The Journal of Family Practice

The FP suspected that this was a case of dermatographism. To confirm his suspicions, he used the end of a cotton-tipped applicator and wrote on the patient’s skin. Within 3 minutes, the writing turned into a triple reaction with some erythema, blanching, and swelling—confirming the diagnosis.

Dermatographism often accompanies urticaria, but can occur without it. If one writes on the skin, one is able to see the resulting words or shapes. The cause of this condition is unknown, but the pathophysiology involves degranulation of mast cells and the release of histamine.

No treatment is required for asymptomatic dermatographism. If patients are symptomatic, they should be advised to avoid precipitating physical stimuli. Dry skin may stimulate scratching, so the use of emollients can help. If the patient wants a medication, start with a second-generation antihistamine such as loratadine or cetirizine. While the recommended over-the-counter dose of these 2 medications is 10 mg/d, the dose may be increased to 20 mg twice daily. It is best to start at the lowest dose and then titrate up according to response and tolerance of adverse effects. (The second-generation antihistamines can still be sedating.) If this doesn’t work, a sedating antihistamine can be added before bedtime.

Dermatographism is not life-threatening and does not lead to anaphylaxis. The patient in this case didn’t want treatment and was pleased to know what was going on with his skin.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Urticaria and angioedema. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 863-870.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The FP suspected that this was a case of dermatographism. To confirm his suspicions, he used the end of a cotton-tipped applicator and wrote on the patient’s skin. Within 3 minutes, the writing turned into a triple reaction with some erythema, blanching, and swelling—confirming the diagnosis.

Dermatographism often accompanies urticaria, but can occur without it. If one writes on the skin, one is able to see the resulting words or shapes. The cause of this condition is unknown, but the pathophysiology involves degranulation of mast cells and the release of histamine.

No treatment is required for asymptomatic dermatographism. If patients are symptomatic, they should be advised to avoid precipitating physical stimuli. Dry skin may stimulate scratching, so the use of emollients can help. If the patient wants a medication, start with a second-generation antihistamine such as loratadine or cetirizine. While the recommended over-the-counter dose of these 2 medications is 10 mg/d, the dose may be increased to 20 mg twice daily. It is best to start at the lowest dose and then titrate up according to response and tolerance of adverse effects. (The second-generation antihistamines can still be sedating.) If this doesn’t work, a sedating antihistamine can be added before bedtime.

Dermatographism is not life-threatening and does not lead to anaphylaxis. The patient in this case didn’t want treatment and was pleased to know what was going on with his skin.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Urticaria and angioedema. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 863-870.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The FP suspected that this was a case of dermatographism. To confirm his suspicions, he used the end of a cotton-tipped applicator and wrote on the patient’s skin. Within 3 minutes, the writing turned into a triple reaction with some erythema, blanching, and swelling—confirming the diagnosis.

Dermatographism often accompanies urticaria, but can occur without it. If one writes on the skin, one is able to see the resulting words or shapes. The cause of this condition is unknown, but the pathophysiology involves degranulation of mast cells and the release of histamine.

No treatment is required for asymptomatic dermatographism. If patients are symptomatic, they should be advised to avoid precipitating physical stimuli. Dry skin may stimulate scratching, so the use of emollients can help. If the patient wants a medication, start with a second-generation antihistamine such as loratadine or cetirizine. While the recommended over-the-counter dose of these 2 medications is 10 mg/d, the dose may be increased to 20 mg twice daily. It is best to start at the lowest dose and then titrate up according to response and tolerance of adverse effects. (The second-generation antihistamines can still be sedating.) If this doesn’t work, a sedating antihistamine can be added before bedtime.

Dermatographism is not life-threatening and does not lead to anaphylaxis. The patient in this case didn’t want treatment and was pleased to know what was going on with his skin.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Urticaria and angioedema. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 863-870.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The FP did a 4-mm punch biopsy to confirm that this was a case of prurigo nodularis and prescribed clobetasol cream to be applied twice daily to the pruritic nodules. The FP recommended that the patient apply the cream instead of scratching the area. The FP also said that if the patient couldn’t avoid touching the area, it would be better to lightly rub the area over his clothing instead.

The biopsy results subsequently confirmed a diagnosis of prurigo nodularis. At the patient’s 2-week follow-up, he indicated that his symptoms were 50% better since using the clobetasol. The FP explained to the patient the nature of prurigo nodularis, including the patient’s itch-scratch cycle and how stress was making it worse. The patient acknowledged that his symptoms had become worse when he began having financial trouble. The FP asked the patient if he wanted to see a counselor, but the patient declined, saying that he just needed to get more work.

At a one-month follow-up, 90% of the nodules were resolved, although there were still some stubborn areas that continued to itch. The patient could not control scratching these areas at times. The FP offered intralesional injections with triamcinolone and/or cryotherapy. The patient consented to liquid nitrogen therapy and the remaining nodules were frozen for approximately 10 seconds each using a liquid nitrogen spray.

Four weeks later, the patient had 4 remaining nodules. The FP injected the nodules with 10 mg/mL triamcinolone and refilled the clobetasol cream. At the next appointment, 2 nodules remained. The patient indicated that he would continue using the cream until the nodules went away. In many cases, prurigo nodularis does not respond especially well to treatment, so this patient was fortunate that standard treatments provided a good outcome.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R, Johnson A. Self-inflicted dermatosis. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 856-862.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The FP did a 4-mm punch biopsy to confirm that this was a case of prurigo nodularis and prescribed clobetasol cream to be applied twice daily to the pruritic nodules. The FP recommended that the patient apply the cream instead of scratching the area. The FP also said that if the patient couldn’t avoid touching the area, it would be better to lightly rub the area over his clothing instead.

The biopsy results subsequently confirmed a diagnosis of prurigo nodularis. At the patient’s 2-week follow-up, he indicated that his symptoms were 50% better since using the clobetasol. The FP explained to the patient the nature of prurigo nodularis, including the patient’s itch-scratch cycle and how stress was making it worse. The patient acknowledged that his symptoms had become worse when he began having financial trouble. The FP asked the patient if he wanted to see a counselor, but the patient declined, saying that he just needed to get more work.

At a one-month follow-up, 90% of the nodules were resolved, although there were still some stubborn areas that continued to itch. The patient could not control scratching these areas at times. The FP offered intralesional injections with triamcinolone and/or cryotherapy. The patient consented to liquid nitrogen therapy and the remaining nodules were frozen for approximately 10 seconds each using a liquid nitrogen spray.

Four weeks later, the patient had 4 remaining nodules. The FP injected the nodules with 10 mg/mL triamcinolone and refilled the clobetasol cream. At the next appointment, 2 nodules remained. The patient indicated that he would continue using the cream until the nodules went away. In many cases, prurigo nodularis does not respond especially well to treatment, so this patient was fortunate that standard treatments provided a good outcome.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R, Johnson A. Self-inflicted dermatosis. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 856-862.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The FP did a 4-mm punch biopsy to confirm that this was a case of prurigo nodularis and prescribed clobetasol cream to be applied twice daily to the pruritic nodules. The FP recommended that the patient apply the cream instead of scratching the area. The FP also said that if the patient couldn’t avoid touching the area, it would be better to lightly rub the area over his clothing instead.

The biopsy results subsequently confirmed a diagnosis of prurigo nodularis. At the patient’s 2-week follow-up, he indicated that his symptoms were 50% better since using the clobetasol. The FP explained to the patient the nature of prurigo nodularis, including the patient’s itch-scratch cycle and how stress was making it worse. The patient acknowledged that his symptoms had become worse when he began having financial trouble. The FP asked the patient if he wanted to see a counselor, but the patient declined, saying that he just needed to get more work.

At a one-month follow-up, 90% of the nodules were resolved, although there were still some stubborn areas that continued to itch. The patient could not control scratching these areas at times. The FP offered intralesional injections with triamcinolone and/or cryotherapy. The patient consented to liquid nitrogen therapy and the remaining nodules were frozen for approximately 10 seconds each using a liquid nitrogen spray.

Four weeks later, the patient had 4 remaining nodules. The FP injected the nodules with 10 mg/mL triamcinolone and refilled the clobetasol cream. At the next appointment, 2 nodules remained. The patient indicated that he would continue using the cream until the nodules went away. In many cases, prurigo nodularis does not respond especially well to treatment, so this patient was fortunate that standard treatments provided a good outcome.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R, Johnson A. Self-inflicted dermatosis. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 856-862.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The FP diagnosed lichen simplex chronicus (LSC) in this patient, based on the lesion’s clinical appearance and location, as well as the patient’s history of repeated daily scratching. LSC is more common in women than in men, and occurs mostly in mid- to late-adulthood, with the highest prevalence in people who are 30 to 50 years of age.

A very common location for LSC in women is the back of the neck. In this case the LSC was coexisting with acanthosis nigricans. Fortunately, this patient did not have diabetes, but her obesity and family history predisposed her to acanthosis nigricans.

The treatment for LSC is topical mid- to high-potency corticosteroids. Oral sedating antihistamines can be added at night if pruritus is bad during the evening. If the patient acknowledges that stress is involved, obtain a good psychosocial history and offer the patient treatment for any problems you uncover.

Patients need to minimize touching, scratching, and rubbing of the affected areas. Explain to patients that they are unintentionally hurting their own skin. Suggest that they gently apply their medication or a moisturizer instead of scratching the pruritic areas.

In this case, the FP prescribed topical triamcinolone ointment and stressed the importance of not rubbing or scratching the area. The patient’s LSC healed well.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R, Johnson A. Self-inflicted dermatoses. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 856-862.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The FP diagnosed lichen simplex chronicus (LSC) in this patient, based on the lesion’s clinical appearance and location, as well as the patient’s history of repeated daily scratching. LSC is more common in women than in men, and occurs mostly in mid- to late-adulthood, with the highest prevalence in people who are 30 to 50 years of age.

A very common location for LSC in women is the back of the neck. In this case the LSC was coexisting with acanthosis nigricans. Fortunately, this patient did not have diabetes, but her obesity and family history predisposed her to acanthosis nigricans.

The treatment for LSC is topical mid- to high-potency corticosteroids. Oral sedating antihistamines can be added at night if pruritus is bad during the evening. If the patient acknowledges that stress is involved, obtain a good psychosocial history and offer the patient treatment for any problems you uncover.

