented for an acute exacerbation of COPD based on the presence of at least 1 Anthonisen criteria (increased dyspnea, increase in sputum volume, and increase in purulent sputum).

Patients were randomized in a 1:1 fashion to receive care guided by point-of-care CRP testing (CRP-guided) or usual care for their COPD exacerbation. Patients in the CRP-guided group received a point-of-care CRP test as part of their assessment at presentation, or at any other appointments for COPD over the following 4 weeks.

The research team provided clinicians with CRP interpretation guidance based on the following CRP values: < 20 mg/L, antibiotics are typically not needed; 20 to 40 mg/L, antibiotics might be beneficial if purulent sputum is present; and > 40 mg/L, antibiotics are usually beneficial. Primary outcomes were patient-reported antibiotic use within 4 weeks and COPD-related health status. Of the patients who received a point-of-care CRP test, the median value was 6 mg/L; 76% had a value < 20 mg/L, 12% had values between 20 and 40 mg/L, and 12% had values > 40 mg/L. In the intention-to-treat analysis, fewer patients in the CRP-guided group reported antibiotic use vs those in the usual-care group (57% vs 77%; adjusted odds ratio [aOR] = 0.31; 95% CI, 0.20-0.47) within 4 weeks. The CRP-guided group also received fewer antibiotics at the initial visit compared to the usual-care group (48% vs 70%; aOR = 0.31; 95% CI, 0.21-0.45).

COPD-related health status was assessed with the Clinical COPD Questionnaire (score range, 0-6; a difference of 0.4 represents minimal clinical importance). At 2 weeks, the adjusted mean difference in the total health status score with the use of CRP was noninferior to usual care and was in favor of the CRP-guided group (mean difference = −0.19 points; two-sided 90% CI, −0.33 to −0.05). There was no evidence of clinically important between-group differences in pneumonia (3% vs 4%; aOR = 0.73; 95% CI, 0.29-1.82) at 6-month follow-up. Rates of hospitalization at 6 months were similar between groups (9.3% vs 8.6%; no P value provided).

Fewer patients in the CRPguided group reported antibiotic use vs those in the usual-care group within 4 weeks.

Limitations of this trial included patient report of antibiotic use and the lack of a sham test.

WHAT'S NEW

RCT provides evidence to support use of CRP testing

Point-of-care CRP testing can reduce antibiotic prescribing in patients presenting with a COPD exacerbation without affecting symptom improvement or adverse events.

CAVEATS

CRP testing may not be cost effective

CRP testing—especially point-of-care ­testing—remains expensive in many parts of the United States. A 2015 cost-effectiveness analysis of point-of-care CRP tests for respiratory tract infection in England concluded the cost of the test per patient was not cost effective.¹⁰ It is unknown if point-of-care CRP testing would be cost effective in guiding antibiotic prescribing for ­primary care providers with a focus on COPD exacerbations.

CHALLENGES TO IMPLEMENTATION 

Virtual visits and variable access may limit use

CRP-guided antibiotic prescribing may be challenging in some clinical scenarios or clinics with the rise of virtual visits and differential access in primary care clinics to point-of-care CRP tests. JFP

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. Copyright © 2021. The Family Physicians Inquiries Network. All rights reserved.

ILLUSTRATIVE CASE

A 55-year-old man with a history of chronic obstructive pulmonary disease (COPD) presents to you with increased sputum volume and increased dyspnea, but no fever. You diagnose a COPD exacerbation. Would point-of-care C-reactive protein (CRP) testing be a useful tool to guide antibiotic prescribing?

COPD is a common respiratory condition and one of the leading causes of death in the world.² COPD requires chronic therapy and frequent treatment for acute exacerbations.³ A systematic review found that exacerbations occur an average of 1.3 times per year for patients with known COPD.⁴ Antibiotics are often prescribed for COPD exacerbations, but which patients benefit most from antibiotic treatment is unclear and identification often is based on clinical features alone. Additionally, overprescribing of antibiotics can lead to unnecessary adverse effects, drive antibiotic resistance, and be a waste of resources.⁵

The European Respiratory Society/American Thoracic Society (ERS/ATS) provides a conditional recommendation to consider antibiotics in ambulatory patients with COPD exacerbation based on moderate-quality evidence.⁶ The 2020 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend antibiotics for moderately or severely ill patients with a COPD exacerbation who have increased cough and sputum purulence.⁷ While the ERS/ATS recommendations do not mention CRP, the GOLD guidelines discuss biomarkers as emerging tools in determining antibiotic utility.

Biomarkers such as procalcitonin and CRP are being examined as potential tools to distinguish which patients would benefit from antibiotic treatment in COPD exacerbations. In a 2013 study, CRP levels > 19.6 mg/L in the serum and > 15.2 mg/L in the sputum indicated a bacterial infection, but more research was needed to determine if CRP could help guide antibiotic prescribing.⁸ In a 2019 randomized trial of 101 patients with COPD exacerbations, researchers compared the GOLD strategy for antibiotic prescribing with a CRP-guided antibiotic strategy (CRP ≥ 50 mg/L) and found no difference in adverse events between study groups.⁹

This trial focused on point-of-care CRP-guided prescribing of antibiotics for patients with COPD exacerbations in the outpatient setting.

STUDY SUMMARY

Point-of-care CRP testing is noninferior to usual care

This open-label, multicenter, randomized controlled trial at 86 general medical practices in the United Kingdom examined whether the use of point-of-care CRP testing could reduce antibiotic use during acute exacerbations of COPD. Patients (N = 653; 650 needed to provide 81% to 90% power) were ages 40 years and older, had a diagnosis of COPD, and presented for an acute exacerbation of COPD based on the presence of at least 1 Anthonisen criteria (increased dyspnea, increase in sputum volume, and increase in purulent sputum).

Patients were randomized in a 1:1 fashion to receive care guided by point-of-care CRP testing (CRP-guided) or usual care for their COPD exacerbation. Patients in the CRP-guided group received a point-of-care CRP test as part of their assessment at presentation, or at any other appointments for COPD over the following 4 weeks.

The research team provided clinicians with CRP interpretation guidance based on the following CRP values: < 20 mg/L, antibiotics are typically not needed; 20 to 40 mg/L, antibiotics might be beneficial if purulent sputum is present; and > 40 mg/L, antibiotics are usually beneficial. Primary outcomes were patient-reported antibiotic use within 4 weeks and COPD-related health status. Of the patients who received a point-of-care CRP test, the median value was 6 mg/L; 76% had a value < 20 mg/L, 12% had values between 20 and 40 mg/L, and 12% had values > 40 mg/L. In the intention-to-treat analysis, fewer patients in the CRP-guided group reported antibiotic use vs those in the usual-care group (57% vs 77%; adjusted odds ratio [aOR] = 0.31; 95% CI, 0.20-0.47) within 4 weeks. The CRP-guided group also received fewer antibiotics at the initial visit compared to the usual-care group (48% vs 70%; aOR = 0.31; 95% CI, 0.21-0.45).

COPD-related health status was assessed with the Clinical COPD Questionnaire (score range, 0-6; a difference of 0.4 represents minimal clinical importance). At 2 weeks, the adjusted mean difference in the total health status score with the use of CRP was noninferior to usual care and was in favor of the CRP-guided group (mean difference = −0.19 points; two-sided 90% CI, −0.33 to −0.05). There was no evidence of clinically important between-group differences in pneumonia (3% vs 4%; aOR = 0.73; 95% CI, 0.29-1.82) at 6-month follow-up. Rates of hospitalization at 6 months were similar between groups (9.3% vs 8.6%; no P value provided).

Fewer patients in the CRPguided group reported antibiotic use vs those in the usual-care group within 4 weeks.

Limitations of this trial included patient report of antibiotic use and the lack of a sham test.

WHAT'S NEW

RCT provides evidence to support use of CRP testing

Point-of-care CRP testing can reduce antibiotic prescribing in patients presenting with a COPD exacerbation without affecting symptom improvement or adverse events.

CAVEATS

CRP testing may not be cost effective

CRP testing—especially point-of-care ­testing—remains expensive in many parts of the United States. A 2015 cost-effectiveness analysis of point-of-care CRP tests for respiratory tract infection in England concluded the cost of the test per patient was not cost effective.¹⁰ It is unknown if point-of-care CRP testing would be cost effective in guiding antibiotic prescribing for ­primary care providers with a focus on COPD exacerbations.

CHALLENGES TO IMPLEMENTATION 

Virtual visits and variable access may limit use

CRP-guided antibiotic prescribing may be challenging in some clinical scenarios or clinics with the rise of virtual visits and differential access in primary care clinics to point-of-care CRP tests. JFP

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. Copyright © 2021. The Family Physicians Inquiries Network. All rights reserved.

ILLUSTRATIVE CASE

A 55-year-old man with a history of chronic obstructive pulmonary disease (COPD) presents to you with increased sputum volume and increased dyspnea, but no fever. You diagnose a COPD exacerbation. Would point-of-care C-reactive protein (CRP) testing be a useful tool to guide antibiotic prescribing?

COPD is a common respiratory condition and one of the leading causes of death in the world.² COPD requires chronic therapy and frequent treatment for acute exacerbations.³ A systematic review found that exacerbations occur an average of 1.3 times per year for patients with known COPD.⁴ Antibiotics are often prescribed for COPD exacerbations, but which patients benefit most from antibiotic treatment is unclear and identification often is based on clinical features alone. Additionally, overprescribing of antibiotics can lead to unnecessary adverse effects, drive antibiotic resistance, and be a waste of resources.⁵

The European Respiratory Society/American Thoracic Society (ERS/ATS) provides a conditional recommendation to consider antibiotics in ambulatory patients with COPD exacerbation based on moderate-quality evidence.⁶ The 2020 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend antibiotics for moderately or severely ill patients with a COPD exacerbation who have increased cough and sputum purulence.⁷ While the ERS/ATS recommendations do not mention CRP, the GOLD guidelines discuss biomarkers as emerging tools in determining antibiotic utility.

