Edward Onusko, MD

As family physicians, we’re accustomed to seeing patients shortly before they’re scheduled for surgery—in the office, the hospital, or other settings. But not all preoperative (preop) visits are created equal in terms of the level of care, the coding, and the documentation required. Test your knowledge:

1. A preop evaluation can be coded as a consultation visit if a request for the evaluation was initiated by:
   1. a surgeon.
   2. a patient or patient’s family member.
   3. physician self-referral.
   4. all of the above.
2. The best reason to code a preop evaluation as a consultation is:
   1. more accurate Current Procedural Terminology Evaluation and Management (CPT E/M) coding.
   2. more accurate diagnostic coding per the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) system.
   3. reimbursement is (usually) better.
   4. all of the above.
3. For outpatient consults for established patients, 2 out of the 3 key components of an encounter must be provided and documented.
   1. True.
   2. False.
4. The correct way to report the primary diagnosis for a preop consultation is to use:
   1. the ICD-9-CM code for the patient’s acute or chronic medical condition that will likely be a concern in the perioperative period (eg, diabetes mellitus, coronary artery disease).
   2. the ICD-9-CM code for the acute or chronic condition for which the patient requires surgery (eg, osteoarthritis for an elective joint replacement, or cholelithiasis for a laparoscopic cholecystectomy).
   3. V codes V72.81-V72.84 (preop exams).
   4. none of the above.
5. A comprehensive level of examination is required for:
   1. a level 4 office consultation.
   2. a level 3 inpatient consultation.
   3. a level 4 established patient office visit.
   4. none of the above.
6. Preop consultations conducted in the hospital setting should be coded using inpatient consultation codes.
   1. True.
   2. False.
   3. It depends.

QUESTION 1: When can a preop evaluation be coded as a consultation?

Answer: A When a surgeon requests the consult. Here’s why.

A consultation is defined as a type of service provided by a physician whose opinion or advice regarding evaluation and/or management of a specific problem is requested by another physician, or other appropriate source. In order to qualify as a consultation—CPT E/M codes 99241-99245 for outpatients and 99251-99255 for inpatients (TABLE 1)—the evaluation must be requested by any of the following:¹

• a physician
• physician assistant
• nurse practitioner
• chiropractor
• physical therapist
• occupational therapist
• speech-language pathologist
• psychologist
• social worker
• lawyer
• insurance company.

If the consultation is mandated by a third-party payer, use modifier -32 to report it.

If the preop encounter does not meet this requirement, use the customary E/M codes instead.

The physician providing the consult must clearly document the request from the surgeon or other source in the medical record.¹ Our office satisfies this requirement by using a form that is faxed to the surgeon’s office at the time the preop visit is scheduled. The surgeon completes and signs the form (sometimes with a little prodding from our office staff) and faxes it back. The signed form is affixed to the patient’s chart and available at the time of the consultation visit.

TABLE 1
Consultation codes: The right way to use them

QUESTION 2: Why should you code a preop evaluation as a consult?

Answer: D There are several reasons to code a preop evaluation performed at the request of a surgeon or other source as a consultation: Doing so offers more accurate E/M coding, more accurate diagnostic coding, and, in most cases, better reimbursement.

The preop evaluation is usually a consultation, sought by a surgeon, regarding the risks to the patient of undergoing the operative procedure and anesthesia, and strategies to provide optimal management of medical problems such as chronic obstructive pulmonary disease (COPD), diabetes mellitus, or asthma in the perioperative period. In general, consultation codes provide significantly better reimbursement than other comparable E/M codes.

For instance, the 2009 Medicare payment for a level 2 outpatient consultation (99242) in the Ohio region is $88.88. In contrast, the fee for a level 2 new patient visit (99202) is $61.71.

Include the 4 Ws: Who, why, what, and where. To bill for a consultation, however, you not only need to provide information about risks and management strategies to the clinician who requests it; you also have to clearly document that you did so. In providing the proper documentation, there are 4 aspects of the consult to consider:

1. Who requested the consult. As noted earlier, our practice requires a signed request from the surgeon for the medical record. (While a note documenting a verbal request would probably satisfy this requirement, a written request would provide much stronger evidence if an audit was done.)
2. Why the consult is being performed. Remember that a consult is initiated as a request for opinion or advice. If you are simply asked to manage a patient’s medical problems in the postoperative (postop) period, you should charge for concurrent management, not for a consultation.
3. What services you provided. Basically, this requirement simply calls for documenting your history, exam, assessment (opinion), and plan (advice). If you provide nonpreop care (such as medication refills or addressing unrelated medical issues) during the consult visit, you can bill separately for these services using modifier -25.
4. Where you sent the results of your evaluation. It is also necessary to document that you completed the loop by sending your report to the surgeon who requested the consultation. Often, I complete a handwritten consult on a history and physical (H&P) form at the request of the surgeon. I document in my note that a copy of the H&P form was faxed to the surgeon, another copy was put into the patient’s medical record in my office, and the original was given to the patient to give to the surgeon on the scheduled day of the procedure. (Electronic health records would accomplish the same thing without paper, of course.)

QUESTION 3: True or false: Outpatient consults for established patients require 2 components of an encounter.

Answer: B False. Unlike other outpatient E/M codes, the consultation codes require that all 3 components of an encounter—history, examination, and medical decision making—be provided and documented for the appropriate level of service for both new and established patients (TABLE 1).

All 3 must be included in an inpatient consultation as well.

QUESTION 4: What’s the primary diagnosis code for a preop consult?

Answer: C V codes for preop exams (V72.81-V72.84) should be used as the primary diagnosis. In general, V codes are used “on occasions when circumstances other than a disease or an injury justify an encounter with the health care delivery system or influence the patient’s current condition.”² The 4 allowable V codes for preoperative visits are:

• V72.81 (preop cardiovascular exam)
• V72.82 (preop respiratory exam)
• V72.83 (other specified preop exam)
• V72.84 (unspecified preop exam)

The acute or chronic medical condition for which the patient requires surgery should be listed as the secondary ICD-9-CM code.³ Additional codes may be used for the patient’s other acute or chronic medical conditions.

QUESTION 5: When is a comprehensive exam required?

Answer: A A level 4 (99244) office consult requires a comprehensive exam level; a level 3 (99253) inpatient consult does not.

The 1997 E/M guidelines⁴ specify that a level 4 office consult in which a general multisystem examination is conducted requires a comprehensive level—with documentation of 2 exam points from each of 9 systems (for a total of 18 points) and performance of all exam points in those 9 systems. The level 3 inpatient consult and level 4 established patient office visit codes require only a detailed exam, which entails documentation of 12 or more of the allowable exam points. Although the 1995 E/M guidelines can be used as a source to ensure that all the requirements are met, the 1997 guidelines are much more specific about the documentation needed for each exam level.

When to conduct a single-system exam. While family physicians frequently use the requirements of the general multisystem exam to determine their level of coding, the CPT rules allow the option of performing certain single-organ system exams. Because the cardiovascular system is the most common concern with a preop consult, it is often easier, and more appropriate, to document the elements of the cardiovascular system exam (TABLE 2) than the general multisystem exam.

In this instance, the V code (V72.81, preop cardiovascular exam) would be used for diagnosis. For patients with COPD or other respiratory problems, it would be appropriate to document the elements of the respiratory system exam (V72.82) instead (TABLE 3).

TABLE 2
The cardiovascular exam: What’s included*

TABLE 3
The respiratory exam: What’s included*

QUESTION 6: Should inpatient codes be used for preop consults in a hospital?

Answer: C It depends. While you’ll typically use inpatient codes, there are exceptions. Patients who are in the hospital but assigned to observation status, in the outpatient surgery area, or in the emergency department and not subsequently admitted, are considered outpatients. Thus, encounters with patients under such circumstances should be billed using outpatient codes.

What’s your score?

Give yourself 1 point for each question you answered correctly. If you scored 5 or better, you’re a coding genius. Please come to my office and help me run my practice!

If you scored 4 or lower, take the opportunity to learn more about coding. Go to http://www.cms.hhs.gov/MLNEdWebGuide, a Centers for Medicare and Medicaid Services site featuring downloadable publications, interactive tutorials, and other coding tools (click on “Documentation Guidelines for E&M Services”). The American Medical Association Web site is also a valuable source of E/M coding. At www.ama-assn.org/ama/pub/category/3113.html, you’ll find CPT/RVU Search, a free search engine you can use to learn more about the relative value unit system and review reimbursement rates for your geographic region.

Correspondence
Edward Onusko, MD, Clinton Memorial Hospital/University of Cincinnati Family Medicine Residency, 825 West Locust, Wilmington, OH 45123; edonusko@cmhregional.com

As family physicians, we’re accustomed to seeing patients shortly before they’re scheduled for surgery—in the office, the hospital, or other settings. But not all preoperative (preop) visits are created equal in terms of the level of care, the coding, and the documentation required. Test your knowledge:

1. A preop evaluation can be coded as a consultation visit if a request for the evaluation was initiated by:
   1. a surgeon.
   2. a patient or patient’s family member.
   3. physician self-referral.
   4. all of the above.
2. The best reason to code a preop evaluation as a consultation is:
   1. more accurate Current Procedural Terminology Evaluation and Management (CPT E/M) coding.
   2. more accurate diagnostic coding per the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) system.
   3. reimbursement is (usually) better.
   4. all of the above.
3. For outpatient consults for established patients, 2 out of the 3 key components of an encounter must be provided and documented.
   1. True.
   2. False.
4. The correct way to report the primary diagnosis for a preop consultation is to use:
   1. the ICD-9-CM code for the patient’s acute or chronic medical condition that will likely be a concern in the perioperative period (eg, diabetes mellitus, coronary artery disease).
   2. the ICD-9-CM code for the acute or chronic condition for which the patient requires surgery (eg, osteoarthritis for an elective joint replacement, or cholelithiasis for a laparoscopic cholecystectomy).
   3. V codes V72.81-V72.84 (preop exams).
   4. none of the above.
5. A comprehensive level of examination is required for:
   1. a level 4 office consultation.
   2. a level 3 inpatient consultation.
   3. a level 4 established patient office visit.
   4. none of the above.
6. Preop consultations conducted in the hospital setting should be coded using inpatient consultation codes.
   1. True.
   2. False.
   3. It depends.

QUESTION 1: When can a preop evaluation be coded as a consultation?

Answer: A When a surgeon requests the consult. Here’s why.

A consultation is defined as a type of service provided by a physician whose opinion or advice regarding evaluation and/or management of a specific problem is requested by another physician, or other appropriate source. In order to qualify as a consultation—CPT E/M codes 99241-99245 for outpatients and 99251-99255 for inpatients (TABLE 1)—the evaluation must be requested by any of the following:¹

• a physician
• physician assistant
• nurse practitioner
• chiropractor
• physical therapist
• occupational therapist
• speech-language pathologist
• psychologist
• social worker
• lawyer
• insurance company.

If the consultation is mandated by a third-party payer, use modifier -32 to report it.

If the preop encounter does not meet this requirement, use the customary E/M codes instead.

The physician providing the consult must clearly document the request from the surgeon or other source in the medical record.¹ Our office satisfies this requirement by using a form that is faxed to the surgeon’s office at the time the preop visit is scheduled. The surgeon completes and signs the form (sometimes with a little prodding from our office staff) and faxes it back. The signed form is affixed to the patient’s chart and available at the time of the consultation visit.

TABLE 1
Consultation codes: The right way to use them

QUESTION 2: Why should you code a preop evaluation as a consult?

Answer: D There are several reasons to code a preop evaluation performed at the request of a surgeon or other source as a consultation: Doing so offers more accurate E/M coding, more accurate diagnostic coding, and, in most cases, better reimbursement.

The preop evaluation is usually a consultation, sought by a surgeon, regarding the risks to the patient of undergoing the operative procedure and anesthesia, and strategies to provide optimal management of medical problems such as chronic obstructive pulmonary disease (COPD), diabetes mellitus, or asthma in the perioperative period. In general, consultation codes provide significantly better reimbursement than other comparable E/M codes.

For instance, the 2009 Medicare payment for a level 2 outpatient consultation (99242) in the Ohio region is $88.88. In contrast, the fee for a level 2 new patient visit (99202) is $61.71.

Include the 4 Ws: Who, why, what, and where. To bill for a consultation, however, you not only need to provide information about risks and management strategies to the clinician who requests it; you also have to clearly document that you did so. In providing the proper documentation, there are 4 aspects of the consult to consider:

1. Who requested the consult. As noted earlier, our practice requires a signed request from the surgeon for the medical record. (While a note documenting a verbal request would probably satisfy this requirement, a written request would provide much stronger evidence if an audit was done.)
2. Why the consult is being performed. Remember that a consult is initiated as a request for opinion or advice. If you are simply asked to manage a patient’s medical problems in the postoperative (postop) period, you should charge for concurrent management, not for a consultation.
3. What services you provided. Basically, this requirement simply calls for documenting your history, exam, assessment (opinion), and plan (advice). If you provide nonpreop care (such as medication refills or addressing unrelated medical issues) during the consult visit, you can bill separately for these services using modifier -25.
4. Where you sent the results of your evaluation. It is also necessary to document that you completed the loop by sending your report to the surgeon who requested the consultation. Often, I complete a handwritten consult on a history and physical (H&P) form at the request of the surgeon. I document in my note that a copy of the H&P form was faxed to the surgeon, another copy was put into the patient’s medical record in my office, and the original was given to the patient to give to the surgeon on the scheduled day of the procedure. (Electronic health records would accomplish the same thing without paper, of course.)

QUESTION 3: True or false: Outpatient consults for established patients require 2 components of an encounter.

Answer: B False. Unlike other outpatient E/M codes, the consultation codes require that all 3 components of an encounter—history, examination, and medical decision making—be provided and documented for the appropriate level of service for both new and established patients (TABLE 1).

All 3 must be included in an inpatient consultation as well.

QUESTION 4: What’s the primary diagnosis code for a preop consult?

Answer: C V codes for preop exams (V72.81-V72.84) should be used as the primary diagnosis. In general, V codes are used “on occasions when circumstances other than a disease or an injury justify an encounter with the health care delivery system or influence the patient’s current condition.”² The 4 allowable V codes for preoperative visits are:

• V72.81 (preop cardiovascular exam)
• V72.82 (preop respiratory exam)
• V72.83 (other specified preop exam)
• V72.84 (unspecified preop exam)

The acute or chronic medical condition for which the patient requires surgery should be listed as the secondary ICD-9-CM code.³ Additional codes may be used for the patient’s other acute or chronic medical conditions.

QUESTION 5: When is a comprehensive exam required?

Answer: A A level 4 (99244) office consult requires a comprehensive exam level; a level 3 (99253) inpatient consult does not.

The 1997 E/M guidelines⁴ specify that a level 4 office consult in which a general multisystem examination is conducted requires a comprehensive level—with documentation of 2 exam points from each of 9 systems (for a total of 18 points) and performance of all exam points in those 9 systems. The level 3 inpatient consult and level 4 established patient office visit codes require only a detailed exam, which entails documentation of 12 or more of the allowable exam points. Although the 1995 E/M guidelines can be used as a source to ensure that all the requirements are met, the 1997 guidelines are much more specific about the documentation needed for each exam level.