Patients need to minimize touching, scratching, and rubbing of the affected areas. Explain to patients that they are unintentionally hurting their own skin. Suggest that they gently apply their medication or a moisturizer instead of scratching the pruritic areas.

In this case, the FP prescribed topical triamcinolone ointment and stressed the importance of not rubbing or scratching the area. The patient’s LSC healed well.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R, Johnson A. Self-inflicted dermatoses. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 856-862.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The FP diagnosed lichen simplex chronicus (LSC) in this patient, based on the lesion’s clinical appearance and location, as well as the patient’s history of repeated daily scratching. LSC is more common in women than in men, and occurs mostly in mid- to late-adulthood, with the highest prevalence in people who are 30 to 50 years of age.

A very common location for LSC in women is the back of the neck. In this case the LSC was coexisting with acanthosis nigricans. Fortunately, this patient did not have diabetes, but her obesity and family history predisposed her to acanthosis nigricans.

The treatment for LSC is topical mid- to high-potency corticosteroids. Oral sedating antihistamines can be added at night if pruritus is bad during the evening. If the patient acknowledges that stress is involved, obtain a good psychosocial history and offer the patient treatment for any problems you uncover.

Patients need to minimize touching, scratching, and rubbing of the affected areas. Explain to patients that they are unintentionally hurting their own skin. Suggest that they gently apply their medication or a moisturizer instead of scratching the pruritic areas.

In this case, the FP prescribed topical triamcinolone ointment and stressed the importance of not rubbing or scratching the area. The patient’s LSC healed well.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R, Johnson A. Self-inflicted dermatoses. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013: 856-862.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

CASE › A 68-year-old woman with hypertension and hyperlipidemia comes into your office for evaluation of a 30-minute episode of sudden-onset right-hand weakness and difficulty speaking that occurred 4 days earlier. The patient, who is also a smoker, has come in at the insistence of her daughter. On examination, her blood pressure (BP) is 145/88 mm Hg and her heart rate is 76 beats/minute and regular. She appears well and her language function is normal. The rest of her examination is normal. How would you proceed?

Stroke—the death of nerve cells due to a lack of blood supply from either infarction or hemorrhage—strikes nearly 800,000 people in the United States every year.^1,2 Of these events, 130,000 are fatal, making stroke the fifth leading cause of death.³ Effective, early evaluation and cause-specific treatment are crucial parts of stroke care.

Data indicate that evaluation of symptoms suggestive of stroke within 24 hours of an event confers substantial benefit.

Research has helped to clarify the critical role primary care physicians play in recognizing, triaging, and managing stroke and transient ischemic attacks (TIA). This article reviews what we know about the different ways that a stroke and a TIA can present, the appropriate diagnostic work-up for patients presenting with symptoms of either event, and management strategies for subacute care (24 hours to up to 14 days after a stroke has occurred).^4,5 Unless otherwise specified, this review will focus on ischemic stroke because 87% of strokes are attributable to ischemia.¹

A follow-up to this article on secondary stroke prevention will appear in the journal next month.

IMAGE: © 2017 ALEX NUBAUM C/O THE ISPOT

Look to onset more than type of symptoms for clues

Stroke presents as a sudden onset of neurologic deficits (language, motor, sensory, cerebellar, or brainstem functions) (TABLE 1⁴). Because presenting symptoms can vary widely, sudden onset, rather than particular symptoms, should raise a red flag for potential stroke.

The differential diagnosis includes: seizure, complex migraine, medication effect (eg, slurred speech or confusion after taking a central nervous system [CNS] depressant), toxin exposure, electrolyte abnormalities (especially hypoglycemia), concussion/trauma, infection of the CNS, peripheral vertigo, demyelination, intracranial mass, Bell’s palsy, and psychogenic disorders. The history and physical, along with laboratory findings and brain imaging (detailed later in this article), will guide the FP toward (or away from) these various etiologies.

Optimal triage is a subject of ongoing interest and research

If stroke or TIA remains a possibility after an initial assessment, it’s time to stratify patients by risk.

One of the most widely accepted tools is the ABCD² score (see TABLE 2⁶). Clinicians can employ the ABCD² risk stratification tool when trying to determine whether it is reasonable to pursue an expedited work-up (ie, <1 day) in the outpatient setting or recommend that the patient be evaluated in an emergency department (ED). The 90-day stroke rate following a TIA ranges from 3% with an ABCD² score of 0 to 3 to 18% with a score of 6 or 7. A score of 0 to 3 is considered relatively low risk; in the absence of other compelling factors, rapid outpatient evaluation is appropriate. For patients with an ABCD² score ≥4, referral to the ED or direct admission to the hospital is advised.

The validity of the ABCD² score for risk stratification has been studied extensively with conflicting results.^7-10 As with any assessment tool, it should be used as a guide, and should not supplant a full assessment of the patient or the judgment of the examining physician. In making the decision regarding inpatient or outpatient evaluation, it’s also important to consider available resources, access to specialists, and patient preference.

In a 2016 population-based study, the 30-day recurrent stroke/TIA rate for patients hospitalized for TIA was 3% compared with 10.7% for those discharged from the ED with referral to a stroke clinic and 10.6% for those discharged from the ED without a referral to a stroke clinic.¹¹ These data suggest that only patients for whom you have a low clinical suspicion of stroke/TIA should be worked up as outpatients, and that hospital admission is advised in moderate- and high-risk cases. The findings also highlight the critical role that primary care physicians can play in triaging and managing these patients for secondary prevention.

CASE › This patient’s recent history of sudden-onset right-sided weakness and expressive language dysfunction is suspicious for left hemispheric ischemia. She has several risk factors for stroke, and her ABCD² score is 5 (hypertension, age ≥60 years, unilateral weakness, and duration 10-59 min), which places her at moderate risk. Thus, the recommendation would be to have her go directly to an ED for rapid evaluation.

The diagnostic work-up

Even when a patient is sent to the ED, the FP plays a critical role in his or her continuing care. FPs will often coordinate with inpatient care and manage transition of care to the outpatient setting. (And in many communities, the ED or hospital physicians may themselves be family practitioners.)

In terms of care, not even an aspirin should be administered in a case like this because the patient has not yet had any neuroimaging, and differentiation of ischemic from hemorrhagic stroke cannot be made on clinical grounds alone. Once an ischemic stroke is confirmed, determining the etiology is critical given the significant management differences between the different types of stroke (atherosclerotic, cardioembolic, lacunar, or other).

Which imaging method, and when?

While a computerized tomography (CT) scan is the preferred initial imaging strategy for acute stroke to discern the ischemic type from the hemorrhagic, MRI is preferred for the evaluation of acute ischemic stroke because the method has a higher sensitivity for infarction and a greater ability to identify findings (such as demyelination) that would suggest an alternative diagnosis.

Because presenting symptoms can vary widely, sudden onset, rather than particular symptoms, should raise the red flag for potential stroke.

In addition to evaluating the brain parenchyma, physicians must also assess the cerebral vasculature. CT angiography (CTA) or MR angiography (MRA) of the head and neck are preferred over carotid ultrasound because they are capable of evaluating the entire cerebrovascular system^12,13 and can be instrumental in identifying potential causes of stroke, as well as guiding therapeutic decisions. Carotid ultrasound is a reasonable alternative for patients presenting with symptoms indicative of anterior circulation involvement when CTA and MRA are unavailable or contraindicated, but it will not identify intracranial vascular disease, proximal common carotid disease, or vertebrobasilar disease.

Getting to the cause of suspected stroke: Labs and other diagnostic tests

A routine work-up includes BP checks, routine labs (complete blood count, complete metabolic panel, coagulation profile, and troponin), an electrocardiogram (EKG), a transthoracic echocardiogram (TTE) with bubble study if possible, and a minimum of 24 to 48 hours of cardiac rhythm monitoring. Cardiac rhythm monitoring should be extended in the setting of clinical concern for unidentified paroxysmal atrial fibrillation, such as an embolism without a proximal vascular source, multiple embolic infarcts in different vascular territories, a dilated left atrium, or other risk factors for atrial fibrillation that include smoking, systolic hypertension, diabetes, and heart failure (see TABLE 3^12,13,17,18).^14-16 This standard diagnostic work-up will identify the cause of stroke in 70% to 80% of patients.¹⁹

Additional investigations to consider if the etiology is not yet elucidated include a transesophageal echocardiogram (TEE), cerebral angiography, a coagulopathy evaluation, a lumbar puncture, and a vasculitis work-up. If available, consultation with a neurologist is appropriate for any patient who has had a stroke or TIA. Patients with unclear etiologies or for whom there are questions concerning strategies for preventing secondary stroke should be referred to Neurology and preferably a stroke specialist.

Timing matters, even when symptoms have resolved (ie, TIA).^11,20 The EXPRESS trial¹⁷ (the Early use of eXisting PREventive Strategies for Stroke) looked at the effect of urgent assessment and treatment (≤1 day) of patients presenting with a TIA or minor stroke on the risk of recurrent stroke within 90 days. The diagnostic work-up included brain and vascular imaging together with an EKG. This intensive approach led to an absolute risk reduction of 8.2% (from 10.3% to 2.1%) in the risk of recurrent stroke at 90 days (number needed to treat [NNT]=12).¹⁷

Expedited work-up and treatment was also recently evaluated in a non-trial, real-world setting and was associated with reducing recurrent stroke by more than half the rate reported in older studies.²⁰ Overall, the data suggest that evaluation within 24 hours confers substantial benefit, and that this evaluation can happen in an outpatient setting.^21-23

Acute management: Use of tPA

Once imaging rules out intracranial hemorrhage, patients should be treated with tissue plasminogen activator (tPA) or an endovascular intervention as per guidelines.²⁴ For patients with ischemic stroke ineligible for tPA or endovascular treatments, the initial focus is to determine the etiology of the symptoms so that the best strategies for prevention of secondary stroke may be employed.

Aspirin should be provided within 24 to 48 hours to all patients after intracranial hemorrhage is ruled out. Aspirin should be delayed for 24 hours in those given thrombolytics. The initial recommended dose of aspirin is 325 mg with continued low-dose (81 mg) aspirin daily.¹³ The addition of clopidogrel to aspirin within 24 hours of an event and continued for 21 days, followed by aspirin alone, was shown to be beneficial in a Chinese population with high-risk TIA (ABCD² score ≥4) or minor stroke (National Institutes of Health Stroke Scale [NIHSS] ≤3).²⁵ Anticoagulation with heparin, warfarin, or a novel oral anticoagulant is generally not indicated in the acute setting due to the risk of hemorrhagic transformation.

