Clinical Topics & News

BERLIN – The presence of infratentorial and deep white matter lesions early in the course of relapse-onset multiple sclerosis was associated with high levels of disability 30 years later in a study looking at MRI predictors.

Sara Freeman/MDedge News

Univariate predictors of an Expanded Disability Status Scale (EDSS) score of more than 3.5, which is indicative of impaired mobility after 30 years, were the presence of an IT lesion at baseline, with an odds ratio (OR) of 12.4 (95% confidence interval [CI], 3.35-3.46; P less than .001), the presence of a deep white matter (DWM) lesion 1 year after presenting with clinically-isolated syndrome (CIS; OR = 10.65; 95% CI, 2.84-38.84; P less than .001), and the presence of an infratentorial (IT) lesion 1 year post CIS presentation (OR = 11.1; 95% CI, 3.31-37.22; P less than .001). At 5 years after a CIS presentation, the EDSS score, EDSS score change, and a DWM lesion score of more than 5 were indicative of worse disability after 30 years.

There was no significant association with age of onset, gender, CIS type, baseline EDSS, or disease duration, study investigator Karen Chung, MBBS, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

“As we know, approximately 85% of people with MS initially present with a clinically isolated syndrome,” said Dr. Chung, a clinical research associate at the Queen Square Multiple Sclerosis Centre in the UCL Institute of Neurology in London. She added that the long-term prognosis after CIS is very variable, with some patients developing little detectable disability over time, while others may experience considerable decline.

There have been few studies examining whether there are any MRI parameters that might help predict patients’ long-term outcomes, so the aim of the study Dr. Chung presented was to see if there were any MRI parameters that might be predictive of clinical outcome 30 years after the onset of CIS.

Dr. Chung and her coauthors examined data on 120 of 132 individuals from the First London CIS Cohort who were prospectively recruited between 1984 and 1987 and had known outcomes. They looked at prospectively gathered MRI data and EDSS data at baseline, 5, 10, 14, 20, and 30 years. MRI data were obtained for 1 year after the CIS event, and data on the lowest EDSS score after the CIS event were retrospectively determined from patient notes or recall. The cohort was predominantly female (61%), with a mean of 31.5 years at CIS onset. Around half (52%) presented with optic neuritis, 27% with a spinal cord syndrome, and 20% with a brainstem syndrome. The high percentage of patients presenting with optic neuritis may be due to the fact that one of the recruiting centers was a specialist eye hospital, Dr. Chung noted later during discussion.

The 2010 McDonald Criteria were used to determine whether patients had CIS, relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), or death related to MS.

“We looked at all the MRIs available to us and quantified the T2 lesion count for whole brain as well as by location,” Dr. Chung explained. The locations considered were juxtacortical, periventricular, infratentorial, and deep white matter.

“I think it is important to remind ourselves that we have come a long way with MRI technology in the 30 years timespan,” she added, noting that there was “clearly a difference in the quality.”

Clinical outcomes at 30 years were as follows: 80 patients (67%) developed MS, of whom 35 (44%) had RRMS, 26 (33%) had SPMS, 15 (20%) had died as a result of MS, and 3 (4%) had died for unknown or unrelated causes. Of the 40 patients (33%) who remained with CIS, 10 (25%) died without developing MS.

“This is a largely untreated cohort where, within the 80 people with MS, 11 (14%) were treated with a DMT [disease-modifying treatment] at some point,” Dr. Chung reported. All DMTs used were first-line injectable agents, she observed.

EDSS scores could be obtained for 107 patients. At 30 years, people with low EDSS scores were those who remained with CIS or RRMS, and as EDSS scores increased, the severity of MS increased.

“Overall, T2 lesions were better predictors of 30-year outcome than EDSS,” Dr. Chung said. For combinations of predictors, patients who had at least one IT and one DWM lesion within 1 year of a CIS had a higher probability (94%) of having an EDSS score of more than 3.5 at 30 years than when compared with those with neither lesion (13%) and those with one DWM but no IT lesions (49%).

Looking at the best independent predictors up to 5 years, the predicted probability of an EDSS score of more than 3.5 if there were no IT lesions and fewer than five DWM lesions was 18%. But if there were no IT but more than 5 DWM lesions, the probability of disability at 30 years rose to 52%. The probabilities rose even higher to 63% if there was one or more IT and five or less DWM lesions and 90% if there was one or more IT and more than five DWM lesions.

“In this cohort, the presence of early infratentorial and deep white matter lesions following a CIS are associated with higher level of disability 30 years later,” Dr. Chung concluded. “Early predictive models can add information to risk-benefit stratification.”

During discussion, one delegate expressed concerns that these data were “not generalizable to the current situation.” This was a cohort of patients that largely wasn’t treated or if they were, treatment was delayed by more than 10 years. These data were interesting “from a historical perspective,” he argued, “but I don’t understand, how in the absence of contemporary therapies this is applicable in a way that will allow us to use this information to make prognoses for the future.”

Dr. Chung agreed, noting that this was more of a natural history study. “However, I think it is applicable in clinical practice in my opinion.

“When you have a patient presenting with a CIS, at the time of diagnosis, especially now when we can diagnose patients earlier with the new 2017 criteria, it will be helpful for the patient and ourselves to apply some of the information I presented to help perhaps in aiding decisions regarding treatment.”

The study was funded by a grant from the MS Society of Great Britain. Dr. Chung disclosed receiving honoraria from Teva, Biogen, and Roche.

SOURCE: Chung K et al. Mult Scler. 2018;24(S2):58-59, Abstract 157.

BERLIN – The presence of infratentorial and deep white matter lesions early in the course of relapse-onset multiple sclerosis was associated with high levels of disability 30 years later in a study looking at MRI predictors.

Sara Freeman/MDedge News

Univariate predictors of an Expanded Disability Status Scale (EDSS) score of more than 3.5, which is indicative of impaired mobility after 30 years, were the presence of an IT lesion at baseline, with an odds ratio (OR) of 12.4 (95% confidence interval [CI], 3.35-3.46; P less than .001), the presence of a deep white matter (DWM) lesion 1 year after presenting with clinically-isolated syndrome (CIS; OR = 10.65; 95% CI, 2.84-38.84; P less than .001), and the presence of an infratentorial (IT) lesion 1 year post CIS presentation (OR = 11.1; 95% CI, 3.31-37.22; P less than .001). At 5 years after a CIS presentation, the EDSS score, EDSS score change, and a DWM lesion score of more than 5 were indicative of worse disability after 30 years.

There was no significant association with age of onset, gender, CIS type, baseline EDSS, or disease duration, study investigator Karen Chung, MBBS, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

“As we know, approximately 85% of people with MS initially present with a clinically isolated syndrome,” said Dr. Chung, a clinical research associate at the Queen Square Multiple Sclerosis Centre in the UCL Institute of Neurology in London. She added that the long-term prognosis after CIS is very variable, with some patients developing little detectable disability over time, while others may experience considerable decline.

There have been few studies examining whether there are any MRI parameters that might help predict patients’ long-term outcomes, so the aim of the study Dr. Chung presented was to see if there were any MRI parameters that might be predictive of clinical outcome 30 years after the onset of CIS.

Dr. Chung and her coauthors examined data on 120 of 132 individuals from the First London CIS Cohort who were prospectively recruited between 1984 and 1987 and had known outcomes. They looked at prospectively gathered MRI data and EDSS data at baseline, 5, 10, 14, 20, and 30 years. MRI data were obtained for 1 year after the CIS event, and data on the lowest EDSS score after the CIS event were retrospectively determined from patient notes or recall. The cohort was predominantly female (61%), with a mean of 31.5 years at CIS onset. Around half (52%) presented with optic neuritis, 27% with a spinal cord syndrome, and 20% with a brainstem syndrome. The high percentage of patients presenting with optic neuritis may be due to the fact that one of the recruiting centers was a specialist eye hospital, Dr. Chung noted later during discussion.

The 2010 McDonald Criteria were used to determine whether patients had CIS, relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), or death related to MS.

“We looked at all the MRIs available to us and quantified the T2 lesion count for whole brain as well as by location,” Dr. Chung explained. The locations considered were juxtacortical, periventricular, infratentorial, and deep white matter.

“I think it is important to remind ourselves that we have come a long way with MRI technology in the 30 years timespan,” she added, noting that there was “clearly a difference in the quality.”

Clinical outcomes at 30 years were as follows: 80 patients (67%) developed MS, of whom 35 (44%) had RRMS, 26 (33%) had SPMS, 15 (20%) had died as a result of MS, and 3 (4%) had died for unknown or unrelated causes. Of the 40 patients (33%) who remained with CIS, 10 (25%) died without developing MS.

“This is a largely untreated cohort where, within the 80 people with MS, 11 (14%) were treated with a DMT [disease-modifying treatment] at some point,” Dr. Chung reported. All DMTs used were first-line injectable agents, she observed.

EDSS scores could be obtained for 107 patients. At 30 years, people with low EDSS scores were those who remained with CIS or RRMS, and as EDSS scores increased, the severity of MS increased.

“Overall, T2 lesions were better predictors of 30-year outcome than EDSS,” Dr. Chung said. For combinations of predictors, patients who had at least one IT and one DWM lesion within 1 year of a CIS had a higher probability (94%) of having an EDSS score of more than 3.5 at 30 years than when compared with those with neither lesion (13%) and those with one DWM but no IT lesions (49%).

Looking at the best independent predictors up to 5 years, the predicted probability of an EDSS score of more than 3.5 if there were no IT lesions and fewer than five DWM lesions was 18%. But if there were no IT but more than 5 DWM lesions, the probability of disability at 30 years rose to 52%. The probabilities rose even higher to 63% if there was one or more IT and five or less DWM lesions and 90% if there was one or more IT and more than five DWM lesions.

“In this cohort, the presence of early infratentorial and deep white matter lesions following a CIS are associated with higher level of disability 30 years later,” Dr. Chung concluded. “Early predictive models can add information to risk-benefit stratification.”

During discussion, one delegate expressed concerns that these data were “not generalizable to the current situation.” This was a cohort of patients that largely wasn’t treated or if they were, treatment was delayed by more than 10 years. These data were interesting “from a historical perspective,” he argued, “but I don’t understand, how in the absence of contemporary therapies this is applicable in a way that will allow us to use this information to make prognoses for the future.”

Dr. Chung agreed, noting that this was more of a natural history study. “However, I think it is applicable in clinical practice in my opinion.

“When you have a patient presenting with a CIS, at the time of diagnosis, especially now when we can diagnose patients earlier with the new 2017 criteria, it will be helpful for the patient and ourselves to apply some of the information I presented to help perhaps in aiding decisions regarding treatment.”

The study was funded by a grant from the MS Society of Great Britain. Dr. Chung disclosed receiving honoraria from Teva, Biogen, and Roche.

SOURCE: Chung K et al. Mult Scler. 2018;24(S2):58-59, Abstract 157.

BERLIN – The presence of infratentorial and deep white matter lesions early in the course of relapse-onset multiple sclerosis was associated with high levels of disability 30 years later in a study looking at MRI predictors.

Sara Freeman/MDedge News

Univariate predictors of an Expanded Disability Status Scale (EDSS) score of more than 3.5, which is indicative of impaired mobility after 30 years, were the presence of an IT lesion at baseline, with an odds ratio (OR) of 12.4 (95% confidence interval [CI], 3.35-3.46; P less than .001), the presence of a deep white matter (DWM) lesion 1 year after presenting with clinically-isolated syndrome (CIS; OR = 10.65; 95% CI, 2.84-38.84; P less than .001), and the presence of an infratentorial (IT) lesion 1 year post CIS presentation (OR = 11.1; 95% CI, 3.31-37.22; P less than .001). At 5 years after a CIS presentation, the EDSS score, EDSS score change, and a DWM lesion score of more than 5 were indicative of worse disability after 30 years.

There was no significant association with age of onset, gender, CIS type, baseline EDSS, or disease duration, study investigator Karen Chung, MBBS, reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

“As we know, approximately 85% of people with MS initially present with a clinically isolated syndrome,” said Dr. Chung, a clinical research associate at the Queen Square Multiple Sclerosis Centre in the UCL Institute of Neurology in London. She added that the long-term prognosis after CIS is very variable, with some patients developing little detectable disability over time, while others may experience considerable decline.

There have been few studies examining whether there are any MRI parameters that might help predict patients’ long-term outcomes, so the aim of the study Dr. Chung presented was to see if there were any MRI parameters that might be predictive of clinical outcome 30 years after the onset of CIS.

Dr. Chung and her coauthors examined data on 120 of 132 individuals from the First London CIS Cohort who were prospectively recruited between 1984 and 1987 and had known outcomes. They looked at prospectively gathered MRI data and EDSS data at baseline, 5, 10, 14, 20, and 30 years. MRI data were obtained for 1 year after the CIS event, and data on the lowest EDSS score after the CIS event were retrospectively determined from patient notes or recall. The cohort was predominantly female (61%), with a mean of 31.5 years at CIS onset. Around half (52%) presented with optic neuritis, 27% with a spinal cord syndrome, and 20% with a brainstem syndrome. The high percentage of patients presenting with optic neuritis may be due to the fact that one of the recruiting centers was a specialist eye hospital, Dr. Chung noted later during discussion.

The 2010 McDonald Criteria were used to determine whether patients had CIS, relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), or death related to MS.

“We looked at all the MRIs available to us and quantified the T2 lesion count for whole brain as well as by location,” Dr. Chung explained. The locations considered were juxtacortical, periventricular, infratentorial, and deep white matter.

“I think it is important to remind ourselves that we have come a long way with MRI technology in the 30 years timespan,” she added, noting that there was “clearly a difference in the quality.”

Clinical outcomes at 30 years were as follows: 80 patients (67%) developed MS, of whom 35 (44%) had RRMS, 26 (33%) had SPMS, 15 (20%) had died as a result of MS, and 3 (4%) had died for unknown or unrelated causes. Of the 40 patients (33%) who remained with CIS, 10 (25%) died without developing MS.

“This is a largely untreated cohort where, within the 80 people with MS, 11 (14%) were treated with a DMT [disease-modifying treatment] at some point,” Dr. Chung reported. All DMTs used were first-line injectable agents, she observed.

EDSS scores could be obtained for 107 patients. At 30 years, people with low EDSS scores were those who remained with CIS or RRMS, and as EDSS scores increased, the severity of MS increased.

“Overall, T2 lesions were better predictors of 30-year outcome than EDSS,” Dr. Chung said. For combinations of predictors, patients who had at least one IT and one DWM lesion within 1 year of a CIS had a higher probability (94%) of having an EDSS score of more than 3.5 at 30 years than when compared with those with neither lesion (13%) and those with one DWM but no IT lesions (49%).

Looking at the best independent predictors up to 5 years, the predicted probability of an EDSS score of more than 3.5 if there were no IT lesions and fewer than five DWM lesions was 18%. But if there were no IT but more than 5 DWM lesions, the probability of disability at 30 years rose to 52%. The probabilities rose even higher to 63% if there was one or more IT and five or less DWM lesions and 90% if there was one or more IT and more than five DWM lesions.

“In this cohort, the presence of early infratentorial and deep white matter lesions following a CIS are associated with higher level of disability 30 years later,” Dr. Chung concluded. “Early predictive models can add information to risk-benefit stratification.”

During discussion, one delegate expressed concerns that these data were “not generalizable to the current situation.” This was a cohort of patients that largely wasn’t treated or if they were, treatment was delayed by more than 10 years. These data were interesting “from a historical perspective,” he argued, “but I don’t understand, how in the absence of contemporary therapies this is applicable in a way that will allow us to use this information to make prognoses for the future.”

Dr. Chung agreed, noting that this was more of a natural history study. “However, I think it is applicable in clinical practice in my opinion.

“When you have a patient presenting with a CIS, at the time of diagnosis, especially now when we can diagnose patients earlier with the new 2017 criteria, it will be helpful for the patient and ourselves to apply some of the information I presented to help perhaps in aiding decisions regarding treatment.”

The study was funded by a grant from the MS Society of Great Britain. Dr. Chung disclosed receiving honoraria from Teva, Biogen, and Roche.

SOURCE: Chung K et al. Mult Scler. 2018;24(S2):58-59, Abstract 157.

Cancer survivors have a higher risk of depression within 2 years after the diagnosis, according to a meta-analysis. But is that true of survivors of all types of cancer? In fact, risk is multifactorial because patients, cancers, comorbidities, and impacts of treatments are all different, say researchers who conducted a study to compare the risk of mood disorders longitudinally.

They matched 190,748 survivors with controls from the Taiwan National Health Insurance Research Database. The median follow-up times were 8.13 and 8.49 years, respectively. The 3 most common cancers were breast, colorectal, and head and neck. Surgery alone was the main treatment, followed by combinations of surgery, chemotherapy, and radiation.

Survivors had a significantly higher risk of mood disorders: 8.38 per 1,000 person-years, compared with 7.21 in the control patients. Major depression and depression disorder were the most common subtypes.

However, the risk of mood disorders (1.13-fold) peaked during the year after the index date and declined thereafter. Moreover, 2 and 5 years later, the risk was similar between the 2 groups. And after 5 years, the risk was even lower in the survivor group than in the control group.

The researchers found patients fell into 3 main categories: persistently increasing risk, higher risk in the first few years and after 5 years of follow-up, and higher risk in the first few years but no difference thereafter. Patients with head and neck cancer, nasopharyngeal cancer, and esophageal cancer were in the first group, with distinct longitudinal patterns. Their risk at 5 years was greater than that of the general population.

Being female, aged 40-59 years, having > 2 primary cancers, having ≥ 2 treatment modalities, Charlson comorbidity index scores > 3, higher urbanization level, and lower income levels were independent risk factors for mood disorders.

The researchers say their findings highlight the importance of taking follow-up time, cancer types, and cancer-related treatment into consideration when evaluating mood disorders in cancer survivors. They also emphasize the need for better psychological management not only in the early postdiagnosis years, but in late follow-up for patients with a “persistent” risk.

Source:
Huang WK, Juang YY, Chung CC, et al. J Affect Disord. 2018;236:80-87.

Cancer survivors have a higher risk of depression within 2 years after the diagnosis, according to a meta-analysis. But is that true of survivors of all types of cancer? In fact, risk is multifactorial because patients, cancers, comorbidities, and impacts of treatments are all different, say researchers who conducted a study to compare the risk of mood disorders longitudinally.

They matched 190,748 survivors with controls from the Taiwan National Health Insurance Research Database. The median follow-up times were 8.13 and 8.49 years, respectively. The 3 most common cancers were breast, colorectal, and head and neck. Surgery alone was the main treatment, followed by combinations of surgery, chemotherapy, and radiation.

Survivors had a significantly higher risk of mood disorders: 8.38 per 1,000 person-years, compared with 7.21 in the control patients. Major depression and depression disorder were the most common subtypes.

However, the risk of mood disorders (1.13-fold) peaked during the year after the index date and declined thereafter. Moreover, 2 and 5 years later, the risk was similar between the 2 groups. And after 5 years, the risk was even lower in the survivor group than in the control group.

The researchers found patients fell into 3 main categories: persistently increasing risk, higher risk in the first few years and after 5 years of follow-up, and higher risk in the first few years but no difference thereafter. Patients with head and neck cancer, nasopharyngeal cancer, and esophageal cancer were in the first group, with distinct longitudinal patterns. Their risk at 5 years was greater than that of the general population.

Being female, aged 40-59 years, having > 2 primary cancers, having ≥ 2 treatment modalities, Charlson comorbidity index scores > 3, higher urbanization level, and lower income levels were independent risk factors for mood disorders.

The researchers say their findings highlight the importance of taking follow-up time, cancer types, and cancer-related treatment into consideration when evaluating mood disorders in cancer survivors. They also emphasize the need for better psychological management not only in the early postdiagnosis years, but in late follow-up for patients with a “persistent” risk.

Source:
Huang WK, Juang YY, Chung CC, et al. J Affect Disord. 2018;236:80-87.

Cancer survivors have a higher risk of depression within 2 years after the diagnosis, according to a meta-analysis. But is that true of survivors of all types of cancer? In fact, risk is multifactorial because patients, cancers, comorbidities, and impacts of treatments are all different, say researchers who conducted a study to compare the risk of mood disorders longitudinally.

They matched 190,748 survivors with controls from the Taiwan National Health Insurance Research Database. The median follow-up times were 8.13 and 8.49 years, respectively. The 3 most common cancers were breast, colorectal, and head and neck. Surgery alone was the main treatment, followed by combinations of surgery, chemotherapy, and radiation.

Survivors had a significantly higher risk of mood disorders: 8.38 per 1,000 person-years, compared with 7.21 in the control patients. Major depression and depression disorder were the most common subtypes.

