Applied Evidence

When shoppers at the grocery store are leaning forward on their carts, many of them could be trying to relieve the pain of lumbar spinal stenosis. This way of finding temporary relief is one we replicated with a wheeled walker for prolonged periods in a retrospective case series to see what further benefits might be gained.

Symptoms are affected by body position and activity level. For patients with lumbar spinal stenosis, lower extremity symptoms can be debilitating and include loss of sensation, paresthesias, burning, pain, weakness, claudication, difficulty standing or walking, or nocturnal neuropathic pain in the feet, legs, or thighs. Axial loading¹ (as occurs during walking) and spinal extension² (as occurs in an erect position) both decrease the diameter of the central spinal canal and lateral recesses, and may cause nerve compression and lower extremity symptoms. In contrast, lumbosacral flexion—facilitated, for example, by leaning forward on a grocery cart³—opens the spine and may reduce nerve compression and related symptoms.

Exhaust all medical options before turning to surgery. The North American Spine Society (NASS) has issued clinical guidelines for spinal stenosis that make recommendations regarding the value of pharmacologic interventions, manipulative techniques, behavioral therapies, and other conservative measures (www. guideline.gov).⁴ For patients with severe or unremitting symptoms requiring specialized care by spine specialists, NASS further outlines 3 phases of gradually intensifying medical therapy before turning to surgery, which is associated with increased morbidity and costs.⁵

A previously untested medical approach. Most patients may return to productivity within 2 to 4 months after starting conservative treatment, but some will still require treatment recommended for greater levels of severity.⁶ For these latter patients, no randomized trials have evaluated the efficacy of medical management with a wheeled walker. This new intervention, if effective, could avoid or delay the expense and side effects of surgery.⁷ In addition, a wheeled walker may decrease pain from spinal stenosis.⁸

To explore whether positional therapy with a wheeled walker relieves lower extremity symptoms of lumbar spinal stenosis, we conducted a retrospective case series of 52 patients with spinal imaging confirmed lumbar spinal stenosis and walking limitations.⁹

Methods

These observations were based on retrospective chart reviews of all patients in a podiatric private practice (SMG) over 1 year to identify those with lower extremity symptoms of lumbar spinal stenosis who were evaluated with positional testing.

Identifying possible stenosis by positional history

Patients were suspected of having spinal stenosis contributing to, or entirely responsible for, lower extremity neuropathic or claudication symptoms based on a positive positional history, including any of the following patterns:

• walking limitation in which the patient needed to sit or lean forward to get relief
• significant improvement in ambulation when pushing a grocery cart, walker, or baby stroller, or when on a treadmill that induced lumbosacral flexion
• constant, frequent, or occasional lower extremity symptoms of a neuropathic nature with an unclear cause that was exacerbated by walking or standing
• nocturnal exacerbation of neuropathic symptoms affected by sleep position.

Symptoms linked to the cause radiologically. Spinal stenosis was confirmed by spinal imaging (magnetic resonance imaging or computed tomography scan) showing stenosis in areas corresponding to symptoms in the lower extremities. Patients without confirmatory spinal imaging were excluded from our study.

Peripheral neuropathy was diagnosed by changes in nerve conduction studies interpreted as being consistent with axonal or demyelinating peripheral neuropathy. Using these criteria, we assembled a case series of 52 patients with imaging-confirmed lumbar spinal stenosis and walking limitations. Of the 52 patients, 33 had received a previous diagnosis of spinal stenosis confirmed by spinal imaging, but only 10 considered that to be the cause of their lower extremity symptoms, with the remainder presenting with a primary diagnosis of peripheral neuropathy—with or without arterial claudication.

Using positional testing to confirm suitability of rollator walker

Patients with lower extremity symptoms of lumbar spinal stenosis underwent a therapeutic trial of “positional testing” involving full-time use of a 3- or 4-wheeled rollator walker (usually provided as a loan) set to induce lumbosacral flexion for 3 days. For patients no taller than 4’ 9” to 5’ 2”, a reduced-height walker (29” to 32”) was usually necessary; patients shorter than 4’ 9” usually needed a modified pediatric walker.

Patients returned for adjustment of the walker if it was uncomfortable or unhelpful. We recommended they also use a shower stool and kitchen stool to minimize erect posture. If they experienced nocturnal exacerbation of neuropathic symptoms, we encouraged them to try sleeping in a recliner. If patients with neuropathic symptoms wanted to continue sleeping in bed, we encouraged them to try sleeping with a pillow beneath their thighs (if sleeping on their back), or sleeping in a fetal position with a pillow between their thighs (if sleeping on their side).¹⁰

We usually reevaluated patients in 3 to 5 days, comparing current pain severity and walking capability with previous levels. Patients reporting improvement were encouraged to maintain this full-time positional testing for a total of 10 days. During the subsequent “positional therapy” phase, they gradually reduced their use of the walker, if possible, to an amount just needed to maintain improvement. The therapy phase lasted for 3 months, bringing the total time that patients used a walker to nearly 14 weeks.

Criteria for successful treatment

We gauged treatment success according to self-reported walking capabilities and subjective descriptions of uncomfortable symptoms, using criteria previously described.¹⁰

Walking distance. Patients reported uninterrupted walking distance before using the walker and after they had begun using the walker. We classified improvement in walking distance as excellent (over 400% increase), good (250%– 399%), moderate (100%–249%), or poor (≤99%). (The distance a patient can walk—before pain sets in—may vary from day to day. We therefore gauged improvement in this distance by contrasting consistent walking distances achieved and maintained with positional management to the shortest usual walking distance before the intervention.)

Pain reduction. To define a decrease in discomfort reported during the positional testing phase and maintained with positional therapy, we used a verbal analog pain scale (1–3 out of 10=mild pain; 4–7=moderate pain; 8–10=severe pain). We classified reduction in discomfort stemming from spinal stenosis as excellent (75%–100%), good (50%–74%), moderate (25%–49%), or poor (≤24%).

Results

Rapid and dramatic improvement for most patients

The 52 patients in our case series ranged in age from 67 to 90 years; 19 were men. Of the 52, improvement in ambulation was excellent for 30 (58%), good for 7 (13%), moderate for 8 (16%), and poor for 7 (13%) after 3 to 5 days.

Of 48 patients with neurogenic pain, grading with the verbal analog pain scale showed relief was excellent for 22 (46%), good for 11 (23%), moderate for 7 (14.5%), and poor for 8 (16.5%) after 3 to 5 days.

Of the 37 patients with excellent or good improvement in ambulation, 11 needed to keep using the walker extensively, 22 frequently, and 4 occasionally or not at all. Of the 6 patients who had undergone spinal stenosis surgery, improvement was excellent for 3, good for 1, and poor for 2.

A subgroup of 36 patients in our study had diabetes. Of these, 25 had concomitant peripheral neuropathy; 18 reported good to excellent improvement of ambulation or reduction of pain.

Conclusion

Patients deserve a trial of positional therapy with the wheeled walker

These descriptive data support the hypothesis that positional therapy with a wheeled walker set to induce lumbosacral flexion alleviates lower extremity symptoms of spinal stenosis. Limitations of this case series:

• the lack of any comparison group
• improvements in ambulation are based on subjective criteria
• findings can be generalized only to older patients potentially eligible for surgery,¹¹ those who have not benefited from surgery, or those who are undergoing medical therapies recommended by the North American Spine Society⁴
• patients seen in a podiatry office who present for lower extremity symptoms of spinal stenosis may differ from those seen in a family practitioner’s office who present with low back pain.

Nonetheless, this conservative strategy may be applicable to the evaluation and management of lower extremity symptoms of spinal stenosis regardless of presenting symptoms or source of medical care.

Walking limitations and lower extremity pain caused by spinal stenosis are physically and psychologically disabling. Relief can dramatically improve a person’s quality of life. Improved ambulation may also aid in the management of concurrent medical conditions, such as diabetes and cardiovascular disease.

Our hypothesis requires direct testing in randomized trials of sufficient size and duration. Such trials should include longer term and more objective clinical endpoints, such as quality of life measures, complications due to immobility and need for drugs, physical therapy, procedures such as epidural injections, or spinal surgery. Validation of this hypothesis would substantially reduce morbidity and costs, as well as increase the quality of life of patients with lower extremity symptoms of lumbar spinal stenosis. Until such studies are conducted, this conservative strategy may increase ambulation and decrease pain over the short term, with minimal risks and costs. It may also be helpful for those with contraindications (or aversions) to surgery or epidural injections or those who have found these approaches ineffective.

Correspondence
Charles H. Hennekens, MD, Sir Richard Doll Research Professor, College of Biomedical Science, Department of Clinical Science and Medical Education and Center of Excellence, Florida Atlantic University, Building 10–Administration, Division of Research, Room 244D, 777 Glades Road, Boca Raton, FL 33432; [email protected]

When shoppers at the grocery store are leaning forward on their carts, many of them could be trying to relieve the pain of lumbar spinal stenosis. This way of finding temporary relief is one we replicated with a wheeled walker for prolonged periods in a retrospective case series to see what further benefits might be gained.

Symptoms are affected by body position and activity level. For patients with lumbar spinal stenosis, lower extremity symptoms can be debilitating and include loss of sensation, paresthesias, burning, pain, weakness, claudication, difficulty standing or walking, or nocturnal neuropathic pain in the feet, legs, or thighs. Axial loading¹ (as occurs during walking) and spinal extension² (as occurs in an erect position) both decrease the diameter of the central spinal canal and lateral recesses, and may cause nerve compression and lower extremity symptoms. In contrast, lumbosacral flexion—facilitated, for example, by leaning forward on a grocery cart³—opens the spine and may reduce nerve compression and related symptoms.

Exhaust all medical options before turning to surgery. The North American Spine Society (NASS) has issued clinical guidelines for spinal stenosis that make recommendations regarding the value of pharmacologic interventions, manipulative techniques, behavioral therapies, and other conservative measures (www. guideline.gov).⁴ For patients with severe or unremitting symptoms requiring specialized care by spine specialists, NASS further outlines 3 phases of gradually intensifying medical therapy before turning to surgery, which is associated with increased morbidity and costs.⁵

A previously untested medical approach. Most patients may return to productivity within 2 to 4 months after starting conservative treatment, but some will still require treatment recommended for greater levels of severity.⁶ For these latter patients, no randomized trials have evaluated the efficacy of medical management with a wheeled walker. This new intervention, if effective, could avoid or delay the expense and side effects of surgery.⁷ In addition, a wheeled walker may decrease pain from spinal stenosis.⁸

To explore whether positional therapy with a wheeled walker relieves lower extremity symptoms of lumbar spinal stenosis, we conducted a retrospective case series of 52 patients with spinal imaging confirmed lumbar spinal stenosis and walking limitations.⁹

Methods

These observations were based on retrospective chart reviews of all patients in a podiatric private practice (SMG) over 1 year to identify those with lower extremity symptoms of lumbar spinal stenosis who were evaluated with positional testing.

Identifying possible stenosis by positional history

Patients were suspected of having spinal stenosis contributing to, or entirely responsible for, lower extremity neuropathic or claudication symptoms based on a positive positional history, including any of the following patterns:

• walking limitation in which the patient needed to sit or lean forward to get relief
• significant improvement in ambulation when pushing a grocery cart, walker, or baby stroller, or when on a treadmill that induced lumbosacral flexion
• constant, frequent, or occasional lower extremity symptoms of a neuropathic nature with an unclear cause that was exacerbated by walking or standing
• nocturnal exacerbation of neuropathic symptoms affected by sleep position.

Symptoms linked to the cause radiologically. Spinal stenosis was confirmed by spinal imaging (magnetic resonance imaging or computed tomography scan) showing stenosis in areas corresponding to symptoms in the lower extremities. Patients without confirmatory spinal imaging were excluded from our study.

Peripheral neuropathy was diagnosed by changes in nerve conduction studies interpreted as being consistent with axonal or demyelinating peripheral neuropathy. Using these criteria, we assembled a case series of 52 patients with imaging-confirmed lumbar spinal stenosis and walking limitations. Of the 52 patients, 33 had received a previous diagnosis of spinal stenosis confirmed by spinal imaging, but only 10 considered that to be the cause of their lower extremity symptoms, with the remainder presenting with a primary diagnosis of peripheral neuropathy—with or without arterial claudication.

Using positional testing to confirm suitability of rollator walker

Patients with lower extremity symptoms of lumbar spinal stenosis underwent a therapeutic trial of “positional testing” involving full-time use of a 3- or 4-wheeled rollator walker (usually provided as a loan) set to induce lumbosacral flexion for 3 days. For patients no taller than 4’ 9” to 5’ 2”, a reduced-height walker (29” to 32”) was usually necessary; patients shorter than 4’ 9” usually needed a modified pediatric walker.

Patients returned for adjustment of the walker if it was uncomfortable or unhelpful. We recommended they also use a shower stool and kitchen stool to minimize erect posture. If they experienced nocturnal exacerbation of neuropathic symptoms, we encouraged them to try sleeping in a recliner. If patients with neuropathic symptoms wanted to continue sleeping in bed, we encouraged them to try sleeping with a pillow beneath their thighs (if sleeping on their back), or sleeping in a fetal position with a pillow between their thighs (if sleeping on their side).¹⁰

We usually reevaluated patients in 3 to 5 days, comparing current pain severity and walking capability with previous levels. Patients reporting improvement were encouraged to maintain this full-time positional testing for a total of 10 days. During the subsequent “positional therapy” phase, they gradually reduced their use of the walker, if possible, to an amount just needed to maintain improvement. The therapy phase lasted for 3 months, bringing the total time that patients used a walker to nearly 14 weeks.

Criteria for successful treatment

We gauged treatment success according to self-reported walking capabilities and subjective descriptions of uncomfortable symptoms, using criteria previously described.¹⁰

Walking distance. Patients reported uninterrupted walking distance before using the walker and after they had begun using the walker. We classified improvement in walking distance as excellent (over 400% increase), good (250%– 399%), moderate (100%–249%), or poor (≤99%). (The distance a patient can walk—before pain sets in—may vary from day to day. We therefore gauged improvement in this distance by contrasting consistent walking distances achieved and maintained with positional management to the shortest usual walking distance before the intervention.)

Pain reduction. To define a decrease in discomfort reported during the positional testing phase and maintained with positional therapy, we used a verbal analog pain scale (1–3 out of 10=mild pain; 4–7=moderate pain; 8–10=severe pain). We classified reduction in discomfort stemming from spinal stenosis as excellent (75%–100%), good (50%–74%), moderate (25%–49%), or poor (≤24%).

Results

Rapid and dramatic improvement for most patients

The 52 patients in our case series ranged in age from 67 to 90 years; 19 were men. Of the 52, improvement in ambulation was excellent for 30 (58%), good for 7 (13%), moderate for 8 (16%), and poor for 7 (13%) after 3 to 5 days.

Of 48 patients with neurogenic pain, grading with the verbal analog pain scale showed relief was excellent for 22 (46%), good for 11 (23%), moderate for 7 (14.5%), and poor for 8 (16.5%) after 3 to 5 days.

Of the 37 patients with excellent or good improvement in ambulation, 11 needed to keep using the walker extensively, 22 frequently, and 4 occasionally or not at all. Of the 6 patients who had undergone spinal stenosis surgery, improvement was excellent for 3, good for 1, and poor for 2.

A subgroup of 36 patients in our study had diabetes. Of these, 25 had concomitant peripheral neuropathy; 18 reported good to excellent improvement of ambulation or reduction of pain.

Conclusion

Patients deserve a trial of positional therapy with the wheeled walker

These descriptive data support the hypothesis that positional therapy with a wheeled walker set to induce lumbosacral flexion alleviates lower extremity symptoms of spinal stenosis. Limitations of this case series:

• the lack of any comparison group
• improvements in ambulation are based on subjective criteria
• findings can be generalized only to older patients potentially eligible for surgery,¹¹ those who have not benefited from surgery, or those who are undergoing medical therapies recommended by the North American Spine Society⁴
• patients seen in a podiatry office who present for lower extremity symptoms of spinal stenosis may differ from those seen in a family practitioner’s office who present with low back pain.

Nonetheless, this conservative strategy may be applicable to the evaluation and management of lower extremity symptoms of spinal stenosis regardless of presenting symptoms or source of medical care.

Walking limitations and lower extremity pain caused by spinal stenosis are physically and psychologically disabling. Relief can dramatically improve a person’s quality of life. Improved ambulation may also aid in the management of concurrent medical conditions, such as diabetes and cardiovascular disease.

Our hypothesis requires direct testing in randomized trials of sufficient size and duration. Such trials should include longer term and more objective clinical endpoints, such as quality of life measures, complications due to immobility and need for drugs, physical therapy, procedures such as epidural injections, or spinal surgery. Validation of this hypothesis would substantially reduce morbidity and costs, as well as increase the quality of life of patients with lower extremity symptoms of lumbar spinal stenosis. Until such studies are conducted, this conservative strategy may increase ambulation and decrease pain over the short term, with minimal risks and costs. It may also be helpful for those with contraindications (or aversions) to surgery or epidural injections or those who have found these approaches ineffective.

Correspondence
Charles H. Hennekens, MD, Sir Richard Doll Research Professor, College of Biomedical Science, Department of Clinical Science and Medical Education and Center of Excellence, Florida Atlantic University, Building 10–Administration, Division of Research, Room 244D, 777 Glades Road, Boca Raton, FL 33432; [email protected]

When shoppers at the grocery store are leaning forward on their carts, many of them could be trying to relieve the pain of lumbar spinal stenosis. This way of finding temporary relief is one we replicated with a wheeled walker for prolonged periods in a retrospective case series to see what further benefits might be gained.

