Applied Evidence

Visit #1: Simple steps to take right away

When a patient confides that she suffers from urinary incontinence, even if it’s near the end of her visit, there are 3 critical steps that can be taken without delay:

1. Collect a urine sample for urinalysis (if the patient is capable of providing a clean-catch sample and did not already do so at the start of the visit).
2. Ask her to keep a voiding diary for 3 days, using the clip-and-copy patient handout. (Tech-savvy patients may prefer to use the voiding diary app available at no charge at http://itunes.apple.com/us/app/bladder-pal/id435763473?mt=8.) Review the instructions for filling out the voiding diary with the patient, or have a nurse or medical assistant do so. Call the patient’s attention to the numerical (1-4) formula recommended for approximating the quantity of urine lost in an episode of incontinence, as this is often the component of the diary that patients have the most trouble with. ⁷
3. Schedule a follow-up visit. If the urinalysis shows that the patient has a urinary tract infection, initiate treatment as soon as possible. Treatment should be completed by the time she arrives for visit#2 so that her incontinence can be reassessed in the absence of infection.

Tell your patient to bring the completed voiding diary to this visit and to avoid emptying her bladder before she sees you. When the patient checks in, she should be reminded again not to urinate until you have completed the examination.

What to do during Visit #2

This visit will begin with a targeted assessment to determine what type of incontinence the patient has and whether you should initiate treatment or refer her to a specialist.

Start with a targeted history and review of the voiding diary
Ask the patient about timing, quantity, and the overall circumstances of typical incontinence episodes, as well as the incidents that she finds most troubling. A medication history should be included, with information not only about what she’s taking, but also about when she takes her medications. A careful review of the voiding diary will provide additional information, including fluid intake quantity and quality (eg, caffeine or alcohol) and urinary frequency, quantity, and timing.

The initial goal is to classify her incontinence as urge (occurring simultaneously with, or right after, a strong feeling of the need to void); stress (the result of an acute increase in abdominal pressure, typically associated with a physical act such as coughing, sneezing, bending over, heavy lifting, or starting to run); or mixed, which involves some episodes of both.⁸ “High-yield” questions like the ones that follow are particularly helpful in pinpointing the type of incontinence and guiding treatment decisions:

• Do you worry about leakage when you cough or sneeze? (Stress incontinence.)
• When your bladder is full, do you typically have to stop what you’re doing and go right away, or can you wait until a convenient time to find a bathroom? (Urge incontinence.)

And, for patients who report both stress and urge episodes (mixed incontinence):

• Which is more upsetting to you: leakage that occurs when you cough or sneeze or the inability to wait until it’s convenient to get to a bathroom?

A pelvic exam and cough stress test
Next, perform a pelvic examination and assess the following:

External genitalia. Look for signs of chronic urine exposure (eg, erythema, skin breakdown) and urethral abnormalities.

Cystoceles or rectoceles. Ask the patient to bear down strongly to allow you to visualize cystoceles and rectoceles, which usually present as a significant bulging of the tissues of the anterior or posterior vaginal walls. Reassure her that urine leakage and flatus are completely acceptable—and expected—during this part of the exam.

Pelvic mass. Palpate for evidence of a pelvic mass, which can cause urinary obstruction and lead to overflow incontinence.

Kegel exercises. Ask her to perform a Kegel maneuver. If she’s doing it correctly, her perineal body should be easily seen moving upward toward her clitoris and inward toward her introitus. If you place a finger in the vagina and ask her to begin Kegel exercises, you’ll feel the tightening of the pelvic muscles if she’s doing it right. When she does this on her own, she can insert her own finger into the vagina to ensure that her technique is correct or simply practice stopping the flow of urine.

After completing the pelvic exam, perform a cough stress test. With the patient in the lithotomy position, ask her to cough while you hold the labia apart, both to observe for any leakage of urine and to approximate the volume leaked, if any ( FIGURE ). To encourage her to bear down with ample force, remind her that here, too, both leakage of urine and passing of flatus are expected.

Postvoid residual (PVr). After the pelvic exam and cough stress test, the patient should urinate and the PVR should be promptly measured. If you have doubts about her ability to provide a clean-catch urine sample (or your clinic does not have a bladder scanning ultrasound), consider obtaining the PVR via a straight catheterization. A normal PVR is 0 to 200 cc.

By now you should have the information you need to determine whether to treat the incontinence yourself or refer the patient to a urologist or urogynecologist.

FIGURE
Positive cough stress test

Treat these conditions yourself

Dx: Uncomplicated stress incontinence. The patient has a positive cough stress test, and most urinary incontinence episodes she recorded are stress type. Urinalysis and PVR are normal, with no evidence of pelvic organ prolapse on exam.

Well-timed pelvic floor (Kegel) exercises have been shown to significantly reduce symptoms of both stress and urge incontinence when they’re done regularly, starting with 4 times a day and increased slowly to 8 times twice a day.⁹ Review Kegel technique and advise the patient to perform this maneuver and hold the contraction, if possible, whenever she is about to cough, laugh, sneeze, or otherwise exert herself. Tell her to practice Kegel exercises until they become second nature. If she continues to have trouble, she may need a referral to pelvic floor physical therapy to learn to do them effectively. (You can go to http://www.apta.org/apta/findapt/index.aspx?navID=10737422525 to find a therapist specializing in women’s health in your area.)

Dx: Uncomplicated urge incontinence. The patient has a normal cough stress test and most of her urinary incontinence episodes are the urge type. Her pelvic exam and PVR are within normal limits.

Prescribe an anticholinergic bladder agent. Medication with antimuscarinic properties has been shown to decrease urge incontinence and significantly improve patient-reported measures of quality of life.¹⁰

A reasonable approach is to start her on an inexpensive generic medication ( TABLE )^11,12 and follow up in one month. If the medication helps and does not cause adverse effects, she can be maintained on it; if it’s effective but she has significant adverse effects (eg, constipation, dry mouth, blurred vision, urinary retention, as well as confusion and sedation in the elderly), the patient can be switched to a more expensive brand-name drug with fewer adverse effects.

Behavioral training, including timed voiding and Kegel exercises, has been shown to significantly decrease symptoms of urge incontinence.⁹ Timed voiding can be especially helpful for nocturnal urge incontinence; advise the patient to set an alarm for an hour before the usual time she awakens with a sense of urgency, and to empty her bladder before it is so full that she leaks.

Point out, too, that not every urinary urge requires immediately running to the toilet. A randomized, placebo-controlled trial found that patients who were taught to respond to visual cues, such as a toilet, by walking past it, then sitting down, relaxing, and contracting their pelvic muscles repeatedly had diminished urgency. Their actions also inhibited detrusor contractions, and often prevented urine loss. When the training was combined with one or 2 lessons in proper Kegel technique—reinforced at several visits—weekly incontinence episodes were reduced by 80%. The controls, who had the same number of clinic visits but did not receive specific education on urgency-reduction strategies, reduced incontinence episodes by 40%.¹³

Dx: Fluid overuse. The patient is drinking an excessive quantity of fluid, as evidenced by urine volume >2100 cc. (The International Continence Society defines polyuria as >40 mL/kg per day.¹⁴ )

Advise the patient to decrease her overall fluid intake, particularly within several hours of bedtime. Studies of tea and coffee consumption and incontinence have had conflicting results,^15,16 and data on caffeinated soda consumption and incontinence are lacking. Nonetheless, patients should be advised that there is a possible association between caffeinated beverages and urinary incontinence. (In one small study, caffeine was found to cause a significant increase in detrusor pressure.¹⁷ ) Giving women one-time general instructions on fluid intake modification has been shown to significantly decrease incontinence episodes.¹⁸

Dx: Badly timed medication intake. This patient is taking one or more drugs that may contribute to incontinence, such as alpha-blockers or diuretics, either shortly before going to bed or before activities that make a bathroom visit inconvenient or impossible.

Adjust her medication regimen to minimize nocturia or urinary urgency during times of peak activity—eg, taking a diuretic early in the day instead of in the afternoon or evening, if possible. Keep in mind, however, that this strategy is based primarily on expert opinion, as very little evidence exists to show that medication of any type has a significant effect on urinary continence.¹⁹

Dx: Lower extremity edema with postural diuresis. The patient has nocturia, with larger total urine output at night than during the day. She may or may not have some leakage.

Women with lower extremity edema due to a variety of medical causes often experience postural diuresis overnight. If the patient is already on a diuretic, the problem can often be ameliorated by taking it early in the day instead of in the afternoon or evening; if she’s not, prescribe a small dose of a diuretic, to be taken in the morning. This therapeutic intervention has not been rigorously studied, but is relatively easy to implement and worth a try for patients with heart failure or other causes of pedal edema.

Dx: Constipation associated with autonomic dysfunction. Because the rectum and bladder are controlled by the same sacral segments of the spinal cord and share many autonomic ganglia, problems in one compartment often affect another. In a patient for whom incontinence is a minor, or occasional, problem while constipation is a major complaint, the optimal approach is to treat the constipation first and see if the urinary incontinence also resolves.

A trial of polyethylene glycol is a good place to start, particularly if there is no evidence of another correctable cause of the incontinence. Studies have shown that successful treatment of constipation often results in significant improvement of urinary urgency and frequency.²⁰

TABLE
Anticholinergic medications for urge incontinence^11,12

These conditions typically warrant a referral

Dx: Hematuria. Urinalysis with hematuria but no evidence of a urinary tract infection should raise a red flag, regardless of other findings. The patient should be referred for further urologic evaluation, including cystoscopy, although you may want to repeat the urinalysis with another clean-catch specimen first. Straight catheterization is not recommended in such a case, as a traumatized urethra can be a source of hematuria.

Dx: Stress incontinence with an anatomic abnormality. There are 2 options for a patient who has stress incontinence with an obvious cystocele on exam: Fit her with a pessary (or refer her to a physician who has this capability), or provide a referral to a urogynecologist for corrective surgery. Which option to choose should be a collaborative decision between patient and physician. For most women, it makes sense to try the pessary first.

Dx: Urinary retention. A patient with a high normal or elevated PVR (>100-200 cc) and no obvious pelvic organ prolapse needs a work-up for urinary retention. There is a broad differential that can be divided into neurologic, obstructive, and pharmacologic etiologies.²¹ A referral is indicated so that a urologist can oversee the work-up.

Particularly worrisome causes of urinary retention are multiple sclerosis, which is more likely in a relatively young, otherwise healthy woman, and a pelvic mass. Medications are also a likely cause. The list of drugs that can induce urinary retention is extensive, and includes anticholinergics, antidepressants (tricyclics and some heterocyclics), antihistamines, and muscle relaxants, among others. If you’re unable to find a likely cause, a referral is indicated so that a urologist can oversee the work-up.

CORRESPONDENCE Abigail Lowther, MD, University of Michigan Department of Family Medicine, 24 Frank Lloyd Wright Drive, Lobby H, Ann Arbor, MI 48106-5795; abigaill@med.umich.edu

Visit #1: Simple steps to take right away

When a patient confides that she suffers from urinary incontinence, even if it’s near the end of her visit, there are 3 critical steps that can be taken without delay:

1. Collect a urine sample for urinalysis (if the patient is capable of providing a clean-catch sample and did not already do so at the start of the visit).
2. Ask her to keep a voiding diary for 3 days, using the clip-and-copy patient handout. (Tech-savvy patients may prefer to use the voiding diary app available at no charge at http://itunes.apple.com/us/app/bladder-pal/id435763473?mt=8.) Review the instructions for filling out the voiding diary with the patient, or have a nurse or medical assistant do so. Call the patient’s attention to the numerical (1-4) formula recommended for approximating the quantity of urine lost in an episode of incontinence, as this is often the component of the diary that patients have the most trouble with. ⁷
3. Schedule a follow-up visit. If the urinalysis shows that the patient has a urinary tract infection, initiate treatment as soon as possible. Treatment should be completed by the time she arrives for visit#2 so that her incontinence can be reassessed in the absence of infection.

Tell your patient to bring the completed voiding diary to this visit and to avoid emptying her bladder before she sees you. When the patient checks in, she should be reminded again not to urinate until you have completed the examination.

What to do during Visit #2

This visit will begin with a targeted assessment to determine what type of incontinence the patient has and whether you should initiate treatment or refer her to a specialist.

Start with a targeted history and review of the voiding diary
Ask the patient about timing, quantity, and the overall circumstances of typical incontinence episodes, as well as the incidents that she finds most troubling. A medication history should be included, with information not only about what she’s taking, but also about when she takes her medications. A careful review of the voiding diary will provide additional information, including fluid intake quantity and quality (eg, caffeine or alcohol) and urinary frequency, quantity, and timing.

The initial goal is to classify her incontinence as urge (occurring simultaneously with, or right after, a strong feeling of the need to void); stress (the result of an acute increase in abdominal pressure, typically associated with a physical act such as coughing, sneezing, bending over, heavy lifting, or starting to run); or mixed, which involves some episodes of both.⁸ “High-yield” questions like the ones that follow are particularly helpful in pinpointing the type of incontinence and guiding treatment decisions:

• Do you worry about leakage when you cough or sneeze? (Stress incontinence.)
• When your bladder is full, do you typically have to stop what you’re doing and go right away, or can you wait until a convenient time to find a bathroom? (Urge incontinence.)

And, for patients who report both stress and urge episodes (mixed incontinence):

• Which is more upsetting to you: leakage that occurs when you cough or sneeze or the inability to wait until it’s convenient to get to a bathroom?

A pelvic exam and cough stress test
Next, perform a pelvic examination and assess the following:

External genitalia. Look for signs of chronic urine exposure (eg, erythema, skin breakdown) and urethral abnormalities.

Cystoceles or rectoceles. Ask the patient to bear down strongly to allow you to visualize cystoceles and rectoceles, which usually present as a significant bulging of the tissues of the anterior or posterior vaginal walls. Reassure her that urine leakage and flatus are completely acceptable—and expected—during this part of the exam.

Pelvic mass. Palpate for evidence of a pelvic mass, which can cause urinary obstruction and lead to overflow incontinence.

Kegel exercises. Ask her to perform a Kegel maneuver. If she’s doing it correctly, her perineal body should be easily seen moving upward toward her clitoris and inward toward her introitus. If you place a finger in the vagina and ask her to begin Kegel exercises, you’ll feel the tightening of the pelvic muscles if she’s doing it right. When she does this on her own, she can insert her own finger into the vagina to ensure that her technique is correct or simply practice stopping the flow of urine.

After completing the pelvic exam, perform a cough stress test. With the patient in the lithotomy position, ask her to cough while you hold the labia apart, both to observe for any leakage of urine and to approximate the volume leaked, if any ( FIGURE ). To encourage her to bear down with ample force, remind her that here, too, both leakage of urine and passing of flatus are expected.

Postvoid residual (PVr). After the pelvic exam and cough stress test, the patient should urinate and the PVR should be promptly measured. If you have doubts about her ability to provide a clean-catch urine sample (or your clinic does not have a bladder scanning ultrasound), consider obtaining the PVR via a straight catheterization. A normal PVR is 0 to 200 cc.

By now you should have the information you need to determine whether to treat the incontinence yourself or refer the patient to a urologist or urogynecologist.

FIGURE
Positive cough stress test

Treat these conditions yourself

Dx: Uncomplicated stress incontinence. The patient has a positive cough stress test, and most urinary incontinence episodes she recorded are stress type. Urinalysis and PVR are normal, with no evidence of pelvic organ prolapse on exam.

Well-timed pelvic floor (Kegel) exercises have been shown to significantly reduce symptoms of both stress and urge incontinence when they’re done regularly, starting with 4 times a day and increased slowly to 8 times twice a day.⁹ Review Kegel technique and advise the patient to perform this maneuver and hold the contraction, if possible, whenever she is about to cough, laugh, sneeze, or otherwise exert herself. Tell her to practice Kegel exercises until they become second nature. If she continues to have trouble, she may need a referral to pelvic floor physical therapy to learn to do them effectively. (You can go to http://www.apta.org/apta/findapt/index.aspx?navID=10737422525 to find a therapist specializing in women’s health in your area.)