However, the risk of mood disorders (1.13-fold) peaked during the year after the index date and declined thereafter. Moreover, 2 and 5 years later, the risk was similar between the 2 groups. And after 5 years, the risk was even lower in the survivor group than in the control group.

The researchers found patients fell into 3 main categories: persistently increasing risk, higher risk in the first few years and after 5 years of follow-up, and higher risk in the first few years but no difference thereafter. Patients with head and neck cancer, nasopharyngeal cancer, and esophageal cancer were in the first group, with distinct longitudinal patterns. Their risk at 5 years was greater than that of the general population.

Being female, aged 40-59 years, having > 2 primary cancers, having ≥ 2 treatment modalities, Charlson comorbidity index scores > 3, higher urbanization level, and lower income levels were independent risk factors for mood disorders.

The researchers say their findings highlight the importance of taking follow-up time, cancer types, and cancer-related treatment into consideration when evaluating mood disorders in cancer survivors. They also emphasize the need for better psychological management not only in the early postdiagnosis years, but in late follow-up for patients with a “persistent” risk.

Source:
Huang WK, Juang YY, Chung CC, et al. J Affect Disord. 2018;236:80-87.

The National Multiple Sclerosis (MS) Society has developed recommendations for the identification and management of cognitive impairment in MS. The recommendations, which were endorsed by the Consortium of MS Centers and the International MS Cognition Society, were published online ahead of print October 10 in Multiple Sclerosis Journal.

Cognitive change may affect between 34% and 65% of adults with MS. Decreases in information processing and memory are the most common changes, and cognitive impairment may arise before MRI abnormalities that indicate MS. These changes can affect patients’ ability to work, drive, manage money, and participate in activities.

Patients and Clinicians Need Information

Patients and caregivers should receive information about common cognitive changes in MS and how they affect everyday life, said Rosalind Kalb, PhD, Vice President of the Professional Resource Center at the National MS Society in New York, and coauthors. Patients and caregivers also should be told about the high prevalence of cognitive symptoms in MS and the need for ongoing assessments. Similarly, clinicians need information about how cognitive impairments affect medical decision-making and adherence, said the authors. Clinicians also need referral resources for cognitive assessment and treatment.

All adults and children age 8 or older diagnosed with MS should, as a minimum, undergo early baseline screening with the Symbol Digit Modalities Test (SDMT) or another validated screening tool, according to the recommendations. These patients should be reassessed with the same instrument annually or more often, as needed, to detect disease activity, assess for treatment effects or relapse recovery, monitor progression of cognitive impairment, and screen for new cognitive problems.

In addition to the SDMT, screening tools that have been validated in patients with MS include the Processing Speed Test, Computerized Speed Cognitive Test, MS Neuropsychological Screening Questionnaire, Brief International Cognitive Assessment for MS, Brief Repeatable Neuropsychological Battery, and Minimal Assessment of Cognitive Function in MS.

Interventions May Improve or Maintain Function

An adult who tests positive for cognitive impairment on initial screening should undergo a more comprehensive assessment, especially if the person has comorbidities that raise concerns or is applying for disability due to cognitive impairment. A child with an unexplained change in school performance should receive a neuropsychologic evaluation, said Dr. Kalb and colleagues.

Furthermore, adults and children should be offered remedial interventions or accommodations to improve function at home, work, or school. Appropriately trained professionals should deliver these interventions to address “objectively measured deficits in attention, processing speed, memory and learning, and performance of everyday functional tasks,” said the authors. Clinicians can consider contextualized treatment (eg, self-generated learning tasks) and noncontextualized treatment (eg, memory-retrieval practice and computer-based attention interventions) for remediation of everyday activities, according to the recommendations.

Emerging research supports the potential for exercise to benefit cognitive processing speed in patients with MS. Trials of symptomatic pharmacologic treatments for cognitive impairment related to MS have yielded inconclusive results, however. In addition, few pivotal trials of disease-modifying therapies have incorporated cognitive outcome measures.

—Erik Greb

Suggested Reading

Kalb R, Beier M, Benedict RH, et al. Recommendations for cognitive screening and management in multiple sclerosis care. Mult Scler. 2018 Oct 10 [Epub ahead of print].

The National Multiple Sclerosis (MS) Society has developed recommendations for the identification and management of cognitive impairment in MS. The recommendations, which were endorsed by the Consortium of MS Centers and the International MS Cognition Society, were published online ahead of print October 10 in Multiple Sclerosis Journal.

Cognitive change may affect between 34% and 65% of adults with MS. Decreases in information processing and memory are the most common changes, and cognitive impairment may arise before MRI abnormalities that indicate MS. These changes can affect patients’ ability to work, drive, manage money, and participate in activities.

Patients and Clinicians Need Information

Patients and caregivers should receive information about common cognitive changes in MS and how they affect everyday life, said Rosalind Kalb, PhD, Vice President of the Professional Resource Center at the National MS Society in New York, and coauthors. Patients and caregivers also should be told about the high prevalence of cognitive symptoms in MS and the need for ongoing assessments. Similarly, clinicians need information about how cognitive impairments affect medical decision-making and adherence, said the authors. Clinicians also need referral resources for cognitive assessment and treatment.

All adults and children age 8 or older diagnosed with MS should, as a minimum, undergo early baseline screening with the Symbol Digit Modalities Test (SDMT) or another validated screening tool, according to the recommendations. These patients should be reassessed with the same instrument annually or more often, as needed, to detect disease activity, assess for treatment effects or relapse recovery, monitor progression of cognitive impairment, and screen for new cognitive problems.

In addition to the SDMT, screening tools that have been validated in patients with MS include the Processing Speed Test, Computerized Speed Cognitive Test, MS Neuropsychological Screening Questionnaire, Brief International Cognitive Assessment for MS, Brief Repeatable Neuropsychological Battery, and Minimal Assessment of Cognitive Function in MS.

Interventions May Improve or Maintain Function

An adult who tests positive for cognitive impairment on initial screening should undergo a more comprehensive assessment, especially if the person has comorbidities that raise concerns or is applying for disability due to cognitive impairment. A child with an unexplained change in school performance should receive a neuropsychologic evaluation, said Dr. Kalb and colleagues.

Furthermore, adults and children should be offered remedial interventions or accommodations to improve function at home, work, or school. Appropriately trained professionals should deliver these interventions to address “objectively measured deficits in attention, processing speed, memory and learning, and performance of everyday functional tasks,” said the authors. Clinicians can consider contextualized treatment (eg, self-generated learning tasks) and noncontextualized treatment (eg, memory-retrieval practice and computer-based attention interventions) for remediation of everyday activities, according to the recommendations.

Emerging research supports the potential for exercise to benefit cognitive processing speed in patients with MS. Trials of symptomatic pharmacologic treatments for cognitive impairment related to MS have yielded inconclusive results, however. In addition, few pivotal trials of disease-modifying therapies have incorporated cognitive outcome measures.

—Erik Greb

Suggested Reading

Kalb R, Beier M, Benedict RH, et al. Recommendations for cognitive screening and management in multiple sclerosis care. Mult Scler. 2018 Oct 10 [Epub ahead of print].

The National Multiple Sclerosis (MS) Society has developed recommendations for the identification and management of cognitive impairment in MS. The recommendations, which were endorsed by the Consortium of MS Centers and the International MS Cognition Society, were published online ahead of print October 10 in Multiple Sclerosis Journal.

Cognitive change may affect between 34% and 65% of adults with MS. Decreases in information processing and memory are the most common changes, and cognitive impairment may arise before MRI abnormalities that indicate MS. These changes can affect patients’ ability to work, drive, manage money, and participate in activities.

Patients and Clinicians Need Information

Patients and caregivers should receive information about common cognitive changes in MS and how they affect everyday life, said Rosalind Kalb, PhD, Vice President of the Professional Resource Center at the National MS Society in New York, and coauthors. Patients and caregivers also should be told about the high prevalence of cognitive symptoms in MS and the need for ongoing assessments. Similarly, clinicians need information about how cognitive impairments affect medical decision-making and adherence, said the authors. Clinicians also need referral resources for cognitive assessment and treatment.

All adults and children age 8 or older diagnosed with MS should, as a minimum, undergo early baseline screening with the Symbol Digit Modalities Test (SDMT) or another validated screening tool, according to the recommendations. These patients should be reassessed with the same instrument annually or more often, as needed, to detect disease activity, assess for treatment effects or relapse recovery, monitor progression of cognitive impairment, and screen for new cognitive problems.

In addition to the SDMT, screening tools that have been validated in patients with MS include the Processing Speed Test, Computerized Speed Cognitive Test, MS Neuropsychological Screening Questionnaire, Brief International Cognitive Assessment for MS, Brief Repeatable Neuropsychological Battery, and Minimal Assessment of Cognitive Function in MS.

Interventions May Improve or Maintain Function

An adult who tests positive for cognitive impairment on initial screening should undergo a more comprehensive assessment, especially if the person has comorbidities that raise concerns or is applying for disability due to cognitive impairment. A child with an unexplained change in school performance should receive a neuropsychologic evaluation, said Dr. Kalb and colleagues.

Furthermore, adults and children should be offered remedial interventions or accommodations to improve function at home, work, or school. Appropriately trained professionals should deliver these interventions to address “objectively measured deficits in attention, processing speed, memory and learning, and performance of everyday functional tasks,” said the authors. Clinicians can consider contextualized treatment (eg, self-generated learning tasks) and noncontextualized treatment (eg, memory-retrieval practice and computer-based attention interventions) for remediation of everyday activities, according to the recommendations.

Emerging research supports the potential for exercise to benefit cognitive processing speed in patients with MS. Trials of symptomatic pharmacologic treatments for cognitive impairment related to MS have yielded inconclusive results, however. In addition, few pivotal trials of disease-modifying therapies have incorporated cognitive outcome measures.

—Erik Greb

Suggested Reading

Kalb R, Beier M, Benedict RH, et al. Recommendations for cognitive screening and management in multiple sclerosis care. Mult Scler. 2018 Oct 10 [Epub ahead of print].

BERLIN – In children with an incident acquired demyelinating episode, the presence of antibodies against myelin oligodendrocyte glycoprotein (MOG) weighs against an eventual diagnosis of multiple sclerosis, especially if the child is younger than 11 years.

“Anti-MOG antibodies are present in about 30% of children with acquired demyelinating syndromes,” Giulia Fadda, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. “About 80% experience a monophasic disease course.”

The antibodies are found in almost all children who have a relapsing non-MS demyelinating disease, said Dr. Fadda, who is a postdoctoral research fellow at the University of Pennsylvania, Philadelphia. But when the antibodies are present in children with an MS diagnosis, they identify a very specific subset with atypical clinical and imaging features.

The large prospective Canadian Pediatric Demyelinating Disease Study provided the sample for the study she presented at ECTRIMS. Children are recruited into the study soon after a first demyelinating event, and they are followed clinically, serologically, and with regular brain MRI.


The cohort in Dr. Fadda’s study comprised 275 children who were a mean of about 11 years old at symptom onset. The mean clinical follow-up was 6.7 years; the mean serologic follow-up, 4 years, and the mean imaging follow-up, 3.5 years. The study examined 1,368 serum samples and 1,459 MRI scans.

Overall, 32% of the children were positive for anti-MOG antibodies. Positivity was not associated with sex, but children with antibodies were significantly younger than those without (7 vs. 12 years). In fact, 77% of anti-MOG–positive children were younger than 11 years; just 15% of older children were positive for the antibodies.

Anti-MOG positivity was also associated with certain clinical phenotypes. Among positive children, 40% presented with optic neuritis, 37% with acute disseminated encephalomyelitis, and 14% with transverse myelitis; the rest had other phenotypes. Optic neuritis was significantly less common among antibody-negative patients (22%), as was encephalomyelitis (17%). Transverse myelitis was significantly more common (31%).

The analysis of MRI scans was stratified according to age younger than 11 years and 11 years and older. “The first thing we noticed among the younger MOG-positive children is that they had a high number of lesions, which were more commonly ill-defined, diffuse, and bilateral,” Dr. Fadda said. “Almost all the brain areas were affected, with a slight preponderance of thalamic and juxtacortical lesions. Among the MOG-negative children, lesions were more often perpendicular to the major axis of the corpus callosum.”

Among the older MOG antibody–positive children, the diffuse pattern was rarer, and the lesions were frequently cerebellar. “But by far, the features that best differentiated positivity from negativity were black holes and enhancing lesions, which we saw in a high proportion of children without the antibodies” at 73% and 49%, respectively.

Over a mean imaging follow-up period of 4 years, lesions were more likely to resolve completely in antibody-positive children than in those without antibodies (50% vs. 21%). Serologically, children who were MOG-antibody negative at baseline were likely to stay that way, with 99% remaining seronegative. Positive children, on the other hand, were significantly more likely to change serologic status, with 56% turning negative and 8% serologically fluctuating over the follow-up period; only 36% remained persistently seropositive. Persistent positive status was significantly associated with younger age (7 vs. 9 years) and an optic neuritis presentation (62% vs. 27%).

Most children (81%) who were antibody positive at baseline experienced no relapses. Among the 16 children who did experience a clinical relapse, the mean time to a second event was about 1 year. Nine of these children stayed persistently positive, while five seroconverted and two had fluctuating status.

Of the 60 antibody-positive children who had a monophasic course, 23 were persistently positive, 34 seroconverted, and 3 had fluctuating serology.

Eventually, 54 children received an MS diagnosis. Of these, 83% were antibody negative at baseline. Ten children received a diagnosis of a relapsing non-MS demyelinating disorder; of these, 91% were antibody positive at baseline.

Dr. Fadda disclosed relationships with Atara Biotherapeutic and Sanofi-Genzyme.

[email protected]

SOURCE: Waters P et al. Mult Scler. 2018;24(S2):29-30, Abstract 65.

BERLIN – In children with an incident acquired demyelinating episode, the presence of antibodies against myelin oligodendrocyte glycoprotein (MOG) weighs against an eventual diagnosis of multiple sclerosis, especially if the child is younger than 11 years.

“Anti-MOG antibodies are present in about 30% of children with acquired demyelinating syndromes,” Giulia Fadda, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. “About 80% experience a monophasic disease course.”

The antibodies are found in almost all children who have a relapsing non-MS demyelinating disease, said Dr. Fadda, who is a postdoctoral research fellow at the University of Pennsylvania, Philadelphia. But when the antibodies are present in children with an MS diagnosis, they identify a very specific subset with atypical clinical and imaging features.

The large prospective Canadian Pediatric Demyelinating Disease Study provided the sample for the study she presented at ECTRIMS. Children are recruited into the study soon after a first demyelinating event, and they are followed clinically, serologically, and with regular brain MRI.


The cohort in Dr. Fadda’s study comprised 275 children who were a mean of about 11 years old at symptom onset. The mean clinical follow-up was 6.7 years; the mean serologic follow-up, 4 years, and the mean imaging follow-up, 3.5 years. The study examined 1,368 serum samples and 1,459 MRI scans.

Overall, 32% of the children were positive for anti-MOG antibodies. Positivity was not associated with sex, but children with antibodies were significantly younger than those without (7 vs. 12 years). In fact, 77% of anti-MOG–positive children were younger than 11 years; just 15% of older children were positive for the antibodies.

Anti-MOG positivity was also associated with certain clinical phenotypes. Among positive children, 40% presented with optic neuritis, 37% with acute disseminated encephalomyelitis, and 14% with transverse myelitis; the rest had other phenotypes. Optic neuritis was significantly less common among antibody-negative patients (22%), as was encephalomyelitis (17%). Transverse myelitis was significantly more common (31%).

The analysis of MRI scans was stratified according to age younger than 11 years and 11 years and older. “The first thing we noticed among the younger MOG-positive children is that they had a high number of lesions, which were more commonly ill-defined, diffuse, and bilateral,” Dr. Fadda said. “Almost all the brain areas were affected, with a slight preponderance of thalamic and juxtacortical lesions. Among the MOG-negative children, lesions were more often perpendicular to the major axis of the corpus callosum.”

Among the older MOG antibody–positive children, the diffuse pattern was rarer, and the lesions were frequently cerebellar. “But by far, the features that best differentiated positivity from negativity were black holes and enhancing lesions, which we saw in a high proportion of children without the antibodies” at 73% and 49%, respectively.

Over a mean imaging follow-up period of 4 years, lesions were more likely to resolve completely in antibody-positive children than in those without antibodies (50% vs. 21%). Serologically, children who were MOG-antibody negative at baseline were likely to stay that way, with 99% remaining seronegative. Positive children, on the other hand, were significantly more likely to change serologic status, with 56% turning negative and 8% serologically fluctuating over the follow-up period; only 36% remained persistently seropositive. Persistent positive status was significantly associated with younger age (7 vs. 9 years) and an optic neuritis presentation (62% vs. 27%).

Most children (81%) who were antibody positive at baseline experienced no relapses. Among the 16 children who did experience a clinical relapse, the mean time to a second event was about 1 year. Nine of these children stayed persistently positive, while five seroconverted and two had fluctuating status.

Of the 60 antibody-positive children who had a monophasic course, 23 were persistently positive, 34 seroconverted, and 3 had fluctuating serology.

Eventually, 54 children received an MS diagnosis. Of these, 83% were antibody negative at baseline. Ten children received a diagnosis of a relapsing non-MS demyelinating disorder; of these, 91% were antibody positive at baseline.

Dr. Fadda disclosed relationships with Atara Biotherapeutic and Sanofi-Genzyme.

[email protected]

SOURCE: Waters P et al. Mult Scler. 2018;24(S2):29-30, Abstract 65.

BERLIN – In children with an incident acquired demyelinating episode, the presence of antibodies against myelin oligodendrocyte glycoprotein (MOG) weighs against an eventual diagnosis of multiple sclerosis, especially if the child is younger than 11 years.

“Anti-MOG antibodies are present in about 30% of children with acquired demyelinating syndromes,” Giulia Fadda, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. “About 80% experience a monophasic disease course.”

The antibodies are found in almost all children who have a relapsing non-MS demyelinating disease, said Dr. Fadda, who is a postdoctoral research fellow at the University of Pennsylvania, Philadelphia. But when the antibodies are present in children with an MS diagnosis, they identify a very specific subset with atypical clinical and imaging features.

The large prospective Canadian Pediatric Demyelinating Disease Study provided the sample for the study she presented at ECTRIMS. Children are recruited into the study soon after a first demyelinating event, and they are followed clinically, serologically, and with regular brain MRI.


The cohort in Dr. Fadda’s study comprised 275 children who were a mean of about 11 years old at symptom onset. The mean clinical follow-up was 6.7 years; the mean serologic follow-up, 4 years, and the mean imaging follow-up, 3.5 years. The study examined 1,368 serum samples and 1,459 MRI scans.

Overall, 32% of the children were positive for anti-MOG antibodies. Positivity was not associated with sex, but children with antibodies were significantly younger than those without (7 vs. 12 years). In fact, 77% of anti-MOG–positive children were younger than 11 years; just 15% of older children were positive for the antibodies.

Anti-MOG positivity was also associated with certain clinical phenotypes. Among positive children, 40% presented with optic neuritis, 37% with acute disseminated encephalomyelitis, and 14% with transverse myelitis; the rest had other phenotypes. Optic neuritis was significantly less common among antibody-negative patients (22%), as was encephalomyelitis (17%). Transverse myelitis was significantly more common (31%).

The analysis of MRI scans was stratified according to age younger than 11 years and 11 years and older. “The first thing we noticed among the younger MOG-positive children is that they had a high number of lesions, which were more commonly ill-defined, diffuse, and bilateral,” Dr. Fadda said. “Almost all the brain areas were affected, with a slight preponderance of thalamic and juxtacortical lesions. Among the MOG-negative children, lesions were more often perpendicular to the major axis of the corpus callosum.”

Among the older MOG antibody–positive children, the diffuse pattern was rarer, and the lesions were frequently cerebellar. “But by far, the features that best differentiated positivity from negativity were black holes and enhancing lesions, which we saw in a high proportion of children without the antibodies” at 73% and 49%, respectively.

Over a mean imaging follow-up period of 4 years, lesions were more likely to resolve completely in antibody-positive children than in those without antibodies (50% vs. 21%). Serologically, children who were MOG-antibody negative at baseline were likely to stay that way, with 99% remaining seronegative. Positive children, on the other hand, were significantly more likely to change serologic status, with 56% turning negative and 8% serologically fluctuating over the follow-up period; only 36% remained persistently seropositive. Persistent positive status was significantly associated with younger age (7 vs. 9 years) and an optic neuritis presentation (62% vs. 27%).

Most children (81%) who were antibody positive at baseline experienced no relapses. Among the 16 children who did experience a clinical relapse, the mean time to a second event was about 1 year. Nine of these children stayed persistently positive, while five seroconverted and two had fluctuating status.

Of the 60 antibody-positive children who had a monophasic course, 23 were persistently positive, 34 seroconverted, and 3 had fluctuating serology.

