Among patients with hepatitis C virus, antiviral treatment is associated with a reduced risk of Parkinson’s disease, according to a cohort study published online June 5 in JAMA Neurology. The results provide evidence that hepatitis C virus is a risk factor for Parkinson’s disease.

In the past several years, epidemiologic studies have suggested an association between hepatitis C virus infection and Parkinson’s disease. A study published in 2017, however, found no association between the two. In addition, these investigations did not consider antiviral therapy as a potential modifying factor.

Wey-Yil Lin, MD, a neurologist at Landseed International Hospital in Taoyuan, Taiwan, and colleagues examined claims data from the Taiwan National Health Insurance Research Database to identify the risk of incident Parkinson’s disease in patients with hepatitis C virus infection who received antiviral treatment, compared with those who did not receive treatment.

The investigators selected all patients with a new diagnosis of hepatitis C virus infection with or without hepatitis from January 1, 2003, to December 31, 2013. They excluded patients who were aged 20 years or younger; had Parkinson’s disease, dementia, or stroke; or had had major hepatic diseases on the index date. To ensure that treated patients had had an effective course of therapy, the researchers excluded patients who were lost to follow-up within 6 months of the index date, received antiviral therapy for fewer than 16 weeks, or developed Parkinson’s disease within 6 months of the index date.

The primary outcome was incident Parkinson’s disease. Dr. Lin and colleagues excluded participants with a diagnosis of stroke and dementia before the index date to reduce the possibility of enrolling participants with secondary and atypical parkinsonism.

To minimize the potential selection bias to which observational studies are subject, the investigators performed propensity score matching with sex, age, comorbidities, and medication as covariates. This method was intended to create treated and untreated cohorts with comparable characteristics.

Dr. Lin and colleagues included 188,152 patients in their analysis. After matching, each group included 39,936 participants. In the group that received antiviral treatment, 45.0% of participants were female, and mean age was 52.8 years. In the untreated group, 44.4% of participants were female, and mean age was 52.5 years.

The incidence density of Parkinson’s disease per 1,000 person-years was 1.00 in the treated group and 1.39 in the untreated group. The difference in risk of Parkinson’s disease between the treated and untreated groups was statistically significant at year 5 of follow-up (hazard ratio [HR], 0.75) and at the end of the cohort (HR, 0.71). The risk did not differ significantly at year 1 and year 3, however. A subgroup analysis found a greater benefit of antiviral therapy among patients who concurrently used dihydropyridine calcium channel blockers.

“To our knowledge, this is the first cohort study to investigate the association between antiviral therapy and risk of Parkinson’s disease in patients with chronic hepatitis C viral infection,” said Dr. Lin and colleagues. Although it is possible that interferon-based antiviral therapy directly protected against the development of Parkinson’s disease, the short time of exposure to the antiviral agent “makes protecting against Parkinson’s disease development in 5 years less likely,” they added.

Among the study limitations that the authors acknowledged was the lack of data about hepatic function profile, serum virologic response, viral genotype, and hepatitis C virus RNA-level. The database that the investigators used also lacked data about behavioral factors (e.g., smoking status, coffee consumption, and alcohol consumption) that may have affected the incidence of Parkinson’s disease in the cohort. Investigations with longer follow-up periods will be needed to provide clearer information, they concluded.

The authors reported no conflicts of interest. The study was funded by grants from Chang Gung Medical Research Fund and from Chang Gung Memorial Hospital.

egreb@mdedge.com

SOURCE: Lin W-Y et al. JAMA Neurol. 2019 Jun 5. doi: 10.1001/jamaneurol.2019.1368.

Among patients with hepatitis C virus, antiviral treatment is associated with a reduced risk of Parkinson’s disease, according to a cohort study published online June 5 in JAMA Neurology. The results provide evidence that hepatitis C virus is a risk factor for Parkinson’s disease.

In the past several years, epidemiologic studies have suggested an association between hepatitis C virus infection and Parkinson’s disease. A study published in 2017, however, found no association between the two. In addition, these investigations did not consider antiviral therapy as a potential modifying factor.

Wey-Yil Lin, MD, a neurologist at Landseed International Hospital in Taoyuan, Taiwan, and colleagues examined claims data from the Taiwan National Health Insurance Research Database to identify the risk of incident Parkinson’s disease in patients with hepatitis C virus infection who received antiviral treatment, compared with those who did not receive treatment.

The investigators selected all patients with a new diagnosis of hepatitis C virus infection with or without hepatitis from January 1, 2003, to December 31, 2013. They excluded patients who were aged 20 years or younger; had Parkinson’s disease, dementia, or stroke; or had had major hepatic diseases on the index date. To ensure that treated patients had had an effective course of therapy, the researchers excluded patients who were lost to follow-up within 6 months of the index date, received antiviral therapy for fewer than 16 weeks, or developed Parkinson’s disease within 6 months of the index date.

The primary outcome was incident Parkinson’s disease. Dr. Lin and colleagues excluded participants with a diagnosis of stroke and dementia before the index date to reduce the possibility of enrolling participants with secondary and atypical parkinsonism.

To minimize the potential selection bias to which observational studies are subject, the investigators performed propensity score matching with sex, age, comorbidities, and medication as covariates. This method was intended to create treated and untreated cohorts with comparable characteristics.

Dr. Lin and colleagues included 188,152 patients in their analysis. After matching, each group included 39,936 participants. In the group that received antiviral treatment, 45.0% of participants were female, and mean age was 52.8 years. In the untreated group, 44.4% of participants were female, and mean age was 52.5 years.

The incidence density of Parkinson’s disease per 1,000 person-years was 1.00 in the treated group and 1.39 in the untreated group. The difference in risk of Parkinson’s disease between the treated and untreated groups was statistically significant at year 5 of follow-up (hazard ratio [HR], 0.75) and at the end of the cohort (HR, 0.71). The risk did not differ significantly at year 1 and year 3, however. A subgroup analysis found a greater benefit of antiviral therapy among patients who concurrently used dihydropyridine calcium channel blockers.

“To our knowledge, this is the first cohort study to investigate the association between antiviral therapy and risk of Parkinson’s disease in patients with chronic hepatitis C viral infection,” said Dr. Lin and colleagues. Although it is possible that interferon-based antiviral therapy directly protected against the development of Parkinson’s disease, the short time of exposure to the antiviral agent “makes protecting against Parkinson’s disease development in 5 years less likely,” they added.

Among the study limitations that the authors acknowledged was the lack of data about hepatic function profile, serum virologic response, viral genotype, and hepatitis C virus RNA-level. The database that the investigators used also lacked data about behavioral factors (e.g., smoking status, coffee consumption, and alcohol consumption) that may have affected the incidence of Parkinson’s disease in the cohort. Investigations with longer follow-up periods will be needed to provide clearer information, they concluded.

The authors reported no conflicts of interest. The study was funded by grants from Chang Gung Medical Research Fund and from Chang Gung Memorial Hospital.

egreb@mdedge.com

SOURCE: Lin W-Y et al. JAMA Neurol. 2019 Jun 5. doi: 10.1001/jamaneurol.2019.1368.

Among patients with hepatitis C virus, antiviral treatment is associated with a reduced risk of Parkinson’s disease, according to a cohort study published online June 5 in JAMA Neurology. The results provide evidence that hepatitis C virus is a risk factor for Parkinson’s disease.

In the past several years, epidemiologic studies have suggested an association between hepatitis C virus infection and Parkinson’s disease. A study published in 2017, however, found no association between the two. In addition, these investigations did not consider antiviral therapy as a potential modifying factor.

Wey-Yil Lin, MD, a neurologist at Landseed International Hospital in Taoyuan, Taiwan, and colleagues examined claims data from the Taiwan National Health Insurance Research Database to identify the risk of incident Parkinson’s disease in patients with hepatitis C virus infection who received antiviral treatment, compared with those who did not receive treatment.

The investigators selected all patients with a new diagnosis of hepatitis C virus infection with or without hepatitis from January 1, 2003, to December 31, 2013. They excluded patients who were aged 20 years or younger; had Parkinson’s disease, dementia, or stroke; or had had major hepatic diseases on the index date. To ensure that treated patients had had an effective course of therapy, the researchers excluded patients who were lost to follow-up within 6 months of the index date, received antiviral therapy for fewer than 16 weeks, or developed Parkinson’s disease within 6 months of the index date.

The primary outcome was incident Parkinson’s disease. Dr. Lin and colleagues excluded participants with a diagnosis of stroke and dementia before the index date to reduce the possibility of enrolling participants with secondary and atypical parkinsonism.

To minimize the potential selection bias to which observational studies are subject, the investigators performed propensity score matching with sex, age, comorbidities, and medication as covariates. This method was intended to create treated and untreated cohorts with comparable characteristics.

Dr. Lin and colleagues included 188,152 patients in their analysis. After matching, each group included 39,936 participants. In the group that received antiviral treatment, 45.0% of participants were female, and mean age was 52.8 years. In the untreated group, 44.4% of participants were female, and mean age was 52.5 years.