Dx: Uncomplicated urge incontinence. The patient has a normal cough stress test and most of her urinary incontinence episodes are the urge type. Her pelvic exam and PVR are within normal limits.

Prescribe an anticholinergic bladder agent. Medication with antimuscarinic properties has been shown to decrease urge incontinence and significantly improve patient-reported measures of quality of life.¹⁰

A reasonable approach is to start her on an inexpensive generic medication ( TABLE )^11,12 and follow up in one month. If the medication helps and does not cause adverse effects, she can be maintained on it; if it’s effective but she has significant adverse effects (eg, constipation, dry mouth, blurred vision, urinary retention, as well as confusion and sedation in the elderly), the patient can be switched to a more expensive brand-name drug with fewer adverse effects.

Behavioral training, including timed voiding and Kegel exercises, has been shown to significantly decrease symptoms of urge incontinence.⁹ Timed voiding can be especially helpful for nocturnal urge incontinence; advise the patient to set an alarm for an hour before the usual time she awakens with a sense of urgency, and to empty her bladder before it is so full that she leaks.

Point out, too, that not every urinary urge requires immediately running to the toilet. A randomized, placebo-controlled trial found that patients who were taught to respond to visual cues, such as a toilet, by walking past it, then sitting down, relaxing, and contracting their pelvic muscles repeatedly had diminished urgency. Their actions also inhibited detrusor contractions, and often prevented urine loss. When the training was combined with one or 2 lessons in proper Kegel technique—reinforced at several visits—weekly incontinence episodes were reduced by 80%. The controls, who had the same number of clinic visits but did not receive specific education on urgency-reduction strategies, reduced incontinence episodes by 40%.¹³

Dx: Fluid overuse. The patient is drinking an excessive quantity of fluid, as evidenced by urine volume >2100 cc. (The International Continence Society defines polyuria as >40 mL/kg per day.¹⁴ )

Advise the patient to decrease her overall fluid intake, particularly within several hours of bedtime. Studies of tea and coffee consumption and incontinence have had conflicting results,^15,16 and data on caffeinated soda consumption and incontinence are lacking. Nonetheless, patients should be advised that there is a possible association between caffeinated beverages and urinary incontinence. (In one small study, caffeine was found to cause a significant increase in detrusor pressure.¹⁷ ) Giving women one-time general instructions on fluid intake modification has been shown to significantly decrease incontinence episodes.¹⁸

Dx: Badly timed medication intake. This patient is taking one or more drugs that may contribute to incontinence, such as alpha-blockers or diuretics, either shortly before going to bed or before activities that make a bathroom visit inconvenient or impossible.

Adjust her medication regimen to minimize nocturia or urinary urgency during times of peak activity—eg, taking a diuretic early in the day instead of in the afternoon or evening, if possible. Keep in mind, however, that this strategy is based primarily on expert opinion, as very little evidence exists to show that medication of any type has a significant effect on urinary continence.¹⁹

Dx: Lower extremity edema with postural diuresis. The patient has nocturia, with larger total urine output at night than during the day. She may or may not have some leakage.

Women with lower extremity edema due to a variety of medical causes often experience postural diuresis overnight. If the patient is already on a diuretic, the problem can often be ameliorated by taking it early in the day instead of in the afternoon or evening; if she’s not, prescribe a small dose of a diuretic, to be taken in the morning. This therapeutic intervention has not been rigorously studied, but is relatively easy to implement and worth a try for patients with heart failure or other causes of pedal edema.

Dx: Constipation associated with autonomic dysfunction. Because the rectum and bladder are controlled by the same sacral segments of the spinal cord and share many autonomic ganglia, problems in one compartment often affect another. In a patient for whom incontinence is a minor, or occasional, problem while constipation is a major complaint, the optimal approach is to treat the constipation first and see if the urinary incontinence also resolves.

A trial of polyethylene glycol is a good place to start, particularly if there is no evidence of another correctable cause of the incontinence. Studies have shown that successful treatment of constipation often results in significant improvement of urinary urgency and frequency.²⁰

TABLE
Anticholinergic medications for urge incontinence^11,12

These conditions typically warrant a referral

Dx: Hematuria. Urinalysis with hematuria but no evidence of a urinary tract infection should raise a red flag, regardless of other findings. The patient should be referred for further urologic evaluation, including cystoscopy, although you may want to repeat the urinalysis with another clean-catch specimen first. Straight catheterization is not recommended in such a case, as a traumatized urethra can be a source of hematuria.

Dx: Stress incontinence with an anatomic abnormality. There are 2 options for a patient who has stress incontinence with an obvious cystocele on exam: Fit her with a pessary (or refer her to a physician who has this capability), or provide a referral to a urogynecologist for corrective surgery. Which option to choose should be a collaborative decision between patient and physician. For most women, it makes sense to try the pessary first.

Dx: Urinary retention. A patient with a high normal or elevated PVR (>100-200 cc) and no obvious pelvic organ prolapse needs a work-up for urinary retention. There is a broad differential that can be divided into neurologic, obstructive, and pharmacologic etiologies.²¹ A referral is indicated so that a urologist can oversee the work-up.

Particularly worrisome causes of urinary retention are multiple sclerosis, which is more likely in a relatively young, otherwise healthy woman, and a pelvic mass. Medications are also a likely cause. The list of drugs that can induce urinary retention is extensive, and includes anticholinergics, antidepressants (tricyclics and some heterocyclics), antihistamines, and muscle relaxants, among others. If you’re unable to find a likely cause, a referral is indicated so that a urologist can oversee the work-up.

CORRESPONDENCE Abigail Lowther, MD, University of Michigan Department of Family Medicine, 24 Frank Lloyd Wright Drive, Lobby H, Ann Arbor, MI 48106-5795; abigaill@med.umich.edu

Visit #1: Simple steps to take right away

When a patient confides that she suffers from urinary incontinence, even if it’s near the end of her visit, there are 3 critical steps that can be taken without delay:

1. Collect a urine sample for urinalysis (if the patient is capable of providing a clean-catch sample and did not already do so at the start of the visit).
2. Ask her to keep a voiding diary for 3 days, using the clip-and-copy patient handout. (Tech-savvy patients may prefer to use the voiding diary app available at no charge at http://itunes.apple.com/us/app/bladder-pal/id435763473?mt=8.) Review the instructions for filling out the voiding diary with the patient, or have a nurse or medical assistant do so. Call the patient’s attention to the numerical (1-4) formula recommended for approximating the quantity of urine lost in an episode of incontinence, as this is often the component of the diary that patients have the most trouble with. ⁷
3. Schedule a follow-up visit. If the urinalysis shows that the patient has a urinary tract infection, initiate treatment as soon as possible. Treatment should be completed by the time she arrives for visit#2 so that her incontinence can be reassessed in the absence of infection.

Tell your patient to bring the completed voiding diary to this visit and to avoid emptying her bladder before she sees you. When the patient checks in, she should be reminded again not to urinate until you have completed the examination.

What to do during Visit #2

This visit will begin with a targeted assessment to determine what type of incontinence the patient has and whether you should initiate treatment or refer her to a specialist.

Start with a targeted history and review of the voiding diary
Ask the patient about timing, quantity, and the overall circumstances of typical incontinence episodes, as well as the incidents that she finds most troubling. A medication history should be included, with information not only about what she’s taking, but also about when she takes her medications. A careful review of the voiding diary will provide additional information, including fluid intake quantity and quality (eg, caffeine or alcohol) and urinary frequency, quantity, and timing.

The initial goal is to classify her incontinence as urge (occurring simultaneously with, or right after, a strong feeling of the need to void); stress (the result of an acute increase in abdominal pressure, typically associated with a physical act such as coughing, sneezing, bending over, heavy lifting, or starting to run); or mixed, which involves some episodes of both.⁸ “High-yield” questions like the ones that follow are particularly helpful in pinpointing the type of incontinence and guiding treatment decisions:

• Do you worry about leakage when you cough or sneeze? (Stress incontinence.)
• When your bladder is full, do you typically have to stop what you’re doing and go right away, or can you wait until a convenient time to find a bathroom? (Urge incontinence.)

And, for patients who report both stress and urge episodes (mixed incontinence):

• Which is more upsetting to you: leakage that occurs when you cough or sneeze or the inability to wait until it’s convenient to get to a bathroom?

A pelvic exam and cough stress test
Next, perform a pelvic examination and assess the following:

External genitalia. Look for signs of chronic urine exposure (eg, erythema, skin breakdown) and urethral abnormalities.

Cystoceles or rectoceles. Ask the patient to bear down strongly to allow you to visualize cystoceles and rectoceles, which usually present as a significant bulging of the tissues of the anterior or posterior vaginal walls. Reassure her that urine leakage and flatus are completely acceptable—and expected—during this part of the exam.

Pelvic mass. Palpate for evidence of a pelvic mass, which can cause urinary obstruction and lead to overflow incontinence.

Kegel exercises. Ask her to perform a Kegel maneuver. If she’s doing it correctly, her perineal body should be easily seen moving upward toward her clitoris and inward toward her introitus. If you place a finger in the vagina and ask her to begin Kegel exercises, you’ll feel the tightening of the pelvic muscles if she’s doing it right. When she does this on her own, she can insert her own finger into the vagina to ensure that her technique is correct or simply practice stopping the flow of urine.

After completing the pelvic exam, perform a cough stress test. With the patient in the lithotomy position, ask her to cough while you hold the labia apart, both to observe for any leakage of urine and to approximate the volume leaked, if any ( FIGURE ). To encourage her to bear down with ample force, remind her that here, too, both leakage of urine and passing of flatus are expected.

Postvoid residual (PVr). After the pelvic exam and cough stress test, the patient should urinate and the PVR should be promptly measured. If you have doubts about her ability to provide a clean-catch urine sample (or your clinic does not have a bladder scanning ultrasound), consider obtaining the PVR via a straight catheterization. A normal PVR is 0 to 200 cc.

By now you should have the information you need to determine whether to treat the incontinence yourself or refer the patient to a urologist or urogynecologist.

FIGURE
Positive cough stress test

Treat these conditions yourself

Dx: Uncomplicated stress incontinence. The patient has a positive cough stress test, and most urinary incontinence episodes she recorded are stress type. Urinalysis and PVR are normal, with no evidence of pelvic organ prolapse on exam.

Well-timed pelvic floor (Kegel) exercises have been shown to significantly reduce symptoms of both stress and urge incontinence when they’re done regularly, starting with 4 times a day and increased slowly to 8 times twice a day.⁹ Review Kegel technique and advise the patient to perform this maneuver and hold the contraction, if possible, whenever she is about to cough, laugh, sneeze, or otherwise exert herself. Tell her to practice Kegel exercises until they become second nature. If she continues to have trouble, she may need a referral to pelvic floor physical therapy to learn to do them effectively. (You can go to http://www.apta.org/apta/findapt/index.aspx?navID=10737422525 to find a therapist specializing in women’s health in your area.)

Dx: Uncomplicated urge incontinence. The patient has a normal cough stress test and most of her urinary incontinence episodes are the urge type. Her pelvic exam and PVR are within normal limits.

Prescribe an anticholinergic bladder agent. Medication with antimuscarinic properties has been shown to decrease urge incontinence and significantly improve patient-reported measures of quality of life.¹⁰

A reasonable approach is to start her on an inexpensive generic medication ( TABLE )^11,12 and follow up in one month. If the medication helps and does not cause adverse effects, she can be maintained on it; if it’s effective but she has significant adverse effects (eg, constipation, dry mouth, blurred vision, urinary retention, as well as confusion and sedation in the elderly), the patient can be switched to a more expensive brand-name drug with fewer adverse effects.

Behavioral training, including timed voiding and Kegel exercises, has been shown to significantly decrease symptoms of urge incontinence.⁹ Timed voiding can be especially helpful for nocturnal urge incontinence; advise the patient to set an alarm for an hour before the usual time she awakens with a sense of urgency, and to empty her bladder before it is so full that she leaks.

Point out, too, that not every urinary urge requires immediately running to the toilet. A randomized, placebo-controlled trial found that patients who were taught to respond to visual cues, such as a toilet, by walking past it, then sitting down, relaxing, and contracting their pelvic muscles repeatedly had diminished urgency. Their actions also inhibited detrusor contractions, and often prevented urine loss. When the training was combined with one or 2 lessons in proper Kegel technique—reinforced at several visits—weekly incontinence episodes were reduced by 80%. The controls, who had the same number of clinic visits but did not receive specific education on urgency-reduction strategies, reduced incontinence episodes by 40%.¹³

Dx: Fluid overuse. The patient is drinking an excessive quantity of fluid, as evidenced by urine volume >2100 cc. (The International Continence Society defines polyuria as >40 mL/kg per day.¹⁴ )

Advise the patient to decrease her overall fluid intake, particularly within several hours of bedtime. Studies of tea and coffee consumption and incontinence have had conflicting results,^15,16 and data on caffeinated soda consumption and incontinence are lacking. Nonetheless, patients should be advised that there is a possible association between caffeinated beverages and urinary incontinence. (In one small study, caffeine was found to cause a significant increase in detrusor pressure.¹⁷ ) Giving women one-time general instructions on fluid intake modification has been shown to significantly decrease incontinence episodes.¹⁸

Dx: Badly timed medication intake. This patient is taking one or more drugs that may contribute to incontinence, such as alpha-blockers or diuretics, either shortly before going to bed or before activities that make a bathroom visit inconvenient or impossible.

Adjust her medication regimen to minimize nocturia or urinary urgency during times of peak activity—eg, taking a diuretic early in the day instead of in the afternoon or evening, if possible. Keep in mind, however, that this strategy is based primarily on expert opinion, as very little evidence exists to show that medication of any type has a significant effect on urinary continence.¹⁹

Dx: Lower extremity edema with postural diuresis. The patient has nocturia, with larger total urine output at night than during the day. She may or may not have some leakage.

Women with lower extremity edema due to a variety of medical causes often experience postural diuresis overnight. If the patient is already on a diuretic, the problem can often be ameliorated by taking it early in the day instead of in the afternoon or evening; if she’s not, prescribe a small dose of a diuretic, to be taken in the morning. This therapeutic intervention has not been rigorously studied, but is relatively easy to implement and worth a try for patients with heart failure or other causes of pedal edema.

Dx: Constipation associated with autonomic dysfunction. Because the rectum and bladder are controlled by the same sacral segments of the spinal cord and share many autonomic ganglia, problems in one compartment often affect another. In a patient for whom incontinence is a minor, or occasional, problem while constipation is a major complaint, the optimal approach is to treat the constipation first and see if the urinary incontinence also resolves.

A trial of polyethylene glycol is a good place to start, particularly if there is no evidence of another correctable cause of the incontinence. Studies have shown that successful treatment of constipation often results in significant improvement of urinary urgency and frequency.²⁰

TABLE
Anticholinergic medications for urge incontinence^11,12

These conditions typically warrant a referral

Dx: Hematuria. Urinalysis with hematuria but no evidence of a urinary tract infection should raise a red flag, regardless of other findings. The patient should be referred for further urologic evaluation, including cystoscopy, although you may want to repeat the urinalysis with another clean-catch specimen first. Straight catheterization is not recommended in such a case, as a traumatized urethra can be a source of hematuria.

Dx: Stress incontinence with an anatomic abnormality. There are 2 options for a patient who has stress incontinence with an obvious cystocele on exam: Fit her with a pessary (or refer her to a physician who has this capability), or provide a referral to a urogynecologist for corrective surgery. Which option to choose should be a collaborative decision between patient and physician. For most women, it makes sense to try the pessary first.

Dx: Urinary retention. A patient with a high normal or elevated PVR (>100-200 cc) and no obvious pelvic organ prolapse needs a work-up for urinary retention. There is a broad differential that can be divided into neurologic, obstructive, and pharmacologic etiologies.²¹ A referral is indicated so that a urologist can oversee the work-up.

Particularly worrisome causes of urinary retention are multiple sclerosis, which is more likely in a relatively young, otherwise healthy woman, and a pelvic mass. Medications are also a likely cause. The list of drugs that can induce urinary retention is extensive, and includes anticholinergics, antidepressants (tricyclics and some heterocyclics), antihistamines, and muscle relaxants, among others. If you’re unable to find a likely cause, a referral is indicated so that a urologist can oversee the work-up.

