To the Editor:

It is with great interest that I read the article by Ware et al,¹ “Racial Limitations of Fitzpatrick Skin Type.” Within my own department, the issue of the appropriateness of using Fitzpatrick skin type (FST) as a surrogate to describe skin color has been raised with mixed responses.

As in many dermatology residency programs across the country, first-year dermatology residents are asked to describe the morphology of a lesion/eruption seen on a patient during Grand Rounds. Preceding the morphologic description, many providers describe the appearance of the patient including their skin color, as constitutive skin color can impact understanding of the morphologic descriptions, favor different diagnoses based on disease epidemiology, and guide subsequent treatment recommendations.^2,3 During one of my first Grand Rounds as an early dermatology resident, a patient was described as a “well-appearing brown boy,” which led to a lively discussion regarding the terms that should be used to describe skin color, with some in the audience preferring FST, others including myself preferring degree of pigmentation (eg, light, moderate, dark), and lastly others preferring an inferred ethnicity based on the patient’s appearance. One audience member commented, “I am brown, therefore I think it is fine to say ‘brown boy,’” which adds to findings from Ware et al¹ that there may be differences in what providers prefer to utilize to describe a patient’s skin color based on their own constitutive skin color.

I inquired with 2 other first-year dermatology residents with skin of color at other programs. When asked what terminology they use to describe a patient for Grand Rounds or in clinic, one resident replied, “It’s stylistic but if it’s your one liner [for assessment and plan] use their ethnicity [whereas] if it’s [for] a physical exam use their Fitzpatrick skin type.” The other resident replied, “I use Fitzpatrick skin type even though it’s technically subjective and therefore not appropriate for use within objective data, such as the physical exam, however it’s a language that most colleagues understand as a substitute for skin color.” I also raised the same question to an attending dermatologist at a primarily skin-of-color community hospital. She replied, “I think when unsure about ethnicity, Fitzpatrick type is an appropriate way to describe someone. It’s not really correct to say [a patient’s ethnicity] when you don’t know for sure.”

Unfortunately, as Ware and colleagues¹ indicated, there is no consensus by which to objectively classify nonwhite skin color. Within the dermatology literature, it has been proposed that race should not be used to express skin color, and this article proposes that FST is an inappropriate surrogate for race/ethnicity.⁴ Although I agree that appropriate use of FST should be emphasized in training, is there a vocabulary that Ware et al¹ recommend we use instead? Does the Skin of Color Society have suggestions on preferred language among its members? Finally, what efforts are being made to develop “culturally appropriate and clinically relevant methods for describing skin of color,” as the authors stated, within our own Skin of Color Society, or to whom does this responsibility ultimately fall?

References

1. Ware OR, Dawson JE, Shinohara MM, et al. Racial limitations of Fitzpatrick skin type. Cutis. 2020;105:77-80.

2. Sachdeva S. Fitzpatrick skin typing: applications in dermatology. Indian J Dermatol Venereol Leprol. 2009;75:93-96.

3. Kelly AP, Taylor SC, Lim HW, et al. Taylor and Kelly’s Dermatology for Skin of Color. 2nd ed. New York, NY: McGraw-Hill Education; 2016.

4. Bigby M, Thaler D. Describing patients’ “race” in clinical presentations should be abandoned. J Am Acad Dermatol. 2006;54:1074-1076.

Author’s Response

My colleagues and I thank Dr. Pimentel for his insights regarding the article, “Racial Limitations of Fitzpatrick Skin Type.”¹ The conundrum on how to appropriately categorize skin color for descriptive and epidemiologic purposes continues to remain unsolved today. However, attempts have been made in the past. For example, in September 2006, Dr. Susan C. Taylor (Philadelphia, Pennsylvania), formed and chaired a workshop session titled “A New Classification System for All Skin Types.” Dermatology leaders with skin of color expertise were invited from around the world for a weekend in New York, New York, to brainstorm a new skin color classification system. This endeavor did not produce any successful alternatives, but it has remained a pertinent topic of discussion in academic dermatology, including the Skin of Color Society, since then.

When unsure about ethnicity, my colleagues and I continue to advocate that the Fitzpatrick scale is not an appropriate substitute to describe skin color. This usage of Fitzpatrick skin type (FST) perpetuates the idea that the Fitzpatrick scale is a suitable proxy to describe ethnicity or race, which it is not. It is important to remember that race is a social classification construct, not a biological one.² The topic of race in contemporary culture undoubtedly invokes strong emotional connotations. The language around race is constantly evolving. I would argue that fear and discomfort of using incorrect racial language promotes the inappropriate use of FST, as the FST may be perceived as a more scientific and pseudoapplicable form of classification. To gain knowledge about a patient’s ethnicity/race to assess epidemiologic ethnic trends, we recommend asking the patient in an intake form or during consultation to self-identify his/her ethnicity or race,³ which takes the guesswork out for providers. However, caution must be exercised to avoid using race and ethnicity to later describe skin color.

Until a more culturally and medically relevant method of skin color classification is created, my colleagues and I recommend using basic color adjectives such as brown, black, pink, tan, or white supplemented with light, medium, or dark predescriptors. For example, “A 35-year-old self-identified African American woman with a dark brown skin hue presents with a 2-week flare of itchy, dark purple plaques with white scale on the scalp and extensor surfaces of the knees and elbows.” These basic descriptions for constitutive skin color conjure ample visual information for the listener/reader to understand morphologic descriptions, presentation of erythema, changes in pigmentation, and more. For a more specific skin color classification, we recommend developing a user-friendly Pantone-like color system to classify constitutive skin color.⁴

Jessica E. Dawson, MD

From the University of Washington School of Medicine, Seattle.

The author reports no conflict of interest.

Correspondence: Jessica E. Dawson, MD, University of Washington School of Medicine, 1959 NE Pacific St, Seattle, WA 98195 ([email protected]).

References

1. Ware OR, Dawson JE, Shinohara MM, et al. Racial limitations of Fitzpatrick skin type. Cutis. 2020;105:77-80.

2. Ifekwunigwe JO, Wagner JK, Yu JH, et al. A qualitative analysis of how anthropologists interpret the race construct. Am Anthropol. 2017;119:422-434.

3. Hasnain-Wynia R, Baker DW. Obtaining data on patient race, ethnicity, and primary language in health care organizations: current challenges and proposed solutions. Health Serv Res. 2006;41:1501-1518.

4. What is the Pantone color system? Pantone website. https://www.pantone.com/color-systems/pantone-color-systems-explained. Accesed May 13, 2020.

To the Editor:

It is with great interest that I read the article by Ware et al,¹ “Racial Limitations of Fitzpatrick Skin Type.” Within my own department, the issue of the appropriateness of using Fitzpatrick skin type (FST) as a surrogate to describe skin color has been raised with mixed responses.

As in many dermatology residency programs across the country, first-year dermatology residents are asked to describe the morphology of a lesion/eruption seen on a patient during Grand Rounds. Preceding the morphologic description, many providers describe the appearance of the patient including their skin color, as constitutive skin color can impact understanding of the morphologic descriptions, favor different diagnoses based on disease epidemiology, and guide subsequent treatment recommendations.^2,3 During one of my first Grand Rounds as an early dermatology resident, a patient was described as a “well-appearing brown boy,” which led to a lively discussion regarding the terms that should be used to describe skin color, with some in the audience preferring FST, others including myself preferring degree of pigmentation (eg, light, moderate, dark), and lastly others preferring an inferred ethnicity based on the patient’s appearance. One audience member commented, “I am brown, therefore I think it is fine to say ‘brown boy,’” which adds to findings from Ware et al¹ that there may be differences in what providers prefer to utilize to describe a patient’s skin color based on their own constitutive skin color.

I inquired with 2 other first-year dermatology residents with skin of color at other programs. When asked what terminology they use to describe a patient for Grand Rounds or in clinic, one resident replied, “It’s stylistic but if it’s your one liner [for assessment and plan] use their ethnicity [whereas] if it’s [for] a physical exam use their Fitzpatrick skin type.” The other resident replied, “I use Fitzpatrick skin type even though it’s technically subjective and therefore not appropriate for use within objective data, such as the physical exam, however it’s a language that most colleagues understand as a substitute for skin color.” I also raised the same question to an attending dermatologist at a primarily skin-of-color community hospital. She replied, “I think when unsure about ethnicity, Fitzpatrick type is an appropriate way to describe someone. It’s not really correct to say [a patient’s ethnicity] when you don’t know for sure.”

Unfortunately, as Ware and colleagues¹ indicated, there is no consensus by which to objectively classify nonwhite skin color. Within the dermatology literature, it has been proposed that race should not be used to express skin color, and this article proposes that FST is an inappropriate surrogate for race/ethnicity.⁴ Although I agree that appropriate use of FST should be emphasized in training, is there a vocabulary that Ware et al¹ recommend we use instead? Does the Skin of Color Society have suggestions on preferred language among its members? Finally, what efforts are being made to develop “culturally appropriate and clinically relevant methods for describing skin of color,” as the authors stated, within our own Skin of Color Society, or to whom does this responsibility ultimately fall?

References

1. Ware OR, Dawson JE, Shinohara MM, et al. Racial limitations of Fitzpatrick skin type. Cutis. 2020;105:77-80.

2. Sachdeva S. Fitzpatrick skin typing: applications in dermatology. Indian J Dermatol Venereol Leprol. 2009;75:93-96.

3. Kelly AP, Taylor SC, Lim HW, et al. Taylor and Kelly’s Dermatology for Skin of Color. 2nd ed. New York, NY: McGraw-Hill Education; 2016.

4. Bigby M, Thaler D. Describing patients’ “race” in clinical presentations should be abandoned. J Am Acad Dermatol. 2006;54:1074-1076.

Author’s Response

My colleagues and I thank Dr. Pimentel for his insights regarding the article, “Racial Limitations of Fitzpatrick Skin Type.”¹ The conundrum on how to appropriately categorize skin color for descriptive and epidemiologic purposes continues to remain unsolved today. However, attempts have been made in the past. For example, in September 2006, Dr. Susan C. Taylor (Philadelphia, Pennsylvania), formed and chaired a workshop session titled “A New Classification System for All Skin Types.” Dermatology leaders with skin of color expertise were invited from around the world for a weekend in New York, New York, to brainstorm a new skin color classification system. This endeavor did not produce any successful alternatives, but it has remained a pertinent topic of discussion in academic dermatology, including the Skin of Color Society, since then.

When unsure about ethnicity, my colleagues and I continue to advocate that the Fitzpatrick scale is not an appropriate substitute to describe skin color. This usage of Fitzpatrick skin type (FST) perpetuates the idea that the Fitzpatrick scale is a suitable proxy to describe ethnicity or race, which it is not. It is important to remember that race is a social classification construct, not a biological one.² The topic of race in contemporary culture undoubtedly invokes strong emotional connotations. The language around race is constantly evolving. I would argue that fear and discomfort of using incorrect racial language promotes the inappropriate use of FST, as the FST may be perceived as a more scientific and pseudoapplicable form of classification. To gain knowledge about a patient’s ethnicity/race to assess epidemiologic ethnic trends, we recommend asking the patient in an intake form or during consultation to self-identify his/her ethnicity or race,³ which takes the guesswork out for providers. However, caution must be exercised to avoid using race and ethnicity to later describe skin color.

Until a more culturally and medically relevant method of skin color classification is created, my colleagues and I recommend using basic color adjectives such as brown, black, pink, tan, or white supplemented with light, medium, or dark predescriptors. For example, “A 35-year-old self-identified African American woman with a dark brown skin hue presents with a 2-week flare of itchy, dark purple plaques with white scale on the scalp and extensor surfaces of the knees and elbows.” These basic descriptions for constitutive skin color conjure ample visual information for the listener/reader to understand morphologic descriptions, presentation of erythema, changes in pigmentation, and more. For a more specific skin color classification, we recommend developing a user-friendly Pantone-like color system to classify constitutive skin color.⁴

Jessica E. Dawson, MD

From the University of Washington School of Medicine, Seattle.

The author reports no conflict of interest.

Correspondence: Jessica E. Dawson, MD, University of Washington School of Medicine, 1959 NE Pacific St, Seattle, WA 98195 ([email protected]).

References

1. Ware OR, Dawson JE, Shinohara MM, et al. Racial limitations of Fitzpatrick skin type. Cutis. 2020;105:77-80.

2. Ifekwunigwe JO, Wagner JK, Yu JH, et al. A qualitative analysis of how anthropologists interpret the race construct. Am Anthropol. 2017;119:422-434.

3. Hasnain-Wynia R, Baker DW. Obtaining data on patient race, ethnicity, and primary language in health care organizations: current challenges and proposed solutions. Health Serv Res. 2006;41:1501-1518.

4. What is the Pantone color system? Pantone website. https://www.pantone.com/color-systems/pantone-color-systems-explained. Accesed May 13, 2020.

To the Editor:

It is with great interest that I read the article by Ware et al,¹ “Racial Limitations of Fitzpatrick Skin Type.” Within my own department, the issue of the appropriateness of using Fitzpatrick skin type (FST) as a surrogate to describe skin color has been raised with mixed responses.

As in many dermatology residency programs across the country, first-year dermatology residents are asked to describe the morphology of a lesion/eruption seen on a patient during Grand Rounds. Preceding the morphologic description, many providers describe the appearance of the patient including their skin color, as constitutive skin color can impact understanding of the morphologic descriptions, favor different diagnoses based on disease epidemiology, and guide subsequent treatment recommendations.^2,3 During one of my first Grand Rounds as an early dermatology resident, a patient was described as a “well-appearing brown boy,” which led to a lively discussion regarding the terms that should be used to describe skin color, with some in the audience preferring FST, others including myself preferring degree of pigmentation (eg, light, moderate, dark), and lastly others preferring an inferred ethnicity based on the patient’s appearance. One audience member commented, “I am brown, therefore I think it is fine to say ‘brown boy,’” which adds to findings from Ware et al¹ that there may be differences in what providers prefer to utilize to describe a patient’s skin color based on their own constitutive skin color.

I inquired with 2 other first-year dermatology residents with skin of color at other programs. When asked what terminology they use to describe a patient for Grand Rounds or in clinic, one resident replied, “It’s stylistic but if it’s your one liner [for assessment and plan] use their ethnicity [whereas] if it’s [for] a physical exam use their Fitzpatrick skin type.” The other resident replied, “I use Fitzpatrick skin type even though it’s technically subjective and therefore not appropriate for use within objective data, such as the physical exam, however it’s a language that most colleagues understand as a substitute for skin color.” I also raised the same question to an attending dermatologist at a primarily skin-of-color community hospital. She replied, “I think when unsure about ethnicity, Fitzpatrick type is an appropriate way to describe someone. It’s not really correct to say [a patient’s ethnicity] when you don’t know for sure.”

Unfortunately, as Ware and colleagues¹ indicated, there is no consensus by which to objectively classify nonwhite skin color. Within the dermatology literature, it has been proposed that race should not be used to express skin color, and this article proposes that FST is an inappropriate surrogate for race/ethnicity.⁴ Although I agree that appropriate use of FST should be emphasized in training, is there a vocabulary that Ware et al¹ recommend we use instead? Does the Skin of Color Society have suggestions on preferred language among its members? Finally, what efforts are being made to develop “culturally appropriate and clinically relevant methods for describing skin of color,” as the authors stated, within our own Skin of Color Society, or to whom does this responsibility ultimately fall?

References

1. Ware OR, Dawson JE, Shinohara MM, et al. Racial limitations of Fitzpatrick skin type. Cutis. 2020;105:77-80.

2. Sachdeva S. Fitzpatrick skin typing: applications in dermatology. Indian J Dermatol Venereol Leprol. 2009;75:93-96.

3. Kelly AP, Taylor SC, Lim HW, et al. Taylor and Kelly’s Dermatology for Skin of Color. 2nd ed. New York, NY: McGraw-Hill Education; 2016.

