Clinical Review

It’s a scenario all office-based clinicians are familiar with: Your day has been going well, and all your appointments have been (relatively) on time. But when you scan your afternoon schedule your mood shifts from buoyant to crestfallen. The reason: Three patients whom you find particularly frustrating are slotted for the last appointments of the day.

Case 1: Mr. E, a 44-year-old high-powered attorney, has chronic headache that he has complained off and on about for several years. He has no other past medical history. Physical examination strongly suggests that Mr. E experiences tension-type headaches, but he continues to demand MRI of the brain. “I think there’s something wrong in there,” he has stated repeatedly. “If my last doctor, who is one of the best in the country, ordered an MRI for me, why can’t you?”

Case 2: Mr. A is a 37-year-old man who lost his home in a hurricane three years ago. Although he sustained only minor physical injuries, Mr. A appears to have lost his sense of well-being. He has developed chronic—and debilitating—musculoskeletal pain in his neck and low back in the aftermath of the storm and has been unable to work since then.

At his last two visits, Mr. A requested increasing doses of oxycodone, insisting that nothing else alleviates the pain. When you suggested a nonopioid analgesic, he broke down in tears. “Nobody takes my injuries seriously! My insurance doesn’t want to compensate me for my losses. Now you don’t even believe I’m in pain.”

Case 3: Ms. S is a 65-year-old socially isolated widow who lost her husband several years ago. She has a history of multiple somatic complaints, including fatigue, abdominal pain, back pain, joint pain, and dizziness. As a result, she has undergone numerous diagnostic procedures, including esophagastro­duodenoscopy, colonoscopy, and various blood tests, all of which have been negative. Ms. S consistently requires longer than the usual 20-minute visit. When you try to end an appointment, she typically brings up new issues. “Two days ago, I had this pain by my belly button and left shoulder blade. I think that there must be something wrong with me. Can you examine me?” she asked toward the end of her last visit, six weeks ago.

THE BURDEN OF DIFFICULT PATIENT ENCOUNTERS

Cases such as these are frustrating, not so much for their clinical complexity but rather because of the elusiveness of satisfying doctor-patient interactions. Besides a litany of physical complaints, such patients typically present with anxiety, depression, and other psychiatric symptoms; express dissatisfaction with the care they are receiving; and repeatedly request tests and interventions that are not medically indicated.¹

From a primary care perspective, such cases can be frustrating and time-consuming, significantly contribute to exhaustion and burnout, and result in unnecessary health care expenditures.¹ Studies suggest that family physicians see such patients on a daily basis, and rate about one patient in six as a “difficult” case.^2,3

Attitudes, training play a role

Research has established other critical spheres of influence that conspire to create difficult or frustrating patient encounters, including “system” factors (ie, reduced duration of visits and interrupted visits)⁴ and clinician factors. In fact, negative attitudes toward psychosocial aspects of patient care may be a more potent factor in shaping difficult encounters than any patient characteristic.^3,5

Consider the following statements:
• “Talking about psychosocial issues causes more trouble than it is worth.”

• “I do not focus on psychosocial problems until I have ruled out organic disease.”

• “I am too pressed for time to routinely investigate psychosocial issues.”

Such sentiments, which have been associated with difficult encounters, are part of the 32-item Physician Belief Scale, developed 30 years ago and still used to assess beliefs about psychosocial aspects of patient care held by primary care physicians.⁶

Lack of training is a potential problem, as well. In one survey, more than half of directors of family medicine programs agreed that training in mental health is inadequate.⁷ Thus, family practice providers often respond to patients like Mr. E, Mr. A, and Ms. S by becoming irritated or avoiding further interaction. A more appropriate response is for the clinician to self-acknowledge his or her emotions, then to engage in an empathic interaction in keeping with patient expectations.⁴

As mental health treatment becomes more integrated within family medicine,⁸ pointers for handling difficult patient encounters can be gleaned from the traditional psychiatric approach to difficult or frustrating cases. Indeed, we believe that what is now known as a “patient-centered approach” is rooted in traditions and techniques that psychiatrists and psychologists have used for decades.⁹

CORE PRINCIPLES FOR HANDLING FRUSTRATING CASES

A useful approach to the difficult patient encounter, detailed in Table 1, is based on three key principles:

• The clinician-patient relationship should be the target for change.

• The patient’s emotional experience should be an explicit focus of the clinical interaction.

• The patient’s perspective should guide the clinical encounter.

In our experience, when the interaction between patient and clinician shifts from searching for specific pathologies to building a collaborative relationship, previously recalcitrant symptoms often improve.

Use these communication techniques

There are two main ways to elicit a conversation about personal issues, including emotions, with patients. One is to directly ask patients to describe the distress they are experiencing and elicit the emotions connected to this distress. The other is to invite a discussion about emotional issues indirectly, by asking patients how the symptoms affect their lives and what they think is causing the problem or by selectively sharing an emotional experience of your own.

Once a patient has shared emotions, you will need to show support and empathy in order to build an alliance. There is more than one way to do this, and methods can be used alone or in combination, depending on the particular situation. (You’ll find examples in Table 1.)

Name the affect. The simple act of naming the patient’s affect or emotional expression (eg, “You sound sad”) is surprisingly helpful, as it lets patients know they have been “heard.”

Validate. You can also validate patients like Mr. E, Mr. A, and Ms. S by stating that their emotional reactions are legitimate, praising them for how well they have coped with difficult symptoms, and acknowledging the seriousness and complexity of their situations.

Align. Once a patient expresses his or her interests and goals, aligning yourself with them (eg, “I want to do everything in my power to help you reduce your pain …”) will elicit hope and improve patient satisfaction.

And two mnemonic devices—detailed in the box above—can help you improve the way you communicate with patients.^10,11

Communication can also be nonverbal, such as thoughtful nodding or a timely therapeutic silence. The former is characterized by slow, steady, and purposeful movement accompanied by eye contact; in the latter case, you simply resist the urge to immediately respond after a patient has revealed something emotionally laden, and wait a few seconds to take in what has been said.

HOW TO PROVIDE THERAPEUTIC STRUCTURE

Family practice clinicians can further manage patient behaviors that they find bothersome by implementing changes in the way they organize and conduct patient visits. Studies of patients with complex somatic symptoms offer additional hints for the management of frustrating cases. The following strategies can lead to positive outcomes, including a decrease in disability and health care
costs.¹²

Schedule regular brief visits. Mr. E, Mr. A, and Ms. S should have frequent and regular, but brief, appointments (eg, 15 minutes every two weeks for two months). Proactively schedule return visits, rather than waiting for the patient to call for an appointment prn.¹¹ Sharing this kind of plan gives such patients a concrete time line and clear evidence of support. Avoid the temptation to schedule difficult cases for the last time slot of the day, as going over the allotted time can insidiously give some patients the expectation of progressively longer visits.

Set the agenda. To prevent “doorknob questions” like Ms. S’s new symptoms, reported just as you’re about to leave the exam room, the agenda must be set at the outset of the visit. This can be done by asking, “What did you want to discuss today?”, “Is there anything else you want to address today?”, or “What else did you need taken care of?”¹³

Explicitly inquiring about patient expectations at the start of the visit lets patients like Ms. S know that they are being taken seriously. If the agenda still balloons, you can simply state, “You deserve more than 15 minutes for all these issues. Let’s pick the top two for today and tackle others at our next visit in two weeks.” To further save time, you can ask the patient to bring a symptom diary or written agenda to the appointment. We’ve found that many anxious patients benefit from this exercise.

Avoid the urge to act. When a patient has unexplained symptoms, effective interventions require clinicians to avoid certain “reflex” behaviors—repeatedly performing diagnostic tests, prescribing medications for symptoms of unknown etiology, insinuating that the problem is “in your head,” formulating ambiguous diagnoses, and repeating physical exams.¹² Such behaviors tend to reinforce the pathology in patients with unexplained symptoms. The time saved avoiding these pitfalls is better invested in exploring personal issues and stressors.

The point is that such patients should be reassured via discussion, rather than with dubious diagnostic labels and potentially dangerous drugs. This approach has been shown to improve patients’ physical functioning while reducing medical expenditures.¹²

INTO ACTION WITH OUR THREE CASES

Case 1: Given these principles, how would you handle Mr. E, the patient who is demanding an MRI for a simple tension headache? Although placating him by ordering the test, providing a referral to a specialist, or defending your recommendation through medical reasoning may seem to be more intuitive (or a “quick fix”), these strategies often lead to excessive medical spending, transfer of the burden to a specialist colleague, and ongoing frustration and dissatisfaction on the part of the patient. In this case, validation may be a more useful approach.

“I can totally understand why you’re frustrated that we disagree,” you might say to Mr. E. “But you’re right! You definitely deserve the best care. That’s why I’m recommending against the MRI, as I feel that would be a suboptimal approach.”

Often patients like Mr. E will require repeated validation of their suffering and frustration. The key is to be persistent in validating their feelings without compromising your own principles in providing optimal medical care.

Case 2:  Let’s turn now to Mr. A, who is requesting escalating doses of opioids. Some clinicians might write the prescription for the dose he’s insisting on, while others draw a hard boundary by refusing to prescribe above a certain dose or beyond a specific time frame. Both strategies may compromise optimal care or endanger the clinician-patient alliance. Another quick solution would be to provide a referral to a psychiatrist, without further discussion.

In cases like that of Mr. A, however, the patient’s demands are often a sign of more complicated emotions and dynamics below the surface. So you might respond by stating, “I’m sorry to hear that things haven’t been going well. How are you feeling about these things? How does the oxycodone help you? In what way doesn’t it help?”

It is important here to understand how the medication serves the patient—in addition to the ways it hurts him—in order for him to feel understood. Inviting Mr. A to have an open-ended discussion may allow him to reveal what is the real source of his distress—losing his job and his home.

Case 3: Now let’s turn to Ms. S, who is convinced that she has a physical malady despite negative exams and tests. In truth, she may be depressed or anxious over her husband’s death. One way to address this is to confront the patient directly by suggesting that she has depression triggered by her husband’s death. But this strategy—if used too early—may feel like an accusation, make her angry, and jeopardize your relationship with her.

An alternative approach would be to say, “I think your problems are long-standing and could require a while to treat. Let’s see each other every two weeks for the next two months so we get adequate time to work on them.” This would be an example of structuring more frequent visits, while also validating the distressing nature of her symptoms.

These strategies are evidence-based

These techniques, while easily adaptable to primary care, are grounded in psychotherapy theory and are evidence-based. A seminal randomized controlled trial conducted more than 30 years ago showed that a patient-centered interview incorporating a number of these techniques bolstered clinicians’ knowledge, interviewing skills, attitudes, and ability to manage patients with unexplained complaints.¹⁴

A multicenter study analyzed audio recordings of strategies used by primary care physicians to deny patient requests for a particular medication. It revealed that explanations based on patient perspectives were significantly more likely to result in excellent patient satisfaction than biomedical explanations or other explanatory approaches.¹⁵ Research has also shown that agenda-setting improves both patient and provider satisfaction.¹⁶

Some cases will still be frustrating, and some “difficult” patients will still need a psychiatric referral at some point—ideally, to a psychiatric or psychological consultant who collaborates closely with the primary care clinic.^17,18

Clinicians sometimes worry that the communication techniques outlined here cannot be incorporated into an already harried primary care visit. Many may think it’s better not to ask at all than risk opening a Pandora’s box. We urge you to reconsider. Although the techniques we’ve outlined certainly require practice, they need not be time-consuming.¹⁹ By embracing this management approach, you can improve patient satisfaction while enhancing your own repertoire of doctoring skills.

The authors thank Drs. Michael Fetters and Rod Hayward for their help in the development of this manuscript.

ACKNOWLEDGEMENT

This work was supported by a grant from the Robert Wood Johnson Foundation.

REFERENCES

1.Hahn SR, Kroenke K, Spitzer RL, et al. The difficult patient: prevalence, psychopathology, and functional impairment. J Gen Intern Med. 1996;11:1-8.

2. An PG, Rabatin JS, Manwell LB, et al. Burden of difficult encounters in primary care: data from the minimizing error, maximizing outcomes study. Arch Intern Med. 2009;169:410-414.

3. Hinchey SA, Jackson JL. A cohort study assessing difficult patient encounters in a walk-in primary care clinic, predictors and outcomes. J Gen Intern Med. 2011;26:588-594.

4. Haas LJ, Leiser JP, Magill MK, et al. Management of the difficult patient. Am Fam Physician. 2005;72:2063-2068.

5. Jackson JL, Kroenke K. Difficult patient encounters in the ambulatory clinic: clinical predictors and outcomes. Arch Intern Med. 1999;159:1069-1075.

6. Ashworth CD, Williamson P, Montano D. A scale to measure physician beliefs about psychosocial aspects of patient care. Soc Sci Med. 1984;19:1235-1238.

7. Leigh H, Stewart D, Mallios R. Mental health and psychiatry training in primary care residency programs. Gen Hosp Psychiatry. 2006;28:189-194.

8. Katon W, Unützer J. Collaborative care models for depression: time to move from evidence to practice. Arch Intern Med. 2006;166:2304-2306.

9. Groves JE. Taking care of the hateful patient. N Engl J Med. 1978;298:883-887.

10. Fortin AH, Dwamena FC, Frankel RM, et al. Smith’s Patient-Centered Interviewing: An Evidence-Based Method. 3rd ed. New York, NY: McGraw-Hill; 2012.

11. Stuart MR, Lieberman JA. The Fifteen Minute Hour: Therapeutic Talk in Primary Care. 4th ed. Milton Keynes, UK: Radcliffe Publishing; 2008.

12. Smith GR Jr, Rost K, Kashner TM. A trial of the effect of a standardized psychiatric consultation on health outcomes and costs in somatizing patients. Arch Gen Psychiatry. 1995;52:238-243.

13. Baker LH, O’Connell D, Platt FW. “What else?” Setting the agenda for the clinical interview. Ann Intern Med. 2005;143:766 -770.

14. Smith RC, Lyles JS, Mettler J, et al. The effectiveness of intensive training for residents in interviewing: a randomized, controlled study. Ann Intern Med. 1998;128:118-126.

15. Paterniti DA, Fancher TL, Cipri CS, et al. Getting to “no”: strategies primary care physicians use to deny patient requests. Arch Intern Med. 2010;170: 381-388.

16. Kroenke K. Unburdening the difficult clinical encounter. Arch Intern Med. 2009;169:333-334.

17. Katon W, Unützer J, Wells K, et al. Collaborative depression care: history, evolution and ways to enhance dissemination and sustainability. Gen Hosp Psychiatry. 2010;32:456-464.

18. Williams M, Angstman K, Johnson I, et al. Implementation of a care management model for depression at two primary care clinics. J Ambul Care Manage. 2011;34:163-173.

19. Lieberman JA III, Stuart MR. The BATHE method: incorporating counseling and psychotherapy into the everyday management of patients. Prim Care Companion J Clin Psychiatry. 1999;1:35-38.

It’s a scenario all office-based clinicians are familiar with: Your day has been going well, and all your appointments have been (relatively) on time. But when you scan your afternoon schedule your mood shifts from buoyant to crestfallen. The reason: Three patients whom you find particularly frustrating are slotted for the last appointments of the day.

Case 1: Mr. E, a 44-year-old high-powered attorney, has chronic headache that he has complained off and on about for several years. He has no other past medical history. Physical examination strongly suggests that Mr. E experiences tension-type headaches, but he continues to demand MRI of the brain. “I think there’s something wrong in there,” he has stated repeatedly. “If my last doctor, who is one of the best in the country, ordered an MRI for me, why can’t you?”

Case 2: Mr. A is a 37-year-old man who lost his home in a hurricane three years ago. Although he sustained only minor physical injuries, Mr. A appears to have lost his sense of well-being. He has developed chronic—and debilitating—musculoskeletal pain in his neck and low back in the aftermath of the storm and has been unable to work since then.

At his last two visits, Mr. A requested increasing doses of oxycodone, insisting that nothing else alleviates the pain. When you suggested a nonopioid analgesic, he broke down in tears. “Nobody takes my injuries seriously! My insurance doesn’t want to compensate me for my losses. Now you don’t even believe I’m in pain.”

Case 3: Ms. S is a 65-year-old socially isolated widow who lost her husband several years ago. She has a history of multiple somatic complaints, including fatigue, abdominal pain, back pain, joint pain, and dizziness. As a result, she has undergone numerous diagnostic procedures, including esophagastro­duodenoscopy, colonoscopy, and various blood tests, all of which have been negative. Ms. S consistently requires longer than the usual 20-minute visit. When you try to end an appointment, she typically brings up new issues. “Two days ago, I had this pain by my belly button and left shoulder blade. I think that there must be something wrong with me. Can you examine me?” she asked toward the end of her last visit, six weeks ago.

THE BURDEN OF DIFFICULT PATIENT ENCOUNTERS

Cases such as these are frustrating, not so much for their clinical complexity but rather because of the elusiveness of satisfying doctor-patient interactions. Besides a litany of physical complaints, such patients typically present with anxiety, depression, and other psychiatric symptoms; express dissatisfaction with the care they are receiving; and repeatedly request tests and interventions that are not medically indicated.¹

From a primary care perspective, such cases can be frustrating and time-consuming, significantly contribute to exhaustion and burnout, and result in unnecessary health care expenditures.¹ Studies suggest that family physicians see such patients on a daily basis, and rate about one patient in six as a “difficult” case.^2,3

Attitudes, training play a role

Research has established other critical spheres of influence that conspire to create difficult or frustrating patient encounters, including “system” factors (ie, reduced duration of visits and interrupted visits)⁴ and clinician factors. In fact, negative attitudes toward psychosocial aspects of patient care may be a more potent factor in shaping difficult encounters than any patient characteristic.^3,5

Consider the following statements:
• “Talking about psychosocial issues causes more trouble than it is worth.”

• “I do not focus on psychosocial problems until I have ruled out organic disease.”

• “I am too pressed for time to routinely investigate psychosocial issues.”

Such sentiments, which have been associated with difficult encounters, are part of the 32-item Physician Belief Scale, developed 30 years ago and still used to assess beliefs about psychosocial aspects of patient care held by primary care physicians.⁶

Lack of training is a potential problem, as well. In one survey, more than half of directors of family medicine programs agreed that training in mental health is inadequate.⁷ Thus, family practice providers often respond to patients like Mr. E, Mr. A, and Ms. S by becoming irritated or avoiding further interaction. A more appropriate response is for the clinician to self-acknowledge his or her emotions, then to engage in an empathic interaction in keeping with patient expectations.⁴

As mental health treatment becomes more integrated within family medicine,⁸ pointers for handling difficult patient encounters can be gleaned from the traditional psychiatric approach to difficult or frustrating cases. Indeed, we believe that what is now known as a “patient-centered approach” is rooted in traditions and techniques that psychiatrists and psychologists have used for decades.⁹

CORE PRINCIPLES FOR HANDLING FRUSTRATING CASES

A useful approach to the difficult patient encounter, detailed in Table 1, is based on three key principles:

• The clinician-patient relationship should be the target for change.

• The patient’s emotional experience should be an explicit focus of the clinical interaction.

• The patient’s perspective should guide the clinical encounter.

In our experience, when the interaction between patient and clinician shifts from searching for specific pathologies to building a collaborative relationship, previously recalcitrant symptoms often improve.

Use these communication techniques

There are two main ways to elicit a conversation about personal issues, including emotions, with patients. One is to directly ask patients to describe the distress they are experiencing and elicit the emotions connected to this distress. The other is to invite a discussion about emotional issues indirectly, by asking patients how the symptoms affect their lives and what they think is causing the problem or by selectively sharing an emotional experience of your own.

Once a patient has shared emotions, you will need to show support and empathy in order to build an alliance. There is more than one way to do this, and methods can be used alone or in combination, depending on the particular situation. (You’ll find examples in Table 1.)

Name the affect. The simple act of naming the patient’s affect or emotional expression (eg, “You sound sad”) is surprisingly helpful, as it lets patients know they have been “heard.”

Validate. You can also validate patients like Mr. E, Mr. A, and Ms. S by stating that their emotional reactions are legitimate, praising them for how well they have coped with difficult symptoms, and acknowledging the seriousness and complexity of their situations.

Align. Once a patient expresses his or her interests and goals, aligning yourself with them (eg, “I want to do everything in my power to help you reduce your pain …”) will elicit hope and improve patient satisfaction.

And two mnemonic devices—detailed in the box above—can help you improve the way you communicate with patients.^10,11

Communication can also be nonverbal, such as thoughtful nodding or a timely therapeutic silence. The former is characterized by slow, steady, and purposeful movement accompanied by eye contact; in the latter case, you simply resist the urge to immediately respond after a patient has revealed something emotionally laden, and wait a few seconds to take in what has been said.

HOW TO PROVIDE THERAPEUTIC STRUCTURE

Family practice clinicians can further manage patient behaviors that they find bothersome by implementing changes in the way they organize and conduct patient visits. Studies of patients with complex somatic symptoms offer additional hints for the management of frustrating cases. The following strategies can lead to positive outcomes, including a decrease in disability and health care
costs.¹²

Schedule regular brief visits. Mr. E, Mr. A, and Ms. S should have frequent and regular, but brief, appointments (eg, 15 minutes every two weeks for two months). Proactively schedule return visits, rather than waiting for the patient to call for an appointment prn.¹¹ Sharing this kind of plan gives such patients a concrete time line and clear evidence of support. Avoid the temptation to schedule difficult cases for the last time slot of the day, as going over the allotted time can insidiously give some patients the expectation of progressively longer visits.

Set the agenda. To prevent “doorknob questions” like Ms. S’s new symptoms, reported just as you’re about to leave the exam room, the agenda must be set at the outset of the visit. This can be done by asking, “What did you want to discuss today?”, “Is there anything else you want to address today?”, or “What else did you need taken care of?”¹³

Explicitly inquiring about patient expectations at the start of the visit lets patients like Ms. S know that they are being taken seriously. If the agenda still balloons, you can simply state, “You deserve more than 15 minutes for all these issues. Let’s pick the top two for today and tackle others at our next visit in two weeks.” To further save time, you can ask the patient to bring a symptom diary or written agenda to the appointment. We’ve found that many anxious patients benefit from this exercise.

Avoid the urge to act. When a patient has unexplained symptoms, effective interventions require clinicians to avoid certain “reflex” behaviors—repeatedly performing diagnostic tests, prescribing medications for symptoms of unknown etiology, insinuating that the problem is “in your head,” formulating ambiguous diagnoses, and repeating physical exams.¹² Such behaviors tend to reinforce the pathology in patients with unexplained symptoms. The time saved avoiding these pitfalls is better invested in exploring personal issues and stressors.

The point is that such patients should be reassured via discussion, rather than with dubious diagnostic labels and potentially dangerous drugs. This approach has been shown to improve patients’ physical functioning while reducing medical expenditures.¹²

INTO ACTION WITH OUR THREE CASES

Case 1: Given these principles, how would you handle Mr. E, the patient who is demanding an MRI for a simple tension headache? Although placating him by ordering the test, providing a referral to a specialist, or defending your recommendation through medical reasoning may seem to be more intuitive (or a “quick fix”), these strategies often lead to excessive medical spending, transfer of the burden to a specialist colleague, and ongoing frustration and dissatisfaction on the part of the patient. In this case, validation may be a more useful approach.

“I can totally understand why you’re frustrated that we disagree,” you might say to Mr. E. “But you’re right! You definitely deserve the best care. That’s why I’m recommending against the MRI, as I feel that would be a suboptimal approach.”

Often patients like Mr. E will require repeated validation of their suffering and frustration. The key is to be persistent in validating their feelings without compromising your own principles in providing optimal medical care.

Case 2:  Let’s turn now to Mr. A, who is requesting escalating doses of opioids. Some clinicians might write the prescription for the dose he’s insisting on, while others draw a hard boundary by refusing to prescribe above a certain dose or beyond a specific time frame. Both strategies may compromise optimal care or endanger the clinician-patient alliance. Another quick solution would be to provide a referral to a psychiatrist, without further discussion.

In cases like that of Mr. A, however, the patient’s demands are often a sign of more complicated emotions and dynamics below the surface. So you might respond by stating, “I’m sorry to hear that things haven’t been going well. How are you feeling about these things? How does the oxycodone help you? In what way doesn’t it help?”

It is important here to understand how the medication serves the patient—in addition to the ways it hurts him—in order for him to feel understood. Inviting Mr. A to have an open-ended discussion may allow him to reveal what is the real source of his distress—losing his job and his home.

Case 3: Now let’s turn to Ms. S, who is convinced that she has a physical malady despite negative exams and tests. In truth, she may be depressed or anxious over her husband’s death. One way to address this is to confront the patient directly by suggesting that she has depression triggered by her husband’s death. But this strategy—if used too early—may feel like an accusation, make her angry, and jeopardize your relationship with her.