When to conduct a single-system exam. While family physicians frequently use the requirements of the general multisystem exam to determine their level of coding, the CPT rules allow the option of performing certain single-organ system exams. Because the cardiovascular system is the most common concern with a preop consult, it is often easier, and more appropriate, to document the elements of the cardiovascular system exam (TABLE 2) than the general multisystem exam.

In this instance, the V code (V72.81, preop cardiovascular exam) would be used for diagnosis. For patients with COPD or other respiratory problems, it would be appropriate to document the elements of the respiratory system exam (V72.82) instead (TABLE 3).

TABLE 2
The cardiovascular exam: What’s included*

TABLE 3
The respiratory exam: What’s included*

QUESTION 6: Should inpatient codes be used for preop consults in a hospital?

Answer: C It depends. While you’ll typically use inpatient codes, there are exceptions. Patients who are in the hospital but assigned to observation status, in the outpatient surgery area, or in the emergency department and not subsequently admitted, are considered outpatients. Thus, encounters with patients under such circumstances should be billed using outpatient codes.

What’s your score?

Give yourself 1 point for each question you answered correctly. If you scored 5 or better, you’re a coding genius. Please come to my office and help me run my practice!

If you scored 4 or lower, take the opportunity to learn more about coding. Go to http://www.cms.hhs.gov/MLNEdWebGuide, a Centers for Medicare and Medicaid Services site featuring downloadable publications, interactive tutorials, and other coding tools (click on “Documentation Guidelines for E&M Services”). The American Medical Association Web site is also a valuable source of E/M coding. At www.ama-assn.org/ama/pub/category/3113.html, you’ll find CPT/RVU Search, a free search engine you can use to learn more about the relative value unit system and review reimbursement rates for your geographic region.

Correspondence
Edward Onusko, MD, Clinton Memorial Hospital/University of Cincinnati Family Medicine Residency, 825 West Locust, Wilmington, OH 45123; edonusko@cmhregional.com

As family physicians, we’re accustomed to seeing patients shortly before they’re scheduled for surgery—in the office, the hospital, or other settings. But not all preoperative (preop) visits are created equal in terms of the level of care, the coding, and the documentation required. Test your knowledge:

1. A preop evaluation can be coded as a consultation visit if a request for the evaluation was initiated by:
   1. a surgeon.
   2. a patient or patient’s family member.
   3. physician self-referral.
   4. all of the above.
2. The best reason to code a preop evaluation as a consultation is:
   1. more accurate Current Procedural Terminology Evaluation and Management (CPT E/M) coding.
   2. more accurate diagnostic coding per the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) system.
   3. reimbursement is (usually) better.
   4. all of the above.
3. For outpatient consults for established patients, 2 out of the 3 key components of an encounter must be provided and documented.
   1. True.
   2. False.
4. The correct way to report the primary diagnosis for a preop consultation is to use:
   1. the ICD-9-CM code for the patient’s acute or chronic medical condition that will likely be a concern in the perioperative period (eg, diabetes mellitus, coronary artery disease).
   2. the ICD-9-CM code for the acute or chronic condition for which the patient requires surgery (eg, osteoarthritis for an elective joint replacement, or cholelithiasis for a laparoscopic cholecystectomy).
   3. V codes V72.81-V72.84 (preop exams).
   4. none of the above.
5. A comprehensive level of examination is required for:
   1. a level 4 office consultation.
   2. a level 3 inpatient consultation.
   3. a level 4 established patient office visit.
   4. none of the above.
6. Preop consultations conducted in the hospital setting should be coded using inpatient consultation codes.
   1. True.
   2. False.
   3. It depends.

QUESTION 1: When can a preop evaluation be coded as a consultation?

Answer: A When a surgeon requests the consult. Here’s why.

A consultation is defined as a type of service provided by a physician whose opinion or advice regarding evaluation and/or management of a specific problem is requested by another physician, or other appropriate source. In order to qualify as a consultation—CPT E/M codes 99241-99245 for outpatients and 99251-99255 for inpatients (TABLE 1)—the evaluation must be requested by any of the following:¹

• a physician
• physician assistant
• nurse practitioner
• chiropractor
• physical therapist
• occupational therapist
• speech-language pathologist
• psychologist
• social worker
• lawyer
• insurance company.

If the consultation is mandated by a third-party payer, use modifier -32 to report it.

If the preop encounter does not meet this requirement, use the customary E/M codes instead.

The physician providing the consult must clearly document the request from the surgeon or other source in the medical record.¹ Our office satisfies this requirement by using a form that is faxed to the surgeon’s office at the time the preop visit is scheduled. The surgeon completes and signs the form (sometimes with a little prodding from our office staff) and faxes it back. The signed form is affixed to the patient’s chart and available at the time of the consultation visit.

TABLE 1
Consultation codes: The right way to use them

QUESTION 2: Why should you code a preop evaluation as a consult?

Answer: D There are several reasons to code a preop evaluation performed at the request of a surgeon or other source as a consultation: Doing so offers more accurate E/M coding, more accurate diagnostic coding, and, in most cases, better reimbursement.

The preop evaluation is usually a consultation, sought by a surgeon, regarding the risks to the patient of undergoing the operative procedure and anesthesia, and strategies to provide optimal management of medical problems such as chronic obstructive pulmonary disease (COPD), diabetes mellitus, or asthma in the perioperative period. In general, consultation codes provide significantly better reimbursement than other comparable E/M codes.

For instance, the 2009 Medicare payment for a level 2 outpatient consultation (99242) in the Ohio region is $88.88. In contrast, the fee for a level 2 new patient visit (99202) is $61.71.

Include the 4 Ws: Who, why, what, and where. To bill for a consultation, however, you not only need to provide information about risks and management strategies to the clinician who requests it; you also have to clearly document that you did so. In providing the proper documentation, there are 4 aspects of the consult to consider:

1. Who requested the consult. As noted earlier, our practice requires a signed request from the surgeon for the medical record. (While a note documenting a verbal request would probably satisfy this requirement, a written request would provide much stronger evidence if an audit was done.)
2. Why the consult is being performed. Remember that a consult is initiated as a request for opinion or advice. If you are simply asked to manage a patient’s medical problems in the postoperative (postop) period, you should charge for concurrent management, not for a consultation.
3. What services you provided. Basically, this requirement simply calls for documenting your history, exam, assessment (opinion), and plan (advice). If you provide nonpreop care (such as medication refills or addressing unrelated medical issues) during the consult visit, you can bill separately for these services using modifier -25.
4. Where you sent the results of your evaluation. It is also necessary to document that you completed the loop by sending your report to the surgeon who requested the consultation. Often, I complete a handwritten consult on a history and physical (H&P) form at the request of the surgeon. I document in my note that a copy of the H&P form was faxed to the surgeon, another copy was put into the patient’s medical record in my office, and the original was given to the patient to give to the surgeon on the scheduled day of the procedure. (Electronic health records would accomplish the same thing without paper, of course.)

QUESTION 3: True or false: Outpatient consults for established patients require 2 components of an encounter.

Answer: B False. Unlike other outpatient E/M codes, the consultation codes require that all 3 components of an encounter—history, examination, and medical decision making—be provided and documented for the appropriate level of service for both new and established patients (TABLE 1).

All 3 must be included in an inpatient consultation as well.

QUESTION 4: What’s the primary diagnosis code for a preop consult?

Answer: C V codes for preop exams (V72.81-V72.84) should be used as the primary diagnosis. In general, V codes are used “on occasions when circumstances other than a disease or an injury justify an encounter with the health care delivery system or influence the patient’s current condition.”² The 4 allowable V codes for preoperative visits are:

• V72.81 (preop cardiovascular exam)
• V72.82 (preop respiratory exam)
• V72.83 (other specified preop exam)
• V72.84 (unspecified preop exam)

The acute or chronic medical condition for which the patient requires surgery should be listed as the secondary ICD-9-CM code.³ Additional codes may be used for the patient’s other acute or chronic medical conditions.

QUESTION 5: When is a comprehensive exam required?

Answer: A A level 4 (99244) office consult requires a comprehensive exam level; a level 3 (99253) inpatient consult does not.

The 1997 E/M guidelines⁴ specify that a level 4 office consult in which a general multisystem examination is conducted requires a comprehensive level—with documentation of 2 exam points from each of 9 systems (for a total of 18 points) and performance of all exam points in those 9 systems. The level 3 inpatient consult and level 4 established patient office visit codes require only a detailed exam, which entails documentation of 12 or more of the allowable exam points. Although the 1995 E/M guidelines can be used as a source to ensure that all the requirements are met, the 1997 guidelines are much more specific about the documentation needed for each exam level.

When to conduct a single-system exam. While family physicians frequently use the requirements of the general multisystem exam to determine their level of coding, the CPT rules allow the option of performing certain single-organ system exams. Because the cardiovascular system is the most common concern with a preop consult, it is often easier, and more appropriate, to document the elements of the cardiovascular system exam (TABLE 2) than the general multisystem exam.

In this instance, the V code (V72.81, preop cardiovascular exam) would be used for diagnosis. For patients with COPD or other respiratory problems, it would be appropriate to document the elements of the respiratory system exam (V72.82) instead (TABLE 3).

TABLE 2
The cardiovascular exam: What’s included*

TABLE 3
The respiratory exam: What’s included*

QUESTION 6: Should inpatient codes be used for preop consults in a hospital?

Answer: C It depends. While you’ll typically use inpatient codes, there are exceptions. Patients who are in the hospital but assigned to observation status, in the outpatient surgery area, or in the emergency department and not subsequently admitted, are considered outpatients. Thus, encounters with patients under such circumstances should be billed using outpatient codes.

What’s your score?

Give yourself 1 point for each question you answered correctly. If you scored 5 or better, you’re a coding genius. Please come to my office and help me run my practice!

If you scored 4 or lower, take the opportunity to learn more about coding. Go to http://www.cms.hhs.gov/MLNEdWebGuide, a Centers for Medicare and Medicaid Services site featuring downloadable publications, interactive tutorials, and other coding tools (click on “Documentation Guidelines for E&M Services”). The American Medical Association Web site is also a valuable source of E/M coding. At www.ama-assn.org/ama/pub/category/3113.html, you’ll find CPT/RVU Search, a free search engine you can use to learn more about the relative value unit system and review reimbursement rates for your geographic region.

Correspondence
Edward Onusko, MD, Clinton Memorial Hospital/University of Cincinnati Family Medicine Residency, 825 West Locust, Wilmington, OH 45123; edonusko@cmhregional.com

Are we more aggressive than ever when it comes to our use of statins? You bet.

Should this prompt a heightened attention to hepatic safety? In a word, no. The more detailed, evidence-based answer (which follows) makes 2 things clear:

1. Clinically significant hepatic injury following statin use is very rare.

2. While US Food and Drug Administration (FDA) labeling recommends routine monitoring of serum transaminase levels prior to and during statin therapy, the evidence suggests that such routine monitoring is not clinically necessary.

More potent statins, more combination therapy

Our prescribing has become more aggressive to keep pace with National Cholesterol Education Program (NCEP) recommendations. In 2001, the NCEP Adult Treatment Panel III indicated:

• LDL cholesterol should be the primary target of therapy.
• The LDL cholesterol goal should be based on the patient’s risk of cardiovascular disease.
• Statins are the most effective agents to achieve treatment goals.¹

Three years later, the NCEP advised that in light of more recent clinical trials, even more aggressive (ie, lower) LDL goals should be considered for patients at very high risk, high risk, and moderately high risk for cardiovascular disease.²

As a result, we are prescribing higher doses of statins, more potent statins, and more combination therapies of statins with other lipid-altering agents. Not surprisingly, this trend has prompted concerns about the potential increase in toxicities/side effects of statins.

This review examines the hepatic safety profile of statins and details why there’s no need to stop treatment based on moderate elevations in liver function tests. The most common serious side effect of statins—muscle damage/rhabdomyolysis—is rare, and is not extensively discussed here.

Clinical trials: Risk is small

A review of 35 randomized clinical statin trials reported from 1966 to 2005, involving 74,102 patients, reported an absolute risk of transaminase (also referred to as aminotransferase) elevations from statin therapy of only about 4 per 1000 patients (risk difference [RD]=4.2; 95% confidence interval [CI], 1.5-6.9).³ The same researchers’ analysis of 28 clinical trials involving 62,184 patients showed a relative risk of increased transaminase of 1.3 (95% CI, 1.06-1.59), achieving statistical significance only for the fluvastatin and lovastatin trials.³

High-dose statin therapy. A review of clinical trials involving high-dose statin therapy found rates of hepatic enzyme elevation (defined as ALT or AST >3 times the ULN on 2 or more consecutive occasions) to be quite low (<1.3%).⁴ Higher statin doses were more likely to increase enzyme levels, though reduction in the dose or withdrawal of the statin resulted in normalization of the liver enzymes.

A study of patients ages 65 to 85 years who were treated with high-dose atorvastatin (80 mg per day) vs moderate dose pravastatin (40 mg per day) resulted in only 11 of 893 (1.23%) patients discontinuing the drug following abnormal liver function tests; most of these were in the high-dose treatment arm.⁵

Small risk in clinical practice, too

Clinical trials often have lower rates of adverse effects from medications than are seen in usual clinical practice.⁶ This may be because the stringent application of patient selection and exclusion criteria used in the administration of clinical trials does not occur in the “real world.”

However, the FDA database reported only 0.69 cases of hepatitis/liver failure per million statin prescriptions through 2004.⁴ A retrospective review of 1194 patients treated with a statin showed that 85% (1014) of patients had at least 1 monitoring test of transaminases performed during the year of the study. Of these, 10 (1.0%) had a significant elevation and 5 (0.5%) had a moderate elevation of transaminases. A review of the patient records demonstrated that none of these abnormalities appeared to be related to the use of statins, suggesting that routine monitoring of transaminases with statin therapy is not clinically necessary.⁷

A retrospective review over a 5-year period of 23,000 patients receiving statins in a large health maintenance organization found that only 17 (0.1%) patients had severe elevations of ALT (defined as >10 times the ULN). Of those 17 patients, 13 cases were associated with drug-drug interactions, and all but 1 resolved with discontinuation of the statin.⁸

What to monitor, how often

Product labeling for all statins advises measurement of transaminases (AST as well as ALT), although some liver experts would recommend ALT alone. ALT is found primarily in the liver, while AST is also found in muscle (cardiac and skeletal), kidneys, brain, pancreas, lungs, leukocytes, and erythrocytes. AST is, therefore, less specific for hepatic damage than ALT.

Routine monitoring of other liver function tests that measure the liver’s transport ability (eg, bilirubin, alkaline phosphate) or synthetic ability (eg, albumin, prothrombin time) will increase the likelihood of false-positive results and increase expense; they should not be done.