The incidence density of Parkinson’s disease per 1,000 person-years was 1.00 in the treated group and 1.39 in the untreated group. The difference in risk of Parkinson’s disease between the treated and untreated groups was statistically significant at year 5 of follow-up (hazard ratio [HR], 0.75) and at the end of the cohort (HR, 0.71). The risk did not differ significantly at year 1 and year 3, however. A subgroup analysis found a greater benefit of antiviral therapy among patients who concurrently used dihydropyridine calcium channel blockers.

“To our knowledge, this is the first cohort study to investigate the association between antiviral therapy and risk of Parkinson’s disease in patients with chronic hepatitis C viral infection,” said Dr. Lin and colleagues. Although it is possible that interferon-based antiviral therapy directly protected against the development of Parkinson’s disease, the short time of exposure to the antiviral agent “makes protecting against Parkinson’s disease development in 5 years less likely,” they added.

Among the study limitations that the authors acknowledged was the lack of data about hepatic function profile, serum virologic response, viral genotype, and hepatitis C virus RNA-level. The database that the investigators used also lacked data about behavioral factors (e.g., smoking status, coffee consumption, and alcohol consumption) that may have affected the incidence of Parkinson’s disease in the cohort. Investigations with longer follow-up periods will be needed to provide clearer information, they concluded.

The authors reported no conflicts of interest. The study was funded by grants from Chang Gung Medical Research Fund and from Chang Gung Memorial Hospital.

egreb@mdedge.com

SOURCE: Lin W-Y et al. JAMA Neurol. 2019 Jun 5. doi: 10.1001/jamaneurol.2019.1368.

Brenda L. Banwell, MD, is Chief of the Division of Neurology at Children’s Hospital of Philadelphia and holder of the Grace R. Loeb Endowed Chair in Neurosciences. Dr. Banwell is an expert in pediatric-onset multiple sclerosis (MS) with a clinical focus on cognitive features, neuroimaging, T and B-cell autoimmunity studies, and studies of viral triggers. We spoke with Dr. Banwell to discuss the disease course of pediatric-onset MS and the impact of magnetic resonance imaging (MRI).

How does the disease course of pediatric-onset MS differ from that of adult-onset MS?

DR. BANWELL:  Pediatric-onset MS is almost universally a relapsing-remitting disease at onset. Primary progressive MS is typically not seen in children younger than 18 years of age.

Children with progressive disability from onset should be considered more likely to have either a mitochondrial disease, genetic leukodystrophy or other disorder. Multiple sclerosis would not be a consideration for a child with progressive disability at the beginning.

Secondary progressive MS does not appear to occur for most children during the first 10 years of disease. Retrospective cohort studies suggest that secondary progressive MS in patients with pediatric-onset MS likely takes, on average, at least 20 years to occur from onset.

However, we should remember that pediatric-onset MS patients are at risk for secondary progression when they are only 30 or 35 years of age, depending on when they experienced their first attack. With the availability of numerous MS therapies, we are optimistic that secondary progressive MS may now be less likely to occur, or may be delayed even further from onset.

How often are MRIs performed on children with MS?

DR. BANWELL:  The most pivotal MRI is the one that helps you confirm the diagnosis. It is ideally obtained very close to the first onset of symptoms. That MRI could include the orbits, brain, and spine, depending on the clinical symptoms.

Following the first MRI scan, most of us would image our patients approximately every 3 months in the first year. After the first year, we would typically image our patients at least every 6 months, until, if they have been stable for an extended period of time, we might move to annual imaging.

The frequency of MRI scanning is determined by clinical disease activity, treatment decisions, and the age of the child. For example, very young children may require repeated exposure to anesthetics in order to obtain an MRI. We might have to think strategically about how often to put them under that degree of anesthesia to obtain imaging. Many young children are able to lie still for MRI if the facility has the option for viewing a video during the scan.

How do those MRI results influence your treatment decisions for the pediatric patient?

DR. BANWELL:  The International Pediatric Multiple Sclerosis Study Group recently had an international consensus discussion with respect to monitoring disease activity and are working as a collective toward the concept of defining a standard interpretation of adequate disease control for given treatments. Standardized protocols for clinical evaluations and for MRI scan interpretation will be essential. Determining what constitutes “adequate treatment response”, both in terms of relapse frequency and frequency of new lesions on MRI will be important components to consider.

What have the MRI studies shown us about the brain volume in pediatric patients with MS?

DR. BANWELL:  There are several things that we have learned about the impact of MS in the brains of children and teenagers.

With respect to brain growth and brain volume, we have learned that at the time of a first attack, children and teenagers with MS already have brain volumes that are about one standard deviation below what you would expect for someone their age and sex.

The inner skull size is also reduced, which suggests that there has been a failure of head and skull growth even before the first attack.

Following identification of MS in a child, the subsequent serial MRI studies have shown that children with MS fail to have age-expected brain growth. We do not see the age-expected rate of growth in our pediatric patients.

Around age 16 to 17 is when our brain volumes are the largest in our lifetime, but our pediatric patients show brain atrophy or progressive loss of brain volume after age 15, a time when normal brain volumes are pretty stable for at least a decade.

When we age, there is a gradual rate of brain volume loss, but this has not been imaged yet in our pediatric patients with MS since we do not have serial studies of individuals who are 30 or 40 yet who had pediatric-onset MS.

What else have MRI studies shown?

DR. BANWELL:  Another point to add is that when we look at patients with pediatric-onset MS compared with those with adult-onset MS matched for disease duration, pediatric patients on average have higher T2 and T1 lesion volumes compared with adults. This suggests that despite their young age, pediatric-onset MS patients have had sufficient time to accrue subclinical disease/lesions and may have an accelerated rate of new lesion formation.

MRI and some of the newer more advanced MRI techniques are also informing on brain tissue integrity. In studies that examine whether the white matter highways in the brain or the pathways in the brain are normal, we find that in both pediatric-onset and adult-onset MS, even normal-appearing white matter is not normal. It is not as well structured as it should be compared with age- and sex-matched controls. Further, the myelin integrity or the structural alignment in the brain of our pediatric patients may not be normal.

I think that emphasizes to all of us that MS is much more than just multiple areas of “sclerosis”  or scarring, which is what MS actually means. It is indeed a disease that has a more widespread impact on the central nervous system,  beyond the very bright T2 lesions that we normally count and measure.

That is important because it speaks to the subsequent requirement that we think about when considering treatment for MS. Our goal is to not only suppress the acquisition of new lesions, which is the common metric for clinical trials, but we also think about brain protection, brain preservation, and brain repair, which, I think, is potentially the underlying substrate that is not yet fully addressed by the evolving treatment.

Brenda L. Banwell, MD, is Chief of the Division of Neurology at Children’s Hospital of Philadelphia and holder of the Grace R. Loeb Endowed Chair in Neurosciences. Dr. Banwell is an expert in pediatric-onset multiple sclerosis (MS) with a clinical focus on cognitive features, neuroimaging, T and B-cell autoimmunity studies, and studies of viral triggers. We spoke with Dr. Banwell to discuss the disease course of pediatric-onset MS and the impact of magnetic resonance imaging (MRI).

How does the disease course of pediatric-onset MS differ from that of adult-onset MS?

DR. BANWELL:  Pediatric-onset MS is almost universally a relapsing-remitting disease at onset. Primary progressive MS is typically not seen in children younger than 18 years of age.

Children with progressive disability from onset should be considered more likely to have either a mitochondrial disease, genetic leukodystrophy or other disorder. Multiple sclerosis would not be a consideration for a child with progressive disability at the beginning.

Secondary progressive MS does not appear to occur for most children during the first 10 years of disease. Retrospective cohort studies suggest that secondary progressive MS in patients with pediatric-onset MS likely takes, on average, at least 20 years to occur from onset.

However, we should remember that pediatric-onset MS patients are at risk for secondary progression when they are only 30 or 35 years of age, depending on when they experienced their first attack. With the availability of numerous MS therapies, we are optimistic that secondary progressive MS may now be less likely to occur, or may be delayed even further from onset.

How often are MRIs performed on children with MS?

DR. BANWELL:  The most pivotal MRI is the one that helps you confirm the diagnosis. It is ideally obtained very close to the first onset of symptoms. That MRI could include the orbits, brain, and spine, depending on the clinical symptoms.

Following the first MRI scan, most of us would image our patients approximately every 3 months in the first year. After the first year, we would typically image our patients at least every 6 months, until, if they have been stable for an extended period of time, we might move to annual imaging.

The frequency of MRI scanning is determined by clinical disease activity, treatment decisions, and the age of the child. For example, very young children may require repeated exposure to anesthetics in order to obtain an MRI. We might have to think strategically about how often to put them under that degree of anesthesia to obtain imaging. Many young children are able to lie still for MRI if the facility has the option for viewing a video during the scan.

How do those MRI results influence your treatment decisions for the pediatric patient?

DR. BANWELL:  The International Pediatric Multiple Sclerosis Study Group recently had an international consensus discussion with respect to monitoring disease activity and are working as a collective toward the concept of defining a standard interpretation of adequate disease control for given treatments. Standardized protocols for clinical evaluations and for MRI scan interpretation will be essential. Determining what constitutes “adequate treatment response”, both in terms of relapse frequency and frequency of new lesions on MRI will be important components to consider.