An alternative approach would be to say, “I think your problems are long-standing and could require a while to treat. Let’s see each other every two weeks for the next two months so we get adequate time to work on them.” This would be an example of structuring more frequent visits, while also validating the distressing nature of her symptoms.

These strategies are evidence-based

These techniques, while easily adaptable to primary care, are grounded in psychotherapy theory and are evidence-based. A seminal randomized controlled trial conducted more than 30 years ago showed that a patient-centered interview incorporating a number of these techniques bolstered clinicians’ knowledge, interviewing skills, attitudes, and ability to manage patients with unexplained complaints.¹⁴

A multicenter study analyzed audio recordings of strategies used by primary care physicians to deny patient requests for a particular medication. It revealed that explanations based on patient perspectives were significantly more likely to result in excellent patient satisfaction than biomedical explanations or other explanatory approaches.¹⁵ Research has also shown that agenda-setting improves both patient and provider satisfaction.¹⁶

Some cases will still be frustrating, and some “difficult” patients will still need a psychiatric referral at some point—ideally, to a psychiatric or psychological consultant who collaborates closely with the primary care clinic.^17,18

Clinicians sometimes worry that the communication techniques outlined here cannot be incorporated into an already harried primary care visit. Many may think it’s better not to ask at all than risk opening a Pandora’s box. We urge you to reconsider. Although the techniques we’ve outlined certainly require practice, they need not be time-consuming.¹⁹ By embracing this management approach, you can improve patient satisfaction while enhancing your own repertoire of doctoring skills.

The authors thank Drs. Michael Fetters and Rod Hayward for their help in the development of this manuscript.

ACKNOWLEDGEMENT

This work was supported by a grant from the Robert Wood Johnson Foundation.

REFERENCES

1.Hahn SR, Kroenke K, Spitzer RL, et al. The difficult patient: prevalence, psychopathology, and functional impairment. J Gen Intern Med. 1996;11:1-8.

2. An PG, Rabatin JS, Manwell LB, et al. Burden of difficult encounters in primary care: data from the minimizing error, maximizing outcomes study. Arch Intern Med. 2009;169:410-414.

3. Hinchey SA, Jackson JL. A cohort study assessing difficult patient encounters in a walk-in primary care clinic, predictors and outcomes. J Gen Intern Med. 2011;26:588-594.

4. Haas LJ, Leiser JP, Magill MK, et al. Management of the difficult patient. Am Fam Physician. 2005;72:2063-2068.

5. Jackson JL, Kroenke K. Difficult patient encounters in the ambulatory clinic: clinical predictors and outcomes. Arch Intern Med. 1999;159:1069-1075.

6. Ashworth CD, Williamson P, Montano D. A scale to measure physician beliefs about psychosocial aspects of patient care. Soc Sci Med. 1984;19:1235-1238.

7. Leigh H, Stewart D, Mallios R. Mental health and psychiatry training in primary care residency programs. Gen Hosp Psychiatry. 2006;28:189-194.

8. Katon W, Unützer J. Collaborative care models for depression: time to move from evidence to practice. Arch Intern Med. 2006;166:2304-2306.

9. Groves JE. Taking care of the hateful patient. N Engl J Med. 1978;298:883-887.

10. Fortin AH, Dwamena FC, Frankel RM, et al. Smith’s Patient-Centered Interviewing: An Evidence-Based Method. 3rd ed. New York, NY: McGraw-Hill; 2012.

11. Stuart MR, Lieberman JA. The Fifteen Minute Hour: Therapeutic Talk in Primary Care. 4th ed. Milton Keynes, UK: Radcliffe Publishing; 2008.

12. Smith GR Jr, Rost K, Kashner TM. A trial of the effect of a standardized psychiatric consultation on health outcomes and costs in somatizing patients. Arch Gen Psychiatry. 1995;52:238-243.

13. Baker LH, O’Connell D, Platt FW. “What else?” Setting the agenda for the clinical interview. Ann Intern Med. 2005;143:766 -770.

14. Smith RC, Lyles JS, Mettler J, et al. The effectiveness of intensive training for residents in interviewing: a randomized, controlled study. Ann Intern Med. 1998;128:118-126.

15. Paterniti DA, Fancher TL, Cipri CS, et al. Getting to “no”: strategies primary care physicians use to deny patient requests. Arch Intern Med. 2010;170: 381-388.

16. Kroenke K. Unburdening the difficult clinical encounter. Arch Intern Med. 2009;169:333-334.

17. Katon W, Unützer J, Wells K, et al. Collaborative depression care: history, evolution and ways to enhance dissemination and sustainability. Gen Hosp Psychiatry. 2010;32:456-464.

18. Williams M, Angstman K, Johnson I, et al. Implementation of a care management model for depression at two primary care clinics. J Ambul Care Manage. 2011;34:163-173.

19. Lieberman JA III, Stuart MR. The BATHE method: incorporating counseling and psychotherapy into the everyday management of patients. Prim Care Companion J Clin Psychiatry. 1999;1:35-38.

It’s a scenario all office-based clinicians are familiar with: Your day has been going well, and all your appointments have been (relatively) on time. But when you scan your afternoon schedule your mood shifts from buoyant to crestfallen. The reason: Three patients whom you find particularly frustrating are slotted for the last appointments of the day.

Case 1: Mr. E, a 44-year-old high-powered attorney, has chronic headache that he has complained off and on about for several years. He has no other past medical history. Physical examination strongly suggests that Mr. E experiences tension-type headaches, but he continues to demand MRI of the brain. “I think there’s something wrong in there,” he has stated repeatedly. “If my last doctor, who is one of the best in the country, ordered an MRI for me, why can’t you?”

Case 2: Mr. A is a 37-year-old man who lost his home in a hurricane three years ago. Although he sustained only minor physical injuries, Mr. A appears to have lost his sense of well-being. He has developed chronic—and debilitating—musculoskeletal pain in his neck and low back in the aftermath of the storm and has been unable to work since then.

At his last two visits, Mr. A requested increasing doses of oxycodone, insisting that nothing else alleviates the pain. When you suggested a nonopioid analgesic, he broke down in tears. “Nobody takes my injuries seriously! My insurance doesn’t want to compensate me for my losses. Now you don’t even believe I’m in pain.”

Case 3: Ms. S is a 65-year-old socially isolated widow who lost her husband several years ago. She has a history of multiple somatic complaints, including fatigue, abdominal pain, back pain, joint pain, and dizziness. As a result, she has undergone numerous diagnostic procedures, including esophagastro­duodenoscopy, colonoscopy, and various blood tests, all of which have been negative. Ms. S consistently requires longer than the usual 20-minute visit. When you try to end an appointment, she typically brings up new issues. “Two days ago, I had this pain by my belly button and left shoulder blade. I think that there must be something wrong with me. Can you examine me?” she asked toward the end of her last visit, six weeks ago.

THE BURDEN OF DIFFICULT PATIENT ENCOUNTERS

Cases such as these are frustrating, not so much for their clinical complexity but rather because of the elusiveness of satisfying doctor-patient interactions. Besides a litany of physical complaints, such patients typically present with anxiety, depression, and other psychiatric symptoms; express dissatisfaction with the care they are receiving; and repeatedly request tests and interventions that are not medically indicated.¹

From a primary care perspective, such cases can be frustrating and time-consuming, significantly contribute to exhaustion and burnout, and result in unnecessary health care expenditures.¹ Studies suggest that family physicians see such patients on a daily basis, and rate about one patient in six as a “difficult” case.^2,3

Attitudes, training play a role

Research has established other critical spheres of influence that conspire to create difficult or frustrating patient encounters, including “system” factors (ie, reduced duration of visits and interrupted visits)⁴ and clinician factors. In fact, negative attitudes toward psychosocial aspects of patient care may be a more potent factor in shaping difficult encounters than any patient characteristic.^3,5

Consider the following statements:
• “Talking about psychosocial issues causes more trouble than it is worth.”

• “I do not focus on psychosocial problems until I have ruled out organic disease.”

• “I am too pressed for time to routinely investigate psychosocial issues.”

Such sentiments, which have been associated with difficult encounters, are part of the 32-item Physician Belief Scale, developed 30 years ago and still used to assess beliefs about psychosocial aspects of patient care held by primary care physicians.⁶

Lack of training is a potential problem, as well. In one survey, more than half of directors of family medicine programs agreed that training in mental health is inadequate.⁷ Thus, family practice providers often respond to patients like Mr. E, Mr. A, and Ms. S by becoming irritated or avoiding further interaction. A more appropriate response is for the clinician to self-acknowledge his or her emotions, then to engage in an empathic interaction in keeping with patient expectations.⁴

As mental health treatment becomes more integrated within family medicine,⁸ pointers for handling difficult patient encounters can be gleaned from the traditional psychiatric approach to difficult or frustrating cases. Indeed, we believe that what is now known as a “patient-centered approach” is rooted in traditions and techniques that psychiatrists and psychologists have used for decades.⁹

CORE PRINCIPLES FOR HANDLING FRUSTRATING CASES

A useful approach to the difficult patient encounter, detailed in Table 1, is based on three key principles:

• The clinician-patient relationship should be the target for change.

• The patient’s emotional experience should be an explicit focus of the clinical interaction.

• The patient’s perspective should guide the clinical encounter.

In our experience, when the interaction between patient and clinician shifts from searching for specific pathologies to building a collaborative relationship, previously recalcitrant symptoms often improve.

Use these communication techniques

There are two main ways to elicit a conversation about personal issues, including emotions, with patients. One is to directly ask patients to describe the distress they are experiencing and elicit the emotions connected to this distress. The other is to invite a discussion about emotional issues indirectly, by asking patients how the symptoms affect their lives and what they think is causing the problem or by selectively sharing an emotional experience of your own.

Once a patient has shared emotions, you will need to show support and empathy in order to build an alliance. There is more than one way to do this, and methods can be used alone or in combination, depending on the particular situation. (You’ll find examples in Table 1.)

Name the affect. The simple act of naming the patient’s affect or emotional expression (eg, “You sound sad”) is surprisingly helpful, as it lets patients know they have been “heard.”

Validate. You can also validate patients like Mr. E, Mr. A, and Ms. S by stating that their emotional reactions are legitimate, praising them for how well they have coped with difficult symptoms, and acknowledging the seriousness and complexity of their situations.

Align. Once a patient expresses his or her interests and goals, aligning yourself with them (eg, “I want to do everything in my power to help you reduce your pain …”) will elicit hope and improve patient satisfaction.

And two mnemonic devices—detailed in the box above—can help you improve the way you communicate with patients.^10,11

Communication can also be nonverbal, such as thoughtful nodding or a timely therapeutic silence. The former is characterized by slow, steady, and purposeful movement accompanied by eye contact; in the latter case, you simply resist the urge to immediately respond after a patient has revealed something emotionally laden, and wait a few seconds to take in what has been said.

HOW TO PROVIDE THERAPEUTIC STRUCTURE

Family practice clinicians can further manage patient behaviors that they find bothersome by implementing changes in the way they organize and conduct patient visits. Studies of patients with complex somatic symptoms offer additional hints for the management of frustrating cases. The following strategies can lead to positive outcomes, including a decrease in disability and health care
costs.¹²

Schedule regular brief visits. Mr. E, Mr. A, and Ms. S should have frequent and regular, but brief, appointments (eg, 15 minutes every two weeks for two months). Proactively schedule return visits, rather than waiting for the patient to call for an appointment prn.¹¹ Sharing this kind of plan gives such patients a concrete time line and clear evidence of support. Avoid the temptation to schedule difficult cases for the last time slot of the day, as going over the allotted time can insidiously give some patients the expectation of progressively longer visits.

Set the agenda. To prevent “doorknob questions” like Ms. S’s new symptoms, reported just as you’re about to leave the exam room, the agenda must be set at the outset of the visit. This can be done by asking, “What did you want to discuss today?”, “Is there anything else you want to address today?”, or “What else did you need taken care of?”¹³

Explicitly inquiring about patient expectations at the start of the visit lets patients like Ms. S know that they are being taken seriously. If the agenda still balloons, you can simply state, “You deserve more than 15 minutes for all these issues. Let’s pick the top two for today and tackle others at our next visit in two weeks.” To further save time, you can ask the patient to bring a symptom diary or written agenda to the appointment. We’ve found that many anxious patients benefit from this exercise.

Avoid the urge to act. When a patient has unexplained symptoms, effective interventions require clinicians to avoid certain “reflex” behaviors—repeatedly performing diagnostic tests, prescribing medications for symptoms of unknown etiology, insinuating that the problem is “in your head,” formulating ambiguous diagnoses, and repeating physical exams.¹² Such behaviors tend to reinforce the pathology in patients with unexplained symptoms. The time saved avoiding these pitfalls is better invested in exploring personal issues and stressors.

The point is that such patients should be reassured via discussion, rather than with dubious diagnostic labels and potentially dangerous drugs. This approach has been shown to improve patients’ physical functioning while reducing medical expenditures.¹²

INTO ACTION WITH OUR THREE CASES

Case 1: Given these principles, how would you handle Mr. E, the patient who is demanding an MRI for a simple tension headache? Although placating him by ordering the test, providing a referral to a specialist, or defending your recommendation through medical reasoning may seem to be more intuitive (or a “quick fix”), these strategies often lead to excessive medical spending, transfer of the burden to a specialist colleague, and ongoing frustration and dissatisfaction on the part of the patient. In this case, validation may be a more useful approach.

“I can totally understand why you’re frustrated that we disagree,” you might say to Mr. E. “But you’re right! You definitely deserve the best care. That’s why I’m recommending against the MRI, as I feel that would be a suboptimal approach.”

Often patients like Mr. E will require repeated validation of their suffering and frustration. The key is to be persistent in validating their feelings without compromising your own principles in providing optimal medical care.

Case 2:  Let’s turn now to Mr. A, who is requesting escalating doses of opioids. Some clinicians might write the prescription for the dose he’s insisting on, while others draw a hard boundary by refusing to prescribe above a certain dose or beyond a specific time frame. Both strategies may compromise optimal care or endanger the clinician-patient alliance. Another quick solution would be to provide a referral to a psychiatrist, without further discussion.

In cases like that of Mr. A, however, the patient’s demands are often a sign of more complicated emotions and dynamics below the surface. So you might respond by stating, “I’m sorry to hear that things haven’t been going well. How are you feeling about these things? How does the oxycodone help you? In what way doesn’t it help?”

It is important here to understand how the medication serves the patient—in addition to the ways it hurts him—in order for him to feel understood. Inviting Mr. A to have an open-ended discussion may allow him to reveal what is the real source of his distress—losing his job and his home.

Case 3: Now let’s turn to Ms. S, who is convinced that she has a physical malady despite negative exams and tests. In truth, she may be depressed or anxious over her husband’s death. One way to address this is to confront the patient directly by suggesting that she has depression triggered by her husband’s death. But this strategy—if used too early—may feel like an accusation, make her angry, and jeopardize your relationship with her.

An alternative approach would be to say, “I think your problems are long-standing and could require a while to treat. Let’s see each other every two weeks for the next two months so we get adequate time to work on them.” This would be an example of structuring more frequent visits, while also validating the distressing nature of her symptoms.

These strategies are evidence-based

These techniques, while easily adaptable to primary care, are grounded in psychotherapy theory and are evidence-based. A seminal randomized controlled trial conducted more than 30 years ago showed that a patient-centered interview incorporating a number of these techniques bolstered clinicians’ knowledge, interviewing skills, attitudes, and ability to manage patients with unexplained complaints.¹⁴

A multicenter study analyzed audio recordings of strategies used by primary care physicians to deny patient requests for a particular medication. It revealed that explanations based on patient perspectives were significantly more likely to result in excellent patient satisfaction than biomedical explanations or other explanatory approaches.¹⁵ Research has also shown that agenda-setting improves both patient and provider satisfaction.¹⁶

Some cases will still be frustrating, and some “difficult” patients will still need a psychiatric referral at some point—ideally, to a psychiatric or psychological consultant who collaborates closely with the primary care clinic.^17,18

Clinicians sometimes worry that the communication techniques outlined here cannot be incorporated into an already harried primary care visit. Many may think it’s better not to ask at all than risk opening a Pandora’s box. We urge you to reconsider. Although the techniques we’ve outlined certainly require practice, they need not be time-consuming.¹⁹ By embracing this management approach, you can improve patient satisfaction while enhancing your own repertoire of doctoring skills.

The authors thank Drs. Michael Fetters and Rod Hayward for their help in the development of this manuscript.

ACKNOWLEDGEMENT

This work was supported by a grant from the Robert Wood Johnson Foundation.

REFERENCES

1.Hahn SR, Kroenke K, Spitzer RL, et al. The difficult patient: prevalence, psychopathology, and functional impairment. J Gen Intern Med. 1996;11:1-8.

2. An PG, Rabatin JS, Manwell LB, et al. Burden of difficult encounters in primary care: data from the minimizing error, maximizing outcomes study. Arch Intern Med. 2009;169:410-414.

3. Hinchey SA, Jackson JL. A cohort study assessing difficult patient encounters in a walk-in primary care clinic, predictors and outcomes. J Gen Intern Med. 2011;26:588-594.

4. Haas LJ, Leiser JP, Magill MK, et al. Management of the difficult patient. Am Fam Physician. 2005;72:2063-2068.

5. Jackson JL, Kroenke K. Difficult patient encounters in the ambulatory clinic: clinical predictors and outcomes. Arch Intern Med. 1999;159:1069-1075.

6. Ashworth CD, Williamson P, Montano D. A scale to measure physician beliefs about psychosocial aspects of patient care. Soc Sci Med. 1984;19:1235-1238.

7. Leigh H, Stewart D, Mallios R. Mental health and psychiatry training in primary care residency programs. Gen Hosp Psychiatry. 2006;28:189-194.

8. Katon W, Unützer J. Collaborative care models for depression: time to move from evidence to practice. Arch Intern Med. 2006;166:2304-2306.

9. Groves JE. Taking care of the hateful patient. N Engl J Med. 1978;298:883-887.

10. Fortin AH, Dwamena FC, Frankel RM, et al. Smith’s Patient-Centered Interviewing: An Evidence-Based Method. 3rd ed. New York, NY: McGraw-Hill; 2012.

11. Stuart MR, Lieberman JA. The Fifteen Minute Hour: Therapeutic Talk in Primary Care. 4th ed. Milton Keynes, UK: Radcliffe Publishing; 2008.

12. Smith GR Jr, Rost K, Kashner TM. A trial of the effect of a standardized psychiatric consultation on health outcomes and costs in somatizing patients. Arch Gen Psychiatry. 1995;52:238-243.

13. Baker LH, O’Connell D, Platt FW. “What else?” Setting the agenda for the clinical interview. Ann Intern Med. 2005;143:766 -770.

14. Smith RC, Lyles JS, Mettler J, et al. The effectiveness of intensive training for residents in interviewing: a randomized, controlled study. Ann Intern Med. 1998;128:118-126.

15. Paterniti DA, Fancher TL, Cipri CS, et al. Getting to “no”: strategies primary care physicians use to deny patient requests. Arch Intern Med. 2010;170: 381-388.

16. Kroenke K. Unburdening the difficult clinical encounter. Arch Intern Med. 2009;169:333-334.

17. Katon W, Unützer J, Wells K, et al. Collaborative depression care: history, evolution and ways to enhance dissemination and sustainability. Gen Hosp Psychiatry. 2010;32:456-464.

18. Williams M, Angstman K, Johnson I, et al. Implementation of a care management model for depression at two primary care clinics. J Ambul Care Manage. 2011;34:163-173.

19. Lieberman JA III, Stuart MR. The BATHE method: incorporating counseling and psychotherapy into the everyday management of patients. Prim Care Companion J Clin Psychiatry. 1999;1:35-38.

Evidence Summary
Even though clinical research is lacking, acetaminophen is widely used to relieve low-back pain with no documented teratogenic effect (US Food and Drug Administration [FDA] category B). Nonsteroidal anti-inflammatory drugs are classified as FDA category D in the third trimester because of their documented association with oligohydramnios, premature closure of the ductus arteriosus, nephrotoxicity, and periventricular hemorrhage in the fetus.¹ Opioids are category C and a poor choice to treat low-back pain in pregnancy.²

Physical therapy and water aerobics relieve pain, reduce sick days
A 2007 Cochrane review of interventions for treating back pain in pregnancy analyzed eight studies with a total of 1305 patients that examined the effects of adding physical therapy and acupuncture to usual care.³ In one RCT, 407 patients with and without pain received five 30-minute individualized physical therapy exercise sessions, two 45-minute group physical therapy classes, or standard care.^3,4 Low-back pain decreased with group physical therapy (P <.05; number needed to treat [NNT] = 3.2) and individual therapy (NNT = 2.1). Patients who received individual therapy had a 12% decrease in sick days.

A prospective trial of 258 patients, half of whom did water aerobics and half physical therapy, showed comparable results for the two interventions (NNT = 11.4 for decreased sick days; odds ratio = 0.38, 95% confidence interval [CI], 0.16–0.88).³

Acupuncture reduces pain and analgesic use
A prospective, randomized open study cited in the 2007 Cochrane review divided 72 patients at 24 to 37 weeks’ gestational age into a group that received acupuncture plus standard care and a standard-care–only control group.^3,5 Treatment sessions occurred one or two times per week until delivery or recovery. The acupuncture group reported decreased pain (60% vs 14% for controls; P <.01; NNT = 2.2) and improved function (43% vs 9% for controls; P <.001; NNT = 2.9). There was also a difference in analgesic use: 0% for the acupuncture group vs 14% for controls; P <.05; NNT = 7.1.

A 2009 RCT divided 159 patients at 25 to 38 weeks’ gestational age into three groups: auricular acupuncture at specific points for one week, sham auricular acupuncture at nonspecific points for one week, and controls. At the end of Week 1, 80% of the acupuncture group had a clinically significant reduction in pain compared with 56% in the sham acupuncture group and 36% in the control group (P = .001 acupuncture vs sham, NNT = 4.2; P <.0001 acupuncture vs controls, NNT = 2.3).⁶

Osteopathic manipulative therapy (OMT) decreases disability, but not pain
A 2010 RCT divided 144 third trimester patients into three groups that received usual obstetric care, sham ultrasound therapy plus usual obstetric care, or OMT.⁷ Pain remained similar among the three groups throughout the study. Using the 24-point Roland-Morris Disability Questionnaire, OMT decreased disability by 0.72 points (95% CI, 0.31–1.14; P <.001) compared with 0.35 points in the usual obstetric-care–only group (95% CI, −0.06 to 0.76; P = .09). Ultrasound had no effect.

Corticosteroid injection reduces pain in a small trial
A small RCT of injection with the corticosteroid triamcinolone at the sacrospinous ligament insertion in 36 women with low-back pain showed significant reduction in pain in 17 of 18 women in the triamcinolone group compared with 9 of 18 women in the control group (P <.01; NNT = 2).⁸

Evidence lacking on maternity support garments
A poor-quality systematic review of 10 studies (N = 1909) of maternity support garments found insufficient evidence because of the heterogeneity of the trials.⁹

RECOMMENDATIONS
The American College of Obstetricians and Gynecologists suggests the following measures to prevent and treat low-back pain in pregnancy:¹⁰

• wear low-heeled (not flat) shoes with good arch support

• get help when lifting heavy objects

• place one foot on a stool or box when standing for long periods

• place a board between the mattress and box spring if the bed is too soft

• squat down, bend knees, and keep back straight when lifting

• sit in chairs with good back support or use a small pillow to provide support

• sleep on side with pillows between knees for support

• apply heat, cold, or massage to the painful area.

WE WANT TO HEAR FROM YOU!
Drop us a line and let us know what you think about current articles, which topics you'd like to see covered in future issues, and what challenges you face in daily practice. Tell us what you think by emailing us at: [email protected]This article was originally published in The Journal of Family Practice (J Fam Pract. 2013;62(5):260, 268).

Evidence Summary
Even though clinical research is lacking, acetaminophen is widely used to relieve low-back pain with no documented teratogenic effect (US Food and Drug Administration [FDA] category B). Nonsteroidal anti-inflammatory drugs are classified as FDA category D in the third trimester because of their documented association with oligohydramnios, premature closure of the ductus arteriosus, nephrotoxicity, and periventricular hemorrhage in the fetus.¹ Opioids are category C and a poor choice to treat low-back pain in pregnancy.²

Physical therapy and water aerobics relieve pain, reduce sick days
A 2007 Cochrane review of interventions for treating back pain in pregnancy analyzed eight studies with a total of 1305 patients that examined the effects of adding physical therapy and acupuncture to usual care.³ In one RCT, 407 patients with and without pain received five 30-minute individualized physical therapy exercise sessions, two 45-minute group physical therapy classes, or standard care.^3,4 Low-back pain decreased with group physical therapy (P <.05; number needed to treat [NNT] = 3.2) and individual therapy (NNT = 2.1). Patients who received individual therapy had a 12% decrease in sick days.