Eventually, 54 children received an MS diagnosis. Of these, 83% were antibody negative at baseline. Ten children received a diagnosis of a relapsing non-MS demyelinating disorder; of these, 91% were antibody positive at baseline.

Dr. Fadda disclosed relationships with Atara Biotherapeutic and Sanofi-Genzyme.

[email protected]

SOURCE: Waters P et al. Mult Scler. 2018;24(S2):29-30, Abstract 65.

BERLIN – Switching to alemtuzumab from fingolimod is associated with improved disease activity in patients with relapsing-remitting multiple sclerosis (RRMS), according to the results of a real-world study reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Sara Freeman/MDedge News

Jessica Frau, MD, of the University of Cagliari (Italy) reported that a switch from fingolimod (Gilenya) to alemtuzumab (Lemtrada) in 77 patients treated at 11 Italian centers was able to “reduce dramatically disease activity in patients who did not respond to fingolimod.”

Dr. Frau reported: “When we compared in our cohort the last year of fingolimod with the first year after the first course of alemtuzumab, we found a significant decrease in the annualized relapse rate [ARR].” The ARRs were 0.60 for fingolimod and 0.20 after 1 year of alemtuzumab treatment.

“We found also a trend towards an improvement in the EDSS [Expanded Disability Status Scale] score (P = .23), and less evidence of disease activity on MRI, both in terms of new T2 lesions and gadolinium-enhancing (Gd+) lesions.”

The last MRI during fingolimod treatment showed new T2 and Gd+ enhancing lesions in 69.2% and 58.6% of patients, respectively. Corresponding figures for the first MRI during alemtuzumab treatment were 10.4% and 2.2% of patients.

The beneficial effects of switching to fingolimod in the Italian study “was not influenced by a shorter washout [period] or a low lymphocyte count when alemtuzumab was started,” Dr. Frau said. A shorter washout period has been hypothesized to account for recent accounts of disease flares seen when switching from fingolimod to alemtuzumab, she explained.


Indeed, Dr. Frau noted that there had been a few studies that reported MS disease reactivation soon after the switch to alemtuzumab was made, which could be because lymphocytes remain in the lymph nodes when alemtuzumab is administered, this means that potentially they could repopulate the central nervous system and reactivate the disease.

However, “when alemtuzumab is started after fingolimod it is not a risk factor for reactivation of the disease,” Dr. Frau said, based on the current study’s findings.

As expected, the frequency of relapses increased during the washout period after stopping fingolimod, going from 12.7% of patients with relapse in the first month, 18.2% at 2 months, and 22.2% at 3 months. The time to first relapse from the start of alemtuzumab treatment was 6 months for 2.9% of patients, 9 months for 10.5% of patients, and 1 year for 20.7% of patients.

Asked to comment on when the optimal time to switch from fingolimod to alemtuzumab might be, Dr. Frau said: “The optimal time could be 1 month when the lymphocyte count is not too low.” However, lymphocyte counts were not measured in the entire cohort, so “these data perhaps need to have more strength.”

The switch from natalizumab to alemtuzumab

Other data on switching to alemtuzumab, this time from natalizumab (Tysabri), in the ANSWERS MS study were presented by Paul Gallagher, MBChB, of Queen Elizabeth University Hospital, London, and the University of Glasgow (Scotland).

Sara Freeman/MDedge News

ANSWERS MS (Alemtuzumab after Natalizumab Switch in Evolving Rapidly Severe MS) is a retrospective, observational analysis of routinely collected data on the use of alemtuzumab by 13 centers the United Kingdom and Ireland. These centers have been collecting data since before alemtuzumab was licensed in 2014 for MS, Dr. Gallagher observed, with some centers having experience of making the switch for more than a decade.

SOURCE: Frau J et al. Mult Scler. 2018;24(S2):100-1, Abstract 265; Gallagher P et al. Mult Scler. 2018;24(S2):99-100, Abstract 264.

BERLIN – Switching to alemtuzumab from fingolimod is associated with improved disease activity in patients with relapsing-remitting multiple sclerosis (RRMS), according to the results of a real-world study reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Sara Freeman/MDedge News

Jessica Frau, MD, of the University of Cagliari (Italy) reported that a switch from fingolimod (Gilenya) to alemtuzumab (Lemtrada) in 77 patients treated at 11 Italian centers was able to “reduce dramatically disease activity in patients who did not respond to fingolimod.”

Dr. Frau reported: “When we compared in our cohort the last year of fingolimod with the first year after the first course of alemtuzumab, we found a significant decrease in the annualized relapse rate [ARR].” The ARRs were 0.60 for fingolimod and 0.20 after 1 year of alemtuzumab treatment.

“We found also a trend towards an improvement in the EDSS [Expanded Disability Status Scale] score (P = .23), and less evidence of disease activity on MRI, both in terms of new T2 lesions and gadolinium-enhancing (Gd+) lesions.”

The last MRI during fingolimod treatment showed new T2 and Gd+ enhancing lesions in 69.2% and 58.6% of patients, respectively. Corresponding figures for the first MRI during alemtuzumab treatment were 10.4% and 2.2% of patients.

The beneficial effects of switching to fingolimod in the Italian study “was not influenced by a shorter washout [period] or a low lymphocyte count when alemtuzumab was started,” Dr. Frau said. A shorter washout period has been hypothesized to account for recent accounts of disease flares seen when switching from fingolimod to alemtuzumab, she explained.


Indeed, Dr. Frau noted that there had been a few studies that reported MS disease reactivation soon after the switch to alemtuzumab was made, which could be because lymphocytes remain in the lymph nodes when alemtuzumab is administered, this means that potentially they could repopulate the central nervous system and reactivate the disease.

However, “when alemtuzumab is started after fingolimod it is not a risk factor for reactivation of the disease,” Dr. Frau said, based on the current study’s findings.

As expected, the frequency of relapses increased during the washout period after stopping fingolimod, going from 12.7% of patients with relapse in the first month, 18.2% at 2 months, and 22.2% at 3 months. The time to first relapse from the start of alemtuzumab treatment was 6 months for 2.9% of patients, 9 months for 10.5% of patients, and 1 year for 20.7% of patients.

Asked to comment on when the optimal time to switch from fingolimod to alemtuzumab might be, Dr. Frau said: “The optimal time could be 1 month when the lymphocyte count is not too low.” However, lymphocyte counts were not measured in the entire cohort, so “these data perhaps need to have more strength.”

The switch from natalizumab to alemtuzumab

Other data on switching to alemtuzumab, this time from natalizumab (Tysabri), in the ANSWERS MS study were presented by Paul Gallagher, MBChB, of Queen Elizabeth University Hospital, London, and the University of Glasgow (Scotland).

Sara Freeman/MDedge News

ANSWERS MS (Alemtuzumab after Natalizumab Switch in Evolving Rapidly Severe MS) is a retrospective, observational analysis of routinely collected data on the use of alemtuzumab by 13 centers the United Kingdom and Ireland. These centers have been collecting data since before alemtuzumab was licensed in 2014 for MS, Dr. Gallagher observed, with some centers having experience of making the switch for more than a decade.

SOURCE: Frau J et al. Mult Scler. 2018;24(S2):100-1, Abstract 265; Gallagher P et al. Mult Scler. 2018;24(S2):99-100, Abstract 264.

BERLIN – Switching to alemtuzumab from fingolimod is associated with improved disease activity in patients with relapsing-remitting multiple sclerosis (RRMS), according to the results of a real-world study reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Sara Freeman/MDedge News

Jessica Frau, MD, of the University of Cagliari (Italy) reported that a switch from fingolimod (Gilenya) to alemtuzumab (Lemtrada) in 77 patients treated at 11 Italian centers was able to “reduce dramatically disease activity in patients who did not respond to fingolimod.”

Dr. Frau reported: “When we compared in our cohort the last year of fingolimod with the first year after the first course of alemtuzumab, we found a significant decrease in the annualized relapse rate [ARR].” The ARRs were 0.60 for fingolimod and 0.20 after 1 year of alemtuzumab treatment.

“We found also a trend towards an improvement in the EDSS [Expanded Disability Status Scale] score (P = .23), and less evidence of disease activity on MRI, both in terms of new T2 lesions and gadolinium-enhancing (Gd+) lesions.”

The last MRI during fingolimod treatment showed new T2 and Gd+ enhancing lesions in 69.2% and 58.6% of patients, respectively. Corresponding figures for the first MRI during alemtuzumab treatment were 10.4% and 2.2% of patients.

The beneficial effects of switching to fingolimod in the Italian study “was not influenced by a shorter washout [period] or a low lymphocyte count when alemtuzumab was started,” Dr. Frau said. A shorter washout period has been hypothesized to account for recent accounts of disease flares seen when switching from fingolimod to alemtuzumab, she explained.


Indeed, Dr. Frau noted that there had been a few studies that reported MS disease reactivation soon after the switch to alemtuzumab was made, which could be because lymphocytes remain in the lymph nodes when alemtuzumab is administered, this means that potentially they could repopulate the central nervous system and reactivate the disease.

However, “when alemtuzumab is started after fingolimod it is not a risk factor for reactivation of the disease,” Dr. Frau said, based on the current study’s findings.

As expected, the frequency of relapses increased during the washout period after stopping fingolimod, going from 12.7% of patients with relapse in the first month, 18.2% at 2 months, and 22.2% at 3 months. The time to first relapse from the start of alemtuzumab treatment was 6 months for 2.9% of patients, 9 months for 10.5% of patients, and 1 year for 20.7% of patients.

Asked to comment on when the optimal time to switch from fingolimod to alemtuzumab might be, Dr. Frau said: “The optimal time could be 1 month when the lymphocyte count is not too low.” However, lymphocyte counts were not measured in the entire cohort, so “these data perhaps need to have more strength.”

The switch from natalizumab to alemtuzumab

Other data on switching to alemtuzumab, this time from natalizumab (Tysabri), in the ANSWERS MS study were presented by Paul Gallagher, MBChB, of Queen Elizabeth University Hospital, London, and the University of Glasgow (Scotland).

Sara Freeman/MDedge News

ANSWERS MS (Alemtuzumab after Natalizumab Switch in Evolving Rapidly Severe MS) is a retrospective, observational analysis of routinely collected data on the use of alemtuzumab by 13 centers the United Kingdom and Ireland. These centers have been collecting data since before alemtuzumab was licensed in 2014 for MS, Dr. Gallagher observed, with some centers having experience of making the switch for more than a decade.

SOURCE: Frau J et al. Mult Scler. 2018;24(S2):100-1, Abstract 265; Gallagher P et al. Mult Scler. 2018;24(S2):99-100, Abstract 264.

WASHINGTON, DC—The Drug Enforcement Administration (DEA) has reclassified Epidiolex, an oral cannabidiol (CBD) solution, from Schedule I to Schedule V, the lowest category of scheduled substances. The FDA approved Epidiolex earlier this year for the adjunctive treatment of seizures in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome aged 2 and older. The DEA’s action paves the way for the manufacturer, GW Pharmaceuticals, to begin marketing Epidiolex, which is expected to be available in the United States this fall.

The DEA’s final rescheduling order is limited to drugs approved by the FDA that contain cannabis-derived CBD and no more than 0.1% tetrahydrocannabinol (THC). In practice, this means that the rescheduling currently applies only to Epidiolex, since this is the only formulation of CBD that has received FDA approval.

A Low Potential for Abuse

“We are pleased that the DEA has placed Epidiolex in the lowest restriction schedule, because it will help ensure that patients with LGS and Dravet syndrome, two of the most debilitating forms of epilepsy, can access this important new treatment option through their physicians,” said GW Pharmaceutical’s Chief Executive Officer Justin Gover in a statement.

During the FDA advisory committee meeting for the approval of Epidiolex to treat LGS and Dravet syndrome, the FDA and GW Pharmaceuticals concluded that the potential to abuse CBD was low, since it does not contain THC, the primary psychoactive component of cannabis.

All other marijuana products are currently classified as Schedule I, along with illegal substances such as heroin and cocaine.

An Established Medical Use

Epidiolex had received fast track and rare pediatric designations from the FDA for LGS and Dravet syndrome; the approval was based on three pivotal randomized, double-blind, placebo-controlled clinical trials. The drug met its primary end point of reduced seizure frequency in all trials when added to standard of care for patients with drug-resistant LGS and those with Dravet syndrome.

Safety evaluations assessed data from 1,756 patients and found that the 20 deaths seen during the study period were not clearly linked to Epidiolex and may be expected for children with severe seizure disorders.

In supplementary information accompanying the order, the DEA’s Acting Administrator Uttam Dhillon noted that the FDA’s approval of Epidiolex means that “it has a currently accepted medical use in treatment for purposes of the Controlled Substances Act [CSA]. Accordingly, Epidiolex no longer meets the criteria for placement in Schedule I of the CSA.” Schedule I drugs do not have a currently accepted medical use.

Schedule V drugs, according to the DEA, are defined as “drugs with lower potential for abuse than Schedule IV and [that] consist of preparations containing limited quantities of certain narcotics.” Other Schedule V drugs include cough medicine with less than 200 mg of codeine or per 100 mL, antidiarrheal medications, pregabalin, and the antiepileptic drugs brivaracetam and lacosamide. “Schedule V drugs represent the least potential for abuse,” according to the DEA.

Initial dosing recommendations for Epidiolex are to titrate to a dose of 10 mg/kg/day. Dose adjustments to 20 mg/kg/day are permissible, depending on clinical response and tolerability. The manufacturer has submitted a marketing agreement to the European Medicines Agency and has received orphan drug designation for Epidiolex in the treatment of tuberous sclerosis complex.

—Kari Oakes

WASHINGTON, DC—The Drug Enforcement Administration (DEA) has reclassified Epidiolex, an oral cannabidiol (CBD) solution, from Schedule I to Schedule V, the lowest category of scheduled substances. The FDA approved Epidiolex earlier this year for the adjunctive treatment of seizures in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome aged 2 and older. The DEA’s action paves the way for the manufacturer, GW Pharmaceuticals, to begin marketing Epidiolex, which is expected to be available in the United States this fall.

The DEA’s final rescheduling order is limited to drugs approved by the FDA that contain cannabis-derived CBD and no more than 0.1% tetrahydrocannabinol (THC). In practice, this means that the rescheduling currently applies only to Epidiolex, since this is the only formulation of CBD that has received FDA approval.

A Low Potential for Abuse

“We are pleased that the DEA has placed Epidiolex in the lowest restriction schedule, because it will help ensure that patients with LGS and Dravet syndrome, two of the most debilitating forms of epilepsy, can access this important new treatment option through their physicians,” said GW Pharmaceutical’s Chief Executive Officer Justin Gover in a statement.

During the FDA advisory committee meeting for the approval of Epidiolex to treat LGS and Dravet syndrome, the FDA and GW Pharmaceuticals concluded that the potential to abuse CBD was low, since it does not contain THC, the primary psychoactive component of cannabis.

All other marijuana products are currently classified as Schedule I, along with illegal substances such as heroin and cocaine.

An Established Medical Use

Epidiolex had received fast track and rare pediatric designations from the FDA for LGS and Dravet syndrome; the approval was based on three pivotal randomized, double-blind, placebo-controlled clinical trials. The drug met its primary end point of reduced seizure frequency in all trials when added to standard of care for patients with drug-resistant LGS and those with Dravet syndrome.

Safety evaluations assessed data from 1,756 patients and found that the 20 deaths seen during the study period were not clearly linked to Epidiolex and may be expected for children with severe seizure disorders.

In supplementary information accompanying the order, the DEA’s Acting Administrator Uttam Dhillon noted that the FDA’s approval of Epidiolex means that “it has a currently accepted medical use in treatment for purposes of the Controlled Substances Act [CSA]. Accordingly, Epidiolex no longer meets the criteria for placement in Schedule I of the CSA.” Schedule I drugs do not have a currently accepted medical use.

Schedule V drugs, according to the DEA, are defined as “drugs with lower potential for abuse than Schedule IV and [that] consist of preparations containing limited quantities of certain narcotics.” Other Schedule V drugs include cough medicine with less than 200 mg of codeine or per 100 mL, antidiarrheal medications, pregabalin, and the antiepileptic drugs brivaracetam and lacosamide. “Schedule V drugs represent the least potential for abuse,” according to the DEA.

Initial dosing recommendations for Epidiolex are to titrate to a dose of 10 mg/kg/day. Dose adjustments to 20 mg/kg/day are permissible, depending on clinical response and tolerability. The manufacturer has submitted a marketing agreement to the European Medicines Agency and has received orphan drug designation for Epidiolex in the treatment of tuberous sclerosis complex.

—Kari Oakes

WASHINGTON, DC—The Drug Enforcement Administration (DEA) has reclassified Epidiolex, an oral cannabidiol (CBD) solution, from Schedule I to Schedule V, the lowest category of scheduled substances. The FDA approved Epidiolex earlier this year for the adjunctive treatment of seizures in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome aged 2 and older. The DEA’s action paves the way for the manufacturer, GW Pharmaceuticals, to begin marketing Epidiolex, which is expected to be available in the United States this fall.

The DEA’s final rescheduling order is limited to drugs approved by the FDA that contain cannabis-derived CBD and no more than 0.1% tetrahydrocannabinol (THC). In practice, this means that the rescheduling currently applies only to Epidiolex, since this is the only formulation of CBD that has received FDA approval.

A Low Potential for Abuse

“We are pleased that the DEA has placed Epidiolex in the lowest restriction schedule, because it will help ensure that patients with LGS and Dravet syndrome, two of the most debilitating forms of epilepsy, can access this important new treatment option through their physicians,” said GW Pharmaceutical’s Chief Executive Officer Justin Gover in a statement.

During the FDA advisory committee meeting for the approval of Epidiolex to treat LGS and Dravet syndrome, the FDA and GW Pharmaceuticals concluded that the potential to abuse CBD was low, since it does not contain THC, the primary psychoactive component of cannabis.

All other marijuana products are currently classified as Schedule I, along with illegal substances such as heroin and cocaine.

An Established Medical Use

Epidiolex had received fast track and rare pediatric designations from the FDA for LGS and Dravet syndrome; the approval was based on three pivotal randomized, double-blind, placebo-controlled clinical trials. The drug met its primary end point of reduced seizure frequency in all trials when added to standard of care for patients with drug-resistant LGS and those with Dravet syndrome.

Safety evaluations assessed data from 1,756 patients and found that the 20 deaths seen during the study period were not clearly linked to Epidiolex and may be expected for children with severe seizure disorders.

In supplementary information accompanying the order, the DEA’s Acting Administrator Uttam Dhillon noted that the FDA’s approval of Epidiolex means that “it has a currently accepted medical use in treatment for purposes of the Controlled Substances Act [CSA]. Accordingly, Epidiolex no longer meets the criteria for placement in Schedule I of the CSA.” Schedule I drugs do not have a currently accepted medical use.

Schedule V drugs, according to the DEA, are defined as “drugs with lower potential for abuse than Schedule IV and [that] consist of preparations containing limited quantities of certain narcotics.” Other Schedule V drugs include cough medicine with less than 200 mg of codeine or per 100 mL, antidiarrheal medications, pregabalin, and the antiepileptic drugs brivaracetam and lacosamide. “Schedule V drugs represent the least potential for abuse,” according to the DEA.

Initial dosing recommendations for Epidiolex are to titrate to a dose of 10 mg/kg/day. Dose adjustments to 20 mg/kg/day are permissible, depending on clinical response and tolerability. The manufacturer has submitted a marketing agreement to the European Medicines Agency and has received orphan drug designation for Epidiolex in the treatment of tuberous sclerosis complex.

—Kari Oakes

Myth: Pick Psoriasis Scales to Remove Them

Patients may be inclined to pick psoriasis scales that appear in noticeable areas or on the scalp. However, they should be counseled to avoid this practice, which could cause an infection. Instead, Dr. Steven Feldman (Winston-Salem, North Carolina) suggests putting on an ointment or oil-like medication to soften the scale. “Almost any kind of moisturizer will change the reflective properties of the scale so that you don’t see the scale,” he advised. He also suggested descaling agents such as topical salicylic acid or lactic acid. His patient education video is available on the American Academy of Dermatology website should you wish to direct your patients to it.

Because salicylic acid is a keratolytic (or peeling agent), it works by causing the outer layer of skin to shed. When applied topically, it helps to soften and lift psoriasis scales. Coal tar over-the-counter products also can be used for the same purpose. The over-the-counter product guide from the National Psoriasis Foundation is a valuable resource to share with patients.

Expert Commentary

I agree that it is very important to treat scale very gently. In addition to risk for infection, picking and traumatizing scale can lead to worsening of the psoriasis. This is known as the Koebner phenomenon. The phenomenon was first described by Heinrich Koebner in 1876 as the formation of psoriatic lesions in uninvolved skin of patients with psoriasis after cutaneous trauma. This isomorphic phenomenon is now known to involve numerous diseases, among them vitiligo, lichen planus, and Darier disease.