Biomarkers such as procalcitonin and CRP are being examined as potential tools to distinguish which patients would benefit from antibiotic treatment in COPD exacerbations. In a 2013 study, CRP levels > 19.6 mg/L in the serum and > 15.2 mg/L in the sputum indicated a bacterial infection, but more research was needed to determine if CRP could help guide antibiotic prescribing.⁸ In a 2019 randomized trial of 101 patients with COPD exacerbations, researchers compared the GOLD strategy for antibiotic prescribing with a CRP-guided antibiotic strategy (CRP ≥ 50 mg/L) and found no difference in adverse events between study groups.⁹

This trial focused on point-of-care CRP-guided prescribing of antibiotics for patients with COPD exacerbations in the outpatient setting.

STUDY SUMMARY

Point-of-care CRP testing is noninferior to usual care

This open-label, multicenter, randomized controlled trial at 86 general medical practices in the United Kingdom examined whether the use of point-of-care CRP testing could reduce antibiotic use during acute exacerbations of COPD. Patients (N = 653; 650 needed to provide 81% to 90% power) were ages 40 years and older, had a diagnosis of COPD, and presented for an acute exacerbation of COPD based on the presence of at least 1 Anthonisen criteria (increased dyspnea, increase in sputum volume, and increase in purulent sputum).

Patients were randomized in a 1:1 fashion to receive care guided by point-of-care CRP testing (CRP-guided) or usual care for their COPD exacerbation. Patients in the CRP-guided group received a point-of-care CRP test as part of their assessment at presentation, or at any other appointments for COPD over the following 4 weeks.

The research team provided clinicians with CRP interpretation guidance based on the following CRP values: < 20 mg/L, antibiotics are typically not needed; 20 to 40 mg/L, antibiotics might be beneficial if purulent sputum is present; and > 40 mg/L, antibiotics are usually beneficial. Primary outcomes were patient-reported antibiotic use within 4 weeks and COPD-related health status. Of the patients who received a point-of-care CRP test, the median value was 6 mg/L; 76% had a value < 20 mg/L, 12% had values between 20 and 40 mg/L, and 12% had values > 40 mg/L. In the intention-to-treat analysis, fewer patients in the CRP-guided group reported antibiotic use vs those in the usual-care group (57% vs 77%; adjusted odds ratio [aOR] = 0.31; 95% CI, 0.20-0.47) within 4 weeks. The CRP-guided group also received fewer antibiotics at the initial visit compared to the usual-care group (48% vs 70%; aOR = 0.31; 95% CI, 0.21-0.45).

COPD-related health status was assessed with the Clinical COPD Questionnaire (score range, 0-6; a difference of 0.4 represents minimal clinical importance). At 2 weeks, the adjusted mean difference in the total health status score with the use of CRP was noninferior to usual care and was in favor of the CRP-guided group (mean difference = −0.19 points; two-sided 90% CI, −0.33 to −0.05). There was no evidence of clinically important between-group differences in pneumonia (3% vs 4%; aOR = 0.73; 95% CI, 0.29-1.82) at 6-month follow-up. Rates of hospitalization at 6 months were similar between groups (9.3% vs 8.6%; no P value provided).

Fewer patients in the CRPguided group reported antibiotic use vs those in the usual-care group within 4 weeks.

Limitations of this trial included patient report of antibiotic use and the lack of a sham test.

WHAT'S NEW

RCT provides evidence to support use of CRP testing

Point-of-care CRP testing can reduce antibiotic prescribing in patients presenting with a COPD exacerbation without affecting symptom improvement or adverse events.

CAVEATS

CRP testing may not be cost effective

CRP testing—especially point-of-care ­testing—remains expensive in many parts of the United States. A 2015 cost-effectiveness analysis of point-of-care CRP tests for respiratory tract infection in England concluded the cost of the test per patient was not cost effective.¹⁰ It is unknown if point-of-care CRP testing would be cost effective in guiding antibiotic prescribing for ­primary care providers with a focus on COPD exacerbations.

CHALLENGES TO IMPLEMENTATION 

Virtual visits and variable access may limit use

CRP-guided antibiotic prescribing may be challenging in some clinical scenarios or clinics with the rise of virtual visits and differential access in primary care clinics to point-of-care CRP tests. JFP

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. Copyright © 2021. The Family Physicians Inquiries Network. All rights reserved.

In this issue of JFP, Smith et al recommend following guidelines from the American Academy of Pediatrics to annually screen children for hypertension (see page 220). This recommendation appears to be at odds with the recent US Preventive Services Task Force (USPSTF) statement that concluded there is insufficient evidence for screening children and adolescents for hypertension. But an “I” recommendation from the USPSTF is not the same as a “D” recommendation. “D” means don’t do it, because the evidence indicates that the harms outweigh the benefits. “I” means we don’t have enough evidence to weigh the harms and benefits, so it is up to you and your patients to decide what to do.

So whose recommendations should we follow?

Our decision should be based on a thorough understanding of the evidence, and that evidence is well summarized in the recent USPSTF report.¹ The reviewers found no studies that evaluated the benefits and harms of screening children and adolescents for hypertension and no studies evaluating disease outcomes from treating hypertension in these patients.

What we can all agree on is that, when hypertension is identified in a child or adolescent, it is important to determine if there is a treatable cause.

There is, however, an association between elevated blood pressure in childhood and outcomes such as left ventricular hypertrophy and carotid intimal thickness.² Some physicians contend that these “disease-oriented outcomes” are sufficient reason to identify and treat hypertension in children and adolescents.³ The USPSTF, however, requires a higher level of evidence that includes patient-oriented outcomes, such as a lower risk of congestive heart failure, renal failure, or death, before recommending treatment. Physicians and patients have to choose what level of evidence is sufficient to take action.

Dr. Smith comments: “As noted in their report, the USPSTF acknowledges that observational studies indicate an association between hypertension in childhood and hypertension in adulthood, but there have been no randomized trials to determine if treating hypertension in children and adolescents reduces risk of cardiovascular events. Although it is a cohort study, not a randomized trial, the ongoing i3C Consortium Outcomes Study⁴ may provide better information to guide decision-making for children and adolescents with elevated blood pressure.”

What we can all agree on is that, when hypertension is identified in a child or adolescent, it is important to determine if there is a treatable cause of elevated blood pressure such as coarctation of the aorta or renal disease. It is also important to address risk factors for elevated blood pressure and cardiovascular disease, such as obesity, poor dietary habits, and smoking. The treatment is lifestyle modification with diet, exercise, and smoking cessation. 

In this issue of JFP, Smith et al recommend following guidelines from the American Academy of Pediatrics to annually screen children for hypertension (see page 220). This recommendation appears to be at odds with the recent US Preventive Services Task Force (USPSTF) statement that concluded there is insufficient evidence for screening children and adolescents for hypertension. But an “I” recommendation from the USPSTF is not the same as a “D” recommendation. “D” means don’t do it, because the evidence indicates that the harms outweigh the benefits. “I” means we don’t have enough evidence to weigh the harms and benefits, so it is up to you and your patients to decide what to do.

So whose recommendations should we follow?

Our decision should be based on a thorough understanding of the evidence, and that evidence is well summarized in the recent USPSTF report.¹ The reviewers found no studies that evaluated the benefits and harms of screening children and adolescents for hypertension and no studies evaluating disease outcomes from treating hypertension in these patients.

What we can all agree on is that, when hypertension is identified in a child or adolescent, it is important to determine if there is a treatable cause.

There is, however, an association between elevated blood pressure in childhood and outcomes such as left ventricular hypertrophy and carotid intimal thickness.² Some physicians contend that these “disease-oriented outcomes” are sufficient reason to identify and treat hypertension in children and adolescents.³ The USPSTF, however, requires a higher level of evidence that includes patient-oriented outcomes, such as a lower risk of congestive heart failure, renal failure, or death, before recommending treatment. Physicians and patients have to choose what level of evidence is sufficient to take action.

Dr. Smith comments: “As noted in their report, the USPSTF acknowledges that observational studies indicate an association between hypertension in childhood and hypertension in adulthood, but there have been no randomized trials to determine if treating hypertension in children and adolescents reduces risk of cardiovascular events. Although it is a cohort study, not a randomized trial, the ongoing i3C Consortium Outcomes Study⁴ may provide better information to guide decision-making for children and adolescents with elevated blood pressure.”

What we can all agree on is that, when hypertension is identified in a child or adolescent, it is important to determine if there is a treatable cause of elevated blood pressure such as coarctation of the aorta or renal disease. It is also important to address risk factors for elevated blood pressure and cardiovascular disease, such as obesity, poor dietary habits, and smoking. The treatment is lifestyle modification with diet, exercise, and smoking cessation. 

In this issue of JFP, Smith et al recommend following guidelines from the American Academy of Pediatrics to annually screen children for hypertension (see page 220). This recommendation appears to be at odds with the recent US Preventive Services Task Force (USPSTF) statement that concluded there is insufficient evidence for screening children and adolescents for hypertension. But an “I” recommendation from the USPSTF is not the same as a “D” recommendation. “D” means don’t do it, because the evidence indicates that the harms outweigh the benefits. “I” means we don’t have enough evidence to weigh the harms and benefits, so it is up to you and your patients to decide what to do.

So whose recommendations should we follow?

Our decision should be based on a thorough understanding of the evidence, and that evidence is well summarized in the recent USPSTF report.¹ The reviewers found no studies that evaluated the benefits and harms of screening children and adolescents for hypertension and no studies evaluating disease outcomes from treating hypertension in these patients.

What we can all agree on is that, when hypertension is identified in a child or adolescent, it is important to determine if there is a treatable cause.

There is, however, an association between elevated blood pressure in childhood and outcomes such as left ventricular hypertrophy and carotid intimal thickness.² Some physicians contend that these “disease-oriented outcomes” are sufficient reason to identify and treat hypertension in children and adolescents.³ The USPSTF, however, requires a higher level of evidence that includes patient-oriented outcomes, such as a lower risk of congestive heart failure, renal failure, or death, before recommending treatment. Physicians and patients have to choose what level of evidence is sufficient to take action.

Dr. Smith comments: “As noted in their report, the USPSTF acknowledges that observational studies indicate an association between hypertension in childhood and hypertension in adulthood, but there have been no randomized trials to determine if treating hypertension in children and adolescents reduces risk of cardiovascular events. Although it is a cohort study, not a randomized trial, the ongoing i3C Consortium Outcomes Study⁴ may provide better information to guide decision-making for children and adolescents with elevated blood pressure.”