A prospective trial of 258 patients, half of whom did water aerobics and half physical therapy, showed comparable results for the two interventions (NNT = 11.4 for decreased sick days; odds ratio = 0.38, 95% confidence interval [CI], 0.16–0.88).³

Acupuncture reduces pain and analgesic use
A prospective, randomized open study cited in the 2007 Cochrane review divided 72 patients at 24 to 37 weeks’ gestational age into a group that received acupuncture plus standard care and a standard-care–only control group.^3,5 Treatment sessions occurred one or two times per week until delivery or recovery. The acupuncture group reported decreased pain (60% vs 14% for controls; P <.01; NNT = 2.2) and improved function (43% vs 9% for controls; P <.001; NNT = 2.9). There was also a difference in analgesic use: 0% for the acupuncture group vs 14% for controls; P <.05; NNT = 7.1.

A 2009 RCT divided 159 patients at 25 to 38 weeks’ gestational age into three groups: auricular acupuncture at specific points for one week, sham auricular acupuncture at nonspecific points for one week, and controls. At the end of Week 1, 80% of the acupuncture group had a clinically significant reduction in pain compared with 56% in the sham acupuncture group and 36% in the control group (P = .001 acupuncture vs sham, NNT = 4.2; P <.0001 acupuncture vs controls, NNT = 2.3).⁶

Osteopathic manipulative therapy (OMT) decreases disability, but not pain
A 2010 RCT divided 144 third trimester patients into three groups that received usual obstetric care, sham ultrasound therapy plus usual obstetric care, or OMT.⁷ Pain remained similar among the three groups throughout the study. Using the 24-point Roland-Morris Disability Questionnaire, OMT decreased disability by 0.72 points (95% CI, 0.31–1.14; P <.001) compared with 0.35 points in the usual obstetric-care–only group (95% CI, −0.06 to 0.76; P = .09). Ultrasound had no effect.

Corticosteroid injection reduces pain in a small trial
A small RCT of injection with the corticosteroid triamcinolone at the sacrospinous ligament insertion in 36 women with low-back pain showed significant reduction in pain in 17 of 18 women in the triamcinolone group compared with 9 of 18 women in the control group (P <.01; NNT = 2).⁸

Evidence lacking on maternity support garments
A poor-quality systematic review of 10 studies (N = 1909) of maternity support garments found insufficient evidence because of the heterogeneity of the trials.⁹

RECOMMENDATIONS
The American College of Obstetricians and Gynecologists suggests the following measures to prevent and treat low-back pain in pregnancy:¹⁰

• wear low-heeled (not flat) shoes with good arch support

• get help when lifting heavy objects

• place one foot on a stool or box when standing for long periods

• place a board between the mattress and box spring if the bed is too soft

• squat down, bend knees, and keep back straight when lifting

• sit in chairs with good back support or use a small pillow to provide support

• sleep on side with pillows between knees for support

• apply heat, cold, or massage to the painful area.

WE WANT TO HEAR FROM YOU!
Drop us a line and let us know what you think about current articles, which topics you'd like to see covered in future issues, and what challenges you face in daily practice. Tell us what you think by emailing us at: [email protected]This article was originally published in The Journal of Family Practice (J Fam Pract. 2013;62(5):260, 268).

Evidence Summary
Even though clinical research is lacking, acetaminophen is widely used to relieve low-back pain with no documented teratogenic effect (US Food and Drug Administration [FDA] category B). Nonsteroidal anti-inflammatory drugs are classified as FDA category D in the third trimester because of their documented association with oligohydramnios, premature closure of the ductus arteriosus, nephrotoxicity, and periventricular hemorrhage in the fetus.¹ Opioids are category C and a poor choice to treat low-back pain in pregnancy.²

Physical therapy and water aerobics relieve pain, reduce sick days
A 2007 Cochrane review of interventions for treating back pain in pregnancy analyzed eight studies with a total of 1305 patients that examined the effects of adding physical therapy and acupuncture to usual care.³ In one RCT, 407 patients with and without pain received five 30-minute individualized physical therapy exercise sessions, two 45-minute group physical therapy classes, or standard care.^3,4 Low-back pain decreased with group physical therapy (P <.05; number needed to treat [NNT] = 3.2) and individual therapy (NNT = 2.1). Patients who received individual therapy had a 12% decrease in sick days.

A prospective trial of 258 patients, half of whom did water aerobics and half physical therapy, showed comparable results for the two interventions (NNT = 11.4 for decreased sick days; odds ratio = 0.38, 95% confidence interval [CI], 0.16–0.88).³

Acupuncture reduces pain and analgesic use
A prospective, randomized open study cited in the 2007 Cochrane review divided 72 patients at 24 to 37 weeks’ gestational age into a group that received acupuncture plus standard care and a standard-care–only control group.^3,5 Treatment sessions occurred one or two times per week until delivery or recovery. The acupuncture group reported decreased pain (60% vs 14% for controls; P <.01; NNT = 2.2) and improved function (43% vs 9% for controls; P <.001; NNT = 2.9). There was also a difference in analgesic use: 0% for the acupuncture group vs 14% for controls; P <.05; NNT = 7.1.

A 2009 RCT divided 159 patients at 25 to 38 weeks’ gestational age into three groups: auricular acupuncture at specific points for one week, sham auricular acupuncture at nonspecific points for one week, and controls. At the end of Week 1, 80% of the acupuncture group had a clinically significant reduction in pain compared with 56% in the sham acupuncture group and 36% in the control group (P = .001 acupuncture vs sham, NNT = 4.2; P <.0001 acupuncture vs controls, NNT = 2.3).⁶

Osteopathic manipulative therapy (OMT) decreases disability, but not pain
A 2010 RCT divided 144 third trimester patients into three groups that received usual obstetric care, sham ultrasound therapy plus usual obstetric care, or OMT.⁷ Pain remained similar among the three groups throughout the study. Using the 24-point Roland-Morris Disability Questionnaire, OMT decreased disability by 0.72 points (95% CI, 0.31–1.14; P <.001) compared with 0.35 points in the usual obstetric-care–only group (95% CI, −0.06 to 0.76; P = .09). Ultrasound had no effect.

Corticosteroid injection reduces pain in a small trial
A small RCT of injection with the corticosteroid triamcinolone at the sacrospinous ligament insertion in 36 women with low-back pain showed significant reduction in pain in 17 of 18 women in the triamcinolone group compared with 9 of 18 women in the control group (P <.01; NNT = 2).⁸

Evidence lacking on maternity support garments
A poor-quality systematic review of 10 studies (N = 1909) of maternity support garments found insufficient evidence because of the heterogeneity of the trials.⁹

RECOMMENDATIONS
The American College of Obstetricians and Gynecologists suggests the following measures to prevent and treat low-back pain in pregnancy:¹⁰

• wear low-heeled (not flat) shoes with good arch support

• get help when lifting heavy objects

• place one foot on a stool or box when standing for long periods

• place a board between the mattress and box spring if the bed is too soft

• squat down, bend knees, and keep back straight when lifting

• sit in chairs with good back support or use a small pillow to provide support

• sleep on side with pillows between knees for support

• apply heat, cold, or massage to the painful area.

WE WANT TO HEAR FROM YOU!
Drop us a line and let us know what you think about current articles, which topics you'd like to see covered in future issues, and what challenges you face in daily practice. Tell us what you think by emailing us at: [email protected]This article was originally published in The Journal of Family Practice (J Fam Pract. 2013;62(5):260, 268).

Over the past 20 years, the incidence of preeclampsia in the United States has increased 25%,¹ and the disorder is a leading cause of morbidity and death among both mothers and infants. Although considerable progress has been achieved in elucidating the pathophysiology of preeclampsia, greater understanding has not yet carried over into improved clinical practice.

To address this disconnect between data and practice, the American College of Obstetricians and Gynecologists (ACOG) issued a 99-page document in November 2013 to help establish best practices in the diagnosis and management of hypertensive disorders in pregnancy. We begin this article with a look at its major recommendations.

Other notable developments in obstetrics over the past year have been the rapid evolution of noninvasive prenatal testing and the publication of new guidance on screening, diagnosis, and management of gestational diabetes, all of which are addressed in this article.

ACOG AIMS TO CLARIFY BEST PRACTICES IN THE MANAGEMENT OF HYPERTENSION IN PREGNANCY

American College of Obstetricians and Gynecologists, Task Force on Hypertension in Pregnancy. Hypertension in Pregnancy. Washington, DC: ACOG; November 2013.

The biggest news of the past year is probably the November 2013 report on hypertension in pregnancy from ACOG, which was developed with three goals in mind:

• to summarize current knowledge

• to provide best-practice guidelines

• to identify areas in which further research is needed.

The classification, diagnosis, prediction, prevention, and management of gestational hypertension, preeclampsia, and chronic hypertension are addressed in the report. Although space constraints prevent us from summarizing the entire document, we would like to highlight the biggest changes and most relevant additions to clinical practice.

Notable recommendations
Classification. Preeclampsia is no longer characterized as “mild” or “severe” but as “preeclampsia without severe features” and “preeclampsia with severe features.” As justification for these changes, the ACOG Task Force on Hypertension in Pregnancy noted that preeclampsia is progressive by nature, so a characterization of “mild” disease is appropriate only at the time of diagnosis. Therefore, “appropriate management mandates frequent reevaluation for severe features.”

Diagnosis of proteinuria. The options are a 24-hour urine collection demonstrating more than 300 mg of protein or a single-specimen urine protein:creatinine ratio of 0.3 mg/dL or higher. Dipstick values should only be used if these quantitative measures are unavailable.

Signs of severe disease. Fetal growth restriction and proteinuria of more than 5 g/24 hr are no longer considered defining features of severe disease.

Severe features now include any of these:

• systolic blood pressure (BP) of 160 mm Hg or higher, or diastolic BP of 110 mm Hg or higher on two occasions at least 4 hours apart while the patient is on bed rest (unless antihypertensive therapy is initiated before this time)

• thrombocytopenia (platelets <100 x 109/L)

• impaired liver function, as indicated by abnormally elevated blood concentrations of liver enzymes (to twice normal concentration) and/or severe, persistent right upper quadrant or epigastric pain unresponsive to medication and not accounted for by alternative diagnoses

• progressive renal insufficiency (serum creatinine concentration >1.1 mg/dL or a doubling of the serum creatinine concentration in the absence of other renal disease)

• pulmonary edema

• new-onset visual or central nervous system disturbances.

Related Article: Does an unfavorable cervix preclude induction of labor at term in women who have gestational hypertension or mild preeclampsia? George Macones, MD (Examining the Evidence, December 2012)

Screening for preeclampsia. The use of Doppler studies and serum biomarkers is not recommended, as there is no evidence that early identification translates to improved outcomes.

Prevention of preeclampsia. Low-dose aspirin (60–80 mg/d, starting in the late first trimester) should be offered as primary prevention to:

• women with a history of early-onset preeclampsia and delivery before 34 weeks’ gestation

• women with a history of preeclampsia in multiple pregnancies

• other high-risk patients (chronic hypertension, diabetes).

No other treatments (vitamin C or E, salt restriction, or bed rest) are recommended for the prevention of preeclampsia, although calcium supplementation may be recommended for women with a low baseline dietary intake of calcium.

Use of magnesium sulfate. Universal prophylaxis with magnesium sulfate is not recommended for preeclampsia unless severe features are present or the patient’s clinical condition changes to severe during labor.

Timing of delivery. Recommendations for delivery for patients with hypertensive disorders are:

• gestational hypertension or preeclampsia without severe features: 37 weeks’ gestation

• preeclampsia with severe features: by 34 weeks

• chronic hypertension: not before 38 weeks

• chronic hypertension with superimposed preeclampsia: 34 or 37 weeks, depending on the presence of severe features.

All of these recommendations are contingent upon the clinical status of the patient and her fetus. For example, if the fetus develops severe growth restriction (<5%) or oligohydramnios, delivery may be recommended regardless of gestational age, based on fetal testing and maternal stability.

Related Article: A stepwise approach to managing eclampsia and other hypertensive emergencies Baha M. Sibai (October 2013)

Postpartum hypertension. The need for recognition of hypertension in the postpartum period is emphasized, as well as appropriate management, using the following guidelines:

• Be aware that BP decreases initially after delivery and then increases 3 to 6 days postpartum, requiring vigilance on the part of the clinician. For this reason, BP monitoring is recommended 72 hours postpartum (inpatient or outpatient) and again in 7 to 10 days in women diagnosed with a hypertensive disorder of pregnancy.

• Counsel patients who experience a hypertensive disorder and/or preeclampsia during pregnancy about postpartum preeclampsia, providing strict precautions and explicit instructions regarding its signs and symptoms

• If BP remains elevated after the first postpartum day, consider discontinuing nonsteroidal anti-inflammatory drugs (NSAIDs), as they may be related to hypertension

• Treat BP that remains above 150/100 mm Hg with antihypertensive therapy

• If postpartum preeclampsia is suspected, administer magnesium sulfate for 24 hours.

A culture shift is needed
At our institution, the most significant potential changes to clinical practice may be the elimination of universal magnesium sulfate prophylaxis and the removal of severe fetal growth restriction from the definition of “severe” preeclampsia.

Also, because the use of NSAIDs is widespread for postpartum pain control, a culture change is needed if we are to follow the postpartum recommendations.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Although we suggest that you read the ACOG report thoroughly, remember that its recommendations are only that—recommendations. Also keep in mind that only six of the approximately 60 “recommendations” provided in this report were accompanied by both high-quality evidence and a strong recommendation. There still is room for clinical judgment and individualization of management to specific patient populations.

NONINVASIVE PRENATAL SCREENING IS EXPANDING RAPIDLY—BUT DON’T THROW OUT THAT CVS KIT JUST YET!

ACOG Committee on Genetics.Committee Opinion #545: Noninvasive prenatal testing for fetal aneuploidy. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2012;120(6):1532–1534.

Mennuti MT, Cherry AM, Morrissette JJD, Dugoff L. Is it time to sound an alarm about false-positive cell-free DNA testing for fetal aneuploidy? Am J Obstet Gynecol. 2013;209(5):415–419.

In last year’s Update in Obstetrics, we discussed noninvasive prenatal genetic screening via cell-free fetal DNA, noting that it is a safer (no risk of miscarriage) and faster (starting at 10 weeks’ gestation) way to screen for aneuploidy. The sensitivity and specificity of this test for Trisomy 21 and 18 are over 99%, with slightly lower sensitivity for Trisomy 13 and sex chromosome abnormalities and a false-positive rate of 0.5%.

In a committee opinion published in December 2012, ACOG concluded that
cell-free fetal DNA is an appropriate screening option only for specific groups of patients at risk for aneuploidy:

• women older than age 35

• women with fetal ultrasonography findings that are concerning for aneuploidy

• women with aneuploidy in a prior pregnancy

• women with abnormal first- or second-trimester genetic screening tests

• parents with a balanced translocation and an increased risk of Trisomy 21 or 13.

Noninvasive aneuploidy testing is for screening only
Negative results are not diagnostic, and all positive results should be confirmed with invasive testing (chorionic villus sampling [CVS] or amniocentesis).

ACOG does not recommend routine use of cell-free fetal DNA without a comprehensive history and adequate patient counseling, as well as a designation of “high risk.”

Over the past year, more options have become available for aneuploidy screening via cell-free fetal DNA, including screening in twin gestations (for Trisomy 21, 18, 13, and the presence of a Y chromosome only) and screening for:

• 22q deletion (DiGeorge syndrome)

• 5p– (Cri-du-chat syndrome)

• 15q (Prader-Willi and Angelman syndromes)

• 1p (1p36 deletion syndrome)

• Trisomy 16

• Trisomy 22.

At this rate, the genetic information potentially available via noninvasive testing seems unlimited. It is easy to see how the fact that this is a screening test—not a diagnostic test—could get lost in the excitement.

Other limitations: Noninvasive testing is still not validated in low-risk patients, and the false-positive risk may be higher than original estimates.

Related Article: Noninvasive prenatal DNA testing: A survey of who is using it, and how (Audiocast, June 2013)

The problem of false positives
This issue was addressed by Mennuti and colleagues, who presented eight cases of abnormal cell-free fetal DNA results that were not confirmed by invasive testing.

There are few prospective data about the source of false-positive results; potential mechanisms include an inadequate fetal fraction of cell-free DNA, maternal or placental mosaicism, and a vanishing twin.

Mennuti and colleagues propose that a registry of false-positive and false-negative results be established to gather further data. They also note that as low-risk patients and aneuploidies of lower and lower prevalence are incorporated into noninvasive testing, the false-positive rate will rise. Their findings have implications for patient counseling, patient distress, invasive testing, and reimbursement.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Cell-free fetal DNA is a rapidly expanding screening technology, but it is not ready to replace diagnostic testing. Don’t throw away those CVS and amniocentesis kits just yet—we are a long way from a completely noninvasive world.

WHEN IT COMES TO GESTATIONAL DIABETES, LESS MAY BE MORE

ACOG Committee on Practice Bulletins–Obstetrics. Practice Bulletin #137: Gestational diabetes mellitus. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2013;122(2 Pt 1):406–416.

Gestational diabetes accounts for 90% of diabetic pregnancies, and its incidence has been increasing in the United States along with the obesity epidemic. In recent years, there has been some debate about the best way to screen for, diagnose, and treat gestational diabetes.

Multiple criteria exist for a positive 1-hour (130–140 mg/dL) or 3-hour glucose tolerance test (Carpenter and Coustan vs National Diabetes Data Group), without comparative trials or consensus as to which version is best. Lower cutoffs increase the rate of gestational diabetes by as much as 50%, whereas higher cutoffs lower the false-positive rate and reduce the need for additional tests.

Some groups have recommended moving away from the traditional two-step process to a one-step approach that utilizes the 2-hour, 75-g glucose tolerance test commonly used outside of pregnancy. They argue that this approach would simplify and standardize the process and could improve outcomes in “borderline” pregnancies that would have been missed by less stringent guidelines.

However, the baseline rate of gestational diabetes using this one-step approach would likely increase from 7% to 18% or higher, depending on the patient population. Such an increase would trigger a huge rise in costs and resources needed to care for these patients, without data on outcomes or appropriate therapy for this expanded group of women with gestational diabetes.

Treatment isn't clear-cut, either
Treatment of gestational diabetes centers on labor-intensive glucose monitoring, nutritional interventions, and insulin therapy.

Until recently, the use of oral hypoglycemic agents was not recommended due to limited data. Multiple studies now have been performed to evaluate the safety and efficacy of glyburide and metformin in pregnancy, demonstrating glucose control similar to that achieved with insulin without short-term adverse effects in the mother or newborn. However, as many as 20% to 40% of women using glyburide and 50% of those using metformin require the addition of insulin for adequate glucose control. The long-term effects of these medications are unknown.

Related Article: Does myo-inositol supplementation reduce the rate of gestational diabetes in pregnant women with a family history of type 2 diabetes? E. Albert Reece, MD, PhD, MBA (Examining the Evidence, June 2013)

ACOG weighs in
In an attempt to clarify optimal screening, diagnosis, and treatment, ACOG updated its practice bulletin on gestational diabetes in August 2013. Among its recommendations:

• Avoid the 2-hour glucose tolerance test because there is no demonstrated benefit for the increased number of mothers (and their fetuses) that would be identified by this approach. Rather, use the two-step approach of a 1-hour 50-g glucose tolerance test followed by a 3-hour 100-g glucose tolerance test.

• In regard to the 1-hour test, ACOG finds either 135 or 140 mg/dL acceptable as a cutoff but recommends that each practice choose one value as a standard and use it consistently. For the 3-hour test, ACOG recommends that each practice choose the version that best fits its population and prevalence of diabetes. At our institution, for example, we have chosen a 1-hour cutoff of 140 mg/dL and the National Diabetes Data Group criteria for the 3-hour test (105, 190, 165, and 145 mg/dL).

• Oral glyburide or metformin may be used to treat gestational diabetes, but glyburide (starting at 2.5 mg/d) may be the better choice for glucose control.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Use the two-step screening process to identify gestational diabetes, picking your cutoffs and sticking to them. Oral hypoglycemic agents now are acceptable for treatment, but be prepared to go back to insulin if necessary.

WE WANT TO HEAR FROM YOU. Tell us what you think.

Over the past 20 years, the incidence of preeclampsia in the United States has increased 25%,¹ and the disorder is a leading cause of morbidity and death among both mothers and infants. Although considerable progress has been achieved in elucidating the pathophysiology of preeclampsia, greater understanding has not yet carried over into improved clinical practice.

To address this disconnect between data and practice, the American College of Obstetricians and Gynecologists (ACOG) issued a 99-page document in November 2013 to help establish best practices in the diagnosis and management of hypertensive disorders in pregnancy. We begin this article with a look at its major recommendations.

Other notable developments in obstetrics over the past year have been the rapid evolution of noninvasive prenatal testing and the publication of new guidance on screening, diagnosis, and management of gestational diabetes, all of which are addressed in this article.

ACOG AIMS TO CLARIFY BEST PRACTICES IN THE MANAGEMENT OF HYPERTENSION IN PREGNANCY

American College of Obstetricians and Gynecologists, Task Force on Hypertension in Pregnancy. Hypertension in Pregnancy. Washington, DC: ACOG; November 2013.

The biggest news of the past year is probably the November 2013 report on hypertension in pregnancy from ACOG, which was developed with three goals in mind:

• to summarize current knowledge

• to provide best-practice guidelines

• to identify areas in which further research is needed.

The classification, diagnosis, prediction, prevention, and management of gestational hypertension, preeclampsia, and chronic hypertension are addressed in the report. Although space constraints prevent us from summarizing the entire document, we would like to highlight the biggest changes and most relevant additions to clinical practice.

Notable recommendations
Classification. Preeclampsia is no longer characterized as “mild” or “severe” but as “preeclampsia without severe features” and “preeclampsia with severe features.” As justification for these changes, the ACOG Task Force on Hypertension in Pregnancy noted that preeclampsia is progressive by nature, so a characterization of “mild” disease is appropriate only at the time of diagnosis. Therefore, “appropriate management mandates frequent reevaluation for severe features.”

Diagnosis of proteinuria. The options are a 24-hour urine collection demonstrating more than 300 mg of protein or a single-specimen urine protein:creatinine ratio of 0.3 mg/dL or higher. Dipstick values should only be used if these quantitative measures are unavailable.

Signs of severe disease. Fetal growth restriction and proteinuria of more than 5 g/24 hr are no longer considered defining features of severe disease.

Severe features now include any of these:

• systolic blood pressure (BP) of 160 mm Hg or higher, or diastolic BP of 110 mm Hg or higher on two occasions at least 4 hours apart while the patient is on bed rest (unless antihypertensive therapy is initiated before this time)

• thrombocytopenia (platelets <100 x 109/L)

• impaired liver function, as indicated by abnormally elevated blood concentrations of liver enzymes (to twice normal concentration) and/or severe, persistent right upper quadrant or epigastric pain unresponsive to medication and not accounted for by alternative diagnoses

• progressive renal insufficiency (serum creatinine concentration >1.1 mg/dL or a doubling of the serum creatinine concentration in the absence of other renal disease)

• pulmonary edema

• new-onset visual or central nervous system disturbances.

Related Article: Does an unfavorable cervix preclude induction of labor at term in women who have gestational hypertension or mild preeclampsia? George Macones, MD (Examining the Evidence, December 2012)

Screening for preeclampsia. The use of Doppler studies and serum biomarkers is not recommended, as there is no evidence that early identification translates to improved outcomes.

Prevention of preeclampsia. Low-dose aspirin (60–80 mg/d, starting in the late first trimester) should be offered as primary prevention to:

• women with a history of early-onset preeclampsia and delivery before 34 weeks’ gestation

• women with a history of preeclampsia in multiple pregnancies

• other high-risk patients (chronic hypertension, diabetes).

No other treatments (vitamin C or E, salt restriction, or bed rest) are recommended for the prevention of preeclampsia, although calcium supplementation may be recommended for women with a low baseline dietary intake of calcium.

Use of magnesium sulfate. Universal prophylaxis with magnesium sulfate is not recommended for preeclampsia unless severe features are present or the patient’s clinical condition changes to severe during labor.

Timing of delivery. Recommendations for delivery for patients with hypertensive disorders are:

• gestational hypertension or preeclampsia without severe features: 37 weeks’ gestation

• preeclampsia with severe features: by 34 weeks

• chronic hypertension: not before 38 weeks

• chronic hypertension with superimposed preeclampsia: 34 or 37 weeks, depending on the presence of severe features.

All of these recommendations are contingent upon the clinical status of the patient and her fetus. For example, if the fetus develops severe growth restriction (<5%) or oligohydramnios, delivery may be recommended regardless of gestational age, based on fetal testing and maternal stability.