What have the MRI studies shown us about the brain volume in pediatric patients with MS?

DR. BANWELL:  There are several things that we have learned about the impact of MS in the brains of children and teenagers.

With respect to brain growth and brain volume, we have learned that at the time of a first attack, children and teenagers with MS already have brain volumes that are about one standard deviation below what you would expect for someone their age and sex.

The inner skull size is also reduced, which suggests that there has been a failure of head and skull growth even before the first attack.

Following identification of MS in a child, the subsequent serial MRI studies have shown that children with MS fail to have age-expected brain growth. We do not see the age-expected rate of growth in our pediatric patients.

Around age 16 to 17 is when our brain volumes are the largest in our lifetime, but our pediatric patients show brain atrophy or progressive loss of brain volume after age 15, a time when normal brain volumes are pretty stable for at least a decade.

When we age, there is a gradual rate of brain volume loss, but this has not been imaged yet in our pediatric patients with MS since we do not have serial studies of individuals who are 30 or 40 yet who had pediatric-onset MS.

What else have MRI studies shown?

DR. BANWELL:  Another point to add is that when we look at patients with pediatric-onset MS compared with those with adult-onset MS matched for disease duration, pediatric patients on average have higher T2 and T1 lesion volumes compared with adults. This suggests that despite their young age, pediatric-onset MS patients have had sufficient time to accrue subclinical disease/lesions and may have an accelerated rate of new lesion formation.

MRI and some of the newer more advanced MRI techniques are also informing on brain tissue integrity. In studies that examine whether the white matter highways in the brain or the pathways in the brain are normal, we find that in both pediatric-onset and adult-onset MS, even normal-appearing white matter is not normal. It is not as well structured as it should be compared with age- and sex-matched controls. Further, the myelin integrity or the structural alignment in the brain of our pediatric patients may not be normal.

I think that emphasizes to all of us that MS is much more than just multiple areas of “sclerosis”  or scarring, which is what MS actually means. It is indeed a disease that has a more widespread impact on the central nervous system,  beyond the very bright T2 lesions that we normally count and measure.

That is important because it speaks to the subsequent requirement that we think about when considering treatment for MS. Our goal is to not only suppress the acquisition of new lesions, which is the common metric for clinical trials, but we also think about brain protection, brain preservation, and brain repair, which, I think, is potentially the underlying substrate that is not yet fully addressed by the evolving treatment.

Brenda L. Banwell, MD, is Chief of the Division of Neurology at Children’s Hospital of Philadelphia and holder of the Grace R. Loeb Endowed Chair in Neurosciences. Dr. Banwell is an expert in pediatric-onset multiple sclerosis (MS) with a clinical focus on cognitive features, neuroimaging, T and B-cell autoimmunity studies, and studies of viral triggers. We spoke with Dr. Banwell to discuss the disease course of pediatric-onset MS and the impact of magnetic resonance imaging (MRI).

How does the disease course of pediatric-onset MS differ from that of adult-onset MS?

DR. BANWELL:  Pediatric-onset MS is almost universally a relapsing-remitting disease at onset. Primary progressive MS is typically not seen in children younger than 18 years of age.

Children with progressive disability from onset should be considered more likely to have either a mitochondrial disease, genetic leukodystrophy or other disorder. Multiple sclerosis would not be a consideration for a child with progressive disability at the beginning.

Secondary progressive MS does not appear to occur for most children during the first 10 years of disease. Retrospective cohort studies suggest that secondary progressive MS in patients with pediatric-onset MS likely takes, on average, at least 20 years to occur from onset.

However, we should remember that pediatric-onset MS patients are at risk for secondary progression when they are only 30 or 35 years of age, depending on when they experienced their first attack. With the availability of numerous MS therapies, we are optimistic that secondary progressive MS may now be less likely to occur, or may be delayed even further from onset.

How often are MRIs performed on children with MS?

DR. BANWELL:  The most pivotal MRI is the one that helps you confirm the diagnosis. It is ideally obtained very close to the first onset of symptoms. That MRI could include the orbits, brain, and spine, depending on the clinical symptoms.

Following the first MRI scan, most of us would image our patients approximately every 3 months in the first year. After the first year, we would typically image our patients at least every 6 months, until, if they have been stable for an extended period of time, we might move to annual imaging.

The frequency of MRI scanning is determined by clinical disease activity, treatment decisions, and the age of the child. For example, very young children may require repeated exposure to anesthetics in order to obtain an MRI. We might have to think strategically about how often to put them under that degree of anesthesia to obtain imaging. Many young children are able to lie still for MRI if the facility has the option for viewing a video during the scan.

How do those MRI results influence your treatment decisions for the pediatric patient?

DR. BANWELL:  The International Pediatric Multiple Sclerosis Study Group recently had an international consensus discussion with respect to monitoring disease activity and are working as a collective toward the concept of defining a standard interpretation of adequate disease control for given treatments. Standardized protocols for clinical evaluations and for MRI scan interpretation will be essential. Determining what constitutes “adequate treatment response”, both in terms of relapse frequency and frequency of new lesions on MRI will be important components to consider.

What have the MRI studies shown us about the brain volume in pediatric patients with MS?

DR. BANWELL:  There are several things that we have learned about the impact of MS in the brains of children and teenagers.

With respect to brain growth and brain volume, we have learned that at the time of a first attack, children and teenagers with MS already have brain volumes that are about one standard deviation below what you would expect for someone their age and sex.

The inner skull size is also reduced, which suggests that there has been a failure of head and skull growth even before the first attack.

Following identification of MS in a child, the subsequent serial MRI studies have shown that children with MS fail to have age-expected brain growth. We do not see the age-expected rate of growth in our pediatric patients.

Around age 16 to 17 is when our brain volumes are the largest in our lifetime, but our pediatric patients show brain atrophy or progressive loss of brain volume after age 15, a time when normal brain volumes are pretty stable for at least a decade.

When we age, there is a gradual rate of brain volume loss, but this has not been imaged yet in our pediatric patients with MS since we do not have serial studies of individuals who are 30 or 40 yet who had pediatric-onset MS.

What else have MRI studies shown?

DR. BANWELL:  Another point to add is that when we look at patients with pediatric-onset MS compared with those with adult-onset MS matched for disease duration, pediatric patients on average have higher T2 and T1 lesion volumes compared with adults. This suggests that despite their young age, pediatric-onset MS patients have had sufficient time to accrue subclinical disease/lesions and may have an accelerated rate of new lesion formation.

MRI and some of the newer more advanced MRI techniques are also informing on brain tissue integrity. In studies that examine whether the white matter highways in the brain or the pathways in the brain are normal, we find that in both pediatric-onset and adult-onset MS, even normal-appearing white matter is not normal. It is not as well structured as it should be compared with age- and sex-matched controls. Further, the myelin integrity or the structural alignment in the brain of our pediatric patients may not be normal.

I think that emphasizes to all of us that MS is much more than just multiple areas of “sclerosis”  or scarring, which is what MS actually means. It is indeed a disease that has a more widespread impact on the central nervous system,  beyond the very bright T2 lesions that we normally count and measure.

That is important because it speaks to the subsequent requirement that we think about when considering treatment for MS. Our goal is to not only suppress the acquisition of new lesions, which is the common metric for clinical trials, but we also think about brain protection, brain preservation, and brain repair, which, I think, is potentially the underlying substrate that is not yet fully addressed by the evolving treatment.

A study suggests that allowing patients to read their physician’s notes may help many of them better manage and adhere to their medications.

Lead authors Tom Delbanco, MD, and Jan Walker, RN, MBA, of Harvard University and Beth Israel Deaconess Medical Center, both in Boston, conducted an online survey in 2017 of 19,411 patients in three separate health systems who participated in the OpenNotes pilot, an initiative that provided patients access to online clinical notes about their care. Eligible survey participants were 18 years or older and had logged into their respective patient portal at least once in the last 12 months and had an ambulatory visit note available.

Of the patients surveyed, a combined 14% of patients from Beth Israel Deaconess Medical Center and Geisinger Health reported that reading their notes made them more likely to take their medications as prescribed, while 86% reported no change, according to the study published in the Annals of Internal Medicine. At the University of Washington, Seattle, 33% of patients rated notes as “extremely important” in assisting with medication regimens. (The wording and response categories used by the University of Washington were not the same as those used by the other sites.)

The majority of patients at all three sites reported that note reading helped them understand why a medication was prescribed, answered their questions, and made them feel more comfortable with and in control of their medications, according to the study.

Of patients with a primary language other than English, 75% reported that reading their clinical notes helped them understand why a medication was prescribed, compared with 64% of patients who spoke English as their primary language. Of patients with high school or less education, 74% reported that reading their notes helped answer their questions about their medications, compared with 53% of college graduates.

The researchers also found that about 8 out of 10 survey participants reported looking at their medication list on the patient portal at least once. Of those patients who checked the portal for their medications, 18% said that the list was not accurate, and 85% wanted to submit corrections online.

The authors concluded that although note sharing means a substantial change in the culture of medicine, the practice of inviting patients to review clinicians’ notes online is spreading rapidly.

