MINNEAPOLIS – Whether a young female patient has a refractory flare of inflammatory acne, or has a condition that can predispose to androgen excess, using a hormonal approach can be an effective management tool for controlling adolescent acne.

During a presentation at the annual meeting of the Society for Pediatric Dermatology, Dr. Diane Thiboutot outlined tips and tricks for optimizing hormonal therapy for acne in teens, and referred to the new acne treatment guidelines from the American Academy of Dermatology, which clarify when to treat with hormones, which to choose, and when further testing might be indicated.

The full range of hormonal therapy options for acne can include oral contraceptives, which block ovarian hormone production; antiandrogens such as spironolactone, and the less commonly used flutamide, which blocks the effects of androgen on the skin; and glucocorticoids, which block adrenal production.

The 2016 guidelines recommend oral contraceptives as an effective treatment for inflammatory acne in females (J Am Acad Dermatol. 2016 May;74[5]; 945-973.e33). Combined oral contraceptives (COCs) reduce serum androgens, and reduce free testosterone by increasing sex hormone binding globulin production, thus reducing sebum production. “The only things that really decrease sebum are oral contraceptives in women, and isotretinoin,” said Dr. Thiboutot, professor of dermatology at Penn State University, Hershey.

For most female adolescents with acne, hormonal testing is not indicated. The AAD guidelines recommend laboratory evaluation for younger patients with acne who have clinical signs of androgen excess, such as early onset body odor and axillary and/or pubic hair, accelerated growth, advanced bone age, or early genital maturation. Just obtaining a hand film for bone age and mapping growth against a growth chart can be a good initial screening tool when considering whether to perform hormonal testing, she noted.

For postpubertal females in whom polycystic ovary syndrome (PCOS) or other hyperandrogenic states are suspected, hormonal testing is indicated in the presence of the clinical signs of infrequent menses and infertility, hirsutism, truncal obesity, androgenetic alopecia, polycystic ovaries, or clitoromegaly.

In searching for an endocrine disorder, Dr. Thiboutot recommends checking total and free testosterone, luteinizing hormone/follicle stimulating hormone ratio, 17-hydroxyprogesterone levels, and dehydroepiandrosterone (DHEA-S) levels. These tests should be performed at least 6 weeks after the patient has been off hormonal contraception, and should be done during the menstrual period, or during the week prior to menses, in order to avoid ovulation-related hormonal changes.

Lab findings consistent with congenital adrenal hyperplasia include elevated serum DHEA-S, together with elevated 17-hydroxyprogesterone or testosterone. A PCOS diagnosis can be made in adolescent females if there is clinical or laboratory evidence of hyperandrogenism with concomitant persistent oligomenorrhea.

Acne related to hyperandrogenism may respond well to oral contraceptives, but COCs can also be an effective alternative to repeated courses of isotretinoin and antibiotics, as well as an effective adjunct to topical therapy, Dr. Thiboutot said.

When beginning a patient on oral contraceptives, it’s not necessary to perform a pelvic exam or obtain a Pap smear before initiating the COC, but it is important to obtain a thorough medical history and an accurate blood pressure measurement at the outset, she noted. The World Health Organization (WHO) has established recommendations outlining contraindications to COC use, also identifying populations in whom COCs should be used with caution, and who should be monitored.

Headaches are a condition frequently seen among healthy teens and young women, and one for which the WHO advises caution. There are concerns that women with migraines may be at increased risk of stroke if they take COCs, but the overall risk is low, and the American College of Obstetricians and Gynecologists (ACOG) advises that COCs can be considered for women younger than 35 with migraines if they have no focal neurologic signs, are nonsmokers, and are otherwise healthy, Dr. Thiboutot added.

A large Food and Drug Administration–sponsored retrospective cohort study examined the risk of venous thromboembolism in contraceptive users. In April 2012, the FDA concluded that though the risk of blood clots may be higher for those on hormonal contraception methods than for those who are not using them, the risk of blood clots during pregnancy and the postpartum period is higher than the thromboembolism risk for contraceptive users.

Regarding the potential for antibiotics to reduce contraceptive efficacy, Dr. Thiboutot said,“it’s okay to use oral contraceptives with antibiotics. There’s a lot of misunderstanding about antibiotics and combined oral contraceptives.” She cited an ACOG practice bulletin that reported that only rifampin has been shown to reduce serum steroid levels when taken with oral contraceptives (Obstet Gynecol. 2006 Jun;107[6]:1453-72).

According to the 2016 AAD guidelines, the use of oral glucocorticoids may be appropriate over the short term when initiating therapy for severe inflammatory acne. “Pharmacokinetic studies have not demonstrated decreased oral contraceptive levels with common antibiotics,” Dr. Thiboutot said.

Spironolactone, according to the new guidelines, is useful for acne in select females. Spironolactone is an androgen receptor and 5a-reductase blocker, and its antiandrogen effects can improve acne. Many patients do well with 25-50 mg twice daily, though breast tenderness and menstrual irregularities are commonly seen side effects, she noted. If a woman taking spironolactone becomes pregnant, there’s a risk of hypospadias for a male fetus.

Though spironolactone carries a boxed warning because of tumorigenicity observed in animal studies, Dr. Thiboutot said that a large Danish study searched for any association between breast, uterine, or ovarian cancers and spironolactone use. Among the 2.3 million women studied, no increased association was seen (Cancer Epidemiol. 2013 Dec;37:870-5).

She also noted that there’s “low usefulness in monitoring potassium levels in young healthy women on spironolactone.” She cited a study that compared 974 healthy young women taking spironolactone with 1,165 women who were not on spironolactone, which found that the hyperkalemia rate of 0.72% among those on spironolactone was equivalent to the 0.76% baseline rate of hyperkalemia in the young, healthy female population (JAMA Dermatol. 2015;151[9];941-944).

Oral corticosteroids for acne, Dr. Thiboutot said, should be reserved to quiet a severe bout of inflammatory acne while standard therapies are being initiated.

She reported being an investigator or a consultant for a number of pharmaceutical companies.

[email protected]

On Twitter @karioakes

MINNEAPOLIS – Whether a young female patient has a refractory flare of inflammatory acne, or has a condition that can predispose to androgen excess, using a hormonal approach can be an effective management tool for controlling adolescent acne.

During a presentation at the annual meeting of the Society for Pediatric Dermatology, Dr. Diane Thiboutot outlined tips and tricks for optimizing hormonal therapy for acne in teens, and referred to the new acne treatment guidelines from the American Academy of Dermatology, which clarify when to treat with hormones, which to choose, and when further testing might be indicated.

The full range of hormonal therapy options for acne can include oral contraceptives, which block ovarian hormone production; antiandrogens such as spironolactone, and the less commonly used flutamide, which blocks the effects of androgen on the skin; and glucocorticoids, which block adrenal production.

The 2016 guidelines recommend oral contraceptives as an effective treatment for inflammatory acne in females (J Am Acad Dermatol. 2016 May;74[5]; 945-973.e33). Combined oral contraceptives (COCs) reduce serum androgens, and reduce free testosterone by increasing sex hormone binding globulin production, thus reducing sebum production. “The only things that really decrease sebum are oral contraceptives in women, and isotretinoin,” said Dr. Thiboutot, professor of dermatology at Penn State University, Hershey.

For most female adolescents with acne, hormonal testing is not indicated. The AAD guidelines recommend laboratory evaluation for younger patients with acne who have clinical signs of androgen excess, such as early onset body odor and axillary and/or pubic hair, accelerated growth, advanced bone age, or early genital maturation. Just obtaining a hand film for bone age and mapping growth against a growth chart can be a good initial screening tool when considering whether to perform hormonal testing, she noted.

For postpubertal females in whom polycystic ovary syndrome (PCOS) or other hyperandrogenic states are suspected, hormonal testing is indicated in the presence of the clinical signs of infrequent menses and infertility, hirsutism, truncal obesity, androgenetic alopecia, polycystic ovaries, or clitoromegaly.

In searching for an endocrine disorder, Dr. Thiboutot recommends checking total and free testosterone, luteinizing hormone/follicle stimulating hormone ratio, 17-hydroxyprogesterone levels, and dehydroepiandrosterone (DHEA-S) levels. These tests should be performed at least 6 weeks after the patient has been off hormonal contraception, and should be done during the menstrual period, or during the week prior to menses, in order to avoid ovulation-related hormonal changes.

Lab findings consistent with congenital adrenal hyperplasia include elevated serum DHEA-S, together with elevated 17-hydroxyprogesterone or testosterone. A PCOS diagnosis can be made in adolescent females if there is clinical or laboratory evidence of hyperandrogenism with concomitant persistent oligomenorrhea.

Acne related to hyperandrogenism may respond well to oral contraceptives, but COCs can also be an effective alternative to repeated courses of isotretinoin and antibiotics, as well as an effective adjunct to topical therapy, Dr. Thiboutot said.

When beginning a patient on oral contraceptives, it’s not necessary to perform a pelvic exam or obtain a Pap smear before initiating the COC, but it is important to obtain a thorough medical history and an accurate blood pressure measurement at the outset, she noted. The World Health Organization (WHO) has established recommendations outlining contraindications to COC use, also identifying populations in whom COCs should be used with caution, and who should be monitored.

Headaches are a condition frequently seen among healthy teens and young women, and one for which the WHO advises caution. There are concerns that women with migraines may be at increased risk of stroke if they take COCs, but the overall risk is low, and the American College of Obstetricians and Gynecologists (ACOG) advises that COCs can be considered for women younger than 35 with migraines if they have no focal neurologic signs, are nonsmokers, and are otherwise healthy, Dr. Thiboutot added.

A large Food and Drug Administration–sponsored retrospective cohort study examined the risk of venous thromboembolism in contraceptive users. In April 2012, the FDA concluded that though the risk of blood clots may be higher for those on hormonal contraception methods than for those who are not using them, the risk of blood clots during pregnancy and the postpartum period is higher than the thromboembolism risk for contraceptive users.

Regarding the potential for antibiotics to reduce contraceptive efficacy, Dr. Thiboutot said,“it’s okay to use oral contraceptives with antibiotics. There’s a lot of misunderstanding about antibiotics and combined oral contraceptives.” She cited an ACOG practice bulletin that reported that only rifampin has been shown to reduce serum steroid levels when taken with oral contraceptives (Obstet Gynecol. 2006 Jun;107[6]:1453-72).

According to the 2016 AAD guidelines, the use of oral glucocorticoids may be appropriate over the short term when initiating therapy for severe inflammatory acne. “Pharmacokinetic studies have not demonstrated decreased oral contraceptive levels with common antibiotics,” Dr. Thiboutot said.

Spironolactone, according to the new guidelines, is useful for acne in select females. Spironolactone is an androgen receptor and 5a-reductase blocker, and its antiandrogen effects can improve acne. Many patients do well with 25-50 mg twice daily, though breast tenderness and menstrual irregularities are commonly seen side effects, she noted. If a woman taking spironolactone becomes pregnant, there’s a risk of hypospadias for a male fetus.

Though spironolactone carries a boxed warning because of tumorigenicity observed in animal studies, Dr. Thiboutot said that a large Danish study searched for any association between breast, uterine, or ovarian cancers and spironolactone use. Among the 2.3 million women studied, no increased association was seen (Cancer Epidemiol. 2013 Dec;37:870-5).

She also noted that there’s “low usefulness in monitoring potassium levels in young healthy women on spironolactone.” She cited a study that compared 974 healthy young women taking spironolactone with 1,165 women who were not on spironolactone, which found that the hyperkalemia rate of 0.72% among those on spironolactone was equivalent to the 0.76% baseline rate of hyperkalemia in the young, healthy female population (JAMA Dermatol. 2015;151[9];941-944).

Oral corticosteroids for acne, Dr. Thiboutot said, should be reserved to quiet a severe bout of inflammatory acne while standard therapies are being initiated.

She reported being an investigator or a consultant for a number of pharmaceutical companies.

[email protected]

On Twitter @karioakes

MINNEAPOLIS – Whether a young female patient has a refractory flare of inflammatory acne, or has a condition that can predispose to androgen excess, using a hormonal approach can be an effective management tool for controlling adolescent acne.

During a presentation at the annual meeting of the Society for Pediatric Dermatology, Dr. Diane Thiboutot outlined tips and tricks for optimizing hormonal therapy for acne in teens, and referred to the new acne treatment guidelines from the American Academy of Dermatology, which clarify when to treat with hormones, which to choose, and when further testing might be indicated.

The full range of hormonal therapy options for acne can include oral contraceptives, which block ovarian hormone production; antiandrogens such as spironolactone, and the less commonly used flutamide, which blocks the effects of androgen on the skin; and glucocorticoids, which block adrenal production.