Symptoms are affected by body position and activity level. For patients with lumbar spinal stenosis, lower extremity symptoms can be debilitating and include loss of sensation, paresthesias, burning, pain, weakness, claudication, difficulty standing or walking, or nocturnal neuropathic pain in the feet, legs, or thighs. Axial loading¹ (as occurs during walking) and spinal extension² (as occurs in an erect position) both decrease the diameter of the central spinal canal and lateral recesses, and may cause nerve compression and lower extremity symptoms. In contrast, lumbosacral flexion—facilitated, for example, by leaning forward on a grocery cart³—opens the spine and may reduce nerve compression and related symptoms.

Exhaust all medical options before turning to surgery. The North American Spine Society (NASS) has issued clinical guidelines for spinal stenosis that make recommendations regarding the value of pharmacologic interventions, manipulative techniques, behavioral therapies, and other conservative measures (www. guideline.gov).⁴ For patients with severe or unremitting symptoms requiring specialized care by spine specialists, NASS further outlines 3 phases of gradually intensifying medical therapy before turning to surgery, which is associated with increased morbidity and costs.⁵

A previously untested medical approach. Most patients may return to productivity within 2 to 4 months after starting conservative treatment, but some will still require treatment recommended for greater levels of severity.⁶ For these latter patients, no randomized trials have evaluated the efficacy of medical management with a wheeled walker. This new intervention, if effective, could avoid or delay the expense and side effects of surgery.⁷ In addition, a wheeled walker may decrease pain from spinal stenosis.⁸

To explore whether positional therapy with a wheeled walker relieves lower extremity symptoms of lumbar spinal stenosis, we conducted a retrospective case series of 52 patients with spinal imaging confirmed lumbar spinal stenosis and walking limitations.⁹

Methods

These observations were based on retrospective chart reviews of all patients in a podiatric private practice (SMG) over 1 year to identify those with lower extremity symptoms of lumbar spinal stenosis who were evaluated with positional testing.

Identifying possible stenosis by positional history

Patients were suspected of having spinal stenosis contributing to, or entirely responsible for, lower extremity neuropathic or claudication symptoms based on a positive positional history, including any of the following patterns:

• walking limitation in which the patient needed to sit or lean forward to get relief
• significant improvement in ambulation when pushing a grocery cart, walker, or baby stroller, or when on a treadmill that induced lumbosacral flexion
• constant, frequent, or occasional lower extremity symptoms of a neuropathic nature with an unclear cause that was exacerbated by walking or standing
• nocturnal exacerbation of neuropathic symptoms affected by sleep position.

Symptoms linked to the cause radiologically. Spinal stenosis was confirmed by spinal imaging (magnetic resonance imaging or computed tomography scan) showing stenosis in areas corresponding to symptoms in the lower extremities. Patients without confirmatory spinal imaging were excluded from our study.

Peripheral neuropathy was diagnosed by changes in nerve conduction studies interpreted as being consistent with axonal or demyelinating peripheral neuropathy. Using these criteria, we assembled a case series of 52 patients with imaging-confirmed lumbar spinal stenosis and walking limitations. Of the 52 patients, 33 had received a previous diagnosis of spinal stenosis confirmed by spinal imaging, but only 10 considered that to be the cause of their lower extremity symptoms, with the remainder presenting with a primary diagnosis of peripheral neuropathy—with or without arterial claudication.

Using positional testing to confirm suitability of rollator walker

Patients with lower extremity symptoms of lumbar spinal stenosis underwent a therapeutic trial of “positional testing” involving full-time use of a 3- or 4-wheeled rollator walker (usually provided as a loan) set to induce lumbosacral flexion for 3 days. For patients no taller than 4’ 9” to 5’ 2”, a reduced-height walker (29” to 32”) was usually necessary; patients shorter than 4’ 9” usually needed a modified pediatric walker.

Patients returned for adjustment of the walker if it was uncomfortable or unhelpful. We recommended they also use a shower stool and kitchen stool to minimize erect posture. If they experienced nocturnal exacerbation of neuropathic symptoms, we encouraged them to try sleeping in a recliner. If patients with neuropathic symptoms wanted to continue sleeping in bed, we encouraged them to try sleeping with a pillow beneath their thighs (if sleeping on their back), or sleeping in a fetal position with a pillow between their thighs (if sleeping on their side).¹⁰

We usually reevaluated patients in 3 to 5 days, comparing current pain severity and walking capability with previous levels. Patients reporting improvement were encouraged to maintain this full-time positional testing for a total of 10 days. During the subsequent “positional therapy” phase, they gradually reduced their use of the walker, if possible, to an amount just needed to maintain improvement. The therapy phase lasted for 3 months, bringing the total time that patients used a walker to nearly 14 weeks.

Criteria for successful treatment

We gauged treatment success according to self-reported walking capabilities and subjective descriptions of uncomfortable symptoms, using criteria previously described.¹⁰

Walking distance. Patients reported uninterrupted walking distance before using the walker and after they had begun using the walker. We classified improvement in walking distance as excellent (over 400% increase), good (250%– 399%), moderate (100%–249%), or poor (≤99%). (The distance a patient can walk—before pain sets in—may vary from day to day. We therefore gauged improvement in this distance by contrasting consistent walking distances achieved and maintained with positional management to the shortest usual walking distance before the intervention.)

Pain reduction. To define a decrease in discomfort reported during the positional testing phase and maintained with positional therapy, we used a verbal analog pain scale (1–3 out of 10=mild pain; 4–7=moderate pain; 8–10=severe pain). We classified reduction in discomfort stemming from spinal stenosis as excellent (75%–100%), good (50%–74%), moderate (25%–49%), or poor (≤24%).

Results

Rapid and dramatic improvement for most patients

The 52 patients in our case series ranged in age from 67 to 90 years; 19 were men. Of the 52, improvement in ambulation was excellent for 30 (58%), good for 7 (13%), moderate for 8 (16%), and poor for 7 (13%) after 3 to 5 days.

Of 48 patients with neurogenic pain, grading with the verbal analog pain scale showed relief was excellent for 22 (46%), good for 11 (23%), moderate for 7 (14.5%), and poor for 8 (16.5%) after 3 to 5 days.

Of the 37 patients with excellent or good improvement in ambulation, 11 needed to keep using the walker extensively, 22 frequently, and 4 occasionally or not at all. Of the 6 patients who had undergone spinal stenosis surgery, improvement was excellent for 3, good for 1, and poor for 2.

A subgroup of 36 patients in our study had diabetes. Of these, 25 had concomitant peripheral neuropathy; 18 reported good to excellent improvement of ambulation or reduction of pain.

Conclusion

Patients deserve a trial of positional therapy with the wheeled walker

These descriptive data support the hypothesis that positional therapy with a wheeled walker set to induce lumbosacral flexion alleviates lower extremity symptoms of spinal stenosis. Limitations of this case series:

• the lack of any comparison group
• improvements in ambulation are based on subjective criteria
• findings can be generalized only to older patients potentially eligible for surgery,¹¹ those who have not benefited from surgery, or those who are undergoing medical therapies recommended by the North American Spine Society⁴
• patients seen in a podiatry office who present for lower extremity symptoms of spinal stenosis may differ from those seen in a family practitioner’s office who present with low back pain.

Nonetheless, this conservative strategy may be applicable to the evaluation and management of lower extremity symptoms of spinal stenosis regardless of presenting symptoms or source of medical care.

Walking limitations and lower extremity pain caused by spinal stenosis are physically and psychologically disabling. Relief can dramatically improve a person’s quality of life. Improved ambulation may also aid in the management of concurrent medical conditions, such as diabetes and cardiovascular disease.

Our hypothesis requires direct testing in randomized trials of sufficient size and duration. Such trials should include longer term and more objective clinical endpoints, such as quality of life measures, complications due to immobility and need for drugs, physical therapy, procedures such as epidural injections, or spinal surgery. Validation of this hypothesis would substantially reduce morbidity and costs, as well as increase the quality of life of patients with lower extremity symptoms of lumbar spinal stenosis. Until such studies are conducted, this conservative strategy may increase ambulation and decrease pain over the short term, with minimal risks and costs. It may also be helpful for those with contraindications (or aversions) to surgery or epidural injections or those who have found these approaches ineffective.

Correspondence
Charles H. Hennekens, MD, Sir Richard Doll Research Professor, College of Biomedical Science, Department of Clinical Science and Medical Education and Center of Excellence, Florida Atlantic University, Building 10–Administration, Division of Research, Room 244D, 777 Glades Road, Boca Raton, FL 33432; [email protected]

Through with Chew Week” and the “Great American Spitout.” Do they ring a bell?

If you answered no, you’re not alone.

“Through with Chew Week” was established by the American Academy of Otolaryngology—Head and Neck Surgery (AAO-HNS) in 1989, but it hasn’t quite garnered the same kind of recognition as the American Cancer Society’s Great American Smokeout.

When it comes to tobacco use—and more importantly, cessation—smokeless tobacco just doesn’t generate the kind of attention that cigarette smoking does. In fact, smokeless tobacco’s low profile extends beyond talk of “smokeouts” and “spitouts” to research on effective ways to quit.

We found this out first-hand when we conducted a literature search of Medline, PubMed, and a number of other databases to learn which cessation methods have proven efficacy. What we learned is that not only is research on the subject of smokeless tobacco cessation limited, but there is no recommended medication therapy to help these patients quit. Specifically:

• Nicotine-replacement therapies have failed to demonstrate a clear benefit in smokeless tobacco cessation, but under-dosing may be a factor for some patients.
• Bupropion’s (Zyban) usefulness in smokeless tobacco cessation is unclear. Data, thus far, have been inconclusive.
• Varenicline’s (Chantix) usefulness in smokeless tobacco cessation is unknown. There are no published case reports or clinical trials on the subject.

Millions of “chew” users are at risk

Tobacco use is the leading preventable cause of premature death in the United States, with more than 440,000 Americans dying of tobacco-related disease each year.¹ Cigarette smoking is by far the most common form of tobacco used; however, smokeless tobacco, also known as chew, spit tobacco, or snuff, is used by 8.2 million Americans.² More men than women use tobacco products overall, and smokeless tobacco, in particular.²

Health risks include MI. Specific health risks associated with smokeless tobacco include cancer of the oral cavity and pharynx, oral and periodontal disease, tooth decay, and pregnancy-related problems.¹ (See “Smokeless tobacco was to blame”)

In addition, an international, case-control study evaluating the risk of myocardial infarction associated with various forms of tobacco use found an increased risk of myocardial infarction associated with smokeless tobacco use compared to non-tobacco users (odds ratio [OR]=2.23; 95% confidence interval [CI], 1.41-3.52).³

Notably, smokeless tobacco users in the study who also smoked cigarettes had the highest risk of all tobacco users when compared to non-users (OR=4.09; 95% CI, 2.98-5.61). These findings demonstrate that nicotine dependence is detrimental to health—regardless of the form of tobacco used. Even more worrisome is the notion that risk may actually be increased when multiple forms of tobacco are used by the same patient.

Patients want medication to help them quit

Current guidelines for tobacco cessation recommend that patients using smokeless tobacco should be identified, urged to quit, and treated with counseling interventions.⁴ Despite this recommendation, many patients are interested in using a medication to aid them in their quit effort, and many physicians would like to prescribe medication to help patients succeed.

To that end, it seemed logical to us that the same treatments used for smoking cessation would also be effective for smokeless tobacco cessation, given that the underlying problem—despite the form of tobacco used—is nicotine dependence. So we did a literature review to determine the optimal treatment for smokeless tobacco cessation. Our search included: Medline (1950-2007), PubMed (1966-2006), International Pharmaceutical Abstracts (1970-2006), Science Direct, CINAHL, PsycArticles, and Dissertation Abstracts. We used the following search terms: smokeless tobacco, spit tobacco, chew tobacco, cessation, bupropion, nicotine, and nicotine replacement. (Searches in Medline for nicotine replacement therapy in smokeless tobacco cessation were limited to clinical trials.) What we found were a limited number of studies, which we’ve summarized here.

Nicotine patch is useful, but to what degree?

We reviewed four studies involving the use of a nicotine patch for smokeless tobacco cessation (TABLE 1). In chronological order:

Study #1: 15-mg patch. The first study to evaluate the nicotine patch was a randomized, double-blind, placebo controlled trial published in 1999. A 15-mg nicotine patch was used by approximately 420 patients.⁵ Patients included in the trial were at least 18 years of age, nonsmokers, and used at least 1 can of smokeless tobacco per week. The main outcome of this trial was cessation at 6 months.

A significant difference was found in abstinence rates between patients treated with active therapy compared to those treated with placebo early in the study; however, by study end, there were no significant differences between groups. The medication was well tolerated, though patients receiving active therapy did report an increase in adverse effects related to patch use, such as rash and itching.

TABLE 1
Conflicting findings on the nicotine patch for smokeless tobacco cessation

Study #2: Nicotine plus mint snuff. The second trial to evaluate nicotine patches randomized approximately 400 patients to 1 of 4 groups: active nicotine patch plus mint snuff (non-nicotine mint-leaf product), active nicotine patch and no mint snuff, placebo plus mint snuff, or placebo patch and no mint snuff.⁶ To be enrolled in the study, patients had to use 1 can of smokeless tobacco per week and express a desire to quit. Patients given the active nicotine patch were begun on 22 mg and tapered to 7 mg by the end of 10 weeks. At 10 weeks, continuous abstinence and abstinence since the last clinic visit were evaluated. (Researchers tracked the patients for a total of 62 weeks.)

Patients who received active nicotine patches had significantly higher cessation rates compared to placebo at 10 (P=0.002) and 15 (P=0.016) weeks, but not at any other time during the study. No information regarding adverse effects was reported.

Study #3: Patch in adolescents. In a third, randomized, placebo-controlled trial, the effect of nicotine replacement in adolescents was evaluated. Patients were randomized to an active patch, placebo patch, or usual care (1 counseling session with a follow-up phone call).⁷

Patients who received an active patch also received 6 weeks of behavior counseling sessions. Smokeless tobacco users were further stratified according to light/moderate or heavy use according to saliva cotinine levels: light/moderate users were started on 14 mg and heavy users on 21 mg of nicotine. All patients were tapered to 7 mg over a 6-week period. Approximately 300 males between the ages of 14 and 19 who used smokeless tobacco at least 5 days a week were enrolled in the study.

Cessation rates at 1 year were not statistically significant between the placebo and active patch (P=0.22). The nicotine patch was well tolerated, with the exception of 5 patients who experienced skin irritation or headache; however, 3 patients were removed from patch therapy due to skin hyper-reaction or headache.

Study #4: Dosing. A fourth study, by Ebbert et al,⁸ addressed potential under-dosing of nicotine patches. This study was a randomized, double-blind, placebo controlled trial that evaluated 21, 42, or 63 mg/day of nicotine delivered by patch or placebo in 42 patients. (The 21 mg/day dose is the highest recommended starting dose for smokers.) The patients had to be 18 years of age or older, in good health, and use 3 or more cans/pouches of smokeless tobacco per day.

The study took place in 3 phases: outpatient preadmission, inpatient research phase, and an outpatient follow-up phase. The inpatient phase measured nicotine and cotinine concentrations during active smokeless tobacco use and while receiving treatment or placebo. Patients treated with the 42 mg/day patch had levels closer to those measured during active smokeless tobacco use, while patients treated with 63 mg/day tended to be “over-replaced” and experienced more severe adverse effects, such as nausea, vomiting, and headache. Overall, nicotine replacement therapy was well tolerated throughout the trial.

Nicotine gum: No lasting benefit

The earliest trial to evaluate nicotine gum for smokeless tobacco cessation was conducted by Boyle⁹ and was only available in abstract form (TABLE 2). This randomized, double-blind, placebo-controlled trial evaluated 2 mg of nicotine gum vs placebo in 100 patients. The main outcome was quit rates at the end of 6 weeks. The quit rate was similar for each group, and did not reach statistical significance (no P value provided). No information regarding adverse effects was reported.

A second trial¹⁰ to evaluate nicotine gum was also a randomized placebo-controlled trial that enrolled just over 200 adult patients that used ≥1 tin of smokeless tobacco per week (TABLE 2). Patients were randomized to 2 mg of nicotine gum or placebo and group therapy sessions or minimal behavioral intervention contact for a 2-month treatment period.

This trial did show a significant difference at week 4 (P<0.01) in point prevalence abstinence—that is, the number of people reporting to be abstinent at the 4-week mark, regardless of whether their abstinence was continuous or not. Significance, however, was lost by week 8. Cessation rates were also significant at 1- and 6-month follow-up exams (P<0.05), but were not maintained at the 12-month follow-up.

TABLE 2
Nicotine gum for smokeless tobacco cessation: Benefit doesn’t last

Continuous abstinence rates were similar for all groups except the 2 mg nicotine and minimal intervention group. Patients in this group had significantly lower abstinence rates from all other groups (P<0.003). No information regarding adverse effects was reported.

