Neurology

Watch for the symptoms of acute flaccid myelitis early and report any suspected cases to your health department, the CDC said in a telebriefing.

Acute flaccid myelitis (AFM) is defined as acute, flaccid muscle weakness that occurs less than 1 week after a fever or respiratory illness. Viruses, including enterovirus, are believed to play a role in AFM, but the cause still is unknown. The disease appears mostly in children, and the average age of a patient diagnosed with AFM is 5 years.

“Doctors and other clinicians in the United States play a critical role,” Anne Schuchat, MD, principal deputy director of the Centers for Disease Control and Prevention, said in the telebriefing. “We ask for your help with early recognition of patients with AFM symptoms, prompt specimen collection for testing, and immediate reporting of suspected AFM cases to health departments.”

While there is no proven treatment for AFM, early diagnosis is critical to getting patients the best care possible, according to a Vital Signs report released today. This means that clinicians should not wait for the CDC’s case definition before diagnosis, the CDC said.

“When specimens are collected as soon as possible after symptom onset, we have a better chance of understanding the causes of AFM, these recurrent outbreaks, and developing a diagnostic test,” Dr. Schuchat said. “Rapid reporting also helps us to identify and respond to outbreaks early and alert other clinicians and the public.”

AFM appears to follow a seasonal and biennial pattern, with the number of cases increasing mainly in the late summer and early fall. As the season approaches where AFM cases increase, CDC is asking clinicians to look out for patients with suspected AFM so cases can be reported as early as possible.

Since the CDC began tracking AFM, the number of cases has risen every 2 years. In 2018, there were 233 cases in 41 states, the highest number of reported cases since the CDC began tracking AFM following an outbreak in 2014, according to a Vital Signs report. Overall, there have been 570 cases of AFM reported in 48 states and the District of Columbia since 2014.

There is yet to be a confirmatory test for AFM, but clinicians should obtain cerebrospinal fluid, serum, stool and nasopharyngeal swab from patients with suspected AFM as soon as possible, followed by an MRI. AFM has unique MRI features , such as gray matter involvement, that can help distinguish it from other diseases characterized by acute weakness.

In the Vital Signs report, which examined AFM in 2018, 92% of confirmed cases had respiratory symptoms or fever, and 42% of confirmed cases had upper limb involvement. The median time from limb weakness to hospitalization was 1 day, and time from weakness to MRI was 2 days. Cases were reported to the CDC a median of 18 days from onset of limb weakness, but time to reporting ranged between 18 days and 36 days, said Tom Clark, MD, MPH, deputy director of the division of viral diseases at CDC.

“This delay hampers our ability to understand the causes AFM,” he said. “We believe that recognizing AFM early is critical and can lead to better patient management.”

In lieu of a diagnostic test for AFM, clinicians should make management decisions through review of patient symptoms, exam findings, MRI, other test results, and in consulting with neurology experts. The Transverse Myelitis Association also has created a support portal for 24/7 physician consultation in AFM cases.

SOURCE: Lopez A et al. MMWR Morb Mortal Wkly Rep. 2019;68:1-7 .

Watch for the symptoms of acute flaccid myelitis early and report any suspected cases to your health department, the CDC said in a telebriefing.

Acute flaccid myelitis (AFM) is defined as acute, flaccid muscle weakness that occurs less than 1 week after a fever or respiratory illness. Viruses, including enterovirus, are believed to play a role in AFM, but the cause still is unknown. The disease appears mostly in children, and the average age of a patient diagnosed with AFM is 5 years.

“Doctors and other clinicians in the United States play a critical role,” Anne Schuchat, MD, principal deputy director of the Centers for Disease Control and Prevention, said in the telebriefing. “We ask for your help with early recognition of patients with AFM symptoms, prompt specimen collection for testing, and immediate reporting of suspected AFM cases to health departments.”

While there is no proven treatment for AFM, early diagnosis is critical to getting patients the best care possible, according to a Vital Signs report released today. This means that clinicians should not wait for the CDC’s case definition before diagnosis, the CDC said.

“When specimens are collected as soon as possible after symptom onset, we have a better chance of understanding the causes of AFM, these recurrent outbreaks, and developing a diagnostic test,” Dr. Schuchat said. “Rapid reporting also helps us to identify and respond to outbreaks early and alert other clinicians and the public.”

AFM appears to follow a seasonal and biennial pattern, with the number of cases increasing mainly in the late summer and early fall. As the season approaches where AFM cases increase, CDC is asking clinicians to look out for patients with suspected AFM so cases can be reported as early as possible.

Since the CDC began tracking AFM, the number of cases has risen every 2 years. In 2018, there were 233 cases in 41 states, the highest number of reported cases since the CDC began tracking AFM following an outbreak in 2014, according to a Vital Signs report. Overall, there have been 570 cases of AFM reported in 48 states and the District of Columbia since 2014.

There is yet to be a confirmatory test for AFM, but clinicians should obtain cerebrospinal fluid, serum, stool and nasopharyngeal swab from patients with suspected AFM as soon as possible, followed by an MRI. AFM has unique MRI features , such as gray matter involvement, that can help distinguish it from other diseases characterized by acute weakness.

In the Vital Signs report, which examined AFM in 2018, 92% of confirmed cases had respiratory symptoms or fever, and 42% of confirmed cases had upper limb involvement. The median time from limb weakness to hospitalization was 1 day, and time from weakness to MRI was 2 days. Cases were reported to the CDC a median of 18 days from onset of limb weakness, but time to reporting ranged between 18 days and 36 days, said Tom Clark, MD, MPH, deputy director of the division of viral diseases at CDC.

“This delay hampers our ability to understand the causes AFM,” he said. “We believe that recognizing AFM early is critical and can lead to better patient management.”

In lieu of a diagnostic test for AFM, clinicians should make management decisions through review of patient symptoms, exam findings, MRI, other test results, and in consulting with neurology experts. The Transverse Myelitis Association also has created a support portal for 24/7 physician consultation in AFM cases.

SOURCE: Lopez A et al. MMWR Morb Mortal Wkly Rep. 2019;68:1-7 .

Watch for the symptoms of acute flaccid myelitis early and report any suspected cases to your health department, the CDC said in a telebriefing.

Acute flaccid myelitis (AFM) is defined as acute, flaccid muscle weakness that occurs less than 1 week after a fever or respiratory illness. Viruses, including enterovirus, are believed to play a role in AFM, but the cause still is unknown. The disease appears mostly in children, and the average age of a patient diagnosed with AFM is 5 years.

“Doctors and other clinicians in the United States play a critical role,” Anne Schuchat, MD, principal deputy director of the Centers for Disease Control and Prevention, said in the telebriefing. “We ask for your help with early recognition of patients with AFM symptoms, prompt specimen collection for testing, and immediate reporting of suspected AFM cases to health departments.”

While there is no proven treatment for AFM, early diagnosis is critical to getting patients the best care possible, according to a Vital Signs report released today. This means that clinicians should not wait for the CDC’s case definition before diagnosis, the CDC said.

“When specimens are collected as soon as possible after symptom onset, we have a better chance of understanding the causes of AFM, these recurrent outbreaks, and developing a diagnostic test,” Dr. Schuchat said. “Rapid reporting also helps us to identify and respond to outbreaks early and alert other clinicians and the public.”

AFM appears to follow a seasonal and biennial pattern, with the number of cases increasing mainly in the late summer and early fall. As the season approaches where AFM cases increase, CDC is asking clinicians to look out for patients with suspected AFM so cases can be reported as early as possible.

Since the CDC began tracking AFM, the number of cases has risen every 2 years. In 2018, there were 233 cases in 41 states, the highest number of reported cases since the CDC began tracking AFM following an outbreak in 2014, according to a Vital Signs report. Overall, there have been 570 cases of AFM reported in 48 states and the District of Columbia since 2014.

There is yet to be a confirmatory test for AFM, but clinicians should obtain cerebrospinal fluid, serum, stool and nasopharyngeal swab from patients with suspected AFM as soon as possible, followed by an MRI. AFM has unique MRI features , such as gray matter involvement, that can help distinguish it from other diseases characterized by acute weakness.

In the Vital Signs report, which examined AFM in 2018, 92% of confirmed cases had respiratory symptoms or fever, and 42% of confirmed cases had upper limb involvement. The median time from limb weakness to hospitalization was 1 day, and time from weakness to MRI was 2 days. Cases were reported to the CDC a median of 18 days from onset of limb weakness, but time to reporting ranged between 18 days and 36 days, said Tom Clark, MD, MPH, deputy director of the division of viral diseases at CDC.

“This delay hampers our ability to understand the causes AFM,” he said. “We believe that recognizing AFM early is critical and can lead to better patient management.”

In lieu of a diagnostic test for AFM, clinicians should make management decisions through review of patient symptoms, exam findings, MRI, other test results, and in consulting with neurology experts. The Transverse Myelitis Association also has created a support portal for 24/7 physician consultation in AFM cases.

SOURCE: Lopez A et al. MMWR Morb Mortal Wkly Rep. 2019;68:1-7 .

Black individuals who develop type 2 diabetes are more likely than their white counterparts to develop dementia. Now, findings from a new study point to a possible preventive strategy: Putting older patients on metformin when they are diagnosed could reduce their risk for dementia by as much as 40%, whereas sulfonylureas do not seem to have such an effect.

The researchers did not examine cause and effect, so their findings are not conclusive, and very few women were included in the study. Still, the authors said that their data showing a 29% lower risk of dementia associated with metformin use in black patients aged 65-74 years, and a 40% lower risk in those aged 50-64 years, suggested that “this inexpensive, widely available treatment could be broadly prescribed to substantially reduce the risk of dementia in younger [black] patients with [type 2 diabetes]” (Ann Fam Med. 2019;17:352-62).

Previous findings have suggested that black patients with type 2 diabetes face a 10%-18% higher risk of dementia, compared with white patients (Diabetes Care. 2014; 37[4]:1009-15). Another study linked type 2 diabetes in middle-aged black patients to a 41% decrease in cognition per test results over 14 years. There was no such decrease in white patients (Neuroepidemiology. 2014;43[3-4]: 220-7).

For the new study, researchers led by Jeffrey F. Scherrer, PhD, of Saint Louis University tracked 73,761 patients aged 50 years or older from 2000-2001 (when they were free of dementia and not taking diabetes) to 2015. Among the patients, 86% were white and 14% were black. In the white and black groups, 97% and 95% were men, respectively, and 61% and 55% were obese, respectively.

All participants began metformin (76%) or sulfonylurea (24%) monotherapy after the baseline period. Guidelines recommend metformin as a first-line treatment for type 2 diabetes, whereas sulfonylureas are considered second-line drugs that should be added to metformin.

After adjustment for confounders such as socioeconomic status and other medical conditions, the researchers found a significantly lower risk of dementia in black patients who took metformin, compared with those taking a sulfonylurea (hazard ratio, 0.73; 95% confidence interval, 0.6-0.89). There was no difference between the drugs among white patients (HR, 0.96; 95% CI, 0.9-1.03, both P = .008)

The results were not statistically significant among age groups, but there were trends. In black patients, the dementia-lowering benefit was largest among those aged 50-64 years (HR, 0.6; 95% CI, 0.45-0.81), followed by those aged 65-74 years (HR, 0.71; 95% CI, 0.53-0.94), and there was no benefit among those aged at least 75 (HR, 1.17; 95% CI, 0.73-1.85) all P = .055. There was a slight benefit among white patients in one of the age groups – 65-74 years (HR, 0.9; 95% CI, 0.82-0.99; P = .315).

The authors suggested that the findings could have been the result of an effect of metformin to reduce vascular disease and chronic inflammation in black patients.

They also noted that further research is needed to identify the demographic and clinical subgroups in which metformin is most strongly associated with a reduction in the risk of dementia. In addition, they emphasized that clinical trials are needed to confirm the study findings.

The National Institutes of Health funded the study. The authors report no relevant disclosures.

SOURCE: Scherrer JF et al. Ann Fam Med. 2019;17:352-62.

Black individuals who develop type 2 diabetes are more likely than their white counterparts to develop dementia. Now, findings from a new study point to a possible preventive strategy: Putting older patients on metformin when they are diagnosed could reduce their risk for dementia by as much as 40%, whereas sulfonylureas do not seem to have such an effect.

The researchers did not examine cause and effect, so their findings are not conclusive, and very few women were included in the study. Still, the authors said that their data showing a 29% lower risk of dementia associated with metformin use in black patients aged 65-74 years, and a 40% lower risk in those aged 50-64 years, suggested that “this inexpensive, widely available treatment could be broadly prescribed to substantially reduce the risk of dementia in younger [black] patients with [type 2 diabetes]” (Ann Fam Med. 2019;17:352-62).

Previous findings have suggested that black patients with type 2 diabetes face a 10%-18% higher risk of dementia, compared with white patients (Diabetes Care. 2014; 37[4]:1009-15). Another study linked type 2 diabetes in middle-aged black patients to a 41% decrease in cognition per test results over 14 years. There was no such decrease in white patients (Neuroepidemiology. 2014;43[3-4]: 220-7).

For the new study, researchers led by Jeffrey F. Scherrer, PhD, of Saint Louis University tracked 73,761 patients aged 50 years or older from 2000-2001 (when they were free of dementia and not taking diabetes) to 2015. Among the patients, 86% were white and 14% were black. In the white and black groups, 97% and 95% were men, respectively, and 61% and 55% were obese, respectively.

All participants began metformin (76%) or sulfonylurea (24%) monotherapy after the baseline period. Guidelines recommend metformin as a first-line treatment for type 2 diabetes, whereas sulfonylureas are considered second-line drugs that should be added to metformin.

After adjustment for confounders such as socioeconomic status and other medical conditions, the researchers found a significantly lower risk of dementia in black patients who took metformin, compared with those taking a sulfonylurea (hazard ratio, 0.73; 95% confidence interval, 0.6-0.89). There was no difference between the drugs among white patients (HR, 0.96; 95% CI, 0.9-1.03, both P = .008)

The results were not statistically significant among age groups, but there were trends. In black patients, the dementia-lowering benefit was largest among those aged 50-64 years (HR, 0.6; 95% CI, 0.45-0.81), followed by those aged 65-74 years (HR, 0.71; 95% CI, 0.53-0.94), and there was no benefit among those aged at least 75 (HR, 1.17; 95% CI, 0.73-1.85) all P = .055. There was a slight benefit among white patients in one of the age groups – 65-74 years (HR, 0.9; 95% CI, 0.82-0.99; P = .315).

The authors suggested that the findings could have been the result of an effect of metformin to reduce vascular disease and chronic inflammation in black patients.

They also noted that further research is needed to identify the demographic and clinical subgroups in which metformin is most strongly associated with a reduction in the risk of dementia. In addition, they emphasized that clinical trials are needed to confirm the study findings.

The National Institutes of Health funded the study. The authors report no relevant disclosures.

SOURCE: Scherrer JF et al. Ann Fam Med. 2019;17:352-62.

Black individuals who develop type 2 diabetes are more likely than their white counterparts to develop dementia. Now, findings from a new study point to a possible preventive strategy: Putting older patients on metformin when they are diagnosed could reduce their risk for dementia by as much as 40%, whereas sulfonylureas do not seem to have such an effect.

The researchers did not examine cause and effect, so their findings are not conclusive, and very few women were included in the study. Still, the authors said that their data showing a 29% lower risk of dementia associated with metformin use in black patients aged 65-74 years, and a 40% lower risk in those aged 50-64 years, suggested that “this inexpensive, widely available treatment could be broadly prescribed to substantially reduce the risk of dementia in younger [black] patients with [type 2 diabetes]” (Ann Fam Med. 2019;17:352-62).

Previous findings have suggested that black patients with type 2 diabetes face a 10%-18% higher risk of dementia, compared with white patients (Diabetes Care. 2014; 37[4]:1009-15). Another study linked type 2 diabetes in middle-aged black patients to a 41% decrease in cognition per test results over 14 years. There was no such decrease in white patients (Neuroepidemiology. 2014;43[3-4]: 220-7).

For the new study, researchers led by Jeffrey F. Scherrer, PhD, of Saint Louis University tracked 73,761 patients aged 50 years or older from 2000-2001 (when they were free of dementia and not taking diabetes) to 2015. Among the patients, 86% were white and 14% were black. In the white and black groups, 97% and 95% were men, respectively, and 61% and 55% were obese, respectively.

All participants began metformin (76%) or sulfonylurea (24%) monotherapy after the baseline period. Guidelines recommend metformin as a first-line treatment for type 2 diabetes, whereas sulfonylureas are considered second-line drugs that should be added to metformin.

After adjustment for confounders such as socioeconomic status and other medical conditions, the researchers found a significantly lower risk of dementia in black patients who took metformin, compared with those taking a sulfonylurea (hazard ratio, 0.73; 95% confidence interval, 0.6-0.89). There was no difference between the drugs among white patients (HR, 0.96; 95% CI, 0.9-1.03, both P = .008)

The results were not statistically significant among age groups, but there were trends. In black patients, the dementia-lowering benefit was largest among those aged 50-64 years (HR, 0.6; 95% CI, 0.45-0.81), followed by those aged 65-74 years (HR, 0.71; 95% CI, 0.53-0.94), and there was no benefit among those aged at least 75 (HR, 1.17; 95% CI, 0.73-1.85) all P = .055. There was a slight benefit among white patients in one of the age groups – 65-74 years (HR, 0.9; 95% CI, 0.82-0.99; P = .315).

The authors suggested that the findings could have been the result of an effect of metformin to reduce vascular disease and chronic inflammation in black patients.

They also noted that further research is needed to identify the demographic and clinical subgroups in which metformin is most strongly associated with a reduction in the risk of dementia. In addition, they emphasized that clinical trials are needed to confirm the study findings.

The National Institutes of Health funded the study. The authors report no relevant disclosures.

SOURCE: Scherrer JF et al. Ann Fam Med. 2019;17:352-62.

Patients with gout who visit the emergency department are regularly prescribed opioids, based on a review of electronic medical records.

“In addition to regulatory changes, the burden of opioid prescription could be potentially reduced by creating prompts for providers in electronic record systems to avoid prescribing opioids in opioid-naive patients or using lower intensity and shorter duration of prescription,” wrote Deepan S. Dalal, MD, of Brown University, Providence, R.I., and coauthors. The study was published in Arthritis Care & Research.

To determine frequency, dose, and duration of opioid prescription at ED discharge, the researchers reviewed the records of 456 patients with acute gout who were discharged in Rhode Island between March 30, 2015, and Sept. 30, 2017. All data were gathered via electronic medical system records.

Of the 456 discharged patients, 129 (28.3%) were prescribed opioids; 102 (79%) were not on opioids at the time. A full prescription description was available for 119 of the 129 patients; 96 (81%) were prescribed oxycodone or oxycodone combinations. Hydrocodone was prescribed for 9 patients (8%) and tramadol was prescribed for 11 patients (9%).

The median duration of each prescription was 8 days (interquartile range, 5-14 days) and the average daily dose was 37.9 mg of morphine equivalent. Patients who were prescribed opioids tended to be younger and male. After multivariable analysis, diabetes, polyarticular gout attack, and prior opioid use were all associated with a more than 100% higher odds of receiving an opioid prescription.

The authors acknowledged their study’s limitations, including their inability to determine the physicians’ reasoning behind each prescription or the prescribing habits of each provider. In addition, they were only able to assess the prescriptions as being written and not the number of pills actually taken or not taken.

No conflicts of interest were reported.

SOURCE: Dalal DS et al. Arthritis Care Res. 2019 Jul 3. doi: 10.1002/acr.23928.

Patients with gout who visit the emergency department are regularly prescribed opioids, based on a review of electronic medical records.

“In addition to regulatory changes, the burden of opioid prescription could be potentially reduced by creating prompts for providers in electronic record systems to avoid prescribing opioids in opioid-naive patients or using lower intensity and shorter duration of prescription,” wrote Deepan S. Dalal, MD, of Brown University, Providence, R.I., and coauthors. The study was published in Arthritis Care & Research.

To determine frequency, dose, and duration of opioid prescription at ED discharge, the researchers reviewed the records of 456 patients with acute gout who were discharged in Rhode Island between March 30, 2015, and Sept. 30, 2017. All data were gathered via electronic medical system records.

Of the 456 discharged patients, 129 (28.3%) were prescribed opioids; 102 (79%) were not on opioids at the time. A full prescription description was available for 119 of the 129 patients; 96 (81%) were prescribed oxycodone or oxycodone combinations. Hydrocodone was prescribed for 9 patients (8%) and tramadol was prescribed for 11 patients (9%).

The median duration of each prescription was 8 days (interquartile range, 5-14 days) and the average daily dose was 37.9 mg of morphine equivalent. Patients who were prescribed opioids tended to be younger and male. After multivariable analysis, diabetes, polyarticular gout attack, and prior opioid use were all associated with a more than 100% higher odds of receiving an opioid prescription.

The authors acknowledged their study’s limitations, including their inability to determine the physicians’ reasoning behind each prescription or the prescribing habits of each provider. In addition, they were only able to assess the prescriptions as being written and not the number of pills actually taken or not taken.

No conflicts of interest were reported.

SOURCE: Dalal DS et al. Arthritis Care Res. 2019 Jul 3. doi: 10.1002/acr.23928.

Patients with gout who visit the emergency department are regularly prescribed opioids, based on a review of electronic medical records.

“In addition to regulatory changes, the burden of opioid prescription could be potentially reduced by creating prompts for providers in electronic record systems to avoid prescribing opioids in opioid-naive patients or using lower intensity and shorter duration of prescription,” wrote Deepan S. Dalal, MD, of Brown University, Providence, R.I., and coauthors. The study was published in Arthritis Care & Research.

To determine frequency, dose, and duration of opioid prescription at ED discharge, the researchers reviewed the records of 456 patients with acute gout who were discharged in Rhode Island between March 30, 2015, and Sept. 30, 2017. All data were gathered via electronic medical system records.

Of the 456 discharged patients, 129 (28.3%) were prescribed opioids; 102 (79%) were not on opioids at the time. A full prescription description was available for 119 of the 129 patients; 96 (81%) were prescribed oxycodone or oxycodone combinations. Hydrocodone was prescribed for 9 patients (8%) and tramadol was prescribed for 11 patients (9%).

The median duration of each prescription was 8 days (interquartile range, 5-14 days) and the average daily dose was 37.9 mg of morphine equivalent. Patients who were prescribed opioids tended to be younger and male. After multivariable analysis, diabetes, polyarticular gout attack, and prior opioid use were all associated with a more than 100% higher odds of receiving an opioid prescription.

