The healthcare industry is under major stress from steady declines in all sources of revenue. The drivers are multifactorial but include declining reimbursement from payors, a shift from fee-for-service to pay-for-performance, and state-by-state variability in patients covered by Medicaid, by high-deductible plans, or by being uninsured. In academic medical centers, rising overhead costs coupled with a reticence to raise student tuition and declining research funding streams have further compounded the situation.

Regardless of the actual numbers, all healthcare institutions are feeling the financial pinch. Most are intensely focused on cost-reduction efforts. The question is, what do physicians think about their role in these efforts, and what efforts will be most effective?

A recent survey of a large physician group practice found that many physicians do not know what their cost drivers are or do not think it is their role to participate in cost-reduction efforts.1 Of note, the group practice in the survey is a Pioneer Medicare accountable care organization (ACO) and participates in a combination of fee-for-service and capitated contracts.

Within the survey, the researchers embedded a cost-consciousness scale, which is a validated survey tool designed to assess daily cost consciousness. They also embedded other survey items to determine the physicians’ concerns for malpractice, comfort with diagnostic uncertainty, and perception of patient-family pressure for utilization of services. The average overall cost-consciousness score was 29 out of 44, with higher scores indicating more cost consciousness.

Almost all physicians agreed that they need to reduce unnecessary testing (97%), need to adhere to guidelines (98%), and have a responsibility to control costs (92%). However, 33% felt it was unfair for them to have to be both cost-conscious and concerned with the welfare of their patients.

Approximately a third of respondents also felt that there was too much emphasis on cost and that physicians are too busy to worry about costs.

More than a third (37%) said they did not have good knowledge about test-procedure cost within their system.

More than half of physicians felt pressure from patients to perform tests and procedures (from 68% of primary-care physicians, 58% of medical specialists, and 56% of surgical specialists) and felt pressure to refer to consultants (from 65% of primary-care physicians, 35% of medical specialists, and 34% of surgical specialists).

Based on this survey and other literature about physicians’ perceptions of their role and their ability to control costs, it is clear that the first step in understanding how to engage physicians in cost-reducing efforts is to understand what the drivers are for utilization and what the concerns are for reducing cost. Many hypothesize that the drivers to support the status quo include a fear of litigation, fear of missing a diagnosis, and patient demands for services. Another major driver of current utilization is that there is ongoing support for the status quo, as the majority of reimbursement for providers is still based on fee-for-service.

Change Efforts

One cost-reducing effort that has gained widespread enthusiasm from medical societies is the Choosing Wisely campaign. This campaign is an effort originally driven by the American Board of Internal Medicine (ABIM) Foundation to help physicians become aware of and reduce unnecessary utilization of resources. Each Choosing Wisely list is generated and endorsed by the relevant medical society and widely advertised to physicians via a variety of mechanisms. More than 70 medical societies have participated in the effort to date.

The recommendations are often widely accepted by those in the specialty since they are evidence-based and derived and advertised by their own specialty societies. In the survey mentioned above, almost all physicians agreed that their Choosing Wisely was a good source of guidance (ranging from 92% of surgical specialties to 97% of primary-care physicians). In order to drive the movement from the patient perspective, Consumer Reports has developed educational materials aimed at the consumer side of healthcare (ie, patients and families).

As Consumer Reports suggests, the first step to implementing cost-conscious care is to measure awareness of cost and causes of overutilization. By first understanding behaviors, a group can then work to impact such behaviors. It is highly likely that the drivers are different based on the specialty of the physician, the patient population being served, and the local healthcare market drivers. As such, there will not be a single, across-the-board solution to reducing unnecessary utilization of services (and therefore cost), but interventions will need to be tailored to different groups depending on the drivers of cost locally.

Depending on the issues within a group, successful interventions could include:

• Decision support tools (for appropriate use of consultants and diagnostic tests)
• Display of testing costs (not just at the time of ordering)
• Efforts aimed at patient education (both as general consumers as well as at the point of care)
• Malpractice reform to support physicians trying to balance cost consciousness with patient welfare

In Sum

We have a long way to go in engaging physicians in efforts to reduce unnecessary utilization and cost. I recommend that hospitalist practices utilize the survey tool used in this study to understand the perceived barriers and drivers of cost within their practice and work with their local administrative teams to better understand patterns of overutilization among their group. Then interventions can be designed to be evidence-based, tailored to local workflow, and both reliable and sustainable.

If done well, hospitalists can have a huge impact on utilization and cost and position their groups and their hospitals well to succeed in this cost-constrained era of healthcare. TH

References

1. Colla CH, Kinsella EA, Morden NE, Meyers DJ, Rosenthal MB, Sequist TD. Physician perception of Choosing Wisely and drivers of overuse. Am J Manag Care. 2016;22(5):337-343.

The healthcare industry is under major stress from steady declines in all sources of revenue. The drivers are multifactorial but include declining reimbursement from payors, a shift from fee-for-service to pay-for-performance, and state-by-state variability in patients covered by Medicaid, by high-deductible plans, or by being uninsured. In academic medical centers, rising overhead costs coupled with a reticence to raise student tuition and declining research funding streams have further compounded the situation.

Regardless of the actual numbers, all healthcare institutions are feeling the financial pinch. Most are intensely focused on cost-reduction efforts. The question is, what do physicians think about their role in these efforts, and what efforts will be most effective?

A recent survey of a large physician group practice found that many physicians do not know what their cost drivers are or do not think it is their role to participate in cost-reduction efforts.1 Of note, the group practice in the survey is a Pioneer Medicare accountable care organization (ACO) and participates in a combination of fee-for-service and capitated contracts.

Within the survey, the researchers embedded a cost-consciousness scale, which is a validated survey tool designed to assess daily cost consciousness. They also embedded other survey items to determine the physicians’ concerns for malpractice, comfort with diagnostic uncertainty, and perception of patient-family pressure for utilization of services. The average overall cost-consciousness score was 29 out of 44, with higher scores indicating more cost consciousness.

Almost all physicians agreed that they need to reduce unnecessary testing (97%), need to adhere to guidelines (98%), and have a responsibility to control costs (92%). However, 33% felt it was unfair for them to have to be both cost-conscious and concerned with the welfare of their patients.

Approximately a third of respondents also felt that there was too much emphasis on cost and that physicians are too busy to worry about costs.

More than a third (37%) said they did not have good knowledge about test-procedure cost within their system.

More than half of physicians felt pressure from patients to perform tests and procedures (from 68% of primary-care physicians, 58% of medical specialists, and 56% of surgical specialists) and felt pressure to refer to consultants (from 65% of primary-care physicians, 35% of medical specialists, and 34% of surgical specialists).

Based on this survey and other literature about physicians’ perceptions of their role and their ability to control costs, it is clear that the first step in understanding how to engage physicians in cost-reducing efforts is to understand what the drivers are for utilization and what the concerns are for reducing cost. Many hypothesize that the drivers to support the status quo include a fear of litigation, fear of missing a diagnosis, and patient demands for services. Another major driver of current utilization is that there is ongoing support for the status quo, as the majority of reimbursement for providers is still based on fee-for-service.

Change Efforts

One cost-reducing effort that has gained widespread enthusiasm from medical societies is the Choosing Wisely campaign. This campaign is an effort originally driven by the American Board of Internal Medicine (ABIM) Foundation to help physicians become aware of and reduce unnecessary utilization of resources. Each Choosing Wisely list is generated and endorsed by the relevant medical society and widely advertised to physicians via a variety of mechanisms. More than 70 medical societies have participated in the effort to date.

The recommendations are often widely accepted by those in the specialty since they are evidence-based and derived and advertised by their own specialty societies. In the survey mentioned above, almost all physicians agreed that their Choosing Wisely was a good source of guidance (ranging from 92% of surgical specialties to 97% of primary-care physicians). In order to drive the movement from the patient perspective, Consumer Reports has developed educational materials aimed at the consumer side of healthcare (ie, patients and families).

As Consumer Reports suggests, the first step to implementing cost-conscious care is to measure awareness of cost and causes of overutilization. By first understanding behaviors, a group can then work to impact such behaviors. It is highly likely that the drivers are different based on the specialty of the physician, the patient population being served, and the local healthcare market drivers. As such, there will not be a single, across-the-board solution to reducing unnecessary utilization of services (and therefore cost), but interventions will need to be tailored to different groups depending on the drivers of cost locally.

Depending on the issues within a group, successful interventions could include:

• Decision support tools (for appropriate use of consultants and diagnostic tests)
• Display of testing costs (not just at the time of ordering)
• Efforts aimed at patient education (both as general consumers as well as at the point of care)
• Malpractice reform to support physicians trying to balance cost consciousness with patient welfare

In Sum

We have a long way to go in engaging physicians in efforts to reduce unnecessary utilization and cost. I recommend that hospitalist practices utilize the survey tool used in this study to understand the perceived barriers and drivers of cost within their practice and work with their local administrative teams to better understand patterns of overutilization among their group. Then interventions can be designed to be evidence-based, tailored to local workflow, and both reliable and sustainable.

If done well, hospitalists can have a huge impact on utilization and cost and position their groups and their hospitals well to succeed in this cost-constrained era of healthcare. TH

References

1. Colla CH, Kinsella EA, Morden NE, Meyers DJ, Rosenthal MB, Sequist TD. Physician perception of Choosing Wisely and drivers of overuse. Am J Manag Care. 2016;22(5):337-343.

The healthcare industry is under major stress from steady declines in all sources of revenue. The drivers are multifactorial but include declining reimbursement from payors, a shift from fee-for-service to pay-for-performance, and state-by-state variability in patients covered by Medicaid, by high-deductible plans, or by being uninsured. In academic medical centers, rising overhead costs coupled with a reticence to raise student tuition and declining research funding streams have further compounded the situation.

Regardless of the actual numbers, all healthcare institutions are feeling the financial pinch. Most are intensely focused on cost-reduction efforts. The question is, what do physicians think about their role in these efforts, and what efforts will be most effective?

A recent survey of a large physician group practice found that many physicians do not know what their cost drivers are or do not think it is their role to participate in cost-reduction efforts.1 Of note, the group practice in the survey is a Pioneer Medicare accountable care organization (ACO) and participates in a combination of fee-for-service and capitated contracts.

Within the survey, the researchers embedded a cost-consciousness scale, which is a validated survey tool designed to assess daily cost consciousness. They also embedded other survey items to determine the physicians’ concerns for malpractice, comfort with diagnostic uncertainty, and perception of patient-family pressure for utilization of services. The average overall cost-consciousness score was 29 out of 44, with higher scores indicating more cost consciousness.

Almost all physicians agreed that they need to reduce unnecessary testing (97%), need to adhere to guidelines (98%), and have a responsibility to control costs (92%). However, 33% felt it was unfair for them to have to be both cost-conscious and concerned with the welfare of their patients.

Approximately a third of respondents also felt that there was too much emphasis on cost and that physicians are too busy to worry about costs.

More than a third (37%) said they did not have good knowledge about test-procedure cost within their system.

More than half of physicians felt pressure from patients to perform tests and procedures (from 68% of primary-care physicians, 58% of medical specialists, and 56% of surgical specialists) and felt pressure to refer to consultants (from 65% of primary-care physicians, 35% of medical specialists, and 34% of surgical specialists).

Based on this survey and other literature about physicians’ perceptions of their role and their ability to control costs, it is clear that the first step in understanding how to engage physicians in cost-reducing efforts is to understand what the drivers are for utilization and what the concerns are for reducing cost. Many hypothesize that the drivers to support the status quo include a fear of litigation, fear of missing a diagnosis, and patient demands for services. Another major driver of current utilization is that there is ongoing support for the status quo, as the majority of reimbursement for providers is still based on fee-for-service.

Change Efforts

One cost-reducing effort that has gained widespread enthusiasm from medical societies is the Choosing Wisely campaign. This campaign is an effort originally driven by the American Board of Internal Medicine (ABIM) Foundation to help physicians become aware of and reduce unnecessary utilization of resources. Each Choosing Wisely list is generated and endorsed by the relevant medical society and widely advertised to physicians via a variety of mechanisms. More than 70 medical societies have participated in the effort to date.

The recommendations are often widely accepted by those in the specialty since they are evidence-based and derived and advertised by their own specialty societies. In the survey mentioned above, almost all physicians agreed that their Choosing Wisely was a good source of guidance (ranging from 92% of surgical specialties to 97% of primary-care physicians). In order to drive the movement from the patient perspective, Consumer Reports has developed educational materials aimed at the consumer side of healthcare (ie, patients and families).

As Consumer Reports suggests, the first step to implementing cost-conscious care is to measure awareness of cost and causes of overutilization. By first understanding behaviors, a group can then work to impact such behaviors. It is highly likely that the drivers are different based on the specialty of the physician, the patient population being served, and the local healthcare market drivers. As such, there will not be a single, across-the-board solution to reducing unnecessary utilization of services (and therefore cost), but interventions will need to be tailored to different groups depending on the drivers of cost locally.

Depending on the issues within a group, successful interventions could include:

• Decision support tools (for appropriate use of consultants and diagnostic tests)
• Display of testing costs (not just at the time of ordering)
• Efforts aimed at patient education (both as general consumers as well as at the point of care)
• Malpractice reform to support physicians trying to balance cost consciousness with patient welfare

In Sum

We have a long way to go in engaging physicians in efforts to reduce unnecessary utilization and cost. I recommend that hospitalist practices utilize the survey tool used in this study to understand the perceived barriers and drivers of cost within their practice and work with their local administrative teams to better understand patterns of overutilization among their group. Then interventions can be designed to be evidence-based, tailored to local workflow, and both reliable and sustainable.

If done well, hospitalists can have a huge impact on utilization and cost and position their groups and their hospitals well to succeed in this cost-constrained era of healthcare. TH

References

1. Colla CH, Kinsella EA, Morden NE, Meyers DJ, Rosenthal MB, Sequist TD. Physician perception of Choosing Wisely and drivers of overuse. Am J Manag Care. 2016;22(5):337-343.

Couple watching TV

Photo courtesy of LG

The amount of TV a person watches each day may influence his risk of dying from pulmonary embolism (PE), according to research published in Circulation.

Researchers evaluated more than 80,000 people in Japan and found the risk of PE death rose as TV viewing time increased.

People who watched TV for 2.5 to 4.9 hours each day had a 70% greater risk of dying from PE than people who watched less than 2.5 hours of TV a day.

For each additional 2 hours of TV watched each day, a person’s risk of PE death increased by 40%.

“Pulmonary embolism occurs at a lower rate in Japan than it does in Western countries, but it may be on the rise,” said study author Hiroyasu Iso, MD, PhD, of Osaka University Graduate School of Medicine.

“The Japanese people are increasingly adopting sedentary lifestyles, which we believe is putting them at increased risk.”

To assess the link between TV viewing and PE death in Japan, Dr Iso and colleagues analyzed information on 86,024 subjects participating in the JACC study. This included 50,017 women and 36,007 men, ranging in age from 40 to 79.

From 1988 to 1990, the subjects completed a questionnaire that included information about average time spent watching TV each day.

The subjects were followed for a median of 19.2 years, until 2009. Mortality from PE was determined from death certificates. In all, 59 of the subjects died of PE.

The researchers calculated the risk of death from PE according to the amount of TV watched after adjusting for subjects’ age at baseline, sex, body mass index, history of hypertension, history of diabetes mellitus, smoking status, perceived mental stress, educational level, walking activity, and sports activity.

Compared to subjects who watched less than 2.5 hours of TV per day, those who watched 2.5 to 4.9 hours had an increased risk of PE death, with a hazard ratio of 1.7.

The risk was greater among subjects whose average TV viewing time was more than 5 hours per day, with a hazard ratio of 2.5.

The researchers said the actual risk of PE death may be higher because PE can be difficult to diagnose. They also pointed out that this study was conducted before computers, tablets, and smartphones became popular sources of information and entertainment.

“Nowadays, with online video streaming, the term ‘binge-watching’ to describe viewing multiple episodes of television programs in one sitting has become popular,” said study author Toru Shirakawa, MD, of Osaka University Graduate School of Medicine. “This popularity may reflect a rapidly growing habit.”

Earlier results from this study were presented at the ESC Congress 2015.

Couple watching TV

Photo courtesy of LG

The amount of TV a person watches each day may influence his risk of dying from pulmonary embolism (PE), according to research published in Circulation.

Researchers evaluated more than 80,000 people in Japan and found the risk of PE death rose as TV viewing time increased.

People who watched TV for 2.5 to 4.9 hours each day had a 70% greater risk of dying from PE than people who watched less than 2.5 hours of TV a day.

For each additional 2 hours of TV watched each day, a person’s risk of PE death increased by 40%.

“Pulmonary embolism occurs at a lower rate in Japan than it does in Western countries, but it may be on the rise,” said study author Hiroyasu Iso, MD, PhD, of Osaka University Graduate School of Medicine.

“The Japanese people are increasingly adopting sedentary lifestyles, which we believe is putting them at increased risk.”

To assess the link between TV viewing and PE death in Japan, Dr Iso and colleagues analyzed information on 86,024 subjects participating in the JACC study. This included 50,017 women and 36,007 men, ranging in age from 40 to 79.

From 1988 to 1990, the subjects completed a questionnaire that included information about average time spent watching TV each day.

The subjects were followed for a median of 19.2 years, until 2009. Mortality from PE was determined from death certificates. In all, 59 of the subjects died of PE.

The researchers calculated the risk of death from PE according to the amount of TV watched after adjusting for subjects’ age at baseline, sex, body mass index, history of hypertension, history of diabetes mellitus, smoking status, perceived mental stress, educational level, walking activity, and sports activity.

Compared to subjects who watched less than 2.5 hours of TV per day, those who watched 2.5 to 4.9 hours had an increased risk of PE death, with a hazard ratio of 1.7.

The risk was greater among subjects whose average TV viewing time was more than 5 hours per day, with a hazard ratio of 2.5.

The researchers said the actual risk of PE death may be higher because PE can be difficult to diagnose. They also pointed out that this study was conducted before computers, tablets, and smartphones became popular sources of information and entertainment.

“Nowadays, with online video streaming, the term ‘binge-watching’ to describe viewing multiple episodes of television programs in one sitting has become popular,” said study author Toru Shirakawa, MD, of Osaka University Graduate School of Medicine. “This popularity may reflect a rapidly growing habit.”