4. Bigby M, Thaler D. Describing patients’ “race” in clinical presentations should be abandoned. J Am Acad Dermatol. 2006;54:1074-1076.

Author’s Response

My colleagues and I thank Dr. Pimentel for his insights regarding the article, “Racial Limitations of Fitzpatrick Skin Type.”¹ The conundrum on how to appropriately categorize skin color for descriptive and epidemiologic purposes continues to remain unsolved today. However, attempts have been made in the past. For example, in September 2006, Dr. Susan C. Taylor (Philadelphia, Pennsylvania), formed and chaired a workshop session titled “A New Classification System for All Skin Types.” Dermatology leaders with skin of color expertise were invited from around the world for a weekend in New York, New York, to brainstorm a new skin color classification system. This endeavor did not produce any successful alternatives, but it has remained a pertinent topic of discussion in academic dermatology, including the Skin of Color Society, since then.

When unsure about ethnicity, my colleagues and I continue to advocate that the Fitzpatrick scale is not an appropriate substitute to describe skin color. This usage of Fitzpatrick skin type (FST) perpetuates the idea that the Fitzpatrick scale is a suitable proxy to describe ethnicity or race, which it is not. It is important to remember that race is a social classification construct, not a biological one.² The topic of race in contemporary culture undoubtedly invokes strong emotional connotations. The language around race is constantly evolving. I would argue that fear and discomfort of using incorrect racial language promotes the inappropriate use of FST, as the FST may be perceived as a more scientific and pseudoapplicable form of classification. To gain knowledge about a patient’s ethnicity/race to assess epidemiologic ethnic trends, we recommend asking the patient in an intake form or during consultation to self-identify his/her ethnicity or race,³ which takes the guesswork out for providers. However, caution must be exercised to avoid using race and ethnicity to later describe skin color.

Until a more culturally and medically relevant method of skin color classification is created, my colleagues and I recommend using basic color adjectives such as brown, black, pink, tan, or white supplemented with light, medium, or dark predescriptors. For example, “A 35-year-old self-identified African American woman with a dark brown skin hue presents with a 2-week flare of itchy, dark purple plaques with white scale on the scalp and extensor surfaces of the knees and elbows.” These basic descriptions for constitutive skin color conjure ample visual information for the listener/reader to understand morphologic descriptions, presentation of erythema, changes in pigmentation, and more. For a more specific skin color classification, we recommend developing a user-friendly Pantone-like color system to classify constitutive skin color.⁴

Jessica E. Dawson, MD

From the University of Washington School of Medicine, Seattle.

The author reports no conflict of interest.

Correspondence: Jessica E. Dawson, MD, University of Washington School of Medicine, 1959 NE Pacific St, Seattle, WA 98195 ([email protected]).

References

1. Ware OR, Dawson JE, Shinohara MM, et al. Racial limitations of Fitzpatrick skin type. Cutis. 2020;105:77-80.

2. Ifekwunigwe JO, Wagner JK, Yu JH, et al. A qualitative analysis of how anthropologists interpret the race construct. Am Anthropol. 2017;119:422-434.

3. Hasnain-Wynia R, Baker DW. Obtaining data on patient race, ethnicity, and primary language in health care organizations: current challenges and proposed solutions. Health Serv Res. 2006;41:1501-1518.

4. What is the Pantone color system? Pantone website. https://www.pantone.com/color-systems/pantone-color-systems-explained. Accesed May 13, 2020.

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease that can have devastating effects on many organs. Despite the considerable morbidity and mortality associated with SLE, treatment options have been largely unchanged since the 1950s.¹ It was not until the last decade that a new biologic medication was approved, and several other promising treatments currently are being evaluated in clinical trials. Dermatologists are most likely to encounter cutaneous lupus erythematosus (CLE) with or without SLE, which can present with a variety of skin manifestations. Cutaneous lupus erythematosus can have devastating effects on quality of life and can be a visible sign of the internal activity and damage of SLE.^2,3 Although many trials have been completed evaluating SLE treatments, few medications have been evaluated specifically for CLE despite the availability of validated measures of CLE skin activity.⁴ There is a recent shortage of antimalarial medications, the current first-line therapy for CLE, due to both an import alert in the United States on quinacrine placed in 2019 as well as the use of hydroxychloroquine and chloroquine in treating coronavirus disease 2019.^5,6 Due to this shortage, the need for new and effective treatments is more critical than ever, as alternatives to first-line therapy frequently require immunosuppression. We review recent drug approvals for SLE and their efficacy in CLE. We also provide an update on new agents currently being studied to treat this disease.

Belimumab

Belimumab is a B-lymphocyte stimulator–specific inhibitor that was first approved for treatment of SLE in 2011. It was the first monoclonal antibody approved to treat SLE.⁷ B-lymphocyte stimulator plays a critical role in B-cell survival; thus, its inhibition increases apoptosis of autoreactive B cells involved in the pathogenesis of SLE. More recently, belimumab was approved for pediatric SLE in April 2019 based on the PLUTO study, a phase 2 randomized, double-blind study of 93 patients.⁸ Although patients with cutaneous manifestations of lupus were included in trials for belimumab, they lacked CLE-specific outcome measurements to truly evaluate the efficacy in treating skin disease.⁹ This medication currently is not approved by the US Food and Drug Administration (FDA) for CLE; however, it is used off label in some cases for recalcitrant disease.¹⁰

Baricitinib

Baricitinib is a selective and reversible inhibitor of JAK1 and JAK2 that was granted fast-track status by the FDA in December 2018. In a phase 2 trial, baricitinib was superior to placebo plus standard of care, primarily for arthritis and lupus nephritis.¹¹ Although improvement of cutaneous disease was measured as an end point, it did not show significant improvement in disease. The presence of skin disease was high, but the activity of disease was low, which can make it difficult to show meaningful improvement, as there is not much room for patients to objectively improve.¹² Showing meaningful improvement in skin disease often is difficult in phase 2 trials, especially when the trial design is focused on SLE rather than CLE activity. Further studies of baricitinib that include more severe patients with CLE disease are needed to truly understand its effects on the skin.

Lenalidomide

There have been several CLE studies in the last several years surrounding lenalidomide, an analog of thalidomide.^13-15 This molecule has a number of immunomodulatory effects including antiangiogenic effects, increased natural killer cell–dependent cytotoxicity, and cytokine and interleukin inhibition. Lenalidomide is of particular interest in treating CLE, as it was shown to be more potent than thalidomide at low doses and with a better side-effect profile. Multiple small, open-label trials have shown lenalidomide to be both safe and efficacious in the treatment of CLE.^13,14 In addition, iberdomide, a derivative of lenalidomide, recently completed a phase 2 dose-escalation study showing improvement in both SLE and CLE end points.¹⁶ A phase 2b proof-of-concept study currently is underway (ClinicalTrials.gov Identifier NCT03161483).

Monoclonal Antibodies

Many developing therapies target specific components of the type I interferon pathway, which is a primary driver of CLE lesions. Innate immune system pathways involving type I interferon were shown to be active in the pathogenesis of CLE, and levels of interferon correlate with skin disease activity.¹⁷ One molecule in development that targets this pathway is BIIB059, a humanized IgG1 monoclonal antibody that binds to blood dendritic cell antigen 2. This cell surface protein is uniquely expressed on plasmacytoid dendritic cells, which are the main source of type I interferon overproduction in SLE. The binding of this antibody to the blood dendritic cell antigen 2 receptor both blocks type I interferon production and decreases the overall number of active plasmacytoid dendritic cells present.¹⁸ In the completed phase 1b study, a response in cutaneous disease was shown through a reduction in the CLE disease area and severity index score following single-dose administration.¹⁹ More recently, a phase 2 study met primary end points in both SLE and CLE compared to placebo.²⁰

Anifrolumab is a human IgG1k monoclonal antibody that binds to type I interferon receptor, blocking all type I interferon signaling. Following a successful phase 2 trial, it failed to meet its primary end point in its first phase 3 trial.²¹ Several secondary end points suggested a clinical benefit. A second phase 3 trial of 362 patients randomized to treatment with anifrolumab or placebo over 48 weeks showed anifrolumab to be superior to placebo for multiple end points, including the overall disease primary end point as well as a notable reduction in skin activity.²²

Final Thoughts

Outside of the approval of belimumab, there have been no new FDA-approved treatments for SLE since the approval of antimalarial agents nearly 50 years ago. For CLE specifically, there is an even greater scarcity of evidence-based treatments. Recently studied medications, such as belimumab and lenalidomide, are available off label for CLE patients when other options have failed. Recent studies have evaluated the efficacy of these agents in the treatment of CLE using the CLE disease area and severity index.^10,13,14 Enrollment in CLE trials is difficult due to the rarity of the disease, and careful attention must be paid to evaluating skin end points. As experts in CLE and the nuances of these assessments, it is critical that dermatologists be involved in clinical trials. Future SLE trials must consider CLE as an important end point for CLE patients to get access to much-needed novel therapies.

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease that can have devastating effects on many organs. Despite the considerable morbidity and mortality associated with SLE, treatment options have been largely unchanged since the 1950s.¹ It was not until the last decade that a new biologic medication was approved, and several other promising treatments currently are being evaluated in clinical trials. Dermatologists are most likely to encounter cutaneous lupus erythematosus (CLE) with or without SLE, which can present with a variety of skin manifestations. Cutaneous lupus erythematosus can have devastating effects on quality of life and can be a visible sign of the internal activity and damage of SLE.^2,3 Although many trials have been completed evaluating SLE treatments, few medications have been evaluated specifically for CLE despite the availability of validated measures of CLE skin activity.⁴ There is a recent shortage of antimalarial medications, the current first-line therapy for CLE, due to both an import alert in the United States on quinacrine placed in 2019 as well as the use of hydroxychloroquine and chloroquine in treating coronavirus disease 2019.^5,6 Due to this shortage, the need for new and effective treatments is more critical than ever, as alternatives to first-line therapy frequently require immunosuppression. We review recent drug approvals for SLE and their efficacy in CLE. We also provide an update on new agents currently being studied to treat this disease.

Belimumab

Belimumab is a B-lymphocyte stimulator–specific inhibitor that was first approved for treatment of SLE in 2011. It was the first monoclonal antibody approved to treat SLE.⁷ B-lymphocyte stimulator plays a critical role in B-cell survival; thus, its inhibition increases apoptosis of autoreactive B cells involved in the pathogenesis of SLE. More recently, belimumab was approved for pediatric SLE in April 2019 based on the PLUTO study, a phase 2 randomized, double-blind study of 93 patients.⁸ Although patients with cutaneous manifestations of lupus were included in trials for belimumab, they lacked CLE-specific outcome measurements to truly evaluate the efficacy in treating skin disease.⁹ This medication currently is not approved by the US Food and Drug Administration (FDA) for CLE; however, it is used off label in some cases for recalcitrant disease.¹⁰

Baricitinib

Baricitinib is a selective and reversible inhibitor of JAK1 and JAK2 that was granted fast-track status by the FDA in December 2018. In a phase 2 trial, baricitinib was superior to placebo plus standard of care, primarily for arthritis and lupus nephritis.¹¹ Although improvement of cutaneous disease was measured as an end point, it did not show significant improvement in disease. The presence of skin disease was high, but the activity of disease was low, which can make it difficult to show meaningful improvement, as there is not much room for patients to objectively improve.¹² Showing meaningful improvement in skin disease often is difficult in phase 2 trials, especially when the trial design is focused on SLE rather than CLE activity. Further studies of baricitinib that include more severe patients with CLE disease are needed to truly understand its effects on the skin.

Lenalidomide

There have been several CLE studies in the last several years surrounding lenalidomide, an analog of thalidomide.^13-15 This molecule has a number of immunomodulatory effects including antiangiogenic effects, increased natural killer cell–dependent cytotoxicity, and cytokine and interleukin inhibition. Lenalidomide is of particular interest in treating CLE, as it was shown to be more potent than thalidomide at low doses and with a better side-effect profile. Multiple small, open-label trials have shown lenalidomide to be both safe and efficacious in the treatment of CLE.^13,14 In addition, iberdomide, a derivative of lenalidomide, recently completed a phase 2 dose-escalation study showing improvement in both SLE and CLE end points.¹⁶ A phase 2b proof-of-concept study currently is underway (ClinicalTrials.gov Identifier NCT03161483).

Monoclonal Antibodies

Many developing therapies target specific components of the type I interferon pathway, which is a primary driver of CLE lesions. Innate immune system pathways involving type I interferon were shown to be active in the pathogenesis of CLE, and levels of interferon correlate with skin disease activity.¹⁷ One molecule in development that targets this pathway is BIIB059, a humanized IgG1 monoclonal antibody that binds to blood dendritic cell antigen 2. This cell surface protein is uniquely expressed on plasmacytoid dendritic cells, which are the main source of type I interferon overproduction in SLE. The binding of this antibody to the blood dendritic cell antigen 2 receptor both blocks type I interferon production and decreases the overall number of active plasmacytoid dendritic cells present.¹⁸ In the completed phase 1b study, a response in cutaneous disease was shown through a reduction in the CLE disease area and severity index score following single-dose administration.¹⁹ More recently, a phase 2 study met primary end points in both SLE and CLE compared to placebo.²⁰

Anifrolumab is a human IgG1k monoclonal antibody that binds to type I interferon receptor, blocking all type I interferon signaling. Following a successful phase 2 trial, it failed to meet its primary end point in its first phase 3 trial.²¹ Several secondary end points suggested a clinical benefit. A second phase 3 trial of 362 patients randomized to treatment with anifrolumab or placebo over 48 weeks showed anifrolumab to be superior to placebo for multiple end points, including the overall disease primary end point as well as a notable reduction in skin activity.²²

Final Thoughts

Outside of the approval of belimumab, there have been no new FDA-approved treatments for SLE since the approval of antimalarial agents nearly 50 years ago. For CLE specifically, there is an even greater scarcity of evidence-based treatments. Recently studied medications, such as belimumab and lenalidomide, are available off label for CLE patients when other options have failed. Recent studies have evaluated the efficacy of these agents in the treatment of CLE using the CLE disease area and severity index.^10,13,14 Enrollment in CLE trials is difficult due to the rarity of the disease, and careful attention must be paid to evaluating skin end points. As experts in CLE and the nuances of these assessments, it is critical that dermatologists be involved in clinical trials. Future SLE trials must consider CLE as an important end point for CLE patients to get access to much-needed novel therapies.

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease that can have devastating effects on many organs. Despite the considerable morbidity and mortality associated with SLE, treatment options have been largely unchanged since the 1950s.¹ It was not until the last decade that a new biologic medication was approved, and several other promising treatments currently are being evaluated in clinical trials. Dermatologists are most likely to encounter cutaneous lupus erythematosus (CLE) with or without SLE, which can present with a variety of skin manifestations. Cutaneous lupus erythematosus can have devastating effects on quality of life and can be a visible sign of the internal activity and damage of SLE.^2,3 Although many trials have been completed evaluating SLE treatments, few medications have been evaluated specifically for CLE despite the availability of validated measures of CLE skin activity.⁴ There is a recent shortage of antimalarial medications, the current first-line therapy for CLE, due to both an import alert in the United States on quinacrine placed in 2019 as well as the use of hydroxychloroquine and chloroquine in treating coronavirus disease 2019.^5,6 Due to this shortage, the need for new and effective treatments is more critical than ever, as alternatives to first-line therapy frequently require immunosuppression. We review recent drug approvals for SLE and their efficacy in CLE. We also provide an update on new agents currently being studied to treat this disease.