Acute BP management depends upon the type of stroke (ischemic or hemorrhagic), eligibility for thrombolytics, timing of presentation, and possible comorbidities such as myocardial infarction or aortic dissection (see TABLE 4^13,26). In the absence of contraindications, high-intensity statins should be initiated in all patients able to take oral medications.

CASE › You appropriately referred your patient to the local ED. A head CT with head and neck CTA was performed. While the head CT did not show any abnormalities, the CTA demonstrated high-grade left internal carotid artery stenosis. The patient was given an initial dose of aspirin 325 mg and a high-intensity statin and admitted for further management. An MRI revealed a small shower of emboli in the left hemisphere, confirming the diagnosis of stroke over TIA. Labs were marginally remarkable with a low-density lipoprotein level of 115 mg/dL and an HbA1c of 6.2. Telemetry monitoring did not reveal any arrhythmias, and TTE was normal. BP remained in the high-normal to low-hypertensive range.

Timing matters, even when symptoms have resolved, such as with a TIA.

A Vascular Surgery consultation was obtained and the patient underwent a left carotid endarterectomy the following day. She did well without surgical complications. Her BP medications were adjusted; a combination of an angiotensin-converting enzyme inhibitor and a thiazide diuretic achieved a goal BP <140/90 mm Hg.

Permissive hypertension was not indicated due to her presentation >48 hours beyond the acute event. Low-dose aspirin and a high-intensity statin were continued, for secondary stroke prevention in the setting of atherosclerotic disease. She received smoking cessation counseling, which will continue.

CORRESPONDENCE
Stephen A. Martin, MD, EdM, Barre Family Health Center, 151 Worcester Road, Barre, MA 01005; [email protected].

CASE › A 68-year-old woman with hypertension and hyperlipidemia comes into your office for evaluation of a 30-minute episode of sudden-onset right-hand weakness and difficulty speaking that occurred 4 days earlier. The patient, who is also a smoker, has come in at the insistence of her daughter. On examination, her blood pressure (BP) is 145/88 mm Hg and her heart rate is 76 beats/minute and regular. She appears well and her language function is normal. The rest of her examination is normal. How would you proceed?

Stroke—the death of nerve cells due to a lack of blood supply from either infarction or hemorrhage—strikes nearly 800,000 people in the United States every year.^1,2 Of these events, 130,000 are fatal, making stroke the fifth leading cause of death.³ Effective, early evaluation and cause-specific treatment are crucial parts of stroke care.

Data indicate that evaluation of symptoms suggestive of stroke within 24 hours of an event confers substantial benefit.

Research has helped to clarify the critical role primary care physicians play in recognizing, triaging, and managing stroke and transient ischemic attacks (TIA). This article reviews what we know about the different ways that a stroke and a TIA can present, the appropriate diagnostic work-up for patients presenting with symptoms of either event, and management strategies for subacute care (24 hours to up to 14 days after a stroke has occurred).^4,5 Unless otherwise specified, this review will focus on ischemic stroke because 87% of strokes are attributable to ischemia.¹

A follow-up to this article on secondary stroke prevention will appear in the journal next month.

IMAGE: © 2017 ALEX NUBAUM C/O THE ISPOT

Look to onset more than type of symptoms for clues

Stroke presents as a sudden onset of neurologic deficits (language, motor, sensory, cerebellar, or brainstem functions) (TABLE 1⁴). Because presenting symptoms can vary widely, sudden onset, rather than particular symptoms, should raise a red flag for potential stroke.

The differential diagnosis includes: seizure, complex migraine, medication effect (eg, slurred speech or confusion after taking a central nervous system [CNS] depressant), toxin exposure, electrolyte abnormalities (especially hypoglycemia), concussion/trauma, infection of the CNS, peripheral vertigo, demyelination, intracranial mass, Bell’s palsy, and psychogenic disorders. The history and physical, along with laboratory findings and brain imaging (detailed later in this article), will guide the FP toward (or away from) these various etiologies.

Optimal triage is a subject of ongoing interest and research

If stroke or TIA remains a possibility after an initial assessment, it’s time to stratify patients by risk.

One of the most widely accepted tools is the ABCD² score (see TABLE 2⁶). Clinicians can employ the ABCD² risk stratification tool when trying to determine whether it is reasonable to pursue an expedited work-up (ie, <1 day) in the outpatient setting or recommend that the patient be evaluated in an emergency department (ED). The 90-day stroke rate following a TIA ranges from 3% with an ABCD² score of 0 to 3 to 18% with a score of 6 or 7. A score of 0 to 3 is considered relatively low risk; in the absence of other compelling factors, rapid outpatient evaluation is appropriate. For patients with an ABCD² score ≥4, referral to the ED or direct admission to the hospital is advised.

The validity of the ABCD² score for risk stratification has been studied extensively with conflicting results.^7-10 As with any assessment tool, it should be used as a guide, and should not supplant a full assessment of the patient or the judgment of the examining physician. In making the decision regarding inpatient or outpatient evaluation, it’s also important to consider available resources, access to specialists, and patient preference.

In a 2016 population-based study, the 30-day recurrent stroke/TIA rate for patients hospitalized for TIA was 3% compared with 10.7% for those discharged from the ED with referral to a stroke clinic and 10.6% for those discharged from the ED without a referral to a stroke clinic.¹¹ These data suggest that only patients for whom you have a low clinical suspicion of stroke/TIA should be worked up as outpatients, and that hospital admission is advised in moderate- and high-risk cases. The findings also highlight the critical role that primary care physicians can play in triaging and managing these patients for secondary prevention.

CASE › This patient’s recent history of sudden-onset right-sided weakness and expressive language dysfunction is suspicious for left hemispheric ischemia. She has several risk factors for stroke, and her ABCD² score is 5 (hypertension, age ≥60 years, unilateral weakness, and duration 10-59 min), which places her at moderate risk. Thus, the recommendation would be to have her go directly to an ED for rapid evaluation.

The diagnostic work-up

Even when a patient is sent to the ED, the FP plays a critical role in his or her continuing care. FPs will often coordinate with inpatient care and manage transition of care to the outpatient setting. (And in many communities, the ED or hospital physicians may themselves be family practitioners.)

In terms of care, not even an aspirin should be administered in a case like this because the patient has not yet had any neuroimaging, and differentiation of ischemic from hemorrhagic stroke cannot be made on clinical grounds alone. Once an ischemic stroke is confirmed, determining the etiology is critical given the significant management differences between the different types of stroke (atherosclerotic, cardioembolic, lacunar, or other).

Which imaging method, and when?

While a computerized tomography (CT) scan is the preferred initial imaging strategy for acute stroke to discern the ischemic type from the hemorrhagic, MRI is preferred for the evaluation of acute ischemic stroke because the method has a higher sensitivity for infarction and a greater ability to identify findings (such as demyelination) that would suggest an alternative diagnosis.

Because presenting symptoms can vary widely, sudden onset, rather than particular symptoms, should raise the red flag for potential stroke.

In addition to evaluating the brain parenchyma, physicians must also assess the cerebral vasculature. CT angiography (CTA) or MR angiography (MRA) of the head and neck are preferred over carotid ultrasound because they are capable of evaluating the entire cerebrovascular system^12,13 and can be instrumental in identifying potential causes of stroke, as well as guiding therapeutic decisions. Carotid ultrasound is a reasonable alternative for patients presenting with symptoms indicative of anterior circulation involvement when CTA and MRA are unavailable or contraindicated, but it will not identify intracranial vascular disease, proximal common carotid disease, or vertebrobasilar disease.

Getting to the cause of suspected stroke: Labs and other diagnostic tests

A routine work-up includes BP checks, routine labs (complete blood count, complete metabolic panel, coagulation profile, and troponin), an electrocardiogram (EKG), a transthoracic echocardiogram (TTE) with bubble study if possible, and a minimum of 24 to 48 hours of cardiac rhythm monitoring. Cardiac rhythm monitoring should be extended in the setting of clinical concern for unidentified paroxysmal atrial fibrillation, such as an embolism without a proximal vascular source, multiple embolic infarcts in different vascular territories, a dilated left atrium, or other risk factors for atrial fibrillation that include smoking, systolic hypertension, diabetes, and heart failure (see TABLE 3^12,13,17,18).^14-16 This standard diagnostic work-up will identify the cause of stroke in 70% to 80% of patients.¹⁹

Additional investigations to consider if the etiology is not yet elucidated include a transesophageal echocardiogram (TEE), cerebral angiography, a coagulopathy evaluation, a lumbar puncture, and a vasculitis work-up. If available, consultation with a neurologist is appropriate for any patient who has had a stroke or TIA. Patients with unclear etiologies or for whom there are questions concerning strategies for preventing secondary stroke should be referred to Neurology and preferably a stroke specialist.

Timing matters, even when symptoms have resolved (ie, TIA).^11,20 The EXPRESS trial¹⁷ (the Early use of eXisting PREventive Strategies for Stroke) looked at the effect of urgent assessment and treatment (≤1 day) of patients presenting with a TIA or minor stroke on the risk of recurrent stroke within 90 days. The diagnostic work-up included brain and vascular imaging together with an EKG. This intensive approach led to an absolute risk reduction of 8.2% (from 10.3% to 2.1%) in the risk of recurrent stroke at 90 days (number needed to treat [NNT]=12).¹⁷

Expedited work-up and treatment was also recently evaluated in a non-trial, real-world setting and was associated with reducing recurrent stroke by more than half the rate reported in older studies.²⁰ Overall, the data suggest that evaluation within 24 hours confers substantial benefit, and that this evaluation can happen in an outpatient setting.^21-23

Acute management: Use of tPA

Once imaging rules out intracranial hemorrhage, patients should be treated with tissue plasminogen activator (tPA) or an endovascular intervention as per guidelines.²⁴ For patients with ischemic stroke ineligible for tPA or endovascular treatments, the initial focus is to determine the etiology of the symptoms so that the best strategies for prevention of secondary stroke may be employed.