Earlier results from this study were presented at the ESC Congress 2015.

Couple watching TV

Photo courtesy of LG

The amount of TV a person watches each day may influence his risk of dying from pulmonary embolism (PE), according to research published in Circulation.

Researchers evaluated more than 80,000 people in Japan and found the risk of PE death rose as TV viewing time increased.

People who watched TV for 2.5 to 4.9 hours each day had a 70% greater risk of dying from PE than people who watched less than 2.5 hours of TV a day.

For each additional 2 hours of TV watched each day, a person’s risk of PE death increased by 40%.

“Pulmonary embolism occurs at a lower rate in Japan than it does in Western countries, but it may be on the rise,” said study author Hiroyasu Iso, MD, PhD, of Osaka University Graduate School of Medicine.

“The Japanese people are increasingly adopting sedentary lifestyles, which we believe is putting them at increased risk.”

To assess the link between TV viewing and PE death in Japan, Dr Iso and colleagues analyzed information on 86,024 subjects participating in the JACC study. This included 50,017 women and 36,007 men, ranging in age from 40 to 79.

From 1988 to 1990, the subjects completed a questionnaire that included information about average time spent watching TV each day.

The subjects were followed for a median of 19.2 years, until 2009. Mortality from PE was determined from death certificates. In all, 59 of the subjects died of PE.

The researchers calculated the risk of death from PE according to the amount of TV watched after adjusting for subjects’ age at baseline, sex, body mass index, history of hypertension, history of diabetes mellitus, smoking status, perceived mental stress, educational level, walking activity, and sports activity.

Compared to subjects who watched less than 2.5 hours of TV per day, those who watched 2.5 to 4.9 hours had an increased risk of PE death, with a hazard ratio of 1.7.

The risk was greater among subjects whose average TV viewing time was more than 5 hours per day, with a hazard ratio of 2.5.

The researchers said the actual risk of PE death may be higher because PE can be difficult to diagnose. They also pointed out that this study was conducted before computers, tablets, and smartphones became popular sources of information and entertainment.

“Nowadays, with online video streaming, the term ‘binge-watching’ to describe viewing multiple episodes of television programs in one sitting has become popular,” said study author Toru Shirakawa, MD, of Osaka University Graduate School of Medicine. “This popularity may reflect a rapidly growing habit.”

Earlier results from this study were presented at the ESC Congress 2015.

Doctor and patient

Photo courtesy of NIH

The American Society of Clinical Oncology (ASCO) has issued a new clinical practice guideline on the management of chronic pain in adult cancer survivors.

ASCO’s recommendations comprise both long-standing and new approaches, including routine screening for chronic pain, the use of alternative pain management approaches, the use of medical cannabis in certain settings where it is legal, and assessing the potential for opioid overuse.

“Many oncologists and primary care physicians are not trained to recognize or treat long-term pain associated with cancer,” said Judith A. Paice, PhD, RN, a co-chair of the ASCO expert panel that developed the guideline.

“This guideline will help clinicians identify pain early and develop comprehensive treatment plans, using a broad range of approaches.”

The guideline recommendations were developed by a multidisciplinary panel of experts in medical oncology, hematology/oncology, pain medicine, palliative care, hospice, radiation oncology, social work, symptom management research, rehabilitation, psychology, and anesthesiology, as well as a patient representative.

The panel conducted a systematic review of the medical literature published from 1996 to 2015. The resulting guideline includes the following key recommendations.

Clinicians should screen for pain at each encounter with a patient. Recurrent disease, second malignancy, or late-onset treatment effects should be evaluated, treated, and monitored.

Clinicians may prescribe non-pharmacologic interventions such as physical medicine and rehabilitation, integrative therapies (eg, acupuncture and massage), interventional therapies, and psychological approaches (eg, guided imagery, hypnosis, and meditation).

Systemic non-opioid analgesics (NSAIDS, acetaminophen) and adjuvant analgesics (selected antidepressants and anticonvulsants) may be prescribed to relieve chronic pain and/or improve physical function.

Clinicians may follow specific state regulations that allow access to medical cannabis or cannabinoids for patients with chronic pain after considering the potential benefits and risks of the available formulations.

Clinicians may prescribe a trial of opioids in carefully selected cancer patients who do not respond to more conservative pain management and who continue to experience pain-related distress or impairment of physical function.

Clinicians should assess the risk of adverse effects of opioids used in pain management and incorporate universal precautions to minimize abuse, addiction, and adverse consequences.

“Of great importance is the attention to appropriate assessment, not only of the individual’s pain, but also of their potential for over-reliance on opioids,” Dr Paice said. “This guideline outlines precautions that help ensure cancer survivors with persistent pain use opioids safely and effectively, while limiting access to those who are struggling with addiction.”

Doctor and patient

Photo courtesy of NIH

The American Society of Clinical Oncology (ASCO) has issued a new clinical practice guideline on the management of chronic pain in adult cancer survivors.

ASCO’s recommendations comprise both long-standing and new approaches, including routine screening for chronic pain, the use of alternative pain management approaches, the use of medical cannabis in certain settings where it is legal, and assessing the potential for opioid overuse.

“Many oncologists and primary care physicians are not trained to recognize or treat long-term pain associated with cancer,” said Judith A. Paice, PhD, RN, a co-chair of the ASCO expert panel that developed the guideline.

“This guideline will help clinicians identify pain early and develop comprehensive treatment plans, using a broad range of approaches.”

The guideline recommendations were developed by a multidisciplinary panel of experts in medical oncology, hematology/oncology, pain medicine, palliative care, hospice, radiation oncology, social work, symptom management research, rehabilitation, psychology, and anesthesiology, as well as a patient representative.

The panel conducted a systematic review of the medical literature published from 1996 to 2015. The resulting guideline includes the following key recommendations.

Clinicians should screen for pain at each encounter with a patient. Recurrent disease, second malignancy, or late-onset treatment effects should be evaluated, treated, and monitored.

Clinicians may prescribe non-pharmacologic interventions such as physical medicine and rehabilitation, integrative therapies (eg, acupuncture and massage), interventional therapies, and psychological approaches (eg, guided imagery, hypnosis, and meditation).

Systemic non-opioid analgesics (NSAIDS, acetaminophen) and adjuvant analgesics (selected antidepressants and anticonvulsants) may be prescribed to relieve chronic pain and/or improve physical function.

Clinicians may follow specific state regulations that allow access to medical cannabis or cannabinoids for patients with chronic pain after considering the potential benefits and risks of the available formulations.

Clinicians may prescribe a trial of opioids in carefully selected cancer patients who do not respond to more conservative pain management and who continue to experience pain-related distress or impairment of physical function.

Clinicians should assess the risk of adverse effects of opioids used in pain management and incorporate universal precautions to minimize abuse, addiction, and adverse consequences.

“Of great importance is the attention to appropriate assessment, not only of the individual’s pain, but also of their potential for over-reliance on opioids,” Dr Paice said. “This guideline outlines precautions that help ensure cancer survivors with persistent pain use opioids safely and effectively, while limiting access to those who are struggling with addiction.”

Doctor and patient

Photo courtesy of NIH

The American Society of Clinical Oncology (ASCO) has issued a new clinical practice guideline on the management of chronic pain in adult cancer survivors.

ASCO’s recommendations comprise both long-standing and new approaches, including routine screening for chronic pain, the use of alternative pain management approaches, the use of medical cannabis in certain settings where it is legal, and assessing the potential for opioid overuse.

“Many oncologists and primary care physicians are not trained to recognize or treat long-term pain associated with cancer,” said Judith A. Paice, PhD, RN, a co-chair of the ASCO expert panel that developed the guideline.

“This guideline will help clinicians identify pain early and develop comprehensive treatment plans, using a broad range of approaches.”

The guideline recommendations were developed by a multidisciplinary panel of experts in medical oncology, hematology/oncology, pain medicine, palliative care, hospice, radiation oncology, social work, symptom management research, rehabilitation, psychology, and anesthesiology, as well as a patient representative.

The panel conducted a systematic review of the medical literature published from 1996 to 2015. The resulting guideline includes the following key recommendations.

Clinicians should screen for pain at each encounter with a patient. Recurrent disease, second malignancy, or late-onset treatment effects should be evaluated, treated, and monitored.

Clinicians may prescribe non-pharmacologic interventions such as physical medicine and rehabilitation, integrative therapies (eg, acupuncture and massage), interventional therapies, and psychological approaches (eg, guided imagery, hypnosis, and meditation).

Systemic non-opioid analgesics (NSAIDS, acetaminophen) and adjuvant analgesics (selected antidepressants and anticonvulsants) may be prescribed to relieve chronic pain and/or improve physical function.

Clinicians may follow specific state regulations that allow access to medical cannabis or cannabinoids for patients with chronic pain after considering the potential benefits and risks of the available formulations.

Clinicians may prescribe a trial of opioids in carefully selected cancer patients who do not respond to more conservative pain management and who continue to experience pain-related distress or impairment of physical function.

Clinicians should assess the risk of adverse effects of opioids used in pain management and incorporate universal precautions to minimize abuse, addiction, and adverse consequences.

“Of great importance is the attention to appropriate assessment, not only of the individual’s pain, but also of their potential for over-reliance on opioids,” Dr Paice said. “This guideline outlines precautions that help ensure cancer survivors with persistent pain use opioids safely and effectively, while limiting access to those who are struggling with addiction.”

 

 

Lenalidomide (Revlimid)

Photo courtesy of Celgene

 

Initial results from the phase 3 REMARC study suggest that lenalidomide (Revlimid) maintenance does not prolong overall survival (OS) in patients with diffuse large B-cell lymphoma (DLBCL) who have responded to first-line treatment with R-CHOP.

Based on these results, Celgene Corporation, the company developing lenalidomide, said it does not plan to seek approval for the drug for this indication.

REMARC is a randomized, double-blind study designed to compare lenalidomide maintenance to placebo in 650 patients responding to induction therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

Patients in REMARC had received 6 to 8 cycles of the R-CHOP-14 regimen, 6 to 8 cycles of the R-CHOP-21 regimen, or 6 cycles of R-CHOP-14/R-CHOP-21 completed by 2 cycles of rituximab alone.

The primary endpoint of the study—a significant improvement in progression-free survival for patients receiving lenalidomide—was met.

However, the interim analysis of OS showed no benefit for patients in the lenalidomide arm.

Celgene said that, based on these results, the company is not planning to seek approval for lenalidomide as maintenance in this patient population.

“We are continuing to partner with LYSA [Lymphoma Study Association] to complete the analyses of the REMARC study,” said Michael Pehl, of Celgene.

“We remain committed to finishing the 4 ongoing phase 3 trials evaluating Revlimid and are confident about its potential as a treatment option across different settings in lymphoma.”

The REMARC study is part of a research program focused on non-Hodgkin lymphoma. In addition to the REMARC study, lenalidomide is also being evaluated in:

• The RELEVANCE study—in combination with rituximab in previously untreated follicular lymphoma (FL)
• The AUGMENT study—in combination with rituximab in relapsed/refractory FL and marginal zone lymphoma
• The MAGNIFY study—in combination with rituximab in relapsed/refractory FL, marginal zone lymphoma, and mantle cell lymphoma
• The ROBUST study—in combination with R-CHOP in previously untreated ABC-subtype DLBCL.

Data from RELEVANCE and AUGMENT are expected in the first and second half of 2017, respectively.

 

 

Lenalidomide (Revlimid)

Photo courtesy of Celgene

 

Initial results from the phase 3 REMARC study suggest that lenalidomide (Revlimid) maintenance does not prolong overall survival (OS) in patients with diffuse large B-cell lymphoma (DLBCL) who have responded to first-line treatment with R-CHOP.

Based on these results, Celgene Corporation, the company developing lenalidomide, said it does not plan to seek approval for the drug for this indication.

REMARC is a randomized, double-blind study designed to compare lenalidomide maintenance to placebo in 650 patients responding to induction therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

Patients in REMARC had received 6 to 8 cycles of the R-CHOP-14 regimen, 6 to 8 cycles of the R-CHOP-21 regimen, or 6 cycles of R-CHOP-14/R-CHOP-21 completed by 2 cycles of rituximab alone.

The primary endpoint of the study—a significant improvement in progression-free survival for patients receiving lenalidomide—was met.

However, the interim analysis of OS showed no benefit for patients in the lenalidomide arm.

Celgene said that, based on these results, the company is not planning to seek approval for lenalidomide as maintenance in this patient population.

“We are continuing to partner with LYSA [Lymphoma Study Association] to complete the analyses of the REMARC study,” said Michael Pehl, of Celgene.

“We remain committed to finishing the 4 ongoing phase 3 trials evaluating Revlimid and are confident about its potential as a treatment option across different settings in lymphoma.”

The REMARC study is part of a research program focused on non-Hodgkin lymphoma. In addition to the REMARC study, lenalidomide is also being evaluated in:

• The RELEVANCE study—in combination with rituximab in previously untreated follicular lymphoma (FL)
• The AUGMENT study—in combination with rituximab in relapsed/refractory FL and marginal zone lymphoma
• The MAGNIFY study—in combination with rituximab in relapsed/refractory FL, marginal zone lymphoma, and mantle cell lymphoma
• The ROBUST study—in combination with R-CHOP in previously untreated ABC-subtype DLBCL.

Data from RELEVANCE and AUGMENT are expected in the first and second half of 2017, respectively.

 

 

Lenalidomide (Revlimid)

Photo courtesy of Celgene

 

Initial results from the phase 3 REMARC study suggest that lenalidomide (Revlimid) maintenance does not prolong overall survival (OS) in patients with diffuse large B-cell lymphoma (DLBCL) who have responded to first-line treatment with R-CHOP.

Based on these results, Celgene Corporation, the company developing lenalidomide, said it does not plan to seek approval for the drug for this indication.

REMARC is a randomized, double-blind study designed to compare lenalidomide maintenance to placebo in 650 patients responding to induction therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

Patients in REMARC had received 6 to 8 cycles of the R-CHOP-14 regimen, 6 to 8 cycles of the R-CHOP-21 regimen, or 6 cycles of R-CHOP-14/R-CHOP-21 completed by 2 cycles of rituximab alone.

The primary endpoint of the study—a significant improvement in progression-free survival for patients receiving lenalidomide—was met.

However, the interim analysis of OS showed no benefit for patients in the lenalidomide arm.

Celgene said that, based on these results, the company is not planning to seek approval for lenalidomide as maintenance in this patient population.

“We are continuing to partner with LYSA [Lymphoma Study Association] to complete the analyses of the REMARC study,” said Michael Pehl, of Celgene.

“We remain committed to finishing the 4 ongoing phase 3 trials evaluating Revlimid and are confident about its potential as a treatment option across different settings in lymphoma.”

The REMARC study is part of a research program focused on non-Hodgkin lymphoma. In addition to the REMARC study, lenalidomide is also being evaluated in:

• The RELEVANCE study—in combination with rituximab in previously untreated follicular lymphoma (FL)
• The AUGMENT study—in combination with rituximab in relapsed/refractory FL and marginal zone lymphoma
• The MAGNIFY study—in combination with rituximab in relapsed/refractory FL, marginal zone lymphoma, and mantle cell lymphoma
• The ROBUST study—in combination with R-CHOP in previously untreated ABC-subtype DLBCL.

Data from RELEVANCE and AUGMENT are expected in the first and second half of 2017, respectively.

Daratumumab (Darzalex)

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for daratumumab (Darzalex), a CD38-directed monoclonal antibody (mAb), as part of combination therapy for patients with multiple myeloma (MM).

The designation is for daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for the treatment of MM patients who have received at least 1 prior therapy.

This is the second breakthrough designation the FDA has granted to daratumumab.

The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

In May 2013, the FDA granted daratumumab breakthrough designation for the treatment of MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.

In November 2015, daratumumab received accelerated approval from the FDA for this indication. Continued approval of the mAb may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Phase 3 trials

The newest breakthrough designation for daratumumab was based on data from two phase 3 studies—CASTOR (MMY3004) and POLLUX (MMY3003). Both studies were sponsored by Janssen Biotech, Inc., the company developing daratumumab.

In the CASTOR trial, researchers compared daratumumab-bortezomib-dexamethasone to bortezomib-dexamethasone in MM patients who had received at least 1 prior therapy.

The researchers said the addition of daratumumab significantly improved progression-free survival without increasing the cumulative toxicity or the toxicity of the bortezomib-dexamethasone combination.

Results from this trial were presented at the 2016 ASCO Annual Meeting.

In the POLLUX trial, researchers compared daratumumab-lenalidomide-dexamethasone to lenalidomide-dexamethasone in MM patients who had received at least 1 prior therapy.

According to the researchers, daratumumab-lenalidomide-dexamethasone conferred the highest response rate reported to date in the treatment of relapsed/refractory MM, significantly improved progression-free survival compared to lenalidomide-dexamethasone, and had a manageable safety profile.

These results were presented at the 21st Congress of the European Hematology Association.

Daratumumab (Darzalex)

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for daratumumab (Darzalex), a CD38-directed monoclonal antibody (mAb), as part of combination therapy for patients with multiple myeloma (MM).

The designation is for daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for the treatment of MM patients who have received at least 1 prior therapy.

This is the second breakthrough designation the FDA has granted to daratumumab.

The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

In May 2013, the FDA granted daratumumab breakthrough designation for the treatment of MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.

In November 2015, daratumumab received accelerated approval from the FDA for this indication. Continued approval of the mAb may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Phase 3 trials

The newest breakthrough designation for daratumumab was based on data from two phase 3 studies—CASTOR (MMY3004) and POLLUX (MMY3003). Both studies were sponsored by Janssen Biotech, Inc., the company developing daratumumab.

In the CASTOR trial, researchers compared daratumumab-bortezomib-dexamethasone to bortezomib-dexamethasone in MM patients who had received at least 1 prior therapy.

The researchers said the addition of daratumumab significantly improved progression-free survival without increasing the cumulative toxicity or the toxicity of the bortezomib-dexamethasone combination.

Results from this trial were presented at the 2016 ASCO Annual Meeting.

In the POLLUX trial, researchers compared daratumumab-lenalidomide-dexamethasone to lenalidomide-dexamethasone in MM patients who had received at least 1 prior therapy.