The authors acknowledged their study’s limitations, including their inability to determine the physicians’ reasoning behind each prescription or the prescribing habits of each provider. In addition, they were only able to assess the prescriptions as being written and not the number of pills actually taken or not taken.

No conflicts of interest were reported.

SOURCE: Dalal DS et al. Arthritis Care Res. 2019 Jul 3. doi: 10.1002/acr.23928.

SAN ANTONIO – Patients with obstructive sleep apnea who complain of feeling tired when they wake up, being sleepy during the day, and have a high score on the Epworth Sleepiness Scale face an increased risk for cardiovascular disease, results from a population-based analysis suggest.

Doug Brunk/MDedge News

“OSA is a highly heterogeneous disease, with multiple clinical presentations and consequences,” the study’s first author, Diego R. Mazzotti, PhD, said at the annual meeting of the Associated Professional Sleep Societies. “These patients also have diverse comorbidities, and there are arbitrary severity definitions and variable therapeutic responses. It’s difficult to lump these patients together.”

Symptom subtypes of OSA were originally described in the Icelandic Sleep Apnea Cohort, and defined as excessively sleepy, minimally symptomatic, and disturbed sleep (Eur Respir J. 2014; 44[6]:1600-7). These distinct clusters were identified based on symptom experiences and the existence of major comorbidities. “This concept is more popular today, trying to identify symptom clusters, or groups of individuals, that share similar polysomnographic data, and then compare differences in prevalence or incidence of cardiovascular disease,” said Dr. Mazzotti, a research associate at the University of Pennsylvania, Philadelphia. “That’s a concept that needs to be moving forward.”

Dr. Mazzotti and colleagues set out to determine if OSA symptom subtypes are present in the Sleep Heart Health Study, a multicenter, prospective, community-based cohort of individuals aged 40 years and older designed to assess the cardiovascular (CV) consequences of OSA. They also wanted to know if there is additional evidence of the relevance of OSA symptom subtypes, particularly with respect to cardiovascular disease .

Participant-reported symptoms, such as difficulty falling and staying asleep, snoring, fatigue, drowsy driving and daytime sleepiness, and responses to the Epworth Sleepiness Scale were used to determine the patient’s subtype. Assessments including questionnaires and in-home polysomnography were conducted at baseline (between 1995 and 1998) and follow-up (between 2001 and 2003), while CV outcomes were assessed until the end of follow-up (between 2008 and 2011).

In all, 1,207 patients from the Sleep Heart Health Study met criteria for moderate to severe OSA (apnea-hypopnea index, or AHI, of 15 or greater) and were included in the final analysis. They were followed for a mean of 12 years. Based on the clustering of symptoms, the researchers identified four OSA symptom subtypes: disturbed sleep (12%), minimally symptomatic (33%), excessively sleepy (17%), and moderately sleepy (38%) – proportions that were similar to those observed in prior studies.

The disturbed sleep subtype presented with increased prevalence of “insomnialike” symptoms, such as difficulty initiating or maintaining sleep, according to Dr. Mazzotti. “On the other hand, the excessively sleepy subtype presented with a very high prevalence of several symptoms related to excessive daytime sleepiness, while the moderately sleepy showed a moderately high prevalence of such symptoms, but not as much when compared to the excessively sleepy subtype,” he explained. “Finally, the minimally symptomatic subtype was found to have the lowest prevalence of all investigated symptoms, suggesting that these patients have low symptom burden. They do not complain as much, even though they have moderate-to-severe OSA.”

Next, Dr. Mazzotti and colleagues used Kaplan-Meier survival analysis and Cox proportional hazards models to evaluate whether subtypes were associated with incident coronary heart disease (CHD), heart failure, and CV disease, including CV mortality. Similar analyses were performed comparing each symptom subtype with 2,830 individuals without OSA (AHI less than 5).

Compared with other subtypes, the excessively sleepy group had a more than threefold increased odds of prevalent heart failure, after adjustment for other CV risk factors. They also had a 1.7- to 2.3-fold increased risk for incident CV disease (P less than .001), CHD (P = .015) and heart failure (P = 0.018), after adjustment for other CV risk factors.

“Compared to individuals without OSA, the excessively sleepy subtype is the only subtype with increased risk of incident CV disease and CHD,” Dr. Mazzotti said. “It is possible that excessively sleepy OSA patients are more likely to benefit from CPAP therapy in preventing CV disease.” These results were published online earlier this year (Am J Respir Crit Care Med. 2019 Feb 15. doi: 10.1164/rccm.201808-1509OC).

Dr. Mazzotti reported having no financial disclosures.

dbrunk@mdedge.com

SOURCE: Mazzotti D et al. SLEEP 2019, Abstract 0586.

SAN ANTONIO – Patients with obstructive sleep apnea who complain of feeling tired when they wake up, being sleepy during the day, and have a high score on the Epworth Sleepiness Scale face an increased risk for cardiovascular disease, results from a population-based analysis suggest.

Doug Brunk/MDedge News

“OSA is a highly heterogeneous disease, with multiple clinical presentations and consequences,” the study’s first author, Diego R. Mazzotti, PhD, said at the annual meeting of the Associated Professional Sleep Societies. “These patients also have diverse comorbidities, and there are arbitrary severity definitions and variable therapeutic responses. It’s difficult to lump these patients together.”

Symptom subtypes of OSA were originally described in the Icelandic Sleep Apnea Cohort, and defined as excessively sleepy, minimally symptomatic, and disturbed sleep (Eur Respir J. 2014; 44[6]:1600-7). These distinct clusters were identified based on symptom experiences and the existence of major comorbidities. “This concept is more popular today, trying to identify symptom clusters, or groups of individuals, that share similar polysomnographic data, and then compare differences in prevalence or incidence of cardiovascular disease,” said Dr. Mazzotti, a research associate at the University of Pennsylvania, Philadelphia. “That’s a concept that needs to be moving forward.”

Dr. Mazzotti and colleagues set out to determine if OSA symptom subtypes are present in the Sleep Heart Health Study, a multicenter, prospective, community-based cohort of individuals aged 40 years and older designed to assess the cardiovascular (CV) consequences of OSA. They also wanted to know if there is additional evidence of the relevance of OSA symptom subtypes, particularly with respect to cardiovascular disease .

Participant-reported symptoms, such as difficulty falling and staying asleep, snoring, fatigue, drowsy driving and daytime sleepiness, and responses to the Epworth Sleepiness Scale were used to determine the patient’s subtype. Assessments including questionnaires and in-home polysomnography were conducted at baseline (between 1995 and 1998) and follow-up (between 2001 and 2003), while CV outcomes were assessed until the end of follow-up (between 2008 and 2011).

In all, 1,207 patients from the Sleep Heart Health Study met criteria for moderate to severe OSA (apnea-hypopnea index, or AHI, of 15 or greater) and were included in the final analysis. They were followed for a mean of 12 years. Based on the clustering of symptoms, the researchers identified four OSA symptom subtypes: disturbed sleep (12%), minimally symptomatic (33%), excessively sleepy (17%), and moderately sleepy (38%) – proportions that were similar to those observed in prior studies.

The disturbed sleep subtype presented with increased prevalence of “insomnialike” symptoms, such as difficulty initiating or maintaining sleep, according to Dr. Mazzotti. “On the other hand, the excessively sleepy subtype presented with a very high prevalence of several symptoms related to excessive daytime sleepiness, while the moderately sleepy showed a moderately high prevalence of such symptoms, but not as much when compared to the excessively sleepy subtype,” he explained. “Finally, the minimally symptomatic subtype was found to have the lowest prevalence of all investigated symptoms, suggesting that these patients have low symptom burden. They do not complain as much, even though they have moderate-to-severe OSA.”

Next, Dr. Mazzotti and colleagues used Kaplan-Meier survival analysis and Cox proportional hazards models to evaluate whether subtypes were associated with incident coronary heart disease (CHD), heart failure, and CV disease, including CV mortality. Similar analyses were performed comparing each symptom subtype with 2,830 individuals without OSA (AHI less than 5).

Compared with other subtypes, the excessively sleepy group had a more than threefold increased odds of prevalent heart failure, after adjustment for other CV risk factors. They also had a 1.7- to 2.3-fold increased risk for incident CV disease (P less than .001), CHD (P = .015) and heart failure (P = 0.018), after adjustment for other CV risk factors.

“Compared to individuals without OSA, the excessively sleepy subtype is the only subtype with increased risk of incident CV disease and CHD,” Dr. Mazzotti said. “It is possible that excessively sleepy OSA patients are more likely to benefit from CPAP therapy in preventing CV disease.” These results were published online earlier this year (Am J Respir Crit Care Med. 2019 Feb 15. doi: 10.1164/rccm.201808-1509OC).

Dr. Mazzotti reported having no financial disclosures.

dbrunk@mdedge.com

SOURCE: Mazzotti D et al. SLEEP 2019, Abstract 0586.

SAN ANTONIO – Patients with obstructive sleep apnea who complain of feeling tired when they wake up, being sleepy during the day, and have a high score on the Epworth Sleepiness Scale face an increased risk for cardiovascular disease, results from a population-based analysis suggest.

Doug Brunk/MDedge News

“OSA is a highly heterogeneous disease, with multiple clinical presentations and consequences,” the study’s first author, Diego R. Mazzotti, PhD, said at the annual meeting of the Associated Professional Sleep Societies. “These patients also have diverse comorbidities, and there are arbitrary severity definitions and variable therapeutic responses. It’s difficult to lump these patients together.”

Symptom subtypes of OSA were originally described in the Icelandic Sleep Apnea Cohort, and defined as excessively sleepy, minimally symptomatic, and disturbed sleep (Eur Respir J. 2014; 44[6]:1600-7). These distinct clusters were identified based on symptom experiences and the existence of major comorbidities. “This concept is more popular today, trying to identify symptom clusters, or groups of individuals, that share similar polysomnographic data, and then compare differences in prevalence or incidence of cardiovascular disease,” said Dr. Mazzotti, a research associate at the University of Pennsylvania, Philadelphia. “That’s a concept that needs to be moving forward.”

Dr. Mazzotti and colleagues set out to determine if OSA symptom subtypes are present in the Sleep Heart Health Study, a multicenter, prospective, community-based cohort of individuals aged 40 years and older designed to assess the cardiovascular (CV) consequences of OSA. They also wanted to know if there is additional evidence of the relevance of OSA symptom subtypes, particularly with respect to cardiovascular disease .

Participant-reported symptoms, such as difficulty falling and staying asleep, snoring, fatigue, drowsy driving and daytime sleepiness, and responses to the Epworth Sleepiness Scale were used to determine the patient’s subtype. Assessments including questionnaires and in-home polysomnography were conducted at baseline (between 1995 and 1998) and follow-up (between 2001 and 2003), while CV outcomes were assessed until the end of follow-up (between 2008 and 2011).

In all, 1,207 patients from the Sleep Heart Health Study met criteria for moderate to severe OSA (apnea-hypopnea index, or AHI, of 15 or greater) and were included in the final analysis. They were followed for a mean of 12 years. Based on the clustering of symptoms, the researchers identified four OSA symptom subtypes: disturbed sleep (12%), minimally symptomatic (33%), excessively sleepy (17%), and moderately sleepy (38%) – proportions that were similar to those observed in prior studies.

The disturbed sleep subtype presented with increased prevalence of “insomnialike” symptoms, such as difficulty initiating or maintaining sleep, according to Dr. Mazzotti. “On the other hand, the excessively sleepy subtype presented with a very high prevalence of several symptoms related to excessive daytime sleepiness, while the moderately sleepy showed a moderately high prevalence of such symptoms, but not as much when compared to the excessively sleepy subtype,” he explained. “Finally, the minimally symptomatic subtype was found to have the lowest prevalence of all investigated symptoms, suggesting that these patients have low symptom burden. They do not complain as much, even though they have moderate-to-severe OSA.”

Next, Dr. Mazzotti and colleagues used Kaplan-Meier survival analysis and Cox proportional hazards models to evaluate whether subtypes were associated with incident coronary heart disease (CHD), heart failure, and CV disease, including CV mortality. Similar analyses were performed comparing each symptom subtype with 2,830 individuals without OSA (AHI less than 5).

Compared with other subtypes, the excessively sleepy group had a more than threefold increased odds of prevalent heart failure, after adjustment for other CV risk factors. They also had a 1.7- to 2.3-fold increased risk for incident CV disease (P less than .001), CHD (P = .015) and heart failure (P = 0.018), after adjustment for other CV risk factors.

“Compared to individuals without OSA, the excessively sleepy subtype is the only subtype with increased risk of incident CV disease and CHD,” Dr. Mazzotti said. “It is possible that excessively sleepy OSA patients are more likely to benefit from CPAP therapy in preventing CV disease.” These results were published online earlier this year (Am J Respir Crit Care Med. 2019 Feb 15. doi: 10.1164/rccm.201808-1509OC).

Dr. Mazzotti reported having no financial disclosures.

dbrunk@mdedge.com

SOURCE: Mazzotti D et al. SLEEP 2019, Abstract 0586.

SEATTLE – Among patients with multiple sclerosis (MS), functional gastrointestinal (GI) disorders are prevalent and associated with health-related quality of life, according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. Managing patients’ psychiatric comorbidities could effectively reduce the burden of functional GI disorders, the researchers said.

Knowledge about the prevalence of functional GI disorders in the population of patients with MS is limited. For the most part, previous studies in this population have focused on irritable bowel syndrome (IBS). A 2013 study by Levinthal et al. (Mult Scler Int. 2013. doi: 10.1155/2013/319201) investigated the prevalence of other functional GI disorders in MS, but the literature contains little information about the clinical and demographic characteristics associated with these disorders. In addition, the extent to which comorbid functional GI disorders influence health-related quality of life in MS is also unknown.

Ruth Ann Marrie, MD, PhD, professor of neurology at the University of Manitoba in Winnipeg, and colleagues sought to determine the prevalence of functional bowel disorders, the demographic and clinical characteristics associated with functional bowel disorders, and the effects of these disorders on health-related quality of life in a large, diverse population of persons with MS. In 2014, the investigators used the Rome III questionnaire to survey participants in the North American Research Committee on MS (NARCOMS) registry about functional bowel disorders. Participants also provided information about their sociodemographic characteristics, their disability status (using Patient-Determined Disease Steps), and any comorbid depression or anxiety, their health behaviors, and their health-related quality of life (using the RAND-12).

Dr. Marrie and colleagues used these data to determine the prevalence of IBS, functional bloating, functional constipation, functional diarrhea, and functional dyspepsia. They used multivariable logistic regression models to examine the factors associated with any functional GI disorder, and they used linear regression to analyze the association between functional GI disorders and health-related quality of life using linear regression.

Dr. Marrie and colleagues identified 6,312 eligible respondents. Approximately 77% of the population was female, and the sample’s mean age was 58.3 years. In all, 2,647 respondents (42%) had a functional GI disorder. The most common was IBS, which affected 28.2% of participants. The prevalence of all functional GI disorders increased with increasing disability. Depression and anxiety were associated with increased odds of IBS and functional dyspepsia. After adjustment for sociodemographic and clinical characteristics, functional GI disorders were associated with lower physical and mental health-related quality of life.

The research was not supported by outside funding. Dr. Marrie had no disclosures, but other researchers had financial relationships with pharmaceutical companies, such as Merck, Novartis, Roche, Sanofi-Aventis, and Teva.
 

egreb@mdedge.com

SOURCE: Marrie RA et al. CMSC 2019, Abstract QOL13.

SEATTLE – Among patients with multiple sclerosis (MS), functional gastrointestinal (GI) disorders are prevalent and associated with health-related quality of life, according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. Managing patients’ psychiatric comorbidities could effectively reduce the burden of functional GI disorders, the researchers said.

Knowledge about the prevalence of functional GI disorders in the population of patients with MS is limited. For the most part, previous studies in this population have focused on irritable bowel syndrome (IBS). A 2013 study by Levinthal et al. (Mult Scler Int. 2013. doi: 10.1155/2013/319201) investigated the prevalence of other functional GI disorders in MS, but the literature contains little information about the clinical and demographic characteristics associated with these disorders. In addition, the extent to which comorbid functional GI disorders influence health-related quality of life in MS is also unknown.

Ruth Ann Marrie, MD, PhD, professor of neurology at the University of Manitoba in Winnipeg, and colleagues sought to determine the prevalence of functional bowel disorders, the demographic and clinical characteristics associated with functional bowel disorders, and the effects of these disorders on health-related quality of life in a large, diverse population of persons with MS. In 2014, the investigators used the Rome III questionnaire to survey participants in the North American Research Committee on MS (NARCOMS) registry about functional bowel disorders. Participants also provided information about their sociodemographic characteristics, their disability status (using Patient-Determined Disease Steps), and any comorbid depression or anxiety, their health behaviors, and their health-related quality of life (using the RAND-12).

Dr. Marrie and colleagues used these data to determine the prevalence of IBS, functional bloating, functional constipation, functional diarrhea, and functional dyspepsia. They used multivariable logistic regression models to examine the factors associated with any functional GI disorder, and they used linear regression to analyze the association between functional GI disorders and health-related quality of life using linear regression.

Dr. Marrie and colleagues identified 6,312 eligible respondents. Approximately 77% of the population was female, and the sample’s mean age was 58.3 years. In all, 2,647 respondents (42%) had a functional GI disorder. The most common was IBS, which affected 28.2% of participants. The prevalence of all functional GI disorders increased with increasing disability. Depression and anxiety were associated with increased odds of IBS and functional dyspepsia. After adjustment for sociodemographic and clinical characteristics, functional GI disorders were associated with lower physical and mental health-related quality of life.

The research was not supported by outside funding. Dr. Marrie had no disclosures, but other researchers had financial relationships with pharmaceutical companies, such as Merck, Novartis, Roche, Sanofi-Aventis, and Teva.
 

egreb@mdedge.com

SOURCE: Marrie RA et al. CMSC 2019, Abstract QOL13.

SEATTLE – Among patients with multiple sclerosis (MS), functional gastrointestinal (GI) disorders are prevalent and associated with health-related quality of life, according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. Managing patients’ psychiatric comorbidities could effectively reduce the burden of functional GI disorders, the researchers said.

Knowledge about the prevalence of functional GI disorders in the population of patients with MS is limited. For the most part, previous studies in this population have focused on irritable bowel syndrome (IBS). A 2013 study by Levinthal et al. (Mult Scler Int. 2013. doi: 10.1155/2013/319201) investigated the prevalence of other functional GI disorders in MS, but the literature contains little information about the clinical and demographic characteristics associated with these disorders. In addition, the extent to which comorbid functional GI disorders influence health-related quality of life in MS is also unknown.

Ruth Ann Marrie, MD, PhD, professor of neurology at the University of Manitoba in Winnipeg, and colleagues sought to determine the prevalence of functional bowel disorders, the demographic and clinical characteristics associated with functional bowel disorders, and the effects of these disorders on health-related quality of life in a large, diverse population of persons with MS. In 2014, the investigators used the Rome III questionnaire to survey participants in the North American Research Committee on MS (NARCOMS) registry about functional bowel disorders. Participants also provided information about their sociodemographic characteristics, their disability status (using Patient-Determined Disease Steps), and any comorbid depression or anxiety, their health behaviors, and their health-related quality of life (using the RAND-12).

Dr. Marrie and colleagues used these data to determine the prevalence of IBS, functional bloating, functional constipation, functional diarrhea, and functional dyspepsia. They used multivariable logistic regression models to examine the factors associated with any functional GI disorder, and they used linear regression to analyze the association between functional GI disorders and health-related quality of life using linear regression.

Dr. Marrie and colleagues identified 6,312 eligible respondents. Approximately 77% of the population was female, and the sample’s mean age was 58.3 years. In all, 2,647 respondents (42%) had a functional GI disorder. The most common was IBS, which affected 28.2% of participants. The prevalence of all functional GI disorders increased with increasing disability. Depression and anxiety were associated with increased odds of IBS and functional dyspepsia. After adjustment for sociodemographic and clinical characteristics, functional GI disorders were associated with lower physical and mental health-related quality of life.

The research was not supported by outside funding. Dr. Marrie had no disclosures, but other researchers had financial relationships with pharmaceutical companies, such as Merck, Novartis, Roche, Sanofi-Aventis, and Teva.
 

egreb@mdedge.com

SOURCE: Marrie RA et al. CMSC 2019, Abstract QOL13.

Let’s begin with a brief case. A 25-year-old patient with a history of injection heroin use is in your care. He is admitted for treatment of endocarditis and will remain in the hospital for intravenous antibiotics for several weeks. Over the first few days of hospitalization, he frequently asks for pain medicine, stating that he is in severe pain, withdrawal, and having opioid cravings. On day 3, he leaves the hospital against medical advice. After 2 weeks, he presents to the ED in septic shock and spends several weeks in the ICU. Or, alternatively, he is found down in the community and pronounced dead from a heroin overdose.

These cases occur all too often, and hospitalists across the nation are actively building knowledge and programs to improve care for patients with opioid use disorder (OUD). It is evident that opioid misuse is the public health crisis of our time. In 2017, over 70,000 patients died from an overdose, and over 2 million patients in the United States have a diagnosis of OUD.^1,2 Many of these patients interact with the hospital at some point during the course of their illness for management of overdose, withdrawal, and other complications of OUD, including endocarditis, osteomyelitis, and skin and soft tissue infections. Moreover, just 20% of the 580,000 patients hospitalized with OUD in 2015 presented as a direct sequelae of the disease.³ Patients with OUD are often admitted for unrelated reasons, but their addiction goes unaddressed.

Opioid use disorder, like many of the other conditions we see, is a chronic relapsing remitting medical disease and a risk factor for premature mortality. When a patient with diabetes is admitted with cellulitis, we might check an A_1C, provide diabetic counseling, and offer evidence-based diabetes treatment, including medications like insulin. We rarely build similar systems of care within the walls of our hospitals to treat OUD like we do for diabetes or other commonly encountered diseases like heart failure and chronic obstructive pulmonary disease.

We should be intentional about separating prevention from treatment. Significant work has gone into reducing the availability of prescription opioids and increasing utilization of prescription drug monitoring programs. As a result, the average morphine milligram equivalent per opioid prescription has decreased since 2010.⁴ An unintended consequence of restricting legal opioids is potentially pushing patients with opioid addiction towards heroin and fentanyl. Limiting opioid prescriptions alone will only decrease opioid overdose mortality by 5% through 2025.⁵ Thus, treatment of OUD is critical and something that hospitalists should be trained and engaged in.

