Psoriasis

Psoriasis is a chronic and relapsing systemic inflammatory disease that predisposes patients to a host of other conditions. It is believed that these widespread effects are due to chronic inflammation and cytokine activation, which affect multiple body processes and lead to the development of various comorbidities that need to be proactively managed.

In April 2019, the American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) released recommendation guidelines for managing psoriasis in adults with an emphasis on common disease comorbidities, including psoriatic arthritis (PsA), cardiovascular disease (CVD), inflammatory bowel disease (IBD), metabolic syndrome, and mood disorders. Psychosocial wellness, mental health, and quality of life (QOL) measures in relation to psoriatic disease also were discussed.¹

The AAD-NPF guidelines address current screening, monitoring, education, and treatment recommendations for the management of psoriatic comorbidities. The Table and eTable summarize the screening recommendations. These guidelines aim to assist dermatologists with comprehensive disease management by addressing potential extracutaneous manifestations of psoriasis in adults.

Screening and Risk Assessment

Patients with psoriasis should receive a thorough history and physical examination to assess disease severity and risk for potential comorbidities. Patients with greater disease severity—as measured by body surface area (BSA) involvement and type of therapy required—have a greater risk for other disease-related comorbidities, specifically metabolic syndrome, renal disease, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, uveitis, IBD, malignancy, and increased mortality.² Because the likelihood of comorbidities is greatest with severe disease, more frequent monitoring is recommended for these patients.

Psoriatic Arthritis

Patients with psoriasis need to be evaluated for PsA at every visit. Patients presenting with signs and symptoms suspicious for PsA—joint swelling, peripheral joint involvement, and joint inflammation—warrant further evaluation and consultation. Early detection and treatment of PsA is essential for preventing unnecessary suffering and progressive joint destruction.³

There are several PsA screening questionnaires currently available, including the Psoriatic Arthritis Screening Evaluation, Psoriasis Epidemiology Screening Tool, and Toronto Psoriatic Arthritis Screen. No significant differences in sensitivity and specificity were found among these questionnaires when using the Classification Criteria for Psoriatic Arthritis as the gold standard. All 3 questionnaires—the Psoriatic Arthritis Screening Evaluation and the Psoriasis Epidemiology Screening Tool were developed for use in dermatology and rheumatology clinics, and the Toronto Psoriatic Arthritis Screen was developed for use in the primary care setting—were found to be effective in dermatology/rheumatology clinics and primary care clinics, respectively.³ False-positive results predominantly were seen in patients with degenerative joint disease or osteoarthritis. Dermatologists should conduct a thorough physical examination to distinguish PsA from degenerative joint disease. Imaging and laboratory tests to evaluate for signs of systemic inflammation (erythrocyte sedimentation rate, C-reactive protein) also can be helpful in distinguishing the 2 conditions; however, these metrics have not been shown to contribute to PsA diagnosis.¹ Full rheumatologic consultation is warranted in challenging cases.

Cardiovascular Disease

The American Heart Association and the American College of Cardiology have identified chronic inflammatory states, such as psoriasis, as inducing factors that predispose patients to CVD. Many studies have found an association among psoriasis, coronary artery disease, myocardial infarction (MI), and stroke.^4-7 It is strongly recommended that dermatologists educate patients of their increased risk for CVD, given the association between psoriasis and major adverse cardiovascular events (eg, stroke, heart failure, MI) and cardiovascular health. However, patients with congestive heart failure were found to have an increased risk of mortality associated with use of tumor necrosis factor (TNF) α inhibitors (P=.016).⁸ Thus, TNF inhibitors are contraindicated in patients with New York Heart Association Class III or Class IV congestive heart failure.⁹

Primary care physicians (PCPs) are recommended to screen patients for CVD risk factors using height, weight, blood pressure, blood glucose, hemoglobin A_1C, lipid levels, abdominal circumference, and body mass index (BMI). Lifestyle modifications such as smoking cessation, exercise, and dietary changes are encouraged to achieve and maintain a normal BMI.

Dermatologists also need to give special consideration to comorbidities when selecting medications and/or therapies for disease management. Patients on TNF inhibitors have a lower risk for MI compared with patients using topical medications, phototherapy, and other oral agents.¹⁰ Additionally, patients on TNF inhibitors have a lower risk for occurrence of major adverse cardiovascular events compared with patients treated with methotrexate or phototherapy.^11,12

Metabolic Syndrome

Numerous studies have demonstrated an association between psoriasis and metabolic syndrome. Patients with increased BSA involvement and psoriasis area and severity index scores have a higher prevalence of metabolic syndrome.¹³ Patients with psoriasis have an increased risk for the following conditions compared to controls: obesity (38% vs 31%; odds ratio [OR], 1.38; 95% CI, 1.29-1.48), elevated triglycerides (36% vs 28%; OR, 1.49; 95% CI, 1.39-1.60), hypertension (31% vs 28%; OR, 1.20; 95% CI, 1.11-12.9), and elevated glucose levels (22% vs 16%; OR, 1.44; 95% CI, 1.33-1.56).¹⁴ Dermatologists are strongly recommended to inform patients about the risk for metabolic syndrome and to encourage the measurement of blood pressure, waist circumference, fasting blood glucose, hemoglobin A_1C, and fasting lipid levels with their PCP when indicated. Body mass index and waist circumference also should be measured annually in patients with moderate to severe psoriasis because of the association with disease severity.

The association between psoriasis and weight loss has been analyzed in several studies. Weight loss, particularly in obese patients, has been shown to improve psoriasis severity, as measured by psoriasis area and severity index score and QOL measures.¹⁵ Another study found that gastric bypass was associated with a significant risk reduction in the development of psoriasis (P=.004) and the disease prognosis (P=.02 for severe psoriasis; P=.01 for PsA).¹⁶ Therefore, patients with moderate to severe psoriasis are recommended to have their obesity status determined according to national guidelines. For patients with a BMI above 40 kg/m² and standard weight-loss measures fail, bariatric surgery is recommended. Additionally, the impact of psoriasis medications on weight has been studied. Apremilast has been associated with weight loss, whereas etanercept and infliximab have been linked to weight gain.^17,18

An association between psoriasis and hypertension also has been demonstrated by studies, especially among patients with severe disease. Therefore, patients with moderate to severe psoriasis are recommended to have their blood pressure evaluated according to national guidelines, and those with a blood pressure of 140/90 mm Hg or higher should be referred to their PCP for assessment and treatment. Current evidence does not support restrictions on antihypertensive medications in patients with psoriasis. Physicians should be aware of the potential for cyclosporine to induce hypertension, which should be treated, specifically with amlodipine.¹⁹

Many studies have demonstrated an association between psoriasis and dyslipidemia, though the results are somewhat conflicting. In 2018, the American Heart Association and the American College of Cardiology deemed psoriasis as an atherosclerotic CVD risk-enhancing condition, favoring early initiation of statin therapy. Because dyslipidemia plays a prominent role in atherosclerosis and CVD, patients with moderate to severe psoriasis are recommended to undergo periodic screening with lipid tests (eg, fasting total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides).²⁰ Patients with elevated fasting triglycerides or low-density lipoprotein cholesterol should be referred to their PCP for further management. Certain psoriasis medications also have been linked to dyslipidemia. Acitretin and cyclosporine are known to adversely affect lipid levels, so patients treated with either agent should undergo routine monitoring of serum lipid levels.

Psoriasis is strongly associated with diabetes mellitus. Because of the increased risk for diabetes in patients with severe disease, regular monitoring of fasting blood glucose and/or hemoglobin A_1C levels in patients with moderate to severe psoriasis is recommended. Patients who meet criteria for prediabetes or diabetes should be referred to their PCP for further assessment and management.^21,22

Mood Disorders

Psoriasis affects QOL and can have a major impact on patients’ interpersonal relationships. Studies have shown an association between psoriasis and mood disorders, specifically depression and anxiety. Unfortunately, patients with mood disorders are less likely to seek intervention for their skin disease, which poses a tremendous treatment barrier. Dermatologists should regularly monitor patients for psychiatric symptoms so that resources and treatments can be offered.

Certain psoriasis therapies have been shown to help alleviate associated depression and anxiety. Improvements in Beck Depression Inventory and Hamilton Depression Rating Scale scores were seen with etanercept.²³ Adalimumab and ustekinumab showed improvement in Dermatology Life Quality Index compared with placebo.^24,25 Patients receiving Goeckerman treatment also had improvement in anxiety and depression scores compared with conventional therapy.²⁶ Biologic medications had the largest impact on improving depression symptoms compared with conventional systemic therapy and phototherapy.²⁷ The recommendations support use of biologics and the Goeckerman regimen for the concomitant treatment of mood disorders and psoriasis.

Renal Disease

Studies have supported an association between psoriasis and chronic kidney disease (CKD), independent of risk factors including vascular disease, hypertension, and diabetes. The prevalence of moderate to advanced CKD also has been found to be directly related to increasing BSA affected by psoriasis.²⁸ Patients should receive testing of blood urea nitrogen, creatinine, and urine microalbumin levels to assess for occult renal disease. In addition, physicians should be cautious when prescribing nephrotoxic drugs (nonsteroidal anti-inflammatory drugs and cyclosporine) and renally excreted agents (methotrexate and apremilast) because of the risk for underlying renal disease in patients with psoriasis. If newly acquired renal disease is suspected, physicians should withhold the offending agents. Patients with psoriasis with CKD are recommended to follow up with their PCP or nephrologist for evaluation and management.

Pulmonary Disease

Psoriasis also has an independent association with COPD. Patients with psoriasis have a higher likelihood of developing COPD (hazard ratio, 2.35; 95% CI, 1.42-3.89; P<.01) than controls.²⁹ The prevalence of COPD also was found to correlate with psoriasis severity. Dermatologists should educate patients about the association between smoking and psoriasis as well as advise patients to discontinue smoking to reduce their risk for developing COPD and cancer.

Patients with psoriasis also are at an increased risk for obstructive sleep apnea. Obstructive sleep apnea should be considered in patients with risk factors including snoring, obesity, hypertension, or diabetes.

Inflammatory Bowel Disease

Patients with psoriasis have an increased risk for developing IBD. The prevalence ratios of both Crohn disease (2.49) and ulcerative colitis (1.64) are increased in patients with psoriasis relative to patients without psoriasis.³⁰ Physicians need to be aware of the association between psoriasis and IBD and the effect that their coexistence may have on treatment choice for patients.

Adalimumab and infliximab are approved for the treatment of IBD, and certolizumab and ustekinumab are approved for Crohn disease. Use of TNF inhibitors in patients with IBD may cause psoriasiform lesions to develop.³¹ Nonetheless, treatment should be individualized and psoriasiform lesions treated with standard psoriasis measures. Psoriasis patients with IBD are recommended to avoid IL-17–inhibitor therapy, given its potential to worsen IBD flares.

Malignancy

Psoriasis patients aged 0 to 79 years have a greater overall risk for malignancy compared with patients without psoriasis.³² Patients with psoriasis have an increased risk for respiratory tract cancer, upper aerodigestive tract cancer, urinary tract cancer, and non-Hodgkin lymphoma.³³ A mild association exists between PsA and lymphoma, nonmelanoma skin cancer (NMSC), and lung cancer.³⁴ More severe psoriasis is associated with greater risk for lymphoma and NMSC. Dermatologists are recommended to educate patients on their risk for certain malignancies and to refer patients to specialists upon suspicion of malignancy.

Risk for malignancy has been shown to be affected by psoriasis treatments. Patients treated with UVB have reduced overall cancer rates for all age groups (hazard ratio, 0.52; P=.3), while those treated with psoralen plus UVA have an increased incidence of squamous cell carcinoma.^32,33 Adalimumab was correlated with increased risk for NMSC in patients with psoriasis but did not have an increased risk for all cancers collectively when used for various immune-mediated inflammatory diseases.³⁵ In contrast, a meta-analysis of randomized clinical trials found no association with TNF inhibitor use and NMSC.³⁶ Ustekinumab had no association with malignancy.³⁷ Treatment history should be elucidated because of higher rates of squamous cell carcinoma in patients with prior psoralen plus UVA, cyclosporine, or methotrexate use.³³ To address malignancy risk, patients with psoriasis should undergo regular screenings for skin cancer and follow national guidelines for age-appropriate cancer screenings.

Lifestyle Choices and QOL

A crucial aspect of successful psoriasis management is patient education. The strongest recommendations support lifestyle changes, such as smoking cessation and limitation of alcohol use. A tactful discussion regarding substance use, work productivity, interpersonal relationships, and sexual function can address substantial effects of psoriasis on QOL so that support and resources can be provided.

Final Thoughts

Management of psoriasis is multifaceted and involves screening, education, monitoring, and collaboration with PCPs and specialists. Regular follow-up with a dermatologist and PCP is strongly recommended for patients with psoriasis given the systemic nature of the disease. The 2019 AAD-NPF recommendations provide important information for dermatologists to coordinate care for complicated psoriasis cases, but clinical judgment is paramount when making medical decisions. The consideration of comorbidities is critical for developing a comprehensive treatment approach, and this approach will lead to better health outcomes and improved QOL for patients with psoriasis.

Psoriasis is a chronic and relapsing systemic inflammatory disease that predisposes patients to a host of other conditions. It is believed that these widespread effects are due to chronic inflammation and cytokine activation, which affect multiple body processes and lead to the development of various comorbidities that need to be proactively managed.

In April 2019, the American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) released recommendation guidelines for managing psoriasis in adults with an emphasis on common disease comorbidities, including psoriatic arthritis (PsA), cardiovascular disease (CVD), inflammatory bowel disease (IBD), metabolic syndrome, and mood disorders. Psychosocial wellness, mental health, and quality of life (QOL) measures in relation to psoriatic disease also were discussed.¹

The AAD-NPF guidelines address current screening, monitoring, education, and treatment recommendations for the management of psoriatic comorbidities. The Table and eTable summarize the screening recommendations. These guidelines aim to assist dermatologists with comprehensive disease management by addressing potential extracutaneous manifestations of psoriasis in adults.

Screening and Risk Assessment

Patients with psoriasis should receive a thorough history and physical examination to assess disease severity and risk for potential comorbidities. Patients with greater disease severity—as measured by body surface area (BSA) involvement and type of therapy required—have a greater risk for other disease-related comorbidities, specifically metabolic syndrome, renal disease, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, uveitis, IBD, malignancy, and increased mortality.² Because the likelihood of comorbidities is greatest with severe disease, more frequent monitoring is recommended for these patients.

Psoriatic Arthritis

Patients with psoriasis need to be evaluated for PsA at every visit. Patients presenting with signs and symptoms suspicious for PsA—joint swelling, peripheral joint involvement, and joint inflammation—warrant further evaluation and consultation. Early detection and treatment of PsA is essential for preventing unnecessary suffering and progressive joint destruction.³

There are several PsA screening questionnaires currently available, including the Psoriatic Arthritis Screening Evaluation, Psoriasis Epidemiology Screening Tool, and Toronto Psoriatic Arthritis Screen. No significant differences in sensitivity and specificity were found among these questionnaires when using the Classification Criteria for Psoriatic Arthritis as the gold standard. All 3 questionnaires—the Psoriatic Arthritis Screening Evaluation and the Psoriasis Epidemiology Screening Tool were developed for use in dermatology and rheumatology clinics, and the Toronto Psoriatic Arthritis Screen was developed for use in the primary care setting—were found to be effective in dermatology/rheumatology clinics and primary care clinics, respectively.³ False-positive results predominantly were seen in patients with degenerative joint disease or osteoarthritis. Dermatologists should conduct a thorough physical examination to distinguish PsA from degenerative joint disease. Imaging and laboratory tests to evaluate for signs of systemic inflammation (erythrocyte sedimentation rate, C-reactive protein) also can be helpful in distinguishing the 2 conditions; however, these metrics have not been shown to contribute to PsA diagnosis.¹ Full rheumatologic consultation is warranted in challenging cases.

Cardiovascular Disease

The American Heart Association and the American College of Cardiology have identified chronic inflammatory states, such as psoriasis, as inducing factors that predispose patients to CVD. Many studies have found an association among psoriasis, coronary artery disease, myocardial infarction (MI), and stroke.^4-7 It is strongly recommended that dermatologists educate patients of their increased risk for CVD, given the association between psoriasis and major adverse cardiovascular events (eg, stroke, heart failure, MI) and cardiovascular health. However, patients with congestive heart failure were found to have an increased risk of mortality associated with use of tumor necrosis factor (TNF) α inhibitors (P=.016).⁸ Thus, TNF inhibitors are contraindicated in patients with New York Heart Association Class III or Class IV congestive heart failure.⁹

Primary care physicians (PCPs) are recommended to screen patients for CVD risk factors using height, weight, blood pressure, blood glucose, hemoglobin A_1C, lipid levels, abdominal circumference, and body mass index (BMI). Lifestyle modifications such as smoking cessation, exercise, and dietary changes are encouraged to achieve and maintain a normal BMI.

Dermatologists also need to give special consideration to comorbidities when selecting medications and/or therapies for disease management. Patients on TNF inhibitors have a lower risk for MI compared with patients using topical medications, phototherapy, and other oral agents.¹⁰ Additionally, patients on TNF inhibitors have a lower risk for occurrence of major adverse cardiovascular events compared with patients treated with methotrexate or phototherapy.^11,12

Metabolic Syndrome

Numerous studies have demonstrated an association between psoriasis and metabolic syndrome. Patients with increased BSA involvement and psoriasis area and severity index scores have a higher prevalence of metabolic syndrome.¹³ Patients with psoriasis have an increased risk for the following conditions compared to controls: obesity (38% vs 31%; odds ratio [OR], 1.38; 95% CI, 1.29-1.48), elevated triglycerides (36% vs 28%; OR, 1.49; 95% CI, 1.39-1.60), hypertension (31% vs 28%; OR, 1.20; 95% CI, 1.11-12.9), and elevated glucose levels (22% vs 16%; OR, 1.44; 95% CI, 1.33-1.56).¹⁴ Dermatologists are strongly recommended to inform patients about the risk for metabolic syndrome and to encourage the measurement of blood pressure, waist circumference, fasting blood glucose, hemoglobin A_1C, and fasting lipid levels with their PCP when indicated. Body mass index and waist circumference also should be measured annually in patients with moderate to severe psoriasis because of the association with disease severity.

The association between psoriasis and weight loss has been analyzed in several studies. Weight loss, particularly in obese patients, has been shown to improve psoriasis severity, as measured by psoriasis area and severity index score and QOL measures.¹⁵ Another study found that gastric bypass was associated with a significant risk reduction in the development of psoriasis (P=.004) and the disease prognosis (P=.02 for severe psoriasis; P=.01 for PsA).¹⁶ Therefore, patients with moderate to severe psoriasis are recommended to have their obesity status determined according to national guidelines. For patients with a BMI above 40 kg/m² and standard weight-loss measures fail, bariatric surgery is recommended. Additionally, the impact of psoriasis medications on weight has been studied. Apremilast has been associated with weight loss, whereas etanercept and infliximab have been linked to weight gain.^17,18

An association between psoriasis and hypertension also has been demonstrated by studies, especially among patients with severe disease. Therefore, patients with moderate to severe psoriasis are recommended to have their blood pressure evaluated according to national guidelines, and those with a blood pressure of 140/90 mm Hg or higher should be referred to their PCP for assessment and treatment. Current evidence does not support restrictions on antihypertensive medications in patients with psoriasis. Physicians should be aware of the potential for cyclosporine to induce hypertension, which should be treated, specifically with amlodipine.¹⁹

Many studies have demonstrated an association between psoriasis and dyslipidemia, though the results are somewhat conflicting. In 2018, the American Heart Association and the American College of Cardiology deemed psoriasis as an atherosclerotic CVD risk-enhancing condition, favoring early initiation of statin therapy. Because dyslipidemia plays a prominent role in atherosclerosis and CVD, patients with moderate to severe psoriasis are recommended to undergo periodic screening with lipid tests (eg, fasting total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides).²⁰ Patients with elevated fasting triglycerides or low-density lipoprotein cholesterol should be referred to their PCP for further management. Certain psoriasis medications also have been linked to dyslipidemia. Acitretin and cyclosporine are known to adversely affect lipid levels, so patients treated with either agent should undergo routine monitoring of serum lipid levels.

Psoriasis is strongly associated with diabetes mellitus. Because of the increased risk for diabetes in patients with severe disease, regular monitoring of fasting blood glucose and/or hemoglobin A_1C levels in patients with moderate to severe psoriasis is recommended. Patients who meet criteria for prediabetes or diabetes should be referred to their PCP for further assessment and management.^21,22

Mood Disorders

Psoriasis affects QOL and can have a major impact on patients’ interpersonal relationships. Studies have shown an association between psoriasis and mood disorders, specifically depression and anxiety. Unfortunately, patients with mood disorders are less likely to seek intervention for their skin disease, which poses a tremendous treatment barrier. Dermatologists should regularly monitor patients for psychiatric symptoms so that resources and treatments can be offered.

Certain psoriasis therapies have been shown to help alleviate associated depression and anxiety. Improvements in Beck Depression Inventory and Hamilton Depression Rating Scale scores were seen with etanercept.²³ Adalimumab and ustekinumab showed improvement in Dermatology Life Quality Index compared with placebo.^24,25 Patients receiving Goeckerman treatment also had improvement in anxiety and depression scores compared with conventional therapy.²⁶ Biologic medications had the largest impact on improving depression symptoms compared with conventional systemic therapy and phototherapy.²⁷ The recommendations support use of biologics and the Goeckerman regimen for the concomitant treatment of mood disorders and psoriasis.

Renal Disease

Studies have supported an association between psoriasis and chronic kidney disease (CKD), independent of risk factors including vascular disease, hypertension, and diabetes. The prevalence of moderate to advanced CKD also has been found to be directly related to increasing BSA affected by psoriasis.²⁸ Patients should receive testing of blood urea nitrogen, creatinine, and urine microalbumin levels to assess for occult renal disease. In addition, physicians should be cautious when prescribing nephrotoxic drugs (nonsteroidal anti-inflammatory drugs and cyclosporine) and renally excreted agents (methotrexate and apremilast) because of the risk for underlying renal disease in patients with psoriasis. If newly acquired renal disease is suspected, physicians should withhold the offending agents. Patients with psoriasis with CKD are recommended to follow up with their PCP or nephrologist for evaluation and management.

Pulmonary Disease

Psoriasis also has an independent association with COPD. Patients with psoriasis have a higher likelihood of developing COPD (hazard ratio, 2.35; 95% CI, 1.42-3.89; P<.01) than controls.²⁹ The prevalence of COPD also was found to correlate with psoriasis severity. Dermatologists should educate patients about the association between smoking and psoriasis as well as advise patients to discontinue smoking to reduce their risk for developing COPD and cancer.

Patients with psoriasis also are at an increased risk for obstructive sleep apnea. Obstructive sleep apnea should be considered in patients with risk factors including snoring, obesity, hypertension, or diabetes.

Inflammatory Bowel Disease

Patients with psoriasis have an increased risk for developing IBD. The prevalence ratios of both Crohn disease (2.49) and ulcerative colitis (1.64) are increased in patients with psoriasis relative to patients without psoriasis.³⁰ Physicians need to be aware of the association between psoriasis and IBD and the effect that their coexistence may have on treatment choice for patients.

Adalimumab and infliximab are approved for the treatment of IBD, and certolizumab and ustekinumab are approved for Crohn disease. Use of TNF inhibitors in patients with IBD may cause psoriasiform lesions to develop.³¹ Nonetheless, treatment should be individualized and psoriasiform lesions treated with standard psoriasis measures. Psoriasis patients with IBD are recommended to avoid IL-17–inhibitor therapy, given its potential to worsen IBD flares.

Malignancy

Psoriasis patients aged 0 to 79 years have a greater overall risk for malignancy compared with patients without psoriasis.³² Patients with psoriasis have an increased risk for respiratory tract cancer, upper aerodigestive tract cancer, urinary tract cancer, and non-Hodgkin lymphoma.³³ A mild association exists between PsA and lymphoma, nonmelanoma skin cancer (NMSC), and lung cancer.³⁴ More severe psoriasis is associated with greater risk for lymphoma and NMSC. Dermatologists are recommended to educate patients on their risk for certain malignancies and to refer patients to specialists upon suspicion of malignancy.

Risk for malignancy has been shown to be affected by psoriasis treatments. Patients treated with UVB have reduced overall cancer rates for all age groups (hazard ratio, 0.52; P=.3), while those treated with psoralen plus UVA have an increased incidence of squamous cell carcinoma.^32,33 Adalimumab was correlated with increased risk for NMSC in patients with psoriasis but did not have an increased risk for all cancers collectively when used for various immune-mediated inflammatory diseases.³⁵ In contrast, a meta-analysis of randomized clinical trials found no association with TNF inhibitor use and NMSC.³⁶ Ustekinumab had no association with malignancy.³⁷ Treatment history should be elucidated because of higher rates of squamous cell carcinoma in patients with prior psoralen plus UVA, cyclosporine, or methotrexate use.³³ To address malignancy risk, patients with psoriasis should undergo regular screenings for skin cancer and follow national guidelines for age-appropriate cancer screenings.

Lifestyle Choices and QOL

A crucial aspect of successful psoriasis management is patient education. The strongest recommendations support lifestyle changes, such as smoking cessation and limitation of alcohol use. A tactful discussion regarding substance use, work productivity, interpersonal relationships, and sexual function can address substantial effects of psoriasis on QOL so that support and resources can be provided.

Final Thoughts

Management of psoriasis is multifaceted and involves screening, education, monitoring, and collaboration with PCPs and specialists. Regular follow-up with a dermatologist and PCP is strongly recommended for patients with psoriasis given the systemic nature of the disease. The 2019 AAD-NPF recommendations provide important information for dermatologists to coordinate care for complicated psoriasis cases, but clinical judgment is paramount when making medical decisions. The consideration of comorbidities is critical for developing a comprehensive treatment approach, and this approach will lead to better health outcomes and improved QOL for patients with psoriasis.

Psoriasis is a chronic and relapsing systemic inflammatory disease that predisposes patients to a host of other conditions. It is believed that these widespread effects are due to chronic inflammation and cytokine activation, which affect multiple body processes and lead to the development of various comorbidities that need to be proactively managed.

In April 2019, the American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) released recommendation guidelines for managing psoriasis in adults with an emphasis on common disease comorbidities, including psoriatic arthritis (PsA), cardiovascular disease (CVD), inflammatory bowel disease (IBD), metabolic syndrome, and mood disorders. Psychosocial wellness, mental health, and quality of life (QOL) measures in relation to psoriatic disease also were discussed.¹

The AAD-NPF guidelines address current screening, monitoring, education, and treatment recommendations for the management of psoriatic comorbidities. The Table and eTable summarize the screening recommendations. These guidelines aim to assist dermatologists with comprehensive disease management by addressing potential extracutaneous manifestations of psoriasis in adults.

Screening and Risk Assessment

Patients with psoriasis should receive a thorough history and physical examination to assess disease severity and risk for potential comorbidities. Patients with greater disease severity—as measured by body surface area (BSA) involvement and type of therapy required—have a greater risk for other disease-related comorbidities, specifically metabolic syndrome, renal disease, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, uveitis, IBD, malignancy, and increased mortality.² Because the likelihood of comorbidities is greatest with severe disease, more frequent monitoring is recommended for these patients.

Psoriatic Arthritis

Patients with psoriasis need to be evaluated for PsA at every visit. Patients presenting with signs and symptoms suspicious for PsA—joint swelling, peripheral joint involvement, and joint inflammation—warrant further evaluation and consultation. Early detection and treatment of PsA is essential for preventing unnecessary suffering and progressive joint destruction.³

There are several PsA screening questionnaires currently available, including the Psoriatic Arthritis Screening Evaluation, Psoriasis Epidemiology Screening Tool, and Toronto Psoriatic Arthritis Screen. No significant differences in sensitivity and specificity were found among these questionnaires when using the Classification Criteria for Psoriatic Arthritis as the gold standard. All 3 questionnaires—the Psoriatic Arthritis Screening Evaluation and the Psoriasis Epidemiology Screening Tool were developed for use in dermatology and rheumatology clinics, and the Toronto Psoriatic Arthritis Screen was developed for use in the primary care setting—were found to be effective in dermatology/rheumatology clinics and primary care clinics, respectively.³ False-positive results predominantly were seen in patients with degenerative joint disease or osteoarthritis. Dermatologists should conduct a thorough physical examination to distinguish PsA from degenerative joint disease. Imaging and laboratory tests to evaluate for signs of systemic inflammation (erythrocyte sedimentation rate, C-reactive protein) also can be helpful in distinguishing the 2 conditions; however, these metrics have not been shown to contribute to PsA diagnosis.¹ Full rheumatologic consultation is warranted in challenging cases.

Cardiovascular Disease

The American Heart Association and the American College of Cardiology have identified chronic inflammatory states, such as psoriasis, as inducing factors that predispose patients to CVD. Many studies have found an association among psoriasis, coronary artery disease, myocardial infarction (MI), and stroke.^4-7 It is strongly recommended that dermatologists educate patients of their increased risk for CVD, given the association between psoriasis and major adverse cardiovascular events (eg, stroke, heart failure, MI) and cardiovascular health. However, patients with congestive heart failure were found to have an increased risk of mortality associated with use of tumor necrosis factor (TNF) α inhibitors (P=.016).⁸ Thus, TNF inhibitors are contraindicated in patients with New York Heart Association Class III or Class IV congestive heart failure.⁹

Primary care physicians (PCPs) are recommended to screen patients for CVD risk factors using height, weight, blood pressure, blood glucose, hemoglobin A_1C, lipid levels, abdominal circumference, and body mass index (BMI). Lifestyle modifications such as smoking cessation, exercise, and dietary changes are encouraged to achieve and maintain a normal BMI.

Dermatologists also need to give special consideration to comorbidities when selecting medications and/or therapies for disease management. Patients on TNF inhibitors have a lower risk for MI compared with patients using topical medications, phototherapy, and other oral agents.¹⁰ Additionally, patients on TNF inhibitors have a lower risk for occurrence of major adverse cardiovascular events compared with patients treated with methotrexate or phototherapy.^11,12

Metabolic Syndrome

Numerous studies have demonstrated an association between psoriasis and metabolic syndrome. Patients with increased BSA involvement and psoriasis area and severity index scores have a higher prevalence of metabolic syndrome.¹³ Patients with psoriasis have an increased risk for the following conditions compared to controls: obesity (38% vs 31%; odds ratio [OR], 1.38; 95% CI, 1.29-1.48), elevated triglycerides (36% vs 28%; OR, 1.49; 95% CI, 1.39-1.60), hypertension (31% vs 28%; OR, 1.20; 95% CI, 1.11-12.9), and elevated glucose levels (22% vs 16%; OR, 1.44; 95% CI, 1.33-1.56).¹⁴ Dermatologists are strongly recommended to inform patients about the risk for metabolic syndrome and to encourage the measurement of blood pressure, waist circumference, fasting blood glucose, hemoglobin A_1C, and fasting lipid levels with their PCP when indicated. Body mass index and waist circumference also should be measured annually in patients with moderate to severe psoriasis because of the association with disease severity.

The association between psoriasis and weight loss has been analyzed in several studies. Weight loss, particularly in obese patients, has been shown to improve psoriasis severity, as measured by psoriasis area and severity index score and QOL measures.¹⁵ Another study found that gastric bypass was associated with a significant risk reduction in the development of psoriasis (P=.004) and the disease prognosis (P=.02 for severe psoriasis; P=.01 for PsA).¹⁶ Therefore, patients with moderate to severe psoriasis are recommended to have their obesity status determined according to national guidelines. For patients with a BMI above 40 kg/m² and standard weight-loss measures fail, bariatric surgery is recommended. Additionally, the impact of psoriasis medications on weight has been studied. Apremilast has been associated with weight loss, whereas etanercept and infliximab have been linked to weight gain.^17,18

An association between psoriasis and hypertension also has been demonstrated by studies, especially among patients with severe disease. Therefore, patients with moderate to severe psoriasis are recommended to have their blood pressure evaluated according to national guidelines, and those with a blood pressure of 140/90 mm Hg or higher should be referred to their PCP for assessment and treatment. Current evidence does not support restrictions on antihypertensive medications in patients with psoriasis. Physicians should be aware of the potential for cyclosporine to induce hypertension, which should be treated, specifically with amlodipine.¹⁹

Many studies have demonstrated an association between psoriasis and dyslipidemia, though the results are somewhat conflicting. In 2018, the American Heart Association and the American College of Cardiology deemed psoriasis as an atherosclerotic CVD risk-enhancing condition, favoring early initiation of statin therapy. Because dyslipidemia plays a prominent role in atherosclerosis and CVD, patients with moderate to severe psoriasis are recommended to undergo periodic screening with lipid tests (eg, fasting total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides).²⁰ Patients with elevated fasting triglycerides or low-density lipoprotein cholesterol should be referred to their PCP for further management. Certain psoriasis medications also have been linked to dyslipidemia. Acitretin and cyclosporine are known to adversely affect lipid levels, so patients treated with either agent should undergo routine monitoring of serum lipid levels.