According to the researchers, daratumumab-lenalidomide-dexamethasone conferred the highest response rate reported to date in the treatment of relapsed/refractory MM, significantly improved progression-free survival compared to lenalidomide-dexamethasone, and had a manageable safety profile.

These results were presented at the 21st Congress of the European Hematology Association.

Daratumumab (Darzalex)

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for daratumumab (Darzalex), a CD38-directed monoclonal antibody (mAb), as part of combination therapy for patients with multiple myeloma (MM).

The designation is for daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for the treatment of MM patients who have received at least 1 prior therapy.

This is the second breakthrough designation the FDA has granted to daratumumab.

The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

In May 2013, the FDA granted daratumumab breakthrough designation for the treatment of MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.

In November 2015, daratumumab received accelerated approval from the FDA for this indication. Continued approval of the mAb may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Phase 3 trials

The newest breakthrough designation for daratumumab was based on data from two phase 3 studies—CASTOR (MMY3004) and POLLUX (MMY3003). Both studies were sponsored by Janssen Biotech, Inc., the company developing daratumumab.

In the CASTOR trial, researchers compared daratumumab-bortezomib-dexamethasone to bortezomib-dexamethasone in MM patients who had received at least 1 prior therapy.

The researchers said the addition of daratumumab significantly improved progression-free survival without increasing the cumulative toxicity or the toxicity of the bortezomib-dexamethasone combination.

Results from this trial were presented at the 2016 ASCO Annual Meeting.

In the POLLUX trial, researchers compared daratumumab-lenalidomide-dexamethasone to lenalidomide-dexamethasone in MM patients who had received at least 1 prior therapy.

According to the researchers, daratumumab-lenalidomide-dexamethasone conferred the highest response rate reported to date in the treatment of relapsed/refractory MM, significantly improved progression-free survival compared to lenalidomide-dexamethasone, and had a manageable safety profile.

These results were presented at the 21st Congress of the European Hematology Association.

ANSWERThe correct diagnosis is discoid lupus erythematosus (DLE; choice “c”). For those unfamiliar with DLE, it is often mistaken for the other items listed. Biopsy can distinguish among them.

Fungal infection (dermatophytosis; choice “a”) of the face is unusual and would have responded in some way to the antifungal cream. Likewise, the use of steroid creams would have markedly worsened a fungal infection.

Although this could have been psoriasis (choice “b”), it’s rare for that condition to be confined to the face. It almost always appears elsewhere—the scalp, elbows, knees, and/or nails.

Dermatomyositis (choice “d”), an autoimmune condition, can certainly present with a bimalar rash. However, it is usually accompanied by additional symptoms, such as progressive weakness and muscle pain.

DISCUSSION
DLE can represent a stand-alone diagnosis, or it can be a manifestation of systemic lupus erythematosus (SLE). When present in this bimalar form, the lesions are often mistaken for the “butterfly rash” commonly seen in SLE.

This patient was thoroughly tested for SLE, and no evidence of it was found. Biopsy did, however, show changes consistent with DLE (interface dermatitis with increased mucin formation, among others).

The treatment for DLE is rather simple: It consists of sun protection and oral hydroxychloroquine. This helps reduce inflammation, although the patient will still have residual scarring.

ANSWERThe correct diagnosis is discoid lupus erythematosus (DLE; choice “c”). For those unfamiliar with DLE, it is often mistaken for the other items listed. Biopsy can distinguish among them.

Fungal infection (dermatophytosis; choice “a”) of the face is unusual and would have responded in some way to the antifungal cream. Likewise, the use of steroid creams would have markedly worsened a fungal infection.

Although this could have been psoriasis (choice “b”), it’s rare for that condition to be confined to the face. It almost always appears elsewhere—the scalp, elbows, knees, and/or nails.

Dermatomyositis (choice “d”), an autoimmune condition, can certainly present with a bimalar rash. However, it is usually accompanied by additional symptoms, such as progressive weakness and muscle pain.

DISCUSSION
DLE can represent a stand-alone diagnosis, or it can be a manifestation of systemic lupus erythematosus (SLE). When present in this bimalar form, the lesions are often mistaken for the “butterfly rash” commonly seen in SLE.

This patient was thoroughly tested for SLE, and no evidence of it was found. Biopsy did, however, show changes consistent with DLE (interface dermatitis with increased mucin formation, among others).

The treatment for DLE is rather simple: It consists of sun protection and oral hydroxychloroquine. This helps reduce inflammation, although the patient will still have residual scarring.

ANSWERThe correct diagnosis is discoid lupus erythematosus (DLE; choice “c”). For those unfamiliar with DLE, it is often mistaken for the other items listed. Biopsy can distinguish among them.

Fungal infection (dermatophytosis; choice “a”) of the face is unusual and would have responded in some way to the antifungal cream. Likewise, the use of steroid creams would have markedly worsened a fungal infection.

Although this could have been psoriasis (choice “b”), it’s rare for that condition to be confined to the face. It almost always appears elsewhere—the scalp, elbows, knees, and/or nails.

Dermatomyositis (choice “d”), an autoimmune condition, can certainly present with a bimalar rash. However, it is usually accompanied by additional symptoms, such as progressive weakness and muscle pain.

DISCUSSION
DLE can represent a stand-alone diagnosis, or it can be a manifestation of systemic lupus erythematosus (SLE). When present in this bimalar form, the lesions are often mistaken for the “butterfly rash” commonly seen in SLE.

This patient was thoroughly tested for SLE, and no evidence of it was found. Biopsy did, however, show changes consistent with DLE (interface dermatitis with increased mucin formation, among others).

The treatment for DLE is rather simple: It consists of sun protection and oral hydroxychloroquine. This helps reduce inflammation, although the patient will still have residual scarring.

ANSWER
The correct interpretation includes sinus rhythm with complete heart block and a junctional rhythm, a rightward axis, and evidence of an anterior myocardial infarction (MI).

Sinus rhythm is evidenced by the regular rate and rhythm of the P waves.

Complete heart block is identified by the atrioventricular (AV) dissociation (QRS independent of the P wave), while the normal QRS duration—despite AV dissociation—confirms the existence of a junctional rhythm.

A positive R-wave axis slightly above the upper limit of normal, as seen with this patient, constitutes a rightward axis.

Finally, the posteriorly directed forces in the anterior precordial leads with poor R-wave progression denote an anterior MI.

ANSWER
The correct interpretation includes sinus rhythm with complete heart block and a junctional rhythm, a rightward axis, and evidence of an anterior myocardial infarction (MI).

Sinus rhythm is evidenced by the regular rate and rhythm of the P waves.

Complete heart block is identified by the atrioventricular (AV) dissociation (QRS independent of the P wave), while the normal QRS duration—despite AV dissociation—confirms the existence of a junctional rhythm.

A positive R-wave axis slightly above the upper limit of normal, as seen with this patient, constitutes a rightward axis.

Finally, the posteriorly directed forces in the anterior precordial leads with poor R-wave progression denote an anterior MI.

ANSWER
The correct interpretation includes sinus rhythm with complete heart block and a junctional rhythm, a rightward axis, and evidence of an anterior myocardial infarction (MI).

Sinus rhythm is evidenced by the regular rate and rhythm of the P waves.

Complete heart block is identified by the atrioventricular (AV) dissociation (QRS independent of the P wave), while the normal QRS duration—despite AV dissociation—confirms the existence of a junctional rhythm.

A positive R-wave axis slightly above the upper limit of normal, as seen with this patient, constitutes a rightward axis.

Finally, the posteriorly directed forces in the anterior precordial leads with poor R-wave progression denote an anterior MI.

I was relaxing after work in my local American Legion a few weeks ago when a quiet young man entered with a backpack. He set it down to use the restroom, and when he returned a few minutes later, he picked up the backpack and walked away. After he left, a group of us discussed how lax we were about this situation. Yes, it was probably innocent—but what if it wasn’t? A sign over the bar reads, “Don’t let anyone leave a stranger.” The purpose of that sign is, of course, to make everyone feel welcome, but these days I think it also means to be aware of your surroundings. I have seen too many American flags at half-staff this year to overlook a potential tragedy.

Today, clinicians must be prepared for all possible emergencies, including terrorism. Acts of terrorism (as the word implies) are designed to instill terror and ­panic, disrupt security and communication systems, destroy property, and kill or injure innocent civilians.

Recent terrorist attacks in 2016, while shocking in their brutality, were not inconceivable—public locations where large groups gather are logical targets. Terrorists often target high-traffic areas, such as airports or shopping malls, where they can quickly disappear into a crowd if necessary (hence the concern circling the Olympic Games to be held in Brazil this month).

Attacks at restaurants, airports, and other public “hot spots” are especially frightening. With terrorist attack locations in the past year ranging from nightclubs (the Pulse Nightclub shooting in Orlando, Florida, left 49 dead) to restaurants (a bomb in Dhaka, Bangladesh, killed 20) to conference rooms (a shooting in San Bernardino, California, left 14 dead and 21 injured), it’s clear that the fundamental message terrorists want to send is: You are not safe—anywhere!

While organized events and big crowds are a bull’s-eye for terrorists, our personal surroundings have risk factors, too. Because a terrorist attack can happen anywhere at any time, you need to be prepared by knowing what to do and how to maximize your chan­ces of survival.

As this year’s attacks exemplify, we shouldn’t assume we understand the “logic” or thinking of terrorist organizations or individuals. Preparation for a terrorist attack boils down to being aware of the warning signs and being cautious and alert. Terrorists use a range of weapons and tactics, including bombs, arson, hijacking, and kidnapping (see Table).^1,2

According to Dr. Howard Mell, an EMS director in North Carolina, the overwhelming majority of gunfire in the emergency department—or anywhere—is not the result of an active shooter. Most gunfire is targeted at a specific goal (ie, escaping or avoiding capture) or person. However, should there be an active shooter, he recommends three steps to take: Run (if the path is open), hide (if your exit is blocked), or fight (if there are no other alternatives).³

Wherever you are, always have multiple potential escape routes in mind. If you run, leave all belongings behind. Help others escape if possible, and take steps to prevent others from entering once you have left the area.

If you are unable to run, decide where to hide. If possible, barricade the area; if you are in a room, turn out the lights and stay away from the door. Be silent and put your cell phone on silent. While you are hiding, prepare to fight.

Fighting is the last resort. Act aggressively and improvise weapons to use against the assailant. If you have family, friends, or colleagues with you, put them to work!

When law enforcement officers arrive, understand that their job is to go right to the source and contain the danger. Keep your hands visible at all times, with fingers spread. Do not grab them for protection, and avoid yelling or pointing. Be prepared to give the authorities any pertinent information (eg, shooter description, last known location, direction of travel, or weapons seen).

Many health care facilities and organizations have valuable disaster and terrorism training programs, which include emergency evacuation procedures. I encourage you to take advantage of them, particularly if you travel internationally.⁴

Continue for personal preparedness >>

This is about personal preparedness. While I am not promoting paranoia, I do believe the risk for terrorist activity has increased in recent years.

I therefore urge you to have a healthy suspicion when you see or hear people
• Asking unusual questions about safety procedures at work
• Engaging in behaviors that provoke suspicion
• Loitering, parking, or standing in the same area over multiple days
• Attempting to disguise themselves from visit to visit
• Obtaining unusual quantities of weapons, ammunition, or explosive precursors
• Wearing clothing not appropriate for the season
• Leaving items, including backpacks or packages, unattended
• Leaving anonymous threats via telephone or e-mail

If after conducting a risk assessment of your surroundings, you believe you could (directly or indirectly) be impacted by terrorism, you must implement evacuation plans, notification of appropriate personnel, and personal safety measures.

In the event of a terrorist incident, remain calm, follow the advice of local emergency officials, and follow radio, television, and cell phone updates for news and instructions. ⁵

If an attack occurs near you or your home, here are practical steps you can take: Check for injuries. Give first aid and get help for seriously injured people. Check for damage using a flashlight—do not light matches or candles, or use electrical switches. Check for fires, fire hazards, and other household hazards. Sniff for gas leaks, starting at the water heater. If you smell gas or suspect a leak, turn off the main gas valve, open windows, and evacuate quickly. Shut off any damaged utilities, and confine or secure your pets. Call your family contact—but do not use the telephone again unless it is a life-threatening emergency. Cell phones may or may not be working. Check on your neighbors, especially those who are elderly or disabled.

Terrorist attacks leave citizens concerned about future incidents of terrorism in the United States and their potential impact. They raise ambiguity about what might happen next and increase stress levels. You can take steps to prepare for terrorist attacks and reduce the stress you may feel, now and later, should an emergency arise. Taking preparatory action can reassure you, your family, and your children that you have a measure of control—even in the face of terrorism. If you have additional suggestions for terrorist defense preparation, you can email your ideas to [email protected].

References
1. Dworkin RW. Preparing hospitals, doctors, and nurses for a terrorist attack. Hudson Institute. www.hudson.org/content/researchattach ments/attachment/291/dworkin_white_paper.pdf. Accessed July 6, 2016.
2. Markenson F, DiMaggio C, Redlener I. Preparing health professions students for terrorism, disaster, and public health emergencies: core competencies. Acad Med. 2005;80(6):517-526.
3. Mell HK. Run, hide, fight: how to react when there’s gunfire in the emergency department. ACEP NOW. June 21, 2016. www.acepnow.com/react-theres-gunfire-emergency-department/?elq_mid=10369&elq_cid=5274988. Accessed July 6, 2016.
4. Uniformed Services University of the Health Sciences, Center for the Study of Traumatic Stress. Workplace preparedness for terrorism. www.cstsonline.org/assets/media/docu ments/CSTS_report_sloan_workplace_prepare_terrorism_preparedness.pdf. Accessed July 6, 2016.
5. American Red Cross. Terrorism Preparedness. www.redcross.org/prepare/disaster/terrorism. Accessed July 6, 2016.

I was relaxing after work in my local American Legion a few weeks ago when a quiet young man entered with a backpack. He set it down to use the restroom, and when he returned a few minutes later, he picked up the backpack and walked away. After he left, a group of us discussed how lax we were about this situation. Yes, it was probably innocent—but what if it wasn’t? A sign over the bar reads, “Don’t let anyone leave a stranger.” The purpose of that sign is, of course, to make everyone feel welcome, but these days I think it also means to be aware of your surroundings. I have seen too many American flags at half-staff this year to overlook a potential tragedy.

Today, clinicians must be prepared for all possible emergencies, including terrorism. Acts of terrorism (as the word implies) are designed to instill terror and ­panic, disrupt security and communication systems, destroy property, and kill or injure innocent civilians.

Recent terrorist attacks in 2016, while shocking in their brutality, were not inconceivable—public locations where large groups gather are logical targets. Terrorists often target high-traffic areas, such as airports or shopping malls, where they can quickly disappear into a crowd if necessary (hence the concern circling the Olympic Games to be held in Brazil this month).

Attacks at restaurants, airports, and other public “hot spots” are especially frightening. With terrorist attack locations in the past year ranging from nightclubs (the Pulse Nightclub shooting in Orlando, Florida, left 49 dead) to restaurants (a bomb in Dhaka, Bangladesh, killed 20) to conference rooms (a shooting in San Bernardino, California, left 14 dead and 21 injured), it’s clear that the fundamental message terrorists want to send is: You are not safe—anywhere!

While organized events and big crowds are a bull’s-eye for terrorists, our personal surroundings have risk factors, too. Because a terrorist attack can happen anywhere at any time, you need to be prepared by knowing what to do and how to maximize your chan­ces of survival.

As this year’s attacks exemplify, we shouldn’t assume we understand the “logic” or thinking of terrorist organizations or individuals. Preparation for a terrorist attack boils down to being aware of the warning signs and being cautious and alert. Terrorists use a range of weapons and tactics, including bombs, arson, hijacking, and kidnapping (see Table).^1,2

According to Dr. Howard Mell, an EMS director in North Carolina, the overwhelming majority of gunfire in the emergency department—or anywhere—is not the result of an active shooter. Most gunfire is targeted at a specific goal (ie, escaping or avoiding capture) or person. However, should there be an active shooter, he recommends three steps to take: Run (if the path is open), hide (if your exit is blocked), or fight (if there are no other alternatives).³

Wherever you are, always have multiple potential escape routes in mind. If you run, leave all belongings behind. Help others escape if possible, and take steps to prevent others from entering once you have left the area.

If you are unable to run, decide where to hide. If possible, barricade the area; if you are in a room, turn out the lights and stay away from the door. Be silent and put your cell phone on silent. While you are hiding, prepare to fight.

Fighting is the last resort. Act aggressively and improvise weapons to use against the assailant. If you have family, friends, or colleagues with you, put them to work!

When law enforcement officers arrive, understand that their job is to go right to the source and contain the danger. Keep your hands visible at all times, with fingers spread. Do not grab them for protection, and avoid yelling or pointing. Be prepared to give the authorities any pertinent information (eg, shooter description, last known location, direction of travel, or weapons seen).

Many health care facilities and organizations have valuable disaster and terrorism training programs, which include emergency evacuation procedures. I encourage you to take advantage of them, particularly if you travel internationally.⁴

Continue for personal preparedness >>

This is about personal preparedness. While I am not promoting paranoia, I do believe the risk for terrorist activity has increased in recent years.

I therefore urge you to have a healthy suspicion when you see or hear people
• Asking unusual questions about safety procedures at work
• Engaging in behaviors that provoke suspicion
• Loitering, parking, or standing in the same area over multiple days
• Attempting to disguise themselves from visit to visit
• Obtaining unusual quantities of weapons, ammunition, or explosive precursors
• Wearing clothing not appropriate for the season
• Leaving items, including backpacks or packages, unattended
• Leaving anonymous threats via telephone or e-mail

If after conducting a risk assessment of your surroundings, you believe you could (directly or indirectly) be impacted by terrorism, you must implement evacuation plans, notification of appropriate personnel, and personal safety measures.

In the event of a terrorist incident, remain calm, follow the advice of local emergency officials, and follow radio, television, and cell phone updates for news and instructions. ⁵

If an attack occurs near you or your home, here are practical steps you can take: Check for injuries. Give first aid and get help for seriously injured people. Check for damage using a flashlight—do not light matches or candles, or use electrical switches. Check for fires, fire hazards, and other household hazards. Sniff for gas leaks, starting at the water heater. If you smell gas or suspect a leak, turn off the main gas valve, open windows, and evacuate quickly. Shut off any damaged utilities, and confine or secure your pets. Call your family contact—but do not use the telephone again unless it is a life-threatening emergency. Cell phones may or may not be working. Check on your neighbors, especially those who are elderly or disabled.