Case report suggests bupropion has potential

Bupropion is a non-nicotine smoking cessation therapy that inhibits the uptake of norepinephrine and dopamine. It is unclear how bupropion aids in smoking cessation, though its ability to do so appears to be related to its dopaminergic properties.¹¹

Given its utility in treatment for smoking cessation, it seems plausible that the drug may serve as an effective treatment for smokeless tobacco, as well. However, the literature regarding the use of bupropion for smokeless tobacco cessation is even more limited than that for nicotine replacement therapy.

Berigan and Deagle first described the use of bupropion for smokeless tobacco cessation in 1999 (TABLE 3).¹² Their case report focused on a 31-year-old man who reported using 1 can of smokeless tobacco per day for 11 years. The patient reported having tried nicotine patches and attempting to quit “cold turkey,” with limited success.

The patient was started on a trial of bupropion along with approximately 1 month of behavioral counseling. After 1 week of medication, the patient reported a reduction in cravings. By 5 weeks, the patient reported no use of smokeless tobacco. A total of 10 weeks of medication was given to the patient and he experienced no withdrawal effects after cessation. At 8 months, the patient was still tobacco free. The patient also reported few adverse effects from bupropion.

2 bupropion clinical trials are less encouraging

We found 2 clinical trials evaluating sustained-release bupropion 300 mg/day (TABLE 3). The first was a randomized, placebo-controlled trial in which patients received 7 weeks of active or placebo medication, and were then followed (with minimal counseling) for an additional 5 weeks.¹³ A total of 70 men, 18 years of age and older, were enrolled in the study; all had expressed a desire to quit and used at least one-half can of smokeless tobacco a day in the past year.

The primary endpoint was smokeless tobacco abstinence during weeks 4 through 7 of the trial. At the end of week 7 (end of treatment), significantly more patients in the treatment group were free of smokeless tobacco, compared to the placebo group (OR=2.73; 95% CI, 1.07-7.72; P=0.04). However, significance was lost by week 12 (OR=1.93; 95% CI, 0.71-5.47; P=0.2). Bupropion was well tolerated throughout this trial and no serious adverse effects were reported.

TABLE 3
Usefulness of bupropion for smokeless tobacco cessation is unclear

The second trial¹⁴ evaluating the efficacy of bupropion for smokeless tobacco cessation was also a randomized, placebo-controlled trial. Enrollees were randomly assigned to bupropion SR 300 mg/day or matching placebo for 12 weeks. In addition, minimal behavioral intervention was provided until week 24. Researchers enrolled 68 patients; all but one were men. Participants in this study were 18 years of age or older who regularly used smokeless tobacco. The efficacy of bupropion SR for nicotine dependence was the primary endpoint evaluated.

At the completion of the treatment phase, more patients in the bupropion group reported cessation (44%) compared to placebo (26%). The difference between the 2 groups was nonsignificant and remained so until the end of the study. By study end, each group had a reported cessation rate of 29%.

One patient experienced a diffuse skin rash that resulted in discontinuation of the study medication; otherwise buproprion was well tolerated.

Is varenicline useful?

A product that shows promise for smoking cessation is varenicline, which was approved by the FDA in May 2006.¹⁵ Varenicline acts as an agonist at the α₄β₂ neuronal nicotinic acetylcholine receptors. Its action at this receptor subtype blocks the ability of nicotine to bind to the receptor and is therefore thought to blunt the feeling of reward experienced by smokers.¹⁶ In addition, the medication may possess some nicotine-like action at the nicotinic receptor that may decrease the amount of withdrawal symptoms experienced by patients.¹⁵

In theory, this mechanism of action may help smokeless tobacco users to succeed in their quit attempts. Unfortunately, though, there have been no published case reports or clinical trials to date regarding the use of varenicline in the treatment of smokeless tobacco cessation.

Helping patients despite the information gap

Our knowledge of the effectiveness of various tools in smokeless tobacco cessation is hampered on a number of fronts.

Nicotine replacement therapy. The conflicting evidence regarding nicotine replacement therapy may be the result of a number of factors. First, although many of the trials used a randomized, placebo-controlled design, there were a number of variations in the patient populations studied, inconsistencies in the amount and type of counseling used, and differences in the amount of smokeless tobacco used by the patients.

Smokeless tobacco was to blame

These 2 cases illustrate the damage that chew can do

Oral leukoplakia

Gum recession

This 24-year-old patient sought treatment for an asymptomatic oral lesion that he noticed while brushing his teeth. The patient, who did not smoke tobacco and drank alcohol socially on weekends, told us that he had started chewing tobacco while playing baseball in high school 8 years earlier. He said that over the past 3 years, he had increased the habit.

On examination, we noted a well-defined, macular, white lesion on his left buccal mucosa. The lesion was not painful with palpation and remained unchanged when scraped with a tongue depressor.

Our patient had an oral leukoplakia, which can result from the chronic use of chewing tobacco. Cessation of the habit typically results in the resolution of the lesion in approximately 4 weeks. That was the case with our patient: He quit the habit and in 4 weeks, 80% of the lesion resolved. He was closely monitored, and at 3 months the lesion was undetectable.

If, however, a patient discontinues the habit and there is no change in the lesion after 4 weeks, biopsy is indicated. The most serious consequence of a malignant transformation of leukoplakia is oral squamous cell carcinoma.

A 30-year-old man was referred to us for evaluation of gum recession that had worsened over the past year. The patient complained that his teeth were sensitive to hot and cold drinks, but had no other symptoms. He had a 5-year history of smokeless tobacco use and said he usually placed the tobacco along his inner vestibule. He said that he did not smoke tobacco, nor did he drink alcohol.

On examination, we noted that the patient had localized recession along the cervical area of his lower teeth. With manipulation, there was bleeding from the gingival surface. His teeth were otherwise in good shape and there were no other lesions within the oral mucosa.

Gingival recession is a common consequence of smokeless tobacco use. Treatment consists of a gingival graft, in which palatal connective tissue is removed and used to reestablish gingival attachment to the tooth. (Tissue harvesting surgery from the palate can be quite painful.) Left untreated, teeth can become loose and fall out.

We advised our patient to follow up for gingival grafting, but he did not return for his follow-up visit.

Denise Rizzolo, PA-C, PhD is a physician assistant at Care Station in Springfield, NJ and Thomas A. Chiodo, DDS, is an oral and maxillofacial surgeon in private practice in Somerville, NJ. Dr. Chiodo also teaches at UMDNJ Dental School in Newark, NJ; [email protected]

Additionally, recent evidence suggests it may be important to consider dosing nicotine replacement according to number of cans of smokeless tobacco the patient uses per week. Heavy smokeless tobacco users may require higher initial doses than routinely used for smoking cessation therapy (eg, 42 mg/day if >3 cans of smokeless tobacco/day used).⁸

Further clinical research is needed to validate this recommendation, as well as to give specific dosing recommendations.

Nicotine gum. Two issues come to mind when considering the research on nicotine gum. First, the studies had relatively small sample sizes and it’s possible that the studies were not properly designed to detect a difference between groups.^6,7 Second, the concept of dosing nicotine gum based on the number of cans of smokeless tobacco used per day has not been explored.

Bupropion. Studies involving bupropion and smokeless tobacco cessation share several of the limitations we’ve just discussed. Differing results reported in the literature regarding bupropion’s effectiveness makes its potential benefit unclear. Use should be determined on a case-by-case basis with the understanding that it may—or may not—be useful in decreasing cravings or increasing abstinence rates.

Varenicline. There is currently no literature available to help us evaluate the usefulness of varenicline in smokeless tobacco cessation. The mechanism of action of varenicline is such that use in smokeless tobacco cessation is plausible. Again, consideration of patients on a case-by-case basis is warranted.

One size does not fit all

Although nicotine dependence is the underlying problem for patients who utilize smokeless tobacco, current literature does not support a “one-size-fits-all” approach to treatment of various forms of tobacco abuse. Further clinical investigations are needed to determine the true utility of bupropion and varenicline, as well as the appropriate dosing of nicotine replacement therapy when prescribed for smokeless tobacco cessation.

Through with Chew Week” and the “Great American Spitout.” Do they ring a bell?

If you answered no, you’re not alone.

“Through with Chew Week” was established by the American Academy of Otolaryngology—Head and Neck Surgery (AAO-HNS) in 1989, but it hasn’t quite garnered the same kind of recognition as the American Cancer Society’s Great American Smokeout.

When it comes to tobacco use—and more importantly, cessation—smokeless tobacco just doesn’t generate the kind of attention that cigarette smoking does. In fact, smokeless tobacco’s low profile extends beyond talk of “smokeouts” and “spitouts” to research on effective ways to quit.

We found this out first-hand when we conducted a literature search of Medline, PubMed, and a number of other databases to learn which cessation methods have proven efficacy. What we learned is that not only is research on the subject of smokeless tobacco cessation limited, but there is no recommended medication therapy to help these patients quit. Specifically:

• Nicotine-replacement therapies have failed to demonstrate a clear benefit in smokeless tobacco cessation, but under-dosing may be a factor for some patients.
• Bupropion’s (Zyban) usefulness in smokeless tobacco cessation is unclear. Data, thus far, have been inconclusive.
• Varenicline’s (Chantix) usefulness in smokeless tobacco cessation is unknown. There are no published case reports or clinical trials on the subject.

Millions of “chew” users are at risk

Tobacco use is the leading preventable cause of premature death in the United States, with more than 440,000 Americans dying of tobacco-related disease each year.¹ Cigarette smoking is by far the most common form of tobacco used; however, smokeless tobacco, also known as chew, spit tobacco, or snuff, is used by 8.2 million Americans.² More men than women use tobacco products overall, and smokeless tobacco, in particular.²

Health risks include MI. Specific health risks associated with smokeless tobacco include cancer of the oral cavity and pharynx, oral and periodontal disease, tooth decay, and pregnancy-related problems.¹ (See “Smokeless tobacco was to blame”)

In addition, an international, case-control study evaluating the risk of myocardial infarction associated with various forms of tobacco use found an increased risk of myocardial infarction associated with smokeless tobacco use compared to non-tobacco users (odds ratio [OR]=2.23; 95% confidence interval [CI], 1.41-3.52).³

Notably, smokeless tobacco users in the study who also smoked cigarettes had the highest risk of all tobacco users when compared to non-users (OR=4.09; 95% CI, 2.98-5.61). These findings demonstrate that nicotine dependence is detrimental to health—regardless of the form of tobacco used. Even more worrisome is the notion that risk may actually be increased when multiple forms of tobacco are used by the same patient.

Patients want medication to help them quit

Current guidelines for tobacco cessation recommend that patients using smokeless tobacco should be identified, urged to quit, and treated with counseling interventions.⁴ Despite this recommendation, many patients are interested in using a medication to aid them in their quit effort, and many physicians would like to prescribe medication to help patients succeed.

To that end, it seemed logical to us that the same treatments used for smoking cessation would also be effective for smokeless tobacco cessation, given that the underlying problem—despite the form of tobacco used—is nicotine dependence. So we did a literature review to determine the optimal treatment for smokeless tobacco cessation. Our search included: Medline (1950-2007), PubMed (1966-2006), International Pharmaceutical Abstracts (1970-2006), Science Direct, CINAHL, PsycArticles, and Dissertation Abstracts. We used the following search terms: smokeless tobacco, spit tobacco, chew tobacco, cessation, bupropion, nicotine, and nicotine replacement. (Searches in Medline for nicotine replacement therapy in smokeless tobacco cessation were limited to clinical trials.) What we found were a limited number of studies, which we’ve summarized here.

Nicotine patch is useful, but to what degree?

We reviewed four studies involving the use of a nicotine patch for smokeless tobacco cessation (TABLE 1). In chronological order:

Study #1: 15-mg patch. The first study to evaluate the nicotine patch was a randomized, double-blind, placebo controlled trial published in 1999. A 15-mg nicotine patch was used by approximately 420 patients.⁵ Patients included in the trial were at least 18 years of age, nonsmokers, and used at least 1 can of smokeless tobacco per week. The main outcome of this trial was cessation at 6 months.

A significant difference was found in abstinence rates between patients treated with active therapy compared to those treated with placebo early in the study; however, by study end, there were no significant differences between groups. The medication was well tolerated, though patients receiving active therapy did report an increase in adverse effects related to patch use, such as rash and itching.

TABLE 1
Conflicting findings on the nicotine patch for smokeless tobacco cessation

Study #2: Nicotine plus mint snuff. The second trial to evaluate nicotine patches randomized approximately 400 patients to 1 of 4 groups: active nicotine patch plus mint snuff (non-nicotine mint-leaf product), active nicotine patch and no mint snuff, placebo plus mint snuff, or placebo patch and no mint snuff.⁶ To be enrolled in the study, patients had to use 1 can of smokeless tobacco per week and express a desire to quit. Patients given the active nicotine patch were begun on 22 mg and tapered to 7 mg by the end of 10 weeks. At 10 weeks, continuous abstinence and abstinence since the last clinic visit were evaluated. (Researchers tracked the patients for a total of 62 weeks.)

Patients who received active nicotine patches had significantly higher cessation rates compared to placebo at 10 (P=0.002) and 15 (P=0.016) weeks, but not at any other time during the study. No information regarding adverse effects was reported.

Study #3: Patch in adolescents. In a third, randomized, placebo-controlled trial, the effect of nicotine replacement in adolescents was evaluated. Patients were randomized to an active patch, placebo patch, or usual care (1 counseling session with a follow-up phone call).⁷

Patients who received an active patch also received 6 weeks of behavior counseling sessions. Smokeless tobacco users were further stratified according to light/moderate or heavy use according to saliva cotinine levels: light/moderate users were started on 14 mg and heavy users on 21 mg of nicotine. All patients were tapered to 7 mg over a 6-week period. Approximately 300 males between the ages of 14 and 19 who used smokeless tobacco at least 5 days a week were enrolled in the study.

Cessation rates at 1 year were not statistically significant between the placebo and active patch (P=0.22). The nicotine patch was well tolerated, with the exception of 5 patients who experienced skin irritation or headache; however, 3 patients were removed from patch therapy due to skin hyper-reaction or headache.

Study #4: Dosing. A fourth study, by Ebbert et al,⁸ addressed potential under-dosing of nicotine patches. This study was a randomized, double-blind, placebo controlled trial that evaluated 21, 42, or 63 mg/day of nicotine delivered by patch or placebo in 42 patients. (The 21 mg/day dose is the highest recommended starting dose for smokers.) The patients had to be 18 years of age or older, in good health, and use 3 or more cans/pouches of smokeless tobacco per day.

The study took place in 3 phases: outpatient preadmission, inpatient research phase, and an outpatient follow-up phase. The inpatient phase measured nicotine and cotinine concentrations during active smokeless tobacco use and while receiving treatment or placebo. Patients treated with the 42 mg/day patch had levels closer to those measured during active smokeless tobacco use, while patients treated with 63 mg/day tended to be “over-replaced” and experienced more severe adverse effects, such as nausea, vomiting, and headache. Overall, nicotine replacement therapy was well tolerated throughout the trial.

Nicotine gum: No lasting benefit

The earliest trial to evaluate nicotine gum for smokeless tobacco cessation was conducted by Boyle⁹ and was only available in abstract form (TABLE 2). This randomized, double-blind, placebo-controlled trial evaluated 2 mg of nicotine gum vs placebo in 100 patients. The main outcome was quit rates at the end of 6 weeks. The quit rate was similar for each group, and did not reach statistical significance (no P value provided). No information regarding adverse effects was reported.

A second trial¹⁰ to evaluate nicotine gum was also a randomized placebo-controlled trial that enrolled just over 200 adult patients that used ≥1 tin of smokeless tobacco per week (TABLE 2). Patients were randomized to 2 mg of nicotine gum or placebo and group therapy sessions or minimal behavioral intervention contact for a 2-month treatment period.

This trial did show a significant difference at week 4 (P<0.01) in point prevalence abstinence—that is, the number of people reporting to be abstinent at the 4-week mark, regardless of whether their abstinence was continuous or not. Significance, however, was lost by week 8. Cessation rates were also significant at 1- and 6-month follow-up exams (P<0.05), but were not maintained at the 12-month follow-up.

TABLE 2
Nicotine gum for smokeless tobacco cessation: Benefit doesn’t last

Continuous abstinence rates were similar for all groups except the 2 mg nicotine and minimal intervention group. Patients in this group had significantly lower abstinence rates from all other groups (P<0.003). No information regarding adverse effects was reported.

Case report suggests bupropion has potential

Bupropion is a non-nicotine smoking cessation therapy that inhibits the uptake of norepinephrine and dopamine. It is unclear how bupropion aids in smoking cessation, though its ability to do so appears to be related to its dopaminergic properties.¹¹

Given its utility in treatment for smoking cessation, it seems plausible that the drug may serve as an effective treatment for smokeless tobacco, as well. However, the literature regarding the use of bupropion for smokeless tobacco cessation is even more limited than that for nicotine replacement therapy.

Berigan and Deagle first described the use of bupropion for smokeless tobacco cessation in 1999 (TABLE 3).¹² Their case report focused on a 31-year-old man who reported using 1 can of smokeless tobacco per day for 11 years. The patient reported having tried nicotine patches and attempting to quit “cold turkey,” with limited success.

The patient was started on a trial of bupropion along with approximately 1 month of behavioral counseling. After 1 week of medication, the patient reported a reduction in cravings. By 5 weeks, the patient reported no use of smokeless tobacco. A total of 10 weeks of medication was given to the patient and he experienced no withdrawal effects after cessation. At 8 months, the patient was still tobacco free. The patient also reported few adverse effects from bupropion.