Psoriasis is strongly associated with diabetes mellitus. Because of the increased risk for diabetes in patients with severe disease, regular monitoring of fasting blood glucose and/or hemoglobin A_1C levels in patients with moderate to severe psoriasis is recommended. Patients who meet criteria for prediabetes or diabetes should be referred to their PCP for further assessment and management.^21,22

Mood Disorders

Psoriasis affects QOL and can have a major impact on patients’ interpersonal relationships. Studies have shown an association between psoriasis and mood disorders, specifically depression and anxiety. Unfortunately, patients with mood disorders are less likely to seek intervention for their skin disease, which poses a tremendous treatment barrier. Dermatologists should regularly monitor patients for psychiatric symptoms so that resources and treatments can be offered.

Certain psoriasis therapies have been shown to help alleviate associated depression and anxiety. Improvements in Beck Depression Inventory and Hamilton Depression Rating Scale scores were seen with etanercept.²³ Adalimumab and ustekinumab showed improvement in Dermatology Life Quality Index compared with placebo.^24,25 Patients receiving Goeckerman treatment also had improvement in anxiety and depression scores compared with conventional therapy.²⁶ Biologic medications had the largest impact on improving depression symptoms compared with conventional systemic therapy and phototherapy.²⁷ The recommendations support use of biologics and the Goeckerman regimen for the concomitant treatment of mood disorders and psoriasis.

Renal Disease

Studies have supported an association between psoriasis and chronic kidney disease (CKD), independent of risk factors including vascular disease, hypertension, and diabetes. The prevalence of moderate to advanced CKD also has been found to be directly related to increasing BSA affected by psoriasis.²⁸ Patients should receive testing of blood urea nitrogen, creatinine, and urine microalbumin levels to assess for occult renal disease. In addition, physicians should be cautious when prescribing nephrotoxic drugs (nonsteroidal anti-inflammatory drugs and cyclosporine) and renally excreted agents (methotrexate and apremilast) because of the risk for underlying renal disease in patients with psoriasis. If newly acquired renal disease is suspected, physicians should withhold the offending agents. Patients with psoriasis with CKD are recommended to follow up with their PCP or nephrologist for evaluation and management.

Pulmonary Disease

Psoriasis also has an independent association with COPD. Patients with psoriasis have a higher likelihood of developing COPD (hazard ratio, 2.35; 95% CI, 1.42-3.89; P<.01) than controls.²⁹ The prevalence of COPD also was found to correlate with psoriasis severity. Dermatologists should educate patients about the association between smoking and psoriasis as well as advise patients to discontinue smoking to reduce their risk for developing COPD and cancer.

Patients with psoriasis also are at an increased risk for obstructive sleep apnea. Obstructive sleep apnea should be considered in patients with risk factors including snoring, obesity, hypertension, or diabetes.

Inflammatory Bowel Disease

Patients with psoriasis have an increased risk for developing IBD. The prevalence ratios of both Crohn disease (2.49) and ulcerative colitis (1.64) are increased in patients with psoriasis relative to patients without psoriasis.³⁰ Physicians need to be aware of the association between psoriasis and IBD and the effect that their coexistence may have on treatment choice for patients.

Adalimumab and infliximab are approved for the treatment of IBD, and certolizumab and ustekinumab are approved for Crohn disease. Use of TNF inhibitors in patients with IBD may cause psoriasiform lesions to develop.³¹ Nonetheless, treatment should be individualized and psoriasiform lesions treated with standard psoriasis measures. Psoriasis patients with IBD are recommended to avoid IL-17–inhibitor therapy, given its potential to worsen IBD flares.

Malignancy

Psoriasis patients aged 0 to 79 years have a greater overall risk for malignancy compared with patients without psoriasis.³² Patients with psoriasis have an increased risk for respiratory tract cancer, upper aerodigestive tract cancer, urinary tract cancer, and non-Hodgkin lymphoma.³³ A mild association exists between PsA and lymphoma, nonmelanoma skin cancer (NMSC), and lung cancer.³⁴ More severe psoriasis is associated with greater risk for lymphoma and NMSC. Dermatologists are recommended to educate patients on their risk for certain malignancies and to refer patients to specialists upon suspicion of malignancy.

Risk for malignancy has been shown to be affected by psoriasis treatments. Patients treated with UVB have reduced overall cancer rates for all age groups (hazard ratio, 0.52; P=.3), while those treated with psoralen plus UVA have an increased incidence of squamous cell carcinoma.^32,33 Adalimumab was correlated with increased risk for NMSC in patients with psoriasis but did not have an increased risk for all cancers collectively when used for various immune-mediated inflammatory diseases.³⁵ In contrast, a meta-analysis of randomized clinical trials found no association with TNF inhibitor use and NMSC.³⁶ Ustekinumab had no association with malignancy.³⁷ Treatment history should be elucidated because of higher rates of squamous cell carcinoma in patients with prior psoralen plus UVA, cyclosporine, or methotrexate use.³³ To address malignancy risk, patients with psoriasis should undergo regular screenings for skin cancer and follow national guidelines for age-appropriate cancer screenings.

Lifestyle Choices and QOL

A crucial aspect of successful psoriasis management is patient education. The strongest recommendations support lifestyle changes, such as smoking cessation and limitation of alcohol use. A tactful discussion regarding substance use, work productivity, interpersonal relationships, and sexual function can address substantial effects of psoriasis on QOL so that support and resources can be provided.

Final Thoughts

Management of psoriasis is multifaceted and involves screening, education, monitoring, and collaboration with PCPs and specialists. Regular follow-up with a dermatologist and PCP is strongly recommended for patients with psoriasis given the systemic nature of the disease. The 2019 AAD-NPF recommendations provide important information for dermatologists to coordinate care for complicated psoriasis cases, but clinical judgment is paramount when making medical decisions. The consideration of comorbidities is critical for developing a comprehensive treatment approach, and this approach will lead to better health outcomes and improved QOL for patients with psoriasis.

With the rise of telehealth utilization during the COVID-19 pandemic, clinical care delivery has undergone a substantial shift. This is especially true in dermatology, as utilization of telehealth has jumped from under 15% to more than 95% of dermatologists after the COVID-19 pandemic.¹ However, with this new form of care delivery, it is important to ensure that patients don’t get left behind, either due to socioeconomic/language barriers² or hesitancy about the conditions being treated.

It may not be surprising to know that the idea of using telemedicine for rheumatology is not new. Indeed, a report from 20 years ago outlined the high level of both satisfaction with live interactive telehealth visits for rheumatologic conditions and diagnostic accuracy as compared to in-person visits.³ Through guided palpation and careful history taking, it is possible to conduct a thorough visit and even manage biologics, diagnose active arthritis/enthesitis via photographs, and evaluate pain through a visual analog scale.⁴ As far as dermatology is concerned, it is clear that certain situations seem to be better suited for teledermatology, such as follow-up visits for acne/rosacea.¹ But what of psoriatic arthritis (PsA)? Does telehealth have the potential to mitigate our undertreatment of this important condition, which finds about half of patients being treated with only topical therapy or no treatment at all?⁵ Or can we modulate our visits to accommodate these patients, taking care of not only their visible psoriasis but also the underlying PsA?

Psoriasis is well suited for teledermatology management in general, especially once the diagnosis is made. Multiple studies have shown diagnostic equivalence with in-person care and even similar outcomes after treatment.^6,7 However, most studies have looked at telemedicine primarily for cutaneous psoriasis, and translating this to screening for and management of PsA is paramount. After all, a delay of only 6 months in diagnosing and treating PsA has been associated with poor outcomes.⁸ Thankfully, we do have some tools that can help. There are 3 validated screening tools for PsA: the Psoriasis Epidemiology Screening Tool (PEST), the Psoriatic Arthritis Screening and Evaluation (PASE), and the Toronto Psoriatic Arthritis Screen (ToPAS) questionnaire.⁹ Of these, the PEST seems to be a reasonable option that is quick and easily deployed; it has shown strong performance in terms of sensitivity, specificity, and negative predictive value/positive predictive value when compared to similar screening tools.¹⁰ It also should be facile to direct patients to complete the screening tool, as an online version is available on the National Psoriasis Foundation’s website (https://www.psoriasis.org/psoriatic-arthritis-screening-test/) where patients can be directed to answer 5 simple questions and report back the outcome. For treatment decisions, this tool also can be used to help identify patients who are good candidates for systemic or biologic therapy or those who should see a rheumatologist. Of course, an in-depth discussion of joint pain, morning stiffness, and tender/swollen joints may be more fruitful but also more challenging to conduct. I would propose that this can be pared down to a more direct conversation about finger pain/tenderness, tenderness at the elbow/knee (lateral epicondyle/medial femoral condyle), or heel (Achilles) as more common sites of enthesitis, and questioning about back pain or stiffness that improves with movement.⁹ By combining the screening tool with these pointed questions, even via telehealth, we can greatly improve our yield in diagnosing PsA while only adding a minute or two to our visits. I’d argue that this is much more fruitful than asking the patient to contort their bodies and camera to show an obscure lesion!

It is interesting to consider areas in dermatology where we might make a notable impact on mortality and morbidity by expanding access to care. Earlier diagnosis of melanoma, for instance, certainly would be in consideration, especially in areas of the country where access to dermatologic care is challenging. Better management of PsA has to be up there on the list of conditions where we immediately can make a tangible difference; we have the tools to do so and excellent therapeutics that are safe and effective. Our colleagues in rheumatology have embraced telemedicine with a “how, not if” approach to embracing new technology,¹¹ and it is about time that dermatology takes a similar attitude. The gap between access to dermatologic care in urban areas vs either nonmetropolitan or rural areas is increasing, and dermatology tends to be much more available in well-resourced, urban areas.¹² There are patients who need our expertise, and if it takes the compromise of adopting a technology that sometimes gives us headaches (we’ve all been on video visits with a choppy signal and inadequate lighting), we still should try to figure out the best way to do it because it’s the right thing to do for these patients. If we don’t, the determination of how to conduct teledermatology care will be taken away from us and either insurance companies or corporations not guided by dermatologists may try to enter this health care void and decide how to provide these services.

With the rise of telehealth utilization during the COVID-19 pandemic, clinical care delivery has undergone a substantial shift. This is especially true in dermatology, as utilization of telehealth has jumped from under 15% to more than 95% of dermatologists after the COVID-19 pandemic.¹ However, with this new form of care delivery, it is important to ensure that patients don’t get left behind, either due to socioeconomic/language barriers² or hesitancy about the conditions being treated.

It may not be surprising to know that the idea of using telemedicine for rheumatology is not new. Indeed, a report from 20 years ago outlined the high level of both satisfaction with live interactive telehealth visits for rheumatologic conditions and diagnostic accuracy as compared to in-person visits.³ Through guided palpation and careful history taking, it is possible to conduct a thorough visit and even manage biologics, diagnose active arthritis/enthesitis via photographs, and evaluate pain through a visual analog scale.⁴ As far as dermatology is concerned, it is clear that certain situations seem to be better suited for teledermatology, such as follow-up visits for acne/rosacea.¹ But what of psoriatic arthritis (PsA)? Does telehealth have the potential to mitigate our undertreatment of this important condition, which finds about half of patients being treated with only topical therapy or no treatment at all?⁵ Or can we modulate our visits to accommodate these patients, taking care of not only their visible psoriasis but also the underlying PsA?

Psoriasis is well suited for teledermatology management in general, especially once the diagnosis is made. Multiple studies have shown diagnostic equivalence with in-person care and even similar outcomes after treatment.^6,7 However, most studies have looked at telemedicine primarily for cutaneous psoriasis, and translating this to screening for and management of PsA is paramount. After all, a delay of only 6 months in diagnosing and treating PsA has been associated with poor outcomes.⁸ Thankfully, we do have some tools that can help. There are 3 validated screening tools for PsA: the Psoriasis Epidemiology Screening Tool (PEST), the Psoriatic Arthritis Screening and Evaluation (PASE), and the Toronto Psoriatic Arthritis Screen (ToPAS) questionnaire.⁹ Of these, the PEST seems to be a reasonable option that is quick and easily deployed; it has shown strong performance in terms of sensitivity, specificity, and negative predictive value/positive predictive value when compared to similar screening tools.¹⁰ It also should be facile to direct patients to complete the screening tool, as an online version is available on the National Psoriasis Foundation’s website (https://www.psoriasis.org/psoriatic-arthritis-screening-test/) where patients can be directed to answer 5 simple questions and report back the outcome. For treatment decisions, this tool also can be used to help identify patients who are good candidates for systemic or biologic therapy or those who should see a rheumatologist. Of course, an in-depth discussion of joint pain, morning stiffness, and tender/swollen joints may be more fruitful but also more challenging to conduct. I would propose that this can be pared down to a more direct conversation about finger pain/tenderness, tenderness at the elbow/knee (lateral epicondyle/medial femoral condyle), or heel (Achilles) as more common sites of enthesitis, and questioning about back pain or stiffness that improves with movement.⁹ By combining the screening tool with these pointed questions, even via telehealth, we can greatly improve our yield in diagnosing PsA while only adding a minute or two to our visits. I’d argue that this is much more fruitful than asking the patient to contort their bodies and camera to show an obscure lesion!

It is interesting to consider areas in dermatology where we might make a notable impact on mortality and morbidity by expanding access to care. Earlier diagnosis of melanoma, for instance, certainly would be in consideration, especially in areas of the country where access to dermatologic care is challenging. Better management of PsA has to be up there on the list of conditions where we immediately can make a tangible difference; we have the tools to do so and excellent therapeutics that are safe and effective. Our colleagues in rheumatology have embraced telemedicine with a “how, not if” approach to embracing new technology,¹¹ and it is about time that dermatology takes a similar attitude. The gap between access to dermatologic care in urban areas vs either nonmetropolitan or rural areas is increasing, and dermatology tends to be much more available in well-resourced, urban areas.¹² There are patients who need our expertise, and if it takes the compromise of adopting a technology that sometimes gives us headaches (we’ve all been on video visits with a choppy signal and inadequate lighting), we still should try to figure out the best way to do it because it’s the right thing to do for these patients. If we don’t, the determination of how to conduct teledermatology care will be taken away from us and either insurance companies or corporations not guided by dermatologists may try to enter this health care void and decide how to provide these services.

With the rise of telehealth utilization during the COVID-19 pandemic, clinical care delivery has undergone a substantial shift. This is especially true in dermatology, as utilization of telehealth has jumped from under 15% to more than 95% of dermatologists after the COVID-19 pandemic.¹ However, with this new form of care delivery, it is important to ensure that patients don’t get left behind, either due to socioeconomic/language barriers² or hesitancy about the conditions being treated.

It may not be surprising to know that the idea of using telemedicine for rheumatology is not new. Indeed, a report from 20 years ago outlined the high level of both satisfaction with live interactive telehealth visits for rheumatologic conditions and diagnostic accuracy as compared to in-person visits.³ Through guided palpation and careful history taking, it is possible to conduct a thorough visit and even manage biologics, diagnose active arthritis/enthesitis via photographs, and evaluate pain through a visual analog scale.⁴ As far as dermatology is concerned, it is clear that certain situations seem to be better suited for teledermatology, such as follow-up visits for acne/rosacea.¹ But what of psoriatic arthritis (PsA)? Does telehealth have the potential to mitigate our undertreatment of this important condition, which finds about half of patients being treated with only topical therapy or no treatment at all?⁵ Or can we modulate our visits to accommodate these patients, taking care of not only their visible psoriasis but also the underlying PsA?

Psoriasis is well suited for teledermatology management in general, especially once the diagnosis is made. Multiple studies have shown diagnostic equivalence with in-person care and even similar outcomes after treatment.^6,7 However, most studies have looked at telemedicine primarily for cutaneous psoriasis, and translating this to screening for and management of PsA is paramount. After all, a delay of only 6 months in diagnosing and treating PsA has been associated with poor outcomes.⁸ Thankfully, we do have some tools that can help. There are 3 validated screening tools for PsA: the Psoriasis Epidemiology Screening Tool (PEST), the Psoriatic Arthritis Screening and Evaluation (PASE), and the Toronto Psoriatic Arthritis Screen (ToPAS) questionnaire.⁹ Of these, the PEST seems to be a reasonable option that is quick and easily deployed; it has shown strong performance in terms of sensitivity, specificity, and negative predictive value/positive predictive value when compared to similar screening tools.¹⁰ It also should be facile to direct patients to complete the screening tool, as an online version is available on the National Psoriasis Foundation’s website (https://www.psoriasis.org/psoriatic-arthritis-screening-test/) where patients can be directed to answer 5 simple questions and report back the outcome. For treatment decisions, this tool also can be used to help identify patients who are good candidates for systemic or biologic therapy or those who should see a rheumatologist. Of course, an in-depth discussion of joint pain, morning stiffness, and tender/swollen joints may be more fruitful but also more challenging to conduct. I would propose that this can be pared down to a more direct conversation about finger pain/tenderness, tenderness at the elbow/knee (lateral epicondyle/medial femoral condyle), or heel (Achilles) as more common sites of enthesitis, and questioning about back pain or stiffness that improves with movement.⁹ By combining the screening tool with these pointed questions, even via telehealth, we can greatly improve our yield in diagnosing PsA while only adding a minute or two to our visits. I’d argue that this is much more fruitful than asking the patient to contort their bodies and camera to show an obscure lesion!

It is interesting to consider areas in dermatology where we might make a notable impact on mortality and morbidity by expanding access to care. Earlier diagnosis of melanoma, for instance, certainly would be in consideration, especially in areas of the country where access to dermatologic care is challenging. Better management of PsA has to be up there on the list of conditions where we immediately can make a tangible difference; we have the tools to do so and excellent therapeutics that are safe and effective. Our colleagues in rheumatology have embraced telemedicine with a “how, not if” approach to embracing new technology,¹¹ and it is about time that dermatology takes a similar attitude. The gap between access to dermatologic care in urban areas vs either nonmetropolitan or rural areas is increasing, and dermatology tends to be much more available in well-resourced, urban areas.¹² There are patients who need our expertise, and if it takes the compromise of adopting a technology that sometimes gives us headaches (we’ve all been on video visits with a choppy signal and inadequate lighting), we still should try to figure out the best way to do it because it’s the right thing to do for these patients. If we don’t, the determination of how to conduct teledermatology care will be taken away from us and either insurance companies or corporations not guided by dermatologists may try to enter this health care void and decide how to provide these services.

Biologics have transformed the management of moderate to severe psoriasis. There currently are 11 biologics approved by the US Food and Drug Administration (Table) for psoriasis treatment that have been affirmed by various clinical studies. This article provides dosing initiation, maintenance information, and updated clinical data using phase 3 studies (N=8) published between May 2020 and February 2021. Generic names of the 11 biologics were searched separately in the PubMed database within the specified date range. Subsequent results were reviewed by title and selected for phase 3 and 4 trials. Clinical data in this review focus on reducing patient disease burden by allocating a biologic best fit for each patient’s individual health profile.

IL-17A Inhibitors Update

Secukinumab is safe and efficacious for skin clearance in the presence of comorbidities and can be used for improving plaque psoriasis and palmoplantar pustular psoriasis. An extension of a phase 3 randomized controlled trial (RCT)—2PRECISE—evaluated the efficacy and safety of secukinumab dosing at 300 mg (n=79) and 150 mg (n=80) in adults with moderate to severe palmoplantar pustular psoriasis (palmoplantar psoriasis area and severity index [PPPASI] score ≥12 and dermatology life quality index [DLQI] ≥10) over 148 weeks.¹ Extension patients were included from the 52-week 2PRECISE study per the investigator’s judgement of a meaningful clinical response (exact criteria not described). All treatment groups demonstrated a mean (SD) PPPASI of 22.7 (9.5) by the extension trial’s start. Results affirmed that clinical response waned after week 148 in all groups excluding placebo/secukinumab 150 mg, which maintained a mean (SD) PPPASI of 22.7 (9.5). The most frequent adverse events were nasopharyngitis, pustular psoriasis, headache, and pruritus.¹

Comorbidities do not have a major impact on secukinumab’s efficacy. A post hoc analysis of 4 phase 3 RCTs—ERASURE, FIXTURE, FEATURE, and JUNCTURE—gathered data from adult patients (N=2401) to assess baseline comorbidities with efficacy and safety of secukinumab vs etanercept after 12 weeks of treatment.² Sixty-one percent (n=1469) had at least 1 comorbidity, most frequently obesity, hypertension, psoriatic arthritis, hyperlipidemia, or diabetes mellitus. All patient groups had a greater likelihood of a psoriasis area and severity index (PASI) response with any dose of secukinumab vs patients with comorbidities who were taking etanercept or placebo (P<.05) at week 12. All groups had a greater likelihood of achieving investigator global assessment scores of 0/1 (clear/almost clear) vs patients with comorbidities taking etanercept or placebo (P<.05). Baseline comorbidities did not significantly affect treatment response, except obesity, which was associated with decreased probability of achieving all PASI and investigator global assessment (P<.01) responses. Secukinumab-treated patients with and without comorbidities had equivalent likelihood of treatment-emergent adverse events (TEAEs).²

Brodalumab is an effective biologic that has shown long-term safety with continuous administration. Continuous brodalumab and brodalumab after placebo demonstrated impactful skin clearance after 120 weeks in AMAGINE-1, a phase 3 RCT involving adults (N=442) with moderate to severe plaque psoriasis.³ Patients randomized to brodalumab 210 mg (n=222) or placebo (n=220) were rerandomized according to initial treatment response. In patients switching from brodalumab to placebo at week 12, 55% and 94% achieved PASI 75 at week 20 and week 120, respectively, and 75% reached PASI 100 at week 120. Of patients with static physician global assessment (sPGA) scores of 0/1 (clear/almost clear) at week 12 who were rerandomized to brodalumab, 96% and 80% (using observed data) achieved PASI 75 and PASI 100, respectively. Mean (SD) time to return of skin disease following withdrawal of brodalumab was 74.7 (50.5) days. Treatment-emergent adverse events included headaches, arthralgia, diarrhea, and nausea. Suicidal ideation was rare (this study had 1 completed suicide), and authors cited that no causal association has been made between brodalumab and suicidality. Brodalumab also demonstrated favorable treatment response in patients who underwent a lapse in treatment, offering real-world value, as intermittent treatment administration can occur because of personal or financial reasons.³

Ixekizumab is associated with more rapid skin clearance, better resolution of nail psoriasis, and superior improvement in quality-of-life measures when compared with guselkumab. The phase 3 study IXORA-R compared skin and nail clearance as well as patient-reported outcomes over 24 weeks with ixekizumab 80 mg (n=520) vs guselkumab 100 mg (n=507) in adults with moderate to severe plaque psoriasis.⁴ Ixekizumab (50%) was shown to be no worse than guselkumab (52%; difference, –2.3%) using a noninferiority test (noninferiority margin of –11.4%). The treatments exhibited similar efficacy, with no significant difference in proportion of patients reaching PASI 100 (P=.41). Ixekizumab patients tended to have skin clearance sooner than guselkumab patients, reaching PASI 50/75/90 and PASI 100 in a median time that was 2 weeks and 7.5 weeks earlier, respectively. More ixekizumab patients (52%) achieved clear nails vs guselkumab patients (31%; P=.007). Ixekizumab patients reported greater satisfaction with their skin disease affecting quality of life (DLQI), with more DLQI 0/1 (no effect at all on patient’s life) scores and being itch free (P<.05). Ixekizumab was associated with significantly more days of complete skin clearance (PASI 100) vs guselkumab (55.6 days vs 42.2 days; P<.001). Although an upper respiratory tract infection was the most common TEAE, the proportion of TEAEs was similar between treatments.⁴

IL-23 Inhibitors Update

Tildrakizumab has similar long-term skin clearance efficacy and safety in patients with psoriasis with and without comorbid metabolic syndrome (MetS). A post hoc analysis of 2 phase 2 RCTs (reSURFACE 1/2) involving adults (N=338 and N=307) with moderate to severe plaque psoriasis assessed long-term efficacy (3 years), drug survival, and safety for 5 years of continuous tildrakizumab 100 mg and 200 mg in adults with comorbid MetS.⁵ Although no difference in efficacy was concluded, greater body mass index of the MetS population was shown to be associated with lower biologic efficacy compared to the general population. The proportion of patients who achieved PASI 75 at week 52 was comparable in patients with MetS and patients without MetS (tildrakizumab 100 mg, 85% and 86% vs 86% and 94% for reSURFACE 1/2, respectively; tildrakizumab 200 mg, 76% and 87% vs 76% and 87% for reSURFACE 1/2, respectively).⁵

Tildrakizumab also demonstrated efficacy and safety for up to 5 years in 2 other phase 3 RCTs with no dose-related differences in frequency of injections and malignancies. Tildrakizumab 100 mg is the recommended dose. The 200-mg dose can be utilized in patients with a high burden of disease and disability. reSURFACE 1 and reSURFACE 2 involved adults with chronic moderate to severe plaque psoriasis randomized to tildrakizumab 100 mg, 200 mg, or placebo with the option of long-term extension to week 244 if patients reached 50% or greater improvement from baseline PASI score.⁶ Patients in reSURFACE 2 also were randomized to etanercept 50 mg with partial responders and nonresponders at week 28 switching to tildrakizumab 200 mg until week 244. Extension results showed PASI 75 achievement in 88.7% (95% CI, 84.6%-92.1%) of patients taking tildrakizumab 100 mg (n=235), 92.5% (95% CI, 88.1%-95.7%) of patients taking tildrakizumab 200 mg (n=176), and 81.3% (95% CI, 72.6%-88.2%) of patients taking etanercept/partial nonresponders (n=85). The most common TEAE was nasopharyngitis (10.5/100 patient-years for tildrakizumab 100 mg and 10.7/100 patient-years for tildrakizumab 200 mg). The frequency of severe infections (eg, diverticulitis, pneumonia, cellulitis, appendicitis) was 1.2 per 100 patient-years for tildrakizumab 100 mg and 1.3 per 100 patient-years for tildrakizumab 200 mg.⁶

Risankizumab and tildrakizumab require the lowest number of injections, thereby providing sustainable skin clearance with a convenient injection dosing schedule for patients. Risankizumab efficacy (8.2% with inferiority margin of 12%) was noninferior to secukinumab when assessing the proportion of PASI 90 responders at week 16 (after 2 doses of risankizumab vs 7 doses of secukinumab).⁷ IMMerge, an international phase 3 RCT, involved adults (N=327) with moderate to severe plaque psoriasis to compare the safety and efficacy of risankizumab 150 mg (n=164) vs secukinumab 300 mg (n=163) up to 52 weeks. A greater proportion of the risankizumab arm (86.6%) achieved PASI 90 in 52 weeks compared to the secukinumab arm (57.1%). Superior skin clearance (PASI 90) at week 52 was achieved after 5 doses with risankizumab vs 16 doses of secukinumab. Risankizumab TEAEs were nasopharyngitis, upper respiratory tract infection, headache, arthralgia, diarrhea, and bronchitis.⁷

Continuous risankizumab treatment shows substantially stronger skin clearing performance compared with intermittent treatment following drug withdrawal, demonstrating that treatment gaps minimize therapeutic response. IMMhance, an international phase 3 RCT involving adults (N=507) with moderate to severe plaque psoriasis, evaluated the safety and efficacy with risankizumab 150 mg after 52 weeks and 104 weeks.⁸ Part A randomized patients to risankizumab 150 mg (n=407) or placebo (n=100). Part B rerandomized patients at week 28 to continue risankizumab 150 mg or placebo (designated as withdrawal of treatment; later re-treated with risankizumab 150 mg if patients had sPGA ≥3). At week 52, significantly more patients reached sPGA score of 0/1 with risankizumab/risankizumab (n=97 [87.4%]) vs risankizumab/placebo (n=138 [61.3%]; P<.001). At week 104, significantly more patients reached an sPGA score of 0/1 with risankizumab/risankizumab (n=90 [81.1%]) vs risankizumab/placebo (n=16 [7.1%]; P<.001). Risankizumab exhibited longevity following withdrawal, as median time to loss of response and relapse was 42 weeks (sPGA ≥3). The extent of TEAEs was similar between risankizumab and placebo and included nasopharyngitis, upper respiratory tract infection, headache, and back pain.⁸

Final Thoughts

Biologics for psoriasis help produce intended results for skin disease clearance and are tools for precision medicine. Recent data demonstrate safe, durable, and continuous efficacy with biologics, which offer patients a better chance of treatment success. This guide may serve as a quick reference for biologic selection with special consideration of individual disease characteristics and comorbidities.

Biologics have transformed the management of moderate to severe psoriasis. There currently are 11 biologics approved by the US Food and Drug Administration (Table) for psoriasis treatment that have been affirmed by various clinical studies. This article provides dosing initiation, maintenance information, and updated clinical data using phase 3 studies (N=8) published between May 2020 and February 2021. Generic names of the 11 biologics were searched separately in the PubMed database within the specified date range. Subsequent results were reviewed by title and selected for phase 3 and 4 trials. Clinical data in this review focus on reducing patient disease burden by allocating a biologic best fit for each patient’s individual health profile.