Terrorist attacks leave citizens concerned about future incidents of terrorism in the United States and their potential impact. They raise ambiguity about what might happen next and increase stress levels. You can take steps to prepare for terrorist attacks and reduce the stress you may feel, now and later, should an emergency arise. Taking preparatory action can reassure you, your family, and your children that you have a measure of control—even in the face of terrorism. If you have additional suggestions for terrorist defense preparation, you can email your ideas to [email protected].

References
1. Dworkin RW. Preparing hospitals, doctors, and nurses for a terrorist attack. Hudson Institute. www.hudson.org/content/researchattach ments/attachment/291/dworkin_white_paper.pdf. Accessed July 6, 2016.
2. Markenson F, DiMaggio C, Redlener I. Preparing health professions students for terrorism, disaster, and public health emergencies: core competencies. Acad Med. 2005;80(6):517-526.
3. Mell HK. Run, hide, fight: how to react when there’s gunfire in the emergency department. ACEP NOW. June 21, 2016. www.acepnow.com/react-theres-gunfire-emergency-department/?elq_mid=10369&elq_cid=5274988. Accessed July 6, 2016.
4. Uniformed Services University of the Health Sciences, Center for the Study of Traumatic Stress. Workplace preparedness for terrorism. www.cstsonline.org/assets/media/docu ments/CSTS_report_sloan_workplace_prepare_terrorism_preparedness.pdf. Accessed July 6, 2016.
5. American Red Cross. Terrorism Preparedness. www.redcross.org/prepare/disaster/terrorism. Accessed July 6, 2016.

I was relaxing after work in my local American Legion a few weeks ago when a quiet young man entered with a backpack. He set it down to use the restroom, and when he returned a few minutes later, he picked up the backpack and walked away. After he left, a group of us discussed how lax we were about this situation. Yes, it was probably innocent—but what if it wasn’t? A sign over the bar reads, “Don’t let anyone leave a stranger.” The purpose of that sign is, of course, to make everyone feel welcome, but these days I think it also means to be aware of your surroundings. I have seen too many American flags at half-staff this year to overlook a potential tragedy.

Today, clinicians must be prepared for all possible emergencies, including terrorism. Acts of terrorism (as the word implies) are designed to instill terror and ­panic, disrupt security and communication systems, destroy property, and kill or injure innocent civilians.

Recent terrorist attacks in 2016, while shocking in their brutality, were not inconceivable—public locations where large groups gather are logical targets. Terrorists often target high-traffic areas, such as airports or shopping malls, where they can quickly disappear into a crowd if necessary (hence the concern circling the Olympic Games to be held in Brazil this month).

Attacks at restaurants, airports, and other public “hot spots” are especially frightening. With terrorist attack locations in the past year ranging from nightclubs (the Pulse Nightclub shooting in Orlando, Florida, left 49 dead) to restaurants (a bomb in Dhaka, Bangladesh, killed 20) to conference rooms (a shooting in San Bernardino, California, left 14 dead and 21 injured), it’s clear that the fundamental message terrorists want to send is: You are not safe—anywhere!

While organized events and big crowds are a bull’s-eye for terrorists, our personal surroundings have risk factors, too. Because a terrorist attack can happen anywhere at any time, you need to be prepared by knowing what to do and how to maximize your chan­ces of survival.

As this year’s attacks exemplify, we shouldn’t assume we understand the “logic” or thinking of terrorist organizations or individuals. Preparation for a terrorist attack boils down to being aware of the warning signs and being cautious and alert. Terrorists use a range of weapons and tactics, including bombs, arson, hijacking, and kidnapping (see Table).^1,2

According to Dr. Howard Mell, an EMS director in North Carolina, the overwhelming majority of gunfire in the emergency department—or anywhere—is not the result of an active shooter. Most gunfire is targeted at a specific goal (ie, escaping or avoiding capture) or person. However, should there be an active shooter, he recommends three steps to take: Run (if the path is open), hide (if your exit is blocked), or fight (if there are no other alternatives).³

Wherever you are, always have multiple potential escape routes in mind. If you run, leave all belongings behind. Help others escape if possible, and take steps to prevent others from entering once you have left the area.

If you are unable to run, decide where to hide. If possible, barricade the area; if you are in a room, turn out the lights and stay away from the door. Be silent and put your cell phone on silent. While you are hiding, prepare to fight.

Fighting is the last resort. Act aggressively and improvise weapons to use against the assailant. If you have family, friends, or colleagues with you, put them to work!

When law enforcement officers arrive, understand that their job is to go right to the source and contain the danger. Keep your hands visible at all times, with fingers spread. Do not grab them for protection, and avoid yelling or pointing. Be prepared to give the authorities any pertinent information (eg, shooter description, last known location, direction of travel, or weapons seen).

Many health care facilities and organizations have valuable disaster and terrorism training programs, which include emergency evacuation procedures. I encourage you to take advantage of them, particularly if you travel internationally.⁴

Continue for personal preparedness >>

This is about personal preparedness. While I am not promoting paranoia, I do believe the risk for terrorist activity has increased in recent years.

I therefore urge you to have a healthy suspicion when you see or hear people
• Asking unusual questions about safety procedures at work
• Engaging in behaviors that provoke suspicion
• Loitering, parking, or standing in the same area over multiple days
• Attempting to disguise themselves from visit to visit
• Obtaining unusual quantities of weapons, ammunition, or explosive precursors
• Wearing clothing not appropriate for the season
• Leaving items, including backpacks or packages, unattended
• Leaving anonymous threats via telephone or e-mail

If after conducting a risk assessment of your surroundings, you believe you could (directly or indirectly) be impacted by terrorism, you must implement evacuation plans, notification of appropriate personnel, and personal safety measures.

In the event of a terrorist incident, remain calm, follow the advice of local emergency officials, and follow radio, television, and cell phone updates for news and instructions. ⁵

If an attack occurs near you or your home, here are practical steps you can take: Check for injuries. Give first aid and get help for seriously injured people. Check for damage using a flashlight—do not light matches or candles, or use electrical switches. Check for fires, fire hazards, and other household hazards. Sniff for gas leaks, starting at the water heater. If you smell gas or suspect a leak, turn off the main gas valve, open windows, and evacuate quickly. Shut off any damaged utilities, and confine or secure your pets. Call your family contact—but do not use the telephone again unless it is a life-threatening emergency. Cell phones may or may not be working. Check on your neighbors, especially those who are elderly or disabled.

Terrorist attacks leave citizens concerned about future incidents of terrorism in the United States and their potential impact. They raise ambiguity about what might happen next and increase stress levels. You can take steps to prepare for terrorist attacks and reduce the stress you may feel, now and later, should an emergency arise. Taking preparatory action can reassure you, your family, and your children that you have a measure of control—even in the face of terrorism. If you have additional suggestions for terrorist defense preparation, you can email your ideas to [email protected].

References
1. Dworkin RW. Preparing hospitals, doctors, and nurses for a terrorist attack. Hudson Institute. www.hudson.org/content/researchattach ments/attachment/291/dworkin_white_paper.pdf. Accessed July 6, 2016.
2. Markenson F, DiMaggio C, Redlener I. Preparing health professions students for terrorism, disaster, and public health emergencies: core competencies. Acad Med. 2005;80(6):517-526.
3. Mell HK. Run, hide, fight: how to react when there’s gunfire in the emergency department. ACEP NOW. June 21, 2016. www.acepnow.com/react-theres-gunfire-emergency-department/?elq_mid=10369&elq_cid=5274988. Accessed July 6, 2016.
4. Uniformed Services University of the Health Sciences, Center for the Study of Traumatic Stress. Workplace preparedness for terrorism. www.cstsonline.org/assets/media/docu ments/CSTS_report_sloan_workplace_prepare_terrorism_preparedness.pdf. Accessed July 6, 2016.
5. American Red Cross. Terrorism Preparedness. www.redcross.org/prepare/disaster/terrorism. Accessed July 6, 2016.

CE/CME No: CR-1608

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES
• Describe the pathophysiology and explain the various clinical manifestations of systemic lupus erythematosus (SLE).
• Define the differential diagnosis for SLE.
• List the elements of the laboratory work-up used in the diagnosis of lupus.
• Describe the therapeutic options for patients with SLE.

FACULTY

Michael Felz is an Assistant Professor at Augusta University (formerly Georgia Regents University) in Augusta, Georgia. Mary Bailey Wickham is a PA student in her final year at Augusta University.
The authors have no financial relationships to disclose.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.0 hour of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of August 2016.

Article begins on next page >>

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that often goes undiagnosed initially. Timely detection of SLE is important, because prompt treatment can prevent its many major complications—notably, end organ damage. Here’s how to distinguish SLE from other illnesses with similar presentations and how to recognize the complications of undiagnosed SLE, which can progress rapidly and fatally.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disorder that can involve multiple organ systems. The presence of antinuclear antibodies (ANA) is a common marker for this disease. In autoimmune diseases such as SLE, the immune system attacks the cells of healthy tissues throughout the body. Genetic, hormonal, and environmental factors (eg, ultraviolet light, infectious viruses, and even use of certain medications) have been implicated in the pathogenesis.^1-3

It is estimated that 1.5 million people in the United States and up to 5 million people worldwide have SLE.⁴ It is nine to 10 times more prevalent in women—especially those of reproductive age—than menand occurs more frequently in African-American, Hispanic, and Asian women than in non-Hispanic Caucasian women.^1,2,4-6 Siblings of SLE patients are 30 times more likely to develop the disease, compared to individuals without an affected relative.² Increased mortality in persons with SLE is attributed to accelerated atherosclerosis, infection, malignancy, and target organ damage, particularly end-stage renal disease.³ Women ages 33 to 45 with SLE are at increased risk (50x greater) for myocardial infarction due to premature atherosclerosis than age-matched women in the general population.⁷ The life expectancy of SLE ­patients with renal damage is 23.7 years less than that of the general population.⁸

Increased awareness of SLE has led to drastic improvements in associated mortality over the past five decades. The survival rate in the 1950s was 50% at 2 years, while current rates are about 95% at 5 years and about 90% at 10 years.^3,9 These improvements likely reflect earlier diagnosis and treatment on the part of well-informed clinicians, as well as more effective treatment.

SLE MANIFESTATIONS
SLE can affect any organ in the body with a broad spectrum of clinical manifestations, making it a devastatingly deceptive disease. Disease severity may vary by age, by organ involvement, and over time. Onset may be gradual and mild or rapidly progressive with severe organ involvement. Constitutional manifestations such as fatigue, weight loss, anorexia, and low-grade fever often serve as initial complaints. However, these features are common to a variety of infectious and inflammatory conditions, making early SLE easily overlooked and frequently mis­diagnosed. ²

A mix of manifestations involving the joints, skin, mouth, kidneys, lungs, heart, and nervous system offers clues to the diagnosis of SLE (see Table 1). Arthritis is the most common symptom, occurring in 85% to 90% of SLE cases.^1,10 It is typically nonerosive, inflammatory, symmetric or asymmetric, and polyarticular (involving five or more joints)and may be accompanied by constitutional symptoms.^1,2,11 The joints most commonly affected are the proximal interphalangeals, metacarpophalangeals (MCP), knees, and wrists.² Morning stiffness is a common complaint.^1,11 Jaccoud arthropathy, which is characterized by reducible, nonerosive joint subluxations (eg, swan neck deformities, ulnar deviation, boutonniere deformities, and z-shaped thumbs), can be seen in SLE patients.³ When patients present with articular and constitutional symptoms but lack other typical manifestations of SLE, such as skin rash, appropriate measures—for example, arthrocentesis—should be taken to evaluate for infection.¹¹

Cutaneous manifestations are the second most common feature at disease onset, with photosensitivity and malar rash being the most prevalent.¹⁰ Nearly all patients experience skin lesions at some point during the disease course.¹ Diagnostic, or lupus-specific, lesions can be classified into three types: acute, subacute, and chronic.

Acute cutaneous lupus erythematosus (ACLE) is almost always associated with SLE, while subacute cutaneous lupus erythematosus (SCLE) is seen in about 50% of SLE patients.¹² ACLE is usually precipitated by sunlight exposure and includes the classic erythematous, macular, “butterfly” rash located on the malar regions of the face, which may remain for days to weeks.^2,12 Diffuse or discoid alopecia also may develop in ACLE, along with oral ulcers arising in purpuric necrotic lesions on the palate, buccal mucosa, or gums. Generalized erythematous, papular, or urticarial lesions may affect the face, arms, dorsa of the hands, or “V” of the neck.¹²

SCLE tends to be sudden in onset, with annular lesions or psoriasiform plaques on the upper trunk, arms, and dorsa of the hands that often coalesce into polycyclic lesions.¹² These subacute rashes are often associated with anti-SSA/Ro antibodies.

Chronic cutaneous lupus erythematosus is usually characterized by skin disease alone.¹² Discoid lupus is the most common type, with circular scaly plaques with erythematous, hyperpigmented rims and atrophic hypopigmented centers that leave scars.^2,12 It is commonly seen on the face, neck, and scalp.

During the course of SLE, mucous membrane involvement—typically painless oral or nasal ulcers—occurs in 25% to 45% of patients.² Oral lesions are most commonly found on the hard palate and buccal mucosa.^3,12

Lupus nephritis, perhaps the most dangerous manifestation of SLE, conveys high risk for organ failure, a higher mortality rate compared to patients without renal involvement, and lower life expectancy.^8,11 Up to 60% of Asians, African Americans, and Hispanics develop renal disease during the course of their illness.⁸ The dominant feature is proteinuria, typically accompanied by microscopic hematuria.²

Neuropsychiatric SLE (NPSLE) is a clinical manifestation that is poorly understood.¹³ An estimated 28% to 40% of NPSLE manifestations develop prior to or synchronous with the diagnosis, and 63% arise within the first year of diagnosis.¹³ Mild cognitive impairment is the most common manifestation,reported in up to 20% to 30% of SLE patients.^2,13 Seizures and psychosis are reported in 7% to 10% of SLE patients, and psychosis—characterized by hallucinations or delusions—in 3.5%.²

Cardiac findings are common among SLE patients, with an estimated prevalence of 50%, but are rarely the presenting manifestation.¹⁴ Pericarditis with effusion is the most common cardiac manifestation, occurring in 25% of SLE patients.² Advancing atherosclerosis due to chronic inflammation becomes a major cause of mortality in the later years for SLE patients.¹ Compared to the general population, the incidence of myocardial infarction in SLE patients is increased fivefold.¹ Pleuritis is the most common pleuropulmonary manifestation in SLE.¹¹ Pleuritic chest pain with or without a pleural effusion occurs in 45% to 60% of SLE patients.²

Continue for differential diagnoses >>

DIFFERENTIAL DIAGNOSES
The differential diagnosis for SLE includes rheumatoid arthritis (RA), septic arthritis, mixed connective tissue disease (MCTD), Sjögren syndrome, systemic sclerosis (SSc), polymyositis (PM), fibromyalgia, and drug-induced lupus. Symmetrical, inflammatory, polyarticular arthritis with a predilection for the wrist and MCP joints occurs in both RA and SLE.^1,15 And, because the initial articular features of SLE are symmetric arthralgias, patients with SLE are frequently misdiagnosed with RA. The absence of destructive bony erosions on radiographs and large joint effusions, along with the joint reducibility in SLE, can help distinguish it from RA.¹⁶ Asymmetric arthritis, which can be a presenting feature in both RA and SLE, is more commonly seen in the latter. ANA and rheumatoid factor test results can be positive in both disorders, but antibodies to anti-cyclic citrullinated peptides, with a 95% specificity for RA but absent in SLE, distinguish RA from SLE.^1,16

Patients with MCTD display an array of overlapping features of SLE, PM, and SSc, making the diagnosis difficult.¹⁷ Although MCTD can evolve into other connective tissue diseases, such as SLE, it is nonetheless considered a distinct entity.¹⁷ High titers of anti-U1 ribonucleoprotein (anti-U1RNP) antibodies are indicative of MCTD. Anti-U1RNP is rarely detected in SLE and almost never seen in other rheumatic diseases.¹⁷ Typical manifestations of MCTD are Raynaud phenomenon, swollen fingers (referred to as “sausage digits”), and protuberant polyarthritis.¹⁷

Anti-SSA/Ro and anti-SSB/La antibodies, although detectable in SLE patients, are more commonly associated with Sjögren syndrome. In addition, patients with Sjögren syndrome frequently demonstrate signs of keratoconjunctivitis sicca and xerostomia.¹⁶

The clinical features of fibromyalgia include diffuse musculoskeletal pain that readily mimics SLE arthralgias. The 2011 modification of the 2010 American College of Rheumatology (ACR) preliminary diagnostic criteria for fibromyalgia serves as a reliable tool for diagnosing patients with nonspecific, diffuse pain.¹⁸ This 2011 modification includes 19 pain locations and the six self-reported symptoms: fatigue, impaired sleep, headaches, depression, poor cognition, and abdominal pain.¹⁸

SSc, also known as scleroderma, is characterized by skin thickening and/or CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia). The presence of anti-Scl-70 and anti-centromere antibodies are noted as well.¹⁶

Finally, a suspicion of SLE mandates an evaluation for drug-induced lupus by assessing the patient’s exposure to culprit medications, such as hydralazine, procainamide, isoniazid, methyldopa, chlorpromazine, quinidine, minocycline, and tumor necrosis factor inhibitiors.^1,11 Four key features point toward drug-induced lupus:
• The female-to-male ratio is nearly equivalent.
• Nephritis and central nervous system (CNS) manifestations are not commonly present.
• Anti–double-stranded DNA (anti-dsDNA) antibodies and hypocomplementemia are absent.
• The clinical features and laboratory abnormalities return to baseline once the offending agent is removed.¹

Anti-histone antibodies are present in approximately 75% of patients with drug-induced lupus but can also be seen in patients with SLE.¹¹

Continue for laboratory work-up >>

LABORATORY WORK-UP
Laboratory abnormalities associated with SLE include anemia, leukopenia, lymphopenia, thrombocytopenia, hypocomplementemia, and proteinuria. A typical work-up includes a routine complete blood count (CBC) with differential, serum creatinine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), urinalysis with microscopy, and serologic ANA titer.^1,16,19 A CBC with differential may reveal hematologic abnormalities, such as anemia of chronic disease (most commonly) or autoimmune hemolytic anemia, as well as leukopenia and thrombocytopenia due to circulating autoantibodies.³ An elevated ESR and CRP indicate the severity of the systemic inflammation and/or infection. Urinalysis is effective for detecting lupus with renal diseaseand may reveal proteinuria due to renal dysfunction.²

A positive ANA titer indicates widespread activation of the immune system targeted against nuclear and cytoplasmic subparticles. The vast majority of patients with SLE will develop a positive ANA with a high titer at some point during the course of their disease.¹⁶ The ANA is highly sensitive for SLE (93% to 95%) but lacks specificity (57%).²⁰The most common tests for ANA are enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence assay (IFA). ELISA is more sensitive in detecting ANA, while IFA is the gold standard due to its high specificity.²¹ Some laboratories may use immunoassay as a screening tool for ANA and then use IFA to confirm positive or equivocal results.²¹ Positive ANA results can be seen in patients with other rheumatologic diseases and in up to 15% of all healthy persons, but with low or borderline titers.²² For these reasons, ANA testing alone is a poor predictor of SLE.