2 bupropion clinical trials are less encouraging

We found 2 clinical trials evaluating sustained-release bupropion 300 mg/day (TABLE 3). The first was a randomized, placebo-controlled trial in which patients received 7 weeks of active or placebo medication, and were then followed (with minimal counseling) for an additional 5 weeks.¹³ A total of 70 men, 18 years of age and older, were enrolled in the study; all had expressed a desire to quit and used at least one-half can of smokeless tobacco a day in the past year.

The primary endpoint was smokeless tobacco abstinence during weeks 4 through 7 of the trial. At the end of week 7 (end of treatment), significantly more patients in the treatment group were free of smokeless tobacco, compared to the placebo group (OR=2.73; 95% CI, 1.07-7.72; P=0.04). However, significance was lost by week 12 (OR=1.93; 95% CI, 0.71-5.47; P=0.2). Bupropion was well tolerated throughout this trial and no serious adverse effects were reported.

TABLE 3
Usefulness of bupropion for smokeless tobacco cessation is unclear

The second trial¹⁴ evaluating the efficacy of bupropion for smokeless tobacco cessation was also a randomized, placebo-controlled trial. Enrollees were randomly assigned to bupropion SR 300 mg/day or matching placebo for 12 weeks. In addition, minimal behavioral intervention was provided until week 24. Researchers enrolled 68 patients; all but one were men. Participants in this study were 18 years of age or older who regularly used smokeless tobacco. The efficacy of bupropion SR for nicotine dependence was the primary endpoint evaluated.

At the completion of the treatment phase, more patients in the bupropion group reported cessation (44%) compared to placebo (26%). The difference between the 2 groups was nonsignificant and remained so until the end of the study. By study end, each group had a reported cessation rate of 29%.

One patient experienced a diffuse skin rash that resulted in discontinuation of the study medication; otherwise buproprion was well tolerated.

Is varenicline useful?

A product that shows promise for smoking cessation is varenicline, which was approved by the FDA in May 2006.¹⁵ Varenicline acts as an agonist at the α₄β₂ neuronal nicotinic acetylcholine receptors. Its action at this receptor subtype blocks the ability of nicotine to bind to the receptor and is therefore thought to blunt the feeling of reward experienced by smokers.¹⁶ In addition, the medication may possess some nicotine-like action at the nicotinic receptor that may decrease the amount of withdrawal symptoms experienced by patients.¹⁵

In theory, this mechanism of action may help smokeless tobacco users to succeed in their quit attempts. Unfortunately, though, there have been no published case reports or clinical trials to date regarding the use of varenicline in the treatment of smokeless tobacco cessation.

Helping patients despite the information gap

Our knowledge of the effectiveness of various tools in smokeless tobacco cessation is hampered on a number of fronts.

Nicotine replacement therapy. The conflicting evidence regarding nicotine replacement therapy may be the result of a number of factors. First, although many of the trials used a randomized, placebo-controlled design, there were a number of variations in the patient populations studied, inconsistencies in the amount and type of counseling used, and differences in the amount of smokeless tobacco used by the patients.

Smokeless tobacco was to blame

These 2 cases illustrate the damage that chew can do

Oral leukoplakia

Gum recession

This 24-year-old patient sought treatment for an asymptomatic oral lesion that he noticed while brushing his teeth. The patient, who did not smoke tobacco and drank alcohol socially on weekends, told us that he had started chewing tobacco while playing baseball in high school 8 years earlier. He said that over the past 3 years, he had increased the habit.

On examination, we noted a well-defined, macular, white lesion on his left buccal mucosa. The lesion was not painful with palpation and remained unchanged when scraped with a tongue depressor.

Our patient had an oral leukoplakia, which can result from the chronic use of chewing tobacco. Cessation of the habit typically results in the resolution of the lesion in approximately 4 weeks. That was the case with our patient: He quit the habit and in 4 weeks, 80% of the lesion resolved. He was closely monitored, and at 3 months the lesion was undetectable.

If, however, a patient discontinues the habit and there is no change in the lesion after 4 weeks, biopsy is indicated. The most serious consequence of a malignant transformation of leukoplakia is oral squamous cell carcinoma.

A 30-year-old man was referred to us for evaluation of gum recession that had worsened over the past year. The patient complained that his teeth were sensitive to hot and cold drinks, but had no other symptoms. He had a 5-year history of smokeless tobacco use and said he usually placed the tobacco along his inner vestibule. He said that he did not smoke tobacco, nor did he drink alcohol.

On examination, we noted that the patient had localized recession along the cervical area of his lower teeth. With manipulation, there was bleeding from the gingival surface. His teeth were otherwise in good shape and there were no other lesions within the oral mucosa.

Gingival recession is a common consequence of smokeless tobacco use. Treatment consists of a gingival graft, in which palatal connective tissue is removed and used to reestablish gingival attachment to the tooth. (Tissue harvesting surgery from the palate can be quite painful.) Left untreated, teeth can become loose and fall out.

We advised our patient to follow up for gingival grafting, but he did not return for his follow-up visit.

Denise Rizzolo, PA-C, PhD is a physician assistant at Care Station in Springfield, NJ and Thomas A. Chiodo, DDS, is an oral and maxillofacial surgeon in private practice in Somerville, NJ. Dr. Chiodo also teaches at UMDNJ Dental School in Newark, NJ; [email protected]

Additionally, recent evidence suggests it may be important to consider dosing nicotine replacement according to number of cans of smokeless tobacco the patient uses per week. Heavy smokeless tobacco users may require higher initial doses than routinely used for smoking cessation therapy (eg, 42 mg/day if >3 cans of smokeless tobacco/day used).⁸

Further clinical research is needed to validate this recommendation, as well as to give specific dosing recommendations.

Nicotine gum. Two issues come to mind when considering the research on nicotine gum. First, the studies had relatively small sample sizes and it’s possible that the studies were not properly designed to detect a difference between groups.^6,7 Second, the concept of dosing nicotine gum based on the number of cans of smokeless tobacco used per day has not been explored.

Bupropion. Studies involving bupropion and smokeless tobacco cessation share several of the limitations we’ve just discussed. Differing results reported in the literature regarding bupropion’s effectiveness makes its potential benefit unclear. Use should be determined on a case-by-case basis with the understanding that it may—or may not—be useful in decreasing cravings or increasing abstinence rates.

Varenicline. There is currently no literature available to help us evaluate the usefulness of varenicline in smokeless tobacco cessation. The mechanism of action of varenicline is such that use in smokeless tobacco cessation is plausible. Again, consideration of patients on a case-by-case basis is warranted.

One size does not fit all

Although nicotine dependence is the underlying problem for patients who utilize smokeless tobacco, current literature does not support a “one-size-fits-all” approach to treatment of various forms of tobacco abuse. Further clinical investigations are needed to determine the true utility of bupropion and varenicline, as well as the appropriate dosing of nicotine replacement therapy when prescribed for smokeless tobacco cessation.

Through with Chew Week” and the “Great American Spitout.” Do they ring a bell?

If you answered no, you’re not alone.

“Through with Chew Week” was established by the American Academy of Otolaryngology—Head and Neck Surgery (AAO-HNS) in 1989, but it hasn’t quite garnered the same kind of recognition as the American Cancer Society’s Great American Smokeout.

When it comes to tobacco use—and more importantly, cessation—smokeless tobacco just doesn’t generate the kind of attention that cigarette smoking does. In fact, smokeless tobacco’s low profile extends beyond talk of “smokeouts” and “spitouts” to research on effective ways to quit.

We found this out first-hand when we conducted a literature search of Medline, PubMed, and a number of other databases to learn which cessation methods have proven efficacy. What we learned is that not only is research on the subject of smokeless tobacco cessation limited, but there is no recommended medication therapy to help these patients quit. Specifically:

• Nicotine-replacement therapies have failed to demonstrate a clear benefit in smokeless tobacco cessation, but under-dosing may be a factor for some patients.
• Bupropion’s (Zyban) usefulness in smokeless tobacco cessation is unclear. Data, thus far, have been inconclusive.
• Varenicline’s (Chantix) usefulness in smokeless tobacco cessation is unknown. There are no published case reports or clinical trials on the subject.

Millions of “chew” users are at risk

Tobacco use is the leading preventable cause of premature death in the United States, with more than 440,000 Americans dying of tobacco-related disease each year.¹ Cigarette smoking is by far the most common form of tobacco used; however, smokeless tobacco, also known as chew, spit tobacco, or snuff, is used by 8.2 million Americans.² More men than women use tobacco products overall, and smokeless tobacco, in particular.²

Health risks include MI. Specific health risks associated with smokeless tobacco include cancer of the oral cavity and pharynx, oral and periodontal disease, tooth decay, and pregnancy-related problems.¹ (See “Smokeless tobacco was to blame”)

In addition, an international, case-control study evaluating the risk of myocardial infarction associated with various forms of tobacco use found an increased risk of myocardial infarction associated with smokeless tobacco use compared to non-tobacco users (odds ratio [OR]=2.23; 95% confidence interval [CI], 1.41-3.52).³

Notably, smokeless tobacco users in the study who also smoked cigarettes had the highest risk of all tobacco users when compared to non-users (OR=4.09; 95% CI, 2.98-5.61). These findings demonstrate that nicotine dependence is detrimental to health—regardless of the form of tobacco used. Even more worrisome is the notion that risk may actually be increased when multiple forms of tobacco are used by the same patient.

Patients want medication to help them quit

Current guidelines for tobacco cessation recommend that patients using smokeless tobacco should be identified, urged to quit, and treated with counseling interventions.⁴ Despite this recommendation, many patients are interested in using a medication to aid them in their quit effort, and many physicians would like to prescribe medication to help patients succeed.

To that end, it seemed logical to us that the same treatments used for smoking cessation would also be effective for smokeless tobacco cessation, given that the underlying problem—despite the form of tobacco used—is nicotine dependence. So we did a literature review to determine the optimal treatment for smokeless tobacco cessation. Our search included: Medline (1950-2007), PubMed (1966-2006), International Pharmaceutical Abstracts (1970-2006), Science Direct, CINAHL, PsycArticles, and Dissertation Abstracts. We used the following search terms: smokeless tobacco, spit tobacco, chew tobacco, cessation, bupropion, nicotine, and nicotine replacement. (Searches in Medline for nicotine replacement therapy in smokeless tobacco cessation were limited to clinical trials.) What we found were a limited number of studies, which we’ve summarized here.

Nicotine patch is useful, but to what degree?

We reviewed four studies involving the use of a nicotine patch for smokeless tobacco cessation (TABLE 1). In chronological order:

Study #1: 15-mg patch. The first study to evaluate the nicotine patch was a randomized, double-blind, placebo controlled trial published in 1999. A 15-mg nicotine patch was used by approximately 420 patients.⁵ Patients included in the trial were at least 18 years of age, nonsmokers, and used at least 1 can of smokeless tobacco per week. The main outcome of this trial was cessation at 6 months.

A significant difference was found in abstinence rates between patients treated with active therapy compared to those treated with placebo early in the study; however, by study end, there were no significant differences between groups. The medication was well tolerated, though patients receiving active therapy did report an increase in adverse effects related to patch use, such as rash and itching.

TABLE 1
Conflicting findings on the nicotine patch for smokeless tobacco cessation

Study #2: Nicotine plus mint snuff. The second trial to evaluate nicotine patches randomized approximately 400 patients to 1 of 4 groups: active nicotine patch plus mint snuff (non-nicotine mint-leaf product), active nicotine patch and no mint snuff, placebo plus mint snuff, or placebo patch and no mint snuff.⁶ To be enrolled in the study, patients had to use 1 can of smokeless tobacco per week and express a desire to quit. Patients given the active nicotine patch were begun on 22 mg and tapered to 7 mg by the end of 10 weeks. At 10 weeks, continuous abstinence and abstinence since the last clinic visit were evaluated. (Researchers tracked the patients for a total of 62 weeks.)

Patients who received active nicotine patches had significantly higher cessation rates compared to placebo at 10 (P=0.002) and 15 (P=0.016) weeks, but not at any other time during the study. No information regarding adverse effects was reported.

Study #3: Patch in adolescents. In a third, randomized, placebo-controlled trial, the effect of nicotine replacement in adolescents was evaluated. Patients were randomized to an active patch, placebo patch, or usual care (1 counseling session with a follow-up phone call).⁷

Patients who received an active patch also received 6 weeks of behavior counseling sessions. Smokeless tobacco users were further stratified according to light/moderate or heavy use according to saliva cotinine levels: light/moderate users were started on 14 mg and heavy users on 21 mg of nicotine. All patients were tapered to 7 mg over a 6-week period. Approximately 300 males between the ages of 14 and 19 who used smokeless tobacco at least 5 days a week were enrolled in the study.

Cessation rates at 1 year were not statistically significant between the placebo and active patch (P=0.22). The nicotine patch was well tolerated, with the exception of 5 patients who experienced skin irritation or headache; however, 3 patients were removed from patch therapy due to skin hyper-reaction or headache.

Study #4: Dosing. A fourth study, by Ebbert et al,⁸ addressed potential under-dosing of nicotine patches. This study was a randomized, double-blind, placebo controlled trial that evaluated 21, 42, or 63 mg/day of nicotine delivered by patch or placebo in 42 patients. (The 21 mg/day dose is the highest recommended starting dose for smokers.) The patients had to be 18 years of age or older, in good health, and use 3 or more cans/pouches of smokeless tobacco per day.

The study took place in 3 phases: outpatient preadmission, inpatient research phase, and an outpatient follow-up phase. The inpatient phase measured nicotine and cotinine concentrations during active smokeless tobacco use and while receiving treatment or placebo. Patients treated with the 42 mg/day patch had levels closer to those measured during active smokeless tobacco use, while patients treated with 63 mg/day tended to be “over-replaced” and experienced more severe adverse effects, such as nausea, vomiting, and headache. Overall, nicotine replacement therapy was well tolerated throughout the trial.

Nicotine gum: No lasting benefit

The earliest trial to evaluate nicotine gum for smokeless tobacco cessation was conducted by Boyle⁹ and was only available in abstract form (TABLE 2). This randomized, double-blind, placebo-controlled trial evaluated 2 mg of nicotine gum vs placebo in 100 patients. The main outcome was quit rates at the end of 6 weeks. The quit rate was similar for each group, and did not reach statistical significance (no P value provided). No information regarding adverse effects was reported.

A second trial¹⁰ to evaluate nicotine gum was also a randomized placebo-controlled trial that enrolled just over 200 adult patients that used ≥1 tin of smokeless tobacco per week (TABLE 2). Patients were randomized to 2 mg of nicotine gum or placebo and group therapy sessions or minimal behavioral intervention contact for a 2-month treatment period.

This trial did show a significant difference at week 4 (P<0.01) in point prevalence abstinence—that is, the number of people reporting to be abstinent at the 4-week mark, regardless of whether their abstinence was continuous or not. Significance, however, was lost by week 8. Cessation rates were also significant at 1- and 6-month follow-up exams (P<0.05), but were not maintained at the 12-month follow-up.

TABLE 2
Nicotine gum for smokeless tobacco cessation: Benefit doesn’t last

Continuous abstinence rates were similar for all groups except the 2 mg nicotine and minimal intervention group. Patients in this group had significantly lower abstinence rates from all other groups (P<0.003). No information regarding adverse effects was reported.

Case report suggests bupropion has potential

Bupropion is a non-nicotine smoking cessation therapy that inhibits the uptake of norepinephrine and dopamine. It is unclear how bupropion aids in smoking cessation, though its ability to do so appears to be related to its dopaminergic properties.¹¹

Given its utility in treatment for smoking cessation, it seems plausible that the drug may serve as an effective treatment for smokeless tobacco, as well. However, the literature regarding the use of bupropion for smokeless tobacco cessation is even more limited than that for nicotine replacement therapy.

Berigan and Deagle first described the use of bupropion for smokeless tobacco cessation in 1999 (TABLE 3).¹² Their case report focused on a 31-year-old man who reported using 1 can of smokeless tobacco per day for 11 years. The patient reported having tried nicotine patches and attempting to quit “cold turkey,” with limited success.

The patient was started on a trial of bupropion along with approximately 1 month of behavioral counseling. After 1 week of medication, the patient reported a reduction in cravings. By 5 weeks, the patient reported no use of smokeless tobacco. A total of 10 weeks of medication was given to the patient and he experienced no withdrawal effects after cessation. At 8 months, the patient was still tobacco free. The patient also reported few adverse effects from bupropion.

2 bupropion clinical trials are less encouraging

We found 2 clinical trials evaluating sustained-release bupropion 300 mg/day (TABLE 3). The first was a randomized, placebo-controlled trial in which patients received 7 weeks of active or placebo medication, and were then followed (with minimal counseling) for an additional 5 weeks.¹³ A total of 70 men, 18 years of age and older, were enrolled in the study; all had expressed a desire to quit and used at least one-half can of smokeless tobacco a day in the past year.

The primary endpoint was smokeless tobacco abstinence during weeks 4 through 7 of the trial. At the end of week 7 (end of treatment), significantly more patients in the treatment group were free of smokeless tobacco, compared to the placebo group (OR=2.73; 95% CI, 1.07-7.72; P=0.04). However, significance was lost by week 12 (OR=1.93; 95% CI, 0.71-5.47; P=0.2). Bupropion was well tolerated throughout this trial and no serious adverse effects were reported.