What we can all agree on is that, when hypertension is identified in a child or adolescent, it is important to determine if there is a treatable cause of elevated blood pressure such as coarctation of the aorta or renal disease. It is also important to address risk factors for elevated blood pressure and cardiovascular disease, such as obesity, poor dietary habits, and smoking. The treatment is lifestyle modification with diet, exercise, and smoking cessation. 

As the population of older adults rises, primary osteoporosis has become a problem of public health significance, resulting in more than 2 million fractures and $19 billion in related costs annually in the United States.¹ Despite the availability of effective primary and secondary preventive measures, many older adults do not receive adequate information on bone health from their primary care provider.² Initiation of osteoporosis treatment is low even among patients who have had an osteoporotic fracture: Fewer than one-­quarter of older adults with hip fracture have begun taking osteoporosis medication within 12 months of hospital discharge.³

In this overview of osteoporosis care, we provide information on how to evaluate and manage older adults in primary care settings who are at risk of, or have been given a diagnosis of, primary osteoporosis. The guidance that we offer reflects the most recent updates and recommendations by relevant professional societies.^1,4-7

The nature and scope of an urgent problem

Osteoporosis is a skeletal disorder characterized by low bone mass and deterioration of bone structure that causes bone fragility and increases the risk of fracture.⁸ Operationally, it is defined by the World Health Organization as a bone mineral density (BMD) score below 2.5 SD from the mean value for a young White woman (ie, T-score ≤ –2.5).⁹ Primary osteoporosis is age related and occurs mostly in postmenopausal women and older men, affecting 25% of women and 5% of men ≥ 65 years.¹⁰

An osteoporotic fracture is particularly devastating in an older adult because it can cause pain, reduced mobility, depression, and social isolation and can increase the risk of related mortality.¹ The National Osteoporosis Foundation estimates that 20% of older adults who sustain a hip fracture die within 1 year due to complications of the fracture itself or surgical repair.¹ Therefore, it is of paramount importance to identify patients who are at increased risk of fracture and intervene early.

The National Osteoporosis Foundation estimates that 20% of older adults who sustain a hip fracture die within 1 year due to complications of the fracture itself or surgical repair.

Clinical manifestations

Osteoporosis does not have a primary presentation; rather, disease manifests clinically when a patient develops complications. Often, a fragility fracture is the first sign in an older person.¹¹

A fracture is the most important complication of osteoporosis and can result from low-trauma injury or a fall from standing height—thus, the term “fragility fracture.” Osteoporotic fractures commonly involve the vertebra, hip, and wrist. Hip and extremity fractures can result in limited or lost mobility and depression. Vertebral fractures can be asymptomatic or result in kyphosis and loss of height. Fractures can give rise to pain.

Age and female sexare risk factors

TABLE 1^1,6,10 lists risk factors associated with osteoporosis. Age is the most important; prevalence of osteoporosis increases with age. Other nonmodifiable risk factors include female sex (the disease appears earlier in women who enter menopause prematurely), family history of osteoporosis, and race and ethnicity. Twenty percent of Asian and non-Hispanic White women > 50 years have osteoporosis.¹ A study showed that Mexican Americans are at higher risk of osteoporosis than non-Hispanic Whites; non-Hispanic Blacks are least affected.¹⁰

Other risk factors include low body weight (< 127 lb) and a history of fractures after age 50. Behavioral risk factors include smoking, excessive alcohol intake (> 3 drinks/d), poor nutrition, and a sedentary lifestyle.^1,6

Continue to: Who should be screened?...

Who should be screened?

Screening is generally performed with a clinical evaluation and a dual-energy x-ray absorptiometry (DXA) scan of BMD. Measurement of BMD is generally recommended for screening all women ≥ 65 years and those < 65 years whose 10-year risk of fracture is equivalent to that of a 65-year-old White woman (see “Assessment of fracture risk” later in the article). For men, the US Preventive Services Task Force recommends screening those with a prior fracture or a secondary risk factor for disease.⁵ However, the National Osteoporosis Foundation recommends screening all men ≥ 70 years and those 50 to 69 years whose risk profile shows heightened risk.^1,4

DXA of the spine and hip is preferred; the distal one-third of the radius (termed “33% radius”) of the nondominant arm can be used when spine and hip BMD cannot be interpreted because of bone changes from the disease process or artifacts, or in certain diseases in which the wrist region shows the earliest change (eg, primary hyperparathyroidism).^6,7

Clinical evaluation includes a detailed history, physical examination, laboratory screening, and assessment for risk of fracture.

❚ History. Explore the presence of risk factors, including fractures in adulthood, falls, medication use, alcohol and tobacco use, family history of osteoporosis, and chronic disease.^6,7

❚ Physical exam. Assess height, including any loss (> 1.5 in) since the patient’s second or third decade of life; kyphosis; frailty; and balance and mobility problems.^4,6,7

❚  Laboratory and imaging studies. Perform basic laboratory testing when DXA is abnormal, including thyroid function, serum calcium, and renal function.^6,12 Radiography of the lateral spine might be necessary, especially when there is kyphosis or loss of height. Assess for vertebral fracture, using lateral spine radiography, when vertebral involvement is suspected.^6,7

❚ Assessment of fracture risk. Fracture risk can be assessed with any of a number of tools, including:

• Simplified Calculated Osteoporosis Risk Estimation (SCORE): www.medicalalgorithms.com/simplified-calculated-osteoporosis-risk-estimation-tool
• Osteoporosis Risk Assessment Instrument (ORAI): www.physio-pedia.com/The_Osteoporosis_Risk_Assessment_Instrument_(ORAI)

• Osteoporosis Index of Risk (OSIRIS): https://www.tandfonline.com/doi/abs/10.1080/gye.16.3.245.250?journalCode=igye20
• Osteoporosis Self-Assessment Tool (OST): www.ncbi.nlm.nih.gov/books/NBK45516/figure/ch10.f2/
• FRAX tool⁵: www.sheffield.ac.uk/FRAX.

The FRAX tool is widely used. It assesses a patient’s 10-year risk of fracture.

Diagnosis is based on these criteria

Diagnosis of osteoporosis is based on any 1 or more of the following criteria⁶:

• a history of fragility fracture not explained by metabolic bone disease
• T-score ≤ –2.5 (lumbar, hip, femoral neck, or 33% radius)
• a nation-specific FRAX score (in the absence of access to DXA).

❚ Secondary disease. Patients in whom secondary osteoporosis is suspected should undergo laboratory investigation to ascertain the cause; treatment of the underlying pathology might then be required. Evaluation for a secondary cause might include a complete blood count, comprehensive metabolic panel, protein electrophoresis and urinary protein electrophoresis (to rule out myeloproliferative and hematologic diseases), and tests of serum 25-hydroxyvitamin D, parathyroid hormone, serum calcium, alkaline phosphatase, 24-hour urinary calcium, sodium, and creatinine.^6,7 Specialized testing for biochemical markers of bone turnover—so-called bone-turnover markers—can be considered as part of the initial evaluation and follow-up, although the tests are not recommended by the US Preventive Services Task Force (see “Monitoring the efficacy of treatment,” later in the article, for more information about these markers).⁶

Although BMD by DXA remains the gold standard in screening for and diagnosing osteoporosis, a high rate of fracture is seen in patients with certain diseases, such as type 2 diabetes and ankylosing spondylitis, who have a nonosteoporotic low T-score. This raises concerns about the usefulness of BMD for diagnosing osteoporosis in patients who have one of these diseases.^13-16

❚ Pharmacotherapy is recommended in all cases of osteoporosis and osteopenia when risk of fracture is high. Oral bisphosphonates can be used as initial treatment.

❚ Trabecular bone score (TBS), a surrogate bone-quality measure that is calculated based on the spine DXA image, has recently been introduced in clinical practice, and can be used to predict fracture risk in conjunction with BMD assessment by DXA and the FRAX score.¹⁷ TBS provides an indirect index of the trabecular microarchitecture using pixel gray-level variation in lumbar spine DXA images.¹⁸ Three categories of TBS (≤ 1.200, degraded microarchitecture; 1.200-1.350, partially degraded microarchitecture; and > 1.350, normal microarchitecture) have been reported to correspond with a T-score of, respectively, ≤ −2.5; −2.5 to −1.0; and > −1.0.¹⁸ TBS can be used only in patients with a body mass index of 15 to 37.5.^19,20

There is no recommendation for monitoring bone quality using TBS after osteoporosis treatment. Such monitoring is at the clinician’s discretion for appropriate patients who might not show a risk of fracture, based on BMD measurement.

Continue to: Putting preventive measures into practice...

Putting preventive measures into practice

Measures to prevent osteoporosis and preserve bone health (TABLE 2^1,6) are best started in childhood but can be initiated at any age and maintained through the lifespan. Encourage older adults to adopt dietary and behavioral strategies to improve their bone health and prevent fracture. We recommend the following strategies; take each patient’s individual situation into consideration when electing to adopt any of these measures.

❚ Vitamin D. Consider checking the serum 25-hydroxyvitamin D level and providing supplementation (800-1000 IU daily, the National Osteoporosis Foundation recommends¹) as necessary to maintain the level at 30-50 ng/mL.⁶

❚ Calcium. Encourage a daily dietary calcium intake of 1000-1200 mg. Supplement calcium if you determine that diet does not provide an adequate amount.

❚ Alcohol. Advise patients to limit consumption to < 3 drinks a day.

❚ Tobacco. Advise smoking cessation.

❚ Activity. Encourage an active lifestyle, including regular weight-bearing and balance exercises and resistance exercises such as Pilates, weightlifting, and tai chi. The regimen should be tailored to the patient’s individual situation.