Belimumab

Belimumab is a B-lymphocyte stimulator–specific inhibitor that was first approved for treatment of SLE in 2011. It was the first monoclonal antibody approved to treat SLE.⁷ B-lymphocyte stimulator plays a critical role in B-cell survival; thus, its inhibition increases apoptosis of autoreactive B cells involved in the pathogenesis of SLE. More recently, belimumab was approved for pediatric SLE in April 2019 based on the PLUTO study, a phase 2 randomized, double-blind study of 93 patients.⁸ Although patients with cutaneous manifestations of lupus were included in trials for belimumab, they lacked CLE-specific outcome measurements to truly evaluate the efficacy in treating skin disease.⁹ This medication currently is not approved by the US Food and Drug Administration (FDA) for CLE; however, it is used off label in some cases for recalcitrant disease.¹⁰

Baricitinib

Baricitinib is a selective and reversible inhibitor of JAK1 and JAK2 that was granted fast-track status by the FDA in December 2018. In a phase 2 trial, baricitinib was superior to placebo plus standard of care, primarily for arthritis and lupus nephritis.¹¹ Although improvement of cutaneous disease was measured as an end point, it did not show significant improvement in disease. The presence of skin disease was high, but the activity of disease was low, which can make it difficult to show meaningful improvement, as there is not much room for patients to objectively improve.¹² Showing meaningful improvement in skin disease often is difficult in phase 2 trials, especially when the trial design is focused on SLE rather than CLE activity. Further studies of baricitinib that include more severe patients with CLE disease are needed to truly understand its effects on the skin.

Lenalidomide

There have been several CLE studies in the last several years surrounding lenalidomide, an analog of thalidomide.^13-15 This molecule has a number of immunomodulatory effects including antiangiogenic effects, increased natural killer cell–dependent cytotoxicity, and cytokine and interleukin inhibition. Lenalidomide is of particular interest in treating CLE, as it was shown to be more potent than thalidomide at low doses and with a better side-effect profile. Multiple small, open-label trials have shown lenalidomide to be both safe and efficacious in the treatment of CLE.^13,14 In addition, iberdomide, a derivative of lenalidomide, recently completed a phase 2 dose-escalation study showing improvement in both SLE and CLE end points.¹⁶ A phase 2b proof-of-concept study currently is underway (ClinicalTrials.gov Identifier NCT03161483).

Monoclonal Antibodies

Many developing therapies target specific components of the type I interferon pathway, which is a primary driver of CLE lesions. Innate immune system pathways involving type I interferon were shown to be active in the pathogenesis of CLE, and levels of interferon correlate with skin disease activity.¹⁷ One molecule in development that targets this pathway is BIIB059, a humanized IgG1 monoclonal antibody that binds to blood dendritic cell antigen 2. This cell surface protein is uniquely expressed on plasmacytoid dendritic cells, which are the main source of type I interferon overproduction in SLE. The binding of this antibody to the blood dendritic cell antigen 2 receptor both blocks type I interferon production and decreases the overall number of active plasmacytoid dendritic cells present.¹⁸ In the completed phase 1b study, a response in cutaneous disease was shown through a reduction in the CLE disease area and severity index score following single-dose administration.¹⁹ More recently, a phase 2 study met primary end points in both SLE and CLE compared to placebo.²⁰

Anifrolumab is a human IgG1k monoclonal antibody that binds to type I interferon receptor, blocking all type I interferon signaling. Following a successful phase 2 trial, it failed to meet its primary end point in its first phase 3 trial.²¹ Several secondary end points suggested a clinical benefit. A second phase 3 trial of 362 patients randomized to treatment with anifrolumab or placebo over 48 weeks showed anifrolumab to be superior to placebo for multiple end points, including the overall disease primary end point as well as a notable reduction in skin activity.²²

Final Thoughts

Outside of the approval of belimumab, there have been no new FDA-approved treatments for SLE since the approval of antimalarial agents nearly 50 years ago. For CLE specifically, there is an even greater scarcity of evidence-based treatments. Recently studied medications, such as belimumab and lenalidomide, are available off label for CLE patients when other options have failed. Recent studies have evaluated the efficacy of these agents in the treatment of CLE using the CLE disease area and severity index.^10,13,14 Enrollment in CLE trials is difficult due to the rarity of the disease, and careful attention must be paid to evaluating skin end points. As experts in CLE and the nuances of these assessments, it is critical that dermatologists be involved in clinical trials. Future SLE trials must consider CLE as an important end point for CLE patients to get access to much-needed novel therapies.

Experts may be moving toward accepting cannabis as a useful tool to treat neuropathic pain, a recent debate on the topic suggests. During the debate, one expert argued for, and another against, there being sufficient evidence for the use of cannabis to treat neuropathic pain, but in the end, they agreed that some patients do benefit.

Anatoliy Sizov/Getty Images

The discussion took place at the Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual online meeting because of the COVID-19 pandemic.

The cannabis plant has 460 constituents. The two main components are tetrahydrocannabinol (THC) and cannabidiol (CBD). It can be consumed by swallowing oil extracts, by the sublingual route, or by smoking or eating the plant. Cannabis medications already in use include oral THC (nabilone, dronabinol) and an oral mucosal spray, nabiximols (Sativex).

Arguing that therapeutic cannabis is helpful for neuropathic pain, Elon Eisenberg, MD, professor of neurology and pain medicine, Israel Institute of Technology, Haifa, cited a number of encouraging randomized, controlled trials and meta-analyses of studies on the subject.
 

Opioid substitute

Dr. Eisenberg discussed three relevant articles. One was a 2016 viewpoint article published in JAMA that concluded that “cannabis seems to be a substitute, a rather good one, for opioids,” said Dr. Eisenberg.

A “comprehensive” 440-page review, published by the National Academies Press in 2017, evaluated the evidence to that point and “came to the conclusion there is substantial evidence that cannabis is an effective treatment for chronic pain in adults,” said Dr. Eisenberg.

And a 2018 position paper from the European Pain Federation determined that “the quantity and quality of evidence is such that cannabis-based medicines may be reasonably considered for chronic neuropathic pain,” he said.

He noted that the most recent results from an Israeli prospective cohort registry study that is following more than 851 patients who are taking cannabis over 1 year are positive. Analyses show a steady reduction in pain intensity and improvements in catastrophizing and disability. Importantly, he said, participants are using fewer opioids. However, about 40% of patients in that registry study experienced some adverse event, although most were not serious, said Dr. Eisenberg.
 

Not convinced

Arguing on the other side – that therapeutic cannabis is not helpful for neuropathic pain – was Nadine Attal, MD, PhD, professor of therapeutics and pain at the University Versailles Saint Quentin, France. She questioned the quality of some of the research to date and stressed that studies should consider neuropathic pain as a primary outcome – not spasticity or pain in general. They should also be double-blind, randomized, and placebo controlled, she said.

In addition, she said these studies should enroll at least 10 patients per group and should continue for 3 weeks or longer.

Dr. Attal wondered which of the many plant derivatives (phytocannabinoids) are used in cannabis studies.

She discussed four meta-analyses or reviews on the topic, some of which she said are “heterogeneous” and don’t provide convincing evidence for cannabis use in neuropathic pain.

For example, one review examined only marijuana, and all studies in it were short term. One of the studies in this review was of spasticity. Another review included two studies of cancer pain, and the most positive study in NP used short-term inhaled THC.

“There is no evidence to date that cannabinoids, including nabiximols or oral THC, administered for at least 3 weeks are more effective than placebo in neuropathic pain,” she concluded.
 

Some responders

However, Dr. Attal acknowledged that cannabis might be effective for some patients. In her experience, which has been borne out by some observational studies, patients with paroxysmal pain, or sudden stabbing pain, seem to get more relief from cannabis. “It’s absolutely possible that there’s a subgroup of symptoms or a subgroup of patients with specific symptoms who are much better responders to cannabis than others,” she said.

Asked if patients experience increased pain after withdrawing from cannabis, Dr. Eisenberg said he has observed that many patients stop taking cannabis when they start feeling better, but he hasn’t seen severe withdrawal symptoms.

However, there are other concerns related to cannabis use, said Dr. Eisenberg. A major concern regards driving a vehicle. In Israel, getting behind the wheel is prohibited within 6 hours of using cannabis.

But Dr. Eisenberg pointed out that published data on the safety of cannabis and driving were based on recreational users. “We need to keep in mind that recreational users typically use other substances, so we’re not sure the data is accurate,” he said.

There are increasing reports of stroke, transient ischemic attack, and MI among cannabis users. This is especially concerning because many of these cases involve young male adults who have no risk factors, said Dr. Eisenberg.

One conference delegate asked whether legal issues make it difficult to properly investigate cannabis in large studies. Dr. Eisenberg noted that legal concerns may help explain why there have not been any new randomized, controlled trials for about 2 years. “In the U.S., you can’t do clinical trials; cannabis is still regarded as schedule I substance,” he said.

Some physicians “are reluctant to deal with cannabis unless they get better data,” he said. “Doing research on cannabis seems to be somehow out of the mainstream.” Moreover, the research is difficult to carry out, owing to the complexity of the cannabis plant, which has many constituents. Perhaps it’s a matter of identifying and adding particular components to better demonstrate reduced pain, said Dr. Eisenberg.

Another complicating factor is that bioavailability differs considerably from one patient to another, “sometimes even by 10-fold,” he said.

Dr. Attal’s group will be starting a study next January that will enroll a large sample of patients with neuropathic pain or spasticity. In that study, cannabis will be dispensed through pharmacies and primary care. The aim of the study is “to see how it works in a real-life setting,” she said

Those participating in the virtual session were asked to vote on which side they agreed with. About 57% voted in favor of cannabis use, 14% voted against, and 28% had no opinion.

Dr. Eisenberg has received research grants from Rafa Laboratories, Saga Medical Ltd., Israel Pain Association, and Teva Israel. Dr. Attal has received support from Merck Sharp & Dohme, Sanofi, Ipsen, Novartis, Aptinyx, Air Liquide, Lilly, and Grunenthal.

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

Experts may be moving toward accepting cannabis as a useful tool to treat neuropathic pain, a recent debate on the topic suggests. During the debate, one expert argued for, and another against, there being sufficient evidence for the use of cannabis to treat neuropathic pain, but in the end, they agreed that some patients do benefit.

Anatoliy Sizov/Getty Images

The discussion took place at the Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual online meeting because of the COVID-19 pandemic.

The cannabis plant has 460 constituents. The two main components are tetrahydrocannabinol (THC) and cannabidiol (CBD). It can be consumed by swallowing oil extracts, by the sublingual route, or by smoking or eating the plant. Cannabis medications already in use include oral THC (nabilone, dronabinol) and an oral mucosal spray, nabiximols (Sativex).

Arguing that therapeutic cannabis is helpful for neuropathic pain, Elon Eisenberg, MD, professor of neurology and pain medicine, Israel Institute of Technology, Haifa, cited a number of encouraging randomized, controlled trials and meta-analyses of studies on the subject.
 

Opioid substitute

Dr. Eisenberg discussed three relevant articles. One was a 2016 viewpoint article published in JAMA that concluded that “cannabis seems to be a substitute, a rather good one, for opioids,” said Dr. Eisenberg.

A “comprehensive” 440-page review, published by the National Academies Press in 2017, evaluated the evidence to that point and “came to the conclusion there is substantial evidence that cannabis is an effective treatment for chronic pain in adults,” said Dr. Eisenberg.

And a 2018 position paper from the European Pain Federation determined that “the quantity and quality of evidence is such that cannabis-based medicines may be reasonably considered for chronic neuropathic pain,” he said.

He noted that the most recent results from an Israeli prospective cohort registry study that is following more than 851 patients who are taking cannabis over 1 year are positive. Analyses show a steady reduction in pain intensity and improvements in catastrophizing and disability. Importantly, he said, participants are using fewer opioids. However, about 40% of patients in that registry study experienced some adverse event, although most were not serious, said Dr. Eisenberg.
 

Not convinced

Arguing on the other side – that therapeutic cannabis is not helpful for neuropathic pain – was Nadine Attal, MD, PhD, professor of therapeutics and pain at the University Versailles Saint Quentin, France. She questioned the quality of some of the research to date and stressed that studies should consider neuropathic pain as a primary outcome – not spasticity or pain in general. They should also be double-blind, randomized, and placebo controlled, she said.

In addition, she said these studies should enroll at least 10 patients per group and should continue for 3 weeks or longer.

Dr. Attal wondered which of the many plant derivatives (phytocannabinoids) are used in cannabis studies.

She discussed four meta-analyses or reviews on the topic, some of which she said are “heterogeneous” and don’t provide convincing evidence for cannabis use in neuropathic pain.

For example, one review examined only marijuana, and all studies in it were short term. One of the studies in this review was of spasticity. Another review included two studies of cancer pain, and the most positive study in NP used short-term inhaled THC.

“There is no evidence to date that cannabinoids, including nabiximols or oral THC, administered for at least 3 weeks are more effective than placebo in neuropathic pain,” she concluded.
 

Some responders

However, Dr. Attal acknowledged that cannabis might be effective for some patients. In her experience, which has been borne out by some observational studies, patients with paroxysmal pain, or sudden stabbing pain, seem to get more relief from cannabis. “It’s absolutely possible that there’s a subgroup of symptoms or a subgroup of patients with specific symptoms who are much better responders to cannabis than others,” she said.

Asked if patients experience increased pain after withdrawing from cannabis, Dr. Eisenberg said he has observed that many patients stop taking cannabis when they start feeling better, but he hasn’t seen severe withdrawal symptoms.

However, there are other concerns related to cannabis use, said Dr. Eisenberg. A major concern regards driving a vehicle. In Israel, getting behind the wheel is prohibited within 6 hours of using cannabis.

But Dr. Eisenberg pointed out that published data on the safety of cannabis and driving were based on recreational users. “We need to keep in mind that recreational users typically use other substances, so we’re not sure the data is accurate,” he said.

There are increasing reports of stroke, transient ischemic attack, and MI among cannabis users. This is especially concerning because many of these cases involve young male adults who have no risk factors, said Dr. Eisenberg.

One conference delegate asked whether legal issues make it difficult to properly investigate cannabis in large studies. Dr. Eisenberg noted that legal concerns may help explain why there have not been any new randomized, controlled trials for about 2 years. “In the U.S., you can’t do clinical trials; cannabis is still regarded as schedule I substance,” he said.

Some physicians “are reluctant to deal with cannabis unless they get better data,” he said. “Doing research on cannabis seems to be somehow out of the mainstream.” Moreover, the research is difficult to carry out, owing to the complexity of the cannabis plant, which has many constituents. Perhaps it’s a matter of identifying and adding particular components to better demonstrate reduced pain, said Dr. Eisenberg.

Another complicating factor is that bioavailability differs considerably from one patient to another, “sometimes even by 10-fold,” he said.

Dr. Attal’s group will be starting a study next January that will enroll a large sample of patients with neuropathic pain or spasticity. In that study, cannabis will be dispensed through pharmacies and primary care. The aim of the study is “to see how it works in a real-life setting,” she said

Those participating in the virtual session were asked to vote on which side they agreed with. About 57% voted in favor of cannabis use, 14% voted against, and 28% had no opinion.

Dr. Eisenberg has received research grants from Rafa Laboratories, Saga Medical Ltd., Israel Pain Association, and Teva Israel. Dr. Attal has received support from Merck Sharp & Dohme, Sanofi, Ipsen, Novartis, Aptinyx, Air Liquide, Lilly, and Grunenthal.