“Reading visit notes may be important for sustained improvements in the use of medications over time in ambulatory care,” they noted.

agallegos@mdedge.com

SOURCE: Delbanco et. al. Ann Intern Med. 2019 May 28. doi: 0.7326/M18-3197

A study suggests that allowing patients to read their physician’s notes may help many of them better manage and adhere to their medications.

Lead authors Tom Delbanco, MD, and Jan Walker, RN, MBA, of Harvard University and Beth Israel Deaconess Medical Center, both in Boston, conducted an online survey in 2017 of 19,411 patients in three separate health systems who participated in the OpenNotes pilot, an initiative that provided patients access to online clinical notes about their care. Eligible survey participants were 18 years or older and had logged into their respective patient portal at least once in the last 12 months and had an ambulatory visit note available.

Of the patients surveyed, a combined 14% of patients from Beth Israel Deaconess Medical Center and Geisinger Health reported that reading their notes made them more likely to take their medications as prescribed, while 86% reported no change, according to the study published in the Annals of Internal Medicine. At the University of Washington, Seattle, 33% of patients rated notes as “extremely important” in assisting with medication regimens. (The wording and response categories used by the University of Washington were not the same as those used by the other sites.)

The majority of patients at all three sites reported that note reading helped them understand why a medication was prescribed, answered their questions, and made them feel more comfortable with and in control of their medications, according to the study.

Of patients with a primary language other than English, 75% reported that reading their clinical notes helped them understand why a medication was prescribed, compared with 64% of patients who spoke English as their primary language. Of patients with high school or less education, 74% reported that reading their notes helped answer their questions about their medications, compared with 53% of college graduates.

The researchers also found that about 8 out of 10 survey participants reported looking at their medication list on the patient portal at least once. Of those patients who checked the portal for their medications, 18% said that the list was not accurate, and 85% wanted to submit corrections online.

The authors concluded that although note sharing means a substantial change in the culture of medicine, the practice of inviting patients to review clinicians’ notes online is spreading rapidly.

“Reading visit notes may be important for sustained improvements in the use of medications over time in ambulatory care,” they noted.

agallegos@mdedge.com

SOURCE: Delbanco et. al. Ann Intern Med. 2019 May 28. doi: 0.7326/M18-3197

A study suggests that allowing patients to read their physician’s notes may help many of them better manage and adhere to their medications.

Lead authors Tom Delbanco, MD, and Jan Walker, RN, MBA, of Harvard University and Beth Israel Deaconess Medical Center, both in Boston, conducted an online survey in 2017 of 19,411 patients in three separate health systems who participated in the OpenNotes pilot, an initiative that provided patients access to online clinical notes about their care. Eligible survey participants were 18 years or older and had logged into their respective patient portal at least once in the last 12 months and had an ambulatory visit note available.

Of the patients surveyed, a combined 14% of patients from Beth Israel Deaconess Medical Center and Geisinger Health reported that reading their notes made them more likely to take their medications as prescribed, while 86% reported no change, according to the study published in the Annals of Internal Medicine. At the University of Washington, Seattle, 33% of patients rated notes as “extremely important” in assisting with medication regimens. (The wording and response categories used by the University of Washington were not the same as those used by the other sites.)

The majority of patients at all three sites reported that note reading helped them understand why a medication was prescribed, answered their questions, and made them feel more comfortable with and in control of their medications, according to the study.

Of patients with a primary language other than English, 75% reported that reading their clinical notes helped them understand why a medication was prescribed, compared with 64% of patients who spoke English as their primary language. Of patients with high school or less education, 74% reported that reading their notes helped answer their questions about their medications, compared with 53% of college graduates.

The researchers also found that about 8 out of 10 survey participants reported looking at their medication list on the patient portal at least once. Of those patients who checked the portal for their medications, 18% said that the list was not accurate, and 85% wanted to submit corrections online.

The authors concluded that although note sharing means a substantial change in the culture of medicine, the practice of inviting patients to review clinicians’ notes online is spreading rapidly.

“Reading visit notes may be important for sustained improvements in the use of medications over time in ambulatory care,” they noted.

agallegos@mdedge.com

SOURCE: Delbanco et. al. Ann Intern Med. 2019 May 28. doi: 0.7326/M18-3197

It was a slow week at my office. For whatever reason, almost no one called for an appointment. Roughly 80% of my office slots were empty.

As a result, I began to worry.

You’d think that after 20 years in practice I wouldn’t, but I still do. I wonder if someone has actually read my Yelp reviews (most of which aren’t particularly good), or that I’ve done something to upset my referral base, or that some scandal about me broke in the local news that I’m entirely unaware of.

rdegrie/iStock/Getty Images Plus

Of course, the reality is that business comes and goes in waves. It was also the week after local schools closed for summer, and people were fleeing for summer vacation. In Phoenix, the older population leaves town as it heats up, and our winter visitors from elsewhere went home last month. And, like any business, things go in cycles that often don’t have a rational explanation.

I reassure myself that plenty of weeks are crazy. Patients crammed into every nook and cranny of the schedule, more people needing to be worked in, a huge pile of test results to be reviewed and make decisions on, and a lot of phone calls to be returned.

Then I’ll wish for a quieter week. I’ve given up on finding a happy medium – it doesn’t seem to happen.

So I try to live with the quiet. Close up and go home a little early if there’s no one to see. Catch up on my sleep and reading. Do some online surveys for extra dollars. Throw away expired stuff in my drug sample cabinet.

Medicine is, in general, a pretty hectic job. I need to learn to accept the quiet times as a gift and enjoy them, because the crazy days always return.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

It was a slow week at my office. For whatever reason, almost no one called for an appointment. Roughly 80% of my office slots were empty.

As a result, I began to worry.

You’d think that after 20 years in practice I wouldn’t, but I still do. I wonder if someone has actually read my Yelp reviews (most of which aren’t particularly good), or that I’ve done something to upset my referral base, or that some scandal about me broke in the local news that I’m entirely unaware of.

rdegrie/iStock/Getty Images Plus

Of course, the reality is that business comes and goes in waves. It was also the week after local schools closed for summer, and people were fleeing for summer vacation. In Phoenix, the older population leaves town as it heats up, and our winter visitors from elsewhere went home last month. And, like any business, things go in cycles that often don’t have a rational explanation.

I reassure myself that plenty of weeks are crazy. Patients crammed into every nook and cranny of the schedule, more people needing to be worked in, a huge pile of test results to be reviewed and make decisions on, and a lot of phone calls to be returned.

Then I’ll wish for a quieter week. I’ve given up on finding a happy medium – it doesn’t seem to happen.

So I try to live with the quiet. Close up and go home a little early if there’s no one to see. Catch up on my sleep and reading. Do some online surveys for extra dollars. Throw away expired stuff in my drug sample cabinet.

Medicine is, in general, a pretty hectic job. I need to learn to accept the quiet times as a gift and enjoy them, because the crazy days always return.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

It was a slow week at my office. For whatever reason, almost no one called for an appointment. Roughly 80% of my office slots were empty.

As a result, I began to worry.

You’d think that after 20 years in practice I wouldn’t, but I still do. I wonder if someone has actually read my Yelp reviews (most of which aren’t particularly good), or that I’ve done something to upset my referral base, or that some scandal about me broke in the local news that I’m entirely unaware of.

rdegrie/iStock/Getty Images Plus

Of course, the reality is that business comes and goes in waves. It was also the week after local schools closed for summer, and people were fleeing for summer vacation. In Phoenix, the older population leaves town as it heats up, and our winter visitors from elsewhere went home last month. And, like any business, things go in cycles that often don’t have a rational explanation.

I reassure myself that plenty of weeks are crazy. Patients crammed into every nook and cranny of the schedule, more people needing to be worked in, a huge pile of test results to be reviewed and make decisions on, and a lot of phone calls to be returned.

Then I’ll wish for a quieter week. I’ve given up on finding a happy medium – it doesn’t seem to happen.

So I try to live with the quiet. Close up and go home a little early if there’s no one to see. Catch up on my sleep and reading. Do some online surveys for extra dollars. Throw away expired stuff in my drug sample cabinet.

Medicine is, in general, a pretty hectic job. I need to learn to accept the quiet times as a gift and enjoy them, because the crazy days always return.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Overall per-person drug expenditures rose significantly from 2009 to 2016 for those who used a prescribed medicine, while out-of-pocket costs took a significant fall, according to the Agency for Healthcare Research and Quality.

The average expenditure among persons who used at least one prescription drug went from $1,497 per individual in 2009 to $1,955 in 2016, for an increase of almost 31%. These cost figures cover medications obtained in outpatient settings only and “include the amount paid out of pocket plus any third-party payments from health insurance or other sources,” the AHRQ said.

When out-of-pocket spending for drugs obtained in outpatient settings was considered separately, the average per-person cost dropped by 27%, going from $327 per person with use in 2009 to $238 in 2016, the AHRQ researchers reported.

Over that time period, both total and out-of-pocket costs were considerably and consistently higher for those aged 65 years and older than for those under 65. In 2016, total spending was $3,288 each for elderly persons with at least one prescribed drug purchase and $1,539 for those under age 65, with respective out-of-pocket costs of $401 and $188, they said.