When either the ANA test results are positive or are negative but a strong clinical suspicion for SLE remains, clinicians should order tests for antibodies to extractable nuclear antigens (ENA panel; see Table 2).^3,16 Anti-dsDNA and anti-Smith (anti-Sm) antibodies are both specific for SLE, and levels of anti-dsDNA reflect disease activity in many patients.^1,19 In contrast, anti-dsDNA antibodies are found in fewer than 0.5% of healthy individuals and patients with other autoimmune conditions.¹⁹ Among patients with high levels of anti-dsDNA antibodies and clinically inactive disease, 80% will have active disease within five years after elevated antibodies are detected.¹⁹

Autoantibodies, including ANA, anti-SSA/Ro, anti-SSB/La, and antiphospholipid antibodies, are usually detectable for many years prior to the onset of symptomatic SLE, while others, such as anti-Sm and anti-U1RNP, appear just months before the diagnosis.²³ Patients with positive ANA results who do not meet criteria for SLE are still at risk for lupus and other autoimmune diseases, because complex autoimmune changes occur years before the diagnosis of SLE.²³ These patients should be followed closely.

Continue for making the diagnosis >>

MAKING THE DIAGNOSIS
Diagnosing SLE may prove problematic because of the remarkable variety of relapsing and remitting clinical features, mimicry of similar conditions, and lack of a simple, definitive diagnostic test. Initial diagnosis of SLE depends on the disease manifestation, published criteria, and exclusion of alternative diagnoses. Confirmation requires careful clinical assessment, based on a thorough medical history and complete physical examination, along with specific laboratory testing.^1,16 Biopsy results indicative of lupus nephritis in the presence of ANA or anti-dsDNA antibodies also confirm the diagnosis of SLE.²⁴

Although created for research purposes, ACR classification criteria for SLE, published in 1982 and revised in 1997, have been used for more than 30 years to diagnose lupus (see www.rheumatology.org/Practice-Quality/Clinical-Support/Criteria/ACR-Endorsed-Criteria). In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) group revised the 1997 ACR classification criteria to address major flaws and to improve clinical precision.²⁴ According to SLICC, a definitive diagnosis requires the presence of at least four of 17 criteria, including at least one clinical and one immunologic criterion.²⁴ The SLICC revisions have resulted in fewer misclassifications and provide greater sensitivity but lower specificity in the identification of SLE in comparison to the 1997 ACR criteria.²⁴ To date, no one set of criteria allows for early diagnosis of SLE.

MANAGEMENT OPTIONS
Treatment must be tailored to the patient’s specific organ system involvement. Effective therapy hinges on controlling symptoms and reducing underlying inflammation.²⁵ Four classes of drugs are used: NSAIDs, antimalarial drugs, corticosteroids, and cytotoxic drugs (see Table 3). Most patients benefit from NSAIDs to alleviate minor arthritis and arthralgia symptoms, but the risk for peptic ulcers and nephrotoxicity should be addressed; this may require the concomitant use of gastroprotective agents such as proton pump inhibitors.²⁵ Antimalarials are effective for musculoskeletal symptoms that do not respond to NSAIDs and for cutaneous rashes.¹ The current antimalarial drug of choice is hydroxychloroquine (200 to 400 mg/d po), which has been shown to control SLE manifestations by reducing and preventing disease flares.^1,11,26 It is well tolerated and can be used for the duration of treatment.^11,26 Patients should be informed that this drug’s onset of action is one month.²⁶ In rare cases, this drug can cause retinal toxicity; therefore, SLE patients receiving hydroxychloroquine should be referred to an ophthalmologist for a baseline eye examination and yearly assessments to monitor for this rare adverse effect.^25,26

Low-dose corticosteroids, such as oral prednisolone or methylprednisolone, are employed when NSAIDs and antimalarials fail to control arthritis or cutaneous SLE eruptions.²⁵ Major systemic manifestations that occur during a disease flare—such as severe arthritis, hemolytic anemia, glomerulonephritis, alveolar hemorrhage, pericarditis, pleurisy, or CNS involvement—necessitate high-dose IV corticosteroids in conjunction with immunosuppressive agents.^1,11,25 These high-dose glucocorticoids should be gradually withdrawn as soon as remission is achieved.¹¹ Long-term suppressive therapy with oral corticosteroids in addition to other agents is often needed to preserve organ function.²⁵

The major adverse effects of long-term glucocorticoids are osteoporosis, hypertension, hyperlipidemia, glucose intolerance, and susceptibility to infection. It is recommended that patients taking prednisolone 7.5 mg/d or more undergo a bone mineral density scan every two years.²⁵ Those with T scores below –2.5 should be prescribed bisphosphonates.²⁵

Immunosuppressive agents, such as cyclophosphamide, mycophenolate mofetil, and azathioprine, are used in conjunction with corticosteroids or when syndromes are resistant to corticosteroids.¹ Collaboration between primary care, rheumatology, and nephrology is advisable for patients requiring immunosuppressive or disease-modifying pharmacologic agents.

Two new treatments for SLE are the immunologic agents belimumab and rituximab.⁷ Belimumab, a monoclonal human antibody, is the first medication in the past 50 years that has been approved by the FDA for antibody-positive SLE patients with active lupus unresponsive to standard treatment.^7,27 Rituximab is an anti-CD20 monoclonal antibody, approved by the FDA for non-Hodgkin lymphoma, chronic lymphocytic leukemia, and RA, and is now considered an option for SLE refractory to conventional treatment regimens.^7,27 The efficacy of belimumab and rituximab, and the spectrum of indications for their use, are still under study, but these new therapeutic agents hold promise for the treatment of patients with refractory SLE.

Continue for helping patients live with SLE >>

HELPING PATIENTs LIVE WITH SLE
Patients with SLE have a higher mortality rate, as well as a lower quality of life, compared to the general population.²⁸ The major contributors to a decreased quality of life are fatigue, mood disturbances (eg, depression), and chronic pain.²⁸ Practitioners should advise SLE patients to participate in support groups and psychotherapy to alleviate the anxiety and depression associated with this chronic disease.

For patients with long-standing disease, accelerated atherosclerotic cardiovascular disease adds to morbidity and mortality. For this reason, obesity, hypertension, hyperlipidemia, and smoking are targets for intervention. Lifestyle modifications—such as exercise, smoking cessation, a healthy diet with low saturated fat, stress avoidance, and adequate rest—are recommended.²⁶

Avoiding overexposure to sunlight, by using sunscreen with an SPF of at least 30 and wearing sun-protective clothing, is essential for management of cutaneous lupus.^25,26 Yearly influenza vaccination is appropriate, as are other immunizations (eg, pneumococcal vaccine).²⁶

Advise women of childbearing age with SLE that lupus flares result in a high risk for miscarriage. All women should undergo yearly cervical cancer screening.²⁶

Patients taking long-term glucocorticoids should adopt bone-protective behaviors, including quitting smoking, limiting alcohol intake, partaking in weight-bearing exercise, and consuming dietary calcium and vitamin D.²⁵ Patients taking these drugs should avoid live virus vaccines. Those on immunosuppressive therapy should be warned about the hazardous adverse effects of glucocorticoids.

MONITORING AND FOLLOW-UP
Collaborative efforts between primary care providers and several types of specialty providers can facilitate coordinated interventions in the long-term management of lupus. Rheumatologists are experts in making therapeutic decisions for SLE.

Patients being treated for SLE require routine monitoring to assess disease activity and detect flares. The European League Against Rheumatism (EULAR) guidelines recommend that monitoring include assessment for new clinical manifestations, routine laboratory tests, and immunologic assays, chiefly anti-dsDNA, anti-Sm, and serum complement levels, coupled with one of the validated global activity indices, such as the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).²⁹

A routine office visit with a physical examination and laboratory testing for CBC with differential, basic metabolic panel, and urinalysis every three months is recommended for patients with stable disease; patients with uncontrolled SLE may require weekly visits.^11,29 Patients taking immunosuppressive drugs should be provided with adverse-effect profiles alerting them to toxicity symptoms and require frequent laboratory monitoring for potential toxicity.¹¹

CONCLUSION
Advances in immunologically targeted serologic tests have shed more light on the underlying pathogenesis of SLE, which in turn has led to improvements in disease detection and monitoring of complications, as well as advances in therapy. Although SLE cannot be cured, emerging therapies targeting different mechanisms of SLE offer hope for patients diagnosed with this complex disease.

CE/CME No: CR-1608

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES
• Describe the pathophysiology and explain the various clinical manifestations of systemic lupus erythematosus (SLE).
• Define the differential diagnosis for SLE.
• List the elements of the laboratory work-up used in the diagnosis of lupus.
• Describe the therapeutic options for patients with SLE.

FACULTY

Michael Felz is an Assistant Professor at Augusta University (formerly Georgia Regents University) in Augusta, Georgia. Mary Bailey Wickham is a PA student in her final year at Augusta University.
The authors have no financial relationships to disclose.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.0 hour of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of August 2016.

Article begins on next page >>

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that often goes undiagnosed initially. Timely detection of SLE is important, because prompt treatment can prevent its many major complications—notably, end organ damage. Here’s how to distinguish SLE from other illnesses with similar presentations and how to recognize the complications of undiagnosed SLE, which can progress rapidly and fatally.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disorder that can involve multiple organ systems. The presence of antinuclear antibodies (ANA) is a common marker for this disease. In autoimmune diseases such as SLE, the immune system attacks the cells of healthy tissues throughout the body. Genetic, hormonal, and environmental factors (eg, ultraviolet light, infectious viruses, and even use of certain medications) have been implicated in the pathogenesis.^1-3

It is estimated that 1.5 million people in the United States and up to 5 million people worldwide have SLE.⁴ It is nine to 10 times more prevalent in women—especially those of reproductive age—than menand occurs more frequently in African-American, Hispanic, and Asian women than in non-Hispanic Caucasian women.^1,2,4-6 Siblings of SLE patients are 30 times more likely to develop the disease, compared to individuals without an affected relative.² Increased mortality in persons with SLE is attributed to accelerated atherosclerosis, infection, malignancy, and target organ damage, particularly end-stage renal disease.³ Women ages 33 to 45 with SLE are at increased risk (50x greater) for myocardial infarction due to premature atherosclerosis than age-matched women in the general population.⁷ The life expectancy of SLE ­patients with renal damage is 23.7 years less than that of the general population.⁸

Increased awareness of SLE has led to drastic improvements in associated mortality over the past five decades. The survival rate in the 1950s was 50% at 2 years, while current rates are about 95% at 5 years and about 90% at 10 years.^3,9 These improvements likely reflect earlier diagnosis and treatment on the part of well-informed clinicians, as well as more effective treatment.

SLE MANIFESTATIONS
SLE can affect any organ in the body with a broad spectrum of clinical manifestations, making it a devastatingly deceptive disease. Disease severity may vary by age, by organ involvement, and over time. Onset may be gradual and mild or rapidly progressive with severe organ involvement. Constitutional manifestations such as fatigue, weight loss, anorexia, and low-grade fever often serve as initial complaints. However, these features are common to a variety of infectious and inflammatory conditions, making early SLE easily overlooked and frequently mis­diagnosed. ²

A mix of manifestations involving the joints, skin, mouth, kidneys, lungs, heart, and nervous system offers clues to the diagnosis of SLE (see Table 1). Arthritis is the most common symptom, occurring in 85% to 90% of SLE cases.^1,10 It is typically nonerosive, inflammatory, symmetric or asymmetric, and polyarticular (involving five or more joints)and may be accompanied by constitutional symptoms.^1,2,11 The joints most commonly affected are the proximal interphalangeals, metacarpophalangeals (MCP), knees, and wrists.² Morning stiffness is a common complaint.^1,11 Jaccoud arthropathy, which is characterized by reducible, nonerosive joint subluxations (eg, swan neck deformities, ulnar deviation, boutonniere deformities, and z-shaped thumbs), can be seen in SLE patients.³ When patients present with articular and constitutional symptoms but lack other typical manifestations of SLE, such as skin rash, appropriate measures—for example, arthrocentesis—should be taken to evaluate for infection.¹¹

Cutaneous manifestations are the second most common feature at disease onset, with photosensitivity and malar rash being the most prevalent.¹⁰ Nearly all patients experience skin lesions at some point during the disease course.¹ Diagnostic, or lupus-specific, lesions can be classified into three types: acute, subacute, and chronic.

Acute cutaneous lupus erythematosus (ACLE) is almost always associated with SLE, while subacute cutaneous lupus erythematosus (SCLE) is seen in about 50% of SLE patients.¹² ACLE is usually precipitated by sunlight exposure and includes the classic erythematous, macular, “butterfly” rash located on the malar regions of the face, which may remain for days to weeks.^2,12 Diffuse or discoid alopecia also may develop in ACLE, along with oral ulcers arising in purpuric necrotic lesions on the palate, buccal mucosa, or gums. Generalized erythematous, papular, or urticarial lesions may affect the face, arms, dorsa of the hands, or “V” of the neck.¹²

SCLE tends to be sudden in onset, with annular lesions or psoriasiform plaques on the upper trunk, arms, and dorsa of the hands that often coalesce into polycyclic lesions.¹² These subacute rashes are often associated with anti-SSA/Ro antibodies.

Chronic cutaneous lupus erythematosus is usually characterized by skin disease alone.¹² Discoid lupus is the most common type, with circular scaly plaques with erythematous, hyperpigmented rims and atrophic hypopigmented centers that leave scars.^2,12 It is commonly seen on the face, neck, and scalp.

During the course of SLE, mucous membrane involvement—typically painless oral or nasal ulcers—occurs in 25% to 45% of patients.² Oral lesions are most commonly found on the hard palate and buccal mucosa.^3,12

Lupus nephritis, perhaps the most dangerous manifestation of SLE, conveys high risk for organ failure, a higher mortality rate compared to patients without renal involvement, and lower life expectancy.^8,11 Up to 60% of Asians, African Americans, and Hispanics develop renal disease during the course of their illness.⁸ The dominant feature is proteinuria, typically accompanied by microscopic hematuria.²

Neuropsychiatric SLE (NPSLE) is a clinical manifestation that is poorly understood.¹³ An estimated 28% to 40% of NPSLE manifestations develop prior to or synchronous with the diagnosis, and 63% arise within the first year of diagnosis.¹³ Mild cognitive impairment is the most common manifestation,reported in up to 20% to 30% of SLE patients.^2,13 Seizures and psychosis are reported in 7% to 10% of SLE patients, and psychosis—characterized by hallucinations or delusions—in 3.5%.²

Cardiac findings are common among SLE patients, with an estimated prevalence of 50%, but are rarely the presenting manifestation.¹⁴ Pericarditis with effusion is the most common cardiac manifestation, occurring in 25% of SLE patients.² Advancing atherosclerosis due to chronic inflammation becomes a major cause of mortality in the later years for SLE patients.¹ Compared to the general population, the incidence of myocardial infarction in SLE patients is increased fivefold.¹ Pleuritis is the most common pleuropulmonary manifestation in SLE.¹¹ Pleuritic chest pain with or without a pleural effusion occurs in 45% to 60% of SLE patients.²

Continue for differential diagnoses >>

DIFFERENTIAL DIAGNOSES
The differential diagnosis for SLE includes rheumatoid arthritis (RA), septic arthritis, mixed connective tissue disease (MCTD), Sjögren syndrome, systemic sclerosis (SSc), polymyositis (PM), fibromyalgia, and drug-induced lupus. Symmetrical, inflammatory, polyarticular arthritis with a predilection for the wrist and MCP joints occurs in both RA and SLE.^1,15 And, because the initial articular features of SLE are symmetric arthralgias, patients with SLE are frequently misdiagnosed with RA. The absence of destructive bony erosions on radiographs and large joint effusions, along with the joint reducibility in SLE, can help distinguish it from RA.¹⁶ Asymmetric arthritis, which can be a presenting feature in both RA and SLE, is more commonly seen in the latter. ANA and rheumatoid factor test results can be positive in both disorders, but antibodies to anti-cyclic citrullinated peptides, with a 95% specificity for RA but absent in SLE, distinguish RA from SLE.^1,16

Patients with MCTD display an array of overlapping features of SLE, PM, and SSc, making the diagnosis difficult.¹⁷ Although MCTD can evolve into other connective tissue diseases, such as SLE, it is nonetheless considered a distinct entity.¹⁷ High titers of anti-U1 ribonucleoprotein (anti-U1RNP) antibodies are indicative of MCTD. Anti-U1RNP is rarely detected in SLE and almost never seen in other rheumatic diseases.¹⁷ Typical manifestations of MCTD are Raynaud phenomenon, swollen fingers (referred to as “sausage digits”), and protuberant polyarthritis.¹⁷

Anti-SSA/Ro and anti-SSB/La antibodies, although detectable in SLE patients, are more commonly associated with Sjögren syndrome. In addition, patients with Sjögren syndrome frequently demonstrate signs of keratoconjunctivitis sicca and xerostomia.¹⁶