Food and Drug Administration–approved OUD treatment includes buprenorphine, methadone, and extended-release naltrexone. Buprenorphine is a partial opioid agonist that treats withdrawal and cravings. Buprenorphine started in the hospital reduces mortality, increases time spent in outpatient treatment after discharge, and reduces opioid-related 30-day readmissions by over 50%.^6-8 The number needed to treat with buprenorphine to prevent return to illicit opioid use is two.⁹ While physicians require an 8-hour “x-waiver” training (physician assistants and nurse practitioners require a 24-hour training) to prescribe buprenorphine for the outpatient treatment of OUD, such certification is not required to order the medication as part of an acute hospitalization.

Hospitalization represents a reachable moment and unique opportunity to start treatment for OUD. Patients are away from triggering environments and surrounded by supportive staff. Unfortunately, up to 30% of these patients leave the hospital against medical advice because of inadequately treated withdrawal, unaddressed cravings, and fear of mistreatment.¹⁰ Buprenorphine therapy may help tackle the physiological piece of hospital-based treatment, but we also must work on shifting the culture of our institutions. Importantly, OUD is a medical diagnosis. These patients must receive the same dignity, autonomy, and meaningful care afforded to patients with other medical diagnoses. Patients with OUD are not “addicts,” “abusers,” or “frequent fliers.”

Hospitalists have a clear and compelling role in treating OUD. The National Academy of Medicine recently held a workshop where they compared similarities of the HIV crisis with today’s opioid epidemic. The Academy advocated for the development of hospital-based protocols that empower physicians, physician assistants, and nurse practitioners to integrate the treatment of OUD into their practice.¹¹ Some in our field may feel that treating underlying addiction is a role for behavioral health practitioners. This is akin to having said that HIV specialists should be the only providers to treat patients with HIV during its peak. There are simply not enough psychiatrists or addiction medicine specialists to treat all of the patients who need us during this time of national urgency.

Mr. Bottner is a hospitalist at Dell Seton Medical Center, Austin, Texas, and clinical assistant professor at the University of Texas at Austin.

References

1. Katz J. You draw it: Just how bad is the drug overdose epidemic? New York Times. https://www.nytimes.com/interactive/2017/04/14/upshot/drug-overdose-epidemic-you-draw-it.html. Published Oct 26, 2017.

2. National Institute on Drug Abuse. Ohio – Opioid summaries by state. 2018. https://d14rmgtrwzf5a.cloudfront.net/sites/default/files/ohio_2018.pdf.

3. Peterson C et al. U.S. hospital discharges documenting patient opioid use disorder without opioid overdose or treatment services, 2011-2015. J Subst Abuse Treat. 2018;92:35-39. doi: 10.1016/j.jsat.2018.06.008.

4. Guy GP. Vital Signs: Changes in opioid prescribing in the United States, 2006-2015. Morb Mortal Wkly Rep. 2017;66. doi: 10.15585/mmwr.mm6626a4.

5. Chen Q et al. Prevention of prescription opioid misuse and projected overdose deaths in the United States. JAMA Netw Open. doi: 10.1001/jamanetworkopen.2018.7621.

6. Liebschutz J et al. Buprenorphine treatment for hospitalized, opioid-dependent patients: A randomized clinical trial. JAMA Intern Med. 2014;174(8):1369-76.

7. Moreno JL et al. Predictors for 30-day and 90-day hospital readmission among patients with opioid use disorder. J Addict Med. 2019. doi: 10.1097/ADM.0000000000000499.

8. Larochelle MR et al. Medication for opioid use disorder after nonfatal opioid overdose and association with mortality: A cohort study. Ann Intern Med. June 2018. doi: 10.7326/M17-3107.

9. Raleigh MF. Buprenorphine maintenance vs. placebo for opioid dependence. Am Fam Physician. 2017;95(5). https://www.aafp.org/afp/2017/0301/od1.html. Accessed May 12, 2019.

10. Ti L et al. Leaving the hospital against medical advice among people who use illicit drugs: A systematic review. Am J Public Health. 2015;105(12):2587. doi: 10.2105/AJPH.2015.302885a.

11. Springer SAM et al. Integrating treatment at the intersection of opioid use disorder and infectious disease epidemics in medical settings: A call for action after a National Academies of Sciences, Engineering, and Medicine workshop. Ann Intern Med. 2018;169(5):335-6. doi: 10.7326/M18-1203.

Let’s begin with a brief case. A 25-year-old patient with a history of injection heroin use is in your care. He is admitted for treatment of endocarditis and will remain in the hospital for intravenous antibiotics for several weeks. Over the first few days of hospitalization, he frequently asks for pain medicine, stating that he is in severe pain, withdrawal, and having opioid cravings. On day 3, he leaves the hospital against medical advice. After 2 weeks, he presents to the ED in septic shock and spends several weeks in the ICU. Or, alternatively, he is found down in the community and pronounced dead from a heroin overdose.

These cases occur all too often, and hospitalists across the nation are actively building knowledge and programs to improve care for patients with opioid use disorder (OUD). It is evident that opioid misuse is the public health crisis of our time. In 2017, over 70,000 patients died from an overdose, and over 2 million patients in the United States have a diagnosis of OUD.^1,2 Many of these patients interact with the hospital at some point during the course of their illness for management of overdose, withdrawal, and other complications of OUD, including endocarditis, osteomyelitis, and skin and soft tissue infections. Moreover, just 20% of the 580,000 patients hospitalized with OUD in 2015 presented as a direct sequelae of the disease.³ Patients with OUD are often admitted for unrelated reasons, but their addiction goes unaddressed.

Opioid use disorder, like many of the other conditions we see, is a chronic relapsing remitting medical disease and a risk factor for premature mortality. When a patient with diabetes is admitted with cellulitis, we might check an A_1C, provide diabetic counseling, and offer evidence-based diabetes treatment, including medications like insulin. We rarely build similar systems of care within the walls of our hospitals to treat OUD like we do for diabetes or other commonly encountered diseases like heart failure and chronic obstructive pulmonary disease.

We should be intentional about separating prevention from treatment. Significant work has gone into reducing the availability of prescription opioids and increasing utilization of prescription drug monitoring programs. As a result, the average morphine milligram equivalent per opioid prescription has decreased since 2010.⁴ An unintended consequence of restricting legal opioids is potentially pushing patients with opioid addiction towards heroin and fentanyl. Limiting opioid prescriptions alone will only decrease opioid overdose mortality by 5% through 2025.⁵ Thus, treatment of OUD is critical and something that hospitalists should be trained and engaged in.

Food and Drug Administration–approved OUD treatment includes buprenorphine, methadone, and extended-release naltrexone. Buprenorphine is a partial opioid agonist that treats withdrawal and cravings. Buprenorphine started in the hospital reduces mortality, increases time spent in outpatient treatment after discharge, and reduces opioid-related 30-day readmissions by over 50%.^6-8 The number needed to treat with buprenorphine to prevent return to illicit opioid use is two.⁹ While physicians require an 8-hour “x-waiver” training (physician assistants and nurse practitioners require a 24-hour training) to prescribe buprenorphine for the outpatient treatment of OUD, such certification is not required to order the medication as part of an acute hospitalization.

Hospitalization represents a reachable moment and unique opportunity to start treatment for OUD. Patients are away from triggering environments and surrounded by supportive staff. Unfortunately, up to 30% of these patients leave the hospital against medical advice because of inadequately treated withdrawal, unaddressed cravings, and fear of mistreatment.¹⁰ Buprenorphine therapy may help tackle the physiological piece of hospital-based treatment, but we also must work on shifting the culture of our institutions. Importantly, OUD is a medical diagnosis. These patients must receive the same dignity, autonomy, and meaningful care afforded to patients with other medical diagnoses. Patients with OUD are not “addicts,” “abusers,” or “frequent fliers.”

Hospitalists have a clear and compelling role in treating OUD. The National Academy of Medicine recently held a workshop where they compared similarities of the HIV crisis with today’s opioid epidemic. The Academy advocated for the development of hospital-based protocols that empower physicians, physician assistants, and nurse practitioners to integrate the treatment of OUD into their practice.¹¹ Some in our field may feel that treating underlying addiction is a role for behavioral health practitioners. This is akin to having said that HIV specialists should be the only providers to treat patients with HIV during its peak. There are simply not enough psychiatrists or addiction medicine specialists to treat all of the patients who need us during this time of national urgency.

Mr. Bottner is a hospitalist at Dell Seton Medical Center, Austin, Texas, and clinical assistant professor at the University of Texas at Austin.

References

1. Katz J. You draw it: Just how bad is the drug overdose epidemic? New York Times. https://www.nytimes.com/interactive/2017/04/14/upshot/drug-overdose-epidemic-you-draw-it.html. Published Oct 26, 2017.

2. National Institute on Drug Abuse. Ohio – Opioid summaries by state. 2018. https://d14rmgtrwzf5a.cloudfront.net/sites/default/files/ohio_2018.pdf.

3. Peterson C et al. U.S. hospital discharges documenting patient opioid use disorder without opioid overdose or treatment services, 2011-2015. J Subst Abuse Treat. 2018;92:35-39. doi: 10.1016/j.jsat.2018.06.008.

4. Guy GP. Vital Signs: Changes in opioid prescribing in the United States, 2006-2015. Morb Mortal Wkly Rep. 2017;66. doi: 10.15585/mmwr.mm6626a4.

5. Chen Q et al. Prevention of prescription opioid misuse and projected overdose deaths in the United States. JAMA Netw Open. doi: 10.1001/jamanetworkopen.2018.7621.

6. Liebschutz J et al. Buprenorphine treatment for hospitalized, opioid-dependent patients: A randomized clinical trial. JAMA Intern Med. 2014;174(8):1369-76.

7. Moreno JL et al. Predictors for 30-day and 90-day hospital readmission among patients with opioid use disorder. J Addict Med. 2019. doi: 10.1097/ADM.0000000000000499.

8. Larochelle MR et al. Medication for opioid use disorder after nonfatal opioid overdose and association with mortality: A cohort study. Ann Intern Med. June 2018. doi: 10.7326/M17-3107.

9. Raleigh MF. Buprenorphine maintenance vs. placebo for opioid dependence. Am Fam Physician. 2017;95(5). https://www.aafp.org/afp/2017/0301/od1.html. Accessed May 12, 2019.

10. Ti L et al. Leaving the hospital against medical advice among people who use illicit drugs: A systematic review. Am J Public Health. 2015;105(12):2587. doi: 10.2105/AJPH.2015.302885a.

11. Springer SAM et al. Integrating treatment at the intersection of opioid use disorder and infectious disease epidemics in medical settings: A call for action after a National Academies of Sciences, Engineering, and Medicine workshop. Ann Intern Med. 2018;169(5):335-6. doi: 10.7326/M18-1203.

Let’s begin with a brief case. A 25-year-old patient with a history of injection heroin use is in your care. He is admitted for treatment of endocarditis and will remain in the hospital for intravenous antibiotics for several weeks. Over the first few days of hospitalization, he frequently asks for pain medicine, stating that he is in severe pain, withdrawal, and having opioid cravings. On day 3, he leaves the hospital against medical advice. After 2 weeks, he presents to the ED in septic shock and spends several weeks in the ICU. Or, alternatively, he is found down in the community and pronounced dead from a heroin overdose.

These cases occur all too often, and hospitalists across the nation are actively building knowledge and programs to improve care for patients with opioid use disorder (OUD). It is evident that opioid misuse is the public health crisis of our time. In 2017, over 70,000 patients died from an overdose, and over 2 million patients in the United States have a diagnosis of OUD.^1,2 Many of these patients interact with the hospital at some point during the course of their illness for management of overdose, withdrawal, and other complications of OUD, including endocarditis, osteomyelitis, and skin and soft tissue infections. Moreover, just 20% of the 580,000 patients hospitalized with OUD in 2015 presented as a direct sequelae of the disease.³ Patients with OUD are often admitted for unrelated reasons, but their addiction goes unaddressed.

Opioid use disorder, like many of the other conditions we see, is a chronic relapsing remitting medical disease and a risk factor for premature mortality. When a patient with diabetes is admitted with cellulitis, we might check an A_1C, provide diabetic counseling, and offer evidence-based diabetes treatment, including medications like insulin. We rarely build similar systems of care within the walls of our hospitals to treat OUD like we do for diabetes or other commonly encountered diseases like heart failure and chronic obstructive pulmonary disease.

We should be intentional about separating prevention from treatment. Significant work has gone into reducing the availability of prescription opioids and increasing utilization of prescription drug monitoring programs. As a result, the average morphine milligram equivalent per opioid prescription has decreased since 2010.⁴ An unintended consequence of restricting legal opioids is potentially pushing patients with opioid addiction towards heroin and fentanyl. Limiting opioid prescriptions alone will only decrease opioid overdose mortality by 5% through 2025.⁵ Thus, treatment of OUD is critical and something that hospitalists should be trained and engaged in.

Food and Drug Administration–approved OUD treatment includes buprenorphine, methadone, and extended-release naltrexone. Buprenorphine is a partial opioid agonist that treats withdrawal and cravings. Buprenorphine started in the hospital reduces mortality, increases time spent in outpatient treatment after discharge, and reduces opioid-related 30-day readmissions by over 50%.^6-8 The number needed to treat with buprenorphine to prevent return to illicit opioid use is two.⁹ While physicians require an 8-hour “x-waiver” training (physician assistants and nurse practitioners require a 24-hour training) to prescribe buprenorphine for the outpatient treatment of OUD, such certification is not required to order the medication as part of an acute hospitalization.

Hospitalization represents a reachable moment and unique opportunity to start treatment for OUD. Patients are away from triggering environments and surrounded by supportive staff. Unfortunately, up to 30% of these patients leave the hospital against medical advice because of inadequately treated withdrawal, unaddressed cravings, and fear of mistreatment.¹⁰ Buprenorphine therapy may help tackle the physiological piece of hospital-based treatment, but we also must work on shifting the culture of our institutions. Importantly, OUD is a medical diagnosis. These patients must receive the same dignity, autonomy, and meaningful care afforded to patients with other medical diagnoses. Patients with OUD are not “addicts,” “abusers,” or “frequent fliers.”

Hospitalists have a clear and compelling role in treating OUD. The National Academy of Medicine recently held a workshop where they compared similarities of the HIV crisis with today’s opioid epidemic. The Academy advocated for the development of hospital-based protocols that empower physicians, physician assistants, and nurse practitioners to integrate the treatment of OUD into their practice.¹¹ Some in our field may feel that treating underlying addiction is a role for behavioral health practitioners. This is akin to having said that HIV specialists should be the only providers to treat patients with HIV during its peak. There are simply not enough psychiatrists or addiction medicine specialists to treat all of the patients who need us during this time of national urgency.

Mr. Bottner is a hospitalist at Dell Seton Medical Center, Austin, Texas, and clinical assistant professor at the University of Texas at Austin.

References

1. Katz J. You draw it: Just how bad is the drug overdose epidemic? New York Times. https://www.nytimes.com/interactive/2017/04/14/upshot/drug-overdose-epidemic-you-draw-it.html. Published Oct 26, 2017.

2. National Institute on Drug Abuse. Ohio – Opioid summaries by state. 2018. https://d14rmgtrwzf5a.cloudfront.net/sites/default/files/ohio_2018.pdf.

3. Peterson C et al. U.S. hospital discharges documenting patient opioid use disorder without opioid overdose or treatment services, 2011-2015. J Subst Abuse Treat. 2018;92:35-39. doi: 10.1016/j.jsat.2018.06.008.

4. Guy GP. Vital Signs: Changes in opioid prescribing in the United States, 2006-2015. Morb Mortal Wkly Rep. 2017;66. doi: 10.15585/mmwr.mm6626a4.

5. Chen Q et al. Prevention of prescription opioid misuse and projected overdose deaths in the United States. JAMA Netw Open. doi: 10.1001/jamanetworkopen.2018.7621.

6. Liebschutz J et al. Buprenorphine treatment for hospitalized, opioid-dependent patients: A randomized clinical trial. JAMA Intern Med. 2014;174(8):1369-76.

7. Moreno JL et al. Predictors for 30-day and 90-day hospital readmission among patients with opioid use disorder. J Addict Med. 2019. doi: 10.1097/ADM.0000000000000499.

8. Larochelle MR et al. Medication for opioid use disorder after nonfatal opioid overdose and association with mortality: A cohort study. Ann Intern Med. June 2018. doi: 10.7326/M17-3107.

9. Raleigh MF. Buprenorphine maintenance vs. placebo for opioid dependence. Am Fam Physician. 2017;95(5). https://www.aafp.org/afp/2017/0301/od1.html. Accessed May 12, 2019.

10. Ti L et al. Leaving the hospital against medical advice among people who use illicit drugs: A systematic review. Am J Public Health. 2015;105(12):2587. doi: 10.2105/AJPH.2015.302885a.

11. Springer SAM et al. Integrating treatment at the intersection of opioid use disorder and infectious disease epidemics in medical settings: A call for action after a National Academies of Sciences, Engineering, and Medicine workshop. Ann Intern Med. 2018;169(5):335-6. doi: 10.7326/M18-1203.

High levels of lipoprotein(a) [Lp(a)] and LPA genotypes were linked to increased ischemic stroke risk in a recent large, contemporary general population study, investigators are reporting in the Journal of the American College of Cardiology.

Copyright American Stroke Association

SOURCE: Langsted A, et al. JACC 2019;74[1]: 54-66. doi: 10.1016/j.jacc.2019.03.524

High levels of lipoprotein(a) [Lp(a)] and LPA genotypes were linked to increased ischemic stroke risk in a recent large, contemporary general population study, investigators are reporting in the Journal of the American College of Cardiology.

Copyright American Stroke Association

SOURCE: Langsted A, et al. JACC 2019;74[1]: 54-66. doi: 10.1016/j.jacc.2019.03.524

High levels of lipoprotein(a) [Lp(a)] and LPA genotypes were linked to increased ischemic stroke risk in a recent large, contemporary general population study, investigators are reporting in the Journal of the American College of Cardiology.

Copyright American Stroke Association

SOURCE: Langsted A, et al. JACC 2019;74[1]: 54-66. doi: 10.1016/j.jacc.2019.03.524

Giant cell arteritis (GCA) is a systemic vasculitis involving medium-sized and large arteries, most commonly the temporal, ophthalmic, occipital, vertebral, posterior ciliary, and proximal vertebral arteries. Moreover, involvement of the ophthalmic artery and its branches results in loss of vision. GCA can also involve the aorta and its proximal branches, especially in the upper extremities.

GCA is the most common systemic vasculitis in adults. It occurs almost exclusively in patients over age 50 and affects women more than men. It is most frequent in populations of northern European ancestry, especially Scandinavian. In a retrospective cohort study in Norway, the average annual cumulative incidence rate of GCA was 16.7 per 100,000 people over age 50.¹ Risk factors include older age, history of smoking, current smoking, early menopause, and, possibly, stress-related disorders.²

PATHOGENESIS IS NOT COMPLETELY UNDERSTOOD

The pathogenesis of GCA is not completely understood, but there is evidence of immune activation in the arterial wall leading to activation of macrophages and formation of multinucleated giant cells (which may not always be present in biopsies).

The most relevant cytokines in the ongoing pathogenesis are still being defined, but the presence of interferon gamma and interleukin 6 (IL-6) seem to be critical for the expression of the disease. The primary immunogenic triggers for the elaboration of these cytokines and the arteritis remain elusive.

A SPECTRUM OF PRESENTATIONS

The initial symptoms of GCA may be vague, such as malaise, fever, and night sweats, and are likely due to systemic inflammation. Features of vascular involvement include headache, scalp tenderness, and jaw claudication (cramping pain in the jaw while chewing).

A less common but serious feature associated with GCA is partial or complete vision loss affecting 1 or both eyes.³ Some patients suddenly go completely blind without any visual prodrome.

Overlapping GCA phenotypes exist, with a spectrum of presentations that include classic cranial arteritis, extracranial GCA (also called large-vessel GCA), and polymyalgia rheumatica.²

Cranial GCA, the best-characterized clinical presentation, causes symptoms such as headache or signs such as tenderness of the temporal artery. On examination, the temporal arteries may be tender or nodular, and the pulses may be felt above the zygomatic arch, above and in front of the tragus of the ear. About two-thirds of patients with cranial GCA present with new-onset headache, most often in the temporal area, but possibly anywhere throughout the head.

Visual disturbance, jaw claudication, and tongue pain are less common but, if present, increase the likelihood of this diagnosis.²

Large-vessel involvement in GCA is common and refers to involvement of the aorta and its proximal branches. Imaging methods used in diagnosing large-vessel GCA include color Doppler ultrasonography, computed tomography with angiography, magnetic resonance imaging with angiography, and positron emission tomography. In some centers, such imaging is performed in all patients diagnosed with GCA to survey for large-vessel involvement.

Depending on the imaging study, large-vessel involvement has been found in 30% to 80% of cases of GCA.^4,5 It is often associated with nonspecific symptoms such as fever, weight loss, chills, and malaise, but it can also cause more specific symptoms such as unilateral extremity claudication. In contrast to patients with cranial GCA, patients with large-vessel GCA were younger at onset, less likely to have headaches, and more likely to have arm claudication at presentation.⁶ Aortitis of the ascending aorta can occur with a histopathologic pattern of GCA but without the clinical stigmata of GCA.

The finding of aortitis should prompt the clinician to question the patient about other symptoms of GCA and to order imaging of the whole vascular tree. Ultrasonography and biopsy of the temporal arteries can be considered. Whether idiopathic aortitis is part of the GCA spectrum remains to be seen.

Laboratory tests often show anemia, leukocytosis, and thrombocytosis. Acute-phase reactants such as C-reactive protein and the erythrocyte sedimentation rate are often elevated. The sedimentation rate often exceeds 50 mm/hour and sometimes 100 mm/hour.

In 2 retrospective studies, the number of patients with GCA whose sedimentation rate was less than 50 mm/hour ranged between 5% and 11%.^7,8 However, a small percentage of patients with GCA have normal inflammatory markers. Therefore, if the suspicion for GCA is high, treatment should be started and biopsy pursued.⁹ In patients with paraproteinemia or other causes of a spuriously elevated or low erythrocyte sedimentation rate, C-reactive protein is a more reliable test.

Polymyalgia rheumatica is another rheumatologic condition that can occur independently or in conjunction with GCA. It is characterized by stiffness and pain in the proximal joints such as the hips and shoulders, typically worse in the morning and better with activity. Although the patient may subjectively feel weak, a close neurologic examination will reveal normal muscle strength.