—Jeffrey M. Weinberg, MD (New York, New York)

Myth: Pick Psoriasis Scales to Remove Them

Patients may be inclined to pick psoriasis scales that appear in noticeable areas or on the scalp. However, they should be counseled to avoid this practice, which could cause an infection. Instead, Dr. Steven Feldman (Winston-Salem, North Carolina) suggests putting on an ointment or oil-like medication to soften the scale. “Almost any kind of moisturizer will change the reflective properties of the scale so that you don’t see the scale,” he advised. He also suggested descaling agents such as topical salicylic acid or lactic acid. His patient education video is available on the American Academy of Dermatology website should you wish to direct your patients to it.

Because salicylic acid is a keratolytic (or peeling agent), it works by causing the outer layer of skin to shed. When applied topically, it helps to soften and lift psoriasis scales. Coal tar over-the-counter products also can be used for the same purpose. The over-the-counter product guide from the National Psoriasis Foundation is a valuable resource to share with patients.

Expert Commentary

I agree that it is very important to treat scale very gently. In addition to risk for infection, picking and traumatizing scale can lead to worsening of the psoriasis. This is known as the Koebner phenomenon. The phenomenon was first described by Heinrich Koebner in 1876 as the formation of psoriatic lesions in uninvolved skin of patients with psoriasis after cutaneous trauma. This isomorphic phenomenon is now known to involve numerous diseases, among them vitiligo, lichen planus, and Darier disease.

—Jeffrey M. Weinberg, MD (New York, New York)

Myth: Pick Psoriasis Scales to Remove Them

Patients may be inclined to pick psoriasis scales that appear in noticeable areas or on the scalp. However, they should be counseled to avoid this practice, which could cause an infection. Instead, Dr. Steven Feldman (Winston-Salem, North Carolina) suggests putting on an ointment or oil-like medication to soften the scale. “Almost any kind of moisturizer will change the reflective properties of the scale so that you don’t see the scale,” he advised. He also suggested descaling agents such as topical salicylic acid or lactic acid. His patient education video is available on the American Academy of Dermatology website should you wish to direct your patients to it.

Because salicylic acid is a keratolytic (or peeling agent), it works by causing the outer layer of skin to shed. When applied topically, it helps to soften and lift psoriasis scales. Coal tar over-the-counter products also can be used for the same purpose. The over-the-counter product guide from the National Psoriasis Foundation is a valuable resource to share with patients.

Expert Commentary

I agree that it is very important to treat scale very gently. In addition to risk for infection, picking and traumatizing scale can lead to worsening of the psoriasis. This is known as the Koebner phenomenon. The phenomenon was first described by Heinrich Koebner in 1876 as the formation of psoriatic lesions in uninvolved skin of patients with psoriasis after cutaneous trauma. This isomorphic phenomenon is now known to involve numerous diseases, among them vitiligo, lichen planus, and Darier disease.

—Jeffrey M. Weinberg, MD (New York, New York)

The psychosocial impact of psoriasis is a critical component of disease burden. Psoriatic patients have high rates of depression and anxiety, problems at work, and difficulties with interpersonal relationships and intimacy.¹ A National Psoriasis Foundation (NPF) survey from 2003 to 2011 reported that psoriasis affects overall emotional well-being in 88% of patients and enjoyment of life in 82% of patients.²

The reasons for psychosocial burden stem from public misconceptions and disease stigma. A survey of 1005 individuals (age range, 16–64 years) about their perceptions of psoriasis revealed that 16.5% believed that psoriasis is contagious and 6.8% believed that psoriasis is related to personal hygiene.³ Fifty percent practiced discriminatory behavior toward psoriatic patients, including reluctance to shake hands (28.8%) and engage in sexual relations/intercourse (44.1%). Sixty-five percent of psoriatic patients felt their appearance is unsightly, and 73% felt self-conscious about having psoriasis.²

The psychosocial burden exists despite medical treatment of the disease. In a cross-sectional study of 1184 psoriatic patients, 70.2% had impaired quality of life (QOL) as measured by the dermatology life quality index (DLQI), even after receiving a 4-week treatment for psoriasis.⁴ Medical treatment of psoriasis is not enough; providers need to assess overall QOL and provide treatment and resources for these patients in addition to symptomatic management.

There have been many studies on the psychosocial burden of psoriasis, but few have focused on a dermatology resident’s role in addressing this issue. This article will review psychosocial domains—psychiatric comorbidities and social functioning including occupational functioning, interpersonal relationships, and sexual functioning— and discuss a dermatology resident’s role in assessing and addressing each of these areas.

Methods

A PubMed search of articles indexed for MEDLINE was conducted using the following terms: psoriasis, depression, anxiety, work productivity, sexual functioning, and interpersonal relationships. Selected articles covered prevalence, assessment, and management of each psychosocial domain.

Results

Psychiatric Comorbidities

Prevalence
A high prevalence of psychiatric comorbidities exists in psoriatic patients. In a study of 469,097 patients with psoriasis, depression was the third most prevalent comorbidity (17.91%), following hyperlipidemia (45.64%) and hypertension (42.19%).⁵ In a 10-year longitudinal, population-based, prospective cohort study, antidepressant prescriptions were twice as frequent in psoriatic patients (17.8%) compared to control (7.9%)(P<.001).⁶ In a meta-analysis of 98 studies investigating psoriatic patients and psychiatric comorbidities, patients with psoriasis were 1.5 times more likely to experience depression (odds ratio [OR]: 1.57; 95% CI, 1.40-1.76) and use antidepressants (OR: 4.24; 95% CI, 1.53-11.76) compared to control.⁷ Patients with psoriasis were more likely to attempt suicide (OR: 1.32; 95% CI, 1.14-1.54) and complete suicide (OR: 1.20; 95% CI, 1.04-1.39) compared to people without psoriasis.⁸ A 1-year cross-sectional study of 90 psoriatic patients reported 78.7% were diagnosed with depression and 76.7% were diagnosed with anxiety. Seventy-two percent reported both anxiety and depression, correlating with worse QOL (χ²=26.7; P<.05).⁹

Assessment
Psychiatric comorbidities are assessed using clinical judgment and formal screening questionnaires in research studies. Signs of depression in patients with psoriasis can manifest as poor treatment adherence and recurrent flares of psoriasis.^10,11 Psoriatic patients with psychiatric comorbidities were less likely to be adherent to treatment (risk ratio: 0.35; P<.003).¹⁰ The patient health questionnaire (PHQ) 9 and generalized anxiety disorder scale (GAD) 7 are validated and reliable questionnaires. The first 2 questions in PHQ-9 and GAD-7 screen for depression and anxiety, respectively.^12-14 These 2-question screens are practical in a fast-paced dermatology outpatient setting. Systematic questionnaires specifically targeting mood disorders may be more beneficial than the widely used DLQI, which may not adequately capture mood disorders. Over the course of 10 months, 607 patients with psoriasis were asked to fill out the PHQ-9, GAD-7, and DLQI. Thirty-eight percent of patients with major depressive disorder had a DLQI score lower than 10, while 46% of patients with generalized anxiety disorder had a DLQI score lower than 10.¹⁵ Other questionnaires, including the hospital anxiety and depression scale and Beck depression inventory, are valid instruments with high sensitivity but are commonly used for research purposes and may not be clinically feasible.¹⁶

Management
Dermatologists should refer patients with depression and/or anxiety to psychiatry. Interventions include pharmacologic and nonpharmacologic management. First-line therapy for depression and anxiety is a combination of selective serotonin reuptake inhibitors and cognitive behavioral therapy.¹⁷ In addition, providers can direct patients to online resources such as the NPF website, where patients with psoriasis can access information about the signs and symptoms of mood disorders and contact the patient navigation center for further help.¹⁸

Social Functioning

Occupational Prevalence
The NPF found that 92% of patients with psoriasis or psoriatic arthritis (PsA) surveyed between 2003 and 2011 cited their psoriasis as reason for unemployment.² In a survey of 43 patients asked about social and occupational functioning using the social and occupational assessment scale, 62.5% of psoriatic patients reported distress at work and 51.1% reported decreased efficiency at work.¹⁹ A national online survey that was conducted in France and issued to patients with and without psoriasis assessed overall QOL and work productivity using the work productivity and activity impairment questionnaire for psoriasis (WPAI-PSO). Of 714 patients with psoriasis and PsA, the latter had a 57.6% decrease in work productivity over 7 days compared to 27.9% in controls (P<.05).²⁰ Occupational impairment leads to lost wages and hinders advancement, further exacerbating the psychosocial burden of psoriasis.²¹

Occupational Assessment
Formal assessment of occupational function can be done with the WPAI-PSO, a 6-question valid instrument.²² Providers may look for risk factors associated with greater loss in work productivity to help identify and offer support for patients. Patients with increased severity of itching, pain, and scaling experienced a greater decrease in work productivity.^21,23 Patients with PsA warrant early detection and treatment because they experience greater physical restraints that can interfere with work activities. Of the 459 psoriatic patients without a prior diagnosis of PsA who filled out the PsA screening and evaluation questionnaire, 144 (31.4%) received a score of 44 or higher and were referred to rheumatology for further evaluation with the classification criteria for PsA. Nine percent of patients failed to be screened and remained undiagnosed with PsA.²⁴ In a study using the health assessment questionnaire to assess 400 patients with PsA, those with worse physical function due to joint pain and stiffness were less likely to remain employed (OR: 0.56; P=.02).²⁵

Occupational Management
Identifying and coordinating symptoms of PsA between dermatology and rheumatology is beneficial for patients who experience debilitating symptoms. There are a variety of treatments available for PsA. According to the European League Against Rheumatism 2015 guidelines developed from expert opinion and systematic reviews for PsA management, there are 4 phases of treatment, with reassessment every 3 to 6 months for effectiveness of therapy.^26,27 Phase I involves initiating nonsteroidal anti-inflammatory drugs with or without glucocorticoid injections. Phase II involves synthetic disease-modifying drugs, including methotrexate, leflunomide, sulfasalazine, or cyclosporine. Phase III involves adding a second synthetic disease-modifying drug or starting a biologic, such as an anti–tumor necrosis factor, IL-12/IL-23, or IL-17 inhibitor. Phase IV involves switching to a different drug in either aforementioned class.^26,27 Treatment with biologics improves work productivity as assessed by WPAI-PSO for psoriasis and PsA.^28-30 Encouraging patients to speak up in the workplace and request small accommodations such as timely breaks or ergonomic chairs can help patients feel more comfortable and supported in the work environment.¹⁸ Patients who felt supported at work were more likely to remain employed.²⁵

Interpersonal Relationships Prevalence
Misinformation about psoriasis, fear of rejection, and feelings of isolation may contribute to interpersonal conflict. Patients have feelings of shame and self-consciousness that hinder them from engaging in social activities and seeking out relationships.³¹ Twenty-nine percent of patients feel that psoriasis has interfered with establishing relationships because of negative self-esteem associated with the disease,³² and 26.3% have experienced people avoiding physical contact.³³ Family and spouses of patients with psoriasis may be secondarily affected due to economic and emotional distress. Ninety-eight percent of family members of psoriatic patients experienced emotional distress and 54% experienced the burden of care.³⁴ In a survey of 63 relatives and partners of patients with psoriasis, 57% experienced psychological distress, including anxiety and worry over a psoriatic patient’s future.³⁵

Interpersonal Relationships Assessment
Current available tools, including the DLQI and short form health survey, measure overall QOL, including social functioning, but may not be practical in a clinic setting. Although no quick-screening test to assess for this domain exists, providers are encouraged to ask patients about disease impact on interpersonal relationships. The family DLQI questionnaire, adapted from the DLQI, may help physicians and social workers evaluate the burden on a patient’s family members.³⁴

Interpersonal Relationships Management
It may be difficult for providers to address problems with interpersonal relationships without accessible tools. Patients may not be accompanied by family or friends during appointments, and it is difficult to screen for these issues during visits. Providers may offer resources such as the NPF website, which provides information about support groups. It also provides tips on dating and connecting to others in the community who share similar experiences.¹⁸ Encouraging patients to seek family or couples therapy also may be beneficial. Increased social support can lead to better QOL and fewer depressive symptoms.³⁶

Sexual Functioning Prevalence
Psoriasis affects both physical and psychological components of sexual function. Among 3485 patients with skin conditions who were surveyed about sexual function, 34% of psoriatic patients reported that psoriasis interfered with sexual functioning at least to a certain degree.³⁷ Sexual impairment was strongly associated with depression, anxiety, and suicidal ideation; 24% of depressed patients and 20% of anxious patients experienced sexual problems a lot or very much, based on the DLQI.³⁷ Depending on the questionnaire used, the prevalence of sexual dysfunction due to psoriasis ranged from 35.5% to 71.3%.³⁸ In an observational cohort study of 158 participants (n=79 psoriasis patients and n=79 controls), 34.2% of patients with psoriasis experienced erectile dysfunction compared to 17.7% of controls.³⁹ Forty-two percent of psoriatic patients with genital involvement reported dyspareunia, 32% reported worsening of genital psoriasis after intercourse, and 43% reported decreased frequency of intercourse.⁴⁰

Sexual Functioning Assessment
The Skindex-29, DLQI, and psoriasis disability index are available QOL tools that include one question evaluating difficulties with sexual function. The Massachusetts General Hospital sexual functioning questionnaire is a 5-item validated tool that specifically assesses sexual dysfunction.⁴¹ Distribution of lesions can help identify patients who are more likely to experience sexual dysfunction. In 160 patients who completed the questionnaire and self-reported psoriasis area and severity index, lesions on the abdomen, genitals, lumbar region, and buttocks were associated with worse sexual functioning (OR: 7.9; 95% CI, 2.3-33.4; P<.05).⁴² Dermatologists could assess for sexual problems using either formal questionnaires or direct conversations during the routine psoriasis visit, as patients may be suffering in silence due to this sensitive topic.

Sexual Functioning Management
Better disease control leads to improved sexual function, as patients experience fewer feelings of shame, anxiety, and depression, as well as improvement of physical symptoms that can interfere with sexual functioning.^38,43,44 Reducing friction, warmth, and moisture, as well as avoiding tight clothing, can help those with genital psoriasis. Patients are advised to reapply topical medications after sexual intercourse. Patients also can apply makeup to disguise psoriasis and help reduce feelings of self-consciousness that can impede sexual intimacy.¹⁸

Comment

The psychosocial burden of psoriasis penetrates many facets of patient lives. Psoriasis can invoke feelings of shame and embarrassment that are worsened by the public’s misconceptions about psoriasis, resulting in serious mental health issues that can cause even greater disability. Depression and anxiety are prevalent in patients with psoriasis. The characteristic symptoms of pain and pruritus along with psychiatric comorbidities can have an underestimated impact on daily activities, including employment, interpersonal relationships, and sexual function. Such dysfunctions have serious implications toward wages, professional advancement, social support, and overall QOL.

Dermatology providers play an important role in screening for these problems through validated questionnaires and identifying risks. Simple screening questions such as the PHQ-9 can be beneficial and feasible during dermatology visits. Screening for PsA can help patients avoid problems at work. Sexual dysfunction is a sensitive topic; however, providers can use a 1-question screen from valid questionnaires and inquire about the location of lesions as opportunities to address this issue.

Interventions lead to better disease control, which concurrently improves overall QOL. These interventions depend on both patient adherence and a physician’s commitment to finding an optimal treatment regimen for each individual. Medical management; coordinating care; developing treatment plans with psychiatry, rheumatology, and primary care providers; and psychological counseling and services may be necessary and beneficial (Table). Offering accessible resources such as the NPF website helps patients access information outside the clinic when it is not feasible to address all these concerns in a single visit. Psoriasis requires more than just medical management; it requires dermatology providers to use a multidisciplinary approach to address the psychosocial aspects of the disease.

Conclusion

The psychosocial burden of psoriasis is immense. Stigma, public misconception, mental health concerns, and occupational and interpersonal difficulty are the basis of disease burden. Providers play a vital role in assessing the effect psoriasis has on different areas of patients’ lives and providing appropriate interventions and resources to reduce disease burden.

The psychosocial impact of psoriasis is a critical component of disease burden. Psoriatic patients have high rates of depression and anxiety, problems at work, and difficulties with interpersonal relationships and intimacy.¹ A National Psoriasis Foundation (NPF) survey from 2003 to 2011 reported that psoriasis affects overall emotional well-being in 88% of patients and enjoyment of life in 82% of patients.²

The reasons for psychosocial burden stem from public misconceptions and disease stigma. A survey of 1005 individuals (age range, 16–64 years) about their perceptions of psoriasis revealed that 16.5% believed that psoriasis is contagious and 6.8% believed that psoriasis is related to personal hygiene.³ Fifty percent practiced discriminatory behavior toward psoriatic patients, including reluctance to shake hands (28.8%) and engage in sexual relations/intercourse (44.1%). Sixty-five percent of psoriatic patients felt their appearance is unsightly, and 73% felt self-conscious about having psoriasis.²

The psychosocial burden exists despite medical treatment of the disease. In a cross-sectional study of 1184 psoriatic patients, 70.2% had impaired quality of life (QOL) as measured by the dermatology life quality index (DLQI), even after receiving a 4-week treatment for psoriasis.⁴ Medical treatment of psoriasis is not enough; providers need to assess overall QOL and provide treatment and resources for these patients in addition to symptomatic management.

There have been many studies on the psychosocial burden of psoriasis, but few have focused on a dermatology resident’s role in addressing this issue. This article will review psychosocial domains—psychiatric comorbidities and social functioning including occupational functioning, interpersonal relationships, and sexual functioning— and discuss a dermatology resident’s role in assessing and addressing each of these areas.

Methods

A PubMed search of articles indexed for MEDLINE was conducted using the following terms: psoriasis, depression, anxiety, work productivity, sexual functioning, and interpersonal relationships. Selected articles covered prevalence, assessment, and management of each psychosocial domain.