The clinical features of fibromyalgia include diffuse musculoskeletal pain that readily mimics SLE arthralgias. The 2011 modification of the 2010 American College of Rheumatology (ACR) preliminary diagnostic criteria for fibromyalgia serves as a reliable tool for diagnosing patients with nonspecific, diffuse pain.¹⁸ This 2011 modification includes 19 pain locations and the six self-reported symptoms: fatigue, impaired sleep, headaches, depression, poor cognition, and abdominal pain.¹⁸

SSc, also known as scleroderma, is characterized by skin thickening and/or CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia). The presence of anti-Scl-70 and anti-centromere antibodies are noted as well.¹⁶

Finally, a suspicion of SLE mandates an evaluation for drug-induced lupus by assessing the patient’s exposure to culprit medications, such as hydralazine, procainamide, isoniazid, methyldopa, chlorpromazine, quinidine, minocycline, and tumor necrosis factor inhibitiors.^1,11 Four key features point toward drug-induced lupus:
• The female-to-male ratio is nearly equivalent.
• Nephritis and central nervous system (CNS) manifestations are not commonly present.
• Anti–double-stranded DNA (anti-dsDNA) antibodies and hypocomplementemia are absent.
• The clinical features and laboratory abnormalities return to baseline once the offending agent is removed.¹

Anti-histone antibodies are present in approximately 75% of patients with drug-induced lupus but can also be seen in patients with SLE.¹¹

Continue for laboratory work-up >>

LABORATORY WORK-UP
Laboratory abnormalities associated with SLE include anemia, leukopenia, lymphopenia, thrombocytopenia, hypocomplementemia, and proteinuria. A typical work-up includes a routine complete blood count (CBC) with differential, serum creatinine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), urinalysis with microscopy, and serologic ANA titer.^1,16,19 A CBC with differential may reveal hematologic abnormalities, such as anemia of chronic disease (most commonly) or autoimmune hemolytic anemia, as well as leukopenia and thrombocytopenia due to circulating autoantibodies.³ An elevated ESR and CRP indicate the severity of the systemic inflammation and/or infection. Urinalysis is effective for detecting lupus with renal diseaseand may reveal proteinuria due to renal dysfunction.²

A positive ANA titer indicates widespread activation of the immune system targeted against nuclear and cytoplasmic subparticles. The vast majority of patients with SLE will develop a positive ANA with a high titer at some point during the course of their disease.¹⁶ The ANA is highly sensitive for SLE (93% to 95%) but lacks specificity (57%).²⁰The most common tests for ANA are enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence assay (IFA). ELISA is more sensitive in detecting ANA, while IFA is the gold standard due to its high specificity.²¹ Some laboratories may use immunoassay as a screening tool for ANA and then use IFA to confirm positive or equivocal results.²¹ Positive ANA results can be seen in patients with other rheumatologic diseases and in up to 15% of all healthy persons, but with low or borderline titers.²² For these reasons, ANA testing alone is a poor predictor of SLE.

When either the ANA test results are positive or are negative but a strong clinical suspicion for SLE remains, clinicians should order tests for antibodies to extractable nuclear antigens (ENA panel; see Table 2).^3,16 Anti-dsDNA and anti-Smith (anti-Sm) antibodies are both specific for SLE, and levels of anti-dsDNA reflect disease activity in many patients.^1,19 In contrast, anti-dsDNA antibodies are found in fewer than 0.5% of healthy individuals and patients with other autoimmune conditions.¹⁹ Among patients with high levels of anti-dsDNA antibodies and clinically inactive disease, 80% will have active disease within five years after elevated antibodies are detected.¹⁹

Autoantibodies, including ANA, anti-SSA/Ro, anti-SSB/La, and antiphospholipid antibodies, are usually detectable for many years prior to the onset of symptomatic SLE, while others, such as anti-Sm and anti-U1RNP, appear just months before the diagnosis.²³ Patients with positive ANA results who do not meet criteria for SLE are still at risk for lupus and other autoimmune diseases, because complex autoimmune changes occur years before the diagnosis of SLE.²³ These patients should be followed closely.

Continue for making the diagnosis >>

MAKING THE DIAGNOSIS
Diagnosing SLE may prove problematic because of the remarkable variety of relapsing and remitting clinical features, mimicry of similar conditions, and lack of a simple, definitive diagnostic test. Initial diagnosis of SLE depends on the disease manifestation, published criteria, and exclusion of alternative diagnoses. Confirmation requires careful clinical assessment, based on a thorough medical history and complete physical examination, along with specific laboratory testing.^1,16 Biopsy results indicative of lupus nephritis in the presence of ANA or anti-dsDNA antibodies also confirm the diagnosis of SLE.²⁴

Although created for research purposes, ACR classification criteria for SLE, published in 1982 and revised in 1997, have been used for more than 30 years to diagnose lupus (see www.rheumatology.org/Practice-Quality/Clinical-Support/Criteria/ACR-Endorsed-Criteria). In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) group revised the 1997 ACR classification criteria to address major flaws and to improve clinical precision.²⁴ According to SLICC, a definitive diagnosis requires the presence of at least four of 17 criteria, including at least one clinical and one immunologic criterion.²⁴ The SLICC revisions have resulted in fewer misclassifications and provide greater sensitivity but lower specificity in the identification of SLE in comparison to the 1997 ACR criteria.²⁴ To date, no one set of criteria allows for early diagnosis of SLE.

MANAGEMENT OPTIONS
Treatment must be tailored to the patient’s specific organ system involvement. Effective therapy hinges on controlling symptoms and reducing underlying inflammation.²⁵ Four classes of drugs are used: NSAIDs, antimalarial drugs, corticosteroids, and cytotoxic drugs (see Table 3). Most patients benefit from NSAIDs to alleviate minor arthritis and arthralgia symptoms, but the risk for peptic ulcers and nephrotoxicity should be addressed; this may require the concomitant use of gastroprotective agents such as proton pump inhibitors.²⁵ Antimalarials are effective for musculoskeletal symptoms that do not respond to NSAIDs and for cutaneous rashes.¹ The current antimalarial drug of choice is hydroxychloroquine (200 to 400 mg/d po), which has been shown to control SLE manifestations by reducing and preventing disease flares.^1,11,26 It is well tolerated and can be used for the duration of treatment.^11,26 Patients should be informed that this drug’s onset of action is one month.²⁶ In rare cases, this drug can cause retinal toxicity; therefore, SLE patients receiving hydroxychloroquine should be referred to an ophthalmologist for a baseline eye examination and yearly assessments to monitor for this rare adverse effect.^25,26

Low-dose corticosteroids, such as oral prednisolone or methylprednisolone, are employed when NSAIDs and antimalarials fail to control arthritis or cutaneous SLE eruptions.²⁵ Major systemic manifestations that occur during a disease flare—such as severe arthritis, hemolytic anemia, glomerulonephritis, alveolar hemorrhage, pericarditis, pleurisy, or CNS involvement—necessitate high-dose IV corticosteroids in conjunction with immunosuppressive agents.^1,11,25 These high-dose glucocorticoids should be gradually withdrawn as soon as remission is achieved.¹¹ Long-term suppressive therapy with oral corticosteroids in addition to other agents is often needed to preserve organ function.²⁵

The major adverse effects of long-term glucocorticoids are osteoporosis, hypertension, hyperlipidemia, glucose intolerance, and susceptibility to infection. It is recommended that patients taking prednisolone 7.5 mg/d or more undergo a bone mineral density scan every two years.²⁵ Those with T scores below –2.5 should be prescribed bisphosphonates.²⁵

Immunosuppressive agents, such as cyclophosphamide, mycophenolate mofetil, and azathioprine, are used in conjunction with corticosteroids or when syndromes are resistant to corticosteroids.¹ Collaboration between primary care, rheumatology, and nephrology is advisable for patients requiring immunosuppressive or disease-modifying pharmacologic agents.

Two new treatments for SLE are the immunologic agents belimumab and rituximab.⁷ Belimumab, a monoclonal human antibody, is the first medication in the past 50 years that has been approved by the FDA for antibody-positive SLE patients with active lupus unresponsive to standard treatment.^7,27 Rituximab is an anti-CD20 monoclonal antibody, approved by the FDA for non-Hodgkin lymphoma, chronic lymphocytic leukemia, and RA, and is now considered an option for SLE refractory to conventional treatment regimens.^7,27 The efficacy of belimumab and rituximab, and the spectrum of indications for their use, are still under study, but these new therapeutic agents hold promise for the treatment of patients with refractory SLE.

Continue for helping patients live with SLE >>

HELPING PATIENTs LIVE WITH SLE
Patients with SLE have a higher mortality rate, as well as a lower quality of life, compared to the general population.²⁸ The major contributors to a decreased quality of life are fatigue, mood disturbances (eg, depression), and chronic pain.²⁸ Practitioners should advise SLE patients to participate in support groups and psychotherapy to alleviate the anxiety and depression associated with this chronic disease.

For patients with long-standing disease, accelerated atherosclerotic cardiovascular disease adds to morbidity and mortality. For this reason, obesity, hypertension, hyperlipidemia, and smoking are targets for intervention. Lifestyle modifications—such as exercise, smoking cessation, a healthy diet with low saturated fat, stress avoidance, and adequate rest—are recommended.²⁶

Avoiding overexposure to sunlight, by using sunscreen with an SPF of at least 30 and wearing sun-protective clothing, is essential for management of cutaneous lupus.^25,26 Yearly influenza vaccination is appropriate, as are other immunizations (eg, pneumococcal vaccine).²⁶

Advise women of childbearing age with SLE that lupus flares result in a high risk for miscarriage. All women should undergo yearly cervical cancer screening.²⁶

Patients taking long-term glucocorticoids should adopt bone-protective behaviors, including quitting smoking, limiting alcohol intake, partaking in weight-bearing exercise, and consuming dietary calcium and vitamin D.²⁵ Patients taking these drugs should avoid live virus vaccines. Those on immunosuppressive therapy should be warned about the hazardous adverse effects of glucocorticoids.

MONITORING AND FOLLOW-UP
Collaborative efforts between primary care providers and several types of specialty providers can facilitate coordinated interventions in the long-term management of lupus. Rheumatologists are experts in making therapeutic decisions for SLE.

Patients being treated for SLE require routine monitoring to assess disease activity and detect flares. The European League Against Rheumatism (EULAR) guidelines recommend that monitoring include assessment for new clinical manifestations, routine laboratory tests, and immunologic assays, chiefly anti-dsDNA, anti-Sm, and serum complement levels, coupled with one of the validated global activity indices, such as the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).²⁹

A routine office visit with a physical examination and laboratory testing for CBC with differential, basic metabolic panel, and urinalysis every three months is recommended for patients with stable disease; patients with uncontrolled SLE may require weekly visits.^11,29 Patients taking immunosuppressive drugs should be provided with adverse-effect profiles alerting them to toxicity symptoms and require frequent laboratory monitoring for potential toxicity.¹¹

CONCLUSION
Advances in immunologically targeted serologic tests have shed more light on the underlying pathogenesis of SLE, which in turn has led to improvements in disease detection and monitoring of complications, as well as advances in therapy. Although SLE cannot be cured, emerging therapies targeting different mechanisms of SLE offer hope for patients diagnosed with this complex disease.

CE/CME No: CR-1608

PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.

EDUCATIONAL OBJECTIVES
• Describe the pathophysiology and explain the various clinical manifestations of systemic lupus erythematosus (SLE).
• Define the differential diagnosis for SLE.
• List the elements of the laboratory work-up used in the diagnosis of lupus.
• Describe the therapeutic options for patients with SLE.

FACULTY

Michael Felz is an Assistant Professor at Augusta University (formerly Georgia Regents University) in Augusta, Georgia. Mary Bailey Wickham is a PA student in her final year at Augusta University.
The authors have no financial relationships to disclose.

ACCREDITATION STATEMENT

This program has been reviewed and is approved for a maximum of 1.0 hour of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid for one year from the issue date of August 2016.

Article begins on next page >>

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that often goes undiagnosed initially. Timely detection of SLE is important, because prompt treatment can prevent its many major complications—notably, end organ damage. Here’s how to distinguish SLE from other illnesses with similar presentations and how to recognize the complications of undiagnosed SLE, which can progress rapidly and fatally.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disorder that can involve multiple organ systems. The presence of antinuclear antibodies (ANA) is a common marker for this disease. In autoimmune diseases such as SLE, the immune system attacks the cells of healthy tissues throughout the body. Genetic, hormonal, and environmental factors (eg, ultraviolet light, infectious viruses, and even use of certain medications) have been implicated in the pathogenesis.^1-3

It is estimated that 1.5 million people in the United States and up to 5 million people worldwide have SLE.⁴ It is nine to 10 times more prevalent in women—especially those of reproductive age—than menand occurs more frequently in African-American, Hispanic, and Asian women than in non-Hispanic Caucasian women.^1,2,4-6 Siblings of SLE patients are 30 times more likely to develop the disease, compared to individuals without an affected relative.² Increased mortality in persons with SLE is attributed to accelerated atherosclerosis, infection, malignancy, and target organ damage, particularly end-stage renal disease.³ Women ages 33 to 45 with SLE are at increased risk (50x greater) for myocardial infarction due to premature atherosclerosis than age-matched women in the general population.⁷ The life expectancy of SLE ­patients with renal damage is 23.7 years less than that of the general population.⁸

Increased awareness of SLE has led to drastic improvements in associated mortality over the past five decades. The survival rate in the 1950s was 50% at 2 years, while current rates are about 95% at 5 years and about 90% at 10 years.^3,9 These improvements likely reflect earlier diagnosis and treatment on the part of well-informed clinicians, as well as more effective treatment.

SLE MANIFESTATIONS
SLE can affect any organ in the body with a broad spectrum of clinical manifestations, making it a devastatingly deceptive disease. Disease severity may vary by age, by organ involvement, and over time. Onset may be gradual and mild or rapidly progressive with severe organ involvement. Constitutional manifestations such as fatigue, weight loss, anorexia, and low-grade fever often serve as initial complaints. However, these features are common to a variety of infectious and inflammatory conditions, making early SLE easily overlooked and frequently mis­diagnosed. ²

A mix of manifestations involving the joints, skin, mouth, kidneys, lungs, heart, and nervous system offers clues to the diagnosis of SLE (see Table 1). Arthritis is the most common symptom, occurring in 85% to 90% of SLE cases.^1,10 It is typically nonerosive, inflammatory, symmetric or asymmetric, and polyarticular (involving five or more joints)and may be accompanied by constitutional symptoms.^1,2,11 The joints most commonly affected are the proximal interphalangeals, metacarpophalangeals (MCP), knees, and wrists.² Morning stiffness is a common complaint.^1,11 Jaccoud arthropathy, which is characterized by reducible, nonerosive joint subluxations (eg, swan neck deformities, ulnar deviation, boutonniere deformities, and z-shaped thumbs), can be seen in SLE patients.³ When patients present with articular and constitutional symptoms but lack other typical manifestations of SLE, such as skin rash, appropriate measures—for example, arthrocentesis—should be taken to evaluate for infection.¹¹

Cutaneous manifestations are the second most common feature at disease onset, with photosensitivity and malar rash being the most prevalent.¹⁰ Nearly all patients experience skin lesions at some point during the disease course.¹ Diagnostic, or lupus-specific, lesions can be classified into three types: acute, subacute, and chronic.

Acute cutaneous lupus erythematosus (ACLE) is almost always associated with SLE, while subacute cutaneous lupus erythematosus (SCLE) is seen in about 50% of SLE patients.¹² ACLE is usually precipitated by sunlight exposure and includes the classic erythematous, macular, “butterfly” rash located on the malar regions of the face, which may remain for days to weeks.^2,12 Diffuse or discoid alopecia also may develop in ACLE, along with oral ulcers arising in purpuric necrotic lesions on the palate, buccal mucosa, or gums. Generalized erythematous, papular, or urticarial lesions may affect the face, arms, dorsa of the hands, or “V” of the neck.¹²

SCLE tends to be sudden in onset, with annular lesions or psoriasiform plaques on the upper trunk, arms, and dorsa of the hands that often coalesce into polycyclic lesions.¹² These subacute rashes are often associated with anti-SSA/Ro antibodies.

Chronic cutaneous lupus erythematosus is usually characterized by skin disease alone.¹² Discoid lupus is the most common type, with circular scaly plaques with erythematous, hyperpigmented rims and atrophic hypopigmented centers that leave scars.^2,12 It is commonly seen on the face, neck, and scalp.