Polymyalgia rheumatica is observed in 40% to 60% of patients with GCA at the time of diagnosis; 16% to 21% of patients with polymyalgia rheumatica may develop GCA, especially if untreated.^2,10

Differential diagnosis

Other vasculitides (eg, Takayasu arteritis) can also present with unexplained fever, anemia, and constitutional symptoms.

Infection should be considered if fever is present. An infectious disease accompanied by fever, headache, and elevated inflammatory markers can mimic GCA.

Nonarteritic anterior ischemic optic neuropathy can present with sudden vision loss, prompting concern for underlying GCA. Risk factors include hypertension and diabetes mellitus; other features of GCA, including elevated inflammatory markers, are generally absent.

 

 

TEMPORAL ARTERY BIOPSY: THE GOLD STANDARD FOR DIAGNOSIS

Temporal artery biopsy remains the standard to confirm the diagnosis. However, because inflammation in the temporal arteries can affect some segments but not others, biopsy results on conventional hematoxylin and eosin staining can be falsely negative in patients with GCA. In one study,¹¹ the mean sensitivity of unilateral temporal artery biopsy was 86.9%.

Typical positive histologic findings are inflammation with panarteritis, CD4-positive lymphocytes, macrophages, giant cells, and fragmentation of the internal elastic lamina.¹²

When GCA is suspected, treatment with glucocorticoids should be started immediately and biopsy performed as soon as possible. Delaying biopsy for 14 days or more may not affect the accuracy of biopsy study.¹³ Treatment should never be withheld while awaiting the results of biopsy study.

Biopsy is usually performed unilaterally, on the same side as the symptoms or abnormal findings on examination. Bilateral temporal artery biopsy is also performed and compared with unilateral biopsy; this approach increases the diagnostic yield by about 5%.¹⁴

IMAGING

In patients with suspected GCA, imaging is recommended early to complement the clinical criteria for the diagnosis of GCA.¹⁵ Positron emission tomography, computed tomography angiography, magnetic resonance angiography, or Doppler ultrasonography can reveal inflammation of the arteries in the proximal upper or lower limbs or the aorta.²

In patients with suspected cranial GCA, ultrasonography of the temporal and axillary arteries is recommended first. If ultrasonography is not available or is inconclusive, high-resolution magnetic resonance imaging of the cranial arteries can be used as an alternative. Computed tomography and positron emission tomography of the cranial arteries are not recommended.

In patients with suspected large-vessel GCA, ultrasonography, positron emission tomography, computed tomography, and magnetic resonance imaging may be used to screen for vessel wall inflammation, edema, and luminal narrowing in extracranial arteries. Ultrasonography is of limited value in assessing aortitis.

Color duplex ultrasonography can be applied to assess for vascular inflammation of the temporal or large arteries. The typical finding of the “halo” sign, a hypoechoic ring around the arterial lumen, represents the inflammation-induced thickening of the arterial wall. The “compression sign,” the persistence of the “halo” during compression of the vessel lumen by the ultrasound probe, has high specificity for the diagnosis.¹⁶

Ultrasonography of suspected GCA has yielded sensitivities of 55% to 100% and specificities of 78% to 100%. However, its sensitivity depends on the user’s level of expertise, so it should be done only in medical centers with a high number of GCA cases and with highly experienced sonographers. High-resolution magnetic resonance imaging is an alternative to ultrasonography and has shown similar sensitivity and specificity.³

TREATMENT WITH GLUCOCORTICOIDS

Glucocorticoids remain the standard for treatment of GCA. The therapeutic effect of glucocorticoids in GCA has been established by years of clinical experience, but has never been proven in a placebo-controlled trial. When started appropriately and expeditiously, glucocorticoids produce exquisite resolution of signs and symptoms and prevent the serious complication of vision loss. Rapid resolution of symptoms is so typical of GCA that if the patient’s symptoms persist more than a few days after starting a glucocorticoid, the diagnosis of GCA should be reconsidered.

In a retrospective study of 245 patients with biopsy-proven GCA treated with glucocorticoids, 34 had permanent loss of sight.¹⁷ In 32 (94%) of the 34, the vision loss occurred before glucocorticoids were started. Of the remaining 2 patients, 1 lost vision 8 days into treatment, and the other lost vision 3 years after diagnosis and 1 year after discontinuation of glucocorticoids.

In a series of 144 patients with biopsy-proven GCA, 51 had no vision loss at presentation and no vision loss after starting glucocorticoids, and 93 had vision loss at presentation. In the latter group, symptoms worsened within 5 days of starting glucocorticoids in 9 patients.¹⁸ If vision was intact at the time of presentation, prompt initiation of glucocorticoids reduced the risk of vision loss to less than 1%.

High doses, slowly tapered

The European League Against Rheumatism recommends early initiation of high-dose glucocorticoids for patients with large-vessel vasculitis,¹⁹ and it also recommends glucocorticoids for patients with polymyalgia rheumatica.²⁰ The optimal initial and tapering dosage has never been formally evaluated, but regimens have been devised on the basis of expert opinion.²¹

For patients with GCA who do not have vision loss at the time of diagnosis, the initial dose is prednisone 1 mg/kg or its equivalent daily for 2 to 4 weeks, after which it is tapered.²¹ If the initial dosage is prednisone 60 mg orally daily for 2 to 4 weeks, our practice is to taper it to 50 mg daily for 2 weeks, then 40 mg daily for 2 weeks. Then, it  is decreased by 5 mg every 2 weeks until it is 20 mg daily, and then by 2.5 mg every 2 weeks until it is 10 mg orally daily. Thereafter, the dosage is decreased by 1 mg every 2 to 4 weeks.

For patients with GCA who experience transient vision loss or diplopia at the time of diagnosis, intravenous pulse glucocorticoid therapy should be initiated to reduce the risk of vision loss as rapidly as possible.²² A typical pulse regimen is methylprednisolone 1 g intravenously daily for 3 days. Though not rigorously validated in studies, such an approach is used to avoid vision impairment due to GCA, which is rarely reversible.

 

 

RELAPSE OF DISEASE

Suspect a relapse of GCA if the patient’s initial symptoms recur, if inflammatory markers become elevated, or if classic symptoms of GCA or polymyalgia rheumatica occur. Elevations in inflammatory markers do not definitely indicate a flare of GCA, but they should trigger close monitoring of the patient’s symptoms.

Relapse is treated by increasing the glucocorticoid dosage as appropriate to the nature of the relapse. If vision is affected or the patient has symptoms of GCA, then increments of 30 to 60 mg of prednisone are warranted, whereas if the patient has symptoms of polymyalgia rheumatica, then increments of 5 to 10 mg of prednisone are usually used.

The incidence of relapses of GCA in multiple tertiary care centers has been reported to vary between 34% and 75%.^23,24 Most relapses occur at prednisone dosages of less than 20 mg orally daily and within the first year after diagnosis. The most common symptoms are limb ischemia, jaw claudication, constitutional symptoms, headaches, and polymyalgia rheumatica. In a review of 286 patients,²⁵ 213 (74%) had at least 1 relapse. The first relapse occurred in the first year in 50%, by 2 years in 68%, and by 5 years in 79%.

ADVERSE EFFECTS OF GLUCOCORTICOIDS

In high doses, glucocorticoids have well-known adverse effects. In a population-based study of 120 patients, each patient treated with glucocorticoids experienced at least 1 adverse effect (cataract, fracture, infection, osteonecrosis, diabetes, hypertension, weight gain, capillary fragility, or hair loss).²⁶ The effects were related to aging and cumulative dosage of prednisone but not to the initial dosage.

Glucocorticoids can affect many organs and systems:

• Eyes (cataracts, increased intraocular pressure, exophthalmos)
• Heart (premature atherosclerotic disease, hypertension, fluid retention, hyperlipidemia, arrhythmias)
• Gastrointestinal system (ulcer, gastrointestinal bleeding, gastritis, visceral perforation, hepatic steatosis, acute pancreatitis)
• Bone and muscle (osteopenia, osteoporosis, osteonecrosis, myopathy)
• Brain (mood disorder, psychosis, memory impairment)
• Endocrine system (hyperglycemia, hypothalamic-pituitary-adrenal axis suppression)
• Immune system (immunosuppression, leading to infection and leukocytosis).

Patients receiving a glucocorticoid dose equivalent to 20 mg or more of prednisone daily for 1 month or more who also have another cause of immunocompromise need prophylaxis against Pneumocystis jirovecii pneumonia.²⁷ They should also receive appropriate immunizations before starting glucocorticoids. Live-virus vaccines should not be given to these patients until they have been off glucocorticoids for 1 month.

Glucocorticoids and bone loss

Glucocorticoids are associated with bone loss and fracture, which can occur within the first few months of use and with dosages as low as 2.5 to 7.5 mg orally daily.²⁸ Therefore, glucocorticoid-induced bone loss has to be treated aggressively, particularly in patients who are older and have a history of fragility fracture.

For patients with GCA who need glucocorticoids in doses greater than 5 mg orally daily for more than 3 months, the following measures are advised to decrease the risk of bone loss:

• Weight-bearing exercise
• Smoking cessation
• Moderation in alcohol intake
• Measures to prevent falls²⁹
• Supplementation with 1,200 mg of calcium and 800 IU of vitamin D.³⁰

Pharmacologic therapy should be initiated in men over age 50 who have established osteoporosis and in postmenopausal women with established osteoporosis or osteopenia. For men over age 50 with established osteopenia, risk assessment with the glucocorticoid-corrected FRAX score (www.sheffield.ac.uk/FRAX) should be performed to identify those at high risk in whom pharmacologic therapy is warranted.³¹

Bisphosphonates are the first-line therapy for glucocorticoid-induced osteoporosis.³²

Teriparatide is the second-line therapy and is used in patients who cannot tolerate bis­phosphonates or other osteoporosis therapies, and in those who have severe osteoporosis, with T scores of –3.5 and below if they have not had a fracture, and –2.5 and below if they have had a fragility fracture.³³

Denosumab, a monoclonal antibody to an osteoclast differentiating factor, may be beneficial for some patients with glucocorticoid-induced osteoporosis.³⁴

To assess the efficacy of therapy, measuring bone mineral density at baseline and at 1 year of therapy is recommended. If density is stable or improved, then repeating the measurement at 2- to 3-year intervals is suggested.

 

 

TOCILIZUMAB: A STEROID-SPARING MEDICATION

Due to the adverse effects of long-term use of glucocorticoids and high rates of relapse, there is a pressing need for medications that are more efficacious and less toxic to treat GCA.

The European League Against Rheumatism, in its 2009 management guidelines for large-vessel vasculitis, recommend using an adjunctive immunosuppressant agent.¹⁹ In the case of GCA, they recommend using methotrexate 10 to 15 mg/week, which has shown modest evidence of reducing the relapse rate and lowering the cumulative doses of glucocorticoids needed.^35,36

Studies of tumor necrosis factor inhibitors and abatacept have not yielded significant reductions in the relapse rate or decreased cumulative doses of prednisone.^37,38

Advances in treatment for GCA have stagnated, but recent trials^39,40 have evaluated the IL-6 receptor alpha inhibitor tocilizumab, given the central role of IL-6 in the pathogenesis of GCA. Case reports have revealed rapid induction and maintenance of remission in GCA using tocilizumab.^41,42

Villiger et al³⁹ performed a randomized, placebo-controlled trial to study the efficacy and safety of tocilizumab in induction and maintenance of disease remission in 30 patients with newly diagnosed GCA. The primary outcome, complete remission at 12 weeks, was achieved in 85% of patients who received tocilizumab plus tapered prednisolone, compared with 40% of patients who received placebo plus tapering prednisolone. The tocilizumab group also had favorable results in secondary outcomes including relapse-free survival at 52 weeks, time to first relapse after induction of remission, and cumulative dose of prednisolone.

The GiACTA trial. Stone et al⁴⁰ studied the effect of tocilizumab on rates of relapse during glucocorticoid tapering in 251 GCA patients over the course of 52 weeks. Patients were randomized in a 2:1:1:1 ratio to 4 treatment groups:

• Tocilizumab weekly plus prednisone, with prednisone tapered over 26 weeks
• Tocilizumab every other week plus prednisone tapered over 26 weeks
• Placebo plus prednisone tapered over 26 weeks
• Placebo plus prednisone tapered over 52 weeks.

The primary outcome was the rate of sustained glucocorticoid-free remission at 52 weeks. Secondary outcomes included the remission rate, the cumulative glucocorticoid dose, and safety measures. At 52 weeks, the rates of sustained remission were:

• 56% with tocilizumab weekly
• 53% with tocilizumab every other week
• 14% with placebo plus 26-week prednisone taper
• 18% with placebo plus 52-week taper.

Differences between the active treatment groups and the placebo groups were statistically significant (P < .001).

The cumulative dose of prednisone in tocilizumab recipients was significantly less than in placebo recipients. Rates of adverse events were similar. Ultimately, the study showed that tocilizumab, either weekly or every other week, was more effective than prednisone alone at sustaining glucocorticoid-free remission in patients with GCA.

However, the study also raised questions about tocilizumab’s toxic effect profile and its  long-term efficacy, as well as who are the optimal candidates for this therapy. Data on long-term use of tocilizumab are primarily taken from its use in rheumatoid arthritis.⁴³ As of this writing, Stone et al are conducting an open-label trial to help provide long-term safety and efficacy data in patients with GCA. In the meantime, we must extrapolate data from the long-term use of tocilizumab in rheumatoid arthritis.

Tocilizumab and lower gastrointestinal tract perforation

One of the major adverse effects of long-term use of tocilizumab is lower gastrointestinal tract perforation.

Xie et al,⁴⁴ in 2016, reported that the risk of perforation in patients on tocilizumab for rheumatoid arthritis was more than 2 times higher than in patients taking a tumor necrosis factor inhibitor. However, the absolute rates of perforation were low overall,  roughly 1 to 3 per 1,000 patient-years in the tocilizumab group. Risk factors for perforation included older age, history of diverticulitis or other gastrointestinal tract condition, and prednisone doses of 7.5 mg or more a day.

Does tocilizumab prevent blindness?

Another consideration is that tocilizumab may not prevent optic neuropathy. In the GiACTA trial, 1 patient in the group receiving tocilizumab every other week developed optic neuropathy.⁴⁰ Prednisone had been completely tapered off at the time, and the condition resolved when glucocorticoids were restarted. Thus, it is unknown if tocilizumab would be effective on its own without concomitant use of glucocorticoids.

Vision loss is one of the most severe complications of GCA, and it is still unclear whether tocilizumab can prevent vision loss in GCA. Also, we still have no data on the effect of tocilizumab on histopathologic findings, and whether biopsy yield diminishes over time. We hope future studies will help guide us in this regard.

No guidelines on tocilizumab yet

Clinical guidelines on the appropriate use of tocilizumab in GCA are lacking. The American College of Rheumatology and the European League Against Rheumatism have yet to publish updated guidelines with comments on use of tocilizumab. Therefore, it is unclear if tocilizumab is a first-line treatment in GCA, as its efficacy alone without glucocorticoids and its long-term safety in GCA patients have not been studied.

Treatment with tocilizumab should be individualized; it should be considered in patients who have had adverse effects from glucocorticoids, and in patients who experience a flare or cannot have their glucocorticoid dose lowered to an appropriate range.

The optimal duration of tocilizumab therapy is also unknown. However, using the GiACTA study as a rough guide, we try to limit its use to 1 year until additional data are available.

Patients on IL-6 inhibition may have suppressed C-reactive protein regardless of disease activity.⁴³ Therefore, this laboratory value may not be reliable in determining active disease in patients on tocilizumab.

The GiACTA trial has shown an impressive improvement in the relapse-free remission period in patients with GCA taking tocilizumab. However, much work needs to be done to define the safety of this medication and determine which patients should be started on it. In the meantime, we recommend starting high-dose glucocorticoid therapy as soon as the diagnosis of GCA is suspected. In patients who do not tolerate glucocorticoids or whose disease flares during glucocorticoid taper, we recommend starting treatment with tocilizumab either once a week or every other week for at least 1 year.

Giant cell arteritis (GCA) is a systemic vasculitis involving medium-sized and large arteries, most commonly the temporal, ophthalmic, occipital, vertebral, posterior ciliary, and proximal vertebral arteries. Moreover, involvement of the ophthalmic artery and its branches results in loss of vision. GCA can also involve the aorta and its proximal branches, especially in the upper extremities.

GCA is the most common systemic vasculitis in adults. It occurs almost exclusively in patients over age 50 and affects women more than men. It is most frequent in populations of northern European ancestry, especially Scandinavian. In a retrospective cohort study in Norway, the average annual cumulative incidence rate of GCA was 16.7 per 100,000 people over age 50.¹ Risk factors include older age, history of smoking, current smoking, early menopause, and, possibly, stress-related disorders.²

PATHOGENESIS IS NOT COMPLETELY UNDERSTOOD

The pathogenesis of GCA is not completely understood, but there is evidence of immune activation in the arterial wall leading to activation of macrophages and formation of multinucleated giant cells (which may not always be present in biopsies).

The most relevant cytokines in the ongoing pathogenesis are still being defined, but the presence of interferon gamma and interleukin 6 (IL-6) seem to be critical for the expression of the disease. The primary immunogenic triggers for the elaboration of these cytokines and the arteritis remain elusive.

A SPECTRUM OF PRESENTATIONS

The initial symptoms of GCA may be vague, such as malaise, fever, and night sweats, and are likely due to systemic inflammation. Features of vascular involvement include headache, scalp tenderness, and jaw claudication (cramping pain in the jaw while chewing).

A less common but serious feature associated with GCA is partial or complete vision loss affecting 1 or both eyes.³ Some patients suddenly go completely blind without any visual prodrome.

Overlapping GCA phenotypes exist, with a spectrum of presentations that include classic cranial arteritis, extracranial GCA (also called large-vessel GCA), and polymyalgia rheumatica.²

Cranial GCA, the best-characterized clinical presentation, causes symptoms such as headache or signs such as tenderness of the temporal artery. On examination, the temporal arteries may be tender or nodular, and the pulses may be felt above the zygomatic arch, above and in front of the tragus of the ear. About two-thirds of patients with cranial GCA present with new-onset headache, most often in the temporal area, but possibly anywhere throughout the head.

Visual disturbance, jaw claudication, and tongue pain are less common but, if present, increase the likelihood of this diagnosis.²

Large-vessel involvement in GCA is common and refers to involvement of the aorta and its proximal branches. Imaging methods used in diagnosing large-vessel GCA include color Doppler ultrasonography, computed tomography with angiography, magnetic resonance imaging with angiography, and positron emission tomography. In some centers, such imaging is performed in all patients diagnosed with GCA to survey for large-vessel involvement.

Depending on the imaging study, large-vessel involvement has been found in 30% to 80% of cases of GCA.^4,5 It is often associated with nonspecific symptoms such as fever, weight loss, chills, and malaise, but it can also cause more specific symptoms such as unilateral extremity claudication. In contrast to patients with cranial GCA, patients with large-vessel GCA were younger at onset, less likely to have headaches, and more likely to have arm claudication at presentation.⁶ Aortitis of the ascending aorta can occur with a histopathologic pattern of GCA but without the clinical stigmata of GCA.

The finding of aortitis should prompt the clinician to question the patient about other symptoms of GCA and to order imaging of the whole vascular tree. Ultrasonography and biopsy of the temporal arteries can be considered. Whether idiopathic aortitis is part of the GCA spectrum remains to be seen.

Laboratory tests often show anemia, leukocytosis, and thrombocytosis. Acute-phase reactants such as C-reactive protein and the erythrocyte sedimentation rate are often elevated. The sedimentation rate often exceeds 50 mm/hour and sometimes 100 mm/hour.

In 2 retrospective studies, the number of patients with GCA whose sedimentation rate was less than 50 mm/hour ranged between 5% and 11%.^7,8 However, a small percentage of patients with GCA have normal inflammatory markers. Therefore, if the suspicion for GCA is high, treatment should be started and biopsy pursued.⁹ In patients with paraproteinemia or other causes of a spuriously elevated or low erythrocyte sedimentation rate, C-reactive protein is a more reliable test.

Polymyalgia rheumatica is another rheumatologic condition that can occur independently or in conjunction with GCA. It is characterized by stiffness and pain in the proximal joints such as the hips and shoulders, typically worse in the morning and better with activity. Although the patient may subjectively feel weak, a close neurologic examination will reveal normal muscle strength.

Polymyalgia rheumatica is observed in 40% to 60% of patients with GCA at the time of diagnosis; 16% to 21% of patients with polymyalgia rheumatica may develop GCA, especially if untreated.^2,10

Differential diagnosis

Other vasculitides (eg, Takayasu arteritis) can also present with unexplained fever, anemia, and constitutional symptoms.

Infection should be considered if fever is present. An infectious disease accompanied by fever, headache, and elevated inflammatory markers can mimic GCA.

Nonarteritic anterior ischemic optic neuropathy can present with sudden vision loss, prompting concern for underlying GCA. Risk factors include hypertension and diabetes mellitus; other features of GCA, including elevated inflammatory markers, are generally absent.

 

 

TEMPORAL ARTERY BIOPSY: THE GOLD STANDARD FOR DIAGNOSIS

Temporal artery biopsy remains the standard to confirm the diagnosis. However, because inflammation in the temporal arteries can affect some segments but not others, biopsy results on conventional hematoxylin and eosin staining can be falsely negative in patients with GCA. In one study,¹¹ the mean sensitivity of unilateral temporal artery biopsy was 86.9%.

Typical positive histologic findings are inflammation with panarteritis, CD4-positive lymphocytes, macrophages, giant cells, and fragmentation of the internal elastic lamina.¹²

When GCA is suspected, treatment with glucocorticoids should be started immediately and biopsy performed as soon as possible. Delaying biopsy for 14 days or more may not affect the accuracy of biopsy study.¹³ Treatment should never be withheld while awaiting the results of biopsy study.

Biopsy is usually performed unilaterally, on the same side as the symptoms or abnormal findings on examination. Bilateral temporal artery biopsy is also performed and compared with unilateral biopsy; this approach increases the diagnostic yield by about 5%.¹⁴

IMAGING

In patients with suspected GCA, imaging is recommended early to complement the clinical criteria for the diagnosis of GCA.¹⁵ Positron emission tomography, computed tomography angiography, magnetic resonance angiography, or Doppler ultrasonography can reveal inflammation of the arteries in the proximal upper or lower limbs or the aorta.²

In patients with suspected cranial GCA, ultrasonography of the temporal and axillary arteries is recommended first. If ultrasonography is not available or is inconclusive, high-resolution magnetic resonance imaging of the cranial arteries can be used as an alternative. Computed tomography and positron emission tomography of the cranial arteries are not recommended.