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

Experts may be moving toward accepting cannabis as a useful tool to treat neuropathic pain, a recent debate on the topic suggests. During the debate, one expert argued for, and another against, there being sufficient evidence for the use of cannabis to treat neuropathic pain, but in the end, they agreed that some patients do benefit.

Anatoliy Sizov/Getty Images

The discussion took place at the Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual online meeting because of the COVID-19 pandemic.

The cannabis plant has 460 constituents. The two main components are tetrahydrocannabinol (THC) and cannabidiol (CBD). It can be consumed by swallowing oil extracts, by the sublingual route, or by smoking or eating the plant. Cannabis medications already in use include oral THC (nabilone, dronabinol) and an oral mucosal spray, nabiximols (Sativex).

Arguing that therapeutic cannabis is helpful for neuropathic pain, Elon Eisenberg, MD, professor of neurology and pain medicine, Israel Institute of Technology, Haifa, cited a number of encouraging randomized, controlled trials and meta-analyses of studies on the subject.
 

Opioid substitute

Dr. Eisenberg discussed three relevant articles. One was a 2016 viewpoint article published in JAMA that concluded that “cannabis seems to be a substitute, a rather good one, for opioids,” said Dr. Eisenberg.

A “comprehensive” 440-page review, published by the National Academies Press in 2017, evaluated the evidence to that point and “came to the conclusion there is substantial evidence that cannabis is an effective treatment for chronic pain in adults,” said Dr. Eisenberg.

And a 2018 position paper from the European Pain Federation determined that “the quantity and quality of evidence is such that cannabis-based medicines may be reasonably considered for chronic neuropathic pain,” he said.

He noted that the most recent results from an Israeli prospective cohort registry study that is following more than 851 patients who are taking cannabis over 1 year are positive. Analyses show a steady reduction in pain intensity and improvements in catastrophizing and disability. Importantly, he said, participants are using fewer opioids. However, about 40% of patients in that registry study experienced some adverse event, although most were not serious, said Dr. Eisenberg.
 

Not convinced

Arguing on the other side – that therapeutic cannabis is not helpful for neuropathic pain – was Nadine Attal, MD, PhD, professor of therapeutics and pain at the University Versailles Saint Quentin, France. She questioned the quality of some of the research to date and stressed that studies should consider neuropathic pain as a primary outcome – not spasticity or pain in general. They should also be double-blind, randomized, and placebo controlled, she said.

In addition, she said these studies should enroll at least 10 patients per group and should continue for 3 weeks or longer.

Dr. Attal wondered which of the many plant derivatives (phytocannabinoids) are used in cannabis studies.

She discussed four meta-analyses or reviews on the topic, some of which she said are “heterogeneous” and don’t provide convincing evidence for cannabis use in neuropathic pain.

For example, one review examined only marijuana, and all studies in it were short term. One of the studies in this review was of spasticity. Another review included two studies of cancer pain, and the most positive study in NP used short-term inhaled THC.

“There is no evidence to date that cannabinoids, including nabiximols or oral THC, administered for at least 3 weeks are more effective than placebo in neuropathic pain,” she concluded.
 

Some responders

However, Dr. Attal acknowledged that cannabis might be effective for some patients. In her experience, which has been borne out by some observational studies, patients with paroxysmal pain, or sudden stabbing pain, seem to get more relief from cannabis. “It’s absolutely possible that there’s a subgroup of symptoms or a subgroup of patients with specific symptoms who are much better responders to cannabis than others,” she said.

Asked if patients experience increased pain after withdrawing from cannabis, Dr. Eisenberg said he has observed that many patients stop taking cannabis when they start feeling better, but he hasn’t seen severe withdrawal symptoms.

However, there are other concerns related to cannabis use, said Dr. Eisenberg. A major concern regards driving a vehicle. In Israel, getting behind the wheel is prohibited within 6 hours of using cannabis.

But Dr. Eisenberg pointed out that published data on the safety of cannabis and driving were based on recreational users. “We need to keep in mind that recreational users typically use other substances, so we’re not sure the data is accurate,” he said.

There are increasing reports of stroke, transient ischemic attack, and MI among cannabis users. This is especially concerning because many of these cases involve young male adults who have no risk factors, said Dr. Eisenberg.

One conference delegate asked whether legal issues make it difficult to properly investigate cannabis in large studies. Dr. Eisenberg noted that legal concerns may help explain why there have not been any new randomized, controlled trials for about 2 years. “In the U.S., you can’t do clinical trials; cannabis is still regarded as schedule I substance,” he said.

Some physicians “are reluctant to deal with cannabis unless they get better data,” he said. “Doing research on cannabis seems to be somehow out of the mainstream.” Moreover, the research is difficult to carry out, owing to the complexity of the cannabis plant, which has many constituents. Perhaps it’s a matter of identifying and adding particular components to better demonstrate reduced pain, said Dr. Eisenberg.

Another complicating factor is that bioavailability differs considerably from one patient to another, “sometimes even by 10-fold,” he said.

Dr. Attal’s group will be starting a study next January that will enroll a large sample of patients with neuropathic pain or spasticity. In that study, cannabis will be dispensed through pharmacies and primary care. The aim of the study is “to see how it works in a real-life setting,” she said

Those participating in the virtual session were asked to vote on which side they agreed with. About 57% voted in favor of cannabis use, 14% voted against, and 28% had no opinion.

Dr. Eisenberg has received research grants from Rafa Laboratories, Saga Medical Ltd., Israel Pain Association, and Teva Israel. Dr. Attal has received support from Merck Sharp & Dohme, Sanofi, Ipsen, Novartis, Aptinyx, Air Liquide, Lilly, and Grunenthal.

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

Having a diagnosis of atopic dermatitis (AD) was associated with a greater risk of developing anxiety, depression, bipolar disorder, and other major neuropsychiatric disorders in children, adolescents, and adults, according to a study presented at the annual meeting of the Society for Investigative Dermatology, held virtually.

“The risk increase ranges from as low as 5% up to 59%, depending on the outcome, with generally greater effects observed among the adults,” Joy Wan, MD, a postdoctoral dermatology fellow at the University of Pennsylvania, Philadelphia, said in her presentation. The risk was independent of other atopic disease, gender, age, and socioeconomic status.

Dr. Wan and colleagues conducted a cohort study of patients with AD in the United Kingdom using data from the Health Improvement Network (THIN) electronic records database, matching AD patients in THIN with up to five patients without AD, similar in age and also registered to general practices. The researchers validated AD disease status using an algorithm that identified patients with a diagnostic code and two therapy codes related to AD. Outcomes of interest included anxiety, depression, bipolar disorder, obsessive-compulsive disorder, ADHD, schizophrenia, and autism. Patients entered into the cohort when they were diagnosed with AD, registered by a practice, or when data from a practice was reported to THIN. The researchers stopped following patients when they developed a neuropsychiatric outcome of interest, left a practice, died, or when the study ended.

“Previous studies have found associations between atopic dermatitis and anxiety, depression, and attention-deficit/hyperactivity disorder. However, many previous studies had been cross-sectional and they were unable to evaluate the directionality of association between atopic dermatitis and neuropsychiatric outcomes, while other previous studies have relied on the self-report of atopic dermatitis and outcomes as well,” Dr. Wan said. “Thus, longitudinal studies, using validated measures of atopic dermatitis, and those that include the entire age span, are really needed.”

Overall, 434,859 children and adolescents under aged 18 with AD in the THIN database were matched to 1,983,589 controls, and 644,802 adults with AD were matched to almost 2,900,000 adults without AD. In the pediatric group, demographics were mostly balanced between children with and without AD: the average age ranged between about 5 and almost 6 years. In pediatric patients with AD, there was a higher rate of allergic rhinitis (6.2% vs. 4%) and asthma (13.5% vs. 9.3%) than in the control group.

For adults, the average age was about 48 years in both groups. Compared with patients who did not have AD, adults with AD also had higher rates of allergic rhinitis (15.2% vs. 9.6%) and asthma (19.9% vs. 12.6%).

After adjusting for age, gender, socioeconomic status, asthma, and allergic rhinitis, Dr. Wan and colleagues found greater rates of bipolar disorder (hazard ratio, 1.34; 95% confidence interval, 1.09-1.65), obsessive-compulsive disorder (HR, 1.30; 95% CI, 1.21-1.41), anxiety (HR, 1.09; 95% CI, 1.07-1.11), and depression (HR, 1.06; 95% CI, 1.04-1.08) among children and adolescents with AD, compared with controls.

In the adult cohort, a diagnosis of AD was associated with an increased risk of autism (HR, 1.53; 95% CI, 1.30-1.80), obsessive-compulsive disorder (HR, 1.49; 95% CI, 1.40-1.59), ADHD (HR, 1.31; 95% CI, 1.13-1.53), anxiety (HR, 1.17; 95% CI, 1.15-1.18), depression (HR, 1.15; 95% CI, 1.14-1.16), and bipolar disorder (HR, 1.12; 95% CI, 1.04-1.21), after adjusting for age, gender, socioeconomic status, asthma, and allergic rhinitis.

One reason for the increased associations among the adults, even for ADHD and autism, which are more characteristically diagnosed in childhood, Dr. Wan said, is that, since they looked at incident outcomes, “many children may already have had these prevalent comorbidities at the time of the entry in the cohort.”

She noted that the study may have observation bias or unknown confounders, but she hopes these results raise awareness of the association between AD and neuropsychiatric disorders, although more research is needed to determine how AD severity affects neuropsychiatric outcomes. “Additional work is needed to really understand the mechanisms that drive these associations, whether it’s mediated through symptoms of atopic dermatitis such as itch and poor sleep, or potentially the stigma of having a chronic skin disease, or perhaps shared pathophysiology between atopic dermatitis and these neuropsychiatric diseases,” she said.

The study was funded by a grant from Pfizer. Dr. Wan reports receiving research funding from Pfizer paid to the University of Pennsylvania.

Having a diagnosis of atopic dermatitis (AD) was associated with a greater risk of developing anxiety, depression, bipolar disorder, and other major neuropsychiatric disorders in children, adolescents, and adults, according to a study presented at the annual meeting of the Society for Investigative Dermatology, held virtually.

“The risk increase ranges from as low as 5% up to 59%, depending on the outcome, with generally greater effects observed among the adults,” Joy Wan, MD, a postdoctoral dermatology fellow at the University of Pennsylvania, Philadelphia, said in her presentation. The risk was independent of other atopic disease, gender, age, and socioeconomic status.

Dr. Wan and colleagues conducted a cohort study of patients with AD in the United Kingdom using data from the Health Improvement Network (THIN) electronic records database, matching AD patients in THIN with up to five patients without AD, similar in age and also registered to general practices. The researchers validated AD disease status using an algorithm that identified patients with a diagnostic code and two therapy codes related to AD. Outcomes of interest included anxiety, depression, bipolar disorder, obsessive-compulsive disorder, ADHD, schizophrenia, and autism. Patients entered into the cohort when they were diagnosed with AD, registered by a practice, or when data from a practice was reported to THIN. The researchers stopped following patients when they developed a neuropsychiatric outcome of interest, left a practice, died, or when the study ended.

“Previous studies have found associations between atopic dermatitis and anxiety, depression, and attention-deficit/hyperactivity disorder. However, many previous studies had been cross-sectional and they were unable to evaluate the directionality of association between atopic dermatitis and neuropsychiatric outcomes, while other previous studies have relied on the self-report of atopic dermatitis and outcomes as well,” Dr. Wan said. “Thus, longitudinal studies, using validated measures of atopic dermatitis, and those that include the entire age span, are really needed.”

Overall, 434,859 children and adolescents under aged 18 with AD in the THIN database were matched to 1,983,589 controls, and 644,802 adults with AD were matched to almost 2,900,000 adults without AD. In the pediatric group, demographics were mostly balanced between children with and without AD: the average age ranged between about 5 and almost 6 years. In pediatric patients with AD, there was a higher rate of allergic rhinitis (6.2% vs. 4%) and asthma (13.5% vs. 9.3%) than in the control group.

For adults, the average age was about 48 years in both groups. Compared with patients who did not have AD, adults with AD also had higher rates of allergic rhinitis (15.2% vs. 9.6%) and asthma (19.9% vs. 12.6%).

After adjusting for age, gender, socioeconomic status, asthma, and allergic rhinitis, Dr. Wan and colleagues found greater rates of bipolar disorder (hazard ratio, 1.34; 95% confidence interval, 1.09-1.65), obsessive-compulsive disorder (HR, 1.30; 95% CI, 1.21-1.41), anxiety (HR, 1.09; 95% CI, 1.07-1.11), and depression (HR, 1.06; 95% CI, 1.04-1.08) among children and adolescents with AD, compared with controls.

In the adult cohort, a diagnosis of AD was associated with an increased risk of autism (HR, 1.53; 95% CI, 1.30-1.80), obsessive-compulsive disorder (HR, 1.49; 95% CI, 1.40-1.59), ADHD (HR, 1.31; 95% CI, 1.13-1.53), anxiety (HR, 1.17; 95% CI, 1.15-1.18), depression (HR, 1.15; 95% CI, 1.14-1.16), and bipolar disorder (HR, 1.12; 95% CI, 1.04-1.21), after adjusting for age, gender, socioeconomic status, asthma, and allergic rhinitis.

One reason for the increased associations among the adults, even for ADHD and autism, which are more characteristically diagnosed in childhood, Dr. Wan said, is that, since they looked at incident outcomes, “many children may already have had these prevalent comorbidities at the time of the entry in the cohort.”

She noted that the study may have observation bias or unknown confounders, but she hopes these results raise awareness of the association between AD and neuropsychiatric disorders, although more research is needed to determine how AD severity affects neuropsychiatric outcomes. “Additional work is needed to really understand the mechanisms that drive these associations, whether it’s mediated through symptoms of atopic dermatitis such as itch and poor sleep, or potentially the stigma of having a chronic skin disease, or perhaps shared pathophysiology between atopic dermatitis and these neuropsychiatric diseases,” she said.

The study was funded by a grant from Pfizer. Dr. Wan reports receiving research funding from Pfizer paid to the University of Pennsylvania.

Having a diagnosis of atopic dermatitis (AD) was associated with a greater risk of developing anxiety, depression, bipolar disorder, and other major neuropsychiatric disorders in children, adolescents, and adults, according to a study presented at the annual meeting of the Society for Investigative Dermatology, held virtually.

“The risk increase ranges from as low as 5% up to 59%, depending on the outcome, with generally greater effects observed among the adults,” Joy Wan, MD, a postdoctoral dermatology fellow at the University of Pennsylvania, Philadelphia, said in her presentation. The risk was independent of other atopic disease, gender, age, and socioeconomic status.

Dr. Wan and colleagues conducted a cohort study of patients with AD in the United Kingdom using data from the Health Improvement Network (THIN) electronic records database, matching AD patients in THIN with up to five patients without AD, similar in age and also registered to general practices. The researchers validated AD disease status using an algorithm that identified patients with a diagnostic code and two therapy codes related to AD. Outcomes of interest included anxiety, depression, bipolar disorder, obsessive-compulsive disorder, ADHD, schizophrenia, and autism. Patients entered into the cohort when they were diagnosed with AD, registered by a practice, or when data from a practice was reported to THIN. The researchers stopped following patients when they developed a neuropsychiatric outcome of interest, left a practice, died, or when the study ended.

“Previous studies have found associations between atopic dermatitis and anxiety, depression, and attention-deficit/hyperactivity disorder. However, many previous studies had been cross-sectional and they were unable to evaluate the directionality of association between atopic dermatitis and neuropsychiatric outcomes, while other previous studies have relied on the self-report of atopic dermatitis and outcomes as well,” Dr. Wan said. “Thus, longitudinal studies, using validated measures of atopic dermatitis, and those that include the entire age span, are really needed.”