The AHRQ analysis was based on data from the Medical Expenditure Panel Survey, and expenditures for 2009-2015 were adjusted to 2016 dollars.

rfranki@mdedge.com

Overall per-person drug expenditures rose significantly from 2009 to 2016 for those who used a prescribed medicine, while out-of-pocket costs took a significant fall, according to the Agency for Healthcare Research and Quality.

The average expenditure among persons who used at least one prescription drug went from $1,497 per individual in 2009 to $1,955 in 2016, for an increase of almost 31%. These cost figures cover medications obtained in outpatient settings only and “include the amount paid out of pocket plus any third-party payments from health insurance or other sources,” the AHRQ said.

When out-of-pocket spending for drugs obtained in outpatient settings was considered separately, the average per-person cost dropped by 27%, going from $327 per person with use in 2009 to $238 in 2016, the AHRQ researchers reported.

Over that time period, both total and out-of-pocket costs were considerably and consistently higher for those aged 65 years and older than for those under 65. In 2016, total spending was $3,288 each for elderly persons with at least one prescribed drug purchase and $1,539 for those under age 65, with respective out-of-pocket costs of $401 and $188, they said.

The AHRQ analysis was based on data from the Medical Expenditure Panel Survey, and expenditures for 2009-2015 were adjusted to 2016 dollars.

rfranki@mdedge.com

Overall per-person drug expenditures rose significantly from 2009 to 2016 for those who used a prescribed medicine, while out-of-pocket costs took a significant fall, according to the Agency for Healthcare Research and Quality.

The average expenditure among persons who used at least one prescription drug went from $1,497 per individual in 2009 to $1,955 in 2016, for an increase of almost 31%. These cost figures cover medications obtained in outpatient settings only and “include the amount paid out of pocket plus any third-party payments from health insurance or other sources,” the AHRQ said.

When out-of-pocket spending for drugs obtained in outpatient settings was considered separately, the average per-person cost dropped by 27%, going from $327 per person with use in 2009 to $238 in 2016, the AHRQ researchers reported.

Over that time period, both total and out-of-pocket costs were considerably and consistently higher for those aged 65 years and older than for those under 65. In 2016, total spending was $3,288 each for elderly persons with at least one prescribed drug purchase and $1,539 for those under age 65, with respective out-of-pocket costs of $401 and $188, they said.

The AHRQ analysis was based on data from the Medical Expenditure Panel Survey, and expenditures for 2009-2015 were adjusted to 2016 dollars.

rfranki@mdedge.com

The FP recognized this as classic pyoderma gangrenosum (PG)—a challenging condition to treat and not within the typical scope of practice for an FP. Nonhealing, well-defined leg ulcers in a person with Crohn's disease (or any type of inflammatory bowel disease) are often seen with PG. Pathergy—the development of an exaggerated injury following minor trauma—is known to occur with PG.

The FP also noted the violet-blue coloration around the borders of the ulcers, which is referred to as a “gun-metal border.” He considered doing a biopsy on the edge of the ulcer to rule out other conditions and to see if there was a neutrophilic infiltrate that is typically seen with PG. However, the FP realized that pathergy could be stimulated by a biopsy, so he decided to refer the patient to Dermatology.

Knowing that the patient might have to wait a few months to see a dermatologist, the FP consulted online sources and prescribed topical clobetasol ointment to be applied twice daily as an initial therapy. This was not successful, so after a phone consult with the dermatologist, the FP added oral prednisone 40 mg/d for the next 2 weeks until the dermatologist could see the patient.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux, EJ, Usatine R. Pyoderma gangrenosum. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1147-1152.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP recognized this as classic pyoderma gangrenosum (PG)—a challenging condition to treat and not within the typical scope of practice for an FP. Nonhealing, well-defined leg ulcers in a person with Crohn's disease (or any type of inflammatory bowel disease) are often seen with PG. Pathergy—the development of an exaggerated injury following minor trauma—is known to occur with PG.

The FP also noted the violet-blue coloration around the borders of the ulcers, which is referred to as a “gun-metal border.” He considered doing a biopsy on the edge of the ulcer to rule out other conditions and to see if there was a neutrophilic infiltrate that is typically seen with PG. However, the FP realized that pathergy could be stimulated by a biopsy, so he decided to refer the patient to Dermatology.

Knowing that the patient might have to wait a few months to see a dermatologist, the FP consulted online sources and prescribed topical clobetasol ointment to be applied twice daily as an initial therapy. This was not successful, so after a phone consult with the dermatologist, the FP added oral prednisone 40 mg/d for the next 2 weeks until the dermatologist could see the patient.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux, EJ, Usatine R. Pyoderma gangrenosum. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1147-1152.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP recognized this as classic pyoderma gangrenosum (PG)—a challenging condition to treat and not within the typical scope of practice for an FP. Nonhealing, well-defined leg ulcers in a person with Crohn's disease (or any type of inflammatory bowel disease) are often seen with PG. Pathergy—the development of an exaggerated injury following minor trauma—is known to occur with PG.

The FP also noted the violet-blue coloration around the borders of the ulcers, which is referred to as a “gun-metal border.” He considered doing a biopsy on the edge of the ulcer to rule out other conditions and to see if there was a neutrophilic infiltrate that is typically seen with PG. However, the FP realized that pathergy could be stimulated by a biopsy, so he decided to refer the patient to Dermatology.

Knowing that the patient might have to wait a few months to see a dermatologist, the FP consulted online sources and prescribed topical clobetasol ointment to be applied twice daily as an initial therapy. This was not successful, so after a phone consult with the dermatologist, the FP added oral prednisone 40 mg/d for the next 2 weeks until the dermatologist could see the patient.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux, EJ, Usatine R. Pyoderma gangrenosum. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1147-1152.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The Diagnosis: Plasmablastic Lymphoma 

Histopathologic examination revealed a diffuse dense proliferation of large, atypical, and pleomorphic mononuclear cells with prominent nucleoli and many mitotic figures representing plasmacytoid cells in the dermis (Figure). Immunostaining was positive for MUM-1 (marker of late-stage plasma cells and activated T cells) and BCL-2 (antiapoptotic marker). Fluorescent polymerase chain reaction was positive for clonal IgH gene arrangement, and fluorescence in situ hybridization was positive for C-MYC rearrangement in 94% of cells. Epstein-Barr encoding region in situ hybridization also was positive. Rare cells stained positive for T-cell markers. CD20, BCL-6, and CD30 immunostains were negative, suggesting that these cells were not B or T cells, though terminally differentiated B cells also can lack these markers. Bone marrow biopsy showed a similar staining pattern to the skin with 10% atypical plasmacytoid cells. Computed tomography of the left leg showed an enlargement of the semimembranosus muscle with internal areas of high density and heterogeneous enhancement. The patient underwent decompression of the left peroneal nerve. Biopsy showed a staining pattern similar to the right skin nodule and bone marrow, consistent with lymphoma.  

He was diagnosed with stage IV human immunodeficiency virus (HIV)-associated plasmablastic lymphoma (PBL) and received 6 cycles of R-EPOCH (rituximab, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride) without vincristine with intrathecal methotrexate, followed by 3 cycles of DHAP (dexamethasone, high dose Ara C, cisplatin) with bortezomib and daratumumab after relapse. Ultimately, he underwent autologous stem cell transplantation and was alive 13 months after diagnosis.  

Plasmablastic lymphoma is a rare subtype of non-Hodgkin lymphoma that most commonly arises in the oral cavity of individuals with HIV.¹ In addition to HIV infection, PBL also is seen in patients with other causes of immunodeficiency such as iatrogenic immunosuppression following solid organ transplantation.¹ The typical disease presentation is an expanding mass in the oral cavity; however, 34% (52/151) of reported cases arose at extraoral primary sites, with a minority of cases confined to cutaneous sites with no systemic involvement.² Cutaneous PBL presentations may include flesh-colored or purple, grouped or solitary nodules; an erythematous infiltrated plaque; or purple-red ulcerated nodules. The lesions usually are asymptomatic and located on the arms and legs.³  

On histologic examination, PBL is characterized by a diffuse monomorphic lymphoid infiltrate that sometimes invades the surrounding soft tissue.^4-6 The neoplastic cells have eccentric round nucleoli. Plasmablastic lymphoma characteristically displays a high proliferation index with many mitotic figures and signs of apoptosis.^4-6 Definitive diagnosis requires immunohistochemical staining. Typical B-cell antigens (CD20) as well as CD45 are negative, while plasma cell markers such as CD38 are positive. Other B- and T-cell markers usually are negative.^5,7 The pathogenesis of PBL is thought to be related to Epstein-Barr virus or human herpesvirus 8 infection. In a series of PBL cases, Epstein-Barr virus and human herpesvirus 8 was positive in 75% (97/129) and 17% (13/75) of tested cases, respectively.¹ 

The prognosis for PBL is poor, with a median overall survival of 15 months and a 3-year survival rate of 25% in HIV-infected individuals.⁸ However, cutaneous PBL without systemic involvement has a considerably better prognosis, with only 1 of 12 cases resulting in death.^2,3,9 Treatment of PBL depends on the extent of the disease. Cutaneous PBL can be treated with surgery and adjuvant radiation.³ Chemotherapy is required for patients with multiple lesions or systemic involvement. Current treatment regimens are similar to those used for other aggressive lymphomas such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).¹ Transplant recipients should have their immunosuppression reduced, and HIV-infected patients should have their highly active antiretroviral therapy regimens optimized. Patients presenting with PBL without HIV should be tested for HIV, as PBL has previously been reported to be the presenting manifestation of HIV infection.¹⁰ 

The differential diagnosis for a rapidly expanding, vascular-appearing, red mass on the legs in an immunosuppressed individual includes abscess, malignancy, Kaposi sarcoma, Sweet syndrome, and tertiary syphilis.  