Results

Psychiatric Comorbidities

Prevalence
A high prevalence of psychiatric comorbidities exists in psoriatic patients. In a study of 469,097 patients with psoriasis, depression was the third most prevalent comorbidity (17.91%), following hyperlipidemia (45.64%) and hypertension (42.19%).⁵ In a 10-year longitudinal, population-based, prospective cohort study, antidepressant prescriptions were twice as frequent in psoriatic patients (17.8%) compared to control (7.9%)(P<.001).⁶ In a meta-analysis of 98 studies investigating psoriatic patients and psychiatric comorbidities, patients with psoriasis were 1.5 times more likely to experience depression (odds ratio [OR]: 1.57; 95% CI, 1.40-1.76) and use antidepressants (OR: 4.24; 95% CI, 1.53-11.76) compared to control.⁷ Patients with psoriasis were more likely to attempt suicide (OR: 1.32; 95% CI, 1.14-1.54) and complete suicide (OR: 1.20; 95% CI, 1.04-1.39) compared to people without psoriasis.⁸ A 1-year cross-sectional study of 90 psoriatic patients reported 78.7% were diagnosed with depression and 76.7% were diagnosed with anxiety. Seventy-two percent reported both anxiety and depression, correlating with worse QOL (χ²=26.7; P<.05).⁹

Assessment
Psychiatric comorbidities are assessed using clinical judgment and formal screening questionnaires in research studies. Signs of depression in patients with psoriasis can manifest as poor treatment adherence and recurrent flares of psoriasis.^10,11 Psoriatic patients with psychiatric comorbidities were less likely to be adherent to treatment (risk ratio: 0.35; P<.003).¹⁰ The patient health questionnaire (PHQ) 9 and generalized anxiety disorder scale (GAD) 7 are validated and reliable questionnaires. The first 2 questions in PHQ-9 and GAD-7 screen for depression and anxiety, respectively.^12-14 These 2-question screens are practical in a fast-paced dermatology outpatient setting. Systematic questionnaires specifically targeting mood disorders may be more beneficial than the widely used DLQI, which may not adequately capture mood disorders. Over the course of 10 months, 607 patients with psoriasis were asked to fill out the PHQ-9, GAD-7, and DLQI. Thirty-eight percent of patients with major depressive disorder had a DLQI score lower than 10, while 46% of patients with generalized anxiety disorder had a DLQI score lower than 10.¹⁵ Other questionnaires, including the hospital anxiety and depression scale and Beck depression inventory, are valid instruments with high sensitivity but are commonly used for research purposes and may not be clinically feasible.¹⁶

Management
Dermatologists should refer patients with depression and/or anxiety to psychiatry. Interventions include pharmacologic and nonpharmacologic management. First-line therapy for depression and anxiety is a combination of selective serotonin reuptake inhibitors and cognitive behavioral therapy.¹⁷ In addition, providers can direct patients to online resources such as the NPF website, where patients with psoriasis can access information about the signs and symptoms of mood disorders and contact the patient navigation center for further help.¹⁸

Social Functioning

Occupational Prevalence
The NPF found that 92% of patients with psoriasis or psoriatic arthritis (PsA) surveyed between 2003 and 2011 cited their psoriasis as reason for unemployment.² In a survey of 43 patients asked about social and occupational functioning using the social and occupational assessment scale, 62.5% of psoriatic patients reported distress at work and 51.1% reported decreased efficiency at work.¹⁹ A national online survey that was conducted in France and issued to patients with and without psoriasis assessed overall QOL and work productivity using the work productivity and activity impairment questionnaire for psoriasis (WPAI-PSO). Of 714 patients with psoriasis and PsA, the latter had a 57.6% decrease in work productivity over 7 days compared to 27.9% in controls (P<.05).²⁰ Occupational impairment leads to lost wages and hinders advancement, further exacerbating the psychosocial burden of psoriasis.²¹

Occupational Assessment
Formal assessment of occupational function can be done with the WPAI-PSO, a 6-question valid instrument.²² Providers may look for risk factors associated with greater loss in work productivity to help identify and offer support for patients. Patients with increased severity of itching, pain, and scaling experienced a greater decrease in work productivity.^21,23 Patients with PsA warrant early detection and treatment because they experience greater physical restraints that can interfere with work activities. Of the 459 psoriatic patients without a prior diagnosis of PsA who filled out the PsA screening and evaluation questionnaire, 144 (31.4%) received a score of 44 or higher and were referred to rheumatology for further evaluation with the classification criteria for PsA. Nine percent of patients failed to be screened and remained undiagnosed with PsA.²⁴ In a study using the health assessment questionnaire to assess 400 patients with PsA, those with worse physical function due to joint pain and stiffness were less likely to remain employed (OR: 0.56; P=.02).²⁵

Occupational Management
Identifying and coordinating symptoms of PsA between dermatology and rheumatology is beneficial for patients who experience debilitating symptoms. There are a variety of treatments available for PsA. According to the European League Against Rheumatism 2015 guidelines developed from expert opinion and systematic reviews for PsA management, there are 4 phases of treatment, with reassessment every 3 to 6 months for effectiveness of therapy.^26,27 Phase I involves initiating nonsteroidal anti-inflammatory drugs with or without glucocorticoid injections. Phase II involves synthetic disease-modifying drugs, including methotrexate, leflunomide, sulfasalazine, or cyclosporine. Phase III involves adding a second synthetic disease-modifying drug or starting a biologic, such as an anti–tumor necrosis factor, IL-12/IL-23, or IL-17 inhibitor. Phase IV involves switching to a different drug in either aforementioned class.^26,27 Treatment with biologics improves work productivity as assessed by WPAI-PSO for psoriasis and PsA.^28-30 Encouraging patients to speak up in the workplace and request small accommodations such as timely breaks or ergonomic chairs can help patients feel more comfortable and supported in the work environment.¹⁸ Patients who felt supported at work were more likely to remain employed.²⁵

Interpersonal Relationships Prevalence
Misinformation about psoriasis, fear of rejection, and feelings of isolation may contribute to interpersonal conflict. Patients have feelings of shame and self-consciousness that hinder them from engaging in social activities and seeking out relationships.³¹ Twenty-nine percent of patients feel that psoriasis has interfered with establishing relationships because of negative self-esteem associated with the disease,³² and 26.3% have experienced people avoiding physical contact.³³ Family and spouses of patients with psoriasis may be secondarily affected due to economic and emotional distress. Ninety-eight percent of family members of psoriatic patients experienced emotional distress and 54% experienced the burden of care.³⁴ In a survey of 63 relatives and partners of patients with psoriasis, 57% experienced psychological distress, including anxiety and worry over a psoriatic patient’s future.³⁵

Interpersonal Relationships Assessment
Current available tools, including the DLQI and short form health survey, measure overall QOL, including social functioning, but may not be practical in a clinic setting. Although no quick-screening test to assess for this domain exists, providers are encouraged to ask patients about disease impact on interpersonal relationships. The family DLQI questionnaire, adapted from the DLQI, may help physicians and social workers evaluate the burden on a patient’s family members.³⁴

Interpersonal Relationships Management
It may be difficult for providers to address problems with interpersonal relationships without accessible tools. Patients may not be accompanied by family or friends during appointments, and it is difficult to screen for these issues during visits. Providers may offer resources such as the NPF website, which provides information about support groups. It also provides tips on dating and connecting to others in the community who share similar experiences.¹⁸ Encouraging patients to seek family or couples therapy also may be beneficial. Increased social support can lead to better QOL and fewer depressive symptoms.³⁶

Sexual Functioning Prevalence
Psoriasis affects both physical and psychological components of sexual function. Among 3485 patients with skin conditions who were surveyed about sexual function, 34% of psoriatic patients reported that psoriasis interfered with sexual functioning at least to a certain degree.³⁷ Sexual impairment was strongly associated with depression, anxiety, and suicidal ideation; 24% of depressed patients and 20% of anxious patients experienced sexual problems a lot or very much, based on the DLQI.³⁷ Depending on the questionnaire used, the prevalence of sexual dysfunction due to psoriasis ranged from 35.5% to 71.3%.³⁸ In an observational cohort study of 158 participants (n=79 psoriasis patients and n=79 controls), 34.2% of patients with psoriasis experienced erectile dysfunction compared to 17.7% of controls.³⁹ Forty-two percent of psoriatic patients with genital involvement reported dyspareunia, 32% reported worsening of genital psoriasis after intercourse, and 43% reported decreased frequency of intercourse.⁴⁰

Sexual Functioning Assessment
The Skindex-29, DLQI, and psoriasis disability index are available QOL tools that include one question evaluating difficulties with sexual function. The Massachusetts General Hospital sexual functioning questionnaire is a 5-item validated tool that specifically assesses sexual dysfunction.⁴¹ Distribution of lesions can help identify patients who are more likely to experience sexual dysfunction. In 160 patients who completed the questionnaire and self-reported psoriasis area and severity index, lesions on the abdomen, genitals, lumbar region, and buttocks were associated with worse sexual functioning (OR: 7.9; 95% CI, 2.3-33.4; P<.05).⁴² Dermatologists could assess for sexual problems using either formal questionnaires or direct conversations during the routine psoriasis visit, as patients may be suffering in silence due to this sensitive topic.

Sexual Functioning Management
Better disease control leads to improved sexual function, as patients experience fewer feelings of shame, anxiety, and depression, as well as improvement of physical symptoms that can interfere with sexual functioning.^38,43,44 Reducing friction, warmth, and moisture, as well as avoiding tight clothing, can help those with genital psoriasis. Patients are advised to reapply topical medications after sexual intercourse. Patients also can apply makeup to disguise psoriasis and help reduce feelings of self-consciousness that can impede sexual intimacy.¹⁸

Comment

The psychosocial burden of psoriasis penetrates many facets of patient lives. Psoriasis can invoke feelings of shame and embarrassment that are worsened by the public’s misconceptions about psoriasis, resulting in serious mental health issues that can cause even greater disability. Depression and anxiety are prevalent in patients with psoriasis. The characteristic symptoms of pain and pruritus along with psychiatric comorbidities can have an underestimated impact on daily activities, including employment, interpersonal relationships, and sexual function. Such dysfunctions have serious implications toward wages, professional advancement, social support, and overall QOL.

Dermatology providers play an important role in screening for these problems through validated questionnaires and identifying risks. Simple screening questions such as the PHQ-9 can be beneficial and feasible during dermatology visits. Screening for PsA can help patients avoid problems at work. Sexual dysfunction is a sensitive topic; however, providers can use a 1-question screen from valid questionnaires and inquire about the location of lesions as opportunities to address this issue.

Interventions lead to better disease control, which concurrently improves overall QOL. These interventions depend on both patient adherence and a physician’s commitment to finding an optimal treatment regimen for each individual. Medical management; coordinating care; developing treatment plans with psychiatry, rheumatology, and primary care providers; and psychological counseling and services may be necessary and beneficial (Table). Offering accessible resources such as the NPF website helps patients access information outside the clinic when it is not feasible to address all these concerns in a single visit. Psoriasis requires more than just medical management; it requires dermatology providers to use a multidisciplinary approach to address the psychosocial aspects of the disease.

Conclusion

The psychosocial burden of psoriasis is immense. Stigma, public misconception, mental health concerns, and occupational and interpersonal difficulty are the basis of disease burden. Providers play a vital role in assessing the effect psoriasis has on different areas of patients’ lives and providing appropriate interventions and resources to reduce disease burden.

The psychosocial impact of psoriasis is a critical component of disease burden. Psoriatic patients have high rates of depression and anxiety, problems at work, and difficulties with interpersonal relationships and intimacy.¹ A National Psoriasis Foundation (NPF) survey from 2003 to 2011 reported that psoriasis affects overall emotional well-being in 88% of patients and enjoyment of life in 82% of patients.²

The reasons for psychosocial burden stem from public misconceptions and disease stigma. A survey of 1005 individuals (age range, 16–64 years) about their perceptions of psoriasis revealed that 16.5% believed that psoriasis is contagious and 6.8% believed that psoriasis is related to personal hygiene.³ Fifty percent practiced discriminatory behavior toward psoriatic patients, including reluctance to shake hands (28.8%) and engage in sexual relations/intercourse (44.1%). Sixty-five percent of psoriatic patients felt their appearance is unsightly, and 73% felt self-conscious about having psoriasis.²

The psychosocial burden exists despite medical treatment of the disease. In a cross-sectional study of 1184 psoriatic patients, 70.2% had impaired quality of life (QOL) as measured by the dermatology life quality index (DLQI), even after receiving a 4-week treatment for psoriasis.⁴ Medical treatment of psoriasis is not enough; providers need to assess overall QOL and provide treatment and resources for these patients in addition to symptomatic management.

There have been many studies on the psychosocial burden of psoriasis, but few have focused on a dermatology resident’s role in addressing this issue. This article will review psychosocial domains—psychiatric comorbidities and social functioning including occupational functioning, interpersonal relationships, and sexual functioning— and discuss a dermatology resident’s role in assessing and addressing each of these areas.

Methods

A PubMed search of articles indexed for MEDLINE was conducted using the following terms: psoriasis, depression, anxiety, work productivity, sexual functioning, and interpersonal relationships. Selected articles covered prevalence, assessment, and management of each psychosocial domain.

Results

Psychiatric Comorbidities

Prevalence
A high prevalence of psychiatric comorbidities exists in psoriatic patients. In a study of 469,097 patients with psoriasis, depression was the third most prevalent comorbidity (17.91%), following hyperlipidemia (45.64%) and hypertension (42.19%).⁵ In a 10-year longitudinal, population-based, prospective cohort study, antidepressant prescriptions were twice as frequent in psoriatic patients (17.8%) compared to control (7.9%)(P<.001).⁶ In a meta-analysis of 98 studies investigating psoriatic patients and psychiatric comorbidities, patients with psoriasis were 1.5 times more likely to experience depression (odds ratio [OR]: 1.57; 95% CI, 1.40-1.76) and use antidepressants (OR: 4.24; 95% CI, 1.53-11.76) compared to control.⁷ Patients with psoriasis were more likely to attempt suicide (OR: 1.32; 95% CI, 1.14-1.54) and complete suicide (OR: 1.20; 95% CI, 1.04-1.39) compared to people without psoriasis.⁸ A 1-year cross-sectional study of 90 psoriatic patients reported 78.7% were diagnosed with depression and 76.7% were diagnosed with anxiety. Seventy-two percent reported both anxiety and depression, correlating with worse QOL (χ²=26.7; P<.05).⁹

Assessment
Psychiatric comorbidities are assessed using clinical judgment and formal screening questionnaires in research studies. Signs of depression in patients with psoriasis can manifest as poor treatment adherence and recurrent flares of psoriasis.^10,11 Psoriatic patients with psychiatric comorbidities were less likely to be adherent to treatment (risk ratio: 0.35; P<.003).¹⁰ The patient health questionnaire (PHQ) 9 and generalized anxiety disorder scale (GAD) 7 are validated and reliable questionnaires. The first 2 questions in PHQ-9 and GAD-7 screen for depression and anxiety, respectively.^12-14 These 2-question screens are practical in a fast-paced dermatology outpatient setting. Systematic questionnaires specifically targeting mood disorders may be more beneficial than the widely used DLQI, which may not adequately capture mood disorders. Over the course of 10 months, 607 patients with psoriasis were asked to fill out the PHQ-9, GAD-7, and DLQI. Thirty-eight percent of patients with major depressive disorder had a DLQI score lower than 10, while 46% of patients with generalized anxiety disorder had a DLQI score lower than 10.¹⁵ Other questionnaires, including the hospital anxiety and depression scale and Beck depression inventory, are valid instruments with high sensitivity but are commonly used for research purposes and may not be clinically feasible.¹⁶

Management
Dermatologists should refer patients with depression and/or anxiety to psychiatry. Interventions include pharmacologic and nonpharmacologic management. First-line therapy for depression and anxiety is a combination of selective serotonin reuptake inhibitors and cognitive behavioral therapy.¹⁷ In addition, providers can direct patients to online resources such as the NPF website, where patients with psoriasis can access information about the signs and symptoms of mood disorders and contact the patient navigation center for further help.¹⁸

Social Functioning

Occupational Prevalence
The NPF found that 92% of patients with psoriasis or psoriatic arthritis (PsA) surveyed between 2003 and 2011 cited their psoriasis as reason for unemployment.² In a survey of 43 patients asked about social and occupational functioning using the social and occupational assessment scale, 62.5% of psoriatic patients reported distress at work and 51.1% reported decreased efficiency at work.¹⁹ A national online survey that was conducted in France and issued to patients with and without psoriasis assessed overall QOL and work productivity using the work productivity and activity impairment questionnaire for psoriasis (WPAI-PSO). Of 714 patients with psoriasis and PsA, the latter had a 57.6% decrease in work productivity over 7 days compared to 27.9% in controls (P<.05).²⁰ Occupational impairment leads to lost wages and hinders advancement, further exacerbating the psychosocial burden of psoriasis.²¹

Occupational Assessment
Formal assessment of occupational function can be done with the WPAI-PSO, a 6-question valid instrument.²² Providers may look for risk factors associated with greater loss in work productivity to help identify and offer support for patients. Patients with increased severity of itching, pain, and scaling experienced a greater decrease in work productivity.^21,23 Patients with PsA warrant early detection and treatment because they experience greater physical restraints that can interfere with work activities. Of the 459 psoriatic patients without a prior diagnosis of PsA who filled out the PsA screening and evaluation questionnaire, 144 (31.4%) received a score of 44 or higher and were referred to rheumatology for further evaluation with the classification criteria for PsA. Nine percent of patients failed to be screened and remained undiagnosed with PsA.²⁴ In a study using the health assessment questionnaire to assess 400 patients with PsA, those with worse physical function due to joint pain and stiffness were less likely to remain employed (OR: 0.56; P=.02).²⁵

Occupational Management
Identifying and coordinating symptoms of PsA between dermatology and rheumatology is beneficial for patients who experience debilitating symptoms. There are a variety of treatments available for PsA. According to the European League Against Rheumatism 2015 guidelines developed from expert opinion and systematic reviews for PsA management, there are 4 phases of treatment, with reassessment every 3 to 6 months for effectiveness of therapy.^26,27 Phase I involves initiating nonsteroidal anti-inflammatory drugs with or without glucocorticoid injections. Phase II involves synthetic disease-modifying drugs, including methotrexate, leflunomide, sulfasalazine, or cyclosporine. Phase III involves adding a second synthetic disease-modifying drug or starting a biologic, such as an anti–tumor necrosis factor, IL-12/IL-23, or IL-17 inhibitor. Phase IV involves switching to a different drug in either aforementioned class.^26,27 Treatment with biologics improves work productivity as assessed by WPAI-PSO for psoriasis and PsA.^28-30 Encouraging patients to speak up in the workplace and request small accommodations such as timely breaks or ergonomic chairs can help patients feel more comfortable and supported in the work environment.¹⁸ Patients who felt supported at work were more likely to remain employed.²⁵

Interpersonal Relationships Prevalence
Misinformation about psoriasis, fear of rejection, and feelings of isolation may contribute to interpersonal conflict. Patients have feelings of shame and self-consciousness that hinder them from engaging in social activities and seeking out relationships.³¹ Twenty-nine percent of patients feel that psoriasis has interfered with establishing relationships because of negative self-esteem associated with the disease,³² and 26.3% have experienced people avoiding physical contact.³³ Family and spouses of patients with psoriasis may be secondarily affected due to economic and emotional distress. Ninety-eight percent of family members of psoriatic patients experienced emotional distress and 54% experienced the burden of care.³⁴ In a survey of 63 relatives and partners of patients with psoriasis, 57% experienced psychological distress, including anxiety and worry over a psoriatic patient’s future.³⁵

Interpersonal Relationships Assessment
Current available tools, including the DLQI and short form health survey, measure overall QOL, including social functioning, but may not be practical in a clinic setting. Although no quick-screening test to assess for this domain exists, providers are encouraged to ask patients about disease impact on interpersonal relationships. The family DLQI questionnaire, adapted from the DLQI, may help physicians and social workers evaluate the burden on a patient’s family members.³⁴

Interpersonal Relationships Management
It may be difficult for providers to address problems with interpersonal relationships without accessible tools. Patients may not be accompanied by family or friends during appointments, and it is difficult to screen for these issues during visits. Providers may offer resources such as the NPF website, which provides information about support groups. It also provides tips on dating and connecting to others in the community who share similar experiences.¹⁸ Encouraging patients to seek family or couples therapy also may be beneficial. Increased social support can lead to better QOL and fewer depressive symptoms.³⁶

Sexual Functioning Prevalence
Psoriasis affects both physical and psychological components of sexual function. Among 3485 patients with skin conditions who were surveyed about sexual function, 34% of psoriatic patients reported that psoriasis interfered with sexual functioning at least to a certain degree.³⁷ Sexual impairment was strongly associated with depression, anxiety, and suicidal ideation; 24% of depressed patients and 20% of anxious patients experienced sexual problems a lot or very much, based on the DLQI.³⁷ Depending on the questionnaire used, the prevalence of sexual dysfunction due to psoriasis ranged from 35.5% to 71.3%.³⁸ In an observational cohort study of 158 participants (n=79 psoriasis patients and n=79 controls), 34.2% of patients with psoriasis experienced erectile dysfunction compared to 17.7% of controls.³⁹ Forty-two percent of psoriatic patients with genital involvement reported dyspareunia, 32% reported worsening of genital psoriasis after intercourse, and 43% reported decreased frequency of intercourse.⁴⁰

Sexual Functioning Assessment
The Skindex-29, DLQI, and psoriasis disability index are available QOL tools that include one question evaluating difficulties with sexual function. The Massachusetts General Hospital sexual functioning questionnaire is a 5-item validated tool that specifically assesses sexual dysfunction.⁴¹ Distribution of lesions can help identify patients who are more likely to experience sexual dysfunction. In 160 patients who completed the questionnaire and self-reported psoriasis area and severity index, lesions on the abdomen, genitals, lumbar region, and buttocks were associated with worse sexual functioning (OR: 7.9; 95% CI, 2.3-33.4; P<.05).⁴² Dermatologists could assess for sexual problems using either formal questionnaires or direct conversations during the routine psoriasis visit, as patients may be suffering in silence due to this sensitive topic.

Sexual Functioning Management
Better disease control leads to improved sexual function, as patients experience fewer feelings of shame, anxiety, and depression, as well as improvement of physical symptoms that can interfere with sexual functioning.^38,43,44 Reducing friction, warmth, and moisture, as well as avoiding tight clothing, can help those with genital psoriasis. Patients are advised to reapply topical medications after sexual intercourse. Patients also can apply makeup to disguise psoriasis and help reduce feelings of self-consciousness that can impede sexual intimacy.¹⁸

Comment

The psychosocial burden of psoriasis penetrates many facets of patient lives. Psoriasis can invoke feelings of shame and embarrassment that are worsened by the public’s misconceptions about psoriasis, resulting in serious mental health issues that can cause even greater disability. Depression and anxiety are prevalent in patients with psoriasis. The characteristic symptoms of pain and pruritus along with psychiatric comorbidities can have an underestimated impact on daily activities, including employment, interpersonal relationships, and sexual function. Such dysfunctions have serious implications toward wages, professional advancement, social support, and overall QOL.

Dermatology providers play an important role in screening for these problems through validated questionnaires and identifying risks. Simple screening questions such as the PHQ-9 can be beneficial and feasible during dermatology visits. Screening for PsA can help patients avoid problems at work. Sexual dysfunction is a sensitive topic; however, providers can use a 1-question screen from valid questionnaires and inquire about the location of lesions as opportunities to address this issue.