The 2002 American Gastroenterological Association guidelines recommend that for any hepatotoxic drug, if the ALT and/or AST elevations are <5 times the ULN, the drug should be stopped and the enzymes rechecked after an appropriate interval before pursuing a more extensive evaluation for liver disease.⁹

The FDA labeling information for all statins recommends liver function testing before putting a patient on a statin, 12 weeks after initiation, at any dose increase, and “periodically” for long-term maintenance therapy (TABLE 1).¹⁰ These recommendations are based on expert opinion only, because most data suggest that significant liver damage from statins is very rare and that routine monitoring of liver enzymes is not necessary.

The ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins agrees with the FDA, although it specifies “periodically” to mean annually.¹¹

TABLE 1
When to monitor liver function in patients taking statins^10,11

It’s difficult to predict hepatic effects

Individual statins vary as to potency, efficacy, metabolism, and drug interactions. However, the exact mechanism of how statins cause elevations of ALT and AST is unknown, making it difficult to predict the hepatic effects of an individual statin based on its characteristics.

One analysis of multiple clinical trials concluded that overall statin toxicity (muscle, liver, etc.) was not directly related to the degree of lowering LDL cholesterol; instead, it correlated with the dose of the statin.¹² As seen in TABLE 2, statins have variable drug-drug interactions based on their metabolism by the cytochrome P450 system. Drugs that increase the level of a statin in the blood may potentially increase the risk for toxicity and may warrant more cautious monitoring of liver enzymes, but are not necessarily contraindications to statin therapy.

Cyclosporine, macrolide antibiotics, azole antifungal agents, and other cytochrome P450 inhibitors (TABLE 2) are among the relative contraindications to the use of statins, more for concerns about myopathy than hepatoxicity.¹ If these medications are used with a statin, consider more frequent monitoring of transaminases.

TABLE 2
Statin snapshot: LDL reductions to expect, interactions to avoid

Discontinue the statin?

ACC/AHA/NHLBI recommendations indicate that you should discontinue (or lower the dose of) statin therapy if the ALT or AST are above 3 times the ULN on 2 consecutive occasions.¹¹ When elevations of ALT or AST are <3 times the ULN, consider the following:

• Statins have rigorously proven benefits for preventing morbidity and mortality due to atherosclerotic cardiovascular disease. A meta-analysis of more than 70,000 patients concluded that the number needed to treat to prevent 1 cardiovascular event was 27 and the number needed to harm (NNH) was 197. For more serious events such as creatine kinase >10 times the ULN, the NNH was 3400. Rhabdomyolysis alone was rare with a NNH of 7428.⁴
• Other medications that lower LDL and might be substituted for statins may not improve morbidity and mortality. For example, a recent clinical trial of ezetimibe (Zetia) reminds clinicians to be cautious in assuming that treatments that improve biochemical parameters such as LDL will necessarily result in improved clinical outcomes.¹³
• Mild elevations of ALT or AST (<3 times the ULN) following statin therapy are not known to lead to any significant liver toxicity over time.
• To date, there are no randomized controlled trials evaluating the optimal management of liver enzyme elevations with statin therapy.

Correspondence
Edward Onusko, MD, Family Health Center, 825 W. Locust, Wilmington, OH 45177; edonusko@cmhregional.com.

Are we more aggressive than ever when it comes to our use of statins? You bet.

Should this prompt a heightened attention to hepatic safety? In a word, no. The more detailed, evidence-based answer (which follows) makes 2 things clear:

1. Clinically significant hepatic injury following statin use is very rare.

2. While US Food and Drug Administration (FDA) labeling recommends routine monitoring of serum transaminase levels prior to and during statin therapy, the evidence suggests that such routine monitoring is not clinically necessary.

More potent statins, more combination therapy

Our prescribing has become more aggressive to keep pace with National Cholesterol Education Program (NCEP) recommendations. In 2001, the NCEP Adult Treatment Panel III indicated:

• LDL cholesterol should be the primary target of therapy.
• The LDL cholesterol goal should be based on the patient’s risk of cardiovascular disease.
• Statins are the most effective agents to achieve treatment goals.¹

Three years later, the NCEP advised that in light of more recent clinical trials, even more aggressive (ie, lower) LDL goals should be considered for patients at very high risk, high risk, and moderately high risk for cardiovascular disease.²

As a result, we are prescribing higher doses of statins, more potent statins, and more combination therapies of statins with other lipid-altering agents. Not surprisingly, this trend has prompted concerns about the potential increase in toxicities/side effects of statins.

This review examines the hepatic safety profile of statins and details why there’s no need to stop treatment based on moderate elevations in liver function tests. The most common serious side effect of statins—muscle damage/rhabdomyolysis—is rare, and is not extensively discussed here.

Clinical trials: Risk is small

A review of 35 randomized clinical statin trials reported from 1966 to 2005, involving 74,102 patients, reported an absolute risk of transaminase (also referred to as aminotransferase) elevations from statin therapy of only about 4 per 1000 patients (risk difference [RD]=4.2; 95% confidence interval [CI], 1.5-6.9).³ The same researchers’ analysis of 28 clinical trials involving 62,184 patients showed a relative risk of increased transaminase of 1.3 (95% CI, 1.06-1.59), achieving statistical significance only for the fluvastatin and lovastatin trials.³

High-dose statin therapy. A review of clinical trials involving high-dose statin therapy found rates of hepatic enzyme elevation (defined as ALT or AST >3 times the ULN on 2 or more consecutive occasions) to be quite low (<1.3%).⁴ Higher statin doses were more likely to increase enzyme levels, though reduction in the dose or withdrawal of the statin resulted in normalization of the liver enzymes.

A study of patients ages 65 to 85 years who were treated with high-dose atorvastatin (80 mg per day) vs moderate dose pravastatin (40 mg per day) resulted in only 11 of 893 (1.23%) patients discontinuing the drug following abnormal liver function tests; most of these were in the high-dose treatment arm.⁵

Small risk in clinical practice, too

Clinical trials often have lower rates of adverse effects from medications than are seen in usual clinical practice.⁶ This may be because the stringent application of patient selection and exclusion criteria used in the administration of clinical trials does not occur in the “real world.”

However, the FDA database reported only 0.69 cases of hepatitis/liver failure per million statin prescriptions through 2004.⁴ A retrospective review of 1194 patients treated with a statin showed that 85% (1014) of patients had at least 1 monitoring test of transaminases performed during the year of the study. Of these, 10 (1.0%) had a significant elevation and 5 (0.5%) had a moderate elevation of transaminases. A review of the patient records demonstrated that none of these abnormalities appeared to be related to the use of statins, suggesting that routine monitoring of transaminases with statin therapy is not clinically necessary.⁷

A retrospective review over a 5-year period of 23,000 patients receiving statins in a large health maintenance organization found that only 17 (0.1%) patients had severe elevations of ALT (defined as >10 times the ULN). Of those 17 patients, 13 cases were associated with drug-drug interactions, and all but 1 resolved with discontinuation of the statin.⁸

What to monitor, how often

Product labeling for all statins advises measurement of transaminases (AST as well as ALT), although some liver experts would recommend ALT alone. ALT is found primarily in the liver, while AST is also found in muscle (cardiac and skeletal), kidneys, brain, pancreas, lungs, leukocytes, and erythrocytes. AST is, therefore, less specific for hepatic damage than ALT.

Routine monitoring of other liver function tests that measure the liver’s transport ability (eg, bilirubin, alkaline phosphate) or synthetic ability (eg, albumin, prothrombin time) will increase the likelihood of false-positive results and increase expense; they should not be done.

The 2002 American Gastroenterological Association guidelines recommend that for any hepatotoxic drug, if the ALT and/or AST elevations are <5 times the ULN, the drug should be stopped and the enzymes rechecked after an appropriate interval before pursuing a more extensive evaluation for liver disease.⁹

The FDA labeling information for all statins recommends liver function testing before putting a patient on a statin, 12 weeks after initiation, at any dose increase, and “periodically” for long-term maintenance therapy (TABLE 1).¹⁰ These recommendations are based on expert opinion only, because most data suggest that significant liver damage from statins is very rare and that routine monitoring of liver enzymes is not necessary.

The ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins agrees with the FDA, although it specifies “periodically” to mean annually.¹¹

TABLE 1
When to monitor liver function in patients taking statins^10,11

It’s difficult to predict hepatic effects

Individual statins vary as to potency, efficacy, metabolism, and drug interactions. However, the exact mechanism of how statins cause elevations of ALT and AST is unknown, making it difficult to predict the hepatic effects of an individual statin based on its characteristics.

One analysis of multiple clinical trials concluded that overall statin toxicity (muscle, liver, etc.) was not directly related to the degree of lowering LDL cholesterol; instead, it correlated with the dose of the statin.¹² As seen in TABLE 2, statins have variable drug-drug interactions based on their metabolism by the cytochrome P450 system. Drugs that increase the level of a statin in the blood may potentially increase the risk for toxicity and may warrant more cautious monitoring of liver enzymes, but are not necessarily contraindications to statin therapy.

Cyclosporine, macrolide antibiotics, azole antifungal agents, and other cytochrome P450 inhibitors (TABLE 2) are among the relative contraindications to the use of statins, more for concerns about myopathy than hepatoxicity.¹ If these medications are used with a statin, consider more frequent monitoring of transaminases.

TABLE 2
Statin snapshot: LDL reductions to expect, interactions to avoid

Discontinue the statin?

ACC/AHA/NHLBI recommendations indicate that you should discontinue (or lower the dose of) statin therapy if the ALT or AST are above 3 times the ULN on 2 consecutive occasions.¹¹ When elevations of ALT or AST are <3 times the ULN, consider the following:

• Statins have rigorously proven benefits for preventing morbidity and mortality due to atherosclerotic cardiovascular disease. A meta-analysis of more than 70,000 patients concluded that the number needed to treat to prevent 1 cardiovascular event was 27 and the number needed to harm (NNH) was 197. For more serious events such as creatine kinase >10 times the ULN, the NNH was 3400. Rhabdomyolysis alone was rare with a NNH of 7428.⁴
• Other medications that lower LDL and might be substituted for statins may not improve morbidity and mortality. For example, a recent clinical trial of ezetimibe (Zetia) reminds clinicians to be cautious in assuming that treatments that improve biochemical parameters such as LDL will necessarily result in improved clinical outcomes.¹³
• Mild elevations of ALT or AST (<3 times the ULN) following statin therapy are not known to lead to any significant liver toxicity over time.
• To date, there are no randomized controlled trials evaluating the optimal management of liver enzyme elevations with statin therapy.

Correspondence
Edward Onusko, MD, Family Health Center, 825 W. Locust, Wilmington, OH 45177; edonusko@cmhregional.com.

Are we more aggressive than ever when it comes to our use of statins? You bet.

Should this prompt a heightened attention to hepatic safety? In a word, no. The more detailed, evidence-based answer (which follows) makes 2 things clear:

1. Clinically significant hepatic injury following statin use is very rare.

2. While US Food and Drug Administration (FDA) labeling recommends routine monitoring of serum transaminase levels prior to and during statin therapy, the evidence suggests that such routine monitoring is not clinically necessary.

More potent statins, more combination therapy

Our prescribing has become more aggressive to keep pace with National Cholesterol Education Program (NCEP) recommendations. In 2001, the NCEP Adult Treatment Panel III indicated:

• LDL cholesterol should be the primary target of therapy.
• The LDL cholesterol goal should be based on the patient’s risk of cardiovascular disease.
• Statins are the most effective agents to achieve treatment goals.¹

Three years later, the NCEP advised that in light of more recent clinical trials, even more aggressive (ie, lower) LDL goals should be considered for patients at very high risk, high risk, and moderately high risk for cardiovascular disease.²

As a result, we are prescribing higher doses of statins, more potent statins, and more combination therapies of statins with other lipid-altering agents. Not surprisingly, this trend has prompted concerns about the potential increase in toxicities/side effects of statins.

This review examines the hepatic safety profile of statins and details why there’s no need to stop treatment based on moderate elevations in liver function tests. The most common serious side effect of statins—muscle damage/rhabdomyolysis—is rare, and is not extensively discussed here.

Clinical trials: Risk is small

A review of 35 randomized clinical statin trials reported from 1966 to 2005, involving 74,102 patients, reported an absolute risk of transaminase (also referred to as aminotransferase) elevations from statin therapy of only about 4 per 1000 patients (risk difference [RD]=4.2; 95% confidence interval [CI], 1.5-6.9).³ The same researchers’ analysis of 28 clinical trials involving 62,184 patients showed a relative risk of increased transaminase of 1.3 (95% CI, 1.06-1.59), achieving statistical significance only for the fluvastatin and lovastatin trials.³

High-dose statin therapy. A review of clinical trials involving high-dose statin therapy found rates of hepatic enzyme elevation (defined as ALT or AST >3 times the ULN on 2 or more consecutive occasions) to be quite low (<1.3%).⁴ Higher statin doses were more likely to increase enzyme levels, though reduction in the dose or withdrawal of the statin resulted in normalization of the liver enzymes.

A study of patients ages 65 to 85 years who were treated with high-dose atorvastatin (80 mg per day) vs moderate dose pravastatin (40 mg per day) resulted in only 11 of 893 (1.23%) patients discontinuing the drug following abnormal liver function tests; most of these were in the high-dose treatment arm.⁵

Small risk in clinical practice, too

Clinical trials often have lower rates of adverse effects from medications than are seen in usual clinical practice.⁶ This may be because the stringent application of patient selection and exclusion criteria used in the administration of clinical trials does not occur in the “real world.”

However, the FDA database reported only 0.69 cases of hepatitis/liver failure per million statin prescriptions through 2004.⁴ A retrospective review of 1194 patients treated with a statin showed that 85% (1014) of patients had at least 1 monitoring test of transaminases performed during the year of the study. Of these, 10 (1.0%) had a significant elevation and 5 (0.5%) had a moderate elevation of transaminases. A review of the patient records demonstrated that none of these abnormalities appeared to be related to the use of statins, suggesting that routine monitoring of transaminases with statin therapy is not clinically necessary.⁷

A retrospective review over a 5-year period of 23,000 patients receiving statins in a large health maintenance organization found that only 17 (0.1%) patients had severe elevations of ALT (defined as >10 times the ULN). Of those 17 patients, 13 cases were associated with drug-drug interactions, and all but 1 resolved with discontinuation of the statin.⁸

What to monitor, how often

Product labeling for all statins advises measurement of transaminases (AST as well as ALT), although some liver experts would recommend ALT alone. ALT is found primarily in the liver, while AST is also found in muscle (cardiac and skeletal), kidneys, brain, pancreas, lungs, leukocytes, and erythrocytes. AST is, therefore, less specific for hepatic damage than ALT.

Routine monitoring of other liver function tests that measure the liver’s transport ability (eg, bilirubin, alkaline phosphate) or synthetic ability (eg, albumin, prothrombin time) will increase the likelihood of false-positive results and increase expense; they should not be done.

The 2002 American Gastroenterological Association guidelines recommend that for any hepatotoxic drug, if the ALT and/or AST elevations are <5 times the ULN, the drug should be stopped and the enzymes rechecked after an appropriate interval before pursuing a more extensive evaluation for liver disease.⁹

The FDA labeling information for all statins recommends liver function testing before putting a patient on a statin, 12 weeks after initiation, at any dose increase, and “periodically” for long-term maintenance therapy (TABLE 1).¹⁰ These recommendations are based on expert opinion only, because most data suggest that significant liver damage from statins is very rare and that routine monitoring of liver enzymes is not necessary.

The ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins agrees with the FDA, although it specifies “periodically” to mean annually.¹¹

TABLE 1
When to monitor liver function in patients taking statins^10,11

It’s difficult to predict hepatic effects

Individual statins vary as to potency, efficacy, metabolism, and drug interactions. However, the exact mechanism of how statins cause elevations of ALT and AST is unknown, making it difficult to predict the hepatic effects of an individual statin based on its characteristics.

One analysis of multiple clinical trials concluded that overall statin toxicity (muscle, liver, etc.) was not directly related to the degree of lowering LDL cholesterol; instead, it correlated with the dose of the statin.¹² As seen in TABLE 2, statins have variable drug-drug interactions based on their metabolism by the cytochrome P450 system. Drugs that increase the level of a statin in the blood may potentially increase the risk for toxicity and may warrant more cautious monitoring of liver enzymes, but are not necessarily contraindications to statin therapy.

Cyclosporine, macrolide antibiotics, azole antifungal agents, and other cytochrome P450 inhibitors (TABLE 2) are among the relative contraindications to the use of statins, more for concerns about myopathy than hepatoxicity.¹ If these medications are used with a statin, consider more frequent monitoring of transaminases.

TABLE 2
Statin snapshot: LDL reductions to expect, interactions to avoid

Discontinue the statin?

ACC/AHA/NHLBI recommendations indicate that you should discontinue (or lower the dose of) statin therapy if the ALT or AST are above 3 times the ULN on 2 consecutive occasions.¹¹ When elevations of ALT or AST are <3 times the ULN, consider the following:

• Statins have rigorously proven benefits for preventing morbidity and mortality due to atherosclerotic cardiovascular disease. A meta-analysis of more than 70,000 patients concluded that the number needed to treat to prevent 1 cardiovascular event was 27 and the number needed to harm (NNH) was 197. For more serious events such as creatine kinase >10 times the ULN, the NNH was 3400. Rhabdomyolysis alone was rare with a NNH of 7428.⁴
• Other medications that lower LDL and might be substituted for statins may not improve morbidity and mortality. For example, a recent clinical trial of ezetimibe (Zetia) reminds clinicians to be cautious in assuming that treatments that improve biochemical parameters such as LDL will necessarily result in improved clinical outcomes.¹³
• Mild elevations of ALT or AST (<3 times the ULN) following statin therapy are not known to lead to any significant liver toxicity over time.
• To date, there are no randomized controlled trials evaluating the optimal management of liver enzyme elevations with statin therapy.

Correspondence
Edward Onusko, MD, Family Health Center, 825 W. Locust, Wilmington, OH 45177; edonusko@cmhregional.com.

History of present illness

• Approximately 4 weeks of generalized extremity pain and weakness; left-sided, nonexertional chest pain, which is much less severe than his extremity pains
• Symptoms are most prominent in the proximal upper extremities, especially with movement; the right side is more effected than the left
• Dyspnea on exertion
• Seen twice in local urgent care facilities in the past 10 days; diagnosed with congestive heart failure; treated with furosemide, digoxin, and an unknown antibiotic without relief
• 20- to 30-pound weight loss over the past year

Other medical history

• No chronic medical problems or medications
• Until this past month, last seen by a physician about 3 or 4 years prior

Review of systems

• Up to the day of admission has been ambulatory and able to care for himself despite his weakness
• No fever, chills, or rash; but has night sweats
• Smokes; does not drink alcohol
• Retired; lives with his wife

Physical examination

• Alert, appears mildly uncomfortable
• Temperature 101°F, respirations 32, blood pressure 164/72, pulse 80
• 3/5 strength in proximal upper and lower extremities (can barely lift arms and legs off the bed; movement also limited by pain)
• Normal distal strength (hand grips and dorsi/plantar flexion of foot)
• Normal sensation, reflexes, cranial nerves, and mental status; no neck weakness
• No abnormal joint findings; has pink discoloration over extensor surface of MCP joint, which patient dismisses as scars from previous abrasions that have been present “for a long time”
• Heart, lungs unremarkable; no peripheral edema

Laboratory studies completed in the emergency department

• ECG: normal
• Chest x-ray: bibasilar peribronchial infiltrates
• Hemoglobin/hematocrit: normal
• White blood count: 27,000 with 92% neutrophils
• Erythrocyte sedimentation rate: normal
• Urinalysis: negative for blood
• Brain natriuretic peptide: normal
• Creatine kinase (CK): 2205 IU/L (normal range 35–232)
• Troponin-I: 0.6 ng/mL.
  [Reference range:
    <0.05=Negative
    0.05–0.09=Equivocal
    0.10–0.49=Suspicious
    0.50=Consistent with myocardial injury]

Is this acute non-ST elevation myocardial infarction (NSTEMI)?

The American College of Cardiology and the American Heart Association define myocardial infarction primarily as elevated cardiac-specific enzymes troponin-I and troponin-T in the appropriate clinical setting.^1,2 Elevated cardiac troponins have a sensitivity approaching 100% for myocardial damage. Specificity is much lower for acute ischemic cardiac disease, however, particularly for patients with a low pretest probability (45% false-positive rate in one series of 1000 consecutive patients presenting to a large urban emergency department with symptoms of acute coronary ischemia).³

Mechanisms other than atherosclerotic coronary artery disease that can elevate cardiac troponins:

• Increased cardiac demand (eg, sepsis, hypovolemia)
• Nonatherosclerotic ischemia (eg, cocaine or other sympathomimetic agents, coronary vasospasm)
• Direct myocardial injury (eg, cardiac contusion, myocarditis)
• Myocardial strain (eg, congestive heart failure, pulmonary embolus)
• Chronic renal insufficiency (mechanism unclear).⁴

In light of this patient’s history and physical exam findings, you doubt he’s having an acute cardiac event. The most remarkable features are his weakness, muscle pain, and markedly elevated CK.

Though you have ruled out anemia and several other possibilities, the differential diagnosis of weakness is still broad. You decide to explore the differential diagnosis of elevated CK, a more specific finding in this case.

Pursuing the differential

You consult UpToDate, searching under “creatine kinase,” and find an article entitled “Muscle enzymes in the evaluation of neuromuscular disease.”⁵ You conclude that the most likely cause of your patient’s problems is an idiopathic inflammatory myopathy: polymyositis, dermatomyositis, or inclusion-body myositis.⁶

Other possibilities include post-viral myositis and myositis associated with connective tissue disease, hypothyroidism, or drug reactions.

D-penicillamine, zidovudine (AZT), and viral or bacterial infection may produce inflammatory myopathy similar to polymyositis.⁷ A history of exposure to myotoxic drugs (such as statins) and toxins has been excluded.

The absence of a family history for neuromuscular disease and the relatively recent onset of symptoms rule out an inherited muscular dystrophy or congenital muscle enzyme deficiency.

Myasthenia gravis presents with extraocular muscle involvement. Guillain-Barré syndrome is characterized by ascending muscle weakness. Lyme disease may cause weakness secondary to peripheral neuropathy but it does not produce evidence of muscle inflammation such as elevation of the CK. West Nile virus encephalitis may present with muscle weakness and flaccid paralysis.⁸ Trichinellosis may also cause muscle inflammation with weakness and elevation of CK, but it is rare in the United States.

You repeat parts of your physical exam and confirm that his proximal upper extremity muscles are much weaker than his distal muscles.

In practice settings where specialty consultation is not always immediately available, your diagnostic skills may be challenged by uncommon presentations of disease. In this case, the challenge is “chest pain and positive cardiac enzymes” in a patient who does not appear to have a primary cardiac problem.

DTaP approach

When confronted with a difficult clinical problem, you may find it useful to organize the management plan according to the acronym “DTaP,” which for this patient would include:

• Diagnostic plan: serial ECGs and cardiac enzymes: an echocardiogram
• Therapeutic plan: pain control; antibiotics for possible pneumonia; consider steroids
• Assistance from consultants (who are you going to ask for help?): physiatrist consult for electromyography (EMG); cardiology consult; neurology consult
• Patient education (explain to the patient and his family the current diagnostic possibilities and your management plan)
• Provider education (learn more about myopathies!).

You request specialty consultations:

Neurology: possible polymyositis; recommends rheumatology consultation, multiple labs (most of which are sent out to a reference lab and return only several days later)

Cardiology: ECG normal; cardiologist does not see evidence for congestive heart failure or coronary artery disease

Physical medicine and rehabilitation: EMG performed; findings consistent with inflammatory myopathy

Rheumatology: recommends proceeding with muscle biopsy to differentiate polymyositis and inclusion-body myositis

Surgery: performs muscle biopsy which is sent to a regional neuropathologist; reveals inflammatory myopathy with prominent perivascular lymphocytic inflammation strongly suggestive of dermatomyositis.

Further case management and resolution

You administer solumedrol intravenously 1 g/d for 3 days, then change to prednisone orally 1 mg/kg/d.

The patient improves steadily with 3 months of oral steroid therapy. He tests positive for anti-Jo antibodies but his pulmonary symptoms resolve. He undergoes an outpatient evaluation for cancer screening. Colonoscopy, esophogastroduodenoscopy and chest/abdominal/pelvic computed tomography scans are negative for evidence of malignancy.

Other ways in which you may encounter inflammatory myopathies

Dermatomyositis usually causes a characteristic rash that facilitates early diagnosis (though it did not appear in this case). As shown in FIGURES 1 AND 2, patients may have either a heliotrope rash (blue-purple to dusky erythematous discoloration on the upper eyelids, with or without edema), or Gottron’s papules (slightly raised violaceous papules and plaques overlying bony prominences, particularly the joints in the fingers and the knuckles).¹⁰

A variety of less specific skin and nail changes can occur. Dermatomyositis may present with skin lesions alone (dermatomyositis sine myositis) or rarely with myopathy alone (dermatomyositis sine dermatitis). In our case, multiple examiners failed to detect any classic dermatologic abnormalities, though the pinkish skin changes over the extensor aspect of the MCP joints were, in retrospect, suggestive of dermatomyositis. The weakness associated with this disease may be mild, moderate, or severe enough to result in quadriparesis. Dermatomyositis usually occurs alone but may be present with scleroderma and mixed connective tissue disease.

Inclusion-body myositis is often misdiagnosed as polymyositis or dermatomyositis until identified by muscle biopsy findings (see How inflammatory myopathies develop), although suspicion is raised with a poor response to steroid therapy.⁹ Some patients report falling as a result of quadriceps weakness. On occasion the weakness can be asymmetric or distal (rare with dermatomyositis or polymyositis). Diagnosis is always made by muscle biopsy. Disease progression is slow but steady and most patients end up requiring a walker or assistive device.

Polymyositis is a sub-acute inflammatory myopathy affecting adults and, rarely, children. In most cases the actual onset of polymyositis is not easily determined as patients tend to delay seeking medical evaluation.

Other muscular disorders, as discussed in the case presentation, need to be excluded.

FIGURE 1 Heliotrope rash

Patients with dermatomyositis often have a characteristic rash on their face.

FIGURE 2 Gottron’s papules

Many patients also have papules and plaques on their hands, typically at the joints.

Commonly associated clinical findings

Extramuscular manifestations of inflammatory myopathies. Dermatomyositis is a systemic inflammatory disorder that may extend beyond the dermatologic and muscular systems, and patients can exhibit such symptoms as fever, malaise, and weight loss.

Arthralgia and Raynaud’s phenomenon may occur with associated connective tissue disease.

Dysphagia indicates involvement of the oropharyngeal striated muscles and the upper esophagus.

Cardiac disturbances include atrioventricular conduction defects, tachyarrhythmias, myocarditis, heart failure, and possibly hypertension from long-term steroid use. The elevated troponin-I seen in our index case may have been evidence of a mild myocarditis, though the echocardiogram was normal.

Calcinosis (deposition of calcium in the skin or muscles) occurs in up to 40% of children with dermatomyositis but is unusual in adults.¹⁰

Pulmonary symptoms may be due to weakness of the thoracic muscles, interstitial lung disease, or aspiration. One retrospective study of 156 consecutive patients with dermatomyositis/polymyositis based on clinical criteria found a 23.1% incidence of interstitial lung disease.¹¹

Malignant disorders. The frequency of cancer is increased in association with these diseases. Studies have placed the highest risk of concomitant malignancy with dermatomyositis and the least risk with polymyositis. (The relative risk for malignancy in dermatomyositis as compared with polymyositis was 2.4.) Malignancy associated with dermatomyositis or polymyositis is twice as likely in women than in men.¹²

Risk of associated malignancy was highest within the first year of diagnosis. Therefore, consider a diagnostic evaluation for malignancy at the time myopathy is diagnosed. The optimal diagnostic regimen in this setting is unknown. In one retrospective French study of 40 consecutive adult patients with inflammatory myopathy (33 with dermatomyositis and 7 with polymyositis) between the years 1981 and 2000, malignancy was present at the time of myopathy diagnosis in 16 patients (13 with dermatomyositis and 3 with polymyositis).¹² An Australian population-based, retrospective cohort study of 537 individuals with biopsy-proven idiopathic inflammatory myopathy from 1981–1995 demonstrated 116 cases of malignancy in 104 patients.¹³ The risk was highest in dermatomyositis (standardized incidence ratio [SIR] 6.2), next highest in inclusion-body myositis (SIR 2.4), and lowest in polymyositis (SIR 2.0).

Diagnosis: What helps, what doesn’t

Suspect inflammatory myopathy by the constellation of clinical findings; confirm it by looking for elevated muscle enzymes and characteristic findings on EMG and muscle biopsy (see How inflammatory myopathies develop).

The most sensitive muscle enzyme for inflammatory myopathy is CK, levels of which usually parallel disease activity and may be used to assess response to therapy.^6,10 Needle EMG demonstrates increased spontaneous activity with fibrillations; complex repetitive discharges; positive sharp waves; and voluntary motor units consisting of low-amplitude polyphasic units of short duration.⁶ EMG findings alone are not diagnostic.

Serologic tests are commonly done but their clinical usefulness is controversial.¹⁰ Antinuclear antibodies are found in about 80% of cases but are nonspecific and not clinically useful.¹⁴ Myositis-specific antibodies (MSAs) have been described in about 30% of idiopathic inflammatory myopathies but are also of uncertain diagnostic and pathogenic importance.¹⁴ The most prevalent MSA, anti-Jo, is present in only about 20% of cases and correlates with interstitial lung disease, but has uncertain usefulness in differentiating between dermatomyositis, polymyositis, and inclusion-body myositis.^{6,10,11,14,15}

Differentiate between the inflammatory myopathies based on characteristic pathological findings on muscle biopsy (previously discussed). Muscle biopsy is the definitive test for establishing the diagnosis. In our case presentation, the regional neuropathologist thought the biopsy result was most consistent with dermatomyositis despite the clinical paucity of skin abnormalities, though our consulting neurologist favored a diagnosis of polymyositis on clinical grounds.