CORRESPONDENCE Abigail Lowther, MD, University of Michigan Department of Family Medicine, 24 Frank Lloyd Wright Drive, Lobby H, Ann Arbor, MI 48106-5795; abigaill@med.umich.edu

Your patient comes in complaining of acute eye pain. Is it an ophthalmic emergency? Benign? Something in between?

The varying degrees of severity are reflected in the cases presented here, and in the multiple-choice quiz that follows. After selecting your answer to each of the questions, turn the page to find out if you were right.

CASE 1 A 74-year-old man presents with left eye pain that began when he lowered the shades in his bedroom to get ready for a nap. The pain worsened rapidly, he reports, and now—a half hour later—he has a headache, nausea, and blurred vision in the affected eye.

The patient has a history of hypertension, which is controlled with hydrochlorothiazide, but takes no other drugs. He denies any eye trauma. An eye exam reveals that the pupil is dilated and reacts poorly to light; you note corneal haziness and edema, as well ( FIGURE 1; vertical line is the slit lamp beam).

FIGURE 1

What’s your diagnosis?

1. angle-closure glaucoma
2. macular degeneration
3. open-angle glaucoma
4. retinal detachment.

CASE 2 A 20-year-old man was playing touch football while wearing contact lenses. Soon after, the game, he felt a stinging sensation in his right eye—”like sand under the eyelid,” he said. Exposure to sunlight also produced eye pain. The patient had tried flushing his eye with water, but experienced little pain relief.

An eye exam reveals a grayish-white spot in the line of vision ( FIGURE 2 ), with no sign of a penetrating injury.

FIGURE 2

What’s your next step?

1. Prescribe antibiotic eye drops and send the patient home.
2. Provide an emergent ophthalmology referral for foreign body extraction.
3. Send the patient home with an eye patch to relieve the photophobia.
4. Attempt to conduct a visual acuity test and penlight exam without anesthetic; if necessary, apply anesthetic drops and fluorescein stain.

CASE 3 A 17-year-old woman is brought in by her mother because of pain and vision loss in her right eye. The pain started as soon as she awoke; 2 hours later, the vision in the affected eye became blurry. Soon after, she saw spots of light, followed by complete loss of vision. She denies any trauma and says she has never experienced anything like this before.

The patient’s visual acuity is 20/200 in her right eye, and 20/40 in the left. You follow up with a funduscopic exam of the eye, which shows edema of the optic disc, blurring of the disc margins, and distended veins ( FIGURE 3 ).

FIGURE 3

What diagnostic test should be next?

1. fluorescein angiography
2. intraocular pressure measurement
3. magnetic resonance imaging (MRI) of the brain
4. visual fields assessment.

CASE 4 A 31-year-old woman with a history of sarcoidosis comes in because of spontaneous redness ( FIGURE 4 ) and pain in her left eye, which began early that day. She denies any eye trauma, eye surgery, or recent cold, and has no discharge or crust around the eye.

FIGURE 4

What’s your diagnosis?

1. anterior uveitis
2. conjunctivitis
3. corneal abrasion
4. posterior uveitis.

CASE 5 A 21-year-old college student complains of pain in her left eye that started a day ago. She wears contact lenses and, upon questioning, tells you that she sometimes keeps them in all night.

The patient reports that she used a friend’s steroid eye drops twice yesterday, but the drops didn’t help. The pain is worse today. It feels as if there’s something in her eye, she says, and she finds it hard to open her eye. Penlight examination ( FIGURE 5 ) reveals a branching opacity on the cornea.

FIGURE 5

What’s your next step?

1. Advise the patient to stop wearing her contact lenses overnight, give her a cycloplegic, and follow up in 2 days.
2. Patch the patient’s left eye, prescribe antibiotics, and tell her to return tomorrow.
3. Prescribe steroid eye drops and follow up in 2 days.
4. Provide an urgent referral to an ophthalmologist.

CASE 1 The answer is A: angle-closure glaucoma.

Glaucoma is the world’s leading cause of blindness,^1,2 and angle-closure glaucoma comprises 10% of cases.² In this condition, the anterior chamber angle—formed by the iris and the cornea—is narrow. When the iris dilates in low light (eg, the darkened room in which the patient had planned to nap), it folds into the narrowed angle, preventing the flow of aqueous humor and leading to an increase in intraocular pressure.³

Signs and symptoms
Patients with acute angle-closure glaucoma often develop decreased vision, halos, headaches, severe eye pain, nausea, and vomiting. If the intraocular pressure increases quickly, symptoms can have an acute and dramatic onset; if pressure builds slowly, patients may have limited or no symptoms.⁴

Physical findings
An eye exam will reveal conjunctival erythema, corneal edema and cloudiness, iris irregularity, a shallow anterior chamber (visible with a slit lamp), a dilated pupil (4-6 mm) that reacts sluggishly to light, and increased ocular pressure. The cupping of the optic disc seen in this patient’s retinal exam ( FIGURE 6 ) is more commonly associated with chronic open-angle glaucoma.

FIGURE 6

Management
Acute angle-closure glaucoma is an ophthalmologic emergency, and a referral to a specialist is crucial. If no ophthalmologist can see the patient within an hour of the presentation of symptoms, you’ll need to initiate topical treatment to reduce intraocular pressure and ensure that he or she is seen by a specialist as soon as possible.⁵ First-line treatments for acute angle-closure glaucoma are listed in TABLE 1 .^5,6

In severe cases, topical therapy alone may be ineffective. If there are no contraindications, systemic medications such as acetazolamide, mannitol, glycerol, or isosorbide may be needed. Eye pressure should be checked 30 to 60 minutes after initiating systemic therapy and the patient closely monitored for adverse effects (eg, anaphylaxis, convulsions [acetazolamide]; hypotension [mannitol, isosorbide]).⁵

When the patient does see an ophthalmologist, the evaluation will include assessment of visual acuity, pupillary evaluation, measurement of intraocular pressure, slit lamp examination, gonioscopy to measure the angle of the anterior chamber, and a fundus exam without pupil dilation.⁵ Treatment may include a surgical procedure, such as paracentesis of the eye, peripheral iridotomy, or iridectomy, and chronic administration of topical medication.⁷

TABLE 1
Treatments for acute angle-closure glaucoma^5,6

CASE 2 The answer is D: Attempt to conduct a visual acuity test and penlight exam without anesthetic; if necessary, apply anesthetic drops and fluorescein stain.

This patient likely has a corneal ulcer or abrasion caused by a contact lens. Corneal ulcers—which constitute a loss of the corneal epithelium—can be caused by trauma or a foreign body, or develop spontaneously.

Signs and symptoms
Because of the rich innervation of the corneal epithelium by the trigeminal nerve, the cornea is highly sensitive to pain. Patients with corneal abrasions typically experience eye pain, photophobia, tearing, a foreign body sensation, and discomfort when driving, working, or reading. If a patient has damage to the trigeminal nerve, however (eg, from trauma, a tumor, or a herpes infection), corneal injuries may be painless.⁸

In some cases, corneal abrasions may be so painful that patients become disruptive while waiting to be seen. Thus, any patient suspected of having a corneal ulcer or abrasion should be ushered into a quiet, dark room and instructed to keep his or her eyes closed until the examination.

The patient history should focus on recent trauma, type of work, and use of protective eyewear, which may provide clues to the development of penetrating injuries, retained foreign bodies, or abrasions caused by a foreign body. Ask about the use of contact lenses, as well; corneal injury caused by contacts is associated with specific bacterial infections, most commonly staphylococcal organisms and Pseudomonas.⁹

Physical findings
Attempt to test visual acuity without topical anesthetics. If the patient can’t tolerate the test, a single drop of topical anesthetic (proparacaine 0.5%) may help. Visual acuity provides clues to the location of the injury. If acuity is close to baseline, the corneal abrasion is likely peripheral to the visual axis. Decreased visual acuity indicates either that the abrasion involves the central axis area or that there is corneal edema.⁹

Evaluation of the pupillary reflex and optic fundus should follow. Reactive miosis may be present with corneal abrasions. A large, nonreactive pupil may be a sign of injury to the pupillary sphincter from blunt or penetrating injury—an ophthalmologic emergency that requires urgent referral. The eyelid should be flipped and examined for foreign bodies. ⁹

Some abrasions can be seen with the naked eye, so a penlight exam should be performed before applying fluorescein stain. If a corneal lesion is suspicious for herpesvirus infection ( SEE CASE 5 ), fluorescein should not be applied, as it can interfere with the antibody test.¹⁰ Refer the patient to an ophthalmologist instead.

If there’s no evidence of infection, apply fluorescein and examine the cornea with a Wood’s lamp. A thin line or several vertical lines are suggestive of a foreign body in the cornea or under the eyelid, whereas round defects are often due to contact lenses.⁹ Physical findings associated with specific types of corneal abrasions or ulcers are detailed in TABLE 2 .^9,11,12

TABLE 2
Corneal abrasion or ulcers: The differential diagnosis^9,11,12

Management
Patients with corneal abrasions or ulcers should receive topical antibiotics to prevent infection. Ointments (erythromycin ointment 4 times daily for 3-5 days) are preferable to drops, but may be harder to obtain.⁹ If a patient must use drops, sulfacetamide 10%, polymyxin/trimethoprim, ciprofloxacin, or ofloxacin can be used, with the same frequency and duration.

Aminoglycosides are toxic to the corneal epithelium and should be avoided, except in abrasions caused by contacts.⁹ Because of the likelihood of pseudomonal keratitis in cases involving contact lenses, antibiotics covering Pseudomonas, such as ofloxacin, ciprofloxacin, or tobramycin, should be used.⁹

Pain control is achieved with cycloplegics¹¹ like cyclopentolate 0.5% to 1% or a one-day course of systemic opioids. For children, over-the-counter analgesics for mild pain and mild opioids for severe pain may be used.

Chronic use of topical anesthetics should be avoided in patients of any age. Although they relieve pain, frequent use can lead to delayed healing, ulcerations, perforations, scarring, or even blindness.⁸

Patching has not been found to improve healing or comfort;¹³ instead, it delays healing.^14,15 The “pirate patch,” which hovers over the eye, does not keep the eyelid down and therefore is not recommended.⁹

Follow up within 24 hours of initiating treatment to assure that the abrasion is healing. If it appears to be getting worse or is simply not improving, an immediate referral to an ophthalmologist is needed. Abrasions caused by contact with potentially infected material (eg, farm equipment, tree branches, or soil) require daily monitoring until they heal.¹¹

CASE 3 The answer is C: Order an MRI of the brain.

This patient has optic neuritis, caused by inflammation of the optic nerve and disruption of the nerve’s myelin sheath. It predominantly affects young adults, and is more common in women than in men.¹⁶ The incidence of optic neuritis is higher among Asians, black South Africans, and children under the age of 15.^17,18

Signs and symptoms
Optic neuritis is characterized by monocular (90%) or binocular (10%) complete or partial vision loss, photopsia (flashes of light), and eye pain. Up to 60% of pediatric patients present with blurred vision, bilateral involvement,¹⁹ and no pain, while adults predominantly have pain and unilateral vision loss.²⁰ Optic neuritis is often a presenting symptom of multiple sclerosis (MS).¹⁶

Physical findings
Physical exam findings in optic neuritis include a sluggish direct light reflex, loss of visual acuity and color vision, as well as acute eye pain.¹⁸ Ophthalmoscopic exam may reveal papillitis with edema of the optic disc.²¹ In the Optic Neuritis Treatment Trial (ONTT), however, only one-third of patients presented with papillitis and swelling of the optic disc.²²

MRI of the brain with gadolinium contrast is generally used to confirm the diagnosis. On MRI, 95% of patients with optic neuritis have signs of inflammation of the optic nerve and/or white matter changes consistent with MS (periventricular and ovoid demyelination).^23,24

Patients with evidence of demyelination should also be evaluated for MS and other demyelinating disorders. In the ONTT trial, the risk of developing MS within 15 years of an optic neuritis diagnosis was as low as 25% (95% confidence interval [CI], 18%-32%) for patients with no lesions on a baseline brain MRI and as high as 72% (95% CI, 63%-81%) for those with one or more lesions on a baseline MRI, according to the study’s final follow-up.²²

Management
The recommended treatment for optic neuritis is intravenous (IV) methylprednisolone 250 mg every 6 hours for 3 to 5 days, followed by oral prednisone at 1 mg/kg/d for 7 to 10 days. Vision usually returns slowly over the course of several months to a year. Ophthalmology consultation should be considered to rule out other causes of optic neuritis.²⁵

CASE 4 The answer is A: anterior uveitis.

Uveitis is often associated with systemic disease or infection, and diagnosis is typically suspected based on a history of conditions such as sarcoidosis, juvenile idiopathic arthritis, Kawasaki’s disease, Sjögren’s syndrome, toxoplasmosis, human immunodeficiency virus (HIV), tuberculosis (TB), syphilis, herpes simplex, and herpes zoster.²⁶

Signs and symptoms
Signs and symptoms vary depending on the part of the uveal tract that’s involved. Anterior uveitis, or iritis, is associated with pain, photophobia, redness, and a varying degree of vision loss. Posterior and intermediate uveitis are less likely to be associated with pain, but can be accompanied by decreased visual acuity and floaters.²⁷

Physical findings
Visual acuity in patients with uveitis can range from normal to varying degrees of vision loss. Redness around the iris can be seen; conjunctival infection is most marked around the circumference of the corneal limbus rather than more peripherally, as seen in conjunctivitis. On slit lamp examination, the beam of light can be seen in the aqueous humor due to protein and leukocyte accumulation—a phenomenon known as “flare.” The pupillary light reflex may be abnormal, and the pupillary opening may be irregular rather than round due to anterior and posterior synechia.²⁸

Management
Patients should be referred to an ophthalmologist for management of the immediate condition and to prevent or treat complications such as vision loss, optic nerve damage, and glaucoma. Acute management includes topical steroids, such as prednisolone acetate ophthalmic 1% 2 to 4 times daily, as well as treatment of the underlying condition. Long-term management varies, depending on the cause of the uveitis.^26,29

If the etiology is unknown, a workup should be considered to identify inflammatory and infectious disorders that might be causing uveitis. Chest radiograph is a good beginning to look for evidence of sarcoidosis or TB; serologic testing for syphilis, HIV, and lupus may also be considered.^26,29

CASE 5 The answer is D: Provide an urgent referral to an ophthalmologist.

This patient has viral keratitis caused by herpes. While the pain and foreign body sensation are the same for bacterial and viral keratitis, herpesvirus is distinguishable by the branching opacity that develops on the cornea.

Varicella zoster is the most common cause of viral keratitis, although it can also be caused by herpes simplex and adeno-virus. Because a person who is infected with herpes has the virus for life, however, multiple attacks are possible. Reactivation is associated with stress and a weakened immune system, but may occur spontaneously, as well. Patients who wear contact lenses are no more likely than those who don’t to be infected with the herpesvirus.

Bacterial keratitis is often associated with contact lenses, particularly when they’re continually worn, but also with normal wear.³⁰ Immunosuppression, dry ocular surfaces, and topical corticosteroid use may predispose patients to bacterial keratitis, as well.¹² Staphylococcus aureus, Pseudomonas aeruginosa, coagulase-negative Staphylococcus, diphtheroids, and Streptococcus pneumoniae are the most common pathogens.³¹

Signs and symptoms
Patients with keratitis typically complain of eye pain, a sensation of having a foreign body in the eye, photophobia, tearing, and vision changes; a mucopurulent discharge is sometimes present, as well.³ The condition is easily distinguished from conjunctivitis, which typically does not involve eye pain or vision changes.

Physical findings
Visual acuity may be affected if the lesion or corneal edema involves the visual axis. Physical exam in a patient with bacterial keratitis sometimes shows a gray or white corneal opacity, along with corneal erythema. As already noted, a penlight exam will reveal a branching opacity in patients with herpes keratitis.³⁰

Management
Patients with keratitis should be referred immediately to an ophthalmologist³² for a slit lamp evaluation, treatment, and close follow-up.