In patients with suspected large-vessel GCA, ultrasonography, positron emission tomography, computed tomography, and magnetic resonance imaging may be used to screen for vessel wall inflammation, edema, and luminal narrowing in extracranial arteries. Ultrasonography is of limited value in assessing aortitis.

Color duplex ultrasonography can be applied to assess for vascular inflammation of the temporal or large arteries. The typical finding of the “halo” sign, a hypoechoic ring around the arterial lumen, represents the inflammation-induced thickening of the arterial wall. The “compression sign,” the persistence of the “halo” during compression of the vessel lumen by the ultrasound probe, has high specificity for the diagnosis.¹⁶

Ultrasonography of suspected GCA has yielded sensitivities of 55% to 100% and specificities of 78% to 100%. However, its sensitivity depends on the user’s level of expertise, so it should be done only in medical centers with a high number of GCA cases and with highly experienced sonographers. High-resolution magnetic resonance imaging is an alternative to ultrasonography and has shown similar sensitivity and specificity.³

TREATMENT WITH GLUCOCORTICOIDS

Glucocorticoids remain the standard for treatment of GCA. The therapeutic effect of glucocorticoids in GCA has been established by years of clinical experience, but has never been proven in a placebo-controlled trial. When started appropriately and expeditiously, glucocorticoids produce exquisite resolution of signs and symptoms and prevent the serious complication of vision loss. Rapid resolution of symptoms is so typical of GCA that if the patient’s symptoms persist more than a few days after starting a glucocorticoid, the diagnosis of GCA should be reconsidered.

In a retrospective study of 245 patients with biopsy-proven GCA treated with glucocorticoids, 34 had permanent loss of sight.¹⁷ In 32 (94%) of the 34, the vision loss occurred before glucocorticoids were started. Of the remaining 2 patients, 1 lost vision 8 days into treatment, and the other lost vision 3 years after diagnosis and 1 year after discontinuation of glucocorticoids.

In a series of 144 patients with biopsy-proven GCA, 51 had no vision loss at presentation and no vision loss after starting glucocorticoids, and 93 had vision loss at presentation. In the latter group, symptoms worsened within 5 days of starting glucocorticoids in 9 patients.¹⁸ If vision was intact at the time of presentation, prompt initiation of glucocorticoids reduced the risk of vision loss to less than 1%.

High doses, slowly tapered

The European League Against Rheumatism recommends early initiation of high-dose glucocorticoids for patients with large-vessel vasculitis,¹⁹ and it also recommends glucocorticoids for patients with polymyalgia rheumatica.²⁰ The optimal initial and tapering dosage has never been formally evaluated, but regimens have been devised on the basis of expert opinion.²¹

For patients with GCA who do not have vision loss at the time of diagnosis, the initial dose is prednisone 1 mg/kg or its equivalent daily for 2 to 4 weeks, after which it is tapered.²¹ If the initial dosage is prednisone 60 mg orally daily for 2 to 4 weeks, our practice is to taper it to 50 mg daily for 2 weeks, then 40 mg daily for 2 weeks. Then, it  is decreased by 5 mg every 2 weeks until it is 20 mg daily, and then by 2.5 mg every 2 weeks until it is 10 mg orally daily. Thereafter, the dosage is decreased by 1 mg every 2 to 4 weeks.

For patients with GCA who experience transient vision loss or diplopia at the time of diagnosis, intravenous pulse glucocorticoid therapy should be initiated to reduce the risk of vision loss as rapidly as possible.²² A typical pulse regimen is methylprednisolone 1 g intravenously daily for 3 days. Though not rigorously validated in studies, such an approach is used to avoid vision impairment due to GCA, which is rarely reversible.

 

 

RELAPSE OF DISEASE

Suspect a relapse of GCA if the patient’s initial symptoms recur, if inflammatory markers become elevated, or if classic symptoms of GCA or polymyalgia rheumatica occur. Elevations in inflammatory markers do not definitely indicate a flare of GCA, but they should trigger close monitoring of the patient’s symptoms.

Relapse is treated by increasing the glucocorticoid dosage as appropriate to the nature of the relapse. If vision is affected or the patient has symptoms of GCA, then increments of 30 to 60 mg of prednisone are warranted, whereas if the patient has symptoms of polymyalgia rheumatica, then increments of 5 to 10 mg of prednisone are usually used.

The incidence of relapses of GCA in multiple tertiary care centers has been reported to vary between 34% and 75%.^23,24 Most relapses occur at prednisone dosages of less than 20 mg orally daily and within the first year after diagnosis. The most common symptoms are limb ischemia, jaw claudication, constitutional symptoms, headaches, and polymyalgia rheumatica. In a review of 286 patients,²⁵ 213 (74%) had at least 1 relapse. The first relapse occurred in the first year in 50%, by 2 years in 68%, and by 5 years in 79%.

ADVERSE EFFECTS OF GLUCOCORTICOIDS

In high doses, glucocorticoids have well-known adverse effects. In a population-based study of 120 patients, each patient treated with glucocorticoids experienced at least 1 adverse effect (cataract, fracture, infection, osteonecrosis, diabetes, hypertension, weight gain, capillary fragility, or hair loss).²⁶ The effects were related to aging and cumulative dosage of prednisone but not to the initial dosage.

Glucocorticoids can affect many organs and systems:

• Eyes (cataracts, increased intraocular pressure, exophthalmos)
• Heart (premature atherosclerotic disease, hypertension, fluid retention, hyperlipidemia, arrhythmias)
• Gastrointestinal system (ulcer, gastrointestinal bleeding, gastritis, visceral perforation, hepatic steatosis, acute pancreatitis)
• Bone and muscle (osteopenia, osteoporosis, osteonecrosis, myopathy)
• Brain (mood disorder, psychosis, memory impairment)
• Endocrine system (hyperglycemia, hypothalamic-pituitary-adrenal axis suppression)
• Immune system (immunosuppression, leading to infection and leukocytosis).

Patients receiving a glucocorticoid dose equivalent to 20 mg or more of prednisone daily for 1 month or more who also have another cause of immunocompromise need prophylaxis against Pneumocystis jirovecii pneumonia.²⁷ They should also receive appropriate immunizations before starting glucocorticoids. Live-virus vaccines should not be given to these patients until they have been off glucocorticoids for 1 month.

Glucocorticoids and bone loss

Glucocorticoids are associated with bone loss and fracture, which can occur within the first few months of use and with dosages as low as 2.5 to 7.5 mg orally daily.²⁸ Therefore, glucocorticoid-induced bone loss has to be treated aggressively, particularly in patients who are older and have a history of fragility fracture.

For patients with GCA who need glucocorticoids in doses greater than 5 mg orally daily for more than 3 months, the following measures are advised to decrease the risk of bone loss:

• Weight-bearing exercise
• Smoking cessation
• Moderation in alcohol intake
• Measures to prevent falls²⁹
• Supplementation with 1,200 mg of calcium and 800 IU of vitamin D.³⁰

Pharmacologic therapy should be initiated in men over age 50 who have established osteoporosis and in postmenopausal women with established osteoporosis or osteopenia. For men over age 50 with established osteopenia, risk assessment with the glucocorticoid-corrected FRAX score (www.sheffield.ac.uk/FRAX) should be performed to identify those at high risk in whom pharmacologic therapy is warranted.³¹

Bisphosphonates are the first-line therapy for glucocorticoid-induced osteoporosis.³²

Teriparatide is the second-line therapy and is used in patients who cannot tolerate bis­phosphonates or other osteoporosis therapies, and in those who have severe osteoporosis, with T scores of –3.5 and below if they have not had a fracture, and –2.5 and below if they have had a fragility fracture.³³

Denosumab, a monoclonal antibody to an osteoclast differentiating factor, may be beneficial for some patients with glucocorticoid-induced osteoporosis.³⁴

To assess the efficacy of therapy, measuring bone mineral density at baseline and at 1 year of therapy is recommended. If density is stable or improved, then repeating the measurement at 2- to 3-year intervals is suggested.

 

 

TOCILIZUMAB: A STEROID-SPARING MEDICATION

Due to the adverse effects of long-term use of glucocorticoids and high rates of relapse, there is a pressing need for medications that are more efficacious and less toxic to treat GCA.

The European League Against Rheumatism, in its 2009 management guidelines for large-vessel vasculitis, recommend using an adjunctive immunosuppressant agent.¹⁹ In the case of GCA, they recommend using methotrexate 10 to 15 mg/week, which has shown modest evidence of reducing the relapse rate and lowering the cumulative doses of glucocorticoids needed.^35,36

Studies of tumor necrosis factor inhibitors and abatacept have not yielded significant reductions in the relapse rate or decreased cumulative doses of prednisone.^37,38

Advances in treatment for GCA have stagnated, but recent trials^39,40 have evaluated the IL-6 receptor alpha inhibitor tocilizumab, given the central role of IL-6 in the pathogenesis of GCA. Case reports have revealed rapid induction and maintenance of remission in GCA using tocilizumab.^41,42

Villiger et al³⁹ performed a randomized, placebo-controlled trial to study the efficacy and safety of tocilizumab in induction and maintenance of disease remission in 30 patients with newly diagnosed GCA. The primary outcome, complete remission at 12 weeks, was achieved in 85% of patients who received tocilizumab plus tapered prednisolone, compared with 40% of patients who received placebo plus tapering prednisolone. The tocilizumab group also had favorable results in secondary outcomes including relapse-free survival at 52 weeks, time to first relapse after induction of remission, and cumulative dose of prednisolone.

The GiACTA trial. Stone et al⁴⁰ studied the effect of tocilizumab on rates of relapse during glucocorticoid tapering in 251 GCA patients over the course of 52 weeks. Patients were randomized in a 2:1:1:1 ratio to 4 treatment groups:

• Tocilizumab weekly plus prednisone, with prednisone tapered over 26 weeks
• Tocilizumab every other week plus prednisone tapered over 26 weeks
• Placebo plus prednisone tapered over 26 weeks
• Placebo plus prednisone tapered over 52 weeks.

The primary outcome was the rate of sustained glucocorticoid-free remission at 52 weeks. Secondary outcomes included the remission rate, the cumulative glucocorticoid dose, and safety measures. At 52 weeks, the rates of sustained remission were:

• 56% with tocilizumab weekly
• 53% with tocilizumab every other week
• 14% with placebo plus 26-week prednisone taper
• 18% with placebo plus 52-week taper.

Differences between the active treatment groups and the placebo groups were statistically significant (P < .001).

The cumulative dose of prednisone in tocilizumab recipients was significantly less than in placebo recipients. Rates of adverse events were similar. Ultimately, the study showed that tocilizumab, either weekly or every other week, was more effective than prednisone alone at sustaining glucocorticoid-free remission in patients with GCA.

However, the study also raised questions about tocilizumab’s toxic effect profile and its  long-term efficacy, as well as who are the optimal candidates for this therapy. Data on long-term use of tocilizumab are primarily taken from its use in rheumatoid arthritis.⁴³ As of this writing, Stone et al are conducting an open-label trial to help provide long-term safety and efficacy data in patients with GCA. In the meantime, we must extrapolate data from the long-term use of tocilizumab in rheumatoid arthritis.

Tocilizumab and lower gastrointestinal tract perforation

One of the major adverse effects of long-term use of tocilizumab is lower gastrointestinal tract perforation.

Xie et al,⁴⁴ in 2016, reported that the risk of perforation in patients on tocilizumab for rheumatoid arthritis was more than 2 times higher than in patients taking a tumor necrosis factor inhibitor. However, the absolute rates of perforation were low overall,  roughly 1 to 3 per 1,000 patient-years in the tocilizumab group. Risk factors for perforation included older age, history of diverticulitis or other gastrointestinal tract condition, and prednisone doses of 7.5 mg or more a day.

Does tocilizumab prevent blindness?

Another consideration is that tocilizumab may not prevent optic neuropathy. In the GiACTA trial, 1 patient in the group receiving tocilizumab every other week developed optic neuropathy.⁴⁰ Prednisone had been completely tapered off at the time, and the condition resolved when glucocorticoids were restarted. Thus, it is unknown if tocilizumab would be effective on its own without concomitant use of glucocorticoids.

Vision loss is one of the most severe complications of GCA, and it is still unclear whether tocilizumab can prevent vision loss in GCA. Also, we still have no data on the effect of tocilizumab on histopathologic findings, and whether biopsy yield diminishes over time. We hope future studies will help guide us in this regard.

No guidelines on tocilizumab yet

Clinical guidelines on the appropriate use of tocilizumab in GCA are lacking. The American College of Rheumatology and the European League Against Rheumatism have yet to publish updated guidelines with comments on use of tocilizumab. Therefore, it is unclear if tocilizumab is a first-line treatment in GCA, as its efficacy alone without glucocorticoids and its long-term safety in GCA patients have not been studied.

Treatment with tocilizumab should be individualized; it should be considered in patients who have had adverse effects from glucocorticoids, and in patients who experience a flare or cannot have their glucocorticoid dose lowered to an appropriate range.

The optimal duration of tocilizumab therapy is also unknown. However, using the GiACTA study as a rough guide, we try to limit its use to 1 year until additional data are available.

Patients on IL-6 inhibition may have suppressed C-reactive protein regardless of disease activity.⁴³ Therefore, this laboratory value may not be reliable in determining active disease in patients on tocilizumab.

The GiACTA trial has shown an impressive improvement in the relapse-free remission period in patients with GCA taking tocilizumab. However, much work needs to be done to define the safety of this medication and determine which patients should be started on it. In the meantime, we recommend starting high-dose glucocorticoid therapy as soon as the diagnosis of GCA is suspected. In patients who do not tolerate glucocorticoids or whose disease flares during glucocorticoid taper, we recommend starting treatment with tocilizumab either once a week or every other week for at least 1 year.

Giant cell arteritis (GCA) is a systemic vasculitis involving medium-sized and large arteries, most commonly the temporal, ophthalmic, occipital, vertebral, posterior ciliary, and proximal vertebral arteries. Moreover, involvement of the ophthalmic artery and its branches results in loss of vision. GCA can also involve the aorta and its proximal branches, especially in the upper extremities.

GCA is the most common systemic vasculitis in adults. It occurs almost exclusively in patients over age 50 and affects women more than men. It is most frequent in populations of northern European ancestry, especially Scandinavian. In a retrospective cohort study in Norway, the average annual cumulative incidence rate of GCA was 16.7 per 100,000 people over age 50.¹ Risk factors include older age, history of smoking, current smoking, early menopause, and, possibly, stress-related disorders.²

PATHOGENESIS IS NOT COMPLETELY UNDERSTOOD

The pathogenesis of GCA is not completely understood, but there is evidence of immune activation in the arterial wall leading to activation of macrophages and formation of multinucleated giant cells (which may not always be present in biopsies).

The most relevant cytokines in the ongoing pathogenesis are still being defined, but the presence of interferon gamma and interleukin 6 (IL-6) seem to be critical for the expression of the disease. The primary immunogenic triggers for the elaboration of these cytokines and the arteritis remain elusive.

A SPECTRUM OF PRESENTATIONS

The initial symptoms of GCA may be vague, such as malaise, fever, and night sweats, and are likely due to systemic inflammation. Features of vascular involvement include headache, scalp tenderness, and jaw claudication (cramping pain in the jaw while chewing).

A less common but serious feature associated with GCA is partial or complete vision loss affecting 1 or both eyes.³ Some patients suddenly go completely blind without any visual prodrome.

Overlapping GCA phenotypes exist, with a spectrum of presentations that include classic cranial arteritis, extracranial GCA (also called large-vessel GCA), and polymyalgia rheumatica.²

Cranial GCA, the best-characterized clinical presentation, causes symptoms such as headache or signs such as tenderness of the temporal artery. On examination, the temporal arteries may be tender or nodular, and the pulses may be felt above the zygomatic arch, above and in front of the tragus of the ear. About two-thirds of patients with cranial GCA present with new-onset headache, most often in the temporal area, but possibly anywhere throughout the head.

Visual disturbance, jaw claudication, and tongue pain are less common but, if present, increase the likelihood of this diagnosis.²

Large-vessel involvement in GCA is common and refers to involvement of the aorta and its proximal branches. Imaging methods used in diagnosing large-vessel GCA include color Doppler ultrasonography, computed tomography with angiography, magnetic resonance imaging with angiography, and positron emission tomography. In some centers, such imaging is performed in all patients diagnosed with GCA to survey for large-vessel involvement.

Depending on the imaging study, large-vessel involvement has been found in 30% to 80% of cases of GCA.^4,5 It is often associated with nonspecific symptoms such as fever, weight loss, chills, and malaise, but it can also cause more specific symptoms such as unilateral extremity claudication. In contrast to patients with cranial GCA, patients with large-vessel GCA were younger at onset, less likely to have headaches, and more likely to have arm claudication at presentation.⁶ Aortitis of the ascending aorta can occur with a histopathologic pattern of GCA but without the clinical stigmata of GCA.

The finding of aortitis should prompt the clinician to question the patient about other symptoms of GCA and to order imaging of the whole vascular tree. Ultrasonography and biopsy of the temporal arteries can be considered. Whether idiopathic aortitis is part of the GCA spectrum remains to be seen.

Laboratory tests often show anemia, leukocytosis, and thrombocytosis. Acute-phase reactants such as C-reactive protein and the erythrocyte sedimentation rate are often elevated. The sedimentation rate often exceeds 50 mm/hour and sometimes 100 mm/hour.

In 2 retrospective studies, the number of patients with GCA whose sedimentation rate was less than 50 mm/hour ranged between 5% and 11%.^7,8 However, a small percentage of patients with GCA have normal inflammatory markers. Therefore, if the suspicion for GCA is high, treatment should be started and biopsy pursued.⁹ In patients with paraproteinemia or other causes of a spuriously elevated or low erythrocyte sedimentation rate, C-reactive protein is a more reliable test.

Polymyalgia rheumatica is another rheumatologic condition that can occur independently or in conjunction with GCA. It is characterized by stiffness and pain in the proximal joints such as the hips and shoulders, typically worse in the morning and better with activity. Although the patient may subjectively feel weak, a close neurologic examination will reveal normal muscle strength.

Polymyalgia rheumatica is observed in 40% to 60% of patients with GCA at the time of diagnosis; 16% to 21% of patients with polymyalgia rheumatica may develop GCA, especially if untreated.^2,10

Differential diagnosis

Other vasculitides (eg, Takayasu arteritis) can also present with unexplained fever, anemia, and constitutional symptoms.

Infection should be considered if fever is present. An infectious disease accompanied by fever, headache, and elevated inflammatory markers can mimic GCA.

Nonarteritic anterior ischemic optic neuropathy can present with sudden vision loss, prompting concern for underlying GCA. Risk factors include hypertension and diabetes mellitus; other features of GCA, including elevated inflammatory markers, are generally absent.

 

 

TEMPORAL ARTERY BIOPSY: THE GOLD STANDARD FOR DIAGNOSIS

Temporal artery biopsy remains the standard to confirm the diagnosis. However, because inflammation in the temporal arteries can affect some segments but not others, biopsy results on conventional hematoxylin and eosin staining can be falsely negative in patients with GCA. In one study,¹¹ the mean sensitivity of unilateral temporal artery biopsy was 86.9%.

Typical positive histologic findings are inflammation with panarteritis, CD4-positive lymphocytes, macrophages, giant cells, and fragmentation of the internal elastic lamina.¹²

When GCA is suspected, treatment with glucocorticoids should be started immediately and biopsy performed as soon as possible. Delaying biopsy for 14 days or more may not affect the accuracy of biopsy study.¹³ Treatment should never be withheld while awaiting the results of biopsy study.

Biopsy is usually performed unilaterally, on the same side as the symptoms or abnormal findings on examination. Bilateral temporal artery biopsy is also performed and compared with unilateral biopsy; this approach increases the diagnostic yield by about 5%.¹⁴

IMAGING

In patients with suspected GCA, imaging is recommended early to complement the clinical criteria for the diagnosis of GCA.¹⁵ Positron emission tomography, computed tomography angiography, magnetic resonance angiography, or Doppler ultrasonography can reveal inflammation of the arteries in the proximal upper or lower limbs or the aorta.²

In patients with suspected cranial GCA, ultrasonography of the temporal and axillary arteries is recommended first. If ultrasonography is not available or is inconclusive, high-resolution magnetic resonance imaging of the cranial arteries can be used as an alternative. Computed tomography and positron emission tomography of the cranial arteries are not recommended.

In patients with suspected large-vessel GCA, ultrasonography, positron emission tomography, computed tomography, and magnetic resonance imaging may be used to screen for vessel wall inflammation, edema, and luminal narrowing in extracranial arteries. Ultrasonography is of limited value in assessing aortitis.

Color duplex ultrasonography can be applied to assess for vascular inflammation of the temporal or large arteries. The typical finding of the “halo” sign, a hypoechoic ring around the arterial lumen, represents the inflammation-induced thickening of the arterial wall. The “compression sign,” the persistence of the “halo” during compression of the vessel lumen by the ultrasound probe, has high specificity for the diagnosis.¹⁶

Ultrasonography of suspected GCA has yielded sensitivities of 55% to 100% and specificities of 78% to 100%. However, its sensitivity depends on the user’s level of expertise, so it should be done only in medical centers with a high number of GCA cases and with highly experienced sonographers. High-resolution magnetic resonance imaging is an alternative to ultrasonography and has shown similar sensitivity and specificity.³

TREATMENT WITH GLUCOCORTICOIDS

Glucocorticoids remain the standard for treatment of GCA. The therapeutic effect of glucocorticoids in GCA has been established by years of clinical experience, but has never been proven in a placebo-controlled trial. When started appropriately and expeditiously, glucocorticoids produce exquisite resolution of signs and symptoms and prevent the serious complication of vision loss. Rapid resolution of symptoms is so typical of GCA that if the patient’s symptoms persist more than a few days after starting a glucocorticoid, the diagnosis of GCA should be reconsidered.

In a retrospective study of 245 patients with biopsy-proven GCA treated with glucocorticoids, 34 had permanent loss of sight.¹⁷ In 32 (94%) of the 34, the vision loss occurred before glucocorticoids were started. Of the remaining 2 patients, 1 lost vision 8 days into treatment, and the other lost vision 3 years after diagnosis and 1 year after discontinuation of glucocorticoids.