The 2016 guidelines recommend oral contraceptives as an effective treatment for inflammatory acne in females (J Am Acad Dermatol. 2016 May;74[5]; 945-973.e33). Combined oral contraceptives (COCs) reduce serum androgens, and reduce free testosterone by increasing sex hormone binding globulin production, thus reducing sebum production. “The only things that really decrease sebum are oral contraceptives in women, and isotretinoin,” said Dr. Thiboutot, professor of dermatology at Penn State University, Hershey.

For most female adolescents with acne, hormonal testing is not indicated. The AAD guidelines recommend laboratory evaluation for younger patients with acne who have clinical signs of androgen excess, such as early onset body odor and axillary and/or pubic hair, accelerated growth, advanced bone age, or early genital maturation. Just obtaining a hand film for bone age and mapping growth against a growth chart can be a good initial screening tool when considering whether to perform hormonal testing, she noted.

For postpubertal females in whom polycystic ovary syndrome (PCOS) or other hyperandrogenic states are suspected, hormonal testing is indicated in the presence of the clinical signs of infrequent menses and infertility, hirsutism, truncal obesity, androgenetic alopecia, polycystic ovaries, or clitoromegaly.

In searching for an endocrine disorder, Dr. Thiboutot recommends checking total and free testosterone, luteinizing hormone/follicle stimulating hormone ratio, 17-hydroxyprogesterone levels, and dehydroepiandrosterone (DHEA-S) levels. These tests should be performed at least 6 weeks after the patient has been off hormonal contraception, and should be done during the menstrual period, or during the week prior to menses, in order to avoid ovulation-related hormonal changes.

Lab findings consistent with congenital adrenal hyperplasia include elevated serum DHEA-S, together with elevated 17-hydroxyprogesterone or testosterone. A PCOS diagnosis can be made in adolescent females if there is clinical or laboratory evidence of hyperandrogenism with concomitant persistent oligomenorrhea.

Acne related to hyperandrogenism may respond well to oral contraceptives, but COCs can also be an effective alternative to repeated courses of isotretinoin and antibiotics, as well as an effective adjunct to topical therapy, Dr. Thiboutot said.

When beginning a patient on oral contraceptives, it’s not necessary to perform a pelvic exam or obtain a Pap smear before initiating the COC, but it is important to obtain a thorough medical history and an accurate blood pressure measurement at the outset, she noted. The World Health Organization (WHO) has established recommendations outlining contraindications to COC use, also identifying populations in whom COCs should be used with caution, and who should be monitored.

Headaches are a condition frequently seen among healthy teens and young women, and one for which the WHO advises caution. There are concerns that women with migraines may be at increased risk of stroke if they take COCs, but the overall risk is low, and the American College of Obstetricians and Gynecologists (ACOG) advises that COCs can be considered for women younger than 35 with migraines if they have no focal neurologic signs, are nonsmokers, and are otherwise healthy, Dr. Thiboutot added.

A large Food and Drug Administration–sponsored retrospective cohort study examined the risk of venous thromboembolism in contraceptive users. In April 2012, the FDA concluded that though the risk of blood clots may be higher for those on hormonal contraception methods than for those who are not using them, the risk of blood clots during pregnancy and the postpartum period is higher than the thromboembolism risk for contraceptive users.

Regarding the potential for antibiotics to reduce contraceptive efficacy, Dr. Thiboutot said,“it’s okay to use oral contraceptives with antibiotics. There’s a lot of misunderstanding about antibiotics and combined oral contraceptives.” She cited an ACOG practice bulletin that reported that only rifampin has been shown to reduce serum steroid levels when taken with oral contraceptives (Obstet Gynecol. 2006 Jun;107[6]:1453-72).

According to the 2016 AAD guidelines, the use of oral glucocorticoids may be appropriate over the short term when initiating therapy for severe inflammatory acne. “Pharmacokinetic studies have not demonstrated decreased oral contraceptive levels with common antibiotics,” Dr. Thiboutot said.

Spironolactone, according to the new guidelines, is useful for acne in select females. Spironolactone is an androgen receptor and 5a-reductase blocker, and its antiandrogen effects can improve acne. Many patients do well with 25-50 mg twice daily, though breast tenderness and menstrual irregularities are commonly seen side effects, she noted. If a woman taking spironolactone becomes pregnant, there’s a risk of hypospadias for a male fetus.

Though spironolactone carries a boxed warning because of tumorigenicity observed in animal studies, Dr. Thiboutot said that a large Danish study searched for any association between breast, uterine, or ovarian cancers and spironolactone use. Among the 2.3 million women studied, no increased association was seen (Cancer Epidemiol. 2013 Dec;37:870-5).

She also noted that there’s “low usefulness in monitoring potassium levels in young healthy women on spironolactone.” She cited a study that compared 974 healthy young women taking spironolactone with 1,165 women who were not on spironolactone, which found that the hyperkalemia rate of 0.72% among those on spironolactone was equivalent to the 0.76% baseline rate of hyperkalemia in the young, healthy female population (JAMA Dermatol. 2015;151[9];941-944).

Oral corticosteroids for acne, Dr. Thiboutot said, should be reserved to quiet a severe bout of inflammatory acne while standard therapies are being initiated.

She reported being an investigator or a consultant for a number of pharmaceutical companies.

[email protected]

On Twitter @karioakes

Spectators at baseball games may be exposed to excess solar UV radiation (UVR), which has been linked to the development of both melanoma and nonmelanoma skin cancers.^1,2 Although baseball hats traditionally are worn to demonstrate team support, they also may provide some sun protection for the head and face where skin cancers are commonly found.

The importance of protecting the skin from solar UVR has led to sun-protection programs and community education as well as efforts to evaluate the impact of these programs. Major League Baseball (MLB) has partnered with the American Academy of Dermatology since 1999 to promote the importance of sun protection and raise skin cancer awareness through its Play Sun Smart program.³ A study conducted 10 years ago (N=2030) evaluated hat use in spectators at MLB games and noted that less than half of all spectators in seating sections exposed to direct sunlight wore hats.⁴ The purpose of the current study was to evaluate how public education about sun protection has impacted the use of hats by spectators at MLB games in 2015 compared to the prior study in 2006.

Methods

Data were collected during a 3-game series (2 day games, 1 night game) in August 2015 in New York, New York. During one of the day games, 18,000 fans received a free wide-brimmed hat. High-resolution digital photographs of seating sections were obtained using a camera with a 300-mm lens. Using the same methodology as the prior study,⁴ sunny and shaded seating sections were photographed during all 3 games (Figure). Photographs of each section were analyzed by an independent reviewer using a high-resolution computer screen. Spectators wearing head coverings—baseball hats, visors, or hats with circumferential brims—were defined as using hats. The number of spectators wearing hats versus not wearing hats was recorded for all identical sections of interest. Bleacher seating was analyzed separately, as spectators presumably knew in advance of the continuous direct sun exposure during day games, and a subset of young children in the bleachers (<10 years of age) also was assessed. A continuously sunny section also was evaluated at the second and sixth innings to see if hats were presumably purchased during exposure. Statistical significance was determined using χ² tests with P<.05 indicating statistical significance.

Results

This analysis consisted of 3539 spectators. In both the sunny and shaded sections of a day game, there were more spectators wearing hats (49% and 37%, respectively)(P<.001) than in the same sections at night games (35% and 29%, respectively)(Table 1). During the day game, more spectators wore hats in the sunny section than in the adjacent shaded section (49% vs 37%; P<.001). Analysis of the same 2 sections during the night game revealed no significant differences.

Spectators sitting in the bleachers during a day game who presumably knew to anticipate direct sun exposure showed no significant differences in hat-wearing patterns versus the sunny section (44% vs 49%) but were more likely to wear hats compared to those sitting in the bleachers at the night game (44% vs 33%)(P<.001)(Table 1). There was no significant difference in the number of hats worn by spectators in the sunny section in the second inning (43%) versus the same section after continuous sun exposure at the sixth inning (44%)(Table 2). Significantly more children seated in the bleachers during the day game wore hats compared to adults in the same section (64% vs 42%; P<.001)(Table 3). During the hat giveaway day, significantly more spectators wore hats (the majority of which were the free giveaway hats) across all sections studied (P<.001)(Table 4).

Comment

More than 23 million spectators attended daytime MLB games in 2015, with millions more attending minor league and amateur events.⁵Although sun-protection messages tend to be well understood and received by society, many choose to ignore them.⁶

In partnership with the American Academy of Dermatology, the MLB’s Play Sun Smart program has promoted UVR risk awareness at sporting events since 1999.³ Those affiliated with MLB teams also receive annual skin cancer screenings in conjunction with a public education effort in May of each season. However, despite the years of sun-protection education, our study found that less than half of attendees wore hats for UVR protection. In fact, there were no significant differences noted across all of the hat-wearing parameters studied (day vs night game, sunny vs shaded section, sunny section over course of game) between the current study compared to the results from 10 years prior⁴ (Tables 1 and 2). For spectators in the bleacher section, even presumably knowing in advance that seating would be in the sun did not significantly increase hat-wearing behavior. Although skin cancer rates continue to rise, hat-wearing trends remain stable, revealing a concerning trend.

Increased availability of sunscreen has led to improved sun-protective behaviors in many populations.⁷ In our study, the free hat giveaway had the greatest impact on hat wearing, which suggests that improved availability and access to hats can lead to an important opportunity for sun-protection programs to partner with hat manufacturers to augment their use and protective impact.

Sun avoidance during childhood and adolescence has been shown to decrease the risk for melanoma.¹ Young children had the highest rate of hat usage in the current study, possibly due to parental example or dictates. Research has shown the importance of role models in promoting sun safety to young children,^8,9 so perhaps use of hats by parents or MLB players contributed to the hat-wearing behavior observed in this subpopulation.

Given the limited change observed in hat-wearing behaviors over the last decade, a knowledge and behavioral gap appears to exist that may be able to be exploited to enhance future sun protection. Also, based on our findings, the MLB and other sun-protection education campaigns may wish to augment their UVR protective messages by offering hat giveaways, which appear to have a notable impact.

Acknowledgment

The authors thank Jessie Skapik, BS (New York, New York), for her independent review of the spectator photographs.

Spectators at baseball games may be exposed to excess solar UV radiation (UVR), which has been linked to the development of both melanoma and nonmelanoma skin cancers.^1,2 Although baseball hats traditionally are worn to demonstrate team support, they also may provide some sun protection for the head and face where skin cancers are commonly found.

The importance of protecting the skin from solar UVR has led to sun-protection programs and community education as well as efforts to evaluate the impact of these programs. Major League Baseball (MLB) has partnered with the American Academy of Dermatology since 1999 to promote the importance of sun protection and raise skin cancer awareness through its Play Sun Smart program.³ A study conducted 10 years ago (N=2030) evaluated hat use in spectators at MLB games and noted that less than half of all spectators in seating sections exposed to direct sunlight wore hats.⁴ The purpose of the current study was to evaluate how public education about sun protection has impacted the use of hats by spectators at MLB games in 2015 compared to the prior study in 2006.

Methods

Data were collected during a 3-game series (2 day games, 1 night game) in August 2015 in New York, New York. During one of the day games, 18,000 fans received a free wide-brimmed hat. High-resolution digital photographs of seating sections were obtained using a camera with a 300-mm lens. Using the same methodology as the prior study,⁴ sunny and shaded seating sections were photographed during all 3 games (Figure). Photographs of each section were analyzed by an independent reviewer using a high-resolution computer screen. Spectators wearing head coverings—baseball hats, visors, or hats with circumferential brims—were defined as using hats. The number of spectators wearing hats versus not wearing hats was recorded for all identical sections of interest. Bleacher seating was analyzed separately, as spectators presumably knew in advance of the continuous direct sun exposure during day games, and a subset of young children in the bleachers (<10 years of age) also was assessed. A continuously sunny section also was evaluated at the second and sixth innings to see if hats were presumably purchased during exposure. Statistical significance was determined using χ² tests with P<.05 indicating statistical significance.

Results

This analysis consisted of 3539 spectators. In both the sunny and shaded sections of a day game, there were more spectators wearing hats (49% and 37%, respectively)(P<.001) than in the same sections at night games (35% and 29%, respectively)(Table 1). During the day game, more spectators wore hats in the sunny section than in the adjacent shaded section (49% vs 37%; P<.001). Analysis of the same 2 sections during the night game revealed no significant differences.

Spectators sitting in the bleachers during a day game who presumably knew to anticipate direct sun exposure showed no significant differences in hat-wearing patterns versus the sunny section (44% vs 49%) but were more likely to wear hats compared to those sitting in the bleachers at the night game (44% vs 33%)(P<.001)(Table 1). There was no significant difference in the number of hats worn by spectators in the sunny section in the second inning (43%) versus the same section after continuous sun exposure at the sixth inning (44%)(Table 2). Significantly more children seated in the bleachers during the day game wore hats compared to adults in the same section (64% vs 42%; P<.001)(Table 3). During the hat giveaway day, significantly more spectators wore hats (the majority of which were the free giveaway hats) across all sections studied (P<.001)(Table 4).