Overall, 434,859 children and adolescents under aged 18 with AD in the THIN database were matched to 1,983,589 controls, and 644,802 adults with AD were matched to almost 2,900,000 adults without AD. In the pediatric group, demographics were mostly balanced between children with and without AD: the average age ranged between about 5 and almost 6 years. In pediatric patients with AD, there was a higher rate of allergic rhinitis (6.2% vs. 4%) and asthma (13.5% vs. 9.3%) than in the control group.

For adults, the average age was about 48 years in both groups. Compared with patients who did not have AD, adults with AD also had higher rates of allergic rhinitis (15.2% vs. 9.6%) and asthma (19.9% vs. 12.6%).

After adjusting for age, gender, socioeconomic status, asthma, and allergic rhinitis, Dr. Wan and colleagues found greater rates of bipolar disorder (hazard ratio, 1.34; 95% confidence interval, 1.09-1.65), obsessive-compulsive disorder (HR, 1.30; 95% CI, 1.21-1.41), anxiety (HR, 1.09; 95% CI, 1.07-1.11), and depression (HR, 1.06; 95% CI, 1.04-1.08) among children and adolescents with AD, compared with controls.

In the adult cohort, a diagnosis of AD was associated with an increased risk of autism (HR, 1.53; 95% CI, 1.30-1.80), obsessive-compulsive disorder (HR, 1.49; 95% CI, 1.40-1.59), ADHD (HR, 1.31; 95% CI, 1.13-1.53), anxiety (HR, 1.17; 95% CI, 1.15-1.18), depression (HR, 1.15; 95% CI, 1.14-1.16), and bipolar disorder (HR, 1.12; 95% CI, 1.04-1.21), after adjusting for age, gender, socioeconomic status, asthma, and allergic rhinitis.

One reason for the increased associations among the adults, even for ADHD and autism, which are more characteristically diagnosed in childhood, Dr. Wan said, is that, since they looked at incident outcomes, “many children may already have had these prevalent comorbidities at the time of the entry in the cohort.”

She noted that the study may have observation bias or unknown confounders, but she hopes these results raise awareness of the association between AD and neuropsychiatric disorders, although more research is needed to determine how AD severity affects neuropsychiatric outcomes. “Additional work is needed to really understand the mechanisms that drive these associations, whether it’s mediated through symptoms of atopic dermatitis such as itch and poor sleep, or potentially the stigma of having a chronic skin disease, or perhaps shared pathophysiology between atopic dermatitis and these neuropsychiatric diseases,” she said.

The study was funded by a grant from Pfizer. Dr. Wan reports receiving research funding from Pfizer paid to the University of Pennsylvania.

Neuroimaging of patients with progressive multiple sclerosis (MS) shows that physical behavioral change therapy, specifically, constraint-induced movement therapy (CIMT), leads to improvement in neuroplasticity, compared with alternative interventions with medicines. “The findings suggest for the first time that physical behavioral change therapy can significantly stimulate cortical neuroplasticity in a degenerative central nervous system disorder,” said the authors of research presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

CIMT, an intervention involving 3.5 hours/day of therapist-supervised treatment over 10 consecutive weekdays, has been shown to significantly improve paretic limb use for patients with progressive MS, and the effects are long lasting.

For patients with asymmetric upper limb nonuse, the treatment “is highly successful for promoting increased use by the more-affected arm for everyday activities,” said lead author Victor W. Mark, MD, an associate professor and medical director of the Constraint-Induced Movement Therapy Research Programs at the University of Alabama at Birmingham. “The improvements after CIMT can be found to remain as much as 1 year after the completion of the treatment, and even later. That by itself is novel for MS,” he said.

The team’s previous research in Neurorehabilitation and Neural Repair showed that the CIMT intervention is associated with statistically significant changes in white matter integrity in the brain. In this new study, Dr. Mark and colleagues sought to determine whether the effects would also translate to improvements in cortical gray matter.
 

Promoting neuroplasticity, improving motor function

For their study, they enrolled 20 adults with chronic MS who were matched with respect to unilateral arm disability. The participants were randomly assigned to receive 35 hours of either CIMT or a holistic complementary alternative medicine program, which included yoga, aquatic therapy, massage, and/or relaxation techniques, over the course of 2 weeks.

Both groups expressed the same degree of expectancy of benefits from the intervention. Those who received CIMT showed a significantly larger effect size on the Motor Activity Log, a measure that has been validated against real-world upper-limb accelerometry, compared with the control group (d = 3.2, vs. d = 0.7).

Imaging with tensor-based morphometry showed an increase in the thickness of the primary motor cortex in patients who underwent CIMT but not those who received the alternative medicine treatment. Furthermore, a change in the primary motor cortex was observed in the CIMT group on voxel-based morphometry, suggesting an increase in cortical density or volume, or both. Similar changes were not seen in the alternative medicine group.

“We evaluated the density of the brain cortical gray area before and after treatment, and we found increased gray matter in the area of the brain that is concentrated with voluntary limb movement (the motor cortex),” Dr. Mark said. “As in (previous) studies, we did not find such changes, or any changes, after the other form of treatment,” he said.

The results are important, Dr. Mark noted, “because CIMT seems to specifically promote neuroplasticity changes that appear to be healthy, for what is otherwise a chronically progressive degenerative neurological disorder.”

In addition to the improvements in MS, CIMT has led to improvement in motor function for patients who have experienced other central nervous system injuries, including stroke, traumatic brain injury, cerebral palsy, and, in musicians, focal hand dystonia.

The new findings offer intriguing insights into the effects in progressive MS, commented rehabilitation specialist Patricia Bobryk, MHS, a physical therapist with the UCHealth Yampa Valley Medical Center, in Colorado Springs.

“There is more evidence for CIMT in the area of stroke, which is more acute onset and with more potential recovery, especially early on, so this is exciting initial work in terms of MS,” she said.

“If we’re trying to find new avenues in the brain for better pathways, rather than using something that’s damaged in MS, it makes perfect sense that CIMT really forces and drives those connections, because you’re doing a repetitive, high-intensity patterning throughout the day, so you set up that environment for things to progress, especially in motor functioning,” she said.
 

Repetition, ‘prevention of compensation’

CIMT was developed at the University of Alabama, Birmingham, 30 years ago and involves four components. The first, described as “massed practice,” involves intensive, repetitive arm movements of the affected arm. The second component involves “shaping,” in which the patient is encouraged to perform his or her best attempts at the movements.

For the third component, described as “prevention of compensation,” the patient’s more-functional arm is inhibited from being used in everyday activities by wearing a padded mitt.

“This permits the patient to brace him- or herself whenever needed, but the better hand nonetheless lacks the dexterity to take over the activities that should be performed by the worse arm,” Dr. Mark explained.

“The patient wears the padded mitt after hours, too, except when using water or when sleeping,” he said.

The fourth component is a set of behavioral enforcement techniques involving goal-setting; daily interviews and discussion of progress and challenges; nightly homework; diary keeping; and telephone follow-up.

Dr. Mark noted that the intervention could have benefits that are secondary to motor and movement function. “We consider that the improvement of limb activity in a motor-challenged person with MS could afford a way to offset the deleterious effects of inactivity that can occur, such as weight gain, diabetes, osteoporosis, cardiac disease, and other conditions associated with prolonged inactivity,” he said.

Although it was developed at the University of Alabama, CIMT is currently more widely practiced in Europe than the United States, likely because of differences in care support, which in Europe is provided through socialized medicine, Dr. Mark pointed out.

Although the detailed methods for conducting CIMT are published in peer-reviewed journals, Dr. Mark recommends hands-on and interactive teaching. Such training is offered to clinicians and affiliated physical therapists and occupational therapists through Mark’s program at the University of Alabama in a semiannual, week-long training course, which includes hands-on treatment practice with actual patients.
 

Proof of principle

In further commenting on the study, Kathy M. Zackowski, PhD, of the National MS Society, said the findings provide an intriguing proof of concept that should be tested in a larger cohort. “The question of how much a behavioral (therapy) can impact true brain structural change or change in the pathologic mechanism is intriguing and of high importance,” she said.

“It is important to take this information as ‘proof of principle’ of the importance of CIMT for improving upper limb activity,” according to Dr. Zackowski, senior director, patient management, care and rehabilitation research at the society.

“Importantly, this team needs to move forward testing their hypothesis in a larger randomized, clinical trial with a full control group in order to show causal evidence that one intervention caused the structural brain changes seen,” she said in an interview.

Dr. Zackowski added that a caveat of CIMT is that the approach assumes one limb is more impaired than the other, which is always the case in stroke but is true only in some cases of MS. “Therefore, this method may not be effective for everyone with MS, but offers another option for tailoring an intervention to a person’s abilities and interests,” she said.

“Another important detail is that CIMT is also being explored for lower extremity use,” she added. “This is exciting, as lower extremity dysfunction is a very common problem in MS, and may be useful in treating walking disability.”

The authors, Ms. Bobryk, and Dr. Zackowski have disclosed no relevant financial relationships.

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

Neuroimaging of patients with progressive multiple sclerosis (MS) shows that physical behavioral change therapy, specifically, constraint-induced movement therapy (CIMT), leads to improvement in neuroplasticity, compared with alternative interventions with medicines. “The findings suggest for the first time that physical behavioral change therapy can significantly stimulate cortical neuroplasticity in a degenerative central nervous system disorder,” said the authors of research presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

CIMT, an intervention involving 3.5 hours/day of therapist-supervised treatment over 10 consecutive weekdays, has been shown to significantly improve paretic limb use for patients with progressive MS, and the effects are long lasting.

For patients with asymmetric upper limb nonuse, the treatment “is highly successful for promoting increased use by the more-affected arm for everyday activities,” said lead author Victor W. Mark, MD, an associate professor and medical director of the Constraint-Induced Movement Therapy Research Programs at the University of Alabama at Birmingham. “The improvements after CIMT can be found to remain as much as 1 year after the completion of the treatment, and even later. That by itself is novel for MS,” he said.

The team’s previous research in Neurorehabilitation and Neural Repair showed that the CIMT intervention is associated with statistically significant changes in white matter integrity in the brain. In this new study, Dr. Mark and colleagues sought to determine whether the effects would also translate to improvements in cortical gray matter.
 

Promoting neuroplasticity, improving motor function

For their study, they enrolled 20 adults with chronic MS who were matched with respect to unilateral arm disability. The participants were randomly assigned to receive 35 hours of either CIMT or a holistic complementary alternative medicine program, which included yoga, aquatic therapy, massage, and/or relaxation techniques, over the course of 2 weeks.

Both groups expressed the same degree of expectancy of benefits from the intervention. Those who received CIMT showed a significantly larger effect size on the Motor Activity Log, a measure that has been validated against real-world upper-limb accelerometry, compared with the control group (d = 3.2, vs. d = 0.7).

Imaging with tensor-based morphometry showed an increase in the thickness of the primary motor cortex in patients who underwent CIMT but not those who received the alternative medicine treatment. Furthermore, a change in the primary motor cortex was observed in the CIMT group on voxel-based morphometry, suggesting an increase in cortical density or volume, or both. Similar changes were not seen in the alternative medicine group.

“We evaluated the density of the brain cortical gray area before and after treatment, and we found increased gray matter in the area of the brain that is concentrated with voluntary limb movement (the motor cortex),” Dr. Mark said. “As in (previous) studies, we did not find such changes, or any changes, after the other form of treatment,” he said.

The results are important, Dr. Mark noted, “because CIMT seems to specifically promote neuroplasticity changes that appear to be healthy, for what is otherwise a chronically progressive degenerative neurological disorder.”

In addition to the improvements in MS, CIMT has led to improvement in motor function for patients who have experienced other central nervous system injuries, including stroke, traumatic brain injury, cerebral palsy, and, in musicians, focal hand dystonia.

The new findings offer intriguing insights into the effects in progressive MS, commented rehabilitation specialist Patricia Bobryk, MHS, a physical therapist with the UCHealth Yampa Valley Medical Center, in Colorado Springs.

“There is more evidence for CIMT in the area of stroke, which is more acute onset and with more potential recovery, especially early on, so this is exciting initial work in terms of MS,” she said.

“If we’re trying to find new avenues in the brain for better pathways, rather than using something that’s damaged in MS, it makes perfect sense that CIMT really forces and drives those connections, because you’re doing a repetitive, high-intensity patterning throughout the day, so you set up that environment for things to progress, especially in motor functioning,” she said.
 

Repetition, ‘prevention of compensation’

CIMT was developed at the University of Alabama, Birmingham, 30 years ago and involves four components. The first, described as “massed practice,” involves intensive, repetitive arm movements of the affected arm. The second component involves “shaping,” in which the patient is encouraged to perform his or her best attempts at the movements.

For the third component, described as “prevention of compensation,” the patient’s more-functional arm is inhibited from being used in everyday activities by wearing a padded mitt.

“This permits the patient to brace him- or herself whenever needed, but the better hand nonetheless lacks the dexterity to take over the activities that should be performed by the worse arm,” Dr. Mark explained.

“The patient wears the padded mitt after hours, too, except when using water or when sleeping,” he said.

The fourth component is a set of behavioral enforcement techniques involving goal-setting; daily interviews and discussion of progress and challenges; nightly homework; diary keeping; and telephone follow-up.

Dr. Mark noted that the intervention could have benefits that are secondary to motor and movement function. “We consider that the improvement of limb activity in a motor-challenged person with MS could afford a way to offset the deleterious effects of inactivity that can occur, such as weight gain, diabetes, osteoporosis, cardiac disease, and other conditions associated with prolonged inactivity,” he said.

Although it was developed at the University of Alabama, CIMT is currently more widely practiced in Europe than the United States, likely because of differences in care support, which in Europe is provided through socialized medicine, Dr. Mark pointed out.

Although the detailed methods for conducting CIMT are published in peer-reviewed journals, Dr. Mark recommends hands-on and interactive teaching. Such training is offered to clinicians and affiliated physical therapists and occupational therapists through Mark’s program at the University of Alabama in a semiannual, week-long training course, which includes hands-on treatment practice with actual patients.
 

Proof of principle

In further commenting on the study, Kathy M. Zackowski, PhD, of the National MS Society, said the findings provide an intriguing proof of concept that should be tested in a larger cohort. “The question of how much a behavioral (therapy) can impact true brain structural change or change in the pathologic mechanism is intriguing and of high importance,” she said.

“It is important to take this information as ‘proof of principle’ of the importance of CIMT for improving upper limb activity,” according to Dr. Zackowski, senior director, patient management, care and rehabilitation research at the society.

“Importantly, this team needs to move forward testing their hypothesis in a larger randomized, clinical trial with a full control group in order to show causal evidence that one intervention caused the structural brain changes seen,” she said in an interview.

Dr. Zackowski added that a caveat of CIMT is that the approach assumes one limb is more impaired than the other, which is always the case in stroke but is true only in some cases of MS. “Therefore, this method may not be effective for everyone with MS, but offers another option for tailoring an intervention to a person’s abilities and interests,” she said.

“Another important detail is that CIMT is also being explored for lower extremity use,” she added. “This is exciting, as lower extremity dysfunction is a very common problem in MS, and may be useful in treating walking disability.”

The authors, Ms. Bobryk, and Dr. Zackowski have disclosed no relevant financial relationships.