❚ Medical therapy for concomitant illness. When possible, prescribe medications for chronic comorbidities that can also benefit bone health. For example, long-term use of angiotensin-converting enzyme (ACE) inhibitors and thiazide diuretics for hypertension are associated with a slower decline in BMD in some populations.^21-23

Tailor treatment to patient’s circumstances

TABLE 3^4,6,24 describes indications for pharmacotherapy in osteoporosis. Pharmacotherapy is recommended in all cases of osteoporosis and osteopenia when fracture risk is high.²⁴

Generally, you should undertake a discussion with the patient of the relative risks and benefits of treatment, taking into account their values and preferences, to come to a shared decision. Tailoring treatment, based on the patient’s distinctive circumstances, through shared decision-making is key to compliance.²⁵

Pharmacotherapy is not indicated in patients whose risk of fracture is low; however, you should reassess such patients every 2 to 4 years.²⁶ Women with a very high BMD might not need to be retested with DXA any sooner than every 10 to 15 years.

There are 3 main classes of first-line pharmacotherapeutic agents for osteoporosis in older adults (TABLE 4^4,6,7,26-41): antiresorptives (bisphosphonates and denosumab), anabolics (teriparatide and abaloparatide), and a monoclonal sclerostin antibody (romosozumab). (TABLE 4^4,6,7,26-41 and the discussion in this section also remark on the selective estrogen-receptor modulator raloxifene, which is used in special clinical circumstances but has been removed from the first line of osteoporosis pharmacotherapy.)

Continue to: Influence of chronic...

Influence of chronic diseaseon bone health

Chronic diseases—hypertension, type 2 diabetes, hyperthyroidism, rheumatoid arthritis, ankylosing spondylitis, and gastroenterologic disorders such as celiac disease and ulcerative colitis—are known to affect bone loss that can hasten osteoporosis.^16,18,21 Furthermore, medications used to treat chronic diseases are known to affect bone health: Some, such as statins, ACE inhibitors, and hydrochlorothiazide, are bone protective; others, such as steroids, pioglitazone, and selective serotonin reuptake inhibitors, accelerate bone loss.^1,14,42,43 It is important to be aware of the effect of a patient’s chronic diseases, and treatments for those diseases, on bone health, to help develop an individualized osteoporosis prevention plan.

Monitoring the efficacy of treatment

Treatment of osteoporosis should not be initiated without baseline measurement of BMD of the spine and hip. Subsequent to establishing that baseline, serial measurement of BMD can be used to (1) determine when treatment needs to be initiated for an untreated patient and (2) assess response in a treated patient. There is no consensus on the interval at which DXA should be repeated for the purpose of monitoring treatment response; frequency depends on the individual’s circumstances and the medication used. Notably, many physicians repeat DXA after 2 years of treatment⁸; however, the American College of Physicians recommends against repeating DXA within the first 5 years of pharmacotherapy in women.²⁴

Patients with suspected vertebral fracture or those with loss of height > 1.5 inches require lateral radiographs of the thoracic and lumbar spine to assess the status of fractures.^4,6

❚ Bone-turnover markers measured in serum can be used to assess treatment efficacy and patient adherence. The formation marker procollagen type I N-terminal propeptide (P1NP) and the resorption marker beta C-terminal cross-linking telopeptide of type 1 collagen (bCTX) are preferred for evaluating bone turnover in the clinical setting. Assessing P1NP and bCTX at baseline and after 3 months of treatment might be effective in monitoring adherence, particularly in patients taking a bisphosphonate.⁴⁴

Pharmacotherapy is not indicated in patients whose risk of fracture is low; however, you should reassess such patients every 2 to 4 years.

Be sure to address fall prevention

It is important to address falls, and how to prevent them, in patients with osteoporosis. Falls can precipitate fracture in older adults with reduced BMD, and fractures are the most common and debilitating manifestation of osteoporosis. Your discussion of falls with patients should include⁴⁵:

• consequences of falls
• cautions about medications that can cloud mental alertness
• use of appropriate footwear
• home safety, such as adequate lighting, removal of floor clutter, and installation of handrails in the bathroom and stairwells and on outside steps.
• having an annual comprehensive eye exam.

Osteoporosis is avoidable and treatable

Earlier research reported various expressions of number needed to treat for medical management of osteoporosis—making it difficult to follow a single number as a reference for gauging the effectiveness of pharmacotherapy.^46,47 However, for older adults of different ethnic and racial backgrounds with multiple comorbidities and polypharmacy, it might be more pragmatic in primary care to establish a model of goal-oriented, individualized care. By focusing on prevention of bone loss, and being mindful that the risk of fracture almost doubles with a decrease of 1 SD in BMD, you can translate numbers to goals of care.⁴⁸

In the United States, approximately one-half of osteoporosis cases in adults ≥ 50 years are managed by primary care providers. As a chronic disease, osteoporosis requires that you, first, provide regular monitoring and assessment, because risk can vary with comorbidities,⁴⁹ and, second, discuss and initiate screening and treatment as appropriate, which can be done annually during a well-care visit.

CORRESPONDENCE

Nahid Rianon, MD, DrPH, Department of Family and Community Medicine, UTHealth McGovern Medical School, 6431 Fannin Street #JJL 324C, Houston, TX, 77030; [email protected]

As the population of older adults rises, primary osteoporosis has become a problem of public health significance, resulting in more than 2 million fractures and $19 billion in related costs annually in the United States.¹ Despite the availability of effective primary and secondary preventive measures, many older adults do not receive adequate information on bone health from their primary care provider.² Initiation of osteoporosis treatment is low even among patients who have had an osteoporotic fracture: Fewer than one-­quarter of older adults with hip fracture have begun taking osteoporosis medication within 12 months of hospital discharge.³

In this overview of osteoporosis care, we provide information on how to evaluate and manage older adults in primary care settings who are at risk of, or have been given a diagnosis of, primary osteoporosis. The guidance that we offer reflects the most recent updates and recommendations by relevant professional societies.^1,4-7

The nature and scope of an urgent problem

Osteoporosis is a skeletal disorder characterized by low bone mass and deterioration of bone structure that causes bone fragility and increases the risk of fracture.⁸ Operationally, it is defined by the World Health Organization as a bone mineral density (BMD) score below 2.5 SD from the mean value for a young White woman (ie, T-score ≤ –2.5).⁹ Primary osteoporosis is age related and occurs mostly in postmenopausal women and older men, affecting 25% of women and 5% of men ≥ 65 years.¹⁰

An osteoporotic fracture is particularly devastating in an older adult because it can cause pain, reduced mobility, depression, and social isolation and can increase the risk of related mortality.¹ The National Osteoporosis Foundation estimates that 20% of older adults who sustain a hip fracture die within 1 year due to complications of the fracture itself or surgical repair.¹ Therefore, it is of paramount importance to identify patients who are at increased risk of fracture and intervene early.

The National Osteoporosis Foundation estimates that 20% of older adults who sustain a hip fracture die within 1 year due to complications of the fracture itself or surgical repair.

Clinical manifestations

Osteoporosis does not have a primary presentation; rather, disease manifests clinically when a patient develops complications. Often, a fragility fracture is the first sign in an older person.¹¹

A fracture is the most important complication of osteoporosis and can result from low-trauma injury or a fall from standing height—thus, the term “fragility fracture.” Osteoporotic fractures commonly involve the vertebra, hip, and wrist. Hip and extremity fractures can result in limited or lost mobility and depression. Vertebral fractures can be asymptomatic or result in kyphosis and loss of height. Fractures can give rise to pain.

Age and female sexare risk factors

TABLE 1^1,6,10 lists risk factors associated with osteoporosis. Age is the most important; prevalence of osteoporosis increases with age. Other nonmodifiable risk factors include female sex (the disease appears earlier in women who enter menopause prematurely), family history of osteoporosis, and race and ethnicity. Twenty percent of Asian and non-Hispanic White women > 50 years have osteoporosis.¹ A study showed that Mexican Americans are at higher risk of osteoporosis than non-Hispanic Whites; non-Hispanic Blacks are least affected.¹⁰

Other risk factors include low body weight (< 127 lb) and a history of fractures after age 50. Behavioral risk factors include smoking, excessive alcohol intake (> 3 drinks/d), poor nutrition, and a sedentary lifestyle.^1,6

Continue to: Who should be screened?...

Who should be screened?

Screening is generally performed with a clinical evaluation and a dual-energy x-ray absorptiometry (DXA) scan of BMD. Measurement of BMD is generally recommended for screening all women ≥ 65 years and those < 65 years whose 10-year risk of fracture is equivalent to that of a 65-year-old White woman (see “Assessment of fracture risk” later in the article). For men, the US Preventive Services Task Force recommends screening those with a prior fracture or a secondary risk factor for disease.⁵ However, the National Osteoporosis Foundation recommends screening all men ≥ 70 years and those 50 to 69 years whose risk profile shows heightened risk.^1,4

DXA of the spine and hip is preferred; the distal one-third of the radius (termed “33% radius”) of the nondominant arm can be used when spine and hip BMD cannot be interpreted because of bone changes from the disease process or artifacts, or in certain diseases in which the wrist region shows the earliest change (eg, primary hyperparathyroidism).^6,7

Clinical evaluation includes a detailed history, physical examination, laboratory screening, and assessment for risk of fracture.

❚ History. Explore the presence of risk factors, including fractures in adulthood, falls, medication use, alcohol and tobacco use, family history of osteoporosis, and chronic disease.^6,7

❚ Physical exam. Assess height, including any loss (> 1.5 in) since the patient’s second or third decade of life; kyphosis; frailty; and balance and mobility problems.^4,6,7

❚  Laboratory and imaging studies. Perform basic laboratory testing when DXA is abnormal, including thyroid function, serum calcium, and renal function.^6,12 Radiography of the lateral spine might be necessary, especially when there is kyphosis or loss of height. Assess for vertebral fracture, using lateral spine radiography, when vertebral involvement is suspected.^6,7

❚ Assessment of fracture risk. Fracture risk can be assessed with any of a number of tools, including:

• Simplified Calculated Osteoporosis Risk Estimation (SCORE): www.medicalalgorithms.com/simplified-calculated-osteoporosis-risk-estimation-tool
• Osteoporosis Risk Assessment Instrument (ORAI): www.physio-pedia.com/The_Osteoporosis_Risk_Assessment_Instrument_(ORAI)

• Osteoporosis Index of Risk (OSIRIS): https://www.tandfonline.com/doi/abs/10.1080/gye.16.3.245.250?journalCode=igye20
• Osteoporosis Self-Assessment Tool (OST): www.ncbi.nlm.nih.gov/books/NBK45516/figure/ch10.f2/
• FRAX tool⁵: www.sheffield.ac.uk/FRAX.