Comment

More than 23 million spectators attended daytime MLB games in 2015, with millions more attending minor league and amateur events.⁵Although sun-protection messages tend to be well understood and received by society, many choose to ignore them.⁶

In partnership with the American Academy of Dermatology, the MLB’s Play Sun Smart program has promoted UVR risk awareness at sporting events since 1999.³ Those affiliated with MLB teams also receive annual skin cancer screenings in conjunction with a public education effort in May of each season. However, despite the years of sun-protection education, our study found that less than half of attendees wore hats for UVR protection. In fact, there were no significant differences noted across all of the hat-wearing parameters studied (day vs night game, sunny vs shaded section, sunny section over course of game) between the current study compared to the results from 10 years prior⁴ (Tables 1 and 2). For spectators in the bleacher section, even presumably knowing in advance that seating would be in the sun did not significantly increase hat-wearing behavior. Although skin cancer rates continue to rise, hat-wearing trends remain stable, revealing a concerning trend.

Increased availability of sunscreen has led to improved sun-protective behaviors in many populations.⁷ In our study, the free hat giveaway had the greatest impact on hat wearing, which suggests that improved availability and access to hats can lead to an important opportunity for sun-protection programs to partner with hat manufacturers to augment their use and protective impact.

Sun avoidance during childhood and adolescence has been shown to decrease the risk for melanoma.¹ Young children had the highest rate of hat usage in the current study, possibly due to parental example or dictates. Research has shown the importance of role models in promoting sun safety to young children,^8,9 so perhaps use of hats by parents or MLB players contributed to the hat-wearing behavior observed in this subpopulation.

Given the limited change observed in hat-wearing behaviors over the last decade, a knowledge and behavioral gap appears to exist that may be able to be exploited to enhance future sun protection. Also, based on our findings, the MLB and other sun-protection education campaigns may wish to augment their UVR protective messages by offering hat giveaways, which appear to have a notable impact.

Acknowledgment

The authors thank Jessie Skapik, BS (New York, New York), for her independent review of the spectator photographs.

Spectators at baseball games may be exposed to excess solar UV radiation (UVR), which has been linked to the development of both melanoma and nonmelanoma skin cancers.^1,2 Although baseball hats traditionally are worn to demonstrate team support, they also may provide some sun protection for the head and face where skin cancers are commonly found.

The importance of protecting the skin from solar UVR has led to sun-protection programs and community education as well as efforts to evaluate the impact of these programs. Major League Baseball (MLB) has partnered with the American Academy of Dermatology since 1999 to promote the importance of sun protection and raise skin cancer awareness through its Play Sun Smart program.³ A study conducted 10 years ago (N=2030) evaluated hat use in spectators at MLB games and noted that less than half of all spectators in seating sections exposed to direct sunlight wore hats.⁴ The purpose of the current study was to evaluate how public education about sun protection has impacted the use of hats by spectators at MLB games in 2015 compared to the prior study in 2006.

Methods

Data were collected during a 3-game series (2 day games, 1 night game) in August 2015 in New York, New York. During one of the day games, 18,000 fans received a free wide-brimmed hat. High-resolution digital photographs of seating sections were obtained using a camera with a 300-mm lens. Using the same methodology as the prior study,⁴ sunny and shaded seating sections were photographed during all 3 games (Figure). Photographs of each section were analyzed by an independent reviewer using a high-resolution computer screen. Spectators wearing head coverings—baseball hats, visors, or hats with circumferential brims—were defined as using hats. The number of spectators wearing hats versus not wearing hats was recorded for all identical sections of interest. Bleacher seating was analyzed separately, as spectators presumably knew in advance of the continuous direct sun exposure during day games, and a subset of young children in the bleachers (<10 years of age) also was assessed. A continuously sunny section also was evaluated at the second and sixth innings to see if hats were presumably purchased during exposure. Statistical significance was determined using χ² tests with P<.05 indicating statistical significance.

Results

This analysis consisted of 3539 spectators. In both the sunny and shaded sections of a day game, there were more spectators wearing hats (49% and 37%, respectively)(P<.001) than in the same sections at night games (35% and 29%, respectively)(Table 1). During the day game, more spectators wore hats in the sunny section than in the adjacent shaded section (49% vs 37%; P<.001). Analysis of the same 2 sections during the night game revealed no significant differences.

Spectators sitting in the bleachers during a day game who presumably knew to anticipate direct sun exposure showed no significant differences in hat-wearing patterns versus the sunny section (44% vs 49%) but were more likely to wear hats compared to those sitting in the bleachers at the night game (44% vs 33%)(P<.001)(Table 1). There was no significant difference in the number of hats worn by spectators in the sunny section in the second inning (43%) versus the same section after continuous sun exposure at the sixth inning (44%)(Table 2). Significantly more children seated in the bleachers during the day game wore hats compared to adults in the same section (64% vs 42%; P<.001)(Table 3). During the hat giveaway day, significantly more spectators wore hats (the majority of which were the free giveaway hats) across all sections studied (P<.001)(Table 4).

Comment

More than 23 million spectators attended daytime MLB games in 2015, with millions more attending minor league and amateur events.⁵Although sun-protection messages tend to be well understood and received by society, many choose to ignore them.⁶

In partnership with the American Academy of Dermatology, the MLB’s Play Sun Smart program has promoted UVR risk awareness at sporting events since 1999.³ Those affiliated with MLB teams also receive annual skin cancer screenings in conjunction with a public education effort in May of each season. However, despite the years of sun-protection education, our study found that less than half of attendees wore hats for UVR protection. In fact, there were no significant differences noted across all of the hat-wearing parameters studied (day vs night game, sunny vs shaded section, sunny section over course of game) between the current study compared to the results from 10 years prior⁴ (Tables 1 and 2). For spectators in the bleacher section, even presumably knowing in advance that seating would be in the sun did not significantly increase hat-wearing behavior. Although skin cancer rates continue to rise, hat-wearing trends remain stable, revealing a concerning trend.

Increased availability of sunscreen has led to improved sun-protective behaviors in many populations.⁷ In our study, the free hat giveaway had the greatest impact on hat wearing, which suggests that improved availability and access to hats can lead to an important opportunity for sun-protection programs to partner with hat manufacturers to augment their use and protective impact.

Sun avoidance during childhood and adolescence has been shown to decrease the risk for melanoma.¹ Young children had the highest rate of hat usage in the current study, possibly due to parental example or dictates. Research has shown the importance of role models in promoting sun safety to young children,^8,9 so perhaps use of hats by parents or MLB players contributed to the hat-wearing behavior observed in this subpopulation.

Given the limited change observed in hat-wearing behaviors over the last decade, a knowledge and behavioral gap appears to exist that may be able to be exploited to enhance future sun protection. Also, based on our findings, the MLB and other sun-protection education campaigns may wish to augment their UVR protective messages by offering hat giveaways, which appear to have a notable impact.

Acknowledgment

The authors thank Jessie Skapik, BS (New York, New York), for her independent review of the spectator photographs.

Mass administration of malaria chemoprevention during Ebola virus disease outbreaks may reduce cases of fever, according to a study published in PLOS ONE.

During the October-December 2014 Ebola virus disease (EVD) outbreak in Liberia, health care services were limited, negatively impacting malaria treatment. Hoping to reduce malaria-associated morbidity, investigators targeted four neighborhoods in Monrovia, Liberia – with a total population of 551,971 – for a mass drug administration (MDA) of malaria chemoprevention. MDA participants were divided into two treatment rounds, with 102,372 households verified as receiving treatment with the drug combination artesunate/amodiaquine by community leaders and a malaria committee in round 1, and 103,497 households verified in round 2.

©CDC/Cynthia Goldsmith

Incidences of self-reported fever episodes declined significantly after round 1 (1.5%), compared with the month prior to round 1 (4.2%) (P < .0001). Self-reported fever incidences in children younger than 5 years of age (6.9%) and in older household members (3.8%) both decreased, to 1.1% and 1.6%, respectively, after round 1 of the MDA.

The researchers also found that self-reported fever was 4.9% lower after round 1 in household members who took a full course of artesunate/amodiaquine malaria chemoprevention (ASAQ-CP) but only 0.6% lower among household members who did not start or not complete a full course of ASAQ-CP. Still, reported incidence of fever declined in both groups, although the risk difference (RD) was significantly larger among the group that took part in the ASAQ-CP course (P < .001).

“Despite high acceptance and coverage of the MDA and the small impact of side effects, initiation of malaria chemoprevention was low, possibly due to health messaging and behavior in the pre-Ebola outbreak period and the ongoing lack of health care services,” researchers concluded. “Combining MDAs during Ebola outbreaks with longer-term interventions to prevent malaria and to improve access to health care might reduce the proportion of respondents saving their treatment for future malaria episodes.”

Read the full study in PLOS ONE (doi: 10.1371/journal.pone.0161311).

[email protected]

Mass administration of malaria chemoprevention during Ebola virus disease outbreaks may reduce cases of fever, according to a study published in PLOS ONE.

During the October-December 2014 Ebola virus disease (EVD) outbreak in Liberia, health care services were limited, negatively impacting malaria treatment. Hoping to reduce malaria-associated morbidity, investigators targeted four neighborhoods in Monrovia, Liberia – with a total population of 551,971 – for a mass drug administration (MDA) of malaria chemoprevention. MDA participants were divided into two treatment rounds, with 102,372 households verified as receiving treatment with the drug combination artesunate/amodiaquine by community leaders and a malaria committee in round 1, and 103,497 households verified in round 2.

©CDC/Cynthia Goldsmith

Incidences of self-reported fever episodes declined significantly after round 1 (1.5%), compared with the month prior to round 1 (4.2%) (P < .0001). Self-reported fever incidences in children younger than 5 years of age (6.9%) and in older household members (3.8%) both decreased, to 1.1% and 1.6%, respectively, after round 1 of the MDA.

The researchers also found that self-reported fever was 4.9% lower after round 1 in household members who took a full course of artesunate/amodiaquine malaria chemoprevention (ASAQ-CP) but only 0.6% lower among household members who did not start or not complete a full course of ASAQ-CP. Still, reported incidence of fever declined in both groups, although the risk difference (RD) was significantly larger among the group that took part in the ASAQ-CP course (P < .001).

“Despite high acceptance and coverage of the MDA and the small impact of side effects, initiation of malaria chemoprevention was low, possibly due to health messaging and behavior in the pre-Ebola outbreak period and the ongoing lack of health care services,” researchers concluded. “Combining MDAs during Ebola outbreaks with longer-term interventions to prevent malaria and to improve access to health care might reduce the proportion of respondents saving their treatment for future malaria episodes.”

Read the full study in PLOS ONE (doi: 10.1371/journal.pone.0161311).

[email protected]

Mass administration of malaria chemoprevention during Ebola virus disease outbreaks may reduce cases of fever, according to a study published in PLOS ONE.

During the October-December 2014 Ebola virus disease (EVD) outbreak in Liberia, health care services were limited, negatively impacting malaria treatment. Hoping to reduce malaria-associated morbidity, investigators targeted four neighborhoods in Monrovia, Liberia – with a total population of 551,971 – for a mass drug administration (MDA) of malaria chemoprevention. MDA participants were divided into two treatment rounds, with 102,372 households verified as receiving treatment with the drug combination artesunate/amodiaquine by community leaders and a malaria committee in round 1, and 103,497 households verified in round 2.

©CDC/Cynthia Goldsmith

Incidences of self-reported fever episodes declined significantly after round 1 (1.5%), compared with the month prior to round 1 (4.2%) (P < .0001). Self-reported fever incidences in children younger than 5 years of age (6.9%) and in older household members (3.8%) both decreased, to 1.1% and 1.6%, respectively, after round 1 of the MDA.

The researchers also found that self-reported fever was 4.9% lower after round 1 in household members who took a full course of artesunate/amodiaquine malaria chemoprevention (ASAQ-CP) but only 0.6% lower among household members who did not start or not complete a full course of ASAQ-CP. Still, reported incidence of fever declined in both groups, although the risk difference (RD) was significantly larger among the group that took part in the ASAQ-CP course (P < .001).

“Despite high acceptance and coverage of the MDA and the small impact of side effects, initiation of malaria chemoprevention was low, possibly due to health messaging and behavior in the pre-Ebola outbreak period and the ongoing lack of health care services,” researchers concluded. “Combining MDAs during Ebola outbreaks with longer-term interventions to prevent malaria and to improve access to health care might reduce the proportion of respondents saving their treatment for future malaria episodes.”

Read the full study in PLOS ONE (doi: 10.1371/journal.pone.0161311).