Aspirin should be provided within 24 to 48 hours to all patients after intracranial hemorrhage is ruled out. Aspirin should be delayed for 24 hours in those given thrombolytics. The initial recommended dose of aspirin is 325 mg with continued low-dose (81 mg) aspirin daily.¹³ The addition of clopidogrel to aspirin within 24 hours of an event and continued for 21 days, followed by aspirin alone, was shown to be beneficial in a Chinese population with high-risk TIA (ABCD² score ≥4) or minor stroke (National Institutes of Health Stroke Scale [NIHSS] ≤3).²⁵ Anticoagulation with heparin, warfarin, or a novel oral anticoagulant is generally not indicated in the acute setting due to the risk of hemorrhagic transformation.

Acute BP management depends upon the type of stroke (ischemic or hemorrhagic), eligibility for thrombolytics, timing of presentation, and possible comorbidities such as myocardial infarction or aortic dissection (see TABLE 4^13,26). In the absence of contraindications, high-intensity statins should be initiated in all patients able to take oral medications.

CASE › You appropriately referred your patient to the local ED. A head CT with head and neck CTA was performed. While the head CT did not show any abnormalities, the CTA demonstrated high-grade left internal carotid artery stenosis. The patient was given an initial dose of aspirin 325 mg and a high-intensity statin and admitted for further management. An MRI revealed a small shower of emboli in the left hemisphere, confirming the diagnosis of stroke over TIA. Labs were marginally remarkable with a low-density lipoprotein level of 115 mg/dL and an HbA1c of 6.2. Telemetry monitoring did not reveal any arrhythmias, and TTE was normal. BP remained in the high-normal to low-hypertensive range.

Timing matters, even when symptoms have resolved, such as with a TIA.

A Vascular Surgery consultation was obtained and the patient underwent a left carotid endarterectomy the following day. She did well without surgical complications. Her BP medications were adjusted; a combination of an angiotensin-converting enzyme inhibitor and a thiazide diuretic achieved a goal BP <140/90 mm Hg.

Permissive hypertension was not indicated due to her presentation >48 hours beyond the acute event. Low-dose aspirin and a high-intensity statin were continued, for secondary stroke prevention in the setting of atherosclerotic disease. She received smoking cessation counseling, which will continue.

CORRESPONDENCE
Stephen A. Martin, MD, EdM, Barre Family Health Center, 151 Worcester Road, Barre, MA 01005; [email protected].

CASE › A 68-year-old woman with hypertension and hyperlipidemia comes into your office for evaluation of a 30-minute episode of sudden-onset right-hand weakness and difficulty speaking that occurred 4 days earlier. The patient, who is also a smoker, has come in at the insistence of her daughter. On examination, her blood pressure (BP) is 145/88 mm Hg and her heart rate is 76 beats/minute and regular. She appears well and her language function is normal. The rest of her examination is normal. How would you proceed?

Stroke—the death of nerve cells due to a lack of blood supply from either infarction or hemorrhage—strikes nearly 800,000 people in the United States every year.^1,2 Of these events, 130,000 are fatal, making stroke the fifth leading cause of death.³ Effective, early evaluation and cause-specific treatment are crucial parts of stroke care.

Data indicate that evaluation of symptoms suggestive of stroke within 24 hours of an event confers substantial benefit.

Research has helped to clarify the critical role primary care physicians play in recognizing, triaging, and managing stroke and transient ischemic attacks (TIA). This article reviews what we know about the different ways that a stroke and a TIA can present, the appropriate diagnostic work-up for patients presenting with symptoms of either event, and management strategies for subacute care (24 hours to up to 14 days after a stroke has occurred).^4,5 Unless otherwise specified, this review will focus on ischemic stroke because 87% of strokes are attributable to ischemia.¹

A follow-up to this article on secondary stroke prevention will appear in the journal next month.

IMAGE: © 2017 ALEX NUBAUM C/O THE ISPOT

Look to onset more than type of symptoms for clues

Stroke presents as a sudden onset of neurologic deficits (language, motor, sensory, cerebellar, or brainstem functions) (TABLE 1⁴). Because presenting symptoms can vary widely, sudden onset, rather than particular symptoms, should raise a red flag for potential stroke.

The differential diagnosis includes: seizure, complex migraine, medication effect (eg, slurred speech or confusion after taking a central nervous system [CNS] depressant), toxin exposure, electrolyte abnormalities (especially hypoglycemia), concussion/trauma, infection of the CNS, peripheral vertigo, demyelination, intracranial mass, Bell’s palsy, and psychogenic disorders. The history and physical, along with laboratory findings and brain imaging (detailed later in this article), will guide the FP toward (or away from) these various etiologies.

Optimal triage is a subject of ongoing interest and research

If stroke or TIA remains a possibility after an initial assessment, it’s time to stratify patients by risk.

One of the most widely accepted tools is the ABCD² score (see TABLE 2⁶). Clinicians can employ the ABCD² risk stratification tool when trying to determine whether it is reasonable to pursue an expedited work-up (ie, <1 day) in the outpatient setting or recommend that the patient be evaluated in an emergency department (ED). The 90-day stroke rate following a TIA ranges from 3% with an ABCD² score of 0 to 3 to 18% with a score of 6 or 7. A score of 0 to 3 is considered relatively low risk; in the absence of other compelling factors, rapid outpatient evaluation is appropriate. For patients with an ABCD² score ≥4, referral to the ED or direct admission to the hospital is advised.

The validity of the ABCD² score for risk stratification has been studied extensively with conflicting results.^7-10 As with any assessment tool, it should be used as a guide, and should not supplant a full assessment of the patient or the judgment of the examining physician. In making the decision regarding inpatient or outpatient evaluation, it’s also important to consider available resources, access to specialists, and patient preference.

In a 2016 population-based study, the 30-day recurrent stroke/TIA rate for patients hospitalized for TIA was 3% compared with 10.7% for those discharged from the ED with referral to a stroke clinic and 10.6% for those discharged from the ED without a referral to a stroke clinic.¹¹ These data suggest that only patients for whom you have a low clinical suspicion of stroke/TIA should be worked up as outpatients, and that hospital admission is advised in moderate- and high-risk cases. The findings also highlight the critical role that primary care physicians can play in triaging and managing these patients for secondary prevention.

CASE › This patient’s recent history of sudden-onset right-sided weakness and expressive language dysfunction is suspicious for left hemispheric ischemia. She has several risk factors for stroke, and her ABCD² score is 5 (hypertension, age ≥60 years, unilateral weakness, and duration 10-59 min), which places her at moderate risk. Thus, the recommendation would be to have her go directly to an ED for rapid evaluation.

The diagnostic work-up

Even when a patient is sent to the ED, the FP plays a critical role in his or her continuing care. FPs will often coordinate with inpatient care and manage transition of care to the outpatient setting. (And in many communities, the ED or hospital physicians may themselves be family practitioners.)

In terms of care, not even an aspirin should be administered in a case like this because the patient has not yet had any neuroimaging, and differentiation of ischemic from hemorrhagic stroke cannot be made on clinical grounds alone. Once an ischemic stroke is confirmed, determining the etiology is critical given the significant management differences between the different types of stroke (atherosclerotic, cardioembolic, lacunar, or other).

Which imaging method, and when?

While a computerized tomography (CT) scan is the preferred initial imaging strategy for acute stroke to discern the ischemic type from the hemorrhagic, MRI is preferred for the evaluation of acute ischemic stroke because the method has a higher sensitivity for infarction and a greater ability to identify findings (such as demyelination) that would suggest an alternative diagnosis.

Because presenting symptoms can vary widely, sudden onset, rather than particular symptoms, should raise the red flag for potential stroke.

In addition to evaluating the brain parenchyma, physicians must also assess the cerebral vasculature. CT angiography (CTA) or MR angiography (MRA) of the head and neck are preferred over carotid ultrasound because they are capable of evaluating the entire cerebrovascular system^12,13 and can be instrumental in identifying potential causes of stroke, as well as guiding therapeutic decisions. Carotid ultrasound is a reasonable alternative for patients presenting with symptoms indicative of anterior circulation involvement when CTA and MRA are unavailable or contraindicated, but it will not identify intracranial vascular disease, proximal common carotid disease, or vertebrobasilar disease.

Getting to the cause of suspected stroke: Labs and other diagnostic tests

A routine work-up includes BP checks, routine labs (complete blood count, complete metabolic panel, coagulation profile, and troponin), an electrocardiogram (EKG), a transthoracic echocardiogram (TTE) with bubble study if possible, and a minimum of 24 to 48 hours of cardiac rhythm monitoring. Cardiac rhythm monitoring should be extended in the setting of clinical concern for unidentified paroxysmal atrial fibrillation, such as an embolism without a proximal vascular source, multiple embolic infarcts in different vascular territories, a dilated left atrium, or other risk factors for atrial fibrillation that include smoking, systolic hypertension, diabetes, and heart failure (see TABLE 3^12,13,17,18).^14-16 This standard diagnostic work-up will identify the cause of stroke in 70% to 80% of patients.¹⁹

Additional investigations to consider if the etiology is not yet elucidated include a transesophageal echocardiogram (TEE), cerebral angiography, a coagulopathy evaluation, a lumbar puncture, and a vasculitis work-up. If available, consultation with a neurologist is appropriate for any patient who has had a stroke or TIA. Patients with unclear etiologies or for whom there are questions concerning strategies for preventing secondary stroke should be referred to Neurology and preferably a stroke specialist.

Timing matters, even when symptoms have resolved (ie, TIA).^11,20 The EXPRESS trial¹⁷ (the Early use of eXisting PREventive Strategies for Stroke) looked at the effect of urgent assessment and treatment (≤1 day) of patients presenting with a TIA or minor stroke on the risk of recurrent stroke within 90 days. The diagnostic work-up included brain and vascular imaging together with an EKG. This intensive approach led to an absolute risk reduction of 8.2% (from 10.3% to 2.1%) in the risk of recurrent stroke at 90 days (number needed to treat [NNT]=12).¹⁷

Expedited work-up and treatment was also recently evaluated in a non-trial, real-world setting and was associated with reducing recurrent stroke by more than half the rate reported in older studies.²⁰ Overall, the data suggest that evaluation within 24 hours confers substantial benefit, and that this evaluation can happen in an outpatient setting.^21-23

Acute management: Use of tPA

Once imaging rules out intracranial hemorrhage, patients should be treated with tissue plasminogen activator (tPA) or an endovascular intervention as per guidelines.²⁴ For patients with ischemic stroke ineligible for tPA or endovascular treatments, the initial focus is to determine the etiology of the symptoms so that the best strategies for prevention of secondary stroke may be employed.