The FRAX tool is widely used. It assesses a patient’s 10-year risk of fracture.

Diagnosis is based on these criteria

Diagnosis of osteoporosis is based on any 1 or more of the following criteria⁶:

• a history of fragility fracture not explained by metabolic bone disease
• T-score ≤ –2.5 (lumbar, hip, femoral neck, or 33% radius)
• a nation-specific FRAX score (in the absence of access to DXA).

❚ Secondary disease. Patients in whom secondary osteoporosis is suspected should undergo laboratory investigation to ascertain the cause; treatment of the underlying pathology might then be required. Evaluation for a secondary cause might include a complete blood count, comprehensive metabolic panel, protein electrophoresis and urinary protein electrophoresis (to rule out myeloproliferative and hematologic diseases), and tests of serum 25-hydroxyvitamin D, parathyroid hormone, serum calcium, alkaline phosphatase, 24-hour urinary calcium, sodium, and creatinine.^6,7 Specialized testing for biochemical markers of bone turnover—so-called bone-turnover markers—can be considered as part of the initial evaluation and follow-up, although the tests are not recommended by the US Preventive Services Task Force (see “Monitoring the efficacy of treatment,” later in the article, for more information about these markers).⁶

Although BMD by DXA remains the gold standard in screening for and diagnosing osteoporosis, a high rate of fracture is seen in patients with certain diseases, such as type 2 diabetes and ankylosing spondylitis, who have a nonosteoporotic low T-score. This raises concerns about the usefulness of BMD for diagnosing osteoporosis in patients who have one of these diseases.^13-16

❚ Pharmacotherapy is recommended in all cases of osteoporosis and osteopenia when risk of fracture is high. Oral bisphosphonates can be used as initial treatment.

❚ Trabecular bone score (TBS), a surrogate bone-quality measure that is calculated based on the spine DXA image, has recently been introduced in clinical practice, and can be used to predict fracture risk in conjunction with BMD assessment by DXA and the FRAX score.¹⁷ TBS provides an indirect index of the trabecular microarchitecture using pixel gray-level variation in lumbar spine DXA images.¹⁸ Three categories of TBS (≤ 1.200, degraded microarchitecture; 1.200-1.350, partially degraded microarchitecture; and > 1.350, normal microarchitecture) have been reported to correspond with a T-score of, respectively, ≤ −2.5; −2.5 to −1.0; and > −1.0.¹⁸ TBS can be used only in patients with a body mass index of 15 to 37.5.^19,20

There is no recommendation for monitoring bone quality using TBS after osteoporosis treatment. Such monitoring is at the clinician’s discretion for appropriate patients who might not show a risk of fracture, based on BMD measurement.

Continue to: Putting preventive measures into practice...

Putting preventive measures into practice

Measures to prevent osteoporosis and preserve bone health (TABLE 2^1,6) are best started in childhood but can be initiated at any age and maintained through the lifespan. Encourage older adults to adopt dietary and behavioral strategies to improve their bone health and prevent fracture. We recommend the following strategies; take each patient’s individual situation into consideration when electing to adopt any of these measures.

❚ Vitamin D. Consider checking the serum 25-hydroxyvitamin D level and providing supplementation (800-1000 IU daily, the National Osteoporosis Foundation recommends¹) as necessary to maintain the level at 30-50 ng/mL.⁶

❚ Calcium. Encourage a daily dietary calcium intake of 1000-1200 mg. Supplement calcium if you determine that diet does not provide an adequate amount.

❚ Alcohol. Advise patients to limit consumption to < 3 drinks a day.

❚ Tobacco. Advise smoking cessation.

❚ Activity. Encourage an active lifestyle, including regular weight-bearing and balance exercises and resistance exercises such as Pilates, weightlifting, and tai chi. The regimen should be tailored to the patient’s individual situation.

❚ Medical therapy for concomitant illness. When possible, prescribe medications for chronic comorbidities that can also benefit bone health. For example, long-term use of angiotensin-converting enzyme (ACE) inhibitors and thiazide diuretics for hypertension are associated with a slower decline in BMD in some populations.^21-23

Tailor treatment to patient’s circumstances

TABLE 3^4,6,24 describes indications for pharmacotherapy in osteoporosis. Pharmacotherapy is recommended in all cases of osteoporosis and osteopenia when fracture risk is high.²⁴

Generally, you should undertake a discussion with the patient of the relative risks and benefits of treatment, taking into account their values and preferences, to come to a shared decision. Tailoring treatment, based on the patient’s distinctive circumstances, through shared decision-making is key to compliance.²⁵

Pharmacotherapy is not indicated in patients whose risk of fracture is low; however, you should reassess such patients every 2 to 4 years.²⁶ Women with a very high BMD might not need to be retested with DXA any sooner than every 10 to 15 years.

There are 3 main classes of first-line pharmacotherapeutic agents for osteoporosis in older adults (TABLE 4^4,6,7,26-41): antiresorptives (bisphosphonates and denosumab), anabolics (teriparatide and abaloparatide), and a monoclonal sclerostin antibody (romosozumab). (TABLE 4^4,6,7,26-41 and the discussion in this section also remark on the selective estrogen-receptor modulator raloxifene, which is used in special clinical circumstances but has been removed from the first line of osteoporosis pharmacotherapy.)

Continue to: Influence of chronic...

Influence of chronic diseaseon bone health

Chronic diseases—hypertension, type 2 diabetes, hyperthyroidism, rheumatoid arthritis, ankylosing spondylitis, and gastroenterologic disorders such as celiac disease and ulcerative colitis—are known to affect bone loss that can hasten osteoporosis.^16,18,21 Furthermore, medications used to treat chronic diseases are known to affect bone health: Some, such as statins, ACE inhibitors, and hydrochlorothiazide, are bone protective; others, such as steroids, pioglitazone, and selective serotonin reuptake inhibitors, accelerate bone loss.^1,14,42,43 It is important to be aware of the effect of a patient’s chronic diseases, and treatments for those diseases, on bone health, to help develop an individualized osteoporosis prevention plan.

Monitoring the efficacy of treatment

Treatment of osteoporosis should not be initiated without baseline measurement of BMD of the spine and hip. Subsequent to establishing that baseline, serial measurement of BMD can be used to (1) determine when treatment needs to be initiated for an untreated patient and (2) assess response in a treated patient. There is no consensus on the interval at which DXA should be repeated for the purpose of monitoring treatment response; frequency depends on the individual’s circumstances and the medication used. Notably, many physicians repeat DXA after 2 years of treatment⁸; however, the American College of Physicians recommends against repeating DXA within the first 5 years of pharmacotherapy in women.²⁴

Patients with suspected vertebral fracture or those with loss of height > 1.5 inches require lateral radiographs of the thoracic and lumbar spine to assess the status of fractures.^4,6

❚ Bone-turnover markers measured in serum can be used to assess treatment efficacy and patient adherence. The formation marker procollagen type I N-terminal propeptide (P1NP) and the resorption marker beta C-terminal cross-linking telopeptide of type 1 collagen (bCTX) are preferred for evaluating bone turnover in the clinical setting. Assessing P1NP and bCTX at baseline and after 3 months of treatment might be effective in monitoring adherence, particularly in patients taking a bisphosphonate.⁴⁴

Pharmacotherapy is not indicated in patients whose risk of fracture is low; however, you should reassess such patients every 2 to 4 years.

Be sure to address fall prevention

It is important to address falls, and how to prevent them, in patients with osteoporosis. Falls can precipitate fracture in older adults with reduced BMD, and fractures are the most common and debilitating manifestation of osteoporosis. Your discussion of falls with patients should include⁴⁵:

• consequences of falls
• cautions about medications that can cloud mental alertness
• use of appropriate footwear
• home safety, such as adequate lighting, removal of floor clutter, and installation of handrails in the bathroom and stairwells and on outside steps.
• having an annual comprehensive eye exam.

Osteoporosis is avoidable and treatable

Earlier research reported various expressions of number needed to treat for medical management of osteoporosis—making it difficult to follow a single number as a reference for gauging the effectiveness of pharmacotherapy.^46,47 However, for older adults of different ethnic and racial backgrounds with multiple comorbidities and polypharmacy, it might be more pragmatic in primary care to establish a model of goal-oriented, individualized care. By focusing on prevention of bone loss, and being mindful that the risk of fracture almost doubles with a decrease of 1 SD in BMD, you can translate numbers to goals of care.⁴⁸

In the United States, approximately one-half of osteoporosis cases in adults ≥ 50 years are managed by primary care providers. As a chronic disease, osteoporosis requires that you, first, provide regular monitoring and assessment, because risk can vary with comorbidities,⁴⁹ and, second, discuss and initiate screening and treatment as appropriate, which can be done annually during a well-care visit.

CORRESPONDENCE

Nahid Rianon, MD, DrPH, Department of Family and Community Medicine, UTHealth McGovern Medical School, 6431 Fannin Street #JJL 324C, Houston, TX, 77030; [email protected]

As the population of older adults rises, primary osteoporosis has become a problem of public health significance, resulting in more than 2 million fractures and $19 billion in related costs annually in the United States.¹ Despite the availability of effective primary and secondary preventive measures, many older adults do not receive adequate information on bone health from their primary care provider.² Initiation of osteoporosis treatment is low even among patients who have had an osteoporotic fracture: Fewer than one-­quarter of older adults with hip fracture have begun taking osteoporosis medication within 12 months of hospital discharge.³

In this overview of osteoporosis care, we provide information on how to evaluate and manage older adults in primary care settings who are at risk of, or have been given a diagnosis of, primary osteoporosis. The guidance that we offer reflects the most recent updates and recommendations by relevant professional societies.^1,4-7

The nature and scope of an urgent problem

Osteoporosis is a skeletal disorder characterized by low bone mass and deterioration of bone structure that causes bone fragility and increases the risk of fracture.⁸ Operationally, it is defined by the World Health Organization as a bone mineral density (BMD) score below 2.5 SD from the mean value for a young White woman (ie, T-score ≤ –2.5).⁹ Primary osteoporosis is age related and occurs mostly in postmenopausal women and older men, affecting 25% of women and 5% of men ≥ 65 years.¹⁰

An osteoporotic fracture is particularly devastating in an older adult because it can cause pain, reduced mobility, depression, and social isolation and can increase the risk of related mortality.¹ The National Osteoporosis Foundation estimates that 20% of older adults who sustain a hip fracture die within 1 year due to complications of the fracture itself or surgical repair.¹ Therefore, it is of paramount importance to identify patients who are at increased risk of fracture and intervene early.