[email protected]

The combination of dasatinib and venetoclax had a synergistic effect that was associated with lower toxicity than single-agent therapy, based on responses of primary Philadelphia chromosome–positive acute lymphoblastic leukemia (PH+ALL) samples in xenografted immunodeficient mice, according to Jessica T. Leonard, MD.

Dr. Leonard and her colleagues at Oregon Health and Science University in Portland demonstrated that the combination of venetoclax – a selective inhibitor of B cell lymphoma 2 – was highly synergistic with tyrosine kinase inhibitors in vitro. In the preclinical model of PH+ALL, a stepwise reduction in median inhibitory concentration of dasatinib was observed with increasing doses of venetoclax, as was decreased cell viability and induced apoptosis. Dasatinib – a breakpoint cluster region–Abelson kinase inhibitor – has an additional advantage of potentially overcoming venetoclax resistance by blocking a common mechanism of resistance to the agent, the investigators reported Aug. 31 in Science Translational Medicine (2016; 8[354]:354ra114).

The combination boosted antitumor activity against Ph+ALL cells grown in culture. In the mouse model of Ph+ALL, all of the mice in the combination dosing group remained alive during the 4-week treatment period. The combination therapy was well tolerated, and superior to either agent alone with respect to antileukemic efficacy.

The investigators focused on combining venetoclax with dasatinib because it is “the current backbone for the treatment of adult Ph+ALL ... These results lay the foundation for the testing of this combination in patients with Ph+ALL with the goal of improving treatment,” they concluded.

This study was supported in part by the Leukemia & Lymphoma Society and the Newman’s Own Foundation. Dr. Leonard reported having no other disclosures, but various coauthors reported receiving research support from, and/or serving as a consultant or scientific advisory board member to Genentech, the maker of venetoclax, and Bristol-Myers Squibb, the maker of dasatinib, as well as numerous other drug companies.

[email protected]

The combination of dasatinib and venetoclax had a synergistic effect that was associated with lower toxicity than single-agent therapy, based on responses of primary Philadelphia chromosome–positive acute lymphoblastic leukemia (PH+ALL) samples in xenografted immunodeficient mice, according to Jessica T. Leonard, MD.

Dr. Leonard and her colleagues at Oregon Health and Science University in Portland demonstrated that the combination of venetoclax – a selective inhibitor of B cell lymphoma 2 – was highly synergistic with tyrosine kinase inhibitors in vitro. In the preclinical model of PH+ALL, a stepwise reduction in median inhibitory concentration of dasatinib was observed with increasing doses of venetoclax, as was decreased cell viability and induced apoptosis. Dasatinib – a breakpoint cluster region–Abelson kinase inhibitor – has an additional advantage of potentially overcoming venetoclax resistance by blocking a common mechanism of resistance to the agent, the investigators reported Aug. 31 in Science Translational Medicine (2016; 8[354]:354ra114).

The combination boosted antitumor activity against Ph+ALL cells grown in culture. In the mouse model of Ph+ALL, all of the mice in the combination dosing group remained alive during the 4-week treatment period. The combination therapy was well tolerated, and superior to either agent alone with respect to antileukemic efficacy.

The investigators focused on combining venetoclax with dasatinib because it is “the current backbone for the treatment of adult Ph+ALL ... These results lay the foundation for the testing of this combination in patients with Ph+ALL with the goal of improving treatment,” they concluded.

This study was supported in part by the Leukemia & Lymphoma Society and the Newman’s Own Foundation. Dr. Leonard reported having no other disclosures, but various coauthors reported receiving research support from, and/or serving as a consultant or scientific advisory board member to Genentech, the maker of venetoclax, and Bristol-Myers Squibb, the maker of dasatinib, as well as numerous other drug companies.

[email protected]

The combination of dasatinib and venetoclax had a synergistic effect that was associated with lower toxicity than single-agent therapy, based on responses of primary Philadelphia chromosome–positive acute lymphoblastic leukemia (PH+ALL) samples in xenografted immunodeficient mice, according to Jessica T. Leonard, MD.

Dr. Leonard and her colleagues at Oregon Health and Science University in Portland demonstrated that the combination of venetoclax – a selective inhibitor of B cell lymphoma 2 – was highly synergistic with tyrosine kinase inhibitors in vitro. In the preclinical model of PH+ALL, a stepwise reduction in median inhibitory concentration of dasatinib was observed with increasing doses of venetoclax, as was decreased cell viability and induced apoptosis. Dasatinib – a breakpoint cluster region–Abelson kinase inhibitor – has an additional advantage of potentially overcoming venetoclax resistance by blocking a common mechanism of resistance to the agent, the investigators reported Aug. 31 in Science Translational Medicine (2016; 8[354]:354ra114).

The combination boosted antitumor activity against Ph+ALL cells grown in culture. In the mouse model of Ph+ALL, all of the mice in the combination dosing group remained alive during the 4-week treatment period. The combination therapy was well tolerated, and superior to either agent alone with respect to antileukemic efficacy.

The investigators focused on combining venetoclax with dasatinib because it is “the current backbone for the treatment of adult Ph+ALL ... These results lay the foundation for the testing of this combination in patients with Ph+ALL with the goal of improving treatment,” they concluded.

This study was supported in part by the Leukemia & Lymphoma Society and the Newman’s Own Foundation. Dr. Leonard reported having no other disclosures, but various coauthors reported receiving research support from, and/or serving as a consultant or scientific advisory board member to Genentech, the maker of venetoclax, and Bristol-Myers Squibb, the maker of dasatinib, as well as numerous other drug companies.

[email protected]

ROME – Results of the largest-ever randomized clinical trial of anticoagulation for electrical cardioversion of patients with nonvalvular atrial fibrillation demonstrate that edoxaban is a safe, effective, and convenient alternative to the standard strategy of enoxaparin as a bridge to warfarin.

The ENSURE-AF trial was a phase IIIb study involving 2,199 patients with atrial fibrillation who underwent electrical cardioversion at 239 sites in the United States and 19 European countries. The key finding: The edoxaban-treated group had rates of thromboembolism and major bleeding at 28-30 days follow-up similar to those of the enoxaparin/warfarin-treated controls.

And edoxaban offered a major practical advantage: Because “edoxaban kicks in within 2 hours, you can do the procedure just 2 hours after initiation of therapy in a patient with a reassuring transesophageal echocardiographic exam, which is definitely not possible with warfarin,” Andreas Goette, MD, observed at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

Roughly half of participants were treated at centers that don’t routinely use a transesophageal echo-guided management strategy and therefore delayed cardioversion until patients were anticoagulated for at least 3 weeks. The safety and efficacy outcomes were similar regardless of whether or not transesophageal echocardiography (TEE) guidance was used, according to Dr. Goette of St. Vincenz Hospital in Paderborn, Germany.

Edoxaban (Savaysa) was prescribed at 60 mg once daily except in patients weighing 60 kg or less or having a creatinine clearance rate of 15-50 mL/min, in which case they received 30 mg once daily. In the control arm, enoxaparin (Lovenox) was used until warfarin achieved an International Normalized Ratio of 2.0-3.0. Patients in the enoxaparin/warfarin arm spent a mean of 71% of their treatment time within the target INR range.

The primary efficacy outcome was the 28-day composite of stroke or other systemic embolic events, MI, or cardiovascular mortality. The rate was 0.5% in the edoxaban arm and 1.0% in the enoxaparin/warfarin group. In patients whose management strategy was TEE-guided, the rate was 0.3% in the edoxaban group and 0.8% with enoxaparin/warfarin. In non-TEE-guided patients, the rates were 0.6% and 1.2% with edoxaban and warfarin, respectively.

Although rates were consistently numerically lower in the edoxaban group, the differences did not reach statistical significance, Dr. Goette explained.

The combined rate of major or clinically relevant nonmajor bleeding through 30 days was 1.5% with edoxaban and similar at 1.0% with enoxaparin plus warfarin. Three patients in the edoxaban group experienced a major bleeding event, as did five in the comparator arm.

Because anticoagulation with edoxaban is so convenient and allows cardioversion to safely be performed in short order, the ENSURE-AF investigators are in the process of calculating the potential savings in health care costs obtainable through this strategy, the cardiologist said.

ENSURE-AF provides the first prospective randomized data on the use of edoxaban as an alternative to warfarin for pericardioversion anticoagulation. There has been one other randomized trial of a novel oral anticoagulant (NOAC) in this setting, the 1,504-patient X-VeRT trial (Eur Heart J. 2014 Dec 14;35[47]:3346-55), involving rivaroxaban (Xarelto).

Riccardo Cappato, MD, first author of the X-VeRT publication, served as the designated discussant for ENSURE-AF. He noted that the results of the two trials are “completely superimposable.” Rates of the composite efficacy endpoint were identical at 0.5% for both NOACs versus 1.0% for the vitamin K antagonist arms of X-VeRT and ENSURE-AF. The major bleeding rates also were identical for edoxaban and rivaroxaban in the two studies. Moreover, the major bleeding rates associated with warfarin or other vitamin K antagonists were spot-on the same in the two trials.

Bruce Jancin/Frontline Medical News

“It’s a rather unusual situation for such large numbers of patients,” observed Dr. Cappato of Humanitas Research Institute in Milan.

“These data go very clearly in the same direction. I think a good take-home message here for us today is that both of these novel oral anticoagulants can be safely and efficaciously applied to patients undergoing elective cardioversion of nonvalvular atrial fibrillation,” he added.

In an interview, Mark A. Creager, MD, immediate past president of the American Heart Association, said that many U.S. physicians are switching to NOACs for this purpose.

“We are already using the novel oral anticoagulants to facilitate anticoagulation for patients undergoing cardioversion, so ENSURE-AF provides objective evidence that edoxaban is a reasonable drug,” said Dr. Creager, director of the Dartmouth-Hitchcock Heart and Vascular Center in New Hampshire.

The ENSURE-AF trial was funded by Daiichi Sankyo. Dr. Goette and Dr. Cappato reported receiving research grants from and serving as consultants to that company and other pharmaceutical and medical device manufacturers.

Simultaneously with Dr. Goette’s presentation in Rome, the ENSURE-AF results were published online Aug. 30 in The Lancet.

[email protected]

ROME – Results of the largest-ever randomized clinical trial of anticoagulation for electrical cardioversion of patients with nonvalvular atrial fibrillation demonstrate that edoxaban is a safe, effective, and convenient alternative to the standard strategy of enoxaparin as a bridge to warfarin.

The ENSURE-AF trial was a phase IIIb study involving 2,199 patients with atrial fibrillation who underwent electrical cardioversion at 239 sites in the United States and 19 European countries. The key finding: The edoxaban-treated group had rates of thromboembolism and major bleeding at 28-30 days follow-up similar to those of the enoxaparin/warfarin-treated controls.

And edoxaban offered a major practical advantage: Because “edoxaban kicks in within 2 hours, you can do the procedure just 2 hours after initiation of therapy in a patient with a reassuring transesophageal echocardiographic exam, which is definitely not possible with warfarin,” Andreas Goette, MD, observed at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

Roughly half of participants were treated at centers that don’t routinely use a transesophageal echo-guided management strategy and therefore delayed cardioversion until patients were anticoagulated for at least 3 weeks. The safety and efficacy outcomes were similar regardless of whether or not transesophageal echocardiography (TEE) guidance was used, according to Dr. Goette of St. Vincenz Hospital in Paderborn, Germany.

Edoxaban (Savaysa) was prescribed at 60 mg once daily except in patients weighing 60 kg or less or having a creatinine clearance rate of 15-50 mL/min, in which case they received 30 mg once daily. In the control arm, enoxaparin (Lovenox) was used until warfarin achieved an International Normalized Ratio of 2.0-3.0. Patients in the enoxaparin/warfarin arm spent a mean of 71% of their treatment time within the target INR range.

The primary efficacy outcome was the 28-day composite of stroke or other systemic embolic events, MI, or cardiovascular mortality. The rate was 0.5% in the edoxaban arm and 1.0% in the enoxaparin/warfarin group. In patients whose management strategy was TEE-guided, the rate was 0.3% in the edoxaban group and 0.8% with enoxaparin/warfarin. In non-TEE-guided patients, the rates were 0.6% and 1.2% with edoxaban and warfarin, respectively.

Although rates were consistently numerically lower in the edoxaban group, the differences did not reach statistical significance, Dr. Goette explained.

The combined rate of major or clinically relevant nonmajor bleeding through 30 days was 1.5% with edoxaban and similar at 1.0% with enoxaparin plus warfarin. Three patients in the edoxaban group experienced a major bleeding event, as did five in the comparator arm.

Because anticoagulation with edoxaban is so convenient and allows cardioversion to safely be performed in short order, the ENSURE-AF investigators are in the process of calculating the potential savings in health care costs obtainable through this strategy, the cardiologist said.