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

Neuroimaging of patients with progressive multiple sclerosis (MS) shows that physical behavioral change therapy, specifically, constraint-induced movement therapy (CIMT), leads to improvement in neuroplasticity, compared with alternative interventions with medicines. “The findings suggest for the first time that physical behavioral change therapy can significantly stimulate cortical neuroplasticity in a degenerative central nervous system disorder,” said the authors of research presented at the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

CIMT, an intervention involving 3.5 hours/day of therapist-supervised treatment over 10 consecutive weekdays, has been shown to significantly improve paretic limb use for patients with progressive MS, and the effects are long lasting.

For patients with asymmetric upper limb nonuse, the treatment “is highly successful for promoting increased use by the more-affected arm for everyday activities,” said lead author Victor W. Mark, MD, an associate professor and medical director of the Constraint-Induced Movement Therapy Research Programs at the University of Alabama at Birmingham. “The improvements after CIMT can be found to remain as much as 1 year after the completion of the treatment, and even later. That by itself is novel for MS,” he said.

The team’s previous research in Neurorehabilitation and Neural Repair showed that the CIMT intervention is associated with statistically significant changes in white matter integrity in the brain. In this new study, Dr. Mark and colleagues sought to determine whether the effects would also translate to improvements in cortical gray matter.
 

Promoting neuroplasticity, improving motor function

For their study, they enrolled 20 adults with chronic MS who were matched with respect to unilateral arm disability. The participants were randomly assigned to receive 35 hours of either CIMT or a holistic complementary alternative medicine program, which included yoga, aquatic therapy, massage, and/or relaxation techniques, over the course of 2 weeks.

Both groups expressed the same degree of expectancy of benefits from the intervention. Those who received CIMT showed a significantly larger effect size on the Motor Activity Log, a measure that has been validated against real-world upper-limb accelerometry, compared with the control group (d = 3.2, vs. d = 0.7).

Imaging with tensor-based morphometry showed an increase in the thickness of the primary motor cortex in patients who underwent CIMT but not those who received the alternative medicine treatment. Furthermore, a change in the primary motor cortex was observed in the CIMT group on voxel-based morphometry, suggesting an increase in cortical density or volume, or both. Similar changes were not seen in the alternative medicine group.

“We evaluated the density of the brain cortical gray area before and after treatment, and we found increased gray matter in the area of the brain that is concentrated with voluntary limb movement (the motor cortex),” Dr. Mark said. “As in (previous) studies, we did not find such changes, or any changes, after the other form of treatment,” he said.

The results are important, Dr. Mark noted, “because CIMT seems to specifically promote neuroplasticity changes that appear to be healthy, for what is otherwise a chronically progressive degenerative neurological disorder.”

In addition to the improvements in MS, CIMT has led to improvement in motor function for patients who have experienced other central nervous system injuries, including stroke, traumatic brain injury, cerebral palsy, and, in musicians, focal hand dystonia.

The new findings offer intriguing insights into the effects in progressive MS, commented rehabilitation specialist Patricia Bobryk, MHS, a physical therapist with the UCHealth Yampa Valley Medical Center, in Colorado Springs.

“There is more evidence for CIMT in the area of stroke, which is more acute onset and with more potential recovery, especially early on, so this is exciting initial work in terms of MS,” she said.

“If we’re trying to find new avenues in the brain for better pathways, rather than using something that’s damaged in MS, it makes perfect sense that CIMT really forces and drives those connections, because you’re doing a repetitive, high-intensity patterning throughout the day, so you set up that environment for things to progress, especially in motor functioning,” she said.
 

Repetition, ‘prevention of compensation’

CIMT was developed at the University of Alabama, Birmingham, 30 years ago and involves four components. The first, described as “massed practice,” involves intensive, repetitive arm movements of the affected arm. The second component involves “shaping,” in which the patient is encouraged to perform his or her best attempts at the movements.

For the third component, described as “prevention of compensation,” the patient’s more-functional arm is inhibited from being used in everyday activities by wearing a padded mitt.

“This permits the patient to brace him- or herself whenever needed, but the better hand nonetheless lacks the dexterity to take over the activities that should be performed by the worse arm,” Dr. Mark explained.

“The patient wears the padded mitt after hours, too, except when using water or when sleeping,” he said.

The fourth component is a set of behavioral enforcement techniques involving goal-setting; daily interviews and discussion of progress and challenges; nightly homework; diary keeping; and telephone follow-up.

Dr. Mark noted that the intervention could have benefits that are secondary to motor and movement function. “We consider that the improvement of limb activity in a motor-challenged person with MS could afford a way to offset the deleterious effects of inactivity that can occur, such as weight gain, diabetes, osteoporosis, cardiac disease, and other conditions associated with prolonged inactivity,” he said.

Although it was developed at the University of Alabama, CIMT is currently more widely practiced in Europe than the United States, likely because of differences in care support, which in Europe is provided through socialized medicine, Dr. Mark pointed out.

Although the detailed methods for conducting CIMT are published in peer-reviewed journals, Dr. Mark recommends hands-on and interactive teaching. Such training is offered to clinicians and affiliated physical therapists and occupational therapists through Mark’s program at the University of Alabama in a semiannual, week-long training course, which includes hands-on treatment practice with actual patients.
 

Proof of principle

In further commenting on the study, Kathy M. Zackowski, PhD, of the National MS Society, said the findings provide an intriguing proof of concept that should be tested in a larger cohort. “The question of how much a behavioral (therapy) can impact true brain structural change or change in the pathologic mechanism is intriguing and of high importance,” she said.

“It is important to take this information as ‘proof of principle’ of the importance of CIMT for improving upper limb activity,” according to Dr. Zackowski, senior director, patient management, care and rehabilitation research at the society.

“Importantly, this team needs to move forward testing their hypothesis in a larger randomized, clinical trial with a full control group in order to show causal evidence that one intervention caused the structural brain changes seen,” she said in an interview.

Dr. Zackowski added that a caveat of CIMT is that the approach assumes one limb is more impaired than the other, which is always the case in stroke but is true only in some cases of MS. “Therefore, this method may not be effective for everyone with MS, but offers another option for tailoring an intervention to a person’s abilities and interests,” she said.

“Another important detail is that CIMT is also being explored for lower extremity use,” she added. “This is exciting, as lower extremity dysfunction is a very common problem in MS, and may be useful in treating walking disability.”

The authors, Ms. Bobryk, and Dr. Zackowski have disclosed no relevant financial relationships.

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

I grew up in a family that was pretty much devoid of physical demonstrations of affection. I certainly felt that my folks loved me, but there was no hugging. I don’t recall ever seeing my parents kiss or touch each other. My dad would occasionally physically tease my mother. For example, I can remember one incident at the dinner table when he was playfully and gently laying a hand on my mother’s arm just as she was raising her fork to her mouth. After about three of these gentle holds, she lifted her water glass and tossed its contents in his face. This was the full extent of physicality in our family.

kate_sept2004/thinkstock

It wasn’t just my parents. I can’t remember aunts or uncles or cousins ever hugging us when we met. Grandmothers of course would request a hug. I never knew either of my grandfathers, but I suspect they would not have been the hugging kind.

I never felt I was missing out on anything, because in the generally WASPish atmosphere of the community in which I grew up I saw very few public displays of affection. But somewhere over time, hugging crept into the American repertoire of expression. This incursion may have been a ripple effect from the flower power, free love hippiedom of the ‘60s and ‘70s. Or it may have been a symptom of globalization as Americans became more familiar with other cultures in which physical expression was more common.

Whatever the reason for the more widespread adoption of hugging in our social vocabulary with my somewhat physically impoverished upbringing, it took me longer than most folks to comfortably include it in my greeting options. Although I may have come to the dance late, I have fully adopted hugging as a way to greet people with whom I have more than a passing acquaintance.

In fact, the ability to comfortably hug former coworkers, old friends I haven’t seen in years, and parents with whom I had shared a particularly troublesome child is what I miss most about the restrictions that have come with the COVID-19 pandemic. Now when I meet folks in the grocery store with whom I share a special affection that magnetic spark still leaps between our eyes, just visible over our face masks, but mentally and physically we take a step back and say to ourselves that this hug shouldn’t happen and it isn’t going to happen. And that makes me sad.

One of the great perks of practicing pediatrics in a small town and then remaining there in retirement is that nearly every week I encounter one or two people with whom I have a long and sometimes emotionally charged relationship. Nurses with whom I sweated over difficult delivery room resuscitations. Parents for whom their anxiety was getting in the way of their ability to parent. Parents and caregivers of complex multiply disabled children who are now adults. Peers who have lost a spouse or a child. I’m sure you have your own list of people who send off that we-need-to-hug spark.

I can envision a day sometime in the relatively near future that I will be able to hug my two grandchildren whom I haven’t hugged even though they live a short 10-minute walk away. But I have trouble imagining when I will again be able to enjoy and be enriched by those special grocery store hugs that I have grown to savor.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

I grew up in a family that was pretty much devoid of physical demonstrations of affection. I certainly felt that my folks loved me, but there was no hugging. I don’t recall ever seeing my parents kiss or touch each other. My dad would occasionally physically tease my mother. For example, I can remember one incident at the dinner table when he was playfully and gently laying a hand on my mother’s arm just as she was raising her fork to her mouth. After about three of these gentle holds, she lifted her water glass and tossed its contents in his face. This was the full extent of physicality in our family.

kate_sept2004/thinkstock

It wasn’t just my parents. I can’t remember aunts or uncles or cousins ever hugging us when we met. Grandmothers of course would request a hug. I never knew either of my grandfathers, but I suspect they would not have been the hugging kind.

I never felt I was missing out on anything, because in the generally WASPish atmosphere of the community in which I grew up I saw very few public displays of affection. But somewhere over time, hugging crept into the American repertoire of expression. This incursion may have been a ripple effect from the flower power, free love hippiedom of the ‘60s and ‘70s. Or it may have been a symptom of globalization as Americans became more familiar with other cultures in which physical expression was more common.

Whatever the reason for the more widespread adoption of hugging in our social vocabulary with my somewhat physically impoverished upbringing, it took me longer than most folks to comfortably include it in my greeting options. Although I may have come to the dance late, I have fully adopted hugging as a way to greet people with whom I have more than a passing acquaintance.

In fact, the ability to comfortably hug former coworkers, old friends I haven’t seen in years, and parents with whom I had shared a particularly troublesome child is what I miss most about the restrictions that have come with the COVID-19 pandemic. Now when I meet folks in the grocery store with whom I share a special affection that magnetic spark still leaps between our eyes, just visible over our face masks, but mentally and physically we take a step back and say to ourselves that this hug shouldn’t happen and it isn’t going to happen. And that makes me sad.

One of the great perks of practicing pediatrics in a small town and then remaining there in retirement is that nearly every week I encounter one or two people with whom I have a long and sometimes emotionally charged relationship. Nurses with whom I sweated over difficult delivery room resuscitations. Parents for whom their anxiety was getting in the way of their ability to parent. Parents and caregivers of complex multiply disabled children who are now adults. Peers who have lost a spouse or a child. I’m sure you have your own list of people who send off that we-need-to-hug spark.

I can envision a day sometime in the relatively near future that I will be able to hug my two grandchildren whom I haven’t hugged even though they live a short 10-minute walk away. But I have trouble imagining when I will again be able to enjoy and be enriched by those special grocery store hugs that I have grown to savor.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

I grew up in a family that was pretty much devoid of physical demonstrations of affection. I certainly felt that my folks loved me, but there was no hugging. I don’t recall ever seeing my parents kiss or touch each other. My dad would occasionally physically tease my mother. For example, I can remember one incident at the dinner table when he was playfully and gently laying a hand on my mother’s arm just as she was raising her fork to her mouth. After about three of these gentle holds, she lifted her water glass and tossed its contents in his face. This was the full extent of physicality in our family.

kate_sept2004/thinkstock

It wasn’t just my parents. I can’t remember aunts or uncles or cousins ever hugging us when we met. Grandmothers of course would request a hug. I never knew either of my grandfathers, but I suspect they would not have been the hugging kind.

I never felt I was missing out on anything, because in the generally WASPish atmosphere of the community in which I grew up I saw very few public displays of affection. But somewhere over time, hugging crept into the American repertoire of expression. This incursion may have been a ripple effect from the flower power, free love hippiedom of the ‘60s and ‘70s. Or it may have been a symptom of globalization as Americans became more familiar with other cultures in which physical expression was more common.

Whatever the reason for the more widespread adoption of hugging in our social vocabulary with my somewhat physically impoverished upbringing, it took me longer than most folks to comfortably include it in my greeting options. Although I may have come to the dance late, I have fully adopted hugging as a way to greet people with whom I have more than a passing acquaintance.

In fact, the ability to comfortably hug former coworkers, old friends I haven’t seen in years, and parents with whom I had shared a particularly troublesome child is what I miss most about the restrictions that have come with the COVID-19 pandemic. Now when I meet folks in the grocery store with whom I share a special affection that magnetic spark still leaps between our eyes, just visible over our face masks, but mentally and physically we take a step back and say to ourselves that this hug shouldn’t happen and it isn’t going to happen. And that makes me sad.

One of the great perks of practicing pediatrics in a small town and then remaining there in retirement is that nearly every week I encounter one or two people with whom I have a long and sometimes emotionally charged relationship. Nurses with whom I sweated over difficult delivery room resuscitations. Parents for whom their anxiety was getting in the way of their ability to parent. Parents and caregivers of complex multiply disabled children who are now adults. Peers who have lost a spouse or a child. I’m sure you have your own list of people who send off that we-need-to-hug spark.

I can envision a day sometime in the relatively near future that I will be able to hug my two grandchildren whom I haven’t hugged even though they live a short 10-minute walk away. But I have trouble imagining when I will again be able to enjoy and be enriched by those special grocery store hugs that I have grown to savor.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

I don’t need to tell you that the COVID-19 pandemic has leveled a major hit on outpatient pediatrics. Offices that once had waiting rooms overflowing with tantruming toddlers and anxious adolescents are empty. With income slowed to trickle, support staff has had to be furloughed. Student loans, mortgage loans, and car payments are stretching the budgets of even the most cautious spenders. In many parts of the country, it is an economic apocalypse for outpatient physicians who once saw their jobs as financially secure. Despite the persistent efforts of the American Academy of Pediatrics, pediatricians have been left off the list of recipients for financial support from the federal government.

The recent marketing initiative labeled “Call Your Pediatrician” sounds like an S.O.S. As I mentioned in a recent Letters from Maine column, I never envisioned a scenario in which I wouldn’t be busy and paying the bills if I continued to show up in the office at least 5 days a week. I guess I never thought of my work as a general pediatrician in terms of essentialness. The issue of being essential just wasn’t something anyone ever thought about. I guess if you had asked me, I would have admitted that, compared with some other health care providers, what I did was low on the essential scale. But I figured enough people thought what I provided was of sufficient value that they would pay to come see me.

If I step back and look at what of all the things I did as a pediatrician might be considered essential, it boils down to providing immunizations. If you remove my delivery room experience from the picture, there were very few instances when I might have saved a life. I hope that I calmed a lot of anxious parents and gave them some suggestions that made the job of parenting a bit easier. But while my efforts may have seemed valuable at the time, they certainly wouldn’t pass the straight-faced test of essentialness that is being applied during this pandemic. The young man or woman who stocks the toilet paper shelves at the grocery store and who accepts the risk of contagion working behind the cash register would certainly win more votes than I would garner.

So it is not surprising, given the scope of the pandemic and the anxiety compounded by what we don’t know about the virus, that office pediatrics has been left out in the cold when federal financial support is being handed out. I’m certainly not saying the oversight is warranted. It’s just not surprising. Outpatient pediatricians have always been there and it is unfortunately assumed that we will continue to be there when this whole thing blows over and we are needed again. We, and most unfortunately, the immunizations we provide are being taken for granted.