The National Osteoporosis Foundation estimates that 20% of older adults who sustain a hip fracture die within 1 year due to complications of the fracture itself or surgical repair.

Clinical manifestations

Osteoporosis does not have a primary presentation; rather, disease manifests clinically when a patient develops complications. Often, a fragility fracture is the first sign in an older person.¹¹

A fracture is the most important complication of osteoporosis and can result from low-trauma injury or a fall from standing height—thus, the term “fragility fracture.” Osteoporotic fractures commonly involve the vertebra, hip, and wrist. Hip and extremity fractures can result in limited or lost mobility and depression. Vertebral fractures can be asymptomatic or result in kyphosis and loss of height. Fractures can give rise to pain.

Age and female sexare risk factors

TABLE 1^1,6,10 lists risk factors associated with osteoporosis. Age is the most important; prevalence of osteoporosis increases with age. Other nonmodifiable risk factors include female sex (the disease appears earlier in women who enter menopause prematurely), family history of osteoporosis, and race and ethnicity. Twenty percent of Asian and non-Hispanic White women > 50 years have osteoporosis.¹ A study showed that Mexican Americans are at higher risk of osteoporosis than non-Hispanic Whites; non-Hispanic Blacks are least affected.¹⁰

Other risk factors include low body weight (< 127 lb) and a history of fractures after age 50. Behavioral risk factors include smoking, excessive alcohol intake (> 3 drinks/d), poor nutrition, and a sedentary lifestyle.^1,6

Continue to: Who should be screened?...

Who should be screened?

Screening is generally performed with a clinical evaluation and a dual-energy x-ray absorptiometry (DXA) scan of BMD. Measurement of BMD is generally recommended for screening all women ≥ 65 years and those < 65 years whose 10-year risk of fracture is equivalent to that of a 65-year-old White woman (see “Assessment of fracture risk” later in the article). For men, the US Preventive Services Task Force recommends screening those with a prior fracture or a secondary risk factor for disease.⁵ However, the National Osteoporosis Foundation recommends screening all men ≥ 70 years and those 50 to 69 years whose risk profile shows heightened risk.^1,4

DXA of the spine and hip is preferred; the distal one-third of the radius (termed “33% radius”) of the nondominant arm can be used when spine and hip BMD cannot be interpreted because of bone changes from the disease process or artifacts, or in certain diseases in which the wrist region shows the earliest change (eg, primary hyperparathyroidism).^6,7

Clinical evaluation includes a detailed history, physical examination, laboratory screening, and assessment for risk of fracture.

❚ History. Explore the presence of risk factors, including fractures in adulthood, falls, medication use, alcohol and tobacco use, family history of osteoporosis, and chronic disease.^6,7

❚ Physical exam. Assess height, including any loss (> 1.5 in) since the patient’s second or third decade of life; kyphosis; frailty; and balance and mobility problems.^4,6,7

❚  Laboratory and imaging studies. Perform basic laboratory testing when DXA is abnormal, including thyroid function, serum calcium, and renal function.^6,12 Radiography of the lateral spine might be necessary, especially when there is kyphosis or loss of height. Assess for vertebral fracture, using lateral spine radiography, when vertebral involvement is suspected.^6,7

❚ Assessment of fracture risk. Fracture risk can be assessed with any of a number of tools, including:

• Simplified Calculated Osteoporosis Risk Estimation (SCORE): www.medicalalgorithms.com/simplified-calculated-osteoporosis-risk-estimation-tool
• Osteoporosis Risk Assessment Instrument (ORAI): www.physio-pedia.com/The_Osteoporosis_Risk_Assessment_Instrument_(ORAI)

• Osteoporosis Index of Risk (OSIRIS): https://www.tandfonline.com/doi/abs/10.1080/gye.16.3.245.250?journalCode=igye20
• Osteoporosis Self-Assessment Tool (OST): www.ncbi.nlm.nih.gov/books/NBK45516/figure/ch10.f2/
• FRAX tool⁵: www.sheffield.ac.uk/FRAX.

The FRAX tool is widely used. It assesses a patient’s 10-year risk of fracture.

Diagnosis is based on these criteria

Diagnosis of osteoporosis is based on any 1 or more of the following criteria⁶:

• a history of fragility fracture not explained by metabolic bone disease
• T-score ≤ –2.5 (lumbar, hip, femoral neck, or 33% radius)
• a nation-specific FRAX score (in the absence of access to DXA).

❚ Secondary disease. Patients in whom secondary osteoporosis is suspected should undergo laboratory investigation to ascertain the cause; treatment of the underlying pathology might then be required. Evaluation for a secondary cause might include a complete blood count, comprehensive metabolic panel, protein electrophoresis and urinary protein electrophoresis (to rule out myeloproliferative and hematologic diseases), and tests of serum 25-hydroxyvitamin D, parathyroid hormone, serum calcium, alkaline phosphatase, 24-hour urinary calcium, sodium, and creatinine.^6,7 Specialized testing for biochemical markers of bone turnover—so-called bone-turnover markers—can be considered as part of the initial evaluation and follow-up, although the tests are not recommended by the US Preventive Services Task Force (see “Monitoring the efficacy of treatment,” later in the article, for more information about these markers).⁶

Although BMD by DXA remains the gold standard in screening for and diagnosing osteoporosis, a high rate of fracture is seen in patients with certain diseases, such as type 2 diabetes and ankylosing spondylitis, who have a nonosteoporotic low T-score. This raises concerns about the usefulness of BMD for diagnosing osteoporosis in patients who have one of these diseases.^13-16

❚ Pharmacotherapy is recommended in all cases of osteoporosis and osteopenia when risk of fracture is high. Oral bisphosphonates can be used as initial treatment.

❚ Trabecular bone score (TBS), a surrogate bone-quality measure that is calculated based on the spine DXA image, has recently been introduced in clinical practice, and can be used to predict fracture risk in conjunction with BMD assessment by DXA and the FRAX score.¹⁷ TBS provides an indirect index of the trabecular microarchitecture using pixel gray-level variation in lumbar spine DXA images.¹⁸ Three categories of TBS (≤ 1.200, degraded microarchitecture; 1.200-1.350, partially degraded microarchitecture; and > 1.350, normal microarchitecture) have been reported to correspond with a T-score of, respectively, ≤ −2.5; −2.5 to −1.0; and > −1.0.¹⁸ TBS can be used only in patients with a body mass index of 15 to 37.5.^19,20

There is no recommendation for monitoring bone quality using TBS after osteoporosis treatment. Such monitoring is at the clinician’s discretion for appropriate patients who might not show a risk of fracture, based on BMD measurement.

Continue to: Putting preventive measures into practice...

Putting preventive measures into practice

Measures to prevent osteoporosis and preserve bone health (TABLE 2^1,6) are best started in childhood but can be initiated at any age and maintained through the lifespan. Encourage older adults to adopt dietary and behavioral strategies to improve their bone health and prevent fracture. We recommend the following strategies; take each patient’s individual situation into consideration when electing to adopt any of these measures.

❚ Vitamin D. Consider checking the serum 25-hydroxyvitamin D level and providing supplementation (800-1000 IU daily, the National Osteoporosis Foundation recommends¹) as necessary to maintain the level at 30-50 ng/mL.⁶

❚ Calcium. Encourage a daily dietary calcium intake of 1000-1200 mg. Supplement calcium if you determine that diet does not provide an adequate amount.

❚ Alcohol. Advise patients to limit consumption to < 3 drinks a day.

❚ Tobacco. Advise smoking cessation.

❚ Activity. Encourage an active lifestyle, including regular weight-bearing and balance exercises and resistance exercises such as Pilates, weightlifting, and tai chi. The regimen should be tailored to the patient’s individual situation.

❚ Medical therapy for concomitant illness. When possible, prescribe medications for chronic comorbidities that can also benefit bone health. For example, long-term use of angiotensin-converting enzyme (ACE) inhibitors and thiazide diuretics for hypertension are associated with a slower decline in BMD in some populations.^21-23

Tailor treatment to patient’s circumstances

TABLE 3^4,6,24 describes indications for pharmacotherapy in osteoporosis. Pharmacotherapy is recommended in all cases of osteoporosis and osteopenia when fracture risk is high.²⁴

Generally, you should undertake a discussion with the patient of the relative risks and benefits of treatment, taking into account their values and preferences, to come to a shared decision. Tailoring treatment, based on the patient’s distinctive circumstances, through shared decision-making is key to compliance.²⁵

Pharmacotherapy is not indicated in patients whose risk of fracture is low; however, you should reassess such patients every 2 to 4 years.²⁶ Women with a very high BMD might not need to be retested with DXA any sooner than every 10 to 15 years.

There are 3 main classes of first-line pharmacotherapeutic agents for osteoporosis in older adults (TABLE 4^4,6,7,26-41): antiresorptives (bisphosphonates and denosumab), anabolics (teriparatide and abaloparatide), and a monoclonal sclerostin antibody (romosozumab). (TABLE 4^4,6,7,26-41 and the discussion in this section also remark on the selective estrogen-receptor modulator raloxifene, which is used in special clinical circumstances but has been removed from the first line of osteoporosis pharmacotherapy.)

Continue to: Influence of chronic...

Influence of chronic diseaseon bone health

Chronic diseases—hypertension, type 2 diabetes, hyperthyroidism, rheumatoid arthritis, ankylosing spondylitis, and gastroenterologic disorders such as celiac disease and ulcerative colitis—are known to affect bone loss that can hasten osteoporosis.^16,18,21 Furthermore, medications used to treat chronic diseases are known to affect bone health: Some, such as statins, ACE inhibitors, and hydrochlorothiazide, are bone protective; others, such as steroids, pioglitazone, and selective serotonin reuptake inhibitors, accelerate bone loss.^1,14,42,43 It is important to be aware of the effect of a patient’s chronic diseases, and treatments for those diseases, on bone health, to help develop an individualized osteoporosis prevention plan.