In a series of 144 patients with biopsy-proven GCA, 51 had no vision loss at presentation and no vision loss after starting glucocorticoids, and 93 had vision loss at presentation. In the latter group, symptoms worsened within 5 days of starting glucocorticoids in 9 patients.¹⁸ If vision was intact at the time of presentation, prompt initiation of glucocorticoids reduced the risk of vision loss to less than 1%.

High doses, slowly tapered

The European League Against Rheumatism recommends early initiation of high-dose glucocorticoids for patients with large-vessel vasculitis,¹⁹ and it also recommends glucocorticoids for patients with polymyalgia rheumatica.²⁰ The optimal initial and tapering dosage has never been formally evaluated, but regimens have been devised on the basis of expert opinion.²¹

For patients with GCA who do not have vision loss at the time of diagnosis, the initial dose is prednisone 1 mg/kg or its equivalent daily for 2 to 4 weeks, after which it is tapered.²¹ If the initial dosage is prednisone 60 mg orally daily for 2 to 4 weeks, our practice is to taper it to 50 mg daily for 2 weeks, then 40 mg daily for 2 weeks. Then, it  is decreased by 5 mg every 2 weeks until it is 20 mg daily, and then by 2.5 mg every 2 weeks until it is 10 mg orally daily. Thereafter, the dosage is decreased by 1 mg every 2 to 4 weeks.

For patients with GCA who experience transient vision loss or diplopia at the time of diagnosis, intravenous pulse glucocorticoid therapy should be initiated to reduce the risk of vision loss as rapidly as possible.²² A typical pulse regimen is methylprednisolone 1 g intravenously daily for 3 days. Though not rigorously validated in studies, such an approach is used to avoid vision impairment due to GCA, which is rarely reversible.

 

 

RELAPSE OF DISEASE

Suspect a relapse of GCA if the patient’s initial symptoms recur, if inflammatory markers become elevated, or if classic symptoms of GCA or polymyalgia rheumatica occur. Elevations in inflammatory markers do not definitely indicate a flare of GCA, but they should trigger close monitoring of the patient’s symptoms.

Relapse is treated by increasing the glucocorticoid dosage as appropriate to the nature of the relapse. If vision is affected or the patient has symptoms of GCA, then increments of 30 to 60 mg of prednisone are warranted, whereas if the patient has symptoms of polymyalgia rheumatica, then increments of 5 to 10 mg of prednisone are usually used.

The incidence of relapses of GCA in multiple tertiary care centers has been reported to vary between 34% and 75%.^23,24 Most relapses occur at prednisone dosages of less than 20 mg orally daily and within the first year after diagnosis. The most common symptoms are limb ischemia, jaw claudication, constitutional symptoms, headaches, and polymyalgia rheumatica. In a review of 286 patients,²⁵ 213 (74%) had at least 1 relapse. The first relapse occurred in the first year in 50%, by 2 years in 68%, and by 5 years in 79%.

ADVERSE EFFECTS OF GLUCOCORTICOIDS

In high doses, glucocorticoids have well-known adverse effects. In a population-based study of 120 patients, each patient treated with glucocorticoids experienced at least 1 adverse effect (cataract, fracture, infection, osteonecrosis, diabetes, hypertension, weight gain, capillary fragility, or hair loss).²⁶ The effects were related to aging and cumulative dosage of prednisone but not to the initial dosage.

Glucocorticoids can affect many organs and systems:

• Eyes (cataracts, increased intraocular pressure, exophthalmos)
• Heart (premature atherosclerotic disease, hypertension, fluid retention, hyperlipidemia, arrhythmias)
• Gastrointestinal system (ulcer, gastrointestinal bleeding, gastritis, visceral perforation, hepatic steatosis, acute pancreatitis)
• Bone and muscle (osteopenia, osteoporosis, osteonecrosis, myopathy)
• Brain (mood disorder, psychosis, memory impairment)
• Endocrine system (hyperglycemia, hypothalamic-pituitary-adrenal axis suppression)
• Immune system (immunosuppression, leading to infection and leukocytosis).

Patients receiving a glucocorticoid dose equivalent to 20 mg or more of prednisone daily for 1 month or more who also have another cause of immunocompromise need prophylaxis against Pneumocystis jirovecii pneumonia.²⁷ They should also receive appropriate immunizations before starting glucocorticoids. Live-virus vaccines should not be given to these patients until they have been off glucocorticoids for 1 month.

Glucocorticoids and bone loss

Glucocorticoids are associated with bone loss and fracture, which can occur within the first few months of use and with dosages as low as 2.5 to 7.5 mg orally daily.²⁸ Therefore, glucocorticoid-induced bone loss has to be treated aggressively, particularly in patients who are older and have a history of fragility fracture.

For patients with GCA who need glucocorticoids in doses greater than 5 mg orally daily for more than 3 months, the following measures are advised to decrease the risk of bone loss:

• Weight-bearing exercise
• Smoking cessation
• Moderation in alcohol intake
• Measures to prevent falls²⁹
• Supplementation with 1,200 mg of calcium and 800 IU of vitamin D.³⁰

Pharmacologic therapy should be initiated in men over age 50 who have established osteoporosis and in postmenopausal women with established osteoporosis or osteopenia. For men over age 50 with established osteopenia, risk assessment with the glucocorticoid-corrected FRAX score (www.sheffield.ac.uk/FRAX) should be performed to identify those at high risk in whom pharmacologic therapy is warranted.³¹

Bisphosphonates are the first-line therapy for glucocorticoid-induced osteoporosis.³²

Teriparatide is the second-line therapy and is used in patients who cannot tolerate bis­phosphonates or other osteoporosis therapies, and in those who have severe osteoporosis, with T scores of –3.5 and below if they have not had a fracture, and –2.5 and below if they have had a fragility fracture.³³

Denosumab, a monoclonal antibody to an osteoclast differentiating factor, may be beneficial for some patients with glucocorticoid-induced osteoporosis.³⁴

To assess the efficacy of therapy, measuring bone mineral density at baseline and at 1 year of therapy is recommended. If density is stable or improved, then repeating the measurement at 2- to 3-year intervals is suggested.

 

 

TOCILIZUMAB: A STEROID-SPARING MEDICATION

Due to the adverse effects of long-term use of glucocorticoids and high rates of relapse, there is a pressing need for medications that are more efficacious and less toxic to treat GCA.

The European League Against Rheumatism, in its 2009 management guidelines for large-vessel vasculitis, recommend using an adjunctive immunosuppressant agent.¹⁹ In the case of GCA, they recommend using methotrexate 10 to 15 mg/week, which has shown modest evidence of reducing the relapse rate and lowering the cumulative doses of glucocorticoids needed.^35,36

Studies of tumor necrosis factor inhibitors and abatacept have not yielded significant reductions in the relapse rate or decreased cumulative doses of prednisone.^37,38

Advances in treatment for GCA have stagnated, but recent trials^39,40 have evaluated the IL-6 receptor alpha inhibitor tocilizumab, given the central role of IL-6 in the pathogenesis of GCA. Case reports have revealed rapid induction and maintenance of remission in GCA using tocilizumab.^41,42

Villiger et al³⁹ performed a randomized, placebo-controlled trial to study the efficacy and safety of tocilizumab in induction and maintenance of disease remission in 30 patients with newly diagnosed GCA. The primary outcome, complete remission at 12 weeks, was achieved in 85% of patients who received tocilizumab plus tapered prednisolone, compared with 40% of patients who received placebo plus tapering prednisolone. The tocilizumab group also had favorable results in secondary outcomes including relapse-free survival at 52 weeks, time to first relapse after induction of remission, and cumulative dose of prednisolone.

The GiACTA trial. Stone et al⁴⁰ studied the effect of tocilizumab on rates of relapse during glucocorticoid tapering in 251 GCA patients over the course of 52 weeks. Patients were randomized in a 2:1:1:1 ratio to 4 treatment groups:

• Tocilizumab weekly plus prednisone, with prednisone tapered over 26 weeks
• Tocilizumab every other week plus prednisone tapered over 26 weeks
• Placebo plus prednisone tapered over 26 weeks
• Placebo plus prednisone tapered over 52 weeks.

The primary outcome was the rate of sustained glucocorticoid-free remission at 52 weeks. Secondary outcomes included the remission rate, the cumulative glucocorticoid dose, and safety measures. At 52 weeks, the rates of sustained remission were:

• 56% with tocilizumab weekly
• 53% with tocilizumab every other week
• 14% with placebo plus 26-week prednisone taper
• 18% with placebo plus 52-week taper.

Differences between the active treatment groups and the placebo groups were statistically significant (P < .001).

The cumulative dose of prednisone in tocilizumab recipients was significantly less than in placebo recipients. Rates of adverse events were similar. Ultimately, the study showed that tocilizumab, either weekly or every other week, was more effective than prednisone alone at sustaining glucocorticoid-free remission in patients with GCA.

However, the study also raised questions about tocilizumab’s toxic effect profile and its  long-term efficacy, as well as who are the optimal candidates for this therapy. Data on long-term use of tocilizumab are primarily taken from its use in rheumatoid arthritis.⁴³ As of this writing, Stone et al are conducting an open-label trial to help provide long-term safety and efficacy data in patients with GCA. In the meantime, we must extrapolate data from the long-term use of tocilizumab in rheumatoid arthritis.

Tocilizumab and lower gastrointestinal tract perforation

One of the major adverse effects of long-term use of tocilizumab is lower gastrointestinal tract perforation.

Xie et al,⁴⁴ in 2016, reported that the risk of perforation in patients on tocilizumab for rheumatoid arthritis was more than 2 times higher than in patients taking a tumor necrosis factor inhibitor. However, the absolute rates of perforation were low overall,  roughly 1 to 3 per 1,000 patient-years in the tocilizumab group. Risk factors for perforation included older age, history of diverticulitis or other gastrointestinal tract condition, and prednisone doses of 7.5 mg or more a day.

Does tocilizumab prevent blindness?

Another consideration is that tocilizumab may not prevent optic neuropathy. In the GiACTA trial, 1 patient in the group receiving tocilizumab every other week developed optic neuropathy.⁴⁰ Prednisone had been completely tapered off at the time, and the condition resolved when glucocorticoids were restarted. Thus, it is unknown if tocilizumab would be effective on its own without concomitant use of glucocorticoids.

Vision loss is one of the most severe complications of GCA, and it is still unclear whether tocilizumab can prevent vision loss in GCA. Also, we still have no data on the effect of tocilizumab on histopathologic findings, and whether biopsy yield diminishes over time. We hope future studies will help guide us in this regard.

No guidelines on tocilizumab yet

Clinical guidelines on the appropriate use of tocilizumab in GCA are lacking. The American College of Rheumatology and the European League Against Rheumatism have yet to publish updated guidelines with comments on use of tocilizumab. Therefore, it is unclear if tocilizumab is a first-line treatment in GCA, as its efficacy alone without glucocorticoids and its long-term safety in GCA patients have not been studied.

Treatment with tocilizumab should be individualized; it should be considered in patients who have had adverse effects from glucocorticoids, and in patients who experience a flare or cannot have their glucocorticoid dose lowered to an appropriate range.

The optimal duration of tocilizumab therapy is also unknown. However, using the GiACTA study as a rough guide, we try to limit its use to 1 year until additional data are available.

Patients on IL-6 inhibition may have suppressed C-reactive protein regardless of disease activity.⁴³ Therefore, this laboratory value may not be reliable in determining active disease in patients on tocilizumab.

The GiACTA trial has shown an impressive improvement in the relapse-free remission period in patients with GCA taking tocilizumab. However, much work needs to be done to define the safety of this medication and determine which patients should be started on it. In the meantime, we recommend starting high-dose glucocorticoid therapy as soon as the diagnosis of GCA is suspected. In patients who do not tolerate glucocorticoids or whose disease flares during glucocorticoid taper, we recommend starting treatment with tocilizumab either once a week or every other week for at least 1 year.

Factors that change our brains

I greatly enjoyed Dr. Nasrallah’s editorial, “Your patient’s brain is different at every visit” (From the Editor, Current Psychiatry, May 2019, p. 6,8,10). This is my first time writing to Current Psychiatry, and the journal’s focus and articles have been informative and impactful throughout my training and in my current practice.

In reading this editorial, it is clear that a myriad of factors we consider and address with our patients during each visit underly intricate neurobiologic mechanisms and processes that ever deepen our understanding of the brain. In discussing the changes taking place in our patients, I can’t help but wonder what changes are also occurring in our brains (as Dr. Nasrallah noted). What would be the resulting impact of these changes in our next patient interaction and/or subsequent interaction(s) with the same patient? Looking through the editorial’s bullet points, many (if not all) of the factors contributing to brain changes apply equally and naturally to clinicians as well as patients. In this light, the editorial serves not only as a broad guideline for patient psychoeducation but also as a reminder of wellness and well-being for clinicians.

As a “fresh-out-of-training” psychiatrist, I can definitely work on several of the factors, such as diet and exercise. Trainees and residents can be more susceptible to overlook and befall some of these factors and changes, and may already be basing the clinical advice they give to their patients on these same factors and changes. As a child psychiatrist, I value the importance of modeling healthy behaviors for my patients, and their families and with coworkers or colleagues. In accordance with the impact these factors have on our brains, it’s important to emphasize what we can do to further strengthen rapport and therapeutic value through modeling. I strive to model the desired behaviors, attitudes, and dynamics that are the external, observable manifestation or symptomology of what takes place in my brain. To do so, I understand I need to be mindful in proactively managing the contributing factors, such as those listed in Dr. Nasrallah’s editorial. I imagine patients and their families would easily notice if we are in suboptimal physical and/or mental health that results in us not being prompt, fully engaged, or receptive. I believe that attending to these facets during training falls under the umbrella of professionalism. Being a professional in our field often entails practicing what we preach. So, I’m grateful that what we preach is informed by our field’s exciting research, continued advancements, and expertise that benefits our patients and us professionally and personally.

Philip Yen-Tsun Liu, MD
Child and adolescent psychiatrist
innovaTel Telepsychiatry
San Antonio, Texas

Dr. Nasrallah responds

I would like to thank Dr. Liu for his thoughtful response to my editorial. He seems to be very cognizant of the fact that experiential neuroplasticity and brain tissue remodeling occurs in both the patient and physician. I admire his focus on psychoeducation, wellness, and professionalism. He is right that we as psychiatrists (and nurse practitioners) must be role models for our patients in multiple ways, because it may help enhance clinical outcomes and have a positive impact on their brains.

I would also like to point Dr. Liu to the editorial “The most powerful placebo is not a pill” (From the Editor, Current Psychiatry, August 2011, p. 18-19), which I wrote 8 years ago (before he started his residency), about the importance of what we do and say as physicians.

Henry A. Nasrallah, MD
Editor-in-Chief
Sydney W. Souers Endowed Chair
Professor and Chairman
Department of Psychiatry and Behavioral Neuroscience
Saint Louis University School of Medicine
St. Louis, Missouri

 

 

The APA’s stance on neuroimaging

Can anyone in the modern world argue that the brain is irrelevant to psychiatry? Yet surprisingly, in September 2018, the American Psychiatric Association (APA) officially declared that neuroimaging of the brain has no clinical value in psychiatry.¹

Unfortunately, the APA focused almost exclusively on functional magnetic resonance imaging (fMRI) and neglected an extensive library of studies of single-photon emission computed tomography (SPECT) and positron emission tomography (PET). The APA’s position on neuroimaging is as follows^1,2:

1. A neuroimaging finding must have a sensitivity and specificity (S/sp) of no less than 80%.
2. The psychiatric imaging literature does not support using neuroimaging in psychiatric diagnostics or treatment.
3. Neuroimaging has not had a significant impact on the diagnosis and treatment of psychiatric disorders.

The APA set unrealistic standards for biomarkers in a field that lacks pathologic markers of specific disease entities.³ Moreover, numerous widely used tests fall below the APA’s unrealistic S/sp cutoff, including the Hamilton Depression Rating Scale,⁴ Zung Depression Scale,⁵ the clock drawing test,⁶ and even the chest X-ray.³ Curiously, numerous replicated SPECT and PET studies were not included in the APA’s analysis.^1-3 For example, in a study of 196 veterans, posttraumatic stress disorder was distinguished from traumatic brain injury with an S/sp of 0.92/0.85.^7,8 Also, fluorodeoxyglucose (FDG)-PET has an S/sp of 0.84/0.74 in differentiating patients with Alzheimer’s disease from controls, while perfusion SPECT, using multi-detector cameras, has an S/sp of 0.93/0.84.^3,9 Moreover, both FDG-PET and SPECT can differentiate other forms of dementia from Alzheimer’s disease, yielding an additional benefit compared to amyloid imaging alone.^2,9 As President of the International Society of Applied Neuroimaging, I suggest neuroimaging should not be feared. Neuroimaging does not replace the diagnostician; rather, it aids him/her in a complex case.

Theodore A. Henderson, MD, PhD
President
Neuro-Luminance Brain Health Centers, Inc.
Denver, Colorado
Director
The Synaptic Space
Vice President
The Neuro-Laser Foundation
President
International Society of Applied Neuroimaging
Centennial, Colorado

Disclosure
The author has no ownership in, and receives no remuneration from, any neuroimaging company.

References
1. First MB, Drevets WC, Carter C, et al. Clinical applications of neuroimaging in psychiatric disorders. Am J Psychiatry. 2018:175:915-916.
2. First MB, Drevets WC, Carter C, et al. Data supplement for Clinical applications of neuroimaging in psychiatric disorders. Am J Psychiatry. 2018;175(suppl).
3. Henderson TA. Brain SPECT imaging in neuropsychiatric diagnosis and monitoring. EPatient. http://nmpangea.com/2018/10/09/738/. Published 2018. Accessed May 31, 2019.
4. Bagby RM, Ryder AG, Schuller DR, et al. The Hamilton Depression Rating Scale: has the gold standard become a lead weight? Am J Psychiatry. 2004;161(12):2163-2177.
5. Biggs JT, Wylie LT, Ziegler VE. Validity of the Zung Self-rating Depression Scale. Br J Psychiatry. 1978;132:381-385.
6. Seigerschmidt E, Mösch E, Siemen M, et al. The clock drawing test and questionable dementia: reliability and validity. Int J Geriatr Psychiatry. 2002;17(11):1048-1054.
7. Raji CA, Willeumier K, Taylor D, et al. Functional neuroimaging with default mode network regions distinguishes PTSD from TBI in a military veteran population. Brain Imaging Behav. 2015;9(3):527-534.
8. Amen DG, Raji CA, Willeumier K, et al. Functional neuroimaging distinguishes posttraumatic stress disorder from traumatic brain injury in focused and large community datasets. PLoS One. 2015;10(7):e0129659. doi: 10.1371/journal.pone.0129659.
9. Henderson TA. The diagnosis and evaluation of dementia and mild cognitive impairment with emphasis on SPECT perfusion neuroimaging. CNS Spectr. 2012;17(4):176-206.

Factors that change our brains

I greatly enjoyed Dr. Nasrallah’s editorial, “Your patient’s brain is different at every visit” (From the Editor, Current Psychiatry, May 2019, p. 6,8,10). This is my first time writing to Current Psychiatry, and the journal’s focus and articles have been informative and impactful throughout my training and in my current practice.

In reading this editorial, it is clear that a myriad of factors we consider and address with our patients during each visit underly intricate neurobiologic mechanisms and processes that ever deepen our understanding of the brain. In discussing the changes taking place in our patients, I can’t help but wonder what changes are also occurring in our brains (as Dr. Nasrallah noted). What would be the resulting impact of these changes in our next patient interaction and/or subsequent interaction(s) with the same patient? Looking through the editorial’s bullet points, many (if not all) of the factors contributing to brain changes apply equally and naturally to clinicians as well as patients. In this light, the editorial serves not only as a broad guideline for patient psychoeducation but also as a reminder of wellness and well-being for clinicians.

As a “fresh-out-of-training” psychiatrist, I can definitely work on several of the factors, such as diet and exercise. Trainees and residents can be more susceptible to overlook and befall some of these factors and changes, and may already be basing the clinical advice they give to their patients on these same factors and changes. As a child psychiatrist, I value the importance of modeling healthy behaviors for my patients, and their families and with coworkers or colleagues. In accordance with the impact these factors have on our brains, it’s important to emphasize what we can do to further strengthen rapport and therapeutic value through modeling. I strive to model the desired behaviors, attitudes, and dynamics that are the external, observable manifestation or symptomology of what takes place in my brain. To do so, I understand I need to be mindful in proactively managing the contributing factors, such as those listed in Dr. Nasrallah’s editorial. I imagine patients and their families would easily notice if we are in suboptimal physical and/or mental health that results in us not being prompt, fully engaged, or receptive. I believe that attending to these facets during training falls under the umbrella of professionalism. Being a professional in our field often entails practicing what we preach. So, I’m grateful that what we preach is informed by our field’s exciting research, continued advancements, and expertise that benefits our patients and us professionally and personally.

Philip Yen-Tsun Liu, MD
Child and adolescent psychiatrist
innovaTel Telepsychiatry
San Antonio, Texas

Dr. Nasrallah responds

I would like to thank Dr. Liu for his thoughtful response to my editorial. He seems to be very cognizant of the fact that experiential neuroplasticity and brain tissue remodeling occurs in both the patient and physician. I admire his focus on psychoeducation, wellness, and professionalism. He is right that we as psychiatrists (and nurse practitioners) must be role models for our patients in multiple ways, because it may help enhance clinical outcomes and have a positive impact on their brains.

I would also like to point Dr. Liu to the editorial “The most powerful placebo is not a pill” (From the Editor, Current Psychiatry, August 2011, p. 18-19), which I wrote 8 years ago (before he started his residency), about the importance of what we do and say as physicians.

Henry A. Nasrallah, MD
Editor-in-Chief
Sydney W. Souers Endowed Chair
Professor and Chairman
Department of Psychiatry and Behavioral Neuroscience
Saint Louis University School of Medicine
St. Louis, Missouri

 

 

The APA’s stance on neuroimaging

Can anyone in the modern world argue that the brain is irrelevant to psychiatry? Yet surprisingly, in September 2018, the American Psychiatric Association (APA) officially declared that neuroimaging of the brain has no clinical value in psychiatry.¹

Unfortunately, the APA focused almost exclusively on functional magnetic resonance imaging (fMRI) and neglected an extensive library of studies of single-photon emission computed tomography (SPECT) and positron emission tomography (PET). The APA’s position on neuroimaging is as follows^1,2:

1. A neuroimaging finding must have a sensitivity and specificity (S/sp) of no less than 80%.
2. The psychiatric imaging literature does not support using neuroimaging in psychiatric diagnostics or treatment.
3. Neuroimaging has not had a significant impact on the diagnosis and treatment of psychiatric disorders.