IL-17A Inhibitors Update

Secukinumab is safe and efficacious for skin clearance in the presence of comorbidities and can be used for improving plaque psoriasis and palmoplantar pustular psoriasis. An extension of a phase 3 randomized controlled trial (RCT)—2PRECISE—evaluated the efficacy and safety of secukinumab dosing at 300 mg (n=79) and 150 mg (n=80) in adults with moderate to severe palmoplantar pustular psoriasis (palmoplantar psoriasis area and severity index [PPPASI] score ≥12 and dermatology life quality index [DLQI] ≥10) over 148 weeks.¹ Extension patients were included from the 52-week 2PRECISE study per the investigator’s judgement of a meaningful clinical response (exact criteria not described). All treatment groups demonstrated a mean (SD) PPPASI of 22.7 (9.5) by the extension trial’s start. Results affirmed that clinical response waned after week 148 in all groups excluding placebo/secukinumab 150 mg, which maintained a mean (SD) PPPASI of 22.7 (9.5). The most frequent adverse events were nasopharyngitis, pustular psoriasis, headache, and pruritus.¹

Comorbidities do not have a major impact on secukinumab’s efficacy. A post hoc analysis of 4 phase 3 RCTs—ERASURE, FIXTURE, FEATURE, and JUNCTURE—gathered data from adult patients (N=2401) to assess baseline comorbidities with efficacy and safety of secukinumab vs etanercept after 12 weeks of treatment.² Sixty-one percent (n=1469) had at least 1 comorbidity, most frequently obesity, hypertension, psoriatic arthritis, hyperlipidemia, or diabetes mellitus. All patient groups had a greater likelihood of a psoriasis area and severity index (PASI) response with any dose of secukinumab vs patients with comorbidities who were taking etanercept or placebo (P<.05) at week 12. All groups had a greater likelihood of achieving investigator global assessment scores of 0/1 (clear/almost clear) vs patients with comorbidities taking etanercept or placebo (P<.05). Baseline comorbidities did not significantly affect treatment response, except obesity, which was associated with decreased probability of achieving all PASI and investigator global assessment (P<.01) responses. Secukinumab-treated patients with and without comorbidities had equivalent likelihood of treatment-emergent adverse events (TEAEs).²

Brodalumab is an effective biologic that has shown long-term safety with continuous administration. Continuous brodalumab and brodalumab after placebo demonstrated impactful skin clearance after 120 weeks in AMAGINE-1, a phase 3 RCT involving adults (N=442) with moderate to severe plaque psoriasis.³ Patients randomized to brodalumab 210 mg (n=222) or placebo (n=220) were rerandomized according to initial treatment response. In patients switching from brodalumab to placebo at week 12, 55% and 94% achieved PASI 75 at week 20 and week 120, respectively, and 75% reached PASI 100 at week 120. Of patients with static physician global assessment (sPGA) scores of 0/1 (clear/almost clear) at week 12 who were rerandomized to brodalumab, 96% and 80% (using observed data) achieved PASI 75 and PASI 100, respectively. Mean (SD) time to return of skin disease following withdrawal of brodalumab was 74.7 (50.5) days. Treatment-emergent adverse events included headaches, arthralgia, diarrhea, and nausea. Suicidal ideation was rare (this study had 1 completed suicide), and authors cited that no causal association has been made between brodalumab and suicidality. Brodalumab also demonstrated favorable treatment response in patients who underwent a lapse in treatment, offering real-world value, as intermittent treatment administration can occur because of personal or financial reasons.³

Ixekizumab is associated with more rapid skin clearance, better resolution of nail psoriasis, and superior improvement in quality-of-life measures when compared with guselkumab. The phase 3 study IXORA-R compared skin and nail clearance as well as patient-reported outcomes over 24 weeks with ixekizumab 80 mg (n=520) vs guselkumab 100 mg (n=507) in adults with moderate to severe plaque psoriasis.⁴ Ixekizumab (50%) was shown to be no worse than guselkumab (52%; difference, –2.3%) using a noninferiority test (noninferiority margin of –11.4%). The treatments exhibited similar efficacy, with no significant difference in proportion of patients reaching PASI 100 (P=.41). Ixekizumab patients tended to have skin clearance sooner than guselkumab patients, reaching PASI 50/75/90 and PASI 100 in a median time that was 2 weeks and 7.5 weeks earlier, respectively. More ixekizumab patients (52%) achieved clear nails vs guselkumab patients (31%; P=.007). Ixekizumab patients reported greater satisfaction with their skin disease affecting quality of life (DLQI), with more DLQI 0/1 (no effect at all on patient’s life) scores and being itch free (P<.05). Ixekizumab was associated with significantly more days of complete skin clearance (PASI 100) vs guselkumab (55.6 days vs 42.2 days; P<.001). Although an upper respiratory tract infection was the most common TEAE, the proportion of TEAEs was similar between treatments.⁴

IL-23 Inhibitors Update

Tildrakizumab has similar long-term skin clearance efficacy and safety in patients with psoriasis with and without comorbid metabolic syndrome (MetS). A post hoc analysis of 2 phase 2 RCTs (reSURFACE 1/2) involving adults (N=338 and N=307) with moderate to severe plaque psoriasis assessed long-term efficacy (3 years), drug survival, and safety for 5 years of continuous tildrakizumab 100 mg and 200 mg in adults with comorbid MetS.⁵ Although no difference in efficacy was concluded, greater body mass index of the MetS population was shown to be associated with lower biologic efficacy compared to the general population. The proportion of patients who achieved PASI 75 at week 52 was comparable in patients with MetS and patients without MetS (tildrakizumab 100 mg, 85% and 86% vs 86% and 94% for reSURFACE 1/2, respectively; tildrakizumab 200 mg, 76% and 87% vs 76% and 87% for reSURFACE 1/2, respectively).⁵

Tildrakizumab also demonstrated efficacy and safety for up to 5 years in 2 other phase 3 RCTs with no dose-related differences in frequency of injections and malignancies. Tildrakizumab 100 mg is the recommended dose. The 200-mg dose can be utilized in patients with a high burden of disease and disability. reSURFACE 1 and reSURFACE 2 involved adults with chronic moderate to severe plaque psoriasis randomized to tildrakizumab 100 mg, 200 mg, or placebo with the option of long-term extension to week 244 if patients reached 50% or greater improvement from baseline PASI score.⁶ Patients in reSURFACE 2 also were randomized to etanercept 50 mg with partial responders and nonresponders at week 28 switching to tildrakizumab 200 mg until week 244. Extension results showed PASI 75 achievement in 88.7% (95% CI, 84.6%-92.1%) of patients taking tildrakizumab 100 mg (n=235), 92.5% (95% CI, 88.1%-95.7%) of patients taking tildrakizumab 200 mg (n=176), and 81.3% (95% CI, 72.6%-88.2%) of patients taking etanercept/partial nonresponders (n=85). The most common TEAE was nasopharyngitis (10.5/100 patient-years for tildrakizumab 100 mg and 10.7/100 patient-years for tildrakizumab 200 mg). The frequency of severe infections (eg, diverticulitis, pneumonia, cellulitis, appendicitis) was 1.2 per 100 patient-years for tildrakizumab 100 mg and 1.3 per 100 patient-years for tildrakizumab 200 mg.⁶

Risankizumab and tildrakizumab require the lowest number of injections, thereby providing sustainable skin clearance with a convenient injection dosing schedule for patients. Risankizumab efficacy (8.2% with inferiority margin of 12%) was noninferior to secukinumab when assessing the proportion of PASI 90 responders at week 16 (after 2 doses of risankizumab vs 7 doses of secukinumab).⁷ IMMerge, an international phase 3 RCT, involved adults (N=327) with moderate to severe plaque psoriasis to compare the safety and efficacy of risankizumab 150 mg (n=164) vs secukinumab 300 mg (n=163) up to 52 weeks. A greater proportion of the risankizumab arm (86.6%) achieved PASI 90 in 52 weeks compared to the secukinumab arm (57.1%). Superior skin clearance (PASI 90) at week 52 was achieved after 5 doses with risankizumab vs 16 doses of secukinumab. Risankizumab TEAEs were nasopharyngitis, upper respiratory tract infection, headache, arthralgia, diarrhea, and bronchitis.⁷

Continuous risankizumab treatment shows substantially stronger skin clearing performance compared with intermittent treatment following drug withdrawal, demonstrating that treatment gaps minimize therapeutic response. IMMhance, an international phase 3 RCT involving adults (N=507) with moderate to severe plaque psoriasis, evaluated the safety and efficacy with risankizumab 150 mg after 52 weeks and 104 weeks.⁸ Part A randomized patients to risankizumab 150 mg (n=407) or placebo (n=100). Part B rerandomized patients at week 28 to continue risankizumab 150 mg or placebo (designated as withdrawal of treatment; later re-treated with risankizumab 150 mg if patients had sPGA ≥3). At week 52, significantly more patients reached sPGA score of 0/1 with risankizumab/risankizumab (n=97 [87.4%]) vs risankizumab/placebo (n=138 [61.3%]; P<.001). At week 104, significantly more patients reached an sPGA score of 0/1 with risankizumab/risankizumab (n=90 [81.1%]) vs risankizumab/placebo (n=16 [7.1%]; P<.001). Risankizumab exhibited longevity following withdrawal, as median time to loss of response and relapse was 42 weeks (sPGA ≥3). The extent of TEAEs was similar between risankizumab and placebo and included nasopharyngitis, upper respiratory tract infection, headache, and back pain.⁸

Final Thoughts

Biologics for psoriasis help produce intended results for skin disease clearance and are tools for precision medicine. Recent data demonstrate safe, durable, and continuous efficacy with biologics, which offer patients a better chance of treatment success. This guide may serve as a quick reference for biologic selection with special consideration of individual disease characteristics and comorbidities.

Biologics have transformed the management of moderate to severe psoriasis. There currently are 11 biologics approved by the US Food and Drug Administration (Table) for psoriasis treatment that have been affirmed by various clinical studies. This article provides dosing initiation, maintenance information, and updated clinical data using phase 3 studies (N=8) published between May 2020 and February 2021. Generic names of the 11 biologics were searched separately in the PubMed database within the specified date range. Subsequent results were reviewed by title and selected for phase 3 and 4 trials. Clinical data in this review focus on reducing patient disease burden by allocating a biologic best fit for each patient’s individual health profile.

IL-17A Inhibitors Update

Secukinumab is safe and efficacious for skin clearance in the presence of comorbidities and can be used for improving plaque psoriasis and palmoplantar pustular psoriasis. An extension of a phase 3 randomized controlled trial (RCT)—2PRECISE—evaluated the efficacy and safety of secukinumab dosing at 300 mg (n=79) and 150 mg (n=80) in adults with moderate to severe palmoplantar pustular psoriasis (palmoplantar psoriasis area and severity index [PPPASI] score ≥12 and dermatology life quality index [DLQI] ≥10) over 148 weeks.¹ Extension patients were included from the 52-week 2PRECISE study per the investigator’s judgement of a meaningful clinical response (exact criteria not described). All treatment groups demonstrated a mean (SD) PPPASI of 22.7 (9.5) by the extension trial’s start. Results affirmed that clinical response waned after week 148 in all groups excluding placebo/secukinumab 150 mg, which maintained a mean (SD) PPPASI of 22.7 (9.5). The most frequent adverse events were nasopharyngitis, pustular psoriasis, headache, and pruritus.¹

Comorbidities do not have a major impact on secukinumab’s efficacy. A post hoc analysis of 4 phase 3 RCTs—ERASURE, FIXTURE, FEATURE, and JUNCTURE—gathered data from adult patients (N=2401) to assess baseline comorbidities with efficacy and safety of secukinumab vs etanercept after 12 weeks of treatment.² Sixty-one percent (n=1469) had at least 1 comorbidity, most frequently obesity, hypertension, psoriatic arthritis, hyperlipidemia, or diabetes mellitus. All patient groups had a greater likelihood of a psoriasis area and severity index (PASI) response with any dose of secukinumab vs patients with comorbidities who were taking etanercept or placebo (P<.05) at week 12. All groups had a greater likelihood of achieving investigator global assessment scores of 0/1 (clear/almost clear) vs patients with comorbidities taking etanercept or placebo (P<.05). Baseline comorbidities did not significantly affect treatment response, except obesity, which was associated with decreased probability of achieving all PASI and investigator global assessment (P<.01) responses. Secukinumab-treated patients with and without comorbidities had equivalent likelihood of treatment-emergent adverse events (TEAEs).²

Brodalumab is an effective biologic that has shown long-term safety with continuous administration. Continuous brodalumab and brodalumab after placebo demonstrated impactful skin clearance after 120 weeks in AMAGINE-1, a phase 3 RCT involving adults (N=442) with moderate to severe plaque psoriasis.³ Patients randomized to brodalumab 210 mg (n=222) or placebo (n=220) were rerandomized according to initial treatment response. In patients switching from brodalumab to placebo at week 12, 55% and 94% achieved PASI 75 at week 20 and week 120, respectively, and 75% reached PASI 100 at week 120. Of patients with static physician global assessment (sPGA) scores of 0/1 (clear/almost clear) at week 12 who were rerandomized to brodalumab, 96% and 80% (using observed data) achieved PASI 75 and PASI 100, respectively. Mean (SD) time to return of skin disease following withdrawal of brodalumab was 74.7 (50.5) days. Treatment-emergent adverse events included headaches, arthralgia, diarrhea, and nausea. Suicidal ideation was rare (this study had 1 completed suicide), and authors cited that no causal association has been made between brodalumab and suicidality. Brodalumab also demonstrated favorable treatment response in patients who underwent a lapse in treatment, offering real-world value, as intermittent treatment administration can occur because of personal or financial reasons.³

Ixekizumab is associated with more rapid skin clearance, better resolution of nail psoriasis, and superior improvement in quality-of-life measures when compared with guselkumab. The phase 3 study IXORA-R compared skin and nail clearance as well as patient-reported outcomes over 24 weeks with ixekizumab 80 mg (n=520) vs guselkumab 100 mg (n=507) in adults with moderate to severe plaque psoriasis.⁴ Ixekizumab (50%) was shown to be no worse than guselkumab (52%; difference, –2.3%) using a noninferiority test (noninferiority margin of –11.4%). The treatments exhibited similar efficacy, with no significant difference in proportion of patients reaching PASI 100 (P=.41). Ixekizumab patients tended to have skin clearance sooner than guselkumab patients, reaching PASI 50/75/90 and PASI 100 in a median time that was 2 weeks and 7.5 weeks earlier, respectively. More ixekizumab patients (52%) achieved clear nails vs guselkumab patients (31%; P=.007). Ixekizumab patients reported greater satisfaction with their skin disease affecting quality of life (DLQI), with more DLQI 0/1 (no effect at all on patient’s life) scores and being itch free (P<.05). Ixekizumab was associated with significantly more days of complete skin clearance (PASI 100) vs guselkumab (55.6 days vs 42.2 days; P<.001). Although an upper respiratory tract infection was the most common TEAE, the proportion of TEAEs was similar between treatments.⁴

IL-23 Inhibitors Update

Tildrakizumab has similar long-term skin clearance efficacy and safety in patients with psoriasis with and without comorbid metabolic syndrome (MetS). A post hoc analysis of 2 phase 2 RCTs (reSURFACE 1/2) involving adults (N=338 and N=307) with moderate to severe plaque psoriasis assessed long-term efficacy (3 years), drug survival, and safety for 5 years of continuous tildrakizumab 100 mg and 200 mg in adults with comorbid MetS.⁵ Although no difference in efficacy was concluded, greater body mass index of the MetS population was shown to be associated with lower biologic efficacy compared to the general population. The proportion of patients who achieved PASI 75 at week 52 was comparable in patients with MetS and patients without MetS (tildrakizumab 100 mg, 85% and 86% vs 86% and 94% for reSURFACE 1/2, respectively; tildrakizumab 200 mg, 76% and 87% vs 76% and 87% for reSURFACE 1/2, respectively).⁵

Tildrakizumab also demonstrated efficacy and safety for up to 5 years in 2 other phase 3 RCTs with no dose-related differences in frequency of injections and malignancies. Tildrakizumab 100 mg is the recommended dose. The 200-mg dose can be utilized in patients with a high burden of disease and disability. reSURFACE 1 and reSURFACE 2 involved adults with chronic moderate to severe plaque psoriasis randomized to tildrakizumab 100 mg, 200 mg, or placebo with the option of long-term extension to week 244 if patients reached 50% or greater improvement from baseline PASI score.⁶ Patients in reSURFACE 2 also were randomized to etanercept 50 mg with partial responders and nonresponders at week 28 switching to tildrakizumab 200 mg until week 244. Extension results showed PASI 75 achievement in 88.7% (95% CI, 84.6%-92.1%) of patients taking tildrakizumab 100 mg (n=235), 92.5% (95% CI, 88.1%-95.7%) of patients taking tildrakizumab 200 mg (n=176), and 81.3% (95% CI, 72.6%-88.2%) of patients taking etanercept/partial nonresponders (n=85). The most common TEAE was nasopharyngitis (10.5/100 patient-years for tildrakizumab 100 mg and 10.7/100 patient-years for tildrakizumab 200 mg). The frequency of severe infections (eg, diverticulitis, pneumonia, cellulitis, appendicitis) was 1.2 per 100 patient-years for tildrakizumab 100 mg and 1.3 per 100 patient-years for tildrakizumab 200 mg.⁶

Risankizumab and tildrakizumab require the lowest number of injections, thereby providing sustainable skin clearance with a convenient injection dosing schedule for patients. Risankizumab efficacy (8.2% with inferiority margin of 12%) was noninferior to secukinumab when assessing the proportion of PASI 90 responders at week 16 (after 2 doses of risankizumab vs 7 doses of secukinumab).⁷ IMMerge, an international phase 3 RCT, involved adults (N=327) with moderate to severe plaque psoriasis to compare the safety and efficacy of risankizumab 150 mg (n=164) vs secukinumab 300 mg (n=163) up to 52 weeks. A greater proportion of the risankizumab arm (86.6%) achieved PASI 90 in 52 weeks compared to the secukinumab arm (57.1%). Superior skin clearance (PASI 90) at week 52 was achieved after 5 doses with risankizumab vs 16 doses of secukinumab. Risankizumab TEAEs were nasopharyngitis, upper respiratory tract infection, headache, arthralgia, diarrhea, and bronchitis.⁷

Continuous risankizumab treatment shows substantially stronger skin clearing performance compared with intermittent treatment following drug withdrawal, demonstrating that treatment gaps minimize therapeutic response. IMMhance, an international phase 3 RCT involving adults (N=507) with moderate to severe plaque psoriasis, evaluated the safety and efficacy with risankizumab 150 mg after 52 weeks and 104 weeks.⁸ Part A randomized patients to risankizumab 150 mg (n=407) or placebo (n=100). Part B rerandomized patients at week 28 to continue risankizumab 150 mg or placebo (designated as withdrawal of treatment; later re-treated with risankizumab 150 mg if patients had sPGA ≥3). At week 52, significantly more patients reached sPGA score of 0/1 with risankizumab/risankizumab (n=97 [87.4%]) vs risankizumab/placebo (n=138 [61.3%]; P<.001). At week 104, significantly more patients reached an sPGA score of 0/1 with risankizumab/risankizumab (n=90 [81.1%]) vs risankizumab/placebo (n=16 [7.1%]; P<.001). Risankizumab exhibited longevity following withdrawal, as median time to loss of response and relapse was 42 weeks (sPGA ≥3). The extent of TEAEs was similar between risankizumab and placebo and included nasopharyngitis, upper respiratory tract infection, headache, and back pain.⁸

Final Thoughts

Biologics for psoriasis help produce intended results for skin disease clearance and are tools for precision medicine. Recent data demonstrate safe, durable, and continuous efficacy with biologics, which offer patients a better chance of treatment success. This guide may serve as a quick reference for biologic selection with special consideration of individual disease characteristics and comorbidities.

Biologic medications are highly effective in treating moderate to severe psoriasis, yet many patients are apprehensive about taking a biologic medication for a variety of reasons, such as hearing negative information about the drug from friends or family, being nervous about injection, or seeing the drug or its side effects negatively portrayed in the media.^1-3 Because biologic medications are costly, many patients may fear needing to discontinue use of the medication owing to lack of affordability, which may result in subsequent rebound of psoriasis. Because patients’ fear of a drug is inherently subjective, it can be modified with appropriate reassurance and presentation of evidence. By understanding what information increases patients’ confidence in their willingness to take a biologic medication, patients may be more willing to initiate use of the drug and improve treatment outcomes.

There are mixed findings about whether statistical evidence or an anecdote is more effective in persuasion.^4-6 The specific context in which the persuasion takes place may be important in determining which method is superior. In most nonthreatening situations, people appear to be more easily persuaded by statistical evidence rather than an anecdote. However, in circumstances where emotional engagement is high, such as regarding one’s own health, an anecdote tends to be more persuasive compared to statistical evidence.⁷ The purpose of this study was to evaluate patients’ willingness to take a biologic medication for the management of their psoriasis if presented with either clinical trial evidence of the agent’s efficacy and safety, an anecdote of a single patient’s positive experience, or both.

Methods

Patient Inclusion Criteria
Following Wake Forest School of Medicine institutional review board approval, a prospective parallel-arm survey study was performed on eligible patients 18 years or older with a self-reported diagnosis of psoriasis. Patients were required to have a working knowledge of English and not have been previously prescribed a biologic medication for their psoriasis. If patients did not meet inclusion criteria after answering the survey eligibility screening questions, then they were unable to complete the remainder of the survey and were excluded from the analysis.

Survey Administration
A total of 222 patients were recruited through Amazon Mechanical Turk, an online crowdsourcing platform. (Amazon Mechanical Turk is a validated tool in conducting research in psychology and other social sciences and is considered as diverse as and perhaps more representative than traditional samples.^8,9) Patients received a fact sheet and were taken to the survey hosted on Qualtrics, a secure web-based survey software that supports data collection for research studies. Amazon Mechanical Turk requires some amount of compensation to patients; therefore, recruited patients were compensated $0.03.

Statistical Analysis
Patients were randomized using SPSS Statistics version 23.0 (IBM) in a 1:1 ratio to assess how willing they would be to take a biologic medication for their psoriasis if presented with one of the following: (1) a control that queried patients about their willingness to take treatment without having been informed on its efficacy or safety, (2) clinical trial evidence of the agent’s efficacy and safety, (3) an anecdote of a single patient’s positive experience, or (4) both clinical trial evidence of the agent’s efficacy and safety and an anecdote of a single patient’s positive experience (Table 1). Demographic information including sex, age, ethnicity, and education level was collected, in addition to other baseline characteristics such as having friends or family with a history of psoriasis, history of participation in a clinical trial with use of an experimental drug, and the number of years since clinical diagnosis of psoriasis.

Results

There were no statistically significant differences among the baseline characteristics of the 4 information assignment groups (Table 2). Patients in the control group not given either clinical trial evidence of a biologic medication’s efficacy and safety or anecdote of a single patient’s positive experience had the lowest reported willingness to take treatment (median, 4.0)(Figure). Patients in the group given clinical trial evidence had an intermediate level of reported willingness to take treatment (median, 7.0). Patients in the groups given an anecdote or clinical trial evidence and anecdote had the highest reported willingness to take treatment (median, 8.0). Patients presented with an anecdote or clinical trial evidence and anecdote were significantly more likely to report willingness to take treatment than those not presented with either clinical trial evidence or anecdote (P<.001). Although patients presented with an anecdote or clinical trial evidence and anecdote were more likely to take a biologic medication than those presented with only clinical trial evidence, the difference between these groups was not significant (P=.75).

Based on regression analysis, age, sex, and having friends or family with a history of psoriasis were not significantly associated with patients’ responses (eTable). The number of years since clinical diagnosis of psoriasis (P=.034) and history of participation in a clinical trial with use of an experimental drug (P=.018) were significantly associated with the willingness of patients presented with an anecdote to take a biologic medication.

Comment

Anecdotal Reassurance
The presentation of clinical trial and/or anecdotal evidence had a strong effect on patients’ willingness to take a biologic medication for their psoriasis. Human perception of a treatment is inherently subjective, and such perceptions can be modified with appropriate reassurance and presentation of evidence.¹ Across the population we studied, presenting a brief anecdote of a single patient’s positive experience is a quick and efficient means—and as or more effective as giving details on efficacy and safety—to help patients decide to take a treatment for their psoriasis.

Anecdotal reassurance is powerful. Both health care providers and patients have a natural tendency to focus on anecdotal experiences rather than statistical reasoning when making treatment decisions.^10-12 Although negative anecdotal experiences may make patients unwilling to take a medication (or may make them overly desirous of an inappropriate treatment), clinicians can harness this psychological phenomenon to both increase patient willingness to take potentially beneficial treatments or to deter them from engaging in activities that can be harmful to their health, such as tanning and smoking.

Psoriasis Duration and Willingness to Take a Biologic Medication
In general, patient demographics did not appear to have an association with reported willingness to take a biologic medication for psoriasis. However, the number of years since clinical diagnosis of psoriasis had an effect on willingness to take a biologic medication, with patients with a longer personal history of psoriasis showing a higher willingness to take a treatment after being presented with an anecdote than patients with a shorter personal history of psoriasis. We can only speculate on the reasons why. Patients with a longer personal history of psoriasis may have tried and failed more treatments and therefore have a distrust in the validity of clinical trial evidence. These patients may feel their psoriasis is different than that of other clinical trial participants and thus may be more willing to rely on the success stories of individual patients.

Prior participation in a clinical trial with use of an experimental drug was associated with a lower willingness to choose treatment after being presented with anecdotal reassurance. This finding may be attributable to these patients understanding the subjective nature of anecdotes and preferring more objective information in the form of randomized clinical trials in making treatment decisions. Overall, the presentation of evidence about the efficacy and safety of biologic medications in the treatment of psoriasis has a greater impact on patient decision-making than patients’ age, sex, and having friends or family with a history of psoriasis.

Limitations
Limitations of the study were typical of survey-based research. With closed-ended questions, patients were not able to explain their responses. In addition, hypothetical informational statements of a biologic’s efficacy and safety may not always imitate clinical reality. However, we believe the study is valid in exploring the power of an anecdote in influencing patients’ willingness to take biologic medications for psoriasis. Furthermore, educational level and ethnicity were excluded from the ordinal regression analysis because the assumption of parallel lines was not met.

Ethics Behind an Anecdote
An important consideration is the ethical implications of sharing an anecdote to guide patients’ perceptions of treatment and behavior. Although clinicians rely heavily on the available data to determine the best course of treatment, providing patients with comprehensive information on all risks and benefits is rarely, if ever, feasible. Moreover, even objective clinical data will inevitably be subjectively interpreted by patients. For example, describing a medication side effect as occurring in 1 in 100 patients may discourage patients from pursuing treatment, whereas describing that risk as not occurring in 99 in 100 patients may encourage patients, despite these 2 choices being mathematically identical.¹³ Because the subjective interpretation of data is inevitable, presenting patients with subjective information in the form of an anecdote to help them overcome fears of starting treatment and achieve their desired clinical outcomes may be one of the appropriate approaches to present what is objectively the best option, particularly if the anecdote is representative of the expected treatment response. Clinicians can harness this understanding of human psychology to better educate patients about their treatment options while fulfilling their ethical duty to act in their patients’ best interest.

Conclusion

Using an anecdote to help patients overcome fears of starting a biologic medication may be appropriate if the anecdote is reasonably representative of an expected treatment outcome. Patients should have an accurate understanding of the common risks and benefits of a medication for purposes of shared decision-making.

Biologic medications are highly effective in treating moderate to severe psoriasis, yet many patients are apprehensive about taking a biologic medication for a variety of reasons, such as hearing negative information about the drug from friends or family, being nervous about injection, or seeing the drug or its side effects negatively portrayed in the media.^1-3 Because biologic medications are costly, many patients may fear needing to discontinue use of the medication owing to lack of affordability, which may result in subsequent rebound of psoriasis. Because patients’ fear of a drug is inherently subjective, it can be modified with appropriate reassurance and presentation of evidence. By understanding what information increases patients’ confidence in their willingness to take a biologic medication, patients may be more willing to initiate use of the drug and improve treatment outcomes.

There are mixed findings about whether statistical evidence or an anecdote is more effective in persuasion.^4-6 The specific context in which the persuasion takes place may be important in determining which method is superior. In most nonthreatening situations, people appear to be more easily persuaded by statistical evidence rather than an anecdote. However, in circumstances where emotional engagement is high, such as regarding one’s own health, an anecdote tends to be more persuasive compared to statistical evidence.⁷ The purpose of this study was to evaluate patients’ willingness to take a biologic medication for the management of their psoriasis if presented with either clinical trial evidence of the agent’s efficacy and safety, an anecdote of a single patient’s positive experience, or both.

Methods

Patient Inclusion Criteria
Following Wake Forest School of Medicine institutional review board approval, a prospective parallel-arm survey study was performed on eligible patients 18 years or older with a self-reported diagnosis of psoriasis. Patients were required to have a working knowledge of English and not have been previously prescribed a biologic medication for their psoriasis. If patients did not meet inclusion criteria after answering the survey eligibility screening questions, then they were unable to complete the remainder of the survey and were excluded from the analysis.

Survey Administration
A total of 222 patients were recruited through Amazon Mechanical Turk, an online crowdsourcing platform. (Amazon Mechanical Turk is a validated tool in conducting research in psychology and other social sciences and is considered as diverse as and perhaps more representative than traditional samples.^8,9) Patients received a fact sheet and were taken to the survey hosted on Qualtrics, a secure web-based survey software that supports data collection for research studies. Amazon Mechanical Turk requires some amount of compensation to patients; therefore, recruited patients were compensated $0.03.

Statistical Analysis
Patients were randomized using SPSS Statistics version 23.0 (IBM) in a 1:1 ratio to assess how willing they would be to take a biologic medication for their psoriasis if presented with one of the following: (1) a control that queried patients about their willingness to take treatment without having been informed on its efficacy or safety, (2) clinical trial evidence of the agent’s efficacy and safety, (3) an anecdote of a single patient’s positive experience, or (4) both clinical trial evidence of the agent’s efficacy and safety and an anecdote of a single patient’s positive experience (Table 1). Demographic information including sex, age, ethnicity, and education level was collected, in addition to other baseline characteristics such as having friends or family with a history of psoriasis, history of participation in a clinical trial with use of an experimental drug, and the number of years since clinical diagnosis of psoriasis.

Results

There were no statistically significant differences among the baseline characteristics of the 4 information assignment groups (Table 2). Patients in the control group not given either clinical trial evidence of a biologic medication’s efficacy and safety or anecdote of a single patient’s positive experience had the lowest reported willingness to take treatment (median, 4.0)(Figure). Patients in the group given clinical trial evidence had an intermediate level of reported willingness to take treatment (median, 7.0). Patients in the groups given an anecdote or clinical trial evidence and anecdote had the highest reported willingness to take treatment (median, 8.0). Patients presented with an anecdote or clinical trial evidence and anecdote were significantly more likely to report willingness to take treatment than those not presented with either clinical trial evidence or anecdote (P<.001). Although patients presented with an anecdote or clinical trial evidence and anecdote were more likely to take a biologic medication than those presented with only clinical trial evidence, the difference between these groups was not significant (P=.75).

Based on regression analysis, age, sex, and having friends or family with a history of psoriasis were not significantly associated with patients’ responses (eTable). The number of years since clinical diagnosis of psoriasis (P=.034) and history of participation in a clinical trial with use of an experimental drug (P=.018) were significantly associated with the willingness of patients presented with an anecdote to take a biologic medication.

Comment

Anecdotal Reassurance
The presentation of clinical trial and/or anecdotal evidence had a strong effect on patients’ willingness to take a biologic medication for their psoriasis. Human perception of a treatment is inherently subjective, and such perceptions can be modified with appropriate reassurance and presentation of evidence.¹ Across the population we studied, presenting a brief anecdote of a single patient’s positive experience is a quick and efficient means—and as or more effective as giving details on efficacy and safety—to help patients decide to take a treatment for their psoriasis.

Anecdotal reassurance is powerful. Both health care providers and patients have a natural tendency to focus on anecdotal experiences rather than statistical reasoning when making treatment decisions.^10-12 Although negative anecdotal experiences may make patients unwilling to take a medication (or may make them overly desirous of an inappropriate treatment), clinicians can harness this psychological phenomenon to both increase patient willingness to take potentially beneficial treatments or to deter them from engaging in activities that can be harmful to their health, such as tanning and smoking.

Psoriasis Duration and Willingness to Take a Biologic Medication
In general, patient demographics did not appear to have an association with reported willingness to take a biologic medication for psoriasis. However, the number of years since clinical diagnosis of psoriasis had an effect on willingness to take a biologic medication, with patients with a longer personal history of psoriasis showing a higher willingness to take a treatment after being presented with an anecdote than patients with a shorter personal history of psoriasis. We can only speculate on the reasons why. Patients with a longer personal history of psoriasis may have tried and failed more treatments and therefore have a distrust in the validity of clinical trial evidence. These patients may feel their psoriasis is different than that of other clinical trial participants and thus may be more willing to rely on the success stories of individual patients.

Prior participation in a clinical trial with use of an experimental drug was associated with a lower willingness to choose treatment after being presented with anecdotal reassurance. This finding may be attributable to these patients understanding the subjective nature of anecdotes and preferring more objective information in the form of randomized clinical trials in making treatment decisions. Overall, the presentation of evidence about the efficacy and safety of biologic medications in the treatment of psoriasis has a greater impact on patient decision-making than patients’ age, sex, and having friends or family with a history of psoriasis.

Limitations
Limitations of the study were typical of survey-based research. With closed-ended questions, patients were not able to explain their responses. In addition, hypothetical informational statements of a biologic’s efficacy and safety may not always imitate clinical reality. However, we believe the study is valid in exploring the power of an anecdote in influencing patients’ willingness to take biologic medications for psoriasis. Furthermore, educational level and ethnicity were excluded from the ordinal regression analysis because the assumption of parallel lines was not met.

Ethics Behind an Anecdote
An important consideration is the ethical implications of sharing an anecdote to guide patients’ perceptions of treatment and behavior. Although clinicians rely heavily on the available data to determine the best course of treatment, providing patients with comprehensive information on all risks and benefits is rarely, if ever, feasible. Moreover, even objective clinical data will inevitably be subjectively interpreted by patients. For example, describing a medication side effect as occurring in 1 in 100 patients may discourage patients from pursuing treatment, whereas describing that risk as not occurring in 99 in 100 patients may encourage patients, despite these 2 choices being mathematically identical.¹³ Because the subjective interpretation of data is inevitable, presenting patients with subjective information in the form of an anecdote to help them overcome fears of starting treatment and achieve their desired clinical outcomes may be one of the appropriate approaches to present what is objectively the best option, particularly if the anecdote is representative of the expected treatment response. Clinicians can harness this understanding of human psychology to better educate patients about their treatment options while fulfilling their ethical duty to act in their patients’ best interest.

Conclusion

Using an anecdote to help patients overcome fears of starting a biologic medication may be appropriate if the anecdote is reasonably representative of an expected treatment outcome. Patients should have an accurate understanding of the common risks and benefits of a medication for purposes of shared decision-making.

Biologic medications are highly effective in treating moderate to severe psoriasis, yet many patients are apprehensive about taking a biologic medication for a variety of reasons, such as hearing negative information about the drug from friends or family, being nervous about injection, or seeing the drug or its side effects negatively portrayed in the media.^1-3 Because biologic medications are costly, many patients may fear needing to discontinue use of the medication owing to lack of affordability, which may result in subsequent rebound of psoriasis. Because patients’ fear of a drug is inherently subjective, it can be modified with appropriate reassurance and presentation of evidence. By understanding what information increases patients’ confidence in their willingness to take a biologic medication, patients may be more willing to initiate use of the drug and improve treatment outcomes.

There are mixed findings about whether statistical evidence or an anecdote is more effective in persuasion.^4-6 The specific context in which the persuasion takes place may be important in determining which method is superior. In most nonthreatening situations, people appear to be more easily persuaded by statistical evidence rather than an anecdote. However, in circumstances where emotional engagement is high, such as regarding one’s own health, an anecdote tends to be more persuasive compared to statistical evidence.⁷ The purpose of this study was to evaluate patients’ willingness to take a biologic medication for the management of their psoriasis if presented with either clinical trial evidence of the agent’s efficacy and safety, an anecdote of a single patient’s positive experience, or both.