Treatment recommendations

Corticosteroids are the most efficacious treatment for dermatomyositis (strength of recommendation [SOR]: B).¹⁰ One empirical regimen is to give prednisone 1 mg/kg/d as initial therapy; maintain this therapy for 1 month after symptoms and CK have normalized; then slowly taper (SOR: C).¹⁰ Twenty-five percent of patients will not respond to steroids; others will not tolerate the side effects of steroid therapy.¹⁰

Immunosuppressive drugs such as azothioprine, methotrexate, cyclosporine, mycophenolate mofetil and cyclophosphamide may be used as second-line treatment (SOR: C).⁶ Intravenous immunoglobulin may have some efficacy (SOR: B).¹⁶ Plasmapheresis does not appear to be effective (SOR: B).¹⁷

Determinants of prognosis

Most patients will improve over several weeks or months with therapy, although a third or more are left with mild to severe muscle damage. Dermatomyositis responds better than polymyositis; inclusion-body myositis is the most difficult to treat.¹⁰ Poor prognostic factors include older age, association with cancer, pulmonary fibrosis, dysphagia with aspiration pneumonia, cardiac involvement, steroid-resistant disease, and calcinosis in dermatomyositis.^6,10 Studies have demonstrated 5-year survival rates between 77% and 92%.^18,19 The main causes of death were related to malignancy and cardiac or pulmonary complications.

History of present illness

• Approximately 4 weeks of generalized extremity pain and weakness; left-sided, nonexertional chest pain, which is much less severe than his extremity pains
• Symptoms are most prominent in the proximal upper extremities, especially with movement; the right side is more effected than the left
• Dyspnea on exertion
• Seen twice in local urgent care facilities in the past 10 days; diagnosed with congestive heart failure; treated with furosemide, digoxin, and an unknown antibiotic without relief
• 20- to 30-pound weight loss over the past year

Other medical history

• No chronic medical problems or medications
• Until this past month, last seen by a physician about 3 or 4 years prior

Review of systems

• Up to the day of admission has been ambulatory and able to care for himself despite his weakness
• No fever, chills, or rash; but has night sweats
• Smokes; does not drink alcohol
• Retired; lives with his wife

Physical examination

• Alert, appears mildly uncomfortable
• Temperature 101°F, respirations 32, blood pressure 164/72, pulse 80
• 3/5 strength in proximal upper and lower extremities (can barely lift arms and legs off the bed; movement also limited by pain)
• Normal distal strength (hand grips and dorsi/plantar flexion of foot)
• Normal sensation, reflexes, cranial nerves, and mental status; no neck weakness
• No abnormal joint findings; has pink discoloration over extensor surface of MCP joint, which patient dismisses as scars from previous abrasions that have been present “for a long time”
• Heart, lungs unremarkable; no peripheral edema

Laboratory studies completed in the emergency department

• ECG: normal
• Chest x-ray: bibasilar peribronchial infiltrates
• Hemoglobin/hematocrit: normal
• White blood count: 27,000 with 92% neutrophils
• Erythrocyte sedimentation rate: normal
• Urinalysis: negative for blood
• Brain natriuretic peptide: normal
• Creatine kinase (CK): 2205 IU/L (normal range 35–232)
• Troponin-I: 0.6 ng/mL.
  [Reference range:
    <0.05=Negative
    0.05–0.09=Equivocal
    0.10–0.49=Suspicious
    0.50=Consistent with myocardial injury]

Is this acute non-ST elevation myocardial infarction (NSTEMI)?

The American College of Cardiology and the American Heart Association define myocardial infarction primarily as elevated cardiac-specific enzymes troponin-I and troponin-T in the appropriate clinical setting.^1,2 Elevated cardiac troponins have a sensitivity approaching 100% for myocardial damage. Specificity is much lower for acute ischemic cardiac disease, however, particularly for patients with a low pretest probability (45% false-positive rate in one series of 1000 consecutive patients presenting to a large urban emergency department with symptoms of acute coronary ischemia).³

Mechanisms other than atherosclerotic coronary artery disease that can elevate cardiac troponins:

• Increased cardiac demand (eg, sepsis, hypovolemia)
• Nonatherosclerotic ischemia (eg, cocaine or other sympathomimetic agents, coronary vasospasm)
• Direct myocardial injury (eg, cardiac contusion, myocarditis)
• Myocardial strain (eg, congestive heart failure, pulmonary embolus)
• Chronic renal insufficiency (mechanism unclear).⁴

In light of this patient’s history and physical exam findings, you doubt he’s having an acute cardiac event. The most remarkable features are his weakness, muscle pain, and markedly elevated CK.

Though you have ruled out anemia and several other possibilities, the differential diagnosis of weakness is still broad. You decide to explore the differential diagnosis of elevated CK, a more specific finding in this case.

Pursuing the differential

You consult UpToDate, searching under “creatine kinase,” and find an article entitled “Muscle enzymes in the evaluation of neuromuscular disease.”⁵ You conclude that the most likely cause of your patient’s problems is an idiopathic inflammatory myopathy: polymyositis, dermatomyositis, or inclusion-body myositis.⁶

Other possibilities include post-viral myositis and myositis associated with connective tissue disease, hypothyroidism, or drug reactions.

D-penicillamine, zidovudine (AZT), and viral or bacterial infection may produce inflammatory myopathy similar to polymyositis.⁷ A history of exposure to myotoxic drugs (such as statins) and toxins has been excluded.

The absence of a family history for neuromuscular disease and the relatively recent onset of symptoms rule out an inherited muscular dystrophy or congenital muscle enzyme deficiency.

Myasthenia gravis presents with extraocular muscle involvement. Guillain-Barré syndrome is characterized by ascending muscle weakness. Lyme disease may cause weakness secondary to peripheral neuropathy but it does not produce evidence of muscle inflammation such as elevation of the CK. West Nile virus encephalitis may present with muscle weakness and flaccid paralysis.⁸ Trichinellosis may also cause muscle inflammation with weakness and elevation of CK, but it is rare in the United States.

You repeat parts of your physical exam and confirm that his proximal upper extremity muscles are much weaker than his distal muscles.

In practice settings where specialty consultation is not always immediately available, your diagnostic skills may be challenged by uncommon presentations of disease. In this case, the challenge is “chest pain and positive cardiac enzymes” in a patient who does not appear to have a primary cardiac problem.

DTaP approach

When confronted with a difficult clinical problem, you may find it useful to organize the management plan according to the acronym “DTaP,” which for this patient would include:

• Diagnostic plan: serial ECGs and cardiac enzymes: an echocardiogram
• Therapeutic plan: pain control; antibiotics for possible pneumonia; consider steroids
• Assistance from consultants (who are you going to ask for help?): physiatrist consult for electromyography (EMG); cardiology consult; neurology consult
• Patient education (explain to the patient and his family the current diagnostic possibilities and your management plan)
• Provider education (learn more about myopathies!).

You request specialty consultations:

Neurology: possible polymyositis; recommends rheumatology consultation, multiple labs (most of which are sent out to a reference lab and return only several days later)

Cardiology: ECG normal; cardiologist does not see evidence for congestive heart failure or coronary artery disease

Physical medicine and rehabilitation: EMG performed; findings consistent with inflammatory myopathy

Rheumatology: recommends proceeding with muscle biopsy to differentiate polymyositis and inclusion-body myositis

Surgery: performs muscle biopsy which is sent to a regional neuropathologist; reveals inflammatory myopathy with prominent perivascular lymphocytic inflammation strongly suggestive of dermatomyositis.

Further case management and resolution

You administer solumedrol intravenously 1 g/d for 3 days, then change to prednisone orally 1 mg/kg/d.

The patient improves steadily with 3 months of oral steroid therapy. He tests positive for anti-Jo antibodies but his pulmonary symptoms resolve. He undergoes an outpatient evaluation for cancer screening. Colonoscopy, esophogastroduodenoscopy and chest/abdominal/pelvic computed tomography scans are negative for evidence of malignancy.

Other ways in which you may encounter inflammatory myopathies

Dermatomyositis usually causes a characteristic rash that facilitates early diagnosis (though it did not appear in this case). As shown in FIGURES 1 AND 2, patients may have either a heliotrope rash (blue-purple to dusky erythematous discoloration on the upper eyelids, with or without edema), or Gottron’s papules (slightly raised violaceous papules and plaques overlying bony prominences, particularly the joints in the fingers and the knuckles).¹⁰

A variety of less specific skin and nail changes can occur. Dermatomyositis may present with skin lesions alone (dermatomyositis sine myositis) or rarely with myopathy alone (dermatomyositis sine dermatitis). In our case, multiple examiners failed to detect any classic dermatologic abnormalities, though the pinkish skin changes over the extensor aspect of the MCP joints were, in retrospect, suggestive of dermatomyositis. The weakness associated with this disease may be mild, moderate, or severe enough to result in quadriparesis. Dermatomyositis usually occurs alone but may be present with scleroderma and mixed connective tissue disease.

Inclusion-body myositis is often misdiagnosed as polymyositis or dermatomyositis until identified by muscle biopsy findings (see How inflammatory myopathies develop), although suspicion is raised with a poor response to steroid therapy.⁹ Some patients report falling as a result of quadriceps weakness. On occasion the weakness can be asymmetric or distal (rare with dermatomyositis or polymyositis). Diagnosis is always made by muscle biopsy. Disease progression is slow but steady and most patients end up requiring a walker or assistive device.

Polymyositis is a sub-acute inflammatory myopathy affecting adults and, rarely, children. In most cases the actual onset of polymyositis is not easily determined as patients tend to delay seeking medical evaluation.

Other muscular disorders, as discussed in the case presentation, need to be excluded.

FIGURE 1 Heliotrope rash

Patients with dermatomyositis often have a characteristic rash on their face.

FIGURE 2 Gottron’s papules

Many patients also have papules and plaques on their hands, typically at the joints.

Commonly associated clinical findings

Extramuscular manifestations of inflammatory myopathies. Dermatomyositis is a systemic inflammatory disorder that may extend beyond the dermatologic and muscular systems, and patients can exhibit such symptoms as fever, malaise, and weight loss.

Arthralgia and Raynaud’s phenomenon may occur with associated connective tissue disease.

Dysphagia indicates involvement of the oropharyngeal striated muscles and the upper esophagus.

Cardiac disturbances include atrioventricular conduction defects, tachyarrhythmias, myocarditis, heart failure, and possibly hypertension from long-term steroid use. The elevated troponin-I seen in our index case may have been evidence of a mild myocarditis, though the echocardiogram was normal.

Calcinosis (deposition of calcium in the skin or muscles) occurs in up to 40% of children with dermatomyositis but is unusual in adults.¹⁰

Pulmonary symptoms may be due to weakness of the thoracic muscles, interstitial lung disease, or aspiration. One retrospective study of 156 consecutive patients with dermatomyositis/polymyositis based on clinical criteria found a 23.1% incidence of interstitial lung disease.¹¹

Malignant disorders. The frequency of cancer is increased in association with these diseases. Studies have placed the highest risk of concomitant malignancy with dermatomyositis and the least risk with polymyositis. (The relative risk for malignancy in dermatomyositis as compared with polymyositis was 2.4.) Malignancy associated with dermatomyositis or polymyositis is twice as likely in women than in men.¹²

Risk of associated malignancy was highest within the first year of diagnosis. Therefore, consider a diagnostic evaluation for malignancy at the time myopathy is diagnosed. The optimal diagnostic regimen in this setting is unknown. In one retrospective French study of 40 consecutive adult patients with inflammatory myopathy (33 with dermatomyositis and 7 with polymyositis) between the years 1981 and 2000, malignancy was present at the time of myopathy diagnosis in 16 patients (13 with dermatomyositis and 3 with polymyositis).¹² An Australian population-based, retrospective cohort study of 537 individuals with biopsy-proven idiopathic inflammatory myopathy from 1981–1995 demonstrated 116 cases of malignancy in 104 patients.¹³ The risk was highest in dermatomyositis (standardized incidence ratio [SIR] 6.2), next highest in inclusion-body myositis (SIR 2.4), and lowest in polymyositis (SIR 2.0).

Diagnosis: What helps, what doesn’t

Suspect inflammatory myopathy by the constellation of clinical findings; confirm it by looking for elevated muscle enzymes and characteristic findings on EMG and muscle biopsy (see How inflammatory myopathies develop).

The most sensitive muscle enzyme for inflammatory myopathy is CK, levels of which usually parallel disease activity and may be used to assess response to therapy.^6,10 Needle EMG demonstrates increased spontaneous activity with fibrillations; complex repetitive discharges; positive sharp waves; and voluntary motor units consisting of low-amplitude polyphasic units of short duration.⁶ EMG findings alone are not diagnostic.

Serologic tests are commonly done but their clinical usefulness is controversial.¹⁰ Antinuclear antibodies are found in about 80% of cases but are nonspecific and not clinically useful.¹⁴ Myositis-specific antibodies (MSAs) have been described in about 30% of idiopathic inflammatory myopathies but are also of uncertain diagnostic and pathogenic importance.¹⁴ The most prevalent MSA, anti-Jo, is present in only about 20% of cases and correlates with interstitial lung disease, but has uncertain usefulness in differentiating between dermatomyositis, polymyositis, and inclusion-body myositis.^{6,10,11,14,15}

Differentiate between the inflammatory myopathies based on characteristic pathological findings on muscle biopsy (previously discussed). Muscle biopsy is the definitive test for establishing the diagnosis. In our case presentation, the regional neuropathologist thought the biopsy result was most consistent with dermatomyositis despite the clinical paucity of skin abnormalities, though our consulting neurologist favored a diagnosis of polymyositis on clinical grounds.

Treatment recommendations

Corticosteroids are the most efficacious treatment for dermatomyositis (strength of recommendation [SOR]: B).¹⁰ One empirical regimen is to give prednisone 1 mg/kg/d as initial therapy; maintain this therapy for 1 month after symptoms and CK have normalized; then slowly taper (SOR: C).¹⁰ Twenty-five percent of patients will not respond to steroids; others will not tolerate the side effects of steroid therapy.¹⁰

Immunosuppressive drugs such as azothioprine, methotrexate, cyclosporine, mycophenolate mofetil and cyclophosphamide may be used as second-line treatment (SOR: C).⁶ Intravenous immunoglobulin may have some efficacy (SOR: B).¹⁶ Plasmapheresis does not appear to be effective (SOR: B).¹⁷

Determinants of prognosis

Most patients will improve over several weeks or months with therapy, although a third or more are left with mild to severe muscle damage. Dermatomyositis responds better than polymyositis; inclusion-body myositis is the most difficult to treat.¹⁰ Poor prognostic factors include older age, association with cancer, pulmonary fibrosis, dysphagia with aspiration pneumonia, cardiac involvement, steroid-resistant disease, and calcinosis in dermatomyositis.^6,10 Studies have demonstrated 5-year survival rates between 77% and 92%.^18,19 The main causes of death were related to malignancy and cardiac or pulmonary complications.