Aspirin should be provided within 24 to 48 hours to all patients after intracranial hemorrhage is ruled out. Aspirin should be delayed for 24 hours in those given thrombolytics. The initial recommended dose of aspirin is 325 mg with continued low-dose (81 mg) aspirin daily.¹³ The addition of clopidogrel to aspirin within 24 hours of an event and continued for 21 days, followed by aspirin alone, was shown to be beneficial in a Chinese population with high-risk TIA (ABCD² score ≥4) or minor stroke (National Institutes of Health Stroke Scale [NIHSS] ≤3).²⁵ Anticoagulation with heparin, warfarin, or a novel oral anticoagulant is generally not indicated in the acute setting due to the risk of hemorrhagic transformation.

Acute BP management depends upon the type of stroke (ischemic or hemorrhagic), eligibility for thrombolytics, timing of presentation, and possible comorbidities such as myocardial infarction or aortic dissection (see TABLE 4^13,26). In the absence of contraindications, high-intensity statins should be initiated in all patients able to take oral medications.

CASE › You appropriately referred your patient to the local ED. A head CT with head and neck CTA was performed. While the head CT did not show any abnormalities, the CTA demonstrated high-grade left internal carotid artery stenosis. The patient was given an initial dose of aspirin 325 mg and a high-intensity statin and admitted for further management. An MRI revealed a small shower of emboli in the left hemisphere, confirming the diagnosis of stroke over TIA. Labs were marginally remarkable with a low-density lipoprotein level of 115 mg/dL and an HbA1c of 6.2. Telemetry monitoring did not reveal any arrhythmias, and TTE was normal. BP remained in the high-normal to low-hypertensive range.

Timing matters, even when symptoms have resolved, such as with a TIA.

A Vascular Surgery consultation was obtained and the patient underwent a left carotid endarterectomy the following day. She did well without surgical complications. Her BP medications were adjusted; a combination of an angiotensin-converting enzyme inhibitor and a thiazide diuretic achieved a goal BP <140/90 mm Hg.

Permissive hypertension was not indicated due to her presentation >48 hours beyond the acute event. Low-dose aspirin and a high-intensity statin were continued, for secondary stroke prevention in the setting of atherosclerotic disease. She received smoking cessation counseling, which will continue.

CORRESPONDENCE
Stephen A. Martin, MD, EdM, Barre Family Health Center, 151 Worcester Road, Barre, MA 01005; [email protected].

Based on the clinical presentation and skin biopsy results, the patient was given a diagnosis of cutaneous sarcoidosis. The biopsy from the right side of his nose demonstrated sarcoidal granulomas. A biopsy of one of the tattoo nodules showed sarcoidal granulomas, and close inspection revealed red tattoo pigment within the granulomatous inflammation. X-rays showed bilateral hilar lymphadenopathy, which was consistent with pulmonary sarcoidosis, and the lace-like appearance of the middle and distal phalanges was consistent with skeletal sarcoidosis.

Systemic sarcoidosis is an idiopathic, granulomatous disease that affects multiple organ systems, but primarily the lungs and lymphatic system. Cutaneous sarcoidosis can occur as a manifestation of systemic sarcoidosis. It may present as asymptomatic red or skin-colored papules and firm nodules within tattoos, old scars, or permanent makeup. Sarcoidosis usually occurs in red, black, or blue-black areas of tattoos, in which the pigment acts as a nidus for granuloma formation.

The first-line treatment for limited papules is a high-potency topical corticosteroid (eg, clobetasol 0.05% ointment applied twice weekly) and an intralesional corticosteroid (eg, triamcinolone, one 5-10 mg/mL injection every 4 weeks). Antimalarials such as hydroxychloroquine or methotrexate can also be helpful. Midpotency topical corticosteroids such as triamcinolone 0.1% cream and doxycycline hyclate have been reported to clear cutaneous lesions in tattoos. Oral corticosteroids are often effective for severe cutaneous sarcoidosis, but their multiple adverse effects (eg, diabetes and adrenal suppression) prevent prolonged use except in very low doses in conjunction with other therapies.

The nodules on this patient’s nose were successfully treated with intralesional triamcinolone 5 mg/mL. No treatment was initiated for the tattoo nodules because they were asymptomatic and the patient wasn’t bothered by their appearance. The patient’s hand swelling improved with a treatment of prednisone 10 mg/d. The rheumatologist considered a steroid-sparing immunosuppressive agent such as methotrexate; however, the patient was lost to follow-up.

Adapted from: Zhang J, Jansen R, Lim HW. Nodules on nose and tattoos. J Fam Pract. 2015;64:241-243.

Based on the clinical presentation and skin biopsy results, the patient was given a diagnosis of cutaneous sarcoidosis. The biopsy from the right side of his nose demonstrated sarcoidal granulomas. A biopsy of one of the tattoo nodules showed sarcoidal granulomas, and close inspection revealed red tattoo pigment within the granulomatous inflammation. X-rays showed bilateral hilar lymphadenopathy, which was consistent with pulmonary sarcoidosis, and the lace-like appearance of the middle and distal phalanges was consistent with skeletal sarcoidosis.

Systemic sarcoidosis is an idiopathic, granulomatous disease that affects multiple organ systems, but primarily the lungs and lymphatic system. Cutaneous sarcoidosis can occur as a manifestation of systemic sarcoidosis. It may present as asymptomatic red or skin-colored papules and firm nodules within tattoos, old scars, or permanent makeup. Sarcoidosis usually occurs in red, black, or blue-black areas of tattoos, in which the pigment acts as a nidus for granuloma formation.

The first-line treatment for limited papules is a high-potency topical corticosteroid (eg, clobetasol 0.05% ointment applied twice weekly) and an intralesional corticosteroid (eg, triamcinolone, one 5-10 mg/mL injection every 4 weeks). Antimalarials such as hydroxychloroquine or methotrexate can also be helpful. Midpotency topical corticosteroids such as triamcinolone 0.1% cream and doxycycline hyclate have been reported to clear cutaneous lesions in tattoos. Oral corticosteroids are often effective for severe cutaneous sarcoidosis, but their multiple adverse effects (eg, diabetes and adrenal suppression) prevent prolonged use except in very low doses in conjunction with other therapies.

The nodules on this patient’s nose were successfully treated with intralesional triamcinolone 5 mg/mL. No treatment was initiated for the tattoo nodules because they were asymptomatic and the patient wasn’t bothered by their appearance. The patient’s hand swelling improved with a treatment of prednisone 10 mg/d. The rheumatologist considered a steroid-sparing immunosuppressive agent such as methotrexate; however, the patient was lost to follow-up.

Adapted from: Zhang J, Jansen R, Lim HW. Nodules on nose and tattoos. J Fam Pract. 2015;64:241-243.

Based on the clinical presentation and skin biopsy results, the patient was given a diagnosis of cutaneous sarcoidosis. The biopsy from the right side of his nose demonstrated sarcoidal granulomas. A biopsy of one of the tattoo nodules showed sarcoidal granulomas, and close inspection revealed red tattoo pigment within the granulomatous inflammation. X-rays showed bilateral hilar lymphadenopathy, which was consistent with pulmonary sarcoidosis, and the lace-like appearance of the middle and distal phalanges was consistent with skeletal sarcoidosis.

Systemic sarcoidosis is an idiopathic, granulomatous disease that affects multiple organ systems, but primarily the lungs and lymphatic system. Cutaneous sarcoidosis can occur as a manifestation of systemic sarcoidosis. It may present as asymptomatic red or skin-colored papules and firm nodules within tattoos, old scars, or permanent makeup. Sarcoidosis usually occurs in red, black, or blue-black areas of tattoos, in which the pigment acts as a nidus for granuloma formation.

The first-line treatment for limited papules is a high-potency topical corticosteroid (eg, clobetasol 0.05% ointment applied twice weekly) and an intralesional corticosteroid (eg, triamcinolone, one 5-10 mg/mL injection every 4 weeks). Antimalarials such as hydroxychloroquine or methotrexate can also be helpful. Midpotency topical corticosteroids such as triamcinolone 0.1% cream and doxycycline hyclate have been reported to clear cutaneous lesions in tattoos. Oral corticosteroids are often effective for severe cutaneous sarcoidosis, but their multiple adverse effects (eg, diabetes and adrenal suppression) prevent prolonged use except in very low doses in conjunction with other therapies.

The nodules on this patient’s nose were successfully treated with intralesional triamcinolone 5 mg/mL. No treatment was initiated for the tattoo nodules because they were asymptomatic and the patient wasn’t bothered by their appearance. The patient’s hand swelling improved with a treatment of prednisone 10 mg/d. The rheumatologist considered a steroid-sparing immunosuppressive agent such as methotrexate; however, the patient was lost to follow-up.

Adapted from: Zhang J, Jansen R, Lim HW. Nodules on nose and tattoos. J Fam Pract. 2015;64:241-243.

EVIDENCE SUMMARY

A meta-analysis of 24 RCTs examined the effect of pseudoephedrine on BP and heart rate.¹ Just 5 of the 24 studies specifically included hypertensive patients. In the population of patients with hypertension, the meta-analysis showed a small (1.2 mm Hg) rise in systolic BP with pseudoephedrine that was statistically significant (95% confidence interval [CI], 0.56-1.84 mm Hg), but the slight changes in diastolic BP and heart rate were not significant. No patient-oriented outcomes were measured.

The highest quality study within this group was a randomized, double-blind, placebo-controlled crossover study with 28 patients given sustained-release pseudoephedrine 120 mg twice daily for 72 hours, with BP measurements taken at 48 and 72 hours.² The study was powered to identify an increase in systolic BP of 11 mm Hg, but the results showed just a 3.1 mm Hg rise in systolic BP at 48 hours (see TABLE^1-7 for CI and other data).

In another double-blind, placebo-controlled RCT of 29 adults with hypertension (only 25 were included in the data analysis), there was no significant elevation in BP when oral pseudoephedrine was administered over the course of 3 days.³

Across the 5 studies in the meta-analysis, immediate-release and sustained-release forms of pseudoephedrine were included, hypertension was described as controlled but definitions of control were not always specified, and study length varied from 2 hours to 4 weeks.^2-6 Patients on antihypertensive medications were included in some of the studies; patients who had active cardiovascular disease, peripheral vascular disease, and/or cerebrovascular disease were excluded.