During the course of SLE, mucous membrane involvement—typically painless oral or nasal ulcers—occurs in 25% to 45% of patients.² Oral lesions are most commonly found on the hard palate and buccal mucosa.^3,12

Lupus nephritis, perhaps the most dangerous manifestation of SLE, conveys high risk for organ failure, a higher mortality rate compared to patients without renal involvement, and lower life expectancy.^8,11 Up to 60% of Asians, African Americans, and Hispanics develop renal disease during the course of their illness.⁸ The dominant feature is proteinuria, typically accompanied by microscopic hematuria.²

Neuropsychiatric SLE (NPSLE) is a clinical manifestation that is poorly understood.¹³ An estimated 28% to 40% of NPSLE manifestations develop prior to or synchronous with the diagnosis, and 63% arise within the first year of diagnosis.¹³ Mild cognitive impairment is the most common manifestation,reported in up to 20% to 30% of SLE patients.^2,13 Seizures and psychosis are reported in 7% to 10% of SLE patients, and psychosis—characterized by hallucinations or delusions—in 3.5%.²

Cardiac findings are common among SLE patients, with an estimated prevalence of 50%, but are rarely the presenting manifestation.¹⁴ Pericarditis with effusion is the most common cardiac manifestation, occurring in 25% of SLE patients.² Advancing atherosclerosis due to chronic inflammation becomes a major cause of mortality in the later years for SLE patients.¹ Compared to the general population, the incidence of myocardial infarction in SLE patients is increased fivefold.¹ Pleuritis is the most common pleuropulmonary manifestation in SLE.¹¹ Pleuritic chest pain with or without a pleural effusion occurs in 45% to 60% of SLE patients.²

Continue for differential diagnoses >>

DIFFERENTIAL DIAGNOSES
The differential diagnosis for SLE includes rheumatoid arthritis (RA), septic arthritis, mixed connective tissue disease (MCTD), Sjögren syndrome, systemic sclerosis (SSc), polymyositis (PM), fibromyalgia, and drug-induced lupus. Symmetrical, inflammatory, polyarticular arthritis with a predilection for the wrist and MCP joints occurs in both RA and SLE.^1,15 And, because the initial articular features of SLE are symmetric arthralgias, patients with SLE are frequently misdiagnosed with RA. The absence of destructive bony erosions on radiographs and large joint effusions, along with the joint reducibility in SLE, can help distinguish it from RA.¹⁶ Asymmetric arthritis, which can be a presenting feature in both RA and SLE, is more commonly seen in the latter. ANA and rheumatoid factor test results can be positive in both disorders, but antibodies to anti-cyclic citrullinated peptides, with a 95% specificity for RA but absent in SLE, distinguish RA from SLE.^1,16

Patients with MCTD display an array of overlapping features of SLE, PM, and SSc, making the diagnosis difficult.¹⁷ Although MCTD can evolve into other connective tissue diseases, such as SLE, it is nonetheless considered a distinct entity.¹⁷ High titers of anti-U1 ribonucleoprotein (anti-U1RNP) antibodies are indicative of MCTD. Anti-U1RNP is rarely detected in SLE and almost never seen in other rheumatic diseases.¹⁷ Typical manifestations of MCTD are Raynaud phenomenon, swollen fingers (referred to as “sausage digits”), and protuberant polyarthritis.¹⁷

Anti-SSA/Ro and anti-SSB/La antibodies, although detectable in SLE patients, are more commonly associated with Sjögren syndrome. In addition, patients with Sjögren syndrome frequently demonstrate signs of keratoconjunctivitis sicca and xerostomia.¹⁶

The clinical features of fibromyalgia include diffuse musculoskeletal pain that readily mimics SLE arthralgias. The 2011 modification of the 2010 American College of Rheumatology (ACR) preliminary diagnostic criteria for fibromyalgia serves as a reliable tool for diagnosing patients with nonspecific, diffuse pain.¹⁸ This 2011 modification includes 19 pain locations and the six self-reported symptoms: fatigue, impaired sleep, headaches, depression, poor cognition, and abdominal pain.¹⁸

SSc, also known as scleroderma, is characterized by skin thickening and/or CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia). The presence of anti-Scl-70 and anti-centromere antibodies are noted as well.¹⁶

Finally, a suspicion of SLE mandates an evaluation for drug-induced lupus by assessing the patient’s exposure to culprit medications, such as hydralazine, procainamide, isoniazid, methyldopa, chlorpromazine, quinidine, minocycline, and tumor necrosis factor inhibitiors.^1,11 Four key features point toward drug-induced lupus:
• The female-to-male ratio is nearly equivalent.
• Nephritis and central nervous system (CNS) manifestations are not commonly present.
• Anti–double-stranded DNA (anti-dsDNA) antibodies and hypocomplementemia are absent.
• The clinical features and laboratory abnormalities return to baseline once the offending agent is removed.¹

Anti-histone antibodies are present in approximately 75% of patients with drug-induced lupus but can also be seen in patients with SLE.¹¹

Continue for laboratory work-up >>

LABORATORY WORK-UP
Laboratory abnormalities associated with SLE include anemia, leukopenia, lymphopenia, thrombocytopenia, hypocomplementemia, and proteinuria. A typical work-up includes a routine complete blood count (CBC) with differential, serum creatinine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), urinalysis with microscopy, and serologic ANA titer.^1,16,19 A CBC with differential may reveal hematologic abnormalities, such as anemia of chronic disease (most commonly) or autoimmune hemolytic anemia, as well as leukopenia and thrombocytopenia due to circulating autoantibodies.³ An elevated ESR and CRP indicate the severity of the systemic inflammation and/or infection. Urinalysis is effective for detecting lupus with renal diseaseand may reveal proteinuria due to renal dysfunction.²

A positive ANA titer indicates widespread activation of the immune system targeted against nuclear and cytoplasmic subparticles. The vast majority of patients with SLE will develop a positive ANA with a high titer at some point during the course of their disease.¹⁶ The ANA is highly sensitive for SLE (93% to 95%) but lacks specificity (57%).²⁰The most common tests for ANA are enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence assay (IFA). ELISA is more sensitive in detecting ANA, while IFA is the gold standard due to its high specificity.²¹ Some laboratories may use immunoassay as a screening tool for ANA and then use IFA to confirm positive or equivocal results.²¹ Positive ANA results can be seen in patients with other rheumatologic diseases and in up to 15% of all healthy persons, but with low or borderline titers.²² For these reasons, ANA testing alone is a poor predictor of SLE.

When either the ANA test results are positive or are negative but a strong clinical suspicion for SLE remains, clinicians should order tests for antibodies to extractable nuclear antigens (ENA panel; see Table 2).^3,16 Anti-dsDNA and anti-Smith (anti-Sm) antibodies are both specific for SLE, and levels of anti-dsDNA reflect disease activity in many patients.^1,19 In contrast, anti-dsDNA antibodies are found in fewer than 0.5% of healthy individuals and patients with other autoimmune conditions.¹⁹ Among patients with high levels of anti-dsDNA antibodies and clinically inactive disease, 80% will have active disease within five years after elevated antibodies are detected.¹⁹

Autoantibodies, including ANA, anti-SSA/Ro, anti-SSB/La, and antiphospholipid antibodies, are usually detectable for many years prior to the onset of symptomatic SLE, while others, such as anti-Sm and anti-U1RNP, appear just months before the diagnosis.²³ Patients with positive ANA results who do not meet criteria for SLE are still at risk for lupus and other autoimmune diseases, because complex autoimmune changes occur years before the diagnosis of SLE.²³ These patients should be followed closely.

Continue for making the diagnosis >>

MAKING THE DIAGNOSIS
Diagnosing SLE may prove problematic because of the remarkable variety of relapsing and remitting clinical features, mimicry of similar conditions, and lack of a simple, definitive diagnostic test. Initial diagnosis of SLE depends on the disease manifestation, published criteria, and exclusion of alternative diagnoses. Confirmation requires careful clinical assessment, based on a thorough medical history and complete physical examination, along with specific laboratory testing.^1,16 Biopsy results indicative of lupus nephritis in the presence of ANA or anti-dsDNA antibodies also confirm the diagnosis of SLE.²⁴

Although created for research purposes, ACR classification criteria for SLE, published in 1982 and revised in 1997, have been used for more than 30 years to diagnose lupus (see www.rheumatology.org/Practice-Quality/Clinical-Support/Criteria/ACR-Endorsed-Criteria). In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) group revised the 1997 ACR classification criteria to address major flaws and to improve clinical precision.²⁴ According to SLICC, a definitive diagnosis requires the presence of at least four of 17 criteria, including at least one clinical and one immunologic criterion.²⁴ The SLICC revisions have resulted in fewer misclassifications and provide greater sensitivity but lower specificity in the identification of SLE in comparison to the 1997 ACR criteria.²⁴ To date, no one set of criteria allows for early diagnosis of SLE.

MANAGEMENT OPTIONS
Treatment must be tailored to the patient’s specific organ system involvement. Effective therapy hinges on controlling symptoms and reducing underlying inflammation.²⁵ Four classes of drugs are used: NSAIDs, antimalarial drugs, corticosteroids, and cytotoxic drugs (see Table 3). Most patients benefit from NSAIDs to alleviate minor arthritis and arthralgia symptoms, but the risk for peptic ulcers and nephrotoxicity should be addressed; this may require the concomitant use of gastroprotective agents such as proton pump inhibitors.²⁵ Antimalarials are effective for musculoskeletal symptoms that do not respond to NSAIDs and for cutaneous rashes.¹ The current antimalarial drug of choice is hydroxychloroquine (200 to 400 mg/d po), which has been shown to control SLE manifestations by reducing and preventing disease flares.^1,11,26 It is well tolerated and can be used for the duration of treatment.^11,26 Patients should be informed that this drug’s onset of action is one month.²⁶ In rare cases, this drug can cause retinal toxicity; therefore, SLE patients receiving hydroxychloroquine should be referred to an ophthalmologist for a baseline eye examination and yearly assessments to monitor for this rare adverse effect.^25,26

Low-dose corticosteroids, such as oral prednisolone or methylprednisolone, are employed when NSAIDs and antimalarials fail to control arthritis or cutaneous SLE eruptions.²⁵ Major systemic manifestations that occur during a disease flare—such as severe arthritis, hemolytic anemia, glomerulonephritis, alveolar hemorrhage, pericarditis, pleurisy, or CNS involvement—necessitate high-dose IV corticosteroids in conjunction with immunosuppressive agents.^1,11,25 These high-dose glucocorticoids should be gradually withdrawn as soon as remission is achieved.¹¹ Long-term suppressive therapy with oral corticosteroids in addition to other agents is often needed to preserve organ function.²⁵

The major adverse effects of long-term glucocorticoids are osteoporosis, hypertension, hyperlipidemia, glucose intolerance, and susceptibility to infection. It is recommended that patients taking prednisolone 7.5 mg/d or more undergo a bone mineral density scan every two years.²⁵ Those with T scores below –2.5 should be prescribed bisphosphonates.²⁵

Immunosuppressive agents, such as cyclophosphamide, mycophenolate mofetil, and azathioprine, are used in conjunction with corticosteroids or when syndromes are resistant to corticosteroids.¹ Collaboration between primary care, rheumatology, and nephrology is advisable for patients requiring immunosuppressive or disease-modifying pharmacologic agents.

Two new treatments for SLE are the immunologic agents belimumab and rituximab.⁷ Belimumab, a monoclonal human antibody, is the first medication in the past 50 years that has been approved by the FDA for antibody-positive SLE patients with active lupus unresponsive to standard treatment.^7,27 Rituximab is an anti-CD20 monoclonal antibody, approved by the FDA for non-Hodgkin lymphoma, chronic lymphocytic leukemia, and RA, and is now considered an option for SLE refractory to conventional treatment regimens.^7,27 The efficacy of belimumab and rituximab, and the spectrum of indications for their use, are still under study, but these new therapeutic agents hold promise for the treatment of patients with refractory SLE.

Continue for helping patients live with SLE >>

HELPING PATIENTs LIVE WITH SLE
Patients with SLE have a higher mortality rate, as well as a lower quality of life, compared to the general population.²⁸ The major contributors to a decreased quality of life are fatigue, mood disturbances (eg, depression), and chronic pain.²⁸ Practitioners should advise SLE patients to participate in support groups and psychotherapy to alleviate the anxiety and depression associated with this chronic disease.

For patients with long-standing disease, accelerated atherosclerotic cardiovascular disease adds to morbidity and mortality. For this reason, obesity, hypertension, hyperlipidemia, and smoking are targets for intervention. Lifestyle modifications—such as exercise, smoking cessation, a healthy diet with low saturated fat, stress avoidance, and adequate rest—are recommended.²⁶

Avoiding overexposure to sunlight, by using sunscreen with an SPF of at least 30 and wearing sun-protective clothing, is essential for management of cutaneous lupus.^25,26 Yearly influenza vaccination is appropriate, as are other immunizations (eg, pneumococcal vaccine).²⁶

Advise women of childbearing age with SLE that lupus flares result in a high risk for miscarriage. All women should undergo yearly cervical cancer screening.²⁶

Patients taking long-term glucocorticoids should adopt bone-protective behaviors, including quitting smoking, limiting alcohol intake, partaking in weight-bearing exercise, and consuming dietary calcium and vitamin D.²⁵ Patients taking these drugs should avoid live virus vaccines. Those on immunosuppressive therapy should be warned about the hazardous adverse effects of glucocorticoids.

MONITORING AND FOLLOW-UP
Collaborative efforts between primary care providers and several types of specialty providers can facilitate coordinated interventions in the long-term management of lupus. Rheumatologists are experts in making therapeutic decisions for SLE.

Patients being treated for SLE require routine monitoring to assess disease activity and detect flares. The European League Against Rheumatism (EULAR) guidelines recommend that monitoring include assessment for new clinical manifestations, routine laboratory tests, and immunologic assays, chiefly anti-dsDNA, anti-Sm, and serum complement levels, coupled with one of the validated global activity indices, such as the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).²⁹

A routine office visit with a physical examination and laboratory testing for CBC with differential, basic metabolic panel, and urinalysis every three months is recommended for patients with stable disease; patients with uncontrolled SLE may require weekly visits.^11,29 Patients taking immunosuppressive drugs should be provided with adverse-effect profiles alerting them to toxicity symptoms and require frequent laboratory monitoring for potential toxicity.¹¹

CONCLUSION
Advances in immunologically targeted serologic tests have shed more light on the underlying pathogenesis of SLE, which in turn has led to improvements in disease detection and monitoring of complications, as well as advances in therapy. Although SLE cannot be cured, emerging therapies targeting different mechanisms of SLE offer hope for patients diagnosed with this complex disease.

PRACTICE CHANGER
Consider treatment with bright light therapy, alone or in combination with fluoxetine, for patients with nonseasonal major depressive disorder.¹

Strength of Recommendation
B: Based on a single moderate-quality randomized controlled trial.¹

A 38-year-old woman recently diagnosed with major depressive disorder (MDD) without a seasonal pattern presents to discuss treatment options. Her Hamilton Depression Rating Scale (HAM-D) score is 22, and she is not suicidal. Should you consider bright light therapy in addition to pharmacotherapy?

MDD is one of the most common psychiatric illnesses in the United States, affecting approximately one in five adults at some point in their lives.² Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors are considered effective firstline pharmacotherapy options for MDD.^2,3 Despite their effectiveness, however, studies have shown that only about 40% of patients with MDD achieve remission with firstline or secondline drugs.² In addition, pharmaco­logic agents have a higher frequency of treatment-associated adverse effects than fluorescent light therapy.⁴

A Cochrane systematic review of 20 studies (N = 620) demonstrated the effectiveness of combined light therapy and pharmacotherapy in treating nonseasonal MDD but found no benefit to light used as monotherapy.⁵ However, the majority of the studies were of poor quality, occurred in the inpatient setting, and lasted less than four weeks.

In a five-week, controlled, double-blind trial not included in the Cochrane review, 102 patients with nonseasonal MDD were randomized to receive either active treatment (bright light therapy) plus sertraline (50 mg/d) or sham light treatment (using a dim red light) plus sertraline (50 mg/d). The investigators found a statistically significant reduction in depression score in the active treatment group compared to the sham light group, based on the HAM-D, the Hamilton 6-Item Subscale, the Melancholia Scale, and the seven atypical items from the Structured Interview Guide for the Seasonal Affective Disorder version of the HAM-D.^6,7

Continue for the study summary >>

STUDY SUMMARY
Light therapy improves nonseasonal depression
This latest study was an eight-week, randomized, double-blind, placebo- and sham-controlled clinical trial evaluating the benefit of light therapy with and without pharmacotherapy for nonseasonal MDD.¹ The investigators enrolled 122 adult patients (ages 19 to 60) from outpatient psychiatry clinics who had a diagnosis of MDD (diagnosed by a psychiatrist) and a HAM-D⁸ score of at least 20. Subjects had to be off psychotropic medication for at least two weeks prior to the first visit; they were subsequently monitored for one week to identify spontaneous responders and give patients time to better regulate their sleep-wake cycle (with the goal of sleeping only between 10 PM and 8 AM daily).

The investigators randomly assigned patients to one of four treatment groups:
• Active light monotherapy (10,000-lux fluorescent white light for 30 min/d early in the morning) plus a placebo pill
• Fluoxetine (20 mg/d) plus sham light therapy
• Placebo pills with sham light therapy; or
• Combined active light therapy with fluoxetine (20 mg/d).

Sham light therapy consisted of the use of an inactivated negative ion generator, used in the same fashion as a light box. All patients were analyzed based on modified intention to treat. Adherence was assessed through review of patients’ daily logs of device treatment times and through pill counts.

The primary outcome at eight weeks was the change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item questionnaire with a worst score of 60.⁹ Secondary outcomes were treatment response (≥ 50% reduction in MADRS score) and remission (MADRS score ≤ 10) at the final eighth-week visit. MADRS scoring was used because of its sensitivity to treatment-induced changes and its high correlation with the HAM-D scale.

At the end of eight weeks, the mean changes in MADRS scores from baseline were: light monotherapy, 13.4; fluoxetine monotherapy, 8.8; combination therapy, 16.9; and placebo, 6.5. The improvement was significant in the light monotherapy treatment group and in the combination therapy group, compared with the placebo group, and in the combination group, compared with the fluoxetine treatment group; improvement was not significant for the fluoxetine treatment group compared with the placebo group, however.

The treatment response (≥ 50% MADRS improvement) rate was highest in the combination treatment group (75.9%), followed by light monotherapy (50%), placebo (33.3%), and fluoxetine monotherapy (29%). There was a significant response effect for the combination versus placebo treatment group.

Similarly, there was a higher remission rate in the combination treatment group (58.6%) than in the placebo, light monotherapy, or fluoxetine treatment groups (30%, 43.8%, and 19.4%, respectively). Combination therapy was superior to placebo in treatment response (≥ 50% reduction in the MADRS score) and remission (MADRS ≤ 10), with numbers needed to treat of 2.4 and 3.5, respectively.

By the end of the eight-week study period, 16 of 122 patients had dropped out. Two reported lack of efficacy, five reported adverse effects, and the remainder cited administrative reasons, were lost to follow-up, or withdrew ­consent.

WHAT’S NEW
New evidence on a not-so-new treatment
We now have evidence that bright light therapy, either alone or in combination with fluoxetine, is efficacious for increasing the remission rate of nonseasonal MDD.

Continue for caveats >>

CAVEATS
Variables may have affected results
Among the study’s limitations: use of a single SSRI (other, more potent SSRIs might work better); location (southern Canada; benefits may differ in regions farther south); and exclusion of pregnant and breastfeeding women from the study population.

Furthermore, the trial duration was relatively short, and the investigators did not attain their preplanned sample size for the study. This limited the power to detect clinically significant seasonal treatment effects and differences between the fluoxetine and placebo groups, regardless of whether they received active phototherapy.