Methods

Patient Inclusion Criteria
Following Wake Forest School of Medicine institutional review board approval, a prospective parallel-arm survey study was performed on eligible patients 18 years or older with a self-reported diagnosis of psoriasis. Patients were required to have a working knowledge of English and not have been previously prescribed a biologic medication for their psoriasis. If patients did not meet inclusion criteria after answering the survey eligibility screening questions, then they were unable to complete the remainder of the survey and were excluded from the analysis.

Survey Administration
A total of 222 patients were recruited through Amazon Mechanical Turk, an online crowdsourcing platform. (Amazon Mechanical Turk is a validated tool in conducting research in psychology and other social sciences and is considered as diverse as and perhaps more representative than traditional samples.^8,9) Patients received a fact sheet and were taken to the survey hosted on Qualtrics, a secure web-based survey software that supports data collection for research studies. Amazon Mechanical Turk requires some amount of compensation to patients; therefore, recruited patients were compensated $0.03.

Statistical Analysis
Patients were randomized using SPSS Statistics version 23.0 (IBM) in a 1:1 ratio to assess how willing they would be to take a biologic medication for their psoriasis if presented with one of the following: (1) a control that queried patients about their willingness to take treatment without having been informed on its efficacy or safety, (2) clinical trial evidence of the agent’s efficacy and safety, (3) an anecdote of a single patient’s positive experience, or (4) both clinical trial evidence of the agent’s efficacy and safety and an anecdote of a single patient’s positive experience (Table 1). Demographic information including sex, age, ethnicity, and education level was collected, in addition to other baseline characteristics such as having friends or family with a history of psoriasis, history of participation in a clinical trial with use of an experimental drug, and the number of years since clinical diagnosis of psoriasis.

Results

There were no statistically significant differences among the baseline characteristics of the 4 information assignment groups (Table 2). Patients in the control group not given either clinical trial evidence of a biologic medication’s efficacy and safety or anecdote of a single patient’s positive experience had the lowest reported willingness to take treatment (median, 4.0)(Figure). Patients in the group given clinical trial evidence had an intermediate level of reported willingness to take treatment (median, 7.0). Patients in the groups given an anecdote or clinical trial evidence and anecdote had the highest reported willingness to take treatment (median, 8.0). Patients presented with an anecdote or clinical trial evidence and anecdote were significantly more likely to report willingness to take treatment than those not presented with either clinical trial evidence or anecdote (P<.001). Although patients presented with an anecdote or clinical trial evidence and anecdote were more likely to take a biologic medication than those presented with only clinical trial evidence, the difference between these groups was not significant (P=.75).

Based on regression analysis, age, sex, and having friends or family with a history of psoriasis were not significantly associated with patients’ responses (eTable). The number of years since clinical diagnosis of psoriasis (P=.034) and history of participation in a clinical trial with use of an experimental drug (P=.018) were significantly associated with the willingness of patients presented with an anecdote to take a biologic medication.

Comment

Anecdotal Reassurance
The presentation of clinical trial and/or anecdotal evidence had a strong effect on patients’ willingness to take a biologic medication for their psoriasis. Human perception of a treatment is inherently subjective, and such perceptions can be modified with appropriate reassurance and presentation of evidence.¹ Across the population we studied, presenting a brief anecdote of a single patient’s positive experience is a quick and efficient means—and as or more effective as giving details on efficacy and safety—to help patients decide to take a treatment for their psoriasis.

Anecdotal reassurance is powerful. Both health care providers and patients have a natural tendency to focus on anecdotal experiences rather than statistical reasoning when making treatment decisions.^10-12 Although negative anecdotal experiences may make patients unwilling to take a medication (or may make them overly desirous of an inappropriate treatment), clinicians can harness this psychological phenomenon to both increase patient willingness to take potentially beneficial treatments or to deter them from engaging in activities that can be harmful to their health, such as tanning and smoking.

Psoriasis Duration and Willingness to Take a Biologic Medication
In general, patient demographics did not appear to have an association with reported willingness to take a biologic medication for psoriasis. However, the number of years since clinical diagnosis of psoriasis had an effect on willingness to take a biologic medication, with patients with a longer personal history of psoriasis showing a higher willingness to take a treatment after being presented with an anecdote than patients with a shorter personal history of psoriasis. We can only speculate on the reasons why. Patients with a longer personal history of psoriasis may have tried and failed more treatments and therefore have a distrust in the validity of clinical trial evidence. These patients may feel their psoriasis is different than that of other clinical trial participants and thus may be more willing to rely on the success stories of individual patients.

Prior participation in a clinical trial with use of an experimental drug was associated with a lower willingness to choose treatment after being presented with anecdotal reassurance. This finding may be attributable to these patients understanding the subjective nature of anecdotes and preferring more objective information in the form of randomized clinical trials in making treatment decisions. Overall, the presentation of evidence about the efficacy and safety of biologic medications in the treatment of psoriasis has a greater impact on patient decision-making than patients’ age, sex, and having friends or family with a history of psoriasis.

Limitations
Limitations of the study were typical of survey-based research. With closed-ended questions, patients were not able to explain their responses. In addition, hypothetical informational statements of a biologic’s efficacy and safety may not always imitate clinical reality. However, we believe the study is valid in exploring the power of an anecdote in influencing patients’ willingness to take biologic medications for psoriasis. Furthermore, educational level and ethnicity were excluded from the ordinal regression analysis because the assumption of parallel lines was not met.

Ethics Behind an Anecdote
An important consideration is the ethical implications of sharing an anecdote to guide patients’ perceptions of treatment and behavior. Although clinicians rely heavily on the available data to determine the best course of treatment, providing patients with comprehensive information on all risks and benefits is rarely, if ever, feasible. Moreover, even objective clinical data will inevitably be subjectively interpreted by patients. For example, describing a medication side effect as occurring in 1 in 100 patients may discourage patients from pursuing treatment, whereas describing that risk as not occurring in 99 in 100 patients may encourage patients, despite these 2 choices being mathematically identical.¹³ Because the subjective interpretation of data is inevitable, presenting patients with subjective information in the form of an anecdote to help them overcome fears of starting treatment and achieve their desired clinical outcomes may be one of the appropriate approaches to present what is objectively the best option, particularly if the anecdote is representative of the expected treatment response. Clinicians can harness this understanding of human psychology to better educate patients about their treatment options while fulfilling their ethical duty to act in their patients’ best interest.

Conclusion

Using an anecdote to help patients overcome fears of starting a biologic medication may be appropriate if the anecdote is reasonably representative of an expected treatment outcome. Patients should have an accurate understanding of the common risks and benefits of a medication for purposes of shared decision-making.

A short-term Western diet facilitated the development of interleukin (IL)-23-mediated psoriasis-like skin and joint inflammation and caused shifts in the intestinal microbiota in a murine model – findings that both reaffirm the importance of diet and identify the gut microbiota as a potential pathogenic link between diet and psoriatic inflammation, say the investigators and other experts who reviewed the findings.

The mice did not become obese during the short duration of the multilayered study, which suggests that a Western diet (high sugar, moderate fat) can be impactful independent of obesity, Samuel T. Hwang, MD, PhD, professor and chair of dermatology at the University of California, Davis, and senior author of the study, said in an interview. The study was published in the Journal of Investigative Dermatology.

In an accompanying commentary, Renuka R. Nayak, MD, PhD, of the department of rheumatology at the University of California, San Francisco, wrote that the findings “add to the mounting evidence suggesting that diet has a prominent role in the treatment of psoriasis and [psoriatic arthritis] and raise the possibility that the microbiome may contribute to disease severity”.

Mice were fed a Western diet (WD) or conventional chow diet for 6 weeks and then injected with IL-23 minicircle (MC) DNA to induce systemic IL-23 overexpression – or a control minicircle DNA injection – and continued on these diets for another 4 weeks.

The mice in the WD/IL-23 MC DNA group developed erythema and scaling and increased epidermal thickness in the ears; such changes were “remarkably milder” or nonexistent in the other groups. Skin and joint immune cell populations, such as gamma delta T cells, neutrophils, and T helper type 17 cytokines were elevated in WD-fed mice, as were other markers of IL-23-mediated joint inflammation.

Recent research has suggested that the gut microbiota is dysbiotic in patients with psoriasis, and this new study found that WD-fed mice had less microbial diversity than that of mice fed a conventional diet. After IL-23 MC delivery, WD-fed reduced microbial diversity and pronounced dysbiosis.

“When we combined the Western diet and IL-23, we saw some very different microbes in abundance. The whole landscape changed,” Dr. Hwang said in the interview.

The data “suggest that WD and overexpression of IL-23 may contribute to gut microbiota dysbiosis in a synergistic and complex manner,” he and his coinvestigators wrote.

Treatment with broad-spectrum antibiotics suppressed IL-23-mediated skin and joint inflammation in the WD-fed mice – and moderately affected skin inflammation in conventionally-fed mice as well – which affirmed the role of dysbiosis.

And “notably,” in another layer of the study, mice that switched diets from a WD to a conventional diet had reduced skin and joint inflammation and increased diversity of gut microbiota. (Mice that were fed a WD for 6 weeks and given the IL-23 MC DNA were randomized to continue this diet for another 4 weeks or switch to a conventional diet.)

Commenting on the new research, Wilson Liao, MD, professor and vice chair of research in the department of dermatology at the University of California, San Francisco, said it “provides evidence” that diet can affect not only psoriasis, but psoriatic arthritis (PsA) as well, “through altering the ratio of good to bad bacteria in the gut.”

Going forward, better understanding “which specific gut bacteria and bacterial products lead to increased psoriatic inflammation, and the immunologic mechanism by which this occurs” will be important and could lead to novel treatments for psoriasis and PsA, said Dr. Liao, director of the UCSF Psoriasis and Skin Treatment Center.

Next on his research agenda, Dr. Hwang said, is the question of “how microbiota in the gut are actually able to influence inflammation at very distant sites in the joints and the skin.

“We want to understand the metabolic mechanisms,” he said, noting that “we invariably talk about cytokines, but there are other substances, like certain bile acids that are metabolized through the gut microbiome,” which may play a role.

The findings also offer a basis for treatment experiments in humans – of diet, probiotic therapy, or selective antibiotic modulation, for instance, Dr. Hwang said.

And in the meantime, the findings should encourage patients who are interested in making dietary changes, such as reducing sugar intake. “There’s wide interest – patients will ask, is there something I can change to make this better?” Dr. Hwang said. “Before, we could say it might be logical, but now we have some evidence. The message now is [high-sugar, moderate-fat] diets, apart from their ability to stimulate obesity, probably have some effects.”

Dietary change may not replace the need for other psoriasis treatments, he said, “but I think there’s good reason to believe that if you do change your diet, your treatment will be better than it would be without that dietary change,” he said.

In their discussion, Dr. Hwang and coauthors note that WD with IL-23 overexpression also decreased the mRNA expression of barrier-forming tight junction proteins, thus increasing intestinal permeability. This finding may be relevant, they wrote, because “leaky gut has been proposed as a pathogenic link between unhealthy diet, gut dysbiosis, and enhanced immune response,” and has been observed in a number of autoimmune diseases, including psoriasis.

Dr. Hwang, lead author Zhenrui Shi, MD, PhD, and coauthors reported no conflicts of interest. Their study was supported by the National Psoriasis Foundation, as well as the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Cancer Institute.

A short-term Western diet facilitated the development of interleukin (IL)-23-mediated psoriasis-like skin and joint inflammation and caused shifts in the intestinal microbiota in a murine model – findings that both reaffirm the importance of diet and identify the gut microbiota as a potential pathogenic link between diet and psoriatic inflammation, say the investigators and other experts who reviewed the findings.

The mice did not become obese during the short duration of the multilayered study, which suggests that a Western diet (high sugar, moderate fat) can be impactful independent of obesity, Samuel T. Hwang, MD, PhD, professor and chair of dermatology at the University of California, Davis, and senior author of the study, said in an interview. The study was published in the Journal of Investigative Dermatology.

In an accompanying commentary, Renuka R. Nayak, MD, PhD, of the department of rheumatology at the University of California, San Francisco, wrote that the findings “add to the mounting evidence suggesting that diet has a prominent role in the treatment of psoriasis and [psoriatic arthritis] and raise the possibility that the microbiome may contribute to disease severity”.

Mice were fed a Western diet (WD) or conventional chow diet for 6 weeks and then injected with IL-23 minicircle (MC) DNA to induce systemic IL-23 overexpression – or a control minicircle DNA injection – and continued on these diets for another 4 weeks.

The mice in the WD/IL-23 MC DNA group developed erythema and scaling and increased epidermal thickness in the ears; such changes were “remarkably milder” or nonexistent in the other groups. Skin and joint immune cell populations, such as gamma delta T cells, neutrophils, and T helper type 17 cytokines were elevated in WD-fed mice, as were other markers of IL-23-mediated joint inflammation.

Recent research has suggested that the gut microbiota is dysbiotic in patients with psoriasis, and this new study found that WD-fed mice had less microbial diversity than that of mice fed a conventional diet. After IL-23 MC delivery, WD-fed reduced microbial diversity and pronounced dysbiosis.

“When we combined the Western diet and IL-23, we saw some very different microbes in abundance. The whole landscape changed,” Dr. Hwang said in the interview.

The data “suggest that WD and overexpression of IL-23 may contribute to gut microbiota dysbiosis in a synergistic and complex manner,” he and his coinvestigators wrote.

Treatment with broad-spectrum antibiotics suppressed IL-23-mediated skin and joint inflammation in the WD-fed mice – and moderately affected skin inflammation in conventionally-fed mice as well – which affirmed the role of dysbiosis.

And “notably,” in another layer of the study, mice that switched diets from a WD to a conventional diet had reduced skin and joint inflammation and increased diversity of gut microbiota. (Mice that were fed a WD for 6 weeks and given the IL-23 MC DNA were randomized to continue this diet for another 4 weeks or switch to a conventional diet.)

Commenting on the new research, Wilson Liao, MD, professor and vice chair of research in the department of dermatology at the University of California, San Francisco, said it “provides evidence” that diet can affect not only psoriasis, but psoriatic arthritis (PsA) as well, “through altering the ratio of good to bad bacteria in the gut.”

Going forward, better understanding “which specific gut bacteria and bacterial products lead to increased psoriatic inflammation, and the immunologic mechanism by which this occurs” will be important and could lead to novel treatments for psoriasis and PsA, said Dr. Liao, director of the UCSF Psoriasis and Skin Treatment Center.

Next on his research agenda, Dr. Hwang said, is the question of “how microbiota in the gut are actually able to influence inflammation at very distant sites in the joints and the skin.

“We want to understand the metabolic mechanisms,” he said, noting that “we invariably talk about cytokines, but there are other substances, like certain bile acids that are metabolized through the gut microbiome,” which may play a role.

The findings also offer a basis for treatment experiments in humans – of diet, probiotic therapy, or selective antibiotic modulation, for instance, Dr. Hwang said.

And in the meantime, the findings should encourage patients who are interested in making dietary changes, such as reducing sugar intake. “There’s wide interest – patients will ask, is there something I can change to make this better?” Dr. Hwang said. “Before, we could say it might be logical, but now we have some evidence. The message now is [high-sugar, moderate-fat] diets, apart from their ability to stimulate obesity, probably have some effects.”

Dietary change may not replace the need for other psoriasis treatments, he said, “but I think there’s good reason to believe that if you do change your diet, your treatment will be better than it would be without that dietary change,” he said.

In their discussion, Dr. Hwang and coauthors note that WD with IL-23 overexpression also decreased the mRNA expression of barrier-forming tight junction proteins, thus increasing intestinal permeability. This finding may be relevant, they wrote, because “leaky gut has been proposed as a pathogenic link between unhealthy diet, gut dysbiosis, and enhanced immune response,” and has been observed in a number of autoimmune diseases, including psoriasis.

Dr. Hwang, lead author Zhenrui Shi, MD, PhD, and coauthors reported no conflicts of interest. Their study was supported by the National Psoriasis Foundation, as well as the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Cancer Institute.

A short-term Western diet facilitated the development of interleukin (IL)-23-mediated psoriasis-like skin and joint inflammation and caused shifts in the intestinal microbiota in a murine model – findings that both reaffirm the importance of diet and identify the gut microbiota as a potential pathogenic link between diet and psoriatic inflammation, say the investigators and other experts who reviewed the findings.

The mice did not become obese during the short duration of the multilayered study, which suggests that a Western diet (high sugar, moderate fat) can be impactful independent of obesity, Samuel T. Hwang, MD, PhD, professor and chair of dermatology at the University of California, Davis, and senior author of the study, said in an interview. The study was published in the Journal of Investigative Dermatology.

In an accompanying commentary, Renuka R. Nayak, MD, PhD, of the department of rheumatology at the University of California, San Francisco, wrote that the findings “add to the mounting evidence suggesting that diet has a prominent role in the treatment of psoriasis and [psoriatic arthritis] and raise the possibility that the microbiome may contribute to disease severity”.

Mice were fed a Western diet (WD) or conventional chow diet for 6 weeks and then injected with IL-23 minicircle (MC) DNA to induce systemic IL-23 overexpression – or a control minicircle DNA injection – and continued on these diets for another 4 weeks.

The mice in the WD/IL-23 MC DNA group developed erythema and scaling and increased epidermal thickness in the ears; such changes were “remarkably milder” or nonexistent in the other groups. Skin and joint immune cell populations, such as gamma delta T cells, neutrophils, and T helper type 17 cytokines were elevated in WD-fed mice, as were other markers of IL-23-mediated joint inflammation.

Recent research has suggested that the gut microbiota is dysbiotic in patients with psoriasis, and this new study found that WD-fed mice had less microbial diversity than that of mice fed a conventional diet. After IL-23 MC delivery, WD-fed reduced microbial diversity and pronounced dysbiosis.

“When we combined the Western diet and IL-23, we saw some very different microbes in abundance. The whole landscape changed,” Dr. Hwang said in the interview.

The data “suggest that WD and overexpression of IL-23 may contribute to gut microbiota dysbiosis in a synergistic and complex manner,” he and his coinvestigators wrote.

Treatment with broad-spectrum antibiotics suppressed IL-23-mediated skin and joint inflammation in the WD-fed mice – and moderately affected skin inflammation in conventionally-fed mice as well – which affirmed the role of dysbiosis.

And “notably,” in another layer of the study, mice that switched diets from a WD to a conventional diet had reduced skin and joint inflammation and increased diversity of gut microbiota. (Mice that were fed a WD for 6 weeks and given the IL-23 MC DNA were randomized to continue this diet for another 4 weeks or switch to a conventional diet.)

Commenting on the new research, Wilson Liao, MD, professor and vice chair of research in the department of dermatology at the University of California, San Francisco, said it “provides evidence” that diet can affect not only psoriasis, but psoriatic arthritis (PsA) as well, “through altering the ratio of good to bad bacteria in the gut.”

Going forward, better understanding “which specific gut bacteria and bacterial products lead to increased psoriatic inflammation, and the immunologic mechanism by which this occurs” will be important and could lead to novel treatments for psoriasis and PsA, said Dr. Liao, director of the UCSF Psoriasis and Skin Treatment Center.

Next on his research agenda, Dr. Hwang said, is the question of “how microbiota in the gut are actually able to influence inflammation at very distant sites in the joints and the skin.

“We want to understand the metabolic mechanisms,” he said, noting that “we invariably talk about cytokines, but there are other substances, like certain bile acids that are metabolized through the gut microbiome,” which may play a role.

The findings also offer a basis for treatment experiments in humans – of diet, probiotic therapy, or selective antibiotic modulation, for instance, Dr. Hwang said.

And in the meantime, the findings should encourage patients who are interested in making dietary changes, such as reducing sugar intake. “There’s wide interest – patients will ask, is there something I can change to make this better?” Dr. Hwang said. “Before, we could say it might be logical, but now we have some evidence. The message now is [high-sugar, moderate-fat] diets, apart from their ability to stimulate obesity, probably have some effects.”

Dietary change may not replace the need for other psoriasis treatments, he said, “but I think there’s good reason to believe that if you do change your diet, your treatment will be better than it would be without that dietary change,” he said.

In their discussion, Dr. Hwang and coauthors note that WD with IL-23 overexpression also decreased the mRNA expression of barrier-forming tight junction proteins, thus increasing intestinal permeability. This finding may be relevant, they wrote, because “leaky gut has been proposed as a pathogenic link between unhealthy diet, gut dysbiosis, and enhanced immune response,” and has been observed in a number of autoimmune diseases, including psoriasis.

Dr. Hwang, lead author Zhenrui Shi, MD, PhD, and coauthors reported no conflicts of interest. Their study was supported by the National Psoriasis Foundation, as well as the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Cancer Institute.

To the Editor:

Nail psoriasis is highly prevalent in patients with cutaneous psoriasis and also may present as an isolated finding. There is a strong association between nail psoriasis and development of psoriatic arthritis (PsA). However, publications on nail psoriasis are sparse compared with articles describing cutaneous psoriasis.¹ Our objectives were to analyze the nail psoriasis literature for content, citations, and media attention.

The Web of Science database was searched for the term nail psoriasis on April 27, 2020, and publications by year, subject, and article type were compiled. Total and average yearly citations were calculated to create a list of the top 100 most-cited articles (eTable). First and last authors, sex, and Altmetric Attention Scores were then recorded. The Wilcoxon rank sum test was calculated to compare the relationship of Altmetric scores between nail psoriasis–specific references and others on the list.

In our data set, the average total number of citations was 134.09 (range, 42–1617), with average yearly citations ranging from 2 to 108. Altmetric scores—measures of media attention of scholarly work—were available for 58 of 100 papers (58%), with an average score of 33.2 (range, 1–509).

Of the top 100 most-cited articles using the search term nail psoriasis, only 20% focused on nail psoriasis, with the remainder concentrating on psoriasis/PsA. Only 32% and 24% of first and last authors, respectively, were female. Fifty-two percent and 31% of the articles were published in dermatology and arthritis/rheumatology journals, respectively. There was no statistically significant difference in Altmetric scores between nail psoriasis–specific and other articles in our data set (P=.7551).

For the nail psoriasis–specific articles, all 20 highlighted a lack of nail clinical trials, a positive association with PsA, and a correlation of increased cutaneous psoriasis body surface area with increased onychodystrophy likelihood.² Three of 20 (15%) articles stated that nail psoriasis often is overlooked, despite the negative impact on quality of life,¹ and emphasized the importance of patient compliance owing to the chronic nature of the disease. Only 1 of 20 (5%) articles focused on nail psoriasis treatments.³ There was no overlap between the 100 most-cited psoriasis articles from 1970 to 2012 and our top 100 articles on nail psoriasis.⁴

Treatment recommendations for nail psoriasis by consensus were published by a nail expert group in 2019.⁵ For 3 or fewer nails involved, suggested first-line treatment is intralesional matrix injections with triamcinolone acetonide. For more than 3 affected nails, systemic treatment with oral or biologic therapy is recommended.⁵ Although this article is likely to change clinical practice, it did not qualify for our list because it did not garner sufficient citations in the brief period between its publication date and our search (July 2019–April 2020).

This study is subject to several limitations. Only the Web of Science database was utilized, and only the term nail psoriasis was searched, potentially excluding relevant articles. Using total citations biases toward older articles.

Our bibliometric analysis highlights a lack of publications on nail psoriasis, with most articles focusing on psoriasis and PsA. This deficiency in highly cited nail psoriasis references is likely to be a barrier to physicians in managing patients with nail disease. There is a need for controlled clinical trials and better mechanisms to disseminate information on management of nail psoriasis to practicing physicians.

The eTable is available in the PDF of this article

To the Editor:

Nail psoriasis is highly prevalent in patients with cutaneous psoriasis and also may present as an isolated finding. There is a strong association between nail psoriasis and development of psoriatic arthritis (PsA). However, publications on nail psoriasis are sparse compared with articles describing cutaneous psoriasis.¹ Our objectives were to analyze the nail psoriasis literature for content, citations, and media attention.

The Web of Science database was searched for the term nail psoriasis on April 27, 2020, and publications by year, subject, and article type were compiled. Total and average yearly citations were calculated to create a list of the top 100 most-cited articles (eTable). First and last authors, sex, and Altmetric Attention Scores were then recorded. The Wilcoxon rank sum test was calculated to compare the relationship of Altmetric scores between nail psoriasis–specific references and others on the list.

In our data set, the average total number of citations was 134.09 (range, 42–1617), with average yearly citations ranging from 2 to 108. Altmetric scores—measures of media attention of scholarly work—were available for 58 of 100 papers (58%), with an average score of 33.2 (range, 1–509).

Of the top 100 most-cited articles using the search term nail psoriasis, only 20% focused on nail psoriasis, with the remainder concentrating on psoriasis/PsA. Only 32% and 24% of first and last authors, respectively, were female. Fifty-two percent and 31% of the articles were published in dermatology and arthritis/rheumatology journals, respectively. There was no statistically significant difference in Altmetric scores between nail psoriasis–specific and other articles in our data set (P=.7551).

For the nail psoriasis–specific articles, all 20 highlighted a lack of nail clinical trials, a positive association with PsA, and a correlation of increased cutaneous psoriasis body surface area with increased onychodystrophy likelihood.² Three of 20 (15%) articles stated that nail psoriasis often is overlooked, despite the negative impact on quality of life,¹ and emphasized the importance of patient compliance owing to the chronic nature of the disease. Only 1 of 20 (5%) articles focused on nail psoriasis treatments.³ There was no overlap between the 100 most-cited psoriasis articles from 1970 to 2012 and our top 100 articles on nail psoriasis.⁴

Treatment recommendations for nail psoriasis by consensus were published by a nail expert group in 2019.⁵ For 3 or fewer nails involved, suggested first-line treatment is intralesional matrix injections with triamcinolone acetonide. For more than 3 affected nails, systemic treatment with oral or biologic therapy is recommended.⁵ Although this article is likely to change clinical practice, it did not qualify for our list because it did not garner sufficient citations in the brief period between its publication date and our search (July 2019–April 2020).

This study is subject to several limitations. Only the Web of Science database was utilized, and only the term nail psoriasis was searched, potentially excluding relevant articles. Using total citations biases toward older articles.

Our bibliometric analysis highlights a lack of publications on nail psoriasis, with most articles focusing on psoriasis and PsA. This deficiency in highly cited nail psoriasis references is likely to be a barrier to physicians in managing patients with nail disease. There is a need for controlled clinical trials and better mechanisms to disseminate information on management of nail psoriasis to practicing physicians.

The eTable is available in the PDF of this article

To the Editor:

Nail psoriasis is highly prevalent in patients with cutaneous psoriasis and also may present as an isolated finding. There is a strong association between nail psoriasis and development of psoriatic arthritis (PsA). However, publications on nail psoriasis are sparse compared with articles describing cutaneous psoriasis.¹ Our objectives were to analyze the nail psoriasis literature for content, citations, and media attention.

The Web of Science database was searched for the term nail psoriasis on April 27, 2020, and publications by year, subject, and article type were compiled. Total and average yearly citations were calculated to create a list of the top 100 most-cited articles (eTable). First and last authors, sex, and Altmetric Attention Scores were then recorded. The Wilcoxon rank sum test was calculated to compare the relationship of Altmetric scores between nail psoriasis–specific references and others on the list.

In our data set, the average total number of citations was 134.09 (range, 42–1617), with average yearly citations ranging from 2 to 108. Altmetric scores—measures of media attention of scholarly work—were available for 58 of 100 papers (58%), with an average score of 33.2 (range, 1–509).

Of the top 100 most-cited articles using the search term nail psoriasis, only 20% focused on nail psoriasis, with the remainder concentrating on psoriasis/PsA. Only 32% and 24% of first and last authors, respectively, were female. Fifty-two percent and 31% of the articles were published in dermatology and arthritis/rheumatology journals, respectively. There was no statistically significant difference in Altmetric scores between nail psoriasis–specific and other articles in our data set (P=.7551).

For the nail psoriasis–specific articles, all 20 highlighted a lack of nail clinical trials, a positive association with PsA, and a correlation of increased cutaneous psoriasis body surface area with increased onychodystrophy likelihood.² Three of 20 (15%) articles stated that nail psoriasis often is overlooked, despite the negative impact on quality of life,¹ and emphasized the importance of patient compliance owing to the chronic nature of the disease. Only 1 of 20 (5%) articles focused on nail psoriasis treatments.³ There was no overlap between the 100 most-cited psoriasis articles from 1970 to 2012 and our top 100 articles on nail psoriasis.⁴

Treatment recommendations for nail psoriasis by consensus were published by a nail expert group in 2019.⁵ For 3 or fewer nails involved, suggested first-line treatment is intralesional matrix injections with triamcinolone acetonide. For more than 3 affected nails, systemic treatment with oral or biologic therapy is recommended.⁵ Although this article is likely to change clinical practice, it did not qualify for our list because it did not garner sufficient citations in the brief period between its publication date and our search (July 2019–April 2020).

This study is subject to several limitations. Only the Web of Science database was utilized, and only the term nail psoriasis was searched, potentially excluding relevant articles. Using total citations biases toward older articles.

Our bibliometric analysis highlights a lack of publications on nail psoriasis, with most articles focusing on psoriasis and PsA. This deficiency in highly cited nail psoriasis references is likely to be a barrier to physicians in managing patients with nail disease. There is a need for controlled clinical trials and better mechanisms to disseminate information on management of nail psoriasis to practicing physicians.

The eTable is available in the PDF of this article

Complementary alternative medicine (CAM) has been described by the National Center for Complementary and Integrative Medicine as “health care approaches that are not typically part of conventional medical care or that may have origins outside of usual Western practice.”¹ Although this definition is broad, CAM encompasses therapies such as traditional Chinese medicine, herbal therapies, dietary supplements, and mind/body interventions. The use of CAM has grown, and according to a 2012 National Center for Complementary and Integrative Health survey, more than 30% of US adults and 12% of US children use health care approaches that are considered outside of conventional medical practice. In a survey study of US adults, at least 17.7% of respondents said they had taken a dietary supplement other than a vitamin or mineral in the last year.¹ Data from the 2007 National Health Interview Survey showed that the prevalence of adults with skin conditions using CAM was 84.5% compared to 38.3% in the general population.² In addition, 8.15 million US patients with dermatologic conditions reported using CAM over a 5-year period.³ Complementary alternative medicine has emerged as an alternative or adjunct to standard treatments, making it important for dermatologists to understand the existing literature on these therapies. Herein, we review the current evidence-based literature that exists on CAM for the treatment of atopic dermatitis (AD), psoriasis, and alopecia areata (AA).

Atopic Dermatitis

Atopic dermatitis is a chronic, pruritic, inflammatory skin condition with considerable morbidity.^4,5 The pathophysiology of AD is multifactorial and includes aspects of barrier dysfunction, IgE hypersensitivity, abnormal cell-mediated immune response, and environmental factors.⁶ Atopic dermatitis also is one of the most common inflammatory skin conditions in adults, affecting more than 7% of the US population and up to 20% of the total population in developed countries. Of those affected, 40% have moderate or severe symptoms that result in a substantial impact on quality of life.⁷ Despite advances in understanding disease pathology and treatment, a subset of patients opt to defer conventional treatments such as topical and systemic corticosteroids, antibiotics, nonsteroidal immunomodulators, and biologics. Patients may seek alternative therapies when typical treatments fail or when the perceived side effects outweigh the benefits.^5,8 The use of CAM has been well described in patients with AD; however, the existing evidence supporting its use along with its safety profile have not been thoroughly explored. Herein, we will discuss some of the most well-studied supplements for treatment of AD, including evening primrose oil (EPO), fish oil, and probiotics.⁵

Oral supplementation with polyunsaturated fatty acids commonly is reported in patients with AD.^5,8 The idea that a fatty acid deficiency could lead to atopic skin conditions has been around since 1937, when it was suggested that patients with AD had lower levels of blood unsaturated fatty acids.⁹ Conflicting evidence regarding oral fatty acid ingestion and AD disease severity has emerged.^10,11 One unsaturated fatty acid, γ-linolenic acid (GLA), has demonstrated anti-inflammatory properties and involvement in barrier repair.¹² It is converted to dihomo-GLA in the body, which acts on cyclooxygenase enzymes to produce the inflammatory mediator prostaglandin E₁. The production of GLA is mediated by the enzyme delta-6 desaturase in the metabolization of linoleic acid.¹² However, it has been reported that in a subset of patients with AD, a malfunction of delta-6 desaturase may play a role in disease progression and result in lower baseline levels of GLA.^10,12 Evening primrose oil and borage oil contain high amounts of GLA (8%–10% and 23%, respectively); thus, supplementation with these oils has been studied in AD.¹³

EPO for AD
Studies investigating EPO (Oenothera biennis) and its association with AD severity have shown mixed results. A Cochrane review reported that oral borage oil and EPO were not effective treatments for AD,¹⁴ while another larger randomized controlled trial (RCT) found no statistically significant improvement in AD symptoms.¹⁵ However, multiple smaller studies have found that clinical symptoms of AD, such as erythema, xerosis, pruritus, and total body surface area involved, did improve with oral EPO supplementation when compared to placebo, and the results were statistically significant (P=.04).^16,17 One study looked at different dosages of EPO and found that groups ingesting both 160 mg and 320 mg daily experienced reductions in eczema area and severity index score, with greater improvement noted with the higher dosage.¹⁷ Side effects associated with oral EPO include an anticoagulant effect and transient gastrointestinal tract upset.^8,14 There currently is not enough evidence or safety data to recommend this supplement to AD patients.