One study specifically looked at the effects of a single dose of pseudoephedrine on BP in patients treated with 2 different beta-blockers and found no significant change from baseline, but this study was not powered to show differences less than 5 mm Hg.⁶ The study did show a change of 1 to 2 mm Hg in systolic BP, but this was not statistically significant.

An absence of information on older patients

There is a paucity of literature on treating older adults and medically complex patients (eg, those with uncontrolled or secondary causes of hypertension, cerebrovascular disease, coronary artery disease) with decongestants, as they were excluded in all studies. And the available evidence does not include reports of adverse events other than changes in BP.

EVIDENCE SUMMARY

A meta-analysis of 24 RCTs examined the effect of pseudoephedrine on BP and heart rate.¹ Just 5 of the 24 studies specifically included hypertensive patients. In the population of patients with hypertension, the meta-analysis showed a small (1.2 mm Hg) rise in systolic BP with pseudoephedrine that was statistically significant (95% confidence interval [CI], 0.56-1.84 mm Hg), but the slight changes in diastolic BP and heart rate were not significant. No patient-oriented outcomes were measured.

The highest quality study within this group was a randomized, double-blind, placebo-controlled crossover study with 28 patients given sustained-release pseudoephedrine 120 mg twice daily for 72 hours, with BP measurements taken at 48 and 72 hours.² The study was powered to identify an increase in systolic BP of 11 mm Hg, but the results showed just a 3.1 mm Hg rise in systolic BP at 48 hours (see TABLE^1-7 for CI and other data).

In another double-blind, placebo-controlled RCT of 29 adults with hypertension (only 25 were included in the data analysis), there was no significant elevation in BP when oral pseudoephedrine was administered over the course of 3 days.³

Across the 5 studies in the meta-analysis, immediate-release and sustained-release forms of pseudoephedrine were included, hypertension was described as controlled but definitions of control were not always specified, and study length varied from 2 hours to 4 weeks.^2-6 Patients on antihypertensive medications were included in some of the studies; patients who had active cardiovascular disease, peripheral vascular disease, and/or cerebrovascular disease were excluded.

One study specifically looked at the effects of a single dose of pseudoephedrine on BP in patients treated with 2 different beta-blockers and found no significant change from baseline, but this study was not powered to show differences less than 5 mm Hg.⁶ The study did show a change of 1 to 2 mm Hg in systolic BP, but this was not statistically significant.

An absence of information on older patients

There is a paucity of literature on treating older adults and medically complex patients (eg, those with uncontrolled or secondary causes of hypertension, cerebrovascular disease, coronary artery disease) with decongestants, as they were excluded in all studies. And the available evidence does not include reports of adverse events other than changes in BP.

EVIDENCE SUMMARY

A meta-analysis of 24 RCTs examined the effect of pseudoephedrine on BP and heart rate.¹ Just 5 of the 24 studies specifically included hypertensive patients. In the population of patients with hypertension, the meta-analysis showed a small (1.2 mm Hg) rise in systolic BP with pseudoephedrine that was statistically significant (95% confidence interval [CI], 0.56-1.84 mm Hg), but the slight changes in diastolic BP and heart rate were not significant. No patient-oriented outcomes were measured.

The highest quality study within this group was a randomized, double-blind, placebo-controlled crossover study with 28 patients given sustained-release pseudoephedrine 120 mg twice daily for 72 hours, with BP measurements taken at 48 and 72 hours.² The study was powered to identify an increase in systolic BP of 11 mm Hg, but the results showed just a 3.1 mm Hg rise in systolic BP at 48 hours (see TABLE^1-7 for CI and other data).

In another double-blind, placebo-controlled RCT of 29 adults with hypertension (only 25 were included in the data analysis), there was no significant elevation in BP when oral pseudoephedrine was administered over the course of 3 days.³

Across the 5 studies in the meta-analysis, immediate-release and sustained-release forms of pseudoephedrine were included, hypertension was described as controlled but definitions of control were not always specified, and study length varied from 2 hours to 4 weeks.^2-6 Patients on antihypertensive medications were included in some of the studies; patients who had active cardiovascular disease, peripheral vascular disease, and/or cerebrovascular disease were excluded.

One study specifically looked at the effects of a single dose of pseudoephedrine on BP in patients treated with 2 different beta-blockers and found no significant change from baseline, but this study was not powered to show differences less than 5 mm Hg.⁶ The study did show a change of 1 to 2 mm Hg in systolic BP, but this was not statistically significant.

An absence of information on older patients

There is a paucity of literature on treating older adults and medically complex patients (eg, those with uncontrolled or secondary causes of hypertension, cerebrovascular disease, coronary artery disease) with decongestants, as they were excluded in all studies. And the available evidence does not include reports of adverse events other than changes in BP.

THE CASE

A 57-year-old African American woman was being treated at our clinic for neurogenic urinary incontinence (UI). The UI, which occurred day and night, began 2 years earlier following a laminectomy of vertebrae C3 to C6 with spinal fusion of C3 to C7 for cervical spinal stenosis. The UI persisted despite physical therapy and trials of oxybutynin and imipramine. Since the surgery, the patient had also been experiencing chronic (debilitating) neuropathic pain in both legs, and the sensation of incomplete bladder emptying. She denied bowel incontinence or saddle anesthesia. Her prescription medications included hydrocodone-acetaminophen 7.5/325 mg every 6 hours as needed for pain and lisinopril 20 mg/d for essential hypertension. The patient’s body mass index (BMI) was 23.3.

A urine culture initially grew Klebsiella pneumoniae, which we successfully treated with ciprofloxacin. A urinalysis was unremarkable, and blood urea nitrogen and creatinine levels were within normal limits.

We started the patient on oral duloxetine 30 mg/d for her neuropathic pain. The patient hadn’t undergone a urologic evaluation before starting duloxetine, so no urodynamic studies or measurements had been conducted. At that point, we sent the patient to a urologist for an evaluation.

At a follow-up visit with one of our clinic providers <3 months later, the patient reported that the duloxetine was providing her with some pain relief and that she was “waking up dry” in the mornings and having fewer UI symptoms throughout the day, as well as at night. The patient denied any adverse effects such as nausea, gastrointestinal upset, weight changes, xerostomia, fatigue, insomnia, headaches, or dizziness. Duloxetine was titrated up to 60 mg/d for better control of her neuropathic pain. At the next follow-up visit at our clinic 3 months later, her UI was 80% to 90% improved and she was able to stop her opioid pain medications.

DISCUSSION

UI is a significant problem in the United States and around the world. For women, the prevalence of UI ranges from 15% to 69%; among men, the prevalence is 5% to 24%.^1-3 The economic burden of UI includes both medical and nonmedical (eg, pads, diapers, laundry, and dry cleaning) care. The total national cost was estimated at $66 billion in 2007: $49 billion for direct medical costs, $2 billion for direct nonmedical costs, and $15 billion for indirect costs.⁴ And those costs are expected to increase 25% by 2020, mainly because of the aging population.

Risk factors for UI other than gender include advancing age, obesity, non-Hispanic white race, depression, hypertension, type 2 diabetes mellitus, neurologic disease, and functional limitations/general poor health.^5-7 Comorbid depression and BMI >30, as well as the presence and duration of diabetes, increase the odds for developing UI.^7,8

Duloxetine has been shown to be effective for the treatment of stress and mixed urinary incontinence. This case suggests it may be useful for neurogenic urinary incontinence, as well.

Risk factors for women include hysterectomy,⁷ increasing parity, and delivery of at least one infant >9.5 pounds; the risk is the same for both vaginal and cesarean-section delivery.⁶ Specific risk factors for men include prostate cancer, prostate surgery, and prostate radiation.⁵

Significant, chronic comorbidities of UI include depression and chronic pain. While quality of life is negatively affected by UI alone, the coexistence of depression and UI produces an additive negative effect on quality of life.⁹

Types and treatment of UI

There are 5 types of UI: urge, stress, overflow, functional, and mixed.¹⁰

• Urge incontinence is the leakage of urine following a sensation of sudden urgency to void.
• Stress incontinence is urine leakage associated with increased intra-abdominal pressure such as with coughing or sneezing and is typically associated with weakened pelvic floor musculature.
• Overflow incontinence is more common in men, and is typically caused by prostatic disease. The urethral outlet is obstructed leading to increased pressure within the bladder and subsequent leakage of urine.
• Functional incontinence is caused by physical or cognitive impairment leading to a decreased ability to get to a bathroom quickly enough to void.
• Mixed incontinence is when symptoms of stress and urgency incontinence are present.

There are 3 broad categories of treatment methods for urinary incontinence: behavioral, pharmacologic, and surgical. Behavioral interventions are subdivided into caregiver-dependent (prompted voiding, habit retraining, and timed voiding) and patient-directed (bladder training, pelvic floor muscle training, strategies for bladder control, education, and self-monitoring) techniques. Pharmacologic treatment typically consists of antimuscarinics (eg, oxybutynin, tolterodine, solifenacin) and tricyclic antidepressants (eg, imipramine).¹¹ Injections of onabotulinumtoxinA into the detrusor muscle have also been shown to reduce the symptoms of urinary incontinence.¹² Surgical options for treatment of UI include retro-pubic suspension, slings, and, in some instances, artificial urethral sphincters.¹³

A novel treatment for neurogenic UI?

Despite the many treatments available for UI, none comprehensively addresses UI and its common comorbidities.

The role of duloxetine. Normal micturition is regulated by the somatic nervous system and an autonomic reflex arc; the neurotransmitters serotonin and norepinephrine play an important role in the neural regulation of micturition and urinary continence. Duloxetine, alone or as an adjunctive treatment, is a potential novel therapy that treats 2 common comorbidities of UI—chronic pain and depression.

As a selective serotonin norepinephrine reuptake inhibitor (SNRI), duloxetine acts at the molecular level to block the reuptake of serotonin and norepinephrine from synaptic clefts. Specifically, the medication blocks the 5-hydroxytryptamine (5-HT) reuptake transporters, as well as the norepinephrine transporters, of pre-synaptic neurons.¹⁴ Thus, the concentrations of 5-HT and norepinephrine increase in the synaptic cleft.