Corneal cultures can be difficult to obtain, but before prescribing antibiotics, an attempt to collect samples should be made. This can be done—after the administration of topical anesthesia—with a sterile calcium alginate swab. Gently swab the cornea and then inoculate the appropriate gels or mediums. Avoid contact with lashes and eyelids to prevent culture contamination.³²

When herpesvirus is suspected, start the patient on an antiviral agent such as trifluridine ophthalmic (1%) 9 times a day, vidarabine ophthalmic (3%) 5 times daily, or 400 mg oral acyclovir 5 times a day. Patients with bacterial keratitis should be started on antibiotic eye drops with Pseudomonas coverage, such as ofloxacin (0.3%), ciprofloxacin (0.3%), or tobramycin (0.3%), 6 to 8 times a day.⁹

CORRESPONDENCE Uyen Michelle Le, MD, 967 Galindo Court, Milpitas, CA 95035; mlkala21@aol.com

Your patient comes in complaining of acute eye pain. Is it an ophthalmic emergency? Benign? Something in between?

The varying degrees of severity are reflected in the cases presented here, and in the multiple-choice quiz that follows. After selecting your answer to each of the questions, turn the page to find out if you were right.

CASE 1 A 74-year-old man presents with left eye pain that began when he lowered the shades in his bedroom to get ready for a nap. The pain worsened rapidly, he reports, and now—a half hour later—he has a headache, nausea, and blurred vision in the affected eye.

The patient has a history of hypertension, which is controlled with hydrochlorothiazide, but takes no other drugs. He denies any eye trauma. An eye exam reveals that the pupil is dilated and reacts poorly to light; you note corneal haziness and edema, as well ( FIGURE 1; vertical line is the slit lamp beam).

FIGURE 1

What’s your diagnosis?

1. angle-closure glaucoma
2. macular degeneration
3. open-angle glaucoma
4. retinal detachment.

CASE 2 A 20-year-old man was playing touch football while wearing contact lenses. Soon after, the game, he felt a stinging sensation in his right eye—”like sand under the eyelid,” he said. Exposure to sunlight also produced eye pain. The patient had tried flushing his eye with water, but experienced little pain relief.

An eye exam reveals a grayish-white spot in the line of vision ( FIGURE 2 ), with no sign of a penetrating injury.

FIGURE 2

What’s your next step?

1. Prescribe antibiotic eye drops and send the patient home.
2. Provide an emergent ophthalmology referral for foreign body extraction.
3. Send the patient home with an eye patch to relieve the photophobia.
4. Attempt to conduct a visual acuity test and penlight exam without anesthetic; if necessary, apply anesthetic drops and fluorescein stain.

CASE 3 A 17-year-old woman is brought in by her mother because of pain and vision loss in her right eye. The pain started as soon as she awoke; 2 hours later, the vision in the affected eye became blurry. Soon after, she saw spots of light, followed by complete loss of vision. She denies any trauma and says she has never experienced anything like this before.

The patient’s visual acuity is 20/200 in her right eye, and 20/40 in the left. You follow up with a funduscopic exam of the eye, which shows edema of the optic disc, blurring of the disc margins, and distended veins ( FIGURE 3 ).

FIGURE 3

What diagnostic test should be next?

1. fluorescein angiography
2. intraocular pressure measurement
3. magnetic resonance imaging (MRI) of the brain
4. visual fields assessment.

CASE 4 A 31-year-old woman with a history of sarcoidosis comes in because of spontaneous redness ( FIGURE 4 ) and pain in her left eye, which began early that day. She denies any eye trauma, eye surgery, or recent cold, and has no discharge or crust around the eye.

FIGURE 4

What’s your diagnosis?

1. anterior uveitis
2. conjunctivitis
3. corneal abrasion
4. posterior uveitis.

CASE 5 A 21-year-old college student complains of pain in her left eye that started a day ago. She wears contact lenses and, upon questioning, tells you that she sometimes keeps them in all night.

The patient reports that she used a friend’s steroid eye drops twice yesterday, but the drops didn’t help. The pain is worse today. It feels as if there’s something in her eye, she says, and she finds it hard to open her eye. Penlight examination ( FIGURE 5 ) reveals a branching opacity on the cornea.

FIGURE 5

What’s your next step?

1. Advise the patient to stop wearing her contact lenses overnight, give her a cycloplegic, and follow up in 2 days.
2. Patch the patient’s left eye, prescribe antibiotics, and tell her to return tomorrow.
3. Prescribe steroid eye drops and follow up in 2 days.
4. Provide an urgent referral to an ophthalmologist.

CASE 1 The answer is A: angle-closure glaucoma.

Glaucoma is the world’s leading cause of blindness,^1,2 and angle-closure glaucoma comprises 10% of cases.² In this condition, the anterior chamber angle—formed by the iris and the cornea—is narrow. When the iris dilates in low light (eg, the darkened room in which the patient had planned to nap), it folds into the narrowed angle, preventing the flow of aqueous humor and leading to an increase in intraocular pressure.³

Signs and symptoms
Patients with acute angle-closure glaucoma often develop decreased vision, halos, headaches, severe eye pain, nausea, and vomiting. If the intraocular pressure increases quickly, symptoms can have an acute and dramatic onset; if pressure builds slowly, patients may have limited or no symptoms.⁴

Physical findings
An eye exam will reveal conjunctival erythema, corneal edema and cloudiness, iris irregularity, a shallow anterior chamber (visible with a slit lamp), a dilated pupil (4-6 mm) that reacts sluggishly to light, and increased ocular pressure. The cupping of the optic disc seen in this patient’s retinal exam ( FIGURE 6 ) is more commonly associated with chronic open-angle glaucoma.

FIGURE 6

Management
Acute angle-closure glaucoma is an ophthalmologic emergency, and a referral to a specialist is crucial. If no ophthalmologist can see the patient within an hour of the presentation of symptoms, you’ll need to initiate topical treatment to reduce intraocular pressure and ensure that he or she is seen by a specialist as soon as possible.⁵ First-line treatments for acute angle-closure glaucoma are listed in TABLE 1 .^5,6

In severe cases, topical therapy alone may be ineffective. If there are no contraindications, systemic medications such as acetazolamide, mannitol, glycerol, or isosorbide may be needed. Eye pressure should be checked 30 to 60 minutes after initiating systemic therapy and the patient closely monitored for adverse effects (eg, anaphylaxis, convulsions [acetazolamide]; hypotension [mannitol, isosorbide]).⁵

When the patient does see an ophthalmologist, the evaluation will include assessment of visual acuity, pupillary evaluation, measurement of intraocular pressure, slit lamp examination, gonioscopy to measure the angle of the anterior chamber, and a fundus exam without pupil dilation.⁵ Treatment may include a surgical procedure, such as paracentesis of the eye, peripheral iridotomy, or iridectomy, and chronic administration of topical medication.⁷

TABLE 1
Treatments for acute angle-closure glaucoma^5,6

CASE 2 The answer is D: Attempt to conduct a visual acuity test and penlight exam without anesthetic; if necessary, apply anesthetic drops and fluorescein stain.

This patient likely has a corneal ulcer or abrasion caused by a contact lens. Corneal ulcers—which constitute a loss of the corneal epithelium—can be caused by trauma or a foreign body, or develop spontaneously.

Signs and symptoms
Because of the rich innervation of the corneal epithelium by the trigeminal nerve, the cornea is highly sensitive to pain. Patients with corneal abrasions typically experience eye pain, photophobia, tearing, a foreign body sensation, and discomfort when driving, working, or reading. If a patient has damage to the trigeminal nerve, however (eg, from trauma, a tumor, or a herpes infection), corneal injuries may be painless.⁸

In some cases, corneal abrasions may be so painful that patients become disruptive while waiting to be seen. Thus, any patient suspected of having a corneal ulcer or abrasion should be ushered into a quiet, dark room and instructed to keep his or her eyes closed until the examination.

The patient history should focus on recent trauma, type of work, and use of protective eyewear, which may provide clues to the development of penetrating injuries, retained foreign bodies, or abrasions caused by a foreign body. Ask about the use of contact lenses, as well; corneal injury caused by contacts is associated with specific bacterial infections, most commonly staphylococcal organisms and Pseudomonas.⁹

Physical findings
Attempt to test visual acuity without topical anesthetics. If the patient can’t tolerate the test, a single drop of topical anesthetic (proparacaine 0.5%) may help. Visual acuity provides clues to the location of the injury. If acuity is close to baseline, the corneal abrasion is likely peripheral to the visual axis. Decreased visual acuity indicates either that the abrasion involves the central axis area or that there is corneal edema.⁹

Evaluation of the pupillary reflex and optic fundus should follow. Reactive miosis may be present with corneal abrasions. A large, nonreactive pupil may be a sign of injury to the pupillary sphincter from blunt or penetrating injury—an ophthalmologic emergency that requires urgent referral. The eyelid should be flipped and examined for foreign bodies. ⁹

Some abrasions can be seen with the naked eye, so a penlight exam should be performed before applying fluorescein stain. If a corneal lesion is suspicious for herpesvirus infection ( SEE CASE 5 ), fluorescein should not be applied, as it can interfere with the antibody test.¹⁰ Refer the patient to an ophthalmologist instead.

If there’s no evidence of infection, apply fluorescein and examine the cornea with a Wood’s lamp. A thin line or several vertical lines are suggestive of a foreign body in the cornea or under the eyelid, whereas round defects are often due to contact lenses.⁹ Physical findings associated with specific types of corneal abrasions or ulcers are detailed in TABLE 2 .^9,11,12

TABLE 2
Corneal abrasion or ulcers: The differential diagnosis^9,11,12

Management
Patients with corneal abrasions or ulcers should receive topical antibiotics to prevent infection. Ointments (erythromycin ointment 4 times daily for 3-5 days) are preferable to drops, but may be harder to obtain.⁹ If a patient must use drops, sulfacetamide 10%, polymyxin/trimethoprim, ciprofloxacin, or ofloxacin can be used, with the same frequency and duration.

Aminoglycosides are toxic to the corneal epithelium and should be avoided, except in abrasions caused by contacts.⁹ Because of the likelihood of pseudomonal keratitis in cases involving contact lenses, antibiotics covering Pseudomonas, such as ofloxacin, ciprofloxacin, or tobramycin, should be used.⁹

Pain control is achieved with cycloplegics¹¹ like cyclopentolate 0.5% to 1% or a one-day course of systemic opioids. For children, over-the-counter analgesics for mild pain and mild opioids for severe pain may be used.

Chronic use of topical anesthetics should be avoided in patients of any age. Although they relieve pain, frequent use can lead to delayed healing, ulcerations, perforations, scarring, or even blindness.⁸

Patching has not been found to improve healing or comfort;¹³ instead, it delays healing.^14,15 The “pirate patch,” which hovers over the eye, does not keep the eyelid down and therefore is not recommended.⁹

Follow up within 24 hours of initiating treatment to assure that the abrasion is healing. If it appears to be getting worse or is simply not improving, an immediate referral to an ophthalmologist is needed. Abrasions caused by contact with potentially infected material (eg, farm equipment, tree branches, or soil) require daily monitoring until they heal.¹¹

CASE 3 The answer is C: Order an MRI of the brain.

This patient has optic neuritis, caused by inflammation of the optic nerve and disruption of the nerve’s myelin sheath. It predominantly affects young adults, and is more common in women than in men.¹⁶ The incidence of optic neuritis is higher among Asians, black South Africans, and children under the age of 15.^17,18

Signs and symptoms
Optic neuritis is characterized by monocular (90%) or binocular (10%) complete or partial vision loss, photopsia (flashes of light), and eye pain. Up to 60% of pediatric patients present with blurred vision, bilateral involvement,¹⁹ and no pain, while adults predominantly have pain and unilateral vision loss.²⁰ Optic neuritis is often a presenting symptom of multiple sclerosis (MS).¹⁶

Physical findings
Physical exam findings in optic neuritis include a sluggish direct light reflex, loss of visual acuity and color vision, as well as acute eye pain.¹⁸ Ophthalmoscopic exam may reveal papillitis with edema of the optic disc.²¹ In the Optic Neuritis Treatment Trial (ONTT), however, only one-third of patients presented with papillitis and swelling of the optic disc.²²

MRI of the brain with gadolinium contrast is generally used to confirm the diagnosis. On MRI, 95% of patients with optic neuritis have signs of inflammation of the optic nerve and/or white matter changes consistent with MS (periventricular and ovoid demyelination).^23,24

Patients with evidence of demyelination should also be evaluated for MS and other demyelinating disorders. In the ONTT trial, the risk of developing MS within 15 years of an optic neuritis diagnosis was as low as 25% (95% confidence interval [CI], 18%-32%) for patients with no lesions on a baseline brain MRI and as high as 72% (95% CI, 63%-81%) for those with one or more lesions on a baseline MRI, according to the study’s final follow-up.²²

Management
The recommended treatment for optic neuritis is intravenous (IV) methylprednisolone 250 mg every 6 hours for 3 to 5 days, followed by oral prednisone at 1 mg/kg/d for 7 to 10 days. Vision usually returns slowly over the course of several months to a year. Ophthalmology consultation should be considered to rule out other causes of optic neuritis.²⁵

CASE 4 The answer is A: anterior uveitis.

Uveitis is often associated with systemic disease or infection, and diagnosis is typically suspected based on a history of conditions such as sarcoidosis, juvenile idiopathic arthritis, Kawasaki’s disease, Sjögren’s syndrome, toxoplasmosis, human immunodeficiency virus (HIV), tuberculosis (TB), syphilis, herpes simplex, and herpes zoster.²⁶

Signs and symptoms
Signs and symptoms vary depending on the part of the uveal tract that’s involved. Anterior uveitis, or iritis, is associated with pain, photophobia, redness, and a varying degree of vision loss. Posterior and intermediate uveitis are less likely to be associated with pain, but can be accompanied by decreased visual acuity and floaters.²⁷

Physical findings
Visual acuity in patients with uveitis can range from normal to varying degrees of vision loss. Redness around the iris can be seen; conjunctival infection is most marked around the circumference of the corneal limbus rather than more peripherally, as seen in conjunctivitis. On slit lamp examination, the beam of light can be seen in the aqueous humor due to protein and leukocyte accumulation—a phenomenon known as “flare.” The pupillary light reflex may be abnormal, and the pupillary opening may be irregular rather than round due to anterior and posterior synechia.²⁸

Management
Patients should be referred to an ophthalmologist for management of the immediate condition and to prevent or treat complications such as vision loss, optic nerve damage, and glaucoma. Acute management includes topical steroids, such as prednisolone acetate ophthalmic 1% 2 to 4 times daily, as well as treatment of the underlying condition. Long-term management varies, depending on the cause of the uveitis.^26,29

If the etiology is unknown, a workup should be considered to identify inflammatory and infectious disorders that might be causing uveitis. Chest radiograph is a good beginning to look for evidence of sarcoidosis or TB; serologic testing for syphilis, HIV, and lupus may also be considered.^26,29

CASE 5 The answer is D: Provide an urgent referral to an ophthalmologist.

This patient has viral keratitis caused by herpes. While the pain and foreign body sensation are the same for bacterial and viral keratitis, herpesvirus is distinguishable by the branching opacity that develops on the cornea.

Varicella zoster is the most common cause of viral keratitis, although it can also be caused by herpes simplex and adeno-virus. Because a person who is infected with herpes has the virus for life, however, multiple attacks are possible. Reactivation is associated with stress and a weakened immune system, but may occur spontaneously, as well. Patients who wear contact lenses are no more likely than those who don’t to be infected with the herpesvirus.

Bacterial keratitis is often associated with contact lenses, particularly when they’re continually worn, but also with normal wear.³⁰ Immunosuppression, dry ocular surfaces, and topical corticosteroid use may predispose patients to bacterial keratitis, as well.¹² Staphylococcus aureus, Pseudomonas aeruginosa, coagulase-negative Staphylococcus, diphtheroids, and Streptococcus pneumoniae are the most common pathogens.³¹

Signs and symptoms
Patients with keratitis typically complain of eye pain, a sensation of having a foreign body in the eye, photophobia, tearing, and vision changes; a mucopurulent discharge is sometimes present, as well.³ The condition is easily distinguished from conjunctivitis, which typically does not involve eye pain or vision changes.