Monitoring the efficacy of treatment

Treatment of osteoporosis should not be initiated without baseline measurement of BMD of the spine and hip. Subsequent to establishing that baseline, serial measurement of BMD can be used to (1) determine when treatment needs to be initiated for an untreated patient and (2) assess response in a treated patient. There is no consensus on the interval at which DXA should be repeated for the purpose of monitoring treatment response; frequency depends on the individual’s circumstances and the medication used. Notably, many physicians repeat DXA after 2 years of treatment⁸; however, the American College of Physicians recommends against repeating DXA within the first 5 years of pharmacotherapy in women.²⁴

Patients with suspected vertebral fracture or those with loss of height > 1.5 inches require lateral radiographs of the thoracic and lumbar spine to assess the status of fractures.^4,6

❚ Bone-turnover markers measured in serum can be used to assess treatment efficacy and patient adherence. The formation marker procollagen type I N-terminal propeptide (P1NP) and the resorption marker beta C-terminal cross-linking telopeptide of type 1 collagen (bCTX) are preferred for evaluating bone turnover in the clinical setting. Assessing P1NP and bCTX at baseline and after 3 months of treatment might be effective in monitoring adherence, particularly in patients taking a bisphosphonate.⁴⁴

Pharmacotherapy is not indicated in patients whose risk of fracture is low; however, you should reassess such patients every 2 to 4 years.

Be sure to address fall prevention

It is important to address falls, and how to prevent them, in patients with osteoporosis. Falls can precipitate fracture in older adults with reduced BMD, and fractures are the most common and debilitating manifestation of osteoporosis. Your discussion of falls with patients should include⁴⁵:

• consequences of falls
• cautions about medications that can cloud mental alertness
• use of appropriate footwear
• home safety, such as adequate lighting, removal of floor clutter, and installation of handrails in the bathroom and stairwells and on outside steps.
• having an annual comprehensive eye exam.

Osteoporosis is avoidable and treatable

Earlier research reported various expressions of number needed to treat for medical management of osteoporosis—making it difficult to follow a single number as a reference for gauging the effectiveness of pharmacotherapy.^46,47 However, for older adults of different ethnic and racial backgrounds with multiple comorbidities and polypharmacy, it might be more pragmatic in primary care to establish a model of goal-oriented, individualized care. By focusing on prevention of bone loss, and being mindful that the risk of fracture almost doubles with a decrease of 1 SD in BMD, you can translate numbers to goals of care.⁴⁸

In the United States, approximately one-half of osteoporosis cases in adults ≥ 50 years are managed by primary care providers. As a chronic disease, osteoporosis requires that you, first, provide regular monitoring and assessment, because risk can vary with comorbidities,⁴⁹ and, second, discuss and initiate screening and treatment as appropriate, which can be done annually during a well-care visit.

CORRESPONDENCE

Nahid Rianon, MD, DrPH, Department of Family and Community Medicine, UTHealth McGovern Medical School, 6431 Fannin Street #JJL 324C, Houston, TX, 77030; [email protected]

A 21-year-old man presented to the emergency department (ED) with a 2-month history of joint pain, swelling, and difficulty walking that began with swelling of his right knee (FIGURE 1A). The patient said that over the course of several weeks, the swelling and joint pain spread to his left knee, followed by bilateral elbows and ankles. Nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin produced only modest improvement.

Two weeks prior to presentation, the patient also experienced widespread pruritus and conjunctivitis. His past medical history was significant for a sexual encounter that resulted in urinary tract infection (UTI)–like symptoms approximately 1 month prior to the onset of his joint symptoms. He did not seek care for the UTI-like symptoms.

In the ED, the patient was febrile (102.1 °F) and tachycardic. Skin examination revealed erythematous papules, intact vesicles, and pustules with background hyperkeratosis and desquamation on his right foot (FIGURE 1B). The patient had spotty erythema on his palate and a 4-mm superficial erosion on the right penile shaft. Swelling and tenderness were noted over the elbows, knees, hands, and ankles. No inguinal lymphadenopathy was noted.

An arthrocentesis was performed on the right knee that demonstrated no organisms on Gram stain and a normal joint fluid cell count. A complete blood count (CBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and urinalysis were ordered. A punch biopsy was performed on a scaly patch on the right elbow.

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

The patient’s history, clinical findings, and lab results, including a positive Chlamydia trachomatis polymerase chain reaction (PCR) test from a urethral swab, pointed to a diagnosis of keratoderma blenorrhagicum in association with reactive arthritis (following infection with C trachomatis).

Reactive arthritis features a triad of conjunctivitis, urethritis, and arthritis that follows either gastrointestinal or urogenital infection.

Relevant diagnostic findings included an elevated CRP of 26.5 mg/L (normal range, < 10 mg/L), an elevated ESR of 116 mm/h (normal range, < 15 mm/h) and as noted, a positive C trachomatis PCR test. The patient’s white blood cell count was 9.7/μL (normal range, 4.5-11 μL) and the rest of the CBC was within normal limits. Urinalysis was positive for leukocytes and rare bacteria. A treponemal antibody test was negative.

Additionally, the punch biopsy from the right elbow revealed acanthosis, intercellular spongiosis, and subcorneal pustules consistent with localized pustular psoriasis or keratoderma blenorrhagicum. After the diagnosis was made, human leukocyte antigen B27 allele (HLA-B27) testing was conducted and was positive.

A predisposition exacerbates the infection

Reactive arthritis, a type of spondyloarthropathy, features a triad of conjunctivitis, urethritis, and arthritis that follows either gastrointestinal or urogenital infection.¹ Reactive arthritis occurs with a male predominance of 3:1, and the worldwide prevalence is 1 in 3000.¹ Causative bacteria include C trachomatis, Yersinia, Salmonella, ­Shigella, and Campylobacter, Escherichia coli, Clostridioides (formerly Clostridium) difficile, and C pneumoniae.² Patients with the HLA-B27 allele are 50 times more likely to develop reactive arthritis following infection with the aforementioned bacteria.¹

Findings consistent with a diagnosis of reactive arthritis include a recent history of gastrointestinal or urogenital illness, joint pain, conjunctivitis, oral lesions, cutaneous changes, and genital lesions.³ Diagnostic tests should include arthrocentesis with cultures or PCR and cell count, ESR, CRP, CBC, and urinalysis. HLA-B27 can be used to support the diagnosis but is not routinely recommended.²

Pustules and psoriasiform scaling characterize this diagnosis

The differential diagnosis for the signs and symptoms seen in this patient include disseminated gonococcal arthritis, psoriatic arthritis, rheumatoid arthritis, and secondary syphilis.

Gonococcal arthritis manifests with painful, sterile joints as well as pustules on the palms and soles, but not with the psoriasiform scaling and desquamation that was seen in this case. A culture or PCR from urethral discharge or pustules on the palms and soles could be used to confirm this diagnosis.³

Continue to: Psoriasis in association with psoriatic arthritis

Psoriasis in association with psoriatic arthritis and the psoriasiform rashing of reactive arthritis (keratoderma blenorrhagicum) show similar histopathology; however, patients with psoriatic arthritis generally exhibit fewer constitutional symptoms.⁴

Rheumatoid arthritis also manifests with joint pain and swelling, especially in the hands, wrists, and knees. This diagnosis was unlikely in this patient, where small joints were largely uninvolved.⁴

Secondary syphilis also manifests with papular, scaly, erythematous lesions on the palms and soles along with pityriasis rosea–like rashing on the trunk. However, it rarely produces pustules or hyperkeratotic keratoderma.⁵ As noted earlier, a treponemal antibody test in this patient was negative.

Drug therapy is the best option

First-line therapy for reactive arthritis consists of NSAIDs. If the patient exhibits an inadequate response after a 2-week trial, intra-­articular or systemic glucocorticoids may be considered.³ If the patient fails to respond to the steroids, disease-modifying antirheumatic drugs (DMARDs) may be considered. Reactive arthritis is considered chronic if the disease lasts longer than 6 months, at which point, DMARDs or tumor necrosis factor-α inhibitors may be utilized.³ For cutaneous manifestations, such as keratoderma blenorrhagicum, topical glucocorticoids twice daily may be used along with keratolytic agents.

Our patient received 2 doses of azithromycin (500 mg IV) and 1 dose of ceftriaxone (2 g IV) to treat his infection while in the ED. Over the course of his hospital stay, he received ceftriaxone (1 g IV daily) for 6 days and naproxen (500 mg tid po) which was tapered. Additionally, he received a week of methylprednisolone (60 mg IM daily) before tapering to oral prednisone. His taper consisted of 40 mg po for 1 week and was decreased by 10 mg each week. Augmented betamethasone dipropionate 0.05% cream and urea 20% cream were prescribed for twice-daily application for the hyperkeratotic scale on both of his feet.

A 21-year-old man presented to the emergency department (ED) with a 2-month history of joint pain, swelling, and difficulty walking that began with swelling of his right knee (FIGURE 1A). The patient said that over the course of several weeks, the swelling and joint pain spread to his left knee, followed by bilateral elbows and ankles. Nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin produced only modest improvement.

Two weeks prior to presentation, the patient also experienced widespread pruritus and conjunctivitis. His past medical history was significant for a sexual encounter that resulted in urinary tract infection (UTI)–like symptoms approximately 1 month prior to the onset of his joint symptoms. He did not seek care for the UTI-like symptoms.

In the ED, the patient was febrile (102.1 °F) and tachycardic. Skin examination revealed erythematous papules, intact vesicles, and pustules with background hyperkeratosis and desquamation on his right foot (FIGURE 1B). The patient had spotty erythema on his palate and a 4-mm superficial erosion on the right penile shaft. Swelling and tenderness were noted over the elbows, knees, hands, and ankles. No inguinal lymphadenopathy was noted.

An arthrocentesis was performed on the right knee that demonstrated no organisms on Gram stain and a normal joint fluid cell count. A complete blood count (CBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and urinalysis were ordered. A punch biopsy was performed on a scaly patch on the right elbow.

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

The patient’s history, clinical findings, and lab results, including a positive Chlamydia trachomatis polymerase chain reaction (PCR) test from a urethral swab, pointed to a diagnosis of keratoderma blenorrhagicum in association with reactive arthritis (following infection with C trachomatis).