History of present illness

• Approximately 4 weeks of generalized extremity pain and weakness; left-sided, nonexertional chest pain, which is much less severe than his extremity pains
• Symptoms are most prominent in the proximal upper extremities, especially with movement; the right side is more effected than the left
• Dyspnea on exertion
• Seen twice in local urgent care facilities in the past 10 days; diagnosed with congestive heart failure; treated with furosemide, digoxin, and an unknown antibiotic without relief
• 20- to 30-pound weight loss over the past year

Other medical history

• No chronic medical problems or medications
• Until this past month, last seen by a physician about 3 or 4 years prior

Review of systems

• Up to the day of admission has been ambulatory and able to care for himself despite his weakness
• No fever, chills, or rash; but has night sweats
• Smokes; does not drink alcohol
• Retired; lives with his wife

Physical examination

• Alert, appears mildly uncomfortable
• Temperature 101°F, respirations 32, blood pressure 164/72, pulse 80
• 3/5 strength in proximal upper and lower extremities (can barely lift arms and legs off the bed; movement also limited by pain)
• Normal distal strength (hand grips and dorsi/plantar flexion of foot)
• Normal sensation, reflexes, cranial nerves, and mental status; no neck weakness
• No abnormal joint findings; has pink discoloration over extensor surface of MCP joint, which patient dismisses as scars from previous abrasions that have been present “for a long time”
• Heart, lungs unremarkable; no peripheral edema

Laboratory studies completed in the emergency department

• ECG: normal
• Chest x-ray: bibasilar peribronchial infiltrates
• Hemoglobin/hematocrit: normal
• White blood count: 27,000 with 92% neutrophils
• Erythrocyte sedimentation rate: normal
• Urinalysis: negative for blood
• Brain natriuretic peptide: normal
• Creatine kinase (CK): 2205 IU/L (normal range 35–232)
• Troponin-I: 0.6 ng/mL.
  [Reference range:
    <0.05=Negative
    0.05–0.09=Equivocal
    0.10–0.49=Suspicious
    0.50=Consistent with myocardial injury]

Is this acute non-ST elevation myocardial infarction (NSTEMI)?

The American College of Cardiology and the American Heart Association define myocardial infarction primarily as elevated cardiac-specific enzymes troponin-I and troponin-T in the appropriate clinical setting.^1,2 Elevated cardiac troponins have a sensitivity approaching 100% for myocardial damage. Specificity is much lower for acute ischemic cardiac disease, however, particularly for patients with a low pretest probability (45% false-positive rate in one series of 1000 consecutive patients presenting to a large urban emergency department with symptoms of acute coronary ischemia).³

Mechanisms other than atherosclerotic coronary artery disease that can elevate cardiac troponins:

• Increased cardiac demand (eg, sepsis, hypovolemia)
• Nonatherosclerotic ischemia (eg, cocaine or other sympathomimetic agents, coronary vasospasm)
• Direct myocardial injury (eg, cardiac contusion, myocarditis)
• Myocardial strain (eg, congestive heart failure, pulmonary embolus)
• Chronic renal insufficiency (mechanism unclear).⁴

In light of this patient’s history and physical exam findings, you doubt he’s having an acute cardiac event. The most remarkable features are his weakness, muscle pain, and markedly elevated CK.

Though you have ruled out anemia and several other possibilities, the differential diagnosis of weakness is still broad. You decide to explore the differential diagnosis of elevated CK, a more specific finding in this case.

Pursuing the differential

You consult UpToDate, searching under “creatine kinase,” and find an article entitled “Muscle enzymes in the evaluation of neuromuscular disease.”⁵ You conclude that the most likely cause of your patient’s problems is an idiopathic inflammatory myopathy: polymyositis, dermatomyositis, or inclusion-body myositis.⁶

Other possibilities include post-viral myositis and myositis associated with connective tissue disease, hypothyroidism, or drug reactions.

D-penicillamine, zidovudine (AZT), and viral or bacterial infection may produce inflammatory myopathy similar to polymyositis.⁷ A history of exposure to myotoxic drugs (such as statins) and toxins has been excluded.

The absence of a family history for neuromuscular disease and the relatively recent onset of symptoms rule out an inherited muscular dystrophy or congenital muscle enzyme deficiency.

Myasthenia gravis presents with extraocular muscle involvement. Guillain-Barré syndrome is characterized by ascending muscle weakness. Lyme disease may cause weakness secondary to peripheral neuropathy but it does not produce evidence of muscle inflammation such as elevation of the CK. West Nile virus encephalitis may present with muscle weakness and flaccid paralysis.⁸ Trichinellosis may also cause muscle inflammation with weakness and elevation of CK, but it is rare in the United States.

You repeat parts of your physical exam and confirm that his proximal upper extremity muscles are much weaker than his distal muscles.

In practice settings where specialty consultation is not always immediately available, your diagnostic skills may be challenged by uncommon presentations of disease. In this case, the challenge is “chest pain and positive cardiac enzymes” in a patient who does not appear to have a primary cardiac problem.

DTaP approach

When confronted with a difficult clinical problem, you may find it useful to organize the management plan according to the acronym “DTaP,” which for this patient would include:

• Diagnostic plan: serial ECGs and cardiac enzymes: an echocardiogram
• Therapeutic plan: pain control; antibiotics for possible pneumonia; consider steroids
• Assistance from consultants (who are you going to ask for help?): physiatrist consult for electromyography (EMG); cardiology consult; neurology consult
• Patient education (explain to the patient and his family the current diagnostic possibilities and your management plan)
• Provider education (learn more about myopathies!).

You request specialty consultations:

Neurology: possible polymyositis; recommends rheumatology consultation, multiple labs (most of which are sent out to a reference lab and return only several days later)

Cardiology: ECG normal; cardiologist does not see evidence for congestive heart failure or coronary artery disease

Physical medicine and rehabilitation: EMG performed; findings consistent with inflammatory myopathy

Rheumatology: recommends proceeding with muscle biopsy to differentiate polymyositis and inclusion-body myositis

Surgery: performs muscle biopsy which is sent to a regional neuropathologist; reveals inflammatory myopathy with prominent perivascular lymphocytic inflammation strongly suggestive of dermatomyositis.

Further case management and resolution

You administer solumedrol intravenously 1 g/d for 3 days, then change to prednisone orally 1 mg/kg/d.

The patient improves steadily with 3 months of oral steroid therapy. He tests positive for anti-Jo antibodies but his pulmonary symptoms resolve. He undergoes an outpatient evaluation for cancer screening. Colonoscopy, esophogastroduodenoscopy and chest/abdominal/pelvic computed tomography scans are negative for evidence of malignancy.

Other ways in which you may encounter inflammatory myopathies

Dermatomyositis usually causes a characteristic rash that facilitates early diagnosis (though it did not appear in this case). As shown in FIGURES 1 AND 2, patients may have either a heliotrope rash (blue-purple to dusky erythematous discoloration on the upper eyelids, with or without edema), or Gottron’s papules (slightly raised violaceous papules and plaques overlying bony prominences, particularly the joints in the fingers and the knuckles).¹⁰

A variety of less specific skin and nail changes can occur. Dermatomyositis may present with skin lesions alone (dermatomyositis sine myositis) or rarely with myopathy alone (dermatomyositis sine dermatitis). In our case, multiple examiners failed to detect any classic dermatologic abnormalities, though the pinkish skin changes over the extensor aspect of the MCP joints were, in retrospect, suggestive of dermatomyositis. The weakness associated with this disease may be mild, moderate, or severe enough to result in quadriparesis. Dermatomyositis usually occurs alone but may be present with scleroderma and mixed connective tissue disease.

Inclusion-body myositis is often misdiagnosed as polymyositis or dermatomyositis until identified by muscle biopsy findings (see How inflammatory myopathies develop), although suspicion is raised with a poor response to steroid therapy.⁹ Some patients report falling as a result of quadriceps weakness. On occasion the weakness can be asymmetric or distal (rare with dermatomyositis or polymyositis). Diagnosis is always made by muscle biopsy. Disease progression is slow but steady and most patients end up requiring a walker or assistive device.

Polymyositis is a sub-acute inflammatory myopathy affecting adults and, rarely, children. In most cases the actual onset of polymyositis is not easily determined as patients tend to delay seeking medical evaluation.

Other muscular disorders, as discussed in the case presentation, need to be excluded.

FIGURE 1 Heliotrope rash

Patients with dermatomyositis often have a characteristic rash on their face.

FIGURE 2 Gottron’s papules

Many patients also have papules and plaques on their hands, typically at the joints.

Commonly associated clinical findings

Extramuscular manifestations of inflammatory myopathies. Dermatomyositis is a systemic inflammatory disorder that may extend beyond the dermatologic and muscular systems, and patients can exhibit such symptoms as fever, malaise, and weight loss.

Arthralgia and Raynaud’s phenomenon may occur with associated connective tissue disease.

Dysphagia indicates involvement of the oropharyngeal striated muscles and the upper esophagus.

Cardiac disturbances include atrioventricular conduction defects, tachyarrhythmias, myocarditis, heart failure, and possibly hypertension from long-term steroid use. The elevated troponin-I seen in our index case may have been evidence of a mild myocarditis, though the echocardiogram was normal.

Calcinosis (deposition of calcium in the skin or muscles) occurs in up to 40% of children with dermatomyositis but is unusual in adults.¹⁰

Pulmonary symptoms may be due to weakness of the thoracic muscles, interstitial lung disease, or aspiration. One retrospective study of 156 consecutive patients with dermatomyositis/polymyositis based on clinical criteria found a 23.1% incidence of interstitial lung disease.¹¹

Malignant disorders. The frequency of cancer is increased in association with these diseases. Studies have placed the highest risk of concomitant malignancy with dermatomyositis and the least risk with polymyositis. (The relative risk for malignancy in dermatomyositis as compared with polymyositis was 2.4.) Malignancy associated with dermatomyositis or polymyositis is twice as likely in women than in men.¹²

Risk of associated malignancy was highest within the first year of diagnosis. Therefore, consider a diagnostic evaluation for malignancy at the time myopathy is diagnosed. The optimal diagnostic regimen in this setting is unknown. In one retrospective French study of 40 consecutive adult patients with inflammatory myopathy (33 with dermatomyositis and 7 with polymyositis) between the years 1981 and 2000, malignancy was present at the time of myopathy diagnosis in 16 patients (13 with dermatomyositis and 3 with polymyositis).¹² An Australian population-based, retrospective cohort study of 537 individuals with biopsy-proven idiopathic inflammatory myopathy from 1981–1995 demonstrated 116 cases of malignancy in 104 patients.¹³ The risk was highest in dermatomyositis (standardized incidence ratio [SIR] 6.2), next highest in inclusion-body myositis (SIR 2.4), and lowest in polymyositis (SIR 2.0).

Diagnosis: What helps, what doesn’t

Suspect inflammatory myopathy by the constellation of clinical findings; confirm it by looking for elevated muscle enzymes and characteristic findings on EMG and muscle biopsy (see How inflammatory myopathies develop).

The most sensitive muscle enzyme for inflammatory myopathy is CK, levels of which usually parallel disease activity and may be used to assess response to therapy.^6,10 Needle EMG demonstrates increased spontaneous activity with fibrillations; complex repetitive discharges; positive sharp waves; and voluntary motor units consisting of low-amplitude polyphasic units of short duration.⁶ EMG findings alone are not diagnostic.

Serologic tests are commonly done but their clinical usefulness is controversial.¹⁰ Antinuclear antibodies are found in about 80% of cases but are nonspecific and not clinically useful.¹⁴ Myositis-specific antibodies (MSAs) have been described in about 30% of idiopathic inflammatory myopathies but are also of uncertain diagnostic and pathogenic importance.¹⁴ The most prevalent MSA, anti-Jo, is present in only about 20% of cases and correlates with interstitial lung disease, but has uncertain usefulness in differentiating between dermatomyositis, polymyositis, and inclusion-body myositis.^{6,10,11,14,15}

Differentiate between the inflammatory myopathies based on characteristic pathological findings on muscle biopsy (previously discussed). Muscle biopsy is the definitive test for establishing the diagnosis. In our case presentation, the regional neuropathologist thought the biopsy result was most consistent with dermatomyositis despite the clinical paucity of skin abnormalities, though our consulting neurologist favored a diagnosis of polymyositis on clinical grounds.

Treatment recommendations

Corticosteroids are the most efficacious treatment for dermatomyositis (strength of recommendation [SOR]: B).¹⁰ One empirical regimen is to give prednisone 1 mg/kg/d as initial therapy; maintain this therapy for 1 month after symptoms and CK have normalized; then slowly taper (SOR: C).¹⁰ Twenty-five percent of patients will not respond to steroids; others will not tolerate the side effects of steroid therapy.¹⁰

Immunosuppressive drugs such as azothioprine, methotrexate, cyclosporine, mycophenolate mofetil and cyclophosphamide may be used as second-line treatment (SOR: C).⁶ Intravenous immunoglobulin may have some efficacy (SOR: B).¹⁶ Plasmapheresis does not appear to be effective (SOR: B).¹⁷

Determinants of prognosis

Most patients will improve over several weeks or months with therapy, although a third or more are left with mild to severe muscle damage. Dermatomyositis responds better than polymyositis; inclusion-body myositis is the most difficult to treat.¹⁰ Poor prognostic factors include older age, association with cancer, pulmonary fibrosis, dysphagia with aspiration pneumonia, cardiac involvement, steroid-resistant disease, and calcinosis in dermatomyositis.^6,10 Studies have demonstrated 5-year survival rates between 77% and 92%.^18,19 The main causes of death were related to malignancy and cardiac or pulmonary complications.

Roughly 50 million adult Americans have hypertension.¹ Chances are some of them are—or soon will be—under your care.

Hypertension is common among patients with psychiatric disorders, particularly in those with chronic mental conditions.² Medication-associated weight gain and other reactions to psychotropics, drug-drug interactions, lack of exercise, adverse dietary habits, and pre-existing medical conditions all predispose psychiatric patients to hypertension.

Yet hypertension often goes undetected in psychiatric patients. Hypertension many times is asymptomatic—about 50% of all people with the disorder don’t even know they have it.³ Some symptoms of uncontrolled hypertension—fatigue, headache, palpitations, and dizziness—are also associated with many psychiatric disorders. As a result, psychiatrists may attempt to manage the symptoms but miss the hypertension.

Psychiatrists need to be alert for hypertension, either as a possible contributing factor to a mental disorder or as a potential side effect of a psychiatric disorder or treatment. The following diagnostic and treatment strategies will help you detect and manage this common condition.

Causes of hypertension in mental illness

The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure defines elevated blood pressure as 140 mm Hg systolic and/or 90 mm Hg diastolic. The diagnosis of hypertension should be based on the average of two or more blood pressure readings at each of two or more visits after initial screening.

All patients with elevated blood pressure have an underlying physiologic abnormality that is causing their hypertension. The disorder falls within the following two categories:

• essential hypertension, emanating from an unknown cause
• secondary hypertension, resulting from an underlying, discoverable, often treatable cause.