Physical findings
Visual acuity may be affected if the lesion or corneal edema involves the visual axis. Physical exam in a patient with bacterial keratitis sometimes shows a gray or white corneal opacity, along with corneal erythema. As already noted, a penlight exam will reveal a branching opacity in patients with herpes keratitis.³⁰

Management
Patients with keratitis should be referred immediately to an ophthalmologist³² for a slit lamp evaluation, treatment, and close follow-up.

Corneal cultures can be difficult to obtain, but before prescribing antibiotics, an attempt to collect samples should be made. This can be done—after the administration of topical anesthesia—with a sterile calcium alginate swab. Gently swab the cornea and then inoculate the appropriate gels or mediums. Avoid contact with lashes and eyelids to prevent culture contamination.³²

When herpesvirus is suspected, start the patient on an antiviral agent such as trifluridine ophthalmic (1%) 9 times a day, vidarabine ophthalmic (3%) 5 times daily, or 400 mg oral acyclovir 5 times a day. Patients with bacterial keratitis should be started on antibiotic eye drops with Pseudomonas coverage, such as ofloxacin (0.3%), ciprofloxacin (0.3%), or tobramycin (0.3%), 6 to 8 times a day.⁹

CORRESPONDENCE Uyen Michelle Le, MD, 967 Galindo Court, Milpitas, CA 95035; mlkala21@aol.com

Your patient comes in complaining of acute eye pain. Is it an ophthalmic emergency? Benign? Something in between?

The varying degrees of severity are reflected in the cases presented here, and in the multiple-choice quiz that follows. After selecting your answer to each of the questions, turn the page to find out if you were right.

CASE 1 A 74-year-old man presents with left eye pain that began when he lowered the shades in his bedroom to get ready for a nap. The pain worsened rapidly, he reports, and now—a half hour later—he has a headache, nausea, and blurred vision in the affected eye.

The patient has a history of hypertension, which is controlled with hydrochlorothiazide, but takes no other drugs. He denies any eye trauma. An eye exam reveals that the pupil is dilated and reacts poorly to light; you note corneal haziness and edema, as well ( FIGURE 1; vertical line is the slit lamp beam).

FIGURE 1

What’s your diagnosis?

1. angle-closure glaucoma
2. macular degeneration
3. open-angle glaucoma
4. retinal detachment.

CASE 2 A 20-year-old man was playing touch football while wearing contact lenses. Soon after, the game, he felt a stinging sensation in his right eye—”like sand under the eyelid,” he said. Exposure to sunlight also produced eye pain. The patient had tried flushing his eye with water, but experienced little pain relief.

An eye exam reveals a grayish-white spot in the line of vision ( FIGURE 2 ), with no sign of a penetrating injury.

FIGURE 2

What’s your next step?

1. Prescribe antibiotic eye drops and send the patient home.
2. Provide an emergent ophthalmology referral for foreign body extraction.
3. Send the patient home with an eye patch to relieve the photophobia.
4. Attempt to conduct a visual acuity test and penlight exam without anesthetic; if necessary, apply anesthetic drops and fluorescein stain.

CASE 3 A 17-year-old woman is brought in by her mother because of pain and vision loss in her right eye. The pain started as soon as she awoke; 2 hours later, the vision in the affected eye became blurry. Soon after, she saw spots of light, followed by complete loss of vision. She denies any trauma and says she has never experienced anything like this before.

The patient’s visual acuity is 20/200 in her right eye, and 20/40 in the left. You follow up with a funduscopic exam of the eye, which shows edema of the optic disc, blurring of the disc margins, and distended veins ( FIGURE 3 ).

FIGURE 3

What diagnostic test should be next?

1. fluorescein angiography
2. intraocular pressure measurement
3. magnetic resonance imaging (MRI) of the brain
4. visual fields assessment.

CASE 4 A 31-year-old woman with a history of sarcoidosis comes in because of spontaneous redness ( FIGURE 4 ) and pain in her left eye, which began early that day. She denies any eye trauma, eye surgery, or recent cold, and has no discharge or crust around the eye.

FIGURE 4

What’s your diagnosis?

1. anterior uveitis
2. conjunctivitis
3. corneal abrasion
4. posterior uveitis.

CASE 5 A 21-year-old college student complains of pain in her left eye that started a day ago. She wears contact lenses and, upon questioning, tells you that she sometimes keeps them in all night.

The patient reports that she used a friend’s steroid eye drops twice yesterday, but the drops didn’t help. The pain is worse today. It feels as if there’s something in her eye, she says, and she finds it hard to open her eye. Penlight examination ( FIGURE 5 ) reveals a branching opacity on the cornea.

FIGURE 5

What’s your next step?

1. Advise the patient to stop wearing her contact lenses overnight, give her a cycloplegic, and follow up in 2 days.
2. Patch the patient’s left eye, prescribe antibiotics, and tell her to return tomorrow.
3. Prescribe steroid eye drops and follow up in 2 days.
4. Provide an urgent referral to an ophthalmologist.

CASE 1 The answer is A: angle-closure glaucoma.

Glaucoma is the world’s leading cause of blindness,^1,2 and angle-closure glaucoma comprises 10% of cases.² In this condition, the anterior chamber angle—formed by the iris and the cornea—is narrow. When the iris dilates in low light (eg, the darkened room in which the patient had planned to nap), it folds into the narrowed angle, preventing the flow of aqueous humor and leading to an increase in intraocular pressure.³

Signs and symptoms
Patients with acute angle-closure glaucoma often develop decreased vision, halos, headaches, severe eye pain, nausea, and vomiting. If the intraocular pressure increases quickly, symptoms can have an acute and dramatic onset; if pressure builds slowly, patients may have limited or no symptoms.⁴

Physical findings
An eye exam will reveal conjunctival erythema, corneal edema and cloudiness, iris irregularity, a shallow anterior chamber (visible with a slit lamp), a dilated pupil (4-6 mm) that reacts sluggishly to light, and increased ocular pressure. The cupping of the optic disc seen in this patient’s retinal exam ( FIGURE 6 ) is more commonly associated with chronic open-angle glaucoma.

FIGURE 6

Management
Acute angle-closure glaucoma is an ophthalmologic emergency, and a referral to a specialist is crucial. If no ophthalmologist can see the patient within an hour of the presentation of symptoms, you’ll need to initiate topical treatment to reduce intraocular pressure and ensure that he or she is seen by a specialist as soon as possible.⁵ First-line treatments for acute angle-closure glaucoma are listed in TABLE 1 .^5,6

In severe cases, topical therapy alone may be ineffective. If there are no contraindications, systemic medications such as acetazolamide, mannitol, glycerol, or isosorbide may be needed. Eye pressure should be checked 30 to 60 minutes after initiating systemic therapy and the patient closely monitored for adverse effects (eg, anaphylaxis, convulsions [acetazolamide]; hypotension [mannitol, isosorbide]).⁵

When the patient does see an ophthalmologist, the evaluation will include assessment of visual acuity, pupillary evaluation, measurement of intraocular pressure, slit lamp examination, gonioscopy to measure the angle of the anterior chamber, and a fundus exam without pupil dilation.⁵ Treatment may include a surgical procedure, such as paracentesis of the eye, peripheral iridotomy, or iridectomy, and chronic administration of topical medication.⁷

TABLE 1
Treatments for acute angle-closure glaucoma^5,6

CASE 2 The answer is D: Attempt to conduct a visual acuity test and penlight exam without anesthetic; if necessary, apply anesthetic drops and fluorescein stain.

This patient likely has a corneal ulcer or abrasion caused by a contact lens. Corneal ulcers—which constitute a loss of the corneal epithelium—can be caused by trauma or a foreign body, or develop spontaneously.

Signs and symptoms
Because of the rich innervation of the corneal epithelium by the trigeminal nerve, the cornea is highly sensitive to pain. Patients with corneal abrasions typically experience eye pain, photophobia, tearing, a foreign body sensation, and discomfort when driving, working, or reading. If a patient has damage to the trigeminal nerve, however (eg, from trauma, a tumor, or a herpes infection), corneal injuries may be painless.⁸

In some cases, corneal abrasions may be so painful that patients become disruptive while waiting to be seen. Thus, any patient suspected of having a corneal ulcer or abrasion should be ushered into a quiet, dark room and instructed to keep his or her eyes closed until the examination.

The patient history should focus on recent trauma, type of work, and use of protective eyewear, which may provide clues to the development of penetrating injuries, retained foreign bodies, or abrasions caused by a foreign body. Ask about the use of contact lenses, as well; corneal injury caused by contacts is associated with specific bacterial infections, most commonly staphylococcal organisms and Pseudomonas.⁹

Physical findings
Attempt to test visual acuity without topical anesthetics. If the patient can’t tolerate the test, a single drop of topical anesthetic (proparacaine 0.5%) may help. Visual acuity provides clues to the location of the injury. If acuity is close to baseline, the corneal abrasion is likely peripheral to the visual axis. Decreased visual acuity indicates either that the abrasion involves the central axis area or that there is corneal edema.⁹

Evaluation of the pupillary reflex and optic fundus should follow. Reactive miosis may be present with corneal abrasions. A large, nonreactive pupil may be a sign of injury to the pupillary sphincter from blunt or penetrating injury—an ophthalmologic emergency that requires urgent referral. The eyelid should be flipped and examined for foreign bodies. ⁹

Some abrasions can be seen with the naked eye, so a penlight exam should be performed before applying fluorescein stain. If a corneal lesion is suspicious for herpesvirus infection ( SEE CASE 5 ), fluorescein should not be applied, as it can interfere with the antibody test.¹⁰ Refer the patient to an ophthalmologist instead.

If there’s no evidence of infection, apply fluorescein and examine the cornea with a Wood’s lamp. A thin line or several vertical lines are suggestive of a foreign body in the cornea or under the eyelid, whereas round defects are often due to contact lenses.⁹ Physical findings associated with specific types of corneal abrasions or ulcers are detailed in TABLE 2 .^9,11,12

TABLE 2
Corneal abrasion or ulcers: The differential diagnosis^9,11,12

Management
Patients with corneal abrasions or ulcers should receive topical antibiotics to prevent infection. Ointments (erythromycin ointment 4 times daily for 3-5 days) are preferable to drops, but may be harder to obtain.⁹ If a patient must use drops, sulfacetamide 10%, polymyxin/trimethoprim, ciprofloxacin, or ofloxacin can be used, with the same frequency and duration.

Aminoglycosides are toxic to the corneal epithelium and should be avoided, except in abrasions caused by contacts.⁹ Because of the likelihood of pseudomonal keratitis in cases involving contact lenses, antibiotics covering Pseudomonas, such as ofloxacin, ciprofloxacin, or tobramycin, should be used.⁹

Pain control is achieved with cycloplegics¹¹ like cyclopentolate 0.5% to 1% or a one-day course of systemic opioids. For children, over-the-counter analgesics for mild pain and mild opioids for severe pain may be used.

Chronic use of topical anesthetics should be avoided in patients of any age. Although they relieve pain, frequent use can lead to delayed healing, ulcerations, perforations, scarring, or even blindness.⁸

Patching has not been found to improve healing or comfort;¹³ instead, it delays healing.^14,15 The “pirate patch,” which hovers over the eye, does not keep the eyelid down and therefore is not recommended.⁹

Follow up within 24 hours of initiating treatment to assure that the abrasion is healing. If it appears to be getting worse or is simply not improving, an immediate referral to an ophthalmologist is needed. Abrasions caused by contact with potentially infected material (eg, farm equipment, tree branches, or soil) require daily monitoring until they heal.¹¹

CASE 3 The answer is C: Order an MRI of the brain.

This patient has optic neuritis, caused by inflammation of the optic nerve and disruption of the nerve’s myelin sheath. It predominantly affects young adults, and is more common in women than in men.¹⁶ The incidence of optic neuritis is higher among Asians, black South Africans, and children under the age of 15.^17,18

Signs and symptoms
Optic neuritis is characterized by monocular (90%) or binocular (10%) complete or partial vision loss, photopsia (flashes of light), and eye pain. Up to 60% of pediatric patients present with blurred vision, bilateral involvement,¹⁹ and no pain, while adults predominantly have pain and unilateral vision loss.²⁰ Optic neuritis is often a presenting symptom of multiple sclerosis (MS).¹⁶

Physical findings
Physical exam findings in optic neuritis include a sluggish direct light reflex, loss of visual acuity and color vision, as well as acute eye pain.¹⁸ Ophthalmoscopic exam may reveal papillitis with edema of the optic disc.²¹ In the Optic Neuritis Treatment Trial (ONTT), however, only one-third of patients presented with papillitis and swelling of the optic disc.²²

MRI of the brain with gadolinium contrast is generally used to confirm the diagnosis. On MRI, 95% of patients with optic neuritis have signs of inflammation of the optic nerve and/or white matter changes consistent with MS (periventricular and ovoid demyelination).^23,24

Patients with evidence of demyelination should also be evaluated for MS and other demyelinating disorders. In the ONTT trial, the risk of developing MS within 15 years of an optic neuritis diagnosis was as low as 25% (95% confidence interval [CI], 18%-32%) for patients with no lesions on a baseline brain MRI and as high as 72% (95% CI, 63%-81%) for those with one or more lesions on a baseline MRI, according to the study’s final follow-up.²²

Management
The recommended treatment for optic neuritis is intravenous (IV) methylprednisolone 250 mg every 6 hours for 3 to 5 days, followed by oral prednisone at 1 mg/kg/d for 7 to 10 days. Vision usually returns slowly over the course of several months to a year. Ophthalmology consultation should be considered to rule out other causes of optic neuritis.²⁵

CASE 4 The answer is A: anterior uveitis.

Uveitis is often associated with systemic disease or infection, and diagnosis is typically suspected based on a history of conditions such as sarcoidosis, juvenile idiopathic arthritis, Kawasaki’s disease, Sjögren’s syndrome, toxoplasmosis, human immunodeficiency virus (HIV), tuberculosis (TB), syphilis, herpes simplex, and herpes zoster.²⁶

Signs and symptoms
Signs and symptoms vary depending on the part of the uveal tract that’s involved. Anterior uveitis, or iritis, is associated with pain, photophobia, redness, and a varying degree of vision loss. Posterior and intermediate uveitis are less likely to be associated with pain, but can be accompanied by decreased visual acuity and floaters.²⁷

Physical findings
Visual acuity in patients with uveitis can range from normal to varying degrees of vision loss. Redness around the iris can be seen; conjunctival infection is most marked around the circumference of the corneal limbus rather than more peripherally, as seen in conjunctivitis. On slit lamp examination, the beam of light can be seen in the aqueous humor due to protein and leukocyte accumulation—a phenomenon known as “flare.” The pupillary light reflex may be abnormal, and the pupillary opening may be irregular rather than round due to anterior and posterior synechia.²⁸

Management
Patients should be referred to an ophthalmologist for management of the immediate condition and to prevent or treat complications such as vision loss, optic nerve damage, and glaucoma. Acute management includes topical steroids, such as prednisolone acetate ophthalmic 1% 2 to 4 times daily, as well as treatment of the underlying condition. Long-term management varies, depending on the cause of the uveitis.^26,29

If the etiology is unknown, a workup should be considered to identify inflammatory and infectious disorders that might be causing uveitis. Chest radiograph is a good beginning to look for evidence of sarcoidosis or TB; serologic testing for syphilis, HIV, and lupus may also be considered.^26,29

CASE 5 The answer is D: Provide an urgent referral to an ophthalmologist.

This patient has viral keratitis caused by herpes. While the pain and foreign body sensation are the same for bacterial and viral keratitis, herpesvirus is distinguishable by the branching opacity that develops on the cornea.