Related Article: A stepwise approach to managing eclampsia and other hypertensive emergencies Baha M. Sibai (October 2013)

Postpartum hypertension. The need for recognition of hypertension in the postpartum period is emphasized, as well as appropriate management, using the following guidelines:

• Be aware that BP decreases initially after delivery and then increases 3 to 6 days postpartum, requiring vigilance on the part of the clinician. For this reason, BP monitoring is recommended 72 hours postpartum (inpatient or outpatient) and again in 7 to 10 days in women diagnosed with a hypertensive disorder of pregnancy.

• Counsel patients who experience a hypertensive disorder and/or preeclampsia during pregnancy about postpartum preeclampsia, providing strict precautions and explicit instructions regarding its signs and symptoms

• If BP remains elevated after the first postpartum day, consider discontinuing nonsteroidal anti-inflammatory drugs (NSAIDs), as they may be related to hypertension

• Treat BP that remains above 150/100 mm Hg with antihypertensive therapy

• If postpartum preeclampsia is suspected, administer magnesium sulfate for 24 hours.

A culture shift is needed
At our institution, the most significant potential changes to clinical practice may be the elimination of universal magnesium sulfate prophylaxis and the removal of severe fetal growth restriction from the definition of “severe” preeclampsia.

Also, because the use of NSAIDs is widespread for postpartum pain control, a culture change is needed if we are to follow the postpartum recommendations.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Although we suggest that you read the ACOG report thoroughly, remember that its recommendations are only that—recommendations. Also keep in mind that only six of the approximately 60 “recommendations” provided in this report were accompanied by both high-quality evidence and a strong recommendation. There still is room for clinical judgment and individualization of management to specific patient populations.

NONINVASIVE PRENATAL SCREENING IS EXPANDING RAPIDLY—BUT DON’T THROW OUT THAT CVS KIT JUST YET!

ACOG Committee on Genetics.Committee Opinion #545: Noninvasive prenatal testing for fetal aneuploidy. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2012;120(6):1532–1534.

Mennuti MT, Cherry AM, Morrissette JJD, Dugoff L. Is it time to sound an alarm about false-positive cell-free DNA testing for fetal aneuploidy? Am J Obstet Gynecol. 2013;209(5):415–419.

In last year’s Update in Obstetrics, we discussed noninvasive prenatal genetic screening via cell-free fetal DNA, noting that it is a safer (no risk of miscarriage) and faster (starting at 10 weeks’ gestation) way to screen for aneuploidy. The sensitivity and specificity of this test for Trisomy 21 and 18 are over 99%, with slightly lower sensitivity for Trisomy 13 and sex chromosome abnormalities and a false-positive rate of 0.5%.

In a committee opinion published in December 2012, ACOG concluded that
cell-free fetal DNA is an appropriate screening option only for specific groups of patients at risk for aneuploidy:

• women older than age 35

• women with fetal ultrasonography findings that are concerning for aneuploidy

• women with aneuploidy in a prior pregnancy

• women with abnormal first- or second-trimester genetic screening tests

• parents with a balanced translocation and an increased risk of Trisomy 21 or 13.

Noninvasive aneuploidy testing is for screening only
Negative results are not diagnostic, and all positive results should be confirmed with invasive testing (chorionic villus sampling [CVS] or amniocentesis).

ACOG does not recommend routine use of cell-free fetal DNA without a comprehensive history and adequate patient counseling, as well as a designation of “high risk.”

Over the past year, more options have become available for aneuploidy screening via cell-free fetal DNA, including screening in twin gestations (for Trisomy 21, 18, 13, and the presence of a Y chromosome only) and screening for:

• 22q deletion (DiGeorge syndrome)

• 5p– (Cri-du-chat syndrome)

• 15q (Prader-Willi and Angelman syndromes)

• 1p (1p36 deletion syndrome)

• Trisomy 16

• Trisomy 22.

At this rate, the genetic information potentially available via noninvasive testing seems unlimited. It is easy to see how the fact that this is a screening test—not a diagnostic test—could get lost in the excitement.

Other limitations: Noninvasive testing is still not validated in low-risk patients, and the false-positive risk may be higher than original estimates.

Related Article: Noninvasive prenatal DNA testing: A survey of who is using it, and how (Audiocast, June 2013)

The problem of false positives
This issue was addressed by Mennuti and colleagues, who presented eight cases of abnormal cell-free fetal DNA results that were not confirmed by invasive testing.

There are few prospective data about the source of false-positive results; potential mechanisms include an inadequate fetal fraction of cell-free DNA, maternal or placental mosaicism, and a vanishing twin.

Mennuti and colleagues propose that a registry of false-positive and false-negative results be established to gather further data. They also note that as low-risk patients and aneuploidies of lower and lower prevalence are incorporated into noninvasive testing, the false-positive rate will rise. Their findings have implications for patient counseling, patient distress, invasive testing, and reimbursement.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Cell-free fetal DNA is a rapidly expanding screening technology, but it is not ready to replace diagnostic testing. Don’t throw away those CVS and amniocentesis kits just yet—we are a long way from a completely noninvasive world.

WHEN IT COMES TO GESTATIONAL DIABETES, LESS MAY BE MORE

ACOG Committee on Practice Bulletins–Obstetrics. Practice Bulletin #137: Gestational diabetes mellitus. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2013;122(2 Pt 1):406–416.

Gestational diabetes accounts for 90% of diabetic pregnancies, and its incidence has been increasing in the United States along with the obesity epidemic. In recent years, there has been some debate about the best way to screen for, diagnose, and treat gestational diabetes.

Multiple criteria exist for a positive 1-hour (130–140 mg/dL) or 3-hour glucose tolerance test (Carpenter and Coustan vs National Diabetes Data Group), without comparative trials or consensus as to which version is best. Lower cutoffs increase the rate of gestational diabetes by as much as 50%, whereas higher cutoffs lower the false-positive rate and reduce the need for additional tests.

Some groups have recommended moving away from the traditional two-step process to a one-step approach that utilizes the 2-hour, 75-g glucose tolerance test commonly used outside of pregnancy. They argue that this approach would simplify and standardize the process and could improve outcomes in “borderline” pregnancies that would have been missed by less stringent guidelines.

However, the baseline rate of gestational diabetes using this one-step approach would likely increase from 7% to 18% or higher, depending on the patient population. Such an increase would trigger a huge rise in costs and resources needed to care for these patients, without data on outcomes or appropriate therapy for this expanded group of women with gestational diabetes.

Treatment isn't clear-cut, either
Treatment of gestational diabetes centers on labor-intensive glucose monitoring, nutritional interventions, and insulin therapy.

Until recently, the use of oral hypoglycemic agents was not recommended due to limited data. Multiple studies now have been performed to evaluate the safety and efficacy of glyburide and metformin in pregnancy, demonstrating glucose control similar to that achieved with insulin without short-term adverse effects in the mother or newborn. However, as many as 20% to 40% of women using glyburide and 50% of those using metformin require the addition of insulin for adequate glucose control. The long-term effects of these medications are unknown.

Related Article: Does myo-inositol supplementation reduce the rate of gestational diabetes in pregnant women with a family history of type 2 diabetes? E. Albert Reece, MD, PhD, MBA (Examining the Evidence, June 2013)

ACOG weighs in
In an attempt to clarify optimal screening, diagnosis, and treatment, ACOG updated its practice bulletin on gestational diabetes in August 2013. Among its recommendations:

• Avoid the 2-hour glucose tolerance test because there is no demonstrated benefit for the increased number of mothers (and their fetuses) that would be identified by this approach. Rather, use the two-step approach of a 1-hour 50-g glucose tolerance test followed by a 3-hour 100-g glucose tolerance test.

• In regard to the 1-hour test, ACOG finds either 135 or 140 mg/dL acceptable as a cutoff but recommends that each practice choose one value as a standard and use it consistently. For the 3-hour test, ACOG recommends that each practice choose the version that best fits its population and prevalence of diabetes. At our institution, for example, we have chosen a 1-hour cutoff of 140 mg/dL and the National Diabetes Data Group criteria for the 3-hour test (105, 190, 165, and 145 mg/dL).

• Oral glyburide or metformin may be used to treat gestational diabetes, but glyburide (starting at 2.5 mg/d) may be the better choice for glucose control.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Use the two-step screening process to identify gestational diabetes, picking your cutoffs and sticking to them. Oral hypoglycemic agents now are acceptable for treatment, but be prepared to go back to insulin if necessary.

WE WANT TO HEAR FROM YOU. Tell us what you think.

Over the past 20 years, the incidence of preeclampsia in the United States has increased 25%,¹ and the disorder is a leading cause of morbidity and death among both mothers and infants. Although considerable progress has been achieved in elucidating the pathophysiology of preeclampsia, greater understanding has not yet carried over into improved clinical practice.

To address this disconnect between data and practice, the American College of Obstetricians and Gynecologists (ACOG) issued a 99-page document in November 2013 to help establish best practices in the diagnosis and management of hypertensive disorders in pregnancy. We begin this article with a look at its major recommendations.

Other notable developments in obstetrics over the past year have been the rapid evolution of noninvasive prenatal testing and the publication of new guidance on screening, diagnosis, and management of gestational diabetes, all of which are addressed in this article.

ACOG AIMS TO CLARIFY BEST PRACTICES IN THE MANAGEMENT OF HYPERTENSION IN PREGNANCY

American College of Obstetricians and Gynecologists, Task Force on Hypertension in Pregnancy. Hypertension in Pregnancy. Washington, DC: ACOG; November 2013.

The biggest news of the past year is probably the November 2013 report on hypertension in pregnancy from ACOG, which was developed with three goals in mind:

• to summarize current knowledge

• to provide best-practice guidelines

• to identify areas in which further research is needed.

The classification, diagnosis, prediction, prevention, and management of gestational hypertension, preeclampsia, and chronic hypertension are addressed in the report. Although space constraints prevent us from summarizing the entire document, we would like to highlight the biggest changes and most relevant additions to clinical practice.

Notable recommendations
Classification. Preeclampsia is no longer characterized as “mild” or “severe” but as “preeclampsia without severe features” and “preeclampsia with severe features.” As justification for these changes, the ACOG Task Force on Hypertension in Pregnancy noted that preeclampsia is progressive by nature, so a characterization of “mild” disease is appropriate only at the time of diagnosis. Therefore, “appropriate management mandates frequent reevaluation for severe features.”

Diagnosis of proteinuria. The options are a 24-hour urine collection demonstrating more than 300 mg of protein or a single-specimen urine protein:creatinine ratio of 0.3 mg/dL or higher. Dipstick values should only be used if these quantitative measures are unavailable.

Signs of severe disease. Fetal growth restriction and proteinuria of more than 5 g/24 hr are no longer considered defining features of severe disease.

Severe features now include any of these:

• systolic blood pressure (BP) of 160 mm Hg or higher, or diastolic BP of 110 mm Hg or higher on two occasions at least 4 hours apart while the patient is on bed rest (unless antihypertensive therapy is initiated before this time)

• thrombocytopenia (platelets <100 x 109/L)

• impaired liver function, as indicated by abnormally elevated blood concentrations of liver enzymes (to twice normal concentration) and/or severe, persistent right upper quadrant or epigastric pain unresponsive to medication and not accounted for by alternative diagnoses

• progressive renal insufficiency (serum creatinine concentration >1.1 mg/dL or a doubling of the serum creatinine concentration in the absence of other renal disease)

• pulmonary edema

• new-onset visual or central nervous system disturbances.

Related Article: Does an unfavorable cervix preclude induction of labor at term in women who have gestational hypertension or mild preeclampsia? George Macones, MD (Examining the Evidence, December 2012)

Screening for preeclampsia. The use of Doppler studies and serum biomarkers is not recommended, as there is no evidence that early identification translates to improved outcomes.

Prevention of preeclampsia. Low-dose aspirin (60–80 mg/d, starting in the late first trimester) should be offered as primary prevention to:

• women with a history of early-onset preeclampsia and delivery before 34 weeks’ gestation

• women with a history of preeclampsia in multiple pregnancies

• other high-risk patients (chronic hypertension, diabetes).

No other treatments (vitamin C or E, salt restriction, or bed rest) are recommended for the prevention of preeclampsia, although calcium supplementation may be recommended for women with a low baseline dietary intake of calcium.

Use of magnesium sulfate. Universal prophylaxis with magnesium sulfate is not recommended for preeclampsia unless severe features are present or the patient’s clinical condition changes to severe during labor.

Timing of delivery. Recommendations for delivery for patients with hypertensive disorders are:

• gestational hypertension or preeclampsia without severe features: 37 weeks’ gestation

• preeclampsia with severe features: by 34 weeks

• chronic hypertension: not before 38 weeks

• chronic hypertension with superimposed preeclampsia: 34 or 37 weeks, depending on the presence of severe features.

All of these recommendations are contingent upon the clinical status of the patient and her fetus. For example, if the fetus develops severe growth restriction (<5%) or oligohydramnios, delivery may be recommended regardless of gestational age, based on fetal testing and maternal stability.

Related Article: A stepwise approach to managing eclampsia and other hypertensive emergencies Baha M. Sibai (October 2013)

Postpartum hypertension. The need for recognition of hypertension in the postpartum period is emphasized, as well as appropriate management, using the following guidelines:

• Be aware that BP decreases initially after delivery and then increases 3 to 6 days postpartum, requiring vigilance on the part of the clinician. For this reason, BP monitoring is recommended 72 hours postpartum (inpatient or outpatient) and again in 7 to 10 days in women diagnosed with a hypertensive disorder of pregnancy.

• Counsel patients who experience a hypertensive disorder and/or preeclampsia during pregnancy about postpartum preeclampsia, providing strict precautions and explicit instructions regarding its signs and symptoms

• If BP remains elevated after the first postpartum day, consider discontinuing nonsteroidal anti-inflammatory drugs (NSAIDs), as they may be related to hypertension

• Treat BP that remains above 150/100 mm Hg with antihypertensive therapy

• If postpartum preeclampsia is suspected, administer magnesium sulfate for 24 hours.

A culture shift is needed
At our institution, the most significant potential changes to clinical practice may be the elimination of universal magnesium sulfate prophylaxis and the removal of severe fetal growth restriction from the definition of “severe” preeclampsia.

Also, because the use of NSAIDs is widespread for postpartum pain control, a culture change is needed if we are to follow the postpartum recommendations.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Although we suggest that you read the ACOG report thoroughly, remember that its recommendations are only that—recommendations. Also keep in mind that only six of the approximately 60 “recommendations” provided in this report were accompanied by both high-quality evidence and a strong recommendation. There still is room for clinical judgment and individualization of management to specific patient populations.

NONINVASIVE PRENATAL SCREENING IS EXPANDING RAPIDLY—BUT DON’T THROW OUT THAT CVS KIT JUST YET!

ACOG Committee on Genetics.Committee Opinion #545: Noninvasive prenatal testing for fetal aneuploidy. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2012;120(6):1532–1534.

Mennuti MT, Cherry AM, Morrissette JJD, Dugoff L. Is it time to sound an alarm about false-positive cell-free DNA testing for fetal aneuploidy? Am J Obstet Gynecol. 2013;209(5):415–419.

In last year’s Update in Obstetrics, we discussed noninvasive prenatal genetic screening via cell-free fetal DNA, noting that it is a safer (no risk of miscarriage) and faster (starting at 10 weeks’ gestation) way to screen for aneuploidy. The sensitivity and specificity of this test for Trisomy 21 and 18 are over 99%, with slightly lower sensitivity for Trisomy 13 and sex chromosome abnormalities and a false-positive rate of 0.5%.

In a committee opinion published in December 2012, ACOG concluded that
cell-free fetal DNA is an appropriate screening option only for specific groups of patients at risk for aneuploidy:

• women older than age 35

• women with fetal ultrasonography findings that are concerning for aneuploidy

• women with aneuploidy in a prior pregnancy

• women with abnormal first- or second-trimester genetic screening tests

• parents with a balanced translocation and an increased risk of Trisomy 21 or 13.

Noninvasive aneuploidy testing is for screening only
Negative results are not diagnostic, and all positive results should be confirmed with invasive testing (chorionic villus sampling [CVS] or amniocentesis).

ACOG does not recommend routine use of cell-free fetal DNA without a comprehensive history and adequate patient counseling, as well as a designation of “high risk.”

Over the past year, more options have become available for aneuploidy screening via cell-free fetal DNA, including screening in twin gestations (for Trisomy 21, 18, 13, and the presence of a Y chromosome only) and screening for:

• 22q deletion (DiGeorge syndrome)

• 5p– (Cri-du-chat syndrome)

• 15q (Prader-Willi and Angelman syndromes)

• 1p (1p36 deletion syndrome)

• Trisomy 16

• Trisomy 22.

At this rate, the genetic information potentially available via noninvasive testing seems unlimited. It is easy to see how the fact that this is a screening test—not a diagnostic test—could get lost in the excitement.

Other limitations: Noninvasive testing is still not validated in low-risk patients, and the false-positive risk may be higher than original estimates.

Related Article: Noninvasive prenatal DNA testing: A survey of who is using it, and how (Audiocast, June 2013)

The problem of false positives
This issue was addressed by Mennuti and colleagues, who presented eight cases of abnormal cell-free fetal DNA results that were not confirmed by invasive testing.

There are few prospective data about the source of false-positive results; potential mechanisms include an inadequate fetal fraction of cell-free DNA, maternal or placental mosaicism, and a vanishing twin.

Mennuti and colleagues propose that a registry of false-positive and false-negative results be established to gather further data. They also note that as low-risk patients and aneuploidies of lower and lower prevalence are incorporated into noninvasive testing, the false-positive rate will rise. Their findings have implications for patient counseling, patient distress, invasive testing, and reimbursement.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Cell-free fetal DNA is a rapidly expanding screening technology, but it is not ready to replace diagnostic testing. Don’t throw away those CVS and amniocentesis kits just yet—we are a long way from a completely noninvasive world.

WHEN IT COMES TO GESTATIONAL DIABETES, LESS MAY BE MORE

ACOG Committee on Practice Bulletins–Obstetrics. Practice Bulletin #137: Gestational diabetes mellitus. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2013;122(2 Pt 1):406–416.

Gestational diabetes accounts for 90% of diabetic pregnancies, and its incidence has been increasing in the United States along with the obesity epidemic. In recent years, there has been some debate about the best way to screen for, diagnose, and treat gestational diabetes.

Multiple criteria exist for a positive 1-hour (130–140 mg/dL) or 3-hour glucose tolerance test (Carpenter and Coustan vs National Diabetes Data Group), without comparative trials or consensus as to which version is best. Lower cutoffs increase the rate of gestational diabetes by as much as 50%, whereas higher cutoffs lower the false-positive rate and reduce the need for additional tests.

Some groups have recommended moving away from the traditional two-step process to a one-step approach that utilizes the 2-hour, 75-g glucose tolerance test commonly used outside of pregnancy. They argue that this approach would simplify and standardize the process and could improve outcomes in “borderline” pregnancies that would have been missed by less stringent guidelines.

However, the baseline rate of gestational diabetes using this one-step approach would likely increase from 7% to 18% or higher, depending on the patient population. Such an increase would trigger a huge rise in costs and resources needed to care for these patients, without data on outcomes or appropriate therapy for this expanded group of women with gestational diabetes.

Treatment isn't clear-cut, either
Treatment of gestational diabetes centers on labor-intensive glucose monitoring, nutritional interventions, and insulin therapy.

Until recently, the use of oral hypoglycemic agents was not recommended due to limited data. Multiple studies now have been performed to evaluate the safety and efficacy of glyburide and metformin in pregnancy, demonstrating glucose control similar to that achieved with insulin without short-term adverse effects in the mother or newborn. However, as many as 20% to 40% of women using glyburide and 50% of those using metformin require the addition of insulin for adequate glucose control. The long-term effects of these medications are unknown.

Related Article: Does myo-inositol supplementation reduce the rate of gestational diabetes in pregnant women with a family history of type 2 diabetes? E. Albert Reece, MD, PhD, MBA (Examining the Evidence, June 2013)

ACOG weighs in
In an attempt to clarify optimal screening, diagnosis, and treatment, ACOG updated its practice bulletin on gestational diabetes in August 2013. Among its recommendations:

• Avoid the 2-hour glucose tolerance test because there is no demonstrated benefit for the increased number of mothers (and their fetuses) that would be identified by this approach. Rather, use the two-step approach of a 1-hour 50-g glucose tolerance test followed by a 3-hour 100-g glucose tolerance test.

• In regard to the 1-hour test, ACOG finds either 135 or 140 mg/dL acceptable as a cutoff but recommends that each practice choose one value as a standard and use it consistently. For the 3-hour test, ACOG recommends that each practice choose the version that best fits its population and prevalence of diabetes. At our institution, for example, we have chosen a 1-hour cutoff of 140 mg/dL and the National Diabetes Data Group criteria for the 3-hour test (105, 190, 165, and 145 mg/dL).

• Oral glyburide or metformin may be used to treat gestational diabetes, but glyburide (starting at 2.5 mg/d) may be the better choice for glucose control.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Use the two-step screening process to identify gestational diabetes, picking your cutoffs and sticking to them. Oral hypoglycemic agents now are acceptable for treatment, but be prepared to go back to insulin if necessary.

WE WANT TO HEAR FROM YOU. Tell us what you think.

The English expression, “a pain in the neck” is said to have originated in the early 1900s as a euphemism for the less polite phrase, “a pain in the ass.”¹ While one might wonder how the expressions of such disparate discomforts came to be idiomatically equivalent, the focus of this article is on etiology of the former. All wryness aside, since most ED presentations of neck pain are musculoskeletal in origin, one may easily fail to consider the myriad of less common, but possibly serious, causes.

Pain can originate from any part of the neck and occur as a result of inflammation (eg, infections and arthritides), vascular pathology (eg, cervical artery dissection [CAD]), spaceoccupying lesions (eg, hematomas, cysts, tumors), or even as referred pain from noncervical sources (eg, heart, diaphragm, lung apex). Any lesion encroaching on the limited space of the neck can quickly compromise the airway, compress nerves, or inhibit blood flow to the brain; therefore, knowledge of the causes of such conditions is critical. This article reviews some of the less common and generally atraumatic etiologies of nontraumatic neck pain of which the emergency physician should be familiar.

Vascular Disorders
Vascular-associated neck pain can originate from vessels within the neck or represent referred pain from a more distant structure. In both cases, however, the potential for morbidity is high and the need for consideration and timely recognition crucial.

Cervical Artery Dissection
The typical initial presenting symptom of CAD—ie, internal CAD (ICAD) or vertebral artery dissection (VAD)—is severe pain in the ipsilateral neck and/or head. Onset of pain may be sudden or gradual.² CAD occurs in an estimated 2 or 3 of every 100,000 people per year, mostly in patients between ages 20 and 40 years, and it is considered the most common cause of stroke in patients younger than age 45 years.² The pain associated with CAD generally follows trauma. While the precipitating trauma can be a major blunt or penetrating one, it is often caused by something seemingly trivial, such as “trauma” associated with coughing, painting a ceiling, yoga, or (classically and notoriously) chiropractic manipulation.³ There is frequently some rotational component to CAD-associated trauma,⁴ though dissection may occur spontaneously.⁵

The typical triad of symptoms is ipsilateral neck and/or head pain, partial Horner’s syndrome (ptosis and miosis without anhidrosis), and signs of cerebral ischemia. However, patients do not always present with all three of these symptoms, which can complicate the diagnosis. For example, in some patients, neck pain is the sole presenting symptom and can mimic the musculoskeletal pain expected from the mechanical strain that precipitated the dissection.⁶ In addition, partial Horner’s syndrome occurs in only 50% of cases, and ischemic symptoms might not present for hours to weeks after the onset of neck pain.⁶

In almost all cases of CAD, initial symptoms are otherwise unexplained pain described as a constant, steady aching. ⁷ Since cervical arteries are heavily invested with pain fibers,⁸ an intimal tear with dissecting intramural hematoma provokes pain. Pain associated with VAD is usually severe, unilateral, posterior neck, and/or occipital, while ICAD-associated pain is ipsilateral, anterolateral neck, head, and/or face. It is important to note that head or neck pain caused by a dissection normally precedes the ischemic manifestation as opposed to the more common stroke, in which the ischemia precedes or is simultaneous with the accompanying headache.⁹

Ischemic neurological symptoms can arise from stenosis of the arterial lumen, secondary to an expanding intramural hematoma; a luminal thrombus developing at the intimal defect; or an embolization accompanied by ipsilateral Horner’s syndrome, any cranial nerve abnormality, or followed by cerebral or ocular ischemic symptoms (even if transient). A diagnosis is usually made through vascular ultrasound (Figure 1) and confirmed with computed tomography angiography (CTA) or magnetic resonance angiography. When requesting a CTA of the neck, the emergency physician should specifically make note of suspected CAD in the order. Immediate treatment includes a cervical collar and neurosurgical consultation even though treatment is essentially medical and surgery is rarely required. Anticoagulation therapy is routinely initiated to prevent thrombus propagation or embolization (unless there is brain hemorrhage). Antiplatelet therapy may be equally efficacious, ¹⁰ and can be initiated upon suspicions of CAD and while confirmatory studies are in progress. The prognosis for extracranial dissections is generally good.