The APA set unrealistic standards for biomarkers in a field that lacks pathologic markers of specific disease entities.³ Moreover, numerous widely used tests fall below the APA’s unrealistic S/sp cutoff, including the Hamilton Depression Rating Scale,⁴ Zung Depression Scale,⁵ the clock drawing test,⁶ and even the chest X-ray.³ Curiously, numerous replicated SPECT and PET studies were not included in the APA’s analysis.^1-3 For example, in a study of 196 veterans, posttraumatic stress disorder was distinguished from traumatic brain injury with an S/sp of 0.92/0.85.^7,8 Also, fluorodeoxyglucose (FDG)-PET has an S/sp of 0.84/0.74 in differentiating patients with Alzheimer’s disease from controls, while perfusion SPECT, using multi-detector cameras, has an S/sp of 0.93/0.84.^3,9 Moreover, both FDG-PET and SPECT can differentiate other forms of dementia from Alzheimer’s disease, yielding an additional benefit compared to amyloid imaging alone.^2,9 As President of the International Society of Applied Neuroimaging, I suggest neuroimaging should not be feared. Neuroimaging does not replace the diagnostician; rather, it aids him/her in a complex case.

Theodore A. Henderson, MD, PhD
President
Neuro-Luminance Brain Health Centers, Inc.
Denver, Colorado
Director
The Synaptic Space
Vice President
The Neuro-Laser Foundation
President
International Society of Applied Neuroimaging
Centennial, Colorado

Disclosure
The author has no ownership in, and receives no remuneration from, any neuroimaging company.

References
1. First MB, Drevets WC, Carter C, et al. Clinical applications of neuroimaging in psychiatric disorders. Am J Psychiatry. 2018:175:915-916.
2. First MB, Drevets WC, Carter C, et al. Data supplement for Clinical applications of neuroimaging in psychiatric disorders. Am J Psychiatry. 2018;175(suppl).
3. Henderson TA. Brain SPECT imaging in neuropsychiatric diagnosis and monitoring. EPatient. http://nmpangea.com/2018/10/09/738/. Published 2018. Accessed May 31, 2019.
4. Bagby RM, Ryder AG, Schuller DR, et al. The Hamilton Depression Rating Scale: has the gold standard become a lead weight? Am J Psychiatry. 2004;161(12):2163-2177.
5. Biggs JT, Wylie LT, Ziegler VE. Validity of the Zung Self-rating Depression Scale. Br J Psychiatry. 1978;132:381-385.
6. Seigerschmidt E, Mösch E, Siemen M, et al. The clock drawing test and questionable dementia: reliability and validity. Int J Geriatr Psychiatry. 2002;17(11):1048-1054.
7. Raji CA, Willeumier K, Taylor D, et al. Functional neuroimaging with default mode network regions distinguishes PTSD from TBI in a military veteran population. Brain Imaging Behav. 2015;9(3):527-534.
8. Amen DG, Raji CA, Willeumier K, et al. Functional neuroimaging distinguishes posttraumatic stress disorder from traumatic brain injury in focused and large community datasets. PLoS One. 2015;10(7):e0129659. doi: 10.1371/journal.pone.0129659.
9. Henderson TA. The diagnosis and evaluation of dementia and mild cognitive impairment with emphasis on SPECT perfusion neuroimaging. CNS Spectr. 2012;17(4):176-206.

Factors that change our brains

I greatly enjoyed Dr. Nasrallah’s editorial, “Your patient’s brain is different at every visit” (From the Editor, Current Psychiatry, May 2019, p. 6,8,10). This is my first time writing to Current Psychiatry, and the journal’s focus and articles have been informative and impactful throughout my training and in my current practice.

In reading this editorial, it is clear that a myriad of factors we consider and address with our patients during each visit underly intricate neurobiologic mechanisms and processes that ever deepen our understanding of the brain. In discussing the changes taking place in our patients, I can’t help but wonder what changes are also occurring in our brains (as Dr. Nasrallah noted). What would be the resulting impact of these changes in our next patient interaction and/or subsequent interaction(s) with the same patient? Looking through the editorial’s bullet points, many (if not all) of the factors contributing to brain changes apply equally and naturally to clinicians as well as patients. In this light, the editorial serves not only as a broad guideline for patient psychoeducation but also as a reminder of wellness and well-being for clinicians.

As a “fresh-out-of-training” psychiatrist, I can definitely work on several of the factors, such as diet and exercise. Trainees and residents can be more susceptible to overlook and befall some of these factors and changes, and may already be basing the clinical advice they give to their patients on these same factors and changes. As a child psychiatrist, I value the importance of modeling healthy behaviors for my patients, and their families and with coworkers or colleagues. In accordance with the impact these factors have on our brains, it’s important to emphasize what we can do to further strengthen rapport and therapeutic value through modeling. I strive to model the desired behaviors, attitudes, and dynamics that are the external, observable manifestation or symptomology of what takes place in my brain. To do so, I understand I need to be mindful in proactively managing the contributing factors, such as those listed in Dr. Nasrallah’s editorial. I imagine patients and their families would easily notice if we are in suboptimal physical and/or mental health that results in us not being prompt, fully engaged, or receptive. I believe that attending to these facets during training falls under the umbrella of professionalism. Being a professional in our field often entails practicing what we preach. So, I’m grateful that what we preach is informed by our field’s exciting research, continued advancements, and expertise that benefits our patients and us professionally and personally.

Philip Yen-Tsun Liu, MD
Child and adolescent psychiatrist
innovaTel Telepsychiatry
San Antonio, Texas

Dr. Nasrallah responds

I would like to thank Dr. Liu for his thoughtful response to my editorial. He seems to be very cognizant of the fact that experiential neuroplasticity and brain tissue remodeling occurs in both the patient and physician. I admire his focus on psychoeducation, wellness, and professionalism. He is right that we as psychiatrists (and nurse practitioners) must be role models for our patients in multiple ways, because it may help enhance clinical outcomes and have a positive impact on their brains.

I would also like to point Dr. Liu to the editorial “The most powerful placebo is not a pill” (From the Editor, Current Psychiatry, August 2011, p. 18-19), which I wrote 8 years ago (before he started his residency), about the importance of what we do and say as physicians.

Henry A. Nasrallah, MD
Editor-in-Chief
Sydney W. Souers Endowed Chair
Professor and Chairman
Department of Psychiatry and Behavioral Neuroscience
Saint Louis University School of Medicine
St. Louis, Missouri

 

 

The APA’s stance on neuroimaging

Can anyone in the modern world argue that the brain is irrelevant to psychiatry? Yet surprisingly, in September 2018, the American Psychiatric Association (APA) officially declared that neuroimaging of the brain has no clinical value in psychiatry.¹

Unfortunately, the APA focused almost exclusively on functional magnetic resonance imaging (fMRI) and neglected an extensive library of studies of single-photon emission computed tomography (SPECT) and positron emission tomography (PET). The APA’s position on neuroimaging is as follows^1,2:

1. A neuroimaging finding must have a sensitivity and specificity (S/sp) of no less than 80%.
2. The psychiatric imaging literature does not support using neuroimaging in psychiatric diagnostics or treatment.
3. Neuroimaging has not had a significant impact on the diagnosis and treatment of psychiatric disorders.

The APA set unrealistic standards for biomarkers in a field that lacks pathologic markers of specific disease entities.³ Moreover, numerous widely used tests fall below the APA’s unrealistic S/sp cutoff, including the Hamilton Depression Rating Scale,⁴ Zung Depression Scale,⁵ the clock drawing test,⁶ and even the chest X-ray.³ Curiously, numerous replicated SPECT and PET studies were not included in the APA’s analysis.^1-3 For example, in a study of 196 veterans, posttraumatic stress disorder was distinguished from traumatic brain injury with an S/sp of 0.92/0.85.^7,8 Also, fluorodeoxyglucose (FDG)-PET has an S/sp of 0.84/0.74 in differentiating patients with Alzheimer’s disease from controls, while perfusion SPECT, using multi-detector cameras, has an S/sp of 0.93/0.84.^3,9 Moreover, both FDG-PET and SPECT can differentiate other forms of dementia from Alzheimer’s disease, yielding an additional benefit compared to amyloid imaging alone.^2,9 As President of the International Society of Applied Neuroimaging, I suggest neuroimaging should not be feared. Neuroimaging does not replace the diagnostician; rather, it aids him/her in a complex case.

Theodore A. Henderson, MD, PhD
President
Neuro-Luminance Brain Health Centers, Inc.
Denver, Colorado
Director
The Synaptic Space
Vice President
The Neuro-Laser Foundation
President
International Society of Applied Neuroimaging
Centennial, Colorado

Disclosure
The author has no ownership in, and receives no remuneration from, any neuroimaging company.

References
1. First MB, Drevets WC, Carter C, et al. Clinical applications of neuroimaging in psychiatric disorders. Am J Psychiatry. 2018:175:915-916.
2. First MB, Drevets WC, Carter C, et al. Data supplement for Clinical applications of neuroimaging in psychiatric disorders. Am J Psychiatry. 2018;175(suppl).
3. Henderson TA. Brain SPECT imaging in neuropsychiatric diagnosis and monitoring. EPatient. http://nmpangea.com/2018/10/09/738/. Published 2018. Accessed May 31, 2019.
4. Bagby RM, Ryder AG, Schuller DR, et al. The Hamilton Depression Rating Scale: has the gold standard become a lead weight? Am J Psychiatry. 2004;161(12):2163-2177.
5. Biggs JT, Wylie LT, Ziegler VE. Validity of the Zung Self-rating Depression Scale. Br J Psychiatry. 1978;132:381-385.
6. Seigerschmidt E, Mösch E, Siemen M, et al. The clock drawing test and questionable dementia: reliability and validity. Int J Geriatr Psychiatry. 2002;17(11):1048-1054.
7. Raji CA, Willeumier K, Taylor D, et al. Functional neuroimaging with default mode network regions distinguishes PTSD from TBI in a military veteran population. Brain Imaging Behav. 2015;9(3):527-534.
8. Amen DG, Raji CA, Willeumier K, et al. Functional neuroimaging distinguishes posttraumatic stress disorder from traumatic brain injury in focused and large community datasets. PLoS One. 2015;10(7):e0129659. doi: 10.1371/journal.pone.0129659.
9. Henderson TA. The diagnosis and evaluation of dementia and mild cognitive impairment with emphasis on SPECT perfusion neuroimaging. CNS Spectr. 2012;17(4):176-206.

Dementia is a family of disorders characterized by a decline in multiple cognitive abilities that significantly interferes with an individual’s functioning. An estimated 50 million people are living with a dementia worldwide.¹ Alzheimer’s disease (AD) is the leading cause of dementia, accounting for approximately two-thirds of dementia cases.¹ These numbers are expected to increase dramatically in the upcoming decades.

Sociologist Erving Goffman defined stigma as “an attribute, behaviour, or reputation which is socially discrediting in a particular way: it causes an individual to be mentally classified by others in an undesirable, rejected stereotype rather than in an accepted, normal one.”² Goffman² defined 3 broad categories of stigma: public, self, and courtesy (Table 1²).

Considerable evidence shows that the combined impact of having dementia and the negative response to the diagnosis significantly undermines an individual’s psychosocial well-being and quality of life.³ Persons with dementia (PwD) commonly report a loss of identity and self-worth, and stigma appears to deepen this distress.³ Stigma also negatively affects individuals associated with PwD, including family members and professionals. In this article, we discuss the impact of dementia-related stigma, and steps you can take to address it, including implementing person-centered clinical practices, promoting anti-stigma messaging campaigns, and advocating for public policy action to improve the lives of PwD and their families.

A pervasive problem

Although the Alzheimer’s Society International and the World Health Organi­zation acknowledge that stigma has a central role in defining the experience of AD, how stigma may present, how clinicians and researchers can recognize and measure stigma, and how to best combat it have been understudied.^3-5 A recent systematic literature review examined worldwide evidence on dementia-related stigma over the past decade.⁶ Hermann et al⁶ found that health care providers and the general public may hold stigmatizing attitudes toward PwD, and that stigma may be particularly harsh among racial and ethnic minorities, although the literature is scarce in this area. Cultural factors may also worsen stigma, and stigma may be associated with reduced awareness of dementia services and reduced help-seeking among minority groups.^7,8 Studies show that stigmatizing attitudes are more pronounced in people with limited knowledge of dementia, in those with little contact with PwD, in men, in younger individuals, and in the context of cultural interpretations of dementia.⁶ Health care providers can also sometimes contribute to the perpetuation of stigma.⁶

In terms of standardized scales or instruments for evaluating dementia-related stigma, there is no uniformly accepted “gold standard” measure, which makes it difficult to compare studies.⁶ In order to effectively study efforts to reduce stigma, researchers need to identify and establish a consensus on rating scales for evaluating stigma among PwD, caregivers, and the general public. Three instruments that may be used for this purpose are the Family Stigma in Alzheimer’s Disease Scale (FS-ADS),⁹ the Stigma Scale for Chronic Illness (SSCI),¹⁰ and the Perceptions Regarding Investigational Screening for Memory in Primary Care (PRISM-PC).¹¹

The detrimental effects of stigma

Burgener et al¹² reported that personal stigma impacted functioning and quality of life in PwD. Higher levels of stigma were associated with higher anxiety, depression, and behavioral symptoms and lower self-esteem, social support, participation in activities, personal control, and physical health.¹² Personal characteristics that may affect stigma include gender, location (rural vs urban), ethnicity, education level, and living arrangements (alone vs with family).¹²

In a subset of PwD with early-stage memory loss (n = 22), Burgener and Buckwalter¹³ found that 42% of participants were reluctant to reveal their diagnosis to others, with some fearing they would no longer be allowed to live alone and would be “sent to a facility.” In addition, 46% indicated they did not want “to be talked about like they were not there.” More than 50% of participants reported changes in their social network after receiving the diagnosis, including reducing activities and limiting types of contacts (ie, telephone only) or interacting only when “people come to me.” Participants were most comfortable with good friends “who understand” and persons within their faith communities. When asked about how they were treated by family members, >50% of participants described being treated differently, including loss of financial independence, more limited contact, and being “treated like a baby” by their children, who in general were uncomfortable talking about the diagnosis.

Continue to: In a recent study...

In a recent study by Harper et al,¹⁴ stigma was prevalent in the experience of PwD. One participant disclosed:

“I think there is [are] people I know who don’t ask me to go places or do things ’cause I have a dementia…I think lots of people don’t know what dementia is and I think it scares them ’cause they think of it as crazy. It hurts…”

Another participant said:

“I have had friends for over thirty years. They have turned their backs on me…we used to go for walks and they would phone me and go for coffee. Now I don’t hear from any of them…those aren’t true friends…true friends will stand behind you, not in front of you. That’s why I am not happy.”

Overall, quantitative and qualitative findings indicate multiple, detrimental effects of personal stigma on PwD. These effects fit well with measures of self-stigma, including social rejection (eg, being treated differently, participating in fewer activities, and having fewer friends), internalized shame (eg, being treated like a child, having fewer responsibilities, others acting as if dementia is “contagious”), and social isolation (eg, being less outgoing, feeling more comfortable in small groups, having limited social contacts).¹⁵

Continue to: Receiving a diagnosis of dementia...

Receiving a diagnosis of dementia presents patients and their families with psychological and social challenges.¹⁶ Many of these challenges are the consequence of stigma. A broad range of efforts are underway worldwide to reduce dementia-related stigma. These efforts include programs to promote public awareness and education, campaigns to develop inclusive social policies, and skills-based training initiatives to promote delivery of patient-centered care by clinicians and educators.^3,17,18 Many of these efforts share a common focus on promoting the “dignity” and “personhood” of PwD in order to disrupt stereotypes or fixed, oversimplified beliefs associated with dementia.

Implementing person-centered clinical care

In clinical practice, direct discussion that encourages reflection and the use of effective and sensitive communication can help to limit passing on stigmatizing beliefs and to reduce negative stereotypes associated with the disease. Health care communications that call attention to stereotypes may allow PwD to identify stereotypes as well as inaccuracies in those stereotypes. Interventions that validate the value of diversity can help PwD accept the ways in which they may not conform to social norms. This could include language such as “There is no one way to have Alzheimer’s disease. A person’s experience can differ from what others might experience or expect, and that’s okay.” In addition, the use of language that is accurate, respectful, inclusive, and empowering can support PwD and their caregivers.^19,20 For example, referring to PwD as “individuals living with dementia” rather than “those who are demented” conveys respect and appreciation for personhood. Other clinicians have provided additional practical suggestions.²¹

Anti-stigma messaging campaigns

The mass media is a common source of stereotypes about AD and other dementias. They typically present a “worst-case” scenario that promotes ageism, gerontophobia, and negative emotions, which may worsen stigma and discrimination towards PwD and the people who care for them. However, public messaging campaigns are emerging to counter negative messages and stereotypes in the mass media. Projects such as Typical Day, People with Dementia, and other online anti-stigma messaging campaigns allow a broad audience to gain a more nuanced understanding of the lives of PwD and their caregivers. These projects are rich resources that offer education and personal stories that can counter common stereotypes about dementia.

Typical Day is a photography project developed and maintained by clinicians and researchers at the University of Pennsylvania. Since early 2017, the project has provided a forum for individuals with mild cognitive impairment or dementia to document their lives and show what it means to them to live with dementia. Participants in the project photo-document the people, places, and objects that define their daily lives. They review and explain these photos with researchers at Penn Memory Center, who help them tell their stories. The participants’ stories, the photos they capture, and their portraits are available at www.mytypicalday.org.

People of Dementia. Storytelling is a powerful way to raise awareness of and reduce the stigma associated with dementia. For PwD, telling their stories can be an effective and therapeutic way to communicate their emotions and deliver an important message. In the blog People of Dementia (www.peopleofdementia.com),^22,23 PwD highlight who they were before the disease and how things have changed, with family members highlighting the challenges of caring for a person with dementia.

Continue to: The common thread is...

The common thread is the enduring “person” behind the exterior that is obscured by dementia. By allowing the audience to form a connection with who the individual was prior to the disease, and understanding the changes that have come as a result of dementia to both PwD and their support network, readers gain a greater appreciation of those affected by dementia. Between May 1, 2017 and May 31, 2019, the blog had more than 3,860 visitors. In an accompanying online survey (N = 57), 79% of respondents agreed/strongly agreed that after visiting the People of Dementia blog, they had a better understanding of the changes that occur as a result of cognitive impairment/dementia (Figure 1). Almost two-thirds of respondents (65%) agreed/strongly agreed that they felt more comfortable interacting with PwD (Figure 2). Additionally, 60% of respondents agreed/strongly agreed that they were more encouraged to work with PwD, and 90% agreed/strongly agreed that they had a greater appreciation of the challenges of being a caregiver for PwD. Overall, these findings suggest that the People of Dementia blog is useful for engaging the public and promoting a better understanding of dementia.

Work for policy changes

Clinicians can support public policy through education and advocacy both in the delivery of care and as spokespersons and stakeholders in their local communities. Public policies are important for providing access to medical and social services to meet the needs of PwD and their caregivers. The absence—real or perceived—of sufficient resources exacerbates dementia-related stigma. In addition to facilitating access to resources, national dementia strategies or legal frameworks, such as the National Alzheimer’s Project Act in the United States, include policy initiatives to identify and promote communication approaches that are effective and sensitive with respect to people living with dementia and their caregivers.

State and local legislators and patient advocates are leading policy efforts to reduce dementia-related stigma. For example, Colorado recently changed statutory references from being specific to diseases that cause dementia to the broader, more inclusive phrase “dementia diseases and related disabilities.”¹⁸ In addition to making funds available to support caregiving services for PwD, this legislative change added training for first responders to better meet the needs of missing PwD, and shifted the terminology used to diagnose and communicate about diseases causing dementia. The shift in language added new terminology that was chosen for being more person-centered to replace prior references to “senior senility,” “senility,” and other terms with pejorative meanings.

In Canada, a National Dementia Strategy will commit the Canadian government to action with definitive timelines, targets, reporting structures, and measurable outcomes.²⁴

Table 2 summarizes approaches to addressing dementia-related stigma.

Continue to: An open discussion

 

 

An open discussion

Larger studies and testing of diverse approaches are needed to better understand whether intergenerational initiatives or other approaches can genuinely modify stigmatizing attitudes in various dementia populations, especially considering language, health literacy, cultural preferences, and other needs. The identified effects on physical and mental health, quality of life, self-esteem, and behavioral symptoms further support the extensive, negative effects of self-stigma on PwD, and emphasize the need to develop and test interventions to ameliorate these effects.

We presented at a Stigma Symposium at the 2018 Gerontological Society of America Annual Scientific Meeting in Boston, Massachusetts.²⁵ Attendees of this conference shared our concerns about the detrimental effects of stigma. The main question we were asked was “What can we do to reduce stigma?” Perhaps the most immediate response is that in order to move the stigma dial, clinicians need to recognize that stigma has multiple, broad-reaching, and negative effects on PwD and their families.⁶ Bringing the discussion into the open and targeting stigma at multiple levels needs to be addressed by clinicians, researchers, administrators, and society at large.

Bottom Line

Stigma has multiple, broad-reaching, and negative effects on persons with dementia and their families. In clinical practice, direct discussion that encourages reflection and the use of effective and sensitive communication can help to limit passing on stigmatizing beliefs and to reduce negative stereotypes associated with the disease. Anti-stigma messaging campaigns and public policy changes also can be used to address societal and social inequities of patients with dementia and their caregivers.

Related Resources

• Khoury R, Shach R, Nair A, et al. Can lifestyle modifications delay or prevent Alzheimer’s disease? Current Psychiatry. 2019;18(1):29-36,38.
• Burke AD, Burke WJ. Antipsychotics for patients with dementia: The road less traveled. Current Psychiatry. 2018;17(10):26-32,35-37.

Dementia is a family of disorders characterized by a decline in multiple cognitive abilities that significantly interferes with an individual’s functioning. An estimated 50 million people are living with a dementia worldwide.¹ Alzheimer’s disease (AD) is the leading cause of dementia, accounting for approximately two-thirds of dementia cases.¹ These numbers are expected to increase dramatically in the upcoming decades.