ENSURE-AF provides the first prospective randomized data on the use of edoxaban as an alternative to warfarin for pericardioversion anticoagulation. There has been one other randomized trial of a novel oral anticoagulant (NOAC) in this setting, the 1,504-patient X-VeRT trial (Eur Heart J. 2014 Dec 14;35[47]:3346-55), involving rivaroxaban (Xarelto).

Riccardo Cappato, MD, first author of the X-VeRT publication, served as the designated discussant for ENSURE-AF. He noted that the results of the two trials are “completely superimposable.” Rates of the composite efficacy endpoint were identical at 0.5% for both NOACs versus 1.0% for the vitamin K antagonist arms of X-VeRT and ENSURE-AF. The major bleeding rates also were identical for edoxaban and rivaroxaban in the two studies. Moreover, the major bleeding rates associated with warfarin or other vitamin K antagonists were spot-on the same in the two trials.

Bruce Jancin/Frontline Medical News

“It’s a rather unusual situation for such large numbers of patients,” observed Dr. Cappato of Humanitas Research Institute in Milan.

“These data go very clearly in the same direction. I think a good take-home message here for us today is that both of these novel oral anticoagulants can be safely and efficaciously applied to patients undergoing elective cardioversion of nonvalvular atrial fibrillation,” he added.

In an interview, Mark A. Creager, MD, immediate past president of the American Heart Association, said that many U.S. physicians are switching to NOACs for this purpose.

“We are already using the novel oral anticoagulants to facilitate anticoagulation for patients undergoing cardioversion, so ENSURE-AF provides objective evidence that edoxaban is a reasonable drug,” said Dr. Creager, director of the Dartmouth-Hitchcock Heart and Vascular Center in New Hampshire.

The ENSURE-AF trial was funded by Daiichi Sankyo. Dr. Goette and Dr. Cappato reported receiving research grants from and serving as consultants to that company and other pharmaceutical and medical device manufacturers.

Simultaneously with Dr. Goette’s presentation in Rome, the ENSURE-AF results were published online Aug. 30 in The Lancet.

[email protected]

ROME – Results of the largest-ever randomized clinical trial of anticoagulation for electrical cardioversion of patients with nonvalvular atrial fibrillation demonstrate that edoxaban is a safe, effective, and convenient alternative to the standard strategy of enoxaparin as a bridge to warfarin.

The ENSURE-AF trial was a phase IIIb study involving 2,199 patients with atrial fibrillation who underwent electrical cardioversion at 239 sites in the United States and 19 European countries. The key finding: The edoxaban-treated group had rates of thromboembolism and major bleeding at 28-30 days follow-up similar to those of the enoxaparin/warfarin-treated controls.

And edoxaban offered a major practical advantage: Because “edoxaban kicks in within 2 hours, you can do the procedure just 2 hours after initiation of therapy in a patient with a reassuring transesophageal echocardiographic exam, which is definitely not possible with warfarin,” Andreas Goette, MD, observed at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

Roughly half of participants were treated at centers that don’t routinely use a transesophageal echo-guided management strategy and therefore delayed cardioversion until patients were anticoagulated for at least 3 weeks. The safety and efficacy outcomes were similar regardless of whether or not transesophageal echocardiography (TEE) guidance was used, according to Dr. Goette of St. Vincenz Hospital in Paderborn, Germany.

Edoxaban (Savaysa) was prescribed at 60 mg once daily except in patients weighing 60 kg or less or having a creatinine clearance rate of 15-50 mL/min, in which case they received 30 mg once daily. In the control arm, enoxaparin (Lovenox) was used until warfarin achieved an International Normalized Ratio of 2.0-3.0. Patients in the enoxaparin/warfarin arm spent a mean of 71% of their treatment time within the target INR range.

The primary efficacy outcome was the 28-day composite of stroke or other systemic embolic events, MI, or cardiovascular mortality. The rate was 0.5% in the edoxaban arm and 1.0% in the enoxaparin/warfarin group. In patients whose management strategy was TEE-guided, the rate was 0.3% in the edoxaban group and 0.8% with enoxaparin/warfarin. In non-TEE-guided patients, the rates were 0.6% and 1.2% with edoxaban and warfarin, respectively.

Although rates were consistently numerically lower in the edoxaban group, the differences did not reach statistical significance, Dr. Goette explained.

The combined rate of major or clinically relevant nonmajor bleeding through 30 days was 1.5% with edoxaban and similar at 1.0% with enoxaparin plus warfarin. Three patients in the edoxaban group experienced a major bleeding event, as did five in the comparator arm.

Because anticoagulation with edoxaban is so convenient and allows cardioversion to safely be performed in short order, the ENSURE-AF investigators are in the process of calculating the potential savings in health care costs obtainable through this strategy, the cardiologist said.

ENSURE-AF provides the first prospective randomized data on the use of edoxaban as an alternative to warfarin for pericardioversion anticoagulation. There has been one other randomized trial of a novel oral anticoagulant (NOAC) in this setting, the 1,504-patient X-VeRT trial (Eur Heart J. 2014 Dec 14;35[47]:3346-55), involving rivaroxaban (Xarelto).

Riccardo Cappato, MD, first author of the X-VeRT publication, served as the designated discussant for ENSURE-AF. He noted that the results of the two trials are “completely superimposable.” Rates of the composite efficacy endpoint were identical at 0.5% for both NOACs versus 1.0% for the vitamin K antagonist arms of X-VeRT and ENSURE-AF. The major bleeding rates also were identical for edoxaban and rivaroxaban in the two studies. Moreover, the major bleeding rates associated with warfarin or other vitamin K antagonists were spot-on the same in the two trials.

Bruce Jancin/Frontline Medical News

“It’s a rather unusual situation for such large numbers of patients,” observed Dr. Cappato of Humanitas Research Institute in Milan.

“These data go very clearly in the same direction. I think a good take-home message here for us today is that both of these novel oral anticoagulants can be safely and efficaciously applied to patients undergoing elective cardioversion of nonvalvular atrial fibrillation,” he added.

In an interview, Mark A. Creager, MD, immediate past president of the American Heart Association, said that many U.S. physicians are switching to NOACs for this purpose.

“We are already using the novel oral anticoagulants to facilitate anticoagulation for patients undergoing cardioversion, so ENSURE-AF provides objective evidence that edoxaban is a reasonable drug,” said Dr. Creager, director of the Dartmouth-Hitchcock Heart and Vascular Center in New Hampshire.

The ENSURE-AF trial was funded by Daiichi Sankyo. Dr. Goette and Dr. Cappato reported receiving research grants from and serving as consultants to that company and other pharmaceutical and medical device manufacturers.

Simultaneously with Dr. Goette’s presentation in Rome, the ENSURE-AF results were published online Aug. 30 in The Lancet.

[email protected]

Sport-related concussion (SRC) recovery time can be reduced if athletes are removed from game participation, according to R.J. Elbin, PhD, of the University of Arkansas, Fayetteville, and his associates.

In the prospective study, 95 athletes sought care for an SRC at a concussion specialty clinic between Sept. 1 and Dec. 1, 2014. The athletes were divided into two groups: those who continued to play after experiencing signs and symptoms of an SRC and those who were immediately removed from play. The played group took longer to recover (44 days) than did the removed group (22 days) (P = .003).

©s-c-s/Thinkstock

Post hoc analyses revealed that the played group demonstrated significantly worse verbal and visual memory, processing speed, and reaction time, and higher symptoms (all P less than or equal to .001), compared with the removed group at 1-7 days. From 8 to 30 days post injury, the played group demonstrated worse verbal memory (P = .009), visual memory (P less than or equal to .001), processing speed (P = .001), and greater symptoms (P = .001), compared with the removed group.

The study also showed that athletes in the played group were 8.80 times more likely to experience a protracted recovery, compared with athletes in the removed group (21 days or longer) (P less than .001). Athletes participated in a variety of sports including football, soccer, ice hockey, volleyball, field hockey, rugby, basketball, and wrestling.

“This study is the first to show that athletes who continue to play with an SRC experience a longer recovery and more time away from the sport,” researchers concluded. “These findings should be incorporated into SRC education and awareness programs for athletes, coaches, parents, and medical professionals.”

Find the full study in Pediatrics (doi: 10.1542/peds.2016-0910).

[email protected]

Sport-related concussion (SRC) recovery time can be reduced if athletes are removed from game participation, according to R.J. Elbin, PhD, of the University of Arkansas, Fayetteville, and his associates.

In the prospective study, 95 athletes sought care for an SRC at a concussion specialty clinic between Sept. 1 and Dec. 1, 2014. The athletes were divided into two groups: those who continued to play after experiencing signs and symptoms of an SRC and those who were immediately removed from play. The played group took longer to recover (44 days) than did the removed group (22 days) (P = .003).

©s-c-s/Thinkstock

Post hoc analyses revealed that the played group demonstrated significantly worse verbal and visual memory, processing speed, and reaction time, and higher symptoms (all P less than or equal to .001), compared with the removed group at 1-7 days. From 8 to 30 days post injury, the played group demonstrated worse verbal memory (P = .009), visual memory (P less than or equal to .001), processing speed (P = .001), and greater symptoms (P = .001), compared with the removed group.

The study also showed that athletes in the played group were 8.80 times more likely to experience a protracted recovery, compared with athletes in the removed group (21 days or longer) (P less than .001). Athletes participated in a variety of sports including football, soccer, ice hockey, volleyball, field hockey, rugby, basketball, and wrestling.

“This study is the first to show that athletes who continue to play with an SRC experience a longer recovery and more time away from the sport,” researchers concluded. “These findings should be incorporated into SRC education and awareness programs for athletes, coaches, parents, and medical professionals.”

Find the full study in Pediatrics (doi: 10.1542/peds.2016-0910).

[email protected]

Sport-related concussion (SRC) recovery time can be reduced if athletes are removed from game participation, according to R.J. Elbin, PhD, of the University of Arkansas, Fayetteville, and his associates.

In the prospective study, 95 athletes sought care for an SRC at a concussion specialty clinic between Sept. 1 and Dec. 1, 2014. The athletes were divided into two groups: those who continued to play after experiencing signs and symptoms of an SRC and those who were immediately removed from play. The played group took longer to recover (44 days) than did the removed group (22 days) (P = .003).

©s-c-s/Thinkstock

Post hoc analyses revealed that the played group demonstrated significantly worse verbal and visual memory, processing speed, and reaction time, and higher symptoms (all P less than or equal to .001), compared with the removed group at 1-7 days. From 8 to 30 days post injury, the played group demonstrated worse verbal memory (P = .009), visual memory (P less than or equal to .001), processing speed (P = .001), and greater symptoms (P = .001), compared with the removed group.

The study also showed that athletes in the played group were 8.80 times more likely to experience a protracted recovery, compared with athletes in the removed group (21 days or longer) (P less than .001). Athletes participated in a variety of sports including football, soccer, ice hockey, volleyball, field hockey, rugby, basketball, and wrestling.

“This study is the first to show that athletes who continue to play with an SRC experience a longer recovery and more time away from the sport,” researchers concluded. “These findings should be incorporated into SRC education and awareness programs for athletes, coaches, parents, and medical professionals.”

Find the full study in Pediatrics (doi: 10.1542/peds.2016-0910).

[email protected]

A genetic modification of the plasminogen activator inhibitor-1 gene in conjunction with lower respiratory infections during early life was associated with increased risk of asthma, morbidities, and reduced lung function, according to Seong H. Cho, MD, and his associates.

A history of respiratory syncytial virus (RSV) and a history of other lower respiratory infections (LRIs) before the age of 2 were independently associated with asthma in Latino people aged 8-21, with odd ratios of 9.9 and 9.1, respectively, while PAI-1 was not independently associated. In combination, the OR for PAI-1/RSV increased to 17.7, and the OR for PAI-1/other LRIs increased to 11.7.

©SilverV/Thinkstock

Lung function was also adversely affected by the joint effect of PAI-1 and early life infection. In patients with PAI-1/LRI, forced expiratory volume in 1 second (FEV₁₎ percent predicted and FEV₁/forced vital capacity (FVC) percent predicted were significantly less than in the control group. Similar but less significant results were seen in the PAI-1/RSV group. Recurring hospitalizations were also significantly more likely in the PAI-1/RSV group, with an OR of 3.1.

“Further prospective studies are needed to replicate our RSV-genotype findings in other non-Latino populations, and determine if PAI-1 variants may serve as a biomarker of risk, which may provide impetus for clinical trials of primary prevention of asthma. In the interim, PAI-1 genotype in combination with significant LRI identifies individuals at increased risk of developing asthma,” the investigators wrote.

Find the full study in PLoS One (doi: 10.1371/journal.pone.0157848).

[email protected]

A genetic modification of the plasminogen activator inhibitor-1 gene in conjunction with lower respiratory infections during early life was associated with increased risk of asthma, morbidities, and reduced lung function, according to Seong H. Cho, MD, and his associates.