Cervical Epidural Hematoma Cervical (spinal) epidural hematoma is an uncommon but potentially catastrophic event that can lead to permanent neurological deficits and death from respiratory failure. It presents as sudden and severe local neck pain with rapid development of radicular pain at the corresponding dermatomes. Motor and sensory deficits follow within minutes to days.12,13 Bleeding can occur spontaneously or secondary to trauma, surgery, or coagulopathy (which itself may be pathological—eg, hemophilia or iatrogenic in origin).14,15 Untreated, progressive cord compression can lead to permanent neurological deficits and death from respiratory failure. In the patient with acute neurological deficits, immediate correction of coagulation issues is required before decompressive surgery.

Diagnosis of cervical epidural hematoma is complicated by the rarity of the event and the lack of specific symptoms. When trauma is involved, cervical disc or nerve root injury is a more likely cause of sudden onset of neck pain, with rapid development of a radicular component. However, when symptoms occur following minor exertion (eg, sneezing, coitus, coughing) and in the presence of risk factors such as hematologic disorders, pregnancy, rheumatologic disorders, or liver dysfunction, epidural hematoma must be considered.¹⁶ Emergent magnetic resonance imaging (MRI) is the modality of choice for detecting this condition (Figure 2).

Coronary Ischemia Angina pectoris secondary to coronary ischemia is described as retrosternal “heaviness” or pressure, which may spread to either or both arms, the neck, or jaw. Pathology originating in the neck can be experienced as chest pain and may confound the diagnosis. Because cervical nerve roots C4-C8 contribute to the innervation of the anterior chest wall, irritation of any one of these nerves secondary to neck pathology can mimic true angina.17,18 Conversely, the likelihood that the only pain caused by coronary ischemia might be felt in the neck is low, but possible— especially in women.19,20 Coronary ischemia should be considered in patients with cardiac risk factors but no other obvious etiology for neck pain.21

Secondary Infection
Since emergency physicians are accustomed to dealing with infection, it is hard to imagine that we could fail to recognize infection as the etiology in a patient with a chief complaint of neck pain. Diagnosis in such cases is complicated by the anatomical location of deep neck-space infections, which limits the usefulness of standard physical examination. These sites are difficult to palpate and often impossible to visualize because they are covered with noninfected tissue. Unless specifically considered in the differential, more obscure causes of neck pain associated with infection may be missed, including retropharyngeal abscess, epiglottitis, Ludwig’s angina, vertebral osteomyelitis and discitis, cervical epidural abscess, and Lemierre’s syndrome.

Epiglottitis
Epiglottitis is inflammation of the epiglottis and adjacent supraglottic structures including the pharynx, uvula, and base of the tongue. The first recorded case is thought to have been that of George Washington, who is believed to have died from this disease.²² The high mortality rate (7% to 20% in the adult population) is a direct result of airway obstruction from inflammatory edema of the epiglottis and adjacent tissues.

Epiglottitis was originally considered a childhood disease; however, the widespread use of Haemophilus influenza vaccination has resulted in a decline in pediatric incidence. Most cases are now seen in adults (mean age of 46 years).^23,24

Bacterial infection, especially from the genera Hemophilus, Streptococcus, Staphylococcus, and Klebsiella, is by far the most frequent cause of acute epiglottitis; viral and fungal-associated infections are rare. Thermal injury from swallowing hot foods or liquids, and even from inhaling crack cocaine,²⁵ also has been implicated.

Clinical presentations of epiglottitis differ between children and adults. While children are typically dyspneic, drooling, stridorous and febrile, adults tend to present with a milder form of the disease and have painful swallowing, sore throat, and a muffled voice. In both children and adults, the larynx and upper trachea are tender to light palpation at the anterior neck.26 Although sore throat and odynophagia are more often symptoms of pharyngitis, suspicion should be aroused when pain is severe and/or there is dyspnea, severe pain with an unremarkable oropharynx examination, or anterior neck tenderness. When present, muffled voice and stridor indicate greater potential for airway compromise.27 In cases of significant airway obstruction, patients may assume the “tripod position,” leaning forward with neck extended and mouth open—panting. Since soft-tissue lateral neck radiographs are about 90% sensitive and specific for epiglottitis, a normalappearing film cannot reliably exclude the diagnosis.28 Evaluation for the classic “thumb sign” of epiglottic swelling27 (Figure 3) should be combined with the newly described “vallecula sign” for greatest accuracy.29 The vallecula sign is described as the partial or complete obliteration of a well-defined linear air pocket between the base of the tongue and the epiglottis seen on a closed mouth lateral neck X-ray.

Although CT is a useful modality for detecting epiglottic, peritonsillar, or deep neck space abscess, there are risks to patients with airway compromise; moreover, placing patients in a supine position for the study increases the likelihood of respiratory distress. Despite these risks, when indicated, CT is useful in differentiating these abscesses from similarly presenting entities such as lingual tonsillitis and upper airway foreign body.

Direct visualization via flexible oral or nasolaryngoscopy is the diagnostic gold standard but may be deferred in a stable patient. When absolutely indicated, it must be performed with caution, ideally by an anesthesiologist/otolaryngologist in a controlled setting, lest it precipitate further obstruction. Through the use of fiber optics, the need for emergent intubation can be more directly assessed and, if necessary, performed by “tube-over-scope” technique. In the ED, standby equipment for intubation and cricothyrotomy/needle cricothyrotomy should be immediately available and ready in the event of rapid deterioration, at the same time as intravenous (IV) infusion of third-generation cephalosporin or ampicillin/sulbactam, and methicillin-resistant Staphylococcus aureus (MRSA) coverage. Though the rationale for empirical use of antibiotics is evident, the role of corticosteroids and of nebulized racemic epinephrine is controversial.

Death, airway obstruction, epiglottic abscess, necrotizing epiglottitis, and secondary infections (eg, pneumonia, cervical adenitis, septic arthritis, meningitis) are the potential complications that make this source of neck pain one not to be missed. If epiglottitis is suspected, the patient must be admitted to an intensive care setting.

Retropharyngeal Abscess
The retropharyngeal space, immediately behind the posterior pharynx and esophagus, extends from the base of the skull to the mediastinum. It lies anterior to the deep cervical fascia and is bound laterally by the carotid sheaths.30 Because it is fused down the midline, abscesses in this area tend to be unilateral. The space cannot be directly assessed by physical examination, and infections in this area are rare. Timely diagnosis demands consideration of retropharyngeal abscess in patients presenting with fever, neck stiffness, and sore throat. The potential for serious morbidity and mortality is related to the host of vital structures immediately adjacent to the retropharyngeal space. Complications include mediastinitis, carotid artery erosion, jugular vein thrombosis, pericarditis, epidural abscess, sepsis, and airway compromise.

Most cases are typically observed in children younger than age 6 years. In this pediatric population, the retropharyngeal space has two parallel chains of lymph nodes draining the nose, sinuses, and pharynx; retropharyngeal abscesses usually occur as a suppurative extension from infections of these upper airway structures structures. Penetrating trauma, eg, from objects held in the mouth, is another possible cause. These nodes atrophy around 6 years of age; thereafter, the main cause of retropharyngeal abscess is purulent extension of an adjacent (frequently odontogenic) infection or posterior pharyngeal trauma (eg, from a fish bone or instrumentation).³¹ As befits its origin with oral flora, cultures are almost always polymicrobial (eg, Streptococci viridans and pyogenes, Staphylococcus, H influenza, Klebsiella, anaerobes).

Although retropharyngeal abscess is considered a disease of childhood, like epiglottitis, its incidence in adults is increasing. ³² Presenting symptoms are signs of respiratory distress, such as wheezing, stridor, and drooling with impending airway obstruction from the expanding posterior pharyngeal mass. Late signs of the illness are respiratory failure due to airway obstruction and septic shock, but an astute clinician should recognize the entity long before these symptoms present. Early symptoms include fever, sore throat, odynophagia, and neck pain and stiffness (typically manifesting as a reluctance to turn the neck).³³ Patients may also complain of feeling a lump in the throat or pain in the posterior neck or shoulder with swallowing.³⁴ Ninety-seven percent of pediatric patients present with neck pain,³² which could manifest dramatically as torticollis. Most likely, a child will have a subtle reluctance to move his or her neck during the course of the physical examination. In addition, there may be posterior pharyngeal edema and/or a visible unilateral posterior pharyngeal bulge, cervical adenopathy, and a “croupy” cry or cough resembling a duck’s quack—the “cri du canard.”³⁵ Definitive diagnosis is made using X-ray and/or CT. A lateral soft-tissue neck X-ray will demonstrate widening of the prevertebral soft tissues. CT with contrast provides a more definitive diagnosis, and is also useful to differentiate abscess (ie, a hypodense lesion with ring enhancement) from cellulitis.

Regarding treatment, empiric IV antibiotics must be started immediately and may alone prevent progression if the diagnosis is made before cellulitis has progressed to abscess. Intravenous clindamycin is a reasonable first-line antibiotic; other suggested drugs include a penicillin/ beta lactamase inhibitor, penicillin G plus metronidazole, and cefoxitin.36 Airway protection is mandatory, and an otolaryngologist should be consulted early. Because of the potential for sudden airway deterioration, the emergency physician must be prepared to establish a surgical airway.

Ludwig’s Angina
Ludwig’s angina derives its name from the German physician Wilhelm Friedrich von Ludwig, who first described this deadly, rapidly progressive, fascial space/ connective tissue gangrenous cellulitis of the floor of the mouth and adjoining neck in 1836. In a curious twist of fate, it is believed that Dr Ludwig died from this very disease that bears his name.³⁷

Ninety percent of cases of Ludwig’s angina are odontogenic, often due to periapical abscesses. This condition may result secondary to any oral or parapharyngeal infection that spreads by continuity from the submandibular space into the contiguous sublingual and submental spaces. The potential for airway obstruction comes from elevation and displacement of the tongue, resulting in a mortality rate greater than 50% if untreated. Causative organisms mirror normal, polymicrobial oral flora and include Staphylococcus, Streptococcus, Fusobacterium, and Bacteroides.^38,23

Diagnosis of Ludwig’s angina is primarily clinical. Neck pain and swelling, dental pain, dysphagia, malaise, and fever, along with a protruding or elevated tongue, are typical. Submandibular swelling, which is seen in 95% of patients, develops in advanced cases into an intense “woody” induration above the hyoid bone that portends the impending airway crisis.³⁹ If the patient is sufficiently clinically stable and able to lie flat, definitive diagnosis can be made with a contrastenhanced, soft-tissue neck CT (Figure 4), which can also evaluate for a drainable abscess, soft-tissue gas, and mediastinal extension; this modality can also define the extent of soft-tissue swelling and airway patency.

Airway management is the primary consideration because of its potential for rapid deterioration. Traditional management has been aggressive and surgical, with the standard being early tracheostomy. More recent reports have encouraged more conservative management when possible.40 Impending or actual airway compromise, as manifest by significant trismus, inability to flex the neck without compromising the airway, inability to protrude the tongue, or actual resting dyspnea demand that a surgical airway be readied at bedside until fiber optic nasotracheal intubation is secured.

Antibiotics must be given early and include coverage for gram-positive, gramnegative, and anaerobic organisms. Intravenous metronidazole and penicillin (cefazolin or clindamycin if patient has an allergy to penicillin) are commonly prescribed.^38,23 Although controversial, administration of IV dexamethasone (8 mg to 12 mg) and nebulized epinephrine (1:1000, 1 mL diluted to 5 mL with normal saline) to reduce edema has been advocated. ⁴¹

Lemierre’s Syndrome Lemierre’s syndrome, septic thrombophlebitis of the internal jugular vein, was first described in 1936 by André Lemierre, who published a series of cases of previously healthy young adults in whom oropharyngeal infections were followed by “anaerobic postanginal septicaemias.”42 Most of these patients presented with sore throat (referred to as “angina” in “old skool” speak) and worsening pain and tenderness at the anterolateral neck, with pulmonary symptoms manifesting several days to 2 weeks later. The causative organism, Fusobacterium necrophorum, is a gram-negative anaerobe that is part of the normal commensal oropharyngeal flora. It invades the internal jugular (IJ) vein via the lateral pharyngeal space and releases a hemagglutinin that promotes thrombus formation in the IJ and, ultimately, metastatic septic emboli. These emboli typically invade the lungs and cause multiple nodular infiltrates and small pleural effusions. Unfortunately, as each case is unique, diagnosis is often delayed. Septic emboli can migrate to other sites and cause arthritis (hip, knee, shoulder, sacroiliac, and other joints), osteomyelitis, young adult with a history of recent sore throat and fever who subsequently developed neck pain and tenderness (with or without swelling) over the IJ, rigors, pulmonary infiltrates, and possibly other signs of septic emboli.

Doppler ultrasound or CT will show IJ thrombosis43 (Figure 5). Purulent discharge, if obtained, has a characteristic foul smell that has been likened to “limburger or overripe Camembert cheese.”44 Treatment is with high-dose IV penicillin and metronidazole or with clindamycin as single coverage. Heparin could potentially aid in dissemination of emboli, but it is used only when there is retrograde propagation of clot to the cavernous sinus.

With the routine antibiotic treatment of pharyngitis in the 1960s and 1970s, cases of Lemierre’s syndrome became so rare that it was referred to as the “forgotten disease.”⁴⁵ Unfortunately, its incidence has increased over the past few years.⁴³ It is unclear whether this rise is due to increasing antibiotic resistance or to an increasing resistance of clinicians to use antibiotics for “sore throats.”

Cervical Spinal Infections
Vertebral osteomyelitis, discitis, and spinal epidural abscess are rare in developed countries. Most cases stem from hematogenous seeding, skin abscesses, and urinary tract infections but can also originate from a host of other sites, including penetrating trauma and invasive spinal procedures (eg, lumbar punctures, epidural injections). ^46,47 Cervical spine infections are associated with immune-compromising situations or conditions (eg, IV drug use, diabetes mellitus, malignancy, acquired immunodeficiency syndrome, renal insufficiency, long-term use of systemic corticosteroids).

All three of these conditions present similarly, often as localized neck pain that grows more intense over a period of days to weeks and worsens with neck movement. Neurological signs ordinarily appear late in the course of the illness. Fever is a classic symptom but is not always present.⁴⁸ There is usually tenderness over the involved spinous process. The development of motor or sensory loss suggests formation of an abscess,⁴⁹ which can rapidly lead to further compressive symptoms and sepsis.

Leukocytosis may be absent but erythrocyte sedimentation rate and C-reactive protein are often elevated. A CT scan with contrast is frequently required for diagnosis, though when available, MRI with IV gadolinium is the test of choice (Figure 6). Most cases are caused by S aureus, but antibiotic coverage for gram-positive organisms (including MRSA), gram-negative organisms, and anaerobes should be started as soon as blood cultures are drawn. Neurosurgery should be consulted emergently since, with cervical epidural abscess, neurological deterioration—even to the point of total paralysis—can develop in a matter of hours.⁵⁰

Conclusion
Although most patients presenting to the ED with neck pain are musculoskeletal and associated with a traumatic event, other infrequent but potentially serious atraumatic causes may be present. Based on a patient’s symptoms, emergency physicians should also consider these conditions in the differential diagnosis to ensure rapid treatment to prevent further complications.

The English expression, “a pain in the neck” is said to have originated in the early 1900s as a euphemism for the less polite phrase, “a pain in the ass.”¹ While one might wonder how the expressions of such disparate discomforts came to be idiomatically equivalent, the focus of this article is on etiology of the former. All wryness aside, since most ED presentations of neck pain are musculoskeletal in origin, one may easily fail to consider the myriad of less common, but possibly serious, causes.

Pain can originate from any part of the neck and occur as a result of inflammation (eg, infections and arthritides), vascular pathology (eg, cervical artery dissection [CAD]), spaceoccupying lesions (eg, hematomas, cysts, tumors), or even as referred pain from noncervical sources (eg, heart, diaphragm, lung apex). Any lesion encroaching on the limited space of the neck can quickly compromise the airway, compress nerves, or inhibit blood flow to the brain; therefore, knowledge of the causes of such conditions is critical. This article reviews some of the less common and generally atraumatic etiologies of nontraumatic neck pain of which the emergency physician should be familiar.

Vascular Disorders
Vascular-associated neck pain can originate from vessels within the neck or represent referred pain from a more distant structure. In both cases, however, the potential for morbidity is high and the need for consideration and timely recognition crucial.

Cervical Artery Dissection
The typical initial presenting symptom of CAD—ie, internal CAD (ICAD) or vertebral artery dissection (VAD)—is severe pain in the ipsilateral neck and/or head. Onset of pain may be sudden or gradual.² CAD occurs in an estimated 2 or 3 of every 100,000 people per year, mostly in patients between ages 20 and 40 years, and it is considered the most common cause of stroke in patients younger than age 45 years.² The pain associated with CAD generally follows trauma. While the precipitating trauma can be a major blunt or penetrating one, it is often caused by something seemingly trivial, such as “trauma” associated with coughing, painting a ceiling, yoga, or (classically and notoriously) chiropractic manipulation.³ There is frequently some rotational component to CAD-associated trauma,⁴ though dissection may occur spontaneously.⁵

The typical triad of symptoms is ipsilateral neck and/or head pain, partial Horner’s syndrome (ptosis and miosis without anhidrosis), and signs of cerebral ischemia. However, patients do not always present with all three of these symptoms, which can complicate the diagnosis. For example, in some patients, neck pain is the sole presenting symptom and can mimic the musculoskeletal pain expected from the mechanical strain that precipitated the dissection.⁶ In addition, partial Horner’s syndrome occurs in only 50% of cases, and ischemic symptoms might not present for hours to weeks after the onset of neck pain.⁶

In almost all cases of CAD, initial symptoms are otherwise unexplained pain described as a constant, steady aching. ⁷ Since cervical arteries are heavily invested with pain fibers,⁸ an intimal tear with dissecting intramural hematoma provokes pain. Pain associated with VAD is usually severe, unilateral, posterior neck, and/or occipital, while ICAD-associated pain is ipsilateral, anterolateral neck, head, and/or face. It is important to note that head or neck pain caused by a dissection normally precedes the ischemic manifestation as opposed to the more common stroke, in which the ischemia precedes or is simultaneous with the accompanying headache.⁹

Ischemic neurological symptoms can arise from stenosis of the arterial lumen, secondary to an expanding intramural hematoma; a luminal thrombus developing at the intimal defect; or an embolization accompanied by ipsilateral Horner’s syndrome, any cranial nerve abnormality, or followed by cerebral or ocular ischemic symptoms (even if transient). A diagnosis is usually made through vascular ultrasound (Figure 1) and confirmed with computed tomography angiography (CTA) or magnetic resonance angiography. When requesting a CTA of the neck, the emergency physician should specifically make note of suspected CAD in the order. Immediate treatment includes a cervical collar and neurosurgical consultation even though treatment is essentially medical and surgery is rarely required. Anticoagulation therapy is routinely initiated to prevent thrombus propagation or embolization (unless there is brain hemorrhage). Antiplatelet therapy may be equally efficacious, ¹⁰ and can be initiated upon suspicions of CAD and while confirmatory studies are in progress. The prognosis for extracranial dissections is generally good.

Cervical Epidural Hematoma Cervical (spinal) epidural hematoma is an uncommon but potentially catastrophic event that can lead to permanent neurological deficits and death from respiratory failure. It presents as sudden and severe local neck pain with rapid development of radicular pain at the corresponding dermatomes. Motor and sensory deficits follow within minutes to days.12,13 Bleeding can occur spontaneously or secondary to trauma, surgery, or coagulopathy (which itself may be pathological—eg, hemophilia or iatrogenic in origin).14,15 Untreated, progressive cord compression can lead to permanent neurological deficits and death from respiratory failure. In the patient with acute neurological deficits, immediate correction of coagulation issues is required before decompressive surgery.

Diagnosis of cervical epidural hematoma is complicated by the rarity of the event and the lack of specific symptoms. When trauma is involved, cervical disc or nerve root injury is a more likely cause of sudden onset of neck pain, with rapid development of a radicular component. However, when symptoms occur following minor exertion (eg, sneezing, coitus, coughing) and in the presence of risk factors such as hematologic disorders, pregnancy, rheumatologic disorders, or liver dysfunction, epidural hematoma must be considered.¹⁶ Emergent magnetic resonance imaging (MRI) is the modality of choice for detecting this condition (Figure 2).

Coronary Ischemia Angina pectoris secondary to coronary ischemia is described as retrosternal “heaviness” or pressure, which may spread to either or both arms, the neck, or jaw. Pathology originating in the neck can be experienced as chest pain and may confound the diagnosis. Because cervical nerve roots C4-C8 contribute to the innervation of the anterior chest wall, irritation of any one of these nerves secondary to neck pathology can mimic true angina.17,18 Conversely, the likelihood that the only pain caused by coronary ischemia might be felt in the neck is low, but possible— especially in women.19,20 Coronary ischemia should be considered in patients with cardiac risk factors but no other obvious etiology for neck pain.21

Secondary Infection
Since emergency physicians are accustomed to dealing with infection, it is hard to imagine that we could fail to recognize infection as the etiology in a patient with a chief complaint of neck pain. Diagnosis in such cases is complicated by the anatomical location of deep neck-space infections, which limits the usefulness of standard physical examination. These sites are difficult to palpate and often impossible to visualize because they are covered with noninfected tissue. Unless specifically considered in the differential, more obscure causes of neck pain associated with infection may be missed, including retropharyngeal abscess, epiglottitis, Ludwig’s angina, vertebral osteomyelitis and discitis, cervical epidural abscess, and Lemierre’s syndrome.

Epiglottitis
Epiglottitis is inflammation of the epiglottis and adjacent supraglottic structures including the pharynx, uvula, and base of the tongue. The first recorded case is thought to have been that of George Washington, who is believed to have died from this disease.²² The high mortality rate (7% to 20% in the adult population) is a direct result of airway obstruction from inflammatory edema of the epiglottis and adjacent tissues.

Epiglottitis was originally considered a childhood disease; however, the widespread use of Haemophilus influenza vaccination has resulted in a decline in pediatric incidence. Most cases are now seen in adults (mean age of 46 years).^23,24

Bacterial infection, especially from the genera Hemophilus, Streptococcus, Staphylococcus, and Klebsiella, is by far the most frequent cause of acute epiglottitis; viral and fungal-associated infections are rare. Thermal injury from swallowing hot foods or liquids, and even from inhaling crack cocaine,²⁵ also has been implicated.

Clinical presentations of epiglottitis differ between children and adults. While children are typically dyspneic, drooling, stridorous and febrile, adults tend to present with a milder form of the disease and have painful swallowing, sore throat, and a muffled voice. In both children and adults, the larynx and upper trachea are tender to light palpation at the anterior neck.26 Although sore throat and odynophagia are more often symptoms of pharyngitis, suspicion should be aroused when pain is severe and/or there is dyspnea, severe pain with an unremarkable oropharynx examination, or anterior neck tenderness. When present, muffled voice and stridor indicate greater potential for airway compromise.27 In cases of significant airway obstruction, patients may assume the “tripod position,” leaning forward with neck extended and mouth open—panting. Since soft-tissue lateral neck radiographs are about 90% sensitive and specific for epiglottitis, a normalappearing film cannot reliably exclude the diagnosis.28 Evaluation for the classic “thumb sign” of epiglottic swelling27 (Figure 3) should be combined with the newly described “vallecula sign” for greatest accuracy.29 The vallecula sign is described as the partial or complete obliteration of a well-defined linear air pocket between the base of the tongue and the epiglottis seen on a closed mouth lateral neck X-ray.

Although CT is a useful modality for detecting epiglottic, peritonsillar, or deep neck space abscess, there are risks to patients with airway compromise; moreover, placing patients in a supine position for the study increases the likelihood of respiratory distress. Despite these risks, when indicated, CT is useful in differentiating these abscesses from similarly presenting entities such as lingual tonsillitis and upper airway foreign body.

Direct visualization via flexible oral or nasolaryngoscopy is the diagnostic gold standard but may be deferred in a stable patient. When absolutely indicated, it must be performed with caution, ideally by an anesthesiologist/otolaryngologist in a controlled setting, lest it precipitate further obstruction. Through the use of fiber optics, the need for emergent intubation can be more directly assessed and, if necessary, performed by “tube-over-scope” technique. In the ED, standby equipment for intubation and cricothyrotomy/needle cricothyrotomy should be immediately available and ready in the event of rapid deterioration, at the same time as intravenous (IV) infusion of third-generation cephalosporin or ampicillin/sulbactam, and methicillin-resistant Staphylococcus aureus (MRSA) coverage. Though the rationale for empirical use of antibiotics is evident, the role of corticosteroids and of nebulized racemic epinephrine is controversial.