Varicella zoster is the most common cause of viral keratitis, although it can also be caused by herpes simplex and adeno-virus. Because a person who is infected with herpes has the virus for life, however, multiple attacks are possible. Reactivation is associated with stress and a weakened immune system, but may occur spontaneously, as well. Patients who wear contact lenses are no more likely than those who don’t to be infected with the herpesvirus.

Bacterial keratitis is often associated with contact lenses, particularly when they’re continually worn, but also with normal wear.³⁰ Immunosuppression, dry ocular surfaces, and topical corticosteroid use may predispose patients to bacterial keratitis, as well.¹² Staphylococcus aureus, Pseudomonas aeruginosa, coagulase-negative Staphylococcus, diphtheroids, and Streptococcus pneumoniae are the most common pathogens.³¹

Signs and symptoms
Patients with keratitis typically complain of eye pain, a sensation of having a foreign body in the eye, photophobia, tearing, and vision changes; a mucopurulent discharge is sometimes present, as well.³ The condition is easily distinguished from conjunctivitis, which typically does not involve eye pain or vision changes.

Physical findings
Visual acuity may be affected if the lesion or corneal edema involves the visual axis. Physical exam in a patient with bacterial keratitis sometimes shows a gray or white corneal opacity, along with corneal erythema. As already noted, a penlight exam will reveal a branching opacity in patients with herpes keratitis.³⁰

Management
Patients with keratitis should be referred immediately to an ophthalmologist³² for a slit lamp evaluation, treatment, and close follow-up.

Corneal cultures can be difficult to obtain, but before prescribing antibiotics, an attempt to collect samples should be made. This can be done—after the administration of topical anesthesia—with a sterile calcium alginate swab. Gently swab the cornea and then inoculate the appropriate gels or mediums. Avoid contact with lashes and eyelids to prevent culture contamination.³²

When herpesvirus is suspected, start the patient on an antiviral agent such as trifluridine ophthalmic (1%) 9 times a day, vidarabine ophthalmic (3%) 5 times daily, or 400 mg oral acyclovir 5 times a day. Patients with bacterial keratitis should be started on antibiotic eye drops with Pseudomonas coverage, such as ofloxacin (0.3%), ciprofloxacin (0.3%), or tobramycin (0.3%), 6 to 8 times a day.⁹

CORRESPONDENCE Uyen Michelle Le, MD, 967 Galindo Court, Milpitas, CA 95035; mlkala21@aol.com

The average American woman will spend more than 30 years of her life trying to prevent pregnancy—not always successfully. Each year, half of the approximately 6 million pregnancies in the United States are unintended.¹ Emergency contraception (EC) gives a woman a second chance to prevent pregnancy after a contraceptive failure or unprotected sex. But all too often, it isn’t offered and she doesn’t request it.

Lack of knowledge about EC continues to be a barrier to its use. Some women have heard about the “morning after pill,” but may not know that EC can be effective for up to 5 days after intercourse—or even that it’s available in this country.² Others are unaware that it is possible to prevent pregnancy after intercourse,² and mistakenly believe that EC drugs are abortifacients. In fact, they work primarily by interfering with ovulation and have not been found to prevent implantation or to disrupt an existing pregnancy.^3-5

Providers also contribute to the limited use of EC, often because they’re unfamiliar with the options or uncomfortable discussing them with patients, particularly sexually active teens.²

This update can help you clear up misconceptions about EC with your patients. It also provides evidence-based information about the various types of EC, a review of issues affecting accessibility, and a telephone triage protocol to guide your response to women seeking postcoital contraception.

EC today: Plan B and beyond
Hormonal EC was first studied in the 1920s, when researchers found that estrogenic ovarian extracts interfered with pregnancy in animals. The first regimen was a high-dose estrogen-only formulation. In 1974, a combined estrogen-progestin replaced it. Known as the Yuzpe method for the physician who discovered it,⁶ this regimen used a widely available brand of combined estrogen-progestin oral contraceptive pills. The standard dose consisted of 100 mcg ethinyl estradiol (EE) and 0.5 mg levonorgestrel (LNG) taken 12 hours apart.^2,7

Although the Yuzpe method is still in use, progestin-only EC—Plan B as well as generic (Next Choice) and single-dose (Plan B One-Step) LNG formulations—has become the standard of care because it has greater efficacy and fewer adverse effects.² There are 2 additional options: the copper intrauterine device (IUD), which is highly effective both as EC and as a long-term contraceptive,⁶ and ulipristal acetate (UPA), which received US Food and Drug Administration (FDA) approval in 2010. This second-generation antiprogestin, sold under the brand name Ella, is well tolerated and highly effective.⁸

EC efficacy: What the evidence shows
EC is most likely to work when used within 24 hours, but remains effective—albeit to varying degrees—for up to 120 hours (TABLE).^2,5,8,9 Thus, which EC is best for a particular patient depends, in part, on timing.

TABLE
Emergency contraception: Comparing methods*^2,5,8,9

Copper IUDs have the highest success rate: Studies have found the copper IUD to be >99% effective in preventing pregnancy when inserted within 5 days of unprotected intercourse.^9,10 The copper ions it contains have a toxic effect on sperm, and impair the potential for fertilization; the device may also make the endometrium inhospitable to implantation.^9,10

A just-published systematic review of 42 studies in 6 countries over a period of more than 30 years yielded similar results: Among more than 7000 women who had the IUDs inserted after unprotected intercourse, the pregnancy rate was 0.09%.¹¹

But an IUD is appropriate only for women who want long-term contraception and would otherwise qualify for IUD insertion. By comparison, hormonal EC is not as effective and generally works best when used within a shorter time frame.

Progestin alone vs estrogen-progestin combo. To compare hormonal contraception, many researchers use a “prevented fraction”—an estimated percentage of pregnancies averted by treatment. A large World Health Organization-sponsored study found that the efficacy of progestin-only EC is superior to that of the estrogen-progestin combination, with prevented fractions of 85% and 57%, respectively. The progestin-only EC was also associated with significantly fewer adverse effects.¹²

In more recent studies, the prevented fraction for progestin-only EC has been found to range from 60% to 94%, while a meta-analysis of studies assessing estrogen-progestin EC r evealed a prevented fraction of ≥74%.²

Although there is evidence suggesting that progestin-only EC may work for up to 5 days,^13,14 it has FDA approval only for use within 72 hours of intercourse.¹³ A time-sensitive analysis showed that when it was used within 12 hours of intercourse, the pregnancy rate was 0.5%. The rate increased steadily to 4.1% when the progestin-based EC was taken 61 to 72 hours after intercourse, and rose by an additional 50% after an additional 12-hour delay.¹⁵

Hormonal EC is only effective before ovulation occurs. Once luteinizing hormone (LH) starts to rise, it is ineffective. However, the likelihood of pregnancy drops precipitously after ovulation, and there is no risk of pregnancy in the luteal phase, with or without EC.

One pill or 2? Both Plan B and the generic Next Choice are sold as 2-dose regimens, with one 0.75-mg tablet taken within 72 hours and the second taken 12 hours later. Plan B One-Step, which consists of a single 1.5-mg tablet, is clinically equivalent to the 2-dose formula,¹⁶ but is more convenient and may improve adherence. Notably, though, one large randomized controlled trial (RCT) in China found that the 2-pill regimen was significantly more effective in preventing pregnancy in women who had further acts of unprotected intercourse after treatment.¹⁷

UPA has a 5-day window. UPA has FDA approval for use within 120 hours of unprotected intercourse and has been found to be more effective than progestin-only EC, especially when used on Day 4 or 5 (72-120 hours).⁸ Adverse effects are mild to moderate, similar to those of LNG, and may include headache, abdominal pain, nausea, dysmenorrhea, fatigue, and dizziness.⁸

The medication binds to progesterone receptors, acting as an antagonist as well as a partial agonist. The mechanism of action depends on the phase of the woman’s cycle. Taken during the midfollicular phase, UPA inhibits follicle development.¹⁸ When used in the advanced follicular phase, just prior to ovulation, it delays LH peak and postpones ovulation.¹⁹

In one small study in which women were randomized to either UPA or placebo, researchers found that the drug delayed ovulation for ≥5 days in about 60% of those who took it; in comparison, ovulation occurred by Day 5 in every woman in the placebo group.¹⁹

How accessible is EC?

EC has a tumultuous history in the United States,²⁰ and accessibility depends on a variety of factors—age among them.

Plan B, for instance, is subject to a 2-tier system. It was approved in 1999 as a prescription-only product and has been available over the counter (OTC) to women 17 years and older since 2009. Younger women can get it only by prescription.²¹

Nonetheless, Plan B made the news again last year, when US Health and Human Services Secretary Kathleen Sebelius overruled an FDA decision to give teens younger than 17 OTC access.²² Thus, the age restriction remains in place, although there is no medical evidence to support it.²³ Other forms of EC, including UPA, are available to all women only by prescription.

Accessibility of EC also may vary from one part of the country to another. Some states have enacted laws with conscience clauses that allow pharmacists to refuse to dispense EC. Others have worked to increase access by authorizing pharmacists to initiate and dispense EC on their own, provided they work in collaboration with a doctor or other licensed prescriber. As of 2011, 9 states—Alaska, California, Hawaii, Maine, Massachusetts, New Hampshire, New Mexico, Vermont, and Washington—had such agreements in place.²⁴

Cost is another potential barrier. The cost of oral EC varies from about $10 to $70, plus the cost of a doctor visit for a teen who needs a prescription. Obtaining the copper IUD without insurance coverage would cost hundreds of dollars, to cover the price of insertion as well as the device.⁵

Increasing access: What you can do
In view of the barriers that adolescents face in obtaining EC, the American College of Obstetricians and Gynecologists and the American Academy of Pediatrics, among other organizations, recommend that physicians give advance prescriptions to teens under the age of 17. ^2,25

But how likely are they to actually buy the medication and use it on an emergency basis?

A 2007 Cochrane review found that giving women advance prescriptions for EC did not reduce pregnancy or abortion rates.²⁶ Other studies have found that EC use is highest among women with the lowest risk of pregnancy—those who are already using contraception and are less likely to have unprotected intercourse. Those at the highest risk for unintended pregnancy were found to be less likely to use EC after every episode of unprotected intercourse.^23,26 One RCT demonstrated that rates of pregnancy and sexually transmitted infection were not significantly increased by advance provision of EC, leading the researchers to conclude that it was therefore unreasonable to restrict access.²⁷

While it is prudent to make women aware that EC is available should they need it, the focus should be on the fact that consistent use of a reliable form of contraception—an IUD or hormonal contraception, in particular—gives them the best chance of preventing an unwanted pregnancy.

What to do when that call comes in
When a woman calls to report a contraceptive failure or tells you she has had unprotected intercourse, start by finding out how recently it occurred. Subsequent questions and actions that can be used by triage nurses or physicians on call are detailed in the easy-to-use EC telephone triage protocol (FIGURE)²⁸ on page 395. Whether you prescribe oral EC or schedule an appointment to insert a copper IUD within the next few days, there are a number of key points to keep in mind.

Initiate EC as soon as possible, but make it available to any woman who requests it for up to 5 days after unprotected intercourse.

Advise patients that oral EC is safe for most women—even those with contraindications to oral contraceptives. No physical examination is necessary, and there’s usually no need for a pregnancy test.² The one exception: A woman who has not had a period in the past 30 days should be given a pregnancy test before taking UPA.²

Offer EC at any time in the cycle. Although EC works primarily in the preovulatory phase, it should be offered regardless of the phase of the patient’s menstrual cycle. That’s because of the possibility of late ovulation, as well as the difficulty in accurately determining the phase of a woman’s cycle based on a history alone.

Make EC available to any woman who has been sexually abused. At many emergency departments, EC is not routinely offered to women who come in after being raped, although it clearly should be.²⁹

FIGURE
Telephone triage protocol for emergency contraception

EC, emergency contraception; IUD, intrauterine device; LNG, levonorgestrel; Rx, prescription; UPA, ulipristal acetate.
Adapted from: Reproductive Health Access Project. http://www.reproductiveaccess.org/contraception/tel_triage_ec.htm.²⁸

Patient counseling about EC
Advise patients for whom you prescribe oral EC that the medication delays ovulation, which means they could be at risk for pregnancy later in the cycle. Stress the need to use an alternative means of contraception (a barrier method is recommended for women taking UPA) until their next menses and to come in for a pregnancy test if their period is more than a week late.

Point out, too, that EC can be used more than once within the same cycle, if necessary. That said, even a single request for EC should result in a discussion of effective, longer-term contraception, including the possibility of an IUD.

CORRESPONDENCE Sarina Schrager, MD, MS, University of Wisconsin School of Public Health, Department of Family Medicine, 1100 Delaplaine Court, Madison, WI 53715; sbschrag@wisc.edu

The average American woman will spend more than 30 years of her life trying to prevent pregnancy—not always successfully. Each year, half of the approximately 6 million pregnancies in the United States are unintended.¹ Emergency contraception (EC) gives a woman a second chance to prevent pregnancy after a contraceptive failure or unprotected sex. But all too often, it isn’t offered and she doesn’t request it.

Lack of knowledge about EC continues to be a barrier to its use. Some women have heard about the “morning after pill,” but may not know that EC can be effective for up to 5 days after intercourse—or even that it’s available in this country.² Others are unaware that it is possible to prevent pregnancy after intercourse,² and mistakenly believe that EC drugs are abortifacients. In fact, they work primarily by interfering with ovulation and have not been found to prevent implantation or to disrupt an existing pregnancy.^3-5

Providers also contribute to the limited use of EC, often because they’re unfamiliar with the options or uncomfortable discussing them with patients, particularly sexually active teens.²

This update can help you clear up misconceptions about EC with your patients. It also provides evidence-based information about the various types of EC, a review of issues affecting accessibility, and a telephone triage protocol to guide your response to women seeking postcoital contraception.

EC today: Plan B and beyond
Hormonal EC was first studied in the 1920s, when researchers found that estrogenic ovarian extracts interfered with pregnancy in animals. The first regimen was a high-dose estrogen-only formulation. In 1974, a combined estrogen-progestin replaced it. Known as the Yuzpe method for the physician who discovered it,⁶ this regimen used a widely available brand of combined estrogen-progestin oral contraceptive pills. The standard dose consisted of 100 mcg ethinyl estradiol (EE) and 0.5 mg levonorgestrel (LNG) taken 12 hours apart.^2,7

Although the Yuzpe method is still in use, progestin-only EC—Plan B as well as generic (Next Choice) and single-dose (Plan B One-Step) LNG formulations—has become the standard of care because it has greater efficacy and fewer adverse effects.² There are 2 additional options: the copper intrauterine device (IUD), which is highly effective both as EC and as a long-term contraceptive,⁶ and ulipristal acetate (UPA), which received US Food and Drug Administration (FDA) approval in 2010. This second-generation antiprogestin, sold under the brand name Ella, is well tolerated and highly effective.⁸

EC efficacy: What the evidence shows
EC is most likely to work when used within 24 hours, but remains effective—albeit to varying degrees—for up to 120 hours (TABLE).^2,5,8,9 Thus, which EC is best for a particular patient depends, in part, on timing.

TABLE
Emergency contraception: Comparing methods*^2,5,8,9

Copper IUDs have the highest success rate: Studies have found the copper IUD to be >99% effective in preventing pregnancy when inserted within 5 days of unprotected intercourse.^9,10 The copper ions it contains have a toxic effect on sperm, and impair the potential for fertilization; the device may also make the endometrium inhospitable to implantation.^9,10

A just-published systematic review of 42 studies in 6 countries over a period of more than 30 years yielded similar results: Among more than 7000 women who had the IUDs inserted after unprotected intercourse, the pregnancy rate was 0.09%.¹¹

But an IUD is appropriate only for women who want long-term contraception and would otherwise qualify for IUD insertion. By comparison, hormonal EC is not as effective and generally works best when used within a shorter time frame.