Although topical use of fatty acids with high concentrations of GLA, such as EPO and borage oil, have demonstrated improvement in subjective symptom severity, most studies have not reached statistical significance.^10,11 One study used a 10% EPO cream for 2 weeks compared to placebo and found statistically significant improvement in patient-reported AD symptoms (P=.045). However, this study only included 10 participants, and therefore larger studies are necessary to confirm this result.¹⁸ Some RCTs have shown that topical coconut oil, sunflower seed oil, and sandalwood album oil improve AD symptom severity, but again, large controlled trials are needed.⁵ Unfortunately, many essential oils, including EPO, can cause a secondary allergic contact dermatitis and potentially worsen AD.¹⁹

Fish Oil for AD
Fish oil is a commonly used supplement for AD due to its high content of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acids exert anti-inflammatory effects by displacing arachidonic acid, a proinflammatory omega-6 fatty acid thought to increase IgE, as well as helper T cell (T_H2) cytokines and prostaglandin E₂.^8,20 A 2012 Cochrane review found that, while some studies revealed mild improvement in AD symptoms with oral fish oil supplementation, these RCTs were of poor methodological quality.²¹ Multiple smaller studies have shown a decrease in pruritus, severity, and physician-rated clinical scores with fish oil use.^5,8,20,22 One study with 145 participants reported that 6 g of fish oil once daily compared to isoenergetic corn oil for 16 weeks identified no statistically significant differences between the treatment groups.²⁰ No adverse events were identified in any of the reported trials. Further studies should be conducted to assess the utility and dosing of fish oil supplements in AD patients.

Probiotics for AD
Probiotics consist of live microorganisms that enhance the microflora of the gastrointestinal tract.^8,20 They have been shown to influence food digestion and also have demonstrated potential influence on the skin-gut axis.²³ The theory that intestinal dysbiosis plays a role in AD pathogenesis has been investigated in multiple studies.^23-25 The central premise is that low-fiber and high-fat Western diets lead to fundamental changes in the gut microbiome, resulting in fewer anti-inflammatory metabolites, such as short-chain fatty acids (SCFAs).^23-25 These SCFAs are produced by microbes during the fermentation of dietary fiber and are known for their effect on epithelial barrier integrity and anti-inflammatory properties mediated through G protein–coupled receptor 43.²⁵ Multiple studies have shown that the gut microbiome in patients with AD have higher proportions of Clostridium difficile, Escherichia coli, and Staphylococcus aureus and lower levels of Bifidobacterium, Bacteroidetes, and Bacteroides species compared to healthy controls.^26,27 Metagenomic analysis of fecal samples from patients with AD have shown a reduction of Faecalibacterium prausnitzii species when compared to controls, along with a decreased SCFA production, leading to the hypothesis that the gut microbiome may play a role in epithelial barrier disruption.^28,29 Systematic reviews and smaller studies have found that oral probiotic use does lead to AD symptom improvement.^8,30,31 A systematic review of 25 RCTs with 1599 participants found that supplementation with oral probiotics significantly decreased the SCORAD (SCORing Atopic Dermatitis) index in adults and children older than 1 year with AD but had no effect on infants younger than 1 year (P<.001). They also found that supplementation with diverse microbes or Lactobacillus species showed greater benefit than Bifidobacterium species alone.³⁰ Another study analyzed the effect of oral Lactobacillus fermentum (1×10⁹ CFU twice daily) in 53 children with AD vs placebo for 16 weeks. This study found a statically significant decrease in SCORAD index between oral probiotics and placebo, with 92% (n=24) of participants supplementing with probiotics having a lower SCORAD index than baseline compared to 63% (n=17) in the placebo group (P=.01).³¹ However, the use of probiotics for AD treatment has remained controversial. Two recent systematic reviews, including 39 RCTs of 2599 randomized patients, found that the use of currently available oral probiotics made little or no difference in patient-rated AD symptoms, investigator-rated AD symptoms, or quality of life.^32,33 No adverse effects were observed in the included studies. Unfortunately, the individual RCTs included were heterogeneous, and future studies with standardized probiotic supplementation should be undertaken before probiotics can be routinely recommended.

The use of topical probiotics in AD also has recently emerged. Multiple studies have shown that patients with AD have higher levels of colonization with S aureus, which is associated with T-cell dysfunction, more severe allergic skin reactions, and disruptions in barrier function.^34,35 Therefore, altering the skin microbiota through topical probiotics could theoretically reduce AD symptoms and flares. Multiple RCTs and smaller studies have shown that topical probiotics can alter the skin microbiota, improve erythema, and decrease scaling and pruritus in AD patients.^35-38 One study used a heat-treated Lactobacillus johnsonii 0.3% lotion twice daily for 3 weeks vs placebo in patients with AD with positive S aureus skin cultures. The S aureus load decreased in patients using the topical probiotic lotion, which correlated with lower SCORAD index that was statistically significant compared to placebo (P=.012).³⁶ More robust studies are needed to determine if topical probiotics should routinely be recommended in AD.

Psoriasis

Psoriasis vulgaris is a chronic inflammatory skin condition characterized by pruritic, hyperkeratotic, scaly plaques.^39,40 Keratinocyte hyperproliferation is central to psoriasis pathogenesis and is thought to be a T-cell–driven reaction to antigens or trauma in genetically predisposed individuals. Standard treatments for psoriasis currently include topical corticosteroids and anti-inflammatories, oral immunomodulatory therapy, biologic agents, and phototherapy.⁴⁰ The use of CAM is highly prevalent among patients with psoriasis, with one study reporting that 51% (n=162) of psoriatic patients interviewed had used CAM.⁴¹ The most common reasons for CAM use included dissatisfaction with current treatment, adverse side effects of standard therapy, and patient-reported attempts at “trying everything to heal disease.”⁴² Herein, we will discuss some of the most frequently used supplements for treatment of psoriatic disease.³⁹

Fish Oil for Psoriasis
One of the most common supplements used by patients with psoriasis is fish oil due to its purported anti-inflammatory qualities.^20,39 The consensus on fish oil supplementation for psoriasis is mixed.^43-45 Multiple RCTs have reported reductions in psoriasis area and severity index (PASI) scores or symptomatic improvement with variable doses of fish oil.^44,46 One RCT found that using EPA 1.8 g once daily and DHA 1.2 g once daily for 12 weeks resulted in significant improvement in pruritus, scaling, and erythema (P<.05).⁴⁴ Another study reported a significant decrease in erythema (P=.02) and total body surface area affected (P=.0001) with EPA 3.6 g once daily and DHA 2.4 g once daily supplementation compared to olive oil supplementation for 15 weeks.⁴⁶ Alternatively, multiple studies have failed to show statistically significant improvement in psoriatic symptoms with fish oil supplementation at variable doses and time frames (14–216 mg daily EPA, 9–80 mg daily DHA, from 2 weeks to 9 months).^40,47,48 Fish oil may impart anticoagulant properties and should not be started without the guidance of a physician. Currently, there are no data to make specific recommendations on the use of fish oil as an adjunct psoriatic treatment.

Curcumin for Psoriasis
Another supplement routinely utilized in patients with psoriasis is curcumin,^40,49,50 a yellow phytochemical that is a major component of the spice turmeric. Curcumin has been shown to inhibit certain proinflammatory cytokines including IL-17, IL-6, IFN-γ, and tumor necrosis factor α and has been regarded as having immune-modulating, anti-inflammatory, and antibacterial properties.^40,50 Curcumin also has been reported to suppress phosphorylase kinase, an enzyme that has increased activity in psoriatic plaques that correlates with markers of psoriatic hyperproliferation.^50,51 When applied topically, turmeric microgel 0.5% has been reported to decrease scaling, erythema, and psoriatic plaque thickness over the course of 9 weeks.⁵⁰ In a nonrandomized trial with 10 participants, researchers found that phosphorylase kinase activity levels in psoriatic skin biopsies of patients applying topical curcumin 1% were lower than placebo and topical calcipotriol applied in combination. The lower phosphorylase kinase levels correlated with level of disease severity, and topical curcumin 1% showed a superior outcome when compared to topical calcipotriol.^40,49 Although these preliminary results are interesting, there still are not enough data at this time to recommend topical curcumin as a treatment of psoriasis. No known adverse events have been reported with the use of topical curcumin to date.

Oral curcumin has poor oral bioavailability, and 40% to 90% of oral doses are excreted, making supplementation a challenge.⁴⁰ In one RCT, oral curcumin 2 g daily (using a lecithin-based delivery system to increase bioavailability) was administered in combination with topical methylprednisolone aceponate 0.1%, resulting in significant improvement in psoriatic symptoms and lower IL-22 compared to placebo and topical methylprednisolone aceponate (P<.05).⁵² Other studies also have reported decreased PASI scores with oral curcumin supplementation.^53,54 Adverse effects reported with oral curcumin included gastrointestinal tract upset and hot flashes.⁵³ Although there is early evidence that may support the use of oral curcumin supplementation for psoriasis, more data are needed before recommending this therapy.

Indigo Naturalis for Psoriasis
Topical indigo naturalis (IN) also has been reported to improve psoriasis symptoms.^39,53,55 The antipsoriatic effects are thought to occur through the active ingredient in IN (indirubin), which is responsible for inhibition of keratinocyte proliferation.⁴⁰ One study reported that topical IN 1.4% containing indirubin 0.16% with a petroleum ointment vehicle applied to psoriatic plaques over 12 weeks resulted in a significant decrease in PASI scores from 18.9 at baseline to 6.3 after IN treatment (P<.001).⁵⁶ Another study found that over 8 weeks, topical application of IN 2.83% containing indirubin 0.24% to psoriatic plaques vs petroleum jelly resulted in 56.3% (n=9) of the treatment group achieving PASI 75 compared to 0% in the placebo group (n=24).⁵⁵ One deterrent in topical IN treatment is the dark blue pigment it contains; however, no other adverse outcomes were found with topical IN treatment.⁵⁶ Larger clinical trials are necessary to further explore IN as a potential adjunct treatment in patients with mild psoriatic disease. When taken orally, IN has caused gastrointestinal tract disturbance and elevated liver enzyme levels.⁵⁷

Herbal Toxicities
It is important to consider that oral supplements including curcumin and IN are widely available over-the-counter and online without oversight by the US Food and Drug Administration.⁴⁰ Herbal supplements typically are compounded with other ingredients and have been associated with hepatotoxicity as well as drug-supplement interactions, including abnormal bleeding and clotting.⁵⁸ There exists a lack of general surveillance data, making the true burden of herbal toxicities more difficult to accurately discern. Although some supplements have been associated with anti-inflammatory qualities and disease improvement, other herbal supplements have been shown to possess immunostimulatory characteristics. Herbal supplements such as spirulina, chlorella, Aphanizomenon flos-aquae, and echinacea have been shown to upregulate inflammatory pathways in a variety of autoimmune skin conditions.⁵⁹

Probiotics for Psoriasis
Data on probiotic use in patients with psoriasis are limited.²³ A distinct pattern of dysbiosis has been identified in psoriatic patients, as there is thought to be depletion of beneficial bacteria such as Bifidobacterium, lactobacilli, and F prausnitzii and increased colonization with pathogenic organisms such as Salmonella, E coli, Heliobacter, Campylobacter, and Alcaligenes in psoriasis patients.^23,59,60 Early mouse studies have supported this hypothesis, as mice fed with Lactobacillus pentosus have developed milder forms of imiquimod-induced psoriasis compared to placebo,⁵⁵ and mice receiving probiotic supplementation have lower levels of psoriasis-related proinflammatory markers such as T_H17-associated cytokines.⁶¹ Another study in humans found that daily oral Bifidobacterium infantis supplementation for 8 weeks in psoriatic patients resulted in lower C-reactive protein and tumor necrosis factor α levels compared to placebo.⁶² Studies on the use of topical probiotics in psoriasis have been limited, and more research is needed to explore this relationship.³⁸ At this time, no specific recommendations can be made on the use of probiotics in psoriatic patients.

Alopecia Areata

Alopecia areata is nonscarring hair loss that can affect the scalp, face, or body.^63,64 The pathophysiology of AA involves the attack of the hair follicle matrix epithelium by inflammatory cells without hair follicle stem cell destruction. The precise events that precipitate these episodes are unknown, but triggers such as emotional or physical stress, vaccines, or viral infections have been reported.⁶⁵ There is no cure for AA, and current treatments such as topical minoxidil and corticosteroids (topical, intralesional, or oral) vary widely in efficacy.⁶⁴ Although Janus kinase inhibitors recently have shown promising results in the treatment of AA, the need for prolonged therapy may be frustrating to patients.⁶⁶ Severity of AA also can vary, with 30% of patients experiencing extensive hair loss.⁶⁷ The use of CAM has been widely reported in AA due to high levels of dissatisfaction with existing therapies.⁶⁸ Herein, we discuss the most studied alternative treatments used in AA

Garlic and Onion for Alopecia
One alternative treatment that has shown promising initial results is application of topical garlic and onion extracts to affected areas.^64,69,70 Both garlic and onion belong to the Allium genus and are high in sulfur and phenolic compounds.⁷⁰ They have been reported to possess bactericidal and vasodilatory activity,⁷¹ and it has been hypothesized that onion and garlic extracts may induce therapeutic effects through induction of a mild contact dermatitis.⁷⁰ One single-blinded, controlled trial using topical crude onion juice reported that 86.9% (n=20) of patients had full regrowth of hair compared to 13.3% (n=2) of patients treated with a tap water placebo at 8 weeks (P<.0001). This study also noted that patients using onion juice had a higher rate of erythema at application site; unfortunately, the study was small with only 38 patients.⁷⁰ Another double-blind RCT using garlic gel 5% with betamethasone valerate cream 0.1% compared to betamethasone valerate cream alone found that after 3 months, patients in the garlic gel group had increased terminal hairs and smaller patch sizes compared to the betamethasone valerate cream group.⁶⁹ More studies are needed to confirm these results.

Aromatherapy With Essential Oils for Alopecia
Another alternative treatment in AA that has demonstrated positive results is aromatherapy skin massage with essential oils to patches of alopecia.⁷² Although certain essential oils, such as tea tree oil, have been reported to have specific antibacterial or anti-inflammatory properties, essential oils have been reported to cause allergic contact dermatitis and should be used with caution.^73,74 For example, tea tree oil is a well-known cause of allergic contact dermatitis, and positive patch testing has ranged from 0.1% to 3.5% in studies assessing topical tea tree oil 5% application.⁷⁵ Overall, there have been nearly 80 essential oils implicated in contact dermatitis, with high-concentration products being one of the highest risk factors for an allergic contact reaction.⁷⁶ One RCT compared daily scalp massage with essential oils (rosemary, lavender, thyme, and cedarwood in a carrier oil) to daily scalp massage with a placebo carrier oil in AA patients. The results showed that at 7 months of treatment, 44% (n=19) of the aromatherapy group showed improvement compared to 15% (n=6) in the control group.⁷⁷ Another study used a similar group of essential oils (thyme, rosemary, atlas cedar, lavender, and EPO in a carrier oil) with daily scalp massage and reported similar improvement of AA symptoms compared to control; the investigators also reported irritation at application site in 1 patient.⁷⁸ There currently are not enough data to recommend aromatherapy skin massage for the treatment of AA, and this practice may cause harm to the patient by induction of allergic contact dermatitis.

There have been a few studies to suggest that the use of total glucosides of peony with compound glycyrrhizin and oral Korean red ginseng may have beneficial effects on AA treatment, but efficacy and safety data are lacking, and these therapies should not be recommended without more information.^64,79,80

Final Thoughts

Dermatologic patients frequently are opting for CAM,² and although some therapies may show promising initial results, alternative medicines also can drive adverse events.^19,30 The lack of oversight from the US Food and Drug Administration on the products leads to many unknowns for true health risks with over-the-counter CAM supplements.⁴⁰ As the use of CAM becomes increasingly common among dermatologic patients, it is important for dermatologists to understand the benefits and risks, especially for commonly treated conditions. More data is needed before CAM can be routinely recommended.

Complementary alternative medicine (CAM) has been described by the National Center for Complementary and Integrative Medicine as “health care approaches that are not typically part of conventional medical care or that may have origins outside of usual Western practice.”¹ Although this definition is broad, CAM encompasses therapies such as traditional Chinese medicine, herbal therapies, dietary supplements, and mind/body interventions. The use of CAM has grown, and according to a 2012 National Center for Complementary and Integrative Health survey, more than 30% of US adults and 12% of US children use health care approaches that are considered outside of conventional medical practice. In a survey study of US adults, at least 17.7% of respondents said they had taken a dietary supplement other than a vitamin or mineral in the last year.¹ Data from the 2007 National Health Interview Survey showed that the prevalence of adults with skin conditions using CAM was 84.5% compared to 38.3% in the general population.² In addition, 8.15 million US patients with dermatologic conditions reported using CAM over a 5-year period.³ Complementary alternative medicine has emerged as an alternative or adjunct to standard treatments, making it important for dermatologists to understand the existing literature on these therapies. Herein, we review the current evidence-based literature that exists on CAM for the treatment of atopic dermatitis (AD), psoriasis, and alopecia areata (AA).

Atopic Dermatitis

Atopic dermatitis is a chronic, pruritic, inflammatory skin condition with considerable morbidity.^4,5 The pathophysiology of AD is multifactorial and includes aspects of barrier dysfunction, IgE hypersensitivity, abnormal cell-mediated immune response, and environmental factors.⁶ Atopic dermatitis also is one of the most common inflammatory skin conditions in adults, affecting more than 7% of the US population and up to 20% of the total population in developed countries. Of those affected, 40% have moderate or severe symptoms that result in a substantial impact on quality of life.⁷ Despite advances in understanding disease pathology and treatment, a subset of patients opt to defer conventional treatments such as topical and systemic corticosteroids, antibiotics, nonsteroidal immunomodulators, and biologics. Patients may seek alternative therapies when typical treatments fail or when the perceived side effects outweigh the benefits.^5,8 The use of CAM has been well described in patients with AD; however, the existing evidence supporting its use along with its safety profile have not been thoroughly explored. Herein, we will discuss some of the most well-studied supplements for treatment of AD, including evening primrose oil (EPO), fish oil, and probiotics.⁵

Oral supplementation with polyunsaturated fatty acids commonly is reported in patients with AD.^5,8 The idea that a fatty acid deficiency could lead to atopic skin conditions has been around since 1937, when it was suggested that patients with AD had lower levels of blood unsaturated fatty acids.⁹ Conflicting evidence regarding oral fatty acid ingestion and AD disease severity has emerged.^10,11 One unsaturated fatty acid, γ-linolenic acid (GLA), has demonstrated anti-inflammatory properties and involvement in barrier repair.¹² It is converted to dihomo-GLA in the body, which acts on cyclooxygenase enzymes to produce the inflammatory mediator prostaglandin E₁. The production of GLA is mediated by the enzyme delta-6 desaturase in the metabolization of linoleic acid.¹² However, it has been reported that in a subset of patients with AD, a malfunction of delta-6 desaturase may play a role in disease progression and result in lower baseline levels of GLA.^10,12 Evening primrose oil and borage oil contain high amounts of GLA (8%–10% and 23%, respectively); thus, supplementation with these oils has been studied in AD.¹³

EPO for AD
Studies investigating EPO (Oenothera biennis) and its association with AD severity have shown mixed results. A Cochrane review reported that oral borage oil and EPO were not effective treatments for AD,¹⁴ while another larger randomized controlled trial (RCT) found no statistically significant improvement in AD symptoms.¹⁵ However, multiple smaller studies have found that clinical symptoms of AD, such as erythema, xerosis, pruritus, and total body surface area involved, did improve with oral EPO supplementation when compared to placebo, and the results were statistically significant (P=.04).^16,17 One study looked at different dosages of EPO and found that groups ingesting both 160 mg and 320 mg daily experienced reductions in eczema area and severity index score, with greater improvement noted with the higher dosage.¹⁷ Side effects associated with oral EPO include an anticoagulant effect and transient gastrointestinal tract upset.^8,14 There currently is not enough evidence or safety data to recommend this supplement to AD patients.

Although topical use of fatty acids with high concentrations of GLA, such as EPO and borage oil, have demonstrated improvement in subjective symptom severity, most studies have not reached statistical significance.^10,11 One study used a 10% EPO cream for 2 weeks compared to placebo and found statistically significant improvement in patient-reported AD symptoms (P=.045). However, this study only included 10 participants, and therefore larger studies are necessary to confirm this result.¹⁸ Some RCTs have shown that topical coconut oil, sunflower seed oil, and sandalwood album oil improve AD symptom severity, but again, large controlled trials are needed.⁵ Unfortunately, many essential oils, including EPO, can cause a secondary allergic contact dermatitis and potentially worsen AD.¹⁹

Fish Oil for AD
Fish oil is a commonly used supplement for AD due to its high content of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acids exert anti-inflammatory effects by displacing arachidonic acid, a proinflammatory omega-6 fatty acid thought to increase IgE, as well as helper T cell (T_H2) cytokines and prostaglandin E₂.^8,20 A 2012 Cochrane review found that, while some studies revealed mild improvement in AD symptoms with oral fish oil supplementation, these RCTs were of poor methodological quality.²¹ Multiple smaller studies have shown a decrease in pruritus, severity, and physician-rated clinical scores with fish oil use.^5,8,20,22 One study with 145 participants reported that 6 g of fish oil once daily compared to isoenergetic corn oil for 16 weeks identified no statistically significant differences between the treatment groups.²⁰ No adverse events were identified in any of the reported trials. Further studies should be conducted to assess the utility and dosing of fish oil supplements in AD patients.

Probiotics for AD
Probiotics consist of live microorganisms that enhance the microflora of the gastrointestinal tract.^8,20 They have been shown to influence food digestion and also have demonstrated potential influence on the skin-gut axis.²³ The theory that intestinal dysbiosis plays a role in AD pathogenesis has been investigated in multiple studies.^23-25 The central premise is that low-fiber and high-fat Western diets lead to fundamental changes in the gut microbiome, resulting in fewer anti-inflammatory metabolites, such as short-chain fatty acids (SCFAs).^23-25 These SCFAs are produced by microbes during the fermentation of dietary fiber and are known for their effect on epithelial barrier integrity and anti-inflammatory properties mediated through G protein–coupled receptor 43.²⁵ Multiple studies have shown that the gut microbiome in patients with AD have higher proportions of Clostridium difficile, Escherichia coli, and Staphylococcus aureus and lower levels of Bifidobacterium, Bacteroidetes, and Bacteroides species compared to healthy controls.^26,27 Metagenomic analysis of fecal samples from patients with AD have shown a reduction of Faecalibacterium prausnitzii species when compared to controls, along with a decreased SCFA production, leading to the hypothesis that the gut microbiome may play a role in epithelial barrier disruption.^28,29 Systematic reviews and smaller studies have found that oral probiotic use does lead to AD symptom improvement.^8,30,31 A systematic review of 25 RCTs with 1599 participants found that supplementation with oral probiotics significantly decreased the SCORAD (SCORing Atopic Dermatitis) index in adults and children older than 1 year with AD but had no effect on infants younger than 1 year (P<.001). They also found that supplementation with diverse microbes or Lactobacillus species showed greater benefit than Bifidobacterium species alone.³⁰ Another study analyzed the effect of oral Lactobacillus fermentum (1×10⁹ CFU twice daily) in 53 children with AD vs placebo for 16 weeks. This study found a statically significant decrease in SCORAD index between oral probiotics and placebo, with 92% (n=24) of participants supplementing with probiotics having a lower SCORAD index than baseline compared to 63% (n=17) in the placebo group (P=.01).³¹ However, the use of probiotics for AD treatment has remained controversial. Two recent systematic reviews, including 39 RCTs of 2599 randomized patients, found that the use of currently available oral probiotics made little or no difference in patient-rated AD symptoms, investigator-rated AD symptoms, or quality of life.^32,33 No adverse effects were observed in the included studies. Unfortunately, the individual RCTs included were heterogeneous, and future studies with standardized probiotic supplementation should be undertaken before probiotics can be routinely recommended.

The use of topical probiotics in AD also has recently emerged. Multiple studies have shown that patients with AD have higher levels of colonization with S aureus, which is associated with T-cell dysfunction, more severe allergic skin reactions, and disruptions in barrier function.^34,35 Therefore, altering the skin microbiota through topical probiotics could theoretically reduce AD symptoms and flares. Multiple RCTs and smaller studies have shown that topical probiotics can alter the skin microbiota, improve erythema, and decrease scaling and pruritus in AD patients.^35-38 One study used a heat-treated Lactobacillus johnsonii 0.3% lotion twice daily for 3 weeks vs placebo in patients with AD with positive S aureus skin cultures. The S aureus load decreased in patients using the topical probiotic lotion, which correlated with lower SCORAD index that was statistically significant compared to placebo (P=.012).³⁶ More robust studies are needed to determine if topical probiotics should routinely be recommended in AD.

Psoriasis

Psoriasis vulgaris is a chronic inflammatory skin condition characterized by pruritic, hyperkeratotic, scaly plaques.^39,40 Keratinocyte hyperproliferation is central to psoriasis pathogenesis and is thought to be a T-cell–driven reaction to antigens or trauma in genetically predisposed individuals. Standard treatments for psoriasis currently include topical corticosteroids and anti-inflammatories, oral immunomodulatory therapy, biologic agents, and phototherapy.⁴⁰ The use of CAM is highly prevalent among patients with psoriasis, with one study reporting that 51% (n=162) of psoriatic patients interviewed had used CAM.⁴¹ The most common reasons for CAM use included dissatisfaction with current treatment, adverse side effects of standard therapy, and patient-reported attempts at “trying everything to heal disease.”⁴² Herein, we will discuss some of the most frequently used supplements for treatment of psoriatic disease.³⁹

Fish Oil for Psoriasis
One of the most common supplements used by patients with psoriasis is fish oil due to its purported anti-inflammatory qualities.^20,39 The consensus on fish oil supplementation for psoriasis is mixed.^43-45 Multiple RCTs have reported reductions in psoriasis area and severity index (PASI) scores or symptomatic improvement with variable doses of fish oil.^44,46 One RCT found that using EPA 1.8 g once daily and DHA 1.2 g once daily for 12 weeks resulted in significant improvement in pruritus, scaling, and erythema (P<.05).⁴⁴ Another study reported a significant decrease in erythema (P=.02) and total body surface area affected (P=.0001) with EPA 3.6 g once daily and DHA 2.4 g once daily supplementation compared to olive oil supplementation for 15 weeks.⁴⁶ Alternatively, multiple studies have failed to show statistically significant improvement in psoriatic symptoms with fish oil supplementation at variable doses and time frames (14–216 mg daily EPA, 9–80 mg daily DHA, from 2 weeks to 9 months).^40,47,48 Fish oil may impart anticoagulant properties and should not be started without the guidance of a physician. Currently, there are no data to make specific recommendations on the use of fish oil as an adjunct psoriatic treatment.

Curcumin for Psoriasis
Another supplement routinely utilized in patients with psoriasis is curcumin,^40,49,50 a yellow phytochemical that is a major component of the spice turmeric. Curcumin has been shown to inhibit certain proinflammatory cytokines including IL-17, IL-6, IFN-γ, and tumor necrosis factor α and has been regarded as having immune-modulating, anti-inflammatory, and antibacterial properties.^40,50 Curcumin also has been reported to suppress phosphorylase kinase, an enzyme that has increased activity in psoriatic plaques that correlates with markers of psoriatic hyperproliferation.^50,51 When applied topically, turmeric microgel 0.5% has been reported to decrease scaling, erythema, and psoriatic plaque thickness over the course of 9 weeks.⁵⁰ In a nonrandomized trial with 10 participants, researchers found that phosphorylase kinase activity levels in psoriatic skin biopsies of patients applying topical curcumin 1% were lower than placebo and topical calcipotriol applied in combination. The lower phosphorylase kinase levels correlated with level of disease severity, and topical curcumin 1% showed a superior outcome when compared to topical calcipotriol.^40,49 Although these preliminary results are interesting, there still are not enough data at this time to recommend topical curcumin as a treatment of psoriasis. No known adverse events have been reported with the use of topical curcumin to date.

Oral curcumin has poor oral bioavailability, and 40% to 90% of oral doses are excreted, making supplementation a challenge.⁴⁰ In one RCT, oral curcumin 2 g daily (using a lecithin-based delivery system to increase bioavailability) was administered in combination with topical methylprednisolone aceponate 0.1%, resulting in significant improvement in psoriatic symptoms and lower IL-22 compared to placebo and topical methylprednisolone aceponate (P<.05).⁵² Other studies also have reported decreased PASI scores with oral curcumin supplementation.^53,54 Adverse effects reported with oral curcumin included gastrointestinal tract upset and hot flashes.⁵³ Although there is early evidence that may support the use of oral curcumin supplementation for psoriasis, more data are needed before recommending this therapy.

Indigo Naturalis for Psoriasis
Topical indigo naturalis (IN) also has been reported to improve psoriasis symptoms.^39,53,55 The antipsoriatic effects are thought to occur through the active ingredient in IN (indirubin), which is responsible for inhibition of keratinocyte proliferation.⁴⁰ One study reported that topical IN 1.4% containing indirubin 0.16% with a petroleum ointment vehicle applied to psoriatic plaques over 12 weeks resulted in a significant decrease in PASI scores from 18.9 at baseline to 6.3 after IN treatment (P<.001).⁵⁶ Another study found that over 8 weeks, topical application of IN 2.83% containing indirubin 0.24% to psoriatic plaques vs petroleum jelly resulted in 56.3% (n=9) of the treatment group achieving PASI 75 compared to 0% in the placebo group (n=24).⁵⁵ One deterrent in topical IN treatment is the dark blue pigment it contains; however, no other adverse outcomes were found with topical IN treatment.⁵⁶ Larger clinical trials are necessary to further explore IN as a potential adjunct treatment in patients with mild psoriatic disease. When taken orally, IN has caused gastrointestinal tract disturbance and elevated liver enzyme levels.⁵⁷

Herbal Toxicities
It is important to consider that oral supplements including curcumin and IN are widely available over-the-counter and online without oversight by the US Food and Drug Administration.⁴⁰ Herbal supplements typically are compounded with other ingredients and have been associated with hepatotoxicity as well as drug-supplement interactions, including abnormal bleeding and clotting.⁵⁸ There exists a lack of general surveillance data, making the true burden of herbal toxicities more difficult to accurately discern. Although some supplements have been associated with anti-inflammatory qualities and disease improvement, other herbal supplements have been shown to possess immunostimulatory characteristics. Herbal supplements such as spirulina, chlorella, Aphanizomenon flos-aquae, and echinacea have been shown to upregulate inflammatory pathways in a variety of autoimmune skin conditions.⁵⁹

Probiotics for Psoriasis
Data on probiotic use in patients with psoriasis are limited.²³ A distinct pattern of dysbiosis has been identified in psoriatic patients, as there is thought to be depletion of beneficial bacteria such as Bifidobacterium, lactobacilli, and F prausnitzii and increased colonization with pathogenic organisms such as Salmonella, E coli, Heliobacter, Campylobacter, and Alcaligenes in psoriasis patients.^23,59,60 Early mouse studies have supported this hypothesis, as mice fed with Lactobacillus pentosus have developed milder forms of imiquimod-induced psoriasis compared to placebo,⁵⁵ and mice receiving probiotic supplementation have lower levels of psoriasis-related proinflammatory markers such as T_H17-associated cytokines.⁶¹ Another study in humans found that daily oral Bifidobacterium infantis supplementation for 8 weeks in psoriatic patients resulted in lower C-reactive protein and tumor necrosis factor α levels compared to placebo.⁶² Studies on the use of topical probiotics in psoriasis have been limited, and more research is needed to explore this relationship.³⁸ At this time, no specific recommendations can be made on the use of probiotics in psoriatic patients.