Death, airway obstruction, epiglottic abscess, necrotizing epiglottitis, and secondary infections (eg, pneumonia, cervical adenitis, septic arthritis, meningitis) are the potential complications that make this source of neck pain one not to be missed. If epiglottitis is suspected, the patient must be admitted to an intensive care setting.

Retropharyngeal Abscess
The retropharyngeal space, immediately behind the posterior pharynx and esophagus, extends from the base of the skull to the mediastinum. It lies anterior to the deep cervical fascia and is bound laterally by the carotid sheaths.30 Because it is fused down the midline, abscesses in this area tend to be unilateral. The space cannot be directly assessed by physical examination, and infections in this area are rare. Timely diagnosis demands consideration of retropharyngeal abscess in patients presenting with fever, neck stiffness, and sore throat. The potential for serious morbidity and mortality is related to the host of vital structures immediately adjacent to the retropharyngeal space. Complications include mediastinitis, carotid artery erosion, jugular vein thrombosis, pericarditis, epidural abscess, sepsis, and airway compromise.

Most cases are typically observed in children younger than age 6 years. In this pediatric population, the retropharyngeal space has two parallel chains of lymph nodes draining the nose, sinuses, and pharynx; retropharyngeal abscesses usually occur as a suppurative extension from infections of these upper airway structures structures. Penetrating trauma, eg, from objects held in the mouth, is another possible cause. These nodes atrophy around 6 years of age; thereafter, the main cause of retropharyngeal abscess is purulent extension of an adjacent (frequently odontogenic) infection or posterior pharyngeal trauma (eg, from a fish bone or instrumentation).³¹ As befits its origin with oral flora, cultures are almost always polymicrobial (eg, Streptococci viridans and pyogenes, Staphylococcus, H influenza, Klebsiella, anaerobes).

Although retropharyngeal abscess is considered a disease of childhood, like epiglottitis, its incidence in adults is increasing. ³² Presenting symptoms are signs of respiratory distress, such as wheezing, stridor, and drooling with impending airway obstruction from the expanding posterior pharyngeal mass. Late signs of the illness are respiratory failure due to airway obstruction and septic shock, but an astute clinician should recognize the entity long before these symptoms present. Early symptoms include fever, sore throat, odynophagia, and neck pain and stiffness (typically manifesting as a reluctance to turn the neck).³³ Patients may also complain of feeling a lump in the throat or pain in the posterior neck or shoulder with swallowing.³⁴ Ninety-seven percent of pediatric patients present with neck pain,³² which could manifest dramatically as torticollis. Most likely, a child will have a subtle reluctance to move his or her neck during the course of the physical examination. In addition, there may be posterior pharyngeal edema and/or a visible unilateral posterior pharyngeal bulge, cervical adenopathy, and a “croupy” cry or cough resembling a duck’s quack—the “cri du canard.”³⁵ Definitive diagnosis is made using X-ray and/or CT. A lateral soft-tissue neck X-ray will demonstrate widening of the prevertebral soft tissues. CT with contrast provides a more definitive diagnosis, and is also useful to differentiate abscess (ie, a hypodense lesion with ring enhancement) from cellulitis.

Regarding treatment, empiric IV antibiotics must be started immediately and may alone prevent progression if the diagnosis is made before cellulitis has progressed to abscess. Intravenous clindamycin is a reasonable first-line antibiotic; other suggested drugs include a penicillin/ beta lactamase inhibitor, penicillin G plus metronidazole, and cefoxitin.36 Airway protection is mandatory, and an otolaryngologist should be consulted early. Because of the potential for sudden airway deterioration, the emergency physician must be prepared to establish a surgical airway.

Ludwig’s Angina
Ludwig’s angina derives its name from the German physician Wilhelm Friedrich von Ludwig, who first described this deadly, rapidly progressive, fascial space/ connective tissue gangrenous cellulitis of the floor of the mouth and adjoining neck in 1836. In a curious twist of fate, it is believed that Dr Ludwig died from this very disease that bears his name.³⁷

Ninety percent of cases of Ludwig’s angina are odontogenic, often due to periapical abscesses. This condition may result secondary to any oral or parapharyngeal infection that spreads by continuity from the submandibular space into the contiguous sublingual and submental spaces. The potential for airway obstruction comes from elevation and displacement of the tongue, resulting in a mortality rate greater than 50% if untreated. Causative organisms mirror normal, polymicrobial oral flora and include Staphylococcus, Streptococcus, Fusobacterium, and Bacteroides.^38,23

Diagnosis of Ludwig’s angina is primarily clinical. Neck pain and swelling, dental pain, dysphagia, malaise, and fever, along with a protruding or elevated tongue, are typical. Submandibular swelling, which is seen in 95% of patients, develops in advanced cases into an intense “woody” induration above the hyoid bone that portends the impending airway crisis.³⁹ If the patient is sufficiently clinically stable and able to lie flat, definitive diagnosis can be made with a contrastenhanced, soft-tissue neck CT (Figure 4), which can also evaluate for a drainable abscess, soft-tissue gas, and mediastinal extension; this modality can also define the extent of soft-tissue swelling and airway patency.

Airway management is the primary consideration because of its potential for rapid deterioration. Traditional management has been aggressive and surgical, with the standard being early tracheostomy. More recent reports have encouraged more conservative management when possible.40 Impending or actual airway compromise, as manifest by significant trismus, inability to flex the neck without compromising the airway, inability to protrude the tongue, or actual resting dyspnea demand that a surgical airway be readied at bedside until fiber optic nasotracheal intubation is secured.

Antibiotics must be given early and include coverage for gram-positive, gramnegative, and anaerobic organisms. Intravenous metronidazole and penicillin (cefazolin or clindamycin if patient has an allergy to penicillin) are commonly prescribed.^38,23 Although controversial, administration of IV dexamethasone (8 mg to 12 mg) and nebulized epinephrine (1:1000, 1 mL diluted to 5 mL with normal saline) to reduce edema has been advocated. ⁴¹

Lemierre’s Syndrome Lemierre’s syndrome, septic thrombophlebitis of the internal jugular vein, was first described in 1936 by André Lemierre, who published a series of cases of previously healthy young adults in whom oropharyngeal infections were followed by “anaerobic postanginal septicaemias.”42 Most of these patients presented with sore throat (referred to as “angina” in “old skool” speak) and worsening pain and tenderness at the anterolateral neck, with pulmonary symptoms manifesting several days to 2 weeks later. The causative organism, Fusobacterium necrophorum, is a gram-negative anaerobe that is part of the normal commensal oropharyngeal flora. It invades the internal jugular (IJ) vein via the lateral pharyngeal space and releases a hemagglutinin that promotes thrombus formation in the IJ and, ultimately, metastatic septic emboli. These emboli typically invade the lungs and cause multiple nodular infiltrates and small pleural effusions. Unfortunately, as each case is unique, diagnosis is often delayed. Septic emboli can migrate to other sites and cause arthritis (hip, knee, shoulder, sacroiliac, and other joints), osteomyelitis, young adult with a history of recent sore throat and fever who subsequently developed neck pain and tenderness (with or without swelling) over the IJ, rigors, pulmonary infiltrates, and possibly other signs of septic emboli.

Doppler ultrasound or CT will show IJ thrombosis43 (Figure 5). Purulent discharge, if obtained, has a characteristic foul smell that has been likened to “limburger or overripe Camembert cheese.”44 Treatment is with high-dose IV penicillin and metronidazole or with clindamycin as single coverage. Heparin could potentially aid in dissemination of emboli, but it is used only when there is retrograde propagation of clot to the cavernous sinus.

With the routine antibiotic treatment of pharyngitis in the 1960s and 1970s, cases of Lemierre’s syndrome became so rare that it was referred to as the “forgotten disease.”⁴⁵ Unfortunately, its incidence has increased over the past few years.⁴³ It is unclear whether this rise is due to increasing antibiotic resistance or to an increasing resistance of clinicians to use antibiotics for “sore throats.”

Cervical Spinal Infections
Vertebral osteomyelitis, discitis, and spinal epidural abscess are rare in developed countries. Most cases stem from hematogenous seeding, skin abscesses, and urinary tract infections but can also originate from a host of other sites, including penetrating trauma and invasive spinal procedures (eg, lumbar punctures, epidural injections). ^46,47 Cervical spine infections are associated with immune-compromising situations or conditions (eg, IV drug use, diabetes mellitus, malignancy, acquired immunodeficiency syndrome, renal insufficiency, long-term use of systemic corticosteroids).

All three of these conditions present similarly, often as localized neck pain that grows more intense over a period of days to weeks and worsens with neck movement. Neurological signs ordinarily appear late in the course of the illness. Fever is a classic symptom but is not always present.⁴⁸ There is usually tenderness over the involved spinous process. The development of motor or sensory loss suggests formation of an abscess,⁴⁹ which can rapidly lead to further compressive symptoms and sepsis.

Leukocytosis may be absent but erythrocyte sedimentation rate and C-reactive protein are often elevated. A CT scan with contrast is frequently required for diagnosis, though when available, MRI with IV gadolinium is the test of choice (Figure 6). Most cases are caused by S aureus, but antibiotic coverage for gram-positive organisms (including MRSA), gram-negative organisms, and anaerobes should be started as soon as blood cultures are drawn. Neurosurgery should be consulted emergently since, with cervical epidural abscess, neurological deterioration—even to the point of total paralysis—can develop in a matter of hours.⁵⁰

Conclusion
Although most patients presenting to the ED with neck pain are musculoskeletal and associated with a traumatic event, other infrequent but potentially serious atraumatic causes may be present. Based on a patient’s symptoms, emergency physicians should also consider these conditions in the differential diagnosis to ensure rapid treatment to prevent further complications.

The English expression, “a pain in the neck” is said to have originated in the early 1900s as a euphemism for the less polite phrase, “a pain in the ass.”¹ While one might wonder how the expressions of such disparate discomforts came to be idiomatically equivalent, the focus of this article is on etiology of the former. All wryness aside, since most ED presentations of neck pain are musculoskeletal in origin, one may easily fail to consider the myriad of less common, but possibly serious, causes.

Pain can originate from any part of the neck and occur as a result of inflammation (eg, infections and arthritides), vascular pathology (eg, cervical artery dissection [CAD]), spaceoccupying lesions (eg, hematomas, cysts, tumors), or even as referred pain from noncervical sources (eg, heart, diaphragm, lung apex). Any lesion encroaching on the limited space of the neck can quickly compromise the airway, compress nerves, or inhibit blood flow to the brain; therefore, knowledge of the causes of such conditions is critical. This article reviews some of the less common and generally atraumatic etiologies of nontraumatic neck pain of which the emergency physician should be familiar.

Vascular Disorders
Vascular-associated neck pain can originate from vessels within the neck or represent referred pain from a more distant structure. In both cases, however, the potential for morbidity is high and the need for consideration and timely recognition crucial.

Cervical Artery Dissection
The typical initial presenting symptom of CAD—ie, internal CAD (ICAD) or vertebral artery dissection (VAD)—is severe pain in the ipsilateral neck and/or head. Onset of pain may be sudden or gradual.² CAD occurs in an estimated 2 or 3 of every 100,000 people per year, mostly in patients between ages 20 and 40 years, and it is considered the most common cause of stroke in patients younger than age 45 years.² The pain associated with CAD generally follows trauma. While the precipitating trauma can be a major blunt or penetrating one, it is often caused by something seemingly trivial, such as “trauma” associated with coughing, painting a ceiling, yoga, or (classically and notoriously) chiropractic manipulation.³ There is frequently some rotational component to CAD-associated trauma,⁴ though dissection may occur spontaneously.⁵

The typical triad of symptoms is ipsilateral neck and/or head pain, partial Horner’s syndrome (ptosis and miosis without anhidrosis), and signs of cerebral ischemia. However, patients do not always present with all three of these symptoms, which can complicate the diagnosis. For example, in some patients, neck pain is the sole presenting symptom and can mimic the musculoskeletal pain expected from the mechanical strain that precipitated the dissection.⁶ In addition, partial Horner’s syndrome occurs in only 50% of cases, and ischemic symptoms might not present for hours to weeks after the onset of neck pain.⁶

In almost all cases of CAD, initial symptoms are otherwise unexplained pain described as a constant, steady aching. ⁷ Since cervical arteries are heavily invested with pain fibers,⁸ an intimal tear with dissecting intramural hematoma provokes pain. Pain associated with VAD is usually severe, unilateral, posterior neck, and/or occipital, while ICAD-associated pain is ipsilateral, anterolateral neck, head, and/or face. It is important to note that head or neck pain caused by a dissection normally precedes the ischemic manifestation as opposed to the more common stroke, in which the ischemia precedes or is simultaneous with the accompanying headache.⁹

Ischemic neurological symptoms can arise from stenosis of the arterial lumen, secondary to an expanding intramural hematoma; a luminal thrombus developing at the intimal defect; or an embolization accompanied by ipsilateral Horner’s syndrome, any cranial nerve abnormality, or followed by cerebral or ocular ischemic symptoms (even if transient). A diagnosis is usually made through vascular ultrasound (Figure 1) and confirmed with computed tomography angiography (CTA) or magnetic resonance angiography. When requesting a CTA of the neck, the emergency physician should specifically make note of suspected CAD in the order. Immediate treatment includes a cervical collar and neurosurgical consultation even though treatment is essentially medical and surgery is rarely required. Anticoagulation therapy is routinely initiated to prevent thrombus propagation or embolization (unless there is brain hemorrhage). Antiplatelet therapy may be equally efficacious, ¹⁰ and can be initiated upon suspicions of CAD and while confirmatory studies are in progress. The prognosis for extracranial dissections is generally good.

Cervical Epidural Hematoma Cervical (spinal) epidural hematoma is an uncommon but potentially catastrophic event that can lead to permanent neurological deficits and death from respiratory failure. It presents as sudden and severe local neck pain with rapid development of radicular pain at the corresponding dermatomes. Motor and sensory deficits follow within minutes to days.12,13 Bleeding can occur spontaneously or secondary to trauma, surgery, or coagulopathy (which itself may be pathological—eg, hemophilia or iatrogenic in origin).14,15 Untreated, progressive cord compression can lead to permanent neurological deficits and death from respiratory failure. In the patient with acute neurological deficits, immediate correction of coagulation issues is required before decompressive surgery.

Diagnosis of cervical epidural hematoma is complicated by the rarity of the event and the lack of specific symptoms. When trauma is involved, cervical disc or nerve root injury is a more likely cause of sudden onset of neck pain, with rapid development of a radicular component. However, when symptoms occur following minor exertion (eg, sneezing, coitus, coughing) and in the presence of risk factors such as hematologic disorders, pregnancy, rheumatologic disorders, or liver dysfunction, epidural hematoma must be considered.¹⁶ Emergent magnetic resonance imaging (MRI) is the modality of choice for detecting this condition (Figure 2).

Coronary Ischemia Angina pectoris secondary to coronary ischemia is described as retrosternal “heaviness” or pressure, which may spread to either or both arms, the neck, or jaw. Pathology originating in the neck can be experienced as chest pain and may confound the diagnosis. Because cervical nerve roots C4-C8 contribute to the innervation of the anterior chest wall, irritation of any one of these nerves secondary to neck pathology can mimic true angina.17,18 Conversely, the likelihood that the only pain caused by coronary ischemia might be felt in the neck is low, but possible— especially in women.19,20 Coronary ischemia should be considered in patients with cardiac risk factors but no other obvious etiology for neck pain.21

Secondary Infection
Since emergency physicians are accustomed to dealing with infection, it is hard to imagine that we could fail to recognize infection as the etiology in a patient with a chief complaint of neck pain. Diagnosis in such cases is complicated by the anatomical location of deep neck-space infections, which limits the usefulness of standard physical examination. These sites are difficult to palpate and often impossible to visualize because they are covered with noninfected tissue. Unless specifically considered in the differential, more obscure causes of neck pain associated with infection may be missed, including retropharyngeal abscess, epiglottitis, Ludwig’s angina, vertebral osteomyelitis and discitis, cervical epidural abscess, and Lemierre’s syndrome.

Epiglottitis
Epiglottitis is inflammation of the epiglottis and adjacent supraglottic structures including the pharynx, uvula, and base of the tongue. The first recorded case is thought to have been that of George Washington, who is believed to have died from this disease.²² The high mortality rate (7% to 20% in the adult population) is a direct result of airway obstruction from inflammatory edema of the epiglottis and adjacent tissues.

Epiglottitis was originally considered a childhood disease; however, the widespread use of Haemophilus influenza vaccination has resulted in a decline in pediatric incidence. Most cases are now seen in adults (mean age of 46 years).^23,24

Bacterial infection, especially from the genera Hemophilus, Streptococcus, Staphylococcus, and Klebsiella, is by far the most frequent cause of acute epiglottitis; viral and fungal-associated infections are rare. Thermal injury from swallowing hot foods or liquids, and even from inhaling crack cocaine,²⁵ also has been implicated.

Clinical presentations of epiglottitis differ between children and adults. While children are typically dyspneic, drooling, stridorous and febrile, adults tend to present with a milder form of the disease and have painful swallowing, sore throat, and a muffled voice. In both children and adults, the larynx and upper trachea are tender to light palpation at the anterior neck.26 Although sore throat and odynophagia are more often symptoms of pharyngitis, suspicion should be aroused when pain is severe and/or there is dyspnea, severe pain with an unremarkable oropharynx examination, or anterior neck tenderness. When present, muffled voice and stridor indicate greater potential for airway compromise.27 In cases of significant airway obstruction, patients may assume the “tripod position,” leaning forward with neck extended and mouth open—panting. Since soft-tissue lateral neck radiographs are about 90% sensitive and specific for epiglottitis, a normalappearing film cannot reliably exclude the diagnosis.28 Evaluation for the classic “thumb sign” of epiglottic swelling27 (Figure 3) should be combined with the newly described “vallecula sign” for greatest accuracy.29 The vallecula sign is described as the partial or complete obliteration of a well-defined linear air pocket between the base of the tongue and the epiglottis seen on a closed mouth lateral neck X-ray.

Although CT is a useful modality for detecting epiglottic, peritonsillar, or deep neck space abscess, there are risks to patients with airway compromise; moreover, placing patients in a supine position for the study increases the likelihood of respiratory distress. Despite these risks, when indicated, CT is useful in differentiating these abscesses from similarly presenting entities such as lingual tonsillitis and upper airway foreign body.

Direct visualization via flexible oral or nasolaryngoscopy is the diagnostic gold standard but may be deferred in a stable patient. When absolutely indicated, it must be performed with caution, ideally by an anesthesiologist/otolaryngologist in a controlled setting, lest it precipitate further obstruction. Through the use of fiber optics, the need for emergent intubation can be more directly assessed and, if necessary, performed by “tube-over-scope” technique. In the ED, standby equipment for intubation and cricothyrotomy/needle cricothyrotomy should be immediately available and ready in the event of rapid deterioration, at the same time as intravenous (IV) infusion of third-generation cephalosporin or ampicillin/sulbactam, and methicillin-resistant Staphylococcus aureus (MRSA) coverage. Though the rationale for empirical use of antibiotics is evident, the role of corticosteroids and of nebulized racemic epinephrine is controversial.

Death, airway obstruction, epiglottic abscess, necrotizing epiglottitis, and secondary infections (eg, pneumonia, cervical adenitis, septic arthritis, meningitis) are the potential complications that make this source of neck pain one not to be missed. If epiglottitis is suspected, the patient must be admitted to an intensive care setting.

Retropharyngeal Abscess
The retropharyngeal space, immediately behind the posterior pharynx and esophagus, extends from the base of the skull to the mediastinum. It lies anterior to the deep cervical fascia and is bound laterally by the carotid sheaths.30 Because it is fused down the midline, abscesses in this area tend to be unilateral. The space cannot be directly assessed by physical examination, and infections in this area are rare. Timely diagnosis demands consideration of retropharyngeal abscess in patients presenting with fever, neck stiffness, and sore throat. The potential for serious morbidity and mortality is related to the host of vital structures immediately adjacent to the retropharyngeal space. Complications include mediastinitis, carotid artery erosion, jugular vein thrombosis, pericarditis, epidural abscess, sepsis, and airway compromise.

Most cases are typically observed in children younger than age 6 years. In this pediatric population, the retropharyngeal space has two parallel chains of lymph nodes draining the nose, sinuses, and pharynx; retropharyngeal abscesses usually occur as a suppurative extension from infections of these upper airway structures structures. Penetrating trauma, eg, from objects held in the mouth, is another possible cause. These nodes atrophy around 6 years of age; thereafter, the main cause of retropharyngeal abscess is purulent extension of an adjacent (frequently odontogenic) infection or posterior pharyngeal trauma (eg, from a fish bone or instrumentation).³¹ As befits its origin with oral flora, cultures are almost always polymicrobial (eg, Streptococci viridans and pyogenes, Staphylococcus, H influenza, Klebsiella, anaerobes).

Although retropharyngeal abscess is considered a disease of childhood, like epiglottitis, its incidence in adults is increasing. ³² Presenting symptoms are signs of respiratory distress, such as wheezing, stridor, and drooling with impending airway obstruction from the expanding posterior pharyngeal mass. Late signs of the illness are respiratory failure due to airway obstruction and septic shock, but an astute clinician should recognize the entity long before these symptoms present. Early symptoms include fever, sore throat, odynophagia, and neck pain and stiffness (typically manifesting as a reluctance to turn the neck).³³ Patients may also complain of feeling a lump in the throat or pain in the posterior neck or shoulder with swallowing.³⁴ Ninety-seven percent of pediatric patients present with neck pain,³² which could manifest dramatically as torticollis. Most likely, a child will have a subtle reluctance to move his or her neck during the course of the physical examination. In addition, there may be posterior pharyngeal edema and/or a visible unilateral posterior pharyngeal bulge, cervical adenopathy, and a “croupy” cry or cough resembling a duck’s quack—the “cri du canard.”³⁵ Definitive diagnosis is made using X-ray and/or CT. A lateral soft-tissue neck X-ray will demonstrate widening of the prevertebral soft tissues. CT with contrast provides a more definitive diagnosis, and is also useful to differentiate abscess (ie, a hypodense lesion with ring enhancement) from cellulitis.

Regarding treatment, empiric IV antibiotics must be started immediately and may alone prevent progression if the diagnosis is made before cellulitis has progressed to abscess. Intravenous clindamycin is a reasonable first-line antibiotic; other suggested drugs include a penicillin/ beta lactamase inhibitor, penicillin G plus metronidazole, and cefoxitin.36 Airway protection is mandatory, and an otolaryngologist should be consulted early. Because of the potential for sudden airway deterioration, the emergency physician must be prepared to establish a surgical airway.

Ludwig’s Angina
Ludwig’s angina derives its name from the German physician Wilhelm Friedrich von Ludwig, who first described this deadly, rapidly progressive, fascial space/ connective tissue gangrenous cellulitis of the floor of the mouth and adjoining neck in 1836. In a curious twist of fate, it is believed that Dr Ludwig died from this very disease that bears his name.³⁷

Ninety percent of cases of Ludwig’s angina are odontogenic, often due to periapical abscesses. This condition may result secondary to any oral or parapharyngeal infection that spreads by continuity from the submandibular space into the contiguous sublingual and submental spaces. The potential for airway obstruction comes from elevation and displacement of the tongue, resulting in a mortality rate greater than 50% if untreated. Causative organisms mirror normal, polymicrobial oral flora and include Staphylococcus, Streptococcus, Fusobacterium, and Bacteroides.^38,23

Diagnosis of Ludwig’s angina is primarily clinical. Neck pain and swelling, dental pain, dysphagia, malaise, and fever, along with a protruding or elevated tongue, are typical. Submandibular swelling, which is seen in 95% of patients, develops in advanced cases into an intense “woody” induration above the hyoid bone that portends the impending airway crisis.³⁹ If the patient is sufficiently clinically stable and able to lie flat, definitive diagnosis can be made with a contrastenhanced, soft-tissue neck CT (Figure 4), which can also evaluate for a drainable abscess, soft-tissue gas, and mediastinal extension; this modality can also define the extent of soft-tissue swelling and airway patency.

Airway management is the primary consideration because of its potential for rapid deterioration. Traditional management has been aggressive and surgical, with the standard being early tracheostomy. More recent reports have encouraged more conservative management when possible.40 Impending or actual airway compromise, as manifest by significant trismus, inability to flex the neck without compromising the airway, inability to protrude the tongue, or actual resting dyspnea demand that a surgical airway be readied at bedside until fiber optic nasotracheal intubation is secured.