CHALLENGES TO IMPLEMENTATION
Commercial insurance doesn’t usually cover light therapy
Bright light therapy is fairly safe, and some evidence exists supporting its use in the treatment of nonseasonal MDD; however, the data for its use in this area are limited.¹⁰ Since few studies have tested light therapy for nonseasonal MDD, uncertainty remains about patient selection, as well as optimal dose, timing, and duration in the management of nonseasonal MDD.¹¹ Although the associated risks are minimal, bright light therapy can lead to mania or hypomania; clinicians need to monitor for such effects when initiating therapy.³

Lastly, commercial insurance does not usually cover light therapy. The average price of the bright light devices, which are available in medical supply stores and online, ranges from $118 to $237.^4,11 However, such de­vices are reusable, making the amortized cost almost negligible and perhaps negating this concern.¹²

REFERENCES
1. Lam RW, Levitt AJ, Levitan RD, et al. Efficacy of bright light treatment, fluoxetine, and the combination in patients with nonseasonal major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2016;73:56-63.
2. Weihs K, Wert JM. A primary care focus on the treatment of patients with major depressive disorder. Am J Med Sci. 2011;342:324-330.
3. Gelenberg AJ, Freeman CMP, Markowitz JC, et al. American Psychiatric Association practice guideline for the treatment of patients with major depressive disorder. 3rd ed. 2010. http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf. Accessed July 5, 2016.
4. Lam RW, Tam EM. A Clinician’s Guide to Using Light Therapy. New York, NY: Cambridge University Press; 2009. www.ubcmood.ca/sad/SAD%20resources%20package%202009.pdf. Accessed July 5, 2016.
5. Tuunainen A, Kripke DF, Endo T. Light therapy for non-seasonal depression. Cochrane Database Syst Rev. 2004;2:CD004050.
6. Martiny K. Adjunctive bright light in non-seasonal major depression. Acta Psychiatr Scand Suppl. 2004;425:7-28.
7. Martiny K, Lunde M, Unden M, et al. Adjunctive bright light in non-seasonal major depression: results from clinician-rated depression scales. Acta Psychiatr Scand. 2005;112:117-125.
8. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56-62.
9. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382-389.
10. Oldham MA, Ciraulo DA. Use of bright light therapy among psychiatrists in Massachusetts: an e-mail survey. Prim Care Companion CNS Disord. 2014;16(3). Epub 2014 Jun 26.
11. Sloane PD, Figueiro M, Cohen L. Light as therapy for sleep disorders and depression in older adults. Clin Geriatr. 2008;16:25-31.
12. Kripke DF. A breakthrough treatment for major depression. J Clin Psychiatry. 2015;76:e660-e661.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2016. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2016;65(7):486-488.

PRACTICE CHANGER
Consider treatment with bright light therapy, alone or in combination with fluoxetine, for patients with nonseasonal major depressive disorder.¹

Strength of Recommendation
B: Based on a single moderate-quality randomized controlled trial.¹

A 38-year-old woman recently diagnosed with major depressive disorder (MDD) without a seasonal pattern presents to discuss treatment options. Her Hamilton Depression Rating Scale (HAM-D) score is 22, and she is not suicidal. Should you consider bright light therapy in addition to pharmacotherapy?

MDD is one of the most common psychiatric illnesses in the United States, affecting approximately one in five adults at some point in their lives.² Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors are considered effective firstline pharmacotherapy options for MDD.^2,3 Despite their effectiveness, however, studies have shown that only about 40% of patients with MDD achieve remission with firstline or secondline drugs.² In addition, pharmaco­logic agents have a higher frequency of treatment-associated adverse effects than fluorescent light therapy.⁴

A Cochrane systematic review of 20 studies (N = 620) demonstrated the effectiveness of combined light therapy and pharmacotherapy in treating nonseasonal MDD but found no benefit to light used as monotherapy.⁵ However, the majority of the studies were of poor quality, occurred in the inpatient setting, and lasted less than four weeks.

In a five-week, controlled, double-blind trial not included in the Cochrane review, 102 patients with nonseasonal MDD were randomized to receive either active treatment (bright light therapy) plus sertraline (50 mg/d) or sham light treatment (using a dim red light) plus sertraline (50 mg/d). The investigators found a statistically significant reduction in depression score in the active treatment group compared to the sham light group, based on the HAM-D, the Hamilton 6-Item Subscale, the Melancholia Scale, and the seven atypical items from the Structured Interview Guide for the Seasonal Affective Disorder version of the HAM-D.^6,7

Continue for the study summary >>

STUDY SUMMARY
Light therapy improves nonseasonal depression
This latest study was an eight-week, randomized, double-blind, placebo- and sham-controlled clinical trial evaluating the benefit of light therapy with and without pharmacotherapy for nonseasonal MDD.¹ The investigators enrolled 122 adult patients (ages 19 to 60) from outpatient psychiatry clinics who had a diagnosis of MDD (diagnosed by a psychiatrist) and a HAM-D⁸ score of at least 20. Subjects had to be off psychotropic medication for at least two weeks prior to the first visit; they were subsequently monitored for one week to identify spontaneous responders and give patients time to better regulate their sleep-wake cycle (with the goal of sleeping only between 10 PM and 8 AM daily).

The investigators randomly assigned patients to one of four treatment groups:
• Active light monotherapy (10,000-lux fluorescent white light for 30 min/d early in the morning) plus a placebo pill
• Fluoxetine (20 mg/d) plus sham light therapy
• Placebo pills with sham light therapy; or
• Combined active light therapy with fluoxetine (20 mg/d).

Sham light therapy consisted of the use of an inactivated negative ion generator, used in the same fashion as a light box. All patients were analyzed based on modified intention to treat. Adherence was assessed through review of patients’ daily logs of device treatment times and through pill counts.

The primary outcome at eight weeks was the change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item questionnaire with a worst score of 60.⁹ Secondary outcomes were treatment response (≥ 50% reduction in MADRS score) and remission (MADRS score ≤ 10) at the final eighth-week visit. MADRS scoring was used because of its sensitivity to treatment-induced changes and its high correlation with the HAM-D scale.

At the end of eight weeks, the mean changes in MADRS scores from baseline were: light monotherapy, 13.4; fluoxetine monotherapy, 8.8; combination therapy, 16.9; and placebo, 6.5. The improvement was significant in the light monotherapy treatment group and in the combination therapy group, compared with the placebo group, and in the combination group, compared with the fluoxetine treatment group; improvement was not significant for the fluoxetine treatment group compared with the placebo group, however.

The treatment response (≥ 50% MADRS improvement) rate was highest in the combination treatment group (75.9%), followed by light monotherapy (50%), placebo (33.3%), and fluoxetine monotherapy (29%). There was a significant response effect for the combination versus placebo treatment group.

Similarly, there was a higher remission rate in the combination treatment group (58.6%) than in the placebo, light monotherapy, or fluoxetine treatment groups (30%, 43.8%, and 19.4%, respectively). Combination therapy was superior to placebo in treatment response (≥ 50% reduction in the MADRS score) and remission (MADRS ≤ 10), with numbers needed to treat of 2.4 and 3.5, respectively.

By the end of the eight-week study period, 16 of 122 patients had dropped out. Two reported lack of efficacy, five reported adverse effects, and the remainder cited administrative reasons, were lost to follow-up, or withdrew ­consent.

WHAT’S NEW
New evidence on a not-so-new treatment
We now have evidence that bright light therapy, either alone or in combination with fluoxetine, is efficacious for increasing the remission rate of nonseasonal MDD.

Continue for caveats >>

CAVEATS
Variables may have affected results
Among the study’s limitations: use of a single SSRI (other, more potent SSRIs might work better); location (southern Canada; benefits may differ in regions farther south); and exclusion of pregnant and breastfeeding women from the study population.

Furthermore, the trial duration was relatively short, and the investigators did not attain their preplanned sample size for the study. This limited the power to detect clinically significant seasonal treatment effects and differences between the fluoxetine and placebo groups, regardless of whether they received active phototherapy.

CHALLENGES TO IMPLEMENTATION
Commercial insurance doesn’t usually cover light therapy
Bright light therapy is fairly safe, and some evidence exists supporting its use in the treatment of nonseasonal MDD; however, the data for its use in this area are limited.¹⁰ Since few studies have tested light therapy for nonseasonal MDD, uncertainty remains about patient selection, as well as optimal dose, timing, and duration in the management of nonseasonal MDD.¹¹ Although the associated risks are minimal, bright light therapy can lead to mania or hypomania; clinicians need to monitor for such effects when initiating therapy.³

Lastly, commercial insurance does not usually cover light therapy. The average price of the bright light devices, which are available in medical supply stores and online, ranges from $118 to $237.^4,11 However, such de­vices are reusable, making the amortized cost almost negligible and perhaps negating this concern.¹²

REFERENCES
1. Lam RW, Levitt AJ, Levitan RD, et al. Efficacy of bright light treatment, fluoxetine, and the combination in patients with nonseasonal major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2016;73:56-63.
2. Weihs K, Wert JM. A primary care focus on the treatment of patients with major depressive disorder. Am J Med Sci. 2011;342:324-330.
3. Gelenberg AJ, Freeman CMP, Markowitz JC, et al. American Psychiatric Association practice guideline for the treatment of patients with major depressive disorder. 3rd ed. 2010. http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf. Accessed July 5, 2016.
4. Lam RW, Tam EM. A Clinician’s Guide to Using Light Therapy. New York, NY: Cambridge University Press; 2009. www.ubcmood.ca/sad/SAD%20resources%20package%202009.pdf. Accessed July 5, 2016.
5. Tuunainen A, Kripke DF, Endo T. Light therapy for non-seasonal depression. Cochrane Database Syst Rev. 2004;2:CD004050.
6. Martiny K. Adjunctive bright light in non-seasonal major depression. Acta Psychiatr Scand Suppl. 2004;425:7-28.
7. Martiny K, Lunde M, Unden M, et al. Adjunctive bright light in non-seasonal major depression: results from clinician-rated depression scales. Acta Psychiatr Scand. 2005;112:117-125.
8. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56-62.
9. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382-389.
10. Oldham MA, Ciraulo DA. Use of bright light therapy among psychiatrists in Massachusetts: an e-mail survey. Prim Care Companion CNS Disord. 2014;16(3). Epub 2014 Jun 26.
11. Sloane PD, Figueiro M, Cohen L. Light as therapy for sleep disorders and depression in older adults. Clin Geriatr. 2008;16:25-31.
12. Kripke DF. A breakthrough treatment for major depression. J Clin Psychiatry. 2015;76:e660-e661.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2016. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2016;65(7):486-488.

PRACTICE CHANGER
Consider treatment with bright light therapy, alone or in combination with fluoxetine, for patients with nonseasonal major depressive disorder.¹

Strength of Recommendation
B: Based on a single moderate-quality randomized controlled trial.¹

A 38-year-old woman recently diagnosed with major depressive disorder (MDD) without a seasonal pattern presents to discuss treatment options. Her Hamilton Depression Rating Scale (HAM-D) score is 22, and she is not suicidal. Should you consider bright light therapy in addition to pharmacotherapy?

MDD is one of the most common psychiatric illnesses in the United States, affecting approximately one in five adults at some point in their lives.² Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors are considered effective firstline pharmacotherapy options for MDD.^2,3 Despite their effectiveness, however, studies have shown that only about 40% of patients with MDD achieve remission with firstline or secondline drugs.² In addition, pharmaco­logic agents have a higher frequency of treatment-associated adverse effects than fluorescent light therapy.⁴

A Cochrane systematic review of 20 studies (N = 620) demonstrated the effectiveness of combined light therapy and pharmacotherapy in treating nonseasonal MDD but found no benefit to light used as monotherapy.⁵ However, the majority of the studies were of poor quality, occurred in the inpatient setting, and lasted less than four weeks.

In a five-week, controlled, double-blind trial not included in the Cochrane review, 102 patients with nonseasonal MDD were randomized to receive either active treatment (bright light therapy) plus sertraline (50 mg/d) or sham light treatment (using a dim red light) plus sertraline (50 mg/d). The investigators found a statistically significant reduction in depression score in the active treatment group compared to the sham light group, based on the HAM-D, the Hamilton 6-Item Subscale, the Melancholia Scale, and the seven atypical items from the Structured Interview Guide for the Seasonal Affective Disorder version of the HAM-D.^6,7

Continue for the study summary >>

STUDY SUMMARY
Light therapy improves nonseasonal depression
This latest study was an eight-week, randomized, double-blind, placebo- and sham-controlled clinical trial evaluating the benefit of light therapy with and without pharmacotherapy for nonseasonal MDD.¹ The investigators enrolled 122 adult patients (ages 19 to 60) from outpatient psychiatry clinics who had a diagnosis of MDD (diagnosed by a psychiatrist) and a HAM-D⁸ score of at least 20. Subjects had to be off psychotropic medication for at least two weeks prior to the first visit; they were subsequently monitored for one week to identify spontaneous responders and give patients time to better regulate their sleep-wake cycle (with the goal of sleeping only between 10 PM and 8 AM daily).

The investigators randomly assigned patients to one of four treatment groups:
• Active light monotherapy (10,000-lux fluorescent white light for 30 min/d early in the morning) plus a placebo pill
• Fluoxetine (20 mg/d) plus sham light therapy
• Placebo pills with sham light therapy; or
• Combined active light therapy with fluoxetine (20 mg/d).

Sham light therapy consisted of the use of an inactivated negative ion generator, used in the same fashion as a light box. All patients were analyzed based on modified intention to treat. Adherence was assessed through review of patients’ daily logs of device treatment times and through pill counts.

The primary outcome at eight weeks was the change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item questionnaire with a worst score of 60.⁹ Secondary outcomes were treatment response (≥ 50% reduction in MADRS score) and remission (MADRS score ≤ 10) at the final eighth-week visit. MADRS scoring was used because of its sensitivity to treatment-induced changes and its high correlation with the HAM-D scale.

At the end of eight weeks, the mean changes in MADRS scores from baseline were: light monotherapy, 13.4; fluoxetine monotherapy, 8.8; combination therapy, 16.9; and placebo, 6.5. The improvement was significant in the light monotherapy treatment group and in the combination therapy group, compared with the placebo group, and in the combination group, compared with the fluoxetine treatment group; improvement was not significant for the fluoxetine treatment group compared with the placebo group, however.

The treatment response (≥ 50% MADRS improvement) rate was highest in the combination treatment group (75.9%), followed by light monotherapy (50%), placebo (33.3%), and fluoxetine monotherapy (29%). There was a significant response effect for the combination versus placebo treatment group.

Similarly, there was a higher remission rate in the combination treatment group (58.6%) than in the placebo, light monotherapy, or fluoxetine treatment groups (30%, 43.8%, and 19.4%, respectively). Combination therapy was superior to placebo in treatment response (≥ 50% reduction in the MADRS score) and remission (MADRS ≤ 10), with numbers needed to treat of 2.4 and 3.5, respectively.

By the end of the eight-week study period, 16 of 122 patients had dropped out. Two reported lack of efficacy, five reported adverse effects, and the remainder cited administrative reasons, were lost to follow-up, or withdrew ­consent.

WHAT’S NEW
New evidence on a not-so-new treatment
We now have evidence that bright light therapy, either alone or in combination with fluoxetine, is efficacious for increasing the remission rate of nonseasonal MDD.

Continue for caveats >>

CAVEATS
Variables may have affected results
Among the study’s limitations: use of a single SSRI (other, more potent SSRIs might work better); location (southern Canada; benefits may differ in regions farther south); and exclusion of pregnant and breastfeeding women from the study population.

Furthermore, the trial duration was relatively short, and the investigators did not attain their preplanned sample size for the study. This limited the power to detect clinically significant seasonal treatment effects and differences between the fluoxetine and placebo groups, regardless of whether they received active phototherapy.

CHALLENGES TO IMPLEMENTATION
Commercial insurance doesn’t usually cover light therapy
Bright light therapy is fairly safe, and some evidence exists supporting its use in the treatment of nonseasonal MDD; however, the data for its use in this area are limited.¹⁰ Since few studies have tested light therapy for nonseasonal MDD, uncertainty remains about patient selection, as well as optimal dose, timing, and duration in the management of nonseasonal MDD.¹¹ Although the associated risks are minimal, bright light therapy can lead to mania or hypomania; clinicians need to monitor for such effects when initiating therapy.³

Lastly, commercial insurance does not usually cover light therapy. The average price of the bright light devices, which are available in medical supply stores and online, ranges from $118 to $237.^4,11 However, such de­vices are reusable, making the amortized cost almost negligible and perhaps negating this concern.¹²

REFERENCES
1. Lam RW, Levitt AJ, Levitan RD, et al. Efficacy of bright light treatment, fluoxetine, and the combination in patients with nonseasonal major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2016;73:56-63.
2. Weihs K, Wert JM. A primary care focus on the treatment of patients with major depressive disorder. Am J Med Sci. 2011;342:324-330.
3. Gelenberg AJ, Freeman CMP, Markowitz JC, et al. American Psychiatric Association practice guideline for the treatment of patients with major depressive disorder. 3rd ed. 2010. http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf. Accessed July 5, 2016.
4. Lam RW, Tam EM. A Clinician’s Guide to Using Light Therapy. New York, NY: Cambridge University Press; 2009. www.ubcmood.ca/sad/SAD%20resources%20package%202009.pdf. Accessed July 5, 2016.
5. Tuunainen A, Kripke DF, Endo T. Light therapy for non-seasonal depression. Cochrane Database Syst Rev. 2004;2:CD004050.
6. Martiny K. Adjunctive bright light in non-seasonal major depression. Acta Psychiatr Scand Suppl. 2004;425:7-28.
7. Martiny K, Lunde M, Unden M, et al. Adjunctive bright light in non-seasonal major depression: results from clinician-rated depression scales. Acta Psychiatr Scand. 2005;112:117-125.
8. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56-62.
9. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382-389.
10. Oldham MA, Ciraulo DA. Use of bright light therapy among psychiatrists in Massachusetts: an e-mail survey. Prim Care Companion CNS Disord. 2014;16(3). Epub 2014 Jun 26.
11. Sloane PD, Figueiro M, Cohen L. Light as therapy for sleep disorders and depression in older adults. Clin Geriatr. 2008;16:25-31.
12. Kripke DF. A breakthrough treatment for major depression. J Clin Psychiatry. 2015;76:e660-e661.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2016. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2016;65(7):486-488.