TABLE 3
Usefulness of bupropion for smokeless tobacco cessation is unclear

The second trial¹⁴ evaluating the efficacy of bupropion for smokeless tobacco cessation was also a randomized, placebo-controlled trial. Enrollees were randomly assigned to bupropion SR 300 mg/day or matching placebo for 12 weeks. In addition, minimal behavioral intervention was provided until week 24. Researchers enrolled 68 patients; all but one were men. Participants in this study were 18 years of age or older who regularly used smokeless tobacco. The efficacy of bupropion SR for nicotine dependence was the primary endpoint evaluated.

At the completion of the treatment phase, more patients in the bupropion group reported cessation (44%) compared to placebo (26%). The difference between the 2 groups was nonsignificant and remained so until the end of the study. By study end, each group had a reported cessation rate of 29%.

One patient experienced a diffuse skin rash that resulted in discontinuation of the study medication; otherwise buproprion was well tolerated.

Is varenicline useful?

A product that shows promise for smoking cessation is varenicline, which was approved by the FDA in May 2006.¹⁵ Varenicline acts as an agonist at the α₄β₂ neuronal nicotinic acetylcholine receptors. Its action at this receptor subtype blocks the ability of nicotine to bind to the receptor and is therefore thought to blunt the feeling of reward experienced by smokers.¹⁶ In addition, the medication may possess some nicotine-like action at the nicotinic receptor that may decrease the amount of withdrawal symptoms experienced by patients.¹⁵

In theory, this mechanism of action may help smokeless tobacco users to succeed in their quit attempts. Unfortunately, though, there have been no published case reports or clinical trials to date regarding the use of varenicline in the treatment of smokeless tobacco cessation.

Helping patients despite the information gap

Our knowledge of the effectiveness of various tools in smokeless tobacco cessation is hampered on a number of fronts.

Nicotine replacement therapy. The conflicting evidence regarding nicotine replacement therapy may be the result of a number of factors. First, although many of the trials used a randomized, placebo-controlled design, there were a number of variations in the patient populations studied, inconsistencies in the amount and type of counseling used, and differences in the amount of smokeless tobacco used by the patients.

Smokeless tobacco was to blame

These 2 cases illustrate the damage that chew can do

Oral leukoplakia

Gum recession

This 24-year-old patient sought treatment for an asymptomatic oral lesion that he noticed while brushing his teeth. The patient, who did not smoke tobacco and drank alcohol socially on weekends, told us that he had started chewing tobacco while playing baseball in high school 8 years earlier. He said that over the past 3 years, he had increased the habit.

On examination, we noted a well-defined, macular, white lesion on his left buccal mucosa. The lesion was not painful with palpation and remained unchanged when scraped with a tongue depressor.

Our patient had an oral leukoplakia, which can result from the chronic use of chewing tobacco. Cessation of the habit typically results in the resolution of the lesion in approximately 4 weeks. That was the case with our patient: He quit the habit and in 4 weeks, 80% of the lesion resolved. He was closely monitored, and at 3 months the lesion was undetectable.

If, however, a patient discontinues the habit and there is no change in the lesion after 4 weeks, biopsy is indicated. The most serious consequence of a malignant transformation of leukoplakia is oral squamous cell carcinoma.

A 30-year-old man was referred to us for evaluation of gum recession that had worsened over the past year. The patient complained that his teeth were sensitive to hot and cold drinks, but had no other symptoms. He had a 5-year history of smokeless tobacco use and said he usually placed the tobacco along his inner vestibule. He said that he did not smoke tobacco, nor did he drink alcohol.

On examination, we noted that the patient had localized recession along the cervical area of his lower teeth. With manipulation, there was bleeding from the gingival surface. His teeth were otherwise in good shape and there were no other lesions within the oral mucosa.

Gingival recession is a common consequence of smokeless tobacco use. Treatment consists of a gingival graft, in which palatal connective tissue is removed and used to reestablish gingival attachment to the tooth. (Tissue harvesting surgery from the palate can be quite painful.) Left untreated, teeth can become loose and fall out.

We advised our patient to follow up for gingival grafting, but he did not return for his follow-up visit.

Denise Rizzolo, PA-C, PhD is a physician assistant at Care Station in Springfield, NJ and Thomas A. Chiodo, DDS, is an oral and maxillofacial surgeon in private practice in Somerville, NJ. Dr. Chiodo also teaches at UMDNJ Dental School in Newark, NJ; [email protected]

Additionally, recent evidence suggests it may be important to consider dosing nicotine replacement according to number of cans of smokeless tobacco the patient uses per week. Heavy smokeless tobacco users may require higher initial doses than routinely used for smoking cessation therapy (eg, 42 mg/day if >3 cans of smokeless tobacco/day used).⁸

Further clinical research is needed to validate this recommendation, as well as to give specific dosing recommendations.

Nicotine gum. Two issues come to mind when considering the research on nicotine gum. First, the studies had relatively small sample sizes and it’s possible that the studies were not properly designed to detect a difference between groups.^6,7 Second, the concept of dosing nicotine gum based on the number of cans of smokeless tobacco used per day has not been explored.

Bupropion. Studies involving bupropion and smokeless tobacco cessation share several of the limitations we’ve just discussed. Differing results reported in the literature regarding bupropion’s effectiveness makes its potential benefit unclear. Use should be determined on a case-by-case basis with the understanding that it may—or may not—be useful in decreasing cravings or increasing abstinence rates.

Varenicline. There is currently no literature available to help us evaluate the usefulness of varenicline in smokeless tobacco cessation. The mechanism of action of varenicline is such that use in smokeless tobacco cessation is plausible. Again, consideration of patients on a case-by-case basis is warranted.

One size does not fit all

Although nicotine dependence is the underlying problem for patients who utilize smokeless tobacco, current literature does not support a “one-size-fits-all” approach to treatment of various forms of tobacco abuse. Further clinical investigations are needed to determine the true utility of bupropion and varenicline, as well as the appropriate dosing of nicotine replacement therapy when prescribed for smokeless tobacco cessation.

Nexium, Prevacid, and Protonix were among the 25 most commonly dispensed medications in 2006.¹ With multiple indications, high clinical efficacy, low incidence of adverse events, convenient dosing, and few drug interactions, it is understandable why PPIs are popular with physicians and patients. Use of prescription PPIs has continued to increase even after Prilosec OTC became available.

TABLES 1–3 give recommended dosing for PPI indications, formulations, drug interactions, cost, and adverse event profiles.

Drug action and efficacy. PPIs have a pharmacokinetic elimination half-life of 30 minutes to 2 hours, but once-daily dosing is possible due to long-lasting inactivation of the proton pump.²

Genetic polymorphism. Up to 6% of Caucasian and 23% of Asian patients are CYP P450 2C19 poor metabolizers.^2,3 This is the common hepatic clearance pathway for currently available PPIs. However, due to PPI efficacy, low potential for drug interactions, and infrequent adverse events, this genetic polymorphism is not likely to affect the vast majority of patients on PPI therapy.

Are differences clinically significant? Many trials have compared PPIs using a variety of surrogate endpoints. A new PPI, S-tenatoprazole [not available in the US] has shown greater acid suppression than esomeprazole.⁴ However, no single agent has proven more efficacious than other PPIs at equipotent doses.^5,6 Even though lansoprazole and omeprazole have the most FDA-approved indications, this should not discourage you from using any PPI for a variety of gastrointestinal indications. For example, lansoprazole and esomeprazole are the only PPIs approved for healing or risk reduction of NSAID-related gastric ulcers. Yet other PPIs have been used for this indication without any reason to suspect lack of effectiveness. A meta-analysis of 41 randomized, double-blind studies evaluated head-to-head clinical trials for many conditions, including Helicobacter pylori, gastroesophageal reflux disease (GERD) and peptic ulcer disease.⁵ No clinically important differences were noted when equipotent doses were used.^5-7

Only 1 difference in the treatment of GERD was noted between esomeprazole 40 mg and omeprazole 20 mg in the pooled results (relative risk 1.18; 95% confidence interval 1.14-1.23). This is not surprising because the 2 medications were not given at equipotent doses.

All PPIs are well tolerated. The most common adverse effects are headache, diarrhea, and abdominal pain.^8-12 The side-effect profile is consistent among PPIs. An exception is dose-related increases in the frequency of diarrhea reported with lansoprazole (ranging from 1.4% to 7.4%) and higher dose omeprazole therapy.^2,8

Although considered relatively safe, several considerations have arisen from clinical trials. Some (occurrence of rebound acid hypersecretion after PPI discontinuation) are better documented than others.¹³ Additional data are needed to determine whether there is any significant association with PPI-induced elevated serum gastrin levels and neoplastic changes or an increased risk of hip fracture, community-acquired pneumonia, Clostridium difficile infection, vitamin B₁₂ anemia, iron malabsorption, and atrophic gastritis (TABLE 3).^13-27

It is promising that data which demonstrate safe and effective use of these agents for longer than 10 years are available.^2,28

TABLE 1
Similarities and differences among proton pump inhibitors^{2,8-12,25,34,35}

TABLE 2
Cost comparison of proton pump inhibitor regimens* for 8 conditions^8-12,25,29

TABLE 3
Support vs refutation: Adverse events and long-term PPI therapy^{2,13-23,26,27}

Drug interactions

Two main types of drug interactions may occur with PPIs: those at the cytochrome P450 level, and those due to decreased absorption caused by acid suppression.

PPIs are metabolized by both CYP 2C19 and CYP 3A4. Theoretically, any medication that can induce or inhibit either of these enzymes could affect PPI blood concentration levels.

Evidence suggests omeprazole and its enantiomer esomeprazole have the most potential of the PPIs for drug interactions, as they have been shown to increase blood concentration levels of phenytoin, benzodiazepines, carbamazepine, cilostazol, clarithomycin, and R-warfarin by inhibiting CYP 2C19.^2,3,29 These interactions do not typically require a dose adjustment. However, more frequent monitoring may be appropriate.^2,6

As a class, PPIs may decrease or increase the bioavailability of drugs whose absorption is dependent on gastric pH. Common medications that are pH dependent for absorption are the azole antifungals, ampicillin, cefpodoxime, indinavir, delavirdine, cyanocobalamin, iron, and digoxin.^2,3,6 Digoxin absorption may be increased, resulting in elevated digoxin levels. Enteric-coated medications, which typically dissolve at a higher pH, may also be affected by PPI therapy.²

There may be a decrease in PPI efficacy if given concurrently with other antisecretory medications such as histamine 2 (H₂) antagonists or misoprostol. This interaction is apparently due to the capability of PPIs to exert their effects only on actively secreting proton pumps.^2,29

Step-up and step-down therapy

Step therapy was a much larger issue prior to the availability of generic omeprazole and pantoprazole. The relative novelty of these agents combined with higher cost of therapy and unknown long-term safety information as well as the availability of effective alternatives justified the argument for step-up therapy.

Health care systems and insurance providers encouraged short-term use of PPIs, either prior to H₂ receptor antagonists (step-down therapy) or only after failure of H₂ receptor antagonists (step-up therapy). Those who favored step-up therapy took into account the cost advantage of H₂ receptor antagonists. Those who favored step-down therapy believed patients on H₂ receptor antagonists may experience worsening control of the disease and would therefore need to utilize more health care resources, offsetting the lower costs of H₂ receptor antagonists. Further, for indications like the treatment of H. pylori, compliance to therapy and corresponding efficacy may be compromised by the use of an H₂ receptor antagonist in place of a PPI. Of the 2 approaches, cost effectiveness studies favor the step-down approach.^30-33

Switch to an H₂ blocker? Proponents of step-down therapy reasoned that many patients are placed on PPIs and continued indefinitely without re-evaluation. The only way to see if a PPI is still needed is to decrease the dose, switch to an H₂ receptor antagonist, or completely discontinue acid-suppression therapy after symptom resolution.

At this time, omeprazole is the only PPI available OTC; it typically retails at $22 for 28 capsules. A generic version of the OTC omeprazole product has been approved. The cost is generally $13 to $15 for 28 capsules. Each H₂ receptor antagonist is available as a generic, and OTC at half prescription strength. Of note, famotidine 20-mg tablets and ranitidine 150-mg and 300-mg tablets are available on many of the $4 prescription plans at retail pharmacies.

YOUR PATIENT HAS NO INSURANCE

Your patient reports he has been taking omeprazole 20 mg daily, as you prescribed, for the past 2 weeks. His heart-burn symptoms have improved and he no longer needs to use Tums for breakthrough symptoms, as he did when he was taking Pepcid.

You considered pantoprazole and omeprazole because they are both available in generic form. Since there are no significant differences in efficacy of the 2 drugs for the treatment of GERD, you decided to prescribe pantoprazole because it will cost less for the patient, who has no prescription insurance. The pharmacy calls you, asking if generic omeprazole could be used instead due to the cost difference.

According to http://www.drugstore.com, generic pantoprazole would cost the patient $110 per month and generic omeprazole would cost the patient $63 per month.

Even though costs at local pharmacies vary and are often higher than online costs, the savings to the patient seemed significant enough to change

Nexium, Prevacid, and Protonix were among the 25 most commonly dispensed medications in 2006.¹ With multiple indications, high clinical efficacy, low incidence of adverse events, convenient dosing, and few drug interactions, it is understandable why PPIs are popular with physicians and patients. Use of prescription PPIs has continued to increase even after Prilosec OTC became available.

TABLES 1–3 give recommended dosing for PPI indications, formulations, drug interactions, cost, and adverse event profiles.

Drug action and efficacy. PPIs have a pharmacokinetic elimination half-life of 30 minutes to 2 hours, but once-daily dosing is possible due to long-lasting inactivation of the proton pump.²

Genetic polymorphism. Up to 6% of Caucasian and 23% of Asian patients are CYP P450 2C19 poor metabolizers.^2,3 This is the common hepatic clearance pathway for currently available PPIs. However, due to PPI efficacy, low potential for drug interactions, and infrequent adverse events, this genetic polymorphism is not likely to affect the vast majority of patients on PPI therapy.

Are differences clinically significant? Many trials have compared PPIs using a variety of surrogate endpoints. A new PPI, S-tenatoprazole [not available in the US] has shown greater acid suppression than esomeprazole.⁴ However, no single agent has proven more efficacious than other PPIs at equipotent doses.^5,6 Even though lansoprazole and omeprazole have the most FDA-approved indications, this should not discourage you from using any PPI for a variety of gastrointestinal indications. For example, lansoprazole and esomeprazole are the only PPIs approved for healing or risk reduction of NSAID-related gastric ulcers. Yet other PPIs have been used for this indication without any reason to suspect lack of effectiveness. A meta-analysis of 41 randomized, double-blind studies evaluated head-to-head clinical trials for many conditions, including Helicobacter pylori, gastroesophageal reflux disease (GERD) and peptic ulcer disease.⁵ No clinically important differences were noted when equipotent doses were used.^5-7

Only 1 difference in the treatment of GERD was noted between esomeprazole 40 mg and omeprazole 20 mg in the pooled results (relative risk 1.18; 95% confidence interval 1.14-1.23). This is not surprising because the 2 medications were not given at equipotent doses.

All PPIs are well tolerated. The most common adverse effects are headache, diarrhea, and abdominal pain.^8-12 The side-effect profile is consistent among PPIs. An exception is dose-related increases in the frequency of diarrhea reported with lansoprazole (ranging from 1.4% to 7.4%) and higher dose omeprazole therapy.^2,8

Although considered relatively safe, several considerations have arisen from clinical trials. Some (occurrence of rebound acid hypersecretion after PPI discontinuation) are better documented than others.¹³ Additional data are needed to determine whether there is any significant association with PPI-induced elevated serum gastrin levels and neoplastic changes or an increased risk of hip fracture, community-acquired pneumonia, Clostridium difficile infection, vitamin B₁₂ anemia, iron malabsorption, and atrophic gastritis (TABLE 3).^13-27

It is promising that data which demonstrate safe and effective use of these agents for longer than 10 years are available.^2,28

TABLE 1
Similarities and differences among proton pump inhibitors^{2,8-12,25,34,35}

TABLE 2
Cost comparison of proton pump inhibitor regimens* for 8 conditions^8-12,25,29

TABLE 3
Support vs refutation: Adverse events and long-term PPI therapy^{2,13-23,26,27}

Drug interactions

Two main types of drug interactions may occur with PPIs: those at the cytochrome P450 level, and those due to decreased absorption caused by acid suppression.

PPIs are metabolized by both CYP 2C19 and CYP 3A4. Theoretically, any medication that can induce or inhibit either of these enzymes could affect PPI blood concentration levels.

Evidence suggests omeprazole and its enantiomer esomeprazole have the most potential of the PPIs for drug interactions, as they have been shown to increase blood concentration levels of phenytoin, benzodiazepines, carbamazepine, cilostazol, clarithomycin, and R-warfarin by inhibiting CYP 2C19.^2,3,29 These interactions do not typically require a dose adjustment. However, more frequent monitoring may be appropriate.^2,6

As a class, PPIs may decrease or increase the bioavailability of drugs whose absorption is dependent on gastric pH. Common medications that are pH dependent for absorption are the azole antifungals, ampicillin, cefpodoxime, indinavir, delavirdine, cyanocobalamin, iron, and digoxin.^2,3,6 Digoxin absorption may be increased, resulting in elevated digoxin levels. Enteric-coated medications, which typically dissolve at a higher pH, may also be affected by PPI therapy.²

There may be a decrease in PPI efficacy if given concurrently with other antisecretory medications such as histamine 2 (H₂) antagonists or misoprostol. This interaction is apparently due to the capability of PPIs to exert their effects only on actively secreting proton pumps.^2,29

Step-up and step-down therapy

Step therapy was a much larger issue prior to the availability of generic omeprazole and pantoprazole. The relative novelty of these agents combined with higher cost of therapy and unknown long-term safety information as well as the availability of effective alternatives justified the argument for step-up therapy.