Antibiotics must be given early and include coverage for gram-positive, gramnegative, and anaerobic organisms. Intravenous metronidazole and penicillin (cefazolin or clindamycin if patient has an allergy to penicillin) are commonly prescribed.^38,23 Although controversial, administration of IV dexamethasone (8 mg to 12 mg) and nebulized epinephrine (1:1000, 1 mL diluted to 5 mL with normal saline) to reduce edema has been advocated. ⁴¹

Lemierre’s Syndrome Lemierre’s syndrome, septic thrombophlebitis of the internal jugular vein, was first described in 1936 by André Lemierre, who published a series of cases of previously healthy young adults in whom oropharyngeal infections were followed by “anaerobic postanginal septicaemias.”42 Most of these patients presented with sore throat (referred to as “angina” in “old skool” speak) and worsening pain and tenderness at the anterolateral neck, with pulmonary symptoms manifesting several days to 2 weeks later. The causative organism, Fusobacterium necrophorum, is a gram-negative anaerobe that is part of the normal commensal oropharyngeal flora. It invades the internal jugular (IJ) vein via the lateral pharyngeal space and releases a hemagglutinin that promotes thrombus formation in the IJ and, ultimately, metastatic septic emboli. These emboli typically invade the lungs and cause multiple nodular infiltrates and small pleural effusions. Unfortunately, as each case is unique, diagnosis is often delayed. Septic emboli can migrate to other sites and cause arthritis (hip, knee, shoulder, sacroiliac, and other joints), osteomyelitis, young adult with a history of recent sore throat and fever who subsequently developed neck pain and tenderness (with or without swelling) over the IJ, rigors, pulmonary infiltrates, and possibly other signs of septic emboli.

Doppler ultrasound or CT will show IJ thrombosis43 (Figure 5). Purulent discharge, if obtained, has a characteristic foul smell that has been likened to “limburger or overripe Camembert cheese.”44 Treatment is with high-dose IV penicillin and metronidazole or with clindamycin as single coverage. Heparin could potentially aid in dissemination of emboli, but it is used only when there is retrograde propagation of clot to the cavernous sinus.

With the routine antibiotic treatment of pharyngitis in the 1960s and 1970s, cases of Lemierre’s syndrome became so rare that it was referred to as the “forgotten disease.”⁴⁵ Unfortunately, its incidence has increased over the past few years.⁴³ It is unclear whether this rise is due to increasing antibiotic resistance or to an increasing resistance of clinicians to use antibiotics for “sore throats.”

Cervical Spinal Infections
Vertebral osteomyelitis, discitis, and spinal epidural abscess are rare in developed countries. Most cases stem from hematogenous seeding, skin abscesses, and urinary tract infections but can also originate from a host of other sites, including penetrating trauma and invasive spinal procedures (eg, lumbar punctures, epidural injections). ^46,47 Cervical spine infections are associated with immune-compromising situations or conditions (eg, IV drug use, diabetes mellitus, malignancy, acquired immunodeficiency syndrome, renal insufficiency, long-term use of systemic corticosteroids).

All three of these conditions present similarly, often as localized neck pain that grows more intense over a period of days to weeks and worsens with neck movement. Neurological signs ordinarily appear late in the course of the illness. Fever is a classic symptom but is not always present.⁴⁸ There is usually tenderness over the involved spinous process. The development of motor or sensory loss suggests formation of an abscess,⁴⁹ which can rapidly lead to further compressive symptoms and sepsis.

Leukocytosis may be absent but erythrocyte sedimentation rate and C-reactive protein are often elevated. A CT scan with contrast is frequently required for diagnosis, though when available, MRI with IV gadolinium is the test of choice (Figure 6). Most cases are caused by S aureus, but antibiotic coverage for gram-positive organisms (including MRSA), gram-negative organisms, and anaerobes should be started as soon as blood cultures are drawn. Neurosurgery should be consulted emergently since, with cervical epidural abscess, neurological deterioration—even to the point of total paralysis—can develop in a matter of hours.⁵⁰

Conclusion
Although most patients presenting to the ED with neck pain are musculoskeletal and associated with a traumatic event, other infrequent but potentially serious atraumatic causes may be present. Based on a patient’s symptoms, emergency physicians should also consider these conditions in the differential diagnosis to ensure rapid treatment to prevent further complications.

Because the low bone mass and deterioration of bone microarchitecture and quality that characterize osteoporosis can lead to fragility fracture, it is vital that we intervene in our patients’ health in a timely manner to reduce this risk. One way to accomplish this goal is to understand the role of age in determining a woman’s fracture risk. For example, an 80-year-old woman and a 50-year-old woman with a T-score of –2.5, as measured by dual x-ray absorptiometry (DXA), will have dramatically different fracture risks. According to the World Health Organization’s fracture-risk assessment tool (http://www.shef.ac.uk/FRAX/), the older woman has a 10-year probability of hip fracture approximately five times greater than the younger woman.

Although no new therapies have been approved during the past year, several important findings were published that affect clinical management of menopausal patients or suggest changes likely in the future.

In this article, I review:

• the latest guidance on osteoporosis from the American College of Obstetricians and Gynecologists (ACOG)
• the most recent indications for bone mineral density (BMD) testing from the International Society for Clinical Densitometry (ISCD)
• a study exploring the effect of oral hormonal contraception on the acquisition of peak BMD in adolescents and young women
• results of a randomized trial of the experimental agent odanacatib in postmenopausal women
• a pilot study of teriparatide (Forteo) for idiopathic osteoporosis in premenopausal women.

ACOG ISSUES RECOMMENDATIONS ON SCREENING, TREATMENT, AND LIFESTYLE

Committee on Practice Bulletins–Gynecology. ACOG Practice Bulletin #129: Osteoporosis. Obstet Gynecol. 2012;120(3):718–734.

This comprehensive review of management guidelines for ObGyns deserves “top billing” in this update. It offers recommendations on important interventions, from BMD measurement and subsequent monitoring to calcium and vitamin D supplementation.

When to initiate screening

• Begin BMD screening using DXA at age 65. DXA also may be appropriate for younger women if they are postmenopausal and have other significant risk factors for osteoporosis or fracture (Level A evidence – based on good and consistent scientific evidence).
• In the absence of new risk factors, do not perform DXA screening more frequently than every 2 years (Level B evidence – based on limited or inconsistent scientific evidence).

Which patients should be treated?
Treatment is recommended for:

• women with a T-score of –2.5 or lower
• women who have had a low-trauma ­fracture
• women with a T-score between –1 and –2.5 and a 10-year FRAX hip-fracture risk of 3% or higher or a 10-year FRAX risk of major osteoporotic fracture of 20% or higher, or both. A major osteoporotic fracture involves the forearm, hip, or shoulder, or a clinical vertebral fracture (Level A evidence).
  

Only therapies approved by the US FDA should be used for medical treatment. They are raloxifene (Evista), bisphosphonates (Actonel, Boniva, Fosamax, Reclast), parathyroid hormone, denosumab (Prolia), and calcitonin (Fortical, Miacalcin) (Level A evidence).

Monitoring of therapy
In the absence of new risk factors, do not repeat DXA monitoring of therapy once BMD has been determined to be stable or improved (Level B evidence).

Lifestyle recommendations

• Counsel women about lifestyle factors that may affect BMD and fracture risk, which include smoking, poor nutrition and excessive weight loss, weight-bearing and muscle-strengthening exercise, and fall prevention (Level B evidence).
• Advise patients of current recommendations for calcium and vitamin D intake from the Institute of Medicine, which are calcium 1,200 mg/day and vitamin D 600 IU/day for women aged 51 to 70 years (Level B evidence).
• Counsel girls and women of all ages about the effects of lifestyle on bone health (Level C evidence – based on consensus and expert opinion).

WHAT THIS EVIDENCE MEANS FOR PRACTICE
By utilizing the FRAX risk-assessment tool, we can determine which patients truly require treatment. In the process, we should be able to reduce the overtreatment of younger women with low bone mass as well as the undertreatment of older women who appear to have less deranged bone mass.
ACOG also emphasizes the need to avoid the overutilization of DXA scans in various groups, as well as the importance of lifestyle adjustments to promote bone health in all age groups.

Related Article: STOP performing DXA scans in healthy, perimenopausal women  Lisa Larkin, MD, and Andrew M. Kaunitz, MD (Stop/Start, Januaray 2013)

CLINICAL DENSITOMETRISTS WEIGH IN ON INDICATIONS FOR BMD ASSESSMENT

International Society for Clinical Densitometry (ISCD). Indications for bone mineral density (BMD) testing. http://www.iscd.org/official-positions/2013-iscd-official-positions-adult/. Updated August 15, 2013. Accessed November 7, 2013.

In its comprehensive review of BMD assessment, the ISCD elucidates the process, which typically involves DXA imaging.

Indications for BMD assessment

• The female patient is age 65 or older
• The postmenopausal patient is younger than age 65 but has a risk factor for low bone mass, such as low body weight, a history of fracture, use of a high-risk medication, or a disease or condition associated with bone loss
• The perimenopausal woman has clinical risk factors for fracture, such as low body weight, history of fracture, or use of a high-risk medication
• The adult sustains a fragility fracture
• The adult has a disease or condition associated with low bone mass or bone loss
• The adult is taking a medication associated with low bone mass or bone loss
• The patient is being considered for pharmacologic therapy
• The patient is being treated, to monitor effect
• The patient is not receiving therapy, but evidence of bone loss would lead to ­treatment.

When serial BMD assessment is appropriate

• When it is used to determine whether treatment should be initiated (in untreated patients) because of significant bone loss
• To monitor response to therapy by identifying an increase or stabilization of BMD
• To identify nonresponse by documenting a loss of BMD, suggesting the need for treatment re-evaluation and assessment for a secondary cause of osteoporosis
• To follow-up earlier assessment when the expected change in BMD equals or exceeds the least significant change
• When the interval is appropriate for the patient’s clinical status. (In general, BMD assessment is performed 1 year after initiation or change of therapy, with longer intervals once a therapeutic effect has been established.)
• When the patient is using a medication associated with rapid bone loss, such as glucocorticoid therapy. In such a patient, more frequent testing may be appropriate.
• Note that these recommendations differ slightly from ACOG’s statements regarding the use of DXA.

Diagnosis of osteoporosis

• According to the WHO international reference standard, osteoporosis can be diagnosed when a patient has a T-score of –2.5 or below at the femoral neck. The reference standard from which the T-score is calculated is the white female population aged 20 to 29 years in the National Health and Nutrition Examination Survey (NHANES) III database.
• Osteoporosis also may be diagnosed in postmenopausal women and men aged 50 or older when the T-score of the lumbar spine, total hip, or femoral neck is –2.5 or below. In some circumstances, the
  33% radius (also called the 1/3 radius) may be utilized.
• Other hip regions of interest, including Ward’s area and the greater trochanter, should not be used for diagnosis.

A move away from use of the term “osteopenia”

• The term may be retained, but “low bone mass” or “low bone density” is preferred
• People with low bone mass or low bone density do not necessarily have a high risk of fracture.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
DXA testing remains the cornerstone of diagnosis for patients at risk for fragility fracture. It also is the optimal method to determine the need for pharmacotherapy. In some instances, however, overutilization of DXA imaging has led to overtreatment, especially in younger women with low bone mass, when treatment is based on variables other than diminished bone quality (including, “small-boned” women, genetics, and failure to achieve peak bone mass as high as one’s peer group prior to menopause).
These recommendations help to clarify the rationale for follow-up DXA imaging for patients on therapy, an area in which scientific unanimity is lacking.

Related Article: What is the optimal interval for osteoporosis screening in postmenopausal women before fracture occurrence and osteoporosis treatment initiation? Steven R. Goldstein, MD (Examining the Evidence, August 2012)

IN ADOLESCENTS AND YOUNG WOMEN, CONSIDER THE BONE EFFECTS OF ORAL CONTRACEPTIVES

Ziglar S, Hunter TS. The effect of hormonal oral contraception on acquisition of peak bone mineral density of adolescents and young women. J Pharm Pract. 2012;25(3):331–340.

The bone loss observed in adolescents and young women who use depot medroxyprogesterone acetate (Depo-Provera) for contraception led to an FDA-mandated boxed warning on the medication’s package insert. The effect of oral contraceptives (OCs) on bone growth has received little publicity, however.

The best strategy to offset the natural loss of bone associated with aging and the menopausal transition is to ensure the development of maximal bone mass in youth. When maximal BMD is not achieved, the risk of osteoporosis is increased.

Adolescence is a critical period of bone mineralization, which is mediated by endo­genous estradiol. The highest rate of bone mass accrual occurs 1 year before and 3 years after menarche. Young women who consume a diet low in calcium or who have an eating disorder, who fail to exercise, who smoke, or who have low estrogen status are most likely to have low peak bone mass.

OCs suppress endogenous estradiol production by interrupting the hypothalamic-pituitary-ovarian axis. By replacing endogenous estradiol with ethinyl estradiol (EE), OCs establish and maintain new hormone levels. Early initiation and use of very-low-dose EE increases the likelihood that the accrual of bone mass will be jeopardized at a critical time of bone mineralization.

Details of this meta-analysis
Ziglar and Hunter reviewed 11 prospective trials that showed a decrease in bone mass in adolescents and young women who used low-dose OCs, six trials that showed a neutral effect, and one trial that found an increase in bone mass. This last study involved only members of the US military whose level of daily exercise may not be representative of the general population of women the same age. Investigators also theorized that the use of norethindrone acetate as an androgenic progestin in this study may have exerted a positive effect on bone accrual.

Ziglar and Hunter concluded that the use of OCs containing 20 µg EE prevents adolescents and young women from attaining peak BMD. Evidence on the effect of contraceptives formulated with 30 to 35 µg EE is less definitive, but this dose may also impede BMD acquisition in adolescents.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
To ensure breast health and reduce the risk of venous thromboembolic events, drug makers have developed OCs with lower and lower doses of EE. In the process, however, the beneficial effects of endogenous estradiol on bone acquisition have been suppressed. Therefore, the lowest-dose OC may not necessarily be the most appropriate clinical choice for adolescents and young women seeking contraception.

Related Article: Osteoporosis treatment and breast cancer prevention: Two goals, one treatment? Robert L. Barbieri, MD (Editorial, November 2013)

EXPERIMENTAL DRUG REDUCES BONE RESORPTION WITHOUT IMPEDING BONE FORMATION

Brixen K, Chapurlat R, Cheung AM, et al. Bone density, turnover, and estimated strength in postmenopausal women treated with odanacatib: a randomized trial. J Clin Endocrinol Metab. 2013;98(2):571–580.

Current treatments for osteoporosis include antiresorptive agents, such as bisphosphonates and denosumab, that preserve bone mass by reducing the rate of bone turnover. These drugs reduce the number or activity (or both) of bone-resorbing osteoclasts. Because osteoclasts play a role in stimulating bone formation by osteoblasts, these treatments indirectly lower bone formation.

Odanacatib is a drug in Phase 3 development for the treatment of postmenopausal osteoporosis. It is a highly selective and reversible oral inhibitor of the collagenase activity of cathepsin K, which is secreted by osteoclasts. Odanacatib reduces bone resorption without reducing the number of osteoclasts and, thus, appears to preserve bone formation.

Details of the trial
Brixen and colleagues conducted a randomized, double-blind, international, 2-year, Phase 3 trial comparing odancatib 50 mg once weekly with placebo in postmenopausal women treated with calcium and vitamin D. The primary endpoint was the change from baseline BMD at the lumbar spine at 1 year, as assessed by DXA. Secondary endpoints included the change from baseline BMD at the hip (total hip, femoral neck, and trochanter) at 1 year, the change from baseline BMD at the spine and hip at 2 years, and 1- and 2-year changes in bone-turnover markers. A total of 214 women were enrolled (average age: 64 years; average T-score of 1.8 at the lumbar spine, –1.8 at the femoral neck, and –1.3 at the total hip).

At 1 year, the change from baseline BMD at the lumbar spine was significantly higher (P <.001) in women receiving odanacatib, compared with placebo (treatment difference: 3.5%). At 2 years, the treatment difference was even higher (5.4%). The mean changes in BMD at the femoral neck, total hip, and trochanter also were significantly greater (P <.001) in women receiving odanacatib, with treatment differences at 2 years of 3.8%, 3.3%, and 5.5%, respectively.

During the first 6 months of the trial, serum concentrations of bone-turnover markers (CTX and P1NP) decreased significantly (P <.001) in odanacatib-treated women, compared with those given placebo.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Although no new agents for the treatment of osteoporosis have been introduced over the past year, cathepsin K inhibitors appear to offer great promise for the future. As clinicians, we need to keep abreast of new developments that may be of potential value to our patients.

PILOT STUDY: TERIPARATIDE WAS EFFECTIVE IN 81% OF PREMENOPAUSAL WOMEN WITH IDIOPATHIC OSTEOPOROSIS

Cohen A, Stein EM, Recker RR, et al. Teriparatide for idiopathic osteoporosis in premenopausal women: A pilot study. J Clin Endocrinol Metab. 2013;98(5):1971–1981.

Idiopathic osteoporosis (IOP) affects young, otherwise healthy men and women with intact gonadal function and no secondary cause of bone loss or fragility. Women with IOP have abnormal bone microarchitecture with thinner cortices; fewer, thinner, and more widely separated and heterogeneously distributed trabeculae; more rod-like trabecular structures; less trabecular stiffness; and a higher level of marrow fat.

The osteoanabolic agent teriperatide increases BMD and reduces the incidence of fracture in postmenopausal women and in patients with glucocorticoid-induced osteoporosis, and it increases BMD in men with IOP. This study explored its effect in premenopausal women with IOP.

Details of the study
Cohen and colleagues recruited premenopausal women aged 20 to 48 years who had one or both of the following traits:

• a history of at least one low-trauma fracture more than 6 months before enrollment
• low BMD of the spine or hip (Z-score of –2.0 or below), as assessed by DXA.

All participants had regular menses and early follicular-phase follicle-stimulating hormone (FSH) levels below 20 mIU/mL; none were using hormonal contraception. Women who had secondary osteoporosis related to estrogen deficiency, an eating disorder, an endocrinopathy, celiac or gastrointestinal disease, hyperparathyroidism, marked hypercalciuria, a low serum level of 25-hydroxyvitamin D (<20 ng/mL), and drug exposures were excluded.

All participants (n = 21) received teriparatide 20 µg daily in the morning or evening, according to preference. They also were given calcium 630 mg and vitamin D 800 IU daily.

BMD increased at the spine by 10.8% (standard deviation: 8.3%), total hip by 6.2% (5.6%), and femoral neck by 7.6% (3.4%) (all P <.001). Transiliac biopsies demonstrated significant increases in cortical width and porosity, and trabecular bone volume and number increased as well. Four women had no increase in BMD.

Overall, Cohen and colleagues concluded that teriparatide was associated with increased BMD at the spine and hip and improved trabecular microarchitecture and stiffness at the iliac crest in the majority of women with IOP.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Although ObGyns rarely prescribe teriparatide, often leaving this option for metabolic bone experts to offer, we should keep premenopausal IOP in mind when younger patients sustain low-trauma fractures of the hip or vertebrae, as well as fracture of an upper or lower extremity or the ribs.
Teriparatide appears to be an excellent choice for the majority of premenopausal patients with IOP (81% of patients in this pilot study).

Because the low bone mass and deterioration of bone microarchitecture and quality that characterize osteoporosis can lead to fragility fracture, it is vital that we intervene in our patients’ health in a timely manner to reduce this risk. One way to accomplish this goal is to understand the role of age in determining a woman’s fracture risk. For example, an 80-year-old woman and a 50-year-old woman with a T-score of –2.5, as measured by dual x-ray absorptiometry (DXA), will have dramatically different fracture risks. According to the World Health Organization’s fracture-risk assessment tool (http://www.shef.ac.uk/FRAX/), the older woman has a 10-year probability of hip fracture approximately five times greater than the younger woman.

Although no new therapies have been approved during the past year, several important findings were published that affect clinical management of menopausal patients or suggest changes likely in the future.

In this article, I review:

• the latest guidance on osteoporosis from the American College of Obstetricians and Gynecologists (ACOG)
• the most recent indications for bone mineral density (BMD) testing from the International Society for Clinical Densitometry (ISCD)
• a study exploring the effect of oral hormonal contraception on the acquisition of peak BMD in adolescents and young women
• results of a randomized trial of the experimental agent odanacatib in postmenopausal women
• a pilot study of teriparatide (Forteo) for idiopathic osteoporosis in premenopausal women.

ACOG ISSUES RECOMMENDATIONS ON SCREENING, TREATMENT, AND LIFESTYLE

Committee on Practice Bulletins–Gynecology. ACOG Practice Bulletin #129: Osteoporosis. Obstet Gynecol. 2012;120(3):718–734.

This comprehensive review of management guidelines for ObGyns deserves “top billing” in this update. It offers recommendations on important interventions, from BMD measurement and subsequent monitoring to calcium and vitamin D supplementation.

When to initiate screening

• Begin BMD screening using DXA at age 65. DXA also may be appropriate for younger women if they are postmenopausal and have other significant risk factors for osteoporosis or fracture (Level A evidence – based on good and consistent scientific evidence).
• In the absence of new risk factors, do not perform DXA screening more frequently than every 2 years (Level B evidence – based on limited or inconsistent scientific evidence).

Which patients should be treated?
Treatment is recommended for:

• women with a T-score of –2.5 or lower
• women who have had a low-trauma ­fracture
• women with a T-score between –1 and –2.5 and a 10-year FRAX hip-fracture risk of 3% or higher or a 10-year FRAX risk of major osteoporotic fracture of 20% or higher, or both. A major osteoporotic fracture involves the forearm, hip, or shoulder, or a clinical vertebral fracture (Level A evidence).
  

Only therapies approved by the US FDA should be used for medical treatment. They are raloxifene (Evista), bisphosphonates (Actonel, Boniva, Fosamax, Reclast), parathyroid hormone, denosumab (Prolia), and calcitonin (Fortical, Miacalcin) (Level A evidence).

Monitoring of therapy
In the absence of new risk factors, do not repeat DXA monitoring of therapy once BMD has been determined to be stable or improved (Level B evidence).

Lifestyle recommendations

• Counsel women about lifestyle factors that may affect BMD and fracture risk, which include smoking, poor nutrition and excessive weight loss, weight-bearing and muscle-strengthening exercise, and fall prevention (Level B evidence).
• Advise patients of current recommendations for calcium and vitamin D intake from the Institute of Medicine, which are calcium 1,200 mg/day and vitamin D 600 IU/day for women aged 51 to 70 years (Level B evidence).
• Counsel girls and women of all ages about the effects of lifestyle on bone health (Level C evidence – based on consensus and expert opinion).

WHAT THIS EVIDENCE MEANS FOR PRACTICE
By utilizing the FRAX risk-assessment tool, we can determine which patients truly require treatment. In the process, we should be able to reduce the overtreatment of younger women with low bone mass as well as the undertreatment of older women who appear to have less deranged bone mass.
ACOG also emphasizes the need to avoid the overutilization of DXA scans in various groups, as well as the importance of lifestyle adjustments to promote bone health in all age groups.

Related Article: STOP performing DXA scans in healthy, perimenopausal women  Lisa Larkin, MD, and Andrew M. Kaunitz, MD (Stop/Start, Januaray 2013)

CLINICAL DENSITOMETRISTS WEIGH IN ON INDICATIONS FOR BMD ASSESSMENT

International Society for Clinical Densitometry (ISCD). Indications for bone mineral density (BMD) testing. http://www.iscd.org/official-positions/2013-iscd-official-positions-adult/. Updated August 15, 2013. Accessed November 7, 2013.

In its comprehensive review of BMD assessment, the ISCD elucidates the process, which typically involves DXA imaging.

Indications for BMD assessment

• The female patient is age 65 or older
• The postmenopausal patient is younger than age 65 but has a risk factor for low bone mass, such as low body weight, a history of fracture, use of a high-risk medication, or a disease or condition associated with bone loss
• The perimenopausal woman has clinical risk factors for fracture, such as low body weight, history of fracture, or use of a high-risk medication
• The adult sustains a fragility fracture
• The adult has a disease or condition associated with low bone mass or bone loss
• The adult is taking a medication associated with low bone mass or bone loss
• The patient is being considered for pharmacologic therapy
• The patient is being treated, to monitor effect
• The patient is not receiving therapy, but evidence of bone loss would lead to ­treatment.