The failure to support pediatric offices is shortsighted because, even when we return to the new normal, pediatricians will again be valued. However, without financial support some offices will close and some support staff and physicians will leave the practice of pediatrics. It has been suggested that in the wake of the pandemic, the demand for mental health support for children may increase. The new normal may see our patient mix shift even further toward behavioral problems.

For whatever reason, COVID-19 appears to attack the older end of the age spectrum. It is very possible that the next pandemic targets children. If that happens, whether or not we are considered essential will not be one of our worries.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

Updated on 6/10/2020

I don’t need to tell you that the COVID-19 pandemic has leveled a major hit on outpatient pediatrics. Offices that once had waiting rooms overflowing with tantruming toddlers and anxious adolescents are empty. With income slowed to trickle, support staff has had to be furloughed. Student loans, mortgage loans, and car payments are stretching the budgets of even the most cautious spenders. In many parts of the country, it is an economic apocalypse for outpatient physicians who once saw their jobs as financially secure. Despite the persistent efforts of the American Academy of Pediatrics, pediatricians have been left off the list of recipients for financial support from the federal government.

The recent marketing initiative labeled “Call Your Pediatrician” sounds like an S.O.S. As I mentioned in a recent Letters from Maine column, I never envisioned a scenario in which I wouldn’t be busy and paying the bills if I continued to show up in the office at least 5 days a week. I guess I never thought of my work as a general pediatrician in terms of essentialness. The issue of being essential just wasn’t something anyone ever thought about. I guess if you had asked me, I would have admitted that, compared with some other health care providers, what I did was low on the essential scale. But I figured enough people thought what I provided was of sufficient value that they would pay to come see me.

If I step back and look at what of all the things I did as a pediatrician might be considered essential, it boils down to providing immunizations. If you remove my delivery room experience from the picture, there were very few instances when I might have saved a life. I hope that I calmed a lot of anxious parents and gave them some suggestions that made the job of parenting a bit easier. But while my efforts may have seemed valuable at the time, they certainly wouldn’t pass the straight-faced test of essentialness that is being applied during this pandemic. The young man or woman who stocks the toilet paper shelves at the grocery store and who accepts the risk of contagion working behind the cash register would certainly win more votes than I would garner.

So it is not surprising, given the scope of the pandemic and the anxiety compounded by what we don’t know about the virus, that office pediatrics has been left out in the cold when federal financial support is being handed out. I’m certainly not saying the oversight is warranted. It’s just not surprising. Outpatient pediatricians have always been there and it is unfortunately assumed that we will continue to be there when this whole thing blows over and we are needed again. We, and most unfortunately, the immunizations we provide are being taken for granted.

The failure to support pediatric offices is shortsighted because, even when we return to the new normal, pediatricians will again be valued. However, without financial support some offices will close and some support staff and physicians will leave the practice of pediatrics. It has been suggested that in the wake of the pandemic, the demand for mental health support for children may increase. The new normal may see our patient mix shift even further toward behavioral problems.

For whatever reason, COVID-19 appears to attack the older end of the age spectrum. It is very possible that the next pandemic targets children. If that happens, whether or not we are considered essential will not be one of our worries.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

Updated on 6/10/2020

I don’t need to tell you that the COVID-19 pandemic has leveled a major hit on outpatient pediatrics. Offices that once had waiting rooms overflowing with tantruming toddlers and anxious adolescents are empty. With income slowed to trickle, support staff has had to be furloughed. Student loans, mortgage loans, and car payments are stretching the budgets of even the most cautious spenders. In many parts of the country, it is an economic apocalypse for outpatient physicians who once saw their jobs as financially secure. Despite the persistent efforts of the American Academy of Pediatrics, pediatricians have been left off the list of recipients for financial support from the federal government.

The recent marketing initiative labeled “Call Your Pediatrician” sounds like an S.O.S. As I mentioned in a recent Letters from Maine column, I never envisioned a scenario in which I wouldn’t be busy and paying the bills if I continued to show up in the office at least 5 days a week. I guess I never thought of my work as a general pediatrician in terms of essentialness. The issue of being essential just wasn’t something anyone ever thought about. I guess if you had asked me, I would have admitted that, compared with some other health care providers, what I did was low on the essential scale. But I figured enough people thought what I provided was of sufficient value that they would pay to come see me.

If I step back and look at what of all the things I did as a pediatrician might be considered essential, it boils down to providing immunizations. If you remove my delivery room experience from the picture, there were very few instances when I might have saved a life. I hope that I calmed a lot of anxious parents and gave them some suggestions that made the job of parenting a bit easier. But while my efforts may have seemed valuable at the time, they certainly wouldn’t pass the straight-faced test of essentialness that is being applied during this pandemic. The young man or woman who stocks the toilet paper shelves at the grocery store and who accepts the risk of contagion working behind the cash register would certainly win more votes than I would garner.

So it is not surprising, given the scope of the pandemic and the anxiety compounded by what we don’t know about the virus, that office pediatrics has been left out in the cold when federal financial support is being handed out. I’m certainly not saying the oversight is warranted. It’s just not surprising. Outpatient pediatricians have always been there and it is unfortunately assumed that we will continue to be there when this whole thing blows over and we are needed again. We, and most unfortunately, the immunizations we provide are being taken for granted.

The failure to support pediatric offices is shortsighted because, even when we return to the new normal, pediatricians will again be valued. However, without financial support some offices will close and some support staff and physicians will leave the practice of pediatrics. It has been suggested that in the wake of the pandemic, the demand for mental health support for children may increase. The new normal may see our patient mix shift even further toward behavioral problems.

For whatever reason, COVID-19 appears to attack the older end of the age spectrum. It is very possible that the next pandemic targets children. If that happens, whether or not we are considered essential will not be one of our worries.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

Updated on 6/10/2020

Background: Although multiple randomized, controlled trials have shown that routine preoperative testing prior to cataract surgery has low yield, most Medicare beneficiaries continue to undergo this testing. The American Board of Internal Medicine started the Choosing Wisely campaign to help educate patients and providers about a crisis of unnecessary testing and procedures. This prompted multiple centers to create quality improvement (QI) projects to decrease low-value care.

_

Preoperative visits decreased from 93% to 24% in the intervention group and increased from 89% to 91% in the control group (between-group difference, −71%; 95% confidence interval, –80% to –62%). Chest x-rays, laboratory tests, and electrocardiograms also had a similar decrease in the intervention group.

The intervention hospital lost $42,241 the first year because of training costs but 3-year projections estimated $67,241 in savings. The authors estimated $217,322 savings in 3 years from a societal perspective. Interestingly, the decrease in utilization would lead to financial loss in fee-for-service payment ($88,151 loss in 3 years).

No causal relationship can be established since this was an observational study. Several assumptions were made for the cost analysis. Results are less generalizable since the study was at hospitals in a single city and health system. It is unclear which component of the QI initiative was most effective.

Bottom line: A multidisciplinary, multicomponent initiative can be successful in decreasing low-value preoperative testing of patients undergoing cataract surgery. Although this results in cost savings overall and for capitated payment systems, it would actually cause revenue loss in fee-for-service systems. This emphasizes a potential barrier to eradicate low-value care.

Citation: Mafi JN et al. Evaluation of an intervention to reduce low-value preoperative care for patients undergoing cataract surgery at a safety-net health system. JAMA Intern Med. Published online 2019 Mar 25. doi: 10.1001/jamainternmed.2018.8358.

Dr. Menon is a hospitalist at Duke University Health System.

Background: Although multiple randomized, controlled trials have shown that routine preoperative testing prior to cataract surgery has low yield, most Medicare beneficiaries continue to undergo this testing. The American Board of Internal Medicine started the Choosing Wisely campaign to help educate patients and providers about a crisis of unnecessary testing and procedures. This prompted multiple centers to create quality improvement (QI) projects to decrease low-value care.

_

Preoperative visits decreased from 93% to 24% in the intervention group and increased from 89% to 91% in the control group (between-group difference, −71%; 95% confidence interval, –80% to –62%). Chest x-rays, laboratory tests, and electrocardiograms also had a similar decrease in the intervention group.

The intervention hospital lost $42,241 the first year because of training costs but 3-year projections estimated $67,241 in savings. The authors estimated $217,322 savings in 3 years from a societal perspective. Interestingly, the decrease in utilization would lead to financial loss in fee-for-service payment ($88,151 loss in 3 years).

No causal relationship can be established since this was an observational study. Several assumptions were made for the cost analysis. Results are less generalizable since the study was at hospitals in a single city and health system. It is unclear which component of the QI initiative was most effective.

Bottom line: A multidisciplinary, multicomponent initiative can be successful in decreasing low-value preoperative testing of patients undergoing cataract surgery. Although this results in cost savings overall and for capitated payment systems, it would actually cause revenue loss in fee-for-service systems. This emphasizes a potential barrier to eradicate low-value care.

Citation: Mafi JN et al. Evaluation of an intervention to reduce low-value preoperative care for patients undergoing cataract surgery at a safety-net health system. JAMA Intern Med. Published online 2019 Mar 25. doi: 10.1001/jamainternmed.2018.8358.

Dr. Menon is a hospitalist at Duke University Health System.

Background: Although multiple randomized, controlled trials have shown that routine preoperative testing prior to cataract surgery has low yield, most Medicare beneficiaries continue to undergo this testing. The American Board of Internal Medicine started the Choosing Wisely campaign to help educate patients and providers about a crisis of unnecessary testing and procedures. This prompted multiple centers to create quality improvement (QI) projects to decrease low-value care.

_

Preoperative visits decreased from 93% to 24% in the intervention group and increased from 89% to 91% in the control group (between-group difference, −71%; 95% confidence interval, –80% to –62%). Chest x-rays, laboratory tests, and electrocardiograms also had a similar decrease in the intervention group.

The intervention hospital lost $42,241 the first year because of training costs but 3-year projections estimated $67,241 in savings. The authors estimated $217,322 savings in 3 years from a societal perspective. Interestingly, the decrease in utilization would lead to financial loss in fee-for-service payment ($88,151 loss in 3 years).

No causal relationship can be established since this was an observational study. Several assumptions were made for the cost analysis. Results are less generalizable since the study was at hospitals in a single city and health system. It is unclear which component of the QI initiative was most effective.

Bottom line: A multidisciplinary, multicomponent initiative can be successful in decreasing low-value preoperative testing of patients undergoing cataract surgery. Although this results in cost savings overall and for capitated payment systems, it would actually cause revenue loss in fee-for-service systems. This emphasizes a potential barrier to eradicate low-value care.

Citation: Mafi JN et al. Evaluation of an intervention to reduce low-value preoperative care for patients undergoing cataract surgery at a safety-net health system. JAMA Intern Med. Published online 2019 Mar 25. doi: 10.1001/jamainternmed.2018.8358.

Dr. Menon is a hospitalist at Duke University Health System.

A treatment schedule of very attenuated chemotherapy using standard drugs is feasible and effective in frail and elderly patients with acute lymphoblastic leukemia (ALL), according to a prospective study published in Clinical Lymphoma, Myeloma & Leukemia.

VashiDonsk/Creative Commons/CC ASA 3.0

The study comprised 67 previously untreated patients with B- or T-lineage Philadelphia chromosome–negative ALL from 30 Spanish hospitals who were enrolled in the prospective, multicenter ALL-07FRAIL trial (NCT01358201) from the Spanish PETHEMA (Programa Español de Tratamientos en Hematologia) group from January 2008 to October 2019.

The median patient age in this analysis was 67 years and 51 patients (76%) were older than 70 years. The median Charlson Comorbidity Index was 5, with the main comorbidities being cardiovascular (47 patients), other neoplasia (24), diabetes (17), and very advanced age (>80 years; 12).

The attenuated treatment regimen consisted of a prephase with dexamethasone and intrathecal therapy with methotrexate was given for a maximum of 1 week. Then weekly induction therapy consisted of weekly vincristine (capped at 1 mg/week) and daily dexamethasone with a progressively decreasing dose along 4 weeks, as well as two additional doses of intrathecal methotrexate.

Those patients who achieved complete remission received maintenance therapy with mercaptopurine and methotrexate to complete 2 years of treatment. In addition, reinduction pulses with vincristine and dexamethasone were given every 3 months during the first year, according to Josep-Maria Ribera, MD, of the Universitat Autònoma de Barcelona, Badalona, Spain and colleagues on behalf of the PETHEMA group of the Spanish Society of Hematology.

The complete remission rate was 54% (36/67 patients). The median disease-free survival and overall survival were 6.9 months and 7.6 months, respectively.

Of the 32 patients who initiated maintenance therapy, 5 patients died of infection (2), hemorrhage (2), and acute cognitive impairment (1), and 23 relapsed, with a cumulative incidence of relapse of 74% and a median time to relapse of 12.3 months.

The most frequent toxic events reported were hematologic (neutropenia 77% and thrombocytopenia 54%, of grade III-IV in all cases) followed by infections, metabolic (mainly hyperglycemia), and neurologic, according to the researchers.

“The lack of similar trials specifically directed to this frail population is one of the major strengths of this study, and we consider that this minimal chemotherapy approach could be used as a backbone for addition of immuno/targeted therapy in this subset of infirm patients,” the researchers concluded.

The study was supported by the CERCA Program/Generalitat de Catalunya and the Josep Carreras Leukemia Research Institute. The authors reported having no disclosures.

[email protected]

SOURCE: Ribera J-M et al. Clin Lymphoma Myeloma Leuk. 2020 Apr 5. doi: 10.1016/j.clml.2020.03.011.

A treatment schedule of very attenuated chemotherapy using standard drugs is feasible and effective in frail and elderly patients with acute lymphoblastic leukemia (ALL), according to a prospective study published in Clinical Lymphoma, Myeloma & Leukemia.

VashiDonsk/Creative Commons/CC ASA 3.0

The study comprised 67 previously untreated patients with B- or T-lineage Philadelphia chromosome–negative ALL from 30 Spanish hospitals who were enrolled in the prospective, multicenter ALL-07FRAIL trial (NCT01358201) from the Spanish PETHEMA (Programa Español de Tratamientos en Hematologia) group from January 2008 to October 2019.

The median patient age in this analysis was 67 years and 51 patients (76%) were older than 70 years. The median Charlson Comorbidity Index was 5, with the main comorbidities being cardiovascular (47 patients), other neoplasia (24), diabetes (17), and very advanced age (>80 years; 12).

The attenuated treatment regimen consisted of a prephase with dexamethasone and intrathecal therapy with methotrexate was given for a maximum of 1 week. Then weekly induction therapy consisted of weekly vincristine (capped at 1 mg/week) and daily dexamethasone with a progressively decreasing dose along 4 weeks, as well as two additional doses of intrathecal methotrexate.

Those patients who achieved complete remission received maintenance therapy with mercaptopurine and methotrexate to complete 2 years of treatment. In addition, reinduction pulses with vincristine and dexamethasone were given every 3 months during the first year, according to Josep-Maria Ribera, MD, of the Universitat Autònoma de Barcelona, Badalona, Spain and colleagues on behalf of the PETHEMA group of the Spanish Society of Hematology.

The complete remission rate was 54% (36/67 patients). The median disease-free survival and overall survival were 6.9 months and 7.6 months, respectively.

Of the 32 patients who initiated maintenance therapy, 5 patients died of infection (2), hemorrhage (2), and acute cognitive impairment (1), and 23 relapsed, with a cumulative incidence of relapse of 74% and a median time to relapse of 12.3 months.

The most frequent toxic events reported were hematologic (neutropenia 77% and thrombocytopenia 54%, of grade III-IV in all cases) followed by infections, metabolic (mainly hyperglycemia), and neurologic, according to the researchers.