Interventions lead to better disease control, which concurrently improves overall QOL. These interventions depend on both patient adherence and a physician’s commitment to finding an optimal treatment regimen for each individual. Medical management; coordinating care; developing treatment plans with psychiatry, rheumatology, and primary care providers; and psychological counseling and services may be necessary and beneficial (Table). Offering accessible resources such as the NPF website helps patients access information outside the clinic when it is not feasible to address all these concerns in a single visit. Psoriasis requires more than just medical management; it requires dermatology providers to use a multidisciplinary approach to address the psychosocial aspects of the disease.

Conclusion

The psychosocial burden of psoriasis is immense. Stigma, public misconception, mental health concerns, and occupational and interpersonal difficulty are the basis of disease burden. Providers play a vital role in assessing the effect psoriasis has on different areas of patients’ lives and providing appropriate interventions and resources to reduce disease burden.

Psoriasis is a chronic autoimmune skin disease affecting approximately 6.7 million adults in the United States.¹ Although its pathogenesis is not yet clear, risk factors and triggers provide insight into potential pathways by which psoriasis can occur. There is notable overlap between risk factors and triggers of psoriasis; perceived risk factors might, in fact, be triggers causing manifestation of disease in predisposed persons. In this review, we summarize the key factors contributing to onset and exacerbation of psoriasis. When learning to manage this chronic disease, it also may be helpful to educate patients about how these elements may affect the course of psoriasis.

Genetics

The pathogenesis of psoriasis has a strong genetic component, with approximately 70% and 20% concordance rates in monozygotic and dizygotic twins, respectively.² Moreover, studies have shown a positive family history in approximately 35% of patients.^3,4 Family-based studies have found a 50% risk of developing psoriasis in patients with 2 affected parents.⁵ However, the genetics of psoriasis are complex and are attributed to many different genes. Thus far, genes involving antigen presentation, T-cell receptor development and polarization, and the nuclear factor κβ (NF-κβ) pathway have been identified.⁶

HLA-Cw6
The most well-studied gene implicated in psoriasis is HLA-Cw6, which encodes a major histocompatibility complex class I allele supporting psoriasis as a T cell–mediated reaction to an autoantigen.⁶ Two potential antigens for HLA-Cw6 recently have been identified: LL-37, a cathelicidin-related antimicrobial peptide, and the A disintegrin and metalloproteinase with thrombospondin motifs-like protein 5 (ADAMTSL5), found on melanocytes and keratinocytes.⁷ The percentage of psoriasis patients with HLA-Cw6 ranges from 10.5% to 77.2%, with higher frequency in white individuals than in Asians.⁷

HLA-Cw6 manifests as specific features in psoriasis, including onset of disease before 21 years of age.⁸ It also is more strongly associated with guttate-type psoriasis, greater body surface area involvement, and higher incidence of Köbner phenomenon. Patients with positive HLA-Cw6 also reported worsening of psoriasis during and after throat infection.⁹

Caspase Recruitment Domain Family Member 14
Another gene mutation implicated in psoriasis pathogenesis is caspase recruitment domain family member 14, CARD14 (formerly PSORS2), a gene encoding a scaffolding protein important in the activation of NF-κβ.^10,11 Missense CARD14 mutations cause upregulation of NF-κβ through formation of a complex with adapter protein B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1),¹² which, in turn, causes increased transcription of cytokines IL-8, C-C motif chemokine ligand 20 (CCL-20), and IL-36 gamma in the keratinocyte.¹³ Mutations in CARD14 alone lead to psoriasiform skin in mice through amplified activation of the IL-23/IL-17 axis.^14,15 Patients with a mutation in a CARD14 variant (p.Arg820Trp) have demonstrated better response to tumor necrosis factor (TNF) inhibitors.¹⁶

Further characterization of the genetic pathogenesis of psoriasis might lead to better targeted therapies, including the possibility of MALT1 inhibitors as a treatment option.¹²

Infection

Streptococcus
The association between streptococcal infection and psoriasis was first documented more than 100 years ago, specifically the onset of acute guttate psoriasis.^17,18 Although classically described following throat infection, psoriasis also occurs following streptococcal vulvovaginitis and perianal streptococcal infection.^19,20

This type of psoriasis is typically self-limited but can recur with subsequent streptococcal infections or initiate a more chronic plaque psoriasis. Patients have a 1 in 3 risk of developing chronic psoriasis within 10 years of a single episode of acute guttate psoriasis.²¹ Moreover, in many patients with existing plaque psoriasis, throat infection exacerbates psoriatic symptoms.²² The mechanism of exacerbation is likely due to cross-reactivity between streptococcal M surface antigen and human keratinocytes and might also be influenced by inherited abnormalities in immune response.^23-26 Therefore, tonsillectomy has been studied as a possible treatment of psoriasis but is likely helpful only in patients with exacerbations of disease that are closely associated with recurrent tonsillitis.²⁷

Human Immunodeficiency Virus
The prevalence of psoriasis in human immunodeficiency virus (HIV) patients is similar to or greater than the general population.²⁸ Human immunodeficiency virus infection causes new onset of psoriasis and exacerbation of existing psoriasis; severity often is correlated with worsening immune function.^28,29

The clinical subtypes of psoriasis that occur most frequently with HIV include guttate, inverse, and erythrodermic, though patients may present with any subtype.²⁸ The mechanism is puzzling because HIV is primarily mediated by helper T cell 2 (T_H2) cytokines, whereas psoriasis is mainly driven by helper T cell 1 (T_H1) cytokines.³⁰ Furthermore, despite increased severity with lower CD4⁺ counts, treatments further lowering T-cell counts paradoxically improve symptoms.³¹ Current literature suggests that expansion of CD8⁺ memory T cells might be the primary mechanism in the exacerbation of psoriasis in HIV-mediated immunosuppression.³⁰

Treatment of HIV-associated psoriasis presents challenges because many therapeutics cause further immunosuppression. The National Psoriasis Foundation recommends topical preparations as first-line agents for mild to moderate psoriasis.³² For moderate to severe psoriasis, retroviral agents may be effective as first-line monotherapy or when supplemented by phototherapy with UVB or psoralen plus UVA. Retinoids can be used as second-line agents.³² For cases of severe refractory psoriasis, cyclosporine, methotrexate, TNF inhibitors, or hydroxyurea can be considered. There also is evidence that apremilast is effective without risk for worsening immune function.³³

Other Infections
Other bacteria associated with triggering or exacerbating psoriasis include Staphylococcus aureus and Helicobacter pylori.^34,35 Fungi, such as species of the genera Malassezia and Candida, and other viruses, including papillomaviruses and retroviruses, also have been implicated.³⁴

Medications

Numerous medications can trigger psoriasis, including lithium, nonsteroidal anti-inflammatory drugs, antimalarials, beta-blockers, and angiotensin-converting enzyme inhibitors.³⁴ More recent literature suggests that TNF inhibitors also can paradoxically induce psoriasis in rare cases.³⁵

Lithium
Psoriasis is the most common cutaneous adverse effect of lithium.³⁴ It is more likely to exacerbate existing disease but also can induce onset of psoriasis; it also can cause disease that is more refractory to treatment.^34,36 Current literature hypothesizes that lithium triggers psoriasis by interference of intracellular calcium channels through reduction of inositol, thereby affecting keratinocyte proliferation and differentiation.³⁴ Lithium also inhibits glycogen synthase kinase-3 (GSK-3), a serine threonine kinase, which, in turn, induces human keratinocyte proliferation.³⁷ However, it is unlikely lithium alone can induce psoriasis; genetic predisposition is necessary.

TNF Inhibitors
Tumor necrosis factor inhibitors such as adalimumab, etanercept, certolizumab pegol, golimumab, and infliximab are used in various inflammatory diseases, including psoriasis. Interestingly, there have been more than 200 reported cases of suspected TNF inhibitor–induced or –exacerbated psoriasis.³⁸ This phenomenon appears to occur more frequently with infliximab and is most likely to occur in the first year of treatment of Crohn disease and rheumatoid arthritis.³⁸ Plaque psoriasis is the most common form, but 15% to 26% of cases presented with 2 or more morphologies.^38,39

Treatment options include discontinuing therapy, though many patients experience resolution while continuing treatment or switching to another TNF inhibitor.^38-40 Traditional topical therapies also have been used with success.⁴⁰ The pathogenesis of this phenomenon is still unclear but is thought to involve both the IL-23/helper T cell 17 (T_H17) axis and dysregulation of IFN-α in the setting of TNF suppression.³⁸

Lifestyle

Obesity is a chronic low-grade inflammatory state that can contribute to the onset of psoriasis or exacerbation of existing disease.^41,42 Smoking also is thought to increase the risk for psoriasis, perhaps by a similar mechanism. Lee et al⁴³ found a strong positive correlation between the amount or duration of smoking and the incidence of psoriasis.

The relationship between psoriasis and alcohol consumption is less clear than it is between psoriasis and obesity or smoking; greater consumption is found in psoriasis patients, but evidence is insufficient to deem alcohol a risk factor.⁴⁴

Conclusion

Various factors, including genetics, infection, pharmacotherapeutic, and lifestyle, can all contribute to the induction or exacerbation of psoriasis. These factors can provide clues to the pathogenesis of psoriasis as well as help clinicians better counsel patients about their disease.

Psoriasis is a chronic autoimmune skin disease affecting approximately 6.7 million adults in the United States.¹ Although its pathogenesis is not yet clear, risk factors and triggers provide insight into potential pathways by which psoriasis can occur. There is notable overlap between risk factors and triggers of psoriasis; perceived risk factors might, in fact, be triggers causing manifestation of disease in predisposed persons. In this review, we summarize the key factors contributing to onset and exacerbation of psoriasis. When learning to manage this chronic disease, it also may be helpful to educate patients about how these elements may affect the course of psoriasis.

Genetics

The pathogenesis of psoriasis has a strong genetic component, with approximately 70% and 20% concordance rates in monozygotic and dizygotic twins, respectively.² Moreover, studies have shown a positive family history in approximately 35% of patients.^3,4 Family-based studies have found a 50% risk of developing psoriasis in patients with 2 affected parents.⁵ However, the genetics of psoriasis are complex and are attributed to many different genes. Thus far, genes involving antigen presentation, T-cell receptor development and polarization, and the nuclear factor κβ (NF-κβ) pathway have been identified.⁶

HLA-Cw6
The most well-studied gene implicated in psoriasis is HLA-Cw6, which encodes a major histocompatibility complex class I allele supporting psoriasis as a T cell–mediated reaction to an autoantigen.⁶ Two potential antigens for HLA-Cw6 recently have been identified: LL-37, a cathelicidin-related antimicrobial peptide, and the A disintegrin and metalloproteinase with thrombospondin motifs-like protein 5 (ADAMTSL5), found on melanocytes and keratinocytes.⁷ The percentage of psoriasis patients with HLA-Cw6 ranges from 10.5% to 77.2%, with higher frequency in white individuals than in Asians.⁷

HLA-Cw6 manifests as specific features in psoriasis, including onset of disease before 21 years of age.⁸ It also is more strongly associated with guttate-type psoriasis, greater body surface area involvement, and higher incidence of Köbner phenomenon. Patients with positive HLA-Cw6 also reported worsening of psoriasis during and after throat infection.⁹

Caspase Recruitment Domain Family Member 14
Another gene mutation implicated in psoriasis pathogenesis is caspase recruitment domain family member 14, CARD14 (formerly PSORS2), a gene encoding a scaffolding protein important in the activation of NF-κβ.^10,11 Missense CARD14 mutations cause upregulation of NF-κβ through formation of a complex with adapter protein B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1),¹² which, in turn, causes increased transcription of cytokines IL-8, C-C motif chemokine ligand 20 (CCL-20), and IL-36 gamma in the keratinocyte.¹³ Mutations in CARD14 alone lead to psoriasiform skin in mice through amplified activation of the IL-23/IL-17 axis.^14,15 Patients with a mutation in a CARD14 variant (p.Arg820Trp) have demonstrated better response to tumor necrosis factor (TNF) inhibitors.¹⁶

Further characterization of the genetic pathogenesis of psoriasis might lead to better targeted therapies, including the possibility of MALT1 inhibitors as a treatment option.¹²

Infection

Streptococcus
The association between streptococcal infection and psoriasis was first documented more than 100 years ago, specifically the onset of acute guttate psoriasis.^17,18 Although classically described following throat infection, psoriasis also occurs following streptococcal vulvovaginitis and perianal streptococcal infection.^19,20

This type of psoriasis is typically self-limited but can recur with subsequent streptococcal infections or initiate a more chronic plaque psoriasis. Patients have a 1 in 3 risk of developing chronic psoriasis within 10 years of a single episode of acute guttate psoriasis.²¹ Moreover, in many patients with existing plaque psoriasis, throat infection exacerbates psoriatic symptoms.²² The mechanism of exacerbation is likely due to cross-reactivity between streptococcal M surface antigen and human keratinocytes and might also be influenced by inherited abnormalities in immune response.^23-26 Therefore, tonsillectomy has been studied as a possible treatment of psoriasis but is likely helpful only in patients with exacerbations of disease that are closely associated with recurrent tonsillitis.²⁷

Human Immunodeficiency Virus
The prevalence of psoriasis in human immunodeficiency virus (HIV) patients is similar to or greater than the general population.²⁸ Human immunodeficiency virus infection causes new onset of psoriasis and exacerbation of existing psoriasis; severity often is correlated with worsening immune function.^28,29

The clinical subtypes of psoriasis that occur most frequently with HIV include guttate, inverse, and erythrodermic, though patients may present with any subtype.²⁸ The mechanism is puzzling because HIV is primarily mediated by helper T cell 2 (T_H2) cytokines, whereas psoriasis is mainly driven by helper T cell 1 (T_H1) cytokines.³⁰ Furthermore, despite increased severity with lower CD4⁺ counts, treatments further lowering T-cell counts paradoxically improve symptoms.³¹ Current literature suggests that expansion of CD8⁺ memory T cells might be the primary mechanism in the exacerbation of psoriasis in HIV-mediated immunosuppression.³⁰

Treatment of HIV-associated psoriasis presents challenges because many therapeutics cause further immunosuppression. The National Psoriasis Foundation recommends topical preparations as first-line agents for mild to moderate psoriasis.³² For moderate to severe psoriasis, retroviral agents may be effective as first-line monotherapy or when supplemented by phototherapy with UVB or psoralen plus UVA. Retinoids can be used as second-line agents.³² For cases of severe refractory psoriasis, cyclosporine, methotrexate, TNF inhibitors, or hydroxyurea can be considered. There also is evidence that apremilast is effective without risk for worsening immune function.³³

Other Infections
Other bacteria associated with triggering or exacerbating psoriasis include Staphylococcus aureus and Helicobacter pylori.^34,35 Fungi, such as species of the genera Malassezia and Candida, and other viruses, including papillomaviruses and retroviruses, also have been implicated.³⁴

Medications

Numerous medications can trigger psoriasis, including lithium, nonsteroidal anti-inflammatory drugs, antimalarials, beta-blockers, and angiotensin-converting enzyme inhibitors.³⁴ More recent literature suggests that TNF inhibitors also can paradoxically induce psoriasis in rare cases.³⁵

Lithium
Psoriasis is the most common cutaneous adverse effect of lithium.³⁴ It is more likely to exacerbate existing disease but also can induce onset of psoriasis; it also can cause disease that is more refractory to treatment.^34,36 Current literature hypothesizes that lithium triggers psoriasis by interference of intracellular calcium channels through reduction of inositol, thereby affecting keratinocyte proliferation and differentiation.³⁴ Lithium also inhibits glycogen synthase kinase-3 (GSK-3), a serine threonine kinase, which, in turn, induces human keratinocyte proliferation.³⁷ However, it is unlikely lithium alone can induce psoriasis; genetic predisposition is necessary.

TNF Inhibitors
Tumor necrosis factor inhibitors such as adalimumab, etanercept, certolizumab pegol, golimumab, and infliximab are used in various inflammatory diseases, including psoriasis. Interestingly, there have been more than 200 reported cases of suspected TNF inhibitor–induced or –exacerbated psoriasis.³⁸ This phenomenon appears to occur more frequently with infliximab and is most likely to occur in the first year of treatment of Crohn disease and rheumatoid arthritis.³⁸ Plaque psoriasis is the most common form, but 15% to 26% of cases presented with 2 or more morphologies.^38,39

Treatment options include discontinuing therapy, though many patients experience resolution while continuing treatment or switching to another TNF inhibitor.^38-40 Traditional topical therapies also have been used with success.⁴⁰ The pathogenesis of this phenomenon is still unclear but is thought to involve both the IL-23/helper T cell 17 (T_H17) axis and dysregulation of IFN-α in the setting of TNF suppression.³⁸

Lifestyle

Obesity is a chronic low-grade inflammatory state that can contribute to the onset of psoriasis or exacerbation of existing disease.^41,42 Smoking also is thought to increase the risk for psoriasis, perhaps by a similar mechanism. Lee et al⁴³ found a strong positive correlation between the amount or duration of smoking and the incidence of psoriasis.

The relationship between psoriasis and alcohol consumption is less clear than it is between psoriasis and obesity or smoking; greater consumption is found in psoriasis patients, but evidence is insufficient to deem alcohol a risk factor.⁴⁴

Conclusion

Various factors, including genetics, infection, pharmacotherapeutic, and lifestyle, can all contribute to the induction or exacerbation of psoriasis. These factors can provide clues to the pathogenesis of psoriasis as well as help clinicians better counsel patients about their disease.

Psoriasis is a chronic autoimmune skin disease affecting approximately 6.7 million adults in the United States.¹ Although its pathogenesis is not yet clear, risk factors and triggers provide insight into potential pathways by which psoriasis can occur. There is notable overlap between risk factors and triggers of psoriasis; perceived risk factors might, in fact, be triggers causing manifestation of disease in predisposed persons. In this review, we summarize the key factors contributing to onset and exacerbation of psoriasis. When learning to manage this chronic disease, it also may be helpful to educate patients about how these elements may affect the course of psoriasis.