When serial BMD assessment is appropriate

• When it is used to determine whether treatment should be initiated (in untreated patients) because of significant bone loss
• To monitor response to therapy by identifying an increase or stabilization of BMD
• To identify nonresponse by documenting a loss of BMD, suggesting the need for treatment re-evaluation and assessment for a secondary cause of osteoporosis
• To follow-up earlier assessment when the expected change in BMD equals or exceeds the least significant change
• When the interval is appropriate for the patient’s clinical status. (In general, BMD assessment is performed 1 year after initiation or change of therapy, with longer intervals once a therapeutic effect has been established.)
• When the patient is using a medication associated with rapid bone loss, such as glucocorticoid therapy. In such a patient, more frequent testing may be appropriate.
• Note that these recommendations differ slightly from ACOG’s statements regarding the use of DXA.

Diagnosis of osteoporosis

• According to the WHO international reference standard, osteoporosis can be diagnosed when a patient has a T-score of –2.5 or below at the femoral neck. The reference standard from which the T-score is calculated is the white female population aged 20 to 29 years in the National Health and Nutrition Examination Survey (NHANES) III database.
• Osteoporosis also may be diagnosed in postmenopausal women and men aged 50 or older when the T-score of the lumbar spine, total hip, or femoral neck is –2.5 or below. In some circumstances, the
  33% radius (also called the 1/3 radius) may be utilized.
• Other hip regions of interest, including Ward’s area and the greater trochanter, should not be used for diagnosis.

A move away from use of the term “osteopenia”

• The term may be retained, but “low bone mass” or “low bone density” is preferred
• People with low bone mass or low bone density do not necessarily have a high risk of fracture.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
DXA testing remains the cornerstone of diagnosis for patients at risk for fragility fracture. It also is the optimal method to determine the need for pharmacotherapy. In some instances, however, overutilization of DXA imaging has led to overtreatment, especially in younger women with low bone mass, when treatment is based on variables other than diminished bone quality (including, “small-boned” women, genetics, and failure to achieve peak bone mass as high as one’s peer group prior to menopause).
These recommendations help to clarify the rationale for follow-up DXA imaging for patients on therapy, an area in which scientific unanimity is lacking.

Related Article: What is the optimal interval for osteoporosis screening in postmenopausal women before fracture occurrence and osteoporosis treatment initiation? Steven R. Goldstein, MD (Examining the Evidence, August 2012)

IN ADOLESCENTS AND YOUNG WOMEN, CONSIDER THE BONE EFFECTS OF ORAL CONTRACEPTIVES

Ziglar S, Hunter TS. The effect of hormonal oral contraception on acquisition of peak bone mineral density of adolescents and young women. J Pharm Pract. 2012;25(3):331–340.

The bone loss observed in adolescents and young women who use depot medroxyprogesterone acetate (Depo-Provera) for contraception led to an FDA-mandated boxed warning on the medication’s package insert. The effect of oral contraceptives (OCs) on bone growth has received little publicity, however.

The best strategy to offset the natural loss of bone associated with aging and the menopausal transition is to ensure the development of maximal bone mass in youth. When maximal BMD is not achieved, the risk of osteoporosis is increased.

Adolescence is a critical period of bone mineralization, which is mediated by endo­genous estradiol. The highest rate of bone mass accrual occurs 1 year before and 3 years after menarche. Young women who consume a diet low in calcium or who have an eating disorder, who fail to exercise, who smoke, or who have low estrogen status are most likely to have low peak bone mass.

OCs suppress endogenous estradiol production by interrupting the hypothalamic-pituitary-ovarian axis. By replacing endogenous estradiol with ethinyl estradiol (EE), OCs establish and maintain new hormone levels. Early initiation and use of very-low-dose EE increases the likelihood that the accrual of bone mass will be jeopardized at a critical time of bone mineralization.

Details of this meta-analysis
Ziglar and Hunter reviewed 11 prospective trials that showed a decrease in bone mass in adolescents and young women who used low-dose OCs, six trials that showed a neutral effect, and one trial that found an increase in bone mass. This last study involved only members of the US military whose level of daily exercise may not be representative of the general population of women the same age. Investigators also theorized that the use of norethindrone acetate as an androgenic progestin in this study may have exerted a positive effect on bone accrual.

Ziglar and Hunter concluded that the use of OCs containing 20 µg EE prevents adolescents and young women from attaining peak BMD. Evidence on the effect of contraceptives formulated with 30 to 35 µg EE is less definitive, but this dose may also impede BMD acquisition in adolescents.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
To ensure breast health and reduce the risk of venous thromboembolic events, drug makers have developed OCs with lower and lower doses of EE. In the process, however, the beneficial effects of endogenous estradiol on bone acquisition have been suppressed. Therefore, the lowest-dose OC may not necessarily be the most appropriate clinical choice for adolescents and young women seeking contraception.

Related Article: Osteoporosis treatment and breast cancer prevention: Two goals, one treatment? Robert L. Barbieri, MD (Editorial, November 2013)

EXPERIMENTAL DRUG REDUCES BONE RESORPTION WITHOUT IMPEDING BONE FORMATION

Brixen K, Chapurlat R, Cheung AM, et al. Bone density, turnover, and estimated strength in postmenopausal women treated with odanacatib: a randomized trial. J Clin Endocrinol Metab. 2013;98(2):571–580.

Current treatments for osteoporosis include antiresorptive agents, such as bisphosphonates and denosumab, that preserve bone mass by reducing the rate of bone turnover. These drugs reduce the number or activity (or both) of bone-resorbing osteoclasts. Because osteoclasts play a role in stimulating bone formation by osteoblasts, these treatments indirectly lower bone formation.

Odanacatib is a drug in Phase 3 development for the treatment of postmenopausal osteoporosis. It is a highly selective and reversible oral inhibitor of the collagenase activity of cathepsin K, which is secreted by osteoclasts. Odanacatib reduces bone resorption without reducing the number of osteoclasts and, thus, appears to preserve bone formation.

Details of the trial
Brixen and colleagues conducted a randomized, double-blind, international, 2-year, Phase 3 trial comparing odancatib 50 mg once weekly with placebo in postmenopausal women treated with calcium and vitamin D. The primary endpoint was the change from baseline BMD at the lumbar spine at 1 year, as assessed by DXA. Secondary endpoints included the change from baseline BMD at the hip (total hip, femoral neck, and trochanter) at 1 year, the change from baseline BMD at the spine and hip at 2 years, and 1- and 2-year changes in bone-turnover markers. A total of 214 women were enrolled (average age: 64 years; average T-score of 1.8 at the lumbar spine, –1.8 at the femoral neck, and –1.3 at the total hip).

At 1 year, the change from baseline BMD at the lumbar spine was significantly higher (P <.001) in women receiving odanacatib, compared with placebo (treatment difference: 3.5%). At 2 years, the treatment difference was even higher (5.4%). The mean changes in BMD at the femoral neck, total hip, and trochanter also were significantly greater (P <.001) in women receiving odanacatib, with treatment differences at 2 years of 3.8%, 3.3%, and 5.5%, respectively.

During the first 6 months of the trial, serum concentrations of bone-turnover markers (CTX and P1NP) decreased significantly (P <.001) in odanacatib-treated women, compared with those given placebo.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Although no new agents for the treatment of osteoporosis have been introduced over the past year, cathepsin K inhibitors appear to offer great promise for the future. As clinicians, we need to keep abreast of new developments that may be of potential value to our patients.

PILOT STUDY: TERIPARATIDE WAS EFFECTIVE IN 81% OF PREMENOPAUSAL WOMEN WITH IDIOPATHIC OSTEOPOROSIS

Cohen A, Stein EM, Recker RR, et al. Teriparatide for idiopathic osteoporosis in premenopausal women: A pilot study. J Clin Endocrinol Metab. 2013;98(5):1971–1981.

Idiopathic osteoporosis (IOP) affects young, otherwise healthy men and women with intact gonadal function and no secondary cause of bone loss or fragility. Women with IOP have abnormal bone microarchitecture with thinner cortices; fewer, thinner, and more widely separated and heterogeneously distributed trabeculae; more rod-like trabecular structures; less trabecular stiffness; and a higher level of marrow fat.

The osteoanabolic agent teriperatide increases BMD and reduces the incidence of fracture in postmenopausal women and in patients with glucocorticoid-induced osteoporosis, and it increases BMD in men with IOP. This study explored its effect in premenopausal women with IOP.

Details of the study
Cohen and colleagues recruited premenopausal women aged 20 to 48 years who had one or both of the following traits:

• a history of at least one low-trauma fracture more than 6 months before enrollment
• low BMD of the spine or hip (Z-score of –2.0 or below), as assessed by DXA.

All participants had regular menses and early follicular-phase follicle-stimulating hormone (FSH) levels below 20 mIU/mL; none were using hormonal contraception. Women who had secondary osteoporosis related to estrogen deficiency, an eating disorder, an endocrinopathy, celiac or gastrointestinal disease, hyperparathyroidism, marked hypercalciuria, a low serum level of 25-hydroxyvitamin D (<20 ng/mL), and drug exposures were excluded.

All participants (n = 21) received teriparatide 20 µg daily in the morning or evening, according to preference. They also were given calcium 630 mg and vitamin D 800 IU daily.

BMD increased at the spine by 10.8% (standard deviation: 8.3%), total hip by 6.2% (5.6%), and femoral neck by 7.6% (3.4%) (all P <.001). Transiliac biopsies demonstrated significant increases in cortical width and porosity, and trabecular bone volume and number increased as well. Four women had no increase in BMD.

Overall, Cohen and colleagues concluded that teriparatide was associated with increased BMD at the spine and hip and improved trabecular microarchitecture and stiffness at the iliac crest in the majority of women with IOP.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Although ObGyns rarely prescribe teriparatide, often leaving this option for metabolic bone experts to offer, we should keep premenopausal IOP in mind when younger patients sustain low-trauma fractures of the hip or vertebrae, as well as fracture of an upper or lower extremity or the ribs.
Teriparatide appears to be an excellent choice for the majority of premenopausal patients with IOP (81% of patients in this pilot study).

Because the low bone mass and deterioration of bone microarchitecture and quality that characterize osteoporosis can lead to fragility fracture, it is vital that we intervene in our patients’ health in a timely manner to reduce this risk. One way to accomplish this goal is to understand the role of age in determining a woman’s fracture risk. For example, an 80-year-old woman and a 50-year-old woman with a T-score of –2.5, as measured by dual x-ray absorptiometry (DXA), will have dramatically different fracture risks. According to the World Health Organization’s fracture-risk assessment tool (http://www.shef.ac.uk/FRAX/), the older woman has a 10-year probability of hip fracture approximately five times greater than the younger woman.

Although no new therapies have been approved during the past year, several important findings were published that affect clinical management of menopausal patients or suggest changes likely in the future.

In this article, I review:

• the latest guidance on osteoporosis from the American College of Obstetricians and Gynecologists (ACOG)
• the most recent indications for bone mineral density (BMD) testing from the International Society for Clinical Densitometry (ISCD)
• a study exploring the effect of oral hormonal contraception on the acquisition of peak BMD in adolescents and young women
• results of a randomized trial of the experimental agent odanacatib in postmenopausal women
• a pilot study of teriparatide (Forteo) for idiopathic osteoporosis in premenopausal women.

ACOG ISSUES RECOMMENDATIONS ON SCREENING, TREATMENT, AND LIFESTYLE

Committee on Practice Bulletins–Gynecology. ACOG Practice Bulletin #129: Osteoporosis. Obstet Gynecol. 2012;120(3):718–734.

This comprehensive review of management guidelines for ObGyns deserves “top billing” in this update. It offers recommendations on important interventions, from BMD measurement and subsequent monitoring to calcium and vitamin D supplementation.

When to initiate screening

• Begin BMD screening using DXA at age 65. DXA also may be appropriate for younger women if they are postmenopausal and have other significant risk factors for osteoporosis or fracture (Level A evidence – based on good and consistent scientific evidence).
• In the absence of new risk factors, do not perform DXA screening more frequently than every 2 years (Level B evidence – based on limited or inconsistent scientific evidence).

Which patients should be treated?
Treatment is recommended for:

• women with a T-score of –2.5 or lower
• women who have had a low-trauma ­fracture
• women with a T-score between –1 and –2.5 and a 10-year FRAX hip-fracture risk of 3% or higher or a 10-year FRAX risk of major osteoporotic fracture of 20% or higher, or both. A major osteoporotic fracture involves the forearm, hip, or shoulder, or a clinical vertebral fracture (Level A evidence).
  

Only therapies approved by the US FDA should be used for medical treatment. They are raloxifene (Evista), bisphosphonates (Actonel, Boniva, Fosamax, Reclast), parathyroid hormone, denosumab (Prolia), and calcitonin (Fortical, Miacalcin) (Level A evidence).

Monitoring of therapy
In the absence of new risk factors, do not repeat DXA monitoring of therapy once BMD has been determined to be stable or improved (Level B evidence).

Lifestyle recommendations

• Counsel women about lifestyle factors that may affect BMD and fracture risk, which include smoking, poor nutrition and excessive weight loss, weight-bearing and muscle-strengthening exercise, and fall prevention (Level B evidence).
• Advise patients of current recommendations for calcium and vitamin D intake from the Institute of Medicine, which are calcium 1,200 mg/day and vitamin D 600 IU/day for women aged 51 to 70 years (Level B evidence).
• Counsel girls and women of all ages about the effects of lifestyle on bone health (Level C evidence – based on consensus and expert opinion).

WHAT THIS EVIDENCE MEANS FOR PRACTICE
By utilizing the FRAX risk-assessment tool, we can determine which patients truly require treatment. In the process, we should be able to reduce the overtreatment of younger women with low bone mass as well as the undertreatment of older women who appear to have less deranged bone mass.
ACOG also emphasizes the need to avoid the overutilization of DXA scans in various groups, as well as the importance of lifestyle adjustments to promote bone health in all age groups.

Related Article: STOP performing DXA scans in healthy, perimenopausal women  Lisa Larkin, MD, and Andrew M. Kaunitz, MD (Stop/Start, Januaray 2013)

CLINICAL DENSITOMETRISTS WEIGH IN ON INDICATIONS FOR BMD ASSESSMENT

International Society for Clinical Densitometry (ISCD). Indications for bone mineral density (BMD) testing. http://www.iscd.org/official-positions/2013-iscd-official-positions-adult/. Updated August 15, 2013. Accessed November 7, 2013.

In its comprehensive review of BMD assessment, the ISCD elucidates the process, which typically involves DXA imaging.

Indications for BMD assessment

• The female patient is age 65 or older
• The postmenopausal patient is younger than age 65 but has a risk factor for low bone mass, such as low body weight, a history of fracture, use of a high-risk medication, or a disease or condition associated with bone loss
• The perimenopausal woman has clinical risk factors for fracture, such as low body weight, history of fracture, or use of a high-risk medication
• The adult sustains a fragility fracture
• The adult has a disease or condition associated with low bone mass or bone loss
• The adult is taking a medication associated with low bone mass or bone loss
• The patient is being considered for pharmacologic therapy
• The patient is being treated, to monitor effect
• The patient is not receiving therapy, but evidence of bone loss would lead to ­treatment.

When serial BMD assessment is appropriate

• When it is used to determine whether treatment should be initiated (in untreated patients) because of significant bone loss
• To monitor response to therapy by identifying an increase or stabilization of BMD
• To identify nonresponse by documenting a loss of BMD, suggesting the need for treatment re-evaluation and assessment for a secondary cause of osteoporosis
• To follow-up earlier assessment when the expected change in BMD equals or exceeds the least significant change
• When the interval is appropriate for the patient’s clinical status. (In general, BMD assessment is performed 1 year after initiation or change of therapy, with longer intervals once a therapeutic effect has been established.)
• When the patient is using a medication associated with rapid bone loss, such as glucocorticoid therapy. In such a patient, more frequent testing may be appropriate.
• Note that these recommendations differ slightly from ACOG’s statements regarding the use of DXA.

Diagnosis of osteoporosis

• According to the WHO international reference standard, osteoporosis can be diagnosed when a patient has a T-score of –2.5 or below at the femoral neck. The reference standard from which the T-score is calculated is the white female population aged 20 to 29 years in the National Health and Nutrition Examination Survey (NHANES) III database.
• Osteoporosis also may be diagnosed in postmenopausal women and men aged 50 or older when the T-score of the lumbar spine, total hip, or femoral neck is –2.5 or below. In some circumstances, the
  33% radius (also called the 1/3 radius) may be utilized.
• Other hip regions of interest, including Ward’s area and the greater trochanter, should not be used for diagnosis.

A move away from use of the term “osteopenia”

• The term may be retained, but “low bone mass” or “low bone density” is preferred
• People with low bone mass or low bone density do not necessarily have a high risk of fracture.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
DXA testing remains the cornerstone of diagnosis for patients at risk for fragility fracture. It also is the optimal method to determine the need for pharmacotherapy. In some instances, however, overutilization of DXA imaging has led to overtreatment, especially in younger women with low bone mass, when treatment is based on variables other than diminished bone quality (including, “small-boned” women, genetics, and failure to achieve peak bone mass as high as one’s peer group prior to menopause).
These recommendations help to clarify the rationale for follow-up DXA imaging for patients on therapy, an area in which scientific unanimity is lacking.

Related Article: What is the optimal interval for osteoporosis screening in postmenopausal women before fracture occurrence and osteoporosis treatment initiation? Steven R. Goldstein, MD (Examining the Evidence, August 2012)

IN ADOLESCENTS AND YOUNG WOMEN, CONSIDER THE BONE EFFECTS OF ORAL CONTRACEPTIVES

Ziglar S, Hunter TS. The effect of hormonal oral contraception on acquisition of peak bone mineral density of adolescents and young women. J Pharm Pract. 2012;25(3):331–340.

The bone loss observed in adolescents and young women who use depot medroxyprogesterone acetate (Depo-Provera) for contraception led to an FDA-mandated boxed warning on the medication’s package insert. The effect of oral contraceptives (OCs) on bone growth has received little publicity, however.

The best strategy to offset the natural loss of bone associated with aging and the menopausal transition is to ensure the development of maximal bone mass in youth. When maximal BMD is not achieved, the risk of osteoporosis is increased.

Adolescence is a critical period of bone mineralization, which is mediated by endo­genous estradiol. The highest rate of bone mass accrual occurs 1 year before and 3 years after menarche. Young women who consume a diet low in calcium or who have an eating disorder, who fail to exercise, who smoke, or who have low estrogen status are most likely to have low peak bone mass.

OCs suppress endogenous estradiol production by interrupting the hypothalamic-pituitary-ovarian axis. By replacing endogenous estradiol with ethinyl estradiol (EE), OCs establish and maintain new hormone levels. Early initiation and use of very-low-dose EE increases the likelihood that the accrual of bone mass will be jeopardized at a critical time of bone mineralization.

Details of this meta-analysis
Ziglar and Hunter reviewed 11 prospective trials that showed a decrease in bone mass in adolescents and young women who used low-dose OCs, six trials that showed a neutral effect, and one trial that found an increase in bone mass. This last study involved only members of the US military whose level of daily exercise may not be representative of the general population of women the same age. Investigators also theorized that the use of norethindrone acetate as an androgenic progestin in this study may have exerted a positive effect on bone accrual.

Ziglar and Hunter concluded that the use of OCs containing 20 µg EE prevents adolescents and young women from attaining peak BMD. Evidence on the effect of contraceptives formulated with 30 to 35 µg EE is less definitive, but this dose may also impede BMD acquisition in adolescents.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
To ensure breast health and reduce the risk of venous thromboembolic events, drug makers have developed OCs with lower and lower doses of EE. In the process, however, the beneficial effects of endogenous estradiol on bone acquisition have been suppressed. Therefore, the lowest-dose OC may not necessarily be the most appropriate clinical choice for adolescents and young women seeking contraception.

Related Article: Osteoporosis treatment and breast cancer prevention: Two goals, one treatment? Robert L. Barbieri, MD (Editorial, November 2013)

EXPERIMENTAL DRUG REDUCES BONE RESORPTION WITHOUT IMPEDING BONE FORMATION

Brixen K, Chapurlat R, Cheung AM, et al. Bone density, turnover, and estimated strength in postmenopausal women treated with odanacatib: a randomized trial. J Clin Endocrinol Metab. 2013;98(2):571–580.

Current treatments for osteoporosis include antiresorptive agents, such as bisphosphonates and denosumab, that preserve bone mass by reducing the rate of bone turnover. These drugs reduce the number or activity (or both) of bone-resorbing osteoclasts. Because osteoclasts play a role in stimulating bone formation by osteoblasts, these treatments indirectly lower bone formation.

Odanacatib is a drug in Phase 3 development for the treatment of postmenopausal osteoporosis. It is a highly selective and reversible oral inhibitor of the collagenase activity of cathepsin K, which is secreted by osteoclasts. Odanacatib reduces bone resorption without reducing the number of osteoclasts and, thus, appears to preserve bone formation.

Details of the trial
Brixen and colleagues conducted a randomized, double-blind, international, 2-year, Phase 3 trial comparing odancatib 50 mg once weekly with placebo in postmenopausal women treated with calcium and vitamin D. The primary endpoint was the change from baseline BMD at the lumbar spine at 1 year, as assessed by DXA. Secondary endpoints included the change from baseline BMD at the hip (total hip, femoral neck, and trochanter) at 1 year, the change from baseline BMD at the spine and hip at 2 years, and 1- and 2-year changes in bone-turnover markers. A total of 214 women were enrolled (average age: 64 years; average T-score of 1.8 at the lumbar spine, –1.8 at the femoral neck, and –1.3 at the total hip).

At 1 year, the change from baseline BMD at the lumbar spine was significantly higher (P <.001) in women receiving odanacatib, compared with placebo (treatment difference: 3.5%). At 2 years, the treatment difference was even higher (5.4%). The mean changes in BMD at the femoral neck, total hip, and trochanter also were significantly greater (P <.001) in women receiving odanacatib, with treatment differences at 2 years of 3.8%, 3.3%, and 5.5%, respectively.

During the first 6 months of the trial, serum concentrations of bone-turnover markers (CTX and P1NP) decreased significantly (P <.001) in odanacatib-treated women, compared with those given placebo.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Although no new agents for the treatment of osteoporosis have been introduced over the past year, cathepsin K inhibitors appear to offer great promise for the future. As clinicians, we need to keep abreast of new developments that may be of potential value to our patients.

PILOT STUDY: TERIPARATIDE WAS EFFECTIVE IN 81% OF PREMENOPAUSAL WOMEN WITH IDIOPATHIC OSTEOPOROSIS

Cohen A, Stein EM, Recker RR, et al. Teriparatide for idiopathic osteoporosis in premenopausal women: A pilot study. J Clin Endocrinol Metab. 2013;98(5):1971–1981.

Idiopathic osteoporosis (IOP) affects young, otherwise healthy men and women with intact gonadal function and no secondary cause of bone loss or fragility. Women with IOP have abnormal bone microarchitecture with thinner cortices; fewer, thinner, and more widely separated and heterogeneously distributed trabeculae; more rod-like trabecular structures; less trabecular stiffness; and a higher level of marrow fat.

The osteoanabolic agent teriperatide increases BMD and reduces the incidence of fracture in postmenopausal women and in patients with glucocorticoid-induced osteoporosis, and it increases BMD in men with IOP. This study explored its effect in premenopausal women with IOP.

Details of the study
Cohen and colleagues recruited premenopausal women aged 20 to 48 years who had one or both of the following traits:

• a history of at least one low-trauma fracture more than 6 months before enrollment
• low BMD of the spine or hip (Z-score of –2.0 or below), as assessed by DXA.

All participants had regular menses and early follicular-phase follicle-stimulating hormone (FSH) levels below 20 mIU/mL; none were using hormonal contraception. Women who had secondary osteoporosis related to estrogen deficiency, an eating disorder, an endocrinopathy, celiac or gastrointestinal disease, hyperparathyroidism, marked hypercalciuria, a low serum level of 25-hydroxyvitamin D (<20 ng/mL), and drug exposures were excluded.

All participants (n = 21) received teriparatide 20 µg daily in the morning or evening, according to preference. They also were given calcium 630 mg and vitamin D 800 IU daily.

BMD increased at the spine by 10.8% (standard deviation: 8.3%), total hip by 6.2% (5.6%), and femoral neck by 7.6% (3.4%) (all P <.001). Transiliac biopsies demonstrated significant increases in cortical width and porosity, and trabecular bone volume and number increased as well. Four women had no increase in BMD.

Overall, Cohen and colleagues concluded that teriparatide was associated with increased BMD at the spine and hip and improved trabecular microarchitecture and stiffness at the iliac crest in the majority of women with IOP.

WHAT THIS EVIDENCE MEANS FOR PRACTICE
Although ObGyns rarely prescribe teriparatide, often leaving this option for metabolic bone experts to offer, we should keep premenopausal IOP in mind when younger patients sustain low-trauma fractures of the hip or vertebrae, as well as fracture of an upper or lower extremity or the ribs.
Teriparatide appears to be an excellent choice for the majority of premenopausal patients with IOP (81% of patients in this pilot study).