A history of respiratory syncytial virus (RSV) and a history of other lower respiratory infections (LRIs) before the age of 2 were independently associated with asthma in Latino people aged 8-21, with odd ratios of 9.9 and 9.1, respectively, while PAI-1 was not independently associated. In combination, the OR for PAI-1/RSV increased to 17.7, and the OR for PAI-1/other LRIs increased to 11.7.

©SilverV/Thinkstock

Lung function was also adversely affected by the joint effect of PAI-1 and early life infection. In patients with PAI-1/LRI, forced expiratory volume in 1 second (FEV₁₎ percent predicted and FEV₁/forced vital capacity (FVC) percent predicted were significantly less than in the control group. Similar but less significant results were seen in the PAI-1/RSV group. Recurring hospitalizations were also significantly more likely in the PAI-1/RSV group, with an OR of 3.1.

“Further prospective studies are needed to replicate our RSV-genotype findings in other non-Latino populations, and determine if PAI-1 variants may serve as a biomarker of risk, which may provide impetus for clinical trials of primary prevention of asthma. In the interim, PAI-1 genotype in combination with significant LRI identifies individuals at increased risk of developing asthma,” the investigators wrote.

Find the full study in PLoS One (doi: 10.1371/journal.pone.0157848).

[email protected]

A genetic modification of the plasminogen activator inhibitor-1 gene in conjunction with lower respiratory infections during early life was associated with increased risk of asthma, morbidities, and reduced lung function, according to Seong H. Cho, MD, and his associates.

A history of respiratory syncytial virus (RSV) and a history of other lower respiratory infections (LRIs) before the age of 2 were independently associated with asthma in Latino people aged 8-21, with odd ratios of 9.9 and 9.1, respectively, while PAI-1 was not independently associated. In combination, the OR for PAI-1/RSV increased to 17.7, and the OR for PAI-1/other LRIs increased to 11.7.

©SilverV/Thinkstock

Lung function was also adversely affected by the joint effect of PAI-1 and early life infection. In patients with PAI-1/LRI, forced expiratory volume in 1 second (FEV₁₎ percent predicted and FEV₁/forced vital capacity (FVC) percent predicted were significantly less than in the control group. Similar but less significant results were seen in the PAI-1/RSV group. Recurring hospitalizations were also significantly more likely in the PAI-1/RSV group, with an OR of 3.1.

“Further prospective studies are needed to replicate our RSV-genotype findings in other non-Latino populations, and determine if PAI-1 variants may serve as a biomarker of risk, which may provide impetus for clinical trials of primary prevention of asthma. In the interim, PAI-1 genotype in combination with significant LRI identifies individuals at increased risk of developing asthma,” the investigators wrote.

Find the full study in PLoS One (doi: 10.1371/journal.pone.0157848).

[email protected]

Case Report

A 24-year-old man was referred to the dermatology department for evaluation of pustules, atrophic scars, and alopecia on the scalp of 6 years’ duration. Six years prior, erythema, scaling, and follicular keratotic papules had appeared on the superciliary arches, and he started to lose hair from the eyebrows. Three months later, he developed mildly pruritic and painful scaling and pustules on the scalp. These lesions resolved with atrophic scarring accompanied by alopecia. One year later, follicular keratotic papules developed on the cheeks, chest, abdomen, back, lateral upper arms, thighs, and axillae. Two years later, direct microscopy of the lesions on the scalp and fungal culture were negative. After 2 weeks of treatment with roxithromycin (0.15 g twice daily), the scalp pustules dried out and resolved; however, they recurred when the patient stopped taking the medication. Six months later, he was started on isotretinoin treatment (10 mg once daily) for half a year, but no improvement was seen. His parents were nonconsanguineous, and no other family members were affected.

Dermatologic examination revealed large areas of atrophic scarring and alopecia on the scalp. Only a few solitary hairs remained on the top of the head, with the follicles surrounded by keratotic papules, pustules, and black scabs. There was sparse hair on the forehead and temples and scattered hair clusters in the occipital region near the hairline. These follicles also were associated with keratotic papules (Figure 1A). Erythema, scales, and follicular keratotic papules of the superciliary arches with sparse eyebrows and axillary hairs were noted. Follicular keratotic papules also were observed on the cheeks, axillae, chest, abdomen, back, lateral upper arms, and thighs. Dental examination revealed a large space between the upper anterior teeth and the lower anterior teeth. The upper anterior teeth were anteverted, there was congenital absence of right lower central incisors, and the anterior teeth were in deep overbite and overjet (Figure 1B). There was gingival atrophy and calculus dentalis in the upper and lower teeth. He had a fissured tongue with atrophic filiform papillae (Figure 1C).

Comment

Folliculitis spinulosa decalvans, along with keratosis follicularis spinulosa decalvans (KFSD), keratosis pilaris atrophicans faciei, and atrophoderma vermiculatum, belongs to a group of diseases that includes keratosis pilaris atrophicans. In 1994, Oranje et al¹ suggested the term folliculitis spinulosa decalvans, with signs including persistent pustules, characteristic keratotic papules, and scarring alopecia of the scalp, which may be exacerbated at puberty. Staphylococcus aureus was isolated from the pustules in one study²; however, in another study, repeated cultures were negative.³ Although the main inheritance pattern of KFSD is X-linked, autosomal-dominant inheritance is more common in FSD. Furthermore, there are certain differences in the clinical manifestations of these 2 conditions. Therefore, it remains controversial if FSD is an independent disease or merely a subtype of KFSD.

Our patient’s symptoms manifested after puberty, primarily pustules as well as atrophic and scarring alopecia of the scalp and follicular keratotic papules on the head, face, trunk, lateral upper arms, and thighs. Pathologic examination showed massive infiltration of plasma cells, neutrophils, and multinucleated giant cells around the hair follicles. The clinical and histopathologic findings met the diagnostic criteria for FSD.

Folliculitis spinulosa decalvans is a rare clinical condition with few cases reported.^3-5 In addition to the aforementioned characteristic clinical manifestations, our patient also had dental anomalies, a fissured tongue, and atrophy of the tongue papillae, which are not known to be associated with FSD. Dental anomalies are characteristic of patients with Down syndrome, ectodermal dysplasia, Papillon-Lefèvre syndrome, and other conditions.⁶ Fissured tongue is a normal variant that occurs in 5% to 11% of individuals. It also is a classic but nonspecific feature of Melkersson-Rosenthal syndrome and may occur in psoriasis, Down syndrome, acromegaly, and Sjögren syndrome.⁷ Atrophy of the tongue papillae is associated with anemia, pellagra, Sjögren syndrome, candidiasis, and other conditions.⁸ Because there are no known reports of associations between FSD and any of these oral manifestations, it is possible that they were unrelated to FSD in our patient.

Folliculitis spinulosa decalvans usually is recurrent and there is no consistently effective treatment for it. Kunte et al⁴ reported that dapsone (100 mg/d) led to resolution of scalp inflammation and pustules within 1 month. Romine et al² reported that a 3-week course of dichloroxacillin (250 mg 4 times daily) induced disappearance of pustules around the hair follicles. However, Hallai et al⁵ reported a patient who was resistant to isotretinoin treatment. In our case, after 1 month of treatment with clarithromycin, metronidazole, viaminate, and fusidic acid cream, the pustules had resolved and the black scabs had fallen off, leaving atrophic scars. The long-term efficacy of this regimen is still under observation.

Conclusion

We report a case of FSD with dental anomalies, a fissured tongue, and atrophy of tongue papillae, none of which have previously been reported in association with FSD. We, therefore, believe that our patient’s oral manifestations are unrelated to FSD.

Case Report

A 24-year-old man was referred to the dermatology department for evaluation of pustules, atrophic scars, and alopecia on the scalp of 6 years’ duration. Six years prior, erythema, scaling, and follicular keratotic papules had appeared on the superciliary arches, and he started to lose hair from the eyebrows. Three months later, he developed mildly pruritic and painful scaling and pustules on the scalp. These lesions resolved with atrophic scarring accompanied by alopecia. One year later, follicular keratotic papules developed on the cheeks, chest, abdomen, back, lateral upper arms, thighs, and axillae. Two years later, direct microscopy of the lesions on the scalp and fungal culture were negative. After 2 weeks of treatment with roxithromycin (0.15 g twice daily), the scalp pustules dried out and resolved; however, they recurred when the patient stopped taking the medication. Six months later, he was started on isotretinoin treatment (10 mg once daily) for half a year, but no improvement was seen. His parents were nonconsanguineous, and no other family members were affected.

Dermatologic examination revealed large areas of atrophic scarring and alopecia on the scalp. Only a few solitary hairs remained on the top of the head, with the follicles surrounded by keratotic papules, pustules, and black scabs. There was sparse hair on the forehead and temples and scattered hair clusters in the occipital region near the hairline. These follicles also were associated with keratotic papules (Figure 1A). Erythema, scales, and follicular keratotic papules of the superciliary arches with sparse eyebrows and axillary hairs were noted. Follicular keratotic papules also were observed on the cheeks, axillae, chest, abdomen, back, lateral upper arms, and thighs. Dental examination revealed a large space between the upper anterior teeth and the lower anterior teeth. The upper anterior teeth were anteverted, there was congenital absence of right lower central incisors, and the anterior teeth were in deep overbite and overjet (Figure 1B). There was gingival atrophy and calculus dentalis in the upper and lower teeth. He had a fissured tongue with atrophic filiform papillae (Figure 1C).

Comment

Folliculitis spinulosa decalvans, along with keratosis follicularis spinulosa decalvans (KFSD), keratosis pilaris atrophicans faciei, and atrophoderma vermiculatum, belongs to a group of diseases that includes keratosis pilaris atrophicans. In 1994, Oranje et al¹ suggested the term folliculitis spinulosa decalvans, with signs including persistent pustules, characteristic keratotic papules, and scarring alopecia of the scalp, which may be exacerbated at puberty. Staphylococcus aureus was isolated from the pustules in one study²; however, in another study, repeated cultures were negative.³ Although the main inheritance pattern of KFSD is X-linked, autosomal-dominant inheritance is more common in FSD. Furthermore, there are certain differences in the clinical manifestations of these 2 conditions. Therefore, it remains controversial if FSD is an independent disease or merely a subtype of KFSD.

Our patient’s symptoms manifested after puberty, primarily pustules as well as atrophic and scarring alopecia of the scalp and follicular keratotic papules on the head, face, trunk, lateral upper arms, and thighs. Pathologic examination showed massive infiltration of plasma cells, neutrophils, and multinucleated giant cells around the hair follicles. The clinical and histopathologic findings met the diagnostic criteria for FSD.

Folliculitis spinulosa decalvans is a rare clinical condition with few cases reported.^3-5 In addition to the aforementioned characteristic clinical manifestations, our patient also had dental anomalies, a fissured tongue, and atrophy of the tongue papillae, which are not known to be associated with FSD. Dental anomalies are characteristic of patients with Down syndrome, ectodermal dysplasia, Papillon-Lefèvre syndrome, and other conditions.⁶ Fissured tongue is a normal variant that occurs in 5% to 11% of individuals. It also is a classic but nonspecific feature of Melkersson-Rosenthal syndrome and may occur in psoriasis, Down syndrome, acromegaly, and Sjögren syndrome.⁷ Atrophy of the tongue papillae is associated with anemia, pellagra, Sjögren syndrome, candidiasis, and other conditions.⁸ Because there are no known reports of associations between FSD and any of these oral manifestations, it is possible that they were unrelated to FSD in our patient.

Folliculitis spinulosa decalvans usually is recurrent and there is no consistently effective treatment for it. Kunte et al⁴ reported that dapsone (100 mg/d) led to resolution of scalp inflammation and pustules within 1 month. Romine et al² reported that a 3-week course of dichloroxacillin (250 mg 4 times daily) induced disappearance of pustules around the hair follicles. However, Hallai et al⁵ reported a patient who was resistant to isotretinoin treatment. In our case, after 1 month of treatment with clarithromycin, metronidazole, viaminate, and fusidic acid cream, the pustules had resolved and the black scabs had fallen off, leaving atrophic scars. The long-term efficacy of this regimen is still under observation.

Conclusion

We report a case of FSD with dental anomalies, a fissured tongue, and atrophy of tongue papillae, none of which have previously been reported in association with FSD. We, therefore, believe that our patient’s oral manifestations are unrelated to FSD.

Case Report

A 24-year-old man was referred to the dermatology department for evaluation of pustules, atrophic scars, and alopecia on the scalp of 6 years’ duration. Six years prior, erythema, scaling, and follicular keratotic papules had appeared on the superciliary arches, and he started to lose hair from the eyebrows. Three months later, he developed mildly pruritic and painful scaling and pustules on the scalp. These lesions resolved with atrophic scarring accompanied by alopecia. One year later, follicular keratotic papules developed on the cheeks, chest, abdomen, back, lateral upper arms, thighs, and axillae. Two years later, direct microscopy of the lesions on the scalp and fungal culture were negative. After 2 weeks of treatment with roxithromycin (0.15 g twice daily), the scalp pustules dried out and resolved; however, they recurred when the patient stopped taking the medication. Six months later, he was started on isotretinoin treatment (10 mg once daily) for half a year, but no improvement was seen. His parents were nonconsanguineous, and no other family members were affected.