Genetics

The pathogenesis of psoriasis has a strong genetic component, with approximately 70% and 20% concordance rates in monozygotic and dizygotic twins, respectively.² Moreover, studies have shown a positive family history in approximately 35% of patients.^3,4 Family-based studies have found a 50% risk of developing psoriasis in patients with 2 affected parents.⁵ However, the genetics of psoriasis are complex and are attributed to many different genes. Thus far, genes involving antigen presentation, T-cell receptor development and polarization, and the nuclear factor κβ (NF-κβ) pathway have been identified.⁶

HLA-Cw6
The most well-studied gene implicated in psoriasis is HLA-Cw6, which encodes a major histocompatibility complex class I allele supporting psoriasis as a T cell–mediated reaction to an autoantigen.⁶ Two potential antigens for HLA-Cw6 recently have been identified: LL-37, a cathelicidin-related antimicrobial peptide, and the A disintegrin and metalloproteinase with thrombospondin motifs-like protein 5 (ADAMTSL5), found on melanocytes and keratinocytes.⁷ The percentage of psoriasis patients with HLA-Cw6 ranges from 10.5% to 77.2%, with higher frequency in white individuals than in Asians.⁷

HLA-Cw6 manifests as specific features in psoriasis, including onset of disease before 21 years of age.⁸ It also is more strongly associated with guttate-type psoriasis, greater body surface area involvement, and higher incidence of Köbner phenomenon. Patients with positive HLA-Cw6 also reported worsening of psoriasis during and after throat infection.⁹

Caspase Recruitment Domain Family Member 14
Another gene mutation implicated in psoriasis pathogenesis is caspase recruitment domain family member 14, CARD14 (formerly PSORS2), a gene encoding a scaffolding protein important in the activation of NF-κβ.^10,11 Missense CARD14 mutations cause upregulation of NF-κβ through formation of a complex with adapter protein B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1),¹² which, in turn, causes increased transcription of cytokines IL-8, C-C motif chemokine ligand 20 (CCL-20), and IL-36 gamma in the keratinocyte.¹³ Mutations in CARD14 alone lead to psoriasiform skin in mice through amplified activation of the IL-23/IL-17 axis.^14,15 Patients with a mutation in a CARD14 variant (p.Arg820Trp) have demonstrated better response to tumor necrosis factor (TNF) inhibitors.¹⁶

Further characterization of the genetic pathogenesis of psoriasis might lead to better targeted therapies, including the possibility of MALT1 inhibitors as a treatment option.¹²

Infection

Streptococcus
The association between streptococcal infection and psoriasis was first documented more than 100 years ago, specifically the onset of acute guttate psoriasis.^17,18 Although classically described following throat infection, psoriasis also occurs following streptococcal vulvovaginitis and perianal streptococcal infection.^19,20

This type of psoriasis is typically self-limited but can recur with subsequent streptococcal infections or initiate a more chronic plaque psoriasis. Patients have a 1 in 3 risk of developing chronic psoriasis within 10 years of a single episode of acute guttate psoriasis.²¹ Moreover, in many patients with existing plaque psoriasis, throat infection exacerbates psoriatic symptoms.²² The mechanism of exacerbation is likely due to cross-reactivity between streptococcal M surface antigen and human keratinocytes and might also be influenced by inherited abnormalities in immune response.^23-26 Therefore, tonsillectomy has been studied as a possible treatment of psoriasis but is likely helpful only in patients with exacerbations of disease that are closely associated with recurrent tonsillitis.²⁷

Human Immunodeficiency Virus
The prevalence of psoriasis in human immunodeficiency virus (HIV) patients is similar to or greater than the general population.²⁸ Human immunodeficiency virus infection causes new onset of psoriasis and exacerbation of existing psoriasis; severity often is correlated with worsening immune function.^28,29

The clinical subtypes of psoriasis that occur most frequently with HIV include guttate, inverse, and erythrodermic, though patients may present with any subtype.²⁸ The mechanism is puzzling because HIV is primarily mediated by helper T cell 2 (T_H2) cytokines, whereas psoriasis is mainly driven by helper T cell 1 (T_H1) cytokines.³⁰ Furthermore, despite increased severity with lower CD4⁺ counts, treatments further lowering T-cell counts paradoxically improve symptoms.³¹ Current literature suggests that expansion of CD8⁺ memory T cells might be the primary mechanism in the exacerbation of psoriasis in HIV-mediated immunosuppression.³⁰

Treatment of HIV-associated psoriasis presents challenges because many therapeutics cause further immunosuppression. The National Psoriasis Foundation recommends topical preparations as first-line agents for mild to moderate psoriasis.³² For moderate to severe psoriasis, retroviral agents may be effective as first-line monotherapy or when supplemented by phototherapy with UVB or psoralen plus UVA. Retinoids can be used as second-line agents.³² For cases of severe refractory psoriasis, cyclosporine, methotrexate, TNF inhibitors, or hydroxyurea can be considered. There also is evidence that apremilast is effective without risk for worsening immune function.³³

Other Infections
Other bacteria associated with triggering or exacerbating psoriasis include Staphylococcus aureus and Helicobacter pylori.^34,35 Fungi, such as species of the genera Malassezia and Candida, and other viruses, including papillomaviruses and retroviruses, also have been implicated.³⁴

Medications

Numerous medications can trigger psoriasis, including lithium, nonsteroidal anti-inflammatory drugs, antimalarials, beta-blockers, and angiotensin-converting enzyme inhibitors.³⁴ More recent literature suggests that TNF inhibitors also can paradoxically induce psoriasis in rare cases.³⁵

Lithium
Psoriasis is the most common cutaneous adverse effect of lithium.³⁴ It is more likely to exacerbate existing disease but also can induce onset of psoriasis; it also can cause disease that is more refractory to treatment.^34,36 Current literature hypothesizes that lithium triggers psoriasis by interference of intracellular calcium channels through reduction of inositol, thereby affecting keratinocyte proliferation and differentiation.³⁴ Lithium also inhibits glycogen synthase kinase-3 (GSK-3), a serine threonine kinase, which, in turn, induces human keratinocyte proliferation.³⁷ However, it is unlikely lithium alone can induce psoriasis; genetic predisposition is necessary.

TNF Inhibitors
Tumor necrosis factor inhibitors such as adalimumab, etanercept, certolizumab pegol, golimumab, and infliximab are used in various inflammatory diseases, including psoriasis. Interestingly, there have been more than 200 reported cases of suspected TNF inhibitor–induced or –exacerbated psoriasis.³⁸ This phenomenon appears to occur more frequently with infliximab and is most likely to occur in the first year of treatment of Crohn disease and rheumatoid arthritis.³⁸ Plaque psoriasis is the most common form, but 15% to 26% of cases presented with 2 or more morphologies.^38,39

Treatment options include discontinuing therapy, though many patients experience resolution while continuing treatment or switching to another TNF inhibitor.^38-40 Traditional topical therapies also have been used with success.⁴⁰ The pathogenesis of this phenomenon is still unclear but is thought to involve both the IL-23/helper T cell 17 (T_H17) axis and dysregulation of IFN-α in the setting of TNF suppression.³⁸

Lifestyle

Obesity is a chronic low-grade inflammatory state that can contribute to the onset of psoriasis or exacerbation of existing disease.^41,42 Smoking also is thought to increase the risk for psoriasis, perhaps by a similar mechanism. Lee et al⁴³ found a strong positive correlation between the amount or duration of smoking and the incidence of psoriasis.

The relationship between psoriasis and alcohol consumption is less clear than it is between psoriasis and obesity or smoking; greater consumption is found in psoriasis patients, but evidence is insufficient to deem alcohol a risk factor.⁴⁴

Conclusion

Various factors, including genetics, infection, pharmacotherapeutic, and lifestyle, can all contribute to the induction or exacerbation of psoriasis. These factors can provide clues to the pathogenesis of psoriasis as well as help clinicians better counsel patients about their disease.

Psoriasis is a T cell–mediated inflammatory disease that manifests as erythematous scaling plaques of the skin. In recent decades, our understanding of psoriasis has transformed from a disease isolated to the skin to a systemic disease impacting the overall health of those affected.

With recent elucidation of the pathways driving psoriasis, development of targeted therapies has resulted in an influx of options to the market. Navigating the options can seem overwhelming even to the seasoned clinician. Becoming familiar with a sound treatment approach during residency will create a foundation for biologic use in psoriasis patients throughout your career. Here we offer an approach to choosing biologic treatments based on individual patient characteristics, including disease severity, comorbidities, and ultimate treatment goals.

Immune Pathogenesis

Although the pathogenesis of psoriasis is complex and outside the scope of this article, we do recommend clinicians keep in mind the current understanding of pathways involved and ways our therapies alter them. Briefly, psoriasis is a T cell–mediated disease in which IL-12 and IL-23 released by activated dendritic cells activate T helper cells including T_H1, T_H17, and T_H22. These cells produce additional cytokines, including IFN-γ, tumor necrosis factor (TNF) α, IL-17, and IL-22, which propagate the immune response and lead to keratinocyte hyperproliferation. In general, psoriasis medications work by altering T-cell activation, effector cytokines, or cytokine receptors.

Comorbidities

A targeted approach should take into consideration the immune dysregulation shared by psoriasis and associated comorbidities (Table 1). One goal of biologic treatments is to improve comorbidities when possible. At minimum, selected treatments should not exacerbate these conditions.

Treatment Goals

Establishing treatment goals can help shape patient expectations and provide a plan for clinicians. In 2017, the National Psoriasis Foundation published a treat-to-target approach using body surface area (BSA) measurements at baseline, 3 months, and then every 6 months after starting a new treatment.¹² The target response is a decrease in psoriasis to 1% or less BSA at 3 months and to maintain this response when evaluated at 6-month intervals. Alternatively, a target of 3% BSA after 3 months is satisfactory if the patient improves by 75% BSA overall. If these targets are not met after 6 months, therapeutic alternatives can be considered.¹²

Biologic Treatment of Psoriasis

Treatment options for patients with psoriasis depend first on disease severity. Topicals and phototherapy are first line for mild to moderate disease. For moderate to severe disease, addition of systemic agents such as methotrexate, cyclosporine, or acitretin; small-molecular-weight immunomodulators such as apremilast; or biologic medications should be considered. Current biologics available for moderate to severe plaque psoriasis target TNF-α, IL-12/IL-23, IL-23, IL-17A, or IL-17A receptor.

TNF-α Inhibitors

Tumor necrosis factor α inhibitors have been available for treatment of autoimmune disease for nearly 20 years. These medications block either soluble cytokine or membrane-bound cytokine. All are given as subcutaneous injections, except for infliximab, which is a weight-based infusion.

Efficacy
Tumor necrosis factor α inhibitors are the first class to demonstrate long-term efficacy and safety in both psoriasis and psoriatic arthritis (PsA). Etanercept was approved for adults with PsA in 2002 and psoriasis in 2004, and later for pediatric psoriasis (≥4 years of age) in 2016 (Table 2). Although etanercept has a sustained safety profile, the response rates are not as high as other anti–TNF-α inhibitors. Adalimumab is one of the most prescribed biologics, with a total of 10 indications at present, including PsA. Infliximab is an intravenous infusion that demonstrates a rapid and sustained response in most patients. The dose and dosing interval can be adjusted according to response. Certolizumab pegol was approved for PsA in 2013 and for psoriasis in 2018.

Safety
To evaluate long-term safety, a multicenter prospective registry study (Psoriasis Longitudinal Assessment and Registry [PSOLAR]) was initiated in 2007 to follow clinical outcomes. Data through 2013 showed no significant increase in rates of infection, malignancy, or major adverse cardiovascular events in more than 12,000 patients.¹³

Conflicting information exists in the literature regarding risk for malignancy with TNF-α inhibitors. One recent retrospective cohort study suggested a slightly increased risk for malignancies other than nonmelanoma skin cancers in patients on TNF-α inhibitors for more than 12 months (relative risk, 1.54).¹⁴ Reports of increased risk for cutaneous squamous cell carcinomas necessitate regular skin checks.¹⁵ A potential risk for lymphoma has been noted, though having psoriasis itself imparts an increased risk for Hodgkin and cutaneous T-cell lymphoma.¹⁶

Reactivation of tuberculosis and hepatitis have been reported with TNF-α inhibition. Data suggest that infliximab may be associated with more serious infections.¹³

Demyelinating conditions such as multiple sclerosis have occurred de novo or worsened in patients on TNF-α inhibitors.¹⁷ Tumor necrosis factor α blockers should be avoided in patients with decompensated heart failure. Rare cases of liver enzyme elevation and cytopenia have been noted. Additionally, lupuslike syndromes, which are generally reversible upon discontinuation, have occurred in some patients.

Patient Selection
Tumor necrosis factor α inhibitors are the treatment of choice for patients with comorbid PsA. This class halts progression of joint destruction over time.¹⁸Select TNF-α inhibitors are indicated for inflammatory bowel disease (IBD) and are a preferred treatment in this patient population. Specifically, adalimumab and infliximab are approved for both Crohn disease (CD) and ulcerative colitis. Certolizumab pegol is approved for CD.

Tumor necrosis factor α is upregulated in obesity, cardiovascular disease, and atherosclerotic plaques. Evidence suggests that TNF-α blockers may lower cardiovascular risk over time.¹⁹ For patients with obesity, infliximab is a good option, as it is the only TNF-α inhibitor with weight-based dosing.

In patients with frequent infections or history of hepatitis C, etanercept has been the biologic most commonly used when no alternatives exist, in part due to its shorter half-life.

IL-12/IL-23 Inhibitor

Ustekinumab is a monoclonal antibody that binds the p40 subunit shared by IL-12 and IL-23, blocking their ability to bind receptors. IL-12 and IL-23 play a role in activating naïve T cells to become T_H1 or T_H17 cells, respectively.

Efficacy and Safety
Clinical trials demonstrate long-term efficacy of ustekinumab, which was approved for psoriasis in 2009, PsA in 2013, and later pediatric psoriasis (≥12 years of age) in 2017. Dosing is listed in Table 2.

Laboratory abnormalities did not arise in trials. Periodic tuberculosis screening is required. Prospective data over 5 years showed very low rates of adverse events (AEs), serious infections, malignancies, and major adverse cardiovascular events.²⁰ Ustekinumab did not worsen or improve demyelinating disease and appears safe in this population.

Patient Selection
Ustekinumab is approved for PsA and is a good option for those who are not candidates for TNF-α and IL-17 inhibitors. Ustekinumab also is approved for CD. The dosing interval of 12 weeks makes ustekinumab convenient for patients. Two dosages exist based on the patient’s weight, offering an advantage to obese patients.

IL-17/IL-17R Inhibitors

Activated T_H17 cells produce the IL-17 cytokine family, which stimulates keratinocyte proliferation and dermal inflammation. Secukinumab is a fully human monoclonal antibody, and ixekizumab is a humanized monoclonal antibody; both target IL-17A. Brodalumab targets the IL-17A receptor.

Efficacy and Safety
IL-17 inhibitors showed impressive and rapid responses in trials.^21-23 The subsets of patients who responded well and continued treatment in extension trials demonstrated that these treatments maintain efficacy over time.^24-26

In addition to tuberculosis reactivation, there is a small increased risk for cutaneous candidiasis with IL-17 inhibitors, which can be managed without stopping treatment. Laboratory abnormalities were limited to mild neutropenia, which was not associated with increased risk for infection.^21-23 With ixekizumab, neutropenia was seen more commonly in the first 12 weeks.²²

IL-17 is highly expressed in the gut mucosa, and its inhibition is thought to weaken the barrier function of the gut mucosa, promoting inflammation. As a consequence, this class is contraindicated in patients with IBD due to exacerbations of existing IBD and cases of new-onset IBD.^21-23 Symptoms of diarrhea, abdominal pain, blood in stool, or nighttime stooling on review of gastrointestinal tract symptoms should prompt further evaluation.

Brodalumab has a unique warning for risk for suicidal ideation and behavior.²³ Depression is more common in the psoriasis population in general; therefore, physicians should be aware of this potential comorbidity regardless of the treatment plan. Because the response rates are so impressive with brodalumab, the Risk Evaluation and Mitigation Strategy (REMS) program was established to ensure understanding of this risk so that patients can be appropriately counseled and managed.

Patient Selection
The improvement in psoriasis is rapid and may occur as early as week 2 to 3 of treatment after initiation of IL-17 inhibitors. Ixekizumab and secukinumab also are approved for PsA. Although improvement in joint disease is not as fast as with the anti-TNF inhibitors, notable improvement occurs by week 20 to 24.²⁷

IL-23 Inhibitors

Guselkumab and tildrakizumab are the newest biologics for psoriasis, approved in 2017 and 2018, respectively. Both are monoclonal antibodies against the p19 subunit of IL-23, which blocks activation of T_H17 cells.

Efficacy and Safety
Guselkumab and tildrakizumab demonstrated efficacy with minimal AEs or precautions noted thus far.^28,29 Infections are again a risk, making tuberculosis testing the only recommended monitoring.

Patient Selection
Both medications offer another effective and safe option for patients with psoriasis. Similar to ustekinumab, the dosing interval of 12 weeks for tildrakizumab is ideal for patients who have needle phobia or are unable to administer their own injections.

Special Populations

Pregnancy

Antibodies cross the placenta as pregnancy progresses, with the highest rate in the third trimester. Certolizumab pegol has shown the lowest concentrations in infant serum, possibly due to its unique structure lacking the fragment crystallizable region required for passage through the placenta.³⁰ For this reason, certolizumab pegol is a treatment of choice if biologic therapy is warranted during pregnancy.

Much of the pregnancy data for the remaining TNF-α inhibitors come from patients with rheumatoid arthritis or CD. In these populations, rates of major birth defects and miscarriages do not differ greatly from untreated women with these conditions.³¹ One retrospective study of unintentional pregnancies in women receiving ustekinumab showed rates of AEs similar to the general population.³²

Pregnancy data for IL-17 or IL-23 inhibitors are largely limited to animal studies. One retrospective study of women exposed to secukinumab early in gestation showed no increased risk for pregnancy-related AEs.³³ Discontinuation is still recommended for patients who become pregnant.

Pediatric Patients

Etanercept is approved for pediatric psoriatic patients 4 years and older. Children with juvenile idiopathic arthritis who are 2 years and older can receive etanercept. Ustekinumab is safe and effective for pediatric psoriatic patients 12 years and older, offering a second biologic option in children.

Although not approved for pediatric psoriasis, adalimumab is approved in pediatric CD (≥6 years of age) and for juvenile idiopathic arthritis (≥2 years of age). Infliximab is approved for children 6 years and older with CD or ulcerative colitis.

Monitoring

Periodic tuberculosis screening is recommended for all biologics. For patients with latent tuberculosis, biologics may be restarted after 1 month of treatment of tuberculosis.

Prior to initiation of biologics, patients should be screened for hepatitis with hepatitis B surface antigen and antibody, hepatitis B core antibody, and hepatitis C antibody. Patients at risk for human immunodeficiency virus also should be screened.

Generally, complete blood cell count and comprehensive metabolic profile are advisable prior to starting a biologic. Opinions differ on frequency of repeating laboratory work. Complete blood cell count and comprehensive metabolic profile should be monitored at least every 3 to 6 months in patients on TNF-α inhibitors, and neutrophil count should be monitored during the induction phase of IL-17 inhibitors.

All patients with psoriasis should maintain age-appropriate cancer screenings, especially those on biologics. If malignancy is discovered, biologic medication should be discontinued. Debate exists as to when therapy can be safely restarted following treatment of malignancy. Patients who are considered at low risk for recurrence may opt to restart a biologic after 5 years, or sooner if symptoms warrant.³⁴ This decision should involve the patient’s cancer specialist.

Conclusion

Treatment choices are based on psoriasis type and severity, comorbidities, patient preferences, and drug accessibility. One approach is detailed in Table 3. As research advances the understanding of psoriasis, this field will continue to rapidly change. Knowledge of the immunopathogenesis of psoriasis and its relation to comorbidities can direct your decision-making for individual patients.

Psoriasis is a T cell–mediated inflammatory disease that manifests as erythematous scaling plaques of the skin. In recent decades, our understanding of psoriasis has transformed from a disease isolated to the skin to a systemic disease impacting the overall health of those affected.

With recent elucidation of the pathways driving psoriasis, development of targeted therapies has resulted in an influx of options to the market. Navigating the options can seem overwhelming even to the seasoned clinician. Becoming familiar with a sound treatment approach during residency will create a foundation for biologic use in psoriasis patients throughout your career. Here we offer an approach to choosing biologic treatments based on individual patient characteristics, including disease severity, comorbidities, and ultimate treatment goals.

Immune Pathogenesis

Although the pathogenesis of psoriasis is complex and outside the scope of this article, we do recommend clinicians keep in mind the current understanding of pathways involved and ways our therapies alter them. Briefly, psoriasis is a T cell–mediated disease in which IL-12 and IL-23 released by activated dendritic cells activate T helper cells including T_H1, T_H17, and T_H22. These cells produce additional cytokines, including IFN-γ, tumor necrosis factor (TNF) α, IL-17, and IL-22, which propagate the immune response and lead to keratinocyte hyperproliferation. In general, psoriasis medications work by altering T-cell activation, effector cytokines, or cytokine receptors.

Comorbidities

A targeted approach should take into consideration the immune dysregulation shared by psoriasis and associated comorbidities (Table 1). One goal of biologic treatments is to improve comorbidities when possible. At minimum, selected treatments should not exacerbate these conditions.

Treatment Goals

Establishing treatment goals can help shape patient expectations and provide a plan for clinicians. In 2017, the National Psoriasis Foundation published a treat-to-target approach using body surface area (BSA) measurements at baseline, 3 months, and then every 6 months after starting a new treatment.¹² The target response is a decrease in psoriasis to 1% or less BSA at 3 months and to maintain this response when evaluated at 6-month intervals. Alternatively, a target of 3% BSA after 3 months is satisfactory if the patient improves by 75% BSA overall. If these targets are not met after 6 months, therapeutic alternatives can be considered.¹²

Biologic Treatment of Psoriasis

Treatment options for patients with psoriasis depend first on disease severity. Topicals and phototherapy are first line for mild to moderate disease. For moderate to severe disease, addition of systemic agents such as methotrexate, cyclosporine, or acitretin; small-molecular-weight immunomodulators such as apremilast; or biologic medications should be considered. Current biologics available for moderate to severe plaque psoriasis target TNF-α, IL-12/IL-23, IL-23, IL-17A, or IL-17A receptor.

TNF-α Inhibitors

Tumor necrosis factor α inhibitors have been available for treatment of autoimmune disease for nearly 20 years. These medications block either soluble cytokine or membrane-bound cytokine. All are given as subcutaneous injections, except for infliximab, which is a weight-based infusion.

Efficacy
Tumor necrosis factor α inhibitors are the first class to demonstrate long-term efficacy and safety in both psoriasis and psoriatic arthritis (PsA). Etanercept was approved for adults with PsA in 2002 and psoriasis in 2004, and later for pediatric psoriasis (≥4 years of age) in 2016 (Table 2). Although etanercept has a sustained safety profile, the response rates are not as high as other anti–TNF-α inhibitors. Adalimumab is one of the most prescribed biologics, with a total of 10 indications at present, including PsA. Infliximab is an intravenous infusion that demonstrates a rapid and sustained response in most patients. The dose and dosing interval can be adjusted according to response. Certolizumab pegol was approved for PsA in 2013 and for psoriasis in 2018.