Acknowledgment
We thank Sameera Husain, MD (New York, New York), for her assistance with histopathologic photographs and interpretation.  

The Diagnosis: Plasmablastic Lymphoma 

Histopathologic examination revealed a diffuse dense proliferation of large, atypical, and pleomorphic mononuclear cells with prominent nucleoli and many mitotic figures representing plasmacytoid cells in the dermis (Figure). Immunostaining was positive for MUM-1 (marker of late-stage plasma cells and activated T cells) and BCL-2 (antiapoptotic marker). Fluorescent polymerase chain reaction was positive for clonal IgH gene arrangement, and fluorescence in situ hybridization was positive for C-MYC rearrangement in 94% of cells. Epstein-Barr encoding region in situ hybridization also was positive. Rare cells stained positive for T-cell markers. CD20, BCL-6, and CD30 immunostains were negative, suggesting that these cells were not B or T cells, though terminally differentiated B cells also can lack these markers. Bone marrow biopsy showed a similar staining pattern to the skin with 10% atypical plasmacytoid cells. Computed tomography of the left leg showed an enlargement of the semimembranosus muscle with internal areas of high density and heterogeneous enhancement. The patient underwent decompression of the left peroneal nerve. Biopsy showed a staining pattern similar to the right skin nodule and bone marrow, consistent with lymphoma.  

He was diagnosed with stage IV human immunodeficiency virus (HIV)-associated plasmablastic lymphoma (PBL) and received 6 cycles of R-EPOCH (rituximab, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride) without vincristine with intrathecal methotrexate, followed by 3 cycles of DHAP (dexamethasone, high dose Ara C, cisplatin) with bortezomib and daratumumab after relapse. Ultimately, he underwent autologous stem cell transplantation and was alive 13 months after diagnosis.  

Plasmablastic lymphoma is a rare subtype of non-Hodgkin lymphoma that most commonly arises in the oral cavity of individuals with HIV.¹ In addition to HIV infection, PBL also is seen in patients with other causes of immunodeficiency such as iatrogenic immunosuppression following solid organ transplantation.¹ The typical disease presentation is an expanding mass in the oral cavity; however, 34% (52/151) of reported cases arose at extraoral primary sites, with a minority of cases confined to cutaneous sites with no systemic involvement.² Cutaneous PBL presentations may include flesh-colored or purple, grouped or solitary nodules; an erythematous infiltrated plaque; or purple-red ulcerated nodules. The lesions usually are asymptomatic and located on the arms and legs.³  

On histologic examination, PBL is characterized by a diffuse monomorphic lymphoid infiltrate that sometimes invades the surrounding soft tissue.^4-6 The neoplastic cells have eccentric round nucleoli. Plasmablastic lymphoma characteristically displays a high proliferation index with many mitotic figures and signs of apoptosis.^4-6 Definitive diagnosis requires immunohistochemical staining. Typical B-cell antigens (CD20) as well as CD45 are negative, while plasma cell markers such as CD38 are positive. Other B- and T-cell markers usually are negative.^5,7 The pathogenesis of PBL is thought to be related to Epstein-Barr virus or human herpesvirus 8 infection. In a series of PBL cases, Epstein-Barr virus and human herpesvirus 8 was positive in 75% (97/129) and 17% (13/75) of tested cases, respectively.¹ 

The prognosis for PBL is poor, with a median overall survival of 15 months and a 3-year survival rate of 25% in HIV-infected individuals.⁸ However, cutaneous PBL without systemic involvement has a considerably better prognosis, with only 1 of 12 cases resulting in death.^2,3,9 Treatment of PBL depends on the extent of the disease. Cutaneous PBL can be treated with surgery and adjuvant radiation.³ Chemotherapy is required for patients with multiple lesions or systemic involvement. Current treatment regimens are similar to those used for other aggressive lymphomas such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).¹ Transplant recipients should have their immunosuppression reduced, and HIV-infected patients should have their highly active antiretroviral therapy regimens optimized. Patients presenting with PBL without HIV should be tested for HIV, as PBL has previously been reported to be the presenting manifestation of HIV infection.¹⁰ 

The differential diagnosis for a rapidly expanding, vascular-appearing, red mass on the legs in an immunosuppressed individual includes abscess, malignancy, Kaposi sarcoma, Sweet syndrome, and tertiary syphilis.  

Acknowledgment
We thank Sameera Husain, MD (New York, New York), for her assistance with histopathologic photographs and interpretation.  

The Diagnosis: Plasmablastic Lymphoma 

Histopathologic examination revealed a diffuse dense proliferation of large, atypical, and pleomorphic mononuclear cells with prominent nucleoli and many mitotic figures representing plasmacytoid cells in the dermis (Figure). Immunostaining was positive for MUM-1 (marker of late-stage plasma cells and activated T cells) and BCL-2 (antiapoptotic marker). Fluorescent polymerase chain reaction was positive for clonal IgH gene arrangement, and fluorescence in situ hybridization was positive for C-MYC rearrangement in 94% of cells. Epstein-Barr encoding region in situ hybridization also was positive. Rare cells stained positive for T-cell markers. CD20, BCL-6, and CD30 immunostains were negative, suggesting that these cells were not B or T cells, though terminally differentiated B cells also can lack these markers. Bone marrow biopsy showed a similar staining pattern to the skin with 10% atypical plasmacytoid cells. Computed tomography of the left leg showed an enlargement of the semimembranosus muscle with internal areas of high density and heterogeneous enhancement. The patient underwent decompression of the left peroneal nerve. Biopsy showed a staining pattern similar to the right skin nodule and bone marrow, consistent with lymphoma.  

He was diagnosed with stage IV human immunodeficiency virus (HIV)-associated plasmablastic lymphoma (PBL) and received 6 cycles of R-EPOCH (rituximab, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride) without vincristine with intrathecal methotrexate, followed by 3 cycles of DHAP (dexamethasone, high dose Ara C, cisplatin) with bortezomib and daratumumab after relapse. Ultimately, he underwent autologous stem cell transplantation and was alive 13 months after diagnosis.  

Plasmablastic lymphoma is a rare subtype of non-Hodgkin lymphoma that most commonly arises in the oral cavity of individuals with HIV.¹ In addition to HIV infection, PBL also is seen in patients with other causes of immunodeficiency such as iatrogenic immunosuppression following solid organ transplantation.¹ The typical disease presentation is an expanding mass in the oral cavity; however, 34% (52/151) of reported cases arose at extraoral primary sites, with a minority of cases confined to cutaneous sites with no systemic involvement.² Cutaneous PBL presentations may include flesh-colored or purple, grouped or solitary nodules; an erythematous infiltrated plaque; or purple-red ulcerated nodules. The lesions usually are asymptomatic and located on the arms and legs.³  

On histologic examination, PBL is characterized by a diffuse monomorphic lymphoid infiltrate that sometimes invades the surrounding soft tissue.^4-6 The neoplastic cells have eccentric round nucleoli. Plasmablastic lymphoma characteristically displays a high proliferation index with many mitotic figures and signs of apoptosis.^4-6 Definitive diagnosis requires immunohistochemical staining. Typical B-cell antigens (CD20) as well as CD45 are negative, while plasma cell markers such as CD38 are positive. Other B- and T-cell markers usually are negative.^5,7 The pathogenesis of PBL is thought to be related to Epstein-Barr virus or human herpesvirus 8 infection. In a series of PBL cases, Epstein-Barr virus and human herpesvirus 8 was positive in 75% (97/129) and 17% (13/75) of tested cases, respectively.¹ 

The prognosis for PBL is poor, with a median overall survival of 15 months and a 3-year survival rate of 25% in HIV-infected individuals.⁸ However, cutaneous PBL without systemic involvement has a considerably better prognosis, with only 1 of 12 cases resulting in death.^2,3,9 Treatment of PBL depends on the extent of the disease. Cutaneous PBL can be treated with surgery and adjuvant radiation.³ Chemotherapy is required for patients with multiple lesions or systemic involvement. Current treatment regimens are similar to those used for other aggressive lymphomas such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).¹ Transplant recipients should have their immunosuppression reduced, and HIV-infected patients should have their highly active antiretroviral therapy regimens optimized. Patients presenting with PBL without HIV should be tested for HIV, as PBL has previously been reported to be the presenting manifestation of HIV infection.¹⁰ 

The differential diagnosis for a rapidly expanding, vascular-appearing, red mass on the legs in an immunosuppressed individual includes abscess, malignancy, Kaposi sarcoma, Sweet syndrome, and tertiary syphilis.  