Alopecia Areata

Alopecia areata is nonscarring hair loss that can affect the scalp, face, or body.^63,64 The pathophysiology of AA involves the attack of the hair follicle matrix epithelium by inflammatory cells without hair follicle stem cell destruction. The precise events that precipitate these episodes are unknown, but triggers such as emotional or physical stress, vaccines, or viral infections have been reported.⁶⁵ There is no cure for AA, and current treatments such as topical minoxidil and corticosteroids (topical, intralesional, or oral) vary widely in efficacy.⁶⁴ Although Janus kinase inhibitors recently have shown promising results in the treatment of AA, the need for prolonged therapy may be frustrating to patients.⁶⁶ Severity of AA also can vary, with 30% of patients experiencing extensive hair loss.⁶⁷ The use of CAM has been widely reported in AA due to high levels of dissatisfaction with existing therapies.⁶⁸ Herein, we discuss the most studied alternative treatments used in AA

Garlic and Onion for Alopecia
One alternative treatment that has shown promising initial results is application of topical garlic and onion extracts to affected areas.^64,69,70 Both garlic and onion belong to the Allium genus and are high in sulfur and phenolic compounds.⁷⁰ They have been reported to possess bactericidal and vasodilatory activity,⁷¹ and it has been hypothesized that onion and garlic extracts may induce therapeutic effects through induction of a mild contact dermatitis.⁷⁰ One single-blinded, controlled trial using topical crude onion juice reported that 86.9% (n=20) of patients had full regrowth of hair compared to 13.3% (n=2) of patients treated with a tap water placebo at 8 weeks (P<.0001). This study also noted that patients using onion juice had a higher rate of erythema at application site; unfortunately, the study was small with only 38 patients.⁷⁰ Another double-blind RCT using garlic gel 5% with betamethasone valerate cream 0.1% compared to betamethasone valerate cream alone found that after 3 months, patients in the garlic gel group had increased terminal hairs and smaller patch sizes compared to the betamethasone valerate cream group.⁶⁹ More studies are needed to confirm these results.

Aromatherapy With Essential Oils for Alopecia
Another alternative treatment in AA that has demonstrated positive results is aromatherapy skin massage with essential oils to patches of alopecia.⁷² Although certain essential oils, such as tea tree oil, have been reported to have specific antibacterial or anti-inflammatory properties, essential oils have been reported to cause allergic contact dermatitis and should be used with caution.^73,74 For example, tea tree oil is a well-known cause of allergic contact dermatitis, and positive patch testing has ranged from 0.1% to 3.5% in studies assessing topical tea tree oil 5% application.⁷⁵ Overall, there have been nearly 80 essential oils implicated in contact dermatitis, with high-concentration products being one of the highest risk factors for an allergic contact reaction.⁷⁶ One RCT compared daily scalp massage with essential oils (rosemary, lavender, thyme, and cedarwood in a carrier oil) to daily scalp massage with a placebo carrier oil in AA patients. The results showed that at 7 months of treatment, 44% (n=19) of the aromatherapy group showed improvement compared to 15% (n=6) in the control group.⁷⁷ Another study used a similar group of essential oils (thyme, rosemary, atlas cedar, lavender, and EPO in a carrier oil) with daily scalp massage and reported similar improvement of AA symptoms compared to control; the investigators also reported irritation at application site in 1 patient.⁷⁸ There currently are not enough data to recommend aromatherapy skin massage for the treatment of AA, and this practice may cause harm to the patient by induction of allergic contact dermatitis.

There have been a few studies to suggest that the use of total glucosides of peony with compound glycyrrhizin and oral Korean red ginseng may have beneficial effects on AA treatment, but efficacy and safety data are lacking, and these therapies should not be recommended without more information.^64,79,80

Final Thoughts

Dermatologic patients frequently are opting for CAM,² and although some therapies may show promising initial results, alternative medicines also can drive adverse events.^19,30 The lack of oversight from the US Food and Drug Administration on the products leads to many unknowns for true health risks with over-the-counter CAM supplements.⁴⁰ As the use of CAM becomes increasingly common among dermatologic patients, it is important for dermatologists to understand the benefits and risks, especially for commonly treated conditions. More data is needed before CAM can be routinely recommended.

Complementary alternative medicine (CAM) has been described by the National Center for Complementary and Integrative Medicine as “health care approaches that are not typically part of conventional medical care or that may have origins outside of usual Western practice.”¹ Although this definition is broad, CAM encompasses therapies such as traditional Chinese medicine, herbal therapies, dietary supplements, and mind/body interventions. The use of CAM has grown, and according to a 2012 National Center for Complementary and Integrative Health survey, more than 30% of US adults and 12% of US children use health care approaches that are considered outside of conventional medical practice. In a survey study of US adults, at least 17.7% of respondents said they had taken a dietary supplement other than a vitamin or mineral in the last year.¹ Data from the 2007 National Health Interview Survey showed that the prevalence of adults with skin conditions using CAM was 84.5% compared to 38.3% in the general population.² In addition, 8.15 million US patients with dermatologic conditions reported using CAM over a 5-year period.³ Complementary alternative medicine has emerged as an alternative or adjunct to standard treatments, making it important for dermatologists to understand the existing literature on these therapies. Herein, we review the current evidence-based literature that exists on CAM for the treatment of atopic dermatitis (AD), psoriasis, and alopecia areata (AA).

Atopic Dermatitis

Atopic dermatitis is a chronic, pruritic, inflammatory skin condition with considerable morbidity.^4,5 The pathophysiology of AD is multifactorial and includes aspects of barrier dysfunction, IgE hypersensitivity, abnormal cell-mediated immune response, and environmental factors.⁶ Atopic dermatitis also is one of the most common inflammatory skin conditions in adults, affecting more than 7% of the US population and up to 20% of the total population in developed countries. Of those affected, 40% have moderate or severe symptoms that result in a substantial impact on quality of life.⁷ Despite advances in understanding disease pathology and treatment, a subset of patients opt to defer conventional treatments such as topical and systemic corticosteroids, antibiotics, nonsteroidal immunomodulators, and biologics. Patients may seek alternative therapies when typical treatments fail or when the perceived side effects outweigh the benefits.^5,8 The use of CAM has been well described in patients with AD; however, the existing evidence supporting its use along with its safety profile have not been thoroughly explored. Herein, we will discuss some of the most well-studied supplements for treatment of AD, including evening primrose oil (EPO), fish oil, and probiotics.⁵

Oral supplementation with polyunsaturated fatty acids commonly is reported in patients with AD.^5,8 The idea that a fatty acid deficiency could lead to atopic skin conditions has been around since 1937, when it was suggested that patients with AD had lower levels of blood unsaturated fatty acids.⁹ Conflicting evidence regarding oral fatty acid ingestion and AD disease severity has emerged.^10,11 One unsaturated fatty acid, γ-linolenic acid (GLA), has demonstrated anti-inflammatory properties and involvement in barrier repair.¹² It is converted to dihomo-GLA in the body, which acts on cyclooxygenase enzymes to produce the inflammatory mediator prostaglandin E₁. The production of GLA is mediated by the enzyme delta-6 desaturase in the metabolization of linoleic acid.¹² However, it has been reported that in a subset of patients with AD, a malfunction of delta-6 desaturase may play a role in disease progression and result in lower baseline levels of GLA.^10,12 Evening primrose oil and borage oil contain high amounts of GLA (8%–10% and 23%, respectively); thus, supplementation with these oils has been studied in AD.¹³

EPO for AD
Studies investigating EPO (Oenothera biennis) and its association with AD severity have shown mixed results. A Cochrane review reported that oral borage oil and EPO were not effective treatments for AD,¹⁴ while another larger randomized controlled trial (RCT) found no statistically significant improvement in AD symptoms.¹⁵ However, multiple smaller studies have found that clinical symptoms of AD, such as erythema, xerosis, pruritus, and total body surface area involved, did improve with oral EPO supplementation when compared to placebo, and the results were statistically significant (P=.04).^16,17 One study looked at different dosages of EPO and found that groups ingesting both 160 mg and 320 mg daily experienced reductions in eczema area and severity index score, with greater improvement noted with the higher dosage.¹⁷ Side effects associated with oral EPO include an anticoagulant effect and transient gastrointestinal tract upset.^8,14 There currently is not enough evidence or safety data to recommend this supplement to AD patients.

Although topical use of fatty acids with high concentrations of GLA, such as EPO and borage oil, have demonstrated improvement in subjective symptom severity, most studies have not reached statistical significance.^10,11 One study used a 10% EPO cream for 2 weeks compared to placebo and found statistically significant improvement in patient-reported AD symptoms (P=.045). However, this study only included 10 participants, and therefore larger studies are necessary to confirm this result.¹⁸ Some RCTs have shown that topical coconut oil, sunflower seed oil, and sandalwood album oil improve AD symptom severity, but again, large controlled trials are needed.⁵ Unfortunately, many essential oils, including EPO, can cause a secondary allergic contact dermatitis and potentially worsen AD.¹⁹

Fish Oil for AD
Fish oil is a commonly used supplement for AD due to its high content of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acids exert anti-inflammatory effects by displacing arachidonic acid, a proinflammatory omega-6 fatty acid thought to increase IgE, as well as helper T cell (T_H2) cytokines and prostaglandin E₂.^8,20 A 2012 Cochrane review found that, while some studies revealed mild improvement in AD symptoms with oral fish oil supplementation, these RCTs were of poor methodological quality.²¹ Multiple smaller studies have shown a decrease in pruritus, severity, and physician-rated clinical scores with fish oil use.^5,8,20,22 One study with 145 participants reported that 6 g of fish oil once daily compared to isoenergetic corn oil for 16 weeks identified no statistically significant differences between the treatment groups.²⁰ No adverse events were identified in any of the reported trials. Further studies should be conducted to assess the utility and dosing of fish oil supplements in AD patients.

Probiotics for AD
Probiotics consist of live microorganisms that enhance the microflora of the gastrointestinal tract.^8,20 They have been shown to influence food digestion and also have demonstrated potential influence on the skin-gut axis.²³ The theory that intestinal dysbiosis plays a role in AD pathogenesis has been investigated in multiple studies.^23-25 The central premise is that low-fiber and high-fat Western diets lead to fundamental changes in the gut microbiome, resulting in fewer anti-inflammatory metabolites, such as short-chain fatty acids (SCFAs).^23-25 These SCFAs are produced by microbes during the fermentation of dietary fiber and are known for their effect on epithelial barrier integrity and anti-inflammatory properties mediated through G protein–coupled receptor 43.²⁵ Multiple studies have shown that the gut microbiome in patients with AD have higher proportions of Clostridium difficile, Escherichia coli, and Staphylococcus aureus and lower levels of Bifidobacterium, Bacteroidetes, and Bacteroides species compared to healthy controls.^26,27 Metagenomic analysis of fecal samples from patients with AD have shown a reduction of Faecalibacterium prausnitzii species when compared to controls, along with a decreased SCFA production, leading to the hypothesis that the gut microbiome may play a role in epithelial barrier disruption.^28,29 Systematic reviews and smaller studies have found that oral probiotic use does lead to AD symptom improvement.^8,30,31 A systematic review of 25 RCTs with 1599 participants found that supplementation with oral probiotics significantly decreased the SCORAD (SCORing Atopic Dermatitis) index in adults and children older than 1 year with AD but had no effect on infants younger than 1 year (P<.001). They also found that supplementation with diverse microbes or Lactobacillus species showed greater benefit than Bifidobacterium species alone.³⁰ Another study analyzed the effect of oral Lactobacillus fermentum (1×10⁹ CFU twice daily) in 53 children with AD vs placebo for 16 weeks. This study found a statically significant decrease in SCORAD index between oral probiotics and placebo, with 92% (n=24) of participants supplementing with probiotics having a lower SCORAD index than baseline compared to 63% (n=17) in the placebo group (P=.01).³¹ However, the use of probiotics for AD treatment has remained controversial. Two recent systematic reviews, including 39 RCTs of 2599 randomized patients, found that the use of currently available oral probiotics made little or no difference in patient-rated AD symptoms, investigator-rated AD symptoms, or quality of life.^32,33 No adverse effects were observed in the included studies. Unfortunately, the individual RCTs included were heterogeneous, and future studies with standardized probiotic supplementation should be undertaken before probiotics can be routinely recommended.

The use of topical probiotics in AD also has recently emerged. Multiple studies have shown that patients with AD have higher levels of colonization with S aureus, which is associated with T-cell dysfunction, more severe allergic skin reactions, and disruptions in barrier function.^34,35 Therefore, altering the skin microbiota through topical probiotics could theoretically reduce AD symptoms and flares. Multiple RCTs and smaller studies have shown that topical probiotics can alter the skin microbiota, improve erythema, and decrease scaling and pruritus in AD patients.^35-38 One study used a heat-treated Lactobacillus johnsonii 0.3% lotion twice daily for 3 weeks vs placebo in patients with AD with positive S aureus skin cultures. The S aureus load decreased in patients using the topical probiotic lotion, which correlated with lower SCORAD index that was statistically significant compared to placebo (P=.012).³⁶ More robust studies are needed to determine if topical probiotics should routinely be recommended in AD.

Psoriasis

Psoriasis vulgaris is a chronic inflammatory skin condition characterized by pruritic, hyperkeratotic, scaly plaques.^39,40 Keratinocyte hyperproliferation is central to psoriasis pathogenesis and is thought to be a T-cell–driven reaction to antigens or trauma in genetically predisposed individuals. Standard treatments for psoriasis currently include topical corticosteroids and anti-inflammatories, oral immunomodulatory therapy, biologic agents, and phototherapy.⁴⁰ The use of CAM is highly prevalent among patients with psoriasis, with one study reporting that 51% (n=162) of psoriatic patients interviewed had used CAM.⁴¹ The most common reasons for CAM use included dissatisfaction with current treatment, adverse side effects of standard therapy, and patient-reported attempts at “trying everything to heal disease.”⁴² Herein, we will discuss some of the most frequently used supplements for treatment of psoriatic disease.³⁹

Fish Oil for Psoriasis
One of the most common supplements used by patients with psoriasis is fish oil due to its purported anti-inflammatory qualities.^20,39 The consensus on fish oil supplementation for psoriasis is mixed.^43-45 Multiple RCTs have reported reductions in psoriasis area and severity index (PASI) scores or symptomatic improvement with variable doses of fish oil.^44,46 One RCT found that using EPA 1.8 g once daily and DHA 1.2 g once daily for 12 weeks resulted in significant improvement in pruritus, scaling, and erythema (P<.05).⁴⁴ Another study reported a significant decrease in erythema (P=.02) and total body surface area affected (P=.0001) with EPA 3.6 g once daily and DHA 2.4 g once daily supplementation compared to olive oil supplementation for 15 weeks.⁴⁶ Alternatively, multiple studies have failed to show statistically significant improvement in psoriatic symptoms with fish oil supplementation at variable doses and time frames (14–216 mg daily EPA, 9–80 mg daily DHA, from 2 weeks to 9 months).^40,47,48 Fish oil may impart anticoagulant properties and should not be started without the guidance of a physician. Currently, there are no data to make specific recommendations on the use of fish oil as an adjunct psoriatic treatment.

Curcumin for Psoriasis
Another supplement routinely utilized in patients with psoriasis is curcumin,^40,49,50 a yellow phytochemical that is a major component of the spice turmeric. Curcumin has been shown to inhibit certain proinflammatory cytokines including IL-17, IL-6, IFN-γ, and tumor necrosis factor α and has been regarded as having immune-modulating, anti-inflammatory, and antibacterial properties.^40,50 Curcumin also has been reported to suppress phosphorylase kinase, an enzyme that has increased activity in psoriatic plaques that correlates with markers of psoriatic hyperproliferation.^50,51 When applied topically, turmeric microgel 0.5% has been reported to decrease scaling, erythema, and psoriatic plaque thickness over the course of 9 weeks.⁵⁰ In a nonrandomized trial with 10 participants, researchers found that phosphorylase kinase activity levels in psoriatic skin biopsies of patients applying topical curcumin 1% were lower than placebo and topical calcipotriol applied in combination. The lower phosphorylase kinase levels correlated with level of disease severity, and topical curcumin 1% showed a superior outcome when compared to topical calcipotriol.^40,49 Although these preliminary results are interesting, there still are not enough data at this time to recommend topical curcumin as a treatment of psoriasis. No known adverse events have been reported with the use of topical curcumin to date.

Oral curcumin has poor oral bioavailability, and 40% to 90% of oral doses are excreted, making supplementation a challenge.⁴⁰ In one RCT, oral curcumin 2 g daily (using a lecithin-based delivery system to increase bioavailability) was administered in combination with topical methylprednisolone aceponate 0.1%, resulting in significant improvement in psoriatic symptoms and lower IL-22 compared to placebo and topical methylprednisolone aceponate (P<.05).⁵² Other studies also have reported decreased PASI scores with oral curcumin supplementation.^53,54 Adverse effects reported with oral curcumin included gastrointestinal tract upset and hot flashes.⁵³ Although there is early evidence that may support the use of oral curcumin supplementation for psoriasis, more data are needed before recommending this therapy.

Indigo Naturalis for Psoriasis
Topical indigo naturalis (IN) also has been reported to improve psoriasis symptoms.^39,53,55 The antipsoriatic effects are thought to occur through the active ingredient in IN (indirubin), which is responsible for inhibition of keratinocyte proliferation.⁴⁰ One study reported that topical IN 1.4% containing indirubin 0.16% with a petroleum ointment vehicle applied to psoriatic plaques over 12 weeks resulted in a significant decrease in PASI scores from 18.9 at baseline to 6.3 after IN treatment (P<.001).⁵⁶ Another study found that over 8 weeks, topical application of IN 2.83% containing indirubin 0.24% to psoriatic plaques vs petroleum jelly resulted in 56.3% (n=9) of the treatment group achieving PASI 75 compared to 0% in the placebo group (n=24).⁵⁵ One deterrent in topical IN treatment is the dark blue pigment it contains; however, no other adverse outcomes were found with topical IN treatment.⁵⁶ Larger clinical trials are necessary to further explore IN as a potential adjunct treatment in patients with mild psoriatic disease. When taken orally, IN has caused gastrointestinal tract disturbance and elevated liver enzyme levels.⁵⁷

Herbal Toxicities
It is important to consider that oral supplements including curcumin and IN are widely available over-the-counter and online without oversight by the US Food and Drug Administration.⁴⁰ Herbal supplements typically are compounded with other ingredients and have been associated with hepatotoxicity as well as drug-supplement interactions, including abnormal bleeding and clotting.⁵⁸ There exists a lack of general surveillance data, making the true burden of herbal toxicities more difficult to accurately discern. Although some supplements have been associated with anti-inflammatory qualities and disease improvement, other herbal supplements have been shown to possess immunostimulatory characteristics. Herbal supplements such as spirulina, chlorella, Aphanizomenon flos-aquae, and echinacea have been shown to upregulate inflammatory pathways in a variety of autoimmune skin conditions.⁵⁹

Probiotics for Psoriasis
Data on probiotic use in patients with psoriasis are limited.²³ A distinct pattern of dysbiosis has been identified in psoriatic patients, as there is thought to be depletion of beneficial bacteria such as Bifidobacterium, lactobacilli, and F prausnitzii and increased colonization with pathogenic organisms such as Salmonella, E coli, Heliobacter, Campylobacter, and Alcaligenes in psoriasis patients.^23,59,60 Early mouse studies have supported this hypothesis, as mice fed with Lactobacillus pentosus have developed milder forms of imiquimod-induced psoriasis compared to placebo,⁵⁵ and mice receiving probiotic supplementation have lower levels of psoriasis-related proinflammatory markers such as T_H17-associated cytokines.⁶¹ Another study in humans found that daily oral Bifidobacterium infantis supplementation for 8 weeks in psoriatic patients resulted in lower C-reactive protein and tumor necrosis factor α levels compared to placebo.⁶² Studies on the use of topical probiotics in psoriasis have been limited, and more research is needed to explore this relationship.³⁸ At this time, no specific recommendations can be made on the use of probiotics in psoriatic patients.

Alopecia Areata

Alopecia areata is nonscarring hair loss that can affect the scalp, face, or body.^63,64 The pathophysiology of AA involves the attack of the hair follicle matrix epithelium by inflammatory cells without hair follicle stem cell destruction. The precise events that precipitate these episodes are unknown, but triggers such as emotional or physical stress, vaccines, or viral infections have been reported.⁶⁵ There is no cure for AA, and current treatments such as topical minoxidil and corticosteroids (topical, intralesional, or oral) vary widely in efficacy.⁶⁴ Although Janus kinase inhibitors recently have shown promising results in the treatment of AA, the need for prolonged therapy may be frustrating to patients.⁶⁶ Severity of AA also can vary, with 30% of patients experiencing extensive hair loss.⁶⁷ The use of CAM has been widely reported in AA due to high levels of dissatisfaction with existing therapies.⁶⁸ Herein, we discuss the most studied alternative treatments used in AA

Garlic and Onion for Alopecia
One alternative treatment that has shown promising initial results is application of topical garlic and onion extracts to affected areas.^64,69,70 Both garlic and onion belong to the Allium genus and are high in sulfur and phenolic compounds.⁷⁰ They have been reported to possess bactericidal and vasodilatory activity,⁷¹ and it has been hypothesized that onion and garlic extracts may induce therapeutic effects through induction of a mild contact dermatitis.⁷⁰ One single-blinded, controlled trial using topical crude onion juice reported that 86.9% (n=20) of patients had full regrowth of hair compared to 13.3% (n=2) of patients treated with a tap water placebo at 8 weeks (P<.0001). This study also noted that patients using onion juice had a higher rate of erythema at application site; unfortunately, the study was small with only 38 patients.⁷⁰ Another double-blind RCT using garlic gel 5% with betamethasone valerate cream 0.1% compared to betamethasone valerate cream alone found that after 3 months, patients in the garlic gel group had increased terminal hairs and smaller patch sizes compared to the betamethasone valerate cream group.⁶⁹ More studies are needed to confirm these results.

Aromatherapy With Essential Oils for Alopecia
Another alternative treatment in AA that has demonstrated positive results is aromatherapy skin massage with essential oils to patches of alopecia.⁷² Although certain essential oils, such as tea tree oil, have been reported to have specific antibacterial or anti-inflammatory properties, essential oils have been reported to cause allergic contact dermatitis and should be used with caution.^73,74 For example, tea tree oil is a well-known cause of allergic contact dermatitis, and positive patch testing has ranged from 0.1% to 3.5% in studies assessing topical tea tree oil 5% application.⁷⁵ Overall, there have been nearly 80 essential oils implicated in contact dermatitis, with high-concentration products being one of the highest risk factors for an allergic contact reaction.⁷⁶ One RCT compared daily scalp massage with essential oils (rosemary, lavender, thyme, and cedarwood in a carrier oil) to daily scalp massage with a placebo carrier oil in AA patients. The results showed that at 7 months of treatment, 44% (n=19) of the aromatherapy group showed improvement compared to 15% (n=6) in the control group.⁷⁷ Another study used a similar group of essential oils (thyme, rosemary, atlas cedar, lavender, and EPO in a carrier oil) with daily scalp massage and reported similar improvement of AA symptoms compared to control; the investigators also reported irritation at application site in 1 patient.⁷⁸ There currently are not enough data to recommend aromatherapy skin massage for the treatment of AA, and this practice may cause harm to the patient by induction of allergic contact dermatitis.

There have been a few studies to suggest that the use of total glucosides of peony with compound glycyrrhizin and oral Korean red ginseng may have beneficial effects on AA treatment, but efficacy and safety data are lacking, and these therapies should not be recommended without more information.^64,79,80

Final Thoughts

Dermatologic patients frequently are opting for CAM,² and although some therapies may show promising initial results, alternative medicines also can drive adverse events.^19,30 The lack of oversight from the US Food and Drug Administration on the products leads to many unknowns for true health risks with over-the-counter CAM supplements.⁴⁰ As the use of CAM becomes increasingly common among dermatologic patients, it is important for dermatologists to understand the benefits and risks, especially for commonly treated conditions. More data is needed before CAM can be routinely recommended.

Tumor necrosis factor inhibitors have long been the go-to treatment of choice for patients with psoriasis and psoriatic arthritis (PsA). They’ve served patients well since etanercept was first approved for PsA in 2002, but today, with the availability of more attractive interleukin-17 and IL-23 inhibitors, dermatologists and rheumatologists are asking whether it’s time to reconsider the use of TNF inhibitors as first-line therapy in psoriasis and PsA.

“TNF inhibitors have served psoriasis patients well for many years. The question is, ‘Is it time to move on from them as first-line agents for psoriasis?’ ” said April W. Armstrong, MD, MPH, a dermatologist and associate dean for clinical research at the University of Southern California, Los Angeles. Dr. Armstrong participated in a point/counterpoint debate about the merits of IL-17 and IL-23 inhibitors over TNF inhibitors at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “For the majority of our patients, IL-17 and IL-23 inhibitors are probably rationally better than TNF inhibitors as first-line agents for moderate to severe plaque psoriasis,” she said.

In this debate, dermatologists and rheumatologists cited studies showing the safety and efficacy of IL-17 and IL-23 inhibitors over TNF inhibitors. TNF inhibitors include etanercept (Enbrel and biosimilars), infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), certolizumab pegol (Cimzia), and golimumab (Simponi). IL-12/23 inhibitors are limited to ustekinumab (Stelara). IL-17 inhibitors include secukinumab (Cosentyx), ixekizumab (Taltz), and brodalumab (Siliq). IL-23 inhibitors include guselkumab (Tremfya), tildrakizumab (Ilumya), and risankizumab (Skyrizi).

TNF inhibitors are recommended by the American College of Rheumatology as first-line therapy for treatment-naive patients with active PsA, and they, along with IL-12/23, IL-17, and IL-23 inhibitors are all recommended by the American Academy of Dermatology as monotherapy treatment options in adult patients with moderate to severe plaque psoriasis. However, some studies have shown that non–TNF-inhibitor biologics have a higher efficacy than TNF inhibitors in some cases for some patients, such as those with moderate to severe psoriasis alone or for musculoskeletal efficacy in patients with PsA who have peripheral arthritis, enthesitis, dactylitis, or axial manifestations.

Favorable characteristics of non–TNF-inhibitor biologics

Dr. Armstrong cited a number of head-to-head trials to support her view that IL-17 and IL-23 inhibitors are better than TNF inhibitors as first-line agents for patients with moderate to severe plaque psoriasis. In the first head-to-head study of its kind in patients with moderate to severe psoriasis, ustekinumab proved superior to etanercept. Guselkumab was shown to be superior to adalimumab for patients with moderate to severe psoriasis. Tildrakizumab also proved superior to etanercept for patients with psoriasis. Risankizumab bested adalimumab in patients with moderate to severe psoriasis. Ixekizumab proved superior to etanercept in two pivotal studies of patients with widespread moderate-to-severe psoriasis.

IL-23 and IL-17 inhibitors tend to have less frequent maintenance dosing, with IL-17 inhibitors being once every 2 or 4 weeks and IL-23 inhibitors once every 8 or 12 weeks, compared with frequencies ranging from every week to every 8 weeks with TNF inhibitors, Dr. Armstrong said.

IL-17 and IL-23 inhibitors also appear to have fewer safety concerns than TNF inhibitors, although there is less long-term data for them overall and there are some notable exceptions in certain patient populations. TNF inhibitors should be avoided in patients with a history of demyelinating disease or hepatitis B virus infection, and they are not preferred in patients who have a history of latent tuberculosis or advanced heart failure. IL-17 inhibitors should not be used in patients with a history of inflammatory bowel disease, and their use is associated with a higher rate of oral candidiasis. IL-23 inhibitors have a good safety profile overall, she said.

“The IL-17/23 axis is very important to psoriatic arthritis and should be the focus of our treatments” for PsA, said Deepak Jadon, MBBCh, MRCP, PhD, a rheumatologist and director of the rheumatology research unit at Addenbrooke’s Hospital, Cambridge (England) University Hospitals NHS Foundation Trust. In his presentation, he proposed that IL-17 inhibitors and IL-23 inhibitors be used as first-line therapies in PsA ahead of TNF inhibitors.

One reason to go with IL-17 and IL-23 inhibitors may be to ”get it right immunologically the first time,” Dr. Jadon said. He cited evidence showing substantially better response to guselkumab when given to biologic-naive patients with PsA versus those who had a inadequate response to TNF inhibitors, as well as data indicating better response with secukinumab regardless of previous TNF inhibitor use.

IL-17 inhibitors target more domains of psoriatic disease than do TNF inhibitors, he said, noting that “they have excellent musculoskeletal efficacy in patients with moderate skin psoriasis, not just those with severe psoriasis.” Ixekizumab proved superior to adalimumab in biologic-naive patients with PsA. The results of this study also indicated that IL-17 inhibitors should not be reserved only for patients with severe psoriasis since a higher percentage of patients with moderate psoriasis who were taking ixekizumab achieved very low PsA activity. Secukinumab also beat adalimumab in a head-to-head comparison and showed a greater impact on some measures of health-related quality of life.

IL-17 inhibitors also do not require concomitant methotrexate, he said, “which is a major bonus for our patients. All of my patients wish to stop methotrexate even if tolerated. Not having to cope with prescribed methotrexate improves risk of adverse events and frequency of blood test monitoring.”

IL-17 and IL-23 inhibitors appear to have good efficacy against axial disease in patients with PsA. Randomized trial results for secukinumab versus placebo show high percentages of patients improving either 20% or 40% in Assessment in Spondyloarthritis International Society response criteria and reduced inflammatory MRI lesions in the spine and sacroiliac joints. Analyses of trial results in guselkumab-treated patients with axial manifestations of PsA have shown the IL-23 inhibitor’s efficacy versus placebo across different measures of disease activity.

Dr. Jadon also cited real-world data showing that patients stay longer on IL-17 and IL-12/23 inhibitors versus TNF inhibitors. A 2016 study of patients with psoriasis in the PSOLAR registry showed that patients persisted on treatment longer with ustekinumab than with adalimumab, etanercept, or infliximab. Similarly, a 2020 study of patients with psoriasis from the British Association of Dermatologists Biologics and Immunomodulators Register found that both ustekinumab and secukinumab had better sustained drug survival than did adalimumab.


Accessibility weighs heavily in using TNF inhibitor first

Clinical trials data show that IL-17 inhibitors outperform TNF inhibitors for psoriasis, but in clinical practice, TNF inhibitors still perform very well in individual patients and are well tolerated, said Amit Garg, MD, founding chair of the department of dermatology at Hofstra University, Hempstead, N.Y.

He argued in favor of TNF inhibitors as first-line therapy over IL-17 inhibitors for psoriasis. In this case, treatment decisions often come down to accessibility, Dr. Garg said. Not all insurance companies cover the cost of the newer IL-23 inhibitors. Plus, access to TNF inhibitors is widespread and costs are generally lower.

“As a physician, I don’t have complete autonomy in prescribing what I want. The reality is whether it be because of cross indication or discount pricing, [TNF inhibitors] – in particular adalimumab – is widely available on all plans and is usually the preferred treatment plan, at least in our area,” he said. “I’m not a big fan of plans that allow drugs at low or no cost for a year or 2, and then abandon the patients at that point thereafter. I like to use something that insurance will cover sustainably, and, quite frankly, TNFs have served well in that regard.”

However, TNF inhibitors are associated with more safety signals, plus they carry a greater risk of infection, leading to tolerability and persistence issues with patients.

“Psoriasis is a lifelong disease. I wish I could tell you that every drug is going to work well forever for individual patients, but I don’t think we know that yet. From my perspective, for efficacy, general well tolerance, convenience, and access, TNFs are still an important part of our ability to treat psoriasis effectively. I have no problem starting there and transitioning as needed for individual patients.

“In my experience, I think patients on TNFs generally do well. We don’t always get the patients clear and certainly there’s drop off of efficacy over time, but I’m not sure that’s a rationale for [changing treatment],” Dr. Garg said.

Ying Ying (Katy) Leung, MD, a rheumatologist with Singapore General Hospital, and a member of the GRAPPA peripheral arthritis working group, argued against the use of IL-17 and IL-23 inhibitors as first-line treatment for PsA over TNF inhibitors. She reasoned that TNF blockers are more accessible, have more long-term safety data (including data indicating safety during pregnancy), and have better cardiovascular protection. She also noted that GRAPPA treatment recommendations strongly advise using TNF blockers (or IL-17 inhibitors) for treatment-naive patients with PsA.

“Accessibility is very important as I learned along the way of leading the peripheral arthritis [GRAPPA] working group. Accessibility [issues] can be coming from a lot of sources, but if you don’t take good care of accessibility, you might be developing a guideline that is way out of reality and nobody is going to use it,” she said.

In her native Singapore, Dr. Leung said that patients pay for biologics out of pocket, so cost is a key factor for her patients. She stated that adalimumab is available as a biosimilar at about $200 monthly for patients with PsA in Singapore, while the average monthly costs are $1,400 for originator infliximab and $1,500 for originator etanercept. By comparison, secukinumab sells for about $750 monthly, ixekizumab $540 monthly, and guselkumab $2,000 monthly.