Health care systems and insurance providers encouraged short-term use of PPIs, either prior to H₂ receptor antagonists (step-down therapy) or only after failure of H₂ receptor antagonists (step-up therapy). Those who favored step-up therapy took into account the cost advantage of H₂ receptor antagonists. Those who favored step-down therapy believed patients on H₂ receptor antagonists may experience worsening control of the disease and would therefore need to utilize more health care resources, offsetting the lower costs of H₂ receptor antagonists. Further, for indications like the treatment of H. pylori, compliance to therapy and corresponding efficacy may be compromised by the use of an H₂ receptor antagonist in place of a PPI. Of the 2 approaches, cost effectiveness studies favor the step-down approach.^30-33

Switch to an H₂ blocker? Proponents of step-down therapy reasoned that many patients are placed on PPIs and continued indefinitely without re-evaluation. The only way to see if a PPI is still needed is to decrease the dose, switch to an H₂ receptor antagonist, or completely discontinue acid-suppression therapy after symptom resolution.

At this time, omeprazole is the only PPI available OTC; it typically retails at $22 for 28 capsules. A generic version of the OTC omeprazole product has been approved. The cost is generally $13 to $15 for 28 capsules. Each H₂ receptor antagonist is available as a generic, and OTC at half prescription strength. Of note, famotidine 20-mg tablets and ranitidine 150-mg and 300-mg tablets are available on many of the $4 prescription plans at retail pharmacies.

YOUR PATIENT HAS NO INSURANCE

Your patient reports he has been taking omeprazole 20 mg daily, as you prescribed, for the past 2 weeks. His heart-burn symptoms have improved and he no longer needs to use Tums for breakthrough symptoms, as he did when he was taking Pepcid.

You considered pantoprazole and omeprazole because they are both available in generic form. Since there are no significant differences in efficacy of the 2 drugs for the treatment of GERD, you decided to prescribe pantoprazole because it will cost less for the patient, who has no prescription insurance. The pharmacy calls you, asking if generic omeprazole could be used instead due to the cost difference.

According to http://www.drugstore.com, generic pantoprazole would cost the patient $110 per month and generic omeprazole would cost the patient $63 per month.

Even though costs at local pharmacies vary and are often higher than online costs, the savings to the patient seemed significant enough to change

Nexium, Prevacid, and Protonix were among the 25 most commonly dispensed medications in 2006.¹ With multiple indications, high clinical efficacy, low incidence of adverse events, convenient dosing, and few drug interactions, it is understandable why PPIs are popular with physicians and patients. Use of prescription PPIs has continued to increase even after Prilosec OTC became available.

TABLES 1–3 give recommended dosing for PPI indications, formulations, drug interactions, cost, and adverse event profiles.

Drug action and efficacy. PPIs have a pharmacokinetic elimination half-life of 30 minutes to 2 hours, but once-daily dosing is possible due to long-lasting inactivation of the proton pump.²

Genetic polymorphism. Up to 6% of Caucasian and 23% of Asian patients are CYP P450 2C19 poor metabolizers.^2,3 This is the common hepatic clearance pathway for currently available PPIs. However, due to PPI efficacy, low potential for drug interactions, and infrequent adverse events, this genetic polymorphism is not likely to affect the vast majority of patients on PPI therapy.

Are differences clinically significant? Many trials have compared PPIs using a variety of surrogate endpoints. A new PPI, S-tenatoprazole [not available in the US] has shown greater acid suppression than esomeprazole.⁴ However, no single agent has proven more efficacious than other PPIs at equipotent doses.^5,6 Even though lansoprazole and omeprazole have the most FDA-approved indications, this should not discourage you from using any PPI for a variety of gastrointestinal indications. For example, lansoprazole and esomeprazole are the only PPIs approved for healing or risk reduction of NSAID-related gastric ulcers. Yet other PPIs have been used for this indication without any reason to suspect lack of effectiveness. A meta-analysis of 41 randomized, double-blind studies evaluated head-to-head clinical trials for many conditions, including Helicobacter pylori, gastroesophageal reflux disease (GERD) and peptic ulcer disease.⁵ No clinically important differences were noted when equipotent doses were used.^5-7

Only 1 difference in the treatment of GERD was noted between esomeprazole 40 mg and omeprazole 20 mg in the pooled results (relative risk 1.18; 95% confidence interval 1.14-1.23). This is not surprising because the 2 medications were not given at equipotent doses.

All PPIs are well tolerated. The most common adverse effects are headache, diarrhea, and abdominal pain.^8-12 The side-effect profile is consistent among PPIs. An exception is dose-related increases in the frequency of diarrhea reported with lansoprazole (ranging from 1.4% to 7.4%) and higher dose omeprazole therapy.^2,8

Although considered relatively safe, several considerations have arisen from clinical trials. Some (occurrence of rebound acid hypersecretion after PPI discontinuation) are better documented than others.¹³ Additional data are needed to determine whether there is any significant association with PPI-induced elevated serum gastrin levels and neoplastic changes or an increased risk of hip fracture, community-acquired pneumonia, Clostridium difficile infection, vitamin B₁₂ anemia, iron malabsorption, and atrophic gastritis (TABLE 3).^13-27

It is promising that data which demonstrate safe and effective use of these agents for longer than 10 years are available.^2,28

TABLE 1
Similarities and differences among proton pump inhibitors^{2,8-12,25,34,35}

TABLE 2
Cost comparison of proton pump inhibitor regimens* for 8 conditions^8-12,25,29

TABLE 3
Support vs refutation: Adverse events and long-term PPI therapy^{2,13-23,26,27}

Drug interactions

Two main types of drug interactions may occur with PPIs: those at the cytochrome P450 level, and those due to decreased absorption caused by acid suppression.

PPIs are metabolized by both CYP 2C19 and CYP 3A4. Theoretically, any medication that can induce or inhibit either of these enzymes could affect PPI blood concentration levels.

Evidence suggests omeprazole and its enantiomer esomeprazole have the most potential of the PPIs for drug interactions, as they have been shown to increase blood concentration levels of phenytoin, benzodiazepines, carbamazepine, cilostazol, clarithomycin, and R-warfarin by inhibiting CYP 2C19.^2,3,29 These interactions do not typically require a dose adjustment. However, more frequent monitoring may be appropriate.^2,6

As a class, PPIs may decrease or increase the bioavailability of drugs whose absorption is dependent on gastric pH. Common medications that are pH dependent for absorption are the azole antifungals, ampicillin, cefpodoxime, indinavir, delavirdine, cyanocobalamin, iron, and digoxin.^2,3,6 Digoxin absorption may be increased, resulting in elevated digoxin levels. Enteric-coated medications, which typically dissolve at a higher pH, may also be affected by PPI therapy.²

There may be a decrease in PPI efficacy if given concurrently with other antisecretory medications such as histamine 2 (H₂) antagonists or misoprostol. This interaction is apparently due to the capability of PPIs to exert their effects only on actively secreting proton pumps.^2,29

Step-up and step-down therapy

Step therapy was a much larger issue prior to the availability of generic omeprazole and pantoprazole. The relative novelty of these agents combined with higher cost of therapy and unknown long-term safety information as well as the availability of effective alternatives justified the argument for step-up therapy.

Health care systems and insurance providers encouraged short-term use of PPIs, either prior to H₂ receptor antagonists (step-down therapy) or only after failure of H₂ receptor antagonists (step-up therapy). Those who favored step-up therapy took into account the cost advantage of H₂ receptor antagonists. Those who favored step-down therapy believed patients on H₂ receptor antagonists may experience worsening control of the disease and would therefore need to utilize more health care resources, offsetting the lower costs of H₂ receptor antagonists. Further, for indications like the treatment of H. pylori, compliance to therapy and corresponding efficacy may be compromised by the use of an H₂ receptor antagonist in place of a PPI. Of the 2 approaches, cost effectiveness studies favor the step-down approach.^30-33

Switch to an H₂ blocker? Proponents of step-down therapy reasoned that many patients are placed on PPIs and continued indefinitely without re-evaluation. The only way to see if a PPI is still needed is to decrease the dose, switch to an H₂ receptor antagonist, or completely discontinue acid-suppression therapy after symptom resolution.

At this time, omeprazole is the only PPI available OTC; it typically retails at $22 for 28 capsules. A generic version of the OTC omeprazole product has been approved. The cost is generally $13 to $15 for 28 capsules. Each H₂ receptor antagonist is available as a generic, and OTC at half prescription strength. Of note, famotidine 20-mg tablets and ranitidine 150-mg and 300-mg tablets are available on many of the $4 prescription plans at retail pharmacies.

YOUR PATIENT HAS NO INSURANCE

Your patient reports he has been taking omeprazole 20 mg daily, as you prescribed, for the past 2 weeks. His heart-burn symptoms have improved and he no longer needs to use Tums for breakthrough symptoms, as he did when he was taking Pepcid.

You considered pantoprazole and omeprazole because they are both available in generic form. Since there are no significant differences in efficacy of the 2 drugs for the treatment of GERD, you decided to prescribe pantoprazole because it will cost less for the patient, who has no prescription insurance. The pharmacy calls you, asking if generic omeprazole could be used instead due to the cost difference.

According to http://www.drugstore.com, generic pantoprazole would cost the patient $110 per month and generic omeprazole would cost the patient $63 per month.

Even though costs at local pharmacies vary and are often higher than online costs, the savings to the patient seemed significant enough to change

I’ve seen my share of missed diagnoses over the years while caring for patients who, through physician- or self-referral, have made their way to our multi-specialty group practice where I focus solely on skin.

There was the 93-year-old patient whose “sun spot” had been evaluated and treated by 2 different dermatologists in the past and turned out to be a lentigo maligna melanoma (FIGURE 1).

There was the patient who had a lesion on her lip for “at least 10—maybe 20—years” that neither caught the attention of her physician, nor her dentist (FIGURE 2). Histology showed she had an infiltrative basal cell carcinoma.

And then there was the wife of a healthcare professional who decided she wanted a “second opinion” for the asymptomatic lesion on her leg that her husband assured her was benign. Her diagnosis was not so simple: She had a MELanocytic Tumor of Unknown Malignant Potential (MELTUMP) that required careful follow-up (FIGURE 3).

Early detection, as we all know, is the name of the game when it comes to skin malignancies. Yet every day, opportunities to catch small, early lesions are missed.

During the past couple of years, I’ve had thousands of patient visits for skin problems and diagnosed more than 1000 skin malignancies. The majority of patients have had some treatment for their presenting dermatosis prior to arrival. Based on my experiences with these patients, I’ve developed a list of common dermatology “mistakes.” Here they are, with some tips for avoiding them.

FIGURE 1
Melanoma missed by 2 dermatologists

FIGURE 2
Lesion on lip for “10—maybe 20—years”

FIGURE 3
A case of MELTUMP

Mistake #1: Not looking (and not biopsying)

I had a woman come into the office to have a lesion assessed. She had seen a dermatologist a couple of weeks earlier and even had a number of lesions removed during that visit. The patient told me that she’d repeatedly tried to show the dermatologist one specific lesion—the one of greatest concern to her—just below her underpants line, but the physician was in and out so fast each time, she never had the chance to point out this one melanocytic, changing lesion.

The lesion turned out to be a dysplastic nevus with severe architectural and cytologic atypia. This type of lesion requires histology to differentiate it from melanoma, and could just as easily have been a melanoma.

Almost daily I treat patients who are being seen by their primary care physicians regularly, and have obvious basal cell carcinomas (BCC) or squamous cell carcinomas. I have even found skin malignancies on physicians, their spouses, and their family members.¹ These lesions can be easily missed—if you don’t look carefully.

Consider, the following:

• FIGURE 4 illustrates a superficial BCC on the forearm of a physician who was totally unaware of it. (It was detected on “routine” skin examination.)
• FIGURE 5 illustrates a BCC on a patient’s central forehead that, by her history, had been there for many years, and was not of any concern to her. The patient was referred to our office for evaluation of itchy skin on her legs.
• FIGURE 2 illustrates a lesion that, according to the patient, had been on her lip for at least 10—and perhaps even 20—years and was of no concern to her. (It was not the reason for the visit.) Over the years, this patient certainly had numerous primary care and dental visits, but no one “saw” the lesion. Histology confirmed the clinical impression of BCC.

FIGURE 4
Superficial BCC on physician’s forearm

FIGURE 5
“Mole” on forehead for many years

Mistake #2: Using insufficient light

As a former family practice academic, I used to preach to residents that they needed to use “light, light, and more light” for evaluation of skin lesions. Despite this, I was often asked to evaluate a patient with a resident who hadn’t even bothered to turn on a goose-neck lamp for illumination.

Even with my current “double bank” daylight fluorescent examination room lighting, it often takes additional (surgical-type) lighting to see the diagnostic features of skin lesions. Without such intense light, it is often impossible to see whether there is pearliness, rolled edges, or fine telangiectasia.

Mistake #3: Using insufficient (or no) magnification

I was once examining a patient in a hospital room that had inadequate light, despite my best efforts. So I took out my digital camera with flash and autofocus feature and photographed the lesion. I then looked at the lesion on the camera’s LCD monitor and determined that it was a BCC.

The benefit of the camera was 2-fold: Not only did the flash serve as an instant source of light, but the macro feature also provided magnification. Viewing a magnified digital image on a computer screen also allows unhurried, self “second opinions,” where details can often be ascertained that were not immediately apparent in “real time,” such as rolled edges, telangiectasia, dots, streaks, and subtleties of color.

Mistake #4: Assuming that pathology is a perfect science

Most physicians assume that dermatopathologists have a high rate of interrater concordance with diagnoses such as melanoma. Unfortunately, that is not always the case. Consider the following:

• As part of a National Institutes of Health consensus conference on melanoma, 8 dermatopathologists considered experts in melanoma were asked to provide 5 slides each. The slides were relabeled and sent to the same 8 dermatopathologists. (Three slides were eliminated.) Their findings: At the extremes, 1 pathologist called 21 cases melanoma and 16 benign, whereas another called 10 melanoma, 26 benign, and one indeterminate.² (Remember: These were all experts in melanoma.)
• In a study of 30 melanocytic lesion specimens (including Spitzoid lesions), 10 Harvard dermatopathologists evaluated each sample independently of each other. Given 5 diagnostic categories to choose from, in only one case did as many as 6 of the 10 agree on a diagnosis. In all of these cases, there was long-term clinical follow-up, so the biologic behavior of these lesions was known. Some lesions that proved fatal were categorized by most observers as benign (eg, Spitz nevi or atypical Spitz tumors). The converse, reporting benign lesions as melanoma, also occurred.³

So consider this: If this degree of discordance occurs among dermatopathologists, what results could we expect from non-dermatopathologists?

I have personally seen instances where reports of melanoma from non-dermatopathologists did not even report Clark and Breslow staging information (although one could determine Clark staging from reading the body of the report), and reports of dysplastic nevi that were accompanied by recommendations for re-excision with 1 cm margins.

When I have a report from a general pathologist suggesting a potentially worrisome lesion (melanoma, severely dysplastic nevus, [atypical] Spitz nevus), I always suggest to my patients that we get a dermatopathologic second opinion. (I send all my dermatopathology specimens to dermatopathologists, so this applies to patients referred in with prior pathology in hand.)

Sometimes, even the dermatopathologists do not agree on the nature of the lesion. In such cases, I have my “MELTUMP discussion” with patients. That is, I tell patients that we don’t know for sure what it is, and that ultimately only the final lab test—time—will tell us the true nature of the lesion (FIGURE 3).⁴

Mistake #5: Freezing neoplasms without a definitive Dx

“We’ll freeze it and if it doesn’t go away, then…”

This approach poses a significant risk to you (medicolegally) and your patient.

While most of the time what I see has been inappropriately frozen first by first-line providers, that is not always the case. Dermatologists also fall into this trap. FIGURE 6 shows a lesion just behind the hairline on the frontoparietal scalp that was frozen by a very good, and reputable, dermatologist. The patient came to me for a second opinion with an “obvious” BCC.

Some clinicians are “thrown off” when a lesion (like the one on this patient) has hair. Some sources⁶ indicate that BCCs never have hair, but this is patently untrue.

FIGURE 6
This shouldn’t have been frozen

Mistake #6: Treating psoriasis with systemic corticosteroids

Plaque psoriasis can, albeit uncommonly, be transformed to pustular psoriasis after the administration of oral or injectable systemic corticosteroids.⁷ Although this rarely occurs, most experts consider this poor practice and not worth the risk. In addition, some experts note that systemic glucocorticoids are a drug trigger for inducing or exacerbating psoriasis.⁸

Mistake #7: Doing shave biopsies on melanocytic lesions

For a melanoma, not only can shaving part way through the vertical dimension of the lesion interfere with staging, it can also hinder the pathologist’s ability to arrive at the correct diagnosis.⁹

Mistake #8: Using corticosteroid/antifungal combination products

Corticosteroid/antifungal combination products are generally shunned by dermatologists, although they are used extensively by nondermatologists.⁹ The difficulty with a preparation like Lotrisone, which contains a class III corticosteroid (betamethasone dipropionate [Diprosone]) and the antifungal clotrimazole, is that it is often used long-term for presumed fungal infection on thin-skinned areas. Unfortunately, though, chronic use in these areas can lead to atrophy and striae (FIGURE 7).