“The lack of similar trials specifically directed to this frail population is one of the major strengths of this study, and we consider that this minimal chemotherapy approach could be used as a backbone for addition of immuno/targeted therapy in this subset of infirm patients,” the researchers concluded.

The study was supported by the CERCA Program/Generalitat de Catalunya and the Josep Carreras Leukemia Research Institute. The authors reported having no disclosures.

[email protected]

SOURCE: Ribera J-M et al. Clin Lymphoma Myeloma Leuk. 2020 Apr 5. doi: 10.1016/j.clml.2020.03.011.

A treatment schedule of very attenuated chemotherapy using standard drugs is feasible and effective in frail and elderly patients with acute lymphoblastic leukemia (ALL), according to a prospective study published in Clinical Lymphoma, Myeloma & Leukemia.

VashiDonsk/Creative Commons/CC ASA 3.0

The study comprised 67 previously untreated patients with B- or T-lineage Philadelphia chromosome–negative ALL from 30 Spanish hospitals who were enrolled in the prospective, multicenter ALL-07FRAIL trial (NCT01358201) from the Spanish PETHEMA (Programa Español de Tratamientos en Hematologia) group from January 2008 to October 2019.

The median patient age in this analysis was 67 years and 51 patients (76%) were older than 70 years. The median Charlson Comorbidity Index was 5, with the main comorbidities being cardiovascular (47 patients), other neoplasia (24), diabetes (17), and very advanced age (>80 years; 12).

The attenuated treatment regimen consisted of a prephase with dexamethasone and intrathecal therapy with methotrexate was given for a maximum of 1 week. Then weekly induction therapy consisted of weekly vincristine (capped at 1 mg/week) and daily dexamethasone with a progressively decreasing dose along 4 weeks, as well as two additional doses of intrathecal methotrexate.

Those patients who achieved complete remission received maintenance therapy with mercaptopurine and methotrexate to complete 2 years of treatment. In addition, reinduction pulses with vincristine and dexamethasone were given every 3 months during the first year, according to Josep-Maria Ribera, MD, of the Universitat Autònoma de Barcelona, Badalona, Spain and colleagues on behalf of the PETHEMA group of the Spanish Society of Hematology.

The complete remission rate was 54% (36/67 patients). The median disease-free survival and overall survival were 6.9 months and 7.6 months, respectively.

Of the 32 patients who initiated maintenance therapy, 5 patients died of infection (2), hemorrhage (2), and acute cognitive impairment (1), and 23 relapsed, with a cumulative incidence of relapse of 74% and a median time to relapse of 12.3 months.

The most frequent toxic events reported were hematologic (neutropenia 77% and thrombocytopenia 54%, of grade III-IV in all cases) followed by infections, metabolic (mainly hyperglycemia), and neurologic, according to the researchers.

“The lack of similar trials specifically directed to this frail population is one of the major strengths of this study, and we consider that this minimal chemotherapy approach could be used as a backbone for addition of immuno/targeted therapy in this subset of infirm patients,” the researchers concluded.

The study was supported by the CERCA Program/Generalitat de Catalunya and the Josep Carreras Leukemia Research Institute. The authors reported having no disclosures.

[email protected]

SOURCE: Ribera J-M et al. Clin Lymphoma Myeloma Leuk. 2020 Apr 5. doi: 10.1016/j.clml.2020.03.011.

Compounding is a way of mixing or combining medications in formulations that are not widely available. Because dermatology is a field that includes a variety of topical treatments, compounding topicals is a way to create unique and customized treatment options for patients.

Advantages

Custom compounding topical medications has many benefits in comparison to traditional topical formulations. Compounding is a way of personalizing prescriptions to best suit the individual needs of each patient. Multiple ingredients with different mechanisms of action can be combined in a single medication for patients to use, which ultimately can simplify their treatment regimen.¹ For rare conditions with uncommon treatments, compounding pharmacies can provide medications that are not widely available in retail pharmacies. Compounding topical medications also can be an efficient way of prescribing medications without dealing with the uncertainty of prior authorizations or how much the co-pay will be.

Disadvantages

One of the major disadvantages of compounding topical medications is the lack of safety data. Although most active drugs have been tested independently, there is little data on the safety of compounding 2 or more active drugs. Furthermore, the vehicle used may change the permeability of the topical formulation, and systemic absorption may be possible. Two deaths were reported with the application of compounded topical lidocaine and tetracaine gel due to systemic absorption. In these cases, the gel was used before laser hair removal, and it was applied under occlusion to greater than 50% of the body surface area, leading to fatal systemic absorption.^1,2

One of the hypothetical benefits of compounding topicals is being able to avoid side effects of systemic medications. However, depending on the skin intactness and the strength of the medication used, systemic adverse effects have been reported.¹ In a case series of 2 patients detailing the use of amitriptyline cream 5% and 10% for neuropathic pain, the patient using 10% cream experienced systemic effects of drowsiness and discontinued treatment.³

Another major disadvantage of compounding topicals is a lack of published data about the efficacy, especially given the unique nature of what is being compounded. When combining multiple medications, there are little to no published data about the efficacy of these formulations and how they compare to monotherapy. Although there may be data about the efficacy of an oral agent, it does not translate to the topical form being safe and efficacious. Much of the published data of topical formulations is limited to case reports and case series.

Finally, many compounded medications are not covered by insurance, and the out-of-pocket cost may be prohibitive for some patients. Compounding pharmacies typically will give patients a price estimate before the prescription is filled. When compounding topicals for patient use, it is important to counsel patients about the following:the unknown safety profile; lack of data regarding efficacy; and cost, as the medication likely will not be covered by insurance.

Pharmaceutical Regulations

After a contaminated product at a compounding pharmacy in New England led to an outbreak of fungal meningitis, there has been increased regulation by the US Food and Drug Administration.⁴ To meet safety regulations, compounding pharmacies must adhere to the standards set by the US Pharmacopeia. The US Food and Drug Administration says that physicians are not to prescribe compounded medications that are “unapproved, adulterated, or misbranded drugs,” which has been interpreted to mean that compounded medications should not mimic a branded medication but should instead be a unique formulation or strength.^4,5 Thus, while compounding topicals may provide an alternative when a specific medication is not covered by insurance, it cannot be the same as a branded medication.

Pharmaceutical Options

Most major cities have custom compounding pharmacies or apothecaries. One of the benefits of using a local compounding pharmacy is that you typically can speak directly with the pharmacist about your patient’s diagnosis and his/her specific needs. The pharmacist can guide you through which formulations to compound, which strength to choose, and the best vehicle to use as a base. This expertise is invaluable in the compounding process. There also are online compounding pharmacies available.

Options for Bases

Dermatologists can request for their medications to be compounded in traditional over-the-counter emollients or petrolatum-based products, which work by passively diffusing through the stratum corneum into the superficial epidermis to treat skin conditions.¹ For a topical drug to be absorbed effectively through the skin and into the general circulation, the vehicle needs to have affinity for both lipid and aqueous environments. Lipophilic drugs will absorb better through the stratum corneum, while hydrophilic drugs will absorb better through the aqueous layer of the epidermis. For a topical formulation to be both hydrophobic and hydrophilic, components such as viscosity enhancers and permeation enhancers can be added.¹ Many compounding pharmacies also have proprietary bases that can be used.

Final Thoughts

Compounding topical medications in dermatology provides dermatologists with the ability to provide unique formulations to best suit their patients’ individual needs. However, dermatologists must keep in mind the limitations of compounding topicals, including a lack of data on efficacy and safety.

Compounding is a way of mixing or combining medications in formulations that are not widely available. Because dermatology is a field that includes a variety of topical treatments, compounding topicals is a way to create unique and customized treatment options for patients.

Advantages

Custom compounding topical medications has many benefits in comparison to traditional topical formulations. Compounding is a way of personalizing prescriptions to best suit the individual needs of each patient. Multiple ingredients with different mechanisms of action can be combined in a single medication for patients to use, which ultimately can simplify their treatment regimen.¹ For rare conditions with uncommon treatments, compounding pharmacies can provide medications that are not widely available in retail pharmacies. Compounding topical medications also can be an efficient way of prescribing medications without dealing with the uncertainty of prior authorizations or how much the co-pay will be.

Disadvantages

One of the major disadvantages of compounding topical medications is the lack of safety data. Although most active drugs have been tested independently, there is little data on the safety of compounding 2 or more active drugs. Furthermore, the vehicle used may change the permeability of the topical formulation, and systemic absorption may be possible. Two deaths were reported with the application of compounded topical lidocaine and tetracaine gel due to systemic absorption. In these cases, the gel was used before laser hair removal, and it was applied under occlusion to greater than 50% of the body surface area, leading to fatal systemic absorption.^1,2

One of the hypothetical benefits of compounding topicals is being able to avoid side effects of systemic medications. However, depending on the skin intactness and the strength of the medication used, systemic adverse effects have been reported.¹ In a case series of 2 patients detailing the use of amitriptyline cream 5% and 10% for neuropathic pain, the patient using 10% cream experienced systemic effects of drowsiness and discontinued treatment.³

Another major disadvantage of compounding topicals is a lack of published data about the efficacy, especially given the unique nature of what is being compounded. When combining multiple medications, there are little to no published data about the efficacy of these formulations and how they compare to monotherapy. Although there may be data about the efficacy of an oral agent, it does not translate to the topical form being safe and efficacious. Much of the published data of topical formulations is limited to case reports and case series.

Finally, many compounded medications are not covered by insurance, and the out-of-pocket cost may be prohibitive for some patients. Compounding pharmacies typically will give patients a price estimate before the prescription is filled. When compounding topicals for patient use, it is important to counsel patients about the following:the unknown safety profile; lack of data regarding efficacy; and cost, as the medication likely will not be covered by insurance.

Pharmaceutical Regulations

After a contaminated product at a compounding pharmacy in New England led to an outbreak of fungal meningitis, there has been increased regulation by the US Food and Drug Administration.⁴ To meet safety regulations, compounding pharmacies must adhere to the standards set by the US Pharmacopeia. The US Food and Drug Administration says that physicians are not to prescribe compounded medications that are “unapproved, adulterated, or misbranded drugs,” which has been interpreted to mean that compounded medications should not mimic a branded medication but should instead be a unique formulation or strength.^4,5 Thus, while compounding topicals may provide an alternative when a specific medication is not covered by insurance, it cannot be the same as a branded medication.

Pharmaceutical Options

Most major cities have custom compounding pharmacies or apothecaries. One of the benefits of using a local compounding pharmacy is that you typically can speak directly with the pharmacist about your patient’s diagnosis and his/her specific needs. The pharmacist can guide you through which formulations to compound, which strength to choose, and the best vehicle to use as a base. This expertise is invaluable in the compounding process. There also are online compounding pharmacies available.

Options for Bases

Dermatologists can request for their medications to be compounded in traditional over-the-counter emollients or petrolatum-based products, which work by passively diffusing through the stratum corneum into the superficial epidermis to treat skin conditions.¹ For a topical drug to be absorbed effectively through the skin and into the general circulation, the vehicle needs to have affinity for both lipid and aqueous environments. Lipophilic drugs will absorb better through the stratum corneum, while hydrophilic drugs will absorb better through the aqueous layer of the epidermis. For a topical formulation to be both hydrophobic and hydrophilic, components such as viscosity enhancers and permeation enhancers can be added.¹ Many compounding pharmacies also have proprietary bases that can be used.

Final Thoughts

Compounding topical medications in dermatology provides dermatologists with the ability to provide unique formulations to best suit their patients’ individual needs. However, dermatologists must keep in mind the limitations of compounding topicals, including a lack of data on efficacy and safety.

Compounding is a way of mixing or combining medications in formulations that are not widely available. Because dermatology is a field that includes a variety of topical treatments, compounding topicals is a way to create unique and customized treatment options for patients.

Advantages

Custom compounding topical medications has many benefits in comparison to traditional topical formulations. Compounding is a way of personalizing prescriptions to best suit the individual needs of each patient. Multiple ingredients with different mechanisms of action can be combined in a single medication for patients to use, which ultimately can simplify their treatment regimen.¹ For rare conditions with uncommon treatments, compounding pharmacies can provide medications that are not widely available in retail pharmacies. Compounding topical medications also can be an efficient way of prescribing medications without dealing with the uncertainty of prior authorizations or how much the co-pay will be.

Disadvantages

One of the major disadvantages of compounding topical medications is the lack of safety data. Although most active drugs have been tested independently, there is little data on the safety of compounding 2 or more active drugs. Furthermore, the vehicle used may change the permeability of the topical formulation, and systemic absorption may be possible. Two deaths were reported with the application of compounded topical lidocaine and tetracaine gel due to systemic absorption. In these cases, the gel was used before laser hair removal, and it was applied under occlusion to greater than 50% of the body surface area, leading to fatal systemic absorption.^1,2

One of the hypothetical benefits of compounding topicals is being able to avoid side effects of systemic medications. However, depending on the skin intactness and the strength of the medication used, systemic adverse effects have been reported.¹ In a case series of 2 patients detailing the use of amitriptyline cream 5% and 10% for neuropathic pain, the patient using 10% cream experienced systemic effects of drowsiness and discontinued treatment.³

Another major disadvantage of compounding topicals is a lack of published data about the efficacy, especially given the unique nature of what is being compounded. When combining multiple medications, there are little to no published data about the efficacy of these formulations and how they compare to monotherapy. Although there may be data about the efficacy of an oral agent, it does not translate to the topical form being safe and efficacious. Much of the published data of topical formulations is limited to case reports and case series.

Finally, many compounded medications are not covered by insurance, and the out-of-pocket cost may be prohibitive for some patients. Compounding pharmacies typically will give patients a price estimate before the prescription is filled. When compounding topicals for patient use, it is important to counsel patients about the following:the unknown safety profile; lack of data regarding efficacy; and cost, as the medication likely will not be covered by insurance.

Pharmaceutical Regulations

After a contaminated product at a compounding pharmacy in New England led to an outbreak of fungal meningitis, there has been increased regulation by the US Food and Drug Administration.⁴ To meet safety regulations, compounding pharmacies must adhere to the standards set by the US Pharmacopeia. The US Food and Drug Administration says that physicians are not to prescribe compounded medications that are “unapproved, adulterated, or misbranded drugs,” which has been interpreted to mean that compounded medications should not mimic a branded medication but should instead be a unique formulation or strength.^4,5 Thus, while compounding topicals may provide an alternative when a specific medication is not covered by insurance, it cannot be the same as a branded medication.

Pharmaceutical Options

Most major cities have custom compounding pharmacies or apothecaries. One of the benefits of using a local compounding pharmacy is that you typically can speak directly with the pharmacist about your patient’s diagnosis and his/her specific needs. The pharmacist can guide you through which formulations to compound, which strength to choose, and the best vehicle to use as a base. This expertise is invaluable in the compounding process. There also are online compounding pharmacies available.

Options for Bases

Dermatologists can request for their medications to be compounded in traditional over-the-counter emollients or petrolatum-based products, which work by passively diffusing through the stratum corneum into the superficial epidermis to treat skin conditions.¹ For a topical drug to be absorbed effectively through the skin and into the general circulation, the vehicle needs to have affinity for both lipid and aqueous environments. Lipophilic drugs will absorb better through the stratum corneum, while hydrophilic drugs will absorb better through the aqueous layer of the epidermis. For a topical formulation to be both hydrophobic and hydrophilic, components such as viscosity enhancers and permeation enhancers can be added.¹ Many compounding pharmacies also have proprietary bases that can be used.

Final Thoughts

Compounding topical medications in dermatology provides dermatologists with the ability to provide unique formulations to best suit their patients’ individual needs. However, dermatologists must keep in mind the limitations of compounding topicals, including a lack of data on efficacy and safety.