Reactive arthritis features a triad of conjunctivitis, urethritis, and arthritis that follows either gastrointestinal or urogenital infection.

Relevant diagnostic findings included an elevated CRP of 26.5 mg/L (normal range, < 10 mg/L), an elevated ESR of 116 mm/h (normal range, < 15 mm/h) and as noted, a positive C trachomatis PCR test. The patient’s white blood cell count was 9.7/μL (normal range, 4.5-11 μL) and the rest of the CBC was within normal limits. Urinalysis was positive for leukocytes and rare bacteria. A treponemal antibody test was negative.

Additionally, the punch biopsy from the right elbow revealed acanthosis, intercellular spongiosis, and subcorneal pustules consistent with localized pustular psoriasis or keratoderma blenorrhagicum. After the diagnosis was made, human leukocyte antigen B27 allele (HLA-B27) testing was conducted and was positive.

A predisposition exacerbates the infection

Reactive arthritis, a type of spondyloarthropathy, features a triad of conjunctivitis, urethritis, and arthritis that follows either gastrointestinal or urogenital infection.¹ Reactive arthritis occurs with a male predominance of 3:1, and the worldwide prevalence is 1 in 3000.¹ Causative bacteria include C trachomatis, Yersinia, Salmonella, ­Shigella, and Campylobacter, Escherichia coli, Clostridioides (formerly Clostridium) difficile, and C pneumoniae.² Patients with the HLA-B27 allele are 50 times more likely to develop reactive arthritis following infection with the aforementioned bacteria.¹

Findings consistent with a diagnosis of reactive arthritis include a recent history of gastrointestinal or urogenital illness, joint pain, conjunctivitis, oral lesions, cutaneous changes, and genital lesions.³ Diagnostic tests should include arthrocentesis with cultures or PCR and cell count, ESR, CRP, CBC, and urinalysis. HLA-B27 can be used to support the diagnosis but is not routinely recommended.²

Pustules and psoriasiform scaling characterize this diagnosis

The differential diagnosis for the signs and symptoms seen in this patient include disseminated gonococcal arthritis, psoriatic arthritis, rheumatoid arthritis, and secondary syphilis.

Gonococcal arthritis manifests with painful, sterile joints as well as pustules on the palms and soles, but not with the psoriasiform scaling and desquamation that was seen in this case. A culture or PCR from urethral discharge or pustules on the palms and soles could be used to confirm this diagnosis.³

Continue to: Psoriasis in association with psoriatic arthritis

Psoriasis in association with psoriatic arthritis and the psoriasiform rashing of reactive arthritis (keratoderma blenorrhagicum) show similar histopathology; however, patients with psoriatic arthritis generally exhibit fewer constitutional symptoms.⁴

Rheumatoid arthritis also manifests with joint pain and swelling, especially in the hands, wrists, and knees. This diagnosis was unlikely in this patient, where small joints were largely uninvolved.⁴

Secondary syphilis also manifests with papular, scaly, erythematous lesions on the palms and soles along with pityriasis rosea–like rashing on the trunk. However, it rarely produces pustules or hyperkeratotic keratoderma.⁵ As noted earlier, a treponemal antibody test in this patient was negative.

Drug therapy is the best option

First-line therapy for reactive arthritis consists of NSAIDs. If the patient exhibits an inadequate response after a 2-week trial, intra-­articular or systemic glucocorticoids may be considered.³ If the patient fails to respond to the steroids, disease-modifying antirheumatic drugs (DMARDs) may be considered. Reactive arthritis is considered chronic if the disease lasts longer than 6 months, at which point, DMARDs or tumor necrosis factor-α inhibitors may be utilized.³ For cutaneous manifestations, such as keratoderma blenorrhagicum, topical glucocorticoids twice daily may be used along with keratolytic agents.

Our patient received 2 doses of azithromycin (500 mg IV) and 1 dose of ceftriaxone (2 g IV) to treat his infection while in the ED. Over the course of his hospital stay, he received ceftriaxone (1 g IV daily) for 6 days and naproxen (500 mg tid po) which was tapered. Additionally, he received a week of methylprednisolone (60 mg IM daily) before tapering to oral prednisone. His taper consisted of 40 mg po for 1 week and was decreased by 10 mg each week. Augmented betamethasone dipropionate 0.05% cream and urea 20% cream were prescribed for twice-daily application for the hyperkeratotic scale on both of his feet.

A 21-year-old man presented to the emergency department (ED) with a 2-month history of joint pain, swelling, and difficulty walking that began with swelling of his right knee (FIGURE 1A). The patient said that over the course of several weeks, the swelling and joint pain spread to his left knee, followed by bilateral elbows and ankles. Nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin produced only modest improvement.

Two weeks prior to presentation, the patient also experienced widespread pruritus and conjunctivitis. His past medical history was significant for a sexual encounter that resulted in urinary tract infection (UTI)–like symptoms approximately 1 month prior to the onset of his joint symptoms. He did not seek care for the UTI-like symptoms.

In the ED, the patient was febrile (102.1 °F) and tachycardic. Skin examination revealed erythematous papules, intact vesicles, and pustules with background hyperkeratosis and desquamation on his right foot (FIGURE 1B). The patient had spotty erythema on his palate and a 4-mm superficial erosion on the right penile shaft. Swelling and tenderness were noted over the elbows, knees, hands, and ankles. No inguinal lymphadenopathy was noted.

An arthrocentesis was performed on the right knee that demonstrated no organisms on Gram stain and a normal joint fluid cell count. A complete blood count (CBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and urinalysis were ordered. A punch biopsy was performed on a scaly patch on the right elbow.

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

The patient’s history, clinical findings, and lab results, including a positive Chlamydia trachomatis polymerase chain reaction (PCR) test from a urethral swab, pointed to a diagnosis of keratoderma blenorrhagicum in association with reactive arthritis (following infection with C trachomatis).

Reactive arthritis features a triad of conjunctivitis, urethritis, and arthritis that follows either gastrointestinal or urogenital infection.

Relevant diagnostic findings included an elevated CRP of 26.5 mg/L (normal range, < 10 mg/L), an elevated ESR of 116 mm/h (normal range, < 15 mm/h) and as noted, a positive C trachomatis PCR test. The patient’s white blood cell count was 9.7/μL (normal range, 4.5-11 μL) and the rest of the CBC was within normal limits. Urinalysis was positive for leukocytes and rare bacteria. A treponemal antibody test was negative.

Additionally, the punch biopsy from the right elbow revealed acanthosis, intercellular spongiosis, and subcorneal pustules consistent with localized pustular psoriasis or keratoderma blenorrhagicum. After the diagnosis was made, human leukocyte antigen B27 allele (HLA-B27) testing was conducted and was positive.

A predisposition exacerbates the infection

Reactive arthritis, a type of spondyloarthropathy, features a triad of conjunctivitis, urethritis, and arthritis that follows either gastrointestinal or urogenital infection.¹ Reactive arthritis occurs with a male predominance of 3:1, and the worldwide prevalence is 1 in 3000.¹ Causative bacteria include C trachomatis, Yersinia, Salmonella, ­Shigella, and Campylobacter, Escherichia coli, Clostridioides (formerly Clostridium) difficile, and C pneumoniae.² Patients with the HLA-B27 allele are 50 times more likely to develop reactive arthritis following infection with the aforementioned bacteria.¹

Findings consistent with a diagnosis of reactive arthritis include a recent history of gastrointestinal or urogenital illness, joint pain, conjunctivitis, oral lesions, cutaneous changes, and genital lesions.³ Diagnostic tests should include arthrocentesis with cultures or PCR and cell count, ESR, CRP, CBC, and urinalysis. HLA-B27 can be used to support the diagnosis but is not routinely recommended.²

Pustules and psoriasiform scaling characterize this diagnosis

The differential diagnosis for the signs and symptoms seen in this patient include disseminated gonococcal arthritis, psoriatic arthritis, rheumatoid arthritis, and secondary syphilis.

Gonococcal arthritis manifests with painful, sterile joints as well as pustules on the palms and soles, but not with the psoriasiform scaling and desquamation that was seen in this case. A culture or PCR from urethral discharge or pustules on the palms and soles could be used to confirm this diagnosis.³

Continue to: Psoriasis in association with psoriatic arthritis

Psoriasis in association with psoriatic arthritis and the psoriasiform rashing of reactive arthritis (keratoderma blenorrhagicum) show similar histopathology; however, patients with psoriatic arthritis generally exhibit fewer constitutional symptoms.⁴

Rheumatoid arthritis also manifests with joint pain and swelling, especially in the hands, wrists, and knees. This diagnosis was unlikely in this patient, where small joints were largely uninvolved.⁴

Secondary syphilis also manifests with papular, scaly, erythematous lesions on the palms and soles along with pityriasis rosea–like rashing on the trunk. However, it rarely produces pustules or hyperkeratotic keratoderma.⁵ As noted earlier, a treponemal antibody test in this patient was negative.

Drug therapy is the best option

First-line therapy for reactive arthritis consists of NSAIDs. If the patient exhibits an inadequate response after a 2-week trial, intra-­articular or systemic glucocorticoids may be considered.³ If the patient fails to respond to the steroids, disease-modifying antirheumatic drugs (DMARDs) may be considered. Reactive arthritis is considered chronic if the disease lasts longer than 6 months, at which point, DMARDs or tumor necrosis factor-α inhibitors may be utilized.³ For cutaneous manifestations, such as keratoderma blenorrhagicum, topical glucocorticoids twice daily may be used along with keratolytic agents.

Our patient received 2 doses of azithromycin (500 mg IV) and 1 dose of ceftriaxone (2 g IV) to treat his infection while in the ED. Over the course of his hospital stay, he received ceftriaxone (1 g IV daily) for 6 days and naproxen (500 mg tid po) which was tapered. Additionally, he received a week of methylprednisolone (60 mg IM daily) before tapering to oral prednisone. His taper consisted of 40 mg po for 1 week and was decreased by 10 mg each week. Augmented betamethasone dipropionate 0.05% cream and urea 20% cream were prescribed for twice-daily application for the hyperkeratotic scale on both of his feet.