Researchers have speculated that certain psychiatric disorders might cause, or be risk factors for, hypertension. Anxiety or panic disorders have been associated with acute (and perhaps chronic) blood pressure elevations.² Some research suggests that patients with alexithymia are at risk for developing hypertension.⁴

Other studies suggest that hypertensive patients with certain psychological disorders (e.g., depression) or social factors (e.g., substance abuse) are less likely than nonaffected patients to self-report the presence of hypertension and less likely to receive medical attention for it.⁵

Psychiatric drugs also may affect blood pressure by one of two mechanisms:

• Pharmacodynamic—direct effects at the site of action (e.g., receptors) via physiologic mechanisms (Table 1). For example, amphetamines act directly on the sympathetic nervous system to elevate blood pressure.
• Pharmacokinetic—indirect effects on blood pressure via drug/drug interactions that alter the absorption, distribution, metabolism, or clearance of antihypertensive medications. Thiazide diuretics, angiotensin-converting enzyme (ACE) inhibitors, and salt intake restrictions can raise lithium levels. The calcium-channel blockers verapamil and diltiazem can unpredictably increase or decrease lithium levels, but the combination generally is safe. Verapamil also raises tricyclic antidepressant levels. Monoamine oxidase inhibitors (MAOIs) used in tandem with the antihypertensive reserpine can cause hypomania. Beta-blocker levels are increased when used in concert with selective serotonin reuptake inhibitors. Use of carbamazepine with calcium-channel blockers can elevate carbamazapine levels and diminish the effectiveness of the calcium-channel blocker.

Table 1

POSSIBLE PHARMACODYNAMIC EFFECTS OFPSYCHIATRIC MEDICATIONS ON BLOOD PRESSURE

Symptoms, complications of high blood pressure

Symptoms that may be associated with high blood pressure include headaches, dizziness, lightheadedness, fatigue, palpitations, and chest discomfort. Patients may also experience symptoms secondary to end-organ damage (e.g., shortness of breath from congestive heart failure).

Most people, however, experience no symptoms when their blood pressure is elevated. This is one reason most people with hypertension do not adequately control their blood pressure.

Aside from the long-term end-organ damage caused by persistently elevated blood pressure, hypertension also has been found to cause psychiatric disorders, though not directly. For example, post-MI depression is well-recognized. Hypertension may also cause multi-infarct dementia with resultant depression, paranoia, or other psychotic features.

The psychological burden of having chronic and usually incurable (though controllable) hypertension may worsen depression or anxiety disorders. Patients with a chronic psychiatric illness generally have a higher incidence of chronic medical problems.

Likewise, patients with chronic medical disorders have a higher incidence of psychiatric complaints.⁶

Patient evaluation

When evaluating the patient with elevated blood pressure, it is important to:

• detect and confirm hypertension
• detect target-organ disease (e.g., renal damage or congestive heart failure)
• identify other cardiovascular risk factors (e.g., diabetes mellitus, hyperlipidemia, obesity)
• identify secondary causes of hypertension, such as endocrine abnormalities (e.g., hyperaldosteronism, thyroid disorders), kidney disease, obstructive sleep apnea, and response to medications.

Table 2

ANTIHYPERTENSIVE MEDICATIONS AND SIDE EFFECTS

A thorough history and physical examination should be performed to assess these four areas. Routine laboratory testing for the hypertensive patient should include a urinalysis, a complete blood count, an assessment of blood chemistries (potassium, sodium, creatinine, fasting glucose, fasting lipid profile), and a 12-lead electrocardiogram.

Treating hypertension

Many medications are used to treat hypertension. Most classes of antihypertensive agents have been shown to be about equally effective in lowering blood pressure.

All other factors being equal, the sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-VI) recommends initial treatment with a diuretic or beta-blocker. These classes of drugs have been shown to significantly reduce overall hypertension-related mortality.

Most patients with hypertension—particularly the elderly, patients with diabetes mellitus, and those with renal disease—will need two or more agents to control their blood pressure. Avoid prescribing agents that may worsen an existing condition (e.g., beta-blockers may worsen bronchospasm in patients with asthma). Use agents that may help improve comorbid conditions (e.g., beta-blockers have been shown to reduce mortality in patients with previous MI).

Box

Potential side effects, some of which mimic or are commonly found in psychiatric disorders, must be considered when choosing an antihypertensive agent. Table 2 lists nine classes of antihypertensives and some associated side effects. Also consider the agent’s cost, convenience of administration, direct-to-consumer advertising, and the patient’s age or race. For example, beta-blockers tend to be less effective in black or elderly patients than in other demographic groups.

Nonpharmacologic hypertension management emphasizes weight reduction, moderation of alcohol intake, regular aerobic exercise, dietary restriction of sodium, and smoking cessation. Most studies of these behavioral interventions have demonstrated a short-term benefit in decreasing blood pressure, but long-term adherence to them is disappointing. Relaxation therapies and biofeedback have been advocated for hypertension, but proof of their efficacy is lacking.⁷

As more is learned about genetic and other causes of hypertension, more-effective treatments for hypertension could become available (Box).

Treating high-risk groups

Special considerations apply to two patient groups with a high prevalence of hypertension—those age 65 and older and those with diabetes.

Older patients. Treatment benefits are more pronounced in patients age 65 or older because of their greater absolute risk for cardiovascular events. Also, systolic blood pressures increase with aging as the arterial tree becomes progressively less distensible.

Older patients often will require more than one drug to control their blood pressure. The initial dosages should be low and gradually titrated upward as needed. To minimize side effects, use smaller doses of multiple agents that are well tolerated instead of high-dose monotherapy.

A diuretic is often recommended as initial treatment for older patients, though a long-acting dihydropyridine calcium-channel blocker is a reasonable alternative. An ACE inhibitor is recommended for older patients with diabetes, systolic congestive heart failure, or previous MI. An alpha blocker should not be used as initial therapy for hypertension in the elderly because of relative lack of efficacy in preventing cardiovascular events.

Patients with diabetes. Aggressive blood pressure control is especially important in the patient with diabetes, which is the leading cause of end-stage renal disease. Most patients with diabetes also have hypertension—which accelerates their renal disease as well as cardiovascular disease. Blood pressure control goals significantly below 140/90 mm Hg are recommended (120 to 135 mm Hg systolic, 80 to 85 mm Hg diastolic) if diabetes is present.

ACE inhibitors or angiotensin receptor blockers are preferred for initial treatment of hypertension in diabetes, especially if proteinuria is present. Some authorities feel the level of blood pressure control in diabetes is more important than the agent(s) chosen to achieve that control. Most patients with hypertension and diabetes are not controlled on a single antihypertensive drug, and a diuretic is often added.

Psychological aspects of hypertension management

The diagnosis of hypertension and a resulting perception of loss of health or longevity may trigger a grief reaction in some patients.

Several psychological aspects to hypertension treatment make it difficult to achieve long-term control. Patients may become discouraged as dosages are increased and more medications are added. Asymptomatic patients may have no incentive to control their blood pressure. Many report, “I don’t feel any better” when their blood pressure comes down.

Because the goal of hypertension therapy is control rather than cure, the patient must commit to long-term treatment. Lifestyle changes such as dietary sodium restriction, smoking cessation, and weight loss may be difficult to achieve, especially for patients already dealing with a psychiatric disorder.

Also, the cost of treatment—the price of medications and initial and follow-up laboratory studies, plus the expense of follow-up office visits (possibly requiring time off work)—may be high.

Psychiatrists can help by offering moral support and encouraging patients to manage their medical problems, risk factors, and overall health. Psychiatrists can also educate patients on the importance of blood pressure control in preventing cardiovascular morbidity and mortality.

Brief cognitive-behaviorial therapy can identify the individual’s state of change (precontemplation, contemplation, preparation, action, or maintenance). Process techniques (such as consciousness-raising, commitment, or self-reevaluation) appropriate to the stage of change may then be employed.

For example, a patient in the precontemplation stage may resist returning to his or her primary care doctor to begin treatment for high blood pressure, employing such reasoning as, “I can’t afford those expensive office visits, and the medications would cost too much anyway.”

The psychiatrist might then apply consciousness-raising to motivate the patient: “How serious do you think it is to have high blood pressure that isn’t controlled? Are you aware that many people with high blood pressure are treated by means other than medications, or that many blood pressure medications are inexpensive?”

Providing relaxation techniques or a 12-week course of buproprion also can enhance the efficacy of smoking cessation efforts.

Related resources

• Drugs for hypertension. The Medical Letter 2001;43(1099):17-22.
• Some drugs that cause psychiatric symptoms. The Medical Letter 1998;40(1020):21-4.
• Hypertension—Journal of the American Heart Association. http://hyper.ahajournals.org/
• National Heart, Lung, and Blood institute’s Cardiovascular information site. http://www.nhlbi.nih.gov/health/public/heart/index.htm#hbp

Drug brand names

• Bupropion • Wellbutrin
• Guanadrel • Hylorel
• Lisinopril • Prinivil, Zestril
• Losartan • Hyzaar
• Ramipril • Altace
• Reserpine • Diutensen-R
• Valsartan • Diovan
• Venlafaxine • Effexor
• (Numerous other drugs mentioned in this article are available generically)

Disclosure

The author reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Roughly 50 million adult Americans have hypertension.¹ Chances are some of them are—or soon will be—under your care.

Hypertension is common among patients with psychiatric disorders, particularly in those with chronic mental conditions.² Medication-associated weight gain and other reactions to psychotropics, drug-drug interactions, lack of exercise, adverse dietary habits, and pre-existing medical conditions all predispose psychiatric patients to hypertension.

Yet hypertension often goes undetected in psychiatric patients. Hypertension many times is asymptomatic—about 50% of all people with the disorder don’t even know they have it.³ Some symptoms of uncontrolled hypertension—fatigue, headache, palpitations, and dizziness—are also associated with many psychiatric disorders. As a result, psychiatrists may attempt to manage the symptoms but miss the hypertension.

Psychiatrists need to be alert for hypertension, either as a possible contributing factor to a mental disorder or as a potential side effect of a psychiatric disorder or treatment. The following diagnostic and treatment strategies will help you detect and manage this common condition.

Causes of hypertension in mental illness

The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure defines elevated blood pressure as 140 mm Hg systolic and/or 90 mm Hg diastolic. The diagnosis of hypertension should be based on the average of two or more blood pressure readings at each of two or more visits after initial screening.

All patients with elevated blood pressure have an underlying physiologic abnormality that is causing their hypertension. The disorder falls within the following two categories:

• essential hypertension, emanating from an unknown cause
• secondary hypertension, resulting from an underlying, discoverable, often treatable cause.

Researchers have speculated that certain psychiatric disorders might cause, or be risk factors for, hypertension. Anxiety or panic disorders have been associated with acute (and perhaps chronic) blood pressure elevations.² Some research suggests that patients with alexithymia are at risk for developing hypertension.⁴

Other studies suggest that hypertensive patients with certain psychological disorders (e.g., depression) or social factors (e.g., substance abuse) are less likely than nonaffected patients to self-report the presence of hypertension and less likely to receive medical attention for it.⁵

Psychiatric drugs also may affect blood pressure by one of two mechanisms:

• Pharmacodynamic—direct effects at the site of action (e.g., receptors) via physiologic mechanisms (Table 1). For example, amphetamines act directly on the sympathetic nervous system to elevate blood pressure.
• Pharmacokinetic—indirect effects on blood pressure via drug/drug interactions that alter the absorption, distribution, metabolism, or clearance of antihypertensive medications. Thiazide diuretics, angiotensin-converting enzyme (ACE) inhibitors, and salt intake restrictions can raise lithium levels. The calcium-channel blockers verapamil and diltiazem can unpredictably increase or decrease lithium levels, but the combination generally is safe. Verapamil also raises tricyclic antidepressant levels. Monoamine oxidase inhibitors (MAOIs) used in tandem with the antihypertensive reserpine can cause hypomania. Beta-blocker levels are increased when used in concert with selective serotonin reuptake inhibitors. Use of carbamazepine with calcium-channel blockers can elevate carbamazapine levels and diminish the effectiveness of the calcium-channel blocker.

Table 1

POSSIBLE PHARMACODYNAMIC EFFECTS OFPSYCHIATRIC MEDICATIONS ON BLOOD PRESSURE

Symptoms, complications of high blood pressure

Symptoms that may be associated with high blood pressure include headaches, dizziness, lightheadedness, fatigue, palpitations, and chest discomfort. Patients may also experience symptoms secondary to end-organ damage (e.g., shortness of breath from congestive heart failure).

Most people, however, experience no symptoms when their blood pressure is elevated. This is one reason most people with hypertension do not adequately control their blood pressure.

Aside from the long-term end-organ damage caused by persistently elevated blood pressure, hypertension also has been found to cause psychiatric disorders, though not directly. For example, post-MI depression is well-recognized. Hypertension may also cause multi-infarct dementia with resultant depression, paranoia, or other psychotic features.

The psychological burden of having chronic and usually incurable (though controllable) hypertension may worsen depression or anxiety disorders. Patients with a chronic psychiatric illness generally have a higher incidence of chronic medical problems.

Likewise, patients with chronic medical disorders have a higher incidence of psychiatric complaints.⁶

Patient evaluation

When evaluating the patient with elevated blood pressure, it is important to:

• detect and confirm hypertension
• detect target-organ disease (e.g., renal damage or congestive heart failure)
• identify other cardiovascular risk factors (e.g., diabetes mellitus, hyperlipidemia, obesity)
• identify secondary causes of hypertension, such as endocrine abnormalities (e.g., hyperaldosteronism, thyroid disorders), kidney disease, obstructive sleep apnea, and response to medications.

Table 2

ANTIHYPERTENSIVE MEDICATIONS AND SIDE EFFECTS

A thorough history and physical examination should be performed to assess these four areas. Routine laboratory testing for the hypertensive patient should include a urinalysis, a complete blood count, an assessment of blood chemistries (potassium, sodium, creatinine, fasting glucose, fasting lipid profile), and a 12-lead electrocardiogram.

Treating hypertension

Many medications are used to treat hypertension. Most classes of antihypertensive agents have been shown to be about equally effective in lowering blood pressure.

All other factors being equal, the sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-VI) recommends initial treatment with a diuretic or beta-blocker. These classes of drugs have been shown to significantly reduce overall hypertension-related mortality.

Most patients with hypertension—particularly the elderly, patients with diabetes mellitus, and those with renal disease—will need two or more agents to control their blood pressure. Avoid prescribing agents that may worsen an existing condition (e.g., beta-blockers may worsen bronchospasm in patients with asthma). Use agents that may help improve comorbid conditions (e.g., beta-blockers have been shown to reduce mortality in patients with previous MI).

Box

Potential side effects, some of which mimic or are commonly found in psychiatric disorders, must be considered when choosing an antihypertensive agent. Table 2 lists nine classes of antihypertensives and some associated side effects. Also consider the agent’s cost, convenience of administration, direct-to-consumer advertising, and the patient’s age or race. For example, beta-blockers tend to be less effective in black or elderly patients than in other demographic groups.