Additionally, corticosteroid is essentially “fungus food.” Majocchi’s granulomas can form because the corticosteroid interferes with clotrimazole’s antifungal effect. Note also that these combination products can suppress fungus sufficiently to render cultures and KOH preparations falsely negative and alter the clinical appearance of psoriasiform dermatitis, interfering with subsequent, accurate diagnosis.

FIGURE 7
Striae after corticosteroid combination therapy

Mistake #9: Corticosteroid underdosing and undercounseling

It’s not uncommon during the warm weather months for me to see patients who are near finishing a Medrol Dosepak that was prescribed by their primary care physicians for a case of contact dermatitis (eg, poison ivy). They come to me because the eruption has returned and it is “as bad as ever.”

Underdosing. Medrol Dosepaks are generally underpowered (too low a dosage) and too short a course.^7,10,11

Undercounseling. Patients don’t always realize that contact dermatitis may actually last for 3 weeks or longer. They may also mistakenly believe that systemic treatment will get them through the whole episode (rather than the worst part).

Mistake #10: Requiring red flags in both history and exam

Skin diagnosis is an “or” game—not an “and” game. By that I mean: If either the history (eg, rapid change, bleeding, crusting, nonhealing ulcer) or the examination is worrisome, biopsy. Even dermoscopy can be completely reassuring with biopsy yielding a melanoma.¹² Note, too, our earlier examples of patients with suspect examinations who gave reassuring histories of lesions that had been present for many years. Either a worrisome history or a suspect examination is sufficient for concern. Remember, in general, the worst-case scenario from a biopsy is a scar; from a missed melanoma, an autopsy report.

Correspondence
Gary N. Fox, MD, 1400 E 2nd St, Defiance, OH 43512; [email protected]

I’ve seen my share of missed diagnoses over the years while caring for patients who, through physician- or self-referral, have made their way to our multi-specialty group practice where I focus solely on skin.

There was the 93-year-old patient whose “sun spot” had been evaluated and treated by 2 different dermatologists in the past and turned out to be a lentigo maligna melanoma (FIGURE 1).

There was the patient who had a lesion on her lip for “at least 10—maybe 20—years” that neither caught the attention of her physician, nor her dentist (FIGURE 2). Histology showed she had an infiltrative basal cell carcinoma.

And then there was the wife of a healthcare professional who decided she wanted a “second opinion” for the asymptomatic lesion on her leg that her husband assured her was benign. Her diagnosis was not so simple: She had a MELanocytic Tumor of Unknown Malignant Potential (MELTUMP) that required careful follow-up (FIGURE 3).

Early detection, as we all know, is the name of the game when it comes to skin malignancies. Yet every day, opportunities to catch small, early lesions are missed.

During the past couple of years, I’ve had thousands of patient visits for skin problems and diagnosed more than 1000 skin malignancies. The majority of patients have had some treatment for their presenting dermatosis prior to arrival. Based on my experiences with these patients, I’ve developed a list of common dermatology “mistakes.” Here they are, with some tips for avoiding them.

FIGURE 1
Melanoma missed by 2 dermatologists

FIGURE 2
Lesion on lip for “10—maybe 20—years”

FIGURE 3
A case of MELTUMP

Mistake #1: Not looking (and not biopsying)

I had a woman come into the office to have a lesion assessed. She had seen a dermatologist a couple of weeks earlier and even had a number of lesions removed during that visit. The patient told me that she’d repeatedly tried to show the dermatologist one specific lesion—the one of greatest concern to her—just below her underpants line, but the physician was in and out so fast each time, she never had the chance to point out this one melanocytic, changing lesion.

The lesion turned out to be a dysplastic nevus with severe architectural and cytologic atypia. This type of lesion requires histology to differentiate it from melanoma, and could just as easily have been a melanoma.

Almost daily I treat patients who are being seen by their primary care physicians regularly, and have obvious basal cell carcinomas (BCC) or squamous cell carcinomas. I have even found skin malignancies on physicians, their spouses, and their family members.¹ These lesions can be easily missed—if you don’t look carefully.

Consider, the following:

• FIGURE 4 illustrates a superficial BCC on the forearm of a physician who was totally unaware of it. (It was detected on “routine” skin examination.)
• FIGURE 5 illustrates a BCC on a patient’s central forehead that, by her history, had been there for many years, and was not of any concern to her. The patient was referred to our office for evaluation of itchy skin on her legs.
• FIGURE 2 illustrates a lesion that, according to the patient, had been on her lip for at least 10—and perhaps even 20—years and was of no concern to her. (It was not the reason for the visit.) Over the years, this patient certainly had numerous primary care and dental visits, but no one “saw” the lesion. Histology confirmed the clinical impression of BCC.

FIGURE 4
Superficial BCC on physician’s forearm

FIGURE 5
“Mole” on forehead for many years

Mistake #2: Using insufficient light

As a former family practice academic, I used to preach to residents that they needed to use “light, light, and more light” for evaluation of skin lesions. Despite this, I was often asked to evaluate a patient with a resident who hadn’t even bothered to turn on a goose-neck lamp for illumination.

Even with my current “double bank” daylight fluorescent examination room lighting, it often takes additional (surgical-type) lighting to see the diagnostic features of skin lesions. Without such intense light, it is often impossible to see whether there is pearliness, rolled edges, or fine telangiectasia.

Mistake #3: Using insufficient (or no) magnification

I was once examining a patient in a hospital room that had inadequate light, despite my best efforts. So I took out my digital camera with flash and autofocus feature and photographed the lesion. I then looked at the lesion on the camera’s LCD monitor and determined that it was a BCC.

The benefit of the camera was 2-fold: Not only did the flash serve as an instant source of light, but the macro feature also provided magnification. Viewing a magnified digital image on a computer screen also allows unhurried, self “second opinions,” where details can often be ascertained that were not immediately apparent in “real time,” such as rolled edges, telangiectasia, dots, streaks, and subtleties of color.

Mistake #4: Assuming that pathology is a perfect science

Most physicians assume that dermatopathologists have a high rate of interrater concordance with diagnoses such as melanoma. Unfortunately, that is not always the case. Consider the following:

• As part of a National Institutes of Health consensus conference on melanoma, 8 dermatopathologists considered experts in melanoma were asked to provide 5 slides each. The slides were relabeled and sent to the same 8 dermatopathologists. (Three slides were eliminated.) Their findings: At the extremes, 1 pathologist called 21 cases melanoma and 16 benign, whereas another called 10 melanoma, 26 benign, and one indeterminate.² (Remember: These were all experts in melanoma.)
• In a study of 30 melanocytic lesion specimens (including Spitzoid lesions), 10 Harvard dermatopathologists evaluated each sample independently of each other. Given 5 diagnostic categories to choose from, in only one case did as many as 6 of the 10 agree on a diagnosis. In all of these cases, there was long-term clinical follow-up, so the biologic behavior of these lesions was known. Some lesions that proved fatal were categorized by most observers as benign (eg, Spitz nevi or atypical Spitz tumors). The converse, reporting benign lesions as melanoma, also occurred.³

So consider this: If this degree of discordance occurs among dermatopathologists, what results could we expect from non-dermatopathologists?

I have personally seen instances where reports of melanoma from non-dermatopathologists did not even report Clark and Breslow staging information (although one could determine Clark staging from reading the body of the report), and reports of dysplastic nevi that were accompanied by recommendations for re-excision with 1 cm margins.

When I have a report from a general pathologist suggesting a potentially worrisome lesion (melanoma, severely dysplastic nevus, [atypical] Spitz nevus), I always suggest to my patients that we get a dermatopathologic second opinion. (I send all my dermatopathology specimens to dermatopathologists, so this applies to patients referred in with prior pathology in hand.)

Sometimes, even the dermatopathologists do not agree on the nature of the lesion. In such cases, I have my “MELTUMP discussion” with patients. That is, I tell patients that we don’t know for sure what it is, and that ultimately only the final lab test—time—will tell us the true nature of the lesion (FIGURE 3).⁴

Mistake #5: Freezing neoplasms without a definitive Dx

“We’ll freeze it and if it doesn’t go away, then…”

This approach poses a significant risk to you (medicolegally) and your patient.

While most of the time what I see has been inappropriately frozen first by first-line providers, that is not always the case. Dermatologists also fall into this trap. FIGURE 6 shows a lesion just behind the hairline on the frontoparietal scalp that was frozen by a very good, and reputable, dermatologist. The patient came to me for a second opinion with an “obvious” BCC.

Some clinicians are “thrown off” when a lesion (like the one on this patient) has hair. Some sources⁶ indicate that BCCs never have hair, but this is patently untrue.

FIGURE 6
This shouldn’t have been frozen

Mistake #6: Treating psoriasis with systemic corticosteroids

Plaque psoriasis can, albeit uncommonly, be transformed to pustular psoriasis after the administration of oral or injectable systemic corticosteroids.⁷ Although this rarely occurs, most experts consider this poor practice and not worth the risk. In addition, some experts note that systemic glucocorticoids are a drug trigger for inducing or exacerbating psoriasis.⁸

Mistake #7: Doing shave biopsies on melanocytic lesions

For a melanoma, not only can shaving part way through the vertical dimension of the lesion interfere with staging, it can also hinder the pathologist’s ability to arrive at the correct diagnosis.⁹

Mistake #8: Using corticosteroid/antifungal combination products

Corticosteroid/antifungal combination products are generally shunned by dermatologists, although they are used extensively by nondermatologists.⁹ The difficulty with a preparation like Lotrisone, which contains a class III corticosteroid (betamethasone dipropionate [Diprosone]) and the antifungal clotrimazole, is that it is often used long-term for presumed fungal infection on thin-skinned areas. Unfortunately, though, chronic use in these areas can lead to atrophy and striae (FIGURE 7).

Additionally, corticosteroid is essentially “fungus food.” Majocchi’s granulomas can form because the corticosteroid interferes with clotrimazole’s antifungal effect. Note also that these combination products can suppress fungus sufficiently to render cultures and KOH preparations falsely negative and alter the clinical appearance of psoriasiform dermatitis, interfering with subsequent, accurate diagnosis.

FIGURE 7
Striae after corticosteroid combination therapy

Mistake #9: Corticosteroid underdosing and undercounseling

It’s not uncommon during the warm weather months for me to see patients who are near finishing a Medrol Dosepak that was prescribed by their primary care physicians for a case of contact dermatitis (eg, poison ivy). They come to me because the eruption has returned and it is “as bad as ever.”

Underdosing. Medrol Dosepaks are generally underpowered (too low a dosage) and too short a course.^7,10,11

Undercounseling. Patients don’t always realize that contact dermatitis may actually last for 3 weeks or longer. They may also mistakenly believe that systemic treatment will get them through the whole episode (rather than the worst part).

Mistake #10: Requiring red flags in both history and exam

Skin diagnosis is an “or” game—not an “and” game. By that I mean: If either the history (eg, rapid change, bleeding, crusting, nonhealing ulcer) or the examination is worrisome, biopsy. Even dermoscopy can be completely reassuring with biopsy yielding a melanoma.¹² Note, too, our earlier examples of patients with suspect examinations who gave reassuring histories of lesions that had been present for many years. Either a worrisome history or a suspect examination is sufficient for concern. Remember, in general, the worst-case scenario from a biopsy is a scar; from a missed melanoma, an autopsy report.

Correspondence
Gary N. Fox, MD, 1400 E 2nd St, Defiance, OH 43512; [email protected]

I’ve seen my share of missed diagnoses over the years while caring for patients who, through physician- or self-referral, have made their way to our multi-specialty group practice where I focus solely on skin.

There was the 93-year-old patient whose “sun spot” had been evaluated and treated by 2 different dermatologists in the past and turned out to be a lentigo maligna melanoma (FIGURE 1).

There was the patient who had a lesion on her lip for “at least 10—maybe 20—years” that neither caught the attention of her physician, nor her dentist (FIGURE 2). Histology showed she had an infiltrative basal cell carcinoma.

And then there was the wife of a healthcare professional who decided she wanted a “second opinion” for the asymptomatic lesion on her leg that her husband assured her was benign. Her diagnosis was not so simple: She had a MELanocytic Tumor of Unknown Malignant Potential (MELTUMP) that required careful follow-up (FIGURE 3).

Early detection, as we all know, is the name of the game when it comes to skin malignancies. Yet every day, opportunities to catch small, early lesions are missed.

During the past couple of years, I’ve had thousands of patient visits for skin problems and diagnosed more than 1000 skin malignancies. The majority of patients have had some treatment for their presenting dermatosis prior to arrival. Based on my experiences with these patients, I’ve developed a list of common dermatology “mistakes.” Here they are, with some tips for avoiding them.

FIGURE 1
Melanoma missed by 2 dermatologists

FIGURE 2
Lesion on lip for “10—maybe 20—years”

FIGURE 3
A case of MELTUMP

Mistake #1: Not looking (and not biopsying)

I had a woman come into the office to have a lesion assessed. She had seen a dermatologist a couple of weeks earlier and even had a number of lesions removed during that visit. The patient told me that she’d repeatedly tried to show the dermatologist one specific lesion—the one of greatest concern to her—just below her underpants line, but the physician was in and out so fast each time, she never had the chance to point out this one melanocytic, changing lesion.

The lesion turned out to be a dysplastic nevus with severe architectural and cytologic atypia. This type of lesion requires histology to differentiate it from melanoma, and could just as easily have been a melanoma.

Almost daily I treat patients who are being seen by their primary care physicians regularly, and have obvious basal cell carcinomas (BCC) or squamous cell carcinomas. I have even found skin malignancies on physicians, their spouses, and their family members.¹ These lesions can be easily missed—if you don’t look carefully.

Consider, the following:

• FIGURE 4 illustrates a superficial BCC on the forearm of a physician who was totally unaware of it. (It was detected on “routine” skin examination.)
• FIGURE 5 illustrates a BCC on a patient’s central forehead that, by her history, had been there for many years, and was not of any concern to her. The patient was referred to our office for evaluation of itchy skin on her legs.
• FIGURE 2 illustrates a lesion that, according to the patient, had been on her lip for at least 10—and perhaps even 20—years and was of no concern to her. (It was not the reason for the visit.) Over the years, this patient certainly had numerous primary care and dental visits, but no one “saw” the lesion. Histology confirmed the clinical impression of BCC.

FIGURE 4
Superficial BCC on physician’s forearm

FIGURE 5
“Mole” on forehead for many years

Mistake #2: Using insufficient light

As a former family practice academic, I used to preach to residents that they needed to use “light, light, and more light” for evaluation of skin lesions. Despite this, I was often asked to evaluate a patient with a resident who hadn’t even bothered to turn on a goose-neck lamp for illumination.

Even with my current “double bank” daylight fluorescent examination room lighting, it often takes additional (surgical-type) lighting to see the diagnostic features of skin lesions. Without such intense light, it is often impossible to see whether there is pearliness, rolled edges, or fine telangiectasia.

Mistake #3: Using insufficient (or no) magnification

I was once examining a patient in a hospital room that had inadequate light, despite my best efforts. So I took out my digital camera with flash and autofocus feature and photographed the lesion. I then looked at the lesion on the camera’s LCD monitor and determined that it was a BCC.

The benefit of the camera was 2-fold: Not only did the flash serve as an instant source of light, but the macro feature also provided magnification. Viewing a magnified digital image on a computer screen also allows unhurried, self “second opinions,” where details can often be ascertained that were not immediately apparent in “real time,” such as rolled edges, telangiectasia, dots, streaks, and subtleties of color.

Mistake #4: Assuming that pathology is a perfect science

Most physicians assume that dermatopathologists have a high rate of interrater concordance with diagnoses such as melanoma. Unfortunately, that is not always the case. Consider the following:

• As part of a National Institutes of Health consensus conference on melanoma, 8 dermatopathologists considered experts in melanoma were asked to provide 5 slides each. The slides were relabeled and sent to the same 8 dermatopathologists. (Three slides were eliminated.) Their findings: At the extremes, 1 pathologist called 21 cases melanoma and 16 benign, whereas another called 10 melanoma, 26 benign, and one indeterminate.² (Remember: These were all experts in melanoma.)
• In a study of 30 melanocytic lesion specimens (including Spitzoid lesions), 10 Harvard dermatopathologists evaluated each sample independently of each other. Given 5 diagnostic categories to choose from, in only one case did as many as 6 of the 10 agree on a diagnosis. In all of these cases, there was long-term clinical follow-up, so the biologic behavior of these lesions was known. Some lesions that proved fatal were categorized by most observers as benign (eg, Spitz nevi or atypical Spitz tumors). The converse, reporting benign lesions as melanoma, also occurred.³

So consider this: If this degree of discordance occurs among dermatopathologists, what results could we expect from non-dermatopathologists?

I have personally seen instances where reports of melanoma from non-dermatopathologists did not even report Clark and Breslow staging information (although one could determine Clark staging from reading the body of the report), and reports of dysplastic nevi that were accompanied by recommendations for re-excision with 1 cm margins.

When I have a report from a general pathologist suggesting a potentially worrisome lesion (melanoma, severely dysplastic nevus, [atypical] Spitz nevus), I always suggest to my patients that we get a dermatopathologic second opinion. (I send all my dermatopathology specimens to dermatopathologists, so this applies to patients referred in with prior pathology in hand.)