Dermatologic examination revealed large areas of atrophic scarring and alopecia on the scalp. Only a few solitary hairs remained on the top of the head, with the follicles surrounded by keratotic papules, pustules, and black scabs. There was sparse hair on the forehead and temples and scattered hair clusters in the occipital region near the hairline. These follicles also were associated with keratotic papules (Figure 1A). Erythema, scales, and follicular keratotic papules of the superciliary arches with sparse eyebrows and axillary hairs were noted. Follicular keratotic papules also were observed on the cheeks, axillae, chest, abdomen, back, lateral upper arms, and thighs. Dental examination revealed a large space between the upper anterior teeth and the lower anterior teeth. The upper anterior teeth were anteverted, there was congenital absence of right lower central incisors, and the anterior teeth were in deep overbite and overjet (Figure 1B). There was gingival atrophy and calculus dentalis in the upper and lower teeth. He had a fissured tongue with atrophic filiform papillae (Figure 1C).

Comment

Folliculitis spinulosa decalvans, along with keratosis follicularis spinulosa decalvans (KFSD), keratosis pilaris atrophicans faciei, and atrophoderma vermiculatum, belongs to a group of diseases that includes keratosis pilaris atrophicans. In 1994, Oranje et al¹ suggested the term folliculitis spinulosa decalvans, with signs including persistent pustules, characteristic keratotic papules, and scarring alopecia of the scalp, which may be exacerbated at puberty. Staphylococcus aureus was isolated from the pustules in one study²; however, in another study, repeated cultures were negative.³ Although the main inheritance pattern of KFSD is X-linked, autosomal-dominant inheritance is more common in FSD. Furthermore, there are certain differences in the clinical manifestations of these 2 conditions. Therefore, it remains controversial if FSD is an independent disease or merely a subtype of KFSD.

Our patient’s symptoms manifested after puberty, primarily pustules as well as atrophic and scarring alopecia of the scalp and follicular keratotic papules on the head, face, trunk, lateral upper arms, and thighs. Pathologic examination showed massive infiltration of plasma cells, neutrophils, and multinucleated giant cells around the hair follicles. The clinical and histopathologic findings met the diagnostic criteria for FSD.

Folliculitis spinulosa decalvans is a rare clinical condition with few cases reported.^3-5 In addition to the aforementioned characteristic clinical manifestations, our patient also had dental anomalies, a fissured tongue, and atrophy of the tongue papillae, which are not known to be associated with FSD. Dental anomalies are characteristic of patients with Down syndrome, ectodermal dysplasia, Papillon-Lefèvre syndrome, and other conditions.⁶ Fissured tongue is a normal variant that occurs in 5% to 11% of individuals. It also is a classic but nonspecific feature of Melkersson-Rosenthal syndrome and may occur in psoriasis, Down syndrome, acromegaly, and Sjögren syndrome.⁷ Atrophy of the tongue papillae is associated with anemia, pellagra, Sjögren syndrome, candidiasis, and other conditions.⁸ Because there are no known reports of associations between FSD and any of these oral manifestations, it is possible that they were unrelated to FSD in our patient.

Folliculitis spinulosa decalvans usually is recurrent and there is no consistently effective treatment for it. Kunte et al⁴ reported that dapsone (100 mg/d) led to resolution of scalp inflammation and pustules within 1 month. Romine et al² reported that a 3-week course of dichloroxacillin (250 mg 4 times daily) induced disappearance of pustules around the hair follicles. However, Hallai et al⁵ reported a patient who was resistant to isotretinoin treatment. In our case, after 1 month of treatment with clarithromycin, metronidazole, viaminate, and fusidic acid cream, the pustules had resolved and the black scabs had fallen off, leaving atrophic scars. The long-term efficacy of this regimen is still under observation.

Conclusion

We report a case of FSD with dental anomalies, a fissured tongue, and atrophy of tongue papillae, none of which have previously been reported in association with FSD. We, therefore, believe that our patient’s oral manifestations are unrelated to FSD.

The term nevus spilus (NS), also known as speckled lentiginous nevus, was first used in the 19th century to describe lesions with background café au lait–like lentiginous melanocytic hyperplasia speckled with small, 1- to 3-mm, darker foci. The dark spots reflect lentigines; junctional, compound, and intradermal nevus cell nests; and more rarely Spitz and blue nevi. Both macular and papular subtypes have been described.¹ This birthmark is quite common, occurring in 1.3% to 2.3% of the adult population worldwide.² Hypertrichosis has been described in NS.^3-9 Two subsequent cases of malignant melanoma in hairy NS suggested that lesions may be particularly prone to malignant degeneration.^4,8 We report an additional case of hairy NS that was not associated with melanoma and consider whether dermatologists should warn their patients about this association.

Case Report

A 26-year-old woman presented with a stable 7×8-cm, tan-brown, macular, pigmented birthmark studded with darker 1- to 2-mm, irregular, brown-black and blue, confettilike macules on the left proximal lateral thigh that had been present since birth (Figure 1). Dark terminal hairs were present, arising from both the darker and lighter pigmented areas but not the surrounding normal skin.

A 4-mm punch biopsy from one of the dark blue macules demonstrated uniform lentiginous melanocytic hyperplasia and nevus cell nests adjacent to the sweat glands extending into the mid dermis (Figure 2). No clinical evidence of malignant degeneration was present.

Comment

The risk for melanoma is increased in classic nonspeckled congenital nevi and the risk correlates with the size of the lesion and most probably the number of nevus cells in the lesion that increase the risk for a random mutation.^8,10,11 It is likely that NS with or without hair presages a small increased risk for melanoma,^6,9,12 which is not surprising because NS is a subtype of congenital melanocytic nevus (CMN), a condition that is present at birth and results from a proliferation of melanocytes.⁶ Nevus spilus, however, appears to have a notably lower risk for malignant degeneration than other classic CMN of the same size. The following support for this hypothesis is offered: First, CMN have nevus cells broadly filling the dermis that extend more deeply into the dermis than NS (Figure 2A).¹⁰ In our estimation, CMN have at least 100 times the number of nevus cells per square centimeter compared to NS. The potential for malignant degeneration of any one melanocyte is greater when more are present. Second, although some NS lesions evolve, classic CMN are universally more proliferative than NS.^10,13 The involved skin in CMN thickens over time with increased numbers of melanocytes and marked overgrowth of adjacent tissue. Melanocytes in a proliferative phase may be more likely to undergo malignant degeneration.¹⁰

A PubMed search of articles indexed for MEDLINE using the search term nevus spilus and melanoma yielded 2 cases^4,8 of melanoma arising among 15 cases of hairy NS in the literature, which led to the suggestion that the presence of hair could be associated with an increased risk for malignant degeneration in NS (Table). This apparent high incidence of melanoma most likely reflects referral/publication bias rather than a statistically significant association. In fact, the clinical lesion most clinically similar to hairy NS is Becker nevus, with tan macules demonstrating lentiginous melanocytic hyperplasia associated with numerous coarse terminal hairs. There is no indication that Becker nevi have a considerable premalignant potential, though one case of melanoma arising in a Becker nevus has been reported.⁹ There is no evidence to suggest that classic CMN with hypertrichosis has a greater premalignant potential than similar lesions without hypertrichosis.

The term nevus spilus (NS), also known as speckled lentiginous nevus, was first used in the 19th century to describe lesions with background café au lait–like lentiginous melanocytic hyperplasia speckled with small, 1- to 3-mm, darker foci. The dark spots reflect lentigines; junctional, compound, and intradermal nevus cell nests; and more rarely Spitz and blue nevi. Both macular and papular subtypes have been described.¹ This birthmark is quite common, occurring in 1.3% to 2.3% of the adult population worldwide.² Hypertrichosis has been described in NS.^3-9 Two subsequent cases of malignant melanoma in hairy NS suggested that lesions may be particularly prone to malignant degeneration.^4,8 We report an additional case of hairy NS that was not associated with melanoma and consider whether dermatologists should warn their patients about this association.

Case Report

A 26-year-old woman presented with a stable 7×8-cm, tan-brown, macular, pigmented birthmark studded with darker 1- to 2-mm, irregular, brown-black and blue, confettilike macules on the left proximal lateral thigh that had been present since birth (Figure 1). Dark terminal hairs were present, arising from both the darker and lighter pigmented areas but not the surrounding normal skin.

A 4-mm punch biopsy from one of the dark blue macules demonstrated uniform lentiginous melanocytic hyperplasia and nevus cell nests adjacent to the sweat glands extending into the mid dermis (Figure 2). No clinical evidence of malignant degeneration was present.

Comment

The risk for melanoma is increased in classic nonspeckled congenital nevi and the risk correlates with the size of the lesion and most probably the number of nevus cells in the lesion that increase the risk for a random mutation.^8,10,11 It is likely that NS with or without hair presages a small increased risk for melanoma,^6,9,12 which is not surprising because NS is a subtype of congenital melanocytic nevus (CMN), a condition that is present at birth and results from a proliferation of melanocytes.⁶ Nevus spilus, however, appears to have a notably lower risk for malignant degeneration than other classic CMN of the same size. The following support for this hypothesis is offered: First, CMN have nevus cells broadly filling the dermis that extend more deeply into the dermis than NS (Figure 2A).¹⁰ In our estimation, CMN have at least 100 times the number of nevus cells per square centimeter compared to NS. The potential for malignant degeneration of any one melanocyte is greater when more are present. Second, although some NS lesions evolve, classic CMN are universally more proliferative than NS.^10,13 The involved skin in CMN thickens over time with increased numbers of melanocytes and marked overgrowth of adjacent tissue. Melanocytes in a proliferative phase may be more likely to undergo malignant degeneration.¹⁰

A PubMed search of articles indexed for MEDLINE using the search term nevus spilus and melanoma yielded 2 cases^4,8 of melanoma arising among 15 cases of hairy NS in the literature, which led to the suggestion that the presence of hair could be associated with an increased risk for malignant degeneration in NS (Table). This apparent high incidence of melanoma most likely reflects referral/publication bias rather than a statistically significant association. In fact, the clinical lesion most clinically similar to hairy NS is Becker nevus, with tan macules demonstrating lentiginous melanocytic hyperplasia associated with numerous coarse terminal hairs. There is no indication that Becker nevi have a considerable premalignant potential, though one case of melanoma arising in a Becker nevus has been reported.⁹ There is no evidence to suggest that classic CMN with hypertrichosis has a greater premalignant potential than similar lesions without hypertrichosis.

The term nevus spilus (NS), also known as speckled lentiginous nevus, was first used in the 19th century to describe lesions with background café au lait–like lentiginous melanocytic hyperplasia speckled with small, 1- to 3-mm, darker foci. The dark spots reflect lentigines; junctional, compound, and intradermal nevus cell nests; and more rarely Spitz and blue nevi. Both macular and papular subtypes have been described.¹ This birthmark is quite common, occurring in 1.3% to 2.3% of the adult population worldwide.² Hypertrichosis has been described in NS.^3-9 Two subsequent cases of malignant melanoma in hairy NS suggested that lesions may be particularly prone to malignant degeneration.^4,8 We report an additional case of hairy NS that was not associated with melanoma and consider whether dermatologists should warn their patients about this association.

Case Report

A 26-year-old woman presented with a stable 7×8-cm, tan-brown, macular, pigmented birthmark studded with darker 1- to 2-mm, irregular, brown-black and blue, confettilike macules on the left proximal lateral thigh that had been present since birth (Figure 1). Dark terminal hairs were present, arising from both the darker and lighter pigmented areas but not the surrounding normal skin.

A 4-mm punch biopsy from one of the dark blue macules demonstrated uniform lentiginous melanocytic hyperplasia and nevus cell nests adjacent to the sweat glands extending into the mid dermis (Figure 2). No clinical evidence of malignant degeneration was present.