Functionally, the accumulation of norepinephrine inhibits micturition by relaxing the detrusor muscle and constricting the urethral smooth muscle. In addition, a higher concentration of 5-HT at the neuromuscular junction leads to constriction of the external urethral sphincter.

Duloxetine has been shown to be effective in the treatment of other types of UI, such as stress UI¹⁵ and mixed UI.¹⁶ Additionally, it was found to be effective when compared with placebo in women with overactive bladder syndrome¹⁷ and in women with multiple sclerosis and depression.¹⁸ However, we are not aware of any cases using duloxetine for the treatment of neurogenic UI.

THE TAKEAWAY

Duloxetine is a potential novel drug choice for the treatment of neurogenic UI. Its effects on serotonin and norepinephrine at the synaptic cleft and neuromuscular junction could provide relief for those who have not found relief from other therapies. Further research—particularly a prospective, randomized controlled trial—is needed to determine if duloxetine is, in fact, more than just a theoretical candidate to treat UI and, if so, the most effective dosing.

Offering duloxetine for the treatment of neurogenic urinary incontinence would potentially address coexisting conditions, such as pain or depression.

Offering duloxetine for the treatment of neurogenic UI would potentially address coexisting conditions—such as pain or depression—thus improving patient compliance and reducing health care spending. Before beginning therapy, urodynamic studies to identify the type of UI should be completed, or, at a minimum, post-void residual volume should be measured.

ACKNOWLEDGEMENTS
The authors would like to thank Julie Hughbanks, MLS, Library Manager, Parkview Health Resource Library, for her assistance with the library searches used for this case report.

THE CASE

A 57-year-old African American woman was being treated at our clinic for neurogenic urinary incontinence (UI). The UI, which occurred day and night, began 2 years earlier following a laminectomy of vertebrae C3 to C6 with spinal fusion of C3 to C7 for cervical spinal stenosis. The UI persisted despite physical therapy and trials of oxybutynin and imipramine. Since the surgery, the patient had also been experiencing chronic (debilitating) neuropathic pain in both legs, and the sensation of incomplete bladder emptying. She denied bowel incontinence or saddle anesthesia. Her prescription medications included hydrocodone-acetaminophen 7.5/325 mg every 6 hours as needed for pain and lisinopril 20 mg/d for essential hypertension. The patient’s body mass index (BMI) was 23.3.

A urine culture initially grew Klebsiella pneumoniae, which we successfully treated with ciprofloxacin. A urinalysis was unremarkable, and blood urea nitrogen and creatinine levels were within normal limits.

We started the patient on oral duloxetine 30 mg/d for her neuropathic pain. The patient hadn’t undergone a urologic evaluation before starting duloxetine, so no urodynamic studies or measurements had been conducted. At that point, we sent the patient to a urologist for an evaluation.

At a follow-up visit with one of our clinic providers <3 months later, the patient reported that the duloxetine was providing her with some pain relief and that she was “waking up dry” in the mornings and having fewer UI symptoms throughout the day, as well as at night. The patient denied any adverse effects such as nausea, gastrointestinal upset, weight changes, xerostomia, fatigue, insomnia, headaches, or dizziness. Duloxetine was titrated up to 60 mg/d for better control of her neuropathic pain. At the next follow-up visit at our clinic 3 months later, her UI was 80% to 90% improved and she was able to stop her opioid pain medications.

DISCUSSION

UI is a significant problem in the United States and around the world. For women, the prevalence of UI ranges from 15% to 69%; among men, the prevalence is 5% to 24%.^1-3 The economic burden of UI includes both medical and nonmedical (eg, pads, diapers, laundry, and dry cleaning) care. The total national cost was estimated at $66 billion in 2007: $49 billion for direct medical costs, $2 billion for direct nonmedical costs, and $15 billion for indirect costs.⁴ And those costs are expected to increase 25% by 2020, mainly because of the aging population.

Risk factors for UI other than gender include advancing age, obesity, non-Hispanic white race, depression, hypertension, type 2 diabetes mellitus, neurologic disease, and functional limitations/general poor health.^5-7 Comorbid depression and BMI >30, as well as the presence and duration of diabetes, increase the odds for developing UI.^7,8

Duloxetine has been shown to be effective for the treatment of stress and mixed urinary incontinence. This case suggests it may be useful for neurogenic urinary incontinence, as well.

Risk factors for women include hysterectomy,⁷ increasing parity, and delivery of at least one infant >9.5 pounds; the risk is the same for both vaginal and cesarean-section delivery.⁶ Specific risk factors for men include prostate cancer, prostate surgery, and prostate radiation.⁵

Significant, chronic comorbidities of UI include depression and chronic pain. While quality of life is negatively affected by UI alone, the coexistence of depression and UI produces an additive negative effect on quality of life.⁹

Types and treatment of UI

There are 5 types of UI: urge, stress, overflow, functional, and mixed.¹⁰

• Urge incontinence is the leakage of urine following a sensation of sudden urgency to void.
• Stress incontinence is urine leakage associated with increased intra-abdominal pressure such as with coughing or sneezing and is typically associated with weakened pelvic floor musculature.
• Overflow incontinence is more common in men, and is typically caused by prostatic disease. The urethral outlet is obstructed leading to increased pressure within the bladder and subsequent leakage of urine.
• Functional incontinence is caused by physical or cognitive impairment leading to a decreased ability to get to a bathroom quickly enough to void.
• Mixed incontinence is when symptoms of stress and urgency incontinence are present.

There are 3 broad categories of treatment methods for urinary incontinence: behavioral, pharmacologic, and surgical. Behavioral interventions are subdivided into caregiver-dependent (prompted voiding, habit retraining, and timed voiding) and patient-directed (bladder training, pelvic floor muscle training, strategies for bladder control, education, and self-monitoring) techniques. Pharmacologic treatment typically consists of antimuscarinics (eg, oxybutynin, tolterodine, solifenacin) and tricyclic antidepressants (eg, imipramine).¹¹ Injections of onabotulinumtoxinA into the detrusor muscle have also been shown to reduce the symptoms of urinary incontinence.¹² Surgical options for treatment of UI include retro-pubic suspension, slings, and, in some instances, artificial urethral sphincters.¹³

A novel treatment for neurogenic UI?

Despite the many treatments available for UI, none comprehensively addresses UI and its common comorbidities.

The role of duloxetine. Normal micturition is regulated by the somatic nervous system and an autonomic reflex arc; the neurotransmitters serotonin and norepinephrine play an important role in the neural regulation of micturition and urinary continence. Duloxetine, alone or as an adjunctive treatment, is a potential novel therapy that treats 2 common comorbidities of UI—chronic pain and depression.

As a selective serotonin norepinephrine reuptake inhibitor (SNRI), duloxetine acts at the molecular level to block the reuptake of serotonin and norepinephrine from synaptic clefts. Specifically, the medication blocks the 5-hydroxytryptamine (5-HT) reuptake transporters, as well as the norepinephrine transporters, of pre-synaptic neurons.¹⁴ Thus, the concentrations of 5-HT and norepinephrine increase in the synaptic cleft.

Functionally, the accumulation of norepinephrine inhibits micturition by relaxing the detrusor muscle and constricting the urethral smooth muscle. In addition, a higher concentration of 5-HT at the neuromuscular junction leads to constriction of the external urethral sphincter.

Duloxetine has been shown to be effective in the treatment of other types of UI, such as stress UI¹⁵ and mixed UI.¹⁶ Additionally, it was found to be effective when compared with placebo in women with overactive bladder syndrome¹⁷ and in women with multiple sclerosis and depression.¹⁸ However, we are not aware of any cases using duloxetine for the treatment of neurogenic UI.

THE TAKEAWAY

Duloxetine is a potential novel drug choice for the treatment of neurogenic UI. Its effects on serotonin and norepinephrine at the synaptic cleft and neuromuscular junction could provide relief for those who have not found relief from other therapies. Further research—particularly a prospective, randomized controlled trial—is needed to determine if duloxetine is, in fact, more than just a theoretical candidate to treat UI and, if so, the most effective dosing.

Offering duloxetine for the treatment of neurogenic urinary incontinence would potentially address coexisting conditions, such as pain or depression.

Offering duloxetine for the treatment of neurogenic UI would potentially address coexisting conditions—such as pain or depression—thus improving patient compliance and reducing health care spending. Before beginning therapy, urodynamic studies to identify the type of UI should be completed, or, at a minimum, post-void residual volume should be measured.

ACKNOWLEDGEMENTS
The authors would like to thank Julie Hughbanks, MLS, Library Manager, Parkview Health Resource Library, for her assistance with the library searches used for this case report.

THE CASE

A 57-year-old African American woman was being treated at our clinic for neurogenic urinary incontinence (UI). The UI, which occurred day and night, began 2 years earlier following a laminectomy of vertebrae C3 to C6 with spinal fusion of C3 to C7 for cervical spinal stenosis. The UI persisted despite physical therapy and trials of oxybutynin and imipramine. Since the surgery, the patient had also been experiencing chronic (debilitating) neuropathic pain in both legs, and the sensation of incomplete bladder emptying. She denied bowel incontinence or saddle anesthesia. Her prescription medications included hydrocodone-acetaminophen 7.5/325 mg every 6 hours as needed for pain and lisinopril 20 mg/d for essential hypertension. The patient’s body mass index (BMI) was 23.3.

A urine culture initially grew Klebsiella pneumoniae, which we successfully treated with ciprofloxacin. A urinalysis was unremarkable, and blood urea nitrogen and creatinine levels were within normal limits.

We started the patient on oral duloxetine 30 mg/d for her neuropathic pain. The patient hadn’t undergone a urologic evaluation before starting duloxetine, so no urodynamic studies or measurements had been conducted. At that point, we sent the patient to a urologist for an evaluation.

At a follow-up visit with one of our clinic providers <3 months later, the patient reported that the duloxetine was providing her with some pain relief and that she was “waking up dry” in the mornings and having fewer UI symptoms throughout the day, as well as at night. The patient denied any adverse effects such as nausea, gastrointestinal upset, weight changes, xerostomia, fatigue, insomnia, headaches, or dizziness. Duloxetine was titrated up to 60 mg/d for better control of her neuropathic pain. At the next follow-up visit at our clinic 3 months later, her UI was 80% to 90% improved and she was able to stop her opioid pain medications.