Sociologist Erving Goffman defined stigma as “an attribute, behaviour, or reputation which is socially discrediting in a particular way: it causes an individual to be mentally classified by others in an undesirable, rejected stereotype rather than in an accepted, normal one.”² Goffman² defined 3 broad categories of stigma: public, self, and courtesy (Table 1²).

Considerable evidence shows that the combined impact of having dementia and the negative response to the diagnosis significantly undermines an individual’s psychosocial well-being and quality of life.³ Persons with dementia (PwD) commonly report a loss of identity and self-worth, and stigma appears to deepen this distress.³ Stigma also negatively affects individuals associated with PwD, including family members and professionals. In this article, we discuss the impact of dementia-related stigma, and steps you can take to address it, including implementing person-centered clinical practices, promoting anti-stigma messaging campaigns, and advocating for public policy action to improve the lives of PwD and their families.

A pervasive problem

Although the Alzheimer’s Society International and the World Health Organi­zation acknowledge that stigma has a central role in defining the experience of AD, how stigma may present, how clinicians and researchers can recognize and measure stigma, and how to best combat it have been understudied.^3-5 A recent systematic literature review examined worldwide evidence on dementia-related stigma over the past decade.⁶ Hermann et al⁶ found that health care providers and the general public may hold stigmatizing attitudes toward PwD, and that stigma may be particularly harsh among racial and ethnic minorities, although the literature is scarce in this area. Cultural factors may also worsen stigma, and stigma may be associated with reduced awareness of dementia services and reduced help-seeking among minority groups.^7,8 Studies show that stigmatizing attitudes are more pronounced in people with limited knowledge of dementia, in those with little contact with PwD, in men, in younger individuals, and in the context of cultural interpretations of dementia.⁶ Health care providers can also sometimes contribute to the perpetuation of stigma.⁶

In terms of standardized scales or instruments for evaluating dementia-related stigma, there is no uniformly accepted “gold standard” measure, which makes it difficult to compare studies.⁶ In order to effectively study efforts to reduce stigma, researchers need to identify and establish a consensus on rating scales for evaluating stigma among PwD, caregivers, and the general public. Three instruments that may be used for this purpose are the Family Stigma in Alzheimer’s Disease Scale (FS-ADS),⁹ the Stigma Scale for Chronic Illness (SSCI),¹⁰ and the Perceptions Regarding Investigational Screening for Memory in Primary Care (PRISM-PC).¹¹

The detrimental effects of stigma

Burgener et al¹² reported that personal stigma impacted functioning and quality of life in PwD. Higher levels of stigma were associated with higher anxiety, depression, and behavioral symptoms and lower self-esteem, social support, participation in activities, personal control, and physical health.¹² Personal characteristics that may affect stigma include gender, location (rural vs urban), ethnicity, education level, and living arrangements (alone vs with family).¹²

In a subset of PwD with early-stage memory loss (n = 22), Burgener and Buckwalter¹³ found that 42% of participants were reluctant to reveal their diagnosis to others, with some fearing they would no longer be allowed to live alone and would be “sent to a facility.” In addition, 46% indicated they did not want “to be talked about like they were not there.” More than 50% of participants reported changes in their social network after receiving the diagnosis, including reducing activities and limiting types of contacts (ie, telephone only) or interacting only when “people come to me.” Participants were most comfortable with good friends “who understand” and persons within their faith communities. When asked about how they were treated by family members, >50% of participants described being treated differently, including loss of financial independence, more limited contact, and being “treated like a baby” by their children, who in general were uncomfortable talking about the diagnosis.

Continue to: In a recent study...

In a recent study by Harper et al,¹⁴ stigma was prevalent in the experience of PwD. One participant disclosed:

“I think there is [are] people I know who don’t ask me to go places or do things ’cause I have a dementia…I think lots of people don’t know what dementia is and I think it scares them ’cause they think of it as crazy. It hurts…”

Another participant said:

“I have had friends for over thirty years. They have turned their backs on me…we used to go for walks and they would phone me and go for coffee. Now I don’t hear from any of them…those aren’t true friends…true friends will stand behind you, not in front of you. That’s why I am not happy.”

Overall, quantitative and qualitative findings indicate multiple, detrimental effects of personal stigma on PwD. These effects fit well with measures of self-stigma, including social rejection (eg, being treated differently, participating in fewer activities, and having fewer friends), internalized shame (eg, being treated like a child, having fewer responsibilities, others acting as if dementia is “contagious”), and social isolation (eg, being less outgoing, feeling more comfortable in small groups, having limited social contacts).¹⁵

Continue to: Receiving a diagnosis of dementia...

Receiving a diagnosis of dementia presents patients and their families with psychological and social challenges.¹⁶ Many of these challenges are the consequence of stigma. A broad range of efforts are underway worldwide to reduce dementia-related stigma. These efforts include programs to promote public awareness and education, campaigns to develop inclusive social policies, and skills-based training initiatives to promote delivery of patient-centered care by clinicians and educators.^3,17,18 Many of these efforts share a common focus on promoting the “dignity” and “personhood” of PwD in order to disrupt stereotypes or fixed, oversimplified beliefs associated with dementia.

Implementing person-centered clinical care

In clinical practice, direct discussion that encourages reflection and the use of effective and sensitive communication can help to limit passing on stigmatizing beliefs and to reduce negative stereotypes associated with the disease. Health care communications that call attention to stereotypes may allow PwD to identify stereotypes as well as inaccuracies in those stereotypes. Interventions that validate the value of diversity can help PwD accept the ways in which they may not conform to social norms. This could include language such as “There is no one way to have Alzheimer’s disease. A person’s experience can differ from what others might experience or expect, and that’s okay.” In addition, the use of language that is accurate, respectful, inclusive, and empowering can support PwD and their caregivers.^19,20 For example, referring to PwD as “individuals living with dementia” rather than “those who are demented” conveys respect and appreciation for personhood. Other clinicians have provided additional practical suggestions.²¹

Anti-stigma messaging campaigns

The mass media is a common source of stereotypes about AD and other dementias. They typically present a “worst-case” scenario that promotes ageism, gerontophobia, and negative emotions, which may worsen stigma and discrimination towards PwD and the people who care for them. However, public messaging campaigns are emerging to counter negative messages and stereotypes in the mass media. Projects such as Typical Day, People with Dementia, and other online anti-stigma messaging campaigns allow a broad audience to gain a more nuanced understanding of the lives of PwD and their caregivers. These projects are rich resources that offer education and personal stories that can counter common stereotypes about dementia.

Typical Day is a photography project developed and maintained by clinicians and researchers at the University of Pennsylvania. Since early 2017, the project has provided a forum for individuals with mild cognitive impairment or dementia to document their lives and show what it means to them to live with dementia. Participants in the project photo-document the people, places, and objects that define their daily lives. They review and explain these photos with researchers at Penn Memory Center, who help them tell their stories. The participants’ stories, the photos they capture, and their portraits are available at www.mytypicalday.org.

People of Dementia. Storytelling is a powerful way to raise awareness of and reduce the stigma associated with dementia. For PwD, telling their stories can be an effective and therapeutic way to communicate their emotions and deliver an important message. In the blog People of Dementia (www.peopleofdementia.com),^22,23 PwD highlight who they were before the disease and how things have changed, with family members highlighting the challenges of caring for a person with dementia.

Continue to: The common thread is...

The common thread is the enduring “person” behind the exterior that is obscured by dementia. By allowing the audience to form a connection with who the individual was prior to the disease, and understanding the changes that have come as a result of dementia to both PwD and their support network, readers gain a greater appreciation of those affected by dementia. Between May 1, 2017 and May 31, 2019, the blog had more than 3,860 visitors. In an accompanying online survey (N = 57), 79% of respondents agreed/strongly agreed that after visiting the People of Dementia blog, they had a better understanding of the changes that occur as a result of cognitive impairment/dementia (Figure 1). Almost two-thirds of respondents (65%) agreed/strongly agreed that they felt more comfortable interacting with PwD (Figure 2). Additionally, 60% of respondents agreed/strongly agreed that they were more encouraged to work with PwD, and 90% agreed/strongly agreed that they had a greater appreciation of the challenges of being a caregiver for PwD. Overall, these findings suggest that the People of Dementia blog is useful for engaging the public and promoting a better understanding of dementia.

Work for policy changes

Clinicians can support public policy through education and advocacy both in the delivery of care and as spokespersons and stakeholders in their local communities. Public policies are important for providing access to medical and social services to meet the needs of PwD and their caregivers. The absence—real or perceived—of sufficient resources exacerbates dementia-related stigma. In addition to facilitating access to resources, national dementia strategies or legal frameworks, such as the National Alzheimer’s Project Act in the United States, include policy initiatives to identify and promote communication approaches that are effective and sensitive with respect to people living with dementia and their caregivers.

State and local legislators and patient advocates are leading policy efforts to reduce dementia-related stigma. For example, Colorado recently changed statutory references from being specific to diseases that cause dementia to the broader, more inclusive phrase “dementia diseases and related disabilities.”¹⁸ In addition to making funds available to support caregiving services for PwD, this legislative change added training for first responders to better meet the needs of missing PwD, and shifted the terminology used to diagnose and communicate about diseases causing dementia. The shift in language added new terminology that was chosen for being more person-centered to replace prior references to “senior senility,” “senility,” and other terms with pejorative meanings.

In Canada, a National Dementia Strategy will commit the Canadian government to action with definitive timelines, targets, reporting structures, and measurable outcomes.²⁴

Table 2 summarizes approaches to addressing dementia-related stigma.

Continue to: An open discussion

 

 

An open discussion

Larger studies and testing of diverse approaches are needed to better understand whether intergenerational initiatives or other approaches can genuinely modify stigmatizing attitudes in various dementia populations, especially considering language, health literacy, cultural preferences, and other needs. The identified effects on physical and mental health, quality of life, self-esteem, and behavioral symptoms further support the extensive, negative effects of self-stigma on PwD, and emphasize the need to develop and test interventions to ameliorate these effects.

We presented at a Stigma Symposium at the 2018 Gerontological Society of America Annual Scientific Meeting in Boston, Massachusetts.²⁵ Attendees of this conference shared our concerns about the detrimental effects of stigma. The main question we were asked was “What can we do to reduce stigma?” Perhaps the most immediate response is that in order to move the stigma dial, clinicians need to recognize that stigma has multiple, broad-reaching, and negative effects on PwD and their families.⁶ Bringing the discussion into the open and targeting stigma at multiple levels needs to be addressed by clinicians, researchers, administrators, and society at large.

Bottom Line

Stigma has multiple, broad-reaching, and negative effects on persons with dementia and their families. In clinical practice, direct discussion that encourages reflection and the use of effective and sensitive communication can help to limit passing on stigmatizing beliefs and to reduce negative stereotypes associated with the disease. Anti-stigma messaging campaigns and public policy changes also can be used to address societal and social inequities of patients with dementia and their caregivers.

Related Resources

• Khoury R, Shach R, Nair A, et al. Can lifestyle modifications delay or prevent Alzheimer’s disease? Current Psychiatry. 2019;18(1):29-36,38.
• Burke AD, Burke WJ. Antipsychotics for patients with dementia: The road less traveled. Current Psychiatry. 2018;17(10):26-32,35-37.

Dementia is a family of disorders characterized by a decline in multiple cognitive abilities that significantly interferes with an individual’s functioning. An estimated 50 million people are living with a dementia worldwide.¹ Alzheimer’s disease (AD) is the leading cause of dementia, accounting for approximately two-thirds of dementia cases.¹ These numbers are expected to increase dramatically in the upcoming decades.

Sociologist Erving Goffman defined stigma as “an attribute, behaviour, or reputation which is socially discrediting in a particular way: it causes an individual to be mentally classified by others in an undesirable, rejected stereotype rather than in an accepted, normal one.”² Goffman² defined 3 broad categories of stigma: public, self, and courtesy (Table 1²).

Considerable evidence shows that the combined impact of having dementia and the negative response to the diagnosis significantly undermines an individual’s psychosocial well-being and quality of life.³ Persons with dementia (PwD) commonly report a loss of identity and self-worth, and stigma appears to deepen this distress.³ Stigma also negatively affects individuals associated with PwD, including family members and professionals. In this article, we discuss the impact of dementia-related stigma, and steps you can take to address it, including implementing person-centered clinical practices, promoting anti-stigma messaging campaigns, and advocating for public policy action to improve the lives of PwD and their families.

A pervasive problem

Although the Alzheimer’s Society International and the World Health Organi­zation acknowledge that stigma has a central role in defining the experience of AD, how stigma may present, how clinicians and researchers can recognize and measure stigma, and how to best combat it have been understudied.^3-5 A recent systematic literature review examined worldwide evidence on dementia-related stigma over the past decade.⁶ Hermann et al⁶ found that health care providers and the general public may hold stigmatizing attitudes toward PwD, and that stigma may be particularly harsh among racial and ethnic minorities, although the literature is scarce in this area. Cultural factors may also worsen stigma, and stigma may be associated with reduced awareness of dementia services and reduced help-seeking among minority groups.^7,8 Studies show that stigmatizing attitudes are more pronounced in people with limited knowledge of dementia, in those with little contact with PwD, in men, in younger individuals, and in the context of cultural interpretations of dementia.⁶ Health care providers can also sometimes contribute to the perpetuation of stigma.⁶

In terms of standardized scales or instruments for evaluating dementia-related stigma, there is no uniformly accepted “gold standard” measure, which makes it difficult to compare studies.⁶ In order to effectively study efforts to reduce stigma, researchers need to identify and establish a consensus on rating scales for evaluating stigma among PwD, caregivers, and the general public. Three instruments that may be used for this purpose are the Family Stigma in Alzheimer’s Disease Scale (FS-ADS),⁹ the Stigma Scale for Chronic Illness (SSCI),¹⁰ and the Perceptions Regarding Investigational Screening for Memory in Primary Care (PRISM-PC).¹¹

The detrimental effects of stigma

Burgener et al¹² reported that personal stigma impacted functioning and quality of life in PwD. Higher levels of stigma were associated with higher anxiety, depression, and behavioral symptoms and lower self-esteem, social support, participation in activities, personal control, and physical health.¹² Personal characteristics that may affect stigma include gender, location (rural vs urban), ethnicity, education level, and living arrangements (alone vs with family).¹²

In a subset of PwD with early-stage memory loss (n = 22), Burgener and Buckwalter¹³ found that 42% of participants were reluctant to reveal their diagnosis to others, with some fearing they would no longer be allowed to live alone and would be “sent to a facility.” In addition, 46% indicated they did not want “to be talked about like they were not there.” More than 50% of participants reported changes in their social network after receiving the diagnosis, including reducing activities and limiting types of contacts (ie, telephone only) or interacting only when “people come to me.” Participants were most comfortable with good friends “who understand” and persons within their faith communities. When asked about how they were treated by family members, >50% of participants described being treated differently, including loss of financial independence, more limited contact, and being “treated like a baby” by their children, who in general were uncomfortable talking about the diagnosis.

Continue to: In a recent study...

In a recent study by Harper et al,¹⁴ stigma was prevalent in the experience of PwD. One participant disclosed:

“I think there is [are] people I know who don’t ask me to go places or do things ’cause I have a dementia…I think lots of people don’t know what dementia is and I think it scares them ’cause they think of it as crazy. It hurts…”

Another participant said:

“I have had friends for over thirty years. They have turned their backs on me…we used to go for walks and they would phone me and go for coffee. Now I don’t hear from any of them…those aren’t true friends…true friends will stand behind you, not in front of you. That’s why I am not happy.”

Overall, quantitative and qualitative findings indicate multiple, detrimental effects of personal stigma on PwD. These effects fit well with measures of self-stigma, including social rejection (eg, being treated differently, participating in fewer activities, and having fewer friends), internalized shame (eg, being treated like a child, having fewer responsibilities, others acting as if dementia is “contagious”), and social isolation (eg, being less outgoing, feeling more comfortable in small groups, having limited social contacts).¹⁵

Continue to: Receiving a diagnosis of dementia...

Receiving a diagnosis of dementia presents patients and their families with psychological and social challenges.¹⁶ Many of these challenges are the consequence of stigma. A broad range of efforts are underway worldwide to reduce dementia-related stigma. These efforts include programs to promote public awareness and education, campaigns to develop inclusive social policies, and skills-based training initiatives to promote delivery of patient-centered care by clinicians and educators.^3,17,18 Many of these efforts share a common focus on promoting the “dignity” and “personhood” of PwD in order to disrupt stereotypes or fixed, oversimplified beliefs associated with dementia.

Implementing person-centered clinical care

In clinical practice, direct discussion that encourages reflection and the use of effective and sensitive communication can help to limit passing on stigmatizing beliefs and to reduce negative stereotypes associated with the disease. Health care communications that call attention to stereotypes may allow PwD to identify stereotypes as well as inaccuracies in those stereotypes. Interventions that validate the value of diversity can help PwD accept the ways in which they may not conform to social norms. This could include language such as “There is no one way to have Alzheimer’s disease. A person’s experience can differ from what others might experience or expect, and that’s okay.” In addition, the use of language that is accurate, respectful, inclusive, and empowering can support PwD and their caregivers.^19,20 For example, referring to PwD as “individuals living with dementia” rather than “those who are demented” conveys respect and appreciation for personhood. Other clinicians have provided additional practical suggestions.²¹

Anti-stigma messaging campaigns

The mass media is a common source of stereotypes about AD and other dementias. They typically present a “worst-case” scenario that promotes ageism, gerontophobia, and negative emotions, which may worsen stigma and discrimination towards PwD and the people who care for them. However, public messaging campaigns are emerging to counter negative messages and stereotypes in the mass media. Projects such as Typical Day, People with Dementia, and other online anti-stigma messaging campaigns allow a broad audience to gain a more nuanced understanding of the lives of PwD and their caregivers. These projects are rich resources that offer education and personal stories that can counter common stereotypes about dementia.

Typical Day is a photography project developed and maintained by clinicians and researchers at the University of Pennsylvania. Since early 2017, the project has provided a forum for individuals with mild cognitive impairment or dementia to document their lives and show what it means to them to live with dementia. Participants in the project photo-document the people, places, and objects that define their daily lives. They review and explain these photos with researchers at Penn Memory Center, who help them tell their stories. The participants’ stories, the photos they capture, and their portraits are available at www.mytypicalday.org.

People of Dementia. Storytelling is a powerful way to raise awareness of and reduce the stigma associated with dementia. For PwD, telling their stories can be an effective and therapeutic way to communicate their emotions and deliver an important message. In the blog People of Dementia (www.peopleofdementia.com),^22,23 PwD highlight who they were before the disease and how things have changed, with family members highlighting the challenges of caring for a person with dementia.

Continue to: The common thread is...

The common thread is the enduring “person” behind the exterior that is obscured by dementia. By allowing the audience to form a connection with who the individual was prior to the disease, and understanding the changes that have come as a result of dementia to both PwD and their support network, readers gain a greater appreciation of those affected by dementia. Between May 1, 2017 and May 31, 2019, the blog had more than 3,860 visitors. In an accompanying online survey (N = 57), 79% of respondents agreed/strongly agreed that after visiting the People of Dementia blog, they had a better understanding of the changes that occur as a result of cognitive impairment/dementia (Figure 1). Almost two-thirds of respondents (65%) agreed/strongly agreed that they felt more comfortable interacting with PwD (Figure 2). Additionally, 60% of respondents agreed/strongly agreed that they were more encouraged to work with PwD, and 90% agreed/strongly agreed that they had a greater appreciation of the challenges of being a caregiver for PwD. Overall, these findings suggest that the People of Dementia blog is useful for engaging the public and promoting a better understanding of dementia.

Work for policy changes

Clinicians can support public policy through education and advocacy both in the delivery of care and as spokespersons and stakeholders in their local communities. Public policies are important for providing access to medical and social services to meet the needs of PwD and their caregivers. The absence—real or perceived—of sufficient resources exacerbates dementia-related stigma. In addition to facilitating access to resources, national dementia strategies or legal frameworks, such as the National Alzheimer’s Project Act in the United States, include policy initiatives to identify and promote communication approaches that are effective and sensitive with respect to people living with dementia and their caregivers.

State and local legislators and patient advocates are leading policy efforts to reduce dementia-related stigma. For example, Colorado recently changed statutory references from being specific to diseases that cause dementia to the broader, more inclusive phrase “dementia diseases and related disabilities.”¹⁸ In addition to making funds available to support caregiving services for PwD, this legislative change added training for first responders to better meet the needs of missing PwD, and shifted the terminology used to diagnose and communicate about diseases causing dementia. The shift in language added new terminology that was chosen for being more person-centered to replace prior references to “senior senility,” “senility,” and other terms with pejorative meanings.

In Canada, a National Dementia Strategy will commit the Canadian government to action with definitive timelines, targets, reporting structures, and measurable outcomes.²⁴

Table 2 summarizes approaches to addressing dementia-related stigma.

Continue to: An open discussion

 

 

An open discussion

Larger studies and testing of diverse approaches are needed to better understand whether intergenerational initiatives or other approaches can genuinely modify stigmatizing attitudes in various dementia populations, especially considering language, health literacy, cultural preferences, and other needs. The identified effects on physical and mental health, quality of life, self-esteem, and behavioral symptoms further support the extensive, negative effects of self-stigma on PwD, and emphasize the need to develop and test interventions to ameliorate these effects.

We presented at a Stigma Symposium at the 2018 Gerontological Society of America Annual Scientific Meeting in Boston, Massachusetts.²⁵ Attendees of this conference shared our concerns about the detrimental effects of stigma. The main question we were asked was “What can we do to reduce stigma?” Perhaps the most immediate response is that in order to move the stigma dial, clinicians need to recognize that stigma has multiple, broad-reaching, and negative effects on PwD and their families.⁶ Bringing the discussion into the open and targeting stigma at multiple levels needs to be addressed by clinicians, researchers, administrators, and society at large.

Bottom Line

Stigma has multiple, broad-reaching, and negative effects on persons with dementia and their families. In clinical practice, direct discussion that encourages reflection and the use of effective and sensitive communication can help to limit passing on stigmatizing beliefs and to reduce negative stereotypes associated with the disease. Anti-stigma messaging campaigns and public policy changes also can be used to address societal and social inequities of patients with dementia and their caregivers.

Related Resources

• Khoury R, Shach R, Nair A, et al. Can lifestyle modifications delay or prevent Alzheimer’s disease? Current Psychiatry. 2019;18(1):29-36,38.
• Burke AD, Burke WJ. Antipsychotics for patients with dementia: The road less traveled. Current Psychiatry. 2018;17(10):26-32,35-37.