Progestin alone vs estrogen-progestin combo. To compare hormonal contraception, many researchers use a “prevented fraction”—an estimated percentage of pregnancies averted by treatment. A large World Health Organization-sponsored study found that the efficacy of progestin-only EC is superior to that of the estrogen-progestin combination, with prevented fractions of 85% and 57%, respectively. The progestin-only EC was also associated with significantly fewer adverse effects.¹²

In more recent studies, the prevented fraction for progestin-only EC has been found to range from 60% to 94%, while a meta-analysis of studies assessing estrogen-progestin EC r evealed a prevented fraction of ≥74%.²

Although there is evidence suggesting that progestin-only EC may work for up to 5 days,^13,14 it has FDA approval only for use within 72 hours of intercourse.¹³ A time-sensitive analysis showed that when it was used within 12 hours of intercourse, the pregnancy rate was 0.5%. The rate increased steadily to 4.1% when the progestin-based EC was taken 61 to 72 hours after intercourse, and rose by an additional 50% after an additional 12-hour delay.¹⁵

Hormonal EC is only effective before ovulation occurs. Once luteinizing hormone (LH) starts to rise, it is ineffective. However, the likelihood of pregnancy drops precipitously after ovulation, and there is no risk of pregnancy in the luteal phase, with or without EC.

One pill or 2? Both Plan B and the generic Next Choice are sold as 2-dose regimens, with one 0.75-mg tablet taken within 72 hours and the second taken 12 hours later. Plan B One-Step, which consists of a single 1.5-mg tablet, is clinically equivalent to the 2-dose formula,¹⁶ but is more convenient and may improve adherence. Notably, though, one large randomized controlled trial (RCT) in China found that the 2-pill regimen was significantly more effective in preventing pregnancy in women who had further acts of unprotected intercourse after treatment.¹⁷

UPA has a 5-day window. UPA has FDA approval for use within 120 hours of unprotected intercourse and has been found to be more effective than progestin-only EC, especially when used on Day 4 or 5 (72-120 hours).⁸ Adverse effects are mild to moderate, similar to those of LNG, and may include headache, abdominal pain, nausea, dysmenorrhea, fatigue, and dizziness.⁸

The medication binds to progesterone receptors, acting as an antagonist as well as a partial agonist. The mechanism of action depends on the phase of the woman’s cycle. Taken during the midfollicular phase, UPA inhibits follicle development.¹⁸ When used in the advanced follicular phase, just prior to ovulation, it delays LH peak and postpones ovulation.¹⁹

In one small study in which women were randomized to either UPA or placebo, researchers found that the drug delayed ovulation for ≥5 days in about 60% of those who took it; in comparison, ovulation occurred by Day 5 in every woman in the placebo group.¹⁹

How accessible is EC?

EC has a tumultuous history in the United States,²⁰ and accessibility depends on a variety of factors—age among them.

Plan B, for instance, is subject to a 2-tier system. It was approved in 1999 as a prescription-only product and has been available over the counter (OTC) to women 17 years and older since 2009. Younger women can get it only by prescription.²¹

Nonetheless, Plan B made the news again last year, when US Health and Human Services Secretary Kathleen Sebelius overruled an FDA decision to give teens younger than 17 OTC access.²² Thus, the age restriction remains in place, although there is no medical evidence to support it.²³ Other forms of EC, including UPA, are available to all women only by prescription.

Accessibility of EC also may vary from one part of the country to another. Some states have enacted laws with conscience clauses that allow pharmacists to refuse to dispense EC. Others have worked to increase access by authorizing pharmacists to initiate and dispense EC on their own, provided they work in collaboration with a doctor or other licensed prescriber. As of 2011, 9 states—Alaska, California, Hawaii, Maine, Massachusetts, New Hampshire, New Mexico, Vermont, and Washington—had such agreements in place.²⁴

Cost is another potential barrier. The cost of oral EC varies from about $10 to $70, plus the cost of a doctor visit for a teen who needs a prescription. Obtaining the copper IUD without insurance coverage would cost hundreds of dollars, to cover the price of insertion as well as the device.⁵

Increasing access: What you can do
In view of the barriers that adolescents face in obtaining EC, the American College of Obstetricians and Gynecologists and the American Academy of Pediatrics, among other organizations, recommend that physicians give advance prescriptions to teens under the age of 17. ^2,25

But how likely are they to actually buy the medication and use it on an emergency basis?

A 2007 Cochrane review found that giving women advance prescriptions for EC did not reduce pregnancy or abortion rates.²⁶ Other studies have found that EC use is highest among women with the lowest risk of pregnancy—those who are already using contraception and are less likely to have unprotected intercourse. Those at the highest risk for unintended pregnancy were found to be less likely to use EC after every episode of unprotected intercourse.^23,26 One RCT demonstrated that rates of pregnancy and sexually transmitted infection were not significantly increased by advance provision of EC, leading the researchers to conclude that it was therefore unreasonable to restrict access.²⁷

While it is prudent to make women aware that EC is available should they need it, the focus should be on the fact that consistent use of a reliable form of contraception—an IUD or hormonal contraception, in particular—gives them the best chance of preventing an unwanted pregnancy.

What to do when that call comes in
When a woman calls to report a contraceptive failure or tells you she has had unprotected intercourse, start by finding out how recently it occurred. Subsequent questions and actions that can be used by triage nurses or physicians on call are detailed in the easy-to-use EC telephone triage protocol (FIGURE)²⁸ on page 395. Whether you prescribe oral EC or schedule an appointment to insert a copper IUD within the next few days, there are a number of key points to keep in mind.

Initiate EC as soon as possible, but make it available to any woman who requests it for up to 5 days after unprotected intercourse.

Advise patients that oral EC is safe for most women—even those with contraindications to oral contraceptives. No physical examination is necessary, and there’s usually no need for a pregnancy test.² The one exception: A woman who has not had a period in the past 30 days should be given a pregnancy test before taking UPA.²

Offer EC at any time in the cycle. Although EC works primarily in the preovulatory phase, it should be offered regardless of the phase of the patient’s menstrual cycle. That’s because of the possibility of late ovulation, as well as the difficulty in accurately determining the phase of a woman’s cycle based on a history alone.

Make EC available to any woman who has been sexually abused. At many emergency departments, EC is not routinely offered to women who come in after being raped, although it clearly should be.²⁹

FIGURE
Telephone triage protocol for emergency contraception

EC, emergency contraception; IUD, intrauterine device; LNG, levonorgestrel; Rx, prescription; UPA, ulipristal acetate.
Adapted from: Reproductive Health Access Project. http://www.reproductiveaccess.org/contraception/tel_triage_ec.htm.²⁸

Patient counseling about EC
Advise patients for whom you prescribe oral EC that the medication delays ovulation, which means they could be at risk for pregnancy later in the cycle. Stress the need to use an alternative means of contraception (a barrier method is recommended for women taking UPA) until their next menses and to come in for a pregnancy test if their period is more than a week late.

Point out, too, that EC can be used more than once within the same cycle, if necessary. That said, even a single request for EC should result in a discussion of effective, longer-term contraception, including the possibility of an IUD.

CORRESPONDENCE Sarina Schrager, MD, MS, University of Wisconsin School of Public Health, Department of Family Medicine, 1100 Delaplaine Court, Madison, WI 53715; sbschrag@wisc.edu

The average American woman will spend more than 30 years of her life trying to prevent pregnancy—not always successfully. Each year, half of the approximately 6 million pregnancies in the United States are unintended.¹ Emergency contraception (EC) gives a woman a second chance to prevent pregnancy after a contraceptive failure or unprotected sex. But all too often, it isn’t offered and she doesn’t request it.

Lack of knowledge about EC continues to be a barrier to its use. Some women have heard about the “morning after pill,” but may not know that EC can be effective for up to 5 days after intercourse—or even that it’s available in this country.² Others are unaware that it is possible to prevent pregnancy after intercourse,² and mistakenly believe that EC drugs are abortifacients. In fact, they work primarily by interfering with ovulation and have not been found to prevent implantation or to disrupt an existing pregnancy.^3-5

Providers also contribute to the limited use of EC, often because they’re unfamiliar with the options or uncomfortable discussing them with patients, particularly sexually active teens.²

This update can help you clear up misconceptions about EC with your patients. It also provides evidence-based information about the various types of EC, a review of issues affecting accessibility, and a telephone triage protocol to guide your response to women seeking postcoital contraception.

EC today: Plan B and beyond
Hormonal EC was first studied in the 1920s, when researchers found that estrogenic ovarian extracts interfered with pregnancy in animals. The first regimen was a high-dose estrogen-only formulation. In 1974, a combined estrogen-progestin replaced it. Known as the Yuzpe method for the physician who discovered it,⁶ this regimen used a widely available brand of combined estrogen-progestin oral contraceptive pills. The standard dose consisted of 100 mcg ethinyl estradiol (EE) and 0.5 mg levonorgestrel (LNG) taken 12 hours apart.^2,7

Although the Yuzpe method is still in use, progestin-only EC—Plan B as well as generic (Next Choice) and single-dose (Plan B One-Step) LNG formulations—has become the standard of care because it has greater efficacy and fewer adverse effects.² There are 2 additional options: the copper intrauterine device (IUD), which is highly effective both as EC and as a long-term contraceptive,⁶ and ulipristal acetate (UPA), which received US Food and Drug Administration (FDA) approval in 2010. This second-generation antiprogestin, sold under the brand name Ella, is well tolerated and highly effective.⁸

EC efficacy: What the evidence shows
EC is most likely to work when used within 24 hours, but remains effective—albeit to varying degrees—for up to 120 hours (TABLE).^2,5,8,9 Thus, which EC is best for a particular patient depends, in part, on timing.

TABLE
Emergency contraception: Comparing methods*^2,5,8,9

Copper IUDs have the highest success rate: Studies have found the copper IUD to be >99% effective in preventing pregnancy when inserted within 5 days of unprotected intercourse.^9,10 The copper ions it contains have a toxic effect on sperm, and impair the potential for fertilization; the device may also make the endometrium inhospitable to implantation.^9,10

A just-published systematic review of 42 studies in 6 countries over a period of more than 30 years yielded similar results: Among more than 7000 women who had the IUDs inserted after unprotected intercourse, the pregnancy rate was 0.09%.¹¹

But an IUD is appropriate only for women who want long-term contraception and would otherwise qualify for IUD insertion. By comparison, hormonal EC is not as effective and generally works best when used within a shorter time frame.

Progestin alone vs estrogen-progestin combo. To compare hormonal contraception, many researchers use a “prevented fraction”—an estimated percentage of pregnancies averted by treatment. A large World Health Organization-sponsored study found that the efficacy of progestin-only EC is superior to that of the estrogen-progestin combination, with prevented fractions of 85% and 57%, respectively. The progestin-only EC was also associated with significantly fewer adverse effects.¹²

In more recent studies, the prevented fraction for progestin-only EC has been found to range from 60% to 94%, while a meta-analysis of studies assessing estrogen-progestin EC r evealed a prevented fraction of ≥74%.²

Although there is evidence suggesting that progestin-only EC may work for up to 5 days,^13,14 it has FDA approval only for use within 72 hours of intercourse.¹³ A time-sensitive analysis showed that when it was used within 12 hours of intercourse, the pregnancy rate was 0.5%. The rate increased steadily to 4.1% when the progestin-based EC was taken 61 to 72 hours after intercourse, and rose by an additional 50% after an additional 12-hour delay.¹⁵

Hormonal EC is only effective before ovulation occurs. Once luteinizing hormone (LH) starts to rise, it is ineffective. However, the likelihood of pregnancy drops precipitously after ovulation, and there is no risk of pregnancy in the luteal phase, with or without EC.

One pill or 2? Both Plan B and the generic Next Choice are sold as 2-dose regimens, with one 0.75-mg tablet taken within 72 hours and the second taken 12 hours later. Plan B One-Step, which consists of a single 1.5-mg tablet, is clinically equivalent to the 2-dose formula,¹⁶ but is more convenient and may improve adherence. Notably, though, one large randomized controlled trial (RCT) in China found that the 2-pill regimen was significantly more effective in preventing pregnancy in women who had further acts of unprotected intercourse after treatment.¹⁷

UPA has a 5-day window. UPA has FDA approval for use within 120 hours of unprotected intercourse and has been found to be more effective than progestin-only EC, especially when used on Day 4 or 5 (72-120 hours).⁸ Adverse effects are mild to moderate, similar to those of LNG, and may include headache, abdominal pain, nausea, dysmenorrhea, fatigue, and dizziness.⁸

The medication binds to progesterone receptors, acting as an antagonist as well as a partial agonist. The mechanism of action depends on the phase of the woman’s cycle. Taken during the midfollicular phase, UPA inhibits follicle development.¹⁸ When used in the advanced follicular phase, just prior to ovulation, it delays LH peak and postpones ovulation.¹⁹

In one small study in which women were randomized to either UPA or placebo, researchers found that the drug delayed ovulation for ≥5 days in about 60% of those who took it; in comparison, ovulation occurred by Day 5 in every woman in the placebo group.¹⁹

How accessible is EC?

EC has a tumultuous history in the United States,²⁰ and accessibility depends on a variety of factors—age among them.

Plan B, for instance, is subject to a 2-tier system. It was approved in 1999 as a prescription-only product and has been available over the counter (OTC) to women 17 years and older since 2009. Younger women can get it only by prescription.²¹

Nonetheless, Plan B made the news again last year, when US Health and Human Services Secretary Kathleen Sebelius overruled an FDA decision to give teens younger than 17 OTC access.²² Thus, the age restriction remains in place, although there is no medical evidence to support it.²³ Other forms of EC, including UPA, are available to all women only by prescription.

Accessibility of EC also may vary from one part of the country to another. Some states have enacted laws with conscience clauses that allow pharmacists to refuse to dispense EC. Others have worked to increase access by authorizing pharmacists to initiate and dispense EC on their own, provided they work in collaboration with a doctor or other licensed prescriber. As of 2011, 9 states—Alaska, California, Hawaii, Maine, Massachusetts, New Hampshire, New Mexico, Vermont, and Washington—had such agreements in place.²⁴

Cost is another potential barrier. The cost of oral EC varies from about $10 to $70, plus the cost of a doctor visit for a teen who needs a prescription. Obtaining the copper IUD without insurance coverage would cost hundreds of dollars, to cover the price of insertion as well as the device.⁵

Increasing access: What you can do
In view of the barriers that adolescents face in obtaining EC, the American College of Obstetricians and Gynecologists and the American Academy of Pediatrics, among other organizations, recommend that physicians give advance prescriptions to teens under the age of 17. ^2,25

But how likely are they to actually buy the medication and use it on an emergency basis?

A 2007 Cochrane review found that giving women advance prescriptions for EC did not reduce pregnancy or abortion rates.²⁶ Other studies have found that EC use is highest among women with the lowest risk of pregnancy—those who are already using contraception and are less likely to have unprotected intercourse. Those at the highest risk for unintended pregnancy were found to be less likely to use EC after every episode of unprotected intercourse.^23,26 One RCT demonstrated that rates of pregnancy and sexually transmitted infection were not significantly increased by advance provision of EC, leading the researchers to conclude that it was therefore unreasonable to restrict access.²⁷

While it is prudent to make women aware that EC is available should they need it, the focus should be on the fact that consistent use of a reliable form of contraception—an IUD or hormonal contraception, in particular—gives them the best chance of preventing an unwanted pregnancy.

What to do when that call comes in
When a woman calls to report a contraceptive failure or tells you she has had unprotected intercourse, start by finding out how recently it occurred. Subsequent questions and actions that can be used by triage nurses or physicians on call are detailed in the easy-to-use EC telephone triage protocol (FIGURE)²⁸ on page 395. Whether you prescribe oral EC or schedule an appointment to insert a copper IUD within the next few days, there are a number of key points to keep in mind.

Initiate EC as soon as possible, but make it available to any woman who requests it for up to 5 days after unprotected intercourse.

Advise patients that oral EC is safe for most women—even those with contraindications to oral contraceptives. No physical examination is necessary, and there’s usually no need for a pregnancy test.² The one exception: A woman who has not had a period in the past 30 days should be given a pregnancy test before taking UPA.²

Offer EC at any time in the cycle. Although EC works primarily in the preovulatory phase, it should be offered regardless of the phase of the patient’s menstrual cycle. That’s because of the possibility of late ovulation, as well as the difficulty in accurately determining the phase of a woman’s cycle based on a history alone.