DISCUSSION

UI is a significant problem in the United States and around the world. For women, the prevalence of UI ranges from 15% to 69%; among men, the prevalence is 5% to 24%.^1-3 The economic burden of UI includes both medical and nonmedical (eg, pads, diapers, laundry, and dry cleaning) care. The total national cost was estimated at $66 billion in 2007: $49 billion for direct medical costs, $2 billion for direct nonmedical costs, and $15 billion for indirect costs.⁴ And those costs are expected to increase 25% by 2020, mainly because of the aging population.

Risk factors for UI other than gender include advancing age, obesity, non-Hispanic white race, depression, hypertension, type 2 diabetes mellitus, neurologic disease, and functional limitations/general poor health.^5-7 Comorbid depression and BMI >30, as well as the presence and duration of diabetes, increase the odds for developing UI.^7,8

Duloxetine has been shown to be effective for the treatment of stress and mixed urinary incontinence. This case suggests it may be useful for neurogenic urinary incontinence, as well.

Risk factors for women include hysterectomy,⁷ increasing parity, and delivery of at least one infant >9.5 pounds; the risk is the same for both vaginal and cesarean-section delivery.⁶ Specific risk factors for men include prostate cancer, prostate surgery, and prostate radiation.⁵

Significant, chronic comorbidities of UI include depression and chronic pain. While quality of life is negatively affected by UI alone, the coexistence of depression and UI produces an additive negative effect on quality of life.⁹

Types and treatment of UI

There are 5 types of UI: urge, stress, overflow, functional, and mixed.¹⁰

• Urge incontinence is the leakage of urine following a sensation of sudden urgency to void.
• Stress incontinence is urine leakage associated with increased intra-abdominal pressure such as with coughing or sneezing and is typically associated with weakened pelvic floor musculature.
• Overflow incontinence is more common in men, and is typically caused by prostatic disease. The urethral outlet is obstructed leading to increased pressure within the bladder and subsequent leakage of urine.
• Functional incontinence is caused by physical or cognitive impairment leading to a decreased ability to get to a bathroom quickly enough to void.
• Mixed incontinence is when symptoms of stress and urgency incontinence are present.

There are 3 broad categories of treatment methods for urinary incontinence: behavioral, pharmacologic, and surgical. Behavioral interventions are subdivided into caregiver-dependent (prompted voiding, habit retraining, and timed voiding) and patient-directed (bladder training, pelvic floor muscle training, strategies for bladder control, education, and self-monitoring) techniques. Pharmacologic treatment typically consists of antimuscarinics (eg, oxybutynin, tolterodine, solifenacin) and tricyclic antidepressants (eg, imipramine).¹¹ Injections of onabotulinumtoxinA into the detrusor muscle have also been shown to reduce the symptoms of urinary incontinence.¹² Surgical options for treatment of UI include retro-pubic suspension, slings, and, in some instances, artificial urethral sphincters.¹³

A novel treatment for neurogenic UI?

Despite the many treatments available for UI, none comprehensively addresses UI and its common comorbidities.

The role of duloxetine. Normal micturition is regulated by the somatic nervous system and an autonomic reflex arc; the neurotransmitters serotonin and norepinephrine play an important role in the neural regulation of micturition and urinary continence. Duloxetine, alone or as an adjunctive treatment, is a potential novel therapy that treats 2 common comorbidities of UI—chronic pain and depression.

As a selective serotonin norepinephrine reuptake inhibitor (SNRI), duloxetine acts at the molecular level to block the reuptake of serotonin and norepinephrine from synaptic clefts. Specifically, the medication blocks the 5-hydroxytryptamine (5-HT) reuptake transporters, as well as the norepinephrine transporters, of pre-synaptic neurons.¹⁴ Thus, the concentrations of 5-HT and norepinephrine increase in the synaptic cleft.

Functionally, the accumulation of norepinephrine inhibits micturition by relaxing the detrusor muscle and constricting the urethral smooth muscle. In addition, a higher concentration of 5-HT at the neuromuscular junction leads to constriction of the external urethral sphincter.

Duloxetine has been shown to be effective in the treatment of other types of UI, such as stress UI¹⁵ and mixed UI.¹⁶ Additionally, it was found to be effective when compared with placebo in women with overactive bladder syndrome¹⁷ and in women with multiple sclerosis and depression.¹⁸ However, we are not aware of any cases using duloxetine for the treatment of neurogenic UI.

THE TAKEAWAY

Duloxetine is a potential novel drug choice for the treatment of neurogenic UI. Its effects on serotonin and norepinephrine at the synaptic cleft and neuromuscular junction could provide relief for those who have not found relief from other therapies. Further research—particularly a prospective, randomized controlled trial—is needed to determine if duloxetine is, in fact, more than just a theoretical candidate to treat UI and, if so, the most effective dosing.

Offering duloxetine for the treatment of neurogenic urinary incontinence would potentially address coexisting conditions, such as pain or depression.

Offering duloxetine for the treatment of neurogenic UI would potentially address coexisting conditions—such as pain or depression—thus improving patient compliance and reducing health care spending. Before beginning therapy, urodynamic studies to identify the type of UI should be completed, or, at a minimum, post-void residual volume should be measured.

ACKNOWLEDGEMENTS
The authors would like to thank Julie Hughbanks, MLS, Library Manager, Parkview Health Resource Library, for her assistance with the library searches used for this case report.

The Affordable Care Act (aka Obamacare) may soon be out and the American Health Care Act (AHCA) may soon be in. Despite all of the rhetoric about making health care affordable by reducing insurance premiums, one thing has been conspicuously absent from the debate: how we are going to reduce the actual cost of health care. Yes, the AHCA may help reduce premiums, but what is most likely to result is not less expensive health care, but rather people paying less money on premiums and more out of their pockets for medicines and treatments. Especially troublesome is that older and sicker patients will be hit the hardest.

The American conundrum. Why do Americans pay twice what citizens of most other developed nations pay and get health care outcomes that are worse?^1,2 Two reasons are that those who provide health care charge more in this country for services and medications, and physicians do a lot more testing and treatment here than their counterparts abroad.

If we control the cost of providing care, insurance premiums will follow suit.

One expert estimated that up to $700 billion could be saved by eliminating testing and treatments that provide marginal or no value to patients.³ For example, knee arthroscopy for moderate knee osteoarthritis produces no better outcomes than medical management.⁴ And many medications are much more expensive in the United States than in other countries. It seems that pharmaceutical companies are permitted greater profits here than elsewhere in the world, and these profits are at the expense of sick people and taxpayers.

How do we bend the cost curve downward? This is a tough question with no single correct answer, but we can all help. Some health care organizations have already reduced costs significantly without sacrificing quality by using team-based primary care as their foundation. Two examples are Nuka Health and Iora Health.^5,6

As primary care physicians, we are in an ideal position to constrain unnecessary testing and treatments by establishing trusting relationships with patients, who will believe us when we tell them they don’t need an antibiotic for their chest cold or an MRI for their back pain.

If we control the cost of providing care, insurance premiums will follow suit.

The Affordable Care Act (aka Obamacare) may soon be out and the American Health Care Act (AHCA) may soon be in. Despite all of the rhetoric about making health care affordable by reducing insurance premiums, one thing has been conspicuously absent from the debate: how we are going to reduce the actual cost of health care. Yes, the AHCA may help reduce premiums, but what is most likely to result is not less expensive health care, but rather people paying less money on premiums and more out of their pockets for medicines and treatments. Especially troublesome is that older and sicker patients will be hit the hardest.

The American conundrum. Why do Americans pay twice what citizens of most other developed nations pay and get health care outcomes that are worse?^1,2 Two reasons are that those who provide health care charge more in this country for services and medications, and physicians do a lot more testing and treatment here than their counterparts abroad.

If we control the cost of providing care, insurance premiums will follow suit.

One expert estimated that up to $700 billion could be saved by eliminating testing and treatments that provide marginal or no value to patients.³ For example, knee arthroscopy for moderate knee osteoarthritis produces no better outcomes than medical management.⁴ And many medications are much more expensive in the United States than in other countries. It seems that pharmaceutical companies are permitted greater profits here than elsewhere in the world, and these profits are at the expense of sick people and taxpayers.

How do we bend the cost curve downward? This is a tough question with no single correct answer, but we can all help. Some health care organizations have already reduced costs significantly without sacrificing quality by using team-based primary care as their foundation. Two examples are Nuka Health and Iora Health.^5,6

As primary care physicians, we are in an ideal position to constrain unnecessary testing and treatments by establishing trusting relationships with patients, who will believe us when we tell them they don’t need an antibiotic for their chest cold or an MRI for their back pain.

If we control the cost of providing care, insurance premiums will follow suit.

The Affordable Care Act (aka Obamacare) may soon be out and the American Health Care Act (AHCA) may soon be in. Despite all of the rhetoric about making health care affordable by reducing insurance premiums, one thing has been conspicuously absent from the debate: how we are going to reduce the actual cost of health care. Yes, the AHCA may help reduce premiums, but what is most likely to result is not less expensive health care, but rather people paying less money on premiums and more out of their pockets for medicines and treatments. Especially troublesome is that older and sicker patients will be hit the hardest.

The American conundrum. Why do Americans pay twice what citizens of most other developed nations pay and get health care outcomes that are worse?^1,2 Two reasons are that those who provide health care charge more in this country for services and medications, and physicians do a lot more testing and treatment here than their counterparts abroad.

If we control the cost of providing care, insurance premiums will follow suit.

One expert estimated that up to $700 billion could be saved by eliminating testing and treatments that provide marginal or no value to patients.³ For example, knee arthroscopy for moderate knee osteoarthritis produces no better outcomes than medical management.⁴ And many medications are much more expensive in the United States than in other countries. It seems that pharmaceutical companies are permitted greater profits here than elsewhere in the world, and these profits are at the expense of sick people and taxpayers.

How do we bend the cost curve downward? This is a tough question with no single correct answer, but we can all help. Some health care organizations have already reduced costs significantly without sacrificing quality by using team-based primary care as their foundation. Two examples are Nuka Health and Iora Health.^5,6

As primary care physicians, we are in an ideal position to constrain unnecessary testing and treatments by establishing trusting relationships with patients, who will believe us when we tell them they don’t need an antibiotic for their chest cold or an MRI for their back pain.

If we control the cost of providing care, insurance premiums will follow suit.