Nonpharmacologic hypertension management emphasizes weight reduction, moderation of alcohol intake, regular aerobic exercise, dietary restriction of sodium, and smoking cessation. Most studies of these behavioral interventions have demonstrated a short-term benefit in decreasing blood pressure, but long-term adherence to them is disappointing. Relaxation therapies and biofeedback have been advocated for hypertension, but proof of their efficacy is lacking.⁷

As more is learned about genetic and other causes of hypertension, more-effective treatments for hypertension could become available (Box).

Treating high-risk groups

Special considerations apply to two patient groups with a high prevalence of hypertension—those age 65 and older and those with diabetes.

Older patients. Treatment benefits are more pronounced in patients age 65 or older because of their greater absolute risk for cardiovascular events. Also, systolic blood pressures increase with aging as the arterial tree becomes progressively less distensible.

Older patients often will require more than one drug to control their blood pressure. The initial dosages should be low and gradually titrated upward as needed. To minimize side effects, use smaller doses of multiple agents that are well tolerated instead of high-dose monotherapy.

A diuretic is often recommended as initial treatment for older patients, though a long-acting dihydropyridine calcium-channel blocker is a reasonable alternative. An ACE inhibitor is recommended for older patients with diabetes, systolic congestive heart failure, or previous MI. An alpha blocker should not be used as initial therapy for hypertension in the elderly because of relative lack of efficacy in preventing cardiovascular events.

Patients with diabetes. Aggressive blood pressure control is especially important in the patient with diabetes, which is the leading cause of end-stage renal disease. Most patients with diabetes also have hypertension—which accelerates their renal disease as well as cardiovascular disease. Blood pressure control goals significantly below 140/90 mm Hg are recommended (120 to 135 mm Hg systolic, 80 to 85 mm Hg diastolic) if diabetes is present.

ACE inhibitors or angiotensin receptor blockers are preferred for initial treatment of hypertension in diabetes, especially if proteinuria is present. Some authorities feel the level of blood pressure control in diabetes is more important than the agent(s) chosen to achieve that control. Most patients with hypertension and diabetes are not controlled on a single antihypertensive drug, and a diuretic is often added.

Psychological aspects of hypertension management

The diagnosis of hypertension and a resulting perception of loss of health or longevity may trigger a grief reaction in some patients.

Several psychological aspects to hypertension treatment make it difficult to achieve long-term control. Patients may become discouraged as dosages are increased and more medications are added. Asymptomatic patients may have no incentive to control their blood pressure. Many report, “I don’t feel any better” when their blood pressure comes down.

Because the goal of hypertension therapy is control rather than cure, the patient must commit to long-term treatment. Lifestyle changes such as dietary sodium restriction, smoking cessation, and weight loss may be difficult to achieve, especially for patients already dealing with a psychiatric disorder.

Also, the cost of treatment—the price of medications and initial and follow-up laboratory studies, plus the expense of follow-up office visits (possibly requiring time off work)—may be high.

Psychiatrists can help by offering moral support and encouraging patients to manage their medical problems, risk factors, and overall health. Psychiatrists can also educate patients on the importance of blood pressure control in preventing cardiovascular morbidity and mortality.

Brief cognitive-behaviorial therapy can identify the individual’s state of change (precontemplation, contemplation, preparation, action, or maintenance). Process techniques (such as consciousness-raising, commitment, or self-reevaluation) appropriate to the stage of change may then be employed.

For example, a patient in the precontemplation stage may resist returning to his or her primary care doctor to begin treatment for high blood pressure, employing such reasoning as, “I can’t afford those expensive office visits, and the medications would cost too much anyway.”

The psychiatrist might then apply consciousness-raising to motivate the patient: “How serious do you think it is to have high blood pressure that isn’t controlled? Are you aware that many people with high blood pressure are treated by means other than medications, or that many blood pressure medications are inexpensive?”

Providing relaxation techniques or a 12-week course of buproprion also can enhance the efficacy of smoking cessation efforts.

Related resources

• Drugs for hypertension. The Medical Letter 2001;43(1099):17-22.
• Some drugs that cause psychiatric symptoms. The Medical Letter 1998;40(1020):21-4.
• Hypertension—Journal of the American Heart Association. http://hyper.ahajournals.org/
• National Heart, Lung, and Blood institute’s Cardiovascular information site. http://www.nhlbi.nih.gov/health/public/heart/index.htm#hbp

Drug brand names

• Bupropion • Wellbutrin
• Guanadrel • Hylorel
• Lisinopril • Prinivil, Zestril
• Losartan • Hyzaar
• Ramipril • Altace
• Reserpine • Diutensen-R
• Valsartan • Diovan
• Venlafaxine • Effexor
• (Numerous other drugs mentioned in this article are available generically)

Disclosure

The author reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Roughly 50 million adult Americans have hypertension.¹ Chances are some of them are—or soon will be—under your care.

Hypertension is common among patients with psychiatric disorders, particularly in those with chronic mental conditions.² Medication-associated weight gain and other reactions to psychotropics, drug-drug interactions, lack of exercise, adverse dietary habits, and pre-existing medical conditions all predispose psychiatric patients to hypertension.

Yet hypertension often goes undetected in psychiatric patients. Hypertension many times is asymptomatic—about 50% of all people with the disorder don’t even know they have it.³ Some symptoms of uncontrolled hypertension—fatigue, headache, palpitations, and dizziness—are also associated with many psychiatric disorders. As a result, psychiatrists may attempt to manage the symptoms but miss the hypertension.

Psychiatrists need to be alert for hypertension, either as a possible contributing factor to a mental disorder or as a potential side effect of a psychiatric disorder or treatment. The following diagnostic and treatment strategies will help you detect and manage this common condition.

Causes of hypertension in mental illness

The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure defines elevated blood pressure as 140 mm Hg systolic and/or 90 mm Hg diastolic. The diagnosis of hypertension should be based on the average of two or more blood pressure readings at each of two or more visits after initial screening.

All patients with elevated blood pressure have an underlying physiologic abnormality that is causing their hypertension. The disorder falls within the following two categories:

• essential hypertension, emanating from an unknown cause
• secondary hypertension, resulting from an underlying, discoverable, often treatable cause.

Researchers have speculated that certain psychiatric disorders might cause, or be risk factors for, hypertension. Anxiety or panic disorders have been associated with acute (and perhaps chronic) blood pressure elevations.² Some research suggests that patients with alexithymia are at risk for developing hypertension.⁴

Other studies suggest that hypertensive patients with certain psychological disorders (e.g., depression) or social factors (e.g., substance abuse) are less likely than nonaffected patients to self-report the presence of hypertension and less likely to receive medical attention for it.⁵

Psychiatric drugs also may affect blood pressure by one of two mechanisms:

• Pharmacodynamic—direct effects at the site of action (e.g., receptors) via physiologic mechanisms (Table 1). For example, amphetamines act directly on the sympathetic nervous system to elevate blood pressure.
• Pharmacokinetic—indirect effects on blood pressure via drug/drug interactions that alter the absorption, distribution, metabolism, or clearance of antihypertensive medications. Thiazide diuretics, angiotensin-converting enzyme (ACE) inhibitors, and salt intake restrictions can raise lithium levels. The calcium-channel blockers verapamil and diltiazem can unpredictably increase or decrease lithium levels, but the combination generally is safe. Verapamil also raises tricyclic antidepressant levels. Monoamine oxidase inhibitors (MAOIs) used in tandem with the antihypertensive reserpine can cause hypomania. Beta-blocker levels are increased when used in concert with selective serotonin reuptake inhibitors. Use of carbamazepine with calcium-channel blockers can elevate carbamazapine levels and diminish the effectiveness of the calcium-channel blocker.

Table 1

POSSIBLE PHARMACODYNAMIC EFFECTS OFPSYCHIATRIC MEDICATIONS ON BLOOD PRESSURE

Symptoms, complications of high blood pressure

Symptoms that may be associated with high blood pressure include headaches, dizziness, lightheadedness, fatigue, palpitations, and chest discomfort. Patients may also experience symptoms secondary to end-organ damage (e.g., shortness of breath from congestive heart failure).

Most people, however, experience no symptoms when their blood pressure is elevated. This is one reason most people with hypertension do not adequately control their blood pressure.

Aside from the long-term end-organ damage caused by persistently elevated blood pressure, hypertension also has been found to cause psychiatric disorders, though not directly. For example, post-MI depression is well-recognized. Hypertension may also cause multi-infarct dementia with resultant depression, paranoia, or other psychotic features.

The psychological burden of having chronic and usually incurable (though controllable) hypertension may worsen depression or anxiety disorders. Patients with a chronic psychiatric illness generally have a higher incidence of chronic medical problems.

Likewise, patients with chronic medical disorders have a higher incidence of psychiatric complaints.⁶

Patient evaluation

When evaluating the patient with elevated blood pressure, it is important to:

• detect and confirm hypertension
• detect target-organ disease (e.g., renal damage or congestive heart failure)
• identify other cardiovascular risk factors (e.g., diabetes mellitus, hyperlipidemia, obesity)
• identify secondary causes of hypertension, such as endocrine abnormalities (e.g., hyperaldosteronism, thyroid disorders), kidney disease, obstructive sleep apnea, and response to medications.

Table 2

ANTIHYPERTENSIVE MEDICATIONS AND SIDE EFFECTS

A thorough history and physical examination should be performed to assess these four areas. Routine laboratory testing for the hypertensive patient should include a urinalysis, a complete blood count, an assessment of blood chemistries (potassium, sodium, creatinine, fasting glucose, fasting lipid profile), and a 12-lead electrocardiogram.

Treating hypertension

Many medications are used to treat hypertension. Most classes of antihypertensive agents have been shown to be about equally effective in lowering blood pressure.

All other factors being equal, the sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-VI) recommends initial treatment with a diuretic or beta-blocker. These classes of drugs have been shown to significantly reduce overall hypertension-related mortality.

Most patients with hypertension—particularly the elderly, patients with diabetes mellitus, and those with renal disease—will need two or more agents to control their blood pressure. Avoid prescribing agents that may worsen an existing condition (e.g., beta-blockers may worsen bronchospasm in patients with asthma). Use agents that may help improve comorbid conditions (e.g., beta-blockers have been shown to reduce mortality in patients with previous MI).

Box

Potential side effects, some of which mimic or are commonly found in psychiatric disorders, must be considered when choosing an antihypertensive agent. Table 2 lists nine classes of antihypertensives and some associated side effects. Also consider the agent’s cost, convenience of administration, direct-to-consumer advertising, and the patient’s age or race. For example, beta-blockers tend to be less effective in black or elderly patients than in other demographic groups.

Nonpharmacologic hypertension management emphasizes weight reduction, moderation of alcohol intake, regular aerobic exercise, dietary restriction of sodium, and smoking cessation. Most studies of these behavioral interventions have demonstrated a short-term benefit in decreasing blood pressure, but long-term adherence to them is disappointing. Relaxation therapies and biofeedback have been advocated for hypertension, but proof of their efficacy is lacking.⁷

As more is learned about genetic and other causes of hypertension, more-effective treatments for hypertension could become available (Box).

Treating high-risk groups

Special considerations apply to two patient groups with a high prevalence of hypertension—those age 65 and older and those with diabetes.

Older patients. Treatment benefits are more pronounced in patients age 65 or older because of their greater absolute risk for cardiovascular events. Also, systolic blood pressures increase with aging as the arterial tree becomes progressively less distensible.

Older patients often will require more than one drug to control their blood pressure. The initial dosages should be low and gradually titrated upward as needed. To minimize side effects, use smaller doses of multiple agents that are well tolerated instead of high-dose monotherapy.

A diuretic is often recommended as initial treatment for older patients, though a long-acting dihydropyridine calcium-channel blocker is a reasonable alternative. An ACE inhibitor is recommended for older patients with diabetes, systolic congestive heart failure, or previous MI. An alpha blocker should not be used as initial therapy for hypertension in the elderly because of relative lack of efficacy in preventing cardiovascular events.

Patients with diabetes. Aggressive blood pressure control is especially important in the patient with diabetes, which is the leading cause of end-stage renal disease. Most patients with diabetes also have hypertension—which accelerates their renal disease as well as cardiovascular disease. Blood pressure control goals significantly below 140/90 mm Hg are recommended (120 to 135 mm Hg systolic, 80 to 85 mm Hg diastolic) if diabetes is present.

ACE inhibitors or angiotensin receptor blockers are preferred for initial treatment of hypertension in diabetes, especially if proteinuria is present. Some authorities feel the level of blood pressure control in diabetes is more important than the agent(s) chosen to achieve that control. Most patients with hypertension and diabetes are not controlled on a single antihypertensive drug, and a diuretic is often added.

Psychological aspects of hypertension management

The diagnosis of hypertension and a resulting perception of loss of health or longevity may trigger a grief reaction in some patients.

Several psychological aspects to hypertension treatment make it difficult to achieve long-term control. Patients may become discouraged as dosages are increased and more medications are added. Asymptomatic patients may have no incentive to control their blood pressure. Many report, “I don’t feel any better” when their blood pressure comes down.

Because the goal of hypertension therapy is control rather than cure, the patient must commit to long-term treatment. Lifestyle changes such as dietary sodium restriction, smoking cessation, and weight loss may be difficult to achieve, especially for patients already dealing with a psychiatric disorder.

Also, the cost of treatment—the price of medications and initial and follow-up laboratory studies, plus the expense of follow-up office visits (possibly requiring time off work)—may be high.

Psychiatrists can help by offering moral support and encouraging patients to manage their medical problems, risk factors, and overall health. Psychiatrists can also educate patients on the importance of blood pressure control in preventing cardiovascular morbidity and mortality.

Brief cognitive-behaviorial therapy can identify the individual’s state of change (precontemplation, contemplation, preparation, action, or maintenance). Process techniques (such as consciousness-raising, commitment, or self-reevaluation) appropriate to the stage of change may then be employed.

For example, a patient in the precontemplation stage may resist returning to his or her primary care doctor to begin treatment for high blood pressure, employing such reasoning as, “I can’t afford those expensive office visits, and the medications would cost too much anyway.”

The psychiatrist might then apply consciousness-raising to motivate the patient: “How serious do you think it is to have high blood pressure that isn’t controlled? Are you aware that many people with high blood pressure are treated by means other than medications, or that many blood pressure medications are inexpensive?”

Providing relaxation techniques or a 12-week course of buproprion also can enhance the efficacy of smoking cessation efforts.

Related resources

• Drugs for hypertension. The Medical Letter 2001;43(1099):17-22.
• Some drugs that cause psychiatric symptoms. The Medical Letter 1998;40(1020):21-4.
• Hypertension—Journal of the American Heart Association. http://hyper.ahajournals.org/
• National Heart, Lung, and Blood institute’s Cardiovascular information site. http://www.nhlbi.nih.gov/health/public/heart/index.htm#hbp

Drug brand names

• Bupropion • Wellbutrin
• Guanadrel • Hylorel
• Lisinopril • Prinivil, Zestril
• Losartan • Hyzaar
• Ramipril • Altace
• Reserpine • Diutensen-R
• Valsartan • Diovan
• Venlafaxine • Effexor
• (Numerous other drugs mentioned in this article are available generically)

Disclosure

The author reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.