Comment

The risk for melanoma is increased in classic nonspeckled congenital nevi and the risk correlates with the size of the lesion and most probably the number of nevus cells in the lesion that increase the risk for a random mutation.^8,10,11 It is likely that NS with or without hair presages a small increased risk for melanoma,^6,9,12 which is not surprising because NS is a subtype of congenital melanocytic nevus (CMN), a condition that is present at birth and results from a proliferation of melanocytes.⁶ Nevus spilus, however, appears to have a notably lower risk for malignant degeneration than other classic CMN of the same size. The following support for this hypothesis is offered: First, CMN have nevus cells broadly filling the dermis that extend more deeply into the dermis than NS (Figure 2A).¹⁰ In our estimation, CMN have at least 100 times the number of nevus cells per square centimeter compared to NS. The potential for malignant degeneration of any one melanocyte is greater when more are present. Second, although some NS lesions evolve, classic CMN are universally more proliferative than NS.^10,13 The involved skin in CMN thickens over time with increased numbers of melanocytes and marked overgrowth of adjacent tissue. Melanocytes in a proliferative phase may be more likely to undergo malignant degeneration.¹⁰

A PubMed search of articles indexed for MEDLINE using the search term nevus spilus and melanoma yielded 2 cases^4,8 of melanoma arising among 15 cases of hairy NS in the literature, which led to the suggestion that the presence of hair could be associated with an increased risk for malignant degeneration in NS (Table). This apparent high incidence of melanoma most likely reflects referral/publication bias rather than a statistically significant association. In fact, the clinical lesion most clinically similar to hairy NS is Becker nevus, with tan macules demonstrating lentiginous melanocytic hyperplasia associated with numerous coarse terminal hairs. There is no indication that Becker nevi have a considerable premalignant potential, though one case of melanoma arising in a Becker nevus has been reported.⁹ There is no evidence to suggest that classic CMN with hypertrichosis has a greater premalignant potential than similar lesions without hypertrichosis.

Atopic dermatitis (AD) is the most common inflammatory skin disease in both adults and children.¹ Unfortunately, the current treatment armamentarium is largely confined to topical calcineurin inhibitors, topical and systemic steroids, phototherapy, cyclosporine (not approved by the US Food and Drug Administration for AD), and other oral immunosuppressants.² The availability of partially helpful and highly toxic treatments creates a huge unmet need for more effective and safer treatments, particularly for patients with moderate to severe AD who often require systemic approaches.

Recent extensive translational (bench top to bedside and back) investigations in skin of AD patients has shown that skin phenotype is characterized by increased T-cell infiltration and related inflammatory cytokines as well as epidermal abnormalities (eg, hyperplasia, aberrant differentiation).³ Clinical improvement of AD has been demonstrated with broad T-cell targeted therapeutics, such as cyclosporine and narrowband UVB, coupled with decreases of T-cell infiltrates and inflammatory gene products as well as improvement of the pathologic epidermal phenotype.^4,5

In the past, AD was conceptualized as a T helper cell T_H2 (acute disease)/T_H1 (chronic disease) bipolar cytokine disorder.⁶ Acute lesions are characterized by high T_H2, T_H22, and some T_H17 signals, with intensification of these axes and T_H1 augmentation orchestrating the chronic phenotype.⁷ The identification of the inflammatory pathways underlying AD has led to the development and testing of more than 10 broad or targeted therapeutics (Table).⁸ Phase 1 and phase 2 studies of dupilumab (targeting IL-4Rα) have shown not only tremendous AD improvement (~70%) but also tissue reversal of the immune and barrier abnormalities, including inflammatory cytokines and epidermal hyperplasia.^9-11 As a result, other T_H2 axis inhibitors (anti–IL-13/tralokinumab, anti–IL-31RA/CIM 331) are now in clinical trials. The identification of IL-22 in AD lesions has prompted trials with an anti–IL-22 (ILV 094) and an IL-12/IL-23p40 (ustekinumab) inhibitor.¹² For psoriasis, ustekinumab showed 75% improvement in approximately 70% of patients,¹³ but for AD, despite clear clinical and molecular effects, differences compared to placebo were not statistically significant,¹² probably due to underdosing of the drug in an excessively immune-activated disease¹⁴ as well as allowing topical steroids in patients, which may minimize the differences in treatment effect between drug and placebo.

The developments seen in AD are now moving into other inflammatory skin diseases, particularly alopecia areata (AA), a T-cell–mediated disease that shares phenotypic similarities with AD and often is associated with it.¹⁵ There is a paucity of effective, remission-sustaining treatments of AA, particularly for patients with severe disease who rarely experience spontaneous hair regrowth and who have a limited response to topical interventions.^16,17 Our clinical experience showed that successfully treating patients with concurrent AD and AA has led to hair regrowth. Inspired by these clinical observations and by results obtained in AD,^9-12 studying AA skin showed an upregulation of not only the traditionally suspected culprit T_H1 but also T_H2 and T_H9 axes, IL-23 cytokines, and phosphodiesterase 4.¹⁸ Subsequently, a pilot study of 3 patients with extensive AA treated with ustekinumab showed that all 3 patients not only experienced hair regrowth but also had a reduction in inflammatory markers in scalp lesions.¹⁹ Although these results are promising, AA is an immunologically complex disease and it is yet to be determined if therapeutically targeting 1 (eg, IL-4) rather than a wide array of cytokines can reverse disease phenotype. There are ongoing clinical trials directed at different pathogenic targets (eg, Jak inhibitors, IL-13 antagonist, IL-17 antagonist, phosphodiesterase 4 antagonist); some showed some efficacy in small studies.^20,21

The finding of a commonly upregulated T_H2 pathway in both AD and AA will pave the way for studies with T_H2 antagonists in AA patients. Future targeted therapeutic studies will shed light on the pathogenic pathways of this devastating skin disease and answer the extensive unmet therapeutic need it presents.

Atopic dermatitis (AD) is the most common inflammatory skin disease in both adults and children.¹ Unfortunately, the current treatment armamentarium is largely confined to topical calcineurin inhibitors, topical and systemic steroids, phototherapy, cyclosporine (not approved by the US Food and Drug Administration for AD), and other oral immunosuppressants.² The availability of partially helpful and highly toxic treatments creates a huge unmet need for more effective and safer treatments, particularly for patients with moderate to severe AD who often require systemic approaches.

Recent extensive translational (bench top to bedside and back) investigations in skin of AD patients has shown that skin phenotype is characterized by increased T-cell infiltration and related inflammatory cytokines as well as epidermal abnormalities (eg, hyperplasia, aberrant differentiation).³ Clinical improvement of AD has been demonstrated with broad T-cell targeted therapeutics, such as cyclosporine and narrowband UVB, coupled with decreases of T-cell infiltrates and inflammatory gene products as well as improvement of the pathologic epidermal phenotype.^4,5

In the past, AD was conceptualized as a T helper cell T_H2 (acute disease)/T_H1 (chronic disease) bipolar cytokine disorder.⁶ Acute lesions are characterized by high T_H2, T_H22, and some T_H17 signals, with intensification of these axes and T_H1 augmentation orchestrating the chronic phenotype.⁷ The identification of the inflammatory pathways underlying AD has led to the development and testing of more than 10 broad or targeted therapeutics (Table).⁸ Phase 1 and phase 2 studies of dupilumab (targeting IL-4Rα) have shown not only tremendous AD improvement (~70%) but also tissue reversal of the immune and barrier abnormalities, including inflammatory cytokines and epidermal hyperplasia.^9-11 As a result, other T_H2 axis inhibitors (anti–IL-13/tralokinumab, anti–IL-31RA/CIM 331) are now in clinical trials. The identification of IL-22 in AD lesions has prompted trials with an anti–IL-22 (ILV 094) and an IL-12/IL-23p40 (ustekinumab) inhibitor.¹² For psoriasis, ustekinumab showed 75% improvement in approximately 70% of patients,¹³ but for AD, despite clear clinical and molecular effects, differences compared to placebo were not statistically significant,¹² probably due to underdosing of the drug in an excessively immune-activated disease¹⁴ as well as allowing topical steroids in patients, which may minimize the differences in treatment effect between drug and placebo.

The developments seen in AD are now moving into other inflammatory skin diseases, particularly alopecia areata (AA), a T-cell–mediated disease that shares phenotypic similarities with AD and often is associated with it.¹⁵ There is a paucity of effective, remission-sustaining treatments of AA, particularly for patients with severe disease who rarely experience spontaneous hair regrowth and who have a limited response to topical interventions.^16,17 Our clinical experience showed that successfully treating patients with concurrent AD and AA has led to hair regrowth. Inspired by these clinical observations and by results obtained in AD,^9-12 studying AA skin showed an upregulation of not only the traditionally suspected culprit T_H1 but also T_H2 and T_H9 axes, IL-23 cytokines, and phosphodiesterase 4.¹⁸ Subsequently, a pilot study of 3 patients with extensive AA treated with ustekinumab showed that all 3 patients not only experienced hair regrowth but also had a reduction in inflammatory markers in scalp lesions.¹⁹ Although these results are promising, AA is an immunologically complex disease and it is yet to be determined if therapeutically targeting 1 (eg, IL-4) rather than a wide array of cytokines can reverse disease phenotype. There are ongoing clinical trials directed at different pathogenic targets (eg, Jak inhibitors, IL-13 antagonist, IL-17 antagonist, phosphodiesterase 4 antagonist); some showed some efficacy in small studies.^20,21

The finding of a commonly upregulated T_H2 pathway in both AD and AA will pave the way for studies with T_H2 antagonists in AA patients. Future targeted therapeutic studies will shed light on the pathogenic pathways of this devastating skin disease and answer the extensive unmet therapeutic need it presents.

Atopic dermatitis (AD) is the most common inflammatory skin disease in both adults and children.¹ Unfortunately, the current treatment armamentarium is largely confined to topical calcineurin inhibitors, topical and systemic steroids, phototherapy, cyclosporine (not approved by the US Food and Drug Administration for AD), and other oral immunosuppressants.² The availability of partially helpful and highly toxic treatments creates a huge unmet need for more effective and safer treatments, particularly for patients with moderate to severe AD who often require systemic approaches.

Recent extensive translational (bench top to bedside and back) investigations in skin of AD patients has shown that skin phenotype is characterized by increased T-cell infiltration and related inflammatory cytokines as well as epidermal abnormalities (eg, hyperplasia, aberrant differentiation).³ Clinical improvement of AD has been demonstrated with broad T-cell targeted therapeutics, such as cyclosporine and narrowband UVB, coupled with decreases of T-cell infiltrates and inflammatory gene products as well as improvement of the pathologic epidermal phenotype.^4,5

In the past, AD was conceptualized as a T helper cell T_H2 (acute disease)/T_H1 (chronic disease) bipolar cytokine disorder.⁶ Acute lesions are characterized by high T_H2, T_H22, and some T_H17 signals, with intensification of these axes and T_H1 augmentation orchestrating the chronic phenotype.⁷ The identification of the inflammatory pathways underlying AD has led to the development and testing of more than 10 broad or targeted therapeutics (Table).⁸ Phase 1 and phase 2 studies of dupilumab (targeting IL-4Rα) have shown not only tremendous AD improvement (~70%) but also tissue reversal of the immune and barrier abnormalities, including inflammatory cytokines and epidermal hyperplasia.^9-11 As a result, other T_H2 axis inhibitors (anti–IL-13/tralokinumab, anti–IL-31RA/CIM 331) are now in clinical trials. The identification of IL-22 in AD lesions has prompted trials with an anti–IL-22 (ILV 094) and an IL-12/IL-23p40 (ustekinumab) inhibitor.¹² For psoriasis, ustekinumab showed 75% improvement in approximately 70% of patients,¹³ but for AD, despite clear clinical and molecular effects, differences compared to placebo were not statistically significant,¹² probably due to underdosing of the drug in an excessively immune-activated disease¹⁴ as well as allowing topical steroids in patients, which may minimize the differences in treatment effect between drug and placebo.

The developments seen in AD are now moving into other inflammatory skin diseases, particularly alopecia areata (AA), a T-cell–mediated disease that shares phenotypic similarities with AD and often is associated with it.¹⁵ There is a paucity of effective, remission-sustaining treatments of AA, particularly for patients with severe disease who rarely experience spontaneous hair regrowth and who have a limited response to topical interventions.^16,17 Our clinical experience showed that successfully treating patients with concurrent AD and AA has led to hair regrowth. Inspired by these clinical observations and by results obtained in AD,^9-12 studying AA skin showed an upregulation of not only the traditionally suspected culprit T_H1 but also T_H2 and T_H9 axes, IL-23 cytokines, and phosphodiesterase 4.¹⁸ Subsequently, a pilot study of 3 patients with extensive AA treated with ustekinumab showed that all 3 patients not only experienced hair regrowth but also had a reduction in inflammatory markers in scalp lesions.¹⁹ Although these results are promising, AA is an immunologically complex disease and it is yet to be determined if therapeutically targeting 1 (eg, IL-4) rather than a wide array of cytokines can reverse disease phenotype. There are ongoing clinical trials directed at different pathogenic targets (eg, Jak inhibitors, IL-13 antagonist, IL-17 antagonist, phosphodiesterase 4 antagonist); some showed some efficacy in small studies.^20,21

The finding of a commonly upregulated T_H2 pathway in both AD and AA will pave the way for studies with T_H2 antagonists in AA patients. Future targeted therapeutic studies will shed light on the pathogenic pathways of this devastating skin disease and answer the extensive unmet therapeutic need it presents.