Acknowledgment
We thank Sameera Husain, MD (New York, New York), for her assistance with histopathologic photographs and interpretation.  

Douglas K. Rex, MD, AGAF, MACP, MACG, FASGE; offers advice and insight for colorectal cancer screening, highlighting:

• Clinically relevant facts about the spectrum of precancerous lesions that can be targeted during screening;
• Key practical aspects of the 3 screening tests that receive significant use in the United States.
• Why some tests are used more than others

Click HERE to read the supplement

Douglas K. Rex, MD, AGAF, MACP, MACG, FASGE; offers advice and insight for colorectal cancer screening, highlighting:

• Clinically relevant facts about the spectrum of precancerous lesions that can be targeted during screening;
• Key practical aspects of the 3 screening tests that receive significant use in the United States.
• Why some tests are used more than others

Click HERE to read the supplement

Douglas K. Rex, MD, AGAF, MACP, MACG, FASGE; offers advice and insight for colorectal cancer screening, highlighting:

• Clinically relevant facts about the spectrum of precancerous lesions that can be targeted during screening;
• Key practical aspects of the 3 screening tests that receive significant use in the United States.
• Why some tests are used more than others

Click HERE to read the supplement

Counties in states that expanded Medicaid coverage under the Affordable Care Act have experienced a significantly smaller increase in cardiovascular mortality rates among middle-aged adults, compared with counties in states that did not expand coverage, according to findings from a new study.

In expansion-state counties, the change in cardiovascular mortality was stable between the pre-expansion (2010-2013) and postexpansion (2014-2016) periods, at 146.5-146.4 deaths per 100,000 residents per year, compared with mortality rates in nonexpansion counties during the same periods (176.3-180.9 deaths per 100,000), Sameed Ahmed M. Khatana, MD, and colleagues wrote in JAMA Cardiology.

“After accounting for demographic, clinical, and economic differences, counties in expansion states had 4.3 fewer deaths per 100,000 residents per year from cardiovascular causes after Medicaid expansion than if they had followed the same trends as counties in nonexpansion states,” Dr. Khatana, of the University of Pennsylvania, Philadelphia, and colleagues wrote..

That translated into 2,039 fewer total deaths per year in residents aged between 45 and 64 years from cardiovascular causes after Medicaid expansion, the authors noted.

In all, 29 states, plus Washington, D.C., were included in the expansion group, and 19 states were in the nonexpansion (control) group. During the study period, from 2010 to 2016, the number of expansion counties ranged between 912 and 931, and for the nonexpansion counties, between 985 and 1,029. About half of the residents in each group were women. The percentage of black residents was lower in expansion states, but the percentage of Hispanic residents did not differ. Compared with nonexpansion counties, expansion counties also had a lower prevalence of diabetes (8.5% vs. 9.7% in the nonexpansion counties), obesity (26.2% vs. 29.1%), and smoking (17.1 vs. 18.9%); a lower mean percentage of poor residents (14.4% vs 16.6%; all with P less than .001); and a higher median household income.

Expansion counties also fared better when it came to health insurance coverage. In 2010, 14.6% of their residents had no coverage, compared with 19.5% of residents in nonexpansion counties. During the study period, the decrease in the percentage of middle-aged residents without health coverage was larger in expansion than in nonexpansion counties (7.3% vs. 5.6%, respectively), as was the decrease in low-income residents without coverage (19.8% vs. 13.5%).

However, the authors cautioned that, given the observational nature of the study, they were “not able to make a causal association between expansion of Medicaid eligibility and differences in the cardiovascular mortality rates between the two groups of counties. It is possible that there were other unmeasured time varying factors that can explain the observed association.”

Despite that limitation of the study, which observed adults in all income categories and was not limited to low-income residents, the researchers noted that, given the association between Medicaid expansion and cardiovascular mortality rates, as well as the “high burden of cardiovascular risk factors among individuals without insurance and those with lower socioeconomic status,” policy makers might consider the results in future discussions about changes to eligibility for and expansion of Medicaid.

Dr. Khatana is supported by a grant from the National Institutes of Health. Two authors reported relationships with drug companies outside of the reported study; the rest of the authors had no disclosures to report.

SOURCE: Khatana SAM et al. JAMA Cardiol. 2019 Jun 5. doi: 10.1001/jamacardio.2019.1651.

Counties in states that expanded Medicaid coverage under the Affordable Care Act have experienced a significantly smaller increase in cardiovascular mortality rates among middle-aged adults, compared with counties in states that did not expand coverage, according to findings from a new study.

In expansion-state counties, the change in cardiovascular mortality was stable between the pre-expansion (2010-2013) and postexpansion (2014-2016) periods, at 146.5-146.4 deaths per 100,000 residents per year, compared with mortality rates in nonexpansion counties during the same periods (176.3-180.9 deaths per 100,000), Sameed Ahmed M. Khatana, MD, and colleagues wrote in JAMA Cardiology.

“After accounting for demographic, clinical, and economic differences, counties in expansion states had 4.3 fewer deaths per 100,000 residents per year from cardiovascular causes after Medicaid expansion than if they had followed the same trends as counties in nonexpansion states,” Dr. Khatana, of the University of Pennsylvania, Philadelphia, and colleagues wrote..

That translated into 2,039 fewer total deaths per year in residents aged between 45 and 64 years from cardiovascular causes after Medicaid expansion, the authors noted.

In all, 29 states, plus Washington, D.C., were included in the expansion group, and 19 states were in the nonexpansion (control) group. During the study period, from 2010 to 2016, the number of expansion counties ranged between 912 and 931, and for the nonexpansion counties, between 985 and 1,029. About half of the residents in each group were women. The percentage of black residents was lower in expansion states, but the percentage of Hispanic residents did not differ. Compared with nonexpansion counties, expansion counties also had a lower prevalence of diabetes (8.5% vs. 9.7% in the nonexpansion counties), obesity (26.2% vs. 29.1%), and smoking (17.1 vs. 18.9%); a lower mean percentage of poor residents (14.4% vs 16.6%; all with P less than .001); and a higher median household income.

Expansion counties also fared better when it came to health insurance coverage. In 2010, 14.6% of their residents had no coverage, compared with 19.5% of residents in nonexpansion counties. During the study period, the decrease in the percentage of middle-aged residents without health coverage was larger in expansion than in nonexpansion counties (7.3% vs. 5.6%, respectively), as was the decrease in low-income residents without coverage (19.8% vs. 13.5%).

However, the authors cautioned that, given the observational nature of the study, they were “not able to make a causal association between expansion of Medicaid eligibility and differences in the cardiovascular mortality rates between the two groups of counties. It is possible that there were other unmeasured time varying factors that can explain the observed association.”

Despite that limitation of the study, which observed adults in all income categories and was not limited to low-income residents, the researchers noted that, given the association between Medicaid expansion and cardiovascular mortality rates, as well as the “high burden of cardiovascular risk factors among individuals without insurance and those with lower socioeconomic status,” policy makers might consider the results in future discussions about changes to eligibility for and expansion of Medicaid.

Dr. Khatana is supported by a grant from the National Institutes of Health. Two authors reported relationships with drug companies outside of the reported study; the rest of the authors had no disclosures to report.

SOURCE: Khatana SAM et al. JAMA Cardiol. 2019 Jun 5. doi: 10.1001/jamacardio.2019.1651.

Counties in states that expanded Medicaid coverage under the Affordable Care Act have experienced a significantly smaller increase in cardiovascular mortality rates among middle-aged adults, compared with counties in states that did not expand coverage, according to findings from a new study.

In expansion-state counties, the change in cardiovascular mortality was stable between the pre-expansion (2010-2013) and postexpansion (2014-2016) periods, at 146.5-146.4 deaths per 100,000 residents per year, compared with mortality rates in nonexpansion counties during the same periods (176.3-180.9 deaths per 100,000), Sameed Ahmed M. Khatana, MD, and colleagues wrote in JAMA Cardiology.

“After accounting for demographic, clinical, and economic differences, counties in expansion states had 4.3 fewer deaths per 100,000 residents per year from cardiovascular causes after Medicaid expansion than if they had followed the same trends as counties in nonexpansion states,” Dr. Khatana, of the University of Pennsylvania, Philadelphia, and colleagues wrote..

That translated into 2,039 fewer total deaths per year in residents aged between 45 and 64 years from cardiovascular causes after Medicaid expansion, the authors noted.

In all, 29 states, plus Washington, D.C., were included in the expansion group, and 19 states were in the nonexpansion (control) group. During the study period, from 2010 to 2016, the number of expansion counties ranged between 912 and 931, and for the nonexpansion counties, between 985 and 1,029. About half of the residents in each group were women. The percentage of black residents was lower in expansion states, but the percentage of Hispanic residents did not differ. Compared with nonexpansion counties, expansion counties also had a lower prevalence of diabetes (8.5% vs. 9.7% in the nonexpansion counties), obesity (26.2% vs. 29.1%), and smoking (17.1 vs. 18.9%); a lower mean percentage of poor residents (14.4% vs 16.6%; all with P less than .001); and a higher median household income.