Sometimes, even the dermatopathologists do not agree on the nature of the lesion. In such cases, I have my “MELTUMP discussion” with patients. That is, I tell patients that we don’t know for sure what it is, and that ultimately only the final lab test—time—will tell us the true nature of the lesion (FIGURE 3).⁴

Mistake #5: Freezing neoplasms without a definitive Dx

“We’ll freeze it and if it doesn’t go away, then…”

This approach poses a significant risk to you (medicolegally) and your patient.

While most of the time what I see has been inappropriately frozen first by first-line providers, that is not always the case. Dermatologists also fall into this trap. FIGURE 6 shows a lesion just behind the hairline on the frontoparietal scalp that was frozen by a very good, and reputable, dermatologist. The patient came to me for a second opinion with an “obvious” BCC.

Some clinicians are “thrown off” when a lesion (like the one on this patient) has hair. Some sources⁶ indicate that BCCs never have hair, but this is patently untrue.

FIGURE 6
This shouldn’t have been frozen

Mistake #6: Treating psoriasis with systemic corticosteroids

Plaque psoriasis can, albeit uncommonly, be transformed to pustular psoriasis after the administration of oral or injectable systemic corticosteroids.⁷ Although this rarely occurs, most experts consider this poor practice and not worth the risk. In addition, some experts note that systemic glucocorticoids are a drug trigger for inducing or exacerbating psoriasis.⁸

Mistake #7: Doing shave biopsies on melanocytic lesions

For a melanoma, not only can shaving part way through the vertical dimension of the lesion interfere with staging, it can also hinder the pathologist’s ability to arrive at the correct diagnosis.⁹

Mistake #8: Using corticosteroid/antifungal combination products

Corticosteroid/antifungal combination products are generally shunned by dermatologists, although they are used extensively by nondermatologists.⁹ The difficulty with a preparation like Lotrisone, which contains a class III corticosteroid (betamethasone dipropionate [Diprosone]) and the antifungal clotrimazole, is that it is often used long-term for presumed fungal infection on thin-skinned areas. Unfortunately, though, chronic use in these areas can lead to atrophy and striae (FIGURE 7).

Additionally, corticosteroid is essentially “fungus food.” Majocchi’s granulomas can form because the corticosteroid interferes with clotrimazole’s antifungal effect. Note also that these combination products can suppress fungus sufficiently to render cultures and KOH preparations falsely negative and alter the clinical appearance of psoriasiform dermatitis, interfering with subsequent, accurate diagnosis.

FIGURE 7
Striae after corticosteroid combination therapy

Mistake #9: Corticosteroid underdosing and undercounseling

It’s not uncommon during the warm weather months for me to see patients who are near finishing a Medrol Dosepak that was prescribed by their primary care physicians for a case of contact dermatitis (eg, poison ivy). They come to me because the eruption has returned and it is “as bad as ever.”

Underdosing. Medrol Dosepaks are generally underpowered (too low a dosage) and too short a course.^7,10,11

Undercounseling. Patients don’t always realize that contact dermatitis may actually last for 3 weeks or longer. They may also mistakenly believe that systemic treatment will get them through the whole episode (rather than the worst part).

Mistake #10: Requiring red flags in both history and exam

Skin diagnosis is an “or” game—not an “and” game. By that I mean: If either the history (eg, rapid change, bleeding, crusting, nonhealing ulcer) or the examination is worrisome, biopsy. Even dermoscopy can be completely reassuring with biopsy yielding a melanoma.¹² Note, too, our earlier examples of patients with suspect examinations who gave reassuring histories of lesions that had been present for many years. Either a worrisome history or a suspect examination is sufficient for concern. Remember, in general, the worst-case scenario from a biopsy is a scar; from a missed melanoma, an autopsy report.

Correspondence
Gary N. Fox, MD, 1400 E 2nd St, Defiance, OH 43512; [email protected]

“I’ve always had some stomach pain,” says Mary Jane, a 36-year-old patient, whom you are seeing for the first time. “But this is becoming unmanageable.”

You see from Mary Jane’s chart that she has been to your group practice twice over the last few years with complaints of diarrhea that were diagnosed as gastroenteritis. She tells you that after each visit, it got “a little better,” but it “never really went away.”

She also tells you that her stomach bothers her a few days every month, but that it feels a little better after she defecates. She says that she thinks she may be sensitive to certain foods.

“Things are getting worse,” she tells you. “The bloating, pain, and diarrhea have gotten to the point that I can’t go anywhere without worrying where the nearest bathroom is.”

“I’ve already had my gallbladder and appendix removed,” she says, “but I still feel lousy.”

On exam, Mary Jane appears to be in good health. She is afebrile and has a normal abdominal exam, except for very mild diffuse tenderness. She tells you that she has not traveled to any locations where access to clean food or water is suspect. Her stool is heme negative. Urine dip is negative and she is not pregnant.

“Do you know what’s the matter with me?” she asks you. “Or do I need to see a specialist?”

No need for a specialist

Your patient meets the criteria for irritable bowel syndrome (IBS) set by Rome III, an international panel of experts in the field of functional gastrointestinal disorders. She’s had recurrent abdominal pain/discomfort for at least 6 months, and she’s had symptoms at least 3 days a month for the last 3 months (TABLE 1).¹

Mary Jane tells you that she is relieved to finally get a diagnosis, having struggled for some time with stomach pain that never really went away. Her experience is not unusual: The wide range of concomitant gastrointestinal and extraintestinal symptoms in IBS patients make the initial diagnosis difficult.^2,3 She’s also relieved to learn from you that contrary to popular belief, IBS has a physiologic basis and that psychosocial stressors merely aggravate an already painful and dysfunctional bowel. (See and Irritable bowel syndrome: Not just a functional disorder^4-7)

We have a number of treatment options to offer patients like Mary Jane, including alosetron, tegaserod, lubiprostone, selective serotonin reuptake inhibitors (SSRIs), and tricyclic antidepressants, as well as complementary therapies (such as probiotics) and behavioral therapy. But before we review the evidence behind the different options, let’s take a look at the factors that may be at work in IBS, and the things you’ll want to pay special attention to during your assessment.

TABLE 1
Is it IBS? Rome III criteria provide guidance¹

Infection, bacterial overgrowth may play a role

Between 4% and 26% of patients contract IBS for the first time after gastroenteritis.⁸ Tissue from patients with post-infectious IBS shows chronic mucosal lymphocytosis^9,10 associated with enterochromaffin cell hyperplasia.¹¹ Spiller et al¹² noted these changes, as well as an increase in gut permeability, for more than 1 year after the resolution of Campylobacter enteritis. Using prednisolone for early intervention suppressed T-cell lymphocyte counts but not IBS symptoms.¹³

The role of bacterial overgrowth in IBS is controversial. Pimentel et al¹⁴ reported that 78% of 202 IBS patients had small intestinal bacterial overgrowth. After treatment, almost half no longer met the Rome criteria for IBS and showed a statistically significant improvement in diarrhea and abdominal pain but not in straining, urgency, or bloating.

A second study from the same group demonstrated that 84% of 111 consecutive IBS patients had small intestinal bacterial overgrowth compared with 20% of healthy controls. Thirty-five percent of the IBS patients treated with neomycin had improved composite scores compared with 11.4% of those receiving placebo.¹⁵

Correlation between small intestinal bacterial overgrowth and Rome criteria for IBS has not been replicated by other centers, and other investigators who have looked into this relationship have suggested that small intestinal bacterial overgrowth is not associated with IBS.^16,17

Genetics and the environment may also be at work

Familial clustering of IBS is commonly seen.^3,18 Several studies have suggested a genetic role but a recently published comprehensive review suggests that the evidence of genetic susceptibility to IBS is modest, if present at all.¹⁹

Research tells us that the environment also plays a role; specifically, psychological stress is related to IBS symptoms. In one GI referral practice, women with diagnoses of functional disorders had experienced a high frequency of abuse.²⁰

Abuse history is also associated with more severe symptoms, worse daily function, greater psychological distress, and poor health outcome.²¹ Removal of these stressors provides significant relief to the patient, but IBS still exists in the absence of significant psychosocial pressures.

Few tests (if any) are needed for diagnosis

IBS historically has been a diagnosis of exclusion, but this is no longer the case. You can make the diagnosis with few—if any—diagnostic tests, as long as there are no “red flag” findings or alarm symptoms (TABLE 2^1,22,23). In particular, surgery is not required to make a diagnosis, nor will it improve a patient’s condition, yet the incidence of abdominal and pelvic surgery in IBS patients is 87% greater, and cholecystectomy three-fold higher, than in the general population.²⁴

While taking a history, you will of course ask about the patient’s altered bowel habits. In addition, though, you will need to:

Ask about personal and family history of inflammatory bowel disease (IBD), colon cancer, celiac disease, pregnancy, recent overseas travel or camping exposure to parasites or contaminated food and water, and history of recent gastroenteritis.²⁵

Ask about alarm symptoms and red flags. Red flags on your examination include any focal positive physical findings, such as peritoneal signs, heme-positive stool, abdominal mass, or pelvic findings. Alarm symptoms that the patient may talk about include things like significant weight loss.

Red flags are based on observational data but have become the accepted standard of practice.^1,22,23,26 Extensive testing, including the routine use of blood tests, stool studies, and imaging, however, is not required.^22,25 If you have any doubt about history or findings, your diagnostic testing should focus on the issue in question.

When warranted by the presence of alarm symptoms or family history, you may need to schedule a colonoscopy to rule out IBD, tumors, or melanosis coli, which can be caused by excessive use of laxatives. Screening colonoscopy is the standard of care for all patients older than 50, regardless of symptoms.

Key in on food concerns. If specific foods aggravate symptoms, further investigation or a dietary exclusion trial may be helpful; however, even patients with proven lactase deficiency experience little or no bloating after drinking 240 mL milk.^1,27 You may want to test for celiac disease if indicated by clinical features such as diarrhea, local prevalence, or family history. Routine testing of celiac disease, however, is not supported by the evidence.^28,29

TABLE 2
These red flags and alarm symptoms should prompt further evaluation^1,22,23

Many treatment options, limited quality research

Few pharmaceutical compounds have been tested and proven effective in reproducible, high-quality, double-blind, placebo-controlled trials (TABLE 3).^1,29-43 In addition, no alternative or complementary therapies have been proven in quality clinical trials to date (TABLE 4).^39,44-46,50 Behavioral therapy has shown benefit, but lacks double-blind, placebo-controlled trial data required for a level A strength of recommendation (SOR) (TABLE 5).^1,47,48 That said, there are various options that can help patients with IBS—specifically, those who have IBS with diarrhea, IBS with constipation, IBS with mixed bowel habit (where stools are reported as >25% hard or lumpy and >25% loose or watery¹), or IBS with unspecified bowel habit.

TABLE 3
Pharmacologic options for IBS

TABLE 4
Complementary and alternative therapies for IBS

TABLE 5
Hypnotherapy and psychotherapy for IBS

IBS with diarrhea

Options all have “but” clauses

Alosetron, the 5-HT₃ receptor antagonist, has demonstrated efficacy in women (specifically) with IBS with diarrhea and has a grade A treatment recommendation from the American College of Gastroenterology.^29,30 Given the concerns about severe constipation and ischemic colitis, alosetron was withdrawn from the market in November 2000 but was reintroduced in June 2002 under a limited-use program for patients with severe IBS with diarrhea, in whom standard therapy has failed (SOR: A). Research has since shown that IBS patients have a greater risk for ischemic colitis than the general population.⁴⁹

Loperamide, a μ-opioid receptor agonist, which does not cross the blood-brain barrier, can be started at bedtime or in the morning at 2 mg and slowly titrated daily to effect. The effect, however, is limited to the bowel habits (SOR: B).³⁸

Anticholinergics can be used for abdominal pain or discomfort, particularly in patients with IBS with diarrhea. Despite their lengthy history and broad use in IBS populations, limited evidence supports their efficacy, and many are not available in the US (SOR: B).^35,36

Tricyclic antidepressants (TCAs) exert their effects by blocking the muscarinic receptors. TCAs can provide relief to patients with severe or refractory pain but perceived social stigma associated with taking antidepressants can be a barrier to this therapeutic approach (SOR: B).^36,41

IBS with constipation

Laxatives, lubiprostone are options

Osmotic laxatives such as polyethylene glycol or lactulose can improve constipation. Despite widespread over-the-counter and prescription use, however, evidence is lacking for their efficacy and tolerability in IBS (SOR: B).³⁹

Lubiprostone, a ClC2 chloride-channel opener, improved individual symptoms scores in 50 patients with IBS with constipation compared with placebo in a small phase II dose-ranging study (SOR: B).³⁷

Tegaserod, a partial 5-HT₄ receptor agonist, facilitates neurotransmission in the gut that is involved in motility and secretion and produces global symptom relief.³¹ The American College of Gastroenterology gave tegaserod a grade A recommendation for the treatment of women with IBS with constipation.²⁹

On March 30, 2007, Novartis Pharmaceuticals agreed to stop selling tegaserod maleate (Zelnorm) because a safety analysis found a higher chance of heart attack, stroke, and worsening chest pain that could become a heart attack in patients treated with Zelnorm, compared with those receiving placebo.³² In July 2007, the FDA announced that it would permit restricted use of the drug in patients who meet strict criteria, have no known or pre-existing heart problems, and who are in critical need of the drug.³³

Polycarbophil and ispaghula husk are the only fibers to have demonstrated any significant benefit in clinical trials for constipation,³⁵ but may make pain and bloating worse (SOR: B).

SSRIS and low-dose benzodiazepines are an option for patients who have coexisting psychological illness.⁴¹ There is limited evidence for SSRI treatment (citalopram, paroxetine), either alone or in combination with additional treatments (SOR: B).^35,41-43

IBS with mixed/unspecified bowel habit

Consider therapy

Cognitive behavioral therapy or other standard psychotherapy may be beneficial in many IBS patients (SOR: B).^1,48

Peppermint oil for IBS is efficacious in recurrent abdominal pain compared with placebo and anticholinergic agents (SOR: B).^39,50

Hypnosis has had a therapeutic impact on patients with IBS, even those whose conditions were refractory to other forms of therapy (SOR: B).⁴⁷

Certain probiotic therapies have shown improvement in global symptoms and may prove to be promising therapeutic agents (SOR: B).⁴⁶

Acupuncture has shown no proven efficacy in IBS (SOR: C).⁴⁴

Some Chinese herbal medicines may improve the symptoms of IBS. Positive findings from trials should be interpreted with caution, though, due to inadequate methodology, small sample sizes, and lack of confirming data. In addition, herbal remedies may contain unknown substances that can pose serious risk for adverse events and drug interactions (SOR: C).⁴⁵

Antibiotics for IBS patients with small intestinal bacterial overgrowth can provide some relief, according to Pimentel and colleagues,¹⁴ but other groups have not been able to duplicate these findings. Rifaximin in IBS and IBS-like symptoms has shown a sustained benefit (SOR: B).³⁴

Exercise or dietary therapies have no proven benefit in otherwise healthy IBS patients (SOR: C).¹

Set realistic goals, address patient fears

When caring for a patient with IBS, it’s important to set and discuss realistic goals. Be sure to address patient concerns, as well. IBS patients are frequently frustrated by a lack of diagnostic findings and may worry about being labeled as having a psychological disorder rather than having a true GI abnormality. This concern, especially if the patient feels that the physician is not adequately addressing her (or his) symptoms, may exacerbate the already troublesome IBS symptoms.

Assure your patient that comorbid psychological conditions do not cause symptoms, but can contribute to pain and bowel dysfunction. Consider the possibility of behavioral therapy, if indicated by patient history.

Advise the patient that the initial approach you are taking to alleviate her (or his) symptoms may provide significant improvement. Manage expectations appropriately and be open to discussion about what the patient may need to alleviate both physiologic and psychologic stressors that perpetuate symptoms. Family practitioners, not specialists, are ideally suited to address the patients’ needs and expectations as they are the ones who know the patients’ histories, personalities, and families best.¹ Tell the patient that rather than hoping for a cure, the goal for the both the physician and patient should be to achieve symptom relief.

Mary Jane finally gets some relief

After speaking with Mary Jane and doing a thorough exam, you reassure her that her symptoms meet the criteria for the diagnosis of IBS, and that research indicates that she can safely be treated for the disorder.

You tell your patient that you’d like to begin treatment by putting her on loperamide—2 capsules at onset of diarrhea and 1 capsule after each diarrheal episode to a maximum of 8 capsules a day and a low-dose amitriptyline (25 mg at bed-time). You explain that the tricyclic should provide her with some relief by modifying the way the nervous system of the intestine communicates with the brain.

Two months later, during a follow-up visit, Mary Jane tells you that the medications are providing her with relief, but when she feels particularly stressed at home, she notices that her symptoms flare up. You and she discuss the benefits of cognitive behavioral therapy, and you provide her with the names of some therapists in the area. You suggest that she consult her health plan and make some phone calls to identify a provider that she feels comfortable with.

You advise her to schedule another follow-up visit in 3 months so that you can see how the therapy is working. You also tell her to call any time she experiences significant pain or any symptoms that are persistent or worrisome to her.

Correspondence
Neil T. Moynihan, MD, Johnson Memorial Hospital, 201 Chestnut Hill Road, Stafford Springs, CT 06076; [email protected]