Treatment choices should be aligned with the disease manifestations of PsA, Dr. Leung said, keeping in mind that accessibility and individual patient needs and preferences should be considered as well. She conducted an informal comparison that found TNF inhibitors are most effective for patients with uveitis or inflammatory bowel disease. Evidence from head-to-head studies indicates that TNF inhibitors and IL-17 inhibitors have similar efficacy for peripheral arthritis, enthesitis, and dactylitis. But caution is warranted, she suggested, for determining the best biologics for axial disease because no head-to-head comparison trials have been conducted for IL-17 or IL-23 inhibitors versus TNF inhibitors.

Dr. Armstrong has been a consultant to AbbVie, Bristol-Myers Squibb, Dermira, Genzyme, Incyte, Janssen, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB. Dr. Jadon has been a consultant to, has been on speakers bureaus for, and has received grant/research support from AbbVie, Amgen, Celgene, Celltrion, Gilead, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB. Dr. Garg has consulted for AbbVie, Boehringer Ingelheim, Janssen, and UCB. Dr. Leung has been a consultant to AbbVie, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, and Pfizer. She has been on speakers bureaus for AbbVie, Janssen Eli Lilly, and Novartis. She has received grant/research support from Pfizer and conference support from AbbVie,

Tumor necrosis factor inhibitors have long been the go-to treatment of choice for patients with psoriasis and psoriatic arthritis (PsA). They’ve served patients well since etanercept was first approved for PsA in 2002, but today, with the availability of more attractive interleukin-17 and IL-23 inhibitors, dermatologists and rheumatologists are asking whether it’s time to reconsider the use of TNF inhibitors as first-line therapy in psoriasis and PsA.

“TNF inhibitors have served psoriasis patients well for many years. The question is, ‘Is it time to move on from them as first-line agents for psoriasis?’ ” said April W. Armstrong, MD, MPH, a dermatologist and associate dean for clinical research at the University of Southern California, Los Angeles. Dr. Armstrong participated in a point/counterpoint debate about the merits of IL-17 and IL-23 inhibitors over TNF inhibitors at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “For the majority of our patients, IL-17 and IL-23 inhibitors are probably rationally better than TNF inhibitors as first-line agents for moderate to severe plaque psoriasis,” she said.

In this debate, dermatologists and rheumatologists cited studies showing the safety and efficacy of IL-17 and IL-23 inhibitors over TNF inhibitors. TNF inhibitors include etanercept (Enbrel and biosimilars), infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), certolizumab pegol (Cimzia), and golimumab (Simponi). IL-12/23 inhibitors are limited to ustekinumab (Stelara). IL-17 inhibitors include secukinumab (Cosentyx), ixekizumab (Taltz), and brodalumab (Siliq). IL-23 inhibitors include guselkumab (Tremfya), tildrakizumab (Ilumya), and risankizumab (Skyrizi).

TNF inhibitors are recommended by the American College of Rheumatology as first-line therapy for treatment-naive patients with active PsA, and they, along with IL-12/23, IL-17, and IL-23 inhibitors are all recommended by the American Academy of Dermatology as monotherapy treatment options in adult patients with moderate to severe plaque psoriasis. However, some studies have shown that non–TNF-inhibitor biologics have a higher efficacy than TNF inhibitors in some cases for some patients, such as those with moderate to severe psoriasis alone or for musculoskeletal efficacy in patients with PsA who have peripheral arthritis, enthesitis, dactylitis, or axial manifestations.

Favorable characteristics of non–TNF-inhibitor biologics

Dr. Armstrong cited a number of head-to-head trials to support her view that IL-17 and IL-23 inhibitors are better than TNF inhibitors as first-line agents for patients with moderate to severe plaque psoriasis. In the first head-to-head study of its kind in patients with moderate to severe psoriasis, ustekinumab proved superior to etanercept. Guselkumab was shown to be superior to adalimumab for patients with moderate to severe psoriasis. Tildrakizumab also proved superior to etanercept for patients with psoriasis. Risankizumab bested adalimumab in patients with moderate to severe psoriasis. Ixekizumab proved superior to etanercept in two pivotal studies of patients with widespread moderate-to-severe psoriasis.

IL-23 and IL-17 inhibitors tend to have less frequent maintenance dosing, with IL-17 inhibitors being once every 2 or 4 weeks and IL-23 inhibitors once every 8 or 12 weeks, compared with frequencies ranging from every week to every 8 weeks with TNF inhibitors, Dr. Armstrong said.

IL-17 and IL-23 inhibitors also appear to have fewer safety concerns than TNF inhibitors, although there is less long-term data for them overall and there are some notable exceptions in certain patient populations. TNF inhibitors should be avoided in patients with a history of demyelinating disease or hepatitis B virus infection, and they are not preferred in patients who have a history of latent tuberculosis or advanced heart failure. IL-17 inhibitors should not be used in patients with a history of inflammatory bowel disease, and their use is associated with a higher rate of oral candidiasis. IL-23 inhibitors have a good safety profile overall, she said.

“The IL-17/23 axis is very important to psoriatic arthritis and should be the focus of our treatments” for PsA, said Deepak Jadon, MBBCh, MRCP, PhD, a rheumatologist and director of the rheumatology research unit at Addenbrooke’s Hospital, Cambridge (England) University Hospitals NHS Foundation Trust. In his presentation, he proposed that IL-17 inhibitors and IL-23 inhibitors be used as first-line therapies in PsA ahead of TNF inhibitors.

One reason to go with IL-17 and IL-23 inhibitors may be to ”get it right immunologically the first time,” Dr. Jadon said. He cited evidence showing substantially better response to guselkumab when given to biologic-naive patients with PsA versus those who had a inadequate response to TNF inhibitors, as well as data indicating better response with secukinumab regardless of previous TNF inhibitor use.

IL-17 inhibitors target more domains of psoriatic disease than do TNF inhibitors, he said, noting that “they have excellent musculoskeletal efficacy in patients with moderate skin psoriasis, not just those with severe psoriasis.” Ixekizumab proved superior to adalimumab in biologic-naive patients with PsA. The results of this study also indicated that IL-17 inhibitors should not be reserved only for patients with severe psoriasis since a higher percentage of patients with moderate psoriasis who were taking ixekizumab achieved very low PsA activity. Secukinumab also beat adalimumab in a head-to-head comparison and showed a greater impact on some measures of health-related quality of life.

IL-17 inhibitors also do not require concomitant methotrexate, he said, “which is a major bonus for our patients. All of my patients wish to stop methotrexate even if tolerated. Not having to cope with prescribed methotrexate improves risk of adverse events and frequency of blood test monitoring.”

IL-17 and IL-23 inhibitors appear to have good efficacy against axial disease in patients with PsA. Randomized trial results for secukinumab versus placebo show high percentages of patients improving either 20% or 40% in Assessment in Spondyloarthritis International Society response criteria and reduced inflammatory MRI lesions in the spine and sacroiliac joints. Analyses of trial results in guselkumab-treated patients with axial manifestations of PsA have shown the IL-23 inhibitor’s efficacy versus placebo across different measures of disease activity.

Dr. Jadon also cited real-world data showing that patients stay longer on IL-17 and IL-12/23 inhibitors versus TNF inhibitors. A 2016 study of patients with psoriasis in the PSOLAR registry showed that patients persisted on treatment longer with ustekinumab than with adalimumab, etanercept, or infliximab. Similarly, a 2020 study of patients with psoriasis from the British Association of Dermatologists Biologics and Immunomodulators Register found that both ustekinumab and secukinumab had better sustained drug survival than did adalimumab.


Accessibility weighs heavily in using TNF inhibitor first

Clinical trials data show that IL-17 inhibitors outperform TNF inhibitors for psoriasis, but in clinical practice, TNF inhibitors still perform very well in individual patients and are well tolerated, said Amit Garg, MD, founding chair of the department of dermatology at Hofstra University, Hempstead, N.Y.

He argued in favor of TNF inhibitors as first-line therapy over IL-17 inhibitors for psoriasis. In this case, treatment decisions often come down to accessibility, Dr. Garg said. Not all insurance companies cover the cost of the newer IL-23 inhibitors. Plus, access to TNF inhibitors is widespread and costs are generally lower.

“As a physician, I don’t have complete autonomy in prescribing what I want. The reality is whether it be because of cross indication or discount pricing, [TNF inhibitors] – in particular adalimumab – is widely available on all plans and is usually the preferred treatment plan, at least in our area,” he said. “I’m not a big fan of plans that allow drugs at low or no cost for a year or 2, and then abandon the patients at that point thereafter. I like to use something that insurance will cover sustainably, and, quite frankly, TNFs have served well in that regard.”

However, TNF inhibitors are associated with more safety signals, plus they carry a greater risk of infection, leading to tolerability and persistence issues with patients.

“Psoriasis is a lifelong disease. I wish I could tell you that every drug is going to work well forever for individual patients, but I don’t think we know that yet. From my perspective, for efficacy, general well tolerance, convenience, and access, TNFs are still an important part of our ability to treat psoriasis effectively. I have no problem starting there and transitioning as needed for individual patients.

“In my experience, I think patients on TNFs generally do well. We don’t always get the patients clear and certainly there’s drop off of efficacy over time, but I’m not sure that’s a rationale for [changing treatment],” Dr. Garg said.

Ying Ying (Katy) Leung, MD, a rheumatologist with Singapore General Hospital, and a member of the GRAPPA peripheral arthritis working group, argued against the use of IL-17 and IL-23 inhibitors as first-line treatment for PsA over TNF inhibitors. She reasoned that TNF blockers are more accessible, have more long-term safety data (including data indicating safety during pregnancy), and have better cardiovascular protection. She also noted that GRAPPA treatment recommendations strongly advise using TNF blockers (or IL-17 inhibitors) for treatment-naive patients with PsA.

“Accessibility is very important as I learned along the way of leading the peripheral arthritis [GRAPPA] working group. Accessibility [issues] can be coming from a lot of sources, but if you don’t take good care of accessibility, you might be developing a guideline that is way out of reality and nobody is going to use it,” she said.

In her native Singapore, Dr. Leung said that patients pay for biologics out of pocket, so cost is a key factor for her patients. She stated that adalimumab is available as a biosimilar at about $200 monthly for patients with PsA in Singapore, while the average monthly costs are $1,400 for originator infliximab and $1,500 for originator etanercept. By comparison, secukinumab sells for about $750 monthly, ixekizumab $540 monthly, and guselkumab $2,000 monthly.

Treatment choices should be aligned with the disease manifestations of PsA, Dr. Leung said, keeping in mind that accessibility and individual patient needs and preferences should be considered as well. She conducted an informal comparison that found TNF inhibitors are most effective for patients with uveitis or inflammatory bowel disease. Evidence from head-to-head studies indicates that TNF inhibitors and IL-17 inhibitors have similar efficacy for peripheral arthritis, enthesitis, and dactylitis. But caution is warranted, she suggested, for determining the best biologics for axial disease because no head-to-head comparison trials have been conducted for IL-17 or IL-23 inhibitors versus TNF inhibitors.

Dr. Armstrong has been a consultant to AbbVie, Bristol-Myers Squibb, Dermira, Genzyme, Incyte, Janssen, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB. Dr. Jadon has been a consultant to, has been on speakers bureaus for, and has received grant/research support from AbbVie, Amgen, Celgene, Celltrion, Gilead, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB. Dr. Garg has consulted for AbbVie, Boehringer Ingelheim, Janssen, and UCB. Dr. Leung has been a consultant to AbbVie, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, and Pfizer. She has been on speakers bureaus for AbbVie, Janssen Eli Lilly, and Novartis. She has received grant/research support from Pfizer and conference support from AbbVie,

Tumor necrosis factor inhibitors have long been the go-to treatment of choice for patients with psoriasis and psoriatic arthritis (PsA). They’ve served patients well since etanercept was first approved for PsA in 2002, but today, with the availability of more attractive interleukin-17 and IL-23 inhibitors, dermatologists and rheumatologists are asking whether it’s time to reconsider the use of TNF inhibitors as first-line therapy in psoriasis and PsA.

“TNF inhibitors have served psoriasis patients well for many years. The question is, ‘Is it time to move on from them as first-line agents for psoriasis?’ ” said April W. Armstrong, MD, MPH, a dermatologist and associate dean for clinical research at the University of Southern California, Los Angeles. Dr. Armstrong participated in a point/counterpoint debate about the merits of IL-17 and IL-23 inhibitors over TNF inhibitors at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “For the majority of our patients, IL-17 and IL-23 inhibitors are probably rationally better than TNF inhibitors as first-line agents for moderate to severe plaque psoriasis,” she said.

In this debate, dermatologists and rheumatologists cited studies showing the safety and efficacy of IL-17 and IL-23 inhibitors over TNF inhibitors. TNF inhibitors include etanercept (Enbrel and biosimilars), infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), certolizumab pegol (Cimzia), and golimumab (Simponi). IL-12/23 inhibitors are limited to ustekinumab (Stelara). IL-17 inhibitors include secukinumab (Cosentyx), ixekizumab (Taltz), and brodalumab (Siliq). IL-23 inhibitors include guselkumab (Tremfya), tildrakizumab (Ilumya), and risankizumab (Skyrizi).

TNF inhibitors are recommended by the American College of Rheumatology as first-line therapy for treatment-naive patients with active PsA, and they, along with IL-12/23, IL-17, and IL-23 inhibitors are all recommended by the American Academy of Dermatology as monotherapy treatment options in adult patients with moderate to severe plaque psoriasis. However, some studies have shown that non–TNF-inhibitor biologics have a higher efficacy than TNF inhibitors in some cases for some patients, such as those with moderate to severe psoriasis alone or for musculoskeletal efficacy in patients with PsA who have peripheral arthritis, enthesitis, dactylitis, or axial manifestations.

Favorable characteristics of non–TNF-inhibitor biologics

Dr. Armstrong cited a number of head-to-head trials to support her view that IL-17 and IL-23 inhibitors are better than TNF inhibitors as first-line agents for patients with moderate to severe plaque psoriasis. In the first head-to-head study of its kind in patients with moderate to severe psoriasis, ustekinumab proved superior to etanercept. Guselkumab was shown to be superior to adalimumab for patients with moderate to severe psoriasis. Tildrakizumab also proved superior to etanercept for patients with psoriasis. Risankizumab bested adalimumab in patients with moderate to severe psoriasis. Ixekizumab proved superior to etanercept in two pivotal studies of patients with widespread moderate-to-severe psoriasis.

IL-23 and IL-17 inhibitors tend to have less frequent maintenance dosing, with IL-17 inhibitors being once every 2 or 4 weeks and IL-23 inhibitors once every 8 or 12 weeks, compared with frequencies ranging from every week to every 8 weeks with TNF inhibitors, Dr. Armstrong said.

IL-17 and IL-23 inhibitors also appear to have fewer safety concerns than TNF inhibitors, although there is less long-term data for them overall and there are some notable exceptions in certain patient populations. TNF inhibitors should be avoided in patients with a history of demyelinating disease or hepatitis B virus infection, and they are not preferred in patients who have a history of latent tuberculosis or advanced heart failure. IL-17 inhibitors should not be used in patients with a history of inflammatory bowel disease, and their use is associated with a higher rate of oral candidiasis. IL-23 inhibitors have a good safety profile overall, she said.

“The IL-17/23 axis is very important to psoriatic arthritis and should be the focus of our treatments” for PsA, said Deepak Jadon, MBBCh, MRCP, PhD, a rheumatologist and director of the rheumatology research unit at Addenbrooke’s Hospital, Cambridge (England) University Hospitals NHS Foundation Trust. In his presentation, he proposed that IL-17 inhibitors and IL-23 inhibitors be used as first-line therapies in PsA ahead of TNF inhibitors.

One reason to go with IL-17 and IL-23 inhibitors may be to ”get it right immunologically the first time,” Dr. Jadon said. He cited evidence showing substantially better response to guselkumab when given to biologic-naive patients with PsA versus those who had a inadequate response to TNF inhibitors, as well as data indicating better response with secukinumab regardless of previous TNF inhibitor use.

IL-17 inhibitors target more domains of psoriatic disease than do TNF inhibitors, he said, noting that “they have excellent musculoskeletal efficacy in patients with moderate skin psoriasis, not just those with severe psoriasis.” Ixekizumab proved superior to adalimumab in biologic-naive patients with PsA. The results of this study also indicated that IL-17 inhibitors should not be reserved only for patients with severe psoriasis since a higher percentage of patients with moderate psoriasis who were taking ixekizumab achieved very low PsA activity. Secukinumab also beat adalimumab in a head-to-head comparison and showed a greater impact on some measures of health-related quality of life.

IL-17 inhibitors also do not require concomitant methotrexate, he said, “which is a major bonus for our patients. All of my patients wish to stop methotrexate even if tolerated. Not having to cope with prescribed methotrexate improves risk of adverse events and frequency of blood test monitoring.”

IL-17 and IL-23 inhibitors appear to have good efficacy against axial disease in patients with PsA. Randomized trial results for secukinumab versus placebo show high percentages of patients improving either 20% or 40% in Assessment in Spondyloarthritis International Society response criteria and reduced inflammatory MRI lesions in the spine and sacroiliac joints. Analyses of trial results in guselkumab-treated patients with axial manifestations of PsA have shown the IL-23 inhibitor’s efficacy versus placebo across different measures of disease activity.

Dr. Jadon also cited real-world data showing that patients stay longer on IL-17 and IL-12/23 inhibitors versus TNF inhibitors. A 2016 study of patients with psoriasis in the PSOLAR registry showed that patients persisted on treatment longer with ustekinumab than with adalimumab, etanercept, or infliximab. Similarly, a 2020 study of patients with psoriasis from the British Association of Dermatologists Biologics and Immunomodulators Register found that both ustekinumab and secukinumab had better sustained drug survival than did adalimumab.


Accessibility weighs heavily in using TNF inhibitor first

Clinical trials data show that IL-17 inhibitors outperform TNF inhibitors for psoriasis, but in clinical practice, TNF inhibitors still perform very well in individual patients and are well tolerated, said Amit Garg, MD, founding chair of the department of dermatology at Hofstra University, Hempstead, N.Y.

He argued in favor of TNF inhibitors as first-line therapy over IL-17 inhibitors for psoriasis. In this case, treatment decisions often come down to accessibility, Dr. Garg said. Not all insurance companies cover the cost of the newer IL-23 inhibitors. Plus, access to TNF inhibitors is widespread and costs are generally lower.

“As a physician, I don’t have complete autonomy in prescribing what I want. The reality is whether it be because of cross indication or discount pricing, [TNF inhibitors] – in particular adalimumab – is widely available on all plans and is usually the preferred treatment plan, at least in our area,” he said. “I’m not a big fan of plans that allow drugs at low or no cost for a year or 2, and then abandon the patients at that point thereafter. I like to use something that insurance will cover sustainably, and, quite frankly, TNFs have served well in that regard.”

However, TNF inhibitors are associated with more safety signals, plus they carry a greater risk of infection, leading to tolerability and persistence issues with patients.

“Psoriasis is a lifelong disease. I wish I could tell you that every drug is going to work well forever for individual patients, but I don’t think we know that yet. From my perspective, for efficacy, general well tolerance, convenience, and access, TNFs are still an important part of our ability to treat psoriasis effectively. I have no problem starting there and transitioning as needed for individual patients.

“In my experience, I think patients on TNFs generally do well. We don’t always get the patients clear and certainly there’s drop off of efficacy over time, but I’m not sure that’s a rationale for [changing treatment],” Dr. Garg said.

Ying Ying (Katy) Leung, MD, a rheumatologist with Singapore General Hospital, and a member of the GRAPPA peripheral arthritis working group, argued against the use of IL-17 and IL-23 inhibitors as first-line treatment for PsA over TNF inhibitors. She reasoned that TNF blockers are more accessible, have more long-term safety data (including data indicating safety during pregnancy), and have better cardiovascular protection. She also noted that GRAPPA treatment recommendations strongly advise using TNF blockers (or IL-17 inhibitors) for treatment-naive patients with PsA.

“Accessibility is very important as I learned along the way of leading the peripheral arthritis [GRAPPA] working group. Accessibility [issues] can be coming from a lot of sources, but if you don’t take good care of accessibility, you might be developing a guideline that is way out of reality and nobody is going to use it,” she said.

In her native Singapore, Dr. Leung said that patients pay for biologics out of pocket, so cost is a key factor for her patients. She stated that adalimumab is available as a biosimilar at about $200 monthly for patients with PsA in Singapore, while the average monthly costs are $1,400 for originator infliximab and $1,500 for originator etanercept. By comparison, secukinumab sells for about $750 monthly, ixekizumab $540 monthly, and guselkumab $2,000 monthly.

Treatment choices should be aligned with the disease manifestations of PsA, Dr. Leung said, keeping in mind that accessibility and individual patient needs and preferences should be considered as well. She conducted an informal comparison that found TNF inhibitors are most effective for patients with uveitis or inflammatory bowel disease. Evidence from head-to-head studies indicates that TNF inhibitors and IL-17 inhibitors have similar efficacy for peripheral arthritis, enthesitis, and dactylitis. But caution is warranted, she suggested, for determining the best biologics for axial disease because no head-to-head comparison trials have been conducted for IL-17 or IL-23 inhibitors versus TNF inhibitors.

Dr. Armstrong has been a consultant to AbbVie, Bristol-Myers Squibb, Dermira, Genzyme, Incyte, Janssen, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB. Dr. Jadon has been a consultant to, has been on speakers bureaus for, and has received grant/research support from AbbVie, Amgen, Celgene, Celltrion, Gilead, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB. Dr. Garg has consulted for AbbVie, Boehringer Ingelheim, Janssen, and UCB. Dr. Leung has been a consultant to AbbVie, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, and Pfizer. She has been on speakers bureaus for AbbVie, Janssen Eli Lilly, and Novartis. She has received grant/research support from Pfizer and conference support from AbbVie,

Identifying safe, effective, and affordable evidence-based dermatologic treatments for older adults can be challenging because of age-related changes in the skin, comorbidities, polypharmacy, mobility issues, and cognitive changes. Phototherapy has been shown to be an effective nonpharmacologic treatment option for multiple challenging dermatologic conditions^1-8; however, few studies have specifically examined its effectiveness in older adults. The challenge for older patients with psoriasis and dermatitis is that the conditions can be difficult to control and often require multiple treatment modalities.^9,10 Patients with psoriasis also have a higher risk for diabetes, dyslipidemia, and cardiovascular disease compared to other older patients,^11,12 which poses treatment challenges and makes nonpharmacologic treatments even more appealing.

Recent studies show that phototherapy can help decrease the use of dermatologic medications. Foerster and colleagues² found that adults with psoriasis who were treated with phototherapy significantly decreased their use of topical steroids (24.5% fewer patients required steroid creams and 31.1% fewer patients required psoriasis-specific topicals)(P<.01) while their use of non–psoriasis-specific medications did not change. Click and colleagues¹³ identified a decrease in medication costs, health care utilization, and risk for immunosuppression in patients treated with phototherapy when compared to those treated with biologics and apremilast. Methotrexate is a common dermatologic medication that is highly associated with increased risks in elderly patients because of impaired immune system function and the presence of comorbidities (eg, kidney disease, obesity, diabetes, fatty liver),¹⁴ which increase in prevalence with age. Combining phototherapy with methotrexate can substantially decrease the amount of methotrexate needed to achieve disease control,¹⁵ thereby decreasing the methotrexate-associated risks. Findings from these studies suggest that a safe, effective, cost-effective, and well-tolerated nonpharmacologic alternative, such as phototherapy, is highly desirable and should be optimized. Unfortunately, most studies that report the effectiveness of phototherapy are in younger populations.

This retrospective study aimed to (1) identify the most common dermatologic conditions treated with phototherapy in older adults, (2) examine the effectiveness and safety of phototherapy in older adults, and (3) compare the outcomes with 2 similar studies in the United Kingdom¹⁶ and Turkey.¹⁷

Methods

Design, Setting, Sample, and Statistical Analysis
The institutional review boards of Kaiser Permanente Washington Health Research Institute, Seattle, and the University of Washington, Seattle, approved this study. It was conducted in a large US multispecialty health care system (Group Health, Seattle, Washington [now Kaiser Permanente Washington]) serving approximately 600,000 patients, using billing records to identify all patients treated with phototherapy between January 1, 2015, and December 31, 2015, all who received narrowband UVB (NB-UVB) phototherapy. All adults 65 years and older who received phototherapy treatment during the 12-month study period were included. Patients were included regardless of comorbidities and other dermatologic treatments to maintain as much uniformity as possible between the present study and 2 prior studies examining phototherapy in older adult populations in the United Kingdom¹⁶ and Turkey.¹⁷ Demographic and clinical factors were presented using frequencies (percentages) or means and medians as appropriate. Comparisons of dermatologic conditions and clearance levels used a Fisher exact test. The number of phototherapy treatments to clearance and total number of treatments were compared between groups of patients using independent sample t tests.

Phototherapy Protocol
All patients received treatments administered by specially trained phototherapy nurses using a Daavlin UV Series (The Daavlin Company) or an Ultralite unit (Ultralite Enterprises, Inc), both with 48 lamps. All phototherapy nurses had been previously trained to provide treatments based on standardized protocols (Table 1) and to determine the patient’s level of disease clearance using a high to low clearance scale (Table 2). Daavlin’s treatment protocols were built into the software that accompanied the units and were developed based on the American Academy of Dermatology guidelines. The starting dose for an individual patient was determined based on the estimated minimal erythema dose for each phototype. If the patient was using photosensitizing medications, then the protocol guided the nurse to start the patient at a lower dose appropriate for their phototype. Patients with vitiligo were treated with the same starting and escalation doses as patients with Fitzpatrick phototype I because of the assumption that their vitiliginous skin had an increased risk for photosensitivity. A more recent review of the evidence has indicated that this assumption was overly conservative,¹⁸ and Kaiser Permanente Washington’s vitiligo protocol has been adjusted.

Results

Patients
Billing records identified 229 total patients who received phototherapy in 2015, of whom 52 (22.7%) were at least 65 years old. The median age was 70 years (range, 65–91 years). Twenty-nine (56%) were men and 35 (67%) had previously received phototherapy treatments.

Dermatologic Conditions Treated With Phototherapy
Our primary aim was to identify the most common dermatologic conditions treated with phototherapy in older adults. Psoriasis and dermatitis were the most common conditions treated in the sample (50% [26/52] and 21% [11/52], respectively), with mycosis fungoides being the third most common (10% [5/52]) and vitiligo tied with prurigo nodularis as fourth most common (6% [3/52])(Figure 1).

Effectiveness and Safety of Phototherapy
Our secondary aim was to examine the effectiveness and safety of phototherapy in older adults. Phototherapy was effective in this population, with 50 of 52 patients (96%) achieving a high or medium level of clearance. The degree of clearance for each of the dermatologic conditions is shown in Figure 2. Psoriasis and dermatitis achieved high clearance rates in 81% (21/26) and 82% (9/11) of patients, respectively. Overall, conditions did not have significant differences in clearances rates (Fisher exact test, P=.10). On average, it took patients 33 treatments to achieve medium or high rates of clearance. Psoriasis cleared more quickly, with an average of 30.4 treatments vs 36.1 treatments for other conditions, but the difference was not significant (t test, P=.26). Patients received an average of 98 total phototherapy treatments; the median number of treatments was 81 due to many being on maintenance therapy over several months. There was no relationship between a history of treatment with phototherapy and the total number of treatments needed to achieve clearance (t test, P=.40), but interestingly, those who had a history of phototherapy took approximately 5 more treatments to achieve clearance. The present study found that a slightly larger number of men were being treated for psoriasis (15 men vs 11 women), but there was no significant difference in response rate based on gender.

Comment

Our study found that 94% of patients with psoriasis achieved clearance with an average of 30.4 treatments, which is comparable to the reported 91% response rate with an average of 30 treatments in the United Kingdom.¹⁶ The other similar study in Turkey¹⁷ reported 73.7% of psoriasis patients achieved a 75% or more improvement from baseline with an average of 42 treatments, which may reflect underlying differences in regional skin type. Of note, the scatter chart (Figure 3) shows that several patients in the present study’s analysis are listed as not clear, but many of those patients had low treatment numbers below the mean time to clearance. Thus, the present study’s response rate may have been underestimated.

In the general population, studies show that psoriasis treated with standardized phototherapy protocols typically clears with an average of 20.6 treatments.²¹ The levels of clearance were similar in our study’s older population, but more treatments were required to achieve those results, with an average of 10 more treatments needed (an additional 3.3 weeks). Similar results were found in this sample for dermatitis and mycosis fungoides, indicating comparable clearance rates and levels but a need for more treatments to achieve similar results compared to the general population.

Additionally, in the current study more patients experienced grade 1 (mild) erythema (46%) and grade 2 erythema (25%) at some point in their treatment compared with the United Kingdom¹⁶ (1.89%) and Turkey¹⁷ (35%) studies, though these side effects did not impact the clearance rate. Interestingly, the current study’s scatter chart (Figure 3) illustrates that this side effect did not seem to increase with aging in this population. If anything, the erythema response was more prevalent in the median or younger patients in the sample. Erythema may have been due to the frequent use of photosensitizing medications in older adults in the United States, some of which typically get discontinued in patients 75 years and older (eg, statins). Other potential causes might include the use of phototype vs minimal erythema dose–driven protocols, the standard utilization of protocols originally designed for psoriasis vs other condition-specific protocols, missed treatments leading to increased sensitivity, or possibly shielding mishaps (eg, not wearing a prescribed face shield). Given the number of potential causes and the possibility of overlapping factors, careful analysis is important. With NB-UVB phototherapy, near-erythemogenic doses are optimal to achieve effective treatments, but this delicate balance may be more problematic for older adults. Future studies are needed to fully determine the factors at play for this population. In the interim, it is important for phototherapy-trained nurses to consider this risk carefully in the older population. They must follow the prescribed protocols that guide them to query patients about their responses to the prior treatment (eg, erythema, tenderness, itching), photosensitizing medications, missed treatments, and placement of shielding, and then adjust the treatment dosing accordingly.

Limitations
This study had several limitations. Although clinical outcomes were recorded prospectively, the analysis was retrospective, unblinded, and not placebo controlled. It was conducted in a single organization (Group Health [now Kaiser Permanente Washington]) but did analyze data from 4 medical centers in different cities with diverse demographics and a variety of nursing staff providing the treatments. Although the vitiligo treatment protocol likely slowed the response rate for those patients with vitiligo, the numbers were small (ie, only 3 of 52 patients), so the researchers chose to include them in the current study. The sample population was relatively small, but when these data are evaluated alongside the studies in the United Kingdom¹⁶ and Turkey,¹⁷ they show a consistent picture illustrating the effectiveness and safety of phototherapy in the older population. Further epidemiologic studies could be helpful to further describe the usefulness of this modality compared with other treatments for a variety of dermatoses in this age group. Supplementary analysis specifically examining the relationship between the number and type of photosensitizing medications, frequency of erythema, and time to clearance also could be useful.

Conclusion

Older adults with a variety of dermatoses respond well to phototherapy and should have the opportunity to use it, particularly considering the potential for increased complications and costs from other treatment modalities, such as commonly used immunosuppressive pharmaceuticals. However, the current study and the comparison studies indicate that it is important to carefully consider the slower clearance rates and the potential risk for increased erythema in this population and adjust patient education and treatment dosing accordingly.

Unfortunately, many dermatology centers do not offer phototherapy because of infrastructure limitations such as space and specially trained nursing staff. Increasing accessibility of phototherapy for older adults through home treatments may be an alternative, given its effectiveness in the general population.^22,23 In addition, home phototherapy may be worth pursuing for the older population considering the challenges they may face with transportation to the clinic setting and their increased risk for serious illness if exposed to infections such as COVID-19. The COVID-19 pandemic has brought to light the need for reliable, safe, and effective treatments that can be utilized in the safety of patients’ homes and should therefore be considered as an option for older adults. Issues such as mobility and cognitive decline could pose some complicating factors, but with the help of a well-trained family member or caregiver, home phototherapy could be a viable option that improves accessibility for older patients. Future research opportunities include further examination of the slower but ultimately equivalent response to phototherapy in the older population, the influence of photosensitizing medications on phototherapy effects, and the impact of phototherapy on utilization of immunosuppressive pharmaceuticals in older adults.

Identifying safe, effective, and affordable evidence-based dermatologic treatments for older adults can be challenging because of age-related changes in the skin, comorbidities, polypharmacy, mobility issues, and cognitive changes. Phototherapy has been shown to be an effective nonpharmacologic treatment option for multiple challenging dermatologic conditions^1-8; however, few studies have specifically examined its effectiveness in older adults. The challenge for older patients with psoriasis and dermatitis is that the conditions can be difficult to control and often require multiple treatment modalities.^9,10 Patients with psoriasis also have a higher risk for diabetes, dyslipidemia, and cardiovascular disease compared to other older patients,^11,12 which poses treatment challenges and makes nonpharmacologic treatments even more appealing.