Expansion counties also fared better when it came to health insurance coverage. In 2010, 14.6% of their residents had no coverage, compared with 19.5% of residents in nonexpansion counties. During the study period, the decrease in the percentage of middle-aged residents without health coverage was larger in expansion than in nonexpansion counties (7.3% vs. 5.6%, respectively), as was the decrease in low-income residents without coverage (19.8% vs. 13.5%).

However, the authors cautioned that, given the observational nature of the study, they were “not able to make a causal association between expansion of Medicaid eligibility and differences in the cardiovascular mortality rates between the two groups of counties. It is possible that there were other unmeasured time varying factors that can explain the observed association.”

Despite that limitation of the study, which observed adults in all income categories and was not limited to low-income residents, the researchers noted that, given the association between Medicaid expansion and cardiovascular mortality rates, as well as the “high burden of cardiovascular risk factors among individuals without insurance and those with lower socioeconomic status,” policy makers might consider the results in future discussions about changes to eligibility for and expansion of Medicaid.

Dr. Khatana is supported by a grant from the National Institutes of Health. Two authors reported relationships with drug companies outside of the reported study; the rest of the authors had no disclosures to report.

SOURCE: Khatana SAM et al. JAMA Cardiol. 2019 Jun 5. doi: 10.1001/jamacardio.2019.1651.

For several years, this 16-year-old boy has had severe acne on his chest and back. The condition has steadily worsened despite use of OTC medications, including benzoyl peroxide–containing topical products. He has never received prescription treatment. His primary care provider, concerned that something more than acne could be involved, refers him to dermatology for evaluation and treatment.

The boy’s health is reportedly otherwise excellent. Family history is positive for severe acne on both sides of his family; two of his older siblings have had similar problems.

EXAMINATION
The central portion of the boy’s chest is covered by an impressive collection of discrete and confluent crusts and erosions. Some are quite deep, and the patient admits to picking at them. Little if any erythema surrounds the lesions.

Very little acne is seen on the boy’s face, but fairly dense acne vulgaris is observed on his upper back.

Following a brief but thorough discussion, the decision is made to start therapy with low-dose isotretinoin (20 mg/d), after the appropriate bloodwork is obtained. Within a week, the patient presents to the emergency department (ED) for worsening of his chest acne, along with pain and bleeding from some of the lesions.

What’s the diagnosis?

DISCUSSION
The risk for granulation tissue formation is a well-known though rare adverse effect of isotretinoin use—one that had been discussed thoroughly with the patient and his parents prior to prescription. There is no unanimity of opinion regarding the mechanism whereby this response occurs, but it is real. It can affect such areas as seen in this patient’s case but also causes a similar problem in the perionychial tissues, creating a condition quite similar to an ingrown toenail (cryptonychia). This author has also seen the same phenomenon in fingernails.

In this patient’s case, after discharge from the ED, he presented immediately to his primary care provider, who in turn called the dermatology clinic. When we saw him, there was clear evidence of inappropriate granulation formation—far worse than the initial acne had been.

The patient was given an intramuscular injection of 40 mg triamcinolone and prescribed minocycline 100 mg bid. He had already stopped taking the isotretinoin and was strongly advised not to restart it for the foreseeable future. In hindsight, he probably should have been started on minocycline and a 3-week prednisone taper to calm down his chest acne before the isotretinoin was started.

At a follow-up appointment 3 weeks later, his condition was much improved (at least back to baseline). But he will almost certainly develop hypertrophic scarring on his chest—and given the severity of his acne and the strong family history, he may well have a suboptimal response to isotretinoin when and if we return to that medication.

TAKE-HOME LEARNING POINTS

• In rare instances, isotretinoin therapy can trigger the formation of inappropriate granulation tissue on the face, back, chest, and even perionychial areas.
• There is evidence that the more inflamed the acne, the greater the likelihood of this adverse effect.
• With severely inflamed acne, consideration should be given to using small initial doses of isotretinoin or decreasing the inflammation through use of systemic steroids or doxycycline or minocycline.

For several years, this 16-year-old boy has had severe acne on his chest and back. The condition has steadily worsened despite use of OTC medications, including benzoyl peroxide–containing topical products. He has never received prescription treatment. His primary care provider, concerned that something more than acne could be involved, refers him to dermatology for evaluation and treatment.

The boy’s health is reportedly otherwise excellent. Family history is positive for severe acne on both sides of his family; two of his older siblings have had similar problems.

EXAMINATION
The central portion of the boy’s chest is covered by an impressive collection of discrete and confluent crusts and erosions. Some are quite deep, and the patient admits to picking at them. Little if any erythema surrounds the lesions.

Very little acne is seen on the boy’s face, but fairly dense acne vulgaris is observed on his upper back.

Following a brief but thorough discussion, the decision is made to start therapy with low-dose isotretinoin (20 mg/d), after the appropriate bloodwork is obtained. Within a week, the patient presents to the emergency department (ED) for worsening of his chest acne, along with pain and bleeding from some of the lesions.

What’s the diagnosis?

DISCUSSION
The risk for granulation tissue formation is a well-known though rare adverse effect of isotretinoin use—one that had been discussed thoroughly with the patient and his parents prior to prescription. There is no unanimity of opinion regarding the mechanism whereby this response occurs, but it is real. It can affect such areas as seen in this patient’s case but also causes a similar problem in the perionychial tissues, creating a condition quite similar to an ingrown toenail (cryptonychia). This author has also seen the same phenomenon in fingernails.

In this patient’s case, after discharge from the ED, he presented immediately to his primary care provider, who in turn called the dermatology clinic. When we saw him, there was clear evidence of inappropriate granulation formation—far worse than the initial acne had been.

The patient was given an intramuscular injection of 40 mg triamcinolone and prescribed minocycline 100 mg bid. He had already stopped taking the isotretinoin and was strongly advised not to restart it for the foreseeable future. In hindsight, he probably should have been started on minocycline and a 3-week prednisone taper to calm down his chest acne before the isotretinoin was started.

At a follow-up appointment 3 weeks later, his condition was much improved (at least back to baseline). But he will almost certainly develop hypertrophic scarring on his chest—and given the severity of his acne and the strong family history, he may well have a suboptimal response to isotretinoin when and if we return to that medication.

TAKE-HOME LEARNING POINTS

• In rare instances, isotretinoin therapy can trigger the formation of inappropriate granulation tissue on the face, back, chest, and even perionychial areas.
• There is evidence that the more inflamed the acne, the greater the likelihood of this adverse effect.
• With severely inflamed acne, consideration should be given to using small initial doses of isotretinoin or decreasing the inflammation through use of systemic steroids or doxycycline or minocycline.

For several years, this 16-year-old boy has had severe acne on his chest and back. The condition has steadily worsened despite use of OTC medications, including benzoyl peroxide–containing topical products. He has never received prescription treatment. His primary care provider, concerned that something more than acne could be involved, refers him to dermatology for evaluation and treatment.

The boy’s health is reportedly otherwise excellent. Family history is positive for severe acne on both sides of his family; two of his older siblings have had similar problems.

EXAMINATION
The central portion of the boy’s chest is covered by an impressive collection of discrete and confluent crusts and erosions. Some are quite deep, and the patient admits to picking at them. Little if any erythema surrounds the lesions.

Very little acne is seen on the boy’s face, but fairly dense acne vulgaris is observed on his upper back.

Following a brief but thorough discussion, the decision is made to start therapy with low-dose isotretinoin (20 mg/d), after the appropriate bloodwork is obtained. Within a week, the patient presents to the emergency department (ED) for worsening of his chest acne, along with pain and bleeding from some of the lesions.

What’s the diagnosis?

DISCUSSION
The risk for granulation tissue formation is a well-known though rare adverse effect of isotretinoin use—one that had been discussed thoroughly with the patient and his parents prior to prescription. There is no unanimity of opinion regarding the mechanism whereby this response occurs, but it is real. It can affect such areas as seen in this patient’s case but also causes a similar problem in the perionychial tissues, creating a condition quite similar to an ingrown toenail (cryptonychia). This author has also seen the same phenomenon in fingernails.

In this patient’s case, after discharge from the ED, he presented immediately to his primary care provider, who in turn called the dermatology clinic. When we saw him, there was clear evidence of inappropriate granulation formation—far worse than the initial acne had been.

The patient was given an intramuscular injection of 40 mg triamcinolone and prescribed minocycline 100 mg bid. He had already stopped taking the isotretinoin and was strongly advised not to restart it for the foreseeable future. In hindsight, he probably should have been started on minocycline and a 3-week prednisone taper to calm down his chest acne before the isotretinoin was started.

At a follow-up appointment 3 weeks later, his condition was much improved (at least back to baseline). But he will almost certainly develop hypertrophic scarring on his chest—and given the severity of his acne and the strong family history, he may well have a suboptimal response to isotretinoin when and if we return to that medication.

TAKE-HOME LEARNING POINTS

• In rare instances, isotretinoin therapy can trigger the formation of inappropriate granulation tissue on the face, back, chest, and even perionychial areas.
• There is evidence that the more inflamed the acne, the greater the likelihood of this adverse effect.
• With severely inflamed acne, consideration should be given to using small initial doses of isotretinoin or decreasing the inflammation through use of systemic steroids or doxycycline or minocycline.