Safety
To evaluate long-term safety, a multicenter prospective registry study (Psoriasis Longitudinal Assessment and Registry [PSOLAR]) was initiated in 2007 to follow clinical outcomes. Data through 2013 showed no significant increase in rates of infection, malignancy, or major adverse cardiovascular events in more than 12,000 patients.¹³

Conflicting information exists in the literature regarding risk for malignancy with TNF-α inhibitors. One recent retrospective cohort study suggested a slightly increased risk for malignancies other than nonmelanoma skin cancers in patients on TNF-α inhibitors for more than 12 months (relative risk, 1.54).¹⁴ Reports of increased risk for cutaneous squamous cell carcinomas necessitate regular skin checks.¹⁵ A potential risk for lymphoma has been noted, though having psoriasis itself imparts an increased risk for Hodgkin and cutaneous T-cell lymphoma.¹⁶

Reactivation of tuberculosis and hepatitis have been reported with TNF-α inhibition. Data suggest that infliximab may be associated with more serious infections.¹³

Demyelinating conditions such as multiple sclerosis have occurred de novo or worsened in patients on TNF-α inhibitors.¹⁷ Tumor necrosis factor α blockers should be avoided in patients with decompensated heart failure. Rare cases of liver enzyme elevation and cytopenia have been noted. Additionally, lupuslike syndromes, which are generally reversible upon discontinuation, have occurred in some patients.

Patient Selection
Tumor necrosis factor α inhibitors are the treatment of choice for patients with comorbid PsA. This class halts progression of joint destruction over time.¹⁸Select TNF-α inhibitors are indicated for inflammatory bowel disease (IBD) and are a preferred treatment in this patient population. Specifically, adalimumab and infliximab are approved for both Crohn disease (CD) and ulcerative colitis. Certolizumab pegol is approved for CD.

Tumor necrosis factor α is upregulated in obesity, cardiovascular disease, and atherosclerotic plaques. Evidence suggests that TNF-α blockers may lower cardiovascular risk over time.¹⁹ For patients with obesity, infliximab is a good option, as it is the only TNF-α inhibitor with weight-based dosing.

In patients with frequent infections or history of hepatitis C, etanercept has been the biologic most commonly used when no alternatives exist, in part due to its shorter half-life.

IL-12/IL-23 Inhibitor

Ustekinumab is a monoclonal antibody that binds the p40 subunit shared by IL-12 and IL-23, blocking their ability to bind receptors. IL-12 and IL-23 play a role in activating naïve T cells to become T_H1 or T_H17 cells, respectively.

Efficacy and Safety
Clinical trials demonstrate long-term efficacy of ustekinumab, which was approved for psoriasis in 2009, PsA in 2013, and later pediatric psoriasis (≥12 years of age) in 2017. Dosing is listed in Table 2.

Laboratory abnormalities did not arise in trials. Periodic tuberculosis screening is required. Prospective data over 5 years showed very low rates of adverse events (AEs), serious infections, malignancies, and major adverse cardiovascular events.²⁰ Ustekinumab did not worsen or improve demyelinating disease and appears safe in this population.

Patient Selection
Ustekinumab is approved for PsA and is a good option for those who are not candidates for TNF-α and IL-17 inhibitors. Ustekinumab also is approved for CD. The dosing interval of 12 weeks makes ustekinumab convenient for patients. Two dosages exist based on the patient’s weight, offering an advantage to obese patients.

IL-17/IL-17R Inhibitors

Activated T_H17 cells produce the IL-17 cytokine family, which stimulates keratinocyte proliferation and dermal inflammation. Secukinumab is a fully human monoclonal antibody, and ixekizumab is a humanized monoclonal antibody; both target IL-17A. Brodalumab targets the IL-17A receptor.

Efficacy and Safety
IL-17 inhibitors showed impressive and rapid responses in trials.^21-23 The subsets of patients who responded well and continued treatment in extension trials demonstrated that these treatments maintain efficacy over time.^24-26

In addition to tuberculosis reactivation, there is a small increased risk for cutaneous candidiasis with IL-17 inhibitors, which can be managed without stopping treatment. Laboratory abnormalities were limited to mild neutropenia, which was not associated with increased risk for infection.^21-23 With ixekizumab, neutropenia was seen more commonly in the first 12 weeks.²²

IL-17 is highly expressed in the gut mucosa, and its inhibition is thought to weaken the barrier function of the gut mucosa, promoting inflammation. As a consequence, this class is contraindicated in patients with IBD due to exacerbations of existing IBD and cases of new-onset IBD.^21-23 Symptoms of diarrhea, abdominal pain, blood in stool, or nighttime stooling on review of gastrointestinal tract symptoms should prompt further evaluation.

Brodalumab has a unique warning for risk for suicidal ideation and behavior.²³ Depression is more common in the psoriasis population in general; therefore, physicians should be aware of this potential comorbidity regardless of the treatment plan. Because the response rates are so impressive with brodalumab, the Risk Evaluation and Mitigation Strategy (REMS) program was established to ensure understanding of this risk so that patients can be appropriately counseled and managed.

Patient Selection
The improvement in psoriasis is rapid and may occur as early as week 2 to 3 of treatment after initiation of IL-17 inhibitors. Ixekizumab and secukinumab also are approved for PsA. Although improvement in joint disease is not as fast as with the anti-TNF inhibitors, notable improvement occurs by week 20 to 24.²⁷

IL-23 Inhibitors

Guselkumab and tildrakizumab are the newest biologics for psoriasis, approved in 2017 and 2018, respectively. Both are monoclonal antibodies against the p19 subunit of IL-23, which blocks activation of T_H17 cells.

Efficacy and Safety
Guselkumab and tildrakizumab demonstrated efficacy with minimal AEs or precautions noted thus far.^28,29 Infections are again a risk, making tuberculosis testing the only recommended monitoring.

Patient Selection
Both medications offer another effective and safe option for patients with psoriasis. Similar to ustekinumab, the dosing interval of 12 weeks for tildrakizumab is ideal for patients who have needle phobia or are unable to administer their own injections.

Special Populations

Pregnancy

Antibodies cross the placenta as pregnancy progresses, with the highest rate in the third trimester. Certolizumab pegol has shown the lowest concentrations in infant serum, possibly due to its unique structure lacking the fragment crystallizable region required for passage through the placenta.³⁰ For this reason, certolizumab pegol is a treatment of choice if biologic therapy is warranted during pregnancy.

Much of the pregnancy data for the remaining TNF-α inhibitors come from patients with rheumatoid arthritis or CD. In these populations, rates of major birth defects and miscarriages do not differ greatly from untreated women with these conditions.³¹ One retrospective study of unintentional pregnancies in women receiving ustekinumab showed rates of AEs similar to the general population.³²

Pregnancy data for IL-17 or IL-23 inhibitors are largely limited to animal studies. One retrospective study of women exposed to secukinumab early in gestation showed no increased risk for pregnancy-related AEs.³³ Discontinuation is still recommended for patients who become pregnant.

Pediatric Patients

Etanercept is approved for pediatric psoriatic patients 4 years and older. Children with juvenile idiopathic arthritis who are 2 years and older can receive etanercept. Ustekinumab is safe and effective for pediatric psoriatic patients 12 years and older, offering a second biologic option in children.

Although not approved for pediatric psoriasis, adalimumab is approved in pediatric CD (≥6 years of age) and for juvenile idiopathic arthritis (≥2 years of age). Infliximab is approved for children 6 years and older with CD or ulcerative colitis.

Monitoring

Periodic tuberculosis screening is recommended for all biologics. For patients with latent tuberculosis, biologics may be restarted after 1 month of treatment of tuberculosis.

Prior to initiation of biologics, patients should be screened for hepatitis with hepatitis B surface antigen and antibody, hepatitis B core antibody, and hepatitis C antibody. Patients at risk for human immunodeficiency virus also should be screened.

Generally, complete blood cell count and comprehensive metabolic profile are advisable prior to starting a biologic. Opinions differ on frequency of repeating laboratory work. Complete blood cell count and comprehensive metabolic profile should be monitored at least every 3 to 6 months in patients on TNF-α inhibitors, and neutrophil count should be monitored during the induction phase of IL-17 inhibitors.

All patients with psoriasis should maintain age-appropriate cancer screenings, especially those on biologics. If malignancy is discovered, biologic medication should be discontinued. Debate exists as to when therapy can be safely restarted following treatment of malignancy. Patients who are considered at low risk for recurrence may opt to restart a biologic after 5 years, or sooner if symptoms warrant.³⁴ This decision should involve the patient’s cancer specialist.

Conclusion

Treatment choices are based on psoriasis type and severity, comorbidities, patient preferences, and drug accessibility. One approach is detailed in Table 3. As research advances the understanding of psoriasis, this field will continue to rapidly change. Knowledge of the immunopathogenesis of psoriasis and its relation to comorbidities can direct your decision-making for individual patients.

Psoriasis is a T cell–mediated inflammatory disease that manifests as erythematous scaling plaques of the skin. In recent decades, our understanding of psoriasis has transformed from a disease isolated to the skin to a systemic disease impacting the overall health of those affected.

With recent elucidation of the pathways driving psoriasis, development of targeted therapies has resulted in an influx of options to the market. Navigating the options can seem overwhelming even to the seasoned clinician. Becoming familiar with a sound treatment approach during residency will create a foundation for biologic use in psoriasis patients throughout your career. Here we offer an approach to choosing biologic treatments based on individual patient characteristics, including disease severity, comorbidities, and ultimate treatment goals.

Immune Pathogenesis

Although the pathogenesis of psoriasis is complex and outside the scope of this article, we do recommend clinicians keep in mind the current understanding of pathways involved and ways our therapies alter them. Briefly, psoriasis is a T cell–mediated disease in which IL-12 and IL-23 released by activated dendritic cells activate T helper cells including T_H1, T_H17, and T_H22. These cells produce additional cytokines, including IFN-γ, tumor necrosis factor (TNF) α, IL-17, and IL-22, which propagate the immune response and lead to keratinocyte hyperproliferation. In general, psoriasis medications work by altering T-cell activation, effector cytokines, or cytokine receptors.

Comorbidities

A targeted approach should take into consideration the immune dysregulation shared by psoriasis and associated comorbidities (Table 1). One goal of biologic treatments is to improve comorbidities when possible. At minimum, selected treatments should not exacerbate these conditions.

Treatment Goals

Establishing treatment goals can help shape patient expectations and provide a plan for clinicians. In 2017, the National Psoriasis Foundation published a treat-to-target approach using body surface area (BSA) measurements at baseline, 3 months, and then every 6 months after starting a new treatment.¹² The target response is a decrease in psoriasis to 1% or less BSA at 3 months and to maintain this response when evaluated at 6-month intervals. Alternatively, a target of 3% BSA after 3 months is satisfactory if the patient improves by 75% BSA overall. If these targets are not met after 6 months, therapeutic alternatives can be considered.¹²

Biologic Treatment of Psoriasis

Treatment options for patients with psoriasis depend first on disease severity. Topicals and phototherapy are first line for mild to moderate disease. For moderate to severe disease, addition of systemic agents such as methotrexate, cyclosporine, or acitretin; small-molecular-weight immunomodulators such as apremilast; or biologic medications should be considered. Current biologics available for moderate to severe plaque psoriasis target TNF-α, IL-12/IL-23, IL-23, IL-17A, or IL-17A receptor.

TNF-α Inhibitors

Tumor necrosis factor α inhibitors have been available for treatment of autoimmune disease for nearly 20 years. These medications block either soluble cytokine or membrane-bound cytokine. All are given as subcutaneous injections, except for infliximab, which is a weight-based infusion.

Efficacy
Tumor necrosis factor α inhibitors are the first class to demonstrate long-term efficacy and safety in both psoriasis and psoriatic arthritis (PsA). Etanercept was approved for adults with PsA in 2002 and psoriasis in 2004, and later for pediatric psoriasis (≥4 years of age) in 2016 (Table 2). Although etanercept has a sustained safety profile, the response rates are not as high as other anti–TNF-α inhibitors. Adalimumab is one of the most prescribed biologics, with a total of 10 indications at present, including PsA. Infliximab is an intravenous infusion that demonstrates a rapid and sustained response in most patients. The dose and dosing interval can be adjusted according to response. Certolizumab pegol was approved for PsA in 2013 and for psoriasis in 2018.

Safety
To evaluate long-term safety, a multicenter prospective registry study (Psoriasis Longitudinal Assessment and Registry [PSOLAR]) was initiated in 2007 to follow clinical outcomes. Data through 2013 showed no significant increase in rates of infection, malignancy, or major adverse cardiovascular events in more than 12,000 patients.¹³

Conflicting information exists in the literature regarding risk for malignancy with TNF-α inhibitors. One recent retrospective cohort study suggested a slightly increased risk for malignancies other than nonmelanoma skin cancers in patients on TNF-α inhibitors for more than 12 months (relative risk, 1.54).¹⁴ Reports of increased risk for cutaneous squamous cell carcinomas necessitate regular skin checks.¹⁵ A potential risk for lymphoma has been noted, though having psoriasis itself imparts an increased risk for Hodgkin and cutaneous T-cell lymphoma.¹⁶

Reactivation of tuberculosis and hepatitis have been reported with TNF-α inhibition. Data suggest that infliximab may be associated with more serious infections.¹³

Demyelinating conditions such as multiple sclerosis have occurred de novo or worsened in patients on TNF-α inhibitors.¹⁷ Tumor necrosis factor α blockers should be avoided in patients with decompensated heart failure. Rare cases of liver enzyme elevation and cytopenia have been noted. Additionally, lupuslike syndromes, which are generally reversible upon discontinuation, have occurred in some patients.

Patient Selection
Tumor necrosis factor α inhibitors are the treatment of choice for patients with comorbid PsA. This class halts progression of joint destruction over time.¹⁸Select TNF-α inhibitors are indicated for inflammatory bowel disease (IBD) and are a preferred treatment in this patient population. Specifically, adalimumab and infliximab are approved for both Crohn disease (CD) and ulcerative colitis. Certolizumab pegol is approved for CD.

Tumor necrosis factor α is upregulated in obesity, cardiovascular disease, and atherosclerotic plaques. Evidence suggests that TNF-α blockers may lower cardiovascular risk over time.¹⁹ For patients with obesity, infliximab is a good option, as it is the only TNF-α inhibitor with weight-based dosing.

In patients with frequent infections or history of hepatitis C, etanercept has been the biologic most commonly used when no alternatives exist, in part due to its shorter half-life.

IL-12/IL-23 Inhibitor

Ustekinumab is a monoclonal antibody that binds the p40 subunit shared by IL-12 and IL-23, blocking their ability to bind receptors. IL-12 and IL-23 play a role in activating naïve T cells to become T_H1 or T_H17 cells, respectively.

Efficacy and Safety
Clinical trials demonstrate long-term efficacy of ustekinumab, which was approved for psoriasis in 2009, PsA in 2013, and later pediatric psoriasis (≥12 years of age) in 2017. Dosing is listed in Table 2.

Laboratory abnormalities did not arise in trials. Periodic tuberculosis screening is required. Prospective data over 5 years showed very low rates of adverse events (AEs), serious infections, malignancies, and major adverse cardiovascular events.²⁰ Ustekinumab did not worsen or improve demyelinating disease and appears safe in this population.

Patient Selection
Ustekinumab is approved for PsA and is a good option for those who are not candidates for TNF-α and IL-17 inhibitors. Ustekinumab also is approved for CD. The dosing interval of 12 weeks makes ustekinumab convenient for patients. Two dosages exist based on the patient’s weight, offering an advantage to obese patients.

IL-17/IL-17R Inhibitors

Activated T_H17 cells produce the IL-17 cytokine family, which stimulates keratinocyte proliferation and dermal inflammation. Secukinumab is a fully human monoclonal antibody, and ixekizumab is a humanized monoclonal antibody; both target IL-17A. Brodalumab targets the IL-17A receptor.

Efficacy and Safety
IL-17 inhibitors showed impressive and rapid responses in trials.^21-23 The subsets of patients who responded well and continued treatment in extension trials demonstrated that these treatments maintain efficacy over time.^24-26

In addition to tuberculosis reactivation, there is a small increased risk for cutaneous candidiasis with IL-17 inhibitors, which can be managed without stopping treatment. Laboratory abnormalities were limited to mild neutropenia, which was not associated with increased risk for infection.^21-23 With ixekizumab, neutropenia was seen more commonly in the first 12 weeks.²²

IL-17 is highly expressed in the gut mucosa, and its inhibition is thought to weaken the barrier function of the gut mucosa, promoting inflammation. As a consequence, this class is contraindicated in patients with IBD due to exacerbations of existing IBD and cases of new-onset IBD.^21-23 Symptoms of diarrhea, abdominal pain, blood in stool, or nighttime stooling on review of gastrointestinal tract symptoms should prompt further evaluation.

Brodalumab has a unique warning for risk for suicidal ideation and behavior.²³ Depression is more common in the psoriasis population in general; therefore, physicians should be aware of this potential comorbidity regardless of the treatment plan. Because the response rates are so impressive with brodalumab, the Risk Evaluation and Mitigation Strategy (REMS) program was established to ensure understanding of this risk so that patients can be appropriately counseled and managed.

Patient Selection
The improvement in psoriasis is rapid and may occur as early as week 2 to 3 of treatment after initiation of IL-17 inhibitors. Ixekizumab and secukinumab also are approved for PsA. Although improvement in joint disease is not as fast as with the anti-TNF inhibitors, notable improvement occurs by week 20 to 24.²⁷

IL-23 Inhibitors

Guselkumab and tildrakizumab are the newest biologics for psoriasis, approved in 2017 and 2018, respectively. Both are monoclonal antibodies against the p19 subunit of IL-23, which blocks activation of T_H17 cells.

Efficacy and Safety
Guselkumab and tildrakizumab demonstrated efficacy with minimal AEs or precautions noted thus far.^28,29 Infections are again a risk, making tuberculosis testing the only recommended monitoring.

Patient Selection
Both medications offer another effective and safe option for patients with psoriasis. Similar to ustekinumab, the dosing interval of 12 weeks for tildrakizumab is ideal for patients who have needle phobia or are unable to administer their own injections.

Special Populations

Pregnancy

Antibodies cross the placenta as pregnancy progresses, with the highest rate in the third trimester. Certolizumab pegol has shown the lowest concentrations in infant serum, possibly due to its unique structure lacking the fragment crystallizable region required for passage through the placenta.³⁰ For this reason, certolizumab pegol is a treatment of choice if biologic therapy is warranted during pregnancy.

Much of the pregnancy data for the remaining TNF-α inhibitors come from patients with rheumatoid arthritis or CD. In these populations, rates of major birth defects and miscarriages do not differ greatly from untreated women with these conditions.³¹ One retrospective study of unintentional pregnancies in women receiving ustekinumab showed rates of AEs similar to the general population.³²

Pregnancy data for IL-17 or IL-23 inhibitors are largely limited to animal studies. One retrospective study of women exposed to secukinumab early in gestation showed no increased risk for pregnancy-related AEs.³³ Discontinuation is still recommended for patients who become pregnant.

Pediatric Patients

Etanercept is approved for pediatric psoriatic patients 4 years and older. Children with juvenile idiopathic arthritis who are 2 years and older can receive etanercept. Ustekinumab is safe and effective for pediatric psoriatic patients 12 years and older, offering a second biologic option in children.

Although not approved for pediatric psoriasis, adalimumab is approved in pediatric CD (≥6 years of age) and for juvenile idiopathic arthritis (≥2 years of age). Infliximab is approved for children 6 years and older with CD or ulcerative colitis.

Monitoring

Periodic tuberculosis screening is recommended for all biologics. For patients with latent tuberculosis, biologics may be restarted after 1 month of treatment of tuberculosis.

Prior to initiation of biologics, patients should be screened for hepatitis with hepatitis B surface antigen and antibody, hepatitis B core antibody, and hepatitis C antibody. Patients at risk for human immunodeficiency virus also should be screened.

Generally, complete blood cell count and comprehensive metabolic profile are advisable prior to starting a biologic. Opinions differ on frequency of repeating laboratory work. Complete blood cell count and comprehensive metabolic profile should be monitored at least every 3 to 6 months in patients on TNF-α inhibitors, and neutrophil count should be monitored during the induction phase of IL-17 inhibitors.

All patients with psoriasis should maintain age-appropriate cancer screenings, especially those on biologics. If malignancy is discovered, biologic medication should be discontinued. Debate exists as to when therapy can be safely restarted following treatment of malignancy. Patients who are considered at low risk for recurrence may opt to restart a biologic after 5 years, or sooner if symptoms warrant.³⁴ This decision should involve the patient’s cancer specialist.

Conclusion

Treatment choices are based on psoriasis type and severity, comorbidities, patient preferences, and drug accessibility. One approach is detailed in Table 3. As research advances the understanding of psoriasis, this field will continue to rapidly change. Knowledge of the immunopathogenesis of psoriasis and its relation to comorbidities can direct your decision-making for individual patients.