Make EC available to any woman who has been sexually abused. At many emergency departments, EC is not routinely offered to women who come in after being raped, although it clearly should be.²⁹

FIGURE
Telephone triage protocol for emergency contraception

EC, emergency contraception; IUD, intrauterine device; LNG, levonorgestrel; Rx, prescription; UPA, ulipristal acetate.
Adapted from: Reproductive Health Access Project. http://www.reproductiveaccess.org/contraception/tel_triage_ec.htm.²⁸

Patient counseling about EC
Advise patients for whom you prescribe oral EC that the medication delays ovulation, which means they could be at risk for pregnancy later in the cycle. Stress the need to use an alternative means of contraception (a barrier method is recommended for women taking UPA) until their next menses and to come in for a pregnancy test if their period is more than a week late.

Point out, too, that EC can be used more than once within the same cycle, if necessary. That said, even a single request for EC should result in a discussion of effective, longer-term contraception, including the possibility of an IUD.

CORRESPONDENCE Sarina Schrager, MD, MS, University of Wisconsin School of Public Health, Department of Family Medicine, 1100 Delaplaine Court, Madison, WI 53715; sbschrag@wisc.edu

Psoriasis is a systemic inflammatory disorder altered by environmental and genetic factors that presents as scaly erythematous plaques and affects 2% to 3% of the population.¹ Eighty percent have mild-to-moderate cutaneous disease; disabling arthritis occurs in as many as 42% of cases.^1,2 The devastating effects on quality of life— including social stigmatization, pain, physical disability, and psychological distress—are comparable to the effects of conditions like cancer and depression.² There is no definitive cure, and patients are left with a lifetime of waxing and waning symptoms.

Helping to create an individualized treatment plan tailored to disease type and extent, comorbidities, and needs of the patient can directly impact the quality of his or her life.³ For those with localized disease, topical therapy is a suitable first choice. Phototherapy is generally the first-line treatment for patients with extensive psoriasis or disabling symptoms. When phototherapy is not feasible or is ineffective, systemic treatments with conventional oral agents or biologics are indicated.

Discussions about therapeutic options should include expected results and duration of remission, cost, convenience, adverse effects, insurance coverage, and safety concerns. The patient’s preferences should be taken into account in the treatment plan you create.³ A guiding principle: The optimal protocol is the one the patient is motivated to adhere to.

The limits of topical therapy

Topical treatments are safe and effective when used properly, as monotherapy for localized disease and adjunctive therapy for resistant lesions. Monotherapy with topical agents is not recommended for sites that have a significant impact on quality of life, such as the palms and soles, and is not practical for patients with extensive disease (>10% of body surface).⁴

More potent topicals, such as corticosteroids, are recommended for acute flares; less potent agents with fewer adverse effects, such as calcipotriene, are typically used for maintenance ( TABLE 1 ).^5-8 Topical agents can be used either long term or intermittently. Here, too, the most effective treatment is the one the patient will actually apply.⁵

TABLE 1
A look at nonsteroidal topical treatments^5-8

Steroid selection is based on site, severity
Corticosteroids are antiproliferative, immunosuppressive, anti-inflammatory, and vasoconstrictive, and divided into 7 classes. Low-potency agents (Class 7) are used on thinner skin like the face, intertriginous areas, and groin; high-potency steroids (Class 1) are reserved for thicker, chronic plaques.⁹ As a general rule, Class 1 steroids can be safely used for 2 to 4 weeks, with increased risk of both cutaneous effects and systemic absorption if used continuously for longer periods.⁵ The optimal end point for less potent agents is not known.

Cutaneous adverse effects are more common than systemic ones and include skin atrophy, telangiectasia, striae distensae, acne, folliculitis, and purpura.

Systemic adverse effects include Cushing’s syndrome, osteonecrosis of the femoral head, cataracts, and glaucoma.⁵ The greatest risk of systemic effects is associated with prolonged use of high-potency corticosteroids over large surfaces or under occlusion with dressings or plastic wrap. Patients should be transitioned to the lowest potency possible to maintain efficacy, use corticosteroids intermittently, or combine them with nonsteroidal agents to avoid unwanted effects.

Topicals aren’t working? Move on to phototherapy

Phototherapy is an option for patients with extensive disease or skin manifestations that are recalcitrant to topicals. It is efficacious, cost-effective, and lacks systemic immunosuppression. Ultraviolet (UV) A and B act on Langerhans cells, cytokines, and adhesion molecules, inhibiting epidermal proliferation and angiogenesis.¹⁰

Broadband UVB (BB-UVB) was first used during the 1950s, with crude tar or anthralin, but is rarely used today.

Narrow-band UVB (NB-UVB) (311-313 nm), developed in the 1980s, has largely replaced BB-UVB. In addition to providing more rapid clearing and resolution of psoriasis compared with BB-UVB, NB-UVB may have less phototoxicity.¹¹ Between 20 and 25 NB-UVB treatments, 2 to 3 times a week (in the office or at home) are usually required for significant improvement.

Photocarcinogenesis is a concern but numerous studies, including a review of 3867 patients treated with NB-UVB with a median 5.5-year follow-up, found no significant association with cutaneous malignancies.¹² NB-UVB is considered safe during pregnancy and used as first-line therapy for pregnant patients.¹³

Targeted UVB therapy using a 308-nm excimer laser, another option, selectively targets psoriatic lesions, leaving normal skin untreated. This makes supraerythemogenic doses possible, which increases UVB’s efficacy. Long-term adverse effects and duration of remission have not been clearly established.¹⁴

Psoralen and UVA (PUVA), which uses oral or topical psoralens to sensitize the skin to UVA, has a slightly higher efficacy than NB-UVB, but with increased risk of squamous cell carcinoma (SCC) and possibly melanoma.¹⁵ Clearing can occur within 24 treatments, with remissions lasting 3 to 6 months;¹⁶ monthly maintenance has not been found to lengthen remission.¹³

Common adverse effects include erythema that peaks 48 to 96 hours after a treatment, pruritus, xerosis, irregular pigmentation, and gastrointestinal symptoms that can be reduced by decreasing psoralen and/or UVA doses.¹³ High cumulative doses of oral PUVA (>200 treatments) is associated with a dose-related increased risk of nonmelanoma skin cancer, particularly SCC, in the Caucasian population. This increased risk has not been demonstrated in patients treated with PUVA bath therapy, which is more common in Scandinavian countries.¹⁷ There is no consensus regarding the risk of melanoma.¹⁵

A careful risk-benefit analysis is needed before initiating phototherapy in patients who take photosensitizing drugs, are immunosuppressed, or have a photosensitivity disorder or a history of melanoma, atypical nevi, multiple melanoma risk factors, or multiple nonmelanoma skin cancers.¹³ Regardless of the type of UV therapy administered, eye protection with goggles is required to decrease the risk of UV-related cataract formation, and genital shielding is needed to prevent increased risk of tumors.¹³ Photoaging is a long-term effect.

CASE When questioned further about the challenges that Tom has had with controlling his symptoms, he admitted to being noncompliant. As a busy executive, he said he didn’t have time to use the topical corticosteroids regularly. Phototherapy could alleviate his cutaneous symptoms, but would not address his symptoms that were consistent with psoriatic arthritis.

Pairing therapeutic modalities decreases exposure
Combining therapeutic modalities like emollients and topical or oral retinoids with NB-UVB improves efficacy while reducing the number of treatment sessions and cumulative UVB dosage. If calcipotriene is used, it should be applied after phototherapy because it is degraded upon UVB exposure.¹⁸ Acitretin should be started 2 weeks prior to initiation of phototherapy, and its use accompanied by a 25% reduction in initial UV dosage.¹³

PUVA may also be combined with topical calcipotriene or retinoids.¹⁹ In both cases, the addition of the other agent typically decreases the duration of phototherapy, improves the clinical response, and reduces the risk of cancer.^13,20

Extensive disease? Consider a traditional systemic agent

Traditional systemic therapy is used to treat extensive disease ( FIGURE ), psoriasis refractory to topical agents, and debilitating disease on the palms, soles, or scalp. Biologics are a recent alternative, but traditional systemics have been utilized longer and have a more longstanding adverse effect and safety profile, are administered orally, and are much less expensive than biologics. Monitoring patients on systemic therapy is necessary ( TABLE 2 ).^21-24

Methotrexate (MTX), a competitive inhibitor of dihydrofolate reductase, is the most commonly prescribed traditional systemic psoriasis treatment.²¹ It is administered in a single weekly dose via tablet, parenteral solution, or intramuscular (IM) or subcutaneous (SC) injection.²⁵ A test dose (2.5 or 5 mg) is given initially and complete blood cell count is monitored within one week to evaluate for potential bone marrow toxicity. If none is observed, the dose may be increased to control the disease while minimizing adverse effects.²¹

Common adverse effects of MTX, such as nausea, vomiting, stomatitis, and fatigue, may be minimized by IM or SC administration, splitting the dose, or providing folate supplementation.^21-24 Given in doses of 1 to 5 mg/d, folate may reduce adverse hematologic, gastrointestinal, and hepatic effects without decreasing efficacy.²²

The major severe toxicities are myelosuppression, hepatotoxicity, and pulmonary fibrosis.²⁴ MTX-induced hepatotoxicity is similar to nonalcoholic fatty liver disease (NAFLD) and is thought to exacerbate preexisting NAFLD, which is common in patients with metabolic syndrome. A liver biopsy or serum assays for liver fibrosis (amino-terminal peptide of pro-collagen III) may be warranted during therapy.²⁴

MTX is an abortifacient and teratogen, so contraception during treatment and for up to 3 months thereafter is mandatory for women of childbearing age.²⁶ Men should be advised that MTX decreases sperm count. (For more on methotrexate, see: “When a fetus survives methotrexate exposure,” at http://www.jfponline.com/Pages.asp?AID=10299).

Cyclosporine (CSA), an oral calcineurin inhibitor, is a potent immunosuppressant that rapidly clears psoriasis.²⁷ Because duration of use correlates with permanent nephrotoxicity, hypertension, and potential increased risk of SCC and lymphoma, intermittent 12-week courses are recommended. Calcium channel blockers are the preferred treatment for CSA-induced hypertension because of their effect on smooth muscle vasodilation.²¹

Oral retinoids. Acitretin modulates epidermal proliferation and is anti-inflammatory. Because it lacks immunosuppression, acitretin is generally considered the treatment of choice in HIV patients with severe psoriasis.²⁸ Acitretin is teratogenic and contraindicated in women who plan to become pregnant or who are unwilling to use adequate contraception for 3 years after discontinuing the drug.²¹

CASE Given the significant percentage of body surface area involved and symptoms consistent with psoriatic arthritis, Tom required an aggressive therapeutic regimen. His history of nonalcoholic fatty liver and social drinking precluded the use of methotrexate. A biologic therapy was the next therapeutic choice that could relieve both his cutaneous and joint symptoms.

FIGURE
4 psoriasis patients, 4 different presentations

B. Diffuse erythematous scaly papules coalesce into plaques on this patient’s anterior chest, arms, abdomen, and periumbilicus.

C. The pinpoint pustules on an erythematous base on this patient’s lateral neck, shoulders, and upper back are characteristic of pustular psoriasis.

D. This patient has erythematous plaques with overlying silvery scale on the elbow—a classic

TABLE 2
Traditional systemic therapy^21-24

Biologics require lab work and a detailed medication list

Before beginning biologic therapy for a patient, the National Psoriasis Foundation²⁹ recommends obtaining a complete history, physical, medication list, future plans (ie, pregnancy or travel to locations requiring vaccinations), and baseline labs to identify possible risk factors and/or contraindications. Periodic evaluation to monitor development of new symptoms, including infection and malignancy ( TABLE 3 ),^24,30-33 is needed, as well.

TABLE 3
Is your patient a candidate for biologics?^24,30-33

Biologic therapy is contraindicated in patients with active serious infection. If patients develop infections requiring antibiotics while being treated, holding the biologic until infection resolution is advised.³⁴ Standard vaccinations (eg, pneumococcal, hepatitis A and B, influenza, diphtheria, tetanus) are recommended before initiation of immunosuppressive therapy. After therapy starts, patients should avoid live and live-attenuated vaccines (varicella, mumps, measles, and rubella, oral typhoid, yellow fever, herpes zoster, intranasal influenza).³⁵

Currently, none of the biologics are indicated for use in children or adolescents with psoriasis, despite epidemiologic data suggesting that one-third of adults with psoriasis developed it during childhood, in a form severe enough to warrant the use of systemic medications.³⁴ The FDA is currently reviewing the possibility of indicating etanercept for pediatric psoriasis patients. All biologics are category B for pregnancy as there is no evidence that they negatively affect pregnancy.²⁴

T-cell inhibitor. Alefacept binds CD2 on memory-effector T lymphocytes, inhibiting activation. Weekly intramuscular injections of alefacept for 12 weeks can clear lesions with long remissions.³⁰

TNF-inhibitors. The TNF-inhibitors have been available for more than 10 years, predominantly for inflammatory bowel disease (IBD) and rheumatoid arthritis (RA), and more than 1.5 million patients have used adalimumab, etanercept, and infliximab for these disorders. Safety data, especially long term, are mostly derived from patients with IBD or RA, who have often combined TNF-inhibitors with additional immunosuppressive therapies. Thus, for psoriasis patients, who typically use biologics as monotherapy, the risk may be overestimated.²⁴

TNF-inhibitors increase the risk for infection, most commonly of the upper respiratory tract, and, rarely, have been associated with opportunistic infections. Numerous cases of TB reactivation and an increased incidence of disseminated cases have been associated with TNF-inhibitors, so screening is recommended.²⁴

The impact of TNF inhibition on congestive heart failure (CHF) is not well understood. Studies have variously shown that TNF-inhibitors have no effect on CHF morbidity or mortality, increase CHF mortality, or improve left ventricular function. TNF-inhibitors should be avoided in patients with severe CHF (New York Heart Association class III or IV). In milder CHF patients with worsening of symptoms, treatment should be discontinued.³⁶

The increased risk of malignancy, especially lymphoma, is a concern, as there have been numerous case reports of lymphoma occurring with TNF-inhibitors. Psoriasis patients in general have an increased risk of lymphoma that confounds data interpretation.³¹ A number of case reports and a large observational study have shown patients receiving TNF-inhibitors may be at a greater risk for developing melanoma and nonmelanoma skin cancer.³²

Ustekinumab, an interleukin 12/23 inhibitor, is a human monoclonal antibody that is absorbed and eliminated slowly, making dosing injections every 12 weeks convenient with efficacy maintained for at least one year.³³ Because of its relative novelty, few studies are published regarding long-term safety. A recent head-to-head trial compared the efficacy and safety of ustekinumab with etanercept and found superior efficacy with ustekinumab, with comparable adverse events.^37,38 Similar concerns exist with ustekinumab as with TNF-inhibitors, including infection, malignancy, CHF, and TB.³³

CASE Tom denied having a personal family history of multiple sclerosis, or any demyelinating disorder. Nor did he have a history of cancer, tuberculosis exposure, CHF, or hepatitis. A purified protein derivative (PPD) was negative, as was his hepatitis panel, and his complete blood count with differential and metabolic panel were within normal limits.

Tom was started on the TNF-inhibitor adalimumab, after undergoing patient education and training and receiving instructions to stop the medication if he developed a major illness or infection. He received a loading dose of 80 mg SC, followed by 40 mg every other week. He tolerated the treatment well and 70% of his cutaneous symptoms cleared after 12 weeks of therapy; his joint pain also was reduced.

Tom is followed regularly in the clinic, with labs every 4 to 6 months. He is maintained on the injections and happy with the results. At each visit, weight loss and decreased beer intake are encouraged, both of which have been shown to reduce psoriasis severity. Although the beta-blockers and ACE inhibitors he takes are known to exacerbate psoriasis, the medications are necessary to treat Tom’s coronary artery disease.

CORRESPONDENCE Elizabeth Uhlenhake, MD, 18100 Oakwood Boulevard, Suite 300, Dearborn, MI 48124; eulenha@neomed.edu