Recent studies show that phototherapy can help decrease the use of dermatologic medications. Foerster and colleagues² found that adults with psoriasis who were treated with phototherapy significantly decreased their use of topical steroids (24.5% fewer patients required steroid creams and 31.1% fewer patients required psoriasis-specific topicals)(P<.01) while their use of non–psoriasis-specific medications did not change. Click and colleagues¹³ identified a decrease in medication costs, health care utilization, and risk for immunosuppression in patients treated with phototherapy when compared to those treated with biologics and apremilast. Methotrexate is a common dermatologic medication that is highly associated with increased risks in elderly patients because of impaired immune system function and the presence of comorbidities (eg, kidney disease, obesity, diabetes, fatty liver),¹⁴ which increase in prevalence with age. Combining phototherapy with methotrexate can substantially decrease the amount of methotrexate needed to achieve disease control,¹⁵ thereby decreasing the methotrexate-associated risks. Findings from these studies suggest that a safe, effective, cost-effective, and well-tolerated nonpharmacologic alternative, such as phototherapy, is highly desirable and should be optimized. Unfortunately, most studies that report the effectiveness of phototherapy are in younger populations.

This retrospective study aimed to (1) identify the most common dermatologic conditions treated with phototherapy in older adults, (2) examine the effectiveness and safety of phototherapy in older adults, and (3) compare the outcomes with 2 similar studies in the United Kingdom¹⁶ and Turkey.¹⁷

Methods

Design, Setting, Sample, and Statistical Analysis
The institutional review boards of Kaiser Permanente Washington Health Research Institute, Seattle, and the University of Washington, Seattle, approved this study. It was conducted in a large US multispecialty health care system (Group Health, Seattle, Washington [now Kaiser Permanente Washington]) serving approximately 600,000 patients, using billing records to identify all patients treated with phototherapy between January 1, 2015, and December 31, 2015, all who received narrowband UVB (NB-UVB) phototherapy. All adults 65 years and older who received phototherapy treatment during the 12-month study period were included. Patients were included regardless of comorbidities and other dermatologic treatments to maintain as much uniformity as possible between the present study and 2 prior studies examining phototherapy in older adult populations in the United Kingdom¹⁶ and Turkey.¹⁷ Demographic and clinical factors were presented using frequencies (percentages) or means and medians as appropriate. Comparisons of dermatologic conditions and clearance levels used a Fisher exact test. The number of phototherapy treatments to clearance and total number of treatments were compared between groups of patients using independent sample t tests.

Phototherapy Protocol
All patients received treatments administered by specially trained phototherapy nurses using a Daavlin UV Series (The Daavlin Company) or an Ultralite unit (Ultralite Enterprises, Inc), both with 48 lamps. All phototherapy nurses had been previously trained to provide treatments based on standardized protocols (Table 1) and to determine the patient’s level of disease clearance using a high to low clearance scale (Table 2). Daavlin’s treatment protocols were built into the software that accompanied the units and were developed based on the American Academy of Dermatology guidelines. The starting dose for an individual patient was determined based on the estimated minimal erythema dose for each phototype. If the patient was using photosensitizing medications, then the protocol guided the nurse to start the patient at a lower dose appropriate for their phototype. Patients with vitiligo were treated with the same starting and escalation doses as patients with Fitzpatrick phototype I because of the assumption that their vitiliginous skin had an increased risk for photosensitivity. A more recent review of the evidence has indicated that this assumption was overly conservative,¹⁸ and Kaiser Permanente Washington’s vitiligo protocol has been adjusted.

Results

Patients
Billing records identified 229 total patients who received phototherapy in 2015, of whom 52 (22.7%) were at least 65 years old. The median age was 70 years (range, 65–91 years). Twenty-nine (56%) were men and 35 (67%) had previously received phototherapy treatments.

Dermatologic Conditions Treated With Phototherapy
Our primary aim was to identify the most common dermatologic conditions treated with phototherapy in older adults. Psoriasis and dermatitis were the most common conditions treated in the sample (50% [26/52] and 21% [11/52], respectively), with mycosis fungoides being the third most common (10% [5/52]) and vitiligo tied with prurigo nodularis as fourth most common (6% [3/52])(Figure 1).

Effectiveness and Safety of Phototherapy
Our secondary aim was to examine the effectiveness and safety of phototherapy in older adults. Phototherapy was effective in this population, with 50 of 52 patients (96%) achieving a high or medium level of clearance. The degree of clearance for each of the dermatologic conditions is shown in Figure 2. Psoriasis and dermatitis achieved high clearance rates in 81% (21/26) and 82% (9/11) of patients, respectively. Overall, conditions did not have significant differences in clearances rates (Fisher exact test, P=.10). On average, it took patients 33 treatments to achieve medium or high rates of clearance. Psoriasis cleared more quickly, with an average of 30.4 treatments vs 36.1 treatments for other conditions, but the difference was not significant (t test, P=.26). Patients received an average of 98 total phototherapy treatments; the median number of treatments was 81 due to many being on maintenance therapy over several months. There was no relationship between a history of treatment with phototherapy and the total number of treatments needed to achieve clearance (t test, P=.40), but interestingly, those who had a history of phototherapy took approximately 5 more treatments to achieve clearance. The present study found that a slightly larger number of men were being treated for psoriasis (15 men vs 11 women), but there was no significant difference in response rate based on gender.

Comment

Our study found that 94% of patients with psoriasis achieved clearance with an average of 30.4 treatments, which is comparable to the reported 91% response rate with an average of 30 treatments in the United Kingdom.¹⁶ The other similar study in Turkey¹⁷ reported 73.7% of psoriasis patients achieved a 75% or more improvement from baseline with an average of 42 treatments, which may reflect underlying differences in regional skin type. Of note, the scatter chart (Figure 3) shows that several patients in the present study’s analysis are listed as not clear, but many of those patients had low treatment numbers below the mean time to clearance. Thus, the present study’s response rate may have been underestimated.

In the general population, studies show that psoriasis treated with standardized phototherapy protocols typically clears with an average of 20.6 treatments.²¹ The levels of clearance were similar in our study’s older population, but more treatments were required to achieve those results, with an average of 10 more treatments needed (an additional 3.3 weeks). Similar results were found in this sample for dermatitis and mycosis fungoides, indicating comparable clearance rates and levels but a need for more treatments to achieve similar results compared to the general population.

Additionally, in the current study more patients experienced grade 1 (mild) erythema (46%) and grade 2 erythema (25%) at some point in their treatment compared with the United Kingdom¹⁶ (1.89%) and Turkey¹⁷ (35%) studies, though these side effects did not impact the clearance rate. Interestingly, the current study’s scatter chart (Figure 3) illustrates that this side effect did not seem to increase with aging in this population. If anything, the erythema response was more prevalent in the median or younger patients in the sample. Erythema may have been due to the frequent use of photosensitizing medications in older adults in the United States, some of which typically get discontinued in patients 75 years and older (eg, statins). Other potential causes might include the use of phototype vs minimal erythema dose–driven protocols, the standard utilization of protocols originally designed for psoriasis vs other condition-specific protocols, missed treatments leading to increased sensitivity, or possibly shielding mishaps (eg, not wearing a prescribed face shield). Given the number of potential causes and the possibility of overlapping factors, careful analysis is important. With NB-UVB phototherapy, near-erythemogenic doses are optimal to achieve effective treatments, but this delicate balance may be more problematic for older adults. Future studies are needed to fully determine the factors at play for this population. In the interim, it is important for phototherapy-trained nurses to consider this risk carefully in the older population. They must follow the prescribed protocols that guide them to query patients about their responses to the prior treatment (eg, erythema, tenderness, itching), photosensitizing medications, missed treatments, and placement of shielding, and then adjust the treatment dosing accordingly.

Limitations
This study had several limitations. Although clinical outcomes were recorded prospectively, the analysis was retrospective, unblinded, and not placebo controlled. It was conducted in a single organization (Group Health [now Kaiser Permanente Washington]) but did analyze data from 4 medical centers in different cities with diverse demographics and a variety of nursing staff providing the treatments. Although the vitiligo treatment protocol likely slowed the response rate for those patients with vitiligo, the numbers were small (ie, only 3 of 52 patients), so the researchers chose to include them in the current study. The sample population was relatively small, but when these data are evaluated alongside the studies in the United Kingdom¹⁶ and Turkey,¹⁷ they show a consistent picture illustrating the effectiveness and safety of phototherapy in the older population. Further epidemiologic studies could be helpful to further describe the usefulness of this modality compared with other treatments for a variety of dermatoses in this age group. Supplementary analysis specifically examining the relationship between the number and type of photosensitizing medications, frequency of erythema, and time to clearance also could be useful.

Conclusion

Older adults with a variety of dermatoses respond well to phototherapy and should have the opportunity to use it, particularly considering the potential for increased complications and costs from other treatment modalities, such as commonly used immunosuppressive pharmaceuticals. However, the current study and the comparison studies indicate that it is important to carefully consider the slower clearance rates and the potential risk for increased erythema in this population and adjust patient education and treatment dosing accordingly.

Unfortunately, many dermatology centers do not offer phototherapy because of infrastructure limitations such as space and specially trained nursing staff. Increasing accessibility of phototherapy for older adults through home treatments may be an alternative, given its effectiveness in the general population.^22,23 In addition, home phototherapy may be worth pursuing for the older population considering the challenges they may face with transportation to the clinic setting and their increased risk for serious illness if exposed to infections such as COVID-19. The COVID-19 pandemic has brought to light the need for reliable, safe, and effective treatments that can be utilized in the safety of patients’ homes and should therefore be considered as an option for older adults. Issues such as mobility and cognitive decline could pose some complicating factors, but with the help of a well-trained family member or caregiver, home phototherapy could be a viable option that improves accessibility for older patients. Future research opportunities include further examination of the slower but ultimately equivalent response to phototherapy in the older population, the influence of photosensitizing medications on phototherapy effects, and the impact of phototherapy on utilization of immunosuppressive pharmaceuticals in older adults.

Identifying safe, effective, and affordable evidence-based dermatologic treatments for older adults can be challenging because of age-related changes in the skin, comorbidities, polypharmacy, mobility issues, and cognitive changes. Phototherapy has been shown to be an effective nonpharmacologic treatment option for multiple challenging dermatologic conditions^1-8; however, few studies have specifically examined its effectiveness in older adults. The challenge for older patients with psoriasis and dermatitis is that the conditions can be difficult to control and often require multiple treatment modalities.^9,10 Patients with psoriasis also have a higher risk for diabetes, dyslipidemia, and cardiovascular disease compared to other older patients,^11,12 which poses treatment challenges and makes nonpharmacologic treatments even more appealing.

Recent studies show that phototherapy can help decrease the use of dermatologic medications. Foerster and colleagues² found that adults with psoriasis who were treated with phototherapy significantly decreased their use of topical steroids (24.5% fewer patients required steroid creams and 31.1% fewer patients required psoriasis-specific topicals)(P<.01) while their use of non–psoriasis-specific medications did not change. Click and colleagues¹³ identified a decrease in medication costs, health care utilization, and risk for immunosuppression in patients treated with phototherapy when compared to those treated with biologics and apremilast. Methotrexate is a common dermatologic medication that is highly associated with increased risks in elderly patients because of impaired immune system function and the presence of comorbidities (eg, kidney disease, obesity, diabetes, fatty liver),¹⁴ which increase in prevalence with age. Combining phototherapy with methotrexate can substantially decrease the amount of methotrexate needed to achieve disease control,¹⁵ thereby decreasing the methotrexate-associated risks. Findings from these studies suggest that a safe, effective, cost-effective, and well-tolerated nonpharmacologic alternative, such as phototherapy, is highly desirable and should be optimized. Unfortunately, most studies that report the effectiveness of phototherapy are in younger populations.

This retrospective study aimed to (1) identify the most common dermatologic conditions treated with phototherapy in older adults, (2) examine the effectiveness and safety of phototherapy in older adults, and (3) compare the outcomes with 2 similar studies in the United Kingdom¹⁶ and Turkey.¹⁷

Methods

Design, Setting, Sample, and Statistical Analysis
The institutional review boards of Kaiser Permanente Washington Health Research Institute, Seattle, and the University of Washington, Seattle, approved this study. It was conducted in a large US multispecialty health care system (Group Health, Seattle, Washington [now Kaiser Permanente Washington]) serving approximately 600,000 patients, using billing records to identify all patients treated with phototherapy between January 1, 2015, and December 31, 2015, all who received narrowband UVB (NB-UVB) phototherapy. All adults 65 years and older who received phototherapy treatment during the 12-month study period were included. Patients were included regardless of comorbidities and other dermatologic treatments to maintain as much uniformity as possible between the present study and 2 prior studies examining phototherapy in older adult populations in the United Kingdom¹⁶ and Turkey.¹⁷ Demographic and clinical factors were presented using frequencies (percentages) or means and medians as appropriate. Comparisons of dermatologic conditions and clearance levels used a Fisher exact test. The number of phototherapy treatments to clearance and total number of treatments were compared between groups of patients using independent sample t tests.

Phototherapy Protocol
All patients received treatments administered by specially trained phototherapy nurses using a Daavlin UV Series (The Daavlin Company) or an Ultralite unit (Ultralite Enterprises, Inc), both with 48 lamps. All phototherapy nurses had been previously trained to provide treatments based on standardized protocols (Table 1) and to determine the patient’s level of disease clearance using a high to low clearance scale (Table 2). Daavlin’s treatment protocols were built into the software that accompanied the units and were developed based on the American Academy of Dermatology guidelines. The starting dose for an individual patient was determined based on the estimated minimal erythema dose for each phototype. If the patient was using photosensitizing medications, then the protocol guided the nurse to start the patient at a lower dose appropriate for their phototype. Patients with vitiligo were treated with the same starting and escalation doses as patients with Fitzpatrick phototype I because of the assumption that their vitiliginous skin had an increased risk for photosensitivity. A more recent review of the evidence has indicated that this assumption was overly conservative,¹⁸ and Kaiser Permanente Washington’s vitiligo protocol has been adjusted.

Results

Patients
Billing records identified 229 total patients who received phototherapy in 2015, of whom 52 (22.7%) were at least 65 years old. The median age was 70 years (range, 65–91 years). Twenty-nine (56%) were men and 35 (67%) had previously received phototherapy treatments.

Dermatologic Conditions Treated With Phototherapy
Our primary aim was to identify the most common dermatologic conditions treated with phototherapy in older adults. Psoriasis and dermatitis were the most common conditions treated in the sample (50% [26/52] and 21% [11/52], respectively), with mycosis fungoides being the third most common (10% [5/52]) and vitiligo tied with prurigo nodularis as fourth most common (6% [3/52])(Figure 1).

Effectiveness and Safety of Phototherapy
Our secondary aim was to examine the effectiveness and safety of phototherapy in older adults. Phototherapy was effective in this population, with 50 of 52 patients (96%) achieving a high or medium level of clearance. The degree of clearance for each of the dermatologic conditions is shown in Figure 2. Psoriasis and dermatitis achieved high clearance rates in 81% (21/26) and 82% (9/11) of patients, respectively. Overall, conditions did not have significant differences in clearances rates (Fisher exact test, P=.10). On average, it took patients 33 treatments to achieve medium or high rates of clearance. Psoriasis cleared more quickly, with an average of 30.4 treatments vs 36.1 treatments for other conditions, but the difference was not significant (t test, P=.26). Patients received an average of 98 total phototherapy treatments; the median number of treatments was 81 due to many being on maintenance therapy over several months. There was no relationship between a history of treatment with phototherapy and the total number of treatments needed to achieve clearance (t test, P=.40), but interestingly, those who had a history of phototherapy took approximately 5 more treatments to achieve clearance. The present study found that a slightly larger number of men were being treated for psoriasis (15 men vs 11 women), but there was no significant difference in response rate based on gender.

Comment

Our study found that 94% of patients with psoriasis achieved clearance with an average of 30.4 treatments, which is comparable to the reported 91% response rate with an average of 30 treatments in the United Kingdom.¹⁶ The other similar study in Turkey¹⁷ reported 73.7% of psoriasis patients achieved a 75% or more improvement from baseline with an average of 42 treatments, which may reflect underlying differences in regional skin type. Of note, the scatter chart (Figure 3) shows that several patients in the present study’s analysis are listed as not clear, but many of those patients had low treatment numbers below the mean time to clearance. Thus, the present study’s response rate may have been underestimated.

In the general population, studies show that psoriasis treated with standardized phototherapy protocols typically clears with an average of 20.6 treatments.²¹ The levels of clearance were similar in our study’s older population, but more treatments were required to achieve those results, with an average of 10 more treatments needed (an additional 3.3 weeks). Similar results were found in this sample for dermatitis and mycosis fungoides, indicating comparable clearance rates and levels but a need for more treatments to achieve similar results compared to the general population.

Additionally, in the current study more patients experienced grade 1 (mild) erythema (46%) and grade 2 erythema (25%) at some point in their treatment compared with the United Kingdom¹⁶ (1.89%) and Turkey¹⁷ (35%) studies, though these side effects did not impact the clearance rate. Interestingly, the current study’s scatter chart (Figure 3) illustrates that this side effect did not seem to increase with aging in this population. If anything, the erythema response was more prevalent in the median or younger patients in the sample. Erythema may have been due to the frequent use of photosensitizing medications in older adults in the United States, some of which typically get discontinued in patients 75 years and older (eg, statins). Other potential causes might include the use of phototype vs minimal erythema dose–driven protocols, the standard utilization of protocols originally designed for psoriasis vs other condition-specific protocols, missed treatments leading to increased sensitivity, or possibly shielding mishaps (eg, not wearing a prescribed face shield). Given the number of potential causes and the possibility of overlapping factors, careful analysis is important. With NB-UVB phototherapy, near-erythemogenic doses are optimal to achieve effective treatments, but this delicate balance may be more problematic for older adults. Future studies are needed to fully determine the factors at play for this population. In the interim, it is important for phototherapy-trained nurses to consider this risk carefully in the older population. They must follow the prescribed protocols that guide them to query patients about their responses to the prior treatment (eg, erythema, tenderness, itching), photosensitizing medications, missed treatments, and placement of shielding, and then adjust the treatment dosing accordingly.

Limitations
This study had several limitations. Although clinical outcomes were recorded prospectively, the analysis was retrospective, unblinded, and not placebo controlled. It was conducted in a single organization (Group Health [now Kaiser Permanente Washington]) but did analyze data from 4 medical centers in different cities with diverse demographics and a variety of nursing staff providing the treatments. Although the vitiligo treatment protocol likely slowed the response rate for those patients with vitiligo, the numbers were small (ie, only 3 of 52 patients), so the researchers chose to include them in the current study. The sample population was relatively small, but when these data are evaluated alongside the studies in the United Kingdom¹⁶ and Turkey,¹⁷ they show a consistent picture illustrating the effectiveness and safety of phototherapy in the older population. Further epidemiologic studies could be helpful to further describe the usefulness of this modality compared with other treatments for a variety of dermatoses in this age group. Supplementary analysis specifically examining the relationship between the number and type of photosensitizing medications, frequency of erythema, and time to clearance also could be useful.

Conclusion

Older adults with a variety of dermatoses respond well to phototherapy and should have the opportunity to use it, particularly considering the potential for increased complications and costs from other treatment modalities, such as commonly used immunosuppressive pharmaceuticals. However, the current study and the comparison studies indicate that it is important to carefully consider the slower clearance rates and the potential risk for increased erythema in this population and adjust patient education and treatment dosing accordingly.

Unfortunately, many dermatology centers do not offer phototherapy because of infrastructure limitations such as space and specially trained nursing staff. Increasing accessibility of phototherapy for older adults through home treatments may be an alternative, given its effectiveness in the general population.^22,23 In addition, home phototherapy may be worth pursuing for the older population considering the challenges they may face with transportation to the clinic setting and their increased risk for serious illness if exposed to infections such as COVID-19. The COVID-19 pandemic has brought to light the need for reliable, safe, and effective treatments that can be utilized in the safety of patients’ homes and should therefore be considered as an option for older adults. Issues such as mobility and cognitive decline could pose some complicating factors, but with the help of a well-trained family member or caregiver, home phototherapy could be a viable option that improves accessibility for older patients. Future research opportunities include further examination of the slower but ultimately equivalent response to phototherapy in the older population, the influence of photosensitizing medications on phototherapy effects, and the impact of phototherapy on utilization of immunosuppressive pharmaceuticals in older adults.

In what could be a model for other states, Texas has become the first state to exempt physicians from prior authorizations for meeting insurer benchmarks.

The law was passed in June and will take effect in September. It excuses physicians from having to obtain prior authorization if, during the previous 6 months, 90% of their treatments met medical necessity criteria by the health insurer. Through this law, doctors in the state will spend less time getting approvals for treatments for their patients.

Automatic approval of authorizations for treatments – or what the Texas Medical Association (TMA) calls a “gold card” – “allows patients to get the care they need in a more timely fashion,” says Debra Patt, MD, an Austin, Tex.–based oncologist and former chair of the council on legislation for the TMA.

Eighty-seven percent of Texas physicians reported a “drastic increase over the past five years in the burden of prior authorization on their patients and their practices,” per a 2020 survey by the TMA. Nearly half (48%) of Texas physicians have hired staff whose work focuses on processing requests for prior authorization, according to the survey.

Jack Resneck Jr., MD, a San Francisco–based dermatologist and president-elect of the American Medical Association (AMA), said other states have investigated ways to ease the impact of prior authorizations on physicians, but no other state has passed such a law.

Administrative burdens plague physicians around the country. The Medscape Physician Compensation Report 2021 found that physicians spend on average 15.6 hours per week on paperwork and administrative duties.
 

Better outcomes, less anxiety for patients

Dr. Patt, who testified in support of the law’s passage in the Texas legislature, says automatic approval of authorizations “is better for patients because it reduces their anxiety about whether they’re able to get the treatments they need now, and they will have better outcomes if they’re able to receive more timely care.”

Recently, a chemotherapy treatment Dr. Patt prescribed for one of her patients was not authorized by an insurer. The result is “a lot of anxiety and potentially health problems” for the patient, said Dr. Patt.

She expects that automatic approval for treatments will be based on prescribing patterns during the preceding 6 months. “It means that when I order a test today, the [health insurer] looks back at my record 6 months previously,” she said. Still, Dr. Patt awaits guidance from the Texas Department of Insurance, which regulates health insurers in the state, regarding the law.

Dr. Resneck said the pharmacy counter is where most patients encounter prior authorization delays. “That’s when the pharmacist looks at them and says, ‘Actually, this isn’t covered by your health insurer’s formulary,’ or it isn’t covered fully on their formulary.”

One of Dr. Resneck’s patients had a life-altering case of eczema that lasted many years. Because of the condition, the patient couldn’t work or maintain meaningful bonds with family members. A biologic treatment transformed his patient’s life. The patient was able to return to work and to re-engage with family, said Dr. Resneck. But a year after his patient started the treatment, the health insurer wouldn’t authorize the treatment because the patient wasn’t experiencing the same symptoms.

The patient didn’t have the same symptoms because the biologic treatment worked, said Dr. Resneck.

Kristine Grow, a spokesperson for America’s Health Insurance Plans, a national association for health insurers, said, “The use of prior authorization is relatively small – typically, less than 15% – and can help ensure safer opioid prescribing, help prevent dangerous drug interactions, and help protect patients from unnecessary exposure to potentially harmful radiation for inappropriate diagnostic imaging. Numerous studies show that Americans frequently receive inappropriate care, and 25% of unnecessary treatments are associated with complications or adverse events.”

Medical management tools, such as prior authorization, are an “an important way” to deliver “safe, high-quality care” to patients, she added.
 

State and federal efforts to curb prior authorization

In addition to efforts to curb prior authorization in other states, the AMA supports the Improving Seniors’ Timely Access to Care Act (HR 3173). The act includes a provision related to “gold-carding,” said Robert Mills, an AMA spokesperson.

The bill establishes requirements and standards for prior authorization processes related to Medicare Advantage (MA) plans. The requirements and standards for MA plans include the following:

• Establishing an electronic prior authorization program that meets specific standards, such as the ability to provide real-time decisions in response to requests for items and services that are routinely approved.
• Publishing on an annual basis specific prior authorization information, including the percentage of requests approved and the average response time.
• Meeting standards set by the Centers for Medicare & Medicaid Services related to the quality and timeliness of prior authorization determinations.

The act was introduced to the U.S. House of Representatives in May, after which it was referred to two committees for consideration.

A version of this article first appeared on Medscape.com.

In what could be a model for other states, Texas has become the first state to exempt physicians from prior authorizations for meeting insurer benchmarks.

The law was passed in June and will take effect in September. It excuses physicians from having to obtain prior authorization if, during the previous 6 months, 90% of their treatments met medical necessity criteria by the health insurer. Through this law, doctors in the state will spend less time getting approvals for treatments for their patients.

Automatic approval of authorizations for treatments – or what the Texas Medical Association (TMA) calls a “gold card” – “allows patients to get the care they need in a more timely fashion,” says Debra Patt, MD, an Austin, Tex.–based oncologist and former chair of the council on legislation for the TMA.

Eighty-seven percent of Texas physicians reported a “drastic increase over the past five years in the burden of prior authorization on their patients and their practices,” per a 2020 survey by the TMA. Nearly half (48%) of Texas physicians have hired staff whose work focuses on processing requests for prior authorization, according to the survey.

Jack Resneck Jr., MD, a San Francisco–based dermatologist and president-elect of the American Medical Association (AMA), said other states have investigated ways to ease the impact of prior authorizations on physicians, but no other state has passed such a law.

Administrative burdens plague physicians around the country. The Medscape Physician Compensation Report 2021 found that physicians spend on average 15.6 hours per week on paperwork and administrative duties.
 

Better outcomes, less anxiety for patients

Dr. Patt, who testified in support of the law’s passage in the Texas legislature, says automatic approval of authorizations “is better for patients because it reduces their anxiety about whether they’re able to get the treatments they need now, and they will have better outcomes if they’re able to receive more timely care.”

Recently, a chemotherapy treatment Dr. Patt prescribed for one of her patients was not authorized by an insurer. The result is “a lot of anxiety and potentially health problems” for the patient, said Dr. Patt.

She expects that automatic approval for treatments will be based on prescribing patterns during the preceding 6 months. “It means that when I order a test today, the [health insurer] looks back at my record 6 months previously,” she said. Still, Dr. Patt awaits guidance from the Texas Department of Insurance, which regulates health insurers in the state, regarding the law.

Dr. Resneck said the pharmacy counter is where most patients encounter prior authorization delays. “That’s when the pharmacist looks at them and says, ‘Actually, this isn’t covered by your health insurer’s formulary,’ or it isn’t covered fully on their formulary.”

One of Dr. Resneck’s patients had a life-altering case of eczema that lasted many years. Because of the condition, the patient couldn’t work or maintain meaningful bonds with family members. A biologic treatment transformed his patient’s life. The patient was able to return to work and to re-engage with family, said Dr. Resneck. But a year after his patient started the treatment, the health insurer wouldn’t authorize the treatment because the patient wasn’t experiencing the same symptoms.

The patient didn’t have the same symptoms because the biologic treatment worked, said Dr. Resneck.

Kristine Grow, a spokesperson for America’s Health Insurance Plans, a national association for health insurers, said, “The use of prior authorization is relatively small – typically, less than 15% – and can help ensure safer opioid prescribing, help prevent dangerous drug interactions, and help protect patients from unnecessary exposure to potentially harmful radiation for inappropriate diagnostic imaging. Numerous studies show that Americans frequently receive inappropriate care, and 25% of unnecessary treatments are associated with complications or adverse events.”

Medical management tools, such as prior authorization, are an “an important way” to deliver “safe, high-quality care” to patients, she added.
 

State and federal efforts to curb prior authorization

In addition to efforts to curb prior authorization in other states, the AMA supports the Improving Seniors’ Timely Access to Care Act (HR 3173). The act includes a provision related to “gold-carding,” said Robert Mills, an AMA spokesperson.

The bill establishes requirements and standards for prior authorization processes related to Medicare Advantage (MA) plans. The requirements and standards for MA plans include the following:

• Establishing an electronic prior authorization program that meets specific standards, such as the ability to provide real-time decisions in response to requests for items and services that are routinely approved.
• Publishing on an annual basis specific prior authorization information, including the percentage of requests approved and the average response time.
• Meeting standards set by the Centers for Medicare & Medicaid Services related to the quality and timeliness of prior authorization determinations.

The act was introduced to the U.S. House of Representatives in May, after which it was referred to two committees for consideration.

A version of this article first appeared on Medscape.com.

In what could be a model for other states, Texas has become the first state to exempt physicians from prior authorizations for meeting insurer benchmarks.

The law was passed in June and will take effect in September. It excuses physicians from having to obtain prior authorization if, during the previous 6 months, 90% of their treatments met medical necessity criteria by the health insurer. Through this law, doctors in the state will spend less time getting approvals for treatments for their patients.

Automatic approval of authorizations for treatments – or what the Texas Medical Association (TMA) calls a “gold card” – “allows patients to get the care they need in a more timely fashion,” says Debra Patt, MD, an Austin, Tex.–based oncologist and former chair of the council on legislation for the TMA.

Eighty-seven percent of Texas physicians reported a “drastic increase over the past five years in the burden of prior authorization on their patients and their practices,” per a 2020 survey by the TMA. Nearly half (48%) of Texas physicians have hired staff whose work focuses on processing requests for prior authorization, according to the survey.

Jack Resneck Jr., MD, a San Francisco–based dermatologist and president-elect of the American Medical Association (AMA), said other states have investigated ways to ease the impact of prior authorizations on physicians, but no other state has passed such a law.

Administrative burdens plague physicians around the country. The Medscape Physician Compensation Report 2021 found that physicians spend on average 15.6 hours per week on paperwork and administrative duties.
 

Better outcomes, less anxiety for patients

Dr. Patt, who testified in support of the law’s passage in the Texas legislature, says automatic approval of authorizations “is better for patients because it reduces their anxiety about whether they’re able to get the treatments they need now, and they will have better outcomes if they’re able to receive more timely care.”

Recently, a chemotherapy treatment Dr. Patt prescribed for one of her patients was not authorized by an insurer. The result is “a lot of anxiety and potentially health problems” for the patient, said Dr. Patt.

She expects that automatic approval for treatments will be based on prescribing patterns during the preceding 6 months. “It means that when I order a test today, the [health insurer] looks back at my record 6 months previously,” she said. Still, Dr. Patt awaits guidance from the Texas Department of Insurance, which regulates health insurers in the state, regarding the law.

Dr. Resneck said the pharmacy counter is where most patients encounter prior authorization delays. “That’s when the pharmacist looks at them and says, ‘Actually, this isn’t covered by your health insurer’s formulary,’ or it isn’t covered fully on their formulary.”

One of Dr. Resneck’s patients had a life-altering case of eczema that lasted many years. Because of the condition, the patient couldn’t work or maintain meaningful bonds with family members. A biologic treatment transformed his patient’s life. The patient was able to return to work and to re-engage with family, said Dr. Resneck. But a year after his patient started the treatment, the health insurer wouldn’t authorize the treatment because the patient wasn’t experiencing the same symptoms.

The patient didn’t have the same symptoms because the biologic treatment worked, said Dr. Resneck.

Kristine Grow, a spokesperson for America’s Health Insurance Plans, a national association for health insurers, said, “The use of prior authorization is relatively small – typically, less than 15% – and can help ensure safer opioid prescribing, help prevent dangerous drug interactions, and help protect patients from unnecessary exposure to potentially harmful radiation for inappropriate diagnostic imaging. Numerous studies show that Americans frequently receive inappropriate care, and 25% of unnecessary treatments are associated with complications or adverse events.”

Medical management tools, such as prior authorization, are an “an important way” to deliver “safe, high-quality care” to patients, she added.
 

State and federal efforts to curb prior authorization

In addition to efforts to curb prior authorization in other states, the AMA supports the Improving Seniors’ Timely Access to Care Act (HR 3173). The act includes a provision related to “gold-carding,” said Robert Mills, an AMA spokesperson.

The bill establishes requirements and standards for prior authorization processes related to Medicare Advantage (MA) plans. The requirements and standards for MA plans include the following:

• Establishing an electronic prior authorization program that meets specific standards, such as the ability to provide real-time decisions in response to requests for items and services that are routinely approved.
• Publishing on an annual basis specific prior authorization information, including the percentage of requests approved and the average response time.
• Meeting standards set by the Centers for Medicare & Medicaid Services related to the quality and timeliness of prior authorization determinations.

The act was introduced to the U.S. House of Representatives in May, after which it was referred to two committees for consideration.

A version of this article